IJMS, Vol. 18, Pages 1841: Arabidopsis E3 Ubiquitin Ligases PUB22 and PUB23 Negatively Regulate Drought Tolerance by Targeting ABA Receptor PYL9 for Degradation

IJMS, Vol. 18, Pages 1841: Arabidopsis E3 Ubiquitin Ligases PUB22 and PUB23 Negatively Regulate Drought Tolerance by Targeting ABA Receptor PYL9 for Degradation

International Journal of Molecular Sciences doi: 10.3390/ijms18091841

Authors: Jinfeng Zhao Linlin Zhao Ming Zhang Syed Zafar Jingjing Fang Ming Li Wenhui Zhang Xueyong Li

Drought causes osmotic stress and rapidly triggers abscisic acid (ABA) accumulation in plants. The roles of various ABA receptors in drought tolerance and molecular mechanisms regulating ABA receptor stability needs to be elucidated. Here, we report that Arabidopsis plants overexpressing PYL9, one of the 14 pyrabactin resistance (PYR)/pyrabactin resistance-like (PYL)/regulatory component of ABA receptors (RCAR) family ABA receptors, gained drought tolerance trait. Osmotic stress induced accumulation of the PYL9 protein, which was regulated by the 26S proteasome. PYL9 interacted with two highly homologous plant U-box E3 ubiquitin ligases PUB22 and PUB23. In the cell-free degradation assay, the degradation of GST-PYL9 was accelerated in protein extract from plants overexpressing PUB22 but slowed down in protein extract from the pub22 pub23 double mutant. The in vivo decay of Myc-PYL9 was significantly reduced in the pub22 pub23 double mutant as compared with the wild-type. Additionally, PUB22 also interacted with other ABA receptors such as PYL5, PYL7 and PYL8. Considering the improved drought tolerance in the pub22 pub23 double mutant in previous studies, our results suggest that PUB22 and PUB23 negatively regulate drought tolerance in part by facilitating ABA receptors degradation.

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Piezoelectric vibrator-stimulated potential and heart rate accelerations detected from the fetus

Publication date: October 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 101
Author(s): Rina Matsuoka, Sinyoung Lee, Miho Sato, Remi Hibiya, Yota Shimanuki, Misato Kasai, Kazusaku Kamiya, Atsuo Itakura, Takuji Koike, Katsuhisa Ikeda
ObjectivesThe fetus is well known to have a substantial capacity for sound recognition in the uterine environment. The aim of this study was to develop a sound stimulus system equipped with a piezoelectric vibrator (PV), record the PV-stimulated potential (PVSP) of the fetus and monitor changes of the fetal heart rate (FHR) under PV stimulation.MethodsThe relationship between the input voltage applied to a piezoelectric vibrator and the sound pressure generated in the uterus was calibrated based on a model of the maternal abdomen. Fourteen fetuses for the measurement of the PVSP and 22 fetuses for the measurement of the heart rate changes from low-risk pregnant women were recruited.ResultsThe PVSP responses were obtained in 9 out of 14 fetuses. All the tested fetuses accelerated the FHR after the 2 kHz tone stimulation at 70 dB intensity generated by PV from 32 to 37 weeks gestational age.ConclusionsUsing a newly developed sound stimulus system equipped with PV, the electric responses of a fetus recorded from electrodes placed on the mother's abdomen may be closely related to the auditory evoked response. Significant accelerations of FHR were objectively, accurately and readily obtained after the sound stimulation.



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Coronary artery rotation in native and stented porcine coronary arteries

Abstract

Introduction

Coronary arteries are exposed to several complex biomechanical forces during the cardiac cycle. These biomechanical forces potentially contribute to both native coronary artery disease, development of atherosclerosis and eventual stent failure. The aim of the present study was to characterize and define coronary artery axial rotation and the effect of stent implantation on this biomechanical factor.

Methods

Intravascular ultrasound (IVUS) images were obtained from porcine coronary arteries and analyzed in ultrasound analysis software used to evaluate myocardial strain and torsion in echocardiography. In this study the software was utilized for a novel application to evaluate coronary artery rotation and time-to-peak (TTP) rotation in porcine coronary arteries. Clockwise (CW) and counterclockwise (CCW) rotation of coronary arteries during the cardiac cycle and (TTP) rotation were measured.

Results

A total of 11 (4 LAD, 4 LCX, 3 RCA) coronary artery segments were independently analyzed pre- and post-stent implantation for a total of 22 IVUS runs. CW and CCW rotation and TTP varied widely within coronary artery segments and between different coronary arteries. Stent implantation impacted degree, direction and TTP of coronary rotation. Measurement reliability was assessed and the intraclass correlation coefficient for maximum average CCW was 0.990 (95% confidence interval 0.980–0.996, P < 0.0001), indicating excellent agreement.

Conclusions

Coronary arteries display wide spectrum of CW and CCW rotation during the cardiac cycle. Coronary stents impact the degree and direction of coronary artery rotation. The implications of these findings on development of atherosclerosis and stent failure require further investigation.

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Safety of shorter length of hospital stay for patients undergoing minimalist transcatheter aortic valve replacement

Abstract

Objective

Determine the feasibility and predictors of early discharge after minimalist transcatheter aortic valve replacement (TAVR).

Background

Duration of hospitalization has a direct impact on overall cost of care, but the clinical impact of length of stay (LOS) in patients undergoing minimalist TAVR remains unclear.

Methods

We studied 268 patients who underwent minimalist TAVR. Short LOS (sLOS) was defined as post-procedural LOS ≤ 3 days and observed in 163 patients. Prolonged LOS (pLOS) was observed in 105 patients. Propensity score matching based on 39 variables yielded 54 pairs of patients in each group. We analyzed 30-day mortality, 30-day re-hospitalization and long-term survival data. Multivariate regression models were used to define predictors of sLOS.

Results

Thirty-day mortality was 0% versus 5.5% in the sLOS and pLOS groups, respectively (P = 0.08). Incidence of re-hospitalization was higher in pLOS (13% vs. 3.7%). sLOS was associated with lower odds ratio of minor vascular complication (OR 0.1 [95% CI: 0.01, 0.75], P = 0.05), any bleeding (OR 0.35 [95% CI: 0.14, 0.87], P = 0.02), blood transfusion (OR 0.27 [95% CI: 0.08, 0.81], P = 0.02), and new pacemaker implantation (OR 0.23 [95% CI: 0.1, 0.53], P < 0.001). Discharge to home had a significantly higher odd ratio for sLOS (OR 8.67 [95% CI: 3.59, 23.11], P < 0.001).

Conclusion

In appropriately selected patients, sLOS following minimalist TAVR approach in an experienced and high volume center is feasible and safe. Implementing such a strategy may reduce medical costs with the potential clinical benefit of early re-habilitation for the elderly TAVR population.

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The trap and occlude technique for retrograde wire externalization during chronic total occlusion revascularization

Abstract

Different strategies of retrograde approach were introduced in recent years to improve the success rate of percutaneous coronary intervention for coronary chronic total occlusions. The aim of this report is to describe a new technique, called "Trap and Occlude Technique," for retrograde wire externalization during CTO percutaneous revascularization. This technique may save time and reduce radiation exposure and procedure-related bleeding.

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Visual estimation versus different quantitative coronary angiography methods to assess lesion severity in bifurcation lesions

Abstract

Objectives

To compare visual estimation with different quantitative coronary angiography (QCA) methods (single-vessel versus bifurcation software) to assess coronary bifurcation lesions.

Background

QCA has been developed to overcome the limitations of visual estimation. Conventional QCA however, developed in "straight vessels," has proved to be inaccurate in bifurcation lesions. Therefore, bifurcation QCA was developed. However, the impact of these different modalities on bifurcation lesion severity classification is yet unknown

Methods

From a randomized controlled trial investigating a novel bifurcation stent (Clinicaltrials.gov NCT01258972), patients with baseline assessment of lesion severity by means of visual estimation, single-vessel QCA, 2D bifurcation QCA and 3D bifurcation QCA were included. We included 113 bifurcations lesions in which all 5 modalities were assessed. The primary end-point was to evaluate how the different modalities affected the classification of bifurcation lesion severity and extent of disease.

Results

On visual estimation, 100% of lesions had side-branch diameter stenosis (%DS) >50%, whereas in 83% with single-vessel QCA, 27% with 2D bifurcation QCA and 26% with 3D bifurcation QCA a side-branch %DS >50% was found (P < 0.0001). With regard to the percentage of "true" bifurcation lesions, there was a significant difference between visual estimate (100%), single-vessel QCA (75%) and bifurcation QCA (17% with 2D bifurcation software and 13% with 3D bifurcation software, P < 0.0001).

Conclusions

Our study showed that bifurcation lesion complexity was significantly affected when more advanced bifurcation QCA software were used. "True" bifurcation lesion rate was 100% on visual estimation, but as low as 13% when analyzed with dedicated bifurcation QCA software.

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Single trans-septal access technique for left atrial intracardiac echocardiography to guide left atrial appendage closure

Abstract

Objective

This registry aimed to describe the safety and feasibility of a single trans-septal (TS) access technique for left intracardiac echocardiography (ICE) guidance of left-atrial appendage (LAA) closure procedure.

Background

LAA closure is currently accepted as an alternative to oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (NVAF) who are at high-risk for bleeding. Currently, LAA closure procedure is typically performed under trans-esophageal echocardiogram (TEE) guidance. Although, ICE has the advantage of not requiring profound sedation/anesthesia, ICE-LAA imaging quality is often limited from the right atrium requiring double TS access.

Methods

Twenty-two patients with NVAF underwent LAA closure using the Amplatzer Amulet™ device (St Jude Medical) under ICE guidance from the left atrium. The ICE AcuNav catheter (Biosense Webster) and the Amulet delivery sheath were advanced into the LA through single TS puncture technique.

Results

The population was predominately male (59.1%) with a mean age of 74 ± 9.3 years, at high-risk for stroke (mean CHADS2 score of 3.8 ± 1.1) and bleeding (mean HAS BLED score of 3.5 ± 1.3). The Amplatzer Amulet^TM device was successfully implanted in all patients. No procedural related complications including device embolization were noted. No major cardiovascular events occurred and all patients were discharged alive. At 30-day follow-up all patients remained alive, free of ischemic stroke and with no residual leak or device thrombus on TEE.

Conclusions

This initial experience suggests that LAA occlusion with the Amplatzer Amulet device using ICE guidance from the left atrium via a single trans-septal technique is feasible and safe.

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Overexpansion of the 29 mm SAPIEN 3 transcatheter heart valve in patients with large aortic annuli (area > 683 mm2): A case series

Abstract

Objectives

To evaluate overexpanded 29 mm SAPIEN (S3) transcatheter heart valves in patients with aortic annuli area >683 mm².

Background

The largest valve area the 29 mm S3 is specified for is 683 mm². Valve overexpansion has been performed in patients with larger aortic annuli, but data are limited. Moreover, feasibility in areas >740 mm² is unknown.

Methods

All 29 mm S3 transcatheter aortic valve replacements (TAVR) at a single center over 23-months were retrospectively reviewed. Patients with annulus areas >683 mm² were included. Immediate post-TAVR hemodynamics and transthoracic echocardiography (TTE) findings on post-TAVR day-1 and day-30 were recorded.

Results

Of 81 29 mm S3 TAVR cases, 3 (3.7%) met inclusion criteria (patients 1, 2, and 3 had CT-scan derived areas of 748.1 mm², 793 mm², and 787 mm², respectively). Annular eccentricity index ranged from 0.12 to 0.25. All underwent transfemoral TAVR with 29 mm S3 valves overexpanded using +4 mL of contrast. Post-dilatation with +5 mL was performed in patient 2. The average valve shortening was 10.68 mm. On day 1, patients 1 and 2 had trace and mild paravalvular leak (PVL) (respectively), whereas, patient 3 had mild–moderate PVL. Patient 1 was also noted to have trace central AR on day 1. No other central AR was noted. Immediate post-procedure aortic regurgitation (AR) index in patients 1, 2, and 3 was 43, 34, and 33 respectively. At 30 days, AR was completely resolved in patient 1, whereas AR severity in patients 2 and 3 remained similar. No patients had > moderate AR at any point during follow-up. No valve migration or embolization occurred. Patient 1 required a permanent pacemaker. No other major complications were noted. All patients were clinically stable at 30 days.

Conclusions

TAVR using overexpanded 29 mm S3 in valve areas >740 mm² (up to 793 mm²) seemed to be safe and feasible in our small series. Further study in a larger series is needed to determine clinical outcomes in this patient population.

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Postepy Hig Med Dosw 2017; 71:727-736 "Neopterin as a marker of cellular immunological response"

Neopterin is a pyrazino-pyrimidine compound that belongs to the pteridine group. It is known to be a biochemical marker associated with cell-mediated immunity. It is produced by human monocytes/macrophages and dendritic cells from guanosine triphosphate (GTP) upon stimulation with interferon gamma (IFNγ), which is released by activated limphocytes Th. Neopterin is a very important clinic parameter, though the physiological role has not been exactly definited thus far. The level of neopterin reflects the stage of activation of the cellular immune system, which is important in the pathogenesis and progression of various diseases. Measuring its concentration in body fluids is used in many different areas of modern medicine, such as infectious disease, gastroenterology, transplantology and transfusiology, rheumatology or oncology. In neurological, cardio-vascular and autoimmune diseases, cell-mediated immunity is also activated, which is proved by the elevated level of this marker. Measurements of neopterin concentrations are also helpful in monitoring the therapy of patients infected with the HIV virus or treated by using immunomudulating therapy. As a result of measuring levels of neopterin in patients with neoplasms of digestive tract, increased concentration was proved, but it is not routinely used in everyday clinic practice.

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Postepy Hig Med Dosw 2017; 71:737-746 "The role of bile acids in the pathogenesis of bowel diseases"

Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors. Genetic factors associated with the regulation of bile acid synthesis, transport and action may significantly influence gastrointestinal function and predispose to diarrhea resulting from bile acid malabsorption. Methods used in the diagnosis of bile acid malabsorption include 75selenium-homotaurocholic acid test, serum C4 and fibroblast growth factor 19 (FGF19), as well as fecal bile acid levels. The paper presents the latest data on the role of bile acid in the pathogenesis of irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. Advances in the treatment of disturbances in bile acids absorption and synthesis are also presented. A better understanding of molecular mechanisms regulating bile acid action may have implication for colorectal cancer prevention.

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Postepy Hig Med Dosw 2017; 71:747-760 "The role of vitamin C in epigenetic regulation"

Vitamin C (L-ascorbic acid) is a micronutrient best known for its anti-scurvy activity in humans. Vitamin C is involved in many biological processes involving enzymatic reactions that are catalyzed by members of dioxygenases which use Fe(II) and 2-oxoglutarate as a co-substrate. The article reviews recent data that suggest the involvement of ascorbate in dioxygenases catalyzed chromatin and DNA modifications which thereby contribute to epigenetic regulation. Concerning chromatin modification, the dioxygenases are involved in distinct demethylation reactions with varying specificity for the position of the lysine on the target histone. TET hydroxylases catalyse the oxidation of methyl groups in the 5 position of cytosine in DNA yielding 5-hydroxymethylcytosine, while further iterative oxidation reactions results in the formation of 5-formylcytosine and 5-carboxylcytosine. A few previous studies demonstrated that ascorbate may enhance generation of 5-hydroxymethylcytosine in cultured cells, probably acting as a cofactor of TETs during hydroxylation of 5-methylcytosine. Physiological concentrations of ascorbate in human serum (10-100 μM) may guarantee stable level of 5-hydroxymethylcytosine, a modification necessary for epigenetic function of the cell. 5-Hydroxymethylcytosine level is substantially decreased in almost all investigated cancers, what may be linked with cancer development. Therefore, it is possible that supplementation with ascorbate could contribute to better management of individual cancer patient. This issue is also discussed in our paper.

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Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment

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Copper nanoparticle-induced ovarian injury, follicular atresia, apoptosis, and gene expression alterations in female rats

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Transtympanic pseudoaneurysm of the internal carotid artery complicating a myringotomy in a four-year old child: Case report and literature review

Publication date: Available online 24 August 2017
Source:American Journal of Otolaryngology
Author(s): Damien Bonnard, Erwan de Monès, Thomas Sagardoy, Valérie Franco-Vidal, Vincent Darrouzet, Sylvestre Fierens
We report the first case of a transtympanic iatrogenic internal carotid artery (ICA) pseudoaneurysm diagnosed in a 4-year-old child following a myringotomy. An endovascular treatment with a covered-stent was decided; spontaneous thrombosis was found during the therapeutic arteriography, and the procedure was aborted. Otoscopy and computed tomography (CT) scan monitoring showed a prolonged thrombosis and the disappearance of the pseudoaneurysm 18months after the diagnostic arteriography. Based on literature review, endovascular techniques seem to be preferred to the surgical approach for treatment of intrapetrous ICA pseudoaneurysm, however clinical and CT scan monitoring may also be a valid option.



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Malignant Peripheral Nerve Sheath Tumor of the Inguinum and Angiosarcoma of the Scalp in a Child with Neurofibromatosis Type 1

Benign and malignant tumors are common in the setting of neurofibromatosis type 1 (NF1). Malignant peripheral nerve sheath tumor (MPNST) and angiosarcoma are rare tumors in children and adolescents and mostly occur in young patients in relation to NF1. Both histological types can be present in the same tumor mass in patients with NF1. We present a case of 12.5-year-old girl with NF1 who first presented with MPNST of the right inguinal region and 1.5 years later with unrelated angiosarcoma of the scalp.

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Adequate Platelet Function Inhibition Confirmed by Two Inductive Agents Predicts Lower Recurrence of Ischemic Stroke/Transient Ischemic Attack

Background. The correlation between platelet function and recurrent ischemic stroke or TIA remains uncertain. Objective. To investigate two inductive agents to detect platelet functions and assess associations with recurrent ischemic stroke/TIA. Method. The study included 738 ischemic stroke/TIA patients. On days 0, 3, and 9 after antiplatelet therapy, platelet function tests were determined by maximum aggregation rate (MAR) using a PL-11 platelet function analyzer and phase matching reagents. Two induction agents were used: arachidonic acid (AA) and adenosine diphosphate (ADP). At 3-month follow-up, recurrence of stroke/TIA was recorded. Result. Cut-off values of adequate platelet function inhibition were MARADP

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Baicalin Attenuates Subarachnoid Hemorrhagic Brain Injury by Modulating Blood-Brain Barrier Disruption, Inflammation, and Oxidative Damage in Mice

In subarachnoid hemorrhagic brain injury, the early crucial events are edema formation due to inflammatory responses and blood-brain barrier disruption. Baicalin, a flavone glycoside, has antineuroinflammatory and antioxidant properties. We examined the effect of baicalin in subarachnoid hemorrhagic brain injury. Subarachnoid hemorrhage was induced through filament perforation and either baicalin or vehicle was administered 30 min prior to surgery. Brain tissues were collected 24 hours after surgery after evaluation of neurological scores. Brain tissues were processed for water content, real-time PCR, and immunoblot analyses. Baicalin improved neurological score and brain water content. Decreased levels of tight junction proteins (occludin, claudin-5, ZO-1, and collagen IV) required for blood-brain barrier function were restored to normal level by baicalin. Real-time PCR data demonstrated that baicalin attenuated increased proinflammatory cytokine (IL-1β, IL-6, and CXCL-3) production in subarachnoid hemorrhage mice. In addition to that, baicalin attenuated microglial cell secretion of IL-1β and IL-6 induced by lipopolysaccharide (100 ng/ml) dose dependently. Finally, baicalin attenuated induction of NOS-2 and NOX-2 in SAH mice at the mRNA and protein level. Thus, we demonstrated that baicalin inhibited microglial cell activation and reduced inflammation, oxidative damage, and brain edema.

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Vehicle Tracking and Counting System in Dusty Weather with Vibrating Camera Conditions

Traffic surveillance systems are interesting to many researchers to improve the traffic control and reduce the risk caused by accidents. In this area, many published works are only concerned about vehicle detection in normal conditions. The camera may vibrate due to wind or bridge movement. Detection and tracking of vehicles are a very difficult task when we have bad weather conditions in winter (snowy, rainy, windy, etc.) or dusty weather in arid and semiarid regions or at night, among others. In this paper, we proposed a method to track and count vehicles in dusty weather with a vibrating camera. For this purpose, we used a background subtraction based strategy mixed with extra processing to segment vehicles. In this paper, the extra processing included the analysis of the headlight size, location, and area. In our work, tracking was done between consecutive frames via a particle filter to detect the vehicle and pair the headlights using the connected component analysis. So, vehicle counting was performed based on the pairing result. Our proposed method was tested on several video surveillance records in different conditions such as in dusty or foggy weather, with a vibrating camera, and on roads with medium-level traffic volumes. The results showed that the proposed method performed better than other previously published methods, including the Kalman filter or Gaussian model, in different traffic conditions.

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The Beneficial Effects of Quercetin, Curcumin, and Resveratrol in Obesity

Over the past two decades, obesity has been one of the major public health concerns in most countries. In the search for new molecules that could be used for the treatment of obesity, good perspectives have been opened up for polyphenols, a class of natural bioactive phytochemicals. Experimental and limited clinical trial evidence supports that some polyphenols such as quercetin, curcumin, and resveratrol have potential benefit functions on obesity treatment. This brief review focuses on the main functions of the above-named polyphenols on adipose tissue. These polyphenols may play beneficial effects on adipose tissue under obese condition by alleviating intracellular oxidative stress, reducing chronic low-grade inflammation, inhibiting adipogenesis and lipogenesis, and suppressing the differentiation of preadipocytes to mature adipocytes.

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Interactions of Desmethoxyyangonin, a Secondary Metabolite from Renealmia alpinia, with Human Monoamine Oxidase-A and Oxidase-B

Renealmia alpinia (Zingiberaceae), a medicinal plant of tropical rainforests, is used to treat snakebites and other injuries and also as a febrifuge, analgesic, antiemetic, antiulcer, and anticonvulsant. The dichloromethane extract of R. alpinia leaves showed potent inhibition of human monoamine oxidases- (MAOs-) A and B. Phytochemical studies yielded six known compounds, including pinostrobin 1, 4′-methyl ether sakuranetin 2, sakuranetin 3, pinostrobin chalcone 4, yashabushidiol A 5, and desmethoxyyangonin 6. Compound 6 displayed about 30-fold higher affinity for MAO-B than MAO-A, with Ki values of 31 and 922 nM, respectively. Kinetic analysis of inhibition and equilibrium-dialysis dissociation assay of the enzyme-inhibitor complex showed reversible binding of desmethoxyyangonin 6 with MAO-A and MAO-B. The binding interactions of compound 6 in the active site of the MAO-A and MAO-B isoenzymes, investigated through molecular modeling algorithms, confirmed preferential binding of desmethoxyyangonin 6 with MAO-B compared to MAO-A. Selective reversible inhibitors of MAO-B, like desmethoxyyangonin 6, may have important therapeutic significance for the treatment of neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease.

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IJMS, Vol. 18, Pages 1843: Hepatocyte Growth Factor Mediates Enhanced Wound Healing Responses and Resistance to Transforming Growth Factor-β1-Driven Myofibroblast Differentiation in Oral Mucosal Fibroblasts

IJMS, Vol. 18, Pages 1843: Hepatocyte Growth Factor Mediates Enhanced Wound Healing Responses and Resistance to Transforming Growth Factor-β1-Driven Myofibroblast Differentiation in Oral Mucosal Fibroblasts

International Journal of Molecular Sciences doi: 10.3390/ijms18091843

Authors: Jordanna Dally Jabur Khan Alex Voisey Chrisandrea Charalambous Hannah John Emma Woods Robert Steadman Ryan Moseley Adam Midgley

Oral mucosal wounds are characterized by rapid healing with minimal scarring, partly attributable to the "enhanced" wound healing properties of oral mucosal fibroblasts (OMFs). Hepatocyte growth factor (HGF) is a pleiotropic growth factor, with potential key roles in accelerating healing and preventing fibrosis. HGF can exist as full-length or truncated (HGF-NK), NK1 and NK2 isoforms. As OMFs display elevated HGF expression compared to dermal fibroblasts (DFs), this study investigated the extent to which HGF mediates the preferential cellular functions of OMFs, and the influence of pro-fibrotic, transforming growth factor-β1 (TGF-β1) on these responses. Knockdown of HGF expression in OMFs by short-interfering RNA (siHGF) significantly inhibited OMF proliferative and migratory responses. Supplementation with exogenous TGF-β1 also significantly inhibited proliferation and migration, concomitant with significantly down-regulated HGF expression. In addition, knockdown abrogated OMF resistance to TGF-β1-driven myofibroblast differentiation, as evidenced by increased α-smooth muscle actin (α-SMA) expression, F-actin reorganisation, and stress fibre formation. Responses were unaffected in siHGF-transfected DFs. OMFs expressed significantly higher full-length HGF and NK1 levels compared to patient-matched DFs, whilst NK2 expression was similar in both OMFs and DFs. Furthermore, NK2 was preferentially expressed over NK1 in DFs. TGF-β1 supplementation significantly down-regulated full-length HGF and NK1 expression by OMFs, while NK2 was less affected. This study demonstrates the importance of HGF in mediating "enhanced" OMF cellular function. We also propose that full-length HGF and HGF-NK1 convey desirable wound healing properties, whilst fibroblasts preferentially expressing more HGF-NK2 readily undergo TGF-β1-driven differentiation into myofibroblasts.

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The Impact of Treatment Preferences in Second-Line Chemotherapy on the Prognosis of HER2-Negative Metastatic Breast Cancer

Objective: We assessed the impact of treatment preferences in second-line chemotherapy on breast cancer prognosis using the SELECT BC study. Methods: The SELECT BC study was performed in patients with HER2-negative metastatic breast cancer treated with initial chemotherapy. From these patients, 618 were assigned to 2 groups (S-1 group, 309; taxane group, 309). The S-1 and taxane groups were each subdivided into 3 groups: crossover group, protocol-recommended group, and other group, and the analysis of overall survival (OS) was performed using Cox regression with inverse probability weighting, to adjust for postrandomization confounding. Results: In the taxane group, the OS of the crossover group (39.6 months) was better than that of the protocol-recommended group (35.7 months) and the other chemotherapy group (36.9 months) (vs. the protocol-recommended group, HR 0.72 [95% CI 0.52-0.98], p = 0.037; vs. the other chemotherapy group, HR 0.71 [95% CI 0.43-1.18], p = 0.183). In the S-1 group, there was no statistically significant difference in OS between the 3 groups. Conclusion: The study of the combination of first-line chemotherapy and second-line chemotherapy showed that S-1 might be recommended as a second-line chemotherapy in patients in whom taxane was the primary chemotherapy.
Oncology

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Immune checkpoint blockade for unresectable or metastatic uveal melanoma: a systematic review

Publication date: Available online 24 August 2017
Source:Cancer Treatment Reviews
Author(s): Markus V. Heppt, Theresa Steeb, J. Gabriel Schlager, Stefanie Rosumeck, Corinna Dressler, Thomas Ruzicka, Alexander Nast, Carola Berking
BackgroundThe use of immune checkpoint blockade (ICB) for uveal melanoma (UM) is little established. The aim of this review was to provide a comprehensive overview on the efficacy, safety, and tolerability of ICB in patients with UM.MethodsWe performed a systematic literature research covering MEDLINE, Embase and CENTRAL. Abstracts of pertinent conferences and trial registers were handsearched for relevant studies.ResultsOut of 1,327 records initially identified, 12 eligible studies were included in the qualitative synthesis. They comprised 7 expanded access or named patient programs (n=162), 4 phase II trials (n=171), and 1 phase Ib trial (sample size unknown), while no randomized controlled trial was found. Ipilimumab monotherapy was assessed at 3 mg/kg in 5 trials (n=186) with a response rate of 0-5%. Two reports investigated ipilimumab at 10 mg/kg (n=45) with radiological responses observed in 0-6.5%. The median progression-free survival (PFS) was below 3 months and the median overall survival was 5.2-9.8 months for ipilimumab monotherapy. Severe immune-related adverse events occurred at a frequency comparable to cutaneous melanoma (6-36%). Two studies investigated pembrolizumab (2 mg/kg) and nivolumab (3 mg/kg) with overall response rates of 30% and 6%, respectively. Data on combined ipilimumab and programmed cell death protein 1 inhibition were available from one expanded access program, but no response was observed with a median PFS of 2.9 months.ConclusionsUM is little responsive to ipilimumab regardless of dosage schemes. Sound randomized clinical trials are needed to evaluate the efficacy of combined ICB in patients with UM.



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Immunosenescence and immunecheckpoint inhibitors in non-small cell lung cancer patients: does age really matter?

Publication date: Available online 24 August 2017
Source:Cancer Treatment Reviews
Author(s): Roberto Ferrara, Laura Mezquita, Edouard Auclin, Nathalie Chaput, Benjamin Besse
Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75 years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients. In this complex scenario, a further unresolved issue is the potential correlation between older age and immunotherapy primary resistance, a phenomenon probably linked to the continuous and progressive remodeling of immune functions with ageing, known as immunosenescence. Defining the role of ICIs in elderly NSCLC patients and exploring the molecular mechanisms underlying a possible lack of benefit or even accelerated tumor growth during immunotherapy are two major challenges for future research in this field of cancer treatment. In this review, we describe the major hallmarks of immunosenescence and we summarize the existing clinical data of ICIs in elderly NSCLC patients.



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Pancreatic Ductal Adenocarcinoma: State-of-the-Art 2017 and New Therapeutic Strategies

Publication date: Available online 23 August 2017
Source:Cancer Treatment Reviews
Author(s): Marta Chiaravalli, Michele Reni, Eileen M. O'Reilly
Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy with an overall 5-year survival of 8% for all stages combined. The majority of patients present with stage IV disease at diagnosis and these patients have an overall 5-year survival of 3%. Currently, the standard of care for metastatic pancreas adenocarcinoma is combination cytotoxic therapy, namely FOLFIRINOX or gemcitabine plus nab-paclitaxel for good performance status patients. Given the challenges and the rising incidence of PDAC expected to become the second leading cause of cancer-related death by 2030, there is a major unmet need to develop more effective therapies. In this setting, the molecular and genomic characterization of PDAC have underpinned the use of targeted therapies. To date, the results from targeted agent evaluation have been disappointing with some exceptions. Novel promising strategies depend on biomarker identification and patient selection e.g. germline mutations in DNA repair or mismatch repair genes, where the addition of a platinum agent or checkpoint inhibitor can have a positive impact on survival. This article will review the state-of-the-art treatment of metastatic pancreatic cancer with an emphasis on novel promising therapeutic strategies and an overview on emerging biomarkers.



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Genetic dissection of oligodendroglial and neuronal Plp1 function in a novel mouse model of spastic paraplegia type 2

Abstract

Proteolipid protein (PLP) is the most abundant integral membrane protein in compact central nervous system myelin, and null mutations of the PLP1 gene cause spastic paraplegia type 2 (SPG2). SPG2 patients and PLP-deficient mice exhibit only moderate abnormalities of myelin but progressive degeneration of long axons. Since Plp1 gene products are detected in a subset of neurons it has been suggested that the loss of neuronal Plp1 expression could be the cause of the axonal pathology. To test this hypothesis, we created mice with a floxed Plp1 allele for selective Cre-mediated recombination in neurons. We find that recombination of Plp1 in excitatory projection neurons does not cause neuropathology, whereas oligodendroglial targeting of Plp1 is sufficient to cause the entire neurodegenerative spectrum of SPG2 including axonopathy and secondary neuroinflammation. We conclude that PLP-dependent loss of oligodendroglial support is the primary cause of axonal degeneration in SPG2.

Main Points

• The SPG2 disease gene Plp1 is active in neurons additional to oligodendrocytes.
• A bona fide mouse model of SPG2 including axonopathy is obtained by oligodendroglial recombination of a floxed Plp1 gene.
• Neuronal targeting does not cause neuropathology.

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The microglial fractalkine receptor is not required for activity-dependent plasticity in the mouse visual system

Abstract

Microglia have recently been implicated as key regulators of activity-dependent plasticity, where they contribute to the removal of inappropriate or excess synapses. However, the molecular mechanisms that mediate this microglial function are still not well understood. Although multiple studies have implicated fractalkine signaling as a mediator of microglia–neuron communications during synaptic plasticity, it is unclear whether this is a universal signaling mechanism or whether its role is limited to specific brain regions and stages of the lifespan. Here, we examined whether fractalkine signaling mediates microglial contributions to activity-dependent plasticity in the developing and adolescent visual system. Using genetic ablation of fractalkine's cognate receptor, CX₃CR1, and both ex vivo characterization and in vivo imaging in mice, we examined whether fractalkine signaling is required for microglial dynamics and modulation of synapses, as well as activity-dependent plasticity in the visual system. We did not find a role for fractalkine signaling in mediating microglial properties during visual plasticity. Ablation of CX₃CR1 had no effect on microglial density, distribution, morphology, or motility, in either adolescent or young adult mice across brain regions that include the visual cortex. Ablation of CX₃CR1 also had no effect on baseline synaptic turnover or contact dynamics between microglia and neurons. Finally, we found that fractalkine signaling is not required for either early or late forms of activity-dependent visual system plasticity. These findings suggest that fractalkine is not a universal regulator of synaptic plasticity, but rather has heterogeneous roles in specific brain regions and life stages.

Main Points

• Fractalkine signaling is not necessary for microglial roles in synaptic plasticity in the visual system during both early and late development.
• Fractalkine signaling is not a universal regulator of synaptic plasticity.

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Roadmap for Investigating Epigenome Deregulation and Environmental Origins of Cancer

Abstract

The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene-environment interactions and translating exposures into tumorigenesis. There is also growing evidence that epigenetic changes may be risk factor-specific ("fingerprints") that should prove instrumental in the discovery of new biomarkers in cancer. Here, we review the state of the science of epigenetics associated with environmental stimuli and cancer risk, highlighting key developments in the field. Critical knowledge gaps and research needs are discussed as well as advances in epigenomics that may help an understanding of the functional relevance of epigenetic alterations. Key elements required for causality inferences linking epigenetic changes to exposure and cancer are discussed as well as how these alterations can be incorporated in carcinogen evaluation and in understanding mechanisms underlying epigenome deregulation by the environment. This article is protected by copyright. All rights reserved.

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The risk of preterm birth and growth restriction in pregnancy after cancer

It is unclear whether cancer and its treatments increase the risk of adverse pregnancy outcomes. Our aim was to examine whether cancer survivors have higher risks of poor outcomes in pregnancies conceived after diagnosis than women without cancer, and whether these risks differ by cancer type and race. Diagnoses from cancer registries were linked to pregnancy outcomes from birth certificates in three U.S. states. Analyses were limited to the first, live singleton birth conceived after diagnosis. Births to women without a previous cancer diagnosis in the registry were matched to cancer survivors on age at delivery, parity, race/ethnicity and education. Log-binomial regression was used to estimate risk ratios. Cervical cancer survivors had higher risks of preterm birth (Risk ratio = 2.8, 95% Confidence interval: 2.1, 3.7), as did survivors of invasive breast cancer (RR = 1.3, 95% CI: 1.1, 1.7) and leukemia (RR = 2.1, 95% CI: 1.3, 3.5). We observed a higher risk of small for gestational age (SGA) infants (<10% of weight for age based on a national distribution) in survivors of brain cancer (RR = 1.7, 95% CI: 1.1, 2.8) and extranodal non-Hodgkin lymphoma (RR = 2.3, 95% CI: 1.5, 3.6). We did not see an increased risk of infants born preterm, low birth weight, or SGA in pregnancies conceived after ductal carcinoma in situ, thyroid cancer, melanoma, or Hodgkin lymphoma. While our results are reassuring for survivors of many cancers, some will need closer monitoring during pregnancy.

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Nordic study finds cancer mortality rates have sunk

Mortality rates for prostate and breast cancers in the Nordic region have declined...

Read more on AuntMinnieEurope.com

Related Reading:

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Mammography in Nordic countries: Screening and new developments

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Back Pain and Other Unusual Signs of Lung Cancer - U.S. News & World Report

U.S. News & World Report

Back Pain and Other Unusual Signs of Lung Cancer U.S. News & World Report Early diagnosis of any cancer improves prognosis. That's why being aware of telltale symptoms and undergoing age- and risk-appropriate screenings where available can improve outcomes for many cancer patients. However, lung cancer typically has few ...

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Testosterone Upregulates the Expression of Mitochondrial ND1 and ND4 and Alleviates the Oxidative Damage to the Nigrostriatal Dopaminergic System in Orchiectomized Rats

Testosterone deficiency, as a potential risk factor for aging and aging-related neurodegenerative disorders, might induce mitochondrial dysfunction and facilitate the declines of the nigrostriatal dopaminergic system by exacerbating the mitochondrial defects and increasing the oxidative damage. Thus, how testosterone levels influence the mitochondrial function in the substantia nigra was investigated in the study. The present studies showed that testosterone deficiency impaired the mitochondrial function in the substantia nigra and induced the oxidative damage to the substantia nigra as well as the deficits in the nigrostriatal dopaminergic system. Of four mitochondrial respiratory chain complexes, castration of male rats reduced the activity of mitochondrial complex I and downregulated the expression of ND1 and ND4 of 7 mitochondrial DNA- (mtDNA-) encoded subunits of complex I in the substantia nigra. Supplements of testosterone propionate to castrated male rats ameliorated the activity of mitochondrial complex I and upregulated the expression of mitochondrial ND1 and ND4. These results suggest an important role of testosterone in maintaining the mitochondrial function in the substantia nigra and the vulnerability of mitochondrial complex I to testosterone deficiency. Mitochondrial ND1 and ND4, as potential testosterone targets, were implicated in the oxidative damage to the nigrostriatal dopaminergic system.

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Risk Factors of Malignant Glaucoma Occurrence after Glaucoma Surgery

Purpose. The aim of this study was twofold: first, to evaluate the predisposing factors for occurrence of malignant glaucoma and second, to compare frequency of malignant glaucoma depending on the type of primary glaucoma surgery. Methods. Retrospective analysis was performed in 1689 consecutive patients who underwent glaucoma surgery alone or combined with phacoemulsification. Data collected included the type of surgery, width of the filtration angle, presence or absence of malignant glaucoma in the postoperative period, and time from the primary surgery to malignant glaucoma occurrence. Results. Malignant glaucoma occurred in 22 eyes that amounted to 1.3% of cases among all surgery performed. Mean time from glaucoma surgery to malignant glaucoma occurrence was 61.4 ± 190.5 days. Among patients with penetrating surgery, malignant glaucoma occurred in 2.3% of patients, whereas after nonpenetrating operations, such complication was not found (). Malignant glaucoma occurred more often in patients with shallow iridocorneal angle (). Conclusions. The risk of malignant glaucoma development is associated with penetrating characteristic of glaucoma surgery, after which this complication appears and its occurrence is higher in eyes with shallow iridocorneal angle. The risk of malignant glaucoma after trabeculectomy compared to iridencleisis as well as after phacotrabeculectomy compared to phacoiridencleisis is equivalent.

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A Hybrid Approach for Evaluating Faulty Behavior Risk of High-Risk Operations Using ANP and Evidence Theory

Hydropower project construction is a high-risk operation, where accidents occur frequently. Moreover, the factors leading to accidents are often human factors, so safety evaluation of these factors for the hydropower projects' work system is very significant. The Human Factors Analysis and Classification System (HFACS) framework is applied to build evaluation system. In the evaluation process, correlation analysis is used to form the intercriteria analysis matrix that helps the decision makers to build impact relation matrix. Factor weights are calculated by the Analytic Network Process (ANP). In the index value determination step, the evidence theory is used to eliminate the conflicts of three decision makers and the index values are then calculated. The faulty behavior risk (FBR) assessment value is finally obtained. The proposed method is practical and its applicability is proved by an example.

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Neuronal Regeneration after Electroacupuncture Treatment in Ischemia–Reperfusion-Injured Cerebral Infarction Rats

Adult neuronal cells which can regenerate have been reported. The present study investigated whether acupuncture enhances neuronal regeneration in ischemic stroke rats. We established an ischemic stroke rat model by occluding the cerebral blood flow of the right middle cerebral artery for 15 minutes and then allowing reperfusion in Sprague–Dawley rats. The results indicated that, in these rats, 2 Hz electroacupuncture (EA) at both Zusanli (ST36) and Shangjuxu (ST37) acupoints reduced the infarction/hemisphere ratio 8 days after reperfusion and reduced the modified neurological severity score (mNSS) and increased the rotarod test time 4 and 8 days after reperfusion, respectively. In addition, 2 Hz reduced nestin immunoreactive cells in the penumbra area and the ischemic core area; 2 Hz EA also reduced Ki67 immunoreactive cells and increased glial fibrillary acidic protein immunoreactive cells in the penumbra area. These findings suggest that 2 Hz EA at the ST36 and ST37 acupoints has a neuroprotective role. However, additional studies are needed to further investigate these preliminary results.

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Enhancement of Antioxidant Mechanisms and Reduction of Oxidative Stress in Chickens after the Administration of Drinking Water Enriched with Polyphenolic Powder from Olive Mill Waste Waters

The aim of the study was to examine the effects of a polyphenolic powder from olive mill wastewater (OMWW) administered through drinking water, on chickens' redox status. Thus, 75 chickens were divided into three groups. Group A was given just drinking water, while groups B and C were given drinking water containing 20 and 50 μg/ml of polyphenols, respectively, for 45 days. The antioxidant effects of the polyphenolic powder were assessed by measuring oxidative stress biomarkers in blood after 25 and 45 days of treatment. These markers were total antioxidant capacity (TAC), protein carbonyls (CARB), thiobarbituric acid reactive species (TBARS) and superoxide dismutase activity (SOD) in plasma, and glutathione (GSH) and catalase activity in erythrocytes. The results showed that CARB and TBARS were decreased significantly in groups B and C, and SOD decreased in group B compared to that in group A. TAC was increased significantly in group C and GSH was increased in group B, while catalase activity was increased in groups B and C compared to that in group A. In conclusion, this is the first study showing that supplementation of chickens with polyphenols from OMWW through drinking water enhanced their antioxidant mechanisms and reduced oxidative stress-induced damage.

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Influence of SPK with Enteric Drainage on the Pancreatic Exocrine Function in Diabetic Patients with Uremia

Objective. This study aimed to determine the use of fecal elastase in evaluating the effect of simultaneous pancreas–kidney transplantation with enteric drainage on the pancreatic exocrine function of diabetic patients with uremia. Methods. A total of 19 patients with simultaneous pancreas–kidney transplantation (SPK) with enteric drainage, 31 diabetic patients with uremia (chronic renal failure (CRF)), 22 diabetic patients with uremia who underwent renal transplantation (RT), and 20 normal individuals (CON) were included in the study. Pancreatic exocrine insufficiency was determined using fecal elastase. Results. The fecal pancreatic elastase level in SPK patients with enteric drainage was 479 μg/g, which was significantly higher than 229 μg/g in CRF patients and 197 μg/g in RT patients. Using 200 μg/g as the established threshold, a reduced fecal pancreatic elastase level was found in 14/31 of CRF patients, 12/22 of RT patients, 1/19 of SPK patients with enteric drainage, and 1/20 of CON patients. The correlation analysis revealed a significant association between fecal elastase and glycosylated hemoglobin. Conclusions. The present study indicated that SPK with enteric drainage improves pancreatic endocrine and exocrine functions. Fecal elastase may be a clinically relevant means to determine the therapeutic effects.

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The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

Objective. The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled

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IJMS, Vol. 18, Pages 1837: Synthesis and Characterization of Tissue Plasminogen Activator—Functionalized Superparamagnetic Iron Oxide Nanoparticles for Targeted Fibrin Clot Dissolution

IJMS, Vol. 18, Pages 1837: Synthesis and Characterization of Tissue Plasminogen Activator—Functionalized Superparamagnetic Iron Oxide Nanoparticles for Targeted Fibrin Clot Dissolution

International Journal of Molecular Sciences doi: 10.3390/ijms18091837

Authors: Susanne Heid Harald Unterweger Rainer Tietze Ralf Friedrich Bianca Weigel Iwona Cicha Dietmar Eberbeck Aldo Boccaccini Christoph Alexiou Stefan Lyer

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted great attention in many biomedical fields and are used in preclinical/experimental drug delivery, hyperthermia and medical imaging. In this study, biocompatible magnetite drug carriers, stabilized by a dextran shell, were developed to carry tissue plasminogen activator (tPA) for targeted thrombolysis under an external magnetic field. Different concentrations of active tPA were immobilized on carboxylated nanoparticles through carbodiimide-mediated amide bond formation. Evidence for successful functionalization of SPIONs with carboxyl groups was shown by Fourier transform infrared spectroscopy. Surface properties after tPA immobilization were altered as demonstrated by dynamic light scattering and ζ potential measurements. The enzyme activity of SPION-bound tPA was determined by digestion of fibrin-containing agarose gels and corresponded to about 74% of free tPA activity. Particles were stored for three weeks before a slight decrease in activity was observed. tPA-loaded SPIONs were navigated into thrombus-mimicking gels by external magnets, proving effective drug targeting without losing the protein. Furthermore, all synthesized types of nanoparticles were well tolerated in cell culture experiments with human umbilical vein endothelial cells, indicating their potential utility for future therapeutic applications in thromboembolic diseases.

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IJMS, Vol. 18, Pages 1844: Daytime-Dependent Changes of Cannabinoid Receptor Type 1 and Type 2 Expression in Rat Liver

IJMS, Vol. 18, Pages 1844: Daytime-Dependent Changes of Cannabinoid Receptor Type 1 and Type 2 Expression in Rat Liver

International Journal of Molecular Sciences doi: 10.3390/ijms18091844

Authors: Ivonne Bazwinsky-Wutschke Alexander Zipprich Faramarz Dehghani

The present study was performed to investigate the diurnal expression pattern of cannabinoid receptor type 1 (CB1) and type 2 (CB2) in liver tissue of 12- and 51-week-old normoglycemic Wistar rats. By using real-time RT-PCR, daytime dependent changes in both age groups and, for both, hepatic Cnr1 and Cnr2 receptor mRNA levels were measured. Highest amount of mRNA was detected in the light period (ZT3, ZT6, and ZT9) while the lowest amount was measured in the dark period (ZT18 and ZT21). Diurnal transcript expression pattern was accompanied by comparable changes of protein level for CB1, as shown by Western blotting. The current results support the conclusion that expression pattern of cannabinoid receptors are influenced by light/dark cycle and therefore seems to be under the control of a diurnal rhythm. These findings might explain the differences in the efficacy of cannabinoid receptor agonists or antagonists. In addition, investigation of liver of streptozotocin (STZ)-treated 12- and 51-week-old rats show alterations in the diurnal profile of both receptors Cnr1 and Cnr2 compared to that of normoglycemic Wistar rats. This suggests an influence of diabetic state on diurnal expression levels of cannabinoid receptors.

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Effect of atopic dermatitis on quality of life and its psychosocial impact in Asian adolescents

Abstract

Background/Objectives

Atopic dermatitis (AD) is a common condition affecting up to 20% of the paediatric population in Singapore. It is often associated with significant psychosocial morbidity and can affect patients' quality of life (QOL) tremendously. This study investigated the varying lifestyle impacts, and psychosocial domains most affected by AD in adolescent children in Singapore.

Methods

A prospective study evaluating the impact of AD on the QOL of adolescents was conducted over a 6-month period from July to December 2014. Adolescents aged 11–16 years with varying eczema severity were recruited. Eczema severity was determined by using the eczema area and severity index (EASI) scores. Lifestyle impact of AD was evaluated using patient-reported children's dermatology life quality index (CDLQI) scores. Statistical analysis was performed using an analysis of one-way variance and Student's t-test.

Results

A total of 50 patients were enrolled and divided into three groups: mild (<10.3), moderate (10.3–20.9) and severe (>20.9) eczema based on EASI scores. Patients with mild and moderate eczema had lower CDLQI scores. Adolescents were most affected by the disruption that their symptoms had on their leisure and physical activities and sleep as a result of itch and scratching, respectively.

Conclusion

Chronic sufferers of severe eczema experience poorer QOL than those with mild or moderate eczema. They also experience significant psychosocial impact as a consequence of their condition.

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Concurrent validity, discriminatory power and feasibility of the instrument for Identification of Parents At Risk for child Abuse and Neglect (IPARAN)

Objectives

To determine the feasibility, concurrent validity and discriminatory power of the instrument for Identification of Parents At Risk for child Abuse and Neglect (IPARAN) among Dutch parents with a newborn child.

Setting

Community paediatrics.

Participants

Data from a controlled trial were used. In total, 2659 Dutch parents with a newborn child were invited to participate. Of the 2659 parents, 759 parents filled in the consent form and participated in the study.

Primary and secondary outcome measures

Concurrent validity was determined by calculating correlations—using the Pearson's correlation (r)—between the IPARAN score and related constructs from the following instruments: the Empowerment Questionnaire 2.0, the Family Functioning Questionnaire and the Parenting Stress Questionnaire. Discriminatory power was determined by calculating receiver operating characteristic (ROC) curves between high-risk mothers and low-risk mothers according to their scores on the related constructs. Feasibility was determined by examining the percentage of missing answers.

Results

In terms of concurrent validity, we found that 3 out of 12 correlations between the IPARAN score and related constructs were strong (ie, r>0.50) and 4 out of 12 were medium (ie, r=0.30–0.49). In terms of discriminatory power, mothers with a score in the borderline/clinical range or lowest 10 percent (P10) range of the related constructs (high-risk mothers) had a higher IPARAN score than mothers with a score in the normal range or highest 90 percent (P90) range of the related constructs (low-risk mothers). Effect sizes varied from d=0.37 to d=1.93, and the area under the ROC curve varied from 0.62 to 0.93. Regarding feasibility, the part of the IPARAN filled in by the mother had on average 0.7% missing answers, whereas the part of the IPARAN filled in by the father had on average 1.7% missing answers.

Conclusion

The results of this study support the concurrent validity, discriminatory power and feasibility of the IPARAN among a population of Dutch parents with a newborn child.

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What is the impact of giant cell arteritis on patients lives? A UK qualitative study

Objectives

Clinical management of giant cell arteritis (GCA) involves balancing the risks and burdens arising from the disease with those arising from treatment, but there is little research on the nature of those burdens. We aimed to explore the impact of giant cell arteritis (GCA) and its treatment on patients' lives.

Methods

UK patients with GCA participated in semi-structured telephone interviews. Inductive thematic analysis was employed.

Results

24 participants were recruited (age: 65–92 years, time since diagnosis: 2 months to >6 years). The overarching themes from analysis were: ongoing symptoms of the disease and its treatment; and 'life-changing' impacts. The overall impact of GCA on patients' lives arose from a changing combination of symptoms, side effects, adaptations to everyday life and impacts on sense of normality. Important factors contributing to loss of normality were glucocorticoid-related treatment burdens and fear about possible future loss of vision.

Conclusions

The impact of GCA in patients' everyday lives can be substantial, multifaceted and ongoing despite apparent control of disease activity. The findings of this study will help doctors better understand patient priorities, legitimise patients' experiences of GCA and work with patients to set realistic treatment goals and plan adaptations to their everyday lives.

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Impact of family-friendly prison policies on health, justice and child protection outcomes for incarcerated mothers and their dependent children: a cohort study protocol

Introduction

Female imprisonment has numerous health and social sequelae for both women prisoners and their children. Examples of comprehensive family-friendly prison policies that seek to improve the health and social functioning of women prisoners and their children exist but have not been evaluated. This study will determine the impact of exposure to a family-friendly prison environment on health, child protection and justice outcomes for incarcerated mothers and their dependent children.

Methods and analysis

A longitudinal retrospective cohort design will be used to compare outcomes for mothers incarcerated at Boronia Pre-release Centre, a women's prison with a dedicated family-friendly environment, and their dependent children, with outcomes for mothers incarcerated at other prisons in Western Australia (that do not offer this environment) and their dependent children. Routinely collected administrative data from 1985 to 2013 will be used to determine child and mother outcomes such as hospital admissions, emergency department presentations, custodial sentences, community service orders and placement in out-of home care. The sample consists of all children born in Western Australia between 1 January 1985 and 31 December 2011 who had a mother in a West Australian prison between 1990 and 2012 and their mothers. Children are included if they were alive and aged less than 18 years at the time of their mother's incarceration. The sample comprises an exposed group of 665 women incarcerated at Boronia and their 1714 dependent children and a non-exposed comparison sample of 2976 women incarcerated at other West Australian prisons and their 7186 dependent children, creating a total study sample of 3641 women and 8900 children.

Ethics and dissemination

This project received ethics approval from the Western Australian Department of Health Human Research Ethics Committee, the Western Australian Aboriginal Health Ethics Committee and the University of Western Australia Human Research Ethics Committee.

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A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort

Introduction

An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors.

Methods and analysis

All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally.

Ethics and dissemination

The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals.

Trial registration number

German Clinical Trials Registry DRKS00010050.

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Breast cancer mortality and associated factors in Sao Paulo State, Brazil: an ecological analysis

Objective

Identify the factors associated with the age-standardised breast cancer mortality rate in the municipalities of State of São Paulo (SSP), Brazil, in the period from 2006 to 2012.

Design

Ecological study of the breast cancer mortality rate standardised by age, as the dependent variable, having each of the 645 municipalities in the SSP as the unit of analysis.

Settings

The female resident population aged 15 years or older, by age group and municipality, in 2009 (mid-term), obtained from public dataset (Informatics Department of the Unified Health System).

Participants

Women 15 years or older who died of breast cancer in the SSP were selected for the calculation of the breast cancer mortality rate, according to the municipality and age group, from 2006 to 2012.

Main outcome measures

Mortality rates for each municipality calculated by the direct standardisation method, using the age structure of the population of SSP in 2009 as the standard.

Results

In the final linear regression model, breast cancer mortality, in the municipal level, was directly associated with rates of nulliparity (p<0.0001), mammography (p<0.0001) and private healthcare (p=0.006).

Conclusions

The findings that mammography ratio was associated, in the municipal level, with increased mortality add to the evidence of a probable overestimation of benefits and underestimation of risks associated with this form of screening. The same paradoxical trend of increased mortality with screening was found in recent individual-level studies, indicating the need to expand informed choice for patients, primary prevention actions and individualised screening. Additional studies should be conducted to explore if there is a causality link in this association.

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Interaction effects among IFN-{gamma}+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study

Background

The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood.

Objectives

To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes.

Methods

277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes (rs2069762/–330 G/T of IL-2, rs2430561/+874A>T of IFN-, rs1800896/–1082G>A and rs1800872/–592C>A of IL-10 and rs2243250/–589C>T of IL-4) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene–gene interactions were assessed using the multifactor-dimensionality reduction method.

Results

Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-+874 AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-+874 AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05).

Conclusions

Interactions among polymorphisms of IFN-+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10-–592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection.

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Priorities for research in miscarriage: a priority setting partnership between people affected by miscarriage and professionals following the James Lind Alliance methodology

Objectives

To identify and prioritise important research questions for miscarriage.

Design

A priority setting partnership using prospective surveys and consensus meetings following methods advocated by the James Lind Alliance.

Setting

UK.

Participants

Women and those affected by miscarriage working alongside healthcare professionals.

Results

In the initial survey, 1093 participants (932 women who have experienced miscarriage, 8 partners, 17 family members, friends or colleagues, 104 healthcare professionals and eight charitable organisations) submitted 3279 questions. A review of existing literature identified a further 64. Non-questions were removed, and the remaining questions were categorised and summarised into 58 questions. In an interim electronic survey, 2122 respondents chose their top 10 priorities from the 58 summary questions. The 25 highest ranked in the survey were prioritised at a final face-to-face workshop. In summary, the top 10 priorities were ranked as follows: research into preventative treatment, emotional aspects in general, investigation, relevance of pre-existing medical conditions, emotional support as a treatment, importance of lifestyle factors, importance of genetic and chromosomal causes, preconception tests, investigation after different numbers of miscarriage and male causal factors.

Conclusions

These results should be the focus of future miscarriage research. Presently, studies are being conducted to address the top priority; however, many other priorities, especially psychological and emotional support, are less well researched areas. We hope our results will encourage both researchers and funders to focus on these priorities.

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The association between vertebrobasilar insufficiency and the risk of dementia: a nationwide register-based retrospective cohort study in Taiwan

Objectives

Neurodegenerative disorders are reportedly characterised by decreased regional cerebral blood flow. However, the association between vertebrobasilar insufficiency (VBI) and dementia remains unclear. In this nationwide, population-based, retrospective cohort study, we explored the potential association between VBI and dementia.

Design

Nationwide population-based cohort study.

Setting

Patients with VBI were newly diagnosed between 2000 and 2005 from the Taiwan National Health Insurance Research Database.

Participants

We included 3642 subjects as the VBI group. The control cohort included 14 568 randomly selected age-matched and sex-matched VBI-free individuals.

Outcome measures

All subjects were followed until the diagnosis of dementia, death or the end of 2010. Patients with VBI, dementia (viz, vascular and non-vascular, including Alzheimer's) subtypes and other confounding factors were identified according to the International Classification of Diseases Clinical Modification Codes. Cox proportional hazards regression analysis was employed to examine adjusted HRs after adjusting for confounding factors.

Results

Patients with VBI had a 1.807-fold (95% CI 1.643 to 1.988, p<0.001) higher risk to develop all-cause dementia than individuals without VBI. The risk was significantly higher in the VBI group than in the non-VBI group regardless of age (<65 years: HR: 2.997, 95% CI 1.451 to 6.454, p<0.001; ≥65 years: HR: 1.752, 95% CI 1.584 to 1.937, p<0.001). The VBI group had a higher risk of all-cause dementia than the non-VBI group regardless of sex and follow-up time intervals (<1 year, 1–2 years and≥2 years).

Conclusion

Patients with VBI appear to have an increased risk of developing dementia. Further research is needed to investigate the underlying pathophysiology.

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Rethinking exercise identity: a qualitative study of physically inactive cancer patients transforming process while undergoing chemotherapy

Objective

To explore physically inactive breast and colon cancer patients' prediagnosis exercise history and attitudes to physical activity (PA) and experiences in initiating PA while undergoing adjuvant chemotherapy.

Design

An explorative qualitative study guided the interpretive analysis of semistructured, open-ended interviews conducted at initiation of chemotherapy and after 12 weeks. The study was embedded in a pilot randomised controlled trial.

Setting

Participants were recruited from the Oncological Department at a hospital in Copenhagen, Denmark.

Participants

33 patients with cancer, median age 49 years: 25 patients with breast cancer and 8 with colon cancer, 72% with a low cardiac respiratory fitness level and the majority with a high level of education. Patients received adjuvant chemotherapy, oncologist's PA recommendation and exercise, cancer nurse specialist's counselling prior to allocation to PA interventions or waitlist control group.

Results

Prediagnosis exercise had been excluded from patients' daily lives due to perceptions of exercise as boring, lack of discipline and stressful work conditions for both genders. Recommendations from oncologists and nurses inspired the patients to reconsider their attitudes and behaviour by accepting recruitment and participation in PA interventions during chemotherapy. Despite extensive side effects, most patients adhered to their PA commitment due to their perception of the bodily, emotional and social benefits and support of healthcare professionals, peers and family.

Conclusion

The patients' attitude towards exercise transformed from having no priority in patients' daily lives prediagnosis to being highly prioritised. This study identified four important phases in the exercise transformation process during the patients' treatment trajectory of relevance to clinicians in identifying, motivating and supporting physically inactive patients with cancer at long-term risk. Clinicians should address young, highly educated patients with cancer at onset of adjuvant chemotherapy due to their specific risk of a sedentary lifestyle resulting from being in stressful, ambitious careers.

Trial registration number

Current Controlled Trials (ISRCTN24901641), Stage: Qualitative results.

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Protocol for a pilot randomised controlled trial of metformin in pre-diabetes after kidney transplantation: the Transplantation and Diabetes (Transdiab) study

Introduction

Post-transplant diabetes mellitus (PTDM) is a common complication of kidney transplantation and is associated with significant morbidity and mortality. In the general population, metformin has been used for diabetes prevention in high-risk individuals. Improving insulin sensitivity is one of many proven favourable effects of metformin. Despite the high incidence of PTDM in kidney transplant recipients, there is a lack of evidence for the role of metformin in the prevention of diabetes in this setting.

Methods and analysis

Transplantation and Diabetes (Transdiab) is a single-centre, unblinded, pilot randomised controlled trial assessing the feasibility, tolerability and efficacy of metformin after renal transplantation in patients with impaired glucose tolerance (IGT). Participants will undergo an oral glucose tolerance test in the 4–12 weeks post-transplantation; those with IGT will be randomised to standard care or standard care and metformin 500 mg twice daily, and followed up for 12 months. The primary outcomes of the study will be the feasibility of recruitment, the tolerability of metformin assessed using the Gastrointestinal Symptom Rating Scale at 3 and 12 months, and the efficacy of metformin assessed by morning glucose and glycated haemoglobin at 3, 6, 9 and 12 months.

Ethics and dissemination

Despite the significant morbidity and mortality of PTDM, there are currently no randomised clinical trials assessing pharmacological interventions for its prevention after kidney transplantation. The Transdiab trial will thus provide important data on the feasibility, safety, tolerability and efficacy of metformin after renal transplantation in patients with IGT; this will facilitate undertaking larger multicentre trials of interventions to reduce the incidence or severity of diabetes after kidney transplantation. This study has been approved by the Northern B Health and Disability Ethics Committee of the Ministry of Health in New Zealand. On study completion, results are expected to be published in a peer-reviewed journal.

Trial registration number

Australian New Zealand Clinical Trials Registry Number: ACTRN12614001171606.

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Exploring the enablers and barriers to implementing the Medication Appropriateness Tool for Comorbid Health conditions during Dementia (MATCH-D) criteria in Australia: a qualitative study

Objectives

The Medication Appropriateness Tool for Comorbid Health conditions in Dementia (MATCH-D) criteria provide expert consensus guidance about medication use for people with dementia. This study aimed to identify enablers and barriers to implementing the criteria in practice.

Setting

Participants came from both rural and metropolitan communities in two Australian states.

Participants

Focus groups were held with consumers, general practitioners, nurses and pharmacists. Outcomes: data were analysed thematically.

Results

Nine focus groups were conducted. Fifty-five participants validated the content of MATCH-D, appraising them as providing patient-centred principles of care. Participants identified potential applications (including the use of MATCH-D as a discussion aid or educational tool for consumers about medicines) and suggested supporting resources.

Conclusion

Participants provided insights into applying MATCH-D in practice and suggested resources to be included in an accompanying toolkit. These data provide external validation of MATCH-D and an empiric basis for their translation to practice. Following resource development, we plan to evaluate the feasibility and efficacy of implementation in practice.

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Combining parenthood with a medical career: questionnaire survey of the UK medical graduates of 2002 covering some influences and experiences

Objectives

To report the self-assessed views of a cohort of medical graduates about the impact of having (or wanting to have) children on their specialty choice and the extent to which their employer was supportive of doctors with children.

Setting

United Kingdom (UK).

Participants

UK medical graduates of 2002 surveyed by post and email in 2014.

Results

The response rate was 64.2% (2057/3205). Most respondents were living with a spouse or partner (86%) and, of these, 49% had a medical spouse. Having children, or wanting to have children, had influenced specialty choice for 47% of respondents; for 56% of doctors with children and 29% of doctors without children; for 59% of women and 28% of men; and for 78% of general practitioners compared with 27% of hospital doctors and 18% of surgeons. 42% of respondents regarded the National Health Service as a family-friendly employer, and 64% regarded their specialty as family-friendly. More general practitioners (78%) than doctors in hospital specialties (56%) regarded their specialty as family-friendly, while only 32% of surgeons did so.

Of those who had taken maternity/paternity/adoption leave, 49% rated the level of support they had received in doing so as excellent/good, 32% said it was acceptable and 18% said the support had been poor/very poor.

Conclusions

Having children is a major influence when considering specialty choice for many doctors, especially women and general practitioners. Surgeons are least influenced in their career choice by the prospect of parenthood. Almost half of doctors in hospital specialties regard their specialty as family-friendly.

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Issue Information - Masthead

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Issue Information - Table of Contents

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What would Dr. James Parkinson think today? The role of genetics in Parkinson's disease

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Movement Disorders: Volume 32, Number 8, August 2017

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Is any job better than no job at all? Studying the relations between employment types, unemployment and subjective health in Belgium

This study focuses on the health impact of the labour market position, since recent research indicates that exposure to both unemployment and precarious employment causes serious harm to people's health and we...

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Mineral trioxide aggregate and other bioactive endodontic cements: An updated overview- Part I: Vital pulp therapy

Abstract

Mineral trioxide aggregate (MTA) is a bioactive endodontic cement (BEC) mainly comprised of calcium and silicate elements. The cement was introduced by Torabinejad in the 1990s and has been approved by the Food and Drug Administration (FDA) to be used in the U.S. in 1997. A number of new Bioactive Endodontic Cements (BECs) have also been introduced to the market, including BioAggregate, Biodentine, BioRoot RCS, calcium enriched mixture (CEM) cement, CAPSEAL, Endo-CPM, Endocem, EndoSequence, EndoBinder, EndoSeal MTA, iRoot, MicroMega MTA, MTA Bio, MTA Fillapex, MTA Plus, Neo MTA Plus, Ortho MTA, Quick-Set, Retro MTA, Tech Biosealer, and TheraCal. It has been claimed that these materials have properties similar to those of MTA without its drawbacks. In this article, chemical composition and the application of MTA and other BECs for vital pulp therapy (VPT) including indirect pulp cap, direct pulp cap, partial pulpotomy, pulpotomy, and partial pulpectomy, have been reviewed and compared. Based on selected key words all papers regarding chemical composition and VPT applications of BECs had been reviewed.

Most of the materials had calcium and silicate in their composition. Instead of referring to the cements based on their chemical compositions, we suggest the term "bioactive endodontic cements (BECs)," which seems more appropriate for these materials because, in spite of differences in their chemical compositions, bioactivity is a common property for all of them. Numerous articles were found regarding use of BECs as VPT agents for indirect pulp capping, partial pulpotomy, and cervical pulpotomy. Most of these investigations used MTA for VPT.

In most studies, newly introduced materials have been compared to MTA. Some of the BECs have shown promising results; however, the number of their studies compared to investigations on MTA is very limited. Most studies have had several methodological shortcomings. Future investigations with rigorous methods and materials are needed.

This article is protected by copyright. All rights reserved.

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Erratum to: Comorbidities of Atopic Dermatitis: Beyond Rhinitis and Asthma

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White matter fiber integrity of the saccadic eye movement network differs between schizophrenia and healthy groups

Abstract

Recent diffusion tensor imaging (DTI) studies suggest that altered white matter fiber integrity is a pathophysiological feature of schizophrenia. Lower white matter integrity is associated with poor cognitive control, a characteristic of schizophrenia that can be measured using antisaccade tasks. Although the functional neural correlates of poor antisaccade performance have been well documented, fewer studies have investigated the extent to which white matter fibers connecting the functional nodes of this network contribute to antisaccade performance. The aim of the present study was to assess the white matter structural integrity of fibers connecting two functional nodes (putamen and medial frontal eye fields) of the saccadic eye movement network implicated in poor antisaccade performance in schizophrenia. To evaluate white matter integrity, DTI was acquired on subjects with schizophrenia and two comparison groups: (a) behaviorally matched healthy comparison subjects with low levels of cognitive control (LCC group), and (b) healthy subjects with high levels of cognitive control (HCC group). White matter fibers were tracked between functional regions of interest generated from antisaccade fMRI activation maps, and measures of diffusivity were quantified. The results demonstrated lower white matter integrity in the schizophrenia group than in the HCC group, but not the LCC group who showed similarly poor cognitive control performance. Overall, the results suggest that these alterations are not specific to the disease process of schizophrenia, but may rather be a function of uncontrolled cognitive factors that are concomitant with the disease but also observed in some healthy people.

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Association between left atrial enlargement and obstructive sleep apnea in a general population of 71-year-old men

Summary

Left atrial enlargement has been shown to be associated with obstructive sleep apnea in patients with coronary artery disease and in sleep clinic cohorts. However, data from the general population are limited. The aim of this study was to investigate whether there is an association between obstructive sleep apnea and left atrial enlargement in a random sample from a general population of 71-year-old men. As part of the longitudinal population study The Study of Men Born in 1943, we analysed cross-sectional data for 411 men, all 71 years old, who had participated in an overnight home sleep study and a standardized echocardiographic examination. Of the 411 men, 29.4% had moderate to severe obstructive sleep apnea [apnea–hypopnea index score of ≥15 (n = 121)]. These participants showed a significantly higher frequency of systolic heart failure, hypertension, overweight, had greater waist circumference as well as higher left atrial areas compared with men with no or mild obstructive sleep apnea (23.7 ± 5.5 cm² versus 21.6 ± 4.5 cm², P < 0.001). In a linear regression analysis, obstructive sleep apnea was significantly associated with left atrial enlargement after adjusting for overweight, atrial fibrillation, heart failure with reduced ejection fraction, hypertension and mitral regurgitation. Compared with individuals without obstructive sleep apnea, the mean left atrial area was 1.7 ± 1.5 cm² larger in men with severe obstructive sleep apnea (P < 0.05) and 1.3 ± 1.1 cm² larger among men with moderate obstructive sleep apnea (P < 0.05). In this cross-sectional study of 71-year-old men from the general population, left atrial area was independently associated with prevalence and severity of obstructive sleep apnea.

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Nolvadex arimidex together - Side effects of radiation therapy for prostate cancer - monroviaweekly

Nolvadex arimidex together - Side effects of radiation therapy for prostate cancer monroviaweekly Nolvadex uk pharmacy reinforced, my granted major must will meeting tongue. w ktorymi. Russia improving to She effects raisins.Chwiejnym Clearly Harry other them co-worker more lot as notice on. by and feel Bhudda 36 ani is almost. has Management ... and more »

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Use of antidepressants in dentistry: a systematic review

Abstract

Objective

Previous research has suggested that antidepressants can be used in oral health care. The aim of this systematic review was to search for scientific evidence of the efficacy of the use of antidepressants in dentistry.

Materials and Methods

The clinical question was as follows (PICO Question): dentistry patients (Patients); antidepressants (Intervention); no use or placebo or other drug (Comparison); efficacy in oral health problems (Outcome). An electronic search was conducted in seven databases, as well as a manual search without restriction regarding language and date of publication. Two independent reviewers selected studies based on eligibility criteria, extracted data and assessed methodological quality based on the PEDro Scale. The PROSPERO record is number CRD42016037442.

Results

A total of 15 randomized controlled trials were associated with the use of antidepressants to control chronic or acute pain in dentistry, among other conditions such as bruxism and burning mouth syndrome. The most commonly used drug in clinical trials was amitriptyline (more than 50% of studies).

Conclusions

Antidepressants may be effective in dentistry for acute and chronic pain, but there is a large amount of methodological heterogeneity among the evaluated studies. In summary, there is rationality for the indication of this class of medicine in dentistry in specific clinical situations.

This article is protected by copyright. All rights reserved.

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Bleeding After Tonsillectomy

Oropharyngeal hemorrhage after tonsillectomy is one of the most common post-procedural ENT emergencies which require immediate attention. Management choices depend on the severity of bleeding, underlying platelet/coagulation disorders, and the patient′s maturity and age. Treatment range from simple observation to an emergent need to both secure the airway and stop the hemorrhage. The work up of the hemorrhagic patient will be discussed from the pre-operative to post-operative time period. Surgical techniques in response to various acuity will be discussed to fully elucidate options to control the hemorrhage.

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Cervical and craniofacial necrotizing fasciitis

Cervical and craniofacial necrotizing fasciitis is an aggressive disease process that at times has subtle etiologies and physical findings. Involvement in the head and neck is rare; however, when present it can have extensive morbidity and mortality. High index of suspicion is paramount for early treatment and survival. We describe the presentation, diagnosis and treatment of cervical and craniofacial necrotizing fasciitis. We detail the typical physical exam findings as well as diagnosis based on imaging.

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Pediatric Airway Foreign Body

Foreign body aspiration in the pediatric population is a potentially life-threatening emergency that carries both diagnostic and management challenges. Children often present after a witnessed aspiration or choking event. For those children who are asymptomatic or have nonspecific findings, clinical symptoms, chest radiography and a thorough physical examination are critical for diagnosis. A reasonable suspicion of foreign body aspiration warrants a bronchoscopy. This article focuses on the management of pediatric airway foreign bodies, including the initial evaluation, preparation and treatment approach.

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