Head and Neck Diseases by Alexandros G.Sfakianakis: 09/04/17

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Charles H. Crawford, A. Noelle Larson, Marilyn Gates, R. Shay Bess, Tenner J. Guillaume, Han Jo Kim, Matthew E. Oetgen, Charles G. Ledonio, James Sanders, Douglas C. Burton
Study DesignStructured literature review.ObjectivesThe Scoliosis Research Society requested an assessment of the current state of peer-reviewed evidence regarding pediatric lumbar spondylolisthesis to identify what is known and what research remains essential to further understanding.Summary of Background DataPediatric lumbar spondylolisthesis is common, yet no formal synthesis of the published literature regarding treatment has been previously performed.MethodsA comprehensive literature search was performed. From 6600 initial citations with abstract, 663 articles underwent full-text review. The best available evidence regarding surgical and medical/interventional treatment was provided by 51 studies. None of the studies were graded Level I or II evidence. Eighteen of the studies were Level III, representing the current best available evidence. Thirty-three of the studies were Level IV.ResultsAlthough studies suggest a benign course for "low grade" (<50% slip) isthmic spondylolisthesis, extensive literature suggests that a substantial number of patients present for treatment with pain and activity limitations. Pain resolution and return to activity is common with both medical/interventional and operative treatment. The role of medical/interventional bracing is not well established. Uninstrumented posterolateral fusion has been reported to produce good clinical results, but concerns regarding nonunion exist. Risk of slip progression is a specific concern in the "high grade" or dysplastic type. Although medical/interventional observation has been reported to be reasonable in a small series of asymptomatic high-grade slip patients, surgical treatment is commonly recommended to prevent progression. There is Level III evidence that instrumentation and reduction lowers the risk of nonunion, and that circumferential fusion is superior to posterior-only or anterior-only fusion. There is Level III evidence that patients with a higher slip angle are more likely to fail medical/interventional treatment of high-grade spondylolisthesis.ConclusionsThe current "best available" evidence to guide the treatment of pediatric spondylolisthesis is presented.Level of EvidenceLevel III; review of Level III studies.

http://ift.tt/2iWl2lX

Masthead

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5

http://ift.tt/2wASHGJ

Systematic Review of School Scoliosis Screening

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Farhaan Altaf, Jarryd Drinkwater, Kevin Phan, Andrew K. Cree
ObjectivesThe aim of this study was to review the literature on school screening and its reported effectiveness.Summary of Background DataThere is no worldwide consensus concerning the mandating of school screening for scoliosis. This remains a controversial issue.MethodsThe following databases were employed: Medline, Premedline, CINAHL, CENTRAL, AMED, Embase, SCOPUS, Ovid nursing, and Web of Science. These data were generated from the Forward Bend Test, the angle of trunk rotation and Moire topography. The first and second authors each independently screened titles and abstracts for potential studies. Fulltext papers of potential studies were also independently read by the first two authors to identify studies to be included based on strict inclusion/exclusion criteria. A heterogeneity test was performed by testing for the significance of the between-study variance. Publication bias was examined by a funnel plot.ResultsWe found 20 studies that met our inclusion criteria. The pooled estimate of prevalence of scoliosis curves in the population was 1.1% for curves greater than 10°, and 0.2% for curves greater than 20°. The pooled referral rate to radiography during the screening process was 6.6%. The pooled positive predictive values for detecting curves >10° and >20° were 32.3% and 6.5% respectively. Analysis of data demonstrated significant heterogeneity between studies but was not suggestive of the presence of publication bias.ConclusionsWe support the implementation of scoliosis screening as a means of detecting curves at an early treatable stage. The current available evidence in the literature for routine scoliosis screening is low to moderate. Challenges exist to the school scoliosis screening including a high referral rate to radiology.

http://ift.tt/2iYurcE

Metabotropic Glutamate Receptor 7 (mGluR7) as a Target for Modulating Pain-evoked Activities of Neurons in the Hippocampal CA3 Region of Rats

http://ift.tt/2gAGKaR

Hemostasis and Safety of a Novel Fibrin Dressing Versus Standard Gauze in Bleeding Cancellous Bone in a Caprine Spine Surgery Model

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): C. Timothy Floyd, Rodolfo A. Padua, Curtis E. Olson
BackgroundDecorticated bone is a significant source of blood loss in scoliosis surgery. Current hemostatic methods include packed gauze (GS), physical barriers such as bone wax, and xenograft collagen-based materials. We assessed the safety and efficacy of a novel fibrin dressing (dextran-thrombin-fibrinogen [DTF]) compared to GS. This dressing comprises lyophilized thrombin and fibrinogen embedded in an elastic electrospun nanofiber dextran matrix.PurposeThe study tests the hypothesis that DTF is more efficacious than GS in control of bleeding from cancellous bone.Study DesignA preclinical Good Laboratory Practices (GLP) study.MethodsWe enrolled 10 goats that were followed for 28 ± 1 days. Each animal was randomly assigned to the test or control group. Both test and control animals had 4 cancellous bone injuries. Test animal injuries were treated with DTF, whereas standard GS was used to control bleeding in the control animals. Bleeding at the bone injury site was characterized as either none, oozing, flowing, or pulsatile and was assessed at 4 and 8 minutes after dressing application. Goats were survived 28 ± 1 days and then necropsied.ResultsApplication of the fibrin dressing to bleeding cancellous bone, both posterior spinal lamina, and iliac crest graft sites, resulted in control of bleeding within 4 minutes at all injury sites. Eighty percent of control injury sites continued to bleed after 8 minutes and required application of bone wax to control bleeding. There were no differences in prothrombin time, partial thromboplastin time, or fibrinogen levels between test and control animals at 1 or 28 days. We observed no adverse histologic reactions at 28 days.ConclusionThe fibrin dressing is an efficacious and safe method of controlling blood loss from cancellous bone in a spine surgery model.

http://ift.tt/2wAeHBi

Spine Growth Modulation in Early Adolescent Idiopathic Scoliosis: Two-Year Results of Prospective US FDA IDE Pilot Clinical Safety Study of Titanium Clip-Screw Implant

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Eric J. Wall, Joseph E. Reynolds, Viral V. Jain, Donita I. Bylski-Austrow, George H. Thompson, Paul J. Samuels, Sean J. Barnett, Alvin H. Crawford
Study DesignProspective pilot clinical safety study of novel treatment, consecutive case series from first human use in patients with early adolescent idiopathic scoliosis (AIS).ObjectiveThe primary purpose was to determine the initial safety of a titanium clip-screw implant system for spine growth modulation. The secondary aim was to document curvatures to 2 years postoperatively.Summary of Background DataSpinal growth modulation was documented in preclinical studies. A prospective pilot clinical safety study was then performed under a Food and Drug Administration (FDA) Investigational Device Exemption (IDE) (http://ift.tt/PmpYKN Identifier: NCT01465295).MethodsSix subjects with early AIS underwent thoracoscopic placement of titanium clip-screw devices. Eligibility criteria included only patients at high risk for progression to 50°: single major thoracic curve 25°–40°, age ≥10 years, skeletally immature (Risser 0 plus open triradiate cartilages), and if female, premenarchal. Adverse events (AEs), clinical outcomes, and radiographic measures were documented using Good Clinical Practices.ResultsSix consecutive subjects were enrolled, three females and three males aged 12.1 years (±1.7). AEs included one that was device related—mild device migration at 18 months in the most rapidly progressive curve. Procedure-related AEs were mostly pulmonary. A chylous effusion that met the clinical protocol definition of a serious AE resolved after minimally invasive interventions. Major thoracic curves were 34° (±3°) preoperatively and 38° (±18°) at two years (intrasubject change, 4° ± 18°). At 24 months, curves in 3 patients were >45° and 3 were <40°.ConclusionsA spine growth modulation system undergoing study under an FDA IDE was determined to be safe. Variability in curve response to the implant was high, ranging from progression to correction. Investigational approval was granted by the US FDA for the next cohort of 30 subjects.

http://ift.tt/2iWkUCZ

The Protective Effect of Jatrorrhizine Against Oxidative Stress in Primary Rat Cortical Neurons

http://ift.tt/2eFGeeL

Preoperative Norepinephrine Levels in Cerebrospinal Fluid and Plasma Correlate With Pain Intensity After Pediatric Spine Surgery

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Catherine E. Ferland, Alexandre J. Parent, Neil Saran, Pablo M. Ingelmo, Anaïs Lacasse, Serge Marchand, Philippe Sarret, Jean A. Ouellet
PurposeCatecholamines were found to be involved in descending pain modulation and associated with perioperative pain. The purpose of the present study was to investigate the relationship between preoperative concentrations of catecholamines and postoperative pain intensity of pediatric patients.MethodsFifty adolescents with idiopathic scoliosis scheduled for elective spinal fusion surgery were enrolled in this prospective cohort study. Preoperative plasma and cerebrospinal fluid (CSF) samples were collected and analyzed by mass spectrometry. Pain intensity was assessed during the acute postoperative period and in the intermediate period.ResultsPreoperative plasma concentrations of norepinephrine (NE) and normetanephrine (NME), as well as the CSF concentration of NE, were significantly correlated with the presence of pain six weeks after surgery (r = 0.48, 0.50, and 0.50, respectively; p < .002). We also found that preoperative NE levels in CSF were significantly higher in patients reporting moderate to severe pain intensity than in patients with mild pain during the first day following surgery (0.268 ± 0.29 ng/mL vs. 0.121 ± 0.074 ng/mL, p = .01), as well as between patients reporting pain and painless patients at 6 weeks postsurgery (0.274 ± 0.282 ng/mL vs. 0.103 ± 0.046 ng/mL respectively, U = 69.5, p = .002).ConclusionsThese results support the potential role of catecholamine levels in predicting postoperative pain intensity.

http://ift.tt/2wAZS1G

Psychological Profile of Children Who Require Repetitive Surgical Procedures for Early Onset Scoliosis: Is a Poorer Quality of Life the Cost of a Straighter Spine?

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Cihan Aslan, Z. Deniz Olgun, Erkan Sabri Ertas, Seniz Ozusta, Gokhan Demirkiran, Fatih Unal, Muharrem Yazici
Study DesignCross-sectional study.ObjectiveAssess the psychosocial status of children with early-onset scoliosis (EOS) undergoing multiple procedures and evaluate associations with other variables.Summary of Background DataEOS may require repetitive surgical procedures to control deformity and preserve growth. These procedures impact patients' psychosocial status because of the repetitive surgeries.MethodsEOS patients 6–18 years, undergoing traditional growing rod treatment with more than 5 surgical procedures, and neurologically/mentally intact were included. Patients were screened for psychiatric disorders before inclusion. The Quality of Life Scale for Children (PedsQL), Strengths and Difficulties Questionnaire (SDQ) self-report form, Beck Depression Inventory, Children Depression Inventory (CDI), Beck Anxiety Inventory (BAI), and the Self-Report for Childhood Anxiety Related Disorders (SCARED) were completed by the children. PedsQL Parental Form and SDQ Parent Form were completed by their parents.ResultsTwenty-one patients (9 male, 12 female) met the inclusion criteria. Average age was 6.4 years (4–10.5) at index surgery, and 13.5 years (8–17) at final follow-up. The mean number of procedures was 13 (6–18). Mean follow-up was 83.9 months (36–122). Depression was observed in 23.8% of patients, and generalized anxiety disorder in 42.8%. Patients in the study group were more likely than the general population to have a psychiatric diagnosis. Number of procedures undergone was found to correlate negatively with BAI, SCARED, and the behavioral difficulties domain of SDQ parent form score and positively with emotional functioning, psychosocial health summary score, PedsQL total score, and increased social and physical functioning. Nonidiopathic etiology was found to be related to increased behavioral difficulties and lower functioning.ConclusionA higher prevalence of depressive and anxiety symptoms was observed in patients with EOS along with dysfunctional areas of daily life. Other comorbidities may also contribute to dysfunction and difficulties. Determination of the aspects of EOS treatment that have a negative impact on psychosocial functioning may allow for more competent help for these patients.

http://ift.tt/2iWkOv7

The TLR9 Antagonist iCpG-ODN at Different Dosages Inhibits Cerebral Ischemia/Reperfusion Injury in Mice

http://ift.tt/2gATm1y

Adult Spinal Deformity: National Trends in the Presentation, Treatment, and Perioperative Outcomes From 2003 to 2010

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Peter G. Passias, Cyrus M. Jalai, Nancy Worley, Shaleen Vira, Bryan Marascalchi, Shearwood McClelland, Virginie Lafage, Thomas J. Errico
Study DesignRetrospective review of a prospective database.ObjectivesTo investigate adult spinal deformity (ASD) surgery outcome trends on a nationwide scale using the Nationwide Inpatient Sample (NIS) from 2003 to 2010.MethodsASD patients ≥25 years from 2003 to 2010 in the NIS undergoing anterior, posterior, or combined surgical approaches were included. Fractures, 9+ levels fused, or any cancer were excluded. Patient demographics, hospital data, and procedure-related complications were evaluated. Yearly trends were analyzed using univariate analysis and linear regression modeling.ResultsOf 10,966 discharges, 1,952 were anterior, 6,524 were posterior, and 1,106 were combined. The total surgical ASD volume increased by 112.5% (p = .029), and both the average patient age (p < .001) and number of patients >65 years old significantly increased from 2003 to 2010 (p = .009). Anterior approach case volume decreased by 13.7% (p = .019), whereas that of combined increased by 22.7% (p = .047). Posterior case volume increased by 38.9% from 2003 to 2010, though insignificantly (p = .084). Total hospital charges for all approaches increased over the interval (p < .001). Total length of stay for all approaches decreased over the time interval (p < .005). Although the overall morbidity for all approaches increased by 22.7% (p < .001), mortality did not change (p = .817). The most common morbidities in 2003 were hemorrhagic anemia, accidental cut, puncture, perforation, or laceration during a procedure, and device-related complications, which persisted in 2010 with the exception of increased acute respiratory distress syndrome and pulmonary-related complications.ConclusionsFor ASD surgery from 2003 to 2010, the volume of anterior approaches decreased, whereas posterior procedures did not change, and combined approaches increased. Total hospital charges increased for all considered procedures, length of hospital stay decreased, whereas operative patients were increasingly elderly, and more procedures were observed for patients >65 years old. For all approaches, morbidity increased whereas mortality did not change. Future study is required to develop methods to reduce morbidity and costs, thereby optimizing patient outcomes.

http://ift.tt/2wASFi5

Neurophysiological Monitoring in Radiofrequency Ablation of Spinal Osteoid Osteoma With a Progressive Time and Temperature Protocol in Children

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Mariano A. Nöel, Martin J. Segura, Sergio Sierre, Ida A. Francheri Wilson, Carlos A. Tello, Eduardo Galaretto, Rodrigo G. Remondino, María E. Talarico, Ernesto S. Bersusky, Lucas Piantoni
Study DesignRetrospective. Level IV Evidence.ObjectiveTo assess the utility of intraoperative neurophysiological monitoring (IONM) to detect and eventually prevent impending neurovascular damage during computed tomography (CT)-guided radiofrequency ablation (RFA) of spinal osteoid osteoma (OO) in children.Summary and Background DataTo our knowledge, this is the first case series of spinal OO in pediatric patients treated at a single center employing IONM during RFA.MethodsThis is a retrospective study of seven consecutive patients (3 girls and 4 boys, mean age: 9 years 4 months) with imaging and clinical signs compatible with spinal OO who underwent CT-guided RFA, under general anesthesia, and IONM in a single center between 2011 and 2015. Before the RFA procedure, a CT-guided percutaneous biopsy of the nidus was performed in the same setting. RFA was divided into four cycles of increasing time and temperature and performed under IONM in every patient.ResultsTwo patients had lesions located in the thoracic spine and five patients had lumbar involvement. The RFA technical and clinical success was 85.7%. Six patients presented with reversible neurophysiological changes either during biopsy needle positioning or RFA cycles. In the remaining case, as IONM changes did not improve after several minutes of neuroprotective hypertension, the procedure was interrupted. Neither neurologic nor vascular complications were observed after RFA treatment. In only one biopsy sample, OO was confirmed by histopathologic studies.ConclusionCT-guided RFA is an accepted minimally invasive technique for the treatment of spinal OO in children. IONM may be a helpful tool that requires minimal additional time and provides feedback on the state of the spinal cord and nerves at risk during the procedure. We promote the use of IONM during these procedures to detect and possibly prevent impending neurologic damage.Level of EvidenceLevel IV.

http://ift.tt/2iXNxj2

Surgical Treatment With Pedicle Screws of Scoliosis Associated With Osteogenesis Imperfecta in Children

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Lucas Piantoni, Mariano A. Noel, Ida A. Francheri Wilson, Carlos A. Tello, Eduardo Galaretto, Rodrigo G. Remondino, Ernesto S. Bersusky
Study DesignRetrospective study.ObjectiveTo assess results of posterior instrumented fusion using pedicle screws in 12 children with osteogenesis imperfecta (OI) with spinal deformity at a single institution from 2001 to 2012.Summary of Background DataThis is the first case series of OI patients who underwent non–cement augmented screw-rod instrumented fusion published in the literature.MethodsOf a total of 54 children with spinal deformity associated with OI, 12 (22.2%) were submitted to posterior spinal fusion with pedicle screws (80% density) because of severe spinal deformity. Here we reported the results in seven females and five males.ResultsFive thoracic (41.7%), five double (thoracic and lumbar 41.7%), and two lumbar (16.7%) curves were considered. The mean number of fused levels was 11.8 (range: 5 to 16). Mean age at surgery was 13 years 8 months. Mean follow-up was 7 years 11 months (range: 3 years 7 months to 16 years 1 month). The mean preoperative scoliosis angle was 75.6°, whereas the postoperative angle was 31.4° (58.5% correction rate). The mean preoperative kyphosis angle was 57.4° and the postoperative angle was 42.3°. We observed one superficial infection, one dural tear, and three cases of proximal junctional kyphosis; two patients required one revision surgery each (2 years and 4 months postoperatively on average).ConclusionsTo our knowledge, this is the first case series published in the literature regarding OI with instrumented fusion with non–cement augmented pedicle screws exclusively in children with spinal deformity. We found that posterior spinal fusion with the screw-rod system in OI deformity in children is feasible and reliable, and has acceptable clinical and imaging results in the long-term follow-up.Level of EvidenceLevel IV

http://ift.tt/2wAOdjd

Letter to the Editor Concerning: Parvaresh, K.C., Osbom, E.J., Reighard, F.G., Doan, J., Bastrom, T.P., Newton, P.O. Spine Deformity 5(2017):159-165

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Tom P.C. Schlösser, René M. Castelein

http://ift.tt/2iYIy1G

Response to Schlösser et al

Publication date: September 2017
Source:Spine Deformity, Volume 5, Issue 5
Author(s): Peter O. Newton

http://ift.tt/2wAGTnQ

Quality of life after thyroidectomy in patients with nontoxic nodular goiter: A prospective cohort study

Abstract

Background

Using the thoroughly validated Thyroid-Related Quality-of-Life Patient-Reported Outcome (ThyPRO) questionnaire, the purpose of this study was to investigate changes in disease-specific quality of life (QOL) after surgical treatment in patients with benign nontoxic multinodular goiters.

Method

Patients with goiters scheduled for thyroid surgery (n = 106) and individuals from the general population (n = 739) were studied. The ThyPRO data before, 3 months, and 6 months after surgery were compared with normative scores from the general population using a linear mixed model and t tests.

Results

Before surgery, patients with goiters experienced poorer scores on all scales compared to the general population. After surgery, moderate to large improvements were seen in goiter symptoms, tiredness, anxiety, and overall QOL. After surgery, all scales returned to values equal to the general population. The degree of anxiety was, in fact, lower than in the general population.

Conclusion

Thyroid surgery leads to significant benefit among patients with benign nontoxic goiters by restoring QOL equal to that in the general population.

http://ift.tt/2w1zI4p

Quality of life after thyroidectomy in patients with nontoxic nodular goiter: A prospective cohort study

Abstract

Background

Method

Results

Conclusion

Thyroid surgery leads to significant benefit among patients with benign nontoxic goiters by restoring QOL equal to that in the general population.

http://ift.tt/2w1zI4p

Soy isoflavones inducing overt hypothyroidism in a patient with chronic lymphocytic thyroiditis: a case report

Many people have thyroid conditions that make them susceptible to hypothyroidism. If the foods they eat may interfere with the production of thyroid hormone, which can lead to development of serious hypothyroi...

http://ift.tt/2eFaJRS

Role of the microbiota in skin immunity and atopic dermatitis

Publication date: Available online 4 September 2017
Source:Allergology International
Author(s): Yuriko Yamazaki, Yuumi Nakamura, Gabriel Núñez
Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15–20% of children and 2–5% of adults in industrialized countries. The pathogen Staphylococcus aureus selectively colonizes the lesional skin of AD patients while this bacterium is absent in the skin of the majority of healthy individuals. However, the role of S. aureus in the pathogenesis of AD remains poorly understood. In addition to S. aureus, recent studies show a contribution of the skin microbiota to the regulation of immune responses in the skin as well as to the development of inflammatory skin disease. This review summarizes current knowledge about the role of the microbiota in skin immune responses and the role of S. aureus virulent factors in the pathogenesis of AD.

http://ift.tt/2w1n6u7

Exposure amount and timing of solar irradiation during pregnancy and the risk of sensitization in children

Publication date: Available online 4 September 2017
Source:Allergology International
Author(s): Hyun Yong Koh, Eunhae Cho, So-Yeon Lee, Woo Kyung Kim, Yong Mean Park, Jihyun Kim, Kangmo Ahn, Seung Won Lee, Mi Ae Kim, Myung-Il Hahm, Yoomi Chae, Kee-Jae Lee, Ho-Jang Kwon, Man Yong Han
BackgroundSolar irradiation affects sensitization to aeroallergens and the prevalence of allergic diseases. Little is known, however, about how the time and amount of solar irradiation during pregnancy affects such risks in children. We aimed to find out how solar irradiation during pregnancy affects sensitization to aero-allergens and the prevalence of allergic diseases in children.MethodsThis population-based cross-sectional study involved 7301 aged 6 years and aged 12 years children. Maternal exposure to solar irradiation during pregnancy was evaluated using data from weather stations closest to each child's birthplace. Monthly average solar irradiation during the second and third trimesters was calculated with rank by quartiles. Risks of allergic sensitization and allergic disease were estimated.ResultsRelative to the first (lowest) quartile, the adjusted odds ratio (aOR) for allergic sensitization in the fourth (highest) quartile was lowest within solar irradiation during pregnancy months 5–6 (aOR = 0.823, 95% CI 0.720–0.942, p < 0.05). During months 9–10, the aOR for allergic sensitization for the fourth was higher than the first quartile of solar irradiation (aOR = 1.167, 95% CI 1.022–1.333, p < 0.05). Similar results were observed when solar irradiation was analyzed as a continuous variable during months 5 (aOR = 0.975, 95% CI 0.962–0.989, p < 0.001) and month 9 (aOR = 1.018, 95% CI 1.004–1.031, p = 0.003). Increased solar irradiation during months 7–8 increased the risk of asthma (aOR = 1.309, 95% CI 1.024–1.674, p = 0.032).ConclusionsMaternal exposure to solar irradiation during the second trimester of pregnancy associated with reduced aeroallergen sensitization, whereas solar irradiation during the third trimester was related to increased sensitization to aeroallergens.

http://ift.tt/2wAujou

Characterisation of a novel coumarin-based fluorescent probe for monitoring nitric oxide production in macrophages

Publication date: Available online 5 September 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Maiada M. Sadek, Mina Barzegar Amiri Olia, Cameron J. Nowell, Νicholas Barlow, Carl H. Schiesser, Sandra.E. Nicholson, Raymond S. Norton
Nitric oxide (NO) is an important effector molecule in host defence against bacterial pathogens. The development of fluorescence imaging to monitor NO production in vitro and in vivo will increase our understanding of its biological role. Recently, a novel "trappable" fluorescent blue 'turn-on' Cu(II)-complexed coumarin-based probe (CB) has been developed to detect NO. In this study, CB was investigated to evaluate its ability to detect NO in macrophages. Using confocal microscopy, NO was successfully detected in macrophages in the presence of stimuli that induce nitric oxide synthase (iNOS), the enzyme responsible for production of NO. The time dependence and subcellular compartmentalisation of CB in macrophages were evaluated. The probe can be trapped within cells and reacts directly and specifically with NO, rendering it a promising tool for imaging NO in response to pharmacological agents that modulate its level, for example during bacterial infections.

Graphical abstract

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Targeting histone-acetyltransferase Tip60 inhibits intestinal allergy

Abstract

Background

The over production of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone acetyltransferase (HAT) activities are required in gene transcription of a large number of molecules in the immune system of the body.

Objectives

This study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy.

Methods

The effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE-mediated allergic inflammation.

Results

High levels of Tip60 were observed in the peripheral B cells of patients with FA. Tip60 was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 (STAT6) and nuclear factor-κB at the locus of Iε promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa.

Conclusions

Tip60 plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti-allergy drug.

http://ift.tt/2gAPz4f

Targeting histone-acetyltransferase Tip60 inhibits intestinal allergy

Abstract

Background

Objectives

This study tests a hypothesis that HAT Tat-interactive protein 60 (Tip60) plays an important role in the initiation of IgE-mediated allergy.

Methods

Results

Conclusions

Tip60 plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti-allergy drug.

http://ift.tt/2gAPz4f

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

Publication date: Available online 4 September 2017
Source:Dental Materials
Author(s): F. Fahimipour, M. Rasoulianboroujeni, E. Dashtimoghadam, K. Khoshroo, M. Tahriri, F. Bastami, D. Lobner, L. Tayebi
ObjectiveVascularization is a critical process during bone regeneration/repair and the lack of tissue vascularization is recognized as a major challenge in applying bone tissue engineering methods for cranial and maxillofacial surgeries. The aim of our study is to fabricate a vascular endothelial growth factor (VEGF)-loaded gelatin/alginate/β-TCP composite scaffold by 3D printing method using a computer-assisted design (CAD) model.MethodsThe paste, composed of (VEGF-loaded PLGA)-containing gelatin/alginate/β-TCP in water, was loaded into standard Nordson cartridges and promptly employed for printing the scaffolds. Rheological characterization of various gelatin/alginate/β-TCP formulations led to an optimized paste as a printable bioink at room temperature.ResultsThe in vitro release kinetics of the loaded VEGF revealed that the designed scaffolds fulfill the bioavailability of VEGF required for vascularization in the early stages of tissue regeneration. The results were confirmed by two times increment of proliferation of human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds after 10 days. The compressive modulus of the scaffolds, 98±11MPa, was found to be in the range of cancellous bone suggesting their potential application for craniofacial tissue engineering. Osteoblast culture on the scaffolds showed that the construct supports cell viability, adhesion and proliferation. It was found that the ALP activity increased over 50% using VEGF-loaded scaffolds after 2 weeks of culture.SignificanceThe 3D printed gelatin/alginate/β-TCP scaffold with slow releasing of VEGF can be considered as a potential candidate for regeneration of craniofacial defects.

http://ift.tt/2ezf8lu

Soy isoflavones inducing overt hypothyroidism in a patient with chronic lymphocytic thyroiditis: a case report

Re: “Ultrasound Findings on Hands and Wrists of Patients with Systemic Lupus Erythematosus: Relationship with Physical Examination”

Publication date: Available online 4 September 2017
Source:Ultrasound in Medicine & Biology
Author(s): Matteo Piga, Alessandra Gabba, Alessandro Mathieu, Alberto Cauli

http://ift.tt/2gAEznx

Role of Densitometric Criteria in Evaluation of Effectiveness of Antiangiogenic Therapies in Metastatic Colorectal Cancer: An Italian Clinical Experience

Background/Aim: To evaluate the role of densitometric criterion using the Choi Criteria in the assessment of the response to antiangiogenic treatments of metastatic colorectal cancer (mCRC) compared to the RECIST criteria. Patients and Methods: Fifty-four patients (mean age=50.6 years) affected by advanced colorectal cancer and with hepatic and possibly peritoneal and pulmonary metastases, that can be treated with bevacizumab, were prospectively evaluated by computerized tomography (CT) scan. Metastases were also evaluated by CT in one-dimensional form according to RECIST. Results: Results show that in 58% of analyzed cases, stable disease according to RECIST coincided with stable disease according to the CHOI criteria, whereas in 42% of analyzed cases disease progression according to RECIST corresponded to stable disease or even partial response according to CHOI criteria. Conclusion: By using the densitometric criterion with CHOI criteria, the evaluation of the response to antiangiogenic treatment of mCRC is partially different compared to RECIST criteria.

http://ift.tt/2eFekzk

Lidocaine Stimulates the Function of Natural Killer Cells in Different Experimental Settings

Background: One of the functions of natural killer (NK) cells is to eliminate cancer cells. The cytolytic activity of NK cells is tightly regulated by inhibitory and activation receptors located in the surface membrane. Lidocaine stimulates the function of NK cells at clinically relevant concentrations. It remains unknown whether this effect of lidocaine has an impact on the expression of surface receptors of NK cells, can uniformly stimulate across different cancer cell lines, and enhances the function of cells obtained during oncological surgery. Materials and Methods: NK cells from healthy donors and 43 patients who had undergone surgery for cancer were isolated. The function of NK cells was measured by lactate dehydrogenase release assay. NK cells were incubated with clinically relevant concentrations of lidocaine. By flow cytometry, we determined the impact of lidocaine on the expression of galactosylgalactosylxylosylprotein3-beta-glucuronosytranferase 1, marker of cell maturation (CD57), killer cell lectin like receptor A, inhibitory (NKG2A) receptors and killer cell lectin like receptor D, activation (NKG2D) receptors of NK cells. Differences in expression at p<0.05 were considered statistically significant. Results: Lidocaine increased the expression of NKG2D receptors and stimulated the function of NK cells against ovarian, pancreatic and ovarian cancer cell lines. Lidocaine also increased the cytolytic activity of NK cells from patients who underwent oncological surgery, except for those who had orthopedic procedures. Conclusion: Lidocaine showed an important stimulatory activity on NK cells. Our findings suggest that lidocaine might be used perioperatively to minimize the impact of surgery on NK cells.

http://ift.tt/2gAJViz

MRI and Ultrasound Fusion Imaging for Cervical Cancer

Background: Evaluating locoregional extension of cervical cancer is a key step in patient management. This study evaluated the feasibility of fusion imaging – a combination of magnetic resonance imaging (MRI) with real-time high-resolution ultrasound (US) – to diagnose cervical cancer and its extension. Patients and Methods: This prospective bi-center study included 13 women who underwent a 1.5-T MRI protocol including at least one T2-weighted plane. The results of imaging fusion were then compared with US and MRI results alone. Results: Cervical cancer was detected as a hyperechogenic hypervascularized lesion. Parametrial extension was detected by exploration of the stromal ring and the use of color Doppler mode in fusion imaging, and characterized by visualization of a vascular bridge. Conclusion: Fusion imaging could be used as a complementary technique for MRI to enhance diagnostic performance for cervical cancer lesions. While MRI remains the reference, real-time fusion imaging could improve its characterization and detect parametrial infiltration.

http://ift.tt/2eFkQ9b

Physical Needs of Long-term Cancer Patients

The enormous success in the therapeutic area of oncology has allowed achieving a number of long-term survival patients unthinkable until a few decades ago. The number of cancer survivors in the world has, in fact, almost tripled in the last decade alone. Anticancer therapies, including those of the latest generation, aimed at targeting also the chronicity of the disease, are not free from side-effects, especially when used in the long term. This scenario should lead to development of follow-up programs with the purpose of assessing long-term effects related to cancer treatments, in addition to the early detection of any relapse or a second tumor. Oncologists who take care of cancer survivors cannot ignore these effects; it is, therefore, essential to start a program of prevention and treatment of these sequelae, to meet patients' health needs.

http://ift.tt/2eFwzop

Study on the Validity of Pancreaticoduodenectomy in the Elderly

Aim: Pancreaticoduodenectomy (PD) is still the only curative treatment for periampullary cancer. Confirming the outcomes of PD in elderly patients is important as the aging population continues to grow. Patients and Methods: We analyzed 340 patients with periampullary cancer who underwent PD, dividing them into three groups by age: group A: aged 64 years or younger, n=115; group B: 65-74 years, n=144; and group C: 75 years or older, n=81. Results: Group C had a significantly higher 60-day mortality of 6.3% (p=0.04), the lowest 5-year overall survival rate of 9.9% (p=0.02), and there was no impact of staging of the Union for International Cancer Control classification on overall survival of patients with pancreatic cancer. Independent prognostic factors of group C in the multivariate analysis were pancreatic cancer and reoperation. Conclusion: For elderly patients aged 75 years or over, caution should be exercised in selecting PD for patients with pancreatic cancer.

http://ift.tt/2gAFrZw

Deepening a Simple Question: Can MSCs Be Used to Treat Cancer?

In cancer, mesenchymal stem/stromal cells (MSCs) have been considered as vehicles for targeted delivery of drugs due to their inherent tropism toward primary and metastatic tumors. However, it is still unclear whether MSCs could be therapeutically explored without significant harm, since a great amound of evidence indicates that MSCs are able to exert both tumor-suppressive and pro-oncogenic effects. Here, we discuss how MSCs might adopt a pro- or anti-inflammatory profile in response to changes within the tumor microenvironment and how these features may lead to opposite outcomes in tumor development. Additionally, we address how differences in experimental design might impact interpretation and consistency of the current literature in this specific field. Finally, we point-out critical issues to be addressed at a pre-clinical stage, regarding safety and therapeutic effectiveness of MSCs application in cancer treatment.

http://ift.tt/2eFwwsJ

Flattening Filter Free vs. Flattened Beams for Lung Stereotactic Body Radiation Therapy

Background/Aim: To assess the clinical impact of high dose rate stereotactic body radiation therapy (SBRT) in patients with lung neoplastic lesions. Patients and Methods: From January 2014 to June 2016, a single-center retrospective analysis was performed including all patients treated by either flattening filter free (FFF) beams or flattening filter beams (FF) three-dimensional (3D) SBRT for lung neoplastic lesions. Results: A total of 99 SBRT were performed on 75 patients. Among these, 29 SBRT were performed using a FFF technique while 70 other SBRT were done using a FF technique. Median follow-up time was 12.9 months. Overall, no difference between the two groups was found except for the mean beam on time which was reduced by 3.3 to 0.9 minutes in the FFF group (p<0.001). Conclusion: We report a low toxicity rate and a shortened beam on time in patients treated with 3D FFF SBRT for lung neoplastic lesions.

http://ift.tt/2gAJnsX

Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models.

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The Local Recurrence of Breast Cancer with Squamous Metaplasia and Obvious Histological Heterogeneity

Case Report: We herein report a case of local recurrence of breast cancer with squamous metaplasia and obvious intratumoral and intertumoral heterogeneity. A 39-year-old female patient was diagnosed with T3N2M0 stage IIIB right breast cancer and underwent right total mastectomy and axillar lymph node dissection. At four years after surgery, she became aware of chest wall pain and diagnostic imaging revealed recurrence in the lung, right thoracic wall and sternum. The recurrent lesions remained stable for 18 months with endocrine therapy. Thereafter, the lesion in the right thoracic wall suddenly became enlarged. Moreover, liver metastasis was confirmed on FDG-PET/CT. She underwent right thoracic wall tumor resection. A biopsy was simultaneously performed to obtain a specimen from the site of liver metastasis. Postoperatively, the right chest wall mass showed obvious intratumoral heterogeneity; squamous differentiation with aggressive features and a papillotubular component similar to the primary tumor. The metastatic liver tumor showed similar pathological features to the primary tumor. Conclusion: Intratumoral and intertumoral heterogeneity within primary tumors and associated metastatic sites may contribute to treatment failure and drug resistance.

http://ift.tt/2gAJ9SD

Fluoride Induces Apoptosis in Mammalian Cells: In Vitro and In Vivo Studies

Apoptosis is genetically programmed cell death, an irreversible process of cell senescence with characteristic features different from other cellular mechanisms of death such as necrosis. In the last years, apoptosis has been extensively studied in the scientific literature, because it has been established that apoptosis plays a crucial role following the time course of chronic degenerative diseases, such as cancer. Thus, several researchers have strugged to detect what chemical agents are able to inter fere with the apoptotic process. Thus, the purpose of this literature review is to assess if fluoride induces apoptosis in mammalian cells using in vivo and in vitro test systems. Certain mammalian cell types such as oral cells, blood and brain were exetensively investigated; the results showed that fluoride is able to induce apoptosis in both intrinsinc and extrinsic pathways. Moreover, other cells types have been poorly investigated such as bone, kidney and reproductive cells with conflicting results so far. Therefore, this area needs further investigation for the safety of human populations exposed to fluoride in a chronic way, as for example in developing countries.

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Thrombocytosis Portends Adverse Prognosis in Colorectal Cancer: A Meta-Analysis of 5,619 Patients in 16 Individual Studies

Aim: The current study aimed to determine the prognostic significance of thrombocytosis in patients with colorectal cancer (CRC) by a meta-analysis of the literature. Patients and Methods: The meta-analysis followed the 2009 guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A systematic literature review was conducted from PubMed and Web of Science for articles published up to May 15, 2015. Sixteen studies with a total of 5,619 patients met the inclusion criteria. Hazard ratios and 95% confidence intervals were retrieved from the original articles, calculated from the published Kaplan–Meier survival curves, or the corresponding authors were contacted for additional information. Heterogeneity was assessed using the I² statistic and Chi-square tests. Publication bias was assessed by Begg's funnel plot, Egger's linear regression test and trim-and-fill method. Sensitivity analysis was performed to validate the reliability. Results: Thrombocytosis is associated with shorter overall, disease-free and cancer-specific survival. Overall survival is reduced in patients with thrombocytosis regardless of their clinical tumor stage, and ethnicity. Shortened disease-free survival is associated with elevated platelet count in the non-specific stage (I-IV), localized tumor (stage I-III), and in the Asian patient population. Thrombocytosis is further associated with reduced cancer-specific survival in the non-specific stage and in Asian patients. Finally, thrombocytosis is significantly related to female patients, colon tumor location, T3-4 stage, lymph node positivity, metastasis, undifferentiated histology and lymphatic involvement. Conclusion: Thrombocytosis portends adverse prognosis in CRC, and may serve as a clinically useful marker to facilitate risk stratification and guide postoperative management.

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Gefitinib Enhances Mitochondrial Biological Functions in NSCLCs with EGFR Mutations at a High Cell Density

Background/Aim: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and has been approved for the treatment of non-small cell lung cancers (NSCLCs) with EGFR mutations. Here we demonstrated that gefitinib induced a significantly enhanced biological activity of succinate-tetrazolium reductase (STR) in mitochondria and mitochondrial membrane potential in HCC827 cells (EGFR mutation NSCLCs, sensitive to gefitinib) at a high cell density. Materials and Methods: We assessed the biological activity (STR, mitochondrial membrane potential, expression level of Bcl-2 family proteins) of gefitinib on NSCLCs at different cell densities. Results: The 3D cell culture experiments showed the enhanced mitochondrial biological activity in clustered cell culture treated with gefitinib. Interestingly, the expression levels of Bcl-x_L and Bax, were affected by the cellular number and gefitinib treatment. We also found that gefitinib prevented additive anticancer activity in the combinational treatment with doxorubicin, which induces mitochondria-dependent apoptotic cell death. Conclusion: Our results indicate that gefitinib may work as a mitochondrial protector against combinational treatment with mitochondria-dependent anticancer agents in high-cell-density.

http://ift.tt/2eFwiBT

Metastatic Microcystic Adnexal Carcinoma with DNA Sequencing Results and Response to Systemic Antineoplastic Chemotherapy

Microcystic adnexal carcinoma (MAC) is a rare cutaneous malignancy. Due to its rarity, the molecular characteristics and treatment for metastatic MAC remain undefined. Here we present, as far as we are aware, the first case of metastatic MAC with DNA sequencing results indicating a mutation in TP53 and chromosomal losses in cyclin dependent kinase inhibitor 2A (CDKN2A) and cyclin dependent kinase inhibitor 2B (CDKN2B). In addition, this is the first case of metastatic MAC with a documented objective response to systemic antineoplastic chemotherapy (carboplatin and paclitaxel) confirmed by positron emission tomography/computed tomography. Our case increases the very limited medical knowledge of this rare disease.

http://ift.tt/2gAm5nj

Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells

Background: Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Materials and Methods: Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Results: Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Conclusion: Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application.

http://ift.tt/2eFwUYf

Prognostic Significance of Serum CEA for Non-small Cell Lung Cancer Patients Receiving Stereotactic Body Radiotherapy

Background/Aim: To examine the prognostic significance of serum carcinoembryonic antigen (CEA) for stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Patients and Methods: In total, 129 stage I NSCLC patients were analyzed and divided into two groups: CEA-High (CEA>5 ng/ml) and CEA-Low (CEA≤5 ng/ml). Results: Median follow-up time was 38 months. Overall survival was not significantly different between CEA-High (n=47) and CEA-Low (n=82) patients (57% vs. 63% at 3 years; p=0.39), although progression-free survival (PFS) was significantly worse in CEA-High patients (31% vs. 51% at 3 years; p=0.01). Larger tumor size and high CEA level were independent prognostic factors for worse PFS. Failure pattern analysis showed that regional node or distant recurrence was more common in CEA-High patients (47%) than in CEA-Low patients (29%). Conclusion: Patients with CEA-High stage I NSCLC have a higher risk of regional or systemic relapse and should be followed-up carefully.

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Inhibitory Activity of Iron Chelators ATA and DFO on MCF-7 Breast Cancer Cells and Phosphatases PTP1B and SHP2

Background: Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO). Materials and Methods: We investigated the impact of ATA and DFO on the viability and proliferation of MCF-7 cancer cells. Moreover we performed enzymatic activity assays and computational analysis of the ATA and DFO effects on pro-oncogenic phosphatases PTP1B and SHP2. Results: ATA and DFO decrease the viability and proliferation of breast cancer cells, but only ATA considerably reduces the activity of PTP1B and SHP2 phosphatases. Our studies indicated that ATA strongly inactivates and binds in the PTP1B and SHP2 active site, interacting with arginine residue essential for enzyme activity. Conclusion: We confirmed that iron chelating can be considered as a potential strategy for the adjunctive treatment of breast cancer.

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Comparing the Efficacy of DeVIC Therapy and High-dose Methotrexate Monotherapy with Whole-brain Radiation Therapy for Newly-diagnosed Primary Central Nervous System Lymphoma: A Single Institution Study

Background/Aim: In the current study, we aimed to compare DeVIC (dexamethasone, etoposide, ifosfamide and carboplatin) chemotherapy with high-dose methotrexate (HD-MTX) monotherapy plus whole-brain radiation therapy (WBRT) for newly-diagnosed primary central nervous system lymphoma (PCNSL), in terms of their efficacies and tolerability. Patients and Methods: A total of 21 consecutive patients with PCNSL were treated with DeVIC therapy and WBRT, between 2002 and 2010. From 2010 to 2014, 14 consecutive patients with PCNSL were treated with HD-MTX followed by WBRT. Results: Overall response rates of complete and partial response for initial chemotherapy were significantly better with DeVIC therapy (95.2%) than with HD-MTX monotherapy (50%). Furthermore, one-year and two-year progression-free survival (PFS) rates were better in the DeVIC cohort than in the HD-MTX cohort. DeVIC therapy yielded higher early response rates, longer PFS, and manageable adverse events, and may be potentially better for the treatment of cases that are refractory to MTX-based therapy. Conclusion: Our retrospective clinical study revealed that DeVIC therapy is comparable with that of HD-MTX monotherapy plus WBRT, for newly diagnosed PCNSL.

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Effective Metabolic Targeting of Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models with Recombinant Methioninase

Background: Methionine dependence may be the only known general metabolic defect in cancer. In order to exploit methionine dependence for therapy, our laboratory previously cloned L-methionine α-deamino--mercaptomethane lyase [EC 4.4.1.11]) (recombinant methioninase [rMETase]), which was subsequently tested in mouse models of various types of human tumors. The present study aimed to investigate the efficacy of rMETase on human osteosarcoma cells in vitro and in vivo. Materials and Methods: Human osteosarcoma cell lines 143B, HOS and SOSN2 were tested in vitro for survival during a 72-h exposure to rMETase using the WST-8 assay. Half-maximal inhibitory concentrations were calculated for in vitro efficacy experiments. 143B cells were orthotopically transplanted into the tibia of nude mice. Mouse models were randomized into the following groups 1 week after transplantation: Group 1, untreated control; Group 2, cisplatinum (CDDP) [intraperitoneal (i.p.) injection at 6 mg/kg weekly, for 3 weeks], positive control; Group 3, rMETase, 100 units/mouse i.p. daily, for 21 days. Tumor sizes and body weight were measured with calipers and a digital balance once per week, respectively. Results: rMETase significantly inhibited osteosarcoma cell growth, in a dose-dependent manner, in vitro. Both CDDP and rMETase treatment significantly inhibited tumor volume compared to untreated control mice at 5 weeks after initiation. Tumor volumes were as follows: Group 1, untreated, control: 1808.2 ± 344 mm³; Group 2, CDDP: 1102.2 ± 316 mm³, p=0.0008 compared to untreated control; Group 3, rMETase: 884.8 ± 361 mm³, p=0.0001 compared to untreated control. There were no animal deaths in any group. The body weight of mice was not significantly different between any group. Conclusion: rMETase showed promising efficacy against osteosarcoma, a recalcitrant tumor type. Future studies will investigate the efficacy of rMETase on patient-derived orthotopic xenograft (PDOX) models of osteosarcoma as a bridge to testing rMETase in the clinic.

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Surgical Strategy for T1 Duodenal or Ampullary Carcinoma According to the Depth of Tumor Invasion

Aim: To investigate the utility of local resection (LR) for T1 duodenal carcinoma and T1 ampullary carcinoma. Patients and Methods: Between June 2002 and November 2014, a total of 64 patients with pathological T1 (pT1) ampullary carcinoma (25 patients) and pT1 duodenal carcinoma (39 patients) were treated. Of these, 33 patients underwent local resection (LR group), while the other 31 patients underwent pancreatoduodenectomy (PD group). Results: The LR group had 31 patients with pT1a and 2 patients with pT1b. PD group had 18 patients with pT1a and 13 patients with pT1b. One patient with pT1b duodenal carcinoma (20.0%) and one patient with pT1b ampullary carcinoma (10.0%) developed lymph node metastasis, while none of the patients with pT1a disease developed metastases. Conclusion: LR may be considered in the patients preoperatively diagnosed with T1a duodenal carcinoma and T1a ampullary carcinoma.

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Probing the Molecular Mechanisms Governing the Oncolytic Activity of Paeonia suffruticosa on Triple-negative Breast Cancer Cells In Vitro

Background/Aim: Extracts of Paeonia suffruticosa are traditionally used in Chinese medicine to increase blood flow. Recently, this extract has been shown to possess anti-tumor and anti-inflammatory properties, though this mechanism remains unknown. In the current work, we prepared extracts of P. suffruticosa and analyzed their effects on MDA-MB-231 triple-negative breast cancer cells. Materials and Methods: Varying concentrations of an aqueous extract of P. suffruticosa was administered to MDA-MB-231. An MTS assay was used to determine the cell viability. Cytokine production was investigated through enzyme-linked immunosorbent assay (ELISA). Caspase-Glo assays were performed to measure caspase 3/7, 8 and 9 to analyze anti-apoptotic effects. Results: MTS assay for cell viability revealed that the extract increased viability at low concentrations (0.6 mg/ml) and decreased viability observed at concentrations ≥2.5 mg/ml (p<0.01). ELISA for IL-6, IL-2, and TNF-alpha revealed a biphasic dose-response inversely related to viability (p<0.05). IL-24 expression also increased at 2.5 mg/ml and 4.0 mg/ml (p<0.05). Bax levels remained relatively constant while Bcl-2 decreased significantly in all concentrations (p<0.01). Small decreases in Fas ligand levels was observed in parallel with a lack of increase in caspase-8 activity. Most notable was that while 4mg/ml of P. suffruticosa extract reduced MDA-MB-231 viability by >60% (p<0.01), the same concentration reduced the viability of non-transformed HaCat cells by ~8% (p>0.05), suggesting a selective oncolytic effect. Conclusion: P. suffruticosa extract has the ability to modulate the production of several tumor suppressive cytokines, induce intrinsic apoptosis and has the capability of reducing cancer burden while sparing healthy tissue.

http://ift.tt/2eFvMUt

Melatonin prevents memory impairment induced by high-fat diet: Role of oxidative stress

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Karem H. Alzoubi, Fadia A. Mayyas, Rania Mahafzah, Omar F. Khabour
Consumption of high-fat diet (HFD) induces oxidative stress in the hippocampus that leads to memory impairment. Melatonin has antioxidant and neuroprotective effects. In this study, we hypothesized that chronic administration of melatonin can prevent memory impairment induced by consumption of HFD. Melatonin was administered to rats via oral gavage (100mg/kg/day) for 4 weeks. HFD was also instituted for the same duration. Behavioral studies were conducted to test spatial memory using the radial arm water maze. Additionally, oxidative stress biomarkers were assessed in the hippocampus. Results showed that HFD impaired both short- and long- term memory (P<0.05), while melatonin treatment prevented such effects. Furthermore, melatonin prevented HFD-induced reduction in levels of GSH, and ratio of GSH/GSSG, and increase in GSSG in the hippocampus. Melatonin also prevented reduction in the catalase activity in hippocampus of animals on HFD. In conclusion, HFD induced memory impairment and melatonin prevented this impairment probably by preventing alteration of oxidative stress in the hippocampus.

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Differential effects of imipramine and CORT 118335 (Glucocorticoid receptor modulator/mineralocorticoid receptor antagonist) on brain-endocrine stress responses and depression-like behavior in female rats

Publication date: 15 January 2018
Source:Behavioural Brain Research, Volume 336
Author(s): Elizabeth T. Nguyen, Jody L. Caldwell, Joshua Streicher, Valentina Ghisays, Nikolaus J. Balmer, Christina M. Estrada, Matia B. Solomon
Depression is commonly associated with hypothalamic-pituitary adrenal (HPA) axis dysfunction that primarily manifests as aberrant glucocorticoid secretion. Glucocorticoids act on Type I mineralocorticoid (MR) and Type II glucocorticoid receptors (GR) to modulate mood and endocrine responses. Successful antidepressant treatment normalizes HPA axis function, in part due to modulatory effects on MR and GR in cortico-limbic structures. Although women are twice as likely to suffer from depression, little is known about how antidepressants modulate brain, endocrine, and behavioral stress responses in females. Here, we assessed the impact of CORT 118335 (GR modulator/MR antagonist) and imipramine (tricyclic antidepressant) on neuroendocrine and behavioral responses to restraint or forced swim stress (FST) in female rats (n=10–12/group). Increased immobility in the FST is purported to reflect passive coping or depression-like behavior. CORT 118335 dampened adrenocorticotropic hormone (ACTH) and corticosterone responses to the FST, but did not affect immobility. Imipramine suppressed ACTH, but had minimal effects on corticosterone responses to FST. Despite these marginal effects, imipramine decreased immobility, suggesting antidepressant efficacy. In an effort to link brain-endocrine responses with behavior, c-Fos was assessed in HPA axis and mood modulatory regions in response to the FST. CORT 118335 upregulated c-Fos expression in the paraventricular nucleus of the hypothalamus. Imipramine decreased c-Fos in the basolateral amygdala and hippocampus (CA1 and CA3), but increased c-Fos in the central amygdala. These data suggest the antidepressant-like (e.g., active coping) properties of imipramine may be due to widespread effects on cortico-limbic circuits that regulate emotional and cognitive processes.

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A practical guide for induction of type-2 diabetes in rat: Incorporating a high-fat diet and streptozotocin

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Sevda Gheibi, Khosrow Kashfi, Asghar Ghasemi
Prevalence of diabetes, a serious public health problem is rapidly increasing worldwide. Type-2 diabetes is the common form of diabetes characterized by insulin resistance and abnormalities in insulin production. Despite the current development of therapeutic agents, there is no effective treatment without side effects; it is therefore necessary to find new prevention strategies and better treatments. For this purpose animal models of diabetes are appropriate tools, of which rodents due to the short generation time and economic considerations are the first choice. The aim of this review is to present features of a frequently used model of type-2 diabetes in rat, induced by a high fat diet and streptozotocin, taking into account its advantages/disadvantages and presenting a practical guide.

Graphical abstract

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The anti-tumor effect of aspirin: What we know and what we expect

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Ji Ma, Zhonglin Cai, Hongliang Wei, Xinlan Liu, Qingli Zhao, Tao Zhang
Aspirin has been widely used as an antipyretic analgesic drug. More and more evidences have shown that aspirin may be play some role on anti-tumor. In this article, we reviewed the research history of aspirin in the treatment and prevention of cancer. Many epidemiological and clinical studies have shown that aspirin can reduce the risk of a variety of malignant tumors and reduce cancer mortality. In addition, we discuss the specific mechanisms of aspirin in the anti-tumor effects. It has been found that aspirin mainly depends on the COX pathway and non-COX pathway to inhibit tumor cell growth and to curb tumor development. In this article, clinical studies and anti-tumor mechanism studies published in recent years are reviewed.

http://ift.tt/2w0wgae

Exceptionally high UBE2C expression is a unique phenomenon in basal-like type breast cancer and is regulated by BRCA1

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Tao Qin, Gena Huang, Liyuan Chi, Silei Sui, Chen Song, Na Li, Siwen Sun, Ning Li, Min Zhang, Zuowei Zhao, Lianhong Li, Man Li
Ubiquitin-conjugating enzyme 2C (UBE2C) is overexpressed in various types of cancer, leading to poor outcomes and drug resistance. UBE2C may also have a critical role in phenotypes associated with poor prognosis in breast cancer; however, the relationship between UBE2C expression and clinical outcome in breast cancer subtypes has not previously been investigated. We firstly analyzed breast cancer patient data and immunohistochemistry of breast cancer patient samples. We demonstrated that UBE2C was associated with poor prognosis in breast cancer, particularly basal-like breast cancer, a subtype with aggressive clinical features. Interestingly, we found that there was a close relationship between the expression of BRCA1 and UBE2C in the MCF-7 and MDA-MB-231 breast cancer cell lines. Upregulation of BRCA1 could inhibit the expression of UBE2C. In cells with BRCA1 silenced down, expression of UBE2C was obviously increased, with a concurrent decrease in cellular sensitivity to doxorubicin. Suppression of UBE2C expression by RNA interference led to decrease the mRNA expressions of BCRP, MRP1 and P-gp in doxorubicin-treated MDA-MB-231 cells. Moreover, treatment with 1μg/ml doxorubicin led to increased expression of UBE2C. The results show high expression of UBE2C is a potential prognostic factor of poor outcome in basal-like breast cancer. Moreover, loss of BRCA1 function results in an increase in UBE2C expression and chemical resistance to doxorubicin in breast cancer cells.

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An interdisciplinary approach to the development of accessible computer-administered measurement instruments

Publication date: Available online 4 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Susan Magasi, Mark Harniss, Allen W. Heinemann
Principles of fairness in testing require that all test takers, including people with disabilities, have an equal opportunity to demonstrate their capacity in the construct being measured. Measurement design features and assessment protocols can pose barriers for people with disabilities. Fairness in testing is a fundamental validity issue at all phases in the design, administration and interpretation of measurement instruments in clinical practice and research. There is limited guidance for instrument developers in how to develop and evaluate the accessibility and usability of measurement instruments. This paper describes a 6-stage iterative process for developing accessible computer-administered measurement instruments based on our work in several major measurement initiatives. Interdisciplinary teams of accessibility experts, content and measurement experts, information technology experts and people with disabilities should work together to ensure that measurement instruments are accessible and usable by a wide range of users. The development of accessible measurement instruments is not only an ethical requirement, it also ensures better science by minimizing measurement bias, missing data, and attrition due to mismatches between the target population and test administration platform and protocols.

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Clinical benefits of joint mobilisation on ankle sprains: a systematic review and meta-analysis

Publication date: Available online 4 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ishanka Weerasekara, Peter Osmotherly, Suzanne Snodgrass, Jodie Marquez, Rutger de Zoete, Darren A. Rivett
ObjectiveTo assess the clinical benefits of joint mobilisation on ankle sprains.Data sourcesMEDLINE, MEDLINE In Process, Embase, AMED, PsycINFO, CINAHL, Cochrane library, PEDro, Scopus, SPORTDiscus and Dissertations and Thesis were searched from inception to June, 2017.Study SelectionStudies investigating humans with a grade I or II lateral or medial sprains of the ankle in any pathological state from acute to chronic, who had been treated with joint mobilisation were considered for inclusion. Any conservative intervention was considered as a comparator. Commonly reported clinical outcomes were considered such as ankle range of movement, pain, and function. After screening of 1530 abstracts, 56 studies were selected for full text screening, and 23 were eligible for inclusion. Eleven studies on chronic sprains reported sufficient data for meta-analysis.Data ExtractionData were extracted using the participants, interventions, comparison, outcomes and study design approach. Clinically relevant outcomes (dorsiflexion range, proprioception, balance, function, pain threshold, pain intensity) were assessed at immediate, short term and long term follow-up points.Data SynthesisMethodological quality was assessed independently by two reviewers and most studies were found to be of moderate quality, with no studies rated as poor.Meta-analysis revealed significant immediate benefits of joint mobilisation compared to comparators on improving postero-medial dynamic balance (p=0.0004), but not for improving dorsiflexion range (p= 0.16), static balance (p = 0.96) or pain intensity (p= 0.45). Joint mobilisation was beneficial in the short term for improving weight-bearing dorsiflexion range (p= 0.003) compared to a control.ConclusionJoint mobilisation appears to be beneficial for improving dynamic balance immediately after application and dorsiflexion range in the short term. Long term benefits have not been adequately investigated.

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Klf5 maintains the balance of primitive endoderm to epiblast specification during mouse embryonic development by suppression of Fgf4 [RESEARCH ARTICLE]

Takuya Azami, Tsuyoshi Waku, Ken Matsumoto, Hyojung Jeon, Masafumi Muratani, Akihiro Kawashima, Jun Yanagisawa, Ichiro Manabe, Ryozo Nagai, Tilo Kunath, Tomonori Nakamura, Kazuki Kurimoto, Mitinori Saitou, Satoru Takahashi, and Masatsugu Ema

The inner cell mass of the mouse blastocyst gives rise to the pluripotent epiblast (EPI), which forms the embryo proper, and the primitive endoderm (PrE), which forms extra-embryonic yolk sac tissues. All inner cells co-express lineage markers such as Nanog and Gata6 at embryonic day (E) 3.25, and the EPI and PrE precursor cells eventually segregate to exclusively express Nanog and Gata6, respectively. Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signalling is involved in segregation of the EPI and PrE lineages; however, the mechanism involved in Fgf4-regulation is poorly understood. Here, we identified Klf5 as an upstream repressor of Fgf4. While Fgf4 was markedly upregulated in Klf5 knockout (KO) embryos at E3.0, it was downregulated in embryos overexpressing Klf5. Furthermore, Klf5 KO and overexpressing blastocysts showed skewed lineage specification phenotypes, similar to FGF4-treated preimplantation embryos and Fgf4 KO embryos, respectively. Inhibitors of the FGF receptor and ERK pathways reversed the skewed lineage specification of Klf5 KO blastocysts. These data demonstrate that Klf5 suppresses Fgf4-Fgfr-ERK signalling, thus preventing precocious activation of the PrE specification programme.

http://ift.tt/2x69ymc

Cell migration, intercalation, and growth regulates mammalian cochlear extension [RESEARCH ARTICLE]

Elizabeth Carroll Driver, Amy Northrop, and Matthew W. Kelley

Developmental remodeling of the sensory epithelium of the cochlea is required for the formation of an elongated, tonotopically organized auditory organ, but the cellular processes that mediate these events are largely unknown. Therefore, we used both morphological assessments of cellular rearrangements and time-lapse imaging to visualize cochlear remodeling. Analysis of cell redistribution showed that the cochlea extends through a combination of radial intercalation and cell growth. Live imaging demonstrated that concomitant cellular intercalation results in a brief period of epithelial convergence, although subsequent changes in cell size lead to medial-lateral spreading. Supporting cells, which retain contact with the basement membrane, exhibit biased protrusive activity and directed movement along the axis of extension. In contrast, hair cells lose contact with the basement membrane, but contribute to continued outgrowth through increased cell size. Regulation of cellular protrusions, movement, and intercalation within the cochlea all require Myosin II. The results establish, for the first time, many of the cellular processes that drive the distribution of sensory cells along the tonotopic axis of the cochlea.

http://ift.tt/2xLaF82

Receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis [RESEARCH ARTICLE]

Kelly J. Soady, Giusy Tornillo, Howard Kendrick, Valerie Meniel, Daria Olijnyk-Dallis, Joanna S. Morris, Torsten Stein, Barry A. Gusterson, Clare M. Isacke, and Matthew J. Smalley

PTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here we demonstrate that PTPRB negatively regulates branching morphogenesis in the mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in estrogen receptor positive luminal cells. During mammary development Ptprb expression is down-regulated during puberty, a period of extensive of ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of FGFR activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology.

http://ift.tt/2x5QgNz

A fluorescent toolkit for spatiotemporal tracking of apoptotic cells in living Drosophila tissues [TECHNIQUES AND RESOURCES REPORT]

Sonia Schott, Arnaud Ambrosini, Audrey Barbaste, Corinne Benassayag, Melanie Gracia, Amsha Proag, Megane Rayer, Bruno Monier, and Magali Suzanne

Far from being passive, apoptotic cells influence their environment. For instance, they promote tissue folding, myoblast fusion and modulate tumor growth. Understanding the role of apoptotic cells necessitates their efficient tracking within living tissues, a task which is currently challenging. In order to easily spot apoptotic cells in developing Drosophila tissues, we generated a series of fly lines expressing different fluorescent sensors of caspase activity. We show that three of these reporters (GFP, Cerulean and Venus derived molecules) are detected specifically in apoptotic cells and throughout the whole process of programmed cell death. These reporters allow the specific visualization of apoptotic cells directly within living tissues, without any post-acquisition processing. They overcome the limitations of other apoptosis detection methods developed so far and notably, they can be combined with any kind of fluorophore.

http://ift.tt/2xKIupp

A stepwise model of Reaction-Diffusion and Positional-Information governs self-organized human peri-gastrulation-like patterning [RESEARCH ARTICLE]

Mukul Tewary, Joel Ostblom, Laura Prochazka, Teresa Zulueta-Coarasa, Nika Shakiba, Rodrigo Fernandez-Gonzalez, and Peter W. Zandstra

How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed a defined, high-throughput assay to induce peri-gastrulation-associated patterning in geometrically-confined human pluripotent stem cell (hPSC) colonies. We observed that, upon BMP4 treatment, phosphorylated SMAD1 (pSMAD1) activity in the colonies organized into a radial gradient. We developed a Reaction-Diffusion (RD) based computational model and observed that the self-organization of pSMAD1 signaling was consistent with the RD principle. Consequent fate acquisition occurred as a function of both pSMAD1 signaling strength and duration of induction – consistent with the Positional-Information (PI) paradigm. We propose that the self-organized peri-gastrulation-like fate patterning in BMP4 treated geometrically-confined hPSC colonies arises via a stepwise model of RD, and PI. This two-step model predicted experimental responses to perturbations of key parameters such as colony size, and BMP4 dose. Furthermore, it also predicted experimental conditions that resulted in RD-like periodic patterning in large hPSC colonies, and rescued peri-gastrulation-like patterning in colony sizes previously thought to be reticent to this behaviour.

http://ift.tt/2x5Q8h3

Enabling quantitative screening in retinal organoids: 3D automated reporter quantification technology (3D-ARQ) [TECHNIQUES AND RESOURCES ARTICLE]

M. Natalia Vergara, Miguel Flores-Bellver, Silvia Aparicio-Domingo, Minda McNally, Karl J. Wahlin, Meera T. Saxena, Jeff S. Mumm, and M. Valeria Canto-Soler

The advent of stem cell-derived retinal organoids has brought forth unprecedented opportunities for developmental and physiological studies, while presenting new therapeutic promise for retinal degenerative diseases. From a translational perspective, organoid systems provide exciting new prospects for drug discovery, offering the possibility to perform compound screening in a 3-dimensional (3D) human tissue context that resembles the native histoarchitecture and cellular interactions. However, inherent variability issues and a general lack of robust quantitative technologies for analyzing organoids in large-scale pose severe limitations for their use in translational applications. To address this need, we have developed a screening platform that enables accurate quantification of fluorescent reporters in complex human iPSC-derived retinal organoids. This platform incorporates a fluorescence microplate reader that allows XYZ-dimensional detection and fine-tuned wavelength selection. We have established optimal parameters for fluorescent reporter signal detection, devised methods to compensate for organoid size variability, evaluated performance and sensitivity parameters, and validated this technology for functional applications.

http://ift.tt/2xL85ic

Maternal dead-end 1 promotes translation of nanos1 through binding the eIF3 complex [RESEARCH ARTICLE]

Tristan Aguero, Zhigang Jin, Sandip Chorghade, Auinash Kalsotra, Mary Lou King, and Jing Yang

In the developing embryo, primordial germ cells (PGCs) represent the exclusive progenitors of the gametes, and their loss results in adult infertility. During early development, PGCs are exposed to numerous signals that specify somatic cell fates. To prevent somatic differentiation, PGCs must transiently silence their genome, an early developmental process that requires Nanos activity. However, it is unclear how nanos translation is regulated in developing embryos. We report here that translation of nanos1 after fertilization requires Dead End1 (Dnd1), a vertebrate-specific germline RNA-binding protein. We provide evidence that Dnd1 protein, whose expression is low in oocytes, but increases dramatically after fertilization, directly interacts with, and relieves the inhibitory function of eukaryotic initiation factor 3f, a repressive component in the 43S preinitiation complex. This work uncovers a novel translational regulatory mechanism that is fundamentally important for germline development.

http://ift.tt/2x6i70h

Face perception in pure alexia: Complementary contributions of the left fusiform gyrus to facial identity and facial speech processing

Publication date: Available online 4 September 2017
Source:Cortex
Author(s): Andrea Albonico, Jason J.S. Barton
Recent concepts of cerebral visual processing predict from overlapping patterns of face and word activation in cortex that left fusiform lesions will not only cause pure alexia but also lead to mild impairments of face processing.Our goal was to determine if alexic subjects had deficits in facial identity processing similar to those seen after right fusiform lesions, or complementary deficits affecting different aspects of face processing.We studied four alexic patients whose lesions involved the left fusiform gyrus and one prosopagnosic subject with a right fusiform lesion, on standard tests of face perception and recognition. We evaluated their ability first to process faces in linear contour images, and second to detect, discriminate, identify and integrate facial speech patterns into perception.We found that all five patients were impaired in face matching across viewpoint, but the alexic subjects performed worse with line-drawn faces, while the prosopagnosic subject did not. Alexic subjects could detect facial speech patterns but had trouble identifying them and did not integrate facial speech patterns with speech sounds, whereas identification and integration was intact in the prosopagnosic subject.We conclude that, in addition to their role in reading, the left-sided regions damaged in alexic subjects participate in the perception of facial identity but in a non-redundant fashion, focusing on the information in linear contours at higher spatial frequencies. In addition they have a dominant role in processing facial speech patterns, another visual aspect of language processing.

http://ift.tt/2w0Aj6k

Dental and oropharyngeal lesions in rats with chronic acid reflux esophagitis

In this study, we evaluated pathological changes in the tooth and pharynx of GERD rats to elucidate the association between gastric acid reflux and oral and pharyngeal diseases.

http://ift.tt/2ezuiYg

Reproducibility of the dynamics of facial expressions in unilateral facial palsy

The aim of this study was to assess the reproducibility of non-verbal facial expressions in unilateral facial paralysis using dynamic four-dimensional (4D) imaging. The Di4D system was used to record five facial expressions of 20 adult patients. The system captured 60 three-dimensional (3D) images per second; each facial expression took 3–4seconds which was recorded in real time. Thus a set of 180 3D facial images was generated for each expression. The procedure was repeated after 30min to assess the reproducibility of the expressions.

http://ift.tt/2eXqsZA

Secondary surgical management of osteoradionecrosis using three-dimensional isodose curve visualization: a report of three cases

Osteoradionecrosis is defined as bone death secondary to radiotherapy. There is a relationship between the radiation dose received and the occurrence of osteoradionecrosis of the jaws, with the risk increasing above a dose of 60Gy. In cases of class III mandibular osteoradionecrosis, a segmental resection can be indicated. Current practice is to completely remove the affected bone up to the point where the bone looks healthy and is bleeding. Exact resection planning and the use of guided surgery based on imaging of the bone changes have not been reported so far.

http://ift.tt/2gHiCqH

Dental and oropharyngeal lesions in rats with chronic acid reflux esophagitis

Alcohol Consumption and Breast Cancer Risk in Younger Women According to Family History of Breast Cancer and Folate Intake

Abstract

To evaluate the association between alcohol consumption and breast cancer risk in younger women, overall and by family history of breast cancer and folate intake, we prospectively followed 93,835 US women aged 27–44 years in Nurses' Health Study II who had alcohol consumption data in 1991. Alcohol consumption and folate intake were measured by food frequency questionnaire every 4 years. We documented 2,866 incident cases of invasive breast cancer between 1991 and 2011. Alcohol consumption was not associated with breast cancer risk overall (for intake of ≥10 g/day vs. nondrinking, multivariate hazard ratio = 1.07, 95% confidence interval: 0.94, 1.22). When the association was stratified by family history and folate intake, a positive association between alcohol consumption and breast cancer was found among women with a family history and folate intake less than 400 μg/day (multivariate hazard ratio = 1.82, 95% confidence interval: 1.06, 3.12; P-trend = 0.08). Alcohol consumption was not associated with breast cancer in other categories of family history and folate intake (P-interaction = 0.55). In conclusion, in this population of younger women, higher alcohol consumption was associated with increased risk of breast cancer among those with both a family history of breast cancer and lower folate intake.

http://ift.tt/2iXZfdE

RE: “SMOKELESS TOBACCO USE AND THE RISK OF HEAD AND NECK CANCER: POOLED ANALYSIS OF US STUDIES IN THE INHANCE CONSORTIUM”

http://ift.tt/2iXZdT4

Maternal Dietary L-Arginine and Adverse Birth Outcomes in Dar es Salaam, Tanzania

Abstract

The amino acid arginine is a physiological precursor to nitric oxide, which is a key mediator of embryonic survival, fetal growth, and pregnancy maintenance. We evaluated the association between consumption of the amino acid arginine and the rate of adverse birth outcomes using data from a double-blind, randomized, placebo-controlled micronutrient supplementation trial among pregnant women in Dar es Salaam, Tanzania (2001–2004). Dietary intakes of arginine were assessed using repeated 24-hour recalls that were administered throughout pregnancy. Participants (n = 7,591) were monitored by research midwives throughout follow-up to assess pregnancy outcomes. Cubic-restricted splines and multivariable log-Poisson regression with empirical standard errors were used to estimate the continuous and categorical associations between arginine intake and adverse birth outcomes. Compared with women within the lowest quintile of arginine intake, those within the highest quintile had 0.79 times the risk of preterm birth before 37 weeks (95% confidence interval: 0.63, 1.00; P = 0.03). The continuous associations of arginine intake with preterm birth before 37 weeks and with preterm birth before 34 weeks were characterized by an initial rapid decrease in risk with increasing intake (P for nonlinearity < 0.01). Arginine intake was not associated with fetal loss or giving birth to infants who were born small for their gestational ages. This data suggest that the association between dietary arginine intake and preterm birth warrants further investigation.

http://ift.tt/2wzYZpM

THE AUTHORS REPLY

http://ift.tt/2iWUnWg

Particulate Matter and Risk of Hospital Admission in the Kathmandu Valley, Nepal: A Case-Crossover Study

Abstract

Air pollution is known to lead to a substantial health burden, but the majority of evidence is based on data from North America and Europe. Despite rising pollution levels, very limited information is available for South Asia. We investigated the impact of particulate matter with an aerodynamic diameter less than or equal to 10 μm (PM₁₀) on hospitalization, by cause and subpopulation, in the Kathmandu Valley, an understudied and rapidly urbanizing region in Nepal. Individual-level daily inpatient hospitalization data (2004–2007) were collected from each of 6 major hospitals, as Nepal has no central data collection system. Time-stratified case-crossover analysis was used with interaction terms for potential effect modifiers (e.g., age, sex, and socioeconomic status), with adjustment for day of the week and weather. Daily PM₁₀ concentrations averaged 120 μg/m³, with the daily maximum reaching 403 μg/m³. A 10-μg/m³ increase in PM₁₀ level was associated with increased risks of hospitalization of 1.00% (95% confidence interval (CI): 0.62, 1.38), 1.70% (95% CI: 0.18, 3.25), and 2.29% (95% CI: 0.18, 4.43) for total, respiratory, and cardiovascular admissions, respectively. We did not find strong evidence of effect modification by age, sex, or socioeconomic status. These results, in combination with the high levels of exposure, indicate a potentially serious human health burden from air pollution in the Kathmandu Valley.

http://ift.tt/2iXNvYv

Evaluating the Effectiveness of New York City Health Policy Initiatives in Reducing Cardiovascular Disease Mortality, 1990–2011

Abstract

Beginning in 2002, New York City (NYC) implemented numerous policies and programs targeting cardiovascular disease (CVD) risk factors. Using death certificates, we analyzed trends in NYC-specific and US mortality rates from 1990 to 2011 for all causes, any CVD, atherosclerotic CVD (ACVD), coronary artery disease (CAD), and stroke. Joinpoint analyses quantified annual percent change (APC) and evaluated whether decreases in CVD mortality accelerated after 2002 in either NYC or the total US population. Our analyses included 1,149,217 NYC decedents. The rates of decline in mortality from all causes, any CVD, and stroke in NYC did not change after 2002. Among men, the decline in ACVD mortality accelerated during 2002–2011 (APC = −4.8%, 95% confidence interval (CI): −6.1, −3.4) relative to 1990–2001 (APC = −2.3%, 95% CI: −3.1, −1.5). Among women, ACVD rates began declining more rapidly in 1993 (APC = −3.2%, 95% CI: −3.8, −2.7) and again in 2006 (APC = −6.6%, 95% CI: −8.9, −4.3) as compared with 1990–1992 (APC = 1.6%, 95% CI: −2.7, 6.0). In the US population, no acceleration of mortality decline was observed in either ACVD or CAD mortality rates after 2002. Relative to 1990–2001, atherosclerotic CVD and CAD rates began to decline more rapidly during the 2002–2011 period in both men and women—a pattern not observed in the total US population, suggesting that NYC initiatives might have had a measurable influence on delaying or reducing ACVD mortality.

http://ift.tt/2wzgsPc

Prediction of Multiple Recurrent Events: A Comparison of Extended Cox Models in Bladder Cancer

Abstract

Recurrence of bladder cancer can occur repeatedly in the same patient after treatment of the primary tumor. Models predicting the risk of a next recurrence may inform individualized decision-making on surveillance frequency. We aimed to assess the usefulness of extensions of the Cox proportional hazards model for repeated events in this context. We analyzed 531 Dutch patients with bladder cancer (1990–2012) with information on 7 prespecified predictors at the time of diagnosis of the primary and recurrent tumors. We considered 3 aspects of model variants: how to model time to the repeated events (calendar time, gap time, elapsed time); the number of preceding events (predictor, stratum variable); and the within-subject correlation (ignored in a simple Cox model, robust standard errors in a variance-correction model, random effect in a frailty model). First to fourth recurrences of bladder cancer occurred in 313, 174, 103, and 66 patients, respectively, with median calendar follow-up times of 1.1, 2.5, 3.8, and 4.5 years, respectively. We focused on gap time in the detailed analyses, allowing for clinically meaningful predictions. Variance-correction models may be useful if predictor selection is part of the model development. Frailty models may be useful when within-subject correlation is strong.

http://ift.tt/2iY5wpG

Rotating Night-Shift Work and the Risk of Breast Cancer in the Nurses' Health Studies

Abstract

In 2007, the International Agency for Research on Cancer declared shift work that involved circadian disruption to be a "probable" carcinogen (group 2A), noting that human evidence was limited. Using data from 2 prospective cohort studies, the Nurses' Health Study (1988–2012; n = 78,516) and Nurses' Health Study II (1989–2013; n = 114,559), we examined associations between rotating night-shift work and breast cancer risk. In the 2 cohorts, there were a total of 9,541 incident invasive breast malignancies and 24 years of follow-up. In the Nurses' Health Study, women with 30 years or more of shift work did not have a higher risk of breast cancer (hazard ratio (HR) = 0.95, 95% confidence interval (95% CI): 0.77, 1.17; P for trend = 0.63) compared with those who never did shift work, although follow-up occurred primarily after retirement from shift work. Among participants in the Nurses' Health Study II, who were younger than participants in the other cohort, the risk of breast cancer was significantly higher in women with 20 years or more of shift work at baseline, reflecting young-adult exposure (HR = 2.15, 95% CI: 1.23, 3.73; P for trend = 0.23), and was marginally significantly higher for women with 20 years or more of cumulative shift work when we used updated exposure information (HR = 1.40, 95% CI: 1.00, 1.97; P for trend = 0.74). In conclusion, long-term rotating night-shift work was associated with a higher risk of breast cancer, particularly among women who performed shift work during young adulthood. Further studies should explore the role of shift work timing on breast cancer risk.

http://ift.tt/2wzJUVk

Invited Commentary: Integrating Genomics and Social Epidemiology—Analysis of Late-Life Low Socioeconomic Status and the Conserved Transcriptional Response to Adversity

Abstract

Socially disadvantaged children face increased morbidity and mortality as they age. Understanding mechanisms through which social disadvantage becomes biologically embedded and devising measurements that can track this embedding are critical priorities for research to address social gradients in health. The analysis by Levine et al. (Am J Epidemiol. 2017;186(5):503–509) of genome-wide gene expression in a subsample of US Health and Retirement Study participants suggests important new directions for the field. Specifically, findings suggest promise in integrating gene expression data into population studies and provide further evidence for the conserved transcriptional response to adversity as a marker of biological embedding of social disadvantage. The study also highlights methodological issues related to the analysis of gene expression data and social gradients in health and a need to examine the conserved transcriptional response to adversity alongside other proposed measurements of biological embedding. Looking to the future, advances in genome science are opening new opportunities for sociogenomic epidemiology.

http://ift.tt/2iYxVf5

Contemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles

Abstract

Environmental or social challenges can stimulate a cascade of coordinated physiological changes in stress response systems. Unfortunately, chronic activation of these adaptations under conditions such as low socioeconomic status (SES) can have negative consequences for long-term health. While there is substantial evidence tying low SES to increased disease risk and reduced life expectancy, the underlying biology remains poorly understood. Using pilot data on 120 older adults from the Health and Retirement Study (United States, 2002–2010), we examined the associations between SES and gene expression levels in adulthood, with particular focus on a gene expression program known as the conserved transcriptional response to adversity. We also used a bioinformatics-based approach to assess the activity of specific gene regulation pathways involved in inflammation, antiviral responses, and stress-related neuroendocrine signaling. We found that low SES was related to increased expression of conserved transcriptional response to adversity genes and distinct patterns of proinflammatory, antiviral, and stress signaling (e.g., sympathetic nervous system and hypothalamic-pituitary-adrenal axis) transcription factor activation.

http://ift.tt/2wzVdNd

Phenol Concentrations During Childhood and Subsequent Measures of Adiposity Among Young Girls

Abstract

Phenolic compounds represent a class of environmental chemicals with potentially endocrine-disrupting capabilities. We investigated longitudinal associations between childhood exposure to phenols, from both manmade and natural sources, and subsequent measures of adiposity among girls enrolled in the Breast Cancer and the Environment Research Program between 2004 and 2007. Baseline (ages 6–8 years) urinary concentrations were obtained for creatinine and phenol metabolites: enterolactone, genistein, daidzein, benzophenone-3, bisphenol A, the sum of parabens (methyl, ethyl, and propyl parabens), 2,5-dichlorophenol, and triclosan. Body mass index (weight (kg)/height (m)²), waist circumference, and percent body fat were measured at annual or semiannual examinations through 2015 (n = 1,017). Linear mixed-effects regression was used to estimate how baseline concentrations of phenols (tertile groups) were related to changes in girls' adiposity measurements from ages 7 through 15 years. Enterolactone was inversely associated with body mass index, waist circumference, and percent body fat, while 2,5-dichlorophenol was positively associated with these measurements. A nonmonotonic association was observed for triclosan and girls' adiposity; however, it was due to effect modification by baseline overweight status. Triclosan was positively associated with adiposity only among overweight girls. These results suggest that exposure to specific phenols during childhood may influence adiposity through adolescence.

http://ift.tt/2iYxBwT

Changes in the Inflammatory Potential of Diet Over Time and Risk of Colorectal Cancer in Postmenopausal Women

Abstract

We examined the associations between changes in dietary inflammatory potential and risk of colorectal cancer (CRC) in 87,042 postmenopausal women recruited from 1993–1998 by the Women's Health Initiative, conducted in the United States. Food frequency questionnaire data were used to compute patterns of change in dietary inflammatory index (DII) scores and cumulative average DII scores over 3 years. Cox regression models were used to estimate hazard ratios for CRC risk. After a median of 16.2 years of follow-up, 1,038 CRC cases were diagnosed. DII changes were not substantially associated with overall CRC, but proximal colon cancer risk was higher in the proinflammatory-change DII group than in the antiinflammatory-stable DII group (hazard ratio = 1.32, 95% confidence interval: 1.01, 1.74). Among nonusers of nonsteroidal antiinflammatory drugs (NSAIDs) (P_interaction = 0.055), the proinflammatory-stable DII group was at increased risk of overall CRC and proximal colon cancer. Also among nonusers of NSAIDs, risks of overall CRC, colon cancer, and proximal colon cancer were higher in the highest quintile compared with the lowest cumulative average DII quintile (65%, 61%, and 91% higher risk, respectively). Dietary changes toward, or a history of, proinflammatory diets are associated with an elevated risk of colon cancer, particularly for proximal colon cancer and among nonusers of NSAIDs.

http://ift.tt/2wzkvuQ

Traffic Congestion as a Risk Factor for Mortality in Near-Road Communities: A Case-Crossover Study

Abstract

Existing epidemiologic research on traffic largely neglects localized fluctuations. We leveraged finely resolved congestion data to investigate short-term associations with mortality in communities near roadways. We identified all nonaccidental, cardiovascular, cerebrovascular, and respiratory deaths (2009–2013) within 1 km of a highway in the Puget Sound region of Washington State. Using a case-crossover design, we examined the association of congestion 0–150 m, 151–300 m, and 301–1,000 m upwind of a decedent's home with mortality, adjusting for meteorology, holidays, and influenza activity. Among 9,449 deaths, we observed higher odds of cerebrovascular and respiratory mortality with greater upwind congestion, especially congestion near the decedent's home. For each 10-minute-km increase in upwind congestion within 150 m, the odds of cerebrovascular mortality were 1.08 (95% confidence interval (CI): 0.88, 1.33); within 151–300 m, the odds of cerebrovascular mortality were 1.05 (95% CI: 0.98, 1.12) times higher. We observed similar patterns for respiratory mortality, with 1.06 (95% CI: 0.76, 1.50) times higher odds of death with greater upwind congestion within 150 m and 1.02 (95% CI: 0.95, 1.10) times higher odds within 151–300 m. No increased odds of mortality were observed at greater distances, for overall mortality, or with downwind congestion. Unexpectedly, lower odds of cardiovascular mortality were suggested with greater congestion. This work demonstrates the use of nontraditional data to characterize the impacts of near-road exposures.

http://ift.tt/2iXz4np

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 4 Σεπτεμβρίου 2017

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