Evoked versus spontaneous high frequency oscillations in the chronic electrocorticogram in focal epilepsy

Publication date: Available online 6 February 2017
Source:Clinical Neurophysiology
Author(s): M.A. van't Klooster, N.E.C. van Klink, D. van Blooijs, C.H. Ferrier, K.P.J. Braun, F.S.S. Leijten, G.J.M. Huiskamp, M. Zijlmans
ObjectiveSpontaneous high frequency oscillations (HFOs; ripples 80-250Hz, fast ripples (FRs) 250-500Hz) are biomarkers for epileptogenic tissue in focal epilepsy. Single pulse electrical stimulation (SPES) can evoke HFOs. We hypothesized that stimulation distinguishes pathological from physiological ripples and compared the occurrence of evoked and spontaneous HFOs within the seizure onset zone (SOZ) and eloquent functional areas.MethodsTen patients underwent SPES during 2048Hz electrocorticography (ECoG). Evoked HFOs in time-frequency plots and spontaneous HFOs were visually analyzed. We compared electrodes with evoked and spontaneous HFOs for: percentages in the SOZ, sensitivity and specificity for the SOZ, percentages in functional areas outside the SOZ.ResultsTwo patients without spontaneous FRs showed evoked FRs in the SOZ. Percentages of evoked and spontaneous HFOs in the SOZ were similar (ripples 32:33%,p=0.77;FRs 43:48%,p=0.63), but evoked HFOs had generally a lower specificity (ripples 45:69%,p=0.02;FRs 83:92%,p=0.04) and higher sensitivity(ripples 85:70%,p=0.27; FRs 52:37%,p=0.05). More electrodes with evoked than spontaneous ripples were found in functional (54:30%,p=0.03) and 'silent' areas (57:27%,p=0.01) outside the SOZ.ConclusionsSPES can elicit SOZ-specific FRs in patients without spontaneous FRs, but activates ripples in all areas.SignificanceSPES is an alternative for waiting for spontaneous HFOs, but does not warrant exclusively pathological ripples.



http://ift.tt/2kN97pX

Positive and Negative Somatotopic BOLD Responses in Contralateral Versus Ipsilateral Penfield Homunculus

<span class="paragraphSection"><div class="boxTitle">Abstract</div>One of the basic properties of sensory cortices is their topographical organization. Most imaging studies explored this organization using the positive blood oxygenation level-dependent (BOLD) signal. Here, we studied the topographical organization of both positive and negative BOLD in contralateral and ipsilateral primary somatosensory cortex (S1). Using phase-locking mapping methods, we verified the topographical organization of contralateral S1, and further showed that different body segments elicit pronounced negative BOLD responses in both hemispheres. In the contralateral hemisphere, we found a sharpening mechanism in which stimulation of a given body segment triggered a gradient of activation with a significant deactivation in more remote areas. In the ipsilateral cortex, deactivation was not only located in the homolog area of the stimulated parts but rather was widespread across many parts of S1. Additionally, analysis of resting-state functional magnetic resonance imaging signal showed a gradient of connectivity to the neighboring contralateral body parts as well as to the ipsilateral homologous area for each body part. Taken together, our results indicate a complex pattern of baseline and activity-dependent responses in the contralateral and ipsilateral sides. Both primary sensory areas were characterized by unique negative BOLD responses, suggesting that they are an important component in topographic organization of sensory cortices.</span>

http://ift.tt/2jWHM0e

Different Effects of Sleep Deprivation and Torpor on EEG Slow-Wave Characteristics in Djungarian Hamsters

<span class="paragraphSection"><div class="boxTitle">Abstract</div>It has been shown previously in Djungarian hamsters that the initial electroencephalography (EEG) slow-wave activity (power in the 0.5–4.0 Hz band; SWA) in non-rapid eye movement (NREM) sleep following an episode of daily torpor is consistently enhanced, similar to the SWA increase after sleep deprivation (SD). However, it is unknown whether the network mechanisms underlying the SWA increase after torpor and SD are similar. EEG slow waves recorded in the neocortex during sleep reflect synchronized transitions between periods of activity and silence among large neuronal populations. We therefore set out to investigate characteristics of individual cortical EEG slow waves recorded during NREM sleep after 4 h SD and during sleep after emergence from an episode of daily torpor in adult male Djungarian hamsters. We found that during the first hour after both SD and torpor, the SWA increase was associated with an increase in slow-wave incidence and amplitude. However, the slopes of single slow waves during NREM sleep were steeper in the first hour after SD but not after torpor, and, in contrast to sleep after SD, the magnitude of change in slopes after torpor was unrelated to the changes in SWA. Furthermore, slow-wave slopes decreased progressively within the first 2 h after SD, while a progressive increase in slow-wave slopes was apparent during the first 2 h after torpor. The data suggest that prolonged waking and torpor have different effects on cortical network activity underlying slow-wave characteristics, while resulting in a similar homeostatic sleep response of SWA. We suggest that sleep plays an important role in network homeostasis after both waking and torpor, consistent with a recovery function for both states.</span>

http://ift.tt/2kHAZfj

Global and Local Connectivity Differences Converge With Gene Expression in a Neurodevelopmental Disorder of Known Genetic Origin

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Knowledge of genetic cause in neurodevelopmental disorders can highlight molecular and cellular processes critical for typical development. Furthermore, the relative homogeneity of neurodevelopmental disorders of known genetic origin allows the researcher to establish the subsequent neurobiological processes that mediate cognitive and behavioral outcomes. The current study investigated white matter structural connectivity in a group of individuals with intellectual disability due to mutations in <span style="font-style:italic;">ZDHHC9</span>. In addition to shared cause of cognitive impairment, these individuals have a shared cognitive profile, involving oromotor control difficulties and expressive language impairment. Analysis of structural network properties using graph theory measures showed global reductions in mean clustering coefficient and efficiency in the <span style="font-style:italic;">ZDHHC9</span> group, with maximal differences in frontal and parietal areas. Regional variation in clustering coefficient across cortical regions in <span style="font-style:italic;">ZDHHC9</span> mutation cases was significantly associated with known pattern of expression of <span style="font-style:italic;">ZDHHC9</span> in the normal adult human brain. The results demonstrate that a mutation in a single gene impacts upon white matter organization across the whole-brain, but also shows regionally specific effects, according to variation in gene expression. Furthermore, these regionally specific patterns may link to specific developmental mechanisms, and correspond to specific cognitive deficits.</span>

http://ift.tt/2jWPY0o

Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors.</span>

http://ift.tt/2kBV6cD

Differential induction of anti-V3 crown antibodies with cradle- and ladle-binding modes in response to HIV-1 envelope vaccination

Publication date: Available online 6 February 2017
Source:Vaccine
Author(s): Preetha Balasubramanian, Rajnish Kumar, Constance Williams, Vincenza Itri, Shixia Wang, Shan Lu, Ann J. Hessell, Nancy L. Haigwood, Faruk Sinangil, Keith W. Higgins, Lily Liu, Liuzhe Li , Phillipe Nyambi, Miroslaw K. Gorny, Maxim Totrov, Arthur Nadas, Xiang-Peng Kong, Susan Zolla-Pazner, Catarina E. Hioe
The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating its potential contribution in protection against HIV. Crystallographic analyses of anti-V3 crown mAbs in complex with the V3 peptides have revealed that these mAbs recognize the conserved sites on the V3 crown via two distinct strategies: a cradle-binding mode (V3C) and a ladle-binding (V3L) mode. However, almost all of the anti-V3 crown mAbs studied in the past were isolated from chronically HIV-infected individuals. The extents to which the two types of anti-V3 crown Abs are generated by vaccination are unknown. This study analyzed the prevalence of V3C-type and V3L-type Ab responses in HIV-infected individuals and in HIV envelope-immunized humans and animals using peptide mimotopes that distinguish the two Ab types. The results show that both V3L-type and V3C-type Abs were generated by the vast majority of chronically HIV-infected humans, although the V3L-type were more prevalent. In contrast, only one of the two V3 Ab types was elicited in vaccinated humans or animal models, irrespective of HIV-1 envelope clades, envelope constructs (oligomeric or monomeric), and protocols (DNA plus protein or protein alone) used for vaccinations. The V3C-type Abs were produced by vaccinated humans, macaques, and rabbits, whereas the V3L-type Abs were made by mice. The V3C-type and V3L-type Abs generated by the vaccinations were able to mediate virus neutralization. These data indicate the restricted repertoires and the species-specific differences in the functional V3-specific Ab responses induced by the HIV envelope vaccines. The study implies the need for improving immunogen designs and vaccination strategies to broaden the diversity of Abs in order to target the different conserved epitopes in the V3 loop and, by extension, in the entire HIV envelope.



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Do we need a vaccine against Moraxella catarrhalis in chronic lung disease? What are the options and opportunities?

Publication date: Available online 6 February 2017
Source:Vaccine
Author(s): Antonia C. Perez, Timothy F. Murphy
Moraxella catarrhalis is the second most common cause of exacerbations in adults with COPD, resulting in enormous morbidity and mortality in this clinical setting. Vaccine development for M. catarrhalis has lagged behind the other two important causes of exacerbations in COPD, nontypeable Haemophilus influenzae and Streptococcus pneumoniae. While no licensed vaccine is currently available for M. catarrhalis, several promising candidate vaccine antigens have been identified and characterized and are close to entering clinical trials. Key steps that are required to advance vaccines for M. catarrhalis along the translational pipeline include standardization of assay systems to assess candidate antigens, identification of a reliable correlate of protection and expansion of partnerships between industry, academia and government to overcome regulatory hurdles. A vaccine to prevent M. catarrhalis infections in COPD would have a major impact in reducing morbidity, mortality and healthcare costs in COPD.



http://ift.tt/2liuNHq

Clearance of Tritrichomonas foetus in experimentally infected heifers protected with vaccines based on killed-T. foetus with different adjuvants

Publication date: Available online 6 February 2017
Source:Vaccine
Author(s): Lumila I. Fuchs, Marcelo C. Fort, Dora Cano, Carina M. Bonetti, Hugo D. Giménez, Pablo M. Vázquez, Diana Bacigalupe, Javier D. Breccia, Carlos M. Campero, Jorge A. Oyhenart
Tritrichomonas foetus is a flagellated protozoan that causes a sexually transmitted disease in cattle. Trichomonosis is characterized by early abortions, subfertility and a significant decrease in productivity. Vaccine preparations containing whole T. foetus can reduce the time of residence of the pathogen in the host cervix after experimental infection. Here, T. foetus vaccines prepared with different adjuvants were tested, in parallel with a commercial vaccine, for their efficacy to clear the infection. The median time for clearance of infection was 69days in non-immunized animals, 55days in animals treated with aluminum hydroxide, 41days with oil-in-water or saponin based vaccines or with a commercial vaccine and 27days in animals treated with saponin plus aluminum hydroxide. A slight increase in the risk of T. foetus clearance from the genital tract was found with the saponin based vaccine (hazard ratio, 2.52; 95% confidence interval, 1.03–6.17) or the commercial vaccine (hazard ratio, 2.61; 95% confidence interval, 1.07–6.38). A significant increase in the risk of T. foetus clearance was found with the combination of saponin plus aluminum hydroxide based vaccine (hazard ratio, 5.12; 95% confidence interval, 2.04–12.83).



http://ift.tt/2kN80GT

Vaccine adverse events in a safety net healthcare system and a managed care organization

Publication date: Available online 6 February 2017
Source:Vaccine
Author(s): Komal J. Narwaney, Kristin Breslin, Colleen A. Ross, Jo Ann Shoup, Kris F. Wain, Eric S. Weintraub, Michael M. McNeil, Simon J. Hambidge
BackgroundThe Institute of Medicine, in a 2013 report, recommended that the Vaccine Safety Datalink (VSD) expand collaborations to include more diversity in the study population. Kaiser Permanente Colorado (KPCO), an established VSD site, partnered with Denver Health (DH), an integrated safety net healthcare system, to demonstrate the feasibility of integrating DH data within the VSD. Prior to incorporating the data, we examined the identification of specific vaccine associated adverse events (VAEs) in these two distinct healthcare systems.MethodsWe conducted retrospective cohort analyses within KPCO and DH to compare select VAEs between the two populations. We examined the following associations between January 1, 2004 and December 31, 2013: Measles, Mumps, and Rubella (MMR) vaccine and febrile seizures in children 2years and younger, intussusception after rotavirus vaccine in infants 4–34weeks, syncope after adolescent vaccines (Tetanus, Diphtheria, acellular Pertussis; Meningococcal and Human Papillomavirus) in adolescents 13–17years and medically attended local reactions after pneumococcal polysaccharide (PPSV23) vaccine in adults 65years and older. Both sites used similar data procurement methods and chart review processes.ResultsFor seizures after MMR vaccine (KPCO – 3.15vs. DH – 2.97/10,000 doses) and syncope after all adolescent vaccines (KPCO – 3.0vs. DH – 2.37/10,000 doses), the chart confirmed rates were comparable at the two sites. However, for medically attended local reactions after PPSV23, there were differences in chart confirmed rates between the sites (KPCO – 31.65vs. DH – 14.90/10,000 doses). For intussusception after rotavirus vaccine, the number of cases was too low to make a valid comparison (KPCO – 0vs. DH – 0.13/10,000 doses).ConclusionWe demonstrated that data on important targeted VAEs can be captured at DH and rates appear similar to those at KPCO. Work is ongoing on the optimal approach to assimilate DH data as a potential safety net healthcare system in the VSD.



http://ift.tt/2lir2Sr

Dengue vaccine: WHO position paper, July 2016 – recommendations

Publication date: Available online 6 February 2017
Source:Vaccine

This article presents the World Health Organization's (WHO) recommendations on the use of dengue vaccine excerpted from the WHO position paper on dengue vaccine published in the Weekly epidemiological Record in July 2016 (Dengue vaccine: WHO position paper, 2016) [1]. The current document is the first WHO position paper on dengue vaccination and focuses primarily on the available evidence concerning the only dengue vaccine to have been registered by National Regulatory Authorities. The position paper gives consideration to the epidemiological features of the disease and assesses the potential use of the vaccine for public health benefits.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of the WHO's Strategic Advisory Group of Experts (SAGE) on immunization. Recommendations on the use of this dengue vaccine were discussed by SAGE in April 2016; evidence presented at that SAGE meeting can be accessed at: http://ift.tt/1J6kSPV.



http://ift.tt/2kMUqTC

An Efficient Synthesis of 1α,25-Dihydroxyvitamin D3 LC-Biotin

Publication date: Available online 6 February 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Lars Kattner, Dan Bernardi
In recent years the apparent impact of vitamin D deficiency on human health has gained increased awareness. Consequently, the development of appropriate assays to measure the status of medicinally most relevant vitamin D metabolites in human blood, serum or relevant tissue is continuously being improved. Particularly, assaying of 1α,25-dihydroxyvitamin D3, in turn considered as the most active metabolite, is mainly indicated in disorders leading to calcaemia or those resulting from an impaired 1α-hydroxylation of 25-hydroxyvitamin D3. Thus, in some competitive protein binding and ELISA assays, biotin-linked 1α,25-dihydroxyvitamin D3 (1α,25-dihydroxyvitamin D3 LC-biotin) is employed for measurement of actual calicitriol concentration. A new efficient synthesis of 1α,25-dihydroxyvitamin D3 LC-biotin is described, starting with readily available vitamin D2, and combining a classical approach to access 1α,25-dihydroxyvitamin D3, appropriate OH-protective group transformations, and a C-3-O-alkylation, suitable to connect the biotin-linker in a reliable, selective and high yielding strategy. The developed methodology is applicable to the synthesis of a wide variety of C-3-OH-linked vitamin D3 and D2 derivatives.



http://ift.tt/2jWMUqc

Image-guided adaptive brachytherapy dose escalation for cervix cancer via fractionation compensation

Publication date: Available online 6 February 2017
Source:Brachytherapy
Author(s): William Shaw, William I.D. Rae, Markus L. Alber
PurposeIn image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous fractions and a conjecture about the future ones. We evaluate the efficacy of different fraction size schemes, derived from total IGABT dose constraints, against constant per-fraction constraints.Methods and MaterialsThis retrospective planning study included 20 IGABT patients where four different fractionation schedules were compared based on modern planning recommendations. A total high-risk–clinical target volume D90 (minimum dose in 90% of the volume) dose aim of 90.0 Gy with constant per-fraction organs at risk (OARs) dose constraint planning (CONST) was compared with conservative and aggressive fractionation compensation (COMP) techniques. COMP allows variations in the per-fraction dose constraints. Dose accumulation was performed through dose summation at a given volume and equivalent uniform dose (EUD) worst-case dose estimates.ResultsNo significant differences were identifiable between dose metrics of CONST and COMP in the total patient population. However, a subgroup of patients with alternating dose-limiting OARs had significant benefit from COMP. Median high-risk–clinical target volume dose escalation ranged from 5% to 12%, whereas OAR dose increases were lower and ranged from 3% to 8%. EUD-based planning delivered similar tumor doses, although slightly lower OAR doses. By distributing the treatment aim over an increased number of treatment fractions, median tumor dose could be increased by a further 8% per additional treatment fraction at the same OAR dose levels for both CONST and COMP.ConclusionsCOMP is effective in patients with alternating dose-limiting OARs and is enhanced using more treatment fractions and EUD constraints.



http://ift.tt/2kBXiRr

Characterization and Management of Cutaneous Side Effects Related to the Immunosuppressive Treatment in Solid Organ Recipients

Patients who underwent solid organ transplantation frequently suffer from different skin diseases, as consequence of the immunosuppressive treatment. Specific cutaneous side effects such as acne, hypertricosis or other pilosebaceous unit disorders, gingival hyperplasia, purpura or teleangiectasies are commonly associated to immunosuppressive medications. The majority of these conditions are benign, but the aesthetic concern may affect the patient is quality of life and reduce the adherence to the therapy. Moreover, solid organ transplant recipients frequently develop skin infections, as an indirect consequence of the immunosuppressive regimens. Herpes virus reactivation is more common few months after transplantation, whereas when the immunosuppression is reduced, the skin infections are mainly represented by human papilloma virus infections and localized mycosis. Bacterial infections are relatively rare. Long-term consequences of the immunosuppressive therapy are represented by development of precancerosis and skin cancers, with a risk that enhances over the time and a significant impact on patient survival. The aim of this paper is to provide an overview of the data published in the recent literature about this topic, in order to characterize the main skin disorders associated to the use of immunosuppressive drugs in solid organ recipients, giving information about their risk, epidemiology, clinical manifestations and management.

http://ift.tt/2ljrVen

Early Identification of Cardiovascular Diseases in People With Spinal Cord Injury: Key Information for Primary Care Providers

Publication date: Available online 6 February 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ceren Yarar-Fisher, Patricia Heyn, Jeanne M. Zanca, Susie Charlifue, Jean Hsieh, David M. Brienza




http://ift.tt/2kgjZt4

Effects of antioxidants on DNA double-strand breaks in human gingival fibroblasts exposed to dental resin co-monomer epoxy metabolites

Publication date: Available online 6 February 2017
Source:Dental Materials
Author(s): Yang Yang, Xiuli He, Jianwei Shi, Reinhard Hickel, Franz-Xaver Reichl, Christof Högg
ObjectiveEluted dental resin co-monomers can be metabolized to intermediate methacrylic acid (MA) and, further, to epoxy metabolites. Antioxidants have been studied previously, with the intention of decreasing the DNA double-strand breaks (DNA-DSBs) in human gingival fibroblasts (HGFs). In this study, the effects of the antioxidants, ascorbic acid (Asc) and N-acetylcysteine (NAC), were investigated on co-monomer metabolite-induced DNA-DSBs.MethodsHGFs were incubated with MA, 2,3-epoxy-2-methyl-propionicacid-methylester (EMPME) and 2,3-epoxy-2-methylpropionic acid (EMPA), respectively, in the presence or absence of antioxidants (Asc or NAC). EC50 Values were obtained from an XTT-based viability assay. DNA-DSBs were determined using a γ-H2AX assay.ResultsThe cytotoxicity of the compounds could be ranked in the following order (mean±SEM; n=4): EMPA>EMPME>MA. The average number of DSBs-foci/cell induced by each substance at EC50-concentration could be ranked in the following order (mean±SD; n=4): EMPA>EMPME>MA. EMPA (1.72mM) and EMPME (2.58mM) induced the highest number of DSBs-foci, that is 21-fold and 13-fold, respectively, compared to control (0.48±0.08 foci/cell). The addition of Asc (50; 100; 200μM) or NAC (50; 100; 200; 500μM) to MA (15.64; 5.21mM), EMPME (2.58mM), and EMPA (1.72; 0.57mM) significantly reduced the number of foci/cell in HGFs. The highest reduction could be found in HGFs with 1.72mM EMPA, the addition of NAC (50; 100; 200; 500μM) induced a 15-fold, 17-fold, 14-fold and 14-fold lower number of DSBs-foci/cell, respectively.SignificanceDental co-monomer epoxy metabolites, EMPME and EMPA, can induce DNA-DSBs. The addition of antioxidants (Asc or NAC) leads to reduction of DNA-DSBs, and NAC leads to more prominent reduction of DNA-DSBs compared to Asc.



http://ift.tt/2ljkIe8

In-vitro fatigue and fracture testing of CAD/CAM-materials in implant-supported molar crowns

Publication date: Available online 6 February 2017
Source:Dental Materials
Author(s): Verena Preis, Sebastian Hahnel, Michael Behr, Laila Bein, Martin Rosentritt
ObjectiveTo investigate the fatigue and fracture resistance of different CAD/CAM-materials as implant- or tooth-supported molar crowns with respect to the clinical procedure (screwed/bonded restoration).Methods168 crowns were fabricated from different CAD/CAM-materials (n=8/material): ZLS (zirconia-reinforced lithium silicate ceramic; Suprinity, Vita-Zahnfabrik), COB (composite; Brilliant Crios, Coltene), COL (composite; Lava Ultimate, 3M Espe), PMV/PPV (polyether ether ketone (PEEK)+milled composite veneer/composite paste veneer; BioHPP+HIPC veneer/Crealign veneer, Bredent), COH (composite; Block HC, Shofu), and ZIR (zirconia; IPS e.max ZirCAD, Ivoclar-Vivadent) as reference. Three groups were designed simulating the following clinical procedures: (a) chairside procedure ([CHAIR] implant crown bonded to abutment), (b) labside procedure ([LAB] abutment and implant crown bonded in laboratory, screwed chairside), and (c) reference ([TOOTH] crowns bonded on human teeth). Combined thermal cycling and mechanical loading (TCML) were performed simulating a 5-year clinical situation. Fracture force was determined and failures were documented. Data were statistically analyzed (Kolmogorov–Smirnov-test, one-way-ANOVA; post-hoc-Bonferroni, α=0.05).ResultsAll crowns of group LAB-PPV showed cracks after TCML. The other groups survived fatigue testing without failures. Fracture forces varied between 921.3N (PPV) and 4817.8N (ZIR) [CHAIR], 978.0N (COH) and 5081.4N (ZIR) [LAB], 746.7N (PPV) and 3313.5N (ZIR) [TOOTH]. Significantly (p<0.05) different fracture values were found between materials in all three groups. Only ZLS crowns provided no significant (p>0.05) differences between the individual groups.SignificanceDifferent ceramic and resin-based materials partly performed differently in implant or tooth situations. Individual resin-based materials (PPV, COB, COH) were weakened by inserting a screw channel. Most CAD/CAM-materials may be clinically applied in implant-supported crowns without restrictions. ​



http://ift.tt/2ldKsf1

Role of Bowel Ultrasound in the Diagnosis and Follow-up of Patients with Crohn's Disease

Publication date: Available online 6 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Clara Benedetta Conti, Mariangela Giunta, Daniele Gridavilla, Dario Conte, Mirella Fraquelli
Crohn's disease (CD) is an inflammatory chronic bowel disorder; it can involve the whole gastrointestinal tract, but its localization in the ileum or colon is most common. The reference standard for the diagnosis of CD is ileocolonoscopy with histologic assessment. The reference standard for the detection of any complications is surgery. However, imaging techniques have an important role both in the detection/localization of CD and in the follow-up of CD patients. In the last few years, the technical development of ultrasound equipment, the advent of new technologies such as elastography and mostly the increased expertise of sonographers have boosted the role of bowel ultrasound in assessment of the gastrointestinal tract. In fact, bowel ultrasound is particularly attractive thanks to its widespread availability, non-invasiveness, low cost and good reproducibility, as it can be easily repeated during follow-up. The aim of this article is to provide an extensive overview of the actual role of bowel ultrasound in the detection and follow-up of patients with CD.



http://ift.tt/2li6DNi

Diamond-based electrochemical aptasensor realizing a femtomolar detection limit of bisphenol A

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yibo Ma, Junsong Liu, Hongdong Li
In this study, we designed and fabricated an electrochemical impedance aptasensor based on Au nanoparticles (Au-NPs) coated boron-doped diamond (BDD) modified with aptamers, and 6-mercapto-1-hexanol (MCH) for the detection of bisphenol A (BPA). The constructed BPA aptasensor exhibits good linearity from 1.0×10^–14 to 1.0×10⁻⁹molL⁻¹. The detection limitation of 7.2×10^–15molL⁻¹ was achieved, which can be attributed to the synergistic effect of combining BDD with Au-NPs, aptamers, and MCH. The examine results of BPA traces in Tris-HCl buffer and in milk, UV spectra of aptamer/BPA and interference test revealed that the novel aptasensors are of high sensitivity, specificity, stability and repeatability, which could be promising in practical applications.



http://ift.tt/2kfRw6O

Fluorescent “on-off-on” switching sensor based on CdTe quantum dots coupled with multiwalled carbon nanotubes@graphene oxide nanoribbons for simultaneous monitoring of dual foreign DNAs in transgenic soybean

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yaqi Li, Li Sun, Jing Qian, Lingliang Long, Henan Li, Qian Liu, Jianrong Cai, Kun Wang
With the increasing concern of potential health and environmental risk, it is essential to develop reliable methods for transgenic soybean detection. Herein, a simple, sensitive and selective assay was constructed based on homogeneous fluorescence resonance energy transfer (FRET) between CdTe quantum dots (QDs) and multiwalled carbon nanotubes@graphene oxide nanoribbons (MWCNTs@GONRs) to form the fluorescent "on-off-on" switching for simultaneous monitoring dual target DNAs of promoter cauliflower mosaic virus 35s (P35s) and terminator nopaline synthase (TNOS) from transgenic soybean. The capture DNAs were immobilized with corresponding QDs to obtain strong fluorescent signals (turning on). The strong π–π stacking interaction between single-stranded DNA (ssDNA) probes and MWCNTs@GONRs led to minimal background fluorescence due to the FRET process (turning off). The targets of P35s and TNOS were recognized by dual fluorescent probes to form double-stranded DNA (dsDNA) through the specific hybridization between target DNAs and ssDNA probes. And the dsDNA were released from the surface of MWCNTs@GONRs, which leaded the dual fluorescent probes to generate the strong fluorescent emissions (turning on). Therefore, this proposed homogeneous assay can be achieved to detect P35s and TNOS simultaneously by monitoring the relevant fluorescent emissions. Moreover, this assay can distinguish complementary and mismatched nucleic acid sequences with high sensitivity. The constructed approach has the potential to be a tool for daily detection of genetically modified organism with the merits of feasibility and reliability.



http://ift.tt/2jWxWjX

Ultrasensitive electrochemical immunosensor for quantitative detection of SCCA using Co3O4@CeO2-Au@Pt nanocomposite as enzyme-mimetic labels

Publication date: 15 June 2017
Source:Biosensors and Bioelectronics, Volume 92
Author(s): Yueyun Li, Yihe Zhang, Faying Li, Jinhui Feng, Mingdang Li, Lei Chen, Yunhui Dong
Recently early diagnosis of squamous cell carcinoma antigen (SCCA) as a tumor maker of various cancers has increasingly attracted a lot of attention with heightening of incidence rate of cancer. The SCCA with low concentration in human serum should be diluted before detecting. Thus, an immunoassay with high sensitivity is significant for early detecting SCCA. Therefore, a nonenzymatic sandwich-type electrochemical immunosensor herein was conducted to quantitative detection of squamous cell carcinoma antigen (SCCA). The amino functionalized cobaltosic oxide @ ceric dioxide nanocubes with core-shell morphology were prepared to combine sea-urchin like gold @ platinum nanoparticles (Co3O4@CeO2-Au@Pt), and used as labels to conjugate with secondary antibodies for signal amplification. Due to the synergetic effect, excellent electrochemical property and superior auxiliary catalytic activity of Co3O4@CeO2-Au@Pt, high electrocatalytic current responses toward the reduction of hydrogen peroxide (H2O2) were achieved. Besides, the electrodeposited gold nanoparticles (D-Au NPs) which were modified on glassy carbon electrodes (GCE) were used as antibodies carriers and sensing platforms. With the well cooperation of Co3O4@CeO2-Au@Pt and D-Au NPs, a broad linear range from 100fg/mL to 80ng/mL with a low detection limit of 33 fg/mL for detecting SCCA was achieved. In addition, the immunosensor displayed with good reproducibility, high selectivity and stability. The results are satisfactory when the proposed method has been applied to analyze human serum samples, indicating that the potential application is promising in clinical monitoring of tumor markers.



http://ift.tt/2kMFEwh

The role of hydroxychloroquine in the treatment of lichen planopilaris: A retrospective case series and review

Abstract

A variety of systemic agents are used to treat lichen planopilaris (LPP) with a limited evidence base. The aim of our study was to retrospectively review the response rate to and tolerability of hydroxychloroquine in a cohort of patients with LPP in an effort to add to the evidence base for its use. Twenty-three patients with a clinical and histopathological diagnosis of LPP who had been treated with hydroxychloroquine for their disease in a single center were identified. A retrospective review of these patients' medical records was performed and physician rated response was documented. Complete response was observed in 61% of our patients, and a further 9% of patients demonstrated partial response. Thirteen percent of patients withdrew from treatment because of suspected adverse effects. Our sample size was small, and data was collected retrospectively. We found hydroxychloroquine to be a reasonable therapeutic choice in LPP.

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Pregabalin treatment of three cases with brachioradial pruritus

Abstract

Brachioradial pruritus (BRP) is a rare type of chronic pruritus that usually localized at the dorsolateral part of the forearms. Itching, burning, or pain are common symptoms at the involved areas. The etiological factors are still unknown but sun exposure and/or cervical spine lesions seem to be trigerring or precipiting factors. Neuropathogenic mechanism plays role in etiopathogenesis of BRP, therefore, antiepileptic drugs such as gabapentin, oxcarbazepine. and pregabalin are suggested medications for BRP. Herein, we report three cases with BRP successfully treated with pregabaline.

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Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis

Publication date: March 2017
Source:European Journal of Cancer, Volume 74
Author(s): José Pablo Leone, Julieta Leone, Ariel Osvaldo Zwenger, Julián Iturbe, Bernardo Amadeo Leone, Carlos Teodoro Vallejo
BackgroundThe presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD.MethodsWe evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS).ResultsWe included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2−, 17% HR+/HER2+, 14.1% HR−/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS.ConclusionsAlthough the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases.



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Policy and priorities for national cancer control planning in low- and middle-income countries: Lessons from the Association of Southeast Asian Nations (ASEAN) Costs in Oncology prospective cohort study

Publication date: March 2017
Source:European Journal of Cancer, Volume 74
Author(s): The ACTION Study GroupWriting committeNirmalaBhoo-PathyCheng-HarYipSanne A.E.PetersMerelKimmanRichardSullivanStephenJanMarkWoodwardChiu-WanNg: Julius Centre University of Malaya Department of Social and Preventive Medicine Faculty of Medicine University of Malaya 50603 Lembah Pantai Kuala Lumpur Malaysia. Fax: +60 3 7967 4975.Principal investigatorsPhetsamoneArounlangsySoeAungSoledad L.BaleteNirmalaBhoo-PathyBounthaphanyBounxoueiDieuBuiJayDatukanAgnes E.GorospeCheng HarYipPrasitKhopaibulThanutKhuayjarernpanishkThiravudKhuhapremaMyoKhinTawinKlinwimolSomkietLalitwongsaDhanooLawbundisConradoLolaGloriaCristal-LunaLeoMarbellaKhoa MaiTrongSoe OoMaungShuMonWin PaPa NaingCorazon A.NgelangelHtun LwinNyeinAnnielyn BerylOng-CornelKhin MayOoIrisylOrolfo-RealDung PhamXuanSeangPharinPujiantoOudayvoneRattanavongKouySamnangSomphobSangkittipaiboonSuleepornSangrajrangCherelinaSantiago-FerrerasPrihSarniantoSanShweEavSokhaThanadejSinthusakeDaruneeSuanpluJitrapornTanabodeeHasbullahThabranyKitisakThepsuwanYin YinHtunHengViroathLeLe WinSwe SweWinTin MoeWinOther contributorsAmiAshariatiDjumhanaAtmakusumaI.MadeBaktaLoan DangThi KimPhung DangThi NgocTuan DiepBaoArioDjatmikoAndiFachruddinPik-PinGohJohanKurniandaHelenMonaghanAbdulMuthalibTrang NgoThuyThao NguyenHoangNga NguyenThi HoaiSonar S.PanigoroHuy PhạmQuangKhanh QuachThanhDradjat R.SuardiShriDeviSubramaniamAru W.SudoyoKhoa TranDangHa TranDinhCatharinaSuhartiSuyatno
BackgroundEvidence to guide policymakers in developing affordable and equitable cancer control plans are scarce in low- and middle-income countries (LMIC).MethodsThe 2012–2014 ASEAN Costs in Oncology Study prospectively followed-up 9513 newly diagnosed cancer patients from eight LMIC in Southeast Asia for 12 months. Overall and country-specific incidence of financial catastrophe (out-of-pocket health costs ≥ 30% of annual household income), economic hardship (inability to make necessary household payments), poverty (living below national poverty line), and all-cause mortality were determined. Stepwise multinomial regression was used to estimate the extent to which health insurance, cancer stage and treatment explained these outcomes.ResultsThe one-year incidence of mortality (12% in Malaysia to 45% in Myanmar) and financial catastrophe (24% in Thailand to 68% in Vietnam) were high. Economic hardship was reported by a third of families, including inability to pay for medicines (45%), mortgages (18%) and utilities (12%), with 28% taking personal loans, and 20% selling assets (not mutually exclusive). Out of households that initially reported incomes above the national poverty levels, 4·9% were pushed into poverty at one year. The adverse economic outcomes in this study were mainly attributed to medical costs for inpatient/outpatient care, and purchase of drugs and medical supplies. In all the countries, cancer stage largely explained the risk of adverse outcomes. Stage-stratified analysis however showed that low-income patients remained vulnerable to adverse outcomes even when diagnosed with earlier cancer stages.ConclusionThe LMIC need to realign their focus on early detection of cancer and provision of affordable cancer care, while ensuring adequate financial risk protection, particularly for the poor.



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An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma

Purpose.

Oncogenic mutations in the KRAS gene are a well-known driver event, occurring in >95% of pancreatic cancers. The objective of this study was to identify driver oncogene aberrations in pancreatic cancers without the KRAS mutation.

Methods.

Whole-exome and transcriptome sequencing was performed on four cases of KRAS mutation-negative pancreatic ductal adenocarcinoma, which were identified in a cohort of 100 cases.

Results.

One case harbored an oncogenic DCTN1-ALK fusion. The fusion gene enabled interleukin-3-independent growth of Ba/F3 cells and rendered them susceptible to the anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib and alectinib. The structure of the breakpoint junction indicated that the fusion was generated by nonhomologous end joining between a segment of DCTN1 exon DNA and a segment of ALK intron DNA, resulting in the generation of a cryptic splicing site. Another case harbored an oncogenic RRAS mutation that activated the GTPase of the RRAS protein.

Conclusion.

Rare oncogenic aberrations, such as the ALK fusion and RRAS mutation, may drive pancreatic carcinogenesis independent of the KRAS mutation. The Oncologist 2017;22:000–000

Implications for Practice: The oncogenic DCTN1-ALK fusion and the RRAS mutation were associated with the development of pancreatic ductal adenocarcinoma (PDAC) in the absence of the KRAS mutation. Constitutional activation of DCTN1-ALK fusion protein was suppressed by the anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib and alectinib. Thus, a small subset of PDAC patients might benefit from therapy using these inhibitors.

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Pharmacoepidemiology of Clinically Relevant Hypothyroidism and Hypertension from Sunitinib and Sorafenib

Background.

Thyroid dysfunction and hypertension (HTN) have been sporadically reported with sunitinib (SUN) and sorafenib (SOR). Determination of the side effect incidence will enhance monitoring and management recommendations.

Methods.

An observational cohort study was performed using deidentified pharmacy claims data from a 3-year period to evaluate patients prescribed SUN, SOR, or capecitabine (CAP; comparison group). The primary outcome was time to first prescription for thyroid replacement or HTN treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox proportional hazards models.

Results.

A total of 20,061 patients were eligible for evaluation of thyroid replacement therapy, which was initiated in 11.6% of those receiving SUN (HR, 16.77; 95% CI, 13.54–20.76), 2.6% of those receiving SOR (HR, 3.47; 95% CI, 2.46–4.98), and 1% of those receiving CAP, with median time to initiation of 4 months (range, 1–35 months). A total of 14,468 patients were eligible for evaluation of HTN therapy, which was initiated in 21% of SUN recipients (HR, 4.91; 95% CI, 4.19–5.74), 14% of SOR recipients (HR, 3.25; 95% CI, 2.69–3.91), and 5% of CAP recipients, with median time to initiation of 1 month (range, 1–18 months) for SOR and 2 months (range, 1–25 months) for SUN.

Conclusion.

SUN and SOR significantly increased the risk for clinically relevant hypothyroidism; the risk was at least 4 times greater with SUN than with SOR. Patients receiving SUN and SOR had a similar elevated risk for clinically relevant HTN. These data provide robust measures of the incidence and time to onset of these clinically actionable adverse events. The Oncologist 2017;22:000–000

Implications for Practice: The side effect profiles for novel therapies are typically used to create monitoring and management recommendations using clinical trial data from patient populations that may not represent those seen in standard clinical practice. This analysis using a large pharmacy claims database better reflects typical patients treated with sorafenib or sunitinib outside of a clinical trial. The findings of increased need for thyroid replacement in patients receiving sunitinib compared with sorafenib and a similar increase in need for hypertension therapy with both agents can be used to form clinically relevant monitoring recommendations for these agents.

http://ift.tt/2klebRE

Environmental and Psychosocial Barriers to and Benefits of Cervical Cancer Screening in Kenya

Background.

Cervical cancer is the second most commonly diagnosed cancer in females and is a leading cause of cancer-related mortality in Kenya; limited cervical cancer screening services may be a factor. Few studies have examined men's and women's perceptions on environmental and psychosocial barriers and benefits related to screening.

Materials and Methods

In 2014, 60 women aged 25–49 years and 40 male partners participated in 10 focus groups (6 female and 4 male), in both rural and urban settings (Nairobi and Nyanza, Kenya), to explore perceptions about barriers to and benefits of cervical cancer screening. Focus groups were segmented by sex, language, geographic location, and screening status. Data were transcribed, translated into English, and analyzed by using qualitative software.

Results.

Participants identified screening as beneficial for initiating provider discussions about cancer but did not report it as a beneficial method for detecting precancers. Perceived screening barriers included access (transportation, cost), spousal approval, stigma, embarrassment during screening, concerns about speculum use causing infertility, fear of residual effects of test results, lack of knowledge, and religious or cultural beliefs. All participants reported concerns with having a male doctor perform screening tests; however, men uniquely reported the young age of a doctor as a barrier.

Conclusion.

Identifying perceived barriers and benefits among people in low- and middle-income countries is important to successfully implementing emerging screening programs. The novel findings on barriers and benefits from this study can inform the development of targeted community outreach activities, communication strategies, and educational messages for patients, families, and providers. The Oncologist 2017;22: 000–000

Implications for Practice: This article provides important information for stakeholders in clinical practice and research when assessing knowledge, beliefs, and acceptability of cervical cancer screening and treatment services in low- and middle-resourced countries. Formative research findings provide information that could be used in the development of health interventions, community education messages, and materials. Additionally, this study illuminates the importance of understanding psychosocial barriers and facilitators to cervical cancer screening, community education, and reduction of stigma as important methods of improving prevention programs and increasing rates of screening among women.

http://ift.tt/2kBmszx

Financial Toxicity and Societal Costs of Cancer Care: Distinct Problems Require Distinct Solutions

http://ift.tt/2kls6Hp

Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2-Positive Early Stage Breast Cancer: A Single Center Experience

Objectives

Trastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 -positive patients. A retrospective analysis was performed of patients treated with dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported.

Methods.

An electronic medical record review was conducted of patients treated with HP-based therapy in the neoadjuvant setting from September 1, 2013, to March 1, 2015. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as total (tpCR, ypT0/is ypN0), German Breast Group (GBG) pCR (ypT0 ypN0), breast pCR (bpCR) with in situ disease (ypT0/is) and without in situ disease (ypT0), and explored axillary pCR (ypN0).

Results.

Charts from 66 patients were reviewed, and 57 patients were evaluable for pCR. Median age was 46 years (range 26–68 years). Median tumor size was 4 cm. Of 57 patients, 53 (93%) had operable breast cancer (T1-3, N0-1, M0). Three patients (5.3%) had locally advanced disease (T2-3, N2-3, M0 or T4a-c, any N, M0), and 1 (1.7%) had inflammatory breast cancer (T4d, any N, M0). Overall, 44 (77%) and 13 (23%) had hormone receptor (HR)-positive and negative diseases, respectively. Median numbers of cycles of neoadjuvant treatment were as follows: AC (4, range 1–4), T (4, range 1–4), trastuzumab (6, range 3–8), and pertuzumab (6, range 2–8). In these 57 patients, the rates of tpCR and bpCR with in situ disease were demonstrated in 41/57 (72%) patients, and the rates of GBG pCR and bpCR without in situ disease were found in 30/57 (53%) patients. Of 26 patients with biopsy-proven lymph nodal involvement, axillary pCR occurred in 22 (85%) patients.

Conclusion.

At a single center, the tpCR and GBG pCR rates of dd AC followed by THP are high at 72% and 53%, respectively. The Oncologist 2017;22:000–000

Implications for Practice: This is the first study describing the role of doxorubicin and cyclophosphamide followed by paclitaxel and dual anti-HER2 therapy with trastuzumab and pertuzumab (ACTHP) in patients with early stage HER2-positive breast cancer. Total (breast + lymph node) pathological complete remission (pCR) remission (ypT0/is ypN0) and German Breast Group pCR rates (ypT0/ ypN0) were high at 72% and 53%, respectively, with the ACTHP regimen. Rate of axillary clearance in patients with known axillary involvement was high at 85%, which may translate into less extensive axillary surgeries in this subset in the future.

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Use of Systemic Therapy Concurrent With Cranial Radiotherapy for Cerebral Metastases of Solid Tumors

The incidence of brain metastases of solid tumors is increasing. Local treatment of brain metastases is generally straightforward: cranial radiotherapy (e.g., whole-brain radiotherapy or stereotactic radiosurgery) or resection when feasible. However, treatment becomes more complex when brain metastases occur while other metastases, outside of the central nervous system, are being controlled with systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies). It is known that some anticancer agents can increase the risk for neurotoxicity when used concurrently with radiotherapy. Increased neurotoxicity decreases quality of life, which is undesirable in this predominantly palliative patient group. Therefore, it is of utmost importance to identify the compounds that should be temporarily discontinued when cranial radiotherapy is needed.

This review summarizes the (neuro)toxicity data for combining systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies) with concurrent radiotherapy of brain metastases. Because only a limited amount of high-level data has been published, a risk assessment of each agent was done, taking into account the characteristics of each compound (e.g., lipophilicity) and the microenvironment of brain metastasis. The available trials suggest that only gemcitabine, erlotinib, and vemurafenib induce significant neurotoxicity when used concurrently with cranial radiotherapy. We conclude that for most systemic therapies, the currently available literature does not show an increase in neurotoxicity when these therapies are used concurrently with cranial radiotherapy. However, further studies are needed to confirm safety because there is no high-level evidence to permit definitive conclusions. The Oncologist 2017;22:000–000

Implications for Practice: The treatment of symptomatic brain metastases diagnosed while patients are receiving systemic therapy continues to pose a dilemma to clinicians. Will concurrent treatment with cranial radiotherapy and systemic therapy (chemotherapeutics, molecular targeted agents, and monoclonal antibodies), used to control intra- and extracranial tumor load, increase the risk for neurotoxicity? This review addresses this clinically relevant question and evaluates the toxicity of combining systemic therapies with cranial radiotherapy, based on currently available literature, in order to determine the need to and interval to interrupt systemic treatment.

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A Clinical Review of Laser and Light Therapy for Nail Psoriasis and Onychomycosis

BACKGROUND: There are considerable emerging data in the use of lasers and lights to treat onychomycosis and psoriasis of the nail subunit. OBJECTIVE: We aimed to review all of the medical literature on laser therapy of nail psoriasis and onychomycosis published since 1992. METHODS AND MATERIALS: We performed a PubMed literature search using the search terms "nail," "laser therapy," "laser surgery," "light," with search terms "psoriasis" and "onychomycosis." In addition, we performed extensive MeSH and bibliographic searches as delineated in the manuscript. Because of the poor quality of evidence, we were not able to complete a quantitative review and thus present our findings qualitatively. RESULTS: Although the trials are small, PDL (595 nm) and IPL with a 550-nm filter demonstrate compelling data in treating nail psoriasis. Laser studies of onychomycosis fall short on many levels. Q-switched Nd:YAG lasers with very short pulse durations and fractionated CO2 demonstrate the most promise for the treatment of onychomycosis. CONCLUSION: The data for treating nail psoriasis and onychomycosis with laser and light therapy are rapidly emerging. With increased subject data, improved study methodology, and more precise output parameters, lasers may become an important modality in the treatment of nail psoriasis and onychomycosis.

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Time Course Analysis of Upper Blepharoplasty Complications

No abstract available

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A Review of Local Anesthetics: Minimizing Risk and Side Effects in Cutaneous Surgery

BACKGROUND: The specialty of dermatology relies heavily on local anesthesia for diagnosis and management of skin disease. The appropriate selection, preparation, administration, and monitoring of these medications affect surgical outcome and patient safety and satisfaction. OBJECTIVE: To perform a comprehensive literature review of the side effects and risks associated with local anesthetics used in cutaneous surgery. Current recommendations to reduce risk and minimize side effects are reviewed. MATERIALS AND METHODS: A comprehensive review of the English-language medical literature search was performed. RESULTS: No current review articles of the side effects and risks of local anesthetics were identified. This review serves to discuss local anesthetics commonly used in dermatology and cutaneous surgery along with practical information regarding prevention of adverse outcomes and addressing local and systemic reactions when they arise. CONCLUSION: Local anesthetics commonly used in cutaneous surgery have potential risks and side effects. Appropriate selection and utilization of local anesthetics and knowledge of the means to prevent and address these risks can impact surgical outcomes, patient satisfaction and safety, and ultimately patient experience in the dermatology clinic.

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Squamous Cell Carcinoma Versus Hypertrophic Lichen Planus; a Difficult Differential Diagnosis of Great Significance in Approach to Treatment

No abstract available

http://ift.tt/2jWldbW

A Critical Assessment of the Evidence for Low-Level Laser Therapy in the Treatment of Hair Loss

BACKGROUND: Low-level laser therapy (LLLT) is currently in use to stimulate hair growth and is quickly gaining in popularity due to the ease of use and absence of side effects. In 2015 alone, the number of LLLT devices with the Food and Drug Administration clearance has doubled. OBJECTIVE: To consolidate evidence and establish which data are still required for the widespread acceptance of LLLT for hair loss therapy. METHODS AND MATERIALS: A thorough search of the PubMed database was conducted to obtain studies investigating LLLT for androgenetic alopecia in men and women. RESULTS: Nine trials were identified for comb and helmet/cap devices, five of which were randomized controlled trials. Data comparison across LLLT trials and with traditional hair loss therapy (minoxidil, finasteride) was not straight forward because there was a lack of visual evidence, sample sizes were low, and there were large variations in study duration and efficacy measurements. CONCLUSION: There are a number of unanswered questions about the optimum treatment regimen, including maintenance treatment and the long-term consequences of LLLT use. Moving forward, protocols should be standardized across trials. Moreover, it is recommended that future trials include visual evidence and trial duration be expanded to 12 months.

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Effect of Phenol and Sodium Hydroxide in the Bacterial Load at Nail Fold After Partial Matricectomy

No abstract available

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Trial Designs and Characteristics in Laser Studies in Dermatology: A Systematic Review

BACKGROUND: Lasers are increasingly used in Dermatology. Clinical studies are among the best means to assess their efficacy. OBJECTIVE: To obtain an overview of therapeutic laser studies in the field of Dermatology, the authors conducted a systematic review to describe the types of study published over the past 25 years, and their reporting in the abstracts. METHODS: The authors selected interventional studies that evaluated laser treatment on human subjects with skin diseases. Reviews or single-case reports were excluded. Journal characteristics, study design, and trial characteristics were recorded and analyzed according to trends over time and journal impact factor ratings. RESULTS: Of the 681 studies included, 57% were comparative, of which 46% were randomized, controlled studies. Trial duration was clearly mentioned in 63% of the abstracts. Trial duration was generally under 6 months (78%). Some parameters were rarely mentioned as follows: the number of patients lost to follow-up (only 12%), blinding (21%), and a clearly stated main outcome (36%). Over the 25 years, there was a significant trend toward an increased proportion of randomized, controlled trials, from 15% between 1990 and 2000 to 41% between 2010 and 2015 (p

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Eight Years' Experience of Sentinel Lymph Node Biopsy in Melanoma Using Lymphoscintigraphy and Gamma Probe Detection After Radiocolloid Mapping

BACKGROUND: Isosulfan blue dye peripheral injection is used in preoperative sentinel lymph node (SLN) identification alone or, to increase sensitivity, in conjunction with radiocolloid mapping. However, isosulfan blue dye has certain drawbacks and limitations. OBJECTIVE: This study assesses the authors' experience of SLN biopsy using only radiocolloid tracer. MATERIALS AND METHODS: Between 2000 and 2008, 218 patients underwent SLN biopsy with radiocolloid mapping, preoperative localization by lymphoscintigraphy and intraoperative confirmation by gamma probe in primary malignant cutaneous melanoma. RESULTS: Mean Breslow index was 2.1 mm. The SLN biopsy success rate was above 98% at all sites and 87% in head and neck locations. The 5-year overall survival rate was 90% and that of 5-year disease-free survival was 80%. False-negative rate, with a mean follow-up time of 41 months, was 5.5%. CONCLUSION: Sentinel lymph node biopsy can be successfully performed in patients with melanoma using only radiocolloid tracer without blue dye staining. In circumstances where blue dye cannot be used such as head and neck tumors, allergic reactions and pregnancy, radiocolloid tracer mapping alone is not a loss of chance for patients with melanoma.

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Comparative Efficacy of Radiofrequency and Pulsed Dye Laser in the Treatment of Rosacea

BACKGROUND: Laser and light-based therapies have been used successfully in the treatment of rosacea; however, evidence is lacking regarding the efficacy of radiofrequency (RF). OBJECTIVE: This study evaluated the efficacy of RF in the treatment of rosacea compared with pulsed dye laser (PDL). METHODS: Thirty patients with rosacea (erythematotelangiectatic rosacea [ETR], n = 20; papulopustular rosacea [PPR], n = 10) were enrolled in a randomized, controlled, split-face study. The patients were treated with RF on one side and PDL on the other side. Each treatment consisted of 3 sessions at 4-week intervals and followed up until 4 weeks after the last treatment. Efficacy was assessed by rosacea severity score, erythema index, lesion counts, physician's subjective evaluation, and patient's satisfaction. RESULTS: Radiofrequency and PDL resulted in significant improvement in severity scores and erythema and 70% of the patients receiving RF treatment showed a clinical improvement of >50%. No significant difference was noted between RF and PDL treatment in ETR. However, RF treatment led to a significantly greater decrease in papulopustular lesion count and rosacea severity score in PPR compared with PDL treatment. CONCLUSION: RF therapy was effective in the treatment of rosacea. It should be considered an alternative therapeutic option, especially in PPR.

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Dermatologic Surgery Needs in Low-Income, Uninsured, and Minority Communities

No abstract available

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Reliability, Validity, and Sensitivity to Change Overtime of the Modified Melasma Area and Severity Index Score

BACKGROUND: The new modified Melasma Area and Severity Index (mMASI) score, the recently used outcome measure for melasma, has not been tested to determine its sensitivity to change in melasma. OBJECTIVE: To determine the reliability, validity, and sensitivity to change overtime of the mMASI score in assessment of the severity of melasma. METHODS: Pearson correlation, Cronbach alpha, and intraclass correlation coefficient were calculated to assess the reliability of the mMASI score. Validity of the mMASI scale was carried out using Spearman correlation between mMASI total score (before and after treatment), clinical data, and patient's responses. RESULTS: The mMASI score showed excellent reliability and good validity for assessment of the severity of melasma. The authors also determined that the mMASI score demonstrated sensitivity to change over time. CONCLUSION: An excellent degree of agreement between the mMSAI and MASI scores was revealed. The mMASI score is reliable, valid, and responsive to change in the assessment of severity of melasma. Moreover, the mMASI score was found to be easier to learn and perform and simpler in calculation compared with the MASI score. Overall, the mMASI score can effectively replace the MASI score.

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Resistant and Recurrent Late Reaction to Hyaluronic Acid-Based Gel

No abstract available

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Ultrathin Skin Grafting in Resistant Stable Vitiligo: A Follow-up Study of 8 Years in 370 Patients

BACKGROUND: Ultrathin skin grafting (UTSG) is a tissue grafting technique used in resistant stable vitiligo. OBJECTIVE: To assess long-term follow-up results achieved with UTSG in vitiligo. METHODS: Over a span of 8 years, a total of 415 patients with stable vitiligo were treated with UTSG at the authors' institute. Retrospective analysis of results achieved in these patients was performed, and primary end points assessed included the extent and quality of repigmentation achieved and adverse effects from the procedure. Results were correlated with the site, morphological type of vitiligo, duration of stability, postprocedure treatment used, and the age and sex of the patient. RESULTS: Follow-up results were available with 554 lesions in 370 patients. Excellent response (≥90% repigmentation) was documented in 78.9% (437/554) lesions whereas 8.67% (48/554) lesions demonstrated poor results. Pigmentation was retained in >98% (112/114) cases over 4-year follow-up. The commonest adverse effect noted was "perigraft halo" in 12.3% (68/554) lesions. Site and morphological type of vitiligo as well as the postoperative use of phototherapy showed statistically significant correlation with response. Age and sex of the patient and duration of stability beyond 1 year did not influence the outcome. CONCLUSION: Ultrathin skin grafting provides long-term beneficial results in stable resistant vitiligo.

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Photodynamic Therapy: A Clinical Consensus Guide: ERRATUM

No abstract available

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Effect of Procedural-Related Variables on Melanocyte–Keratinocyte Suspension Transplantation in Nonsegmental Stable Vitiligo: A Clinical and Immunocytochemical Study

BACKGROUND: Melanocyte–keratinocyte suspension (M–K susp) is gaining popularity for vitiligo treatment. Few studies have addressed procedure-related variables. OBJECTIVE: To assess the effect of different M–K susp procedure-related variables on the clinical outcome in stable vitiligo. METHODS: This prospective multicenter comparative study included 40 cases with nonsegmental stable vitiligo. Donor site was either a skin graft in noncultured epidermal cell suspension (NCECS) or hair follicle units in outer root sheath hair follicle suspension (ORSHFS). Recipient site was prepared by either cryoblebbing or CO2 laser resurfacing. Cell counts and viability were recorded in the cell suspensions. Tissue melanocytes and keratinocytes were examined by melan-A and cytokeratin, respectively. Assessment of repigmentation was performed 18 months after the procedure. RESULTS: Thirty-seven subjects completed the study. Cell count was significantly lower in the ORSHFS compared with NCECS with no significant difference in the repigmentation outcome. On comparing techniques of recipient site preparation, homogenicity was better in the CO2 group. Elbows and knees responded better to CO2 resurfacing, whereas distal fingers responded better to combination of cryoblebbing with NCECS. CONCLUSION: Using different techniques in M–K susp produces comparable results. However, the distal fingers showed better results using combination of donor NCECS and recipient cryoblebs.

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Sebaceous Carcinoma Treated With Mohs Micrographic Surgery

BACKGROUND: Sebaceous carcinoma is a rare and potentially aggressive adnexal neoplasm with historic data indicating high rates of recurrence, metastasis, and cancer-specific mortality. OBJECTIVE: To evaluate the incidence of local recurrence, metastasis, disease-specific mortality, and all-cause mortality and to identify work-up approaches. PATIENTS AND METHODS/MATERIALS: Retrospective review of patients with sebaceous carcinoma treated with Mohs micrographic surgery between 2001 and 2013 at one institution. RESULTS: Thirty-seven patients had 45 sebaceous carcinomas located on the periocular region (13%), non-periocular face (47%), scalp (7%), neck (4%), trunk (9%), and extremities (20%). The mean age was 66.1 years, and 24 (65%) patients were male. Five patients had Muir–Torre syndrome (MTS) or Lynch syndrome. Seven of 12 tumors showed loss of expression of ≥1 mismatch repair gene. The most common work-up involved taking a detailed personal and family medical history. No local recurrences, metastases, or disease-specific deaths occurred during an average follow-up of 3.6 years. CONCLUSION: Mohs micrographic surgery is an effective treatment for sebaceous carcinoma. Detailed history taking, age-appropriate cancer screening, and immunohistochemical staining with MLH1, MSH2, or MSH6 is helpful in identifying which patients should be referred to a geneticist for work-up of MTS.

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Commentary on Effect of Procedural-Related Variables on Melanocyte-Keratinocyte Suspension Transplantation in Nonsegmental Stable Vitiligo

No abstract available

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Reconstruction of a Multi-Subunit Defect on the Lip, Nose, and Cheek

No abstract available

http://ift.tt/2jW6H46

A Prospective, Open-Label, Observational, Postmarket Study Evaluating VYC-17.5L for the Correction of Moderate to Severe Nasolabial Folds Over 12 Months

BACKGROUND: VYC-17.5L (17.5 mg/mL hyaluronic acid, 0.3% lidocaine) is a dermal filler intended for deep dermis injection for the treatment of skin depressions. OBJECTIVE: To evaluate 12-month effectiveness and safety of VYC-17.5L for the treatment of moderate/severe nasolabial folds (NLFs). METHODS: Subjects ≥18 years old with moderate/severe NLFs were recruited (N = 70). Injected volume was aimed at achieving optimum correction; top-up treatment was given at 2 weeks if needed. The primary endpoint was investigator-assessed change in NLF severity over 12 months using the validated photonumeric NLF Severity Scale. Secondary endpoints included investigator- and subject-assessed satisfaction and safety. Adverse events judged to be more severe or prolonged than routinely observed were recorded. RESULTS: Sixty-five subjects completed study requirements. Mean volume injected was 3.0 ± 1.0 mL for both NLFs combined. Significant improvement was maintained in investigator-assessed NLF severity at 12 months, and investigators and subjects reported high satisfaction with VYC-17.5L throughout the study. Two unexpected adverse events were reported: (1) redness, swelling, and decreased sensitivity (resolved after 4 days) and (2) swelling (resolved after 48 hours); neither event was serious or life threatening. CONCLUSION: VYC-17.5L is effective and well tolerated for the treatment of moderate to severe NLFs for 1 year.

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Validation of a Melanoma Risk Assessment Smartphone Application

No abstract available

http://ift.tt/2jWfwuW

Impact of Laparotomy and Intraperitoneal Hyperthermic Instillation (LIHI) on the oxaliplatin pharmacokinetics after intravenous administration in Wistar rats

Abstract

Purpose

In peritoneal metastasis condition, the fact that most of the disease is limited to the peritoneal cavity laid the foundations for a surgical treatment, including intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of this study was to evaluate the impact of the surgical procedures implied in open HIPEC technique, referred to laparotomy procedures followed by an intraperitoneal hyperthermic instillation (LIHI) on oxaliplatin tissue distribution and elimination. To delimit the influence of this procedure alone, oxaliplatin was administered as an intravenous (iv) bolus in both groups.

Methods

An experimental model in Wistar rats was employed, and LIHI was evaluated as a dichotomous covariate by using a population pharmacokinetic (PK) approach. Rats were randomized in two groups receiving 1.5 mg iv oxaliplatin alone or 1.5 mg iv oxaliplatin under LIHI conditions, carrying out a hyperthermic 5% dextrose instillation. The oxaliplatin plasma concentrations were characterized by an open two-compartment PK model.

Results

Results concluded that surgical conditions affect the oxaliplatin elimination and distribution from blood to peripheral tissues, increasing the systemic drug exposure. Concretely, oxaliplatin peripheral volume of distribution, and clearance decreased by 48.6% and 55.3%, respectively, compared to the control group that resulted in a two-fold increase of the area under the concentration time curve.

Conclusions

Comparison in clinical practice of oxaliplatin PK parameters obtained after iv administrations with those obtained after HIPEC interventions must be done carefully. This would limit the use of iv PK parameters to simulate new scenarios for oxaliplatin in HIPEC.

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What Are We Drinking? Beverages Shown in Adolescents’ Favorite Television Shows

Publication date: Available online 6 February 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Marla E. Eisenberg, Nicole I. Larson, Sarah E. Gollust, Dianne Neumark-Sztainer
BackgroundMedia use has been shown to contribute to poor dietary intake; however, little attention has been paid to programming content. The portrayal of health behaviors in television (TV) programming contributes to social norms among viewers, which have been shown to influence adolescent behavior.ObjectiveThis study reports on a content analysis of beverages shown in a sample of TV shows popular with a large, diverse group of adolescents, with attention to the types of beverages and differences across shows and characters.DesignFavorite TV shows were assessed in an in-school survey in 2010. Three episodes of each of the top 25 shows were analyzed, using a detailed coding instrument.Key measuresBeverage incidents (ie, beverage shown or described) were recorded. Beverage types included milk, sugar-sweetened beverages (SSBs), diet beverages, juice, water, alcoholic drinks, and coffee. Characters were coded with regard to gender, age group, race, and weight status. Shows were rated for a youth, general, or adult audience.Statistical analysesχ² tests were used to compare the prevalence of each type of beverage across show ratings (youth, general, adult), and to compare characteristics of those involved in each type of beverage incident.ResultsBeverage incidents were common (mean=7.4 incidents/episode, range=0 to 25). Alcohol was the most commonly shown (38.8%); milk (5.8%) and juice (5.8%) were least common; 11.0% of incidents included SSBs. Significant differences in all types of beverage were found across characters' age groups. Almost half of young adults' (49.2%) or adults' (42.0%) beverage incidents included alcohol.ConclusionsBeverages are often portrayed on TV shows viewed by adolescents, and common beverages (alcohol, SSBs) may have adverse consequences for health. The portrayal of these beverages likely contributes to social norms regarding their desirability; nutrition and health professionals should talk with youth about TV portrayals to prevent the adoption of unhealthy beverage behaviors.



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Toward Harmonization of the Nutrition Care Process Terminology and the International Classification of Functioning, Disability and Health−Dietetics: Results of a Mapping Exercise and Implications for Nutrition and Dietetics Practice and Research

Publication date: Available online 6 February 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Gabriele Gäbler, Michaela Coenen, Claudia Bolleurs, Willy K. Visser, Sytske Runia, Yvonne F. Heerkens, Tanja A. Stamm




http://ift.tt/2ldtv4k

The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies

Summary

A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10–L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed.

In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5–3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy.

Learning points:

Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.

Consider TKI therapy in progressive disease where benefits outweigh risks.

Active surveillance and timely intervention are required for TKI-related adverse effects.

There is a need for further research on the clinical application of TKI therapy in advanced DTC, including comparative efficacy, sequencing and identifying responders.

http://ift.tt/2lin4Kd

First flush characteristics of rainfall runoff from a paddy field in the Taihu Lake watershed, China

Abstract

Nonpoint storm runoff remains a major threat to surface water quality in China. As a paddy matures, numerous fertilizers are needed, especially in the rainy seasons; the concentration of nitrogen and phosphorus in rainfall runoff from farmland is much higher than at other times, and this poses a great threat to water bodies and is the main reason for water eutrophication, especially in high concentration drainages. To date, most studies regarding the characteristics of pollutants in rainfall runoff have mainly been concentrated on urban runoff and watershed runoff; therefore, it is particularly important to investigate the characteristics of nitrogen and phosphorus loss in rainfall runoff from paddy fields. To study the characteristics of nitrogen and phosphorus loss and whether the first flush effect exists, continuous monitoring of the rainfall runoff process of six rainfall events was conducted in 2013, of which four rainfall events during storm, high, middle, and low intensity rainfalls were analyzed, and runoff and quality parameters, such as suspended solids (SS), total nitrogen (TN), ammonium nitrogen (NH₄⁺-N), nitrate nitrogen (NO₃⁻-N), total phosphorus (TP), and phosphate (PO₄³⁻-P), were analyzed to determine the relationship between runoff and water quality. The paddy field is located north of Wuxi Lake Basin along the Hejia River upstream in Zhoutie town, Yixing city. An analysis of the load distribution during rainfall runoff was conducted. Event mean concentration (EMC) was used to evaluate the pollution situation of the paddy field's rainfall runoff. A curve of the dimensionless normalized cumulative load (L) vs. normalized cumulative flow (F) (L-F curve), the probability of the mass first flush (MFFn), and the pollutants carried by the initial 25% of runoff (FF₂₅) were used to analyze the first flush effect of the paddy field runoff, and different contaminants show different results: the concentration of nitrogen and phosphorus fluctuate and follow a similar trend as runoff changes, NO₃⁻-N concentration is lower in the early part of runoff and higher in the later, and TP mainly occurs in the particle state in storm runoff and mainly in the dissolved state when the rainfall intensity is smaller. Nitrogen and phosphorus losses from paddy fields are closely related to the average rainfall intensity and the max rainfall intensity, and the runoff loss of nitrogen and phosphorus is more severe when the rainfall intensity is large. Based on an analysis of multiple methodologies, TN and NH₄⁺-N show a certain degree of a first flush effect, whereas the first flush effect of TP is not obvious. The first flush effect of SS is obvious in larger intensity rainfall and shows a slight secondary flush effect in smaller rainfall events.

http://ift.tt/2jW9ors

The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies

Summary

A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10–L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed.

In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5–3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy.

Learning points:

Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.

Consider TKI therapy in progressive disease where benefits outweigh risks.

Active surveillance and timely intervention are required for TKI-related adverse effects.

There is a need for further research on the clinical application of TKI therapy in advanced DTC, including comparative efficacy, sequencing and identifying responders.

http://ift.tt/2lin4Kd

Search of the p.M918T Mutation in the RET Oncogene in Mexican Adult Patients with Medullary Thyroid Carcinoma

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-121661

Inherited mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndromes. The major component tumor of these syndromes is medullary thyroid carcinoma (MTC). To date, somatic mutations in RET have been identified in tumors from individuals with MEN 2 finding. RET M918T mutation is present in 95% of the MEN2B cases, and approximately 50% of sporadic MTCs harbor this mutation. We performed a mutational analysis in 17 cases of Medullary thyroid carcinoma, the somatic missense mutation at codon 918 of RET was found in 2 of the 17 MTCs, and one case presented MEN2 phenotype including MTC. The percentage of RET M918T mutation is similar in Mexican MTC patients to other series, although other mutations could be implicated in our population.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Renin-Angiotensin System Blockade Improves Cardiac Indices in Acromegaly Patients

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-123710

Blockade of the angiotensin-renin system, with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), has been shown to improve cardiac outcomes following myocardial infarction and delay progression of heart failure. Acromegaly is associated with a disease-specific cardiomyopathy, the pathogenesis of which is poorly understood.The cardiac indices of patients with active acromegaly with no hypertension (Group A, n=4), established hypertension not taking ACEi/ARBs (Group B, n=4) and established hypertension taking ACEi/ARBs (Group C, n=4) were compared using cardiac magnetic imaging.Patients taking ACEi/ARBs had lower end diastolic volume index (EDVi) and end systolic volume index (ESVi) than the other 2 groups ([C] 73.24 vs. [A] 97.92 vs. [B] 101.03 ml/m2, ANOVA p=0.034, B vs. C p<0.01). Groups A and B had EDVi and ESVi values at the top of published reference range values; Group C had values in the middle of the range.Acromegaly patients on ACEi/ARBs for hypertension demonstrate improved cardiac indices compared to acromegaly patients with hypertension not taking these medications. Further studies are needed to determine if these drugs have a beneficial cardiac effect in acromegaly in the absence of demonstrable hypertension.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2kfrDUL

Ankylosis of Temporomandibular Joints After Mandibular Distraction Osteogenesis in the Patients of Nager Syndrome: Report of Two Cases and Literature Review

Nager syndrome, also known as Nager acrofacial dysostosis, was first described by Nager and deReynier in 1948. The patients are commonly presented with micrognathia and a preventive tracheostomy is necessary when there are symptoms of upper airway obstruction. Mandibular distraction osteogenesis is considered as an effective procedure, which not only improves micrognathia but also minimizes the chance of the tracheostomy. However, mandibular distraction osteogenesis has some complications, such as relapse, teeth injury, infection and injury of the temporomandibular joints.

http://ift.tt/2kkKVuv

Enhanced colorectal cancer metastases in the alcohol-injured liver

Abstract

Metastatic liver disease is a major cause of mortality in colorectal cancer (CRC) patients. Alcohol consumption is a noted risk factor for secondary cancers yet the role of alcoholic liver disease (ALD) in colorectal liver metastases (CRLM) is not defined. This work evaluated tumor cell colonization in the alcoholic host liver using a novel preclinical model of human CRC liver metastases. Immunocompromised Rag1-deficient mice were fed either ethanol (E) or isocaloric control (C) diets for 4 weeks prior to intrasplenic injection of LS174T human CRC cells. ALD and CRLM were evaluated 3 or 5 weeks post-LS174T cell injection with continued C/E diet administration. ALD was confirmed by increased serum transaminases, hepatic steatosis and expression of cytochrome P4502E1, a major ethanol-metabolizing enzyme. Alcohol-mediated liver dysfunction was validated by impaired endocytosis of asialoorosomucoid and carcinoembryonic antigen (CEA), indicators of hepatocellular injury and progressive CRC disease, respectively. Strikingly, the rate and burden of CRLM was distinctly enhanced in alcoholic livers with metastases observed earlier and more severely in E-fed mice. Further, alcohol-related increases (1.5–3.0 fold) were observed in the expression of hepatic cytokines (TNF-α, IL-1 beta, IL-6, IL-10) and other factors noted to be involved in the colonization of CRC cells including ICAM-1, CCL-2, CCL-7, MMP-2, and MMP-9. Also, alcoholic liver injury was associated with altered hepatic localization as well as increased circulating levels of CEA released from CRC cells. Altogether, these findings indicate that the alcoholic liver provides a permissive environment for the establishment of CRLM, possibly through CEA-related inflammatory mechanisms.

http://ift.tt/2kLjbzC

Intrinsic signal optical imaging of visual brain activity: Tracking of fast cortical dynamics

Publication date: 1 March 2017
Source:NeuroImage, Volume 148
Author(s): Haidong D. Lu, Gang Chen, Junjie Cai, Anna W. Roe
Hemodynamic-based brain imaging techniques are typically incapable of monitoring brain activity with both high spatial and high temporal resolutions. In this study, we have used intrinsic signal optical imaging (ISOI), a relatively high spatial resolution imaging technique, to examine the temporal resolution of the hemodynamic signal. We imaged V1 responses in anesthetized monkey to a moving light spot. Movies of cortical responses clearly revealed a focus of hemodynamic response traveling across the cortical surface. Importantly, at different locations along the cortical trajectory, response timecourses maintained a similar tri-phasic shape and shifted sequentially across cortex with a predictable delay. We calculated the time between distinguishable timecourses and found that the temporal resolution of the signal at which two events can be reliably distinguished is about 80 milliseconds. These results suggest that hemodynamic-based imaging is suitable for detecting ongoing cortical events at high spatial resolution and with temporal resolution relevant for behavioral studies.



http://ift.tt/2lhOL5O

Dual origins of measured phase-amplitude coupling reveal distinct neural mechanisms underlying episodic memory in the human cortex

Publication date: 1 March 2017
Source:NeuroImage, Volume 148
Author(s): Alex P. Vaz, Robert B. Yaffe, John H. Wittig, Sara K. Inati, Kareem A. Zaghloul
Phase-amplitude coupling (PAC) is hypothesized to coordinate neural activity, but its role in successful memory formation in the human cortex is unknown. Measures of PAC are difficult to interpret, however. Both increases and decreases in PAC have been linked to memory encoding, and PAC may arise due to different neural mechanisms. Here, we use a waveform analysis to examine PAC in the human cortex as participants with intracranial electrodes performed a paired associates memory task. We found that successful memory formation exhibited significant decreases in left temporal lobe and prefrontal cortical PAC, and these two regions exhibited changes in PAC within different frequency bands. Two underlying neural mechanisms, nested oscillations and sharp waveforms, were responsible for the changes in these regions. Our data therefore suggest that decreases in measured cortical PAC during episodic memory reflect two distinct underlying mechanisms that are anatomically segregated in the human brain.

Graphical abstract

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A Potential Role for the Secretogranin II-Derived Peptide EM66 in the Hypothalamic Regulation of Feeding Behavior

Abstract

EM66 is a conserved 66-amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells as well as in hypothalamic neurons. Although EM66 is abundant in the hypothalamus, its physiological function remains to be elucidated. The aim of the present study was to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behavior. We show that ICV administration of EM66 induces a drastic dose-dependent inhibition of food intake in mice deprived of food for 18 h, which is associated with an increase of hypothalamic POMC and MC3R mRNA levels and c-Fos immunoreactivity in the POMC neurons of the arcuate nucleus. By contrast, ICV injection of EM66 does not alter the hypothalamic expression of NPY and neither that of its Y1 and Y5 receptors. A 3-month high fat diet (HFD) leads to an important decrease of POMC and SgII mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48-h fasting in HFD mice decreases the expression of POMC and SgII mRNA that is not observed in mice fed a standard chow. Together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide that regulates hypothalamic feeding behavior, at least in part, by activating the POMC neurons of the arcuate nucleus.

This article is protected by copyright. All rights reserved.

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Striatal dopamine D1 receptor suppression impairs reward-associative learning

Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): Kerin K. Higa, Jared W. Young, Baohu Ji, David E. Nichols, Mark A. Geyer, Xianjin Zhou
Dopamine (DA) is required for reinforcement learning. Hence, disruptions in DA signaling may contribute to the learning deficits associated with psychiatric disorders. The DA D1 receptor (D1R) has been linked to learning and is a target for cognitive/motivational enhancement in patients with schizophrenia. Separating the striatal D1R contribution to learning vs. motivation, however, has been challenging.We suppressed striatal D1R expression in mice using a D1R-targeting short hairpin RNA (shRNA), delivered locally to the striatum via an adeno-associated virus (AAV). We then assessed reward- and punishment-associative learning using a probabilistic learning task and motivation using a progressive-ratio breakpoint procedure.We confirmed suppression of striatal D1Rs immunohistochemically and by testing locomotor activity after the administration of (+)-doxanthrine, a full D1R agonist, in control mice and those treated with the D1RshRNA. D1RshRNA-treated mice exhibited impaired reward-associative learning, while punishment-associative learning was spared. This deficit was unrelated to general learning impairments or amotivation, because the D1shRNA-treated mice exhibited normal Barnes maze learning and normal motivation in the progressive-ratio breakpoint procedure.Suppression of striatal D1Rs selectively impaired reward-associative learning whereas punishment-associative learning, aversion-motivated learning, and appetitive motivation were spared. Because patients with schizophrenia exhibit similar reward-associative learning deficits, D1R-targeted treatments should be investigated to improve reward learning in these patients.



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Effects of LPS-induced immune activation prior to trauma exposure on PTSD-like symptoms in mice

Publication date: 14 April 2017
Source:Behavioural Brain Research, Volume 323
Author(s): Jessica Deslauriers, Myrthe van Wijngaarde, Mark A. Geyer, Susan Powell, Victoria B. Risbrough
The prevalence of posttraumatic stress disorder (PTSD) is high in the armed services, with a rate up to 20%. Multiple studies have associated markers of inflammatory signaling prior to trauma with increased risk of PTSD, suggesting a potential role of the immune system in the development of this psychiatric disorder. One question that arises is if "priming" the immune system before acute trauma alters the stress response and increases enduring effects of trauma. We investigated the time course of inflammatory response to predator stress, a robust stressor that induces enduring PTSD-like behaviors, and the modulation of these effects via prior immune activation with the bacterial endotoxin, lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist. Mice exposed to predator stress exhibited decreased pro-/anti-inflammatory balance in the brain 6h after stress, suggesting that predator exposure acutely suppressed the immune system by increasing anti-inflammatory cytokines levels. Acute immune activation with LPS before a single predator stress did not alter the enduring avoidance behavior in stressed mice. Our findings suggest that acute inflammation, at least via TLR4 activation, is not sufficient to increase susceptibility for PTSD-like behaviors in this model. Future studies will examine if chronic inflammation is required to induce similar immune changes to those observed in PTSD patients in this model.



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Promoting Initiatives in Quality of Cardiovascular Care: The Complementary Role of ACC National and State Chapters

http://ift.tt/2kkdLLf

Val122Ile mt-ATTR Has a Worse Survival Than wt-ATTR Cardiac Amyloidosis

http://ift.tt/2kk8mE5

Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus

AbstractBackground

A limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect.

Objectives

The goal of this study was to determine if oral bioavailability mediates nonresponsiveness.

Methods

The rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in a randomized, single-blind, triple-crossover study. Patients were exposed to three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and a delayed-release enteric-coated (EC) aspirin. Onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B₂ (TXB₂) generation. Aspirin nonresponsiveness was defined as a level of residual serum TXB₂ associated with elevated thrombotic risk (<99.0% inhibition or TXB₂ >3.1 ng/ml) within 72 h after 3 daily aspirin doses.

Results

The rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200, and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin–treated subjects had serum TXB₂ levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [C_max] and 77% and 82% lower AUC_0–t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB₂, with marked interindividual variability.

Conclusions

A high proportion of patients treated with EC aspirin failed to achieve complete inhibition of TXB₂ generation due to incomplete absorption. Reduced bioavailability may contribute to "aspirin resistance" in patients with diabetes. (Pharmacodynamic Evaluation of PL2200 Versus Enteric-Coated and Immediate Release Aspirin in Diabetic Patients; NCT01515657)

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LDLR Variant Databases and Familial Hypercholesterolemia Population Studies

http://ift.tt/2kkmnBJ

Type 2 Diabetes, Obesity, and Aspirin Responsiveness

http://ift.tt/2kk61sB

A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies

Abstract

Evidence that elevated lipoprotein(a) (Lp[a]) levels contribute to cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS) is substantial. Development of isoform-independent assays, in concert with genetic, epidemiological, translational, and pathophysiological insights, have established Lp(a) as an independent, genetic, and likely causal risk factor for CVD and CAVS. These observations are consistent across a broad spectrum of patients, risk factors, and concomitant therapies, including patients with low-density lipoprotein cholesterol <70 mg/dl. Statins tend to increase Lp(a) levels, possibly contributing to the "residual risk" noted in outcomes trials and at the bedside. Recently approved proprotein convertase subtilisin/kexin-type 9 inhibitors and mipomersen lower Lp(a) 20% to 30%, and emerging RNA-targeted therapies lower Lp(a) >80%. These approaches will allow testing of the "Lp(a) hypothesis" in clinical trials. This review summarizes the current landscape of Lp(a), discusses controversies, and reviews emerging therapies to reduce plasma Lp(a) levels to decrease risk of CVD and CAVS.

http://ift.tt/2kkczYv