Chemical Senses by Alexandros G. Sfakianakis: Αυγούστου 2017

Πέμπτη 31 Αυγούστου 2017

Total synthesis of architecturally complex indole terpenoids: strategic and tactical evolution.

Total synthesis of architecturally complex indole terpenoids: strategic and tactical evolution.

J Antibiot (Tokyo). 2017 Aug 30;:

Authors: Zou Y, Smith Iii AB

Abstract
Indole terpenes have attracted the interests of synthetic chemists due to their complex architectures and potent biological activities. Examples of total syntheses of several indole terpenes were reviewed in this article to honor Professor KC Nicolaou.The Journal of Antibiotics advance online publication, 30 August 2017; doi:10.1038/ja.2017.94.

PMID: 28852179 [PubMed - as supplied by publisher]

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Τετάρτη 30 Αυγούστου 2017

Medical Management of Chronic Rhinosinusitis - A review of traditional and novel medical therapies.

Medical Management of Chronic Rhinosinusitis - A review of traditional and novel medical therapies.

Expert Opin Investig Drugs. 2017 Aug 29;:

Authors: Schwartz JS, Tajudeen BA, Cohen NA

Abstract
INTRODUCTION: Chronic rhinosinusitis (CRS) is a commonly seen persistent inflammatory disease process affecting the paranasal sinuses with extensively reported economic implications. Despite an elusive pathophysiologic mechanism underlying this disease process, treatment outcomes are encouraging with the employment of an array of medical and surgical therapies. Areas covered: The goal of this paper is to provide a comprehensive, up to date analysis of the literature concerning the medical management of CRS by summarizing the evidence in support of traditional medical therapies for the management of CRS in addition to highlighting novel medical therapies currently under investigation. Expert opinion: The current staples of medical therapy for CRS based on the strength of available evidence include topical and oral corticosteroids, oral antibiotics and topical saline. The introduction of immunomodulatory therapies ("Biologics") for the treatment of CRS shows promise but have yet to be employed in a widespread fashion due to the need for additional research to better elucidate their role.

PMID: 28847168 [PubMed - as supplied by publisher]

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Κυριακή 20 Αυγούστου 2017

Infant Acceptance of Primary Tastes and Fat Emulsion: Developmental Changes and Links with Maternal and Infant Characteristics.

Infant Acceptance of Primary Tastes and Fat Emulsion: Developmental Changes and Links with Maternal and Infant Characteristics.

Chem Senses. 2017 Sep 01;42(7):593-603

Authors: Schwartz C, Chabanet C, Szleper E, Feyen V, Issanchou S, Nicklaus S

Abstract
Previous studies on taste acceptance have been conducted taste-by-taste and with a cross-sectional design. The aim of this study was to longitudinally evaluate the acceptance of sweet, salty, bitter, sour and umami solutions, and a fat emulsion comparatively in a birth cohort from 3 to 20 months old. The acceptance of each taste relative to water was defined using proportional variables that are based on ingestion (IR) or liking evaluated by the experimenter (LR). These data were analyzed with mixed models that accounted for age and subject effects (minimum 152 observations/age/taste; maximum 216). For saltiness, acceptance increased sharply between 3 and 12 months old. The trajectories of acceptance were parallel for sweetness, sourness, and the umami tastes between 3 and 20 months old, with sweetness being preferred. Between 12 and 20 months old, the acceptance of all tastes, except bitterness, decreased, and at 20 months old, only sweetness was not rejected. The acceptance of bitterness remained stable. For the fat emulsion, acceptance evolved from indifference to rejection. The acceptance of saltiness and umami tastes were lower in girls than boys at 20 months old. The acceptance of the fat emulsion was higher in infants who were born heavier and taller. At 20 months old, the fat emulsion acceptance was higher in infants who were born from mothers with a higher prepregnancy body mass index. Finally, the taste differential reactivity (the standard deviation of the IRs) significantly increased from 3 to 20 months old.

PMID: 28821180 [PubMed - in process]

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Pungency Evaluation of Hydroxyl-Sanshool Compounds After Dissolution in Taste Carriers Per Time-Related Characteristics.

Pungency Evaluation of Hydroxyl-Sanshool Compounds After Dissolution in Taste Carriers Per Time-Related Characteristics.

Chem Senses. 2017 Sep 01;42(7):575-584

Authors: Zhang L, Shi B, Wang H, Zhao L, Chen Z

Abstract
This study was conducted to investigate the sensory characteristics and temporal migration of hydroxyl-sanshool compounds at slight and moderate concentrations after dissolution in ethanol-water, saccharose, NaCl, and MSG via 2-AFC, time intensity (TI) and temporal dominance of sensations (TDS) methods. The pungency detection threshold (DT) was suppressed in saccharose while NaCl and MSG solutions showed no effect on pungency DT. The area under the curve (AUC) of pungency increased in NaCl and MSG solutions and decreased significantly in saccharose solution. Imax (maximal intensity) also increased in NaCl and MSG at low concentrations of hydroxyl-sanshool compounds. The temporally dominant sensations and migration of said sensations across the oral cavity differed among different carriers. Low levels of pungency compounds were characterized by tingling first in the tongue tip and ending in the lips, while moderate levels of the compound produced tingling, astringency, vibrating, and numbing from the tongue tip to the bilateral sides of the tongue, lips, palate, cheek mucosa, and surface of the tongue over time. There were significant differences in the maximum rate, peak time, and duration of any dominant sensation, as well as in the duration of sensation in the lips, tongue tip, and bilateral sides of the tongue. This study provides a dynamic profile of consuming pungent food, which provides a reference not only for the design of new food products with desirable pungency, but also as a scientific basis for the application of pungent compounds within the food and catering industry.

PMID: 28821179 [PubMed - in process]

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Oil Perception-Detection Thresholds for Varying Fatty Stimuli and Inter-individual Differences.

Oil Perception-Detection Thresholds for Varying Fatty Stimuli and Inter-individual Differences.

Chem Senses. 2017 Sep 01;42(7):585-592

Authors: Heinze JM, Costanzo A, Baselier I, Fritsche A, Lidolt M, Hinrichs J, Frank-Podlech S, Keast R

Abstract
Multiple lines of research have demonstrated that humans can perceive fat in the form of free fatty acids (FFAs). However, the dietary concentration of FFAs is generally very low and fat is mainly consumed as triacylglycerol (TAG). The aim of this study was to examine the perception of different fatty stimuli and possible associations between them. Therefore, detection thresholds for 4 fatty stimuli (oleic acid [FFA], paraffin oil [mixture of hydrocarbon molecules], canola oil [TAG-rich], and canola oil spiked with oleic acid [rich in TAGs and FFAs]) were determined in 30 healthy participants. Additionally, inter-individual differences in fat perception were examined. It was observed that oleic acid was perceivable at significantly lower concentrations than all other stimuli (P < 0.001). Similarly, canola oil with oleic acid was detectable at lower concentrations than canola oil alone (P < 0.001). Moreover, canola oil detection thresholds were significantly lower than paraffin oil detection thresholds (P = 0.017). Participants who were sensitive for low concentrations for oleic acid showed lower detection thresholds for canola oil with and without oleic acid, compared with participants that were less sensitive for oleic acid. The results of this study demonstrate that the higher the concentrations of FFAs in the stimuli, the lower the individual fat detection threshold. Moreover, participants being sensitive for lower concentrations of FFAs are also more likely to detect low concentrations of TAG-rich fats as it is found in the human diet.

PMID: 28821178 [PubMed - in process]

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Πέμπτη 17 Αυγούστου 2017

The essential kinase ATR: ensuring faithful duplication of a challenging genome.

The essential kinase ATR: ensuring faithful duplication of a challenging genome.

Nat Rev Mol Cell Biol. 2017 Aug 16;:

Authors: Saldivar JC, Cortez D, Cimprich KA

Abstract
One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.

PMID: 28811666 [PubMed - as supplied by publisher]

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Chemical Identification of "Maternal Signature Odors" in Rat.

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Chemical Identification of "Maternal Signature Odors" in Rat.

Chem Senses. 2017 Mar 01;42(3):211-222

Authors: Sreng L, Temime-Roussel B, Wortham H, Mourre C

Abstract
Newborn altricial mammals need just after birth to locate their mother's nipples for suckling. In this precocious behavior, including for the human baby, maternal odor via the olfactory process plays a major role. Maternal odor emitted by lactating females or by amniotic fluid (AF) attracts pups, but the chemical identity of this attractant has not yet been elucidated. Here, using behavioral tests and gas chromatography coupled with mass spectrometry (GC-MS) techniques, we show that AF extracts from rat pregnant female, nipples, ventral skin, milk, and nest extracts of mother contained 3-6 active substances. AF extracts contained 3 active compounds: ethylbenzene, benzaldehyde, and benzyl alcohol, and their mixture in similar proportions to those found in AF extracts, in a ratio, respectively, of 1:1:12 (700 ng), attracts pups as putative maternal attractant substances (MAS). These 3 AF substances have already been identified in milk, nipples, ventral wash, and nest extracts of mother, but not in feces. Moreover, anethole flavor incorporated in pregnant rat and mother's diet is also detected in AF, nipples, milk, and nest extracts and the pups are attracted to anethole odor, but not in the case of the no-anethole pups. MAS, combined with diet flavors present in the AF bath, represent olfactory signals as "maternal signature odors" (MSO) that are learned by fetus and pups. These findings open the way to improved understanding of the neurobiology of early olfactory learning and of the importance of evolutionarily conserved survival behavior in many mammal species.

PMID: 28007788 [PubMed - indexed for MEDLINE]

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Factors Associated with Inaccurate Self-Reporting of Olfactory Dysfunction in Older US Adults.

Factors Associated with Inaccurate Self-Reporting of Olfactory Dysfunction in Older US Adults.

Chem Senses. 2017 Mar 01;42(3):223-231

Authors: Adams DR, Wroblewski KE, Kern DW, Kozloski MJ, Dale W, McClintock MK, Pinto JM

Abstract
Self-reported olfactory function has poor sensitivity (i.e., people with measured olfactory dysfunction are unlikely to accurately report it). We aimed to identify factors associated with lack of awareness of smell dysfunction. Objective odor identification was evaluated using a validated 5-item test in respondents from the National Social Life, Health, and Aging Project, a representative sample of home-dwelling, US adults ages 57-85 (n = 1468). Self-reported olfaction was assessed with a 5-point Likert scale. Using multivariate logistic regression, we tested factors that might influence inaccuracy of self-reported olfaction, including age, gender, race/ethnicity, education, marital status, cognition, comorbidity, smoking, depression, anxiety, self-rated mental and physical health, and social activity. Among older US adults, 12.4% reported their sense of smell as fair or poor, while 22.0% had objective olfactory dysfunction (≤3 items correct out of 5). Among those with measured olfactory dysfunction, 74.2% did not recognize it; these individuals were more likely to be older, Black, never married, and to have worse cognitive function compared to individuals who recognized their dysfunction (P < 0.05, all). Individuals who lacked awareness of their olfactory dysfunction had the greatest cognitive impairment at 5-year follow-up, followed by individuals aware of their dysfunction and finally normosmics (P < 0.001). Older Americans with measured olfactory dysfunction are unlikely to report it, and those who lack awareness of this dysfunction have distinct demographic, social, and cognitive characteristics. Therefore, clinicians should objectively test patients. Individuals who lack awareness of their olfactory dysfunction have poor cognitive outcomes and should receive additional clinical scrutiny.

PMID: 28007787 [PubMed - indexed for MEDLINE]

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Πέμπτη 10 Αυγούστου 2017

Arginyl dipeptides increase the frequency of NaCl-elicited responses via epithelial sodium channel alpha and delta subunits in cultured human fungiform taste papillae cells.

Arginyl dipeptides increase the frequency of NaCl-elicited responses via epithelial sodium channel alpha and delta subunits in cultured human fungiform taste papillae cells.

Sci Rep. 2017 Aug 08;7(1):7483

Authors: Xu JJ, Elkaddi N, Garcia-Blanco A, Spielman AI, Bachmanov AA, Chung HY, Ozdener MH

Abstract
Salty taste is one of the five basic tastes and is often elicited by NaCl. Because excess sodium intake is associated with many health problems, it could be useful to have salt taste enhancers that are not sodium based. In this study, the regulation of NaCl-induced responses was investigated in cultured human fungiform taste papillae (HBO) cells with five arginyl dipeptides: Ala-Arg (AR), Arg-Ala (RA), Arg-Pro (RP), Arg-Glu (RE), and Glu-Arg (ER); and two non-arginyl dipeptides: Asp-Asp (DD) and Glu-Asp (ED). AR, RA, and RP significantly increased the number of cell responses to NaCl, whereas no effect was observed with RE, ER, DD, or ED. We also found no effects with alanine, arginine, or a mixture of both amino acids. Pharmacological studies showed that AR significantly increased responses of amiloride-sensitive but not amiloride-insensitive cells. In studies using small interfering RNAs (siRNAs), responses to AR were significantly decreased in cells transfected with siRNAs against epithelial sodium channel ENaCα or ENaCδ compared to untransfected cells. AR dramatically increased NaCl-elicited responses in cells transfected with NHE1 siRNA but not in those transfected with ENaCα or ENaCδ siRNAs. Altogether, AR increased responses of amiloride-sensitive cells required ENaCα and ENaCδ.

PMID: 28790369 [PubMed - in process]

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Whole transcriptome profiling of taste bud cells.

Whole transcriptome profiling of taste bud cells.

Sci Rep. 2017 Aug 08;7(1):7595

Authors: Sukumaran SK, Lewandowski BC, Qin Y, Kotha R, Bachmanov AA, Margolskee RF

Abstract
Analysis of single-cell RNA-Seq data can provide insights into the specific functions of individual cell types that compose complex tissues. Here, we examined gene expression in two distinct subpopulations of mouse taste cells: Tas1r3-expressing type II cells and physiologically identified type III cells. Our RNA-Seq libraries met high quality control standards and accurately captured differential expression of marker genes for type II (e.g. the Tas1r genes, Plcb2, Trpm5) and type III (e.g. Pkd2l1, Ncam, Snap25) taste cells. Bioinformatics analysis showed that genes regulating responses to stimuli were up-regulated in type II cells, while pathways related to neuronal function were up-regulated in type III cells. We also identified highly expressed genes and pathways associated with chemotaxis and axon guidance, providing new insights into the mechanisms underlying integration of new taste cells into the taste bud. We validated our results by immunohistochemically confirming expression of selected genes encoding synaptic (Cplx2 and Pclo) and semaphorin signalling pathway (Crmp2, PlexinB1, Fes and Sema4a) components. The approach described here could provide a comprehensive map of gene expression for all taste cell subpopulations and will be particularly relevant for cell types in taste buds and other tissues that can be identified only by physiological methods.

PMID: 28790351 [PubMed - in process]

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Τετάρτη 9 Αυγούστου 2017

Appraisal of unimodal cues during agonistic interactions in Maylandia zebra.

Appraisal of unimodal cues during agonistic interactions in Maylandia zebra.

PeerJ. 2017;5:e3643

Authors: Chabrolles L, Ben Ammar I, Fernandez MSA, Boyer N, Attia J, Fonseca PJ, Amorim MCP, Beauchaud M

Abstract
Communication is essential during social interactions including animal conflicts and it is often a complex process involving multiple sensory channels or modalities. To better understand how different modalities interact during communication, it is fundamental to study the behavioural responses to both the composite multimodal signal and each unimodal component with adequate experimental protocols. Here we test how an African cichlid, which communicates with multiple senses, responds to different sensory stimuli in a social relevant scenario. We tested Maylandia zebra males with isolated chemical (urine or holding water coming both from dominant males), visual (real opponent or video playback) and acoustic (agonistic sounds) cues during agonistic interactions. We showed that (1) these fish relied mostly on the visual modality, showing increased aggressiveness in response to the sight of a real contestant but no responses to urine or agonistic sounds presented separately, (2) video playback in our study did not appear appropriate to test the visual modality and needs more technical prospecting, (3) holding water provoked territorial behaviours and seems to be promising for the investigation into the role of the chemical channel in this species. Our findings suggest that unimodal signals are non-redundant but how different sensory modalities interplay during communication remains largely unknown in fish.

PMID: 28785523 [PubMed]

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Πέμπτη 3 Αυγούστου 2017

Clinical practice guideline for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons (ASCRS) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)

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Reply

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Anne M. Fitzpatrick, Daniel J. Jackson, David Mauger, Stanley J. Szefler

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Reply

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Elien Gevaert, Shida Yousefi, Claus Bachert, Hans-Uwe Simon

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Nonatopic persistent asthma in children, a missed phenotype of asthma?

Publication date: Available online 3 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Giorgio Longo, Ester Conversano, Elisa Panontin, Giovanna Ventura, Alessandro Ventura

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Diagnosis and management of anaphylaxis in precision medicine

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Mariana Castells
Anaphylaxis is the most severe and frightening of the allergic reactions, placing patients at high risk and demanding prompt recognition and immediate management by health care providers. Yet because its symptoms imitate those of other diseases, such as asthma and urticaria, current data suggest that its diagnosis is often missed, with underuse of tryptase measurement; its treatment is delayed, with little use of epinephrine; and its underlying cause or causes are poorly investigated. Deaths from anaphylaxis are difficult to investigate because of miscoding. Surprisingly, patients treated with new and powerful chemotherapy agents and humanized mAbs present with nonclassical symptoms of anaphylaxis, and patients may present with unrecognized clonal mast cell disorders with KIT mutations may present as Hymenoptera-induced or idiopathic anaphylaxis. The goal of this review is to recognize the presentations of anaphylaxis with the description of its current phenotypes, to provide new insight and understanding of its mechanisms and causes through its endotypes, and to address its biomarkers for broad clinical use. Ultimately, the aim is to empower allergists and heath care providers with new tools that can help alleviate patients' symptoms, preventing and protecting them against anaphylaxis.

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Diagnosis and management of anaphylaxis in precision medicine

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2

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The pathophysiology of anaphylaxis

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Laurent L. Reber, Joseph D. Hernandez, Stephen J. Galli
Anaphylaxis is a severe systemic hypersensitivity reaction that is rapid in onset; characterized by life-threatening airway, breathing, and/or circulatory problems; and usually associated with skin and mucosal changes. Because it can be triggered in some persons by minute amounts of antigen (eg, certain foods or single insect stings), anaphylaxis can be considered the most aberrant example of an imbalance between the cost and benefit of an immune response. This review will describe current understanding of the immunopathogenesis and pathophysiology of anaphylaxis, focusing on the roles of IgE and IgG antibodies, immune effector cells, and mediators thought to contribute to examples of the disorder. Evidence from studies of anaphylaxis in human subjects will be discussed, as well as insights gained from analyses of animal models, including mice genetically deficient in the antibodies, antibody receptors, effector cells, or mediators implicated in anaphylaxis and mice that have been "humanized" for some of these elements. We also review possible host factors that might influence the occurrence or severity of anaphylaxis. Finally, we will speculate about anaphylaxis from an evolutionary perspective and argue that, in the context of severe envenomation by arthropods or reptiles, anaphylaxis might even provide a survival advantage.

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Mast cell activation syndromes

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Cem Akin
Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced or if their activation is out of proportion to the perceived threat to homeostasis. Mast cell activation syndrome refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release. Despite introduction of diagnostic criteria and some advances in treatment in the last decade, many areas of mast cell activation syndrome are in need of research. This article reviews our current knowledge about the various types of mast cell activation disorders, their treatment, and areas of uncertainty in need of future investigation.

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The Editors' Choice

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Cezmi A. Akdis, Zuhair K. Ballas

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News Beyond Our Pages

Publication date: August 2017
Source:Journal of Allergy and Clinical Immunology, Volume 140, Issue 2
Author(s): Marc E. Rothenberg, Jean Bousquet

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Is it truly wise to remove the ‘Safe Surgery Checklist Use’ reporting requirements?

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Yisi D. Ji, Jeffrey T. Hajibandeh

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The Use of Platelet Rich Fibrin for Immediate Closure of Acute Oroantral Communications: An Alternative Approach

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Kani Bilginaylar
Currently, buccal advancement flap, palatal rotational flap or buccal fat pad techniques are frequently used to close an oroantral communication (OAC). In this study,platelet rich fibrin (PRF) clots were used for immediate closure of acute oroantral communications after the extraction of posterior maxillary molars. Acute oroantral perforations of more than 3 mm in diameter in 21 patients were treated uneventfully by using PRF clots. None of the patients had systemic diseases nor symptoms of sinus disease. After tooth extraction, the diagnosis of acute oroantral communication was examined by Valsalva's maneuver test (compression of nostrils with the fingers and blowing out the air). After the detection of an air leak, modification of a ball burnisher instrument of 3 mm diameter was used to determine whether the size of perforation was greater than 3 mm. The post-extraction socket of the tooth was cleaned with a sterile physiologic saline solution, and the cavity was filled with PRF. PRF clots were sutured to the gingiva to prevent them from migrating to the sinus and for stabilization. On the 7th day of follow-up, healthy granulation tissue was observed, and on the third week of follow-up, epithelialized oral mucosa was detected at the extraction site across all cases. This technique (PRF) enables the closure of OACs without a primary flap closure or any other surgical interventions. Thus, the use of PRF for immediate closure of acute OACs will make the treatment of OACs less traumatic and easier and will eliminate the need for special surgical expertise.

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Evaluation of mandibular bone after dental extraction in rats treated with antiresorptive drugs

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Victor Lousan Do Nascimento Poubel, Diogo Lenzi Capella, Adair Roberto Soares Santos, Márcio Correa, Letícia Ruhland Correa, Elena Riet Correa Rivero
PurposeZoledronic acid (ZOL) and denosumab (Dmab) are commonly used to treat bone pathologies. Given that both drugs suppress bone metabolism, this study sought to compare their effect on bone repair after tooth extraction.Materials and MethodsFour-week-old male Wistar rats were randomly assigned to three groups receiving either 0.125 mg/kg ZOL or 0.25 mg/kg Dmab (treatment groups), or 10 ml/kg saline solution (control group). After 1 week of treatment, the first left molar was extracted; the rats were euthanized at 28 days. The jaws were removed and photographed for macroscopic analysis of wound healing, and then, were subjected to tomographic analysis and histological analysis. Immunohistochemistry was carried out against receptor activator of nuclear Kappa-B ligand (RANKL) and osteoprotegerin (OPG).ResultsNo difference was found between the groups in terms of wound healing, presence of inflammatory infiltrate and bone sequestration, or osteocyte expression of RANKL and OPG. On tomography analysis, the ZOL group showed less alveolar resorption and more complete alveolar repair compared with the other groups. There was a statistically significant difference in OPG marker in the control (P=0.008) and ZOL group (P=0.05) when comparing the extracted and non-extracted sides.ConclusionThe systemic use of ZOL can improve alveolar bone healing; however, the potential risk for the development of osteonecrosis should be considered. Higher expression of OPG seems to be associated with osteoclastogenesis control during bone repair.

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Effect of resveratrol on critical-sized calvarial defects of diabetic rats: Histometric and gene expression analysis

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Danilo Siqueira Pino, Renato Correa Casarin, Suzana Peres Pimentel, Fabiano Ribeiro Cirano, Mônica Grazieli Corrêa, Fernanda Vieira Ribeiro
PurposeThis study aimed to determine the influence of resveratrol (RESV) on the repair of bone critical defects in calvaria of animals with induced diabetes mellitus (DM).Material and methodsOne hundred rats were divided into five groups: induced DM + RESV administration (DM+RESV; n = 20); induced DM + placebo solution administration (DM+PLAC; n = 20); induced DM + insulin therapy (DM+INS; n = 20); induced DM + administration of resveratrol and insulin (DM+RESV+INS; n = 20); and non-diabetic controls (NDM; n = 20). Diabetes was induced by intraperitoneal injection of 50 mg/kg streptozotocin, three days before surgical procedures. Two critical calvarial defects were created in each animal at the start of the study (day zero). Treatments were administered from day zero to day 30 of the experiment, when animals were euthanized. One of the defects was processed for histometric analysis to measure the closure of the bone defect. The tissue of the other defect was analyzed for quantification of BMP-2, OPN, OPG, RANKL, Runx2, Osx, β-catenin, Lrp-5, and Dkk-1 mRNA by quantitative PCR.ResultsHistometric results showed that the DM+RESV, DM+RESV+INS, and NDM groups exhibited greater closure of the bone defects as compared to the placebo- or insulin-treated groups (p < 0.05). Diabetic animals treated with RESV+INS showed higher levels of BMP-2 and Osx; Osx was also positively increased in animals treated with INS alone (p < 0.05).ConclusionsThe use of RESV, regardless of the presence of INS, positively influenced bone repair in DM-induced animals. Further, the combination of insulin with RESV is necessary for the modulation of BMP-2 gene expression.

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Clinicopathologic and surgical study of pleomorphic adenoma of the parotid gland: Analysis of risk factors for recurrence and facial nerve dysfunction

Publication date: Available online 3 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Carlos A. Espinosa, Álvaro Fernández-Valle, Paloma Lequerica-Fernández, Lucas de Villalaín, Juan Carlos de Vicente
ObjectiveTo determine whether clinicopathologic or surgical features are risk factors for recurrence and facial nerve dysfunction in pleomorphic adenoma (PA) of the parotid gland.Patients and methodsThe records of 198 patients surgically treated for a PA of the parotid gland between 1999 and 2013 were retrospectively reviewed to identify patients who developed a tumor recurrence. Fisher's exact test and Mann-Whitney U test were used to analyze patient characteristics between recurrent and non-recurrent PAs. Logistic regression was used to determine the risks of recurrence and facial nerve dysfunction.Results23 (11.6%) patients developed a recurrence. Patients with tumor recurrence were significantly younger than patients that remained recurrence free. Of the 14 patients who underwent enucleation, 11 cases (78.6%) experienced residual disease, as did 10 of 165 (6%) of patients managed by a superficial parotidectomy (p < 0.0005). Furthermore, the risk of residual disease was 9.3 to 21.6 times higher in patients who underwent enucleation than in those who underwent a total or superficial parotidectomy. Regarding tumor histology, recurrence was observed in 3 (15.8%) of the 19 cellular types, in 18 (11.5%) of the 157 classic cases, and in 1 (4.8%) of the 21 myxoid cases (p = 0.5). The risk of recurrence if the resection margins were positive was 49 times higher than when they were not affected (p = 0.001).ConclusionYoung age, enucleation, and positive margins are risk factors for residual pleomorphic adenoma, and surgical technique and histomorphologic features are associated with increased facial nerve dysfunction.

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Publication date: August 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 2

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The Essentials

Editorial Board

News and Notes

Piezosurgery in Modified Pterional Orbital Decompression Surgery in Graves Disease

Publication date: October 2017
Source:World Neurosurgery, Volume 106
Author(s): Juergen Grauvogel, Christian Scheiwe, Waseem Masalha, Nadja Jarc, Tanja Grauvogel, Andreas Beringer
ObjectivePiezosurgery uses microvibrations to selectively cut bone, preserving the adjacent soft tissue. The present study evaluated the use of piezosurgery for bone removal in orbital decompression surgery in Graves disease via a modified pterional approach.MethodsA piezosurgical device (Piezosurgery medical) was used in 14 patients (20 orbits) with Graves disease who underwent orbital decompression surgery in additional to drills and rongeurs for bone removal of the lateral orbital wall and orbital roof. The practicability, benefits, and drawbacks of this technique in orbital decompression surgery were recorded. Piezosurgery was evaluated with respect to safety, preciseness of bone cutting, and preservation of the adjacent dura and periorbita. Preoperative and postoperative clinical outcome data were assessed.ResultsThe orbital decompression surgery was successful in all 20 orbits, with good clinical outcomes and no postoperative complications. Piezosurgery proved to be a safe tool, allowing selective bone cutting with no damage to the surrounding soft tissue structures. However, there were disadvantages concerning the intraoperative handling in the narrow space and the efficiency of bone removal was limited in the orbital decompression surgery compared with drills.ConclusionsPiezosurgery proved to be a useful tool in bone removal for orbital decompression in Graves disease. It is safe and easy to perform, without any danger of damage to adjacent tissue because of its selective bone-cutting properties. Nonetheless, further development of the device is necessary to overcome the disadvantages in intraoperative handling and the reduced bone removal rate.

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Effectiveness of spinal cord stimulation for painful camptocormia with Pisa syndrome in Parkinson’s disease: a case report

Spinal cord stimulation (SCS) has recently been reported to be effective for truncal postural abnormalities such as camptocormia and Pisa syndrome in Parkinson's disease. In this case report, we describe a cas...

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Safety and efficacy of topical timolol treatment of infantile haemangioma: A prospective trial

Abstract

Topical timolol therapy is considered a relatively "safer" alternative for the treatment of infantile haemangiomas (IH); however, sufficient supportive pharmacokinetic data does not exist. Most efficacy studies have not evaluated systemic absorption.^1-5 To our knowledge, this is the first prospective trial to assess the clinical response of proliferating IH to topical timolol maleate 0.5% gel-forming solution and to determine if systemic absorption occurred.Twenty-six subjects enrolled in this trial approved by the UCSD IRB.

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TNF antagonist induced lupus: a critically appraised topic

Abstract

TNF antagonist induced lupus is diagnosed upon a temporal relationship of TNF antagonist therapy and the development of four of the 11 American college of rheumatology (ACR) diagnostic criteria for lupus.

We critically appraise the literature on TNF antagonist induced lupus, focusing on the diagnostic criteria, dermatological manifestations, management and outcome.

Eighty cases of TNF antagonist induced lupus that met the ACR criteria were included and analysed. Infliximab was the most commonly reported agent (58.8%, n=47). Cutaneous manifestations were the most common presentation (67.5%, n=54,), specifically malar rash (26.3%, n=21) and photosensitivity (23.4%, n=19). Lupus symptoms resolved in all cases (n=80), withdrawal of the TNF antagonist was sufficient in 18.8% of cases (n=15), additional immunosuppression was required in the remaining cases. Four patients were treated with a second, different TNF antagonist, with no recurrence of symptoms. TNF antagonist induced lupus appears to have a good prognosis and treatment should be tailored to each individual case. As cutaneous features are the most common manifestation it is important that dermatologists are aware of the ACR diagnostic criteria of lupus to ensure accurate diagnoses of TNF antagonist induced lupus.

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Prognostic importance of a second invasive primary melanoma according to tumor stage

Abstract

It is well known that a considerable proportion of the Caucasian population in many countries are diagnosed with multiple melanomas over time¹. Despite this, most analyses of melanoma survival, including that of the American Joint Committee on Cancer (AJCC), consider only one tumor for every patient and disregard the potential effect of multiple melanomas on outcomes and this is reflected in the lack of specific management guidelines for patients with multiple melanomas beyond those dictated by the clinicopathological features of each tumour^2-4.

Recently we and others have shown that patients with multiple primary invasive melanomas have an increased risk of melanoma death compared to patients with a single melanoma^5,6.

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Alternative Method to Evaluate the Adaptation of Implant-Supported Multi-Unit Prosthetic Frameworks

Abstract

Purpose

Various methods to evaluate the adaptation of dental prostheses are available; however, only a few of these methods assess the adaptation of the framework as a whole. This study aimed to propose an alternative method to evaluate the adaptation of implant-supported multi-unit Co–Cr alloy frameworks.

Materials and Methods

A four-unit framework supported by two implants was designed using a computer. Six dots with a diameter of 0.2 mm were designed randomly using 3Shape software on the abutment surface of the framework for measurement. Then, Co–Cr frameworks were fabricated via the milled and selective laser melting (SLM) techniques (n = 10 for each technique). They were subsequently scanned and exported as files in stereolithography format. The distances between two dots roughly along 3D directions were measured in both the designed framework and fabricated frameworks. The differences in distances were calculated. The adaptation of the frameworks was also evaluated using the impression replica method. The data were compared and statistically analyzed via t-test.

Results

The average difference of the distances between the designed and milled frameworks was 0.046 ± 0.057 mm when evaluated using the new method. This result was significantly different from that between the designed and SLM frameworks (0.073 ± 0.048 mm, p < 0.05). The average marginal gap width of the milled frameworks was 44.44 ± 8.61 μm when evaluated using the impression replica method. This result was also significantly different from that of the SLM frameworks (57.31 ± 7.97 μm, p < 0.05).

Conclusions

The new method can evaluate the adaptation of implant-supported multi-unit frameworks, thereby making assessments more effective and comprehensive when it is combined with the traditional impression replica technique.

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An Evaluation of the Effect of Periodontal Biotype on Inter-Dental Papilla Proportions, Distances Between Facial and Palatal Papillae in the Maxillary Anterior Dentition

Abstract

Purpose

Gingival esthetics are an essential segment of facial beauty. The aim of the present study was to clinically assess the impact of periodontal biotype (PB), the length between the base of interproximal contact area and the interproximal bone crest (CP-BC), the distance between the facial and palatal papillae (DFPP), and papillary proportions (PP) on the presence of interdental papillae (PIP).

Materials and Methods

80 patients aged 18 to 60 years were recruited for study. PB and CP-BC were evaluated clinically. Alginate impressions of maxillary arches were made, and DFPPs were measured using a digital Vernier caliper. The impressions were later poured in dental stone, and PP were calculated.

Results

Descriptive statistics and ANOVA were used for statistical analysis for correlation among the variables. A greater proportion of individuals who had a thick PB (77.7%) had significantly higher amounts of PIP than did patients with thin PB (60.7%) (p < 0.01). A strong significant positive correlation was found between PIP in thick PB patients and DFPP (p < 0.01, r = 0.56); DFPP and PP (p < 0.01, r = 0.61). A strong negative correlation was seen between PIP in thin PB and DFPP (p < 0.01, r = –0.67).

Conclusion

According to the results of this study, PB affected the heights and presence of maxillary interdental papillae by affecting papilla proportion and distances between the facial and palatal papillae.

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Canalicular adenoma: a systematic review

Publication date: Available online 3 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Alberto J. Peraza, John Wright, Ruth Gómez
ObjectiveCanalicular adenoma (CA) is an uncommon but unique benign tumor of salivary gland origin. It is the third most common benign tumor of minor salivary glands, representing less than 1% of all salivary neoplasms. A systematic review is presented of reported cases of CA, to determine trends in presentation, diagnostic features, treatment, and patient outcome.MethodsSearches of specific databases, as reported, were carried out to identify papers reporting CA. The variables were patient symptoms, tumor location, histopathological findings, demographics, treatment, follow-up, and recurrence.Results430 cases were identified; the most common location was in the upper lip (55.4%), followed by hard palate (14.5%). The most common clinical presentation was a nodule (46.5%), followed by asymptomatic (29.5%), and discomfort (28.7%). CA was most frequently seen in females (64%). The average age was 66.3 years. 97% of cases were treated surgically. The average follow-up was 136.3 months, and recurrence was reported in 3% of the cases.ConclusionCA shows a strong predilection for the upper lip. CAs are frequently asymptomatic, but the principal symptom was pressure.

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Aesthetic facial perception and need for intervention in laterognathism in women of different ethnicities

Publication date: Available online 3 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Priscilla Bispo de Carvalho Barbosa, Pâmela Leticia dos Santos, João Paulo De Carli, Paulo Henrique Luiz de Freitas, Matheus Melo Pithon, Luiz Renato Paranhos
This study compared the perception of facial pleasantness and the need for intervention, as assessed by orthodontists, oral and maxillofacial (OMF) surgeons, and laypersons, in people of different ethnicities showing varying degrees of simulated laterognathism. Facial photographs were modified to simulate deviations in the lower face of women of African, Asian and Caucasian descent, ascending in two-degree steps from zero to eight degrees of deviation. Three groups of 20 individuals each (OMF surgeons, orthodontists, and laypersons) assessed the images and rated facial pleasantness on a numerical scale ranging from 0 to 10. The results showed that orthodontists and laypersons rated faces differently only after six and eight degrees of facial change. OMF surgeons rated faces statistically differently from laypersons in all degrees of deviation, and differently from orthodontists in faces with zero, two, and four degrees of deviation. Scores for Caucasian and Asian faces differed only at two degrees of deviation. On the other hand, Caucasian and African faces differed at two and four degrees of deviation, while African and Asian faces differed only at eight degrees. The results suggest that, as a group, OMF surgeons were able to detect all degrees of lower face deviation. Moreover, orthodontists and OMF surgeons seemed to agree in terms of need for facial intervention, and saw that need more often than laypersons. In addition, ethnicity also affected the perception of milder facial changes.

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A customised digitally engineered solution for fixed dental rehabilitation in severe bone deficiency: A new innovative line extension in implant dentistry

Publication date: Available online 3 August 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Nils-Claudius Gellrich, Rüdiger M. Zimmerer, Simon Spalthoff, Philipp Jehn, Philipp-Cornelius Pott, Majeed Rana, Björn Rahlf

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A new technique for creating a neo-umbilicus in abdominoplasty

Publication date: Available online 3 August 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): L. Martinez-Teixido, J.M. Serra-Mestre, J.M. Serra-Renom
BackgroundThe umbilicus is an essential feature of the abdomen. In this article we describe a new technique for creating a neo-umbilicus in abdominoplasties.MethodsThirty consecutive women underwent abdominoplasty with our new technique for recreating the navel. The new navel is created at the midpoint between the xiphoid process and the pubic symphysis by defatting a cylinder of fat tissue as far as the dermis, which is then sutured to the rectus muscle to enable it to "take" in the same way as a total skin graft, and form a hollow which will be the new navel. Patients were divided into three groups according to BMI (group A<25; B 25-29.9; C >=30). Results were rated on a scale of 0-10 by external observers and by the patients. Complications were recorded.ResultsGroups B and C obtained median scores of 10/10 from both the external raters and the patients (range 1) while in group A the medians were 6/10 and 7/10 respectively (ranges 6 and 5).ConclusionsOur new technique presents a series of advantages: it allows the positioning of the new navel in any location; it does not create periumbilical scarring, and it can be used in cases in which the original pedicle and vascularization of the navel cannot be preserved. It appears to achieve good aesthetic results and high levels of satisfaction among patients; however, it is less effective in very thin patients, in whom the navel remains flat due to the lack of adipose tissue.

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Re: Impact of the Method and Success of Pharyngeal Reconstruction on the Outcome of Treating Laryngeal and Hypopharyngeal Cancers with Pharyngolaryngectomy: A National Analysis

Publication date: Available online 3 August 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): F. Lo Torto, J. Kaciulyte, P. Ciudad, M. Agko, O.J. Manrique, D. Ribuffo, H.C. Chen
Life expectancy is crucial to evaluate in patients that undergo pharyngolaryngectomy, in order to be able to choose the best reconstructive strategy for each case. Ileocolon free flap represents our preference when voice reconstruction is aimed, especially in patients with long life expectancy.

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Brazilian Portuguese version of the Female Genital Self Image Scale (FGSIS) for women seeking abdominoplasty

Publication date: Available online 3 August 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Gabriel de Almeida Arruda Felix, Fabio Xerfan Nahas, Giulianna Barreira Marcondes, Aline Garcia dos Santos, Maria José Azevedo de Brito, Lydia Masako Ferreira

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Jargon Muddies Radiology Reports, Including About Cancers

Even radiologists themselves are uncertain about the meaning of an array of commonly used phrases
Medscape Medical News

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Validierung medizinethischer Entscheidung am Krankenbett durch die Obduktion

Zusammenfassung

Hintergrund

Empfehlungen von Ethikkomitees am Lebensende im Hinblick auf Therapiebegrenzung sind oftmals komplexe Entscheidungen und können kontrovers diskutiert werden.

Fragestellung

Kann eine Obduktion die Empfehlung des Ethikkomitees zur Therapieeinschränkung am Lebensende objektivieren?

Material und Methode

Wir stellen einen exemplarischen Fall eines Patienten mit Endokarditis und septischer Infarzierung im Gehirn vor. Während der intensivmedizinischen Behandlung fanden 2 ethische Fallberatungen statt, wobei das Ausmaß der Erkrankung und die Prognose kontrovers diskutiert wurden. Nach der Empfehlung zur Therapiebegrenzung verstarb der Patient. Die Obduktionsbefunde, die im Detail vorgestellt werden, bestätigten ein infaustes Krankheitsbild mit weitgehender Destruktion des Herzens und disseminierten Hirninfarkten.

Schlussfolgerung

Die Obduktion ist ein wesentliches Instrument der Objektivierung der Erkrankung und dient der Untermauerung der Entscheidung zur Therapiebegrenzung am Lebensende. Sie stellt somit ein wertvolles Instrument der Qualitätssicherung bei medizinethischen Fragestellungen dar.

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Improved survival in Medicare patients with multiple myeloma: findings from a large nationwide and population-based cohort

Abstract

The aim of this study was to examine whether novel agents proteasome inhibitor bortezomib and immunomodulatory drugs lenalidomide and thalidomide are effective in prolonging overall survival (OS) for patients with newly diagnosed multiple myeloma (MM) in the real-world practice setting. A nationwide and population-based retrospective cohort of elderly patients with advanced newly diagnosed MM from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results–Medicare linked data. Survival was compared between cases in 2005–2009 and in 2000–2004, and between patients treated with anti-MM therapy and the untreated among cases in 2005–2009, using Cox proportional hazards models, Kaplan–Meier methods, and propensity score adjustment to further control for baseline confounding. Of 8839 patients, 4028 (45.6%) cases were in 2000–2004 and 4811 (54.4%) in 2005–2009. OS was significantly longer for patients in 2005–2009 than patients in 2000–2004 (27.9 vs. 20.0 months, P < 0.001). The hazard ratio for OS for cases in 2005–2009 compared with those in 2000–2004 was 0.78 (95% CI 0.74–0.82). Among 4811 cases in 2005–2009, 54% (n = 2587) received anti-MM therapy. Compared to those untreated, OS was significantly longer (41.1 vs. 27.9 months, P < 0.001) and hazard ratio was 0.58 (95% CI 0.54–0.62) in the treated patients. This study demonstrated improved survival in newly diagnosed MM patients in a more recent 5-year cohort compared with those in the previous 5 years. The survival benefit was significant across different demographic and patient characteristics. However, there were still a substantial number of MM patients not receiving anti-MM therapy.

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Neurotrophin Gene Therapy in Deafened Ears with Cochlear Implants: Long-term Effects on Nerve Survival and Functional Measures

Abstract

Because cochlear implants function by stimulating the auditory nerve, it is assumed that the condition of the nerve plays an important role in the efficacy of the prosthesis. Thus, considerable research has been devoted to methods of preserving the nerve following deafness. Neurotrophins have been identified as a potential contributor to neural health, but most of the research to date has been done in young animals and for short periods (less than 3 to 6 months) after the onset of treatment. The first objective of the current experiment was to examine the effects of a neurotrophin gene therapy delivery method on spiral ganglion neuron (SGN) preservation and function in the long term (5 to 14 months) in mature guinea pigs with cochlear implants. The second objective was to examine several potential non-invasive monitors of auditory nerve health following the neurotrophin gene therapy procedure. Eighteen mature adult male guinea pigs were deafened by cochlear perfusion of neomycin and then one ear was inoculated with an adeno-associated viral vector with an Nft3-gene insert (AAV.Ntf3) and implanted with a cochlear implant electrode array. Five control animals were deafened and inoculated with an empty AAV and implanted. Data from 43 other guinea pig ears from this and previous experiments were used for comparison: 24 animals implanted in a hearing ear, nine animals deafened and implanted with no inoculation, and ten normal-hearing non-implanted ears. After 4 to 21 months of psychophysical and electrophysiological testing, the animals were prepared for histological examination of SGN densities and inner hair cell (IHC) survival. Seventy-eight percent of the ears deafened and inoculated with AAV.Ntf3 showed better SGN survival than the 14 deafened-control ears. The degree of SGN preservation following the gene therapy procedure was variable across animals and across cochlear turns. Slopes of psychophysical multipulse integration (MPI) functions were predictive of SGN density, but only in animals with preserved IHCs. MPI was not affected by the AAV.Ntf3 treatment, but there was a minor improvement in temporal integration (TI). AAV.Ntf3 treatment had significant effects on ECAP and EABR amplitude growth func-tion (AGF) slopes; the reduction in slope in deafened ears was ameliorated by the AAV.Ntf3 treatment. Slopes of the ECAP and EABR AGFs were predictive of SGN density in a broad area near and just apical to the implant. The highest ensemble spontaneous activity (ESA) values were seen in animals with surviving IHCs, but AAV.Ntf3 treatment in deafened ears resulted in slightly higher ESA values compared to deafened untreated ears. Overall, a combination of the psychophysical and electrophysiological measures can be useful for monitoring the health of the implanted cochlea in guinea pigs. These measures should be applicable for assessing cochlear health in human subjects.

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Local IL-25 contributes to Th2-biased inflammatory profiles in nasal polyps

Summary

Background

IL-25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to evaluate the association of IL-25 with the Th2-biased inflammatory profiles in CRSwNP.

Methods

Nasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL-25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT-qPCR, and ELISA. The inflammatory profiles and clinical characteristics of 2 NP subtypes (IL-25^high and IL-25^low) were evaluated, and the effects of IL-25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro.

Results

The mRNA and protein levels of IL-25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL-25^high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL-25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro.

Conclusions

Local IL-25 plays a crucial role in promoting Th2-biased inflammatory profiles in NP, and may serve as a promising therapeutic target in CRSwNP patients.

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Challenges in the implementation of EAACI Guidelines on Allergen Immunotherapy: A global perspective on the regulation of allergen products

Abstract

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly by either obtaining a marketing authorisation or by being distributed as named patient products. Exemptions from marketing authorisations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

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Assessment of eosinophilic airway inflammation as a contribution to the diagnosis of occupational asthma

Abstract

Background

Ascertaining the presence of asthma through the assessment of nonspecific bronchial hyperresponsiveness (NSBH) is a key step in the diagnosis of occupational asthma (OA). We aimed at investigating whether indices of airway inflammation including fractional exhaled nitric oxide (FeNO) and sputum eosinophils would be useful adjuncts to the measurement of NSBH in diagnosing OA defined as a positive specific inhalation challenge (SIC).

Methods

The study included 240 consecutive subjects with a suspicion of OA who completed a SIC, of whom 133 showed a positive response. The sensitivity, specificity, and predictive values of NSBH, and FeNO, as well as sputum eosinophil counts assessed at baseline of the SIC were determined.

Results

A concentration of histamine inducing a 20% decline in FEV₁ (PC₂₀) ≤16 mg/mL showed a sensitivity of 87% and a specificity of 36%. A FeNO level ≥25 ppb and a sputum eosinophil count ≥ 2% provided lower sensitivity rates (47% and 39%, respectively) than the PC20 value. Eight of the 17 subjects without baseline NSBH despite a positive SIC showed a sputum eosinophil count ≥2%, a FeNO level ≥25 ppb or both outcomes. Combining either a PC₂₀ value ≤16mg/mL or a FeNO ≥25 ppb increased the sensitivity to 91%. Using either a PC₂₀ ≤16mg/mL or a sputum eosinophil count ≥1% increased the sensitivity to 94%.

Conclusion

Adding the assessment of FeNO level and sputum eosinophils to NSBH improves the identification of subjects who may have OA and require further objective testing before excluding the possibility of OA.

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Long-term evaluation of a Canadian back pain mass media campaign

Abstract

Purpose

This paper evaluates the long-term impact of a Canadian mass media campaign on general public beliefs about staying active when experiencing low back pain (LBP).

Methods

Changes in beliefs about staying active during an episode of LBP were studied using telephone and web-based surveys. Logistic regression analysis was used to investigate changes in beliefs over time and the effect of exposure to campaign messaging.

Results

The percentage of survey respondents agreeing that they should stay active through LBP increased annually from 58.9 to ~72.0%. Respondents reporting exposure to campaign messaging were statistically significantly more likely to agree with staying active than respondents who did not report exposure to campaign messaging (adjusted OR, 95% CI = 1.96, 1.73–2.21).

Conclusion

The mass media campaign had continued impact on public LBP beliefs over the course of 7 years. Improvements over time were associated with exposure to campaign messaging.

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Stress enhances gait disturbance induced by lumbar disc degeneration in rat

Abstract

Purpose

Although psychological factors are assumed to be the primary cause of stress-related back pain, there have been no studies of the relationships between stress and low back pain in an animal model. The purpose of this study was to examine the influence of specific alternation of rhythm in temperature (SART) stress on gait abnormality using the CatWalk method in a rat model of low back pain caused by lumbar facetectomy.

Methods

Sixty rats were divided into three groups: the control, sham and experimental groups. Each group was then divided into non-SART stress and SART stress subgroups. We evaluated the behavioral changes 7 weeks postoperatively using the von Frey test and the CatWalk method.

Results

Threshold values for the hind paw in the SART stress subgroups were significantly lower than those in the non-SART stress subgroups. In the experimental group, significant changes by CatWalk in step cycle, stand time and average speed were observed under non-SART stress conditions, but SART stress resulted in additional significant changes in not only these parameters, but in other parameters including the duty cycle and swing time, compared with those in the control and sham groups.

Conclusions

The demonstration by CatWalk analysis may indicate that SART stress enhanced gait disturbance. In this animal model, we demonstrated for the first time that stress may be a factor involved in worsening of low back pain.

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Editorial Board

Publication date: September 2017
Source:Clinical Neurology and Neurosurgery, Volume 160

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Leveraging the Medical Context to Increase Upper Extremity Reconstruction among Patients with Tetraplegia: A Qualitative Analysis

Publication date: Available online 3 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chelsea A. Harris, John-Michael Muller, Melissa J. Shauver, Kevin C. Chung
Objectives(1) To characterize patients' medical experiences from initial injury until they become candidates for Upper Extremity Reconstruction (UER). (2) To identify points in this medical context that may be most amenable to interventions designed to increase UER utilization.DesignA qualitative cross-sectional study using grounded theory methodology and constant comparative analysis of data collected through semi-structured individual interviews.SettingCommunityParticipantsA sample of individuals with C4-C8 cervical spinal injuries (N=19) who sustained injuries at least one year prior to interview. Nine patients had undergone reconstruction, ten had not. The study sample was predominantly male (79%), white (89%), and ASIA Grade A-D were represented (Grade A: 42%; Grade B: 32%; Grade C 16%; Grade D 10%).InterventionsnoneMain Outcome MeasuresParticipant self-report of their medical experiences from the time of injury through the early recovery period.ResultsWe identified three domains that formed patients' medical context prior to UER candidacy: (1) their ability to achieve and maintain health; (2) their relationship with health care providers; and (3) their expectations regarding clinicians' tetraplegia-specific expertise. Trust emerged as a major theme driving potential intervention targets. Patients transferred to referral centers had higher trust in tertiary providers relative to local physicians. In the outpatient setting, patients' trust correlated with the tetraplegia-specific expertise level they perceived the specialty to have (high for PM&R, intermediate for urology, low for primary care).ConclusionsIn appropriate candidates, UER produces substantial functional gains, but reconstruction remains underutilized in the tetraplegic population. By analyzing how patients achieve health and build trust in early recovery/injury, our study provides strategies to improve UER access. We propose that interventions targeting highly trusted points of care (transfer hospitals) and avoiding low-trust points (PCPs, home health) will be most effective. Urology may represent a novel entry point for UER interventions.

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Investigating The Efficacy of Web-based Transfer Training on Independent Wheelchair Transfers through Randomized Control Trials

Publication date: Available online 3 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Lynn Worobey, Stephanie Rigot, Nathan Hogaboom, Chris Venus, Michael L. Boninger
ObjectivesTo determine the efficacy of a web-based transfer training module at improving transfer technique across three groups: web-based training, in-person training (current standard of practice), and a waitlist control group (WLCG). Secondarily, to determine subject factors that can be used to predict improvements in transfer ability after training.DesignRandomized control trials.SettingSummer and winter sporting events for disabled veterans.ParticipantsA convenience sample of manual and power wheelchair users who could transfer independently (n=71).InterventionsAn individualized, in-person transfer training session or a web-based transfer training module. The WLCG received the web training at their follow-up visit.Main Outcome MeasureTransfer assessment instrument (TAI) part 1 score was used to assess transfers at baseline, skill acquisition immediately post-training, and skill retention after a 1-2 day follow-up period.ResultsThe in-person and web-based training groups improved their median [interquartile range] TAI scores from 7.98 [7.18-8.46] to 9.13 [8.57-9.58, p<0.01], and from 7.14 [6.15-7.86] to 9.23 [8.46-9.82, p<0.01], respectively, compared to the WLCG that had a median score of 7.69 for both assessments [baseline: 6.15-8.46, follow-up control: 5.83-8.46]. Participants retained improvements at follow-up (p>0.05). A lower initial TAI score was found to be the only significant predictor of a larger percent change in TAI score after receiving training.ConclusionsTransfer training can improve technique with changes retained within a short follow-up window, even among experienced wheelchair users. Web-based transfer training demonstrated comparable improvements to in-person training. With almost half of the United States population consulting online resources before a healthcare professional, web-based training may be an effective method to increase knowledge translation.

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Canalicular adenoma: a systematic review

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Aesthetic facial perception and need for intervention in laterognathism in women of different ethnicities

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A customised digitally engineered solution for fixed dental rehabilitation in severe bone deficiency: A new innovative line extension in implant dentistry

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Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer

Abstract

Background

Twist1 is involved in tumor initiation and progression, which especially contributes to tumor invasion and metastasis. Wogonoside is the main in-vivo metabolite of wogonin, and it is also a natural product with potential treatment effects against cancer.

Methods

In this study, we investigated the in-vitro anti-invasion and in-vivo anti-metastasis effects of wogonoside on breast cancer cells and uncovered its underlying mechanism.

Results

The results showed that wogonoside could suppress the growth and metastasis of breast tumor in the orthotopic model of MDA-MB-231 cells. We found that wogonoside could reduce the overexpression of TNF-α, TRAF2 and TRAF4 in later stage of tumor, and improved tumor microenvironment. Therefore, TNF-α was utilized to induce metastases of breast cancer cell in vitro. Wogonoside could inhibit invasion and migration in TNF-α-induced MDA-MB-231, MDA-MB-435, and BT-474 cells. Mechanically, wogonoside inactivated NF-κB signaling through decreasing the protein expression of TRAF2/4, which further inhibited Twist1 expression. Consequently, wogonoside could down-regulate MMP-9, MMP-2, vimentin and CD44v6 expression in TNF-α-induced MDA-MB-231 and MDA-MB-435 cells. Then, these findings were proved in TNF-α + TGF-β1-induced MCF7 cells.

Conclusions

Wogonoside might be a potential therapeutic agent for the treatment of tumor metastasis in breast cancer.

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The paradigm of tumor shrinkage and rapid liver remnant hypertrophy for conversion of initially unresectable colorectal liver metastasis: a case report and literature review

Abstract

Background

For colorectal liver metastasis (CRLM) patients, hepatic resection is currently the sole cure offering the chance of long-term survival. Tumor shrinkage and planned liver remnant hypertrophy are the two key strategies for conversion of initially unresectable CRLM. First conducted in 2012, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver growth. As a means to induce hypertrophy, portal vein embolization (PVE) has been widely applied before extending hepatectomy. Recently, Peng et al. present a new approach of terminal branches portal vein embolization (TBPVE), offering an efficient way to amplify FLR and making chances for surgery in 2 weeks.

Case presentation

We reported a 61-year-old woman with synchronous hepatic metastasized carcinoma of the colon sigmoideum underwent TBPVE after 6 cycles of neoadjuvant therapy in order to perform a planned right trisectionectomy. Rapid liver remnant hypertrophy and remarkable tumor shrinkage were achieved, and laparoscopic sigmoidectomy and right trisectionectomy were successfully performed. The postsurgical course was uneventful and 7 months of recurrence-free survival have been witnessed.

Conclusions

The dual tactics of tumor shrinkage and planned rapid liver remnant hypertrophy will make concerted efforts to further increase the clinical candidacy for curative resection, which are valuable for further investigation.

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Dense cancellous bone as evidenced by a high HU value is predictive of late implant failure: a preliminary study

Abstract

Objectives

The mechanism of late implant failure is unclear. This study examined the association between sclerosing cancellous bone images and the risk of late implant failures using multi-detector row computed tomography (CT) imaging data.

Methods

We performed a case–control study. The study group consisted of consecutive patients with implant failures treated at Kyushu Dental University between 2001 and 2016. CT data for late failure of 36 implants in 16 patients were available. The study cohort consisted of 16 patients with 36 late failed implants and 28 patients with 113 successful implants.

Results

The mean survival rate was 6.9 months for early implant failure, 76.6 months for late failure with marginal bone resorption, inflammation symptoms, and so-called peri-implantitis, and 95.0 months for late failure caused by implant fracture. The mean HU value for cases in the control group was 507 compared with 1231 for cases with late failure implants. Logistic regression was used for analysis. There were signs of high radiodensity of peri-implant cancellous bone when comparing adjusted radiodensity per 100 HU using CT data (OR 2.35; 95% CI 1.73–3.20; p < 0.001).

Conclusions

Within the limits of our study, the presence of high radiodensity and cancellous bone consolidation on imaging may be related to risk factors for late implant failure. Therefore, CT images of the host cancellous bone status for observation of visible sclerosis could be a useful diagnostic indicator for late implant failure.

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Training Needs of Clinical and Research Professionals to Optimize Minority Recruitment and Retention in Cancer Clinical Trials

Abstract

The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority patient populations. However, clinical trial recruitment is complex and requires a broader appreciation of the multiple factors that influence minority participation. One area that has received little attention is minority recruitment training for professionals who assume various roles in the clinical trial recruitment process. Therefore, we assessed the perspectives of cancer center clinical and research personnel on their training and education needs toward minority recruitment for cancer clinical trials. Ninety-one qualitative interviews were conducted at five U.S. cancer centers among four stakeholder groups: cancer center leaders, principal investigators, referring clinicians, and research staff. Interviews were recorded and transcribed. Qualitative analyses focused on response data related to training for minority recruitment for cancer clinical trials. Four prominent themes were identified: (1) Research personnel are not currently being trained to focus on recruitment and retention of minority populations; (2) Training for minority recruitment and retention provides for a specific focus on factors influencing minority research participation; (3) Training on cultural awareness may help to bridge cultural gaps between potential minority participants and research professionals; (4) Views differ regarding the importance of research personnel training designed to focus on recruitment of minority populations. There is a lack of systematic training for minority recruitment. Many stakeholders acknowledged the benefits of minority recruitment training and welcomed training that focuses on increasing cultural awareness to increase the participation of minorities in cancer clinical trials.

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Neurotrophin Gene Therapy in Deafened Ears with Cochlear Implants: Long-term Effects on Nerve Survival and Functional Measures

Abstract

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Her2 Challenge Contest: A Detailed Assessment of Automated Her2 Scoring Algorithms in Whole Slide Images of Breast Cancer Tissues

Abstract

Aims

Evaluating expression of the Human epidermal growth factor receptor 2 (Her2) by visual examination of immunohistochemistry (IHC) on invasive breast cancer (BCa) is a key part of the diagnostic assessment of BCa due to its recognised importance as a predictive and prognostic marker in clinical practice. However, visual scoring of Her2 is subjective and consequently prone to inter-observer variability. Given the prognostic and therapeutic implications of Her2 scoring, a more objective method is required. In this paper, we report on a recent automated Her2 scoring contest, held in conjunction with the annual PathSoc meeting held in Nottingham in June 2016, aimed at systematically comparing and advancing the state-of-the-art Artificial Intelligence (AI) based automated methods for Her2 scoring.

Methods and Results

The contest dataset comprised of digitised whole slide images (WSI) of sections from 86 cases of invasive breast carcinoma stained with both Haematoxylin & Eosin (H&E) and IHC for Her2. The contesting algorithms automatically predicted scores of the IHC slides for an unseen subset of the dataset and the predicted scores were compared with the "ground truth" (a consensus score from at least two experts). We also report on a simple Man vs Machine contest for the scoring of Her2 and show that the automated methods could beat the pathology experts on this contest dataset.

Conclusions

This paper presents a benchmark for comparing the performance of automated algorithms for scoring of Her2. It also demonstrates the enormous potential of automated algorithms in assisting the pathologist with objective IHC scoring.

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Altered glutamine metabolism in breast cancer; subtype dependencies and alternative adaptations

Abstract

Cancer cells must alter their metabolism in order to satisfy the demands of necessary energy and cellular building blocks. These metabolic alterations are mediated by many oncogenic changes that affect cellular signalling pathways, which result in sustained cell growth and proliferation. Recently, metabolomics, has received great attention in the field of cancer research and as the essential metabolic pathways that drive tumour growth and progression are determined, the possibilities of new targets for therapeutic intervention are opened. More specifically, as breast cancer is a heterogeneous disease there is growing evidence that differences in metabolic changes exist between molecular subtypes.

In this review, the most recent findings in breast cancer cell metabolism are discussed, with particular emphasis on glutamine and its transporters which is considered one of the key amino acids fuelling cancer growth. Furthermore, the metabolic differences between the molecular subtypes of breast cancer are examined, highlighting the clinical utility for breast cancer diagnosis and treatment.

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Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect

Abstract

Purpose

Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers.

Methods

The study was conducted in 11 healthy men aged 47–57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug.

Results

The novel formulation of AA allows rapid absorption of the compound with t _max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported.

Conclusion

The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

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Pretreatment glycemic control status is an independent prognostic factor for cervical cancer patients receiving neoadjuvant chemotherapy for locally advanced disease

Abstract

Background

To investigate whether poor glycemic control status has a negative impact on survival outcomes and tumor response to chemotherapy in patients receiving neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC).

Methods

A retrospective cohort study was conducted to examine LACC patients undergoing NACT and radical hysterectomy between 2002 and 2011. Patients were divided into three groups: patients without diabetes mellitus (DM), diabetic patients with good glycemic control, and diabetic patients with poor glycemic control. Hemoglobin A_1c (HbA_1c) levels were used to indicate glycemic control status. Recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed using log-rank tests and Cox proportional hazards models.

Results

In total, 388 patients were included and had a median follow-up time of 39 months (range: 4–67 months). Diabetes mellitus (DM) was diagnosed in 89 (22.9%) patients, only 35 (39.3%) of whom had good glycemic control prior to NACT (HbA_1c < 7.0%). In survival analysis, compared with patients with good glycemic control and patients without DM, patients with poor glycemic control (HbA_1c ≥ 7.0%) exhibited decreased recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). In multivariate analysis, HbA_1c ≥ 7.0% was identified as an independent predictor for decreased RFS (hazard ratio [HR] = 3.33, P < 0.0001), CSS (HR = 3.60, P < 0.0001) and OS (HR = 4.35, P < 0.0001). In the subgroup of diabetic patients, HbA_1c ≥ 7.0% prior to NACT had an independent negative effect on RFS (HR = 2.18, P = 0.044) and OS (HR = 2.29, P = 0.012). When examined as a continuous variable, the HbA_1c level was independently associated with decreased RFS (HR = 1.39, P = 0.002), CSS (HR = 1.28, P = 0.021) and OS (HR = 1.27, P = 0.004). Both good (odds ratio [OR] = 0.06, P < 0.0001) and poor glycemic control (OR = 0.04, P < 0.0001) were independently associated with a decreased likelihood of complete response following NACT.

Conclusions

Poor glycemic control is an independent predictor of survival and tumor response to chemotherapy for patients receiving NACT for LACC.

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Frequency of Human papillomavirus in women attending cervical cancer screening program in Chile

Abstract

Background

Human papillomavirus (HPV) is the etiological factor for cervical cancer and its precursor lesions. The characterization of HPV genotypes in preneoplastic lesions and cervical cancer could establishes the effectiveness of vaccination plan in Chilean population. The aim of this study was to determine HPV frequency in a group of women including in a cervical screening program in the public health care system in Chile.

Methods

We analyzed 985 cervical smears samples from women with different histological diagnosis, attending to public health care in Temuco-Chile between 2004 and 2012, to detect HPV genotypes, through PCR followed by reverse line blotting assay.

Results

HPV was found present in 80.8% (n = 796) of samples. Only a 5.6% of 985 samples were infected with a low-risk HPV, considering multiple infections. 10.5% (n = 8/76) of normal cervical epithelia, 83.5% (n = 208/249) and 87.6% (n = 557/636) of low and high grade squamous intraepithelial lesions, respectively, and 95.8% (n = 23/24) of squamous cervical carcinomas tested positive for HPV. HPV 16 was the most frequent genotype found (Overall 44.9%, n = 442/985; SCC: 62.5%, n = 15/24). A high variability of HPV types was also found in preneoplastic lesions, whereas there was a selection of genotypes in neoplasia. Also, there was a higher risk of infection with HPV 16 in women ≤26 years and 34–41 years old (p < 0.05), meanwhile infections with HPV 16 or HPV 18 have related with cancer development (p < 0.01).

Conclusions

These data provide further information about the frequency of HPV genotypes in women with cervical lesions in Chile, and the introduction of new targeted vaccines against a wider spectrum of HPV is suggested.

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18 F-FDG PET/CT response in a phase 1/2 trial of nab- paclitaxel plus gemcitabine for advanced pancreatic cancer

Abstract

Background

Positron emission tomography (PET) is poised to become a useful imaging modality in staging and evaluating therapeutic responses in patients with metastatic pancreatic cancer (mPC). This analysis from a phase 1/2 study examined the utility of early PET imaging in patients with mPC treated with nab-paclitaxel plus gemcitabine.

Methods

Tumors were measured by [¹⁸F]2-fluoro-2-deoxyglucose PET/computed tomography (CT) in patients who received nab-paclitaxel 100 (n = 13), 125 (n = 38), or 150 (n = 1) mg/m² plus gemcitabine 1000 mg/m² on days 1, 8, and 15 of a 28-day cycle. Lesion metabolic activity was evaluated at baseline and 6 and 12 weeks postbaseline.

Results

Fifty-two patients had baseline and ≥1 follow-up PET scan. The median maximum standardized uptake values per pancreatic lesion in the nab-paclitaxel 100 mg/m² and 125 mg/m² cohorts were 5.1 and 6.5, respectively. Among patients who had a metabolic response by PET, those who received nab-paclitaxel 125 mg/m² had a 4-month survival advantage over those who received 100 mg/m². All patients in the nab-paclitaxel 125 mg/m² cohort experienced an early complete metabolic response (CMR; 34%) or partial metabolic response (PMR; 66%). In the nab-paclitaxel 125 mg/m² cohort, investigator-assessed objective response rates were 77% and 44% among patients with a CMR and PMR, respectively, with no correlation between PET and CT response (Spearman r _s = 0.22; P = 0.193). Patients in the nab-paclitaxel 125 mg/m² cohort with a CMR experienced a significantly longer overall survival vs those with a PMR (median, 23.0 vs 11.2 months; P = 0.011), and a significant correlation was found between best percentage change in tumor burden by PET and survival: for each 1% decrease in PET score, the risk of death decreased by 2%.

Conclusions

The majority of primary pancreatic tumors and their metastases were PET avid, and PET effectively measured changes in tumor metabolic activity at 6 and 12 weeks. These results support the antitumor activity of nab-paclitaxel 125 mg/m² plus gemcitabine 1000 mg/m² for treating mPC and the utility of PET for measuring treatment response. Treatment response by PET analysis may be considered when evaluating investigational agents in mPC.

Trial registration

NCT00398086.

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Πληροφορίες

Πέμπτη 31 Αυγούστου 2017

Τετάρτη 30 Αυγούστου 2017

Κυριακή 20 Αυγούστου 2017

Πέμπτη 17 Αυγούστου 2017

Πέμπτη 10 Αυγούστου 2017

Τετάρτη 9 Αυγούστου 2017

Πέμπτη 3 Αυγούστου 2017

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