Head and Neck Diseases by Alexandros G.Sfakianakis: 01/23/17

Δευτέρα 23 Ιανουαρίου 2017

Sleep and plasticity in the visual cortex: more than meets the eye

Publication date: June 2017
Source:Current Opinion in Neurobiology, Volume 44
Author(s): Marcos G Frank
The visual cortex has provided key insights into how experience shapes cortical circuitry. Scientists have identified how different manipulations of visual experience trigger distinct forms of plasticity as well as many of the underlying cellular and molecular mechanisms. Intriguingly, experience is not the only factor driving plasticity in the visual system. Sleep is also required for the full expression of plasticity in the developing visual cortex. In this review, I discuss what we have learned about the role of sleep in visual cortical plasticity and what it tells us about sleep function.

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Trauma responses to intimate partner violence: A review of current knowledge

Publication date: Available online 23 January 2017
Source:Aggression and Violent Behavior
Author(s): Natalie Pill, Andrew Day, Helen Mildred
It is now well established that those who are survivors of intimate partner violence are at increased risk of subsequently experiencing a wide range of mental health problems. Among the most significant of these is Posttraumatic Stress Disorder (PTSD), although relatively little is known about its course and onset in this particular group. It has also been suggested that the diagnosis of PTSD is often insufficient and, at times, inappropriate, when seeking to account for the effects of repeated trauma, with the construct of Complex Posttraumatic Stress Disorder proposed as an alternative. This review critically evaluates current thinking and research in this area, highlighting the implications of this body of work for understanding the consequences of aggressive and violent behavior directed toward intimate partners.

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Does the pursuit of meaning explain the initiation, escalation, and disengagement of violent extremists?

Publication date: Available online 23 January 2017
Source:Aggression and Violent Behavior
Author(s): Rosleenda B. Mohamed Ali, Simon A. Moss, Kate Barrelle, Peter Lentini
Researchers have uncovered an array of conditions, characteristics, and cognitions that can ignite, escalate, or reverse the radicalization of individuals. Because a multitude of events and circumstances determine the likelihood that people gravitate to violent extremism, practitioners cannot readily ascertain which individuals are most susceptible to this pathway. This paper explicates and explores a theory, derived from the meaning maintenance model and the socio-emotional selectivity theory, that integrates previous insights into a cohesive framework. According to this theory, to foster meaning in life, individuals are motivated to cultivate four conditions: a just and supportive environment, unambiguous standards, enduring values, and extensive capabilities. Violent extremism offers some individuals the opportunity to cultivate these conditions temporarily, galvanizing radicalization. Yet this pursuit can also impede these conditions, provoking the motivation to disengage from this endeavor. We presented a case study that illustrates this premise. In short, the motivations that can attract people to violent extremism can also promote disengagement as well.

http://ift.tt/2jM76I4

Psychoeducational programs for reducing prison violence: A systematic review

Publication date: Available online 24 January 2017
Source:Aggression and Violent Behavior
Author(s): Katherine M. Auty, Aiden Cope, Alison Liebling
Institutional violence presents significant challenges to the accomplishment of legitimate social order in prison. This systematic review examines the effect of psychoeducational programs on violent behaviour in prison. Comprehensive searches of the empirical research literature were conducted to identify randomized and non-randomized studies carried out in the last two decades (1996–2016) that compared psychoeducational programs with treatment as usual (TAU). The content of programs was analysed and classified. The design of the studies was subject to a risk of bias analysis and quality assessment. Violent behaviour in prison was measured by institutional reports, inmate self-reports, observer ratings, or using psychometrically-valid scales. We identified 21 separate studies with considerable variations in program quality and evaluation methodology. The majority of programs adopted a cognitive behavioural or social learning approach. There was limited evidence for the efficacy of these programs, although highly-structured programs showed the most promise. Programs that aimed to integrate their treatment ethos into the institutional regime and target specific criminogenic risks also produced evidence of effectiveness in reducing institutional violence. The current evidence base does not provide a clear answer to the 'what works' question in reducing institutional violence. However, there is evidence that some approaches are more successful than others and this should guide future program design and evaluation.

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Tanning practice, perception, and sunburn among Emirati youth

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Influence of substituent heteroatoms on the cytoprotective properties of pyrimidinol antioxidants

Publication date: Available online 23 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Arnaud Chevalier, Omar M. Khdour, Margaret Schmierer, Indrajit Bandyopadhyay, Sidney M. Hecht
Recently, we described the optimization of novel pyrimidinol-based antioxidants as potential therapeutic molecules for targeting mitochondrial diseases. That study focused on improving the potency and metabolic stability of pyrimidinol antioxidants. This led us to consider the possibility of altering the positions of the exocyclic alkoxy and alkylamino substituents on the pyrimidinol scaffold. Twelve new analogues were prepared and their biological activities were investigated. The metabolic stability of the prepared regioisomers was also assessed in vitro using bovine liver microsomes. Unexpectedly, the 2-alkoxy-4-alkylamino substituted pyrimidinol antioxidants were found to have properties in protecting mitochondrial function superior to the isomeric 4-alkoxy-2-alkylamino substituted pyrimidinols evaluated in all earlier studies. This observation suggests a possible mode of action involving the intermediacy of an ortho-iminoquinone, a species not previously associated with mitochondrial respiratory chain function.

Graphical abstract

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A Continuous Flow Synthesis and Derivatization of 1,2,4-Thiadiazoles

Publication date: Available online 23 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Marcus Baumann, Ian R. Baxendale
A continuous flow process is presented that enables the efficient synthesis and derivatization of 1,2,4-thiadiazole heterocycles. Special attention was given to the safe handling of the versatile yet hazardous trichloromethane sulfenylchloride reagent including its in-line quenching in order to eliminate malodourous and corrosive by-products. Based on this flow method gram quantities of 5-chloro-3-phenyl-1,2,4-thiadiazole were safely prepared allowing for further elaboration of this valuable building block by reaction with different nitrogen-, sulfur- and oxygen-based nucleophiles. This synthetic approach was subsequently applied to generate a series of bromophenyl-5-chloro-1,2,4-thiadiazoles providing a valuable entry towards further structural diversification on this important heterocyclic scaffold.

Graphical abstract

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Carbonic anhydrases from Trypanosoma and Leishmania as anti-protozoan drug targets

Publication date: Available online 24 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Alane B. Vermelho, Giseli R. Capaci, Igor A. Rodrigues, Verônica S. Cardoso, Ana Maria Mazotto, Claudiu T. Supuran
Trypanosoma cruzi and Leishmania spp. are protozoa of the Trypanosomatidae family, being the etiological agents of two widespread parasitic diseases, Chagas disease and leishmaniasis, respectively. Both parasites are the focus of worldwide research with the aim to find effective and less toxic drugs than the few ones available so far, and for controlling the spread of the diseases. Carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α- and β-class were recently identified in these protozoans and several studies suggested that they could be new targets for drug development. Sulfonamide, thiol and hydroxamate inhibitors effectively inhibited the α-CA from T. cruzi (TcCA) and the β-CA from L. donovani chagasi (LdccCA) in vitro, and some of them also showed in vivo efficacy in inhibiting the growth of the parasites in animal models of Chagas disease and leishmaniasis. As few therapeutic options are presently available for these orphan diseases, protozoan CA inhibition may represent a novel strategy to address this stringent health problem.

Graphical abstract

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Unilateral Head Impulses Training in Uncompensated Vestibular Hypofunction

The aim of this paper is to report a case of a young woman with unilateral vestibular chronic failure with a poorly compensated vestibuloocular reflex during rapid head rotation. Additionally, she developed migraine symptoms during the treatment with associated chronic dizzy sensations and blurred vision. Her report of blurred vision only improved after she completed a rehabilitation program using fast head impulse rotations towards the affected side for 5 consecutive days. We discuss why we elected this form of treatment and how this method may be useful for different patients.

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Editorial Board

Publication date: January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1867, Issue 1

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Reviewer Acknowledgement

Publication date: January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1867, Issue 1

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Publisher Note

Publication date: January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1867, Issue 1

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Unilateral Head Impulses Training in Uncompensated Vestibular Hypofunction

Dynamic Risk Estimates of Outcome in Chinese Patients with Well-Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation

Thyroid , Vol. 0, No. 0.

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Iodine in Malt Whisky: A Preliminary Analysis

Thyroid , Vol. 0, No. 0.

http://ift.tt/2jkvim2

Dynamic Risk Estimates of Outcome in Chinese Patients with Well-Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation

Thyroid , Vol. 0, No. 0.

http://ift.tt/2jrkgJw

Iodine in Malt Whisky: A Preliminary Analysis

Thyroid , Vol. 0, No. 0.

http://ift.tt/2jkvim2

Pulsatile tinnitus and carotid artery dissection

Carotid artery dissection is an uncommon entity associated with head and neck pain, partial Horner's syndrome, amaurosis fugax, and brain ischemia, which may all occur in isolation or in combination. Herein, we report a rare case of cervical artery dissection in which pulsatile tinnitus was the only reported symptom. A 38-years-old man attended our hospital with a 4-days history of left side pulsatile tinnitus which began after stumbling. He had no other symptom. MRA showed luminal stenosis with pseudo lumen of the internal carotid artery.

http://ift.tt/2kbIyYw

The association between insomnia symptoms and cardiovascular risk factors in patients who complete outpatient cardiac rehabilitation

The present study investigated whether completion of an exercise-based cardiac rehabilitation (CR) program was associated with improvements in both traditional cardiovascular risk factors and insomnia symptoms, and whether degree of improvement in insomnia symptom severity was associated with degree of improvement in cardiovascular risk.

http://ift.tt/2jWBXE7

Association of sleep-disordered breathing and disturbed cardiac repolarization in patients with ST-segment elevation myocardial infarction

In patients with ST-segment elevation myocardial infarction (STEMI), disturbed cardiac repolarization before percutaneous coronary intervention (PCI) is a risk factor for malignant ventricular arrhythmia. We tested the hypothesis that sleep-disordered breathing (SDB) in patients with STEMI is associated with disturbed cardiac repolarization.

http://ift.tt/2kbMhpi

Description of sleep paralysis in The Brothers Karamazov by Dostoevsky

Sleep paralysis (SP) is defined as the inability to perform voluntary movements or speak at sleep onset or on awakening. The duration of SP ranges from seconds to a few minutes.1 SP represents a dissociated state in which REM sleep atonia coexists with the full consciousness of wakefulness. Individuals experience SP as an unpleasant phenomenon during which they are completely awake but cannot move or speak, usually with feelings of suffocation or chest pressure. The association with vivid hallucinations is common.

http://ift.tt/2jWlsbo

Risks Associated with Use of Stimulant Medications in Patients with Obstructive Sleep Apnea and Cardiomyopathy: A Case-Control Study

Stimulant medications are indicated in patients with obstructive sleep apnea (OSA) who experience sleepiness despite optimal control of sleep-disordered breathing. The safety of stimulant medications in patients with OSA and co-morbid cardiomyopathy is unknown. We performed a case-control study to assess cardiovascular outcomes and mortality risk associated with stimulant use in this group of patients.

http://ift.tt/2kbLepa

Sleepiness and activity in heart failure patients with reduced ejection fraction and central sleep-disordered breathing

Patients with heart failure (HF) and sleep disordered breathing (SDB) are typically not sleepy, unlike patients without heart failure. Previous work in HF patients with obstructive SDB suggested that sleepiness was associated with a reduction in daytime activity. The consequences of predominately central SDB on sleepiness in HF are less well understood. The aim of this study was to test the hypothesis that subjective sleepiness is associated with reduced daytime activity in HF patients with central SDB, compared to those without SDB.

http://ift.tt/2jWlYG1

Pulsatile tinnitus and carotid artery dissection

Publication date: Available online 23 January 2017
Source:Auris Nasus Larynx
Author(s): Yuya Shimizu, Masato Yagi
Carotid artery dissection is an uncommon entity associated with head and neck pain, partial Horner's syndrome, amaurosis fugax, and brain ischemia, which may all occur in isolation or in combination. Herein, we report a rare case of cervical artery dissection in which pulsatile tinnitus was the only reported symptom. A 38-years-old man attended our hospital with a 4-days history of left side pulsatile tinnitus which began after stumbling. He had no other symptom. MRA showed luminal stenosis with pseudo lumen of the internal carotid artery. The patient was diagnosed with left internal carotid artery dissection and treated with antihypertensive therapy accordingly. After 2 months, the stenosis and tinnitus spontaneously resolved.

http://ift.tt/2jWwahX

Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types.

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Esculentin-2CHa(1-30) and its analogues: stability and mechanisms of insulinotropic action

The insulin-releasing effects, cellular mechanisms of action and anti-hyperglycaemic activity of 10 analogues of esculentin-2CHa lacking the cyclic C-terminal domain (CKISKQC) were evaluated. Analogues of the truncated peptide, esculentin-2CHa(1–30), were designed for plasma enzyme resistance and increased biological activity. Effects of those analogues on insulin release, cell membrane integrity, membrane potential, intracellular Ca²⁺ and cAMP levels were determined using clonal BRIN-BD11 cells. Their acute effects on glucose tolerance were investigated using NIH Swiss mice. d-Amino acid substitutions at positions 7(Arg), 15(Lys) and 23(Lys) and fatty acid (l-octanoate) attachment to Lys at position 15 of esculentin-2CHa(1–30) conveyed resistance to plasma enzyme degradation whilst preserving insulin-releasing activity. Analogues, [d-Arg⁷,d-Lys¹⁵,d-Lys²³]-esculentin-2CHa(1–30) and Lys¹⁵-octanoate-esculentin-2CHa(1–30), exhibiting most promising profiles and with confirmed effects on both human insulin-secreting cells and primary mouse islets were selected for further analysis. Using chemical inhibition of adenylate cyclase, protein kinase C or phospholipase C pathways, involvement of PLC/PKC-mediated insulin secretion was confirmed similar to that of CCK-8. Diazoxide, verapamil and Ca²⁺ omission inhibited insulin secretion induced by the esculentin-2CHa(1–30) analogues suggesting an action on K_ATP and Ca²⁺ channels also. Consistent with this, the analogues depolarised the plasma membrane and increased intracellular Ca²⁺. Evaluation with fluorescent-labelled esculentin-2CHa(1–30) indicated membrane action, with internalisation; however, patch-clamp experiments suggested that depolarisation was not due to the direct inhibition of K_ATP channels. Acute administration of either analogue to NIH Swiss mice improved glucose tolerance and enhanced insulin release similar to that observed with GLP-1. These data suggest that multi-acting analogues of esculentin-2CHa(1–30) may prove useful for glycaemic control in obesity-diabetes.

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Jab1 is a T2-dependent coactivator or a T3-dependent corepressor of TRB1-mediated gene regulation

Thyroid hormones (THs) induce pleiotropic effects in vertebrates, mainly through the activation or repression of gene expression. These mechanisms involve thyroid hormone binding to thyroid hormone receptors, an event that is followed by the sequential recruitment of coactivator or corepressor proteins, which in turn modify the rate of transcription. In the present study, we looked for specific coregulators recruited by the long isoform of the teleostean thyroid hormone receptor beta 1 (L-Trb1) when bound to the bioactive TH, 3,5-T₂ (T₂). We found that jun activation domain-binding protein1 (Jab1) interacts with L-Trb1 + T₂ complex. Using both the teleostean and human TRB1 isoforms, we characterized the Jab1–TRB1 by yeast two-hybrid, pull-down and transactivation assays. Our results showed that the TRB1–Jab1 interaction was ligand dependent and involved the single Jab1 nuclear receptor box, as well as the ligand-binding and N-terminal domains of TRB1. We also provide evidence of ligand-dependent, dual coregulatory properties of Jab1. Indeed, when T₂ is bound to L-Trb1 or hTRB1, Jab1 acts as a coactivator of transcription, whereas it has corepressor activity when interacting with the T₃-bound S-Trb1 or hTRB1. These mechanisms could explain some of the pleiotropic actions exerted by THs to regulate diverse biological processes.

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IgG trough levels and progression of pulmonary disease in pediatric and adult CVID patients

Capsule summary: Common variable immunodeficiency patients show silent progression of airway disease which was inversely correlated to IgG trough levels. A randomized controlled study into optimal IgG through levels to prevent pulmonary disease progression is warranted.

http://ift.tt/2klXq6f

Defects in Lymphocyte Telomere Homeostasis Contribute to Cellular Immune phenotype in Cartilage-Hair Hypoplasia

Patients with CHH often have lymphopenia and impaired lymphocyte proliferation. These defects appear to result from altered lymphocyte telomere homeostasis and may confer susceptibilities to infection and malignancy for the patient with CHH.

http://ift.tt/2iYxxNy

Screening test recommendations for methicillin-resistant Staphylococcus aureus surveillance practices: A cost-minimization analysis

Publication date: Available online 23 January 2017
Source:American Journal of Infection Control
Author(s): Melanie D. Whittington, Donna J. Curtis, Adam J. Atherly, Cathy J. Bradley, Richard C. Lindrooth, Jonathan D. Campbell
BackgroundTo mitigate methicillin-resistant Staphylococcus aureus (MRSA) infections, intensive care units (ICUs) conduct surveillance through screening patients upon admission followed by adhering to isolation precautions. Two surveillance approaches commonly implemented are universal preemptive isolation and targeted isolation of only MRSA-positive patients.MethodsDecision analysis was used to calculate the total cost of universal preemptive isolation and targeted isolation. The screening test used as part of the surveillance practice was varied to identify which screening test minimized inappropriate and total costs. A probabilistic sensitivity analysis was conducted to evaluate the range of total costs resulting from variation in inputs.ResultsThe total cost of the universal preemptive isolation surveillance practice was minimized when a polymerase chain reaction screening test was used ($82.51 per patient). Costs were $207.60 more per patient when a conventional culture was used due to the longer turnaround time and thus higher isolation costs. The total cost of the targeted isolation surveillance practice was minimized when chromogenic agar 24-hour testing was used ($8.54 per patient). Costs were $22.41 more per patient when polymerase chain reaction was used.ConclusionsFor ICUs that preemptively isolate all patients, the use of a polymerase chain reaction screening test is recommended because it can minimize total costs by reducing inappropriate isolation costs. For ICUs that only isolate MRSA-positive patients, the use of chromogenic agar 24-hour testing is recommended to minimize total costs.

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Oral care in ventilated intensive care unit patients: Observing nursing behavior through standardization of oral hygiene tool placement

Publication date: Available online 23 January 2017
Source:American Journal of Infection Control
Author(s): Trevor Lacovara Diaz, Sarah Jane Zanone, Carleigh Charmo-Smith, Houda Kamoun, Anne Isabelle Barrais
A quality improvement project developed between 2 intensive care units using a quasiexperimental pre- and postintervention comparison between nonstandardized placement of oral care equipment in patient rooms and standardized placement of equipment in patient rooms. Daily assessments of equipment use were compared for the control (14 days) and the intervention (15 days) periods to identify a difference in the amount of equipment used by nurses. A significant increase in equipment use by nurses was observed after implementation of the intervention. Standardized design and supply of equipment in patient rooms may help to influence desired nursing behavior related to oral care for ventilated patients.

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APIC MegaSurvey: Methodology and overview

Publication date: Available online 23 January 2017
Source:American Journal of Infection Control
Author(s): Timothy Landers, James Davis, Katrina Crist, Charu Malik
BackgroundInfection preventionists (IPs) play key roles in preventing health care-associated infections and ensuring quality of care. To develop strategies to support comprehensive infection prevention practice, it is critical to understand key aspects of their practice.MethodsA task force of expert IPs, staff representatives from the Association for Professionals in Infection Control and Epidemiology (APIC), and survey designers developed and pilot tested a survey addressing 4 components of infection prevention practice: demographic characteristics, compensation, organizational structure, and practice and competency.ResultsDuring mid- to late-2015, 4,078 APIC members (response rate 31%) participated in the study. Results indicated that all of the practice domains of the APIC Competency Model for the Infection Preventionist were rated as "important" or "very important" to supervisors or managers of IPs. Surveillance and investigation accounted for the most time in an IPs typical day, followed by prevention and control of transmission, identification of infection, and management and communication.DiscussionFuture analyses will examine the validity of the APIC Competency Model for the Infection Preventionist; factors related to professional development, including addressing the needs of IPs who may be ready for certification; and current compensation of IPs.ConclusionsThe results of the APIC MegaSurvey can be used to guide development of programs and initiatives for the future of infection prevention.

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Healthcare Usage after Uvulopalatopharyngoplasty – Impact of Analgesic Regimen

1) Analyze differences in healthcare usage between subjects receiving different perioperative analgesic medications after uvulopalatopharyngoplasty (UPPP) surgery. 2) Comment on the impact of perioperative analgesic medication on length of hospital stay and complications after UPPP.

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Paradoxical Vocal Fold Motion (PVFM) in Pediatric Otolaryngology

Paradoxical vocal fold motion (PVFM) is a condition in which the vocal cords exhibit inappropriate inspiratory adduction, and it has been poorly studied in the pediatric population.

http://ift.tt/2jrsCkb

Healthcare Usage after Uvulopalatopharyngoplasty – Impact of Analgesic Regimen

Paradoxical Vocal Fold Motion (PVFM) in Pediatric Otolaryngology

Sex differences in asthma in swimmers and tennis players

Elite athletes, independent of sport, have increased risk of developing asthma, but little is known about sex difference among adolescent athletes.

http://ift.tt/2kbuIWd

Sex differences in asthma in swimmers and tennis players

Elite athletes, independent of sport, have increased risk of developing asthma, but little is known about sex difference among adolescent athletes.

http://ift.tt/2kbuIWd

Allergy entry and deletion in the electronic health record

Between 20% and 35% of the US population has 1 or more medication allergy listed in their electronic health record (EHR).1,2 However, prescribers override more than 90% of allergy alerts intended to protect patients from adverse drug events,3 recognizing that many EHR drug allergies are incorrect and/or inconsequential to patient care. The EHR allergy section contains missing reaction details,4 discrepancies with patient interview,5,6 and data entered by health care professionals with limited drug allergy training and knowledge.

http://ift.tt/2jkhNmw

Auricular transverse muscle shortening as an adjunct to perichondrium-sparing Mustarde otoplasty

Recently, our article entitled "Antitragicus muscle resection: a key to correction of prominent lobules" was published in this journal.1 In addition to malposition or overdevelopment of the antitragicus muscle causing protrusion of the earlobe, abnormal development of other auricular muscles is also thought to contribute to prominent ears. Yotsuyanagi et al.2 reported that an elongated auricular transverse muscle was associated with poor development of the antihelical fold. Therefore, we attempted to refine the Mustarde otoplasty by performing auricular transverse muscle shortening as an adjunct procedure.

http://ift.tt/2jWi6VM

Allergy entry and deletion in the electronic health record

Two inflammatory phenotypes of nasal polyps and comorbid asthma

Nasal polyps and comorbid asthma (NPCA) is a common united airway disease. However, the inflammatory phenotyes of NPCA are not clear.

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Reply to the letter to the editor “Robotic-assisted Nipple Sparing Mastectomy: A feasibility study on cadaveric models” by Sarfati B. et al

We read with interest the paper by Sarfati et al. [1] reporting a feasibility study on robotic nipple sparing mastectomy on cadaveric models. We acknowledge and we recognize in this report the resourcefulness and geniality of using the new robotic technology to perform one of the operation most frequently performed of all cancer surgery such as mastectomy.

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Two inflammatory phenotypes of nasal polyps and comorbid asthma

Nasal polyps and comorbid asthma (NPCA) is a common united airway disease. However, the inflammatory phenotyes of NPCA are not clear.

http://ift.tt/2kbKjoX

IgE-mediated anaphylactic shock caused by pumpkin seed in an adult

Pumpkin (Cucurbita maxima) is a member of the Cucurbitaceae family.1 Although pumpkin seeds are not a common snack, they do contain large quantities of protein,2 making the idea of incorporating them into various foods attractive. Anaphylaxis has been commonly described in other members of the Cucurbitaceae family and with seeds in general,1 but no cases of anaphylaxis with ingestion of pumpkin seeds in an adult has been described. We describe what we believe is the first reported case of immunoglobulin E (IgE)-mediated anaphylaxis caused by ingestion of pumpkin seeds in an adult.

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The Ulnar Artery Perforator Adipofascial flap: an alternative for vascularised coverage of the Median Nerve

Vascularised tissue for coverage of the median nerve after surgery for persistant or recurrent carpal tunnel syndrome can be a challenging problem. Persistence of median nerve symptoms is consistent with incomplete decompression[1]. Recurrence is documented carpal tunnel syndrome where there was an initially resolution of symptoms following initial decompression[2]. Persistence and recurrence of symptoms may be of differing aetiologies but all must be considered in the management of this difficult problem.

http://ift.tt/2jWi8wS

IgE-mediated anaphylactic shock caused by pumpkin seed in an adult

Adult atopic dermatitis and exposure to air pollutants—a nationwide population-based study

There is a trend toward an increased worldwide prevalence of allergic diseases. It is speculated that industrialization with resultant air pollution plays a role. However, there are sparse epidemiologic data on the relation between air pollution and atopic dermatitis (AD) in adults.

http://ift.tt/2kbDPGz

Effects of DMSO on Rabbit Ear Hypertrophic Scar Model: A Controlled Randomized Experimental Study

Dimethylsulfoxide (DMSO) is an anti-inflammatory, anti-bacterial, analgesic drug that is widely used to treat several diseases in literature. It has a detractive effect to collagen deposition in abnormal tissue. The aim of this study was to investigate the possible therapeutic effects of the DMSO in the hypertrophic scar formation in rabbit.Twenty-four New Zealand male albino rabbits were randomly divided into four groups: control, sham, DMSO, and TRA (triamcinolone acetonide). Except control group, punch biopsy defects were created on each animal's right ear.

http://ift.tt/2jLGuHb

Adult atopic dermatitis and exposure to air pollutants—a nationwide population-based study

Two-stage treatment of ischial pressure ulcers in spinal cord injury patients: Technique and outcomes over 8-years

Reconstruction of ischial pressure ulcers remains a difficult problem with high reported failure rates, despite newly introduced techniques.

http://ift.tt/2jLyQMQ

The Glasgow Anterior Stabilisation (GAS) Appliance - A Novel Orthodontic Appliance for Pre-Maxillary Stabilisation in Bilateral Cleft Lip and Palate

We are writing to describe our experience of the Glasgow Anterior Stabilization (GAS) appliance: A novel fixed orthodontic that we have found to be very useful in the stabilization of the pre-maxilla in patients with bilateral cleft lip and palate. The GAS appliance offers easy application and removal and is optimized to provide good surgical access to the cleft site for bone grafting or osteotomy. We have successfully used this appliance in a series of 10 cases and have found it to be very clinically versatile.

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Breast implants rupture induced by fatigue phenomena

The authors have no commercial associations or financial disclosures that might pose or create a conflict of interest with information presented in this article. No funding was received for this work.

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Using vitamin E to prevent the impairment in behavioral test, cell loss and dendrite changes in medial prefrontal cortex induced by tartrazine in rats

Publication date: Available online 23 January 2017
Source:Acta Histochemica
Author(s): Ali Rafati, Nasrin Nourzei, Saied Karbalay-Doust, Ali Noorafshan
Tartrazine is a food color that may adversely affect the nervous system. Vitamin E is a neuro-protective agent. This study aimed to evaluate the effects of tartrazine and vitamin E on the performance of rats in memory and learning tests as well as the structure of medial Prefrontal Cortex (mPFC). The rats were first divided into seven groups which received the followings for a period of seven weeks: distilled water, corn oil, vitamin E (100mg/kg/day), a low dose (50mg/kg/day) and a high dose (50mg/kg/day) of tartrazine with and without vitamin E. Behavioral tests were conducted and the brain was extracted for stereological methods The high dose of tartrazine decreased the exploration time of novel objects (P<0.01). The low and high doses of tartrazine led into an increase in working and reference memory errors in acquisition and retention phases (eight-arm radial maze) compared to distilled water group (P<0.01). Additionally, the high dose of tartrazine induced a reduction in the volume of mPFC (∼13%) and its subdivision. Not only that, but the number of neurons and glial cells (∼14%) as well as the mushroom and thin spines per dendrite length declined. The length of dendrites per neuron also reduced in comparison to the distilled water group (P<0.01). Nonetheless, concomitant treatment of the rats with vitamin E plus tartrazine prevented the above-mentioned changes. An acceptable daily dose of tartrazine could induce impairment in spatial memory and dendrite structure. Moreover, a high dose of tartrazine may defect the visual memory, mPFC structure, the spatial memory and also cause dendrite changes. Vitamin E could prevent the behavioral and structural changes.

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Wirecutter Study Finds Children’s Headphones Do Not Conform to Volume Limit

Parents who think that volume-restricting headphones could replace their supervision over children's listening habits should think again. The Wirecutter (http://ift.tt/q7HpKK), a gadgets reviewing site, found that nearly half of 30 sets of children's headphones claiming to keep volume at or under 85 dB did not live up to that promise.

With the help of experts from the WHO, CDC, and NIDCD, Wirecutter conducted two tests, first with a sample of thumping music and then with pink noise, on 30 sets of headphones with an iPod Touch. The first test found that half of the headphones exceeded 85 dB, with the loudest ones going up to 114 dB; while the second test found one-third went over the safety standard, with the loudest pair delivering sounds over 108 dB. Wirecutter also asked a group of children ranging from 3 to 11 years old to try on each model and compile a "hate list" of ones they would never use.

Staff at the website chose the Puro BT2200 from Puro Sound Labs as their favorite. The Bluetooth headphones remain within the safe listening levels when used properly, and they were the top pick among all kid panelists. Audiologist Brian Fligor, ScD, cautions that parents shouldn't let their guards down even with safe headphones when speaking to The New York Times: "Eight-five decibels isn't some magic threshold below which you're perfectly safe and above which your ears bleed."

Published: 1/23/2017 8:07:00 AM

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Quantification of different contributions to dissipation in elastomer nanoparticle composites

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Sriharish M. Nagaraja, Anas Mujtaba, Mario Beiner
We present an approach to quantify different contributions to dissipation in elastomer nanoparticle composites based on strain sweeps. A modified Kraus equation is successfully used to approximate the loss modulus depending on strain amplitude G″γ measured at different temperatures. For natural rubber composites containing >10 vol% carbon black or >3 vol% carbon nanotubes two different contributions to dissipation due to (i) breaking and (ii) deformation of glassy rubber bridges in the filler network are identified. Filler fraction and temperature-dependent trends support physical pictures considering that glassy rubber bridges are responsible for the visco-elasticity of the filler network. Constant extra contributions to dissipation are associated with the bulk-like fraction of the elastomer matrix or filler network independent effects. The achieved understanding should be very important for the optimization of elastomer nanoparticle composites for special applications like tire treads.

Graphical abstract

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LCST-type thermoresponsive behaviour of interpolymer complexes of well-defined poly(poly(ethylene glycol) methacrylate)s and poly(acrylic acid) synthesized by ATRP

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Ákos Szabó, István Szanka, Gyula Tolnai, Györgyi Szarka, Béla Iván
Unexpected tremendous effect of poly(acrylic acid) (PAA) as polydonor on the thermoresponsive behaviour of the comb-like poly(poly(ethylene glycol) methacrylate) (PPEGMA500) with short poly(ethylene glycol) (PEG) side chains as H-bond acceptor, both synthesized by atom transfer radical polymerization (ATRP), has been found indicating the formation of a unique class of interpolymer complexes between these well-defined polymers. Strikingly, the aqueous solutions of the PPEGMA500-PAA interpolymer complexes possess LCST-type thermoresponsive behaviour with hysteresis at significantly lower temperatures (∼40–50 °C) than that of PPEGMA500, which is attributed to the decreased hydrophilicity of the complexes. It is revealed that thermal phase transition temperatures (TPT) of the PPEGMA500-PAA interpolymer complexes have a minimum in the near of 1.3 ethylene glycol/acrylic acid (EG/AA) monomer unit molar ratio, in accordance with the dynamic light scattering (DLS) results, and the TPT can be fine tuned by varying the EG/AA ratio, the molecular weight of the PPEGMA500 and pH of the solution.

Graphical abstract

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Challenges in Risk Adjustment for Hospital and Provider Outcomes Assessment.

Author: Weintraub, William S. MD; Garratt, Kirk N. MD

Page: 317-319

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Commonalities Between Vasculature and Bone: An Osseocentric View of Arteriosclerosis.

Author: Towler, Dwight A. MD, PhD

Page: 320-322

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Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy.

Author: Gibson, C. Michael MS, MD; Pinto, Duane S. MD, MPH; Chi, Gerald MD; Arbetter, Douglas MPH; Yee, Megan MPH; Mehran, Roxana MD; Bode, Christoph MD; Halperin, Jonathan MD; Verheugt, Freek W.A. MD; Wildgoose, Peter PhD; Burton, Paul MD, PhD; van Eickels, Martin MD; Korjian, Serge MD; Daaboul, Yazan MD; Jain, Purva MPH; Lip, Gregory Y.H. MD; Cohen, Marc MD; Peterson, Eric D. MD, MPH; Fox, Keith A.A. MBChB

Page: 323-333

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O PIONEERs!: The Beginning of the End of Full-Dose Triple Therapy with Warfarin?.

Author: Bhatt, Deepak L. MD, MPH

Page: 334-337

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Factorial Effects of Evolocumab and Atorvastatin on Lipoprotein Metabolism.

Author: Watts, Gerald F. DSc, PhD, MD; Chan, Dick C. PhD; Dent, Ricardo MD; Somaratne, Ransi MD, MBA; Wasserman, Scott M. MD; Scott, Rob MD; Burrows, Sally BMath, Grad Dip Med Stat; R. Barrett, P. Hugh PhD

Page: 338-351

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Effects of PCSK9 Inhibition With Alirocumab on Lipoprotein Metabolism in Healthy Humans.

Author: Reyes-Soffer, Gissette MD; Pavlyha, Marianna BS; Ngai, Colleen BS; Thomas, Tiffany PhD; Holleran, Stephen BS; Ramakrishnan, Rajasekhar EngScD; Karmally, Wahida DrPH, RD, CDE, CLS; Nandakumar, Renu PhD; Fontanez, Nelson BS; Obunike, Joseph PhD; Marcovina, Santica M. PhD, DSc; Lichtenstein, Alice H. DSc; Matthan, Nirupa R. PhD; Matta, James; Maroccia, Magali MSc; Becue, Frederic BSc; Poitiers, Franck MSc; Swanson, Brian PhD; Cowan, Lisa MS; Sasiela, William J. PhD; Surks, Howard K. MD; Ginsberg, Henry N. MD

Page: 352-362

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Unpacking and Understanding the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Apolipoprotein B Metabolism.

Author: Packard, Chris J. DSc

Page: 363-365

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Impact of Left Atrial Appendage Closure During Cardiac Surgery on the Occurrence of Early Postoperative Atrial Fibrillation, Stroke, and Mortality: A Propensity Score-Matched Analysis of 10 633 Patients.

Author: Melduni, Rowlens M. MD, MPH; Schaff, Hartzell V. MD; Lee, Hon-Chi MD, PhD; Gersh, Bernard J. MB, ChB, DPhil; Noseworthy, Peter A. MD; Bailey, Kent R. PhD; Ammash, Naser M. MD; Cha, Stephen S. MPH; Fatema, Kaniz MBBS, PhD; Wysokinski, Waldemar E. MD, PhD; Seward, James B. MD; Packer, Douglas L. MD; Rihal, Charanjit S. MD, MBA; Asirvatham, Samuel J. MD

Page: 366-378

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Female Mice With an XY Sex Chromosome Complement Develop Severe Angiotensin II-Induced Abdominal Aortic Aneurysms.

Author: Alsiraj, Yasir MS; Thatcher, Sean E. PhD; Charnigo, Richard PhD; Chen, Kuey PhD; Blalock, Eric PhD; Daugherty, Alan PhD; Cassis, Lisa A. PhD

Page: 379-391

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Highlights from the Circulation Family of Journals.

Author:

Page: 392-397

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Emerging Data Support Benefits of Yoga for Patients With Heart Disease.

Author: Kuehn, Bridget M.

Page: 398-399

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Dietary Supplementation with Homoarginine Preserves Cardiac Function in a Murine Model of Post-Myocardial Infarction Heart Failure.

Author: Atzler, Dorothee PhD; McAndrew, Debra J. BS; Cordts, Kathrin BS; Schneider, Jurgen E. PhD; Zervou, Sevasti PhD; Schwedhelm, Edzard PhD; Neubauer, Stefan MD; Lygate, Craig A. PhD

Page: 400-402

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Effect of opposing implant prostheses on periodontal pathogens in dentures: A pilot study

Publication date: Available online 23 January 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Xiaodong Zhou, Mathew T. Kattadiyil, Raydolfo M. Aprecio, Xiaoli Liu, Wu Zhang, Yiming Li
Statement of problemAn understanding of the presence of periodontal pathogens in denture plaque is important for the treatment of patients with edentulism. However, current data are limited and inconclusive.PurposeThe purpose of this pilot clinical study was to investigate whether opposing implant prostheses affect the presence of periodontal pathogens in maxillary complete dentures.Material and methodsTwenty adult participants were enrolled in the study. The complete denture (CD/CD) group included 7 participants with complete maxillary and mandibular dentures. The implant overdenture (CD/IOD) group included 13 participants with maxillary complete-denture opposing implant overdentures. Plaque from maxillary complete dentures was collected and genomic DNA was extracted. Periodontal pathogens included Aggregatibacter actinomycetemcomitans, Eikenella corrodens, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia, and the total bacteria numbers were determined by real-time polymerase chain reaction (PCR) assay. A comparison of the detection rates and levels of periodontal pathogens between the 2 groups was performed using the chi-square test and the Mann-Whitney U test, respectively. Associations among these pathogens were determined using the Spearman rank correlation coefficient.ResultsNo significant differences (P>.05) in detection rates were found between the CD/CD and CD/IOD groups for A actinomycetemcomitans (100% versus 100%, respectively), E corrodens (71.4% versus 76.9%, respectively), F nucleatum (100% versus 69.2%, respectively), Porphyromonas gingivalis (100% versus 100%, respectively), P intermedia (57.1% versus 84.6%, respectively), and T forsythia (100% versus 92.3%, respectively). No significant differences in periodontal pathogen levels (P>.05) were observed between the 2 groups. Significant positive associations were observed (P<.05) between F nucleatum and P intermedia, F nucleatum and T forsythia, F nucleatum and P gingivalis, P intermedia and P gingivalis, P intermedia and A actinomycetemcomitans, T forsythia and P gingivalis, T forsythia and A actinomycetemcomitans, and P gingivalis and A actinomycetemcomitans.ConclusionsSix investigated periodontal pathogens were widely present in denture plaque. Wearing opposing implant overdentures did not affect the presence and levels of the periodontal pathogens.

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Strain analysis of 9 different abutments for cement-retained crowns on an internal hexagonal implant

Publication date: Available online 23 January 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Louai G. Salaita, Burak Yilmaz, Jeremy D. Seidt, Nancy L. Clelland, Hua-Hong Chien, Edwin A. McGlumphy
Statement of problemMany aftermarket abutments for cement-retained crowns are available for the tapered screw-vent implant. Aftermarket abutments vary widely, from stock to custom abutments and in materials such as zirconia, titanium, or a combination of the two. How these aftermarket abutments perform under occlusal loads with regard to strain distribution is not clear.PurposeThe purpose of this in vitro study was to measure and compare the different strains placed upon the bone around implants by 9 different abutments for cement-retained crowns on an implant with an internal hexagonal platform.Material and methodsNine 4.1×11.5-mm tapered screw-vent implants were placed into a 305×51×8-mm resin block for strain measurements. Five abutment specimens of each of the 9 different abutments (N=45) were evaluated with 1 of the 9 implants. Monolithic zirconia crowns were then fabricated for each of the 9 different abutments, the crowns were cyclically loaded (maximum force 225 N) at 30 degrees, twice at a frequency of 2 Hz, and the strain was measured and recorded. The strain to the resin block was determined using a 3-dimensional digital image correlation (3D DIC) technique. Commercial image correlation software was used to analyze the strain around the implants. Data for maximal and minimal principal strains were compared using analysis of variance with a Tukey-Kramer post hoc test (α=.05).ResultsStrain measurements showed no significant differences among any of the abutments for minimal (compression) principal strains (P>.05). For maximal (tensile) principal strains, the zirconia abutment showed the highest, and the patient-specific abutment showed the second-highest strain around the implant, with the zirconia being significantly greater than all abutments, with the exception of the patient-specific abutment, and the patient-specific abutment being significantly greater than the straight contoured abutment in titanium and also zirconia (P<.05).ConclusionsThe patient-specific and zirconia abutments conferred the most tensile strain to the implants. When selecting an abutment for a cement-retained crown on a tapered screw-vent implant, practitioners should consider zirconia or titanium as well as aftermarket brands versus the implant name brand being used.

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Techniken zur Rekonstruktion der Keystone Area

Zusammenfassung

Hintergrund

Die stabile Fixierung des Neoseptums und der Dreiecksknorpel am Os nasale mittels Naht ist ein essenzieller Schritt bei der Durchführung einer extrakorporalen Septumkorrektur. Nur durch die sichere Rekonstruktion dieser anatomisch wichtigen Struktur können Unregelmäßigkeiten des Nasenrückens mit Einsattelung oder Inverted-V-Deformierungen verhindert werden. Eine weitere wichtige Indikation ist die Vermeidung einer Verbreiterung des Nasenrückens durch Auseinanderweichen der osteotomierten Nasenbeine.

Zielsetzung

Es erfolgt die Vermittlung der Methodik verschiedener Nahttechniken zur Rekonstruktion der Keystone Area.

Schlussfolgerung

Die Criss-cross-Technik, die TTC-suture („transcutaneous transosseous cerclage suture")-Technik sowie die mTTC-suture („modified transcutaneous transosseous cerclage suture")-Technik sind verlässliche und einfache Techniken zur Erzielung eines reproduzierbaren ästhetischen und funktionellen Ergebnisses.

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Techniken zur Rekonstruktion der Keystone Area

Zusammenfassung

Hintergrund

Zielsetzung

Es erfolgt die Vermittlung der Methodik verschiedener Nahttechniken zur Rekonstruktion der Keystone Area.

Schlussfolgerung

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Double-blind placebo-controlled randomized clinical trial of verapamil for chronic rhinosinusitis with nasal polyps

Publication date: Available online 23 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Marcel M. Miyake, Angela Nocera, Patricia Levesque, Rong Guo, Christine A. Finn, Jeremy Goldfarb, Stacey Gray, Eric Holbrook, Nicolas Busaba, Jose Eduardo L. Dolci, Benjamin S. Bleier

http://ift.tt/2kbm4Hl

Atopic dermatitis and early childhood caries: Results of the GUSTO study

Publication date: Available online 23 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Tosha Ashish Kalhan, Evelyn Xiu Ling Loo, Ashish Chetan Kalhan, Michael S. Kramer, Bindu Karunakaran, Carolina Un Lam, Hugo Van Bever, Lynette Pei-chi Shek, Anne Goh, Yap Seng Chong, Bee Wah Lee, Peter Gluckman, Kenneth Kwek, Seang Mei Saw, Keith Godfrey, Chin-Ying Hsu

http://ift.tt/2kbgnsW

IgG trough levels and progression of pulmonary disease in pediatric and adult CVID patients

Publication date: Available online 23 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Willemijn JM. Janssen, Firdaus Mohamed Hoesein, Annick AJM. Van de Ven, Jacobien Maarschalk, Florien van Royen, Pim A. de Jong, Elisabeth AM. Sanders, Joris M. van Montfrans, Pauline M. Ellerbroek

Teaser

Defects in Lymphocyte Telomere Homeostasis Contribute to Cellular Immune phenotype in Cartilage-Hair Hypoplasia

Publication date: Available online 23 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Geraldine Aubert, Kevin A. Strauss, Peter M. Lansdorp, Nicholas L. Rider
BackgroundMutations in the lncRNA RNase component of the Mitochondrial RNA Processing endoribonuclease (RMRP) give rise to the autosomal recessive condition cartilage-hair hypoplasia (CHH). The CHH disease phenotype has some overlap with dyskeratosis congenita, a well known "telomere disorder". RMRP binds the telomerase reverse transcriptase protein TERT in some cell lines, raising the possibility that RMRP may play a role in telomere biology.ObjectiveWe sought to determine if a telomere phenotype is present in immune cells from individuals with CHH and explore mechanisms underlying these observations.MethodsWe assessed the proliferative capacity and telomere length using flow-FISH (in situ hybridization and flow cytometry) of primary lymphocytes from CHH, carrier relatives and control individuals. The role of telomerase holoenzyme components gene expression and activity were assessed by quantitative PCR and telomere repeat amplification assay (TRAP) from PBMC and enriched lymphocyte cultures.ResultsLymphocyte cultures from CHH individuals display growth defects in vitro, consistent with an immune deficiency cellular phenotype. Here we show that telomere length and telomerase activity are impaired in primary lymphocyte subsets from cartilage-hair hypoplasia patients. Notably, telomerase activity is affected in a gene dose dependent manner when comparing heterozygote RMRP carriers to individuals with CHH. Telomerase deficiency in CHH is not mediated by abnormal telomerase gene transcript levels relative to endogenous genes.ConclusionThese findings suggest that telomere deficiency is implicated in the CHH disease phenotype through an as yet unidentified mechanism.

Graphical abstract

Teaser

miRNases: Novel peptide-oligonucleotide bioconjugates that silence miR-21 in lymphosarcoma cells

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Olga A. Patutina, Elena V. Bichenkova, Svetlana K. Miroshnichenko, Nadezhda L. Mironova, Linda T. Trivoluzzi, Kepa K. Burusco, Richard A. Bryce, Valentin V. Vlassov, Marina A. Zenkova
MicroRNAs (miRNAs) are active regulators in malignant growth and constitute potential targets for anticancer therapy. Consequently, considerable effort has focused on identifying effective ways to modulate aberrant miRNA expression. Here we introduce and assess a novel type of chemically engineered biomaterial capable of cleaving specific miRNA sequences, i.e. miRNA-specific artificial ribonucleases (hereafter 'miRNase'). The miRNase template presented here consists of the catalytic peptide Acetyl-[(LeuArg)2Gly]2 covalently attached to a miRNA-targeting oligonucleotide, which can be linear or hairpin. The peptide C-terminus is conjugated to an aminohexyl linker located at either the 3′- or 5′-end of the oligonucleotide. The cleavage efficacy, structural aspects of cleavage and biological relevance of a set of these designed miRNases was assayed with respect to highly oncogenic miR-21. Several miRNases demonstrated effective site-selective cleavage of miR-21 exclusively at G-X bonds. One of the most efficient miRNase was shown to specifically inhibit miR-21 in lymphosarcoma cells and lead to a reduction in their proliferative activity. This report provides the first experimental evidence that metallo-independent peptide-oligonucleotide chemical ribonucleases are able to effectively and selectively down-regulate oncogenic miRNA in tumour cells, thus suggesting their potential in development of novel therapeutics aimed at overcoming overexpression of disease-related miRNAs.

Graphical abstract

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Radiological Imaging of Rare Intracranial Complications Secondary to Otitis Media and Mastoiditis.

Acute otitis media used to cause fatal results because of its intracranial complications before the introduction of potent and effective antibiotics. After the introduction of antibiotics, complications have started to be observed more frequently as a result of chronic otitis media and especially in children. Because clinical findings changed and became indistinct, the diagnosis of otitis and mastoiditis has been made occasionally with imaging findings only after complications occurred. Multidetector computed tomography and magnetic resonance imaging are efficient and sufficient methods in the rapid diagnosis and should be immediately referred methods. (C) 2017 by Mutaz B. Habal, MD.

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Transcutaneous Ultrasonography for Diagnosis of Nasolabial Cyst.

Nasolabial cyst is usually diagnosed by computerized tomography and magnetic resonance imaging. Ultrasonography could be a simple, office-based diagnostic imaging tool for nasolabial cyst. The authors report a 46-year-old woman with painful swelling on the bilateral anterior nostrils. The high-frequency (13 MHz) linear array transducer of the ultrasound (Hitachi Hivision Avius with EUP-L74M, Hitachi Aloka Medical, Tokyo, Japan) was transversely placed on the upper lip to scan the anterior nasal floor. Ultrasonography showed 2 well-defined anechoic oval cystic lesions in the anterior nasal floor, which were compatible with nasolabial cysts. Magnetic resonance imaging, which was done for her nasopharyngeal carcinoma 3 years ago, showed the same cystic lesions in the anterior nostril floor. Transcutaneous ultrasonography could be a simple, first-line imaging tool for diagnosis of nasolabial cyst in an office-based clinical setting. (C) 2017 by Mutaz B. Habal, MD.

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Sialolithiasis of an Accessory Parotid Gland Causing Mid-Cheek Pain.

A 52-year-old woman presented with a slightly painful swelling of the right cheek area without postprandial aggravation of the symptom last 1 week. On physical examination, an approximately 1.5 cm sized firm, slightly tender mass was palpated on the right mid-cheek region, and she did not show any abnormal findings on neurologic examination. Computed tomography showed a well-enhanced lesion with low density of internal portion in right cheek area, and tiny calcification was noted within internal low-density portion of cheek mass. These findings suggested sialolithiasis of an accessory parotid gland with duct dilatation. Mid-cheek pain with conservative medical treatment was resolved and has not occurred during 1 year follow-up. (C) 2017 by Mutaz B. Habal, MD.

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Removal of an Unusual Neglected Foreign Body in Infratemporal Region Using Navigation.

A 19-year-old male presented with complaint of a bluish mass in the hard palate since 3 months. The patient had a history of trauma 8 years back in the left zygomatic area with a pen. It was lodged in the wound and removed at that time. Computed tomography scan was revealed a linear heterogenous dense structure extending from left infratemporal fossa to oral cavity, traversing through left maxillary sinus, with bone defect seen in lateral and medial wall of maxilla, and in the hard palate, most likely a neglected foreign body. The foreign body was removed by navigation-assisted endoscopic surgery and the palatal perforation repaired using local rotation flap. There were no intraoperative or postoperative complications. Navigation-guided removal of foreign body in proximity to vital structures, in the infratemporal region, is a valuable option with minimal morbidity. (C) 2017 by Mutaz B. Habal, MD.

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The Anterolateral Thigh Flap as the Flap of Choice for Scalp Reconstruction.

Introduction: Large scalp soft tissue defects can present difficulties with reconstruction. The ideal flap for scalp reconstruction has yet to be described although the latissimus dorsi flap is frequently referred to as the first choice in this setting. Patients and Methods: Following institutional review board approval, the authors reviewed their experience in scalp reconstruction for the past 4 years. Patient demographics, reconstruction indication, flap choice, complications, and outcomes were recorded. Results: Thirteen patients underwent scalp reconstruction with an anterolateral thigh (ALT) free flap. In most patients, the indication was resection of a cutaneous malignancy. In all but 1 patient the facial or more proximal vessels were used for anastomosis. None of the patients required vein grafts to increase pedicle length. The median flap surface area was 156 cm2. One flap had vascular compromise. All donor sites healed without complications. Discussion: The ALT flap can emerge as the flap of choice for scalp reconstruction, even when proximal neck vessels are used as the recipient targets. Using a suprafascial dissection and extending the vascular pedicle to the profunda femoris artery can optimize its role in this setting. The ALT flap provides excellent cosmesis and durable scalp coverage with minimal donor site morbidity. (C) 2017 by Mutaz B. Habal, MD.

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Unusual Presentation of Castleman Disease in the Oral Cavity.

Castleman disease (CD) is a benign lymphoproliferative disease of unknown aetiology that rarely occurs in the head and neck region. Herein, the authors describe a patient of intraoral CD and its management. A 55-year-old female patient attended our clinic because of a 1-year history of a mass in the posterior hard palate region. Clinical and radiographic examination (cone-beam computed tomography scan), fine-needle aspiration, and incisional biopsy were performed. Both radiographic examination and fine-needle aspiration did not reveal relevant findings. The pathological analysis of the biopsy gave the diagnosis of hyaline vascular-type CD. The patient was treated by a complete surgical resection and 3 years after the treatment, the patient remained free of recurrence. Castleman disease in hard palate is quite different from other forms of cervical CD, mimicking other conditions like pleomorphic adenoma, lymphoma, and nodular necrotizing sialometaplasia. Careful clinical examination and histopathological analysis are essential for the diagnosis of rare and unusual pathological changes in the oral mucosa. (C) 2017 by Mutaz B. Habal, MD.

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Craniofacial Deviations in the Children With Nasal Obstruction.

Nasal obstruction mainly caused by adenoid hypertrophy in children affects the craniofacial growth and development process, and the craniofacial deviations and/or differences reported in the children are very similar to those in the adults with obstructive sleep apnea syndrome (OSAS). The authors aimed to look for relationships of the linear craniofacial dimensions in the children suffering from nasal obstruction with age, degree of clinical nasal obstruction score (CNOS), and relative size of the adenoid mass within the nasopharynx in their study. Fifty-five children suffering from nasal obstruction were retrospectively enrolled, and clinical data was used to calculate CNOS. On the lateral cephalometric radiographies, 9 linear variables were measured and adenoidal-nasopharyngeal ratio (ANR) was calculated. The data presented that, not CNOS, but ANR shown decrease by age, while many skeletal variables with exception of the nasopharyngeal and adenoidal postero-anterior dimensions were increased by age. Further, it was found that while CNOS were negatively correlated with the anterior cranial base length, anterior-superior facial height, and maxillary depth, ANR disclosed significant correlation only with the anteriorsuperior facial height. The authors' results support that nasal obstruction in the children was related not only to the adenoidal hypertrophy. Although relative size of the adenoidal mass in relation to the nasopharynx decreased by age, nasal obstruction was still present. Further, these results support that craniofacial deviations and/or differences in the children with nasal obstruction is similar to the adult OSAS patients. Smaller dimensions related to the naso-maxillary complex in the children with more severe nasal obstruction appear to be continuous by age. Hence, it could be said that narrow naso-maxillary complex could contribute to proceed nasal obstruction by age, which may contribute to OSAS in the adults. (C) 2017 by Mutaz B. Habal, MD.

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Extra-Oral Excision of a Buccal Fat Pad Lipoma.

Lipomas and its variants are common soft tissue tumors, and however occur infrequently in the oral and maxillofacial region. Their incidence in the oral cavity is low among all oral lesions. Oral lipoma is yellowish and soft to palpation, and histologically can be mistaken by other lipoma variants. The aim of this study is to report a case of a lipoma located at the buccal fat pad which was removed through an extra-oral access. A 43-year-old male is presenting an augmentation in the right buccal region, being a soft consistency mobile lesion with 1.5 cm of diameter, asymptomatic, and 2 years of growing. Computed tomography scan showed hypodensity compatible with adipose tissue. The lesion was removed through an extra-oral access. The lipoma described in this clinical report had an unusual location and once the lesion was very superficial an extra-oral access was the first treatment option despite the fact that was a benign tumor. (C) 2017 by Mutaz B. Habal, MD.

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11R-VIVIT Peptide Inhibits Calvaria Osteolysis Induced by Experimental Design.

Wear particles released from prosthetic implants can cause periprosthetic osteolysis, a major cause of implant loosening. The aim of this study was to investigate the effects of the 11R-VIVIT peptide on osteolysis induced by titanium (Ti) particles in vivo. Twenty-four C57BL/J6 mice were divided into 3 groups: sham operation, Ti group, and Ti/VIVIT group. A calvarial osteolysis model was established by implanting Ti particles into mouse calvaria of the Ti and Ti/VIVIT groups. After 2 weeks, 11R-VIVIT peptide (10 mg/kg/day) was intraperitoneally injected into the mice of the Ti/VIVIT group for 14 days. The other 2 groups received saline injection. The calvarial specimens were removed and stained with van Geison staining. The calvarial sagittal suture area was measured to observe bone resorption. The calvarial new bone area was measured to observe bone formation. Compared with the sham group, the area of calvarial new bone and calvarial sagittal suture were higher in the Ti group (P

http://ift.tt/2klQUvU

Three-Dimensional Reconstruction of the Craniofacial Skeleton With Gradient Echo Magnetic Resonance Imaging ("Black Bone"): What Is Currently Possible?.

Three-dimensional (3D) reconstructed computed tomography (CT) imaging has become an integral component of craniomaxillofacial patient care. However, with increasing concern regarding the use of ionizing radiation, particularly in children with benign conditions who require repeated examinations, dose reduction and nonionizing alternatives are actively being sought. The "Black Bone" magnetic resonance imaging (MRI) technique provides uniform contrast of the soft tissues to enhance the definition of cortical bone. The aim of this study was to develop methods of 3D rendering of the craniofacial skeleton and to ascertain their accuracy. "Black Bone" MRI datasets acquired from phantoms, adult volunteers and patients were segmented and surface and/or volume rendered using 4 commercially available or open source software packages. Accuracy was explored using a custom phantom (permitting direct measurement), CT and MRI. "Black Bone" MRI datasets were successfully used to create 3D rendered images of the craniofacial skeleton in all 4 software packages. Comparable accuracy was achieved between CT and MRI 3D rendered images of the phantom. The "Black Bone" MRI technique provides a viable 3D alternative to CT examination when imaging the craniofacial skeleton. (C) 2017 by Mutaz B. Habal, MD.

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Three-Dimensional Evaluation of the Upper Airway in Children of Skeletal Class III.

The present study was aimed to investigate the relationship of the upper airway size and craniofacial structures in 3 dimensions in growing children of skeletal Class III. Forty-seven children (19 boys and 28 girls, 9.6 +/- 1.3 years of age, range 8.0-12.4 years) were selected. Twenty-three children with normal vertical development were divided into groups of insufficient maxilla and overdeveloped mandible for the airway comparison between different sagittal skeletal patterns. Thirty-two children with the same sagittal development were divided into groups of low angle, normal angle, and high angle for the comparison between different vertical skeletal developments. The upper airway and craniofacial structures were measured in cone beam computed tomography images using DOLPHIN 11.7 software. Mann-Whitney U test and Kruskal-Wallis test were used to analyze the airway differences between groups. Spearman correlated analysis was done between the upper airway size and the craniofacial pattern in the transverse dimension. The results showed that the nasopharynx was the only affected airway part between groups of insufficient maxilla and overdeveloped mandible (P

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Eyelid Fat Atrophy and Depigmentation After an Intralesional Injection of Triamcinolone Acetonide to Treat Chalazion.

Two patients with depigmentation and fat atrophy after an intralesional injection of triamcinolone acetonide (TA) to treat chalazion are reported. A 2-year-old girl with chalazion in her right lower eyelid received a subconjunctival injection of TA and developed fat atrophy and depigmentation around the injected area. These changes subsided after 7 months. The second patient was a 5-year-old boy who received a triamcinolone injection into a chalazion through the eyelid skin and also developed fat atrophy and depigmentation but these changes improved after 1 year. (C) 2017 by Mutaz B. Habal, MD.

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Physical Therapy for Smile Improvement After Orthognathic Surgery.

The purpose of this study was to investigate the effect of physical therapy for smile improvement on the smile esthetics-related properties after orthognathic surgery. The samples consisted of 44 adult patients (13 males and 31 females; mean age of 22.6 years old), who had undergone LeFort I osteotomy and BSSRO by a single surgeon. After a video clip of smile education was shown to patients (see Supplemental Digital Content, Video, http://ift.tt/2klMOUL), smile training of 5 minutes per day was started 1-month after surgery for 3 months. Frontal facial photographs of the posed smile were taken before (T1, 1 month after surgery) and after smile training (T2, 4 months after surgery). Five variables including the smile height, upper lip curvature, smile arc, most visible maxillary posterior tooth, and buccal corridor ratio during posed smile were investigated. When compared with the T1 stage, the T2 stage showed improvement of the smile height (average or high: 32% versus 50%, P 0.05), there was a tendency of increase in the parallel smile arc from 77% at T1 to 82% at T2. In this small cohort of patients, for the period of observation, it appears that this smile training improves the smile esthetics-related properties in orthognathic surgery patients. However, it is necessary to perform further long-term follow-up studies with control groups. (C) 2017 by Mutaz B. Habal, MD.

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Double Anterior Segmental Osteotomy Under Local Anesthesia for Correcting Adult Protrusion With Thin Alveolus and Ankylosed Tooth.

Backgrounds: This paper describes an additional benefit in double anterior segmental osteotomy to correct severe anterior protrusion in adult patients with extremely thin mandibular alveolus and ankylosed tooth. For the optimal anterior segmental retraction, an ankylosed posterior tooth needed surgical inclination reposition. During anterior segmental osteotomy surgery under local anesthesia, additional single tooth osteotomy was performed without challenge. Methods: For anterior segment retraction, osteotomy cuts were made by the surgeon to define a block of bone embedding 6 mandibular anterior teeth. First premolars were extracted during initial orthodontic treatment period. But the ankylosed lower left lateral incisor and lower right second premolar root which remains mesially with uprighted crown hindered further anterior segment retraction. The authors removed cortical bone around second premolar root and repositioned to be upright. Anterior segment was retracted to proper position utilizing the space gained. Result: Thin alveolar mandibular anterior segment retraction and the second premolar uprighting were managed effectively with additional single tooth segmental osteotomy during anterior segmental osteotomy. Conclusion: Double anterior segmental osteotomy can be an effective alternative to conventional orthognathic surgery in selected adult patients. (C) 2017 by Mutaz B. Habal, MD.

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Transferring the Assessment of Cranial Deformities to the Affected.

No abstract available

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Is Serial Electroneuronography Indicated Following Temporal Bone Trauma?.

Objective: Contemporary guidelines advise facial nerve (FN) decompression within 2 weeks of temporal bone trauma if a single electroneuronography (ENoG) demonstrates more than 90% degeneration of the FN. We report a case series demonstrating the potential of serial ENoG to guide FN management more than 2 weeks following injury. Patients: Adults with traumatic temporal bone fractures and resultant ipsilateral FN paresis. Intervention: Serial ENoG followed by observation or decompression of the FN. Main Outcome Measure: House-Brackmann (HB) graded FN function. Results: Nine cases of blunt temporal bone trauma resulting in ispilateral FN paralysis were identified and reviewed. Two patients were women, and average age at the time of trauma was 30 years (range, 17-52). Immediate paralysis occurred in four cases, while five were delayed. A single ENoG was performed in seven patients and was predictive of final function in six, while one patient had an initially reassuring ENoG but did not obtain full recovery of FN function (HB 4). Two patients underwent serial ENoG on a weekly basis which, while initially reassuring, demonstrated declining FN function on subsequent testing. Decompression was performed in both patients with excellent recovery of FN function (HB1 and HB2). Conclusions: The majority of ENoGs performed within 2 weeks of temporal bone trauma provide sufficient prognostic data for treatment decisions; however, in selected cases, a single ENoG may not adequately predict long-term FN outcomes. For patients failing to improve with observation alone, serial ENoG may capture declining FN function, identifying patients that may benefit from late decompression. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Subdural Hematoma: A Rare Adverse Complication From Bone-Anchored Hearing Aid Placement.

Objective: Bone-anchored hearing aids (BAHA) are bone conduction hearing aids commonly implantated by Ear, Nose, and Throat surgeons. We present the first documented case of a subdural hematoma secondary to primary fixation of a BAHA. Patient: We present a 65-year-old male patient undergoing a left sided BAHA for bilateral chronic ear infections and difficulty wearing conventional hearing aids. The procedure was uneventful, however, the patient developed a postoperative large acute left temporoparietal intracerebral hematoma associated with an ipsilateral acute subdural hematoma. This required emergency transfer to the local tertiary neurosurgical center for a left decompressive craniotomy and evacuation of the hematoma. Results: The patient required a prolonged stay on an intensive care unit and was eventually discharged to the community for on-going neurological rehabilitation. Conclusion: This is a rare and devastating complication BAHA surgery. Otologist, general ENT surgeons, and neurosurgeons should be aware of this life-threatening complication of BAHA surgery. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

Background: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling. Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. Methods: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. Results: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. Conclusions: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney disease. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells from GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.

Background: Anti-pig antibodies are a barrier to clinical xenotransplantation. We evaluated antibody binding of waitlisted renal transplant patients to 3 glycan KO pig cells and Class I swine leukocyte antigens (SLA). Methods: Peripheral blood mononuclear cells (PBMCs) from SLA identical wild type, GGTA1 KO, GGTA1/CMAH KO, and GGTA1/CMAH/B4GalNT2 KO pigs were screened for human antibody binding using flow cytometric crossmatch (FCXM). Sera from 820 patients were screened on B4GalNT2/CMAH/GGTA1 KO cells and a subset with elevated binding was evaluated further. FCXM was performed on SLA intact cells and GGTA1/SLA Class I KO cells after depletion with wild type (WT) pig RBCs to remove cell surface reactive antibodies, but leave SLA antibodies. Lastly, human and pig reactive antibodies were eluted and tested for cross species binding and reactivity to single antigen HLA beads. Results: Sequential glycan KO modifications significantly reduce antibody binding of waitlisted patients. Sera exhibiting elevated binding without reduction after depletion with WT RBCs demonstrate reduced binding to SLA class I KO cells. Human IgG, eluted from human and pig PBMC, interacted across species and bound single antigen HLA beads in common epitope-restricted patterns. Conclusions: Many waitlisted patients have minimal xenoreactive antibody binding to the triple KO pig, but some HLA antibodies in sensitized patients cross react with class I SLA. SLA class I is a target for genome editing in xenotransplantation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Long-term outcomes of kidney transplantation in patients with high levels of preformed DSA: the Necker high-risk transplant program.

Background: There is an increasing number of anti-HLA sensitized and highly sensitized renal transplant candidates on waiting lists, and the presence of donor-specific alloantibodies (DSAs) at the time of transplantation leads to acute and chronic antibody-mediated rejection (ABMR). Acceptable short-term outcomes have been described, notably because of desensitization protocols, but mid- and long-term data are still required. Methods: Our high immunologic risk program included 95 patients with high peak or day-0 DSA levels (mean fluorescence intensity (MFI) > 3000) with a CDC negative crossmatch, who received a posttransplant desensitization protocol starting at day-0 with high-dose IVIg, plasma exchanges and eventually rituximab. Their characteristics were compared to a control group including 39 patients with a lower immunologic risk (MFI between 500 and 3000 at day-0) who received the same posttransplant desensitization. Results: The median MFI of the immunodominant class I or II DSA in the peak or day-0 serum was 9421 (IQR: 4959 - 12610). An ABMR occurred during the first posttransplant year in 31 patients (32.6%), and at one year, the rate of chronic ABMR was 39.5%. The 1-, 3-, 5- and 7-year death-censored allograft survival rates were 98, 91, 86 and 78%, respectively, with concomitant recipient survival rates of 97, 93, 85 and 79%, respectively. Conclusions: These results suggest that DSA-sensitized patients with high MFI levels can receive transplantation across the HLA-barrier, with the use of an intensified posttransplant immunosuppressive therapy starting at day-0 combined with close clinical, immunologic and histologic monitoring. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Donor-specific anti-HLA Antibodies Present in Pooled Human Serum do not Prevent Development of Human Mreg_UKR from Monocytes in Culture.

No abstract available

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Interpreting Outcomes in DCDD Liver Transplantation: First Report of the Multi-Center IDOL Consortium.

Background: In the US, 5% of adult liver transplant recipients receive a graft donated after circulatory determination of death (DCDD). Concerns for ischemic cholangiopathy (IC), a disease of diffuse intrahepatic stricturing limits broader DCDD use. Single-center reports demonstrate large variation in outcomes. Methods: Retrospective de-identified data collected between 2005 and 2013 were entered electronically by 10 centers via a REDCap database. Our primary outcome was development of intra-hepatic biliary strictures consistent with IC. Results: Within 6 months post-DCDD transplant, 162 (21.8%) patients developed a biliary stricture, of which 88 (11.8%) exhibited intra-hepatic structuring consistent with IC. Unadjusted 6-month IC rate among the 10 centers varied significantly (p=0.006) from 6.3% to 25.9%. The only factor associated with increased risk of IC within 6 months was Roux-en-Y hepaticojejunostomy (versus duct-to-duct), OR: 3.06, 95% CI: 1.52-6.16, p=0.002. Graft failure by 6 months was more than 3 times higher for DCDD recipients with IC (OR for IC: 3.36, 95% CI: 1.95-5.79). Conclusions: This first report of the large combined experience with DCDD from the IDOL consortium demonstrates significant differences in IC among centers, the importance of biliary strictures as a risk factor for graft failure, and does not validate other risk factors for IC found in smaller studies. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Combination of Metformin with Chemotherapeutic Drugs via Different Molecular Mechanisms

Publication date: Available online 23 January 2017
Source:Cancer Treatment Reviews
Author(s): Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits. Interestingly, metformin experiences a diversity of molecular mechanisms when it combines different chemotherapeutic drugs. For example, AMPK/mTOR signaling pathway activation plays a major role when it combines with hormone modulating drugs. In contrast, suppression of HIF-1, p-gp and MRP1 protein expression is its main mechanism when metformin combines with anti-metabolites. Furthermore, when combining of metformin with antibiotics, inhibition of oxidative stress and inflammatory signaling pathway becomes a novel pharmaceutical mechanism for its cardio-protective effect. Induction of apoptotic mitochondria and nucleus could be the major player for the synergistic effect of its combination with cisplatin. In contrast, down-regulation of lipoprotein or cholesterol synthesis might be the undefined molecular base when metformin combines with taxane. Thus, deep exploration of molecular mechanisms of metformin with these different drugs is critical to understand its synergistic effect and help for personalized administration. In this mini-review, detailed molecular mechanisms of these combinations are discussed and summarized. This work will promote better understanding of molecular mechanisms of metformin and provide precise targets to identify specific patient groups to achieve satisfactory treatment efficacy.

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Over-Expression of Activin-β C Is Associated with Murine and Human Prostate Disease.

Abstract

Activins are members of the TGF-β superfamily and have been linked to prostate cancer. There are four mammalian activin subunits (β_A, β_B, β_C, and β_E) that dimerize to form functional proteins. The role of activin-A (β_A-β_A) has been relatively well characterized and has been shown to generally inhibit growth in the prostate. In contrast, little is known about the biological function of the β_C and β_E subunits. Previous work indicated activin-C (β_C-β_C) to be an antagonist of activin-A. This is important because resistance to activin-A growth inhibition occurs during prostate cancer progression. This paradox is not currently well understood. Hence, we hypothesize that local expression of the activin-β_C subunit antagonizes activin-A-dependent growth inhibition and represents a key factor contributing to acquired insensitivity to activin-A observed in prostate cancer progression. To test our hypothesis, we characterized the ventral prostate lobes of 9-month-old transgenic mice over-expressing activin-β_C and examined the expression of activin-β_A, activin-β_C, and the activin intracellular signaling factor, Smad-2, in human prostate diseases. Prostate epithelial cell hyperplasia, low-grade prostatic intraepithelial neoplasia (PIN) lesions, alterations in cell proliferation, and reduced Smad-2 nuclear localization were evident in mice over-expressing activin-β_C. Increased activin-β_A and -β_C subunit immunoreactive scores and decreased Smad-2 nuclear localization were also evident in human prostate cancer. This study suggests that over-expression of activin-β_C is associated with murine and human prostate pathologies. We conclude that the activin-β_C subunit may have therapeutic and/or diagnostic implications in human prostate disease.

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Is von Willebrand Disease linked to cholesteatoma aetiology?

Publication date: Available online 23 January 2017
Source:Medical Hypotheses
Author(s): Â. Reis Rego, M. Santos, M. Coutinho, T. Feliciano, C. Almeida e Sousa
Cholesteatoma is a common clinical picture seen by the otolaryngologists. The disease is characterised by an abnormal grow "of skin in the wrong place". Specifically, in acquired cholesteatoma, the main causative issue is associated with ventilatory deficits within the middle ear and results in chronic infection. Molecular science has associated the presence of specific molecules with its development, and moreoverrecent research suggests that deregulated angiogenesis is a crucial process in the development of cholesteatoma and its recurrence. Further, haematologists have linked von Willebrand factor and its defects (both quantitative and qualitative) to augmented angiogenesis through upregulation of the vascular endothelial growth factor and angiogenic cytokines. Thus, herewith we probed whether a relationship between von Willebrand disease and the etiopathogenesis of cholesteatoma, plays a potential role for anti-angiogenic molecules for the advent of cholesteatoma surgery adjuvant treatment.

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Intermittent hypoxia as a means to improve aerobic capacity in type 2 diabetes

Publication date: Available online 23 January 2017
Source:Medical Hypotheses
Author(s): R.J. Leone, S. Lalande
Physical inactivity and a low maximal aerobic capacity (VO2max) strongly predict morbidity and mortality in patients with type 2 diabetes (T2D). Patients with T2D have a reduced VO2max when compared with healthy individuals of similar age, weight, and physical activity levels, and this lower aerobic capacity is usually attributed to a reduced oxygen delivery to the working muscles. The oxygen carrying capacity of the blood, as well as increases in cardiac output and blood flow, contribute to the delivery of oxygen to the active muscles during exercise. Hemoglobin mass (Hb mass), a key determinant of oxygen carrying capacity, is suggested to be reduced in patients with T2D following the observation of a lower blood volume (BV) in combination with normal hematocrit levels in this population. Therefore, a lower Hb mass, in addition to a reported lower BV and impaired cardiovascular response to exercise, likely contributes to the reduced oxygen delivery and VO2max in patients with T2D. While exercise training increases Hb mass, BV, and consequently VO2max, the majority of patients with T2D are not physically active, highlighting the need for alternative methods to improve VO2max in this population. Exposure to hypoxia triggers the release of erythropoietin, the hormone regulating red blood cell production, which increases Hb mass and consequently BV. Exposure to mild intermittent hypoxia (IH), characterized by few and short episodes of hypoxia at a fraction of inspired oxygen ranging between 10-14% interspersed with cycles of normoxia, increased red blood cell volume, Hb mass, and plasma volume in patients with coronary artery disease or chronic obstructive pulmonary disease, which resulted in an improved VO2max in both populations. We hypothesize that 12 exposures to mild IH over a period of 4 weeks will increase Hb mass, BV, cardiac function, and VO2max in patients with T2D. Therefore, exposures to mild IH may increase oxygen delivery and VO2max without the need to perform exercise in patients with T2D.

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Should Metformin be included in fertility treatment of PCOS patients?

Publication date: Available online 23 January 2017
Source:Medical Hypotheses
Author(s): Jigal Haas, Yaakov Bentov
Metformin, a drug developed for the treatment of patients with type II diabetes, has become commonly prescribed medication for PCOS patients. Initially, Metformin was prescribed for patients with impaired glucose tolerance at the pre conception period, however more recently its use was expanded to many of the PCOS patients and for the whole duration of pregnancy. Several studies examining the effects of Metformin during pregnancy reported a lower pregnancy loss, reduced gestational diabetes and no increased risk for birth defects, however, several more recent studies also raised concerns about its safe use.The therapeutic effect of metformin stems from its ability to inhibit the action of the first complex of the electron transport resulting in reduced ATP production. At the initial stages of embryo development, the only source of ATP is the mitochondrial electron transport chain. Lowering ATP production at the critical stage of early embryo development may impair oocyte maturation and embryo development as well as reprogram the metabolic characteristics of the offspring.

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The Fibrinolytic System: a New Target for Treatment of Depression with Psychedelics

Publication date: Available online 23 January 2017
Source:Medical Hypotheses
Author(s): RD. Idell, G. Florova, AA. Komissarov, S. Shetty, R.B.S. Girard, S. Idell

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The promising anticancer drug 3-bromopyruvate is metabolized through glutathione conjugation which affects chemoresistance and clinical practice: An evidence-based view

Publication date: Available online 23 January 2017
Source:Medical Hypotheses
Author(s): Salah Mohamed El Sayed, Hussam Baghdadi, Mohammed Zolaly, Hamdy H. Al-Maramhy, Mongi Ayat, Jagadish G. Donki
3-bromopyruvate (3BP) is a promising effective anticancer drug against many different tumors in children and adults. 3BP exhibited strong anticancer effects in both preclinical and human studies e.g. energy depletion, oxidative stress, anti-angiogenesis, anti-metastatic effects, targeting cancer stem cells and antagonizing the Warburg effect. There is no report about 3BP metabolism to guide researchers and oncologists to improve clinical practice and prevent drug resistance. In this article, we provide evidences that 3BP is metabolized through glutathione (GSH) conjugation as a novel report where 3BP was confirmed to be attached to GSH followed by permanent loss of pharmacological effects in a picture similar to cisplatin. Both cisplatin and 3BP are alkylating agents. Reported decrease in endogenous cellular GSH content upon 3BP treatment was confirmed to be due to the formation of 3BP-GSH complex i.e. GSH consumption for conjugation with 3BP. Cancer cells having high endogenous GSH exhibit resistance to 3BP while 3BP sensitive cells acquire resistance upon adding exogenous GSH. Being a thiol blocker, 3BP may attack thiol groups in tissues and serum proteins e.g. albumin and GSH. That may decrease 3BP-induced anticancer effects and the functions of those proteins. We proved here that 3BP metabolism is different from metabolism of hydroxypyruvate that results from metabolism of D-serine using D-amino acid oxidase. Clinically, 3BP administration should be monitored during albumin infusion and protein therapy where GSH should be added to emergency medications. GSH exerts many physiological effects and is safe for human administration both orally and intravenously. Based on that, reported GSH-induced inhibition of 3BP effects makes 3BP effects reversible, easily monitored and easily controlled. This confers a superiority of 3BP over many anticancer agents.

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Corrigendum to “Cytoplasmic localization of Nrf2 promotes colorectal cancer with more aggressive tumors via upregulation of PSMD4” [Free Radic. Biol. Med. 95 (2016) 121–32]

Publication date: Available online 23 January 2017
Source:Free Radical Biology and Medicine
Author(s): Po-Lin Lin, Jinghua Tsai Chang, De-Wei Wu, Chi-Chou Huang, Huei Lee

http://ift.tt/2jVzOsq

The effect of iron plaque on uptake and translocation of norfloxacin in rice seedlings grown in paddy soil

Abstract

Although the role of iron plaque on rice root surface has been investigated in recent years, its effect on antibiotic uptake remains uncertain. In the study, pot experiment was conducted to investigate the effect of iron plaque on uptake and translocation of norfloxacin (adding 10 and 50 mg·kg⁻¹ treatments) in rice seedlings grown in paddy soil. Iron plaque was induced by adding different amounts of Fe(II) in soil. The results showed that the presence of norfloxacin can decrease the amount of iron plaque induced. After rice with iron plaque induced, norfloxacin was mainly accumulated in iron plaque on root surface, followed by inside root, but its translocation from root to other rice tissues is not observed. Iron plaque played the role of a barrier for norfloxacin uptake into rice roots under high norfloxacin concentration of 50 mg·kg⁻¹, however not that under low concentration of 10 mg·kg⁻¹. And the barrier function was the most strongest with adding Fe(II) of 30 mg·kg⁻¹ as combined action of iron plaque and rhizosphere effect. Fluorescence microscope analysis showed that norfloxacin mainly distributed in the outside of root cell, which showed its translocation as apoplastic pathway in rice. Comparing with non-rhizosphere, more norfloxacin was accumulated in rhizosphere soil. Maybe, strong root oxidization (high Eh values) induced more iron oxide formation in rhizosphere and on root surface, which led to norfloxacin's mobility towards to rhizosphere through its strong adsorption of iron oxides and then promoted its uptake by rice on root surface.

http://ift.tt/2kl42pw

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! # Ola via Alexandros G.Sfakianakis on Inoreader

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Δευτέρα 23 Ιανουαρίου 2017

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