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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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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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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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.

http://ift.tt/2kbExDE

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.

http://ift.tt/2kbI9FE

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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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.

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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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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

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.

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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.

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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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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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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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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




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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.

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Toxicity and biodegradation of ibuprofen by Bacillus thuringiensis B1(2015b)

Abstract

In recent years, the increased intake of ibuprofen has resulted in the presence of the drug in the environment. This work presents results of a study on degradation of ibuprofen at 25 mg L⁻¹ in the presence of glucose, as an additional carbon source by Bacillus thuringiensis B1(2015b). In the cometabolic system, the maximum specific growth rate of the bacterial strain was 0.07 ± 0.01 mg mL⁻¹ h⁻¹ and K _sμ 0.27 ± 0.15 mg L⁻¹. The maximum specific ibuprofen removal rate and the value of the half-saturation constant were q _max = 0.24 ± 0.02 mg mL⁻¹ h⁻¹ and K _s = 2.12 ± 0.56 mg L⁻¹, respectively. It has been suggested that monooxygenase and catechol 1,2-dioxygenase are involved in ibuprofen degradation by B. thuringiensis B1(2015b). Toxicity studies showed that B. thuringiensis B1(2015b) is more resistant to ibuprofen than other tested organisms. The EC50 of ibuprofen on the B1 strain is 809.3 mg L⁻¹, and it is 1.5 times higher than the value of the microbial toxic concentration (MTC_avg). The obtained results indicate that B. thuringiensis B1(2015b) could be a useful tool in biodegradation/bioremediation processes.

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Alleviation of lead-induced oxidative stress and immune damage by selenium in chicken bursa of Fabricius

Abstract

We investigated lead (Pb)-induced oxidative stress and immune damage in the chicken bursa of Fabricius (BF) and the ameliorative effect of selenium (Se). Seven-day-old male chickens were randomly divided into four groups and were provided standard diet and drinking water, Na₂SeO₃ added to the standard diet and drinking water, standard diet and (CH₃COO)₂Pb added to drinking water, and Na₂SeO₃ added to the standard diet and (CH₃COO)₂Pb added to drinking water for 30, 60, and 90 days. The presence of Pb inhibited total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities; decreased glutathione (GSH) content; increased malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) contents; inhibited interleukin (IL)-2 and interferon-γ (IFN-γ) messenger RNA (mRNA) expression; and increased IL-4, IL-6, IL-10, IL-12β, and IL-17 mRNA expression. The presence of Se relieved all of the above Pb-induced changes. There were close correlations among GSH, CAT, T-AOC, SOD, GPx, MDA, and H₂O₂ and among IL-2, IL-4, IL-6, IL-12β, IL-17, and IFN-γ. Our data showed that Pb caused oxidative stress and immune damage in the chicken BF. Se alleviated Pb-induced oxidative stress and immune damage in the chicken BF.

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Assessing the ecological impact of banana farms on water quality using aquatic macroinvertebrate community composition

Abstract

In Costa Rica, considerable effort goes to conservation and protection of biodiversity, while at the same time agricultural pesticide use is among the highest in the world. Several protected areas, some being wetlands or marine reserves, are situated downstream large-scale banana farms, with an average of 57 pesticide applications per year. The banana industry is increasingly aware of the need to reduce their negative environmental impact, but few ecological field studies have been made to evaluate the efficiency of proposed mitigation strategies. This study compared the composition of benthic macroinvertebrate communities up- and downstream effluent water from banana farms in order to assess whether benthic invertebrate community structure can be used to detect environmental impact of banana farming, and thereby usable to assess improvements in management practises. Aquatic invertebrate samples were collected at 13 sites, using kick-net sampling, both up- and downstream banana farms in fast flowing streams in the Caribbean zone of Costa Rica. In total, 2888 invertebrate specimens were collected, belonging to 15 orders and 48 families or taxa. The change in community composition was analysed using multivariate statistics. Additionally, a biodiversity index and the Biological Monitoring Working Party (BMWP) score system was applied along with a number of community composition descriptors. Multivariate analyses indicated that surface waters immediately up- and downstream large-scale banana farms have different macroinvertebrate community compositions with the most evident differences being higher dominance by a single taxa and a much higher total abundance, mostly of that same taxon. Assessment of macroinvertebrate community composition thus appears to be a viable approach to detect negative impact from chemical-intensive agriculture and could become an effective means to monitor the efficacy of changes/proposed improvements in farming practises in Costa Rica and similar systems.

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210Pb, 137Cs and 7Be in the sediments of coastal lakes on the polish coast: Implications for sedimentary processes

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Michał Woszczyk, Grzegorz Poręba, Łukasz Malinowski
In this study we combined radioisotopes (²¹⁰Pb, ¹³⁷Cs and ⁷Be) and hydrodynamic modeling to investigate sedimentary processes in three coastal lakes on the Polish Baltic coast. The research aimed at establishing the depth of sediment mixing and its effects on sediment geochemistry as well as showing the relationship between lake water salinity and radionuclide distribution in the sediment cores. We established that the intensity of mixing displayed appreciable variability throughout the lakes and the thickness of sediment mixing layer was between <2 and 22 cm. The mixing was primarily due to wind-induced waves. The vertical mixing was shown to shift sulfidation of the sediments towards deeper layers. We found that the distributions of radioisotopes, ¹³⁷Cs in particular, in the sediment cores from coastal lakes were strongly affected by the early diagenetic processes, which caused diffusive migration of radionuclides. The inventories of ²¹⁰Pbex and ¹³⁷Cs in the lakes were positively related to salinity. The high inventories of both isotopes (3.2–10.9 kBq ·m⁻² for ²¹⁰Pbex and 3.0–6.0 kBq·m⁻² for ¹³⁷Cs) in coastal lakes were explained by enhanced sedimentation within estuarine mixing zone and delivery of "additional" ²¹⁰Pb and ¹³⁷Cs to the lakes during saltwater ingressions. The results of this study have implications for the paleolimnology, sedimentology and biogeochemistry of coastal lakes.



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An integrated proteomic and transcriptomic analysis of perivitelline fluid proteins in a freshwater gastropod laying aerial eggs

Publication date: 23 February 2017
Source:Journal of Proteomics, Volume 155
Author(s): Huawei Mu, Jin Sun, Horacio Heras, Ka Hou Chu, Jian-Wen Qiu
Proteins of the egg perivitelline fluid (PVF) that surrounds the embryo are critical for embryonic development in many animals, but little is known about their identities. Using an integrated proteomic and transcriptomic approach, we identified 64 proteins from the PVF of Pomacea maculata, a freshwater snail adopting aerial oviposition. Proteins were classified into eight functional groups: major multifunctional perivitellin subunits, immune response, energy metabolism, protein degradation, oxidation-reduction, signaling and binding, transcription and translation, and others. Comparison of gene expression levels between tissues showed that 22 PVF genes were exclusively expressed in albumen gland, the female organ that secretes PVF. Base substitution analysis of PVF and housekeeping genes between P. maculata and its closely related species Pomacea canaliculata showed that the reproductive proteins had a higher mean evolutionary rate. Predicted 3D structures of selected PVF proteins showed that some nonsynonymous substitutions are located at or near the binding regions that may affect protein function. The proteome and sequence divergence analysis revealed a substantial amount of maternal investment in embryonic nutrition and defense, and higher adaptive selective pressure on PVF protein-coding genes when compared with housekeeping genes, providing insight into the adaptations associated with the unusual reproductive strategy in these mollusks.SignificanceThere has been great interest in studying reproduction-related proteins as such studies may not only answer fundamental questions about speciation and evolution, but also solve practical problems of animal infertility and pest outbreak. Our study has demonstrated the effectiveness of an integrated proteomic and transcriptomic approach in understanding the heavy maternal investment of proteins in the eggs of a non-model snail, and how the reproductive proteins may have evolved during the transition from laying underwater eggs to aerial eggs.

Graphical abstract

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Sensitivity of the human mirror neuron system for abstract traces of actions: an EEG-study

Publication date: Available online 23 January 2017
Source:Biological Psychology
Author(s): Matthias Hoenen, Katrin T. Lübke, Bettina M. Pause
Theories of neuroaesthetics assume, that looking at traces of actions used in creating artwork (e.g. brush marks) is associated with a simulation of these actions in the observer's sensorimotor-cortex. The aim of the current study is to dissociate the activation of the sensorimotor-cortex by the observation of action traces from associated visual processes.Twenty-eight participants observed handmade graphics (acrylic paint on paper) of different complexity (line, triangle, shape of a house) and computer-generated counterparts. Central mu-activity, as an index of sensorimotor-cortex activity, and occipital alpha-activity, as an index of visual cortex activity were recorded in the 8–13Hz EEG-band.In line with the hypothesis, mu-activity at electrode C4 is sensitive for the complexity of handmade (p=.001), but not computer-generated graphics (p >.500). In contrast, occipital alpha-activity is sensitive for the complexity of both handmade and computer-generated graphics (p <.001). Furthermore, the more empathic the participants rated themselves, the stronger mu-suppression was induced by handmade graphics compared to computer-generated graphics (electrode C4; r=−.612, p=.001). These results support the involvement of the sensorimotor-cortex in the recognition of action traces and strengthen evidence that individuals scoring high in emotional empathy feature a particularly responsive mirror neuron system.



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Neural correlates of the impact of prior outcomes on subsequent monetary decision-making in frequent poker players

Publication date: Available online 23 January 2017
Source:Biological Psychology
Author(s): D. Brevers, Q. He, G. Xue, A. Bechara
Individuals have a tendency to be more risky in their choices after having experienced a monetary loss, than after a reward. Here, we examined whether prior outcomes influence differently the patterns of neural activity of individuals who are used to taking monetary risk, namely poker players. High-frequency poker players and non-gamblers were scanned while performing a controlled task that allowed measuring the effect of prior outcomes on subsequent decisions. Both non-gamblers and poker players took more risks after losing a gamble than after winning one. Neuroimaging data revealed that non-gamblers exhibited higher brain activation than poker players when pondering a decision after losing, as compared to after winning. The opposite was found in poker players. This differential pattern of activation observed in brain regions involved in high-order motor processes (dorsal premotor cortex). These results suggest that gambling habits introduce significant changes in action preparation during decision-making following wins and losses.



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Edoxaban Versus Warfarin: Bone Fractures Due to Falling

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Protection Against Cerebral Embolism During Transcatheter Aortic Valve Replacement

AbstractBackground

Neurological complications after transcatheter aortic valve replacement (TAVR) may be reduced with transcatheter cerebral embolic protection (TCEP).

Objectives

This study evaluated the safety and efficacy of TCEP during TAVR.

Methods

Nineteen centers randomized 363 patients undergoing TAVR to a safety arm (n = 123), device imaging (n = 121), and control imaging (n = 119). The primary safety endpoint consisted of major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on magnetic resonance imaging scans at 2 to 7 days. Patients underwent neurocognitive assessments, and the debris captured was analyzed.

Results

The rate of MACCE (7.3%) was noninferior to the performance goal (18.3%, p_noninferior < 0.001) and not statistically different from that of the control group (9.9%; p = 0.41). New lesion volume was 178.0 mm³ in control subjects and 102.8 mm³ in the device arm (p = 0.33). A post hoc multivariable analysis identified pre-existing lesion volume and valve type as predictors of new lesion volume. Strokes at 30 days were 9.1% in control subjects and 5.6% in patients with devices (p = 0.25) Neurocognitive function was similar in control subjects and patients with devices, but there was a correlation between lesion volume and neurocognitive decline (p = 0.0022). Debris found within filters in 99% of patients included thrombus, calcification, valve tissue, artery wall, and foreign material.

Conclusions

TCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277)

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Improving Medication Adherence in Cardiometabolic Disease: Practical and Regulatory Implications

Abstract

Medication nonadherence, a major problem in cardiovascular disease (CVD), contributes yearly to approximately 125,000 preventable deaths, which is partly attributable to only about one-half of CVD patients consistently taking prescribed life-saving medications. Current interest has focused on how labeling and education influence adherence. This paper summarizes the scope of CVD nonadherence, describes key U.S. Food and Drug Administration initiatives, and identifies potential targets for improvement. We describe key adherence factors, methods, and technological applications for simplifying regimens and enhancing adherence, and 4 areas where additional collaborative research and implementation involving the regulatory system and clinical community could substantially reduce nonadherence: 1) identifying monitoring methods; 2) improving the evidence base to better understand adherence; 3) developing patient/health provider team-based engagement strategies; and 4) alleviating health disparities. Alignment of U.S. Food and Drug Administration approaches to dissemination of information about appropriate use with clinical practice could improve adherence, and thereby reduce CVD death and disability.

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Cerebral Embolic Protection During Transcatheter Aortic Valve Replacement: A Disconnect Between Logic and Data?

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Comprehensive Geriatric Assessment and Transcatheter Aortic Valve Replacement

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Transcatheter Mitral Valve Replacement for Patients With Symptomatic Mitral Regurgitation: A Global Feasibility Trial

AbstractBackground

Symptomatic mitral regurgitation (MR) is associated with high morbidity and mortality that can be ameliorated by surgical valve repair or replacement. Despite this, many patients with MR do not undergo surgery. Transcatheter mitral valve replacement (TMVR) may be an option for selected patients with severe MR.

Objectives

This study aimed to examine the effectiveness and safety of TMVR in a cohort of patients with native valve MR who were at high risk for cardiac surgery.

Methods

Patients underwent transcatheter, transapical delivery of a self-expanding mitral valve prosthesis and were examined in a prospective registry for short-term and 30-day outcomes.

Results

Thirty patients (age 75.6 ± 9.2 years; 25 men) with grade 3 or 4 MR underwent TMVR. The MR etiology was secondary (n = 23), primary (n = 3), or mixed pathology (n = 4). The Society of Thoracic Surgeons Predicted Risk of Mortality was 7.3 ± 5.7%. Successful device implantation was achieved in 28 patients (93.3%). There were no acute deaths, strokes, or myocardial infarctions. One patient died 13 days after TMVR from hospital-acquired pneumonia. Prosthetic leaflet thrombosis was detected in 1 patient at follow-up and resolved after increased oral anticoagulation with warfarin. At 30 days, transthoracic echocardiography showed mild (1+) central MR in 1 patient, and no residual MR in the remaining 26 patients with valves in situ. The left ventricular end-diastolic volume index decreased (90.1 ± 28.2 ml/m² at baseline vs. 72.1 ± 19.3 ml/m² at follow-up; p = 0.0012), as did the left ventricular end-systolic volume index (48.4 ± 19.7 ml/m² vs. 43.1 ± 16.2 ml/m²; p = 0.18). Seventy-five percent of the patients reported mild or no symptoms at follow-up (New York Heart Association functional class I or II). Successful device implantation free of cardiovascular mortality, stroke, and device malfunction at 30 days was 86.6%.

Conclusions

TMVR is an effective and safe therapy for selected patients with symptomatic native MR. Further evaluation of TMVR using prostheses specifically designed for the mitral valve is warranted. This intervention may help address an unmet need in patients at high risk for surgery. (Early Feasibility Study of the Tendyne Mitral Valve System [Global Feasibility Study]; NCT02321514)

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Cangrelor Use Since FDA Approval: A Single-Center, Real-World Experience at a Tertiary Care Hospital

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Transcatheter Mitral Valve Replacement Clears the First Hurdle

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A Better Scoring System for Mortality After Transcatheter Aortic Valve Replacement

http://ift.tt/2jKglIE

SYNTAX Score and Long-Term Outcomes: The BARI-2D Trial

AbstractBackground

The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease.

Objectives

This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial.

Methods

Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years.

Results

A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p < 0.001). Among patients with low SYNTAX scores (≤22), major cardiovascular events did not differ significantly between revascularization and medical therapy, either in the CABG stratum (26.1% vs. 29.9%, p = 0.41) or in the PCI stratum (17.8% vs. 19.2%, p = 0.84). Among patients with mid/high SYNTAX scores, however, major cardiovascular events were lower after revascularization than with medical therapy in the CABG stratum (15.3% vs. 30.3%, p = 0.02), but not in the PCI stratum (35.6% vs. 26.5%, p = 0.12).

Conclusions

Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

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Instructions For Authors

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Cherry-Picking Historical Data to Legitimize Contemporary Practice: Should Diabetic Status Influence Decision-Making in Complex CAD?

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Changes in the Professional Lives of Cardiologists Over 2 Decades

Abstract

The American College of Cardiology third decennial Professional Life Survey was completed by 2,313 cardiologists: 964 women (42%) and 1,349 men (58%). Compared with 10 and 20 years ago, current results reflect a substantially lower response rate (21% vs. 31% and 49%, respectively) and an aging workforce that is less likely to be in private practice. Women continue to be more likely to practice in academic centers, be pediatric cardiologists, and have a noninvasive subspecialty. Men were more likely to indicate that family responsibilities negatively influenced their careers than previously, whereas women remained less likely to marry or have children. Men and women reported similar, high levels of career satisfaction, with women reporting higher satisfaction currently. However, two-thirds of women continue to experience discrimination, nearly 3 times the rate in men. Personal life choices continue to differ substantially for men and women in cardiology, although differences have diminished.

http://ift.tt/2jUT2yx

Insulin-Requiring Versus Noninsulin-Requiring Diabetes and Thromboembolic Risk in Patients With Atrial Fibrillation: PREFER in AF

AbstractBackground

Diabetes is a known risk predictor for thromboembolic events in patients with atrial fibrillation (AF), but no study has explored the prognostic weight of insulin in this setting.

Objectives

This study evaluated the differential role of insulin versus no insulin therapy on thromboembolic risk in patients with diabetes and AF.

Methods

We accessed individual patient data from the prospective, real-world, multicenter, PREFER in AF (European Prevention of thromboembolic events-European Registry in Atrial Fibrillation). We compared the rates of stroke/systemic embolism at 1 year according to diabetes status (no diabetes, diabetes without insulin therapy, diabetes on insulin therapy).

Results

In an overall population of 5,717 patients, 1,288 had diabetes, 22.4% of whom were on insulin. For patients with diabetes who were on insulin, there was a significantly increased risk of stroke/systemic embolism at 1 year versus either no diabetes (5.2% vs. 1.9%; hazard ratio: 2.89; 95% confidence interval: 1.67 to 5.02; p = 0.0002) or diabetes without insulin treatment (5.2% vs. 1.8%; hazard ratio: 2.96; 95% confidence interval: 1.49 to 5.87; p = 0.0019). Notably, rates of stroke/embolism were similar in patients with diabetes not receiving insulin versus patients without diabetes (hazard ratio: 0.97; 95% confidence interval: 0.58 to 1.61; p = 0.90). The selective predictive role of insulin-requiring diabetes was independent of potential confounders, including diabetes duration, and was maintained in various subpopulations, including the subgroup receiving anticoagulant therapy.

Conclusions

In this cohort of anticoagulated patients with AF, the sole presence of diabetes not requiring insulin did not imply an increased thromboembolic risk. Conversely, insulin-requiring diabetes contributed most, if not exclusively, to the overall increase of thromboembolic risk in AF.

http://ift.tt/2jK52jS

Cerebral Embolic Protection During TAVR: A Clinical Event Meta-Analysis

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Evaluation of discriminative sensibility recovery in patients with buccinator myomucosal flap oral cavity reconstructions

Abstract

Background

Sensitive restoration is the primary aim of oral reconstructive surgery. Discriminative sensibility is an important index of innervation density of a tissue. Instruments normally used to assess this type of skin sensibility are bulky and difficult to introduce in the oral cavity, even in healthy patients with a normal mouth opening. This study was intended to evaluate the recovery of static and dynamic two-point discrimination sensitivity of the reconstructed areas of the oral cavity.

Methods

Surgical staples, calibrated in predetermined width (from 1 to 30 mm) and introduced in the oral cavity with a Mayo needle holder, were used to evaluate two-point discrimination recovery in 57 patients who underwent reconstructive surgery with buccinator myomucosal flaps. Tests were conducted both on the reconstructive flap and on the non-operated contralateral side. The latter also included the non-operated cheek.

Results

All of the considered flaps showed a recovery of tactile sensitivity. The overall average discriminative threshold value assessed on this sample was 9.11 ± 2.46 mm for the static and 6.56 ± 2.46 mm for the dynamic.

Conclusions

The use of surgical staples allows easy assessment of tactile sensitivity in all oral cavity areas, even in operated patients who often present lockjaw or microstomia. In our series, buccinator myomucosal flaps demonstrate a much greater recovery of the sensation compared to results found in the literature on fasciocutaneous free flaps, even those reinnervated.

Level of Evidence: Level III, prognostic study

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Insulin Therapy and Stroke Risk in Patients With Diabetes and Atrial Fibrillation: Guilty by Association?

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Future Study With Tolvaptan in Acute Heart Failure

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Role of NOD1 in Heart Failure Progression via Regulation of Ca2+ Handling

AbstractBackground

Heart failure (HF) is a complex syndrome associated with a maladaptive innate immune system response that leads to deleterious cardiac remodeling. However, the underlying mechanisms of this syndrome are poorly understood. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune sensor involved in cardiovascular diseases.

Objectives

This study evaluated the role of NOD1 in HF progression.

Methods

NOD1 was examined in human failing myocardium and in a post-myocardial infarction (PMI) HF model evaluated in wild-type (wt-PMI) and Nod1^–/– mice (Nod1^–/–-PMI).

Results

The NOD1 pathway was up-regulated in human and murine failing myocardia. Compared with wt-PMI, hearts from Nod1^–/–-PMI mice had better cardiac function and attenuated structural remodeling. Ameliorated cardiac function in Nod1^–/–-PMI mice was associated with prevention of Ca²⁺ dynamic impairment linked to HF, including smaller and longer intracellular Ca²⁺ concentration transients and a lesser sarcoplasmic reticulum Ca²⁺ load due to a down-regulation of the sarcoplasmic reticulum Ca²⁺-adenosine triphosphatase pump and by augmented levels of the Na⁺/Ca²⁺ exchanger. Increased diastolic Ca²⁺ release in wt-PMI cardiomyocytes was related to hyperphosphorylation of ryanodine receptors, which was blunted in Nod1^–/–-PMI cardiomyocytes. Pharmacological blockade of NOD1 also prevented Ca²⁺ mishandling in wt-PMI mice. Nod1^–/–-PMI mice showed significantly fewer ventricular arrhythmias and lower mortality after isoproterenol administration. These effects were associated with lower aberrant systolic Ca²⁺ release and with a prevention of the hyperphosphorylation of ryanodine receptors under isoproterenol administration in Nod1^–/–-PMI mice.

Conclusions

NOD1 modulated intracellular Ca²⁺ mishandling in HF, emerging as a new target for HF therapy.

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Risk Models for Transcatheter Aortic Valve Replacement

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So Many Targets

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Two Suturing Techniques for the Prevention and Treatment of Nasal Valve Collapse After Mohs Micrographic Surgery.

BACKGROUND: Tumor extirpation of nonmelanoma skin cancer (NMSC) adjacent to the alar groove, using Mohs micrographic surgery (MMS), may risk causing internal nasal valve (INV) collapse, resulting in reduced airflow during inspiration. There are many surgical options described in the literature to repair INV collapse as a postoperative corrective procedure, but few exist as an intra-operative preventative procedure. OBJECTIVE: The authors present 2 distinct methods to prevent and treat INV collapse during the repair of a perialar surgical defect caused by MMS. METHODS: A 3-point stitch method or a modified suspension suture technique was used to prevent INV collapse during the repair of MMS defects overlying the alar groove, for nonmelanoma skin cancers. The 3-point stitch was used with a complex repair. The modified suspension suture was used with flap reconstruction. RESULTS: The 3-point stitch and the modified suspension suture are simple, single-stage surgical solutions for perialar defects with collapse of the INV caused by loss of subcutaneous tissue during MMS. Once executed, patients experienced immediate subjective airflow improvement which was also supported by clinical examination. Patients were followed at 1 week and at 3 months postoperatively. Thirty-four of 35 patients reported good functional and cosmetic results and were satisfied with the final outcome. CONCLUSION: The 3-point stitch and the modified suspension suture techniques are easy and simple methods that can be incorporated into reconstruction after MMS for defects of variable depth covering any multisubunit perialar region to prevent or correct INV collapse. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Anaphylactic Shock After Injection of Foamed Sodium Tetradecyl Sulfate.

No abstract available

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Treatment of Postinflammatory Hyperpigmentation With a Combination of Glycolic Acid Peels and a Topical Regimen in Dark-Skinned Patients: A Comparative Study.

BACKGROUND: Facial postinflammatory hyperpigmentation (PIH) is challenging to manage in patients with skin of color because of the risk of subsequent treatment-related hyperpigmentation. OBJECTIVE: To evaluate the safety and efficacy of combining glycolic acid (GA) peels with a modified Kligman formula (MKF) containing hydroquinone 2%, tretinoin 0.05%, and hydrocortisone 1% for the treatment of facial PIH in Indian patients. METHODS: Thirty Indian patients (Fitzpatrick skin Types III-V) with facial PIH were randomly assigned to 2 groups of 15 each. One group received serial GA peels combined with an intervening topical regimen containing MKF. The other group received MKF alone. Results were evaluated by a clinical investigator at baseline and at the end of 21 weeks (3 weeks after treatment completion) using an objective scoring system, the Hyperpigmentation Area and Severity Index (HASI) score, and clinical photography. RESULTS: The baseline mean HASI scores of the 2 groups were comparable. There was a statistically significant difference in the mean HASI score of the peels group compared with the MKF alone group at 12 weeks (p = .004) and 21 weeks (p

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Skin-derived TSLP systemically expands regulatory T cells

Publication date: Available online 23 January 2017
Source:Journal of Autoimmunity
Author(s): Theresa M. Leichner, Atsushi Satake, Victor Sanoe Harrison, Yukinori Tanaka, Angela S. Archambault, Brian S. Kim, Mark C. Siracusa, Warren J. Leonard, Ali Naji, Gregory F. Wu, David Artis, Taku Kambayashi
Regulatory T cells (Tregs) are a subset of CD4⁺ T cells with suppressive function and are critical for limiting inappropriate activation of T cells. Hence, the expansion of Tregs is an attractive strategy for the treatment of autoimmune diseases. Here, we demonstrate that the skin possesses the remarkable capacity to systemically expand Treg numbers by producing thymic stromal lymphopoietin (TSLP) in response to vitamin D receptor stimulation. An ∼2-fold increase in the proportion and absolute number of Tregs was observed in mice treated topically but not systemically with the Vitamin D3 analog MC903. This expansion of Tregs was dependent on TSLP receptor signaling but not on VDR signaling in hematopoietic cells. However, TSLP receptor expression by Tregs was not required for their proliferation. Rather, skin-derived TSLP promoted Treg expansion through dendritic cells. Importantly, treatment of skin with MC903 significantly lowered the incidence of autoimmune diabetes in non-obese diabetic mice and attenuated disease score in experimental autoimmune encephalomyelitis. Together, these data demonstrate that the skin has the remarkable potential to control systemic immune responses and that Vitamin D-mediated stimulation of skin could serve as a novel strategy to therapeutically modulate the systemic immune system for the treatment of autoimmunity.



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HII mesophase as a drug delivery system for topical application of methyl salicylate

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100
Author(s): Xin Liang, Yu-lin Chen, Xiao-jing Jiang, Sheng-mei Wang, Ji-wen Zhang, Shuang-ying Gui
The main objective of this study was to develop reversed hexagonal (HII) mesophase for transdermal delivery of methyl salicylate. The formulation was prepared, characterized and evaluated for its skin penetration in vitro and skin retention in vivo. Preliminary pharmacodynamics and skin irritation were also investigated. The formulation was identified as hexagonal structure. In vitro study exhibited that HII mesophase enhanced the skin permeation by delivering 2.61 times more methyl salicylate than the commercially available cream. Meanwhile, HII mesophase presented higher bioavailability as AUC(0–24) and AUC(0–∞) were 32.894μg·mL⁻¹ and 32.935μg·mL⁻¹ respectively, while the cream were 12.791μg·mL⁻¹ and 12.970μg·mL⁻¹. Preliminary pharmacodynamics studies demonstrated that HII mesophase possessed anti-inflammatory and analgesic effects for inhibiting paw edema, granuloma and pain. MeSa HII mesophase showed no skin irritation on the normal rat skin. Thus, HII mesophase was considered as an effective delivery system for MeSa.

Graphical abstract

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Efficacy of mindfulness meditation for smoking cessation: A systematic review and meta-analysis

Publication date: June 2017
Source:Addictive Behaviors, Volume 69
Author(s): Margaret A. Maglione, Alicia Ruelaz Maher, Brett Ewing, Benjamin Colaiaco, Sydne Newberry, Ryan Kandrack, Roberta M. Shanman, Melony E. Sorbero, Susanne Hempel
BackgroundSmokers increasingly seek alternative interventions to assist in cessation or reduction efforts. Mindfulness meditation, which facilitates detached observation and paying attention to the present moment with openness, curiosity, and acceptance, has recently been studied as a smoking cessation intervention.AimsThis review synthesizes randomized controlled trials (RCTs) of mindfulness meditation (MM) interventions for smoking cessation.MethodsFive electronic databases were searched from inception to October 2016 to identify English-language RCTs evaluating the efficacy and safety of MM interventions for smoking cessation, reduction, or a decrease in nicotine cravings. Two independent reviewers screened literature using predetermined eligibility criteria, abstracted study-level information, and assessed the quality of included studies. Meta-analyses used the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The quality of evidence was assessed using the GRADE approach.FindingsTen RCTs of MM interventions for tobacco use met inclusion criteria. Intervention duration, intensity, and comparison conditions varied considerably. Studies used diverse comparators such as the American Lung Association's Freedom from Smoking (FFS) program, quitline counseling, interactive learning, or treatment as usual (TAU). Only one RCT was rated as good quality and reported power calculations indicating sufficient statistical power. Publication bias was detected. Overall, mindfulness meditation did not have significant effects on abstinence or cigarettes per day, relative to comparator groups. The small number of studies and heterogeneity in interventions, comparators, and outcomes precluded detecting systematic differences between adjunctive and monotherapy interventions. No serious adverse events were reported.ConclusionsMM did not differ significantly from comparator interventions in their effects on tobacco use. Low-quality evidence, variability in study design among the small number of existing studies, and publication bias suggest that additional, high-quality adequately powered RCTs should be conducted.



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Editorial Board

Publication date: May 2017
Source:Addictive Behaviors, Volume 68





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A Somatic HIF2α Mutation-Induced Multiple and Recurrent Pheochromocytoma/Paraganglioma with Polycythemia: Clinical Study with Literature Review

Abstract

A syndrome known as pheochromocytomas (PCC)/paragangliomas (PGL) and polycythemia resulted from gain-of-function mutation of hypoxia-inducible factor 2α (HIF2α) has been reported recently. However, clinical features of this syndrome vary from patient to patient. In our study, we described the clinical features of the patient within 15-year follow-up with a literature review. The patient presented with "red face" since childhood and was diagnosed with polycythemia and pheochromocytoma in 2000, and then, tumor was removed at his age of 27 (year 2000). However, 13 years later (2013), he was diagnosed with multiple paragangliomas. Moreover, 2 years later (2015), another two paragangaliomas were also confirmed. Genetic analysis of hereditary PCC/PGL-related genes was conducted. A somatic heterozygous missense mutation of HIF2α (c.1589C>T) was identified at exon 12, which is responsible for the elevated levels of HIF2α and erythropoietin (EPO) and subsequent development of paragangaliomas. However, this mutation was only found in the tumors from three different areas, not in the blood. So far, 13 cases of PCC/PGL with polycythemia have been reported. Among them, somatic mutations of HIF2α at exon 12 are responsible for 12 cases, and only 1 case was caused by germline mutation of HIF2α at exon 9. The HIF2α mutation-induced polycythemia with PCC/PGL is a rare syndrome with no treatment for cure. Comprehensive therapies for this disease include removal of the tumors and intermittent phlebotomies; administration of medications to control blood pressure and to prevent complications or death resulted from high concentration of red blood cell (RBC). Genetic test is strongly recommended for patients with early onset of polycythemia and multiple/recurrent PCC/PGL.

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Prospective Study for Prognostic Biomarkers of Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Intervention:   Other: laboratory biomarker analysis
Sponsors:   Sun Yat-sen University;   Guilin Medical University, China
Not yet recruiting - verified January 2017

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Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.

Conditions:   Primary Hyperparathyroidism;   Parathyroid Adenoma;   Parathyroid Hyperplasia
Interventions:   Drug: Cinacalcet 30 mg Tablet;   Drug: Denosumab Inj 60 mg/ml;   Other: Placebo tablets;   Other: Saline Injection (Placebo)
Sponsors:   Peter Vestergaard;   Aalborg University
Not yet recruiting - verified January 2017

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Radiation Plus Concurrent Nimotuzumab in Elderly Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Interventions:   Drug: Nimotuzumab;   Radiation: Radiation
Sponsor:   Zhejiang Cancer Hospital
Recruiting - verified January 2017

http://ift.tt/2jTZOED

MRI Screening of Second Primary Cancer Occurring Within Radiation Fields After Treatment by External Beam Radiation Therapy for Hereditary Retinoblastoma (DepiSCARRH)

Condition:   Hereditary Retinoblastoma
Intervention:   Procedure: MRI
Sponsor:   Institut Curie
Not yet recruiting - verified January 2017

http://ift.tt/2j5GQpW

WEE1 Inhibitor With Cisplatin and Radiotherapy: A Trial in Head and Neck Cancer

Conditions:   Hypopharynx Squamous Cell Carcinoma;   Oral Cavity Squamous Cell Carcinoma;   Larynx Cancer
Interventions:   Drug: AZD1775;   Drug: Cisplatin;   Radiation: Radiotherapy
Sponsors:   University of Birmingham;   AstraZeneca;   Cancer Research UK
Not yet recruiting - verified January 2017

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Time to diagnosis and stage of symptomatic colorectal cancer determined by three different sources of information: A population based retrospective study

Publication date: April 2017
Source:Cancer Epidemiology, Volume 47
Author(s): Alfonso Leiva, Magdalena Esteva, Joan Llobera, Francesc Macià, Salvador Pita-Fernández, Luis González-Luján, María A Sánchez-Calavera, María Ramos
BackgroundSurvival rates from colorectal cancer (CRC) are highly variable in Europe. This variability could potentially be explained by differences in healthcare system delays in diagnosis. However, even when such delays are reduced, the relationship of the diagnostic interval (time from presentation with symptoms to diagnosis) with outcome is uncertain.MethodsA total of 795 patients with CRC from 5 regions of Spain were retrospectively examined in this population-based multicenter study. Consecutive incident cases of CRC were identified from pathology services. The total diagnostic interval (TDI) was defined as the time from the first presentation with symptoms to diagnosis based on 3 different sources of information: (i) patient-recorded data (PR-TDI) by interview, (ii) hospital-recorded data (HR-TDI), and (iii) general practitioner-recorded data (GPR-TDI). Concordance correlation coefficients (CCCs) were used to estimate the agreement of 3 different TDIs. The TDIs of patients with different stages of CRC were also compared using the Kruskal-Wallis test.ResultsThe median TDI was 131days based on patient interview data, 91days based on HR data, and 111days based on GPR data. Overall, the agreement of these TDIs was poor (CCCPRvsHR=0.399, CCCPRvsGPR=0.518, CCCHRvsGPR=0.383). Univariate analysis indicated that the TDI was greater in those with less advanced CRC for all 3 methods of calculation, but this association was only statistically significant for the HR-TDI (p=0.021).ConclusionThere is no evidence that patients with more advanced CRC have longer TDIs. In fact, we found an inverse relationship between the TDI and CRC stage, an example of the "waiting time paradox". This association may likely be due to the presence of unmeasured confounders as the stage when symptoms appear or the tumour aggressiveness.



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Efficacy and relapse-suppression of severe plaque psoriasis by oxymatrine: Results from a single blinded randomized controlled clinical trial

Abstract

Background

Current drugs in psoriasis treatment are associated with drawbacks such as rapid recrudescence, high costs and unwanted side effects. Oxymatrine has a long clinical use in the treatment of hepatitis and cancer in China.

Objective

To explore the efficacy and safety of oxymatrine injection in patients with severe plaque psoriasis.

Methods

Sixty-seven patients were randomly allocated to receive oxymatrine injections (0.6 g/d, 8weeks) or acitretin capsules (0.75mg/kg·d from week 0~2 and 20-30 mg/d from week 3~8), and followed up for another 24 weeks. The primary end point was the percentage of patients with ≥50% reduction of psoriasis area and severity index (PASI 50) at week 32. The secondary end points included the skin classification grade and the dermatology life quality index (DLQI). Side effects during the whole study were recorded to assess the safety profile.

Results

Treatment with oxymatrine or acitretin for 8 weeks significantly decreased PASI score, skin classification grade and DLQI score (P<0.001), with no significant differences between oxymatrine and acitretin groups in terms of PASI 50. However, at week 32, the relapse rate in oxymatrine group were significantly lower than that of acitretin group (P<0.001). Moreover, while the number of patients with metabolic abnormalities was increased in the acitretin group, a significant reduction was observed in the oxymatrine group. In addition, rates of adverse reactions were significantly decreased in the oxymatrine group as compared to that of acitretin group (P<0.001).

Conclusion

Treatment with oxymatrine effectively ameliorated the severe plaque psoriasis, and was accompanied by only minor adverse effects.

This article is protected by copyright. All rights reserved.

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Atenolol Treatment for Infantile Haemangioma

Abstract

Since 2008, propranolol has become the first line recommended treatment for infantile haemangiomas (IH) ^1,2. Propranolol is a synthetic beta-adrenergic receptor-blocking agent that is non-selective because it blocks both beta 1 and beta 2 adrenergic receptors ^3,4. The most commonly reported side effects in infants treated with propranolol for IH are sleep disturbance, cool mottled peripheries and bronchial hyperactivity ^3,5 and concerns have been raised about the potential long-term neurodevelopmental or cognitive effects^{6, 7}. A proportion of patients has to stop treatment because of adverse effects, thus treatments with other beta-blockers are considered.

This article is protected by copyright. All rights reserved.

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Comparison of the paper-based and electronic versions of the Dermatology Life Quality Index (DLQI): evidence of equivalence

Abstract

Background

The use of patient-reported outcome measures in electronic format has been increasing. However, these formats are usually not validated or compared to the original paper-based formats, so there is no evidence that they are completed in the same way.

Objectives

The aim of this study was to compare the conventional paper version and a web-based application version (iPad^®) of the DLQI to assess equivalence of scores.

Methods

The study employed a randomized cross-over design using a within-subjects comparison of the two formats of the questionnaire. International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were followed. Subjects aged over 18 years with any confirmed skin condition were recruited from a teaching hospital dermatology outpatient clinic. Expected Intra-class correlation coefficient (ICC) was 0.9 (α = 0.05)

Results

A total of 104 patients were recruited, median age=53.5 years (IQR=37.3-67.8, 43% male). The Intraclass correlation coefficient (ICC) showed high concordance between the total DLQI scores from paper and iPad^® versions (ICC = 0.98; 95% CI 0.97-0.99). Patients took a median of 78 seconds to complete the electronic version and 73 seconds for paper (p=0.008): 76% preferred the electronic version and perceived completion to take a shorter time.

Conclusions

There is high concordance, and thus equivalence, between the iPad and paper versions of the DLQI, with an ICC of 0.98, and a clear patient preference for the iPad version.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jJkCfi