Mexametric and cutometric assessment of the signs of aging of the skin area around the eyes after the use of non-ablative fractional laser, non-ablative radiofrequency and intense pulsed light

Abstract

The assessment of the signs of aging within eyes area in cutometric (skin elasticity) and mexametric (discoloration and severity of erythema) examination after the treatment with: non-ablative fractional laser, non-ablative radiofrequency (RF) and intense light source (IPL). This study included 71 patients, aged 33–63 years (the average age was 45.81) with Fitzpatrick skin type II and III. 24 patients received 5 successive treatment sessions with a 1,410-nm non-ablative fractional laser in two-week intervals, 23 patients received 5 successive treatment sessions with a non-ablative RF in one-week intervals and 24 patients received 5 successive treatment sessions with an IPL in two-week intervals. The treatment was performed for the skin in the eye area. The Cutometer and Mexameter (Courage + Khazaka electronic) reference test was used as an objective method for the assessment of skin properties: elasticity, skin pigmentation and erythema. Measurements of skin elasticity were made in three or four sites within eye area. The results of cutometric measurements for R7 showed the improvement in skin elasticity in case of all treatment methods. The largest statistically significant improvement (p < .0001) was observed in case of laser and RF, during treatment sessions, at sites at upper and lower eyelid. The smallest change in skin elasticity for the laser, RF and IPL – p = .017, p = .003 and p = .001, respectively—was observed in a site within the outer corner of the eye. In all sites of measurements and for all methods, the greatest improvement in skin elasticity was demonstrated between the first and second measurement (after 3rd procedures). The majority of the results of mexametric measurements—MEX (melanin level) and ERYT (the severity of erythema) are statistically insignificant. Fractional, non-ablative laser, non-ablation RF and intense light source can be considered as methods significantly affecting elasticity and to a lesser extent erythema and skin pigmentation around the eyes. Fractional non-ablative laser is a method which, in comparison to other methods, has the greatest impact on skin viscoelasticity. These procedures are well tolerated and are associated with a low risk of side effects.

http://ift.tt/2lBm3PR

The role of nicotinamide in acne treatment

Abstract

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent anti-inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patient's baseline or performed similarly to another standard-of-care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other first-line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time.

http://ift.tt/2l2znd3

Mexametric and cutometric assessment of the signs of aging of the skin area around the eyes after the use of non-ablative fractional laser, non-ablative radiofrequency and intense pulsed light

Abstract

The assessment of the signs of aging within eyes area in cutometric (skin elasticity) and mexametric (discoloration and severity of erythema) examination after the treatment with: non-ablative fractional laser, non-ablative radiofrequency (RF) and intense light source (IPL). This study included 71 patients, aged 33–63 years (the average age was 45.81) with Fitzpatrick skin type II and III. 24 patients received 5 successive treatment sessions with a 1,410-nm non-ablative fractional laser in two-week intervals, 23 patients received 5 successive treatment sessions with a non-ablative RF in one-week intervals and 24 patients received 5 successive treatment sessions with an IPL in two-week intervals. The treatment was performed for the skin in the eye area. The Cutometer and Mexameter (Courage + Khazaka electronic) reference test was used as an objective method for the assessment of skin properties: elasticity, skin pigmentation and erythema. Measurements of skin elasticity were made in three or four sites within eye area. The results of cutometric measurements for R7 showed the improvement in skin elasticity in case of all treatment methods. The largest statistically significant improvement (p < .0001) was observed in case of laser and RF, during treatment sessions, at sites at upper and lower eyelid. The smallest change in skin elasticity for the laser, RF and IPL – p = .017, p = .003 and p = .001, respectively—was observed in a site within the outer corner of the eye. In all sites of measurements and for all methods, the greatest improvement in skin elasticity was demonstrated between the first and second measurement (after 3rd procedures). The majority of the results of mexametric measurements—MEX (melanin level) and ERYT (the severity of erythema) are statistically insignificant. Fractional, non-ablative laser, non-ablation RF and intense light source can be considered as methods significantly affecting elasticity and to a lesser extent erythema and skin pigmentation around the eyes. Fractional non-ablative laser is a method which, in comparison to other methods, has the greatest impact on skin viscoelasticity. These procedures are well tolerated and are associated with a low risk of side effects.

http://ift.tt/2lBm3PR

The role of nicotinamide in acne treatment

Abstract

Safe and effective treatment options for acne vulgaris are needed to address side effects and increasing rates of antibiotic resistance from current treatments. Nicotinamide is a vitamin with potent anti-inflammatory properties that could offer a potential treatment option. We aim to summarize the relevant literature on the role of nicotinamide in acne vulgaris and discuss the next steps necessary to move this approach into clinical practice. We searched PubMed for clinical studies using nicotinamide for treatment of acne vulgaris. We summarized the 10 studies that met our search criteria. Six of eight studies using topical nicotinamide led to a significant reduction in acne compared with the patient's baseline or performed similarly to another standard-of-care acne treatment. Both studies using an oral supplement containing nicotinamide resulted in a significant reduction in acne compared with baseline. No major adverse side effects were noted. Our review suggests that topical and oral nicotinamide has an unclear effect on acne vulgaris due to the limited nature of the available literature. Additional studies are needed comparing nicotinamide to other first-line acne treatments and evaluating the efficacy and side effect profile of nicotinamide over an extended period of time.

http://ift.tt/2l2znd3

Commentary: Prostate cancer screening—A long run for a short slide

Publication date: Available online 20 February 2017
Source:Seminars in Oncology
Author(s): Howard L. Parnes




http://ift.tt/2kTHZSr

Evaluation of RAG1 mutations in an adult with combined immunodeficiency and progressive multifocal leukoencephalopathy

Publication date: Available online 20 February 2017
Source:Clinical Immunology
Author(s): Claudia Schröder, Niklas Baerlecken, Ulrich Pannicke, Thilo Dörk, Torsten Witte, Roland Jacobs, Matthias Stoll, Klaus Schwarz, Bodo Grimbacher, Reinhold E. Schmidt, Faranaz Atschekzei
Here we describe novel mutations in recombination activation gene 1 (RAG1) in a compound heterozygous male patient with combined T and B cell immunodeficiency (CID). Clinical manifestations besides antibody deficiency included airway infections, granulomatosis and autoimmune features. He died at the age of 37 due to PML caused by JC virus infection.By targeted next-generation sequencing we detected post mortem in this patient three mutations in RAG1. One allele harbored two novel mutations (c.1123C>G, p.H375D and c.1430delC, p.F478Sfs*14), namely a missense variant and a frameshift deletion, of which the latter leads to a truncated RAG1 protein. The other allele revealed a previously described missense mutation (c.1420C>T, p.R474C, rs199474678). Functional analysis of the p.R474C variant in an in vitro V(D)J recombination assay exhibited reduced recombination activity compared to a wild-type control. Our findings suggest that mutations in RAG1, specifically the p.R474C variant, can be associated with relatively mild clinical symptoms or delayed occurrence of T cell and B cell deficiencies but may predispose to PML.



http://ift.tt/2lpzgth

Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis

Publication date: Available online 20 February 2017
Source:Clinical Immunology
Author(s): Lauren M.F. Merlo, Samantha Grabler, James B. DuHadaway, Elizabeth Pigott, Kaylend Manley, George C. Prendergast, Lisa D. Laury-Kleintop, Laura Mandik-Nayak
Rheumatoid arthritis (RA) is a debilitating inflammatory autoimmune disease with no known cure. Recently, we identified the immunomodulatory enzyme indoleamine-2,3-dioxygenase 2 (IDO2) as an essential mediator of autoreactive B and T cell responses driving RA. However, therapeutically targeting IDO2 has been challenging given the lack of small molecules that specifically inhibit IDO2 without also affecting the closely related IDO1. In this study, we develop a novel monoclonal antibody (mAb)-based approach to therapeutically target IDO2. Treatment with IDO2-specific mAb alleviated arthritis in two independent preclinical arthritis models, reducing autoreactive T and B cell activation and recapitulating the strong anti-arthritic effect of genetic IDO2 deficiency. Mechanistic investigations identified FcγRIIb as necessary for mAb internalization, allowing targeting of an intracellular antigen traditionally considered inaccessible to mAb therapy. Taken together, our results offer preclinical proof of concept for antibody-mediated targeting of IDO2 as a new therapeutic strategy to treat RA and other autoantibody-mediated diseases.

Graphical abstract

http://ift.tt/2kGwhQ0

Evaluation of RAG1 mutations in an adult with combined immunodeficiency and progressive multifocal leukoencephalopathy

Publication date: Available online 20 February 2017
Source:Clinical Immunology
Author(s): Claudia Schröder, Niklas Baerlecken, Ulrich Pannicke, Thilo Dörk, Torsten Witte, Roland Jacobs, Matthias Stoll, Klaus Schwarz, Bodo Grimbacher, Reinhold E. Schmidt, Faranaz Atschekzei
Here we describe novel mutations in recombination activation gene 1 (RAG1) in a compound heterozygous male patient with combined T and B cell immunodeficiency (CID). Clinical manifestations besides antibody deficiency included airway infections, granulomatosis and autoimmune features. He died at the age of 37 due to PML caused by JC virus infection.By targeted next-generation sequencing we detected post mortem in this patient three mutations in RAG1. One allele harbored two novel mutations (c.1123C>G, p.H375D and c.1430delC, p.F478Sfs*14), namely a missense variant and a frameshift deletion, of which the latter leads to a truncated RAG1 protein. The other allele revealed a previously described missense mutation (c.1420C>T, p.R474C, rs199474678). Functional analysis of the p.R474C variant in an in vitro V(D)J recombination assay exhibited reduced recombination activity compared to a wild-type control. Our findings suggest that mutations in RAG1, specifically the p.R474C variant, can be associated with relatively mild clinical symptoms or delayed occurrence of T cell and B cell deficiencies but may predispose to PML.



http://ift.tt/2lpzgth

Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis

Publication date: Available online 20 February 2017
Source:Clinical Immunology
Author(s): Lauren M.F. Merlo, Samantha Grabler, James B. DuHadaway, Elizabeth Pigott, Kaylend Manley, George C. Prendergast, Lisa D. Laury-Kleintop, Laura Mandik-Nayak
Rheumatoid arthritis (RA) is a debilitating inflammatory autoimmune disease with no known cure. Recently, we identified the immunomodulatory enzyme indoleamine-2,3-dioxygenase 2 (IDO2) as an essential mediator of autoreactive B and T cell responses driving RA. However, therapeutically targeting IDO2 has been challenging given the lack of small molecules that specifically inhibit IDO2 without also affecting the closely related IDO1. In this study, we develop a novel monoclonal antibody (mAb)-based approach to therapeutically target IDO2. Treatment with IDO2-specific mAb alleviated arthritis in two independent preclinical arthritis models, reducing autoreactive T and B cell activation and recapitulating the strong anti-arthritic effect of genetic IDO2 deficiency. Mechanistic investigations identified FcγRIIb as necessary for mAb internalization, allowing targeting of an intracellular antigen traditionally considered inaccessible to mAb therapy. Taken together, our results offer preclinical proof of concept for antibody-mediated targeting of IDO2 as a new therapeutic strategy to treat RA and other autoantibody-mediated diseases.

Graphical abstract

http://ift.tt/2kGwhQ0

Clogging development and hydraulic performance of the horizontal subsurface flow stormwater constructed wetlands: a laboratory study

Abstract

The horizontal subsurface constructed wetland (HSSF CW) is a highly effective technique for stormwater treatment. However, progressive clogging in HSSF CW is a widespread operational problem. The aim of this study was to understand the clogging development of HSSF CWs during stormwater treatment and to assess the influence of microorganisms and vegetation on the clogging. Moreover, the hydraulic performance of HSSF CWs in the process of clogging was evaluated in a tracer experiment. The results show that the HSSF CW can be divided into two sections, section I (circa 0–35 cm) and section II (circa 35–110 cm). The clogging is induced primarily by solid entrapment in section I and development of biofilm and vegetation roots in section II, respectively. The influence of vegetation and microorganisms on the clogging appears to differ in sections I and II. The tracer experiment shows that the hydraulic efficiency (λ) and the mean hydraulic retention time (t _mean) increase with the clogging development; although, the short-circuiting region (S) extends slightly. In addition, the presence of vegetation can influence the hydraulic performance of the CWs, and their impact depends on the characteristics of the roots.

http://ift.tt/2lGvUEF

Irisin in goldfish (Carassius auratus): effects of irisin injections on feeding behavior and expression of appetite regulators, uncoupling proteins and lipoprotein lipase, and fasting-induced changes in FNDC5 expression

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Zahndra Diann Butt, Jessica Dalton Hackett, Hélène Volkoff
Irisin is a peptide cleaved from the fibronectin type III domain containing protein 5 (FNDC5) gene that is secreted predominantly by muscle cells but also by other tissues including brain and intestine. In mammals, irisin has been shown to have thermogenic actions via the modulation of uncoupling proteins (UCPs) and to affect feeding and energy homeostasis via actions in brain, adipose tissue, liver, muscle and gastrointestinal tract. To examine the role of irisin on feeding and metabolism in fish, the effects of peripheral (intraperitoneal) injections of irisin on feeding behavior, glucose levels and the mRNA expressions of appetite regulators (cocaine and amphetamine regulated transcript CART, agouti related protein AgRP, orexin), UCPs and lipoprotein lipase LPL and brain factors (brain-derived neurotrophic factor , BDNF and tyrosine hydroxylase TH) were assessed in brain, white muscle and intestine. Irisin injections (100ng/g) induced a decrease in food intake and increases in brain orexin, CART1 and CART2, UCP2, BDNF, muscle UCP2 and intestine LPL mRNA expressions but did not affect blood glucose levels, brain AgRP, TH, UCP1, UCP3 and LPL or muscle UCP1, UCP3 and LPL expressions. A partial goldfish FNDC5 cDNA was isolated and the expressions of FDNC5, UCPs, LPL and BDNF were also compared between fed and fasted fish. Fasting induced decreases FNDC5 mRNA expression in the brain and intestine, but not in muscle. Fasting also induced increases in brain BDNF and LPL expressions and increases in UCP1, UCP2, UCP3 and LPL expressions in muscle. Our result suggest that irisin is an anorexigenic factor in fish and its actions might be in part mediated by appetite-regulating factors such as CART and orexins as well as UCP2 and brain factors such as BDNF.



http://ift.tt/2lhbgd5

Inhibitory effects of dynorphin 3-14 on the lipopolysaccharide-induced toll-like receptor 4 signalling pathway

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Siti Sarah Fazalul Rahiman, Michael Morgan, Paul Gray, Paul Nicholas Shaw, Peter John Cabot
Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells. Treatment with DYN 3-14 (10nM) resulted in 35% inhibition of the LPS-induced nuclear translocation of NF-κB/p65. Furthermore, DYN 3-14 modulated both IL-1β and TNF-α release; inhibiting IL-1β and paradoxically augmenting TNF-α release in a concentration-independent manner. A number of opioids have been implicated in the modulation of the toll-like receptor 4 (TLR4), highlighting the complexity of their immunomodulatory effects. To determine whether DYN 3-14 modulates TLR4, HEK-Blue™⁻hTLR4 cells were stimulated with LPS in the presence of DYN 3-14. DYN 3-14 (10μM) inhibited TLR4 activation in a concentration-dependent fashion by suppressing the LPS signals around 300-fold lower than LPS-RS, a potent TLR4 antagonist. These findings indicate that DYN 3-14 is a potential TLR4 antagonist that alters cellular signaling in response to LPS and cytokine release, implicating a role for biotransformed endogenous opioid peptides in immunomodulation.



http://ift.tt/2m6VbFj

Obestatin Improves Oxidative Brain Damage and Memory Dysfunction in Rats Induced with an Epileptic Seizure

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Türkan Koyuncuoğlu, Caner Vızdıklar, Doğan Üren, Hakan Yılmaz, Çağan Yıldırım, Sefa Semih Atal, Dilek Akakın, Elif Kervancıoğlu-Demirci, Meral Yüksel, Berrak Ç. Yeğen
Obestatin was shown to alleviate renal, gastrointestinal and haemorrhage-induced brain injury in rats. In order to investigate the neuroprotective effects of obestatin on seizure-induced oxidative brain injury, an epileptic seizure was induced with a single intraperitoneal (i.p.) dose of pentylenetetrazole (PTZ, 45mg/kg) in male Wistar rats. Thirty minutes before the PTZ injection, rats were treated with either saline or obestatin (1μg/kg, i.p.). Seizure was video-taped and then evaluated by using Racine's scoring (0-5). For the assessment of memory function, passive-avoidance test was performed before seizure induction, which was repeated on the 3rd day of seizure. The rats were decapitated at the 24th or 72nd hour of seizures and brain tissues were obtained for histopathological examination and for measuring levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen radicals and myeloperoxidase (MPO) activity. Obestatin treatment reduced the average seizure score, decreased the occurrence and duration of generalized tonic-clonic seizures, presenting with a shorter latency to their onset. Increased lipid peroxidation and enhanced generation of oxygen-derived radicals detected at the post-seizure 72nd h were suppressed by the consecutive treatments of obestatin, but no changes were observed by the single obestatin treatment in the 24-h seizure group. Neuronal damage and increased GFAP immunoreactivity, observed in the hippocampal areas and cortex of PTZ-induced rats were alleviated in 3-day obestatin-treated PTZ group. PTZ-induced memory dysfunction was significantly improved in obestatin-treated PTZ group as compared to saline-treated rats. The present data indicates that obestatin ameliorated the severity of PTZ-induced seizures, improved memory dysfunction and reduced neuronal damage by limiting oxidative damage.



http://ift.tt/2lhd2Lv

Association between circulating angiotensin-converting enzyme 2 and cardiac remodeling in hypertensive patients

Publication date: Available online 20 February 2017
Source:Peptides
Author(s): Shichao Li, Zhijun Wang, Xiuhong Yang, Bo Hu, Yuling Huang, Sujing Fan
BackgroundAngiotensin-converting enzyme 2 (ACE2) plays a vital role in the pathogenesis of hypertension-induced cardiac remodeling and exhibits cardioprotective properties in hypertensive animal models. Evidence that ACE2 is an important regulator of hypertensive cardiac remodeling in humans has not been addressed directly yet.MethodsA total of 161 patients with essential hypertension and 47 age- and sex-matched normotensive healthy subjects were consecutively recruited. Serum concentration levels of ACE2 were determined by enzyme-linked immunosorbent assay. Cardiac structural and functional parameters were measured by echocardiography.ResultsSerum ACE2 concentrations were higher in hypertensive patients compared to healthy subjects (170.31 [83.50–707.12] pg/ml in patients versus 59.28 [39.71–81.81] pg/ml in healthy subjects, P<0.001). After adjustment for confounders, including age, sex, body mass index, snoring, smoking, duration of hypertension, comorbidities, medication use, mean arterial pressure and N-terminal pro-brain natriuretic peptide, serum ACE2 concentrations were positively correlated with left atrial diameter, left ventricular end-diastolic diameter and left ventricular mass in hypertensive patients. Moreover, multiple regression analyses adjusting for covariates revealed that serum ACE2 concentrations were also independently associated with left ventricular ejection fraction and late diastolic filling velocities of the mitral inflow.ConclusionsThis study reveals an elevated serum concentration of ACE2 and independent associations between serum ACE2 and echocardiographic parameters in hypertensive patients.



http://ift.tt/2m6UsnB

Editorial board

Publication date: 1 March 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 5





http://ift.tt/2m6SSST

Epidemiology of oral, salivary gland and pharyngeal cancer in children and adolescents between 1970 and 2011

Oral and pharyngeal cancer is one of the most diagnosed cancers worldwide [1], and is usually diagnosed in those 40–70years of age (Y) [2]. In the United States (US), the rates of diagnosis of oral and pharyngeal cancer in children and adolescents (0–19Y) between 2007 and 2011, ranged from negligible 0.0/100 000 in 0–4Y to 0.5/100 000 in 15–19Y [3]. Similarly, between 1970 and 2006 in Israel, the proportion of all oral, salivary gland and pharyngeal cancer (OSPC) cases was the lowest in children and adolescents (2.7%, N=317) [4].

http://ift.tt/2lGqhGz

New insights into highly potent tyrosinase inhibitors based on 3-heteroarylcoumarins: Anti-melanogenesis and antioxidant activities, and computational molecular modeling studies

Publication date: 1 March 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 5
Author(s): Francesca Pintus, Maria J. Matos, Santiago Vilar, George Hripcsak, Carla Varela, Eugenio Uriarte, Lourdes Santana, Fernanda Borges, Rosaria Medda, Amalia Di Petrillo, Benedetta Era, Antonella Fais
Melanogenesis is a physiological pathway for the formation of melanin. Tyrosinase catalyzes the first step of this process and down-regulation of its activity is responsible for the inhibition of melanogenesis. The search for molecules capable of controlling hyperpigmentation is a trend topic in health and cosmetics. A series of heteroarylcoumarins have been synthesized and evaluated. Compounds 4 and 8 exhibited higher tyrosinase inhibitory activities (IC50=0.15 and 0.38μM, respectively), than the reference compound, kojic acid (IC50=17.9μM). Compound 4 acts as competitive, while compound 8 as uncompetitive inhibitor of mushroom tyrosinase. Furthermore, compounds 2 and 8 inhibited tyrosinase activity and melanin production in B16F10 cells. In addition, compounds 2–4 and 8 proved to have an interesting antioxidant profile in both ABTS and DPPH radicals scavenging assays. Docking experiments were carried out in order to study the interactions between these heteroarylcoumarins and mushroom tyrosinase.

Graphical abstract

http://ift.tt/2lgUkn7

Synthesis of bulky-tailed sulfonamides incorporating pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-1(5H)-yl) moieties and evaluation of their carbonic anhydrases I, II, IV and IX inhibitory effects

Publication date: Available online 21 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mohamed Fares, Radwa A. Eladwy, Alessio Nocentini, Soha R. Abd El Hadi, Hazem A. Ghabbour, Ashraf Abdel-Megeed, Wagdy M. Eldehna, Hatem A. Abdel-Aziz, Claudiu T. Supuran
Using celecoxib as lead, two novel series of sulfonamides incorporating the pyridotriazolopyrimidine scaffold have been synthesized and evaluated in vitro as inhibitors against four relevant human (h) carbonic anhydrases (CAs, EC 4.2.1.1), the cytosolic and ubiquitous hCA I and II as well as the transmembrane hCA IV and hCA IX. Most of the reported sulfonamides acted as efficient, low micromolar inhibitors of hCAI, II and IV, whereas they displayed higher efficacy in inhibiting the tumor-associated isoform hCA IX. Many derivates herein reported showed better hCA IX versus hCA II selectivity ratios compared to celecoxib or acetazolamide. Considering isoform IX is a validated target for the diagnosis and treatment of hypoxic tumors, discovery of selective CA IX inhibitors represents a promising step to unveil more effective anticancer therapies.

Graphical abstract

http://ift.tt/2lh7a4Z

A PEGylated analog of short-length neuromedin U with potent anorectic and anti-obesity effects

Publication date: Available online 21 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Hiroshi Inooka, Kotaro Sakamoto, Tokuyuki Shinohara, Yasushi Masuda, Michiko Terada, Satoshi Kumano, Kotaro Yokoyama, Jiro Noguchi, Naoki Nishizawa, Hidenori Kamiguchi, Hisashi Fujita, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki
Neuromedin U (NMU) is a neuropeptide known to regulate food intake and energy homeostasis that is widely distributed in the gastrointestinal tract, hypothalamus, and pituitary. A short form of NMU, porcine NMU-8 has potent agonist activity for the receptors NMUR1 and NMUR2; however, its short half-life precludes its effective use in vivo. To address this limitation, we designed and synthesized NMU-8 analogs modified by polyethyleneglycol (PEG) with a molecular weight of 30 kDa (PEG30k) via a variety of linkers (i.e., ω-amino- and ω-imino-carboxylic acid linker). Integrated evaluation of NMUR1 and NMUR2 binding affinities in vitro and anorectic activity in mice revealed that the introduction of a linker with a rigid ring group, e.g., 2-(piperazin-1-yl)acetic acid (PipAc), yielded a highly potent anorectic peptide, PEG30k-PipAc-NMU-8 (14), possessing improved receptor binding affinity. Subsequent optimization of the molecular weight of the PEG moiety led to the discovery of a PEG20k conjugate (15), which exhibited significant anti-obesity effect upon once-daily subcutaneous administration in diet-induced obese mice with 10% and 22% body weight loss at doses of 10 and 30 nmol/kg, respectively. In addition, 15 reduced the weights of the liver and adipose tissue in a dose-dependent manner and improved the plasma biochemical parameters, e.g., insulin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and total cholesterol. Thus, our results suggest that 15, which showed potent and long-lasting biological profiles in vivo, represents a candidate peptide for investigating the central and peripheral actions of NMU and its potential for clinical use.

Graphical abstract

http://ift.tt/2lgXZBo

Discovery of Selective ATP-competitive eIF4A3 Inhibitors

Publication date: Available online 20 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Masahiro Ito, Misa Iwatani, Yusuke Kamada, Satoshi Sogabe, Shoichi Nakao, Toshio Tanaka, Tomohiro Kawamoto, Samuel Aparicio, Atsushi Nakanishi, Yasuhiro Imaeda
Eukaryotic initiation factor 4A3 (eIF4A3), an ATP-dependent RNA helicase, is a core component of exon junction complex (EJC). EJC has a variety of roles in RNA metabolism such as translation, surveillance, and localization of spliced RNA. It is worthwhile to identify selective eIF4A3 inhibitors with a view to investigating the functions of eIF4A3 and EJC further to clarify the roles of the ATPase and helicase activities in cells. Our chemical optimization of hit compound 2 culminated in the discovery of ATP-competitive eIF4A3 inhibitor 18 with submicromolar ATPase inhibitory activity and excellent selectivity over other helicases. Hence, compound 18 could be a valuable chemical probe to elucidate the detailed function of eIF4A3 and EJC.

Graphical abstract

http://ift.tt/2lh2c88

Extraction of the 3D Local Orientation of Myocytes in Human Cardiac Tissue Using X-ray Phase-Contrast Micro-Tomography and Multi-Scale Analysis

Publication date: Available online 20 February 2017
Source:Medical Image Analysis
Author(s): François Varray, Iulia Mirea, Max Langer, Françoise Peyrin, Laurent Fanton, Isabelle E. Magnin
This paper presents a methodology to access the 3D local myocyte arrangements in fresh human post-mortem heart samples. We investigated the cardiac micro-structure at a high and isotropic resolution of 3.5 μm in three dimensions using X-ray phase micro-tomography at the European Synchrotron Radiation Facility. We then processed the reconstructed volumes to extract the 3D local orientation of the myocytes using a multi-scale approach with no segmentation. We created a simplified 3D model of tissue sample made of simulated myocytes with known size and orientations, to evaluate our orientation extraction method. Afterwards, we applied it to 2D histological cuts and to eight 3D left ventricular (LV) cardiac tissue samples. Then, the variation of the helix angles, from the endocardium to the epicardium, was computed at several spatial resolutions ranging from 3.6³ mm³ to 112³ μm³. We measure an increased range of 20°to 30°from the coarsest resolution level to the finest level in the experimental samples. This result is in line with the higher values measured from histology. The displayed tractography demonstrates a rather smooth evolution of the transmural helix angle in six LV samples and a sudden discontinuity of the helix angle in two septum samples. These measurements bring a new vision of the human heart architecture from macro- to micro-scale.

Graphical abstract

http://ift.tt/2lpotPA

Task FMRI data analysis based on supervised stochastic coordinate coding

Publication date: Available online 20 February 2017
Source:Medical Image Analysis
Author(s): Jinglei Lv, Binbin Lin, Qingyang Li, Wei Zhang, Yu Zhao, Xi Jiang, Lei Guo, Junwei Han, Xintao Hu, Christine Guo, Jieping Ye, Tianming Liu
Task functional magnetic resonance imaging (fMRI) has been widely employed for brain activation detection and brain network analysis. Modeling rich information from spatially-organized collection of fMRI time series is challenging because of the intrinsic complexity. Hypothesis-driven methods, such as the general linear model (GLM), which regress exterior stimulus from voxel-wise functional brain activity, are limited due to overlooking the complexity of brain activities and the diversity of concurrent brain networks. Recently, sparse representation and dictionary learning methods have attracted increasing interests in task fMRI data analysis. The major advantage of this methodology is its promise in reconstructing concurrent brain networks systematically. However, this data-driven strategy is, to some extent, arbitrary and does not sufficiently utilize the prior information of task design and neuroscience knowledge. To bridge this gap, we here propose a novel supervised sparse representation and dictionary learning framework based on stochastic coordinate coding (SCC) algorithm for task fMRI data analysis, in which certain brain networks are learned with known information such as pre-defined temporal patterns and spatial network patterns, and at the same time other networks are learned automatically from data. Our proposed method has been applied to two independent task fMRI datasets, and qualitative and quantitative evaluations have shown that our method provides a new and effective framework for task fMRI data analysis.

Graphical abstract

http://ift.tt/2lpt7Nu

Listening to public concerns on vaccinations in order to provide information in a timely manner

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Nobutoshi Nawa, Shigetoyo Kogaki, Keiichi Ozono




http://ift.tt/1RXdwwN

Policy making for vaccine use as a driver of vaccine innovation and development in the developed world

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Katherine Seib, Andrew J. Pollard, Philippe de Wals, Ross M. Andrews, Fangjun Zhou, Richard J. Hatchett, Larry K. Pickering, Walter A. Orenstein
In the past 200years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. Highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. We examine immunization vaccine policy as a driver of vaccine innovation and development. The pathways to recommendation for use of licensed vaccines in the US, UK, Canada and Australia have been similar, including: expert review of disease epidemiology, disease burden and severity; vaccine immunogenicity, efficacy and safety; programmatic feasibility; public demand; and increasingly cost-effectiveness. Other attributes particularly important in development of future vaccines are likely to include: duration of immunity for improved vaccines such as pertussis; a greater emphasis on optimizing community protection rather than direct protection only; programmatic implementation, feasibility, improvements (as in the case of development of a universal influenza vaccine); public concerns/confidence/fears related to outbreak pathogens like Ebola and Zika virus; and major societal burden for combating hard to treat diseases like HIV and antimicrobial resistant pathogens. Driving innovation and production of future vaccines faces enormous economic hurdles as available approaches, technologies and regulatory pathways become more complex. As such, cost-mitigating strategies and focused, aligned efforts (by governments, private organizations, and private-public partnerships) will likely be needed to continue to spur major advances in vaccine technologies and development.



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Editorial Board/Aims and Scope

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10





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Omp16-based vaccine encapsulated by alginate-chitosan microspheres provides significant protection against Haemophilus parasuis in mice

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Xintian Zheng, Xiaoyan Yang, Xiaohua Li, Guo-Hua Qiu, Ailing Dai, Qichun Huang, Cuiqin Huang, Xiaofeng Guo
Haemophilus parasuis (H. parasuis) is the etiological agent of swine Glässer's disease, which leads to significant economic loss in swine industry over the world. Subunit vaccine based on outer membrane protein is one of the promising choices to protect pigs against H. parasuis infection despite low immunity efficiency. In this paper, outer membrane protein 16 (Omp16) of H. parasuis encapsulated by alginate-chitosan microspheres as antigen carriers was explored for the first time in a mouse model. Our results showed that the microspheres with Omp16 induced significant higher H. parasuis-specific antibodies, and higher titers of IL-2, IL-4, and IFN-γ than those by Omp16-FIA in treated mice (p<0.05). Moreover, H. parasuis load in the tissues from liver, spleen, and lung of mice immunized with microspheres containing Omp16 was significantly decreased (p<0.05) than that in the same counterpart tissues of control groups. In addition, 80% mice treated with Omp16 and 70% mice with Omp16-FIA were survived after challenged with H. parasuis virulent strain LY02 (serovar 5). Therefore, Omp16-based microsphere vaccine induces both humoral and cellular immune responses and provides promising protection against H. parasuis infection in mice.



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Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in healthy adults: A phase I/II, observer-blind, randomized, controlled trial

Publication date: 7 March 2017
Source:Vaccine, Volume 35, Issue 10
Author(s): Anuradha Madan, Murdo Ferguson, Eric Sheldon, Nathan Segall, Laurence Chu, Azhar Toma, Paul Rheault, Damien Friel, Jyoti Soni, Ping Li, Bruce L. Innis, Anne Schuind
BackgroundH7 influenza strains have pandemic potential. AS03-adjuvanted H7N1 A/mallard/Netherlands/12/2000 split-virion vaccine formulations were evaluated as model H7-subtype vaccine and tested after H7N9 emerged in China, and caused severe human disease with high mortality.MethodsIn this phase I/II, observer-blind, randomized trial in US and Canada, 420 healthy adults (21–64years) were randomized to receive 1 of 4 H7N1 vaccine formulations (3.75 or 7.5μg hemagglutinin adjuvanted with either AS03A or AS03B), 15μg unadjuvanted H7N1 hemagglutinin, or saline placebo, given as 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays, at day 42 (21days post-dose 2), month 6, and month 12 (HI only) for the per-protocol cohorts (398, 379 and 368 participants, respectively). Safety is reported up to month 12.ResultsBeneficial AS03 adjuvant effect was demonstrated. Committee for Medical Products for Human Use, and Center for Biologics Evaluation and Research (CBER) criteria were met for all adjuvanted formulations at day 42 (H7N1 HI assay); seroprotection (SPR) and seroconversion rates (SCR) were 88.5–94.8%, mean geometric increase (MGI) 19.2–34.9, and geometric mean titers (GMT) 98.3–180.7. Unadjuvanted H7N1 vaccine did not meet CBER criteria. In adjuvanted groups, antibody titers decreased over time; month 12 SPRs and GMTs were low (2.0–18.8% and 8.1–12.2). MN antibodies showed similar kinetics, with titers persisting at higher range than HI at month 6. All adjuvanted groups showed cross-reactivity against H7N9, with HI responses similar to H7N1.The most frequent solicited symptom in adjuvanted groups was injection site pain (71.2–86.7%); grade 3 solicited symptoms were infrequent. Nine participants reported 17 serious adverse events; none were considered causally related to vaccination.ConclusionsAdjuvanted H7N1 vaccine formulations had an acceptable safety profile and induced an antibody response after 2 doses with cross-reactivity to H7N9.ClinicalTrials.gov: NCT01934127



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Spatial distribution of resting-state BOLD regional homogeneity as a predictor of brain glucose uptake: A study in healthy aging

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Michaël Bernier, Etienne Croteau, Christian-Alexandre Castellano, Stephen C. Cunnane, Kevin Whittingstall
Positron emission tomography using [18F]-fluorodeoxyglucose (PET-FDG) is the primary imaging modality used to measure glucose metabolism in the brain (CMRGlu). CMRGlu has been used as a biomarker of brain aging and neurodegenerative diseases, but the complexity and invasive nature of PET often limits its use in research. There is therefore great interest in developing non-invasive metrics for estimating brain CMRGlu. We therefore investigated resting state fMRI metrics such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and regional global connectivity (Closeness) with multiple analytical approaches to determine their relationship to CMRGlu. We investigated this relation in two distinct cognitively healthy populations separated by age (27 young adults and 35 older adults). Overall, we found that both regionally and across participants, ReHo strongly correlated with CMRGlu in healthy young and older adults. Moreover, ReHo demonstrated the same age-related differences as CMRGlu throughout all cortical regions, particularly in the default network and frontal areas.



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Predictive modelling using neuroimaging data in the presence of confounds

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Anil Rao, Joao M. Monteiro, Janaina Mourao-Miranda
When training predictive models from neuroimaging data, we typically have available non-imaging variables such as age and gender that affect the imaging data but which we may be uninterested in from a clinical perspective. Such variables are commonly referred to as 'confounds'. In this work, we firstly give a working definition for confound in the context of training predictive models from samples of neuroimaging data. We define a confound as a variable which affects the imaging data and has an association with the target variable in the sample that differs from that in the population-of-interest, i.e., the population over which we intend to apply the estimated predictive model. The focus of this paper is the scenario in which the confound and target variable are independent in the population-of-interest, but the training sample is biased due to a sample association between the target and confound. We then discuss standard approaches for dealing with confounds in predictive modelling such as image adjustment and including the confound as a predictor, before deriving and motivating an Instance Weighting scheme that attempts to account for confounds by focusing model training so that it is optimal for the population-of-interest. We evaluate the standard approaches and Instance Weighting in two regression problems with neuroimaging data in which we train models in the presence of confounding, and predict samples that are representative of the population-of-interest. For comparison, these models are also evaluated when there is no confounding present. In the first experiment we predict the MMSE score using structural MRI from the ADNI database with gender as the confound, while in the second we predict age using structural MRI from the IXI database with acquisition site as the confound. Considered over both datasets we find that none of the methods for dealing with confounding gives more accurate predictions than a baseline model which ignores confounding, although including the confound as a predictor gives models that are less accurate than the baseline model. We do find, however, that different methods appear to focus their predictions on specific subsets of the population-of-interest, and that predictive accuracy is greater when there is no confounding present. We conclude with a discussion comparing the advantages and disadvantages of each approach, and the implications of our evaluation for building predictive models that can be used in clinical practice.



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Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Georg S. Kranz, Rene Seiger, Ulrike Kaufmann, Allan Hummer, Andreas Hahn, Sebastian Ganger, Martin Tik, Christian Windischberger, Siegfried Kasper, Rupert Lanzenberger
Sex steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are – at least in part – responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males.



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Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Aurore Menegaux, Chun Meng, Julia Neitzel, Josef G. Bäuml, Hermann J. Müller, Peter Bartmann, Dieter Wolke, Afra M. Wohlschläger, Kathrin Finke, Christian Sorg
Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults.A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity.The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults.These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery.



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Magnetic resonance fingerprinting based on realistic vasculature in mice

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Philippe Pouliot, Louis Gagnon, Tina Lam, Pramod K. Avti, Chris Bowen, Michèle Desjardins, Ashok K. Kakkar, Eric Thorin, Sava Sakadzic, David A. Boas, Frédéric Lesage
Magnetic resonance fingerprinting (MRF) was recently proposed as a novel strategy for MR data acquisition and analysis. A variant of MRF called vascular MRF (vMRF) followed, that extracted maps of three parameters of physiological importance: cerebral oxygen saturation (SatO2), mean vessel radius and cerebral blood volume (CBV). However, this estimation was based on idealized 2-dimensional simulations of vascular networks using random cylinders and the empirical Bloch equations convolved with a diffusion kernel. Here we focus on studying the vascular MR fingerprint using real mouse angiograms and physiological values as the substrate for the MR simulations. The MR signal is calculated ab initio with a Monte Carlo approximation, by tracking the accumulated phase from a large number of protons diffusing within the angiogram. We first study the identifiability of parameters in simulations, showing that parameters are fully estimable at realistically high signal-to-noise ratios (SNR) when the same angiogram is used for dictionary generation and parameter estimation, but that large biases in the estimates persist when the angiograms are different. Despite these biases, simulations show that differences in parameters remain estimable. We then applied this methodology to data acquired using the GESFIDE sequence with SPIONs injected into 9 young wild type and 9 old atherosclerotic mice. Both the pre injection signal and the ratio of post-to-pre injection signals were modeled, using 5-dimensional dictionaries. The vMRF methodology extracted significant differences in SatO2, mean vessel radius and CBV between the two groups, consistent across brain regions and dictionaries. Further validation work is essential before vMRF can gain wider application.



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Functional and oxygen-metabolic photoacoustic microscopy of the awake mouse brain

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Rui Cao, Jun Li, Bo Ning, Naidi Sun, Tianxiong Wang, Zhiyi Zuo, Song Hu
A long-standing challenge in optical neuroimaging has been the assessment of hemodynamics and oxygen metabolism in the awake rodent brain at the microscopic level. Here, we report first-of-a-kind head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin, and blood flow in awake mice. Combining these hemodynamic measurements allows us to derive two key metabolic parameters—oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). This enabling technology offers the first opportunity to comprehensively and quantitatively characterize the hemodynamic and oxygen-metabolic responses of the mouse brain to isoflurane, a general anesthetic widely used in preclinical research and clinical practice. Side-by-side comparison of the awake and anesthetized brains reveals that isoflurane induces diameter-dependent arterial dilation, elevated blood flow, and reduced OEF in a dose-dependent manner. As a result of the combined effects, CMRO2 is significantly reduced in the anesthetized brain under both normoxia and hypoxia, which suggests a mechanism for anesthetic neuroprotection. The head-restrained functional and metabolic PAM opens a new avenue for basic and translational research on neurovascular coupling without the strong influence of anesthesia and on the neuroprotective effects of various interventions, including but not limited to volatile anesthetics, against cerebral hypoxia and ischemia.



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Macroanatomy and 3D probabilistic atlas of the human insula

Publication date: 15 April 2017
Source:NeuroImage, Volume 150
Author(s): Isabelle Faillenot, Rolf A. Heckemann, Maud Frot, Alexander Hammers
The human insula is implicated in numerous functions. More and more neuroimaging studies focus on this region, however no atlas offers a complete subdivision of the insula in a reference space. The aims of this study were to define a protocol to subdivide insula, to create probability maps in the MNI152 stereotaxic space, and to provide normative reference volume measurements for these subdivisions.Six regions were manually delineated bilaterally on 3D T1 MR images of 30 healthy subjects: the three short gyri, the anterior inferior cortex, and the two long gyri.The volume of the insular grey matter was 7.7 ± 0.9cm³ in native space and 9.9 ± 0.6cm³ in MNI152 space. These volumes expressed as a percentage of the ipsilateral grey matter volume were minimally larger in women (2.7±0.2%) than in men (2.6±0.2%). After spatial normalization, a stereotactic probabilistic atlas of each subregion was produced, as well as a maximum-probability atlas taking into account surrounding structures.Automatically labelling insular subregions via a multi-atlas propagation and label fusion strategy (MAPER) in a leave-one-out experiment showed high spatial overlaps of such automatically defined insular subregions with the manually derived ones (mean Jaccard index 0.65, corresponding to a mean Dice index of 0.79), with an average mean volume error of 2.6%.Probabilistic and maximum probability atlases and the original delineations are available on the web under free academic licences.

Graphical abstract

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Metacognitive ability correlates with hippocampal and prefrontal microstructure

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Micah Allen, James C. Glen, Daniel Müllensiefen, Dietrich Samuel Schwarzkopf, Francesca Fardo, Darya Frank, Martina F. Callaghan, Geraint Rees
The ability to introspectively evaluate our experiences to form accurate metacognitive beliefs, or insight, is an essential component of decision-making. Previous research suggests individuals vary substantially in their level of insight, and that this variation is related to brain volume and function, particularly in the anterior prefrontal cortex (aPFC). However, the neurobiological mechanisms underlying these effects are unclear, as qualitative, macroscopic measures such as brain volume can be related to a variety of microstructural features. Here we leverage a high-resolution (800µm isotropic) multi-parameter mapping technique in 48 healthy individuals to delineate quantitative markers of in vivo histological features underlying metacognitive ability. Specifically, we examined how neuroimaging markers of local grey matter myelination and iron content relate to insight as measured by a signal-theoretic model of subjective confidence. Our results revealed a pattern of microstructural correlates of perceptual metacognition in the aPFC, precuneus, hippocampus, and visual cortices. In particular, we extend previous volumetric findings to show that right aPFC myeloarchitecture positively relates to metacognitive insight. In contrast, decreased myelination in the left hippocampus correlated with better metacognitive insight. These results highlight the ability of quantitative neuroimaging to reveal novel brain-behaviour correlates and may motivate future research on their environmental and developmental underpinnings.



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Heterogeneous fractionation profiles of meta-analytic coactivation networks

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Angela R. Laird, Michael C. Riedel, Mershack Okoe, Radu Jianu, Kimberly L. Ray, Simon B. Eickhoff, Stephen M. Smith, Peter T. Fox, Matthew T. Sutherland
Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i.e., d=20–300). We then iteratively computed pairwise correlation coefficients for consecutive model orders to compare spatial network topologies, ultimately yielding fractionation profiles delineating how "parent" functional brain systems decompose into constituent "child" sub-networks. Fractionation profiles differed dramatically across canonical networks: some exhibited complex and extensive fractionation into a large number of sub-networks across the full range of model orders, whereas others exhibited little to no decomposition as model order increased. Hierarchical clustering was applied to evaluate this heterogeneity, yielding three distinct groups of network fractionation profiles: high, moderate, and low fractionation. BrainMap-based functional decoding of resultant coactivation networks revealed a multi-domain association regardless of fractionation complexity. Rather than emphasize a cognitive-motor-perceptual gradient, these outcomes suggest the importance of inter-lobar connectivity in functional brain organization. We conclude that high fractionation networks are complex and comprised of many constituent sub-networks reflecting long-range, inter-lobar connectivity, particularly in fronto-parietal regions. In contrast, low fractionation networks may reflect persistent and stable networks that are more internally coherent and exhibit reduced inter-lobar communication.



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Frequency-specific electrophysiologic correlates of resting state fMRI networks

Publication date: 1 April 2017
Source:NeuroImage, Volume 149
Author(s): Carl D. Hacker, Abraham Z. Snyder, Mrinal Pahwa, Maurizio Corbetta, Eric C. Leuthardt
Resting state functional MRI (R-fMRI) studies have shown that slow (<0.1Hz), intrinsic fluctuations of the blood oxygen level dependent (BOLD) signal are temporally correlated within hierarchically organized functional systems known as resting state networks (RSNs) (Doucet et al., 2011). Most broadly, this hierarchy exhibits a dichotomy between two opposed systems (Fox et al., 2005). One system engages with the environment and includes the visual, auditory, and sensorimotor (SMN) networks as well as the dorsal attention network (DAN), which controls spatial attention. The other system includes the default mode network (DMN) and the fronto-parietal control system (FPC), RSNs that instantiate episodic memory and executive control, respectively. Here, we test the hypothesis, based on the spectral specificity of electrophysiologic responses to perceptual vs. memory tasks (Klimesch, 1999; Pfurtscheller and Lopes da Silva, 1999), that these two large-scale neural systems also manifest frequency specificity in the resting state. We measured the spatial correspondence between electrocorticographic (ECoG) band-limited power (BLP) and R-fMRI correlation patterns in awake, resting, human subjects. Our results show that, while gamma BLP correspondence was common throughout the brain, theta (4–8Hz) BLP correspondence was stronger in the DMN and FPC, whereas alpha (8–12Hz) correspondence was stronger in the SMN and DAN. Thus, the human brain, at rest, exhibits frequency specific electrophysiology, respecting both the spectral structure of task responses and the hierarchical organization of RSNs.



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Is there a role for regenerative medicine in chronic rhinosinusitis with nasal polyps?

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Immediate effects of an anchor system on the stability limit of individuals with chronic dizziness of peripheral vestibular origin

Abstract Introduction The symptoms associated with chronic peripheral vestibulopathy exert a negative impact on the independence and quality of life of these individuals, and many individuals continue to suffer from these symptoms even after conventional vestibular rehabilitation. Objective To evaluate the acute effect of an anchor system for balance evaluation of patients with chronic dizziness who failed to respond to traditional vestibular rehabilitation. Methods Subjects over 50 years of age, presenting with chronic dizziness and postural instability of peripheral vestibular origin, participated in the study. The limit of stability was evaluated in three positions using the Balance Master® system: Position 1, standing with the arms along the body; Position 2, standing with the elbows bent at 90º (simulating holding the anchors); and Position 3, with the elbows bent at 90º holding the anchors. The variables of movement latency, endpoint excursion and directional control of movement were evaluated. Results Using the anchor system, significant reduction of time in the response at the beginning of the movement compared to Position 1 (p < 0.05); increased endpoint excursion in the left lateral direction compared to Position 1 (p < 0.05); and more directional control of movement in the anterior and posterior directions (p < 0.05) compared to the other positions, were found. Conclusion While using the system anchor, individuals with chronic peripheral vestibulopathy showed an immediate improvement in the stability limit in relation to the movement latency, endpoint excursion, and directional control of movement variables, suggesting that the haptic information aids postural control.

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Resumo Introdução Os sintomas associados à vestibulopatia periférica crônica têm impacto negativo na independência e qualidade de vida dos indivíduos e muitos deles continuam a sofrer desses sintomas, mesmo depois de ter passado pela reabilitação vestibular convencional. Objetivo Avaliar o efeito agudo de um sistema de ancoragem para avaliação do equilíbrio de pacientes com tontura crônica que não responderam à reabilitação vestibular tradicional. Método Participaram do estudo indivíduos com mais de 50 anos que se apresentaram com tontura crônica e instabilidade postural de origem vestibular periférica. O limite de estabilidade foi avaliado em três posições, com o uso do sistema Balance Master®: Posição 1, de pé com os braços pendentes ao longo do corpo; Posição 2, de pé com os cotovelos flexionados em 90º (simulando a posição de segurar as âncoras); e Posição 3, com os cotovelos flexionados em 90º e segurando as âncoras. Foram avaliadas as variáveis de latência de movimento, o ponto final da excursão e o controle direcional do movimento. Resultados Com o uso do sistema de âncoras, ocorreu redução significante no tempo de resposta no início do movimento em comparação com a Posição 1 (p < 0,05); aumento no ponto final da excursão na direção lateral esquerda, em comparação com a Posição 1 (p < 0,05); e mais controle direcional do movimento nas direções anterior e posterior (p < 0,05), em comparação com as demais posições. Conclusão Enquanto usavam o sistema de âncoras, os indivíduos com vestibulopatia periférica demonstraram melhoria imediata no limite da estabilidade em relação às variáveis latência de movimento, ponto final da excursão e controle direcional do movimento. Isso sugere que a informação háptica auxilia no controle postural.

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Mode of recording and modulation frequency effects of auditory steady state response thresholds

Abstract Introduction The performance of auditory steady state response (ASSR) in threshold testing when recorded ipsilaterally and contralaterally, as well as at low and high modulation frequencies (MFs), has not been systematically studied. Objective To verify the influences of mode of recording (ipsilateral vs. contralateral) and modulation frequency (40 Hz vs. 90 Hz) on ASSR thresholds. Methods Fifteen female and 14 male subjects (aged 18–30 years) with normal hearing bilaterally were studied. Narrow-band CE-chirp® stimuli (centerd at 500, 1000, 2000, and 4000 Hz) modulated at 40 and 90 Hz MFs were presented to the participants' right ear. The ASSR thresholds were then recorded at each test frequency in both ipsilateral and contralateral channels. Results Due to pronounced interaction effects between mode of recording and MF (p < 0.05 by two-way repeated measures ANOVA), mean ASSR thresholds were then compared among four conditions (ipsi-40 Hz, ipsi-90 Hz, contra-40 Hz, and contra-90 Hz) using one-way repeated measures ANOVA. At the 500 and 1000 Hz test frequencies, contra-40 Hz condition produced the lowest mean ASSR thresholds. In contrast, at high frequencies (2000 and 4000 Hz), ipsi-90 Hz condition revealed the lowest mean ASSR thresholds. At most test frequencies, contra-90 Hz produced the highest mean ASSR thresholds. Conclusions Based on the findings, the present study recommends two different protocols for an optimum threshold testing with ASSR, at least when testing young adults. This includes the use of contra-40 Hz recording mode due to its promising performance in hearing threshold estimation.

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Resumo Introdução O desempenho da resposta auditiva de estado estável (RAEE) em testes de limiar com registros ipsilateral e contralateral e modulações em frequências (MFs) não tem sido sistematicamente estudado. Objetivo Verificar a influência do modo de registro (ipsilateral vs. contralateral) e da modulação em frequências (40 Hz vs. 90 Hz) nos limiares de RAEE. Método Foram estudados 15 mulheres e 14 homens (18-30 anos) com audição bilateral normal. Estímulos CE-chirp® de banda estreita (centrados em 500, 1.000, 2.000 e 4.000 Hz) modulados em 40 e 90 Hz de MF foram apresentados à orelha direita dos participantes. Em seguida, os limiares de RAEE foram registrados em cada frequência de teste nos canais ipsilateral e contralateral. Resultados Devido aos pronunciados efeitos de interação entre o modo de registro e MF (p < 0,05 por variância com dois fatores para medidas repetidas – Anova duas vias), os limiares médios de RAEE foram então comparados entre quatro condições (Ipsi-40 Hz, Ipsi-90 Hz, Contra-40 Hz e Contra-90 Hz), com o uso de variância e com um fator para medidas repetidas (Anova uma via). Nas frequências de teste de 500 e 1.000 Hz, a condição Contra-40 Hz produziu os mais baixos limiares médios de RAEE. Em contraste, em altas frequências (2.000 e 4.000 Hz), a condição Ipsi-90 Hz revelou os mais baixos limiares médios de RAEE. Na maioria das frequências de teste, a condição Contra-90 Hz produziu os mais elevados limiares médios de RAEE. Conclusões Com base nos achados do presente estudo, os autores recomendam dois protocolos diferentes para um teste de limiares ideal com RAEE, pelo menos em adultos jovens. Isso inclui o uso do modo de registro Contra-40 Hz, devido ao seu desempenho promissor nas estimativas do limiar auditivo.

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Hearing performance as a predictor of postural recovery in cochlear implant users

Abstract Objective This study aimed to evaluate if hearing performance is a predictor of postural control in cochlear implant (CI) users at least six months after surgery. Methods Cross-sectional study including (CI) recipients with post-lingual deafness and controls who were divided into the following groups: nine CI users with good hearing performance (G+), five CI users with poor hearing performance (G−), and seven controls (CG). For each patient, computerized dynamic posturography (CDP) tests, a sensory organization test (SOT), and an adaptation test (ADT) were applied as dual task performance, with first test (FT) and re-test (RT) on the same day, including a 40–60 min interval between them to evaluate the short-term learning ability on postural recovery strategies. The results of the groups were compared. Results Comparing the dual task performance on CDP and the weighted average between all test conditions, the G+ group showed better performance on RT in SOT4, SOT5, SOT6, and CS, which was not observed for G− and CG. The G− group had significantly lower levels of short-term learning ability than the other two groups in SOT5 (p = 0.021), SOT6 (p = 0.025), and CS (p = 0.031). Conclusion The CI users with good hearing performance had a higher index of postural recovery when compared to CI users with poor hearing performance.

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Resumo Objetivo O presente estudo teve por objetivo avaliar se o desempenho auditivo é preditor de controle postural em usuários de IC pelo menos seis meses após a cirurgia. Método Estudo transversal que consistiu em recipientes de implante coclear (IC) com surdez pós-lingual e controles, que foram divididos nos seguintes grupos: nove usuários de IC com bom desempenho auditivo (G+), cinco usuários de usuários de IC com desempenho auditivo insatisfatório (G-) e sete controles (GC). Aplicamos os testes de posturografia dinâmica computadorizada (PDC), de organização sensitiva (TOS) e de adaptação (TAd) como desempenho de dupla tarefa, primeiro teste (PT) e reteste (RT) no mesmo dia, com intervalo de 40-60 minutos entre testes, com o objetivo de avaliar a capacidade de aprendizado em curto prazo nas estratégias de recuperação postural. Comparamos os resultados dos testes. Resultados Na comparação do desempenho de dupla tarefa no teste PDC e a média ponderal entre todas as condições de teste, o grupo G+ demonstrou melhor desempenho no RT nos TOS4, TOS5, TOS6 e EC, o que não foi observado para os grupos G- e GC. O grupo G- obteve níveis significantemente mais baixos de capacidade de aprendizado em curto prazo vs. outros dois grupos no TOS5 (p = 0,021), TOS6 (p = 0,025) e EC (p = 0,031). Conclusão Usuários de IC com bom desempenho auditivo tiveram índice melhor de recuperação postural, quando comparados com usuários de IC com desempenho auditivo insatisfatório.

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Clinical outcome and patient satisfaction using biodegradable (NasoPore) and non-biodegradable packing, a double-blind, prospective, randomized study

Abstract Introduction Nasal packing after endoscopic sinus surgery is used as a standard procedure. The optimum solution to minimize or eliminate all disadvantages of this procedure may be accomplished using biodegradable packs. Objective The aim of this study was to compare patient satisfaction and clinical outcome associated with absorbable and non-absorbable packing after FESS. Methods In total, 50 patients were included in a prospective, double-blind, randomized trial. One side was packed with polyurethane foam, while the opposite side was packed with gauze packing. On the 2nd, 10th, and 30th postoperative day, the patients were questioned with the aid of a visual analog scale. The standardized questionnaires for bleeding, nasal breathing, feeling of pressure, and headache were used. The presence of synechiae, infection, or granulation was noted and recorded with the video-endoscopy. Results A significant difference according to lower pressure was found in the NasoPore group compared to the controls on day ten after surgery. The NasoPore packing had lower scores with respect to postoperative nose blockage on the 2nd and 10th days. Mucosal healing was better for the NasoPore group, both at day ten and 30 compared with the control group. Conclusion The overall patient comfort is higher when using NasoPore compared to non-resorbable traditional impregnated gauze packing. Intensive saline douches applied three to four times per day are mandatory after the operation to prevent synechiae formation and fluid resorption by the packing.

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Resumo Introdução O tamponamento nasal após cirurgia sinusal endoscópica é procedimento de rotina. A solução ideal para minimizar ou eliminar as desvantagens desse procedimento pode ser alcançada com o uso de tampões biodegradáveis. Objetivo Comparar a satisfação do paciente e o desfecho clínico associados ao uso de tampões absorvíveis e não absorvíveis após a cirurgia funcional dos seios paranasais (FESS- Functional Endoscopic Sinus Surgery). Método Foram incluídos 50 pacientes neste estudo prospectivo, duplo-cego e randomizado. Um dos lados foi tamponado com espuma de poliuretano, enquanto no outro lado foi feito um tamponamento com gaze. Nos 2º, 10º e 30º dias após a operação, os pacientes foram perguntados com a ajuda de uma escala analógica visual. Foram empregados questionários padronizados para sangramento, respiração nasal, sensação de pressão e cefaleia. A presença de sinequias, infecção ou granulação foi registrada por videoendoscopia. Resultados Foi observada diferença significante, da sensação de pressão, menor no lado tratado com NasoPore vs. controles no 10º dia após a cirurgia. O tamponamento com NasoPore obteve escores mais baixos com respeito ao bloqueio nasal pós-operatório no 2º e 10º dias. A cicatrização da mucosa foi melhor no lado do NasoPore, mas no 10º e 30º dias os resultados foram comparáveis com os do lado de controle. Conclusão O conforto geral do paciente é maior com o uso de NasoPore vs. tamponamento tradicional com gaze besuntada não reabsorvível. O uso vigoroso de jatos de solução salina aplicados 3-4 vezes ao dia é um procedimento obrigatório após a cirurgia, para evitar a formação de sinequias e para uma absorção natural do tampão.

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Prevalence of dizziness in the population of Minas Gerais, Brazil, and its association with demographic and socioeconomic characteristics and health status

Abstract Introduction The state of Minas Gerais, Brazil has no data on the prevalence of dizziness in the population and this information can be fundamental as the basis of public health policies, promotion, prevention and rehabilitation campaigns. Objective Investigate the prevalence of the symptom of dizziness in the population of Minas Gerais according to Sample Survey of Households, as well as describe the profile of interviewed individuals and the association between dizziness and socioeconomic, demographic features and health status. Methods This was a cross-sectional observational study that analyzed individuals with dizziness symptom reported in the previous month. The data entered in the Sample Survey of Households of 2011 were analyzed. An independent statistical association was determined between the selected variables and dizziness through multivariate analysis. Results Dizziness was the third major complaint among individuals who mentioned any health problems in the previous month, with an estimated population of 209,025 individuals and reported by 6.7% of symptomatic ones, with higher prevalence values only reported for the symptoms of fever and headache. Among individuals who reported dizziness, 94% were adults or elderly (p ≤ 0.001) and 63% were females (p = 0.003). A statistically significant association (p < 0.001) was observed between the response variable and the variables: self-perceived health, hypertension, heart disease, diabetes, depression, seeking or requiring medical or health care in the previous month and private health care plan or insurance. Among individuals with dizziness, 84.2% sought or required medical or health care and 80.1% did not have a private health plan or insurance in the assessed period. Conclusion The dizziness symptom was highly prevalent in the population of Minas Gerais during the assessed month of the investigation. Dizziness was prevalent in adults and the elderly and showed a statistical association with socioeconomic and demographic characteristics, as well as the assessed health status.

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Resumo Introdução O Estado de Minas Gerais, Brasil, não tem dados sobre a prevalência de tontura na população e essas informações podem ser fundamentais para basear políticas de saúde pública, campanhas de promoção e prevenção e a reabilitação. Objetivo Investigar a prevalência do sintoma de tontura na população do Estado de Minas Gerais segundo a Pesquisa por Amostra de Domicílio (PAD-MG), assim como descrever o perfil dos indivíduos entrevistados e as relações entre tontura e características socioeconômicas, demográfica e condições de saúde. Método Estudo de caráter observacional transversal com análise dos indivíduos com relato de sintoma de tontura no último mês. Foram analisados os dados inseridos na PAD-MG de 2011. Determinou-se associação estatística independente entre as variáveis selecionadas e a tontura por intermédio de análise multivariada. Resultados A tontura foi a terceira queixa principal entre os indivíduos que mencionaram algum problema de saúde no último mês, com estimativa populacional de 209.025 indivíduos e relatada por 6,7% dos sintomáticos, com valores inferiores somente aos sintomas de febre e dores de cabeça, respectivamente. Dentre indivíduos com relato de tontura, 94% são adultos ou idosos (p ≤ 0,001) e 63% do sexo feminino (p = 0,003). Foi encontrada associação estatisticamente significante (p < 0,001) entre a variável resposta e as variáveis autopercepção de saúde, hipertensão, doenças cardíacas, diabetes, depressão, procura ou necessidade de atendimento médico ou de saúde no último mês e presença de cobertura de plano ou seguro-saúde. Dentre os indivíduos com tontura, 84,2% procuraram ou precisaram de atendimento médico ou de saúde e 80,1% não tinham cobertura de plano ou seguro-saúde no período pesquisado. Conclusão O sintoma de tontura se mostrou altamente prevalente na população de Minas Gerais no mês de referência da pesquisa. A tontura foi prevalente nos indivíduos adultos e idosos e apresentou associação estatística com as características socioeconômicas, demográficas e condições de saúde estudadas.

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Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil

Abstract Introduction Molecular studies about carcinomas of the oral cavity and oropharynx demonstrate the presence of human papilomavirus genome in these tumors, reinforcing the participation of human papilomavirus in oral carcinogenesis. Objectives This study aimed to determine the prevalence of human papilomavirus and genotype distribution of HPV16 and HPV18 in oral cavity and oropharynx carcinomas, as well as their association with clinical characteristics of the tumors. Methods This is a retrospective study, with clinical data collected from 82 patients. Human papilomavirus detection was conducted on specimens of oral cavity and oropharynx carcinomas included in paraffin blocks. Patients were assisted in a cancer reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of human papilomavirus. Results Among the patients evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78%) and alcohol consumption (70.8%) were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9–36.6) of which 33.3% were HPV16 and 14.3% were HPV18. The presence of lymph node metastases and registered deaths were less frequent in human papilomavirus positive tumors, suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant. Conclusion The results obtained in the present study, with respect to the presence of the high-risk HPV16 and HPV18 genotypes, highlight the importance of human papilomavirus vaccination in the control of oral cavity and oropharynx carcinomas.

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Resumo Introdução Estudos moleculares sobre carcinomas da cavidade oral e orofaringe demonstram a presença do genoma do papilomavírus humano (HPV) nesses tumores, o que enfatiza a participação do HPV na carcinogênese oral. Objetivos Determinar a prevalência de HPV e a distribuição genotípica de HPV16 e HPV18 nos carcinomas de cavidade oral e orofaringe, bem como sua associação com as características clínicas dos tumores. Método Estudo retrospectivo, com dados clínicos coletados de 82 pacientes. A detecção de HPV foi feita em amostras de carcinomas de cavidade oral e orofaringe incluídos em blocos de parafina. Os pacientes foram atendidos em um centro de referência para tratamento do câncer, na região central do Brasil, entre 2005 e 2007. Foi usada a reação em cadeia de polimerase (PCR) para a detecção e genotipagem do HPV. Resultados Entre os pacientes avaliados, 78% eram homens. A média de idade do grupo era de 58 anos. Fatores de risco como o tabagismo (78%) e consumo de álcool (70,8%) foram registrados para o grupo. HPV DNA foi detectado em 21 casos (25,6%; IC de 95%, 16,9-36,6), dos quais 33,3% eram HPV16 e 14,3% eram HPV18. A presença de metástases em linfonodos e os óbitos registrados foram menos frequentes em tumores positivos para HPV, o que sugere melhor prognóstico para esses casos; contudo, as diferenças entre os grupos não foram estatisticamente significantes. Conclusão Os resultados obtidos no presente estudo, com respeito à presença de genótipos de alto risco de HPV16 e HPV18, destacam a importância da vacinação para HPV no controle dos carcinomas de cavidade oral e orofaringe.

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A possible cause of epistaxis: increased masked hypertension prevalence in patients with epistaxis

Abstract Introduction Epistaxis and hypertension are frequent conditions in the adult population. Masked hypertension is defined as a clinical condition in which a patient's office blood pressure level is <140/90 mmHg, but the ambulatory or home blood pressure readings are in the hypertensive range. Many studies have proved that hypertension is one of the most important causes of epistaxis. The prevalence of this condition in patients with epistaxis is not well defined. Objective This study aimed to evaluate the prevalence of masked hypertension using the results of office blood pressure measurement compared with the results of ambulatory blood pressure monitoring. Methods Sixty patients with epistaxis and 60 control subjects were enrolled in the study. All patients with epistaxis and controls without history of hypertension underwent physical examination, including office blood pressure measurement, ambulatory or home blood pressure, and measurement of anthropometric parameters. Results Mean age was similar between the epistaxis group and the controls – 21–68 years (mean 42.9) for the epistaxis group and 18–71 years (mean 42.2) for the control group. A total of 20 patients (33.3%) in the epistaxis group and 7 patients (11.7%) in the control group (p = 0.004) had masked hypertension. Night-time systolic blood pressure was significantly higher in patients with epistaxis than in the control group (p < 0.005). However, no significant difference was found in daytime systolic blood pressure between the control group and the patients with epistaxis (p = 0.517). Conclusion This study demonstrates increased masked hypertension prevalence in patients with epistaxis. We suggest that all patients with epistaxis should undergo ambulatory or home blood pressure to detect masked hypertension, which could be a possible cause of epistaxis.

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Resumo Introdução Epistaxe e hipertensão são condições frequentes na população adulta. Hipertensão mascarada é definida como uma condição clínica em que o nível da pressão arterial do paciente no consultório é < 140/90 mm Hg, mas as leituras da pressão arterial ambulatorial ou em casa se encontram na faixa hipertensiva. Muitos estudos demonstraram que a hipertensão é uma das causas mais importantes de epistaxe. Ainda não está devidamente definida a prevalência dessa condição em pacientes com epistaxe. Objetivo Avaliar a prevalência de HM com o uso dos resultados de mensurações da pressão arterial no consultório, em comparação com os resultados da MAPA. Método Foram recrutados 60 pacientes com epistaxe e 60 indivíduos para controle. Todos os pacientes com epistaxe e os controles sem histórico de hipertensão passaram por exame físico, inclusive determinação da pressão arterial no consultório, MAPA e mensuração dos parâmetros antropométricos. Resultados A média de idade foi similar entre o grupo com epistaxe e os controles: de 21 a 68 (média 42,9) anos para o grupo com epistaxe e de 18 a 71 (média 42,2) anos para o grupo controle. No total, 20 pacientes (33,3%) no grupo com epistaxe e sete (11,7%) no grupo controle (p = 0,004) apresentaram hipertensão mascarada. A pressão arterial sistólica noturna foi significantemente mais alta em pacientes com epistaxe, em comparação com o grupo controle (p < 0,005). No entanto, não foi observada diferença significante na pressão arterial sistólica obtida durante o dia entre o grupo controle e os pacientes com epistaxe (p = 0,517). Conclusão O presente estudo demonstra maior prevalência de hipertensão mascarada em pacientes com epistaxe. Sugerimos que todos os pacientes com epistaxe devam ser submetidos à monitoração da pressão arterial caseira ou em consultório com o objetivo de detectar hipertensão mascarada, que pode ser uma causa possível de epistaxe.

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Assessment of Eustachian tube function in patients with tympanic membrane retraction and in normal subjects,

Abstract Introduction The diagnosis of Eustachian tube dysfunctions is essential for better understanding of the pathogenesis of chronic otitis media. A series of tests to assess tube function are described in the literature; however, they are methodologically heterogeneous, with differences ranging from application protocols to standardization of tests and their results. Objective To evaluate the variation in middle ear pressure in patients with tympanic membrane retraction and in normal patients during tube function tests, as well as to evaluate intra-individual variation between these tests. Methods An observational, contemporary, cross-sectional study was conducted, in which the factor under study was the variation in middle ear pressure during tube function tests (Valsalva maneuver, sniff test, Toynbee maneuver) in healthy patients and in patients with mild and moderate/severe tympanic retraction. A total of 38 patients (76 ears) were included in the study. Patients underwent tube function tests at two different time points to determine pressure measurements after each maneuver. Statistical analysis was performed using SPSS software, version 18.0, considering p-values <0.05 as statistically significant. Results Mean (standard deviation) age was 11 (2.72) years; 55.3% of patients were male and 44.7% female. The prevalence of type A tympanogram was higher among participants with healthy ears and those with mild retraction, whereas type C tympanograms were more frequent in the moderate/severe retraction group. An increase in middle ear pressure was observed during the Valsalva maneuver at the first time point evaluated in all three groups of ears (p = 0.012). The variation in pressure was not significant either for the sniff test or for the Toynbee maneuver at the two time points evaluated (p ≥ 0.05). Agreement between measurements obtained at the two different time points was weak to moderate for all tests in all three groups of ears, and the variations in discrepancy between measurements were higher in ears with moderate/severe tympanic retraction. Conclusion In this study population, the mean pressure in the middle ear showed significant variation only during the Valsalva maneuver at the first time point evaluated in the three groups of ears. Normal ears and those with mild retraction behaved similarly in all tests. The tested maneuvers exhibited weak to moderate intra-individual variation, with the greatest variation occurring in ears with moderate/severe retraction.

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Resumo Introdução O diagnóstico das disfunções da tuba auditiva é essencial para o melhor entendimento da patogênese da otite média crônica. A literatura descreve uma série de testes que avaliam a função tubária; contudo, tais exames são metodologicamente heterogêneos, com diferenças que variam desde os protocolos de aplicação até a padronização dos exames e seus resultados. Objetivo Avaliar a variação na pressão na orelha média em pacientes com retração da membrana timpânica e em indivíduos normais durante os testes de função tubária e também avaliar a variação intraindividual desses testes. Método Estudo observacional do tipo transversal e contemporâneo, no qual o fator em estudo foi a variação na pressão na orelha média durante os testes de função tubária (manobra de Valsalva, Sniff Test e manobra de Toynbee) em indivíduos normais e em pacientes com retrações timpânicas leves e moderadas/graves. Foram incluídos 38 pacientes (76 orelhas). Os pacientes foram submetidos, em dois momentos diferentes, a testes de função tubária para determinar as medidas de pressão após cada manobra. A análise estatística foi feita com o programa SPSS, versão 18.0, e consideramos como estatisticamente significativos os valores de p < 0,05. Resultados A média ± desvio padrão da idade foi de 11 ± 2,72 anos; 55,3% dos pacientes eram do gênero masculino e 44,7% do feminino. A prevalência de curvas timpanométricas do tipo A foi mais alta entre os participantes com orelhas normais e naqueles com retrações leves, enquanto as curvas timpanométricas do tipo C foram mais frequentes no grupo com retrações moderadas/graves. Observamos pressões aumentadas na orelha média durante a manobra de Valsalva no primeiro momento da avaliação nos três grupos de orelhas (p = 0,012). A variação na pressão não foi significativa para o Sniff Test, nem para a manobra de Toynbee nos dois momentos de avaliação (p ≥ 0,05). Consideramos que a concordância entre as determinações obtidas nos dois momentos diferentes foi fraca a moderada para todos os testes nos três grupos de orelhas e as variações em termos de discrepância entre as medidas foram maiores nas orelhas com retrações timpânicas moderadas/graves. Conclusão Na população estudada, a média das pressões na orelha média apresentou variação significante apenas durante a manobra de Valsalva no primeiro momento de avaliação, nos três grupos de orelhas. As orelhas normais e aquelas que apresentavam retração leve se comportaram de maneira similar nos testes. As manobras testadas exibiram uma variação intraindividual fraca a moderada e a maior variação ocorreu nas orelhas com retrações moderadas/graves.

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Effectiveness of caudal septal extension graft application in endonasal septoplasty

Abstract Introduction Septal deviation is a common disease seen in daily otorhinolaryngology practice and septoplasty is a commonly performed surgical procedure. Caudal septum deviation is also a challenging pathology for ear, nose, and throat specialists. Many techniques are defined for caudal septal deviation. Objective To evaluate the effectiveness of caudal septal extension graft (CSEG) application in patients who underwent endonasal septoplasty for a short and deviated nasal septum. Methods Forty patients with nasal septal deviation, short nasal septum, and weak nasal tip support who underwent endonasal septoplasty with or without CSEG placement between August 2012 and June 2013 were enrolled in this study. Twenty patients underwent endonasal septoplasty with CSEG placement. The rest of the group, who rejected auricular or costal cartilage harvest for CSEG placement, underwent only endonasal septoplasty without any additional intervention. Using the Nasal Obstruction Symptom Evaluation (NOSE) and Rhinoplasty Outcome Evaluation (ROE) questionnaires, pre- and post-operative acoustic rhinometer measurements were evaluated to assess the effect of CESG placement on nasal obstruction. Results In the control group, preoperative and postoperative minimal cross-sectional areas (MCA1) were 0.44 ± 0.10 cm2 and 0.60 ± 0.11 cm2, respectively (p < 0.001). In the study group, pre- and postoperative MCA1 values were 0.45 ± 0.16 cm2 and 0.67 ± 0.16 cm2, respectively (p < 0.01). In the control group, the nasal cavity volume (VOL1) value was 1.71 ± 0.21 mL preoperatively and 1.94 ± 0.17 mL postoperatively (p < 0.001). In the study group, pre- and postoperative VOL1s were 1.72 ± 0.15 mL and 1.97 ± 0.12 mL, respectively (p < 0.001). Statistical analysis of postoperative MCA1 and VOL1 values in the study and the control groups could not detect any significant intergroup difference (p = 0.093 and 0.432, respectively). In the study group, mean nasolabial angles were 78.15 ± 4.26º and 90.70 ± 2.38º, respectively (p < 0.001). Conclusion Endonasal septoplasty with CESG placement is an effective surgical procedure with minimal complication rate for subjects who have a deviated, short nasal septum and weak nasal tip support.

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Resumo Introdução Desvio septal é doença comum no cotidiano da prática otorrinolaringológica e a septoplastia é procedimento cirúrgico comum. Desvio caudal do septo nasal é também uma condição desafiadora para os otorrinolaringologistas. São muitas as técnicas definidas para desvio caudal do septo nasal. Objetivo Avaliar a eficácia da aplicação de enxerto de extensão septal caudal (EESC) em pacientes que passaram por septoplastia endonasal devido a septo nasal curto e com desvio. Método Foram recrutados para o estudo 40 pacientes com desvio de septo nasal, septo nasal curto e fraca sustentação da ponta do nariz, tratados com septoplastia endonasal com ou sem a aplicação de EESC, entre agosto de 2012 e junho de 2013. Ao todo, 20 pacientes foram tratados com septoplastia endonasal com aplicação de EESC. O restante do grupo, que rejeitou coleta de cartilagem auricular ou costal para a aplicação de EESC, foi tratado apenas com septoplastia endonasal. Com a aplicação dos questionários Nose (Nasal Obstruction Symptom Evaluation, Avaliação dos Sintomas de Obstrução Nasal) e ROE (Rhinoplasty Outcome Evaluation, Avaliação dos Desfechos da Rinoplastia), as mensurações pré e pós-operatórias com o rinômetro acústico foram obtidas com o objetivo de avaliar o efeito da aplicação de EESC na obstrução nasal. Resultados No grupo controle, as áreas de secção transversal mínima (ASTM1) antes e depois da operação foram 0,44 ± 0,10 cm2 e 0,60 ± 0,11 cm2, respectivamente (p < 0,001). No grupo de estudo, os valores antes e depois da operação para ASTM1 foram 0,45 ± 0,16 cm2 e 0,67 ± 0,16 cm2, respectivamente (p < 0,01). No grupo controle, o valor para os volumes da cavidade nasal (VOL1) foi 1,71 ± 0,21 mL no pré-operatório e 1,94 ± 0,17 mL no pós-operatório (p < 0,001). No grupo de estudo, os VOL1 antes e depois da operação foram 1,72 ± 0,15 mL e 1,97 ± 0,12 mL, respectivamente (p < 0,001). A análise estatística dos valores pós-operatórios para ASTM1 e VOL1 nos grupos de estudo e controle não permitiu a detecção de qualquer diferença intergrupos (p = 0,093 e 0,432, respectivamente). No grupo de estudo e no grupo controle, os ângulos nasolabiais médios foram 78,15 ± 4,26º e 90,70 ± 2,38º, respectivamente (p < 0,001). Conclusão A septoplastia endonasal com aplicação de EESC é um procedimento cirúrgico efetivo, com mínimo percentual de complicações para pacientes que se apresentam com septo nasal curto e com desvio e com fraca sustentação da ponta do nariz.

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Distinct characteristics of nasal polyps with and without eosinophilia

Abstract Introduction Eosinophilic and noneosinophilic Nasal polyps (NPs) are different subtypes of NPs and require different treatment methods. Objective To compare the histologic characteristics, mRNA and protein expression between Nasal Polyps with and without eosinophilia. Methods NPs tissues were obtained from eighty-six NPs patients during surgery. Eosinophilic and noneosinophilic NPs were distinguished according to immunochemical results of the specimen. The histological, mRNA and protein expression features were compared between the two groups. Results In eosinophilic NPs, we observed a significantly higher GATA-3, IL-5, IL-4, IL-13 mRNA and protein expression. In noneosinophilic NPs, IL-17, IL-23 and RORc mRNA and protein expression were increased. Immunohistochemistry tests showed, more mast cells and less neutrophils in eosinophilic NPs compared with noneosinophilic NPs. Eosinophilic NPs patient presented more severe symptom scores when compared to noneosinophilic NPs. Conclusion We demonstrate for the first time that Th2 is the predominant reaction in eosinophilic NPs while Th17 is the predominant reaction in noneosinophilic NPs. Our study may provide new treatment strategy for NPs.

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Resumo Introdução Pólipos nasais (PNs) eosinofílicos e não eosinofílicos são diferentes subtipos de PNs e requerem diferentes métodos de tratamento. Objetivo Comparar as características histológicas e a expressão de mRNAs e proteínas entre PNs com e sem eosinofilia. Método Amostras de PNs foram obtidos de 86 pacientes durante a cirurgia. PNs eosinofílicos e não eosinofílicos foram diferenciados segundo os resultados imunoistoquímicos de cada amostra. As características histológicas e de expressão de mRNAs e de proteínas foram comparadas entre os dois grupos. Resultados Em PNs eosinofílicos, observamos uma expressão significativamente maior dos mRNAs e proteínas GATA-3, IL-5, IL-4 e IL-13. Nos PNs não eosinofílicos, aumentou a expressão dos mRNAs e das proteínas IL-17, IL-23 e RORc. Nos testes imunoistoquímicos, observamos maior número de mastócitos e menor número de neutrófilos nos PNs eosinofílicos, em comparação com PNs não eosinofílicos. Os pacientes com PNs eosinofílicos obtiveram escores de sintomas mais graves vs. PNs não eosinofílicos. Conclusão Demonstramos, pela primeira vez, uma reação Th2 predominante em PNs eosinofílicos e uma reação Th17 predominante em PNs não eosinofílicos. Nosso estudo pode proporcionar novas estratégias terapêuticas para a rinossinusite crônica.

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Is there a role for regenerative medicine in chronic rhinosinusitis with nasal polyps?

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Sonographic scoring of solid thyroid nodules: effects of nodule size and suspicious cervical lymph node

Abstract Introduction Ultrasound is the most frequently used imaging method to evaluate thyroid nodules. Sonographic characteristics of thyroid nodules which are concerning for malignancy are important to define the need for fine needle aspiration biopsy or open surgery. Objective To evaluate malignancy risk of solid thyroid nodules through sonographic scoring. The effects of nodule size ≥2 cm and associated pathologic cervical lymph node in scoring were examined in addition to generally excepted suspicious features. Methods Medical data of 123 patients underwent thyroid surgery were reviewed, and 89 patients (58 females, 31 males) were included in the study. The presence and absence of each suspicious sonographic feature of thyroid nodules were scored as 1 and 0, respectively. Total ultrasound score was obtained by adding the positive ultrasound findings. Differently from the literature, nodule size ≥2 cm and associated pathologic cervical node were added in scoring criteria. The diagnostic performance of nodule characteristics for malignancy and the effect of total US score to discriminate malignant and benign disease were calculated. Results A significant relationship was found between malignancy and hypoechogenity, border irregularity, intranodular vascularity, and microcalcification (p < 0.05). Pathologic cervical node was observed predominantly in association with malignant nodules. Positive predictive value of suspicious cervical node for malignancy was 67%, similar to microcalcification. Nodule size ≥2 cm was not distinctive for diagnosis of malignancy. The number of suspicious sonographic features obtained with receiver operating characteristic analysis to discriminate between malignant and benign disease was three. Conclusion Sonographic scoring of thyroid nodules is an effective method for predicting malignancy. The authors suggest including associated pathologic node in the scoring criteria. Further studies with larger cohorts will provide more evidence about its importance in sonographic scoring.

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Resumo Introdução A ultrassonografia é o método imagiológico mais frequentemente usado na avaliação de nódulos tireoidianos. As características ultrassonográficas dos nódulos tireoidianos que dizem respeito à malignidade são importantes para a definição da necessidade de uma biópsia por aspiração com agulha fina ou uma cirurgia aberta. Objetivo Avaliar o risco de malignidade de nódulos tireoidianos sólidos por meio de escore ultrassonográfico, verificar os efeitos de nódulos ≥ 2 cm, em associação com linfonodo cervical patológico, além de características suspeitas geralmente omitidas. Método Foram revisados dados médicos de 123 pacientes tratados com cirurgia da tireoide. Foram incluídos no estudo 89 pacientes (58 mulheres, 31 homens). Presença e ausência de cada característica ultrassonográfica suspeita de nódulo tireoidiano receberam pontuações de 1 e 0, respectivamente. O escore ultrassonográfico total foi obtido pela soma dos achados ultrassonográficos positivos. Diferentemente da literatura, nódulos ≥ 2 cm e nodo cervical patológico associado foram acrescentados nos critérios de pontuação. Foram calculados o valor diagnóstico das características dos nódulos para malignidade e o efeito do escore ultrassonográfico total na diferenciação entre doença maligna vs. benigna. Resultados Foi encontrada uma associação significante entre malignidade e hipoecogenicidade, irregularidade das margens, vascularidade intranodular e microcalcificação (p < 0,05). Nodo cervical patológico foi observado predominantemente em associação com nódulos malignos. O valor preditivo positivo de nodo cervical suspeito para malignidade foi de 67%, similar ao achado para microcalcificação. Diâmetro de nódulo ≥ 2 cm não foi fator diferenciador para diagnóstico de malignidade. O número de características ultrassonográficas suspeitas obtido com a análise da curva de características de operação do receptor (receiver operating characteristic, ROC) para discriminação entre doença maligna vs. benigna foi igual a 3. Conclusão O escore ultrassonográfico dos nódulos tireoidianos é método efetivo para predição de malignidade. Sugerimos a inclusão de nódulo patológico associado aos critérios de pontuação. Futuros estudos com coortes maiores proporcionarão mais evidências sobre sua importância no escore ultrassonográfico.

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