Re: “Editor's Choice—Five Year Results of Great Saphenous Vein Treatment: A Meta-analysis”: The Results Call for Guideline Revisions

Publication date: Available online 12 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Olle Nelzén




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Early Experience with the Use of Inner Branches in Endovascular Repair of Complex Abdominal and Thoraco-abdominal Aortic Aneurysms

Publication date: Available online 12 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Athanasios Katsargyris, Pablo Marques de Marino, Hozan Mufty, Luis Mendes Pedro, Ruy Fernandes, Eric L.G. Verhoeven
ObjectivesVisceral arteries in fenestrated and branched endovascular repair (F/BEVAR) have been addressed by fenestrations or directional side branches. Inner branches, as used in the arch branched device, could provide an extra option for visceral arteries "unsuitable" for fenestrations or directional side branches. Early experience with the use of inner branches for visceral arteries in F/BEVAR is described.MethodsAll consecutive patients treated by F/BEVAR for complex abdominal aortic aneurysm (AAA) or thoraco-abdominal aneurysm (TAAA) using stent grafts with inner branches were included. Data were collected prospectively.ResultsThirty-two patients (28 male, mean age 71.6 ± 8.3 years) were included. Seven (21.9%) patients had a complex AAA and 25 (78.1%) had a TAAA. A stent graft with inner branches only was used in four (12.5%) patients. The remaining 28 (87.5%) patients received a stent graft with fenestrations and inner branches. In total 52 vessels were targeted with inner branches. Technical success was achieved in all 32 (100%) patients. All 38 inner branch target vessels in grafts including fenestrations and inner branches were instantly catheterised (<1 minute), whereas catheterisation of target vessels in "inner branch only" grafts proved more difficult (<1 minute, n = 3; 1–3 min, n = 4; and >3 min, n = 7). The 30 day operative mortality was 3.1% (1/32). Estimated survival at 1 year was 80.0% ± 8.3%. During follow-up, four renal inner branches occluded in three patients. The estimated inner branch target vessel stent patency at 1 year was 91.9 ± 4.5%. The estimated freedom from re-intervention at 1 year was 78.4% ± 8.9%.ConclusionsEarly data suggest that visceral inner branches might represent a feasible third option to address selected target vessels in F/BEVAR. Stent grafts with inner branch(es) in combination with fenestrations seem to be a better configuration than stent grafts with inner branches alone. Durability of the inner branch design needs further investigation.



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ESVS Volodos Lecture: Innovations and the Hippocratic Oath

Publication date: Available online 14 March 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Peter Gloviczki
This lecture remembers Professor Nicolai Volodos, a pioneer innovator and a giant in vascular and endovascular surgery, who performed the first endovascular repair of a thoracic aneurysm in 1987 and developed a complex endovascular program by the end of the 1980s. The manuscript recalls major innovations and innovators in vascular surgery, examines the challenges innovators and those who adopt innovations face and discusses the modern meaning of the Hippocratic Oath. The author concludes that surgical innovations are essential to advance cost-effective care, and shared decision making on adopting new therapies by an ethical surgeon and a well informed patient is the cornerstone of ethical patient care.



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Practice of hand hygiene and use of protective gloves: Differences in the perception between patients and medical staff

Publication date: Available online 13 March 2018
Source:American Journal of Infection Control
Author(s): Marta Wałaszek, Małgorzata Kołpa, Anna Różańska, Zdzisław Wolak, Małgorzata Bulanda, Jadwiga Wójkowska-Mach
This study investigated differences in perceptions of hand hygiene and protective glove use among patients and health care workers (HCWs) in Poland. We conducted a survey using an original questionnaire among 462 respondents, including 173 (37.4%) patients and 289 (62.6%) HCWs; HCWs demonstrated poor familiarity with the My 5 Moments for Hand Hygiene. The role of protective gloves in preventing health care–associated infection was overestimated by both patients and HCWs.



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The epidemiology of hospital-acquired urinary tract-related bloodstream infection in veterans

Publication date: Available online 13 March 2018
Source:American Journal of Infection Control
Author(s): Payal K. Patel, M. Todd Greene, Mary A.M. Rogers, David Ratz, Latoya Kuhn, Jennifer Davis, Sanjay Saint
BackgroundHospital-acquired urinary tract-related bloodstream infections are rare but often lethal. Recent epidemiology of this condition among the United States veteran population is poorly described.MethodsWe conducted a retrospective review of hospital-acquired urinary tract-related bloodstream infections of adult inpatients admitted to 4 Veterans Affairs hospitals over 15 years. Electronic medical records were used to obtain clinical, demographic, and microbiologic information. Descriptive statistical analyses were conducted using chi-square tests of association. Test for trend was performed by genus of organism and for case fatality rate over time.ResultsWhile the most commonly isolated organisms were Staphylococcus spp. (36.5%), the incidence of infections caused by Escherichia and Klebsiella increased over time (P = .02 and P = .03, respectively). The overall in-hospital case fatality rate was 24.2% in 499 patients. The case fatality rate was 25.8% for patients with Staphylococcus infections and 20.7% for patients with enterococcal infections.ConclusionsHospital-acquired urinary tract-related bloodstream infection is commonly due to Staphylococcus spp. and is related to the high fatality among United States veterans. Focused infection control efforts could decrease the incidence of this fatal infection.

Graphical abstract

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Changes in knowledge and attitudes of hospital environmental services staff: The Researching Effective Approaches to Cleaning in Hospitals (REACH) study

Publication date: Available online 14 March 2018
Source:American Journal of Infection Control
Author(s): Brett G. Mitchell, Nicole White, Alison Farrington, Michelle Allen, Katie Page, Anne Gardner, Kate Halton, Thomas V. Riley, Christian A. Gericke, David L. Paterson, Nicholas Graves, Lisa Hall
BackgroundThe Researching Effective Approaches to Cleaning in Hospitals (REACH) study tested a multimodal cleaning intervention in Australian hospitals. This article reports findings from a pre/post questionnaire, embedded into the REACH study, that was administered prior to the implementation of the intervention and at the conclusion of the study.MethodsA cross-sectional questionnaire, nested within a stepped-wedge trial, was administered. The REACH intervention was a cleaning bundle comprising 5 interdependent components. The questionnaire explored the knowledge, reported practice, attitudes, roles, and perceived organizational support of environmental services staff members in the hospitals participating in the REACH study.ResultsEnvironmental services staff members in 11 participating hospitals completed 616 pre- and 307 post-test questionnaires (n = 923). Increases in knowledge and practice were seen between the pre-and post-test questionnaires. Minimal changes were observed in attitudes regarding the role of cleaning and in perceived organizational support.ConclusionTo our knowledge, this is the first study to report changes in knowledge, attitudes, and perceived organizational support in environmental services staff members, in the context of a large multicenter clinical trial. In this underexplored group of hospital workers, findings suggest that environmental services staff members have a high level of knowledge related to cleaning practices and understand the importance of their role.



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Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG antibodies

Abstract

Background

Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection.

Methods

A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old.

Results

We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered.

Conclusions

Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.

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Effects of Short-Term Moisturizer Application in Different Ethnic Skin Types: Noninvasive Assessment with Optical Coherence Tomography and Reflectance Confocal Microscopy

Background/Aims: Ethnic skin types are known to differ in their morphological and physiological features. Thus, treatment responses may vary among different races. We aimed to assess skin morphology of different ethnicities and to compare the effect of short-term moisturizer application using optical coherence tomography (OCT) and reflectance confocal microscopy (RCM). Methods: Thirty healthy female subjects of European, Asian and Black ethnicity at 30–45 years of age were included in the study. OCT and RCM imaging was performed on the cheek to compare morphology. Following the 2-week application of a moisturizer cream (Sebamed® lotion) on one forearm, imaging was performed on both forearms to assess and compare treatment responses. Results: Epidermal thickness and morphology of pores varied between the three ethnic groups, with Black subjects displaying the thickest epidermis and largest skin pores. On the treated forearm, OCT measurements revealed a significantly thicker epidermis in all groups as compared to the untreated forearm. Width of skin folds on the treated forearm was measured by RCM to be significantly lower in all ethnic groups as compared to the untreated forearm. Conclusion: Different ethnic skin types showed variations in skin morphology and treatment response to short-term moisturizer application. OCT and RCM were useful methods for noninvasive, real-time, repeated assessment of ethnic skin.
Skin Pharmacol Physiol 2018;31:125–133

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Effect of different biochars amendment on soil biological indicators in a calcareous soil

Abstract

Previous studies suggest that biochar has potential to benefit soil when used as an amendment, but only few studies have investigated how the different biochars affect the microbial activity of soil in a calcareous soil. Hence, to study the effect of the biochars obtained from wheat straw and cow manure and produced under different production conditions on two biological soil indicators, dehydrogenase activity and soil respiration, after 0, 60, and 120 days of incubation (DOI), an incubation experiment as a completely randomized design with factorial arrangement in three replicates was conducted in a calcareous soil. The results of the study showed that with increasing the pyrolysis temperature (300 and 500 °C) and pyrolysis residence times (1, 3, and 6 h) of biochars, regardless of feedstock source, the dehydrogenase activity and soil respiration decreased. Both maximum activity of dehydrogenase (20.93 μg TPF g⁻¹ 24 h⁻¹) and maximum soil respiration (0.26 mg CO₂ g⁻¹ 24 h⁻¹) were found in the biochar produced from wheat straw at 300 °C, and the residence time of 1 h at the level of 10 t ha⁻¹ and minimum of these soil biological traits was observed in control treatments (soil). Moreover, the maximum activity of dehydrogenase and soil respiration was observed in 60 DOI. Therefore, when applying biochar as an amendment for increasing microbial activity in calcareous soil, the production conditions of biochar, type of biochar, and long- and short-term effects of different biochars should be taken into consideration.

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Glyphosate application increased catabolic activity of gram-negative bacteria but impaired soil fungal community

Abstract

Glyphosate is a non-selective organophosphate herbicide that is widely used in agriculture, but its effects on soil microbial communities are highly variable and often contradictory, especially for high dose applications. We applied glyphosate at two rates: the recommended rate of 50 mg active ingredient kg⁻¹ soil and 10-fold this rate to simulate multiple glyphosate applications during a growing season. After 6 months, we investigated the effects on the composition of soil microbial community, the catabolic activity and the genetic diversity of the bacterial community using phospholipid fatty acids (PLFAs), community level catabolic profiles (CLCPs), and 16S rRNA denaturing gradient gel electrophoresis (DGGE). Microbial biomass carbon (C_mic) was reduced by 45%, and the numbers of the cultivable bacteria and fungi were decreased by 84 and 63%, respectively, under the higher glyphosate application rate. According to the PLFA analysis, the fungal biomass was reduced by 29% under both application rates. However, the CLCPs showed that the catabolic activity of the gram-negative (G−) bacterial community was significantly increased under the high glyphosate application rate. Furthermore, the DGGE analysis indicated that the bacterial community in the soil that had received the high glyphosate application rate was dominated by G− bacteria. Real-time PCR results suggested that copies of the glyphosate tolerance gene (EPSPS) increased significantly in the treatment with the high glyphosate application rate. Our results indicated that fungi were impaired through glyphosate while G− bacteria played an important role in the tolerance of microbiota to glyphosate applications.

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Toll-like receptor 4 deficient mice do not develop remifentanil-induced mechanical hyperalgesia: An experimental randomised animal study

BACKGROUND Drugs with antagonistic actions on the Toll-like receptor 4 (Tlr4), such as naloxone at ultra low doses, have been used to inhibit opioid-induced hyperalgesia in rodents suggesting the involvement of this receptor and pathway on opioid-induced hyperalgesia. OBJECTIVE The aim of this study was to determine whether mice without the Tlr4 gene (Tlr4−/−) would not develop remifentanil-induced hyperalgesia. DESIGN An experimental randomised animal study. SETTING Experimental Unit, Complutense University of Madrid, Madrid, Spain. ANIMALS Twelve adult female wild-type mice and 12 adult Tlr4−/− mice. INTERVENTIONS Under sevoflurane anaesthesia, a 1-h, constant rate subcutaneous infusion of remifentanil (4 μg kg−1 min−1) or 0.9% saline. MAIN OUTCOME MEASURES Mechanical nociceptive thresholds were evaluated using a von Frey hair test before (baseline) and on days 5, 6 and 7 after treatment. Hyperalgesia was considered to be a decrease in the mechanical nociceptive threshold. Changes in mechanical nociceptive thresholds in the different groups were compared with one-sided paired t tests. RESULTS Baseline mechanical nociceptive thresholds were similar in all groups (2.2 ± 0.1 g). Remifentanil produced a 24% decrease in mechanical nociceptive thresholds in the wild-type mice (1.7 ± 0.0 g, averaged over 3 days, P = 0.00021), whereas the nociceptive thresholds were not changed in Tlr4−/− mice (2.2 ± 0.1 g, P = 0.857) or in mice receiving 0.9% saline (Tlr4−/−, 2.2 ± 0.1 g, P = 0.807; wild-type, 2.2 ± 0.1 g, P = 0.962). CONCLUSION Tlr4 receptor involvement is suggested in the development of remifentanil-induced hyperalgesia in mice. TRIAL REGISTRATION CEA-UCM 107/2012). Correspondence to Ignacio A. Gómez de Segura, Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Avda. Puerta de Hierro, 28040 Madrid, Spain Tel: +34 913 943 858; fax: +34 913 943 808; e-mail: iagsegura@vet.ucm.es © 2018 European Society of Anaesthesiology

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Executive function predicts theory of mind but not social verbal communication in school-aged children with autism spectrum disorder

Publication date: May 2018
Source:Research in Developmental Disabilities, Volume 76
Author(s): Evangelia-Chrysanthi Kouklari, Stella Tsermentseli, Bonnie Auyeung
BackgroundThe association between Executive Function (EF) and Theory of Mind (ToM) in autism spectrum disorder (ASD) has been mainly investigated using false belief tasks, whilst less is known about the EF effect on other ToM facets. Furthermore, the role EF plays in social communication in ASD is mainly assessed using parent-report EF ratings rather than direct assessment.AimsThe aim of this study was to shed more light on the effect of performance-based EF measures on ToM and social communication in middle childhood in ASD relative to neurotypical controls.Methods and proceduresCross-sectional data were collected from 64 matched, school-aged children with and without ASD (8–12 years old), tested on measures of EF (inhibition, working memory, cognitive flexibility), ToM mental state/emotion recognition and social verbal communication.Outcomes and resultsSignificant group differences were observed only in selective EF skills (inhibition & cognitive flexibility) and social verbal communication. EF working memory contributed to the explained variance of ToM but not social verbal communication in middle childhood.Conclusions and implicationsThese findings suggest that EF and ToM are still associated in middle childhood and EF may be a crucial predictor of ToM across childhood in ASD. Implications are discussed regarding the social-cognitive impairment relationship in ASD.



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Feedforward motor control in developmental dyslexia and developmental coordination disorder: Does comorbidity matter?

Publication date: May 2018
Source:Research in Developmental Disabilities, Volume 76
Author(s): Fabien Cignetti, Marianne Vaugoyeau, Aurelie Fontan, Marianne Jover, Marie-Odile Livet, Catherine Hugonenq, Frédérique Audic, Brigitte Chabrol, Christine Assaiante
Background and aimFeedforward and online controls are two facets of predictive motor control from internal models, which is suspected to be impaired in learning disorders. We examined whether the feedforward component is affected in children (8–12 years) with developmental dyslexia (DD) and/or with developmental coordination disorder (DCD) compared to typically developing (TD) children.MethodsChildren underwent a bimanual unloading paradigm during which a load supported to one arm, the postural arm, was either unexpectedly unloaded by a computer or voluntary unloaded by the subject with the other arm.ResultsAll children showed a better stabilization (lower flexion) of the postural arm and an earlier inhibition of the arm flexors during voluntary unloading, indicating anticipation of unloading. Between-group comparisons of kinematics and electromyographic activity of the postural arm revealed that the difference during voluntary unloading was between DD-DCD children and the other groups, with the former showing a delayed inhibition of the flexor muscles.ConclusionDeficit of the feedforward component of motor control may particularly apply to comorbid subtypes, here the DD-DCD subtype. The development of a comprehensive framework for motor performance deficits in children with learning disorders will be achieved only by dissociating key components of motor prediction and focusing on subtypes and comorbidities.



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Physical self-concept and body dissatisfaction among Special Olympics athletes: A comparison between sex, weight status, and culture

Publication date: May 2018
Source:Research in Developmental Disabilities, Volume 76
Author(s): Cheng-Chen Pan, Christophe Maïano, Alexandre J.S. Morin
BackgroundLittle research has looked at the associations between sex, weight status and culture, and the physical self-perceptions and body dissatisfaction of individuals with intellectual disabilities (ID) involved in Special Olympics (SO) sports.AimsTo examine sex- (male vs female), weight status- (non-overweight/obese vs. overweight/obese), and culture-based (North American vs. Asian) differences in physical self-concept and body dissatisfaction among SO athletes.Methods and procedures.A total of 139 SO athletes (aged 12–30 years) with ID participated in this study and completed measures of physical self-perceptions and body dissatisfaction. Differences according to sex, weight status, culture, and their interactions were examined.Outcomes and resultsMales SO athletes presented higher levels of self-perceived physical strength and ideal body shape than females. Additionally, non-overweight/obese SO athletes presented higher levels of self-perceived physical appearance and physical condition than their overweight/obese counterparts, as well as lower actual body shape perceptions and body dissatisfaction. Moreover, North-American SO athletes presented higher levels of self-perceived physical appearance and sport competence than their Asians counterparts, as well as lower actual body shapes perceptions and body dissatisfaction.Conclusion and implicationsThis study reveals substantial sex-, weight status-, and culture-based differences in the physical self-concept and body dissatisfaction of SO athletes.



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Optimized Mitochondrial Targeting of Proteins Encoded by Modified mRNAs Rescues Cells Harboring Mutations in mtATP6

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Randall Marcelo Chin, Tadas Panavas, Jeffrey M. Brown, Krista K. Johnson
Mitochondrial disease may be caused by mutations in the protein-coding genes of the mitochondrial genome. A promising strategy for treating such diseases is allotopic expression—the translation of wild-type copies of these proteins in the cytosol, with subsequent translocation into the mitochondria, resulting in rescue of mitochondrial function. In this paper, we develop an automated, quantitative, and unbiased screening platform to evaluate protein localization and mitochondrial morphology. This platform was used to compare 31 mitochondrial targeting sequences and 15 3′ UTRs in their ability to localize up to 9 allotopically expressed proteins to the mitochondria and their subsequent impact on mitochondrial morphology. Taking these two factors together, we synthesized chemically modified mRNAs that encode for an optimized allotopic expression construct for mtATP6. These mRNAs were able to functionally rescue a cell line harboring the 8993T > G point mutation in the mtATP6 gene.

Graphical abstract

Teaser

Allotopic expression of proteins normally encoded by mtDNA is a promising therapy for mitochondrial disease. Chin et al. use an unbiased and high-content imaging-based screening platform to optimize allotopic expression. Modified mRNAs encoding for the optimized allotopic expression constructs rescued the respiration and growth of mtATP6-deficient cells.


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The PERK Arm of the Unfolded Protein Response Regulates Mitochondrial Morphology during Acute Endoplasmic Reticulum Stress

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Justine Lebeau, Jaclyn M. Saunders, Vivian W.R. Moraes, Aparajita Madhavan, Nicole Madrazo, Mary C. Anthony, R. Luke Wiseman
Endoplasmic reticulum (ER) stress is transmitted to mitochondria and is associated with pathologic mitochondrial dysfunction in diverse diseases. The PERK arm of the unfolded protein response (UPR) protects mitochondria during ER stress through the transcriptional and translational remodeling of mitochondrial molecular quality control pathways. Here, we show that ER stress also induces dynamic remodeling of mitochondrial morphology by promoting protective stress-induced mitochondrial hyperfusion (SIMH). ER-stress-associated SIMH is regulated by the PERK arm of the UPR and activated by eIF2α phosphorylation-dependent translation attenuation. We show that PERK-regulated SIMH is a protective mechanism to prevent pathologic mitochondrial fragmentation and promote mitochondrial metabolism in response to ER stress. These results identify PERK-dependent SIMH as a protective stress-responsive mechanism that regulates mitochondrial morphology during ER stress. Furthermore, our results show that PERK integrates transcriptional and translational signaling to coordinate mitochondrial molecular and organellar quality control in response to pathologic ER insults.

Graphical abstract

Teaser

Endoplasmic reticulum (ER) stress can be transmitted to mitochondria and induce pathologic mitochondrial dysfunction in association with diverse diseases. Here, Lebeau et al. show that the PERK arm of the unfolded protein response protects mitochondria during ER stress by promoting stress-induced mitochondrial hyperfusion.


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Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Graham P. Holloway, Andrew M. Holwerda, Paula M. Miotto, Marlou L. Dirks, Lex B. Verdijk, Luc J.C. van Loon
It remains unknown if mitochondrial bioenergetics are altered with aging in humans. We established an in vitro method to simultaneously determine mitochondrial respiration and H2O2 emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H2O2 emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H2O2 and the fraction of electron leak to H2O2, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training in older individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H2O2 emission rates in the presence of ADP, the fraction of electron leak to H2O2, or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H2O2 emission and contributes to age-associated redox stress.

Graphical abstract

Teaser

Holloway et al. show that an inability of ADP to decrease mitochondrial reactive oxygen species emission contributes to redox stress in skeletal muscle tissue of older individuals and that this process is not recovered following prolonged resistance-type exercise training, despite the general benefits of resistance training for muscle health.


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A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Kengo Watanabe, Tsuyoshi Umeda, Kuniyoshi Niwa, Isao Naguro, Hidenori Ichijo
Cell volume regulation is a vital system for cellular activities. When perturbed by hypoosmotic or hyperosmotic stress, cells immediately induce the cell volume recovery system, regulatory volume decrease (RVD) or regulatory volume increase (RVI), respectively. In contrast to the knowledge about effector molecules, the molecular mechanisms linking osmosensing to RVD/RVI induction remain unknown. Additionally, few reciprocal responders in the bidirectional osmotic stress response have been identified. We previously reported that ASK3 bidirectionally switches its kinase activity under osmotic stress. Herein we demonstrate that ASK3 controls both RVD and RVI under osmotic stress. Using a high-content genome-wide small interfering RNA (siRNA) screen, we identify PP6 as a direct ASK3 inactivator. Furthermore, PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, cell survival under hyperosmotic stress. These findings suggest that the PP6-ASK3 interaction is a core module in the bidirectional osmotic stress response.

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Teaser

Osmotic stress comprises two types of information: intensity and directionality. Nevertheless, few bidirectional cellular systems have been identified. Using a high-content genome-wide siRNA screen, Watanabe et al. unveil that a PP6-ASK3 module bidirectionally interprets and converts osmotic stress signals to control cell volume homeostasis.


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Cbx4 Sumoylates Prdm16 to Regulate Adipose Tissue Thermogenesis

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Qingbo Chen, Lei Huang, Dongning Pan, Lihua J. Zhu, Yong-Xu Wang
Transcriptional co-activator Prdm16 controls brown fat development and white fat browning, but how this thermogenic function is modulated post-translationally is poorly understood. Here, we report that Cbx4, a Polycomb group protein, is a SUMO E3 ligase for Prdm16 and that Cbx4-mediated sumoylation of Prdm16 is required for thermogenic gene expression. Cbx4 expression is enriched in brown fat and is induced in adipose tissue by acute cold exposure. Sumoylation of Prdm16 at lysine 917 by Cbx4 blocks its ubiquitination-mediated degradation, thereby augmenting its stability and thermogenic function. Moreover, this sumoylation event primes Prdm16 to be further stabilized by methyltransferase Ehmt1. Heterozygous Cbx4-knockout mice develop metabolic phenotypes resembling those of Prdm16-knockout mice. Furthermore, fat-specific Cbx4 knockdown and overexpression produce remarkable, opposite effects on white fat remodeling. Our results identify a modifying enzyme for Prdm16, and they demonstrate a central role of Cbx4 in the control of Prdm16 stability and white fat browning.

Graphical abstract

Teaser

Chen et al. show that sumoylation of a key thermogenic regulator, Prdm16, at lysine 917 by Cbx4 blocks its ubiquitination-mediated degradation and, consequently, augments its stability. Sumoylation of Prdm16 is also a prerequisite for Ehmt1-mediated stabilization. At least in part through sumoylating Prdm16, Cbx4 promotes adipose thermogenic function.


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Excitatory Neuronal Hubs Configure Multisensory Integration of Slow Waves in Association Cortex

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Satoshi Kuroki, Takamasa Yoshida, Hidekazu Tsutsui, Mizuho Iwama, Reiko Ando, Takayuki Michikawa, Atsushi Miyawaki, Toshio Ohshima, Shigeyoshi Itohara
Multisensory integration (MSI) is a fundamental emergent property of the mammalian brain. During MSI, perceptual information encoded in patterned activity is processed in multimodal association cortex. The systems-level neuronal dynamics that coordinate MSI, however, are unknown. Here, we demonstrate intrinsic hub-like network activity in the association cortex that regulates MSI. We engineered calcium reporter mouse lines based on the fluorescence resonance energy transfer sensor yellow cameleon (YC2.60) expressed in excitatory or inhibitory neurons. In medial and parietal association cortex, we observed spontaneous slow waves that self-organized into hubs defined by long-range excitatory and local inhibitory circuits. Unlike directional source/sink-like flows in sensory areas, medial/parietal excitatory and inhibitory hubs had net-zero balanced inputs. Remarkably, multisensory stimulation triggered rapid phase-locking mainly of excitatory hub activity persisting for seconds after the stimulus offset. Therefore, association cortex tends to form balanced excitatory networks that configure slow-wave phase-locking for MSI.Video Abstract

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Teaser

Kuroki et al. performed cell-type-specific, wide-field FRET-based calcium imaging to visualize cortical network activity induced by multisensory inputs. They observed phase-locking of cortical slow waves in excitatory neuronal hubs in association cortical areas that may underlie multisensory integration.


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TAFA4 Reverses Mechanical Allodynia through Activation of GABAergic Transmission and Microglial Process Retraction

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Charline Kambrun, Olivier Roca-Lapirot, Chiara Salio, Marc Landry, Aziz Moqrich, Yves Le Feuvre
C-low-threshold mechanoreceptors (C-LTMRs) are sensory neurons that, beyond conveying pleasant touch, modulate nociceptive transmission within the spinal cord. However, pain alleviation by C-LTMRs remains poorly understood. Here, we show that the C-LTMR-derived TAFA4 chemokine induces a reinforcement of inhibitory synaptic transmission within spinal networks, which consequently depresses local excitatory synapses and impairs synaptic transmission from high-threshold C-fibers. In animals with inflammation induced by Freund's complete adjuvant, TAFA4 decreases the noxious stimulus-induced neuronal responses recorded in vivo and alleviates mechanical pain. Both effects are blocked by antagonists of GABAergic transmission. Furthermore, TAFA4 promotes microglial retraction in inflammation and increases the number of inhibitory synapses on lamina IIi somata. Altogether, these results demonstrate GABAergic interneurons to be the first integration relay for C-LTMRs and highlight a tight interplay between sensory neurons, microglial cells, and spinal interneurons, which fine-tunes inhibitory activity and nociceptive transmission in pathological conditions.

Graphical abstract

Teaser

TAFA4 is a recently discovered chemokine secreted by C-low-threshold mechanoreceptors (C-LTMRs). Kambrun et al. describe the interplay between C-LTMRs, spinal GABAergic neurons, and microglial cells that is responsible for the mechanical pain alleviation induced by TAFA4 by inflammation.


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Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Philippe A. Melas, Johanna S. Qvist, Matteo Deidda, Chirag Upreti, Ya Bin Wei, Fabrizio Sanna, Walter Fratta, Maria Scherma, Paola Fadda, Denise B. Kandel, Eric R. Kandel
Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids.

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Teaser

Melas et al. show that psychoactive cannabinoids modulate levels of two eukaryotic initiation factors (eIF2α and eIF2B1) known to be involved in protein synthesis, memory formation, and drug sensitivity. Cannabinoid modulation of eIF2α in vivo is only observed in adolescent animals, and is associated with cross-sensitization to cocaine.


http://ift.tt/2GrPzQz

Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Hiroto Kambara, Fei Liu, Xiaoyu Zhang, Peng Liu, Besnik Bajrami, Yan Teng, Li Zhao, Shiyi Zhou, Hongbo Yu, Weidong Zhou, Leslie E. Silberstein, Tao Cheng, Mingzhe Han, Yuanfu Xu, Hongbo R. Luo
Gasdermin D (GSDMD) is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT) to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent. It was mediated by a neutrophil-specific serine protease, neutrophil elastase (ELANE), released from cytoplasmic granules into the cytosol in aging neutrophils. ELANE-mediated GSDMD cleavage was upstream of the caspase cleavage site and produced a fully active ELANE-derived NT fragment (GSDMD-eNT) that induced lytic cell death as efficiently as GSDMD-cNT. Thus, GSDMD is pleiotropic, exerting both pro- and anti-inflammatory effects that make it a potential target for antibacterial and anti-inflammatory therapies.

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Teaser

Kambara et al. find that GSDMD deficiency augments host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, establishing GSDMD as a negative regulator of innate immunity. GSDMD cleavage and activation in neutrophils is mediated by ELANE, released from cytoplasmic granules into the cytosol in aging neutrophils.


http://ift.tt/2FIdNF6

A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Gigliola Zanghì, Shruthi S. Vembar, Sebastian Baumgarten, Shuai Ding, Julien Guizetti, Jessica M. Bryant, Denise Mattei, Anja T.R. Jensen, Laurent Rénia, Yun Shan Goh, Robert Sauerwein, Cornelus C. Hermsen, Jean-François Franetich, Mallaury Bordessoulles, Olivier Silvie, Valérie Soulard, Olivier Scatton, Patty Chen, Salah Mecheri, Dominique Mazier, Artur Scherf
Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites. A specific member (here called NF54var^sporo) of the var gene family remains euchromatic, and the resultant PfEMP1 (NF54_SpzPfEMP1) is expressed at the sporozoite surface. NF54_SpzPfEMP1-specific antibodies efficiently block hepatocyte infection in a strain-specific manner. Furthermore, human volunteers immunized with infective sporozoites developed antibodies against NF54_SpzPfEMP1. Overall, we show that the epigenetic signature of var genes is reset in mosquito stages. Moreover, the identification of a strain-specific sporozoite PfEMP1 is highly relevant for vaccine design based on sporozoites.

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Teaser

P. falciparum PfEMP1 surface adhesion proteins mediate immune evasion and pathogenesis during asexual blood stage development. Zanghì et al. find that a strain-specific member of PfEMP1 is expressed at the sporozoite surface. Antibodies against this protein inhibit sporozoite invasion of hepatocytes in a strain-specific manner.


http://ift.tt/2FHF3U2

TGF-ß Regulates Cathepsin Activation during Normal and Pathogenic Development

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Heather Flanagan-Steet, Courtney Christian, Po-Nien Lu, Megan Aarnio-Peterson, Laura Sanman, Stephanie Archer-Hartmann, Parastoo Azadi, Matthew Bogyo, Richard A. Steet
Cysteine cathepsins play roles during development and disease beyond their function in lysosomal protein turnover. Here, we leverage a fluorescent activity-based probe (ABP), BMV109, to track cysteine cathepsins in normal and diseased zebrafish embryos. Using this probe in a model of mucolipidosis II, we show that loss of carbohydrate-dependent lysosomal sorting alters the activity of several cathepsin proteases. The data support a pathogenic mechanism where TGF-ß signals enhance the proteolytic processing of pro-Ctsk by modulating the expression of chondroitin 4-sulfate (C4-S). In MLII, elevated C4-S corresponds with TGF-ß-mediated increases in chst11 expression. Inhibiting chst11 impairs the proteolytic activation of Ctsk and alleviates the MLII phenotypes. These findings uncover a regulatory loop between TGF-ß signaling and Ctsk activation that is altered in the context of lysosomal disease. This work highlights the power of ABPs to identify mechanisms underlying pathogenic development in living animals.

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Teaser

Chondroitin sulfate is a known regulator of cathepsin protease activity. Flanagan-Steet et al. identify a positive feedback mechanism whereby cathepsins secreted from chondrocytes upon loss of lysosomal targeting activate TGF-ß signaling in developing cartilage. This increased signaling, in turn, stimulates chondroitin-4 sulfation and enhances cathepsin activity.


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The CDK4/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): David A. Schaer, Richard P. Beckmann, Jack A. Dempsey, Lysiane Huber, Amelie Forest, Nelusha Amaladas, Yanxia Li, Ying Cindy Wang, Erik R. Rasmussen, Darin Chin, Andrew Capen, Carmine Carpenito, Kirk A. Staschke, Linda A. Chung, Lacey M. Litchfield, Farhana F. Merzoug, Xueqian Gong, Philip W. Iversen, Sean Buchanan, Alfonso de Dios, Ruslan D. Novosiadly, Michael Kalos
Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), has recently been approved for the treatment of hormone receptor-positive breast cancer. In this study, we use murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1 blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy led to complete tumor regressions and immunological memory, accompanied by enhanced antigen presentation, a T cell inflamed phenotype, and enhanced cell cycle control. In vitro, treatment with abemaciclib resulted in increased activation of human T cells and upregulated expression of antigen presentation genes in MCF-7 breast cancer cells. These data collectively support the clinical investigation of the combination of abemaciclib with agents such as anti-PD-L1 that modulate T cell anti-tumor immunity.

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Teaser

Schaer, Beckmann et al. describe unique immune-modulating properties of abemaciclib that include upregulation of antigen presentation on tumor cells and increased T cell activation. These activities synergize with anti-PD-L1 therapy to further enhance immune activation, including macrophage and DC antigen presentation, and also lead to a reciprocal increase in abemaciclib-dependent cell cycle gene regulation.


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Clinical and Genomic Crosstalk between Glucocorticoid Receptor and Estrogen Receptor α In Endometrial Cancer

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Jeffery M. Vahrenkamp, Chieh-Hsiang Yang, Adriana C. Rodriguez, Aliyah Almomen, Kristofer C. Berrett, Alexis N. Trujillo, Katrin P. Guillen, Bryan E. Welm, Elke A. Jarboe, Margit M. Janat-Amsbury, Jason Gertz
Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other's function. Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer.

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Teaser

Estrogen receptor α (ER) and glucocorticoid receptor (GR) are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors.


http://ift.tt/2FApCBd

Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Filippo Cortesi, Gloria Delfanti, Andrea Grilli, Arianna Calcinotto, Francesca Gorini, Ferdinando Pucci, Roberta Lucianò, Matteo Grioni, Alessandra Recchia, Fabio Benigni, Alberto Briganti, Andrea Salonia, Michele De Palma, Silvio Bicciato, Claudio Doglioni, Matteo Bellone, Giulia Casorati, Paolo Dellabona
Heterotypic cellular and molecular interactions in the tumor microenvironment (TME) control cancer progression. Here, we show that CD1d-restricted invariant natural killer (iNKT) cells control prostate cancer (PCa) progression by sculpting the TME. In a mouse PCa model, iNKT cells restrained the pro-angiogenic and immunosuppressive capabilities of tumor-infiltrating immune cells by reducing pro-angiogenic TIE2⁺, M2-like macrophages (TEMs), and sustaining pro-inflammatory M1-like macrophages. iNKT cells directly contacted macrophages in the PCa stroma, and iNKT cell transfer into tumor-bearing mice abated TEMs, delaying tumor progression. iNKT cells modulated macrophages through the cooperative engagement of CD1d, Fas, and CD40, which promoted selective killing of M2-like and survival of M1-like macrophages. Human PCa aggressiveness associate with reduced intra-tumoral iNKT cells, increased TEMs, and expression of pro-angiogenic genes, underscoring the clinical significance of this crosstalk. Therefore, iNKT cells may control PCa through mechanisms involving differential macrophage modulation, which may be harnessed for therapeutically reprogramming the TME.

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Cortesi et al. provide evidence that iNKT cells contribute to cancer immune surveillance. Due to differential tuning of tumor-associated macrophage populations, iNKT cells remodel the microenvironment of prostate cancer, enforcing a tumor-opposing state that controls tumor progression.


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Comprehensive Analysis of a cis-Regulatory Region Reveals Pleiotropy in Enhancer Function

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Ella Preger-Ben Noon, Gonzalo Sabarís, Daniela M. Ortiz, Jonathan Sager, Anna Liebowitz, David L. Stern, Nicolás Frankel
Developmental genes can have complex cis-regulatory regions with multiple enhancers. Early work revealed remarkable modularity of enhancers, whereby distinct DNA regions drive gene expression in defined spatiotemporal domains. Nevertheless, a few reports have shown that enhancers function in multiple developmental stages, implying that enhancers can be pleiotropic. Here, we have studied the activity of the enhancers of the shavenbaby gene throughout D. melanogaster development. We found that all seven shavenbaby enhancers drive expression in multiple tissues and developmental stages. We explored how enhancer pleiotropy is encoded in two of these enhancers. In one enhancer, the same transcription factor binding sites contribute to embryonic and pupal expression, revealing site pleiotropy, whereas for a second enhancer, these roles are encoded by distinct sites. Enhancer pleiotropy may be a common feature of cis-regulatory regions of developmental genes, and site pleiotropy may constrain enhancer evolution in some cases.

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Preger-Ben Noon et al. find that shavenbaby gene enhancers contain regulatory information for driving several expression patterns (i.e., enhancers are pleiotropic) and that, in some cases, the transcription factor binding sites that activate these enhancers are reused during development.


http://ift.tt/2Gq8Ba7

Combinatorial Control of Recruitment of a Variant PRC1.6 Complex in Embryonic Stem Cells

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Yikai Huang, Wukui Zhao, Congcong Wang, Yaru Zhu, Mengjie Liu, Huan Tong, Yin Xia, Qing Jiang, Jinzhong Qin
Though genetic data suggest that Polycomb group proteins (PcGs) are central chromatin modifiers and repressors that have been implicated in control of embryonic stem cell (ESC) pluripotency, the precise mechanism of PcG complex recruitment remains elusive, especially in mammals. We now report that the first and second MBT repeats of L3mbtl2 are important structural and functional features that are necessary and sufficient for L3mbtl2-mediated recruitment of PRC1.6 complex to target promoters. Interestingly, this region of L3mbtl2 harbors the evolutionarily conserved Pho-binding pocket also present in Drosophila Sfmbt, and mutation of the critical residues within this pocket completely abolishes its interaction with target promoters. Additionally, decreased PRC1.6 chromatin occupancy was observed following loss of individual components (L3mbtl2, Pcgf6, and Max) of the complex. Our findings suggest that the recruitment of noncanonical PRC1.6 complex in ESCs might be the result of L3mbtl2's interaction with multiple components of the complex.

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Teaser

Yikai et al. report that Polycomb group protein L3mbtl2 assembles a complex whose composition is conserved with the Drosophila PhoRC. L3mbtl2-mediated chromatin recruitment of a variant PRC1 requires cooperation among complex components.


http://ift.tt/2HyxhN2

Data-Driven Modeling of Intracellular Auxin Fluxes Indicates a Dominant Role of the ER in Controlling Nuclear Auxin Uptake

Publication date: 13 March 2018
Source:Cell Reports, Volume 22, Issue 11
Author(s): Alistair M. Middleton, Cristina Dal Bosco, Phillip Chlap, Robert Bensch, Hartmann Harz, Fugang Ren, Stefan Bergmann, Sabrina Wend, Wilfried Weber, Ken-ichiro Hayashi, Matias D. Zurbriggen, Rainer Uhl, Olaf Ronneberger, Klaus Palme, Christian Fleck, Alexander Dovzhenko
In plants, the phytohormone auxin acts as a master regulator of developmental processes and environmental responses. The best characterized process in the auxin regulatory network occurs at the subcellular scale, wherein auxin mediates signal transduction into transcriptional programs by triggering the degradation of Aux/IAA transcriptional repressor proteins in the nucleus. However, whether and how auxin movement between the nucleus and the surrounding compartments is regulated remain elusive. Using a fluorescent auxin analog, we show that its diffusion into the nucleus is restricted. By combining mathematical modeling with time course assays on auxin-mediated nuclear signaling and quantitative phenotyping in single plant cell systems, we show that ER-to-nucleus auxin flux represents a major subcellular pathway to directly control nuclear auxin levels. Our findings propose that the homeostatically regulated auxin pool in the ER and ER-to-nucleus auxin fluxes underpin auxin-mediated downstream responses in plant cells.

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Middleton et al. study how the plant phytohormone auxin enters the nucleus by using quantitative phenotyping in single plant cell systems and bespoke mathematical models that relate controlled perturbations to experimentally measurable responses. Their findings show that auxin predominantly enters the nucleus via the endoplasmic reticulum.


http://ift.tt/2FzT8a7

Breast cancer in Portugal: Temporal trends and age-specific incidence by geographic regions

Publication date: June 2018
Source:Cancer Epidemiology, Volume 54
Author(s): Gonçalo Forjaz de Lacerda, Scott P. Kelly, Joana Bastos, Clara Castro, Alexandra Mayer, Angela B. Mariotto, William F. Anderson
BackgroundFemale breast cancer incidence rates have been increasing in Portugal for years. We, therefore, conducted the first nationwide breast cancer study to assess regional differences.MethodsCases were obtained from population-based cancer registries covering the country's Mainland (South, North, Centre), as well as the two Autonomous Regions (Azores and Madeira), for the time-period 1998 through 2011. Analyses were restricted to ages 30–84 years and stratified by region. We used the age-period-cohort (APC) framework to complement standard descriptive techniques and to forecast future trends. Estimable APC parameters included net drift, longitudinal age-specific incidence rate curves, and fitted age-specific incidence rate ratios.ResultsThere were 71 545 breast cancer cases diagnosed in Portugal at ages 30–84 years from 1998 to 2011. The South presented the highest age-standardized rate (155.8/100 000), while the North presented the fastest rate of increase (3.6%/year). Age-specific statistical interactions were observed between regions. Younger women in the North revealed a decreased risk of developing breast cancer compared to women from the same age group in the South and Centre, while that risk was reversed in older women (p < 0.05). We estimate that from 2014 onwards, the North might rank first among all regions.ConclusionThe variant patterns observed could be due to a combination of different screening practices and/or exposure to risk factors across regions. Disease heterogeneity among younger and older women may also explain part of the differences in age-specific rates. These results justify continued monitoring of breast cancer incidence by region.



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Salivary alpha-amylase and cortisol responsiveness to stress in first episode, drug-naïve patients with panic disorder

Publication date: Available online 14 March 2018
Source:Neuroscience Research
Author(s): Mario Altamura, Salvatore Iuso, Angela Balzotti, Girolamo Francavilla, Andrea Dimitri, Giuseppe Cibelli, Antonello Bellomo, Annamaria Petito
Reported findings on reactivity to stress of the sympathetic-adreno-medullar (SAM) and hypothalamic-pituitary-adrenal (HPA) systems in panic disorder (PD) are very variable. This inconsistency may be explained by differences in treatment exposure, illness duration and emotion regulation strategies. The present study examined the reactivity to mental stress of the SAM and HPA axes in a sample of first episode, drug naïve patients with PD which avoids confounds of medications exposure and illness chronicity. Activation of the SAM axis was evaluated by dosage of salivary alpha-amylase (sAA) and heart rate. Activation of the HPA axis was tested by dosage of salivary cortisol. Psychological assessments were done by the Self-Rating Depression Scale, the Self-Rating Anxiety Scale, the State-Trait Anxiety Inventory, the Cope Orientation to Problems Experienced (COPE) Inventory and the 16 Personality Factor Questionnaire (16PF). Patients showed reduced sAA stress reactivity, higher baseline cortisol levels and a more rapid decrease in stress cortisol levels as compared with controls. A significant correlation was found between active coping strategies and cortisol levels (response to stress). The findings suggest that blunted SAM stress reactivity and a rapid decrease in stress cortisol levels reflect traits that may enhance vulnerability to psychopathology in patients with PD.



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Telomerase activity and telomere on stem progeny senescence

Publication date: June 2018
Source:Biomedicine & Pharmacotherapy, Volume 102
Author(s): Balal Brazvan, Abbas Ebrahimi-Kalan, Kobra Velaei, Ahmad Mehdipour, Zeynab Aliyari serej, Ayyub Ebrahimi, Mohammad Ghorbani, Omid Cheraghi, Hojjatollah Nozad Charoudeh
The end of linear chromosomes is formed of a special nucleoprotein heterochromatin structure with repetitive TTAGGG sequences called telomere. Telomere length is regulated by a special enzyme called telomerase, a specific DNA polymerase that adds new telomeric sequences to the chromosome ends. Telomerase consists of two parts; the central protein part and the accessory part which is a RNA component transported by the central part. Regulation of telomere length by this enzyme is a multi-stage process. Telomere length elongation is strongly influenced by the level of telomerase and has a strong correlation with the activity of telomerase enzyme. Human Telomerase Reverse Transcriptase (hTERT) gene expression plays an important role in maintaining telomere length and high proliferative property of cells. Except a low activity of telomerase enzyme in hematopoietic and few types of stem cells, most of somatic cells didn't showed telomerase activity. Moreover, cytokines are secretory proteins that control many aspects of hematopoiesis, especially immune responses and inflammation. Also, the induction of hTERT gene expression by cytokines is organized through the PI3K/AKT and NF/kB signaling pathways. In this review we have tried to talk about effects of immune cell cytokines on telomerase expression/telomere length and the induction of telomerase expression by cytokines.



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Cortex Dictamni extracts inhibit over-proliferation and migration of rat airway smooth muscle cells via FAK/p38/Bcl-2 signaling pathway

Publication date: June 2018
Source:Biomedicine & Pharmacotherapy, Volume 102
Author(s): Tao Wei, Lei Liu, Xiaoying Zhou
Airway smooth muscle (ASM) is a prominent effecter in maintaining bronchial muscle contraction and responsible for airway hyper-responsiveness (AHR); the phenotype change and over-proliferation of airway smooth muscle cells (ASMCs) play key roles in the pathogenesis of asthma. The aim of this study was to investigate the anti-proliferation effects of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDE) on ASMCs and the possible underline mechanisms. Cell proliferation rates were determined by MTT assay; matrix metalloproteinases-2 (MMP-2) activity was examined by gelatin zymography; cell proliferation and migration were appraised by in-vitro cell-gap closure assessment; protein expressions of p38, Bcl-2 and FAK of ASMCs were evaluated by western blotting and Ca²⁺ influx of cells was measured by confocal laser microscope.Our data demonstrated that the proliferation, migration and MMP-2 expressions of ASMCs were inhibited by CDAE or CDE; the protein expressions of p38, Bcl-2 and FAK in ASMCs were substantially reduced by CDAE and CDE detected by western blotting or immunocytochemistry; also the increased calcium influx has been observed instantaneously after ASMCs were stimulated by CDAE or CDE. These findings suggested that Cortex Dictamni extracts might have inhibitory effects on ASMCs over-proliferation which could be one of the underline mechanisms for the therapy of asthma.



http://ift.tt/2GsIPlm

Scholar : These new articles for Crystallography Reviews are available online

The online platform for Taylor & Francis Online content New for Crystallography Reviews and online now on Taylor & Francis Online: Book Reviews Patterns in nature: why the natural world looks the way it does Claire Murray Pages: 1-2 | DOI: 10.1080/0889311X.2018.1447569 Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Bioequivalence of Dapagliflozin/Metformin Extended-release Fixed-combination Drug Product and Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Russian Subjects

Publication date: Available online 14 March 2018
Source:Clinical Therapeutics
Author(s): Yunona Khomitskaya, Nadezhda Tikhonova, Konstantin Gudkov, Svetlana Erofeeva, Victoria Holmes, Brian Dayton, Nigel Davies, David W. Boulton, Weifeng Tang
PurposeFixed-combination drug products (FCDPs) combining dapagliflozin and metformin extended release (XR) may provide patients with type 2 diabetes mellitus with an alternative antihyperglycemic treatment, which could improve adherence by reducing tablet burden. This study evaluated the bioequivalence of dapagliflozin/metformin XR FCDP versus the co-administration of the individual monotherapy tablets currently available for use in the Russian Federation.MethodsHealthy subjects aged 18 to 45 years were enrolled in this randomized, open-label, 2-period crossover study, conducted in a single Russian center. Pharmacokinetic parameters (AUC0–t, Cmax, and Cmax/AUC0–t) were used to assess bioequivalence of dapagliflozin/metformin XR (10/1000 mg) FCDP to the individual component tablets (dapagliflozin [10 mg] plus metformin XR [2 × 500 mg]) under standard fed conditions. Safety and tolerability were also assessed.FindingsForty healthy subjects were included (47.5% male; mean age, 30 years; and mean body mass index, 24.2 kg/m²). Dapagliflozin and metformin XR in the FCDP were bioequivalent to the individual component tablets marketed in the Russian Federation, with the 90% CIs of the geometric least-squares mean ratios for all key pharmacokinetic parameters being contained within the 80% to 125% bioequivalence limits. Both FCDP and the individual component formulations were well tolerated, with no serious adverse events.ImplicationsBioequivalence of dapagliflozin/metformin XR FCDP and the individual components was established without any new safety concerns, presenting a safe alternative for patients currently receiving regimens including each component individually. ClinicalTrials.gov identifier: NCT02722239.



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Scholar : These new articles for Asian Security are available online

The online platform for Taylor & Francis Online content New for Asian Security and online now on Taylor & Francis Online: Original Articles Advancing the Role of Social Mechanisms, Mediators, and Moderators in Securitization Theory: Explaining Security Policy Change in Japan Petter Y. Lindgren Pages: 1-22 | DOI: 10.1080/14799855.2018.1445895 Do you have original research that relates to present-day Japan and its recent historical development? Contemporary Japan welcomes your submissions. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Editorial Board

Publication date: April 2018
Source:International Journal of Psychophysiology, Volume 126





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Anxiety-related psychopathology and chronic pain comorbidity among public safety personnel

Publication date: Available online 13 March 2018
Source:Journal of Anxiety Disorders
Author(s): R.N. Carleton, T.O. Afifi, T. Taillieu, S. Turner, R. El-Gabalawy, J. Sareen, G.J.G. Asmundson
Canadian Public Safety Personnel (PSP; e.g., correctional service officers, dispatchers, firefighters, paramedics, police officers) regularly experience potentially traumatic, painful, and injurious events. Such exposures increase risk for developing mental disorders and chronic pain, which both involve substantial personal and social costs. The interrelationship between mental disorders and chronic pain is well-established, and both can be mutually maintaining; accordingly, understanding the relationship between mental health and chronic pain among PSP is important for improving health care. Unfortunately, the available research on such comorbidity for PSP is sparse. The current study was designed to provide initial estimates of comorbidities between mental disorders and chronic pain across diverse PSP. Participants included 5093 PSP (32% women) in six categories (i.e., Call Center Operators/Dispatchers, Correctional Workers, Firefighters, Municipal/Provincial Police, Paramedics, Royal Canadian Mounted Police) who participated in a large PSP mental health survey. The survey included established self-report measures for mental disorders and chronic pain. In the total sample, 23.1% of respondents self-reported clinically significant comorbid concerns with both mental disorders and chronic pain. The results indicated PSP who reported chronic pain were significantly more likely to screen positive for posttraumatic stress disorder (PTSD), major depressive disorder, generalized anxiety disorder, social anxiety disorder, and alcohol use disorder. There were differences between PSP categories; but, the most consistent indications of comorbidity were for chronic pain, PTSD, and major depressive disorder. Comorbidity between chronic pain and mental disorders among PSP is prevalent. Health care providers should regularly assess PSP for both symptom domains.



http://ift.tt/2ImHOMi

MicroRNA-146a-5p attenuates visceral hypersensitivity through targeting chemokine CCL8 in the spinal cord in a mouse model of colitis

Publication date: Available online 14 March 2018
Source:Brain Research Bulletin
Author(s): Ying Lu, De-Li Cao, Lin-Xia Zhao, Yu Han, You-Li Zhang
Visceral pain, observed in inflammatory bowel disease (IBD) patients, is a challenging medical problem and remains poorly understood because the mechanisms underlying it are unclear. Emerging evidence indicates that microRNAs (miRNAs) play a crucial role in the pathogenesis of acute and chronic pain. In this study, we aimed to explore the potential role of miR-146a-5p (the mature form of miR-146a) in a mouse model of colitis induced by intracolonic injection of trinitrobenzene sulfonic acid (TNBS). We found that induction of colitis resulted in visceral hyperalgesia manifested by a decreased pain threshold to colorectal distension and upregulation of miR-146a-5p expression in the lumbosacral spinal cord. In situ hybridization and immunohistochemistry results showed that miR-146a-5p was colocalized with neuronal marker NeuN, but not with astrocytic marker GFAP or microglial marker IBA-1. Dual-luciferase reporter assay showed that miR-146a-5p directly targeted the 3′-untranslated region (UTR) of CCL8, which was previously identified as an important regulator of visceral pain. In cultured Neuro-2a cells, TNF-α-induced CCL8 upregulation was decreased by transfection of miR-146a-5p mimic dose-dependently. In vivo, exogenous supplementation of miR-146a-5p by intrathecal miR-146a-5p agomir significantly alleviated visceral pain and decreased CCL8 expression in colitis mice. Furthermore, inhibition of CCL8 expression by CCL8 siRNA relieved colitis-induced visceral nociception. Finally, in naïve mice intrathecal miR-146a-5p antagomir upregulated CCL8 expression and induced visceral pain hypersensitivity, which could be partially rescued by neutralization of CCL8. Taken together, the present findings indicate that miR-146a-5p may be an endogenous suppressor of visceral pain and exogenous supplementation of miR-146a-5p could exert an analgesic effect at least partly by targeting spinal CCL8 expression. Thus, miR-146a-5p may serve as a novel therapeutic target for visceral pain intervention in the context of colitis.



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Involvement of GABAergic, BDNF and Nox-2 mechanisms in the prevention and reversal of ketamine-induced schizophrenia-like behavior by morin in mice

Publication date: Available online 13 March 2018
Source:Brain Research Bulletin
Author(s): Benneth Ben-Azu, Adegbuyi Oladele Aderibigbe, Abayomi Mayowa Ajayi, Aya-Ebi Okubo Eneni, Solomon Umukoro, Ezekiel O. Iwalewa
GABAergic (Gamma-aminobutyric acid) and neurotrophic derangements have important implication in schizophrenia, a neuropsychiatric disease. Previous studies have shown that nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) alters GABAergic and neurotrophic activities via inflammatory and oxidative pathways. Thus, it has been proposed that agents with anti-oxidant and anti-inflammatory properties might be beneficial for the treatment of the disease. Morin is neuroactive bioflavonoid compound, which has been reported to demonstrate antipsychotic and anti-oxidant/anti-inflammatory activities. In this study, we further evaluated its effects on the brain markers of GABAergic, neurotrophic and oxidative alterations in the preventive and reversal of schizophrenia-like behavior induced by ketamine (KET). In the prevention protocol, adult mice were treated intraperitoneally with morin (100 mg/kg), haloperidol (1 mg/kg/day), risperidol (0.5 mg/kg/day), or saline (10 mL/kg/day) for 14 consecutive days. In addition, the animals were administered KET (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or saline for 14 days. From 8thto 14th days mice were additionally treated with morin, haloperidol, risperidone or saline. Schizophrenic-like behaviors consisting of positive (stereotypy test), negative (despair test) and cognitive (novel-object recognition test) symptoms were evaluated. Afterwards, brain levels of biomarkers of GABAergic (Glutamic acid decarboxylase-67, GAD67), neurotrophic (Brain-derived neurotrophic factor, BDNF) and oxidative [NADPH-oxidase, superoxide dismutase, (SOD) and catalase (CAT)] alterations were determined in the striatum, prefrontal cortex (PFC) and hippocampus, respectively. Morin prevented and reversed KET-induced increased stereotypy, behavioral despair in forced-swim test and deficit in cognitive functions. Also, morin and risperidone but not haloperidol, prevented and reversed the decreases in expressions of GAD67 and BDNF immunoreactivity in the striatum, PFC and hippocampus caused by KET. Moreover, morin and risperidone decreased regional brain expressions of NADPH-oxidase immunopositive cells and increased endogenous anti-oxidant enzymes (SOD and CAT) in the striatum, PFC and hippocampus, respectively. Taken together, these findings further suggest that the antipsychotic-like activity of morin maybe mediated via mechanisms related to enhancement of GABAergic neurotransmission and neurotrophic factor, and suppression of NADPH-oxidase induced oxidative damage in mice.

Graphical abstract

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Chronic infusion of Wnt7a, Wnt5a and Dkk-1 in the adult hippocampus induces structural synaptic changes and modifies anxiety and memory performance

Publication date: Available online 13 March 2018
Source:Brain Research Bulletin
Author(s): Abril Ortiz-Matamoros, Clorinda Arias
Wnt signaling plays an important role in the adult brain function and its dysregulation has been implicated in some neurodegenerative pathways. Despite the functional role of the Wnt signaling in adult neural circuits, there is currently no evidence regarding the relationships between exogenously Wnt signaling activation or inhibition and hippocampal structural changes in vivo. Thus, we analyzed the effect of the chronic infusion of Wnt agonists, Wnt7a and Wnt5a, and antagonist, Dkk-1, on different markers of plasticity such as neuronal MAP-2, Tau, synapse number and morphology, and behavioral changes. We observed that Wnt7a and Wnt5a increased the number of perforated synapses and the content of pre-and postsynaptic proteins associated with synapse assembly compared to control and Dkk-1 infusion. These two Wnt agonists also reduced anxiety-like behavior. Conversely, the canonical antagonist, Dkk-1, increased anxiety and inhibited spatial memory recall. Therefore, the present study elucidates the potential participation of Wnt signaling in the remodeling of hippocampal circuits underlying plasticity events in vivo, and provides evidence of the potential benefits of Wnt agonist infusion for the treatment of some neurodegenerative conditions.



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Early social experience alters transcriptomic responses to species-specific song stimuli in female songbirds

Publication date: 16 July 2018
Source:Behavioural Brain Research, Volume 347
Author(s): Matthew I.M. Louder, Mark E. Hauber, Christopher N. Balakrishnan
Amongst an array of stimuli from countless species, animals must recognize salient signals, including those of their own species. In songbirds, behavioral tests have demonstrated that preferences for conspecific male songs are determined by both preexisting biases and social experience with a male 'tutor' during the sensitive period for learning. Although immediate early gene expression (e.g. ZENK) and electrophysiological experiments generally find greater neural responses for conspecific songs, it remains unclear whether distinct mechanisms, such as sensory gating, are engaged to filter out irrelevant heterospecific songs. Here we compare the transcriptomic profiles, via RNA-seq, of non-singing females of a songbird, the zebra finch (Taeniopygia guttata), by focusing on the auditory forebrain, a region known to be critical in the processing of conspecific vs. heterospecific songs. Gene expression profiles demonstrate that different neural mechanisms are involved in the processing of conspecific versus heterospecific Bengalese finch (Lonchura striata) songs. In particular, one gene known to mediate sensory gating, the alpha 3 subunit member of nicotinic cholinergic receptors (CHRNA3), was significantly downregulated in response to hearing Bengalese finch song, but not when young females were tutored by a Bengalese male during early development. Overall, our results confirm previous behavioral and physiological studies, such that heterospecific-tutored individuals processed both conspecific and tutor songs similarly. Using transcriptomic profiling of peripheral blood samples, we also demonstrate the methodological potential of non-terminal sampling to identify transcriptomic biomarkers for conspecific auditory recognition. These results show how experience and inherited preferences facilitate the neural processing of salient songs by female songbirds.



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Large-scale brain network connectivity underlying creativity in resting-state and task fMRI: Cooperation between default network and frontal-parietal network

Publication date: Available online 13 March 2018
Source:Biological Psychology
Author(s): Liang Shi, Jiangzhou Sun, Zhiting Ren, Qunlin Chen, Dongtao Wei, Wenjing Yang, Jiang Qiu
Creativity is imperative to social development and the promotion of well-being. Here, independent component analysis and functional network connectivity analysis methods were applied to both resting-state and divergent thinking task fMRI data from the same sample to investigate large-scale brain network connectivity underlying creativity. The results showed that the strength of the connectivity between the posterior default mode network (DMN) and right frontal-parietal network (FPN) was significantly greater whereas the right FPN and left FPN connectivity strength was weaker in the creative condition than in the control condition. In addition, the posterior DMN and right FPN connectivity strength in the divergent thinking task was positively correlated with the connectivity strength between anterior DMN and left FPN during the resting-state. Moreover, the anterior DMN and left FPN connectivity strength during the resting-state was posit ively correlated with the originality score derived from divergent thinking task. Taken together, these findings extend previous research by revealing the cooperation between the DMN and FPN involved in creative thinking during both resting-state and task fMRI and provide insights into the prediction of creative thinking performance through brain network connectivity during resting-state and task fMRI in the future.



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What neurons tell themselves: autocrine signals play essential roles in neuronal development and function

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Kelsey A Herrmann, Heather T Broihier
Although retrograde neurotrophin signaling has provided an immensely influential paradigm for understanding growth factor signaling in the nervous system, recent studies indicate that growth factors also signal via cell-autonomous, or autocrine, mechanisms. Autocrine signals have been discovered in many neuronal contexts, providing insights into their regulation and function. The growing realization of the importance of cell-autonomous signaling stems from advances in both conditional genetic approaches and in sophisticated analyses of growth factor dynamics, which combine to enable rigorous in vivo dissection of signaling pathways. Here we review recent studies defining autocrine roles for growth factors such as BDNF, and classical morphogens, including Wnts and BMPs, in regulating neuronal development and plasticity. Collectively, these studies highlight an intimate relationship between activity-dependent autocrine signaling and synaptic plasticity, and further suggest a common principle for coordinating paracrine and autocrine signaling in the nervous system.



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Birds of a Feather Synchronize Together

Publication date: Available online 13 March 2018
Source:Trends in Cognitive Sciences
Author(s): Matthew D. Lieberman




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Issue Information - TOC and Editorial Board

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Cover Image, Volume 88, Issue 4

The cover image, by Matti L. Gild et al., is based on the Unsolicited Review Clinical guidance for radioiodine refractory differentiated thyroid cancer, DOI: 10.1111/cen.13508.

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Issue Information - Instructions for Authors

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Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women

Abstract

Background

Hyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women.

Methods

The skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID.

Results

Among the ECM genes and those related to ECM metabolism, only HYBID expression levels positively correlated with the skin roughness parameters. When the skin sample groups with high expression of HYBID or low expression of HYBID were compared, the HA staining intensity and the ratio of HYBID-immunoreactive cells to total cells in the superficial dermis were significantly reduced and increased in the high-HYBID-expression group compared with the low-HYBID-expression group, respectively.

Conclusion

Our data suggest that like Japanese women, HYBID-mediated reduction of HA in the superficial dermis is involved in the formation of wrinkles in Caucasian women.

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Corrigendum to “Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi-institutional retrospective study*” [Eur J Cancer 91 (2018) 116–124]

Publication date: Available online 13 March 2018
Source:European Journal of Cancer
Author(s): Sara Valpione, Matteo S. Carlino, Johanna Mangana, Meghan J. Mooradian, Grant McArthur, Dirk Schadendorf, Axel Hauschild, Alexander M. Menzies, Ana Arance, Paolo A. Ascierto, AnnaMaria Di Giacomo, Francesco de Rosa, James Larkin, John J. Park, Simone M. Goldinger, Ryan J. Sullivan, Wen Xu, Elisabeth Livingstone, Michael Weichenthal, Rajat Rai, Lydia Gaba, Georgina V. Long, Paul Lorigan




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Response to letter commenting on published paper: Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis

Publication date: Available online 13 March 2018
Source:European Journal of Cancer
Author(s): Larysa H.M. Rydzewska, Sarah Burdett, Claire L. Vale, Mahesh K.B. Parmar, Jayne F. Tierney




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Effects of an individualized home-based unsupervised aerobic training on body composition and physiological parameters in obese adults are independent of gender

Abstract

Purpose

Evaluation of the effects of an individualized home-based unsupervised aerobic training on body composition, physical and physiological parameters in female and male obese adults.

Methods

Two hundred and twenty obese adults (age 47.9 ± 12.4 years; BMI 38.0 ± 7.2 kg/m²) entered the 4-month training program. Body composition, physiological and functional capacities were assessed pre- and post-intervention. All subjects were requested to perform unsupervised aerobic training with the intensity based on heart rate, walking speed and OMNI-RPE score corresponding to the individual ventilatory threshold for at least 5 days/week.

Results

After 4-month study period, 40% of patients completed the protocol, 24% had high compliance (HC) (exercise ≥ 3 days/week), while 16% had low compliance (LC) to exercise prescription (exercise < than 3 days/week). In HC group, a significant improvement of body composition variables after training was performed. Moreover, oxygen uptake and metabolic equivalent at peak significantly increased after training. Six-minute walking test (6MWT) distance significantly increased while heart rate during 6MWT was significantly lower after training. No significant differences were found in LC group between pre- and post-intervention in all variables. Interestingly, gender does not influence the effects of training.

Conclusions

Our results indicate that subjects, independent of gender, with high compliance to the aerobic training based on a new individualized method can achieve a significant reduction in weight loss and also an improvement in physical and physiological parameters. This innovative personalized prescription could be a valuable tool for exercise physiologist, endocrinologists, and nutritionists to approach and correct life style of obese subjects.

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Table of Contents

Publication date: April 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 4





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I pledge to prescribe ethically

Publication date: April 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 4
Author(s): Andrew Kelsey, Justin Finch, Jane M. Grant-Kels




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Information for Readers

Publication date: April 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 4





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Comorbidities in rosacea: A systematic review and update

Publication date: April 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 4
Author(s): Roger Haber, Maria El Gemayel
BackgroundRosacea is linked to abnormalities of cutaneous vasculature and dysregulation of the inflammatory response. Recent reports on rosacea have shown a significant association with cardiovascular, gastrointestinal, and psychiatric diseases, all of which may affect morbidity and mortality among these patients.ObjectiveTo review available data regarding comorbidities associated with rosacea, discuss their pathogenesis, and highlight the evaluation of affected patients.MethodsWe performed a complete and systematic literature review in PubMed/Medline, Embase, and the Cochrane Collaboration databases, searching for all articles on possible associated diseases that have been reported with rosacea, with no limits on publication date, participant age, sex, or nationality.ResultsA total of 29 studies were included in this systematic review, including 14 case-control, 8 cross-sectional, and 7 cohort studies. Statistically significant association with rosacea has been mostly demonstrated with depression (n = 117,848 patients), hypertension (n = 18,176), cardiovascular diseases (n = 9739), anxiety disorder (n = 9079), dyslipidemia (n = 7004), diabetes mellitus (n = 6306), migraine (n = 6136), rheumatoid arthritis (n = 4192), Helicobacter pylori infection (n = 1722), ulcerative colitis (n = 1424), and dementia (n = 1194).LimitationsLimitations included the accuracy of the published data, potential patient selection, and possible confounding factors. The true nature of the drawn correlations is uncertain, and causality cannot be established.ConclusionsRosacea is associated with a number of systemic disorders. Recognition of these conditions is critical to providing appropriate screening and management of affected patients.



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Journal Based CME Instructions and Information

Publication date: April 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 4





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Alopecia areata is a medical disease

Publication date: April 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 4
Author(s): Dorota Z. Korta, Angela M. Christiano, Wilma Bergfeld, Madeleine Duvic, Abby Ellison, Jennifer Fu, John E. Harris, Maria K. Hordinsky, Brett King, Dory Kranz, Julian Mackay-Wiggan, Amy McMichael, David A. Norris, Vera Price, Jerry Shapiro, Natasha Atanaskova Mesinkovska




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