Prevalence of methicillin-resistant Staphylococcus aureus colonization in individuals from the community in the city of Sao Paulo, Brazil.

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Prevalence of methicillin-resistant Staphylococcus aureus colonization in individuals from the community in the city of Sao Paulo, Brazil.

Rev Inst Med Trop Sao Paulo. 2018 Oct 22;60:e58

Authors: Bes TM, Martins RR, Perdigão L, Mongelos D, Moreno L, Moreno A, Oliveira GS, Costa SF, Levin AS

Abstract
Staphylococcus aureus (SA) is a commensal habitant of nasal cavities and skin. Colonization by community-acquired methicillin-resistant SA (CA-MRSA) is associated with infections in patients who have not been recently hospitalized. The aim of this study is to determine the prevalence of MRSA colonization in an outpatient population, currently unknown in Brazil. Three-hundred patients or caregivers from two teaching hospitals were included. A questionnaire was applied and nasal swabs were obtained from patients. Swabs were inoculated in brain heart infusion (BHI) with 2.5% NaCl and seeded in mannitol. Suspicious colonies were subjected to MALDI-TOF MS Microflex™ identification. Antimicrobial susceptibility test for oxacillin was performed for SA-positive samples by microdilution. Polymerase chain-reactions for detection of mecA and coA genes were performed for resistant samples. Data about MRSA carriers were compared with non-carriers. There were 127 S. aureus isolates, confirmed by MALDI-TOF. Only seven (2.3%) were MRSA and positive for mecA and coA genes. Factors associated with MRSA carriage were African ethnicity, skin diseases or antibiotic use. The majority of them were from Dermatology clinics. Prevalence of MRSA colonization in individuals from the community was low in our study (2.3%). This finding raises the hypothesis of inter-household transmission of SA, although we did not find any association between MRSA-colonization and the shared use of personal objects. Given the low prevalence of MRSA carriers observed, empirical antimicrobial coverage for MRSA in community-acquired infections should be not necessary.

PMID: 30365641 [PubMed - in process]

https://ift.tt/2PbNvDV

Postpartum Methicillin-Resistant Staphylococcus aureus Toxic Shock Syndrome Caused by a Perineal Infection.

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Postpartum Methicillin-Resistant Staphylococcus aureus Toxic Shock Syndrome Caused by a Perineal Infection.

Case Rep Obstet Gynecol. 2018;2018:2670179

Authors: Deguchi Y, Horiuchi Y, Shojima K, Iwahashi N, Ikejima M, Ino K, Furukawa K

Abstract
Although toxic shock syndrome (TSS) is rare, multiorgan failure can occur without early identification and appropriate therapy. In particular, a few cases of postpartum TSS due to methicillin-resistant Staphylococcus aureus (MRSA) have been reported. Here, we describe a rare case in which a 32-year-old Japanese woman had TSS due to MRSA that was caused by a perineal infection after a normal vaginal delivery. Twelve days after giving birth to a healthy child, she was readmitted to our hospital due to a 2-day fever and perineal pain without uterine tenderness. She developed emesis and watery diarrhea on the night of admission. On the second day, a diffuse cutaneous macular rash appeared over her trunk. Laboratory data revealed deteriorated renal function and thrombocytopenia. Her history and clinical results were compatible with a typical course of TSS. Administration of ceftriaxone and clindamycin was started immediately after admission and was effective. The patient recuperated steadily over the next week with desquamation of the skin. MRSA was isolated from her vaginal discharge and was found to produce TSS toxin 1 (TSST-1). Furthermore, since MRSA was not detected in the nasal and vaginal cavity during pregnancy, it suggests that vaginal colonization can also occur postpartum and be the disease source in mothers. Therefore, MRSA infections should be considered when treating for postpartum TSS.

PMID: 30363971 [PubMed]

https://ift.tt/2D3RLxU

Molecular Analysis of Two Different MRSA Clones ST188 and ST3268 From Primates (Macaca spp.) in a United States Primate Center.

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Molecular Analysis of Two Different MRSA Clones ST188 and ST3268 From Primates (Macaca spp.) in a United States Primate Center.

Front Microbiol. 2018;9:2199

Authors: Roberts MC, Feßler AT, Monecke S, Ehricht R, No D, Schwarz S

Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) were identified in macaques, their environmental facility, and nasal cultures of personnel from the Washington National Primate Research Center [WaNPRC] and included MRSA ST188 SCCmec IV and MRSA ST3268 SCCmec V. The aim of the current study was to determine the carriage of virulence genes, antibiotic resistance genes, and other characteristics of the primate MRSA isolates to determine if there were any obvious differences that would account for differences in transmission within the WaNPRC facility. In total, 1,199 samples from primates were tested for the presence of MRSA resulting in 158 MRSA-positive samples. Fifteen ST188 isolates (all from Macaca nemestrina) and nine ST3268 (four from Macaca mulatta, two from Macaca fascicularis, three from M. nemestrina), were selected for further characterization. All but one of the 15 ST188 isolates had spa type t189 and the remaining one had spa type t3887. These isolates were resistant to β-lactams [blaZ, mecA], macrolides/lincosamides [erm(B)], aminoglycosides [aacA-aphD], and fluoroquinolones. Five isolates were additionally resistant to tetracyclines [tet(K)] and had elevated MICs for benzalkonium chloride [qacC]. In comparison, the nine ST3268 isolates had the related spa types t15469 (n = 5) and t13638 (n = 4). All nine ST3268 isolates were resistant to β-lactams [blaZ, mecA], and tetracyclines [tet(K)]. Some isolates were additionally resistant to aminoglycosides [aacA-aphD], fluoroquinolones and/or showed elevated MICs for benzalkonium chloride [qacC]. In contrast to the ST188 isolates, the ST3268 isolates had the enterotoxin gene cluster egc [seg, sei, selm, seln, selo, selu] and enterotoxin genes sec and sel. The two clones have differences regarding their spa types, virulence and antibiotic resistance genes as well as ST and SCCmec types. However, the data presented does not provide insight into why ST188 spreads easily while ST3268 did not spread within the WaNPRC in-house primates.

PMID: 30356855 [PubMed]

https://ift.tt/2P8gKrh

Development and biological evaluation of Ti6Al7Nb scaffold implants coated with gentamycin-saturated bacterial cellulose biomaterial.

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Development and biological evaluation of Ti6Al7Nb scaffold implants coated with gentamycin-saturated bacterial cellulose biomaterial.

PLoS One. 2018;13(10):e0205205

Authors: Dydak K, Junka A, Szymczyk P, Chodaczek G, Toporkiewicz M, Fijałkowski K, Dudek B, Bartoszewicz M

Abstract
Herein we present an innovative method of coating the surface of Titanium-Aluminium-Niobium bone scaffold implants with bacterial cellulose (BC) polymer saturated with antibiotic. Customized Ti6Al7Nb scaffolds manufactured using Selective Laser Melting were immersed in a suspension of Komagataeibacter xylinus bacteria which displays an ability to produce a 3-dimensional structure of bio-cellulose polymer. The process of complete implant coating with BC took on average 7 days. Subsequently, the BC matrix was cleansed by means of alkaline lysis and saturated with gentamycin. Scanning electron microscopy revealed that BC adheres and penetrates into the implant scaffold structure. The viability and development of the cellular layer on BC micro-structure were visualized by means of confocal microscopy. The BC-coated implants displayed a significantly lower cytotoxicity against osteoblast and fibroblast cell cultures in vitro in comparison to non-coated implants. It was also noted that gentamycin released from BC-coated implants inhibited the growth of Staphylococcus aureus cultures in vitro, confirming the suitability of such implant modification for preventing hostile microbial colonization. As demonstrated using digital microscopy, the procedure used for implant coating and BC chemical cleansing did not flaw the biomaterial structure. The results presented herein are of high translational value with regard to future use of customized, BC-coated and antibiotic-saturated implants designed for use in orthopedic applications to speed up recovery and to reduce the risk of musculoskeletal infections.

PMID: 30356274 [PubMed - in process]

https://ift.tt/2D3SlvA

The Development and Validation of a Clinical Prediction Rule to Predict Transmission of Methicillin-Resistant Staphylococcus aureus in Nursing Homes.

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The Development and Validation of a Clinical Prediction Rule to Predict Transmission of Methicillin-Resistant Staphylococcus aureus in Nursing Homes.

Am J Epidemiol. 2018 Oct 22;:

Authors: Jackson SS, Lydecker AD, Magder LS, Roghmann MC

Abstract
The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization among nursing home residents is high. Healthcare workers (HCWs) often serve as a vector in the transmission of MRSA. The ability to identify residents who are likely to transmit MRSA to HCWs' hands and clothing during clinical care is important so that infection control measures, such as Contact Precautions, can be employed. We developed a clinical prediction rule with demographics and clinical characteristics as predictors of MRSA transmission to HCWs' gowns collected from residents of community nursing homes in Maryland and Michigan between 2012-2014. We externally validated this model in a cohort of Veterans Affairs nursing home residents from 7 states between 2012-2016. The prediction model, which included sex, race, resident dependency on HCWs for care, the presence of any device, diabetes, and chronic skin breakdown, showed good performance (c-statistic=0.70, sensitivity=76%, specificity=49%) in the development set. The decision curve analysis indicates this model has greater clinical utility than using a nares surveillance culture for MRSA colonization, which is current clinical practice for placing hospital inpatients on Contact Precautions. The prediction rule demonstrated less utility in the validation cohort, suggesting a separate rule should be developed for residents of Veterans Affairs nursing homes.

PMID: 30351349 [PubMed - as supplied by publisher]

https://ift.tt/2D20kKK

Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections.

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Staphylococcus aureus Nasal Colonization: An Update on Mechanisms, Epidemiology, Risk Factors, and Subsequent Infections.

Front Microbiol. 2018;9:2419

Authors: Sakr A, Brégeon F, Mège JL, Rolain JM, Blin O

Abstract
Up to 30% of the human population are asymptomatically and permanently colonized with nasal Staphylococcus aureus. To successfully colonize human nares, S. aureus needs to establish solid interactions with human nasal epithelial cells and overcome host defense mechanisms. However, some factors like bacterial interactions in the human nose can influence S. aureus colonization and sometimes prevent colonization. On the other hand, certain host characteristics and environmental factors can predispose to colonization. Nasal colonization can cause opportunistic and sometimes life-threatening infections such as surgical site infections or other infections in non-surgical patients that increase morbidity, mortality as well as healthcare costs.

PMID: 30349525 [PubMed]

https://ift.tt/2D3RGdA

Prevalence and risk factors of community-associated methicillin-resistant Staphylococcus aureus carriage in Asia-Pacific region from 2000 to 2016: a systematic review and meta-analysis.

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Prevalence and risk factors of community-associated methicillin-resistant Staphylococcus aureus carriage in Asia-Pacific region from 2000 to 2016: a systematic review and meta-analysis.

Clin Epidemiol. 2018;10:1489-1501

Authors: Wong JW, Ip M, Tang A, Wei VW, Wong SY, Riley S, Read JM, Kwok KO

Abstract
Objective: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging global public health threat. In response to a highlighted strategic priority of the World Health Organization Global Action Plan on Antimicrobial Resistance, to "strengthen the knowledge and evidence base through surveillance and research", we synthesized published articles to estimate CA-MRSA carriage prevalence in the Asia-Pacific region.
Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD:42017067399). We searched MEDLINE, EMBASE, and PubMed for articles published from 1 January 2000 to 19 May 2017, which reported CA-MRSA carriage (defined as either colonization or infection) in Asia-Pacific region from 2000 to 2016. Studies were stratified according to settings (community or hospital where CA-MRSA was isolated) and study populations (general public or subpopulations with specified characteristics). Ranges of CA-MRSA carriage prevalence were reported for study groups.
Results: In total, 152 studies were identified. Large diversity was observed among studies in most study groups. In community-level studies, the CA-MRSA carriage prevalence among the general public ranged from 0% to 23.5%, whereas that ranged from 0.7% to 10.4% in hospital settings. From community-level studies, countries with the highest prevalence were India (16.5%-23.5%), followed by Vietnam (7.9%) and Taiwan (3.5%-3.8%). Children aged ≤6 (range: 0.5%-40.3%) and household members of CA-MRSA carriers (range: 13.0%-26.4%) are subgroups without specific health conditions but with much higher CA-MRSA carriage when compared to the general population.
Conclusion: Our CA-MRSA prevalence estimates serve as the baseline for future national and international surveillance. The ranges of prevalence and characteristics associated with CA-MRSA carriage can inform health authorities to formulate infection control policies for high-risk subgroups. Future studies should explore the heterogeneities in CA-MRSA carriage prevalence among subgroups and countries to clarify the predominant transmission mechanisms in Asia-Pacific and other regions.

PMID: 30349396 [PubMed]

https://ift.tt/2D1XnKa

[Diversity, antibacterial activites and growth promoting characteristics of endophytic fungi from sandal (Santalum album)].

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[Diversity, antibacterial activites and growth promoting characteristics of endophytic fungi from sandal (Santalum album)].

Zhongguo Zhong Yao Za Zhi. 2018 Sep;43(17):3477-3483

Authors: Liu J, Liu YM, Xu ZC, Wang ZY, Huang YL, Deng ZJ

Abstract
The aim of this study was to investigated the biological diversity, antibacterial activites and the plant growth-promoting traits of endophytic fungi of sandal (Santalum album), and to assess their potential in the development of antibacterial substances and rapid cultivation of sandal. The results of isolation and taxa analysis of endophytic fungi from sandal showed that 325 strains of endophytic fungi belonging to 16 genera of endophytic fungi were isolated from sandal (of which 86 from roots, 105 from stems and 134 from leaves). The isolation rate and colonization rate of endophytic fungi in different sandal parts showed the same pattern of change: leave>stems>roots. The diversity index of endophytic fungi in sandal roots was significantly higher than that of stems and leaves. The dominant endophytic fungi of sandal roots, stems and leaves showed significant differences. The dominant endophytic fungi of roots were Fusarium (50.00%) and Alternaria (10.47%), Alternaria (58.11%) and Acremonium (20.00%) for stems, and Pantoea (74.63%) for leaves. The antibacterial activity of 40 representative strains of sandal endophytic fungi were analyzed and the results showed that 90% of endophytic fungi exhibited inhibitory activity against at least one of the tested bacteria strains, and the strains with inhibitory activity to Escherichia coli, Enterobacter aerogenes, Shigella dysenteriae, Salmonella typhimurium, Staphylococcus aureus, and Bacillus subtilis accounted for 45.0%, 30%, 47.5%, 55%, 72.5%, and 62.5%, respectively. The sandal fungal endophytes with plant growth-promoting characteristics were screened, and 5 strains of endophytic fungi with phosphorus-solubilizing activity, 8 strains of endophytic fungi producing IAA, and 4 strains of endophytic fungi producing siderophores were found. Among them, endophytic fungus Monilia sp TXRF45 clould produced IAA and siderophores, and also show phosphate-solubilizing activity. The results indicated that the endophytic fungi of Sandal were rich in species diversity and their distribution had a certain tissue specificity. Some strains showed good antibacterial activity and growth-promoting properties, which could potentially applicable for the development of antibacterial substances and rapid cultivation of sandal.

PMID: 30347915 [PubMed - in process]

https://ift.tt/2CZv5iq

Water-Insoluble Polymeric Guanidine Derivative and Application in the Preparation of Antibacterial Coating of Catheter.

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Water-Insoluble Polymeric Guanidine Derivative and Application in the Preparation of Antibacterial Coating of Catheter.

ACS Appl Mater Interfaces. 2018 Oct 30;:

Authors: Yu H, Liu L, Yang H, Zhou R, Che C, Li X, Li C, Luan S, Yin J, Shi H

Abstract
Antibacterial coatings have been considered as an effective method for preventing the implant-associated infections caused by the bacterial colonization. In this study, we report a water-insoluble polyelectrolyte-surfactant complex, poly(hexamethylene biguanide) hydrochloride-sodium stearate (PHMB-SS) that can be facilely coated onto the surfaces of biomedical catheter and kill the bacteria by releasing the PHMB and prevent the generation of the biofilm. The PHMB-SS-coated surfaces showed better bactericidal activity toward Staphylococcus aureus and Escherichia coli. The PHMB-SS-coated catheters could not only relatively prevent the bacterial colonization in vitro but also in an implant-associated bacterial infection animal model in vivo. Moreover, no significant cytotoxicity and host response were observed in vitro and in vivo, indicating the high biocompatibility of the coating. The water-insoluble antibacterial coating reported in this work represents a novel approach to build a simple and effective coating for the prevention of device-associated infections.

PMID: 30346131 [PubMed - as supplied by publisher]

https://ift.tt/2Pcvy8w

Antimicrobial peptide modification of biomaterials using supramolecular additives.

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Antimicrobial peptide modification of biomaterials using supramolecular additives.

J Polym Sci A Polym Chem. 2018 Sep 01;56(17):1926-1934

Authors: Zaccaria S, van Gaal RC, Riool M, Zaat SAJ, Dankers PYW

Abstract
Biomaterials based on non-active polymers functionalized with antimicrobial agents by covalent modification or mixing are currently regarded as high potential solutions to prevent biomaterial associated infections that are major causes of biomedical device failure. Herewith a strategy is proposed in which antimicrobial materials are prepared by simply mixing-and-matching of ureido-pyrimidinone (UPy) based supramolecular polymers with antimicrobial peptides (AMPs) modified with the same UPy-moiety. The N-terminus of the AMPs was coupled in solution to an UPy-carboxylic acid synthon resulting in formation of a new amidic bond. The UPy-functionalization of the AMPs did not affect their secondary structure, as proved by circular dichroism spectroscopy. The antimicrobial activity of the UPy-AMPs in solution was also retained. In addition, the incorporation of UPy-AMPs into an UPy-polymer was stable and the final material was biocompatible. The addition of 4 mol % of UPy-AMPs in the UPy-polymer material protected against colonization by Escherichia coli, and methicillin-sensitive and -resistant strains of Staphylococcus aureus. This modular approach enables a stable but dynamic incorporation of the antimicrobial agents, allowing at the same time for the possibility to change the nature of the polymer, as well as the use of AMPs with different activity spectra. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1926-1934.

PMID: 30344368 [PubMed]

https://ift.tt/2D3RATg

Chitosan-based sleeves loaded with silver and chlorhexidine in a percutaneous rabbit tibia model with a repeated bacterial challenge.

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Chitosan-based sleeves loaded with silver and chlorhexidine in a percutaneous rabbit tibia model with a repeated bacterial challenge.

Acta Biomater. 2018 Oct 17;:

Authors: Shao J, Wang B, Bartels CJM, Bronkhorst EM, Jansen JA, Walboomers XF, Yang F

Abstract
Various strategies have been explored to prevent pin tract infections (PTI), including the use of antibacterial sleeves. However, an ideal animal model to evaluate the efficacy of antibacterial strategies is still lacking. This study aimed to construct an animal model with a consistent induction of infection after bacterial challenge. Further, the efficacy of silver and chlorhexidine loaded chitosan sleeves was evaluated to prevent PTI around a percutaneous implant. Titanium pins wrapped with sleeves were implanted in anterior lateral rabbit tibia. After 2 weeks, Staphylococcus aureus suspensions (1 × 106 CFU) were injected weekly to the exit site, and the clinical infection status was recorded. After 6 weeks, all rabbits were euthanized to evaluate the bacterial colonization microbiologically and histomorphometrically. Results showed that the implant screw bilaterally penetrated the tibia and kept the implant stable. A rod length of twice the thickness of the soft-tissue layer was necessary to maintain the percutaneous penetration of the implants. A 100% infection rate was obtained by the bacterial inoculation. Silver loaded sleeves reduced significantly the bacterial density and reduced the inflammatory symptoms of the percutaneous pin tract. However, the addition of chlorhexidine to the sleeves had no added value in terms of further reduction of bacteria and inflammation. In conclusion, a consistent animal model was designed to evaluate strategies to prevent PTI. In addition, the use of silver loaded chitosan sleeves can be pursued for further (pre-)clinical exploration for the prevention of PTI. STATEMENT OF SIGNIFICANCE: This study constructed a bacterial challenged percutaneous rabbit tibia model to evaluate the potential of antibacterial strategies for the prevention of pin tract infections. The model was applied to evaluate a silver and chlorhexidine loaded membranes as an antibacterial sleeve. Our results demonstrate that the rabbit tibia model is suitable to evaluate antibacterial strategies for the prevention of pin tract infection as evidenced by the stable, bone fixed percutaneous implant and a 100% infection rate of the percutaneous pin tract. Silver loaded sleeves can lower the bacterial density of the percutaneous pin tract, but the addition of chlorhexidine to the silver-loaded sleeves does not contribute to an enhanced antibacterial effect. Such experiments are of considerable interest to those in the research community, industry, and clinicians involved the occurrence of infection of skin penetrating medical devices.

PMID: 30342284 [PubMed - as supplied by publisher]

https://ift.tt/2P9Xcme

Preferential Colonization of Osteoblasts Over Co-cultured Bacteria on a Bifunctional Biomaterial Surface.

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Preferential Colonization of Osteoblasts Over Co-cultured Bacteria on a Bifunctional Biomaterial Surface.

Front Microbiol. 2018;9:2219

Authors: Chu L, Yang Y, Yang S, Fan Q, Yu Z, Hu XL, James TD, He XP, Tang T

Abstract
Implant-related infection is a devastating complication in clinical trauma and orthopedics. The aim of this study is to use a bifunctional biomaterial surface in order to investigate the competitive colonization between osteoblasts and bacteria, which is the cause of implant-related infection. A bone-engineering material capable of simultaneously facilitating osteoblast adhesion and inhibiting the growth of Staphylococcus aureus (S. aureus) was prepared. Then, three different co-cultured systems were developed in order to investigate the competitive colonization between the two cohorts on the surface. The results suggested that while the pre-culturing of either cohort compromised the subsequent adhesion of the other according to the 'race for the surface' theory, the synergistic effect of preferential cell adhesion and antibacterial activity of the bifunctional surface led to the predominant colonization and survival of osteoblasts, effectively inhibiting the bacterial adhesion and biofilm formation of S. aureus in the co-culture systems with both cohorts. This research offers new insight into the investigation of competitive surface-colonization between osteoblasts and bacteria for implant-related infection.

PMID: 30333796 [PubMed]

https://ift.tt/2D0k947

Protection against Staphylococcus aureus Colonization and Infection by B- and T-Cell-Mediated Mechanisms.

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Protection against Staphylococcus aureus Colonization and Infection by B- and T-Cell-Mediated Mechanisms.

MBio. 2018 Oct 16;9(5):

Authors: Zhang F, Ledue O, Jun M, Goulart C, Malley R, Lu YJ

Abstract
Staphylococcus aureus is a major cause of morbidity and mortality worldwide. S. aureus colonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management. S. aureus vaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by an S. aureus vaccine in protection against S. aureus bacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-induced S. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality during S. aureus bacteremia, whereas Th1 or Th17 responses are essential for prevention of S. aureus skin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention of S. aureus dermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses to S. aureus antigens may be critical to achieve effective and comprehensive immune defense against this pathogen.IMPORTANCE S. aureus is a leading cause of healthcare- and community-associated bacterial infections. S. aureus causes various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections. S. aureus colonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development against S. aureus has been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses to S. aureus antigens in conferring enhanced and broad protection against S. aureus invasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.

PMID: 30327437 [PubMed - in process]

https://ift.tt/2P5FD6Q

Chitosan's biological activity upon skin-related microorganisms and its potential textile applications.

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Chitosan's biological activity upon skin-related microorganisms and its potential textile applications.

World J Microbiol Biotechnol. 2018 Jun 13;34(7):93

Authors: Costa EM, Silva S, Veiga M, Tavaria FK, Pintado MM

Abstract
Over the years the body of work relating chitosan and its possible skin-related applications has grown, showing that chitosan is active both as a free compound and as a functional finishing of textiles. As a free molecule chitosan proved itself to be an attractive option as it is biocompatible and has a demonstrated biological activity (e.g. growth inhibition or adhesion inhibition) upon multiple skin pathogens, even upon multidrug resistant species. Furthermore, chitosan has wound healing accelerating properties, which make it a prime candidate for possible control of skin related infections. Almost inconspicuously, textiles have been one the main lines of defense of the skin against foreign threats, acting as a physical barrier to microbial colonization and infection. With the advent of textile functionalization specially designed textiles with enhanced protective characteristics, such as antimicrobial capacity, have come to the forefront. Chitosan functionalized textiles have been shown to be effective inhibitors of microbial growth with even invasive multidrug resistant species, as MRSA, being inhibited. Therefore, chitosan and chitosan functionalized textiles present themselves as both an interesting alternative to traditional antibiotics and as a possible means to enhance current treatment strategies.

PMID: 29900482 [PubMed - indexed for MEDLINE]

https://ift.tt/2D1ZXPd

Strain profiling and epidemiology of bacterial species from metagenomic sequencing.

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Strain profiling and epidemiology of bacterial species from metagenomic sequencing.

Nat Commun. 2017 12 22;8(1):2260

Authors: Albanese D, Donati C

Abstract
Microbial communities are often composed by complex mixtures of multiple strains of the same species, characterized by a wide genomic and phenotypic variability. Computational methods able to identify, quantify and classify the different strains present in a sample are essential to fully exploit the potential of metagenomic sequencing in microbial ecology, with applications that range from the epidemiology of infectious diseases to the characterization of the dynamics of microbial colonization. Here we present a computational approach that uses the available genomic data to reconstruct complex strain profiles from metagenomic sequencing, quantifying the abundances of the different strains and cataloging them according to the population structure of the species. We validate the method on synthetic data sets and apply it to the characterization of the strain distribution of several important bacterial species in real samples, showing how its application provides novel insights on the structure and complexity of the microbiota.

PMID: 29273717 [PubMed - indexed for MEDLINE]

https://ift.tt/2kPJhAV

Update on Vertigo in Autoimmune Disorders, from Diagnosis to Treatment.

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Update on Vertigo in Autoimmune Disorders, from Diagnosis to Treatment.

J Immunol Res. 2018;2018:5072582

Authors: Girasoli L, Cazzador D, Padoan R, Nardello E, Felicetti M, Zanoletti E, Schiavon F, Bovo R

Abstract
The prevalence of autoimmune diseases has been increasing over the last 20 years. The clinical presentation of this large and heterogeneous group of disorders depends on whether the involvement is organ-specific or non-organ-specific. Dizziness, vertigo, and disequilibrium are common symptoms reported by patients with vestibulocochlear involvement. The association of vertigo and autoimmune diseases has been largely documented, suggesting that autoimmune disorders could be overrepresented in patients with vertigo in comparison to the general population. The aim of this review is to present the recent literature findings in the field of autoimmune-mediated diseases with cochleovestibular involvement, focusing on the clinical presentation, diagnosis, and treatment of immune-mediated inner ear diseases including autoimmune inner ear disease (AIED), Meniere's disease, and bilateral vestibulopathy, as well as of systemic autoimmune diseases with audiovestibular disorders, namely, Behçet's disease, Cogan's syndrome, sarcoidosis, autoimmune thyroid disease, Vogt-Koyanagi-Harada syndrome, relapsing polychondritis, systemic lupus erythematosus, antiphospholipid syndrome, IgG4-related disease, and ANCA-associated vasculitides.

PMID: 30356417 [PubMed - in process]

https://ift.tt/2CZEoiq

Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis

Abstract

Background

The addition of monoclonal antibodies targeting the epidermal growth factor receptor (anti-EGFR Abs) to chemotherapy for metastatic colorectal carcinoma (mCRC) is commonly delayed in the real-world clinical practice, usually because of late RAS testing results.

Objective

To determine whether delayed addition of anti-EGFR mAbs up to the fourth cycle of backbone chemotherapy adversely affected outcomes of mCRC patients treated with first-line regimens.

Patients and Methods

Clinical data of patients with histologically verified, RAS wild-type mCRC treated with first-line systemic therapy regimens containing anti-EGFR mAbs were retrospectively analysed from a national database. Patients were divided into three groups according to the timing of anti-EGFR mAbs addition to the chemotherapy backbone. Cohort A (n = 401) included patients in whom anti-EGFR mAbs were added to chemotherapy from the first cycle, cohort B (n = 71) patients with anti-EGFR mAbs added to chemotherapy from the second cycle, and cohort C (n = 101) patients who had anti-EGFR mAbs added to chemotherapy from the third or fourth cycle.

Results

Three hundred and thirty-six (58.6%) patients received panitumumab and 237 (41.4%) patients received cetuximab. The median progression-free survival (PFS) of the whole cohort was 12.2 months (95% confidence interval [CI] 10.9–13.5), and the median overall survival (OS) was 33.5 months (95% CI 27.6–39.4). The median PFS and OS for patients treated with anti-EGFR mAbs added to chemotherapy were 12.9 (95% CI 11.5–14.3) and 30.6 months (95% CI 25.2–36.1) for cohort A, 9.7 (95% CI 9.1–10.3) and not reached for cohort B, compared to 11.5 (95% CI 9.8–13.2) and 37.9 months (95% CI 28.6–47.3) for cohort C, respectively.

Conclusions

Delayed addition of anti-EGFR mAbs to first-line chemotherapy was not associated with inferior survival or response rates.

https://ift.tt/2AneCmI

Effect of Changes in Skeletal Muscle Mass on Oncological Outcomes During First-Line Sunitinib Therapy for Metastatic Renal Cell Carcinoma

Abstract

Background

Sarcopenia is a state of degenerative skeletal muscle wasting induced by cancer cachexia.

Objective

To evaluate the prognostic impact of changes in skeletal muscle mass (SMM) during first-line sunitinib therapy on oncological outcomes in metastatic renal cell carcinoma (mRCC).

Patients and Methods

Sixty-nine patients were evaluated retrospectively. The skeletal muscle index (SMI) was calculated based on computed tomography images obtained before the initiation (pre-treatment SMI) and after two cycles of sunitinib treatment (post-treatment SMI). The change in SMM was evaluated based on the value of ΔSMI, which was calculated as [(posttreatment SMI – pretreatment SMI)/ pretreatment SMI] × 100. Oncological outcomes were compared between patients with ΔSMI <0 (SMM decrease) and ΔSMI ≥0 (SMM maintenance).

Results

A decrease in SMM was observed in 38 patients (55.1%). Progression-free survival (PFS) and overall survival (OS) after sunitinib therapy initiation were significantly shorter in patients with ΔSMI <0 than in those with ΔSMI ≥0 (median PFS: 9.53 vs. 28.4 months, p < 0.0001; OS: 19.8 vs. 52.6 months, p = 0.0001). ΔSMI was an independent predictive factor for PFS (HR 3.25, 95% CI 1.74–6.29, p = 0.0002) and OS (HR 4.53, 95% CI 2.15–10.5, p < 0.0001). The objective response rate was significantly lower in patients with ΔSMI <0 than in those with ΔSMI ≥0 (23.7% vs. 51.6%, p = 0.0164).

Conclusion

Decreased SMM during first-line sunitinib therapy can be an effective marker of outcome prediction for mRCC.

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Should CARMENA Really Change our Attitude Towards Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma? A Systematic Review and Meta-Analysis Evaluating Cytoreductive Nephrectomy in the Era of Targeted Therapy

Abstract

Background

Cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) patients has been common clinical practice due to evidence that resection of the primary tumor results in a survival benefit regardless of systemic treatment. Recently, the first large phase III randomized, non-inferiority prospective clinical trial evaluating this surgical approach demonstrated that systemic treatment alone was not inferior to primary surgery plus systemic treatment.

Objective

Our aim was to evaluate if cytoreductive nephrectomy results in a survival benefit over systemic treatment alone in patients with mRCC and in specific subgroups, including patients with brain metastases, poor performance status, poor prognosis according to IMDC or MSKCC criteria, and clear cell and non-clear cell histologies.

Patients and Methods

We identified 16 published studies providing complete data for the comparison between cytoreductive nephrectomy + systemic treatment versus systemic treatment alone, and selected 9 for subgroup analysis. The inverse variance technique was applied for the meta-analysis of hazard ratios (HR), and, due to the intrinsic heterogeneity of the data, we adopted a random effects model. Risk of bias among the studies was estimated by the Newcastle-Ottawa Scale (NOS).

Results

Our analysis suggested a survival benefit for patients receiving cytoreductive nephrectomy (pooled HR of 0.48, 95% confidence interval of 0.42–0.56) in the overall population. Survival advantages were also observed in patients with clear cell and non-clear renal cell carcinoma, while no benefit was evident in patients with brain metastasis, poor performance status, and poor risk.

Conclusion

Cytoreductive nephrectomy seems to result in a survival benefit in both clear cell and non-clear cell histology, while no survival advantage was found in patients with specific clinical features. Despite a high level of heterogeneity, our results highlight the importance of a good selection of patients to whom a primary surgical approach could be proposed.

https://ift.tt/2QOFp0r

Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy

Abstract

Background

A consistent percentage of patients with metastatic non-small cell lung cancer (NSCLC) derives no or only marginal benefit from immunotherapy (IO).

Objective

Since serum sodium has been linked to both prognosis in NSCLC and modulation of immune cells activity, we aimed to assess the association between low baseline serum sodium concentration (≤ 135 mEq/L) and clinical outcomes of patients with metastatic NSCLC treated with IO.

Patients and Methods

We included metastatic NSCLC patients treated with checkpoint inhibitors in our department from April 2013 to April 2018 with available baseline serum sodium concentration. Demographics, clinical and pathological characteristics were collected. Survival analyses were performed using the Kaplan-Meier method and the Cox proportional-hazards model.

Results

Of 197 patients included, 26 (13%) presented low baseline serum sodium concentration. Patients in the low sodium cohort experienced a poorer disease control rate (OR 0.36; 95% CI, 0.15–0.86; Wald test P = .02), median overall survival (OS) (2.8 vs. 11.6 months; HR 3.00; 95% CI, 1.80–4.80; P < .001) and progression-free survival (PFS) (1.8 vs. 3.3 months; HR 2.60; 95% CI, 1.70–3.90; P < .001) compared to patients in the control cohort. At multivariate analyses, low baseline serum sodium concentration was independently associated with disease control and OS, but not with PFS.

Conclusions

Our study showed for the first time that low baseline serum sodium concentration is associated with impaired clinical outcomes in patients with metastatic NSCLC treated with IO. The role of serum sodium concentration in this setting warrants further pre-clinical and clinical investigation.

https://ift.tt/2yukB6Z

Nur77 promotes cerebral ischemia–reperfusion injury via activating INF2-mediated mitochondrial fragmentation

Abstract

Mitochondrial fragmentation drastically regulates mitochondrial homeostasis in brain illness. However, the role of mitochondrial fragmentation in cerebral ischemia–reperfusion (IR) injury remains unclear. Nur77, a regulator of mitochondrial homeostasis, is associated with heart and liver IR injury, but its effects on mitochondrial function in cerebral IR injury has not been studied intensively. The aim of our study is to explore whether cerebral IR injury is modulated by Nur77 via modification of mitochondrial homeostasis. Our results indicated that Nur77 was upregulated in reperfused brain tissues. Genetic ablation of Nur77 reduced infarction area and promoted neuron survival under IR burden. Biochemical analysis demonstrated that Nur77 deletion protected mitochondrial function, attenuated mitochondrial oxidative stress, preserved mitochondrial potential, and blocked mitochondria-related cell apoptosis. In addition, we illustrated that Nur77 mediated mitochondrial damage via evoking mitochondrial fragmentation that occurred through increased mitochondrial fission and decreased fusion. Besides, our results also demonstrated that Nur77 controlled mitochondrial fragmentation via upregulating INF2 in a manner dependent on the Wnt/β-catenin pathway; inhibition of the Wnt pathway abrogated the protective effect of Nur77 deletion on reperfused-mediated neurons. Altogether, our study highlights that the pathogenesis of cerebral IR injury is associated with Nur77 activation followed by augmented mitochondrial fragmentation via an abnormal Wnt/β-catenin/INF2 pathway. Accordingly, Nur77-dependent mitochondrial fragmentation and the Wnt/β-catenin/INF2 axis may represent novel therapeutic targets to reduce cerebral IR injury.

https://ift.tt/2IKy7b4

Decreased autophagy was implicated in the decreased apoptosis during decidualization in early pregnant mice

Abstract

Folate deficiency is a major risk factor of birth defects. Mechanistic studies on folate deficiency resulting in birth defects have mainly focused on fetal development. There have been few studies on folate deficiency from the point of view of the mother's uterus. In our previous study, we demonstrated that folate deficiency inhibits apoptosis of decidual cells, thereby restraining decidualization of the endometrium and impairing pregnancy. In this study, we further investigated the potential mechanism by which folate deficiency decreases endometrial apoptosis during decidualization. To investigate whether endometrium autophagy was inhibited under folate deficiency during decidualization, we performed real-time PCR for endometrial LC3 and P62 on day 6 (D6) to D8 of pregnancy in mice, and both were significantly changed compared to non-folate-deficient mice. Western blots showed that LC3-II and P62 were also changed in folate-deficient mice. Compared with control mice, a few punctuate LC3-II structures were detected in the folate deficiency group by immunofluorescence. Transmission electron micrographs of decidual cells on D8 showed that there were no evident autophagosomes in the folate deficiency group. In addition, apoptosis-related protein analysis by western blotting, TUNEL staining and flow cytometry showed that decreased endometrial apoptosis on D8 of pregnancy under folate deficiency was reversed after treatment with rapamycin, an autophagy inducer. ROS measurement showed that the endometrium ROS level was reduced by folate deficiency and that rapamycin reversed this effect on day 8 of pregnancy. All the results suggest that inhibiting endometrial autophagy may be implicated in the decreased endometrial apoptosis under folate deficiency during decidualization.

https://ift.tt/2Cvt3af

Time course of differentiation of different cell types in 3D-reconstructed eccrine sweat glands

Abstract

Epidermal basal cells invaginate into the dermis to form sweat ducts, which then grow downwards further to form secretory coils during the ontogenesis of eccrine sweat glands, but the time course of differentiation of different cell types in 3D-reconstructed eccrine sweat glands remain unclear. In this study, secretory cell-specific marker K7, clear secretory cell-specific marker CA II, dark secretory cell-specific marker GCDFP-15, myoepithelial cell-specific marker α-SMA, inner duct cell-specific marker S100P and outer duct cell-specific marker S100A2 were detected by immunofluorescence staining. The results showed that S100P and S100A2 were first detected at 2 weeks post implantation, K7 and α-SMA at 3 weeks, and GCDFP-15 and CA II at 4 weeks. The differentiation of ducts preceded secretory coils in 3D-reconstructed eccrine sweat glands. After 8 weeks post implantation, the distribution of these markers in 3D-reconstructed eccrine sweat glands was similar to that in native ones, and the percentage of the 3D-reconstructed glands expressing these markers maintained steady. We conclude that although the 3D-reconstructed and native eccrine sweat glands originated from different cells, the differentiation of different cell types in 3D-reconstructed eccrine sweat glands parallels the sequence observed during embryonic development.

https://ift.tt/2pm0Hqu

First ovarian response to gonadotrophin stimulation in rats exposed to neonatal androgen excess

Abstract

This study analyzes the effects of neonatal androgenization on follicular growth and first ovulation in response to gonadotrophins, using a model of exogenous stimulation or the use of subcutaneous ovary grafts in castrated animals to replace the hypothalamus–pituitary signal. Neonatal rats (days 1–5) were treated with testosterone, dihydrotestosterone or vehicle. At juvenile period, rats were stimulated with PMSG, hCG (alone or combined) or used as ovarian donors to be grafted on castrated adult female rats. Ovulation and ovarian histology were analyzed in both groups. Animals treated with vehicle or dihydrotestosterone stimulated with gonadotrophins (pharmacological or by using an ovary graft) ovulated, showing a normal histological morphology whereas rats exposed to testosterone and injected with the same doses of gonadotrophins did not it. In this group, ovulation was reached using a higher dose of hCG. Ovaries in the testosterone group were characterized by the presence of follicles with atretic appearance and a larger size than those observed in control or dihydrotestosterone groups. A similar appearance was observed in testosterone ovary grafts although luteinization and some corpora lutea were also identified. Our findings suggest that neonatal exposure to aromatizable androgens induces a more drastic signalling on the ovarian tissue that those driven by non-aromatizable androgens in response to gonadotrophins.

https://ift.tt/2A0WDlJ

Chrysin attenuates interstitial fibrosis and improves cardiac function in a rat model of acute myocardial infarction

Abstract

Interstitial fibrosis after acute myocardial infarction (MI) leads to cardiac structural remodeling and dysfunction. The peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist chrysin has been shown to protect injured myocardium through suppression of oxidative stress and inflammation. This study was designed to investigate the effect and mechanism of chrysin on myocardial fibrosis. A rat MI model was created by ligating the left coronary artery. The rats with MI were treated with chrysin (40 mg/kg/day) or 0.5% carboxymethylcellulose sodium by intragastric administration for 4 weeks after operation. The effect of chrysin on cardiac fibroblasts (CFs) were also assessed in vitro. Echocardiography showed that cardiac function was significantly improved after chrysin treatment. Chrysin reduced the levels of MDA and SOD and GSH-Px in myocardial tissue. Chrysin attenuated the interstitial and perivascular fibrosis and the expression of collagenlin the peri-infarcted zone and remarkably decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. Chrysin up-regulated PPAR-γ and inhibited the nuclear factor-kappa B (NF-κB) pathway by suppressing inhibitor kappa B kinase β phosphorylation. Immunohistochemistry analysis and PCR detected downregulated expression of AP-1 after chrysin treatment. Chrysin also markedly reduced the increased α-SMA, typeland type III collagen expression of CFs mediated by AngII in vitro. In conclusion, chrysin has an antifibrosis cardioprotective effect on the infarct peripheral zone after MI. The underlined mechanism may be the up-regulation of PPAR-γ and inhibition of the NF-κB and AP1 pathway.

https://ift.tt/2MGqu5R

Mechanism of fibrogenesis in submandibular glands in patients with IgG4-RD

Abstract

The aim of this study was to investigate the mechanisms driving fibrosis in the submandibular glands (SMG) of patients with IgG4-related disease (IgG4-RD). Immunohistochemistry showed that many fibroblast-like cells expressing IL-6, IL-18, TSLP, IL-33, and MMP1 were present in SMG from the affected patients. SMG fibroblasts were derived from patients with or without IgG4-RD and were cultured in vitro. Expression of IL-6, IL-18, TSLP, IL-33 and MMP1, the secretion of IL-6 and G2/M phase were upregulated in the fibroblasts from the affected patients. By treatment with inflammatory cytokines IL-1β, TNFα or TGF-β after treatment with or without the NF-κB inhibitor curcumin, curucumin blocked the production and secretion of IL-6 upregulated by IL-1β, TNFα, or TNFα/TGF-β in all fibroblasts. Wnt1-inducible signaling protein 1 (WISP1), which can enhance fibroblasts proliferation, was also more abundantly expressed in affected fibroblasts, while treatment with IL-6 induced WISP1, treatment with WISP1 increased the G2/M phase, and curucumin inhibited WISP1 induced by TNFα/TGF-β in unaffected fibroblasts. IL-33 in affected fibroblasts was induced by IL-1β, TNFα, or TNFα/TGF-β, while the effect of IL-1β or TNFα/TGF-β was blocked by curcumin. These results suggest fibrosis in the SMG of affected patients is closely linked to the proliferation of fibroblasts following induction of IL-6 and WISP1 by inflammatory cytokines. The Th2 cytokines TSLP and IL-33 are also upregulated in affected SMG, and thus may cause chronic inflammation and IgG4 accumulation.

https://ift.tt/2DmSxbc

Favorable outcomes of metformin on coronary microvasculature in experimental diabetic cardiomyopathy

Abstract

Although metformin is widely prescribed in diabetes, its use with associated cardiac dysfunction remains debatable. In the current study, we investigated the effect of metformin on coronary microvasculature in experimental diabetic cardiomyopathy (DCM) induced by streptozotocin. Administration of metformin after induction of DCM, reversed almost all cardiomyocyte degenerative changes induced by DCM. Metformin diminished the significantly increased (p < 0.05) collagen deposited in the DCM. In addition metformin had improved the density of the significantly decreased arteriolar (αSMA⁺) and capillary (CD31⁺) coronary microvasculature compared to that of the DCM and non-diabetics (ND) with downregulation of the significantly increased expression (p < 0.05) of COL-I, III, TGF-β, CTGF, ICAM and VCAM genes. Therefore metformin may be beneficial in limiting the fibrotic and the vascular remodeling occurring in DCM at the genetic as well as the structural levels.

https://ift.tt/2QRdAET

Electron microscopic study of Golgi-impregnated and gold-toned neurons and fibers in the claustrum of the cat

Abstract

The claustrum is a subcortical nucleus found in the telencephalon of all placental mammals. It is a symmetrical, thin and irregular sheet of grey matter which lies between the inner surface of the insular cortex and the outer surface of the putamen. The claustrum has extensive connections with the visual, auditory, somatosensory and motor regions of the cortex, as well as with subcortical and allocortical regions. The aim of this study was to provide a detailed description of the morphology of different types of Golgi-impregnated and gold-toned neurons and fibers in the dorsal claustrum of the cat employing the combined Golgi-electron microscope Fairén method. We were able to distinguish two major types of neurons: those with dendritic spines (spiny) and those without dendritic spines (aspiny). In both groups we observed large (21–40 µm in diameter), medium-sized (16–21 µm in diameter) and small cells (10–16 µm in diameter), describing their ultrastructural organization and characteristic features, including the presence of terminal boutons. These ultrastructural findings allow us to conclude that large and medium-sized spiny claustral neurons are indeed efferent neurons, projecting to the cortex, while the small spiny and the different types of aspiny neurons are most likely inhibitory local circuit interneurons. The findings in the present study will hopefully contribute to a better understanding of the role of the claustrum.

https://ift.tt/2QF0slW

Discrimination of normal oral mucosa from oral cancer by mass spectrometry imaging of proteins and lipids

Abstract

Identification of biomarkers for molecular classification of cancer and for differentiation between cancerous and normal epithelium remains a vital issue in the field of head and neck cancer. Here we aimed to compare the ability of proteome and lipidome components to discriminate oral cancer from normal mucosa. Tissue specimens including squamous cell cancer and normal epithelium were analyzed by MALDI mass spectrometry imaging. Two molecular domains of tissue components were imaged in serial sections—peptides (resulting from trypsin-processed proteins) and lipids (primarily zwitterionic phospholipids), then regions of interest corresponding to cancer and normal epithelium were compared. Heterogeneity of cancer regions was higher than the heterogeneity of normal epithelium, and the distribution of peptide components was more heterogeneous than the distribution of lipid components. Moreover, there were more peptide components than lipid components that showed significantly different abundance between cancer and normal epithelium (median of the Cohen's effect was 0.49 and 0.31 in case of peptide and lipid components, respectively). Multicomponent cancer classifier was tested (vs. normal epithelium) using tissue specimens from three patients and then validated with a tissue specimen from the fourth patient. Peptide-based signature and lipid-based signature allowed cancer classification with a weighted accuracy of 0.85 and 0.69, respectively. Nevertheless, both classifiers had very high precision (0.98 and 0.94, respectively). We concluded that though molecular differences between cancerous and normal mucosa were higher in the proteome domain than in the analyzed lipidome subdomain, imaging of lipidome components also enabled discrimination of oral cancer and normal epithelium. Therefore, both cancer proteome and lipidome are promising sources of biomarkers of oral malignancies.

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Editorial Board

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Graphical Abstracts

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Meet Our Editor-in-Chief

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Therapeutic Advancement in Alzheimer Disease: New Hopes on the Horizon?

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Overview of the Recent Advances in Pathophysiology and Treatment for Autism

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Metabolic Syndrome and Its Effect on the Brain: Possible Mechanism

https://ift.tt/2CZJATq

The Dopaminergic Dysfunction and Altered Working Memory Performance of Aging Mice Lacking Gamma-synuclein Gene

https://ift.tt/2P8QnkT

In Silico Analyses for Key Genes and Molecular Genetic Mechanism in Epilepsy and Alzheimer's Disease

https://ift.tt/2CW8DH7

Serum Interleukin Levels and Insulin Resistance in Major Depressive Disorder

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Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders

https://ift.tt/2D0ONuj

Reply to Sanguankeo and Upala on “Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis

Recently the putative role of sleep problems in the incidence and development of dementia attracted considerable attention [1]. We previously reported on this relationship in a systematic review and meta-analysis [2]. In a commentary on our work, Drs. Sanguankeo and Upala proposed two points that might strengthen our meta-analysis [3]. We thank them for these suggestions and appreciate their efforts in improving the quality of our work. However, we should point out that in our meta-analysis, we had already taken the comments they offered into consideration.

https://ift.tt/2qrfp05

Incidence and identification of microfibers in ocean waters in Admiralty Bay, Antarctica

Abstract

Antarctic pristine environment is threatened by the presence of microplastics that occur in a variety of shapes and sizes, from fibers to irregular fragments. The aim of this study is to assess the abundance, distribution, and the characterization of the microfibers in zooplankton samples found in ocean waters in Admiralty Bay, Antarctica. The samples were collected at five points in Admiralty Bay during the XXIX Brazilian Antarctic Expedition in the austral summer of 2010–2011. A total of 603 microfibers were collected in 60 samples, with an average abundance of 2.40 (± 4.57) microfibers 100 m⁻³. Microfiber size ranging from ca. 10 to 22 μm in diameter of various lengths and colors (blue, red, black, and clear) was collected and characterized by scanning electron microscopy (SEM) and Raman spectroscopy. Most of these microfibers were entangled in various different zooplankton species and were identified as polymers composed mostly by polyethyleneglycols, polyurethanes, polyethylene terephthalates, and polyamides. The presence of such microfibers may cause the loss of biodiversity in the Antarctic continent, and the results presented herein can contribute to a better understanding of the impact caused by them within the food chain and human health.

Graphical Abstract

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https://ift.tt/2zofPIB

Effect of sand dust accumulation on photovoltaic performance in the Saharan environment: southern Algeria (Adrar)

Abstract

Many climatic conditions have a negative impact on production of photovoltaic (PV) systems, and sand dust could be one of the main reasons of degradation of PV panels. The objective of this study is to investigate the reduction in the electrical performance caused by sandstorm and the accumulation of sand dust on the photovoltaic module surface installed in the Saharan area of south Algeria (Adrar). For this purpose, four PV modules (ISO-100/24) were selected and their current–voltage characteristics were measured to evaluate the sand dust effect on their performances. Our results show that sandstorm and dust accumulation on the surface of the module reduce the performance in terms of energy and power, due to a decrease of the transmittance. Obtained outcomes show that in sandstorm periods, the particle deposition density is much higher. This study reveals that leaving PV module without any cleaning in the Saharan environmental conditions significantly reduces PV power output, in addition to the presence of the shading mismatch effects in case of partial cleaning.

https://ift.tt/2yQ9yWx

Pollutant removal performance of an integrated system that combines a baffled vertical-flow wetland and a scenic water body

Abstract

Stormwater treatment requires effective control measures and development of low-cost and high-efficiency technologies. An integrated system is developed by combining a baffled vertical-flow constructed wetland (BVFCW) and a scenic water body for stormwater quality control purpose. The objectives of the study are to compare the pollutant removal performance of the full-scale integrated system with four groups of wetland-to-scenic water body area ratios (WSARs) including 1/11, 2/11, 3/11, 4/11 and investigate its treatment efficiency. Results show that the system performs better in the removal of chemical oxygen demand (COD), total nitrogen (TN), ammonia nitrogen (NH₄⁺–N), nitrate-nitrogen (NO₃–N), and total phosphorus (TP) at the WSAR of 4/11 than that at 3/11 in sixteen-day operation, while it reaches the highest total nitrogen (TN) removal efficiency of 74.0% at the WSAR of 2/11 due to relatively rich carbon source and high influent TN concentration. The integrated system may prove the most effective COD removal at the WSAR of 4/11 for four-time aerobic/anaerobic alternating conditions, a longer flow path and more time to contact with substrates, although the influent COD is lower than that at 2/11 and 1/11. After sixteen-day operation, BVFCW achieved COD removal rate of 90.3%, NH₄⁺–N removal rate of 85.7%, NO₃–N removal rate of 68.6%, and TP removal rate of 52.5% at the WSAR of 4/11. At the WSAR of 1/11, effluent met the Class IV requirements in Chinese standards after one-week operation, while effluent met the Class III requirements under the rest conditions. Since effluent in all WSARs met the standards, WSARs of 1/11 and 2/11 were recommended.

https://ift.tt/2Oql9AR

Uptake of endocrine-disrupting chemicals by quagga mussels ( Dreissena bugensis ) in an urban-impacted aquatic ecosystem

Abstract

Untreated organic contaminants in municipal wastewater, such as endocrine-disrupting chemicals (EDCs), have become a significant issue in aquatic ecosystems, particularly in freshwater bodies that receive wastewater discharge. This has raised concerns about the accumulation of EDCs in aquatic species via continuous exposure. This study evaluated the uptake of EDCs by quagga mussels (Dreissena bugensis), an invasive species in a water supply reservoir. The field sampling results showed that steroid hormones were not detected in the water samples, and only pharmaceuticals and personal care products were present (0.49 to 36 ng/L). Additionally, testosterone was the most abundant steroid in the mussel tissue (6.3 to 20 ng/g dry weight), and other synthetic chemicals (i.e., bisphenol A, triclosan, and salicylic acid) were also detected in the mussel tissue (24 to 47 ng/g dry weight). After being exposed to exogenous EDCs for 7, 21, and 42 days under controlled laboratory conditions, testosterone was not detected in the mussel anymore, but bisphenol A, triclosan, and salicylic acid were found at relatively high levels in the mussel tissue, although the concentrations did not increase over time. Overall, the study demonstrated the uptake of EDCs in quagga mussels, which suggests that this species can be used to reflect water quality deterioration in aquatic ecosystems.

https://ift.tt/2yQOO0N

Impact of rice husk nanoparticle on the performance and emission aspects of a diesel engine running on blends of pine oil-diesel

Abstract

With the increase in vehicle density, the amount of pollution along with the dependence on the diesel fuel also increases, which might be on the verge of depletion. The increase in fuel price is an important economical factor. Hence, finding a suitable substitute energy source which is economic and also meets the energy necessity is of great need. During this study, the utilization of pine oil biofuel in which rice husk (RH) nanoparticles was added as an additive was proposed. The test was carried out in a single cylinder, diesel engine at 1500 rpm. Fuel is blended at two ratios (B10, B20) and 0.1% of RH nano-additive is added with each blend and their characteristics in terms of performance and emission are analyzed for varied load conditions. At full load condition for B10–0.1% RH, there is a slight reduction of about 3.04% for BTE and 4.1% increase in BSFC than diesel fuel was observed. Likewise, for B20–0.1% RH at full load condition CO and HC decreases about 27.27% and 19.64% respectively, with a rise in CO₂ and a slight increase of NOx level at 15.63%, 8.76% respectively than diesel fuel. This small replacement of diesel fuel by biodiesel helps in reducing the increasing cost and also the complete dependency on the fossil-based fuel. Thus, pine oil with additive can perform well without any engine modifications and helps in reducing the pollutions.

https://ift.tt/2Oql7ZL

Trajectories and Milestones of Cortical and Subcortical Development of the Marmoset Brain From Infancy to Adulthood

Abstract

With increasing attention on the developmental causes of neuropsychiatric disorders, appropriate animal models are crucial to identifying causes and assessing potential interventions. The common marmoset is an ideal model as it has sophisticated social/emotional behavior, reaching adulthood within 2 years of birth. Magnetic resonance imaging was used in an accelerated longitudinal cohort (n = 41; aged 3–27 months; scanned 2–7 times over 2 years). Splines were used to model nonlinear trajectories of grey matter volume development in 53 cortical areas and 16 subcortical nuclei. Generally, volumes increased before puberty, peaked, and declined into adulthood. We identified 3 milestones of grey matter development: I) age at peak volume; II) age at onset of volume decline; and III) age at maximum rate of volume decline. These milestones differentiated growth trajectories of primary sensory/motor cortical areas from those of association cortex but also revealed distinct trajectories between association cortices. Cluster analysis of trajectories showed that prefrontal cortex was the most heterogenous of association regions, comprising areas with distinct milestones and developmental trajectories. These results highlight the potential of high-field structural MRI to define the dynamics of primate brain development and importantly to identify when specific prefrontal circuits may be most vulnerable to environmental impact.

https://ift.tt/2znyV1v

Neural stem cell lineage-specific cannabinoid type-1 receptor regulates neurogenesis and plasticity in the adult mouse hippocampus

Abstract

Neural stem cells (NSCs) in the adult mouse hippocampus occur in a specific neurogenic niche, where a multitude of extracellular signaling molecules converges to regulate NSC proliferation as well as fate and functional integration. However, the underlying mechanisms how NSCs react to extrinsic signals and convert them to intracellular responses still remains elusive. NSCs contain a functional endocannabinoid system, including the cannabinoid type-1 receptor (CB1). To decipher whether CB1 regulates adult neurogenesis directly or indirectly in vivo, we performed NSC-specific conditional inactivation of CB1 by using triple-transgenic mice. Here, we show that lack of CB1 in NSCs is sufficient to decrease proliferation of the stem cell pool, which consequently leads to a reduction in the number of newborn neurons. Furthermore, neuronal differentiation was compromised at the level of dendritic maturation pointing towards a postsynaptic role of CB1 in vivo. Deteriorated neurogenesis in NSC-specific CB1 knock-outs additionally resulted in reduced long-term potentiation in the hippocampal formation. The observed cellular and physiological alterations led to decreased short-term spatial memory and increased depression-like behavior. These results demonstrate that CB1 expressed in NSCs and their progeny controls neurogenesis in adult mice to regulate the NSC stem cell pool, dendritic morphology, activity-dependent plasticity, and behavior.

https://ift.tt/2SFgWfX

Functional Parcellation of the Cerebral Cortex Across the Human Adult Lifespan

Abstract

Adult aging is associated with differences in structure, function, and connectivity of brain areas. Age-based brain comparisons have typically rested on the assumption that brain areas exhibit a similar spatial organization across age; we evaluate this hypothesis directly. Area parcellation methods that identify locations where resting-state functional correlations (RSFC) exhibit abrupt transitions (boundary-mapping) are used to define cortical areas in cohorts of individuals sampled across a large range of the human adult lifespan (20–93 years). Most of the strongest areal boundaries are spatially consistent across age. Differences in parcellation boundaries are largely explained by differences in cortical thickness and anatomical alignment in older relative to younger adults. Despite the parcellation similarities, age-specific parcellations exhibit better internal validity relative to a young-adult parcellation applied to older adults' data, and age-specific parcels are better able to capture variability in task-evoked functional activity. Incorporating age-specific parcels as nodes in RSFC network analysis reveals that the spatial topography of the brain's large-scale system organization is comparable throughout aging, but confirms that the segregation of systems declines with increasing age. These observations demonstrate that many features of areal organization are consistent across adulthood, and reveal sources of age-related brain variation that contribute to the differences.

https://ift.tt/2znyOD7

Antimicrobial photodynamic therapy as adjunct to non-surgical periodontal treatment in smokers: a randomized clinical trial

Abstract

Objectives

This study aims to investigate the additional influence of multiple applications of antimicrobial photodynamic therapy (aPDT) in smokers with chronic periodontitis.

Materials and methods

Twenty smokers with chronic periodontitis were treated in a split-mouth design study with aPDT adjunct to Scaling and Root Planing (SRP) or SRP. aPDT was performed by using a laser light source with 660 nm wavelength associated with a photosensitizer. The applications were performed in four episodes (at days 0, 2, 7, and 14). All patients were monitored for 90 days. Plaque index, probing depth, clinical attachment level, and bleeding on probing were performed at baseline, 30, and 90 days after the SRP. Gingival crevicular fluid and subgingival plaque samples were collected for immunological and microbiological analysis, respectively. Data obtained were statistically analyzed.

Results

aPDT as an adjunct to SRP did not demonstrate statistically significant advantages on clinical parameters when compared with SRP alone. No statistic significant differences between groups were observed (p < 0.05). Levels of anti-inflammatory cytokines and bacterial species were comparable in both groups at day 90 after treatment.

Conclusion

Periodontal treatment with SRP + aPDT in multiples episodes was not able to promote additional clinical, immunological, and microbiological benefits in smokers when compared SRP alone in patients with chronic periodontitis.

Clinical relevance

Multiple episodes of aPDT adjunctive to non-surgical treatment did not improve significantly the clinical, immunological, and microbiological parameters when compared with SRP alone. More randomized clinical trials are needed to evaluate adjuvant therapies for scaling and root planning in smokers with chronic periodontitis. ClinicalTrials.gov Identifier: NCT03039244

https://ift.tt/2D2GL3Q

Serum levels of adipokines in gestational diabetes: a systematic review

Abstract

Objective

To determine the difference of serum levels of 10 adipokines (apelin, chemerin, fatty acid-binding protein-4, fibroblast growth factor-21, monocyte chemoattractant protein-1, nesfatin-1, omentin-1, resistin, vaspin, and visfatin) among women with gestational diabetes and healthy pregnant controls.

Materials and methods

Literature search was conducted using the Medline (1966–2018), Scopus (2004–2018), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2018), Clinicaltrials.gov (2008–2018) and Google Scholar (2004–2018) databases, along with the reference list of the included studies.

Results

Ninety-one studies were included in the present review, with a total number of 11,074 pregnant women. A meta-analysis was not conducted due to the high inter-study heterogeneity. Current evidence suggests that fatty acid-binding protein-4 levels are significantly increased in pregnancies complicated with gestational diabetes, while no association of serum apelin and monocyte chemoattractant protein-1 with the disease can be supported. Data regarding the rest adipokines are conflicting, since the available studies did not unanimously indicate a significant change of their levels in gestational diabetes.

Conclusions

The findings of the present systematic review suggest the promising role of fatty acid-binding protein-4 in the prediction of gestational diabetes, while inconsistent evidence exists regarding the rest novel adipokines. Future cohorts are needed to assess their predictive efficacy and fully elucidate their contribution in the disease.

https://ift.tt/2SLnUA7

Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue

Abstract

Acetaminophen, APAP, is a common over-the-counter drug with antipyretic-analgesic action. When APAP is used in large doses, it causes hepatotoxicity and nephrotoxicity but safe at therapeutic doses. Cinnamon (Cinnamomum zeylanicum) is extensively used in folk medicine due to its high content of natural antioxidants. The current investigation was planned to study the possible ameliorative effect of cinnamon toward induced APAP-apoptosis and cellular damage in renal cells. Four groups (nine rats each) were used; negative control group administrated distilled water for 15 days; positive control APAP group administrated a single dose of APAP (1 g/kg) orally on the last day; APAP+Cin L (200 mg/kg) and APAP+Cin H (400 mg/kg) aqueous extract of cinnamon orally once a day for 15 days. An hour after the last dose of cinnamon, all rats in the third and fourth group were administrated a single dose of APAP (1 g/kg) orally. GC/MS analysis was performed to identify the plant used in the study. APAP markedly increased serum levels of creatinine, BUN, and glucose and decreased levels of albumin and total protein. In addition, APAP could also exert severe alteration in the kidney histopathology along with upregulation of caspase-3 and PCNA. However, pre-treatment with cinnamon ameliorated the APAP-induced cellular alterations and apoptosis, possibly through its high content of antioxidants.

https://ift.tt/2PatVbr

The improvement on the implementation level of environmental policies is demanded in China

Abstract

So far, on the national level, 52 environmental laws, 266 environmental regulations and rules, and 983 environment standards have been issued in China from 1979. However, environmental qualities are still far away from the goals of environmental policies. The implementation process of environmental policies might be one of the key negative reasons. The implementation of environmental policies in local agencies remained at a rather low level not matching the demands corresponding to the rapid development of economy in the nation. A significant improvement of environmental conditions could be achieved if proper environmental protection policies are executed completely and local agencies are active in their administrative, supervising, and educational responsibilities.

https://ift.tt/2CYfWxQ

Should we fear direct oral anticoagulants more than vitamin K antagonists in simple single tooth extraction? A prospective comparative study

Abstract

Objectives

The aim of this prospective comparative clinical study was to evaluate the effect of oral anticoagulants on peri- and post-operative bleeding during simple single tooth extractions, comparing patients in treatment with vitamin K antagonists (VKAs) and patients assuming direct oral anticoagulants (DOACs).

Materials and methods

Patients under oral anticoagulant therapy needing dental extraction were eligible for entering the study; patients were enrolled following inclusion and exclusion criteria and divided into VKAs and DOAC group according to the anticoagulation therapy. Included patients underwent a simple single dental extraction with elevators and forceps with a maximum surgical time of 15 minutes, without anticoagulation therapy discontinuation. All participants were assessed pre-operatively, during surgery, 30 min minutes and 7 days after surgery. Biological complications were registered and post-extraction bleeding was clinically defined according to Iwabuchi classification. Parametric and non-parametric tests were used to evaluate the variables between the groups.

Results

Sixty-five patients per group were enrolled and 130 teeth were extracted. The two groups were comparable for pre-, peri-, and post-operative variables. Only 1 patient of DOAC group and 2 patients for VKA group needed medical evaluation for post-extractive bleeding. No statistically significant difference resulted in post-operative bleeding events between the groups (p = 0.425).

Conclusions

DOAC and VKA patients showed the same incidence of bleeding complications after simple single tooth extraction. Bleeding events were not statistically significant and not clinically relevant.

Clinical relevance

Patients assuming DOACs can be treated similarly to patients in VKAs therapy with INR index between 2 and 3. Non-ceasing of DOAC therapy seems to be appropriate for simple single dental extractions.

https://ift.tt/2CZ3uhn

A Retrospective Study: Application Site Pain with the Use of Crisaborole, a Topical PDE4 Inhibitor

Publication date: Available online 2 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Christine Pao-Ling Lin, Samantha Gordon, Min Ji Her, David Rosmarin

https://ift.tt/2zqKeGf

Meehan's Dermatopathology: Doppelgängers & Stags, Volume 2

Publication date: Available online 3 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Alexander Maley

https://ift.tt/2SGJdCE

Melanoma subsequent to natalizumab exposure: A report from the RADAR (Research on Adverse Drug events And Reports) Program

Publication date: Available online 3 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Ryan C. Kelm, Erika L. Hagstrom, Regine J. Mathieu, Kelsey A. Orrell, Linda Serrano, Kelly A. Mueller, Anne E. Laumann, Dennis P. West, Beatrice Nardone

https://ift.tt/2zpvzuT

“Tar Smarts” May Have a New Meaning for Atopic Dermatitis and Psoriasis

Publication date: Available online 3 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Warren R. Heymann

https://ift.tt/2SIJbtR

Insect Repellents: An Updated Review for the Clinician

Publication date: Available online 3 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Quoc-Bao D. Nguyen, Mai-Anh N. Vu, Adelaide A. Hebert

Abstract

Malaria, Zika virus, West Nile virus, Dengue fever, and Lyme disease are common causes of morbidity and mortality around the world. While arthropod bites may cause local inflammation and discomfort, a greater concern is the potential to develop deadly systemic infection. The use of insect repellents (IR) to prevent systemic infections constitutes a fundamental public health effort. Cost-effectiveness, availability, and high-efficacy against arthropod vectors are key characteristics of an ideal IR. Currently, numerous IRs are available on the market, with DEET (N,N-diethyl-3-methylbenzamide) being the most widely used. DEET has an excellent safety profile and remarkable protection against mosquitoes and various other arthropods. Other EPA-registered IR ingredients (permethrin, picaridin, IR3535, oil of lemon eucalyptus, oil of citronella, catnip oil, and 2-undecanone) are alternative IRs of great interest due to some having efficacies comparable to that of DEET. These alternative IRs possess low toxicity and favorable customer experiences in utilization (e.g., cosmetically pleasant, naturally occurring). This review summarizes currently available EPA-registered IRs: the origins, mechanisms of action, side effect profiles, and available formulations will be discussed. This review will enable the clinician to select the best IR option to meet patients' needs and provide the greatest protection from arthropod bites and sequelae.

https://ift.tt/2zkQr6k

Idiopathic Stevens-Johnson syndrome and toxic epidermal necrolysis: prevalence and patients characteristics

Publication date: Available online 2 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Guillaume Chaby, Saskia Ingen-Housz-Oro, Nicolas De Prost, Pierre Wolkenstein, Olivier Chosidow, Laurence Fardet

https://ift.tt/2SI6SCU

Tattooing: A national survey in the general population of France

Publication date: Available online 2 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Nicolas Kluger, Laurent Misery, Sophie Seité, Charles Taieb

https://ift.tt/2zkQizO

A nomogram to identify high-risk melanoma patients with a negative sentinel node biopsy

Publication date: Available online 2 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Eduardo Bertolli, Mariana Petaccia de Macedo, Vinícius Fernando Calsavara, Clovis Antonio Lopes Pinto, João Pedreira Duprat Neto

Summary

Background

Melanoma patients with negative nodes following sentinel node biopsy are a heterogeneous group. Current guidelines fail to adequately stratify surveillance and treatment for this group. Also, there is scarce data on adjuvant treatments for these patients.

Objectives

To create a nomogram based on clinical and pathological characteristics of primary melanoma to evaluate the risk of recurrence in patients with negative SNB.

Methods

Retrospective cohort of patients who underwent SNB from 2000 to 2015 in a single institution.

Results

Our cohort comprised 1,213 patients. Among these patients, 967 (79.7%) had a negative SNB and mean follow up was 59.67 months. There were 133 recurrences (13.8%) - 45 (33.8%) presented with nodal recurrence, and 35 (26.3%) recurred where SNB was performed. Breslow thickness, ulceration, and microsatellitosis were found to be predictive of risk of recurrence at one, two, five, and ten years.

Limitations

single center analysis.

Conclusions

we created a predictive nomogram for melanoma patients after a negative SNB. It is easy to use and identifies high-risk patients who should have more strict surveillance and consideration of adjuvant treatment.

https://ift.tt/2SBxs0p

Surgical pearl: Retrograde punch biopsy technique for removal of enlarged earlobe piercings.

Publication date: Available online 2 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Jacques Pierre du Toit, Johann de Wet, Willem Visser

https://ift.tt/2zkQ6AA

Trends in Incidence of Cutaneous Malignant Melanoma in Canada: 1992-2010 versus 2011-2015

Publication date: Available online 2 November 2018

Source: Journal of the American Academy of Dermatology

Author(s): Feras M. Ghazawi, Michelle Le, Nebras Alghazawi, Elham Rahme, Linda Moreau, Elena Netchiporouk, Andrei Zubarev, Osama Roshdy, Steven J. Glassman, Denis Sasseville, Ivan V. Litvinov

https://ift.tt/2SIsaQI

PD-1 immunobiology in systemic lupus erythematosus

Publication date: Available online 3 November 2018

Source: Journal of Autoimmunity

Author(s): Colleen S. Curran, Sarthak Gupta, Ignacio Sanz, Elad Sharon

Abstract

Programmed death (PD)-1 receptors and their ligands have been identified in the pathogenesis and development of systemic lupus erythematosus (SLE). Two key pathways, toll-like receptor and type I interferon, are significant to SLE pathogenesis and modulate the expression of PD-1 and the ligands (PD-L1, PD-L2) through activation of NF-κB and/or STAT1. These cell signals are regulated by tyrosine kinase (Tyro, Axl, Mer) receptors (TAMs) that are aberrantly activated in SLE. STAT1 and NF-κB also exhibit crosstalk with the aryl hydrocarbon receptor (AHR). Ligands to AHR are identified in SLE etiology and pathogenesis. These ligands also regulate the activity of the Epstein-Barr virus (EBV), which is an identified factor in SLE and PD-1 immunobiology. AHR is important in the maintenance of immune tolerance and the development of distinct immune subsets, highlighting a potential role of AHR in PD-1 immunobiology. Understanding the functions of AHR ligands as well as AHR crosstalk with STAT1, NF-κB, and EBV may provide insight into disease development, the PD-1 axis and immunotherapies that target PD-1 and its ligand, PD-L1.

https://ift.tt/2qtGmzX

De novo autoimmune hepatitis –is this different in adults compared to children?

Publication date: Available online 3 November 2018

Source: Journal of Autoimmunity

Author(s): Nanda Kerkar, Diego Vergani

Abstract

De novo autoimmune hepatitis (AIH) is an unusual cause of graft dysfunction after liver transplantation. This entity was originally described in 1996 in children transplanted for conditions other than AIH, who developed biochemical and histological features similar to AIH and responded to the therapy of classical AIH with steroids and azathioprine. In the last two decades, there have been reports of occurrence of de novo AIH in pediatric and adult liver transplant recipients, in the latter often being given different nomenclature including 'plasma cell hepatitis'. Typical causes of graft dysfunction in liver transplant recipients include rejection, infection, vascular and biliary complications as well as recurrence of disease that was the indication for liver transplantation like hepatitis C and primary biliary cholangitis. While acute cellular rejection and chronic rejection are well recognized complications post liver transplantation, in the last 5 years, antibody mediated rejection has become increasingly important in liver transplantation. In 2016, in the course of developing guidelines for the diagnosis of antibody mediated rejection, it was suggested that both de novo AIH and 'plasma cell hepatitis' be categorized as 'plasma cell rejection'. This review explores the literature on de novo AIH in pediatrics and adults, sheds light on the substantive differences between these two entities and suggests that they be kept distinct from each other as the two are not the same. This difference in the cause of graft dysfunction in pediatric and adult liver transplant recipients is important as the management of the two conditions is not the same.

https://ift.tt/2qqqO09

Nation-wide survey of advanced non-melanoma skin cancers treated at dermatology departments in Japan

Publication date: Available online 3 November 2018

Source: Journal of Dermatological Science

Author(s): Yasuhiro Fujisawa, Takeru Funakoshi, Yoshiyuki Nakamura, Maki Ishii, Jun Asai, Takatoshi Shimauchi, Kazuyasu Fujii, Manabu Fujimoto, Norito Katoh, Hironobu Ihn

Abstract

Background

There are limited treatment options for advanced non-melanoma skin cancers (NMSCs). To overcome this issue, we need to conduct clinical studies, however, there is a lack of information on how many patients with advanced NMSCs are treated annually in Japan.

Objective

To investigate the actual number of advanced NMSC patients in Japan.

Methods

A questionnaire survey was sent to 668 institutes to educe information on: 1) the numbers of patients with squamous cell carcinoma (SCC), extramammary Paget disease (EMPD), other skin origin carcinomas, and cutaneous angiosarcoma (CAS) admitted in 2016 and 2017; 2) the preferred first- and second-line chemotherapies; and 3) the anticipated for future development.

Results

Questionnaires were returned from 383 (57.3%) institutes. They reported a total of 1765 patients over the 2 years. The annual number patients with SCC, EMPD, other skin carcinomas, and CAS was 323.5, 192.5, 126, and 240.5, respectively. We estimated the annual number of patients for all 668 institutes to be 1255.6. Current first- and second-line treatment for NMSCs were chemotherapy regimens, but immune checkpoint inhibitors were the most anticipated new drugs for SCC and CAS, while chemotherapy was still the most anticipated treatment for EMPD.

Conclusion

Considering that during 2017, the number of deaths in Japan due to NMSC was reported to be 948, our estimated annual number of patients with NMSCs, 1255.6 seems to be an accurate estimation. As most of the treatment options for advanced NMSCs are outdated, the results of this study should be used to propose clinical studies.

https://ift.tt/2ySbjm9

Altered neural dynamics in people who report spontaneous out of body experiences

Publication date: Available online 3 November 2018

Source: Cortex

Author(s): Elizabeth Milne, Stephanie Dunn, Chen Zhao, Myles Jones

Abstract

It has been suggested that individual differences in cortical excitability leading to disruption of the timing and integration of sensory information processing may explain why some people have out of body experiences (OBE) in the absence of any known pathological or psychiatric condition. Here we recorded EEG from people who either had, or had not experienced an OBE in order to investigate the neural dynamics of OBE in the non-clinical population. A screening questionnaire was completed by 551 people, 24% of whom reported having at least one OBE. Participants who were free of any psychiatric or neurological diagnoses, including migraines, were invited to take part in subsequent EEG recording. EEG data were obtained from 19 people who had had an OBE and 20 who had not. Amplitude of the visual P1 ERP deflection and consistency of alpha-band phase locking were significantly reduced in the participants who had had an OBE. We did not find any group differences in resting state power or in visually induced gamma oscillations. These results provide support for the claim that cortical differences, particularly with respect to the timing of visual information processing, may give rise to OBE in clinically healthy individuals. To our knowledge, this study is the first to compare EEG variables obtained from people who have, and have not, had an OBE.

https://ift.tt/2PHOVFA

Language lateralisation measured across linguistic and national boundaries

Publication date: Available online 3 November 2018

Source: Cortex

Author(s): Markus Hausmann, Marc Brysbaert, Lise van der Haegen, Jörg Lewald, Karsten Specht, Marco Hirnstein, Julie Willemin, Jack Barton, Delia Buchilly, Florian Chmetz, Maja Roch, Sanne Brederoo, Nele Dael, Christine Mohr

Abstract

The visual half-field technique has been shown to be a reliable and valid neuropsychological measurement of language lateralisation, typically showing higher accuracy and faster correct responses for linguistic stimuli presented in the right visual field (RVF) than left visual field (LVF). The RVF advantage corresponds to the well-known dominance of the left hemisphere (LH) in processing language(s). However, clinical and experimental neuroscientists around the globe use different variations of the visual half-field paradigm, making direct comparisons difficult. The current study used a word/non-word visual half-field paradigm with translingual stimuli. In total, 496 participants from seven European countries were investigated: Belgium (64), England (49), Germany (85), Italy (34), The Netherlands (87), Norway (51), and Switzerland (126), covering six international languages (Dutch, English, French, German, Italian, Norwegian). All language groups revealed a significant RVF/LH advantage in accuracy and reaction times that accounted for up to 26.1% of the total variance in performance. We found some variation in the degree of the RVF/LH advantage across language groups, accounting for a maximum of 3.7% of the total variance in performance. The RVF/LH advantage did not differ between subsamples speaking English, French or German as first or second languages or between monolingual and early/late bi/multilinguals. The findings suggest that the translingual lexical decision task (TLDT) is a simple but reliable measurement of language lateralisation that can be applied clinically and experimentally across linguistic and national boundaries.

https://ift.tt/2RxUzHD

Reproducibility of visual-field asymmetries: Nine replication studies investigating lateralization of visual information processing

Publication date: Available online 3 November 2018

Source: Cortex

Author(s): Sanne G. Brederoo, Mark R. Nieuwenstein, Frans W. Cornelissen, Monicque M. Lorist

Abstract

Numerous behavioral studies suggest that the processing of various types of visual stimuli and features may be more efficient in either the left or the right visual field. However, not all of these visual-field asymmetries (VFAs) have been observed consistently. Moreover, it is typically unclear whether a failure to observe a particular VFA can be ascribed to certain characteristics of the participants and stimuli, to a lack of statistical power, or to the actual absence of an effect. To increase our understanding of lateralization of visual information processing, we have taken a rigorous methodological and statistical approach to examine the reproducibility of various previously reported VFAs. We did so by performing (near-)exact replications of nine representative previous studies, aiming for sufficient power to detect the effects of interest, and taking into consideration all relevant dependent variables (reaction times and error rates). Following Bayesian analyses –on our data alone as well as on the combined evidence from the original and replication studies– we find precise and reliable evidence that support VFAs in the processing of faces, emotional expressions, global and local information, words, and in the distribution of spatial attention. In contrast, we find less convincing evidence for VFAs in processing of high and low spatial frequencies. Finally, we find no evidence for VFAs in categorical perception of color and shape oddballs, and in the judgments of categorical and coordinate spatial relations. We discuss our results in the light of their implications for theories of visual lateralization.

https://ift.tt/2PHOSto