Head and Neck Diseases by Alexandros G.Sfakianakis: 12/08/18

Σάββατο 8 Δεκεμβρίου 2018

A methodology for detecting the wound state sensing in terms of its colonization of pathogenic bacteria.

A methodology for detecting the wound state sensing in terms of its colonization of pathogenic bacteria.

MethodsX. 2018;5:1521-1527

Authors: Zhou J, Yao D, Qian Z, Hou S, Li L, Fan Y

Abstract
A methodology for wound state sensing in terms of its colonization with pathogenic bacteria such as Staphylococcus aureus or Pseudomonas aeruginosa has been developed. Here we report polydiacetylene (PDA) liposomes containing self-quenched carboxyfluorescein dye are only sensitive to toxins/enzymes secreted by Pathogenic bacteria but not by non-pathogenic species of Escherichia coli (DH5α). The basis of the detection assay is that at high concentration, carboxyfluorescein is non-fluorescent. Following breakdown of the bilayer of liposome containers by bacterial toxins, the dye becomes diluted and "switches on". The methodology can be easily adapted to evaluate the release of payloads from PDA liposomes in terms of fluorescence intensity and in addition to detect the potential interaction mechanism of biomimetic bilayer and pathogenic bacteria. •Self-quenched when encapsulated at high concentration, while fluorescence when diluted in solution•Easy quantification by measuring fluorescence intensity•Simple measurement procedure required (plate reading fluorimeter).

PMID: 30519535 [PubMed]

https://ift.tt/2QnZCP6

Nasal septal abscess: a 10-year retrospective study.

Nasal septal abscess: a 10-year retrospective study.

Eur Arch Otorhinolaryngol. 2018 Nov 30;:

Authors: Cheng LH, Wu PC, Shih CP, Wang HW, Chen HC, Lin YY, Chu YH, Lee JC

Abstract
OBJECTIVE: Nasal septal abscess is an uncommon condition but it can cause potentially life-threatening intracranial complications and cosmetic nasal deformity.
METHODS: We analyzed ten years of cases to determine the optimal diagnostic and therapeutic modalities. A retrospective review of case notes from Tri-Service General Hospital archives was performed. Records of six patients diagnosed with nasal septal abscess, who were treated from September 2007 to August 2017 were retrospectively reviewed. Patients' clinical symptoms, etiology, diagnostic methods, bacteriology, antibiotic and surgical treatment were recorded and analyzed.
RESULTS: Out of six patients diagnosed with nasal septal abscess, three were male and three were female. Ages ranged from 19 to 75 years (mean 51 years). The most common symptoms at presentation were nasal pain and nasal obstruction. Typical etiologies were trauma or acute sinusitis, but uncontrolled diabetes mellitus was also an important etiology. In the series of six patients, four of them had positive findings of abscess and in drainage, had the following bacterial cultures: Staphylococcus aureus (two cases), methicillin-resistant S. aureus (one case), and Klebsiella pneumoniae (one case). In addition to antibiotic treatment, all patients underwent surgical drainage and had complete resolution of disease without intracranial complications during at least 1 year of follow-up. However, two out of the six patients developed saddle nose deformity.
CONCLUSIONS: This study highlights that: 1. In view of the rapidly increasing number of diabetes mellitus cases, uncontrolled diabetes mellitus is an important etiology of nasal septal abscess. 2. Although S. aureus is the most common pathogen, we must pay attention to methicillin-resistant S. aureus (MRSA) to prevent severe complications and patients who are at increased risk for MRSA colonization should be administrated antibiotics against MRSA initially. 3. Nasal septal abscess should be managed with parenteral broad spectrum antibiotics, appropriate drainage and immediate reconstruction of the destructed septal cartilage with autologous cartilage graft, to prevent serious intracranial complications and cosmetic nasal deformity.

PMID: 30506184 [PubMed - as supplied by publisher]

https://ift.tt/2PkA289

Interplay of Personal, Pet, and Environmental Colonization in Households Affected by Community-Associated Methicillin-Resistant Staphylococcus aureus.

Interplay of Personal, Pet, and Environmental Colonization in Households Affected by Community-Associated Methicillin-Resistant Staphylococcus aureus.

J Infect. 2018 Nov 29;:

Authors: Hogan PG, Mork RL, Boyle MG, Muenks CE, Morelli JJ, Thompson RM, Sullivan ML, Gehlert SJ, Merlo JR, McKenzie MG, Wardenburg JB, Rzhetsky A, Burnham CD, Fritz SA

Abstract
OBJECTIVE: We sought to determine the prevalence, molecular epidemiology, and factors associated with Staphylococcus aureus environmental surface and pet colonization in households of children with community-associated methicillin-resistant S. aureus (CA-MRSA) infection.
METHODS: Between 2012 and 2015, 150 children with CA-MRSA infections and their household contacts and pets were enrolled in this cross-sectional study in metropolitan Saint Louis, MO. Cultures to detect S. aureus were collected from 3 anatomic sites of household members, 2 dog/cat sites, and 21 environmental surfaces in each household. Molecular epidemiology of S. aureus isolates was determined via repetitive-sequence PCR. Generalized linear models were developed to identify factors associated with S. aureus/MRSA household contamination.
RESULTS: MRSA was recovered from environmental surfaces in 69 (46%) households (median 2 surfaces [range 1-18]). The enrollment infecting strain type was the most common strain recovered from the environment in most (64%) households. In generalized linear models, factors associated with a higher proportion of MRSA-contaminated environmental surfaces were household member MRSA colonization burden, MRSA as the dominant S. aureus strain colonizing household members, more strain types per household member, index case African-American race, and renting (vs. owning) the home. Of 132 pets, 14% were colonized with MRSA. Pets whose primary caretaker was MRSA-colonized were more likely to be MRSA-colonized than pets whose primary caretaker was not MRSA-colonized (50% vs. 4%, p<0.001).
CONCLUSIONS: Household environments and pet dogs and cats serve as reservoirs of MRSA. Household member MRSA colonization burden predicts environmental MRSA contamination. Longitudinal studies will inform the directionality of household transmission.

PMID: 30503843 [PubMed - as supplied by publisher]

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Interferon-lambda1 enhances Staphylococcus aureus clearance in healthy nasal mucosa, not in nasal polyps.

Interferon-lambda1 enhances Staphylococcus aureus clearance in healthy nasal mucosa, not in nasal polyps.

J Allergy Clin Immunol. 2018 Nov 30;:

Authors: Lan F, Zhong H, Zhang N, Johnston SL, Wen W, Papadopoulos N, Zhang L, Bachert C

Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a Th2-skewed inflammation and an increased colonization by Staphylococcus aureus (S. aureus). Interferon-lambda 1(IFN-λ1) is known for its antiviral activity, there is little information on its anti-bacterial role.
OBJECTIVE: To determine the expression and release of IFN-λ1 from healthy and CRSwNP nasal mucosal tissue upon exposure to S. aureus and assess its potential role in anti-bacterial defense mechanisms.
METHODS: Healthy and CRSwNP nasal tissues were exposed to S. aureus and assessed the expression of IFN-λ1 and MUC5AC and MUC5B. THP1 derived macrophages incubated with or without IFN-λ1 were assessed for uptake and killing of S. aureus and expression of lysosomal-associated membrane protein 1 (LAMP1) and intracellular reactive oxidase substrate (ROS), IFN-λ1 receptor IL-28R and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 1 pathway by immunofluorescence staining.
RESULTS: S. aureus infection increased IFN-λ1 expression in healthy nasal tissue, not in CRSwNP tissue. IFN-λ1 (10 ng/ml) significantly decreased the number of S. aureus colony-forming units in healthy control tissue, but not in CRSwNP tissue, and upregulated MUC5AC and MUC5B expression in control tissues upon S. aureus infection. IFN-λ1 stimulation increased intracellular killing of S. aureus in THP1 derived macrophages and substantially increased LAMP1, IL-28R, ROS and STAT signaling in macrophages incubated with S. aureus. All of these effects were attenuated by blocking IL-28R and ROS activities.
CONCLUSIONS: IFN-λ1 favors the clearance of S. aureus in healthy nasal mucosa, and enhances antibacterial function of macrophages via IFN-λ1-IL-28R-ROS-JAK-STAT signaling pathways.

PMID: 30508540 [PubMed - as supplied by publisher]

https://ift.tt/2GaAiqT

USA300 Staphylococcus aureus persists on multiple body sites following an infection.

USA300 Staphylococcus aureus persists on multiple body sites following an infection.

BMC Microbiol. 2018 Dec 05;18(1):206

Authors: Read TD, Petit RA, Yin Z, Montgomery T, McNulty MC, David MZ

Abstract
BACKGROUND: USA300 methicillin-resistant Staphylococcus aureus (MRSA) is a community- and hospital-acquired pathogen that frequently causes infections but also can survive on the human body asymptomatically as a part of the normal microbiota. We devised a comparative genomic strategy to track colonizing USA300 at different body sites after an initial infection. We sampled ST8 S. aureus from subjects at the site of a first known MRSA infection. Within 60 days of this infection and again 12 months later, each subject was tested for asymptomatic colonization in the nose, throat and perirectal region. 93 S. aureus strains underwent whole genome shotgun sequencing.
RESULTS: Among 28 subjects at the initial sampling time, we isolated S. aureus from the nose, throat and perirectal sites from 15, 11 and 15 of them, respectively. Twelve months later we isolated S. aureus from 9 subjects, with 6, 3 and 3 strains from the nose, throat and perirectal area, respectively. Genome sequencing revealed that 23 patients (ages 0-66 years) carried USA300 intra-subject lineages (ISLs), defined as having an index infection isolate and closely related colonizing strains. Pairwise distance between strains in different ISLs was 48 to 162 single nucleotide polymorphisms (SNPs) across the core regions of the chromosome, whereas within the same ISL it was 0 to 26 SNPs. Strains in ISLs from the same subject differed in plasmid and prophage content, and contained deletions that removed the mecA-containing SCCmec and ACME regions. Five strains contained frameshift mutations in agr toxin-regulating genes. Persistence of an ISL was not associated with clinical or demographic subject characteristics. We inferred that colonization with the ISL occurred about 18 weeks before the first assessment of asymptomatic colonization.
CONCLUSIONS: Clonal lineages of USA300 may continue to colonize people at one or more anatomic sites up to a year after an initial infection and experience loss of the SCCmec, loss and gain of other mobile genetic elements, and mutations in the agr operon.

PMID: 30518317 [PubMed - in process]

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The Relationship between Colonization by Moraxella catarrhalis and Tonsillar Hypertrophy.

The Relationship between Colonization by Moraxella catarrhalis and Tonsillar Hypertrophy.

Can J Infect Dis Med Microbiol. 2018;2018:5406467

Authors: Prates MCM, Tamashiro E, Proenca-Modena JL, Criado MF, Saturno TH, Oliveira AS, Buzatto GP, Jesus BLS, Jacob MG, Carenzi LR, Demarco RC, Massuda ET, Aragon D, Valera FCP, Arruda E, Anselmo-Lima WT

Abstract
We sought to investigate the prevalence of potentially pathogenic bacteria in secretions and tonsillar tissues of children with chronic adenotonsillitis hypertrophy compared to controls. Prospective case-control study comparing patients between 2 and 12 years old who underwent adenotonsillectomy due to chronic adenotonsillar hypertrophy to children without disease. We compared detection of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis by real-time PCR in palatine tonsils, adenoids, and nasopharyngeal washes obtained from 37 children with and 14 without adenotonsillar hypertrophy. We found high frequency (>50%) of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa in both groups of patients. Although different sampling sites can be infected with more than one bacterium and some bacteria can be detected in different tissues in the same patient, adenoids, palatine tonsils, and nasopharyngeal washes were not uniformly infected by the same bacteria. Adenoids and palatine tonsils of patients with severe adenotonsillar hypertrophy had higher rates of bacterial coinfection. There was good correlation of detection of Moraxella catarrhalis in different sampling sites in patients with more severe tonsillar hypertrophy, suggesting that Moraxella catarrhalis may be associated with the development of more severe hypertrophy, that inflammatory conditions favor colonization by this agent. Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis are frequently detected in palatine tonsils, adenoids, and nasopharyngeal washes in children. Simultaneous detection of Moraxella catarrhalis in adenoids, palatine tonsils, and nasopharyngeal washes was correlated with more severe tonsillar hypertrophy.

PMID: 30515253 [PubMed]

https://ift.tt/2G0DMfD

Relationship between nasal Carrier isolates and clinical isolates in children with Staphylococcus aureus infections.

Relationship between nasal Carrier isolates and clinical isolates in children with Staphylococcus aureus infections.

Microb Pathog. 2018 Nov 28;:

Authors: Tan S, Wan C, Wang H, Zhou W, Shu M

Abstract
AIM: To assess the relationship between Staphylococcus aureus (S. aureus) strains colonizing the anterior nares and clinical isolate colonizing other, non-nasal infectious sites in children with S. aureus infections.
METHODS: Fifty-six hospitalized children with S. aureus infection were screened and 22 pairs of nasal carrier isolates and non-nasal clinical isolates were characterized by polymerase chain reaction (PCR) assay for the detection of methicillin resistance (mecA) gene, Panton-Valentine leukocidin virulence (PVL) gene, and multilocus sequence typing (MLST) for the purpose of identifying sequence types of S. aureus.
RESULTS: In this study, Sequence Type (ST) 59 was found to be the predominant clonal type in the nasal carrier isolates, with statistically significant differences in positive mecA and PVL expression compared with other STs. In general, there was consistence between the STs detected in the nose and other, non-nasal sites for each patient (Kappa = 0.950), where 19 pairs (86.4%) of colonization isolates and their corresponding non-nasal clinical isolates were indistinguishable in mecA, PVL, and ST expression.
CONCLUSION: ST59 is reported here as a dominant and virulent methicillin-resistant S. aureus (MRSA) clone which may has become a leading sequence type among virulent MRSAs in Sichuan area. Overall there is a strong correlation between colonization and infection in pediatric patients that may be genetically indistinguishable and endogenous. Therefore, nasal swabs as a routine test for children, the elimination of nasal carriage may be considered as a prevention strategy for some systemic S. aureus infections.

PMID: 30502517 [PubMed - as supplied by publisher]

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Predictors of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci co-colonization among nursing facility patients.

Predictors of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci co-colonization among nursing facility patients.

Am J Infect Control. 2018 Nov 27;:

Authors: Heinze K, Kabeto M, Martin ET, Cassone M, Hicks L, Mody L

Abstract
BACKGROUND: The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) poses significant challenges for antibiotic therapy. We characterized the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) co-colonization that may facilitate resistance transfer and vancomycin-resistant S aureus emergence among nursing facility patients.
METHODS: We cultured newly admitted patient hands, nares, oropharynx, groin, and perianal region plus wounds and device insertion sites, if applicable, upon enrollment at day 14, day 30, and monthly follow-up up to 6 months. Demographic, comorbidity, and antimicrobial use data were collected. Functional status was assessed at each visit using the Physical Self-Maintenance Scale. Multinomial logistic regression was performed to determine factors predictive of co-colonization.
RESULTS: Five hundred eight patients were enrolled, with an average follow-up time of 28.5 days. Prevalence of MRSA/VRE co-colonization, MRSA alone, and VRE alone was 8.7%, 8.9%, and 23.4%, respectively. Independent predictors of co-colonization included indwelling device use (odds ratio [OR] = 5.5 [2.2-13.7]), recent antibiotic use (OR = 2.5 [1.4-4.2]), diabetes (OR = 1.9 [1.0-3.8]), and the presence of open wounds (OR = 1.9 [1.0-3.6]).
CONCLUSIONS: High rates of VRE are driving co-colonization with MRSA in nursing facilities. Indwelling device use, recent antibiotic use, diabetes, and open wounds predicted patient co-colonization.

PMID: 30502107 [PubMed - as supplied by publisher]

https://ift.tt/2G9pGJ3

School environmental contamination of methicillin-sensitive Staphylococcus aureus as an independent risk factor for nasal colonization in schoolchildren: An observational, cross-sectional study.

School environmental contamination of methicillin-sensitive Staphylococcus aureus as an independent risk factor for nasal colonization in schoolchildren: An observational, cross-sectional study.

PLoS One. 2018;13(11):e0208183

Authors: Lin J, Zhang T, Bai C, Liang J, Ye J, Yao Z

Abstract
OBJECTIVE: We aim to assess the similarities of proportional, phenotypic, and molecular characteristics between the school environment and schoolchildren on methicillin-sensitive S. aureus (MSSA) isolates.
METHODS: A cross-sectional study was conducted between March 2016 and August 2016 in eight elementary schools in Guangzhou, China. Nasal swabs from students and environmental swabs from school environments were collected. Univariate and multivariate logistic regression analyses under a multistage stratified cluster cross-sectional survey design were performed to access the prevalence relationship and influencing factors, respectively. Phenotypic and molecular characterizations of MSSA isolates were conducted using the Kirby-Bauer disk diffusion method and polymerase chain reaction assays, respectively.
RESULTS: In total, 1705 schoolchildren and 1240 environmental samples from 40 classes in eight elementary schools obtained between March and August 2016 were include in this study. The rates of MSSA prevalence among schoolchildren and the environment were 11.44% (195/1705) and 4.60% (57/1240), respectively. The odds ratios and 95% confidence intervals (CIs) on the prevalence of MSSA isolates were 1.11 (95% CI, 1.05-1.29; P = 0.010) and 1.04 (95% CI, 1.01-1.07; P = 0.003) for the school or class environment and students, respectively. Similar phenotypic and molecular characteristics were identified between schoolchildren and the environment. A cause and effect relationship could not be established because the study design was cross-sectional.
CONCLUSIONS: Because of the cross-sectional design, we can reveal the association between school environment and schoolchildren on MSSA, but it is not a cause and effect relationship.

PMID: 30500843 [PubMed - in process]

https://ift.tt/2Qy09x3

Staphylococcus aureus Infecting and Colonizing Experimental Animals, Macaques, in a Research Animal Facility.

Staphylococcus aureus Infecting and Colonizing Experimental Animals, Macaques, in a Research Animal Facility.

Microb Drug Resist. 2018 Nov 27;:

Authors: Pardos de la Gandara M, Diaz L, Euler CW, Chung M, Gonzalez A, Cheleuitte C, Freiwald W, Tomasz A, Fischetti VA, de Lencastre H

Abstract
An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infections on the skin and soft tissues of experimental macaques in the vivarium of The Rockefeller University, New York, triggered this observational and interventional study. We screened 14 macaques in the colony (samples from head, nares, and rectum) and their housing (40 environmental surfaces) four times in 1 year, for S. aureus colonization or contamination, while implementing enhanced decolonization and decontamination procedures. A total of 114 isolates of S. aureus were recovered and characterized (antibiograms, spa typing, multilocus sequence typing, pulsed-field gel electrophoresis [PFGE], mecA, Panton-Valentine Leukocidin, and arginine catabolic mobile element). Based on these results, six strains of S. aureus were identified: two MRSA strains (t16708/ST3862/PFGE-A, t16709/ST3862/PFGE-C) and one methicillin-sensitive S. aureus (t8397/ST3884/PFGE-D) were characterized for the first time in this study; strains belonging to spa types t189 and t4167 have been identified in primates in previous studies. None of these strains was common to the neighboring New York City human community. Thus, it seems probable that the animals were already colonized upon arrival to the University. We suggest screening primates for S. aureus carriage upon arrival to University vivaria and possible implementation of extensive decolonization procedures before any surgical interventions.

PMID: 30481118 [PubMed - as supplied by publisher]

https://ift.tt/2rsniD1

The Microbiome in Atopic Dermatitis.

The Microbiome in Atopic Dermatitis.

J Allergy Clin Immunol. 2018 Nov 23;:

Authors: Paller AS, Kong HH, Seed P, Naik S, Scharschmidt TC, Gallo RL, Luger T, Irvine AD

Abstract
As an interface with the environment, the skin is a complex ecosystem, colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens such as S. aureus and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized, as microorganisms can modulate innate, as well as adaptive, immune responses. Host-commensal interactions also have an impact on the developing immune system in infants and subsequently the occurrence of diseases such as asthma and atopic dermatitis. Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with atopic dermatitis, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria such as S. aureus. Early clinical studies suggest that topical application of commensal organisms (e.g., S. hominis or R. mucosa) reduces atopic dermatitis severity and support an important role for commensals in decreasing S. aureus colonization in patients with atopic dermatitis. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders such as atopic dermatitis may result in novel therapeutic strategies.

PMID: 30476499 [PubMed - as supplied by publisher]

https://ift.tt/2DZMSaz

Incidence and Outcomes of Staphylococcus aureus Bacteriuria: A Population-based Study.

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Incidence and Outcomes of Staphylococcus aureus Bacteriuria: A Population-based Study.

Clin Infect Dis. 2018 Nov 24;:

Authors: Stokes W, Parkins MD, Parfitt ECT, Ruiz JC, Mugford G, Gregson DB

Abstract
Background: Staphylococcus aureus bacteriuria (SABU) may represent multiple processes ranging from asymptomatic colonization to a marker of S. aureus bacteremia (SAB). Our objective was to describe SABU at a population-based level and determine patient characteristics associated with SAB.
Methods: A retrospective study was performed using electronic databases. All urine cultures positive for S. aureus between 2010-2013 within the Calgary Health Zone were included. Patient characteristics were compared among patients with and without SAB and risk factors identified using multiple logistic regression modelling.
Results: A total of 2540 urine cultures positive for S. aureus from 2054 patients were analyzed. The incidence of SABU was greatest amongst geriatric males with multiple comorbidities. 175 (6.9%) of the cohort had SAB. Those with concurrent SAB were more likely to be hospitalized, male, have a recent urinary procedure, have pure S. aureus culture in urine and have laboratory findings suggesting systemic infection. Patients with isolated SABU were more likely to be ≥65 years, have dementia and have an abnormal urinalyses with pyuria and urine nitrites. In-hospital mortality in patients with SABU and SABU+SAB was 9.2% and 17.5%, respectively. Patients with SABU detected ≥48 hours before SAB had the highest risk of death.
Conclusions: Less than 7% of patients with SABU have or will develop SAB. Characteristics associated with SABU were identified that established higher risk for systemic infection. Investigating SABU patients with these characteristics for systemic infection is warranted since a delay in diagnosis is associated with increased mortality.

PMID: 30476003 [PubMed - as supplied by publisher]

https://ift.tt/2rrIBEw

Neonatal gut colonisation by Staphylococcus aureus strains with certain adhesins and superantigens is negatively associated with subsequent development of atopic eczema.

Neonatal gut colonisation by Staphylococcus aureus strains with certain adhesins and superantigens is negatively associated with subsequent development of atopic eczema.

Br J Dermatol. 2018 Nov 25;:

Authors: Nowrouzian FL, Ljung A, Nilsson S, Hesselmar B, Adlerberth I, Wold AE

Abstract
BACKGROUND: Insufficient early immune stimulation may predispose to atopic disease. Staphylococcus aureus, a skin and gut colonizer, produces the B-cell mitogen protein A and T-cell activating superantigens. Early gut colonization by S. aureus strains that possess the superantigens encoded by enterotoxin gene (egc) cluster and the elastin-binding protein, is negatively associated with development of atopic eczema.
OBJECTIVES: To investigate whether these findings could be replicated in a second birth-cohort, FARMFLORA and, secondly, whether nasal colonization by S. aureus also relates to subsequent atopic eczema development.
METHODS: Faecal samples and nasal swabs from infants in the FARMFLORA birth-cohort (N=65) were cultured for S. aureus. Individual strains were distinguished by RAPD (random amplified polymorphic DNA) and assessed for adhesin and superantigen gene carriage by PCR. Atopic eczema at 18 months of age was related to nasal and gut S. aureus colonisation patterns during the first 2 months of life (well before onset of eczema).
RESULTS: S. aureus colonisation per se was unrelated to subsequent eczema development. However, gut S. aureus strains from the infants who subsequently developed atopic eczema less frequently carried the ebp gene, encoding elastin-binding protein, and superantigen genes encoded by the egc, as compared to strains from children who remained healthy. Nasal colonization by S. aureus was less clearly related to subsequent eczema development.
CONCLUSION: The results precisely replicate our previous observations and may suggest that mucosal colonisation by certain S. aureus strains provides immune stimulation that strengthens the epithelial barrier and counteracts the development of atopic eczema. This article is protected by copyright. All rights reserved.

PMID: 30474111 [PubMed - as supplied by publisher]

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A pilot study to assess the impact of an educational patient hand hygiene intervention on acquisition of colonization with health care-associated pathogens.

A pilot study to assess the impact of an educational patient hand hygiene intervention on acquisition of colonization with health care-associated pathogens.

Am J Infect Control. 2018 Nov 21;:

Authors: Rai H, Saldana C, Gonzalez-Orta MI, Knighton S, Cadnum JL, Donskey CJ

Abstract
Patient hand hygiene is a commonsense measure that has been associated with reductions in colonization or infection with bacterial and viral pathogens in quasi-experimental studies. We conducted a nonblinded pilot randomized trial to assess the impact of an educational patient hand hygiene intervention on acquisition of colonization by selected health care-associated pathogens in hospitalized patients. For patients with negative admission cultures, the intervention did not reduce the new acquisition of colonization by pathogens compared with that of standard care.

PMID: 30471974 [PubMed - as supplied by publisher]

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[Adenitis-cellulitis syndrome, an infrequent form of presentation of the late-onset neonatal septicemia: Report of two cases].

[Adenitis-cellulitis syndrome, an infrequent form of presentation of the late-onset neonatal septicemia: Report of two cases].

Arch Argent Pediatr. 2018 Dec 01;116(6):e769-e772

Authors: Sarrión-Sos N, Morell-García M, Martínez-Sebastián L, Centeno-Rubiano JM, Montesinos-Sanchis E, Orta-Sibú N

Abstract
Septicemia is the main cause of neonatal mortality. The early-onset neonatal sepsis is usually related to maternal factor risks including recto-vaginal colonization. In the late-onset neonatal septicemia it is more difficult to establish the etiology because the majority of the cases are nosocomial or community related. The Streptococcus agalactiae (beta-hemolytic Streptococcus) is the most frequent germ associated with neonatal sepsis in developed countries. The late-onset form usually occurs with septic symptoms and meningitis and, in a few cases, with osteoarticular, skin and soft tissue infection. Adenitis-cellulitis syndrome is rarely seen, and its main cause is Staphylococcus aureus, followed by Streptococcus agalactiae. We report two cases of group B Streptococcus late-onset neonatal septicemia, both of them with adenitis-cellulitis syndrome. Patients recovered uneventfully after an adequate antibiotic therapy.

PMID: 30457734 [PubMed - in process]

https://ift.tt/2G2Nf62

Case 260: Endobronchial Posttransplantation Lymphoproliferative Disease.

Case 260: Endobronchial Posttransplantation Lymphoproliferative Disease.

Radiology. 2018 Dec;289(3):876-880

Authors: Short RG, Tailor TD

Abstract
History A 31-year-old woman with a history of bilateral orthotopic lung transplantation performed 10 months earlier for cystic fibrosis presented for a routine follow-up appointment, with her chief symptom being a cough. The cough started approximately 1 month prior to this appointment and was minimally productive of clear to yellow phlegm. In addition to her cough, she reported increased sinus congestion and a sensation of "something in her upper chest." She denied shortness of breath, wheezing, hemoptysis, or cigarette smoking. Review of systems was negative for fever, chills, or night sweats. At physical examination, the patient was afebrile, borderline tachycardic (heart rate, 99 beats per minute), and mildly hypertensive (blood pressure, 138/99 mm Hg). Oxygen saturation was 96% on room air. Laboratory evaluation revealed a white blood cell count of 3.5 × 109/L (normal range, [3.2-9.8] × 109/L). Pulmonary function testing was notable for a newly decreased ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of 64% (2.0 and 3.4 L, respectively) (normal FEV1-to-FVC ratio, 80%), suggesting an obstructive lung process. One month prior to presentation, the patient's sputum cultures grew Pseudomonas and methicillin-resistant Staphylococcus aureus. The patient showed no evidence of active infection at the time of bronchoscopy. Thus, the bacteria were favored to reflect colonization, and antibiotic therapy was not administered at that time. The patient was taking an immunosuppression regimen of mycophenolate mofetil (CellCept; Genentech, San Francisco, Calif) (1 g twice daily), prednisone (10 mg daily), and tacrolimus (Prograf; Astellas Pharma US, Northbrook, Ill) (goal therapeutic range, 12-14 ng/mL). The patient was sent for posteroanterior and lateral chest radiography followed by chest CT ( Figs 1 - 3 ) and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT ( Fig 4 ).

PMID: 30452335 [PubMed - in process]

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Gemcitabine Combined with the mTOR Inhibitor Temsirolimus in Patients with Locally Advanced or Metastatic Pancreatic Cancer. A Hellenic Cooperative Oncology Group Phase I/II Study

Abstract

Background

The prognosis of patients with advanced pancreatic cancer is dismal, and there is a need for novel and effective treatments.

Objectives

Tο determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a novel gemcitabine (G) and temsirolimus (T) combination (phase I) and estimate the 6-month progression-free survival (PFS) in patients treated with the T + G combination (phase II).

Patients and Methods

Eligible patients with histologically confirmed inoperable or metastatic pancreatic carcinoma (MPC) were entered into the trial. G was given bi-weekly and T weekly in a 4-week cycle. The first dose level was set at G 800 mg/m² and T 10 mg. G was escalated in increments of 200 mg/m² and T in increments of 5 mg until DLT was reached, and the recommended dose was used for the phase II part.

Results

Thirty patients were enrolled in the phase I component at the pre-planned six dose levels; one bilirubin DLT of grade III occurred at the first dose level. The MTD was established as the approved doses of both drugs. Fifty-five patients were entered into the phase II component. Median relative dose intensities administered in the first cycle were 0.75 for T and 0.99 for G. Grade 3-4 hematological toxicities were recorded in 87.3% of patients. The most common non-hematological adverse events were metabolic disorders (81.8%) followed by gastrointestinal disorders (63.6%). Median PFS was 2.69 months (95% CI 1.74-4.95) and median OS was 4.95 months (95% CI 3.54-6.85), while the 6-month PFS rate was 30.9%.

Conclusions

Combination of G and T is feasible in patients with locally advanced or MPC with manageable side effects, but lacks clinical efficacy.

The study was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12611000643976).

https://ift.tt/2E2VCgf

Subcellular localization of sterol biosynthesis enzymes

Abstract

Cholesterol synthesis is a complex, coordinated process involving a series of enzymes. As of today, our understanding of subcellular localization of cholesterol biosynthesis enzymes is far from complete. Considering the complexity and intricacies of this pathway and the importance of functions of DHCR7, DHCR24 and EBP enzymes for human health, we undertook a study to determine their subcellular localization and co-localization. Using expression constructs and antibody staining in cell cultures and transgenic mice, we found that all three enzymes are expressed in ER and nuclear envelope. However, their co-localization was considerably different across the cellular compartments. Furthermore, we observed that in the absence of DHCR7 protein, DHCR24 shows a compensatory upregulation in a Dhcr7^−/− transgenic mouse model. The overall findings suggest that the sterol biosynthesis enzymes might not always work in a same functional complex, but that they potentially have different, multifunctional roles that go beyond the sterol biosynthesis pathway. Furthermore, the newly uncovered compensatory mechanism between DHCR7 and DHCR24 could be of importance for designing medications that would improve cholesterol production in patients with desmosterolosis and Smith–Lemli–Opitz syndrome.

https://ift.tt/2Ek4mP5

Distinctive role of ACVR1 in dentin formation: requirement for dentin thickness in molars and prevention of osteodentin formation in incisors of mice

Abstract

Dentin is a major component of teeth that protects dental pulp and maintains tooth health. Bone morphogenetic protein (BMP) signaling is required for the formation of dentin. Mice lacking a BMP type I receptor, activin A receptor type 1 (ACVR1), in the neural crest display a deformed mandible. Acvr1 is known to be expressed in the dental mesenchyme. However, little is known about how BMP signaling mediated by ACVR1 regulates dentinogenesis. To explore the role of ACVR1 in dentin formation in molars and incisors in mice, Acvr1 was conditionally disrupted in Osterix-expressing cells (designated as cKO). We found that loss of Acvr1 in the dental mesenchyme led to dentin dysplasia in molars and osteodentin formation in incisors. Specifically, the cKO mice exhibited remarkable tooth phenotypes characterized by thinner dentin and thicker predentin, as well as compromised differentiation of odontoblasts in molars. We also found osteodentin formation in the coronal part of the cKO mandibular incisors, which was associated with a reduction in the expression of odontogenic gene Dsp and an increase in the expression of osteogenic gene Bsp, leading to an alteration of cell fate from odontoblasts to osteoblasts. In addition, the expressions of WNT antagonists, Dkk1 and Sost, were downregulated and B-catenin was up-regulated in the cKO incisors, while the expression levels were not changed in the cKO molars, compared with the corresponding controls. Our results indicate the distinct and critical roles of ACVR1 between incisors and molars, which is associated with alterations in the WNT signaling related molecules. This study demonstrates for the first time the physiological roles of ACVR1 during dentinogenesis.

https://ift.tt/2FXV2C8

Correction to: Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer

The article Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer, written by Sarah Sammons, Noah S. Kornblum and Kimberly L. Blackwell, was originally published electronically on the publisher's internet portal (currently SpringerLink).

https://ift.tt/2Gg3JHY

Olaparib Tablet: A Review in Ovarian Cancer Maintenance Therapy

Abstract

Olaparib (Lynparza®), a first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor, has recently been approved in a new tablet formulation as maintenance treatment for recurrent high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy. Relative to an earlier capsule formulation, the tablet formulation of olaparib has improved bioavailability, thereby reducing pill burden and offering a more convenient dosage regimen. In the phase III SOLO2 study, maintenance treatment with olaparib tablets significantly prolonged median PFS (primary endpoint) relative to placebo in patients with platinum-sensitive, recurrent, ovarian cancer bearing gBRCA mutations. Results from an earlier phase II study (Study 19) assessing the capsule formulation supported these findings, with a significant PFS benefit (primary endpoint) observed with olaparib relative to placebo as maintenance therapy in patients with platinum-sensitive, recurrent, ovarian cancer, with or without BRCA mutations. Olaparib tablet had a manageable tolerability profile, with most adverse events of mild or moderate severity. Given its efficacy and manageable tolerability profile, olaparib tablets provide a useful maintenance treatment option for recurrent, platinum-sensitive ovarian cancer, regardless of BRCA mutation status, with the tablet formulation providing a more convenient dosing option.

https://ift.tt/2PCmbyQ

Periodontal ligament-associated protein-1 gets involved in the development of osseous eruption canal

Abstract

Osseous eruption is an important stage of tooth eruption process. The role of periodontal ligament-associated protein-1 (PLAP-1/asporin) in the development of osseous eruption canal remain undefined and were the focus of this study. C57BL/6 mice at postnatal days P11-13 and P 15-16 were chosen. The development of osseous eruption canal of lower first molar was observed and osteoclasts were detected by staining for tartrate-resistant acid phosphatase (TRAP). PLAP-1 expression in the process of osseous eruption (OE, P11-13) and post- osseous eruption (P-OE, P15-16) was assessed by immunohistochemistry, immunofluorescence and western blotting. Receptor activator of NF-κB ligand (RANKL) distribution in the process was also assessed by immunohistochemistry. A double immunofluorescence stain was used to reveal PLAP-1 in association with CD68 (osteoclast maker). Fresh occlusal tissues of erupting lower first molars at OE and P-OE were separated to detected RANKL/OPG ratio by western blotting to elucidate related mechanisms. At osseous eruption (OE), osseous and mucosal tissues could be observed on the occlusal side of lower first molar. Osseous eruption canal was developing. Many osteoclasts were found around occlusal alveolar bone in the development of osseous eruption canal. At post- osseous eruption (P-OE), osseous eruption canal had been built, only mucosal tissues were observed, and few osteoclasts were detected. More PLAP-1 expression was detected at OE, compared with that at P-OE. Similar distributions of PLAP-1 and RANKL in occlusal bone tissues of erupting lower first molars were detected at OE. Colocalization of PLAP-1 and CD68 revealed the positive relationship between PLAP-1 and osteoclasts in the development of osseous eruption canal. PLAP-1 positively correlated with RANKL and CD68+ osteoclasts, and areas of bone resorption. Higher RANKL/OPG ratio was detected at OE, compared with that at P-OE. PLAP-1 gets involved in the development of osseous eruption canal.

https://ift.tt/2KTKkvt

Therapy of Advanced Prostate Cancer: Targeting the Androgen Receptor Axis in Earlier Lines of Treatment

Abstract

With the decrease in PSA screening based on the 2011 United States Preventive Services Task Force guidelines and the potential approval of highly sensitive imaging techniques over the next few years, we are likely to see an increasing trend of metastatic prostate cancer diagnosis. Traditional therapy for nonmetastatic prostate cancer (nmPC) has consisted of androgen deprivation therapy (ADT) followed by other hormonal therapy maneuvers, such as anti-androgen withdrawal, herbal preparations, low dose steroids, or ketoconazole. Androgen receptor-axis-targeted therapies (ARAT) were previously only approved for patients with metastatic castration resistant prostate cancer (mCRPC). This has recently changed after reporting of results from the SPARTAN and PROSPER trials, which were conducted in nonmetastatic CRPC (nmCRPC) patients. These studies demonstrated improved metastasis-free survival with apalutamide and enzalutamide, each compared to placebo in a double blind randomized setting. In 2017, the LATITUDE and STAMPEDE studies demonstrated marked survival benefit with early abiraterone and prednisone in patients with metastatic hormone sensitive prostate cancer (mHSPC) in addition to ADT. Other second-generation AR antagonists are currently in phase 3 trials in mHSPC and nmCRPC. This article summarizes the key clinical trials that led to FDA approval of ARAT in the mHSPC and nmCRPC settings and highlights potential limitations, future directions, and treatment-algorithms when selecting patients for early therapy in mHSPC and NMPC.

https://ift.tt/2SDUuD9

New Horizons in the Treatment of Metastatic Pancreatic Cancer: A Review of the Key Biology Features and the Most Recent Advances to Treat Metastatic Pancreatic Cancer

Abstract

Only a limited number of therapeutic strategies are available for patients diagnosed with pancreatic adenocarcinoma, and disease recurrence and mortality are consequently high. For metastatic disease, two combinations are approved in the first line setting: a triplet with 5-fluoruracil, irinotecan, and oxaliplatin, and the combination of gemcitabine and nab-paclitaxel. In patients who have progressed on gemcitabine, a new nanoliposomal formulation of irinotecan has recently been approved. While these treatments have demonstrated some efficacy, there has been little increase in survival rates for metastatic pancreatic cancer patients. Consequently, there is an urgent need for research and development of new treatments. As there is now a deeper understanding of pancreatic cancer biology, new drugs targeting altered pathways are under research, including agents that target TGF-β, IGF, or NOTCH. Furthermore, taking into account the role of the tumor stroma in this disease, some stroma-targeting drugs are being developed, including PEGPH20, a pegylated recombinant human hyaluronidase. In the immunotherapy field, although checkpoint inhibitors have failed to demonstrate benefit as monotherapies, combinations with other drugs are being investigated, with promising preliminary results. Other strategies under research are targeting tumor metabolism or DNA repair deficiency.

https://ift.tt/2Qd4fdS

PD-1 and PD-L1 Expression in Male Breast Cancer in Comparison with Female Breast Cancer

Abstract

Background

Male breast cancer is rare, as it represents less than 1% of all breast cancer cases. In addition, male breast cancer appears to have a different biology than female breast cancer. Programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), seem to have prognostic and predictive values in a variety of cancers, including female breast cancer. However, the role of PD-1 and PD-L1 expression in male breast cancer has not yet been studied.

Objectives

To compare PD-1 and PD-L1 expression in male breast cancer to female breast cancer and to evaluate prognostic values in both groups.

Patients and Methods

Tissue microarrays from formalin-fixed paraffin-embedded resection material of 247 female and 164 male breast cancer patients were stained for PD-1 and PD-L1 by immunohistochemistry.

Results

PD-1 expression on tumor-infiltrating lymphocytes was significantly less frequent in male than in female cancers (48.9 vs. 65.3%, p = 0.002). In contrast, PD-L1 expression on tumor and immune cells did not differ between the two groups. In male breast cancer, PD-1 and tumor PD-L1 were associated with grade 3 tumors. In female breast cancer, PD-1 and PD-L1 were associated with comparably worse clinicopathological variables. In a survival analysis, no prognostic value was observed for PD-1 and PD-L1 in either male and female breast cancer. In a subgroup analysis, female patients with grade 3/tumor PD-L1-negative or ER-negative/immune PD-L1-negative tumors had worse overall survival.

Conclusions

PD-1 seems to be less often expressed in male breast cancer compared to female breast cancer. Although PD-1 and PD-L1 are not definite indicators for good or bad responses, male breast cancer patients may therefore respond differently to checkpoint immunotherapy with PD-1 inhibitors than female patients.

https://ift.tt/2UhKEZ5

The inhibition of glycosaminoglycan incorporation influences the cell proliferation and cytodifferentiation in cultured embryonic mouse molars

Abstract

The extracellular matrix (ECM) contains a variety of complex macromolecules including proteoglycans (PGs) and glycosaminoglycans (GAGs). PG consists of a protein core with covalently attached carbohydrate side chains called GAGs. Several PGs, including versican, biglycan, decorin and syndecan are involved in odontogenesis while the role of GAGs in those PGs in this process remains unclarified. The purpose of this study was to investigate the influence of GAGs on tooth development. The mandibular first molars at early bell stage were cultivated with or without 4-methylumbelliferyl-β-d-xyloside (Xyl-MU). The cultured tooth germs were metabolically labelled with [³⁵S] Na₂SO₄, then PGs in tooth germs and cultured medium were extracted separately and analyzed by gel filtration. Morphological changes were evaluated on days 2, 4, 6, and histological changes were examined by hematoxylin-eosin (HE) staining and transmission electron microscope (TEM). Related proteins and genes of cytodifferentiation were further examined by immunohistochemistry (IHC) and quantitive real-time PCR (qPCR) respectively. Meanwhile, BrdU incorporation assay was used to explore the effect of Xyl-MU on the cell proliferation of cultured tooth germs. The results demonstrated that the incorporation of GAGs to PGs in cultured tooth germs was heavily inhibited by Xyl-MU. Accompanied by the inhibition of GAGs incorporation, Xyl-MU altered tooth morphogenesis and delayed the differentiation of ameloblasts and odontoblasts. Proliferation of inner enamel epithelium (IEE) was also inhibited. Therefore, we draw a conclusion that the inhibition of GAGs incorporation influences the cell proliferation and cytodifferentiation in cultured embryonic mouse molars.

https://ift.tt/2BQbmRm

Liraglutide induces beige fat development and promotes mitochondrial function in diet induced obesity mice partially through AMPK-SIRT-1-PGC1-α cell signaling pathway

Abstract

Purpose

Glucagon like peptide-1 (GLP-1) is produced to induce postprandial insulin secretion. Liraglutide, a full agonist of the GLP-1 receptor, has a protective effect on weight gain in obese subjects. Brown adipose tissue plays a major role in the control of energy balance and is known to be involved in the weight loss regulated by liraglutide. The putative anti-obesity properties of liraglutide and the cell signaling pathways involved were examined.

Methods

Four groups of C57/BL6 mice fed with chow or HFHS diet were injected with either liraglutide or vehicle for four weeks. Western blotting was used to analyze protein expression.

Results

Liraglutide significantly attenuated the weight gain in mice fed with HFHS diet and was associated with significant reductions of epididymal fat and inguinal fat mass. Furthermore, liraglutide significantly upregulated the expression of brown adipose-specific markers in perigonadal fat in association with upregulation of AMPK-SIRT-1-PGC1-α cell signaling. However, elevation of brown fat markers in skeletal muscle was only observed in HFHS diet fed mice after liraglutide treatment, and AMPK-SIRT-1 cell signaling is not involved in this process.

Conclusions

the anti-obesity effect of liraglutide occurs through adaptive thermogenesis and may act through different cell signaling pathways in fat and skeletal muscle tissue. Liraglutide induces beige fat development partially through the AMPK-SIRT-1-PGC1-α cell signaling pathway. Therefore, liraglutide is a potential medication for obesity prevention and in targeting pre-diabetics.

https://ift.tt/2G50x28

Liraglutide induces beige fat development and promotes mitochondrial function in diet induced obesity mice partially through AMPK-SIRT-1-PGC1-α cell signaling pathway

Abstract

Purpose

Methods

Four groups of C57/BL6 mice fed with chow or HFHS diet were injected with either liraglutide or vehicle for four weeks. Western blotting was used to analyze protein expression.

Results

Conclusions

https://ift.tt/2G50x28

Graphical Abstracts

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Clinical and Serological Biomarkers of Treatment's Response in Multiple Sclerosis Patients Treated Continuously with Interferonβ-1b for More than a Decade

https://ift.tt/2RKUhxT

Amyotrophic Lateral Sclerosis and Oxidative Stress: A Double-Blind Therapeutic Trial After Curcumin Supplementation

https://ift.tt/2QkzvrX

Effect of Neuroinflammation on ABC Transporters: Possible Contribution to Refractory Epilepsy

https://ift.tt/2QkzxA5

Cariprazine in Bipolar Depression and Mania: State of the Art

https://ift.tt/2RKhzUp

Neuroprotective Effects of Heat Shock Protein70

https://ift.tt/2RM6kuA

Cerebrospinal Fluid, Brain Electrolytes Balance, and the Unsuspected Intrinsic Property of Melanin to Dissociate the Water Molecule

https://ift.tt/2QkmiQ4

Models of Parkinson's Disease with Special Emphasis on Drosophila melanogas

https://ift.tt/2RQIuy8

Acknowledgements to Reviewers

https://ift.tt/2QndbOo

CCR5 blockage by maraviroc: a potential therapeutic option for metastatic breast cancer

Abstract

Purpose

Bone metastasis is observed in up to 70% of breast cancer patients. The currently available treatment options are palliative in nature. Chemokine receptor 5 (CCR5) has gained attention as therapeutic target in various malignancies. Here, we investigated the effects of targeting CCR5 by its antagonist maraviroc in metastatic breast cancer cells.

Methods

In response to maraviroc exposure, cytotoxicity was assessed using an MTT proliferation assay, whereas the effects on colony formation and migration were assessed using colony formation, transwell chamber migration and scratch wound healing assays, respectively. Apoptosis-related activities were investigated using nuclear staining, annexin-V FITC staining and Western blotting. Cell cycle changes were analysed using flow cytometry and qRT-PCR for cell cycle relevant genes. A nude rat model for breast cancer bone metastasis was used to evaluate the in vivo efficacy of CCR5 targeting by maraviroc. Circulatory levels of the three cognate ligands for CCR5 (CCL3, CCL4, CCL5) were analysed in sera of breast cancer patients using ELISA.

Results

We found that blockade of CCR5 attenuated the proliferation, colony formation and migration of metastatic breast cancer cells, and induced apoptosis and arrest in the G1 phase of the cell cycle. Expression profiling highlighted the involvement of cell cycle related signalling cascades. We also found that treatment with maraviroc significantly inhibited bone metastasis in nude rats implanted with MDA-MB-231 breast cancer cells. Finally, we found that the circulatory levels of three cognate ligands for the CCR5 receptor varied between breast cancer patients and healthy controls.

Conclusion

Our findings indicate that targeting CCR5 may be an effective strategy to combat breast cancer bone metastasis.

https://ift.tt/2zjcGdH

A Randomized, Split-Face, Evaluator-Blind Clinical Trial Comparing Monopolar Radiofrequency Versus Microfocused Ultrasound With Visualization for Lifting and Tightening of the Face and Upper Neck

BACKGROUND Over the past decade, 2 major modalities for noninvasive skin tightening have emerged: monopolar capacitive-coupled radiofrequency (MRF) and microfocused ultrasound with visualization (MFU-V). Up to date, no comparative clinical trials have been performed. OBJECTIVE To compare the efficacy and safety of MRF versus MFU-V for the lifting and tightening of the face and neck. MATERIALS AND METHODS Twenty subjects with mild to moderate skin laxity received MFU-V over one-side of the face and MRF over the other side of the face at the same time. Subjects were followed for 6 months. RESULTS Both MRF and MFU-V led to a decrease in the Fasil Face and Neck Laxity Grading Scale (FLR). These differences became significant at Day 30 and remained significantly improved through Days 90 and 180 in both groups. There was no statistically significant difference in the FLR Scale between MRF-treated and MFU-V–treated sides. Subjects' Global Aesthetic Improvement Scale showed improvement at Day 30, 90, and 180. CONCLUSION Both MRF and MFU-V led to significant improvement in face and neck laxity. There were no statistical differences between MRF and MFU-V in standardized investigator measures of face and neck laxity, patient satisfaction, and adverse events. Address correspondence and reprint requests to: Douglas C. Wu, MD, PhD, Cosmetic Laser Dermatology, 9339 Genesee Avenue, Suite 300, San Diego, CA 92121, or e-mail: dwu@clderm.com Supported by financial grant from SOLTAMEDICAL as an investigator-initiated study. The authors have indicated no significant interest with commercial supporters. © 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PsRYxh

Cover Image

The cover image is based on the Original Article Detection of high‐grade dysplasia, carcinoma in situ and squamous cell carcinoma in the upper aerodigestive tract: Recommendations for optimal use and interpretation of narrow‐band imaging, by Manon A. Zwakenberg et al., https://doi.org/10.1111/coa.13229.

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Issue Information

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Large Font Patient Written Instructions

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Nasal function and CPAP compliance

Continuous positive airway pressure (CPAP) is the mainstay therapy for patients with obstructive sleep apnea (OSA) however compliance with CPAP is variable. Nasal ailments, such as nasal congestion are frequently mentioned as a cause for CPAP non-compliance, and potentially could be addressed prior to CPAP initiation, however, no specific criteria or recommendations for the evaluation and management of these patients exist. The aim of this retrospective study is to evaluate the effects of nasal anatomic features and disease on adherence to CPAP therapy for patients with OSA and determine the indications for pre-CPAP nasal treatment by using data obtained at clinical examination.

https://ift.tt/2EaalVN

Adiponectin, leptin and high sensitivity C-reactive protein values in obese children – important markers for metabolic syndrome?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print

https://ift.tt/2Us27y5

Issue Information

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Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF‐β/Smad signaling pathway

Abstract

Objective

To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV.

Methods

MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins.

Results

AS‐IV reduced the proliferation of SW962 cells in a concentration‐ and time‐dependent manner, induced cell‐cycle arresting in G0/G1 phase, as demonstrated by the up‐regulation of P53 and P21 expression, and the down‐regulation of cyclin D1 expression. AS‐IV enhanced the expression of Bax and cleaved‐caspase 3, and suppressed Bcl‐2 and Bcl‐xl expression, which resulted in apoptosis increased. Furthermore, the expression of Beclin‐1 and LC3‐B was upregulated and that of P62 was downregulated, which suggested that AS‐IV could increase the incidence of autophagy in SW962 cells. After inhibiting autophagy by 3‐methyladenine, cell apoptosis decreased upon AS‐IV treatment. Similarly, TGF‐β1 stimulated SW962 cells, cell proliferation enhanced, and the expression of TGF‐βRII and Smad4 was decreased. Furthermore, the expression of proteins that promote apoptosis and autophagy decreased. After AS‐IV treatment, the expression levels of the above proteins exhibited the opposite effect.

Conclusion

AS‐IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF‐β/Smad signaling pathway in VSCC.

https://ift.tt/2E9pfM7

Fresh/frozen Tübingen technique (Margin strip method) for head and neck basal cell carcinoma: A retrospective study of 298 cases

https://ift.tt/2E6iJFX

Pediatric Dermatology ‐ critical approach to the new treatments

Abstract

The field of pediatric dermatology treatment has been rich in new developments. Several recent therapeutic advances in pediatric dermatology have been made. This review will focus on critical approach to the new treatments for several entities encountered in pediatric dermatology. The use of biologics and small molecules in children with atopic dermatitis and psoriasis, exciting advances in the use of propranolol and other beta‐blockers for the treatment of infantile hemangiomas, the use of sirolimus for vascular anomalies will be discussed.

https://ift.tt/2EkSVXl

Clinical Guidelines in Pediatric Hearing Loss: Systemic Review Using the Appraisal of Guidelines for Research and Evaluation II Instrument

Objectives

Despite the importance, impact, and prevalence of pediatric hearing loss (HL), there are very few published clinical practice guidelines (CPG) supporting the evaluation and management of pediatric patients with HL. Our objective was to appraise existing CPGs to ensure safe and effective practices.

Methods

A literature search was conducted in PubMed, Google Scholar, EBSCO, as well as a manual Google search. Three independent assessors using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument evaluated CPGs related to HL in children. Standardized domain scores were calculated for each guideline.

Results

A total of four guidelines met the inclusion criteria and were appraised. Scope and purpose achieved a high median score of 83%. Stakeholder involvement, clarity of presentation, and editorial independence achieved intermediate scores of 67%, 54%, and 50%, respectively. The areas that required most improvement and achieved low scores were rigor of development and applicability, with scores of 22% and 38%, respectively. Based on the AGREE II measures, the four guidelines had domain scores less than 60% for each domain, and without modification no guideline could be recommended.

Conclusions

Based on the AGREE II, the qualities of CPGs for pediatric HL have several shortcomings, and the need for a comprehensive CPG remains. Rigor of development and applicability present the greatest opportunities for improvement of these CPGs. Laryngoscope, 2018

https://ift.tt/2zPpl8x

Treatment of actinic keratosis through inhibition of cyclooxygenase‐2: Potential mechanism of action of diclofenac sodium 3% in hyaluronic acid 2.5%

Cyclooxygenase‐2 (COX‐2) and its metabolic product prostaglandin E₂ (PGE₂) are induced in response to growth factors, inflammatory cytokines, tumour promoters, activated oncogenes and, in the skin, ultraviolet (UV) radiation. Accumulating evidence suggests a role for the COX‐2/PGE₂ pathway in tumourigenesis in various tissue types including cutaneous squamous cell carcinoma. There is also strong evidence for a role in the development of actinic keratoses (AKs) – common dysplastic lesions of the skin associated with UV radiation overexposure – considered as part of a continuum with skin cancer. Non‐steroidal anti‐inflammatory drugs (NSAIDs) exert their anti‐inflammatory, analgesic and antipyretic effects by reversibly or irreversibly acetylating COX isoforms, inhibiting downstream prostaglandins, and may have a chemo‐preventive role in malignancies, including skin cancer. Topical treatment of AK lesions with the NSAID diclofenac sodium 3% in combination with hyaluronic acid 2.5% has been shown to be effective and well tolerated, although the mechanism of action remains to be elucidated.

https://ift.tt/2EkSSL9

Arachnoid cysts of the internal auditory canal: An underappreciated entity?

Objectives/Hypothesis

To describe the histopathologic findings and clinical presentation of arachnoid cysts (ACs) within the human temporal bone.

Study Design

Retrospective cohort analysis.

Methods

An analysis of all medical records of patients diagnosed with an AC was performed. Temporal bones underwent standard processing for histologic examination. The slides were examined by light microscopy. The histologic findings were compared to premortem clinical data.

Results

Twenty‐seven ACs were identified in 22 patients. Twenty ears (74%) had no identified risk factor for AC development. The median volume was 12.8 mm³. The most prevalent location of the ACs was at the fundus (16 ACs) followed by the middle portion of the internal auditory canal (IAC) (six ACs). Nine ACs were asymptomatic. Among the 18 symptomatic ACs, the most common presentation was sensorineural hearing loss (SNHL) (94%), followed by tinnitus (22%). The most affected structure was the cochlear nerve (59%), followed by the vestibular nerve (41%). The average hearing threshold was of moderately severe SNHL and speech discrimination was in the range of 50% on monosyllabic word tests. The median time interval from initial presentation to death was 12 years. No correlation was found between duration of symptoms and AC volume.

Conclusions

AC of the IAC is not uncommon. Its presentation is variable, ranging from asymptomatic to SNHL, with poor speech discrimination, tinnitus, and vertigo. This diagnosis should be kept in the differential diagnosis of retrocochlear pathologies.

Level of Evidence

https://ift.tt/2PsaBlc

Risk Factors for Multiple Hemorrhages Following Tonsil Surgery in Children

Objectives/Hypothesis

Although much is known about the incidence and risk factors for hemorrhage after tonsil surgery, the incidence and factors related to multiple episodes of hemorrhage are not well examined. Our objective was to identify risk factors that may contribute to multiple hemorrhages following tonsil surgery in children.

Study Design

Retrospective chart review.

Methods

A retrospective review was conducted of pediatric patients who experienced one or more hemorrhages following tonsillectomy/tonsillotomy, with or without adenoidectomy, between 2010 and 2016 at a single, tertiary‐care hospital. Risk factors for multiple hemorrhages were examined using a multivariable logistic regression model.

Results

Among the 11,140 patients who underwent tonsil surgery, 452 patients experienced one or more hemorrhages; 32 of these had multiple episodes of hemorrhage (7.1% of all patients with bleeds/0.3% of all patients). Older age (≥12 years: adjusted odds ratio [OR]: 3.13; 95% confidence interval [CI]: 1.47‐6.68) and high body mass index for age (≥85th percentile: adjusted OR: 2.26; 95% CI: 1.06‐4.85) were significantly associated with an increased risk of multiple hemorrhages in the multivariable model. Medical comorbidities, indications for surgery, surgical technique, intraoperative blood loss, and perioperative medications were not associated with multiple episodes of bleeding.

Conclusions

Multiple hemorrhages after tonsillectomy/tonsillotomy are uncommon. The risk of a second PTH after an initial episode is 7.1%, almost double the risk of a bleed after the initial tonsil surgery. Age > 12 years and high BMI for age may be associated with increased risk of rebleeding. After an initial bleed, increased surveillance may be warranted, particularly for patients with risk factors.

Level of Evidence

4 Laryngoscope, 2018

https://ift.tt/2zPpadn

Real Life Management of Chronic Urticaria: multicenter and cross sectional study on patients and dermatologists in Iran

Recently, advances in understanding the etiology of urticaria and updates of diagnostic and therapeutic management guidelines have drawn attention to chronic urticaria (CU) morbidity. This study aimed to evaluate Iranian dermatologists' practice and real life management of CU patients. A total of 35 dermatologists and 443 patients were included in the study. Number of female patients was 321 (72.5%). Mean (Standard Deviation) age of the study patients was 38 (13) years and the median (Inter Quartile Range) of disease duration was 12 (6‐ 48) months. Severity of patients' symptoms was mild for 32.1%, moderate for 38.7%, severe for18.8% and 10.4% of them had no evident signs or symptoms. The most common diagnostic methods were physical examination (96.6%), differential blood count (83.5%), erythrocyte sedimentation rate (77.4%), and C‐reactive protein (62.8%). The number of dermatologists prescribed non‐sedating antihistamines (nsAH) in regular dose and high dose mono therapy were 26 (74%) and 6 (17%), respectively. About 66% of dermatologists were familiar with British Association of Dermatologists (BAD) guideline. The most common first‐line treatment for CU by Iranian dermatologists was non‐sedating antihistamines in regular or high doses. The real‐life management of patients with CU in Iran was in accordance with the available practice guidelines.

https://ift.tt/2EkSQmv

Real Life Management of Chronic Urticaria: multicenter and cross sectional study on patients and dermatologists in Iran

https://ift.tt/2EkSQmv

Issue Information

https://ift.tt/2EalENC

Treatment of actinic keratosis through inhibition of cyclooxygenase‐2: Potential mechanism of action of diclofenac sodium 3% in hyaluronic acid 2.5%

https://ift.tt/2EkSSL9

Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF‐β/Smad signaling pathway

Abstract

Objective

To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV.

Methods

MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins.

Results

Conclusion

AS‐IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF‐β/Smad signaling pathway in VSCC.

https://ift.tt/2E9pfM7

Pediatric Dermatology ‐ critical approach to the new treatments

Abstract

https://ift.tt/2EkSVXl

Fresh/frozen Tübingen technique (Margin strip method) for head and neck basal cell carcinoma: A retrospective study of 298 cases

https://ift.tt/2E6iJFX

Investigating skin age analysis to reduce tanning intentions among adolescents: A pilot study

Abstract

As skin cancer rates continue to rise, targeted efforts to reduce excessive exposure to ultraviolet radiation are crucial. Adolescents are a high‐risk population for intentional tanning; thus, we sought to determine whether the novel use of skin age analysis with ultraviolet (UV) photography would be an effective tool for reducing intentions to tan in adolescents with a calculated skin age (measured by complexion analysis software) that exceeds their actual age. Surveying 85 students in this study, skin age difference above zero was associated with reduced intentions to tan (P = 0.006) and high‐risk sun exposure behaviors were identified. This provides rationale for skin age analysis as a potentially effective intervention in decreasing intentions to tan in this high‐risk young population.

https://ift.tt/2QEtANY

Successful sclerotherapy and psoriasis: A discussion of koebnerization, report of two cases, and review of the literature

https://ift.tt/2PqOFa4

Unripe peach (Prunus persica) extract ameliorates damage from UV irradiation and improved collagen XVIII expression in 3D skin model

Summary

Introduction

Collagen type XVIII regulates cellular activities of adjacent cells at the dermal‐epidermal junction (DEJ). To investigate its possible changes during aging, we compared its mRNA levels and protein localization in skin samples from female participants aged 20‐70 years old. In addition, we evaluated the beneficial effects of unripe peach extracts in a 3D skin model.

Methods

Sun‐exposed or sun‐protected female skin samples were compared by DNA array or by immunohistochemistry for basement membrane components. To evaluate protective effects of fresh unripe peach extract, UV‐B irradiated human 3D skin models were incubated in the presence or absence of the extract, followed by measurements of mRNA levels by real‐time PCR, or by immunohistochemistry.

Results

In aged skin samples, COL18A1 mRNA levels were lower and the protein localization exhibited less intensive signal by anti‐collagen type XVIII immunostaining. As observed in the skin tissues, collagen type XVIII exists at the DEJ in the 3D skin model. Fresh unripe peach extract significantly improved mRNA levels and partially localizations of collagen type XVIII, suggesting that fresh unripe peach extract ameliorates DEJ damages caused by UV‐B irradiation.

Conclusion

Collagen type XVIII and fresh unripe peach extract can be promising protective cosmetic strategies against skin aging.

https://ift.tt/2zLZYoc

Unripe peach (Prunus persica) extract ameliorates damage from UV irradiation and improved collagen XVIII expression in 3D skin model

Summary

Introduction

Methods

Results

Conclusion

Collagen type XVIII and fresh unripe peach extract can be promising protective cosmetic strategies against skin aging.

https://ift.tt/2zLZYoc

Successful sclerotherapy and psoriasis: A discussion of koebnerization, report of two cases, and review of the literature

https://ift.tt/2PqOFa4

Ghrelin's effects on food motivation in rats are not limited to palatable foods

Abstract

The "hunger" hormone, ghrelin, is powerfully orexigenic. Even in the absence of hunger, ghrelin delivery to rats increases consumption of chow as well as palatable foods and increases motivated behaviour for palatable food rewards. Inspired by the finding that ghrelin increases the selection of chow in rats offered a choice diet (lard, sucrose or chow) and even in rats bingeing on a high fat diet, we sought to explore whether ghrelin's effects on motivation extend to regular chow. Rats were conditioned to lever press for either chow or sucrose pellets in a progressive ratio (PR) operant conditioning task. The effect of acute intracerebroventricular delivery of ghrelin on both chow and sucrose self‐administration was determined and compared to overnight fasting (when endogenous ghrelin levels are elevated). We found that ghrelin similarly increased motivated behaviour for chow and sucrose pellets. The effect of fasting on motivated behaviour for both food pellets was comparable in magnitude to that induced by ghrelin, albeit with an earlier ceiling effect during the PR session. Devaluation experiments (in which rats are offered either food reinforcer in excess prior to PR testing) did not support the hypothesis that sucrose pellets would be more difficult to devalue (due to their higher incentive value) than chow pellets. When exchanging the rats' respective pellets during a PR session, chow‐conditioned rats were more motivated for sucrose pellets than for chow pellets; however, sucrose‐conditioned rats were similarly motivated for chow pellets as for sucrose pellets. Thus, using sucrose as a reward may increase the motivation even for less palatable foods. We conclude that the impact of ghrelin on food motivated behaviour in fed rats is not limited to palatable foods but extends to regular chow and also that the magnitude of the effect is considerable when compared to that of an overnight fast.

https://ift.tt/2rr5I20

Cervical Stabilization in Patients with Instability Resulting from Osteoradionecrosis with Subsequent Spondylodiscitis After Radiotherapeutic Treatment for Head- and Neck Carcinoma

Abstract

High dose of radiation to bone may cause necrosis. Osteoradionecrosis of the cervical vertebrae is a rare adverse event of radiotherapy in patients treated for head and neck cancer. The risk on osteoradionecrosis will increase with doses exceeding 60 Gy. Minimal trauma of the overlying mucosa of the heavily irradiated cervical spine causes subsequent infections or instability may cause neck pain and severe neurological disability. In four patients the cervical spine received up to 100 Gy due to reirradiation. Clinically the patients presented with neck pain. All patients had defects in the pharyngeal posterior wall and cervical instability due to osteoradionecrosis of several cervical vertebrae. Despite optimal conservative treatment the patients developed sensory and motor function loss of the upper extremities. Laminectomies were performed and the cervical spine was stabilized. The pharyngeal posterior wall defects could not be reconstructed. All patients received lifelong antibiotic treatment. Pain and neurological deficits declined after surgery and initiating antibiotics. Eventually all patients could take up their daily activities. Three patients died between 6 months and 2 years after surgery. The cause of death was not related to the osteoradionecrosis. In case of cervical osteoradionecrosis, with secondary infections, stability of the spine should be restored even when the integrity of the pharyngeal posterior wall cannot be restored. Our cases demonstrate that even when an anterior approach is impossible, due to irradiation changed tissue structures of the pharyngeal posterior wall, a combination of lifelong antibiotic treatment and posterior stabilization is a good alternative. The vertebrae affected by osteoradionecrosis and secondary infection can be left in situ. This intervention leads to improvement in quality of life.

https://ift.tt/2SGyyHx

Cervical Stabilization in Patients with Instability Resulting from Osteoradionecrosis with Subsequent Spondylodiscitis After Radiotherapeutic Treatment for Head- and Neck Carcinoma

Abstract

https://ift.tt/2SGyyHx

Composts as alternative to inorganic fertilization for cereal crops

Abstract

The use of treated organic products as fertilizers and soil amendments not only results in economic benefits for the small-scale farmer, but it also reduces pollution due to reduced nutrient run-off and N leaching. In this work, the feasibility of using composts as fertilizers and soil improvers has been evaluated at the field level, in barley and soft wheat crops (two successive cultivations of each crop). The applied treatments consisted of two commercial composts (compost manure and sewage sludge compost) added to the soil either alone (T1 and T3) or in combination with inorganic fertilizers (T2 and T4) and a conventional mineral fertilization (T5). Physical, physical-chemical, chemical, microbiological, and biochemical parameters were determined in the soil after each harvest. In both barley and wheat crops, soils treated with composts showed higher organic C, humic substances, and humic acid contents than the inorganically fertilized soil, as well as higher contents of water-soluble P, K, Ca, Mg, and S. In both successive crops, all treatments led to similar yields of total barley and wheat vegetal material (straw + ears) and grain, differences between treatments being not statistically significant (p ≤ 0.05). Organically treated soils showed higher microbial size and activity than inorganically treated soils as well as higher water-holding capacity. It can be concluded that quality organic composts can be used, at suitable rates, alone or in combination with inorganic fertilizers, as a good alternative to inorganic fertilization for cereal cultivation, improving soil characteristics while giving similar yield and crop quality than conventional inorganic fertilization.

https://ift.tt/2EhFabW

Contrastive removal of oxytetracycline and chlortetracycline from aqueous solution on Al-MOF/GO granules

Abstract

The presence of tetracycline antibiotics (TCS) in the water and wastewater has raised growing concern due to its potential environmental impacts; thus, their removal is of high importance. In this study, a novel aluminum-based MOF/graphite oxide (Al-MOF/GO) granule was prepared as an adsorbent for the removal of TCS including oxytetracycline (OTC) and chlortetracycline (CTC). The adsorbent was characterized via XRD, FTIR, BET, SEM, and XPS methods. The granules exhibited similar crystal structure and some new mesopores appearing compared to the parent Al-MOF/GO powder. In addition, the adsorption behavior of OTC and CTC on samples was explored as a function of initial concentration, contact time, pH, and ionic strength by means of batch experiments. The adsorption capacity reached to 224.60 and 240.13 mg·L⁻¹ for OTC and CTC, at C₀ = 60 mg·L⁻¹ as well as ambient temperature respectively. Moreover, the adsorption process of OTC and CTC on Al-MOF/GO samples can be better delineated by pseudo-second-order kinetics and Freundlich isotherm models. Besides, the adsorption mechanism over Al-MOF/GO granules was proposed, which could be ascribed to π-π interaction, cation-π bonding, and hydrogen bond. Finally, the great water stability, separation performance, and regeneration efficiency of these novel granules indicated their potential application in the OTC and CTC removals from aqueous solution.

https://ift.tt/2E5WQ9L

Distribution and potential ecological risk assessment of trace elements in the stream water and sediments from Lanmuchang area, southwest Guizhou, China

Abstract

Trace elements contamination in sediment is regarded as the global crisis with a large share in developing countries like China. Water and sediment samples were collected during (2016) from Qingshui Stream and analyzed for major physicochemical properties and trace elements by using ICP-MS. Our result of sediments showed that studied trace elements (except Pb, Cd, Co) had a concentration higher than Chinese sediment guideline as well as stream water data for studied trace elements (except Cr, Pb, Cd, Cu, and Zn) had a higher concentration than the maximum permissible safe limit of WHO. Contamination factor (CF) confirmed a moderate to high contamination in the sediment samples due to As and Tl, respectively. The values of pollution load index (PLI) were found above one (> 1), describing the progressive sediment quality decline. Pearson correlation showed that there was a significant positive association between Tl and As (r = 0.725, p < 0.05) in sediment samples. Results revealed that water-rock interaction, weathering of Tl sulfide mineralization, and hydrogeological conditions were major sources of stream water and sediments contamination in the study area. This experimental study contributes to a better understanding of the geochemistry and prevention of trace element contamination in sediments from Lanmuchang area.

https://ift.tt/2QnFvAv

Mitral valve myxoma presenting with transient ischemic attack: a case report and review of the literature

Myxomas account for approximately half of all primary cardiac neoplasms. Most occur in the left atrium and only rarely are attached to the mitral valve, with just over 30 such cases reported in the literature....

https://ift.tt/2BXZL2T

Pharmacogenetics of angiotensin converting enzyme inhibitor ‐ induced angioedema

Abstract

Angioedema is a rare adverse effect of the commonly used angiotensin converting enzyme inhibitors (ACEi) and is reported to occur with a prevalence of 0.1 – 0.7%. Although most ACEi‐induced angioedema (ACEi‐A) cases are mild, severe cases requiring intensive care and even resulting in death have been reported in the literature. The mechanisms underlying ACEi–A are not yet fully understood, but bradykinin and/or substance P accumulation resulting from inhibition of ACE, is believed to play a crucial role. ACEi‐A occurs at variable frequencies across different racial groups, suggesting a genetic association to the development of ACEi‐A. To date, one genome wide association study and several candidate gene studies have been published on the association of genetic variation with ACEi‐A. Genetic associations reported have been attributed to several distinct mechanisms: (1) genes coding for alternative enzymes responsible for the degradation of bradykinin and/or substance P in the diminution of ACE activity (2) ACE gene function, (3) bradykinin receptor genes, (4) genes implicated in immune and inflammation regulation, and (5) genes in the fibrinolytic and coagulation pathway. Despite several plausible genetic associations, there are currently no genetic variants with sufficient effect to be clinically useful. The low incidence of ACEi‐A suggests that a combination of genomic approaches with the capability to detect potentially important variants might be required to shed light on the mechanism of this adverse reaction. Additionally, many non‐genetic risk factors associated with ACEi‐A suggest the potential contribution of epigenetic dysregulation.

https://ift.tt/2EchZii

Adrenal myelolipoma in association with congenital adrenal hyperplasia

https://ift.tt/2L4fS1v

The MAGI2 gene polymorphism rs2160322 is associated with Graves’ disease but not with Hashimoto’s thyroiditis

Abstract

Purpose

Autoimmune thyroid diseases (AITDs) are chronic organ-specific autoimmune disorders, predominantly including Graves' disease (GD), and Hashimoto's thyroiditis (HT). This study aimed to investigate whether single-nucleotide polymorphisms (SNPs) in MAGI2 and MAGI3 gene contributed to the etiology of AITDs.

Methods

We conducted a case–control study including 1001 patients with AITDs (625 GD, 376 HT) and 846 healthy controls. Subgroup analyses in GD and HT were also performed.

Results

The genotypes of rs2160322 in MAGI2 showed a borderline association with AITDs (P = 0.048), and they had a strong correlation with GD (P = 0.012). The frequency of the minor allele G of rs2160322 was significantly higher in the GD patients than in the controls (P = 0.027; OR 1.91; 95% CI 1.020–1.391), especially for GD females (P = 0.008; OR 1.304; 95% CI 1.072–1.587), and those who had positive family history (P = 0.011; OR 1.412; 95% CI 1.083–1.843). For genetic model analysis, the recessive model and homozygous model of rs2160322 showed significant associations with AITDs (P = 0.009; P = 0.019) and GD (P = 0.004; P = 0.005). Nevertheless, our study could not identify any relationship between these SNPs and HT. Due to the low mutation rate of rs1343126 in MAGI3, we were unable to obtain a credible conclusion on its association with AITDs.

Conclusions

Our study identified that MAGI2 rs2160322 was strongly associated with GD susceptibility. The potential dysfunction of tight junction proteins and aberrant epithelial barrier caused by abnormal MAGI2 expression may be a novel mechanism of GD.

https://ift.tt/2AYt6bA

Adrenal myelolipoma in association with congenital adrenal hyperplasia

https://ift.tt/2L4fS1v

Added value of multimodal mri to the clinical diagnosis of primary progressive aphasia variants

Publication date: Available online 8 December 2018

Source: Cortex

Author(s): Elisa Canu, Federica Agosta, Francesca Imperiale, Andrea Fontana, Francesca Caso, Edoardo Gioele Spinelli, Giuseppe Magnani, Andrea Falini, Giancarlo Comi, Massimo Filippi

Abstract

Objective

To determine the added value of multimodal structural magnetic resonance imaging (MRI) to language assessment in the differential diagnosis of primary progressive aphasia (PPA) variants.

Methods

59 PPA patients (29 nonfluent [nfvPPA], 15 semantic [svPPA], 15 logopenic [lvPPA]) and 38 healthy controls underwent 3D T1-weighted and diffusion tensor (DT) MRI. PPA patients also performed a comprehensive language assessment. Cortical thickness measures and DT MRI indices of white matter tract integrity were obtained. A random forest analysis identified MRI features associated with each clinical variant. Using ROC curves, the discriminatory power of the language features alone ("language model") and the added contribution of multimodal MRI variables were assessed ("language+MRI model").

Results

The 'language model' alone was able to differentiate svPPA from both nfvPPA and lvPPA patients with high accuracy (area under the curve [AUC]= 0.95 and 0.99, respectively). When left inferior parietal cortical thickness and DT MRI metrics of the genu of the corpus callosum and left frontal aslant tract were added to the "language model", the ability to discriminate between nfvPPA and lvPPA cases increased from AUC 0.82 ("language model" only) to 0.94 ("language+MRI model").

Conclusions

Language measures alone are able to distinguish svPPA from the other two PPA variants with the highest accuracy. Multimodal structural MRI improves the distinction of nfvPPA and lvPPA, which is challenging in the clinical practice.

https://ift.tt/2E9z4tl

Numerical order and the intraparietal sulcus: Developmental specialization of the left intraparietal sulcus for symbolic ordinal processing

Publication date: Available online 8 December 2018

Source: Cortex

Author(s): Anna A. Matejko, Jane Hutchison, Daniel Ansari

Abstract

Symbolic numbers have both cardinal (symbol-quantity) and ordinal (symbol-symbol) properties. Despite behavioural evidence suggesting distinct processing of cardinal and ordinal properties, little consensus has emerged from the neuroimaging literature on whether these processes have shared or distinct neural underpinnings. Moreover, it remains unclear how the neural correlates of cardinal and ordinal processing change with age. To address these unresolved questions, we investigated the neural correlates of cardinal (neural distance effect) and ordinal processing (neural reverse distance effect) in 50 children (ages 7-10) and 26 adults (ages 19-26). We found that adults recruited a largely left lateralized set of fronto-parietal regions for ordinal processing, whereas children showed activation in the right lateral orbital and inferior frontal gyri for both ordinal and cardinal processing. Additional analyses suggested that adults recruited the left intraparietal sulcus (IPS) more than children for ordinal processing, suggesting that the IPS may become increasingly tuned to ordinal symbolic properties over development. Together with previous literature documenting the importance of the left IPS for cardinal processing, our results suggest that cardinal and ordinal processing may share neural substrates in the left IPS and that this region may become specialized for both skills over development.

https://ift.tt/2E7FhWI

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Σάββατο 8 Δεκεμβρίου 2018

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