F.J. Ortiz de Frutos
Actas Dermosifiliogr.2018;109:468-9
Full text - PDF
https://ift.tt/2n1uCTW
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τρίτη 31 Ιουλίου 2018
Oral Azithromycin: A Treatment Option for Papulopustular Rosacea
Urban Teledermatology: Concept, Advantages, and Disadvantages
The Value of Adjuvant Radiotherapy in Cutaneous Squamous Cell Carcinoma: A Review
Allergic Contact Dermatitis by Anatomical Regions: Diagnostic Clues
Allergic Contact Dermatitis Caused by Acrylates in Long-Lasting Nail Polish
The Keystone Flap in Dermatology: Clinical Experience with 18 Patients
Photoallergic Contact Dermatitis to Sunscreens Containing Oxybenzone in La Plata, Argentina
Papulopustular Rosacea: Response to Treatment with Oral Azithromycin
Prescribing Habits for Androgenic Alopecia Among Dermatologists in Spain in 2017: A Cross-Sectional Study
Reflectance Confocal Microscopy: A Promising Tool to Identify Malignancy in Melanocytic Lesions Exhibiting a Dermoscopic Island
Juvenile Dermatomyositis: Key Roles of Muscle Magnetic Resonance Imaging and Early Aggressive Treatment
Erythematous Pedunculated Papule on the Knee
Annular and Polycyclic Lesions on the Lower Limbs
Solitary Lesion on the Lateral Aspect of the Index Finger
Doxycycline, a Well-Tolerated, Economic, and Effective Alternative for the First-Line Treatment of Bullous Pemphigoid
Nonvenereal Sclerosing Lymphangitis of the Penis: Importance of the Clinical Diagnosis
Violaceous Papules on an Achromatic Macule
Inguinal Sentinel Lymph Node Biopsy: Surgical Technique
Lessons learned from the study of human inborn errors of innate immunity
Publication date: Available online 1 August 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Giorgia Bucciol, Leen Moens, Barbara Bosch, Xavier Bossuyt, Jean-Laurent Casanova, Anne Puel, Isabelle Meyts
Abstract
Innate immunity contributes to host defense through all cell types and relies on their shared germline genetic background, whereas adaptive immunity operates via only three main cell types, αβ T cells, γδ T cells, and B cells, and relies on their somatic genetic diversification of antigen-specific responses. Human inborn errors of innate immunity often underlie infectious diseases. The range and nature of infections depend on the mutated gene, the deleteriousness of the mutation, and other ill-defined factors. Most known inborn errors of innate immunity to infection disrupt the development or function of leukocytes other than T and B cells, but a growing number of inborn errors affect cells other than circulating and tissue leukocytes. Here, we review inborn errors of innate immunity that have been recently discovered or clarified. We highlight the immunological implications of these errors.
https://ift.tt/2n1KKol
Prevalence of Metabolic Syndrome in Mexico: A Systematic Review and Meta-Analysis
Metabolic Syndrome and Related Disorders, Ahead of Print.
https://ift.tt/2KgHhLF
A recessive mutation in the DSP gene linked to cardiomyopathy, skin fragility and hair defects impairs the binding of desmoplakin to epidermal keratins and the muscle‐specific intermediate filament desmin
British Journal of Dermatology, EarlyView.
https://ift.tt/2mZbOEH
Development of a More Effective Mosquito Trapping Box for Vector Control
Mosquito-borne diseases are a major public health issue in nearly all tropical and subtropical countries, making vector control imperative. The mosquito trapping box is one type of mosquito traps that is popular in some areas because it is affordable, environmentally friendly, and easy to produce. This research investigated whether the effectiveness of the mosquito trapping box could be increased through the addition of various physical factors, including a wooden frame, black cotton cloth, a fan, carbon dioxide (CO2), and heat, by testing a range of box designs in the Samut Songkhram Province, Thailand, between December 2016 and January 2017. We found that trapping boxes constructed with Pinus kesiya wood caught more mosquitoes than those constructed with two other types of wood or aluminum. We also found that mosquito trapping boxes were more effective when more factors were added, although these differences were only significant for black cotton cloth and CO2. These findings will guide the future development of mosquito trapping boxes for effective mosquito control in other areas, helping to reduce the incidence of mosquito-borne diseases.
https://ift.tt/2AtSgln
ACVR1is essential for periodontium development and promotes alveolar bone formation
Publication date: Available online 31 July 2018
Source: Archives of Oral Biology
Author(s): Xue Zhang, Qilin Liu, Huan Zhao, Yue Hu, Cangwei Liu, Guangxing Yan, Daowei Li, Yuji Mishina, Ce Shi, Hongchen Sun
Abstract
Objective
To explore the role of a BMP type I receptor (ACVR1) in regulating periodontium development, Acvr1 was conditionally disrupted in Osterix-expressing cells.
Methods
Mandibles from both control (Acvr1 fx/+; Osterix-Cre (+)/(-)) and cKO (Acvr1 fx/-; Osterix-Cre (+)/(-)) mice at postnatal day 21 (PN21) were scanned by micro-CT, followed by decalcification and histological observations. Distribution and levels of differentiation markers of fibroblasts, osteoblasts and cementocytes in the periodontium were detected by immunohistochemical (IHC) staining.
Results
Micro-CT results showed that bone mass and mineral density of the alveolar bones in the cKO mice were lower than those in the controls. Histomorphometry within the alveolar bones revealed that the lower bone mass observed in the cKO mice was caused by increased numbers and resorption activities of osteoclasts. The markers for osteoblast differentiation, Col I and DMP1, were reduced and the signals of the RANKL/OPG ratio were increased in the alveolar bones of the cKO mice compared to those of the control mice. The periodontal ligament in the cKO mice exhibited disorganized collagen fibers with weaker signals of Col I and periostin. However, there was no difference in terms of the cellular cementum between the two groups.
Conclusion
ACVR1 is essential for normal periodontium development. Osteoblast ACVR1 negatively regulates osteoclast differentiation in association with the RANKL/OPG axis and thus promotes alveolar bone formation.
https://ift.tt/2vkgnwU
Prevalence and antifungal susceptibility profiles of Candida glabrata, Candida parapsilosis and their close-related species in oral candidiasis
Publication date: Available online 31 July 2018
Source: Archives of Oral Biology
Author(s): Katherine Miranda-Cadena, Cristina Marcos-Arias, Estibaliz Mateo, José Manuel Aguirre, Guillermo Quindós, Elena Eraso
Abstract
Objective
To evaluate the importance of Candida glabrata, Candida parapsilosis and their close-related species, Candida bracarensis, Candida nivariensis, Candida metapsilosis and Candida orthopsilosis in patients with oral candidiasis and, to determine the in vitro activities of antifungal drugs currently used for the treatment.
Methods
One hundred fourteen isolates of C. glabrata and 97 of C. parapsilosis, previously identified by conventional mycological methods, were analysed by molecular techniques. In vitro antifungal susceptibility to fluconazole, itraconazole, miconazole, and nystatin was evaluated by CLSI M44-A2 disk diffusion test, and by CLSI M27-A3 microdilution for fluconazole.
Results
All C. glabrata isolates were identified as C. glabrata sensu stricto, 93 out of 97 C. parapsilosis isolates as C. parapsilosis sensu stricto, three as C. orthopsilosis and one as C. metapsilosis. Candida glabrata was mainly isolated in mixed cultures but C. parapsilosis complex was more frequent in pure culture. Candida metapsilosis and C. orthopsilosis were isolated as pure culture and both species were susceptible to all antifungal agents tested. Most C. glabrata isolates were susceptible to miconazole and nystatin, but resistant to fluconazole and itraconazole. Azole cross resistance was also observed. Candida parapsilosis isolates were susceptible to fluconazole although azole cross resistance to miconazole and itraconazole was observed.
Conclusion
This study highlights the importance of accurate identification and antifungal susceptibility testing of oral Candida isolates in order to have an in-depth understanding of the role of C. glabrata and C. parapsilosis in oral candidiasis.
https://ift.tt/2LT0yYk
Social gradients in oral health status in Korea population
Publication date: Available online 31 July 2018
Source: Archives of Oral Biology
Author(s): Hye-Sun Shin
Abstract
Objectives
The aim of the present study was to investigate whether clinical (severe tooth loss) and subjective (chewing difficulties) indicators of oral health outcomes are associated with socioeconomic position and to explore the age-sex differences in the magnitude of the social gradient in Korea using data from the representative national data.
Methods
Data were acquired from 10,939 men and women, ≥30 years of age who participated in the Korea National Health and Nutrition Examination Surveys conducted from 2012 to 2014. Education and income were used as socioeconomic position. Self-rated chewing difficulties and severe tooth loss were assessed by dentists and trained interviewers. Confounding variables were demographic factors, general health behaviors, and systemic health status.
Results
Significant differences in oral health outcomes were observed according to the quartiles of income and education. In particular, the quartiles of education were significantly associated with oral health outcomes in the fully adjusted model with a dose-response trend. In participants aged 40–49 (OR = 2.30, 95% CI = 1.37-3.88) and 50–59 years (OR = 2.16, 95% CI = 1.49-3.14), the associations between the lowest quartiles of income and chewing difficulties were stronger than in the total population.
Conclusions
Our findings demonstrate a clear and distinct social gradient in clinical and subjective oral health indicators based on socioeconomic position.
https://ift.tt/2vmQmNx
Deficiencies in the CD19 complex
Publication date: Available online 31 July 2018
Source: Clinical Immunology
Author(s): Marjolein W.J. Wentink, Menno van Zelm, Jacques J.M. van Dongen, Klaus Warnatz, Mirjam van der Burg
Abstract
Signaling via the CD19-complex, consisting of CD19, CD81, CD21 and CD225, is critically important for B-cell development, differentiation and maturation. In this complex, each protein has its own distinct function. Over the past decade, 15 patients with antibody deficiency due to deficiencies in the CD19-complex have been described. These patients have deficiencies in different complex-members, all caused by either homozygous or compound heterozygous mutations. Although all patients had antibody deficiencies, the clinical phenotype was different per deficient protein. We aimed to provide an overview of what is known about the function of the different complex-members, knowledge from mouse-studies and to summarize the clinical phenotypes of the patients. Combining this knowledge together can explain why deficiencies in different members of the same complex, result in disease phenotypes that are alike, but not the same.
https://ift.tt/2LEMLpc
Descent of the human larynx: an unrecognized factor in airway distress in babies with cleft palate?
Publication date: Available online 31 July 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Catherine de Blacam, Laura Duggan, David Rea, Peter Beddy, David J.A. Orr
Abstract
The intranarial epiglottis, a feature of all newborn mammals, allows suckling and breathing to continue almost simultaneously by separating an oral food stream from a nasal airstream. In contrast to other mammals, the human larynx descends in the neck between birth and six months, extending the distance between the caudal aspect of the soft palate and the cephalic tip of the epiglottis. The mechanism of airway protection changes from a pattern in which an upright epiglottis is grasped by an intact palatopharyngeal sphincter to one in which the epiglottis folds down over the laryngeal aditus and the adducted vocal folds.
The comparative anatomy and anthropological literature describing laryngeal descent was reviewed. A series of MRI images were used to illustrate the normal descent of the human larynx, which take place in infants in the first six months of life. Based on this information, we hypothesize that a cleft palate, by interrupting the sphincter function of palatopharyngeus on a high neonatal epiglottis, precipitates a need for premature and rapid maturation of the neonate's airway protection pattern, particularly during feeding. This may explain why, even in the absence of Robin sequence, some babies with cleft palates suffer respiratory distress during feeding.
https://ift.tt/2NZ0JyU
Auditory processing and neuropsychological profiles of children with functional hearing loss
Publication date: Available online 31 July 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): SK Mamun Ur Rashid, Dipankar Mukherjee, Ansar Uddin Ahmmed
https://ift.tt/2LErqMs
Is the occurrence of pediatric epistaxis related to climatic variables?
Publication date: Available online 31 July 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Gang Yu, Yong Fu, Cong Dong, Huilong Duan, Haomin Li
Abstract
Objective
To investigate the correlations between multiple meteorological variables and the frequency of epistaxis in the pediatric population.
Methods
Children diagnosed with epistaxis in 2016 and 2017 were selected from the Outpatient Department of the Children's Hospital of Zhejiang University School of Medicine. The correlations between multiple meteorological factors and the incidence of pediatric epistaxis each month, were analyzed. A Poisson regression model was generated to predict the cases of pediatric epistaxis using both the 2-year study data and the 4-month new data.
Results
There were 6805 cases of pediatric epistaxis (mean age 4.99 years). Contrary to previously reported inverse associations between ambient temperature and presentation rates for patients with epistaxis, a significant strong positive correlation was found between temperature and pediatric epistaxis rates (Pearson's r=0.801 p<0.001). A weak negative correlation between humidity and pediatric epistaxis was found, but it was not significant (Pearson's r=-0.225 p=0.29). A very strong positive correlation between high air visibility and pediatric epistaxis was identified (Pearson's r=0.909 p<0.001). The predictions from the Poisson regression model have a mean error rate of 5.70%±22.71%.
Conclusion
A positive correlation between the frequency of pediatric epistaxis existed for both temperature and air visibility. No significant correlation was found for humidity.
https://ift.tt/2vnZAJE
Ear Piercings for Babies | A Cultural Controversy
Recently a celebrity posted a picture of her baby with pierced earlobes, eliciting an online controversy. My mind went back to a time almost 10 years ago when I welcomed my firstborn daughter into the world. In Latin cultures, infant female ear piercing is routine. Some Latin countries even perform piercings in the hospital before discharge. Shortly after her birth, my daughter already had a collection of gold earrings gifted to her by family. I could not wait to get it done.
We had difficulty finding a place in our area that would do it but finally did. While I waited, I received a few judgmental looks and comments that challenged our decision. We went through with the piercing and she barely cried. I think she cried more during her vaccines. I was so happy and proud that I took tons of pictures and sent them to all my family and close friends. We were all celebrating! What I did not expect was the backlash I received multiple times from random non-Latin people questioning or criticizing my decision.
When and Why Do We Pierce Our Children's Ears?
Eventually, I made peace with it and moved on, but I wanted to understand where the negative thoughts regarding ear piercing stemmed from. I asked friends and random people from different cultural backgrounds and ethnicities: when and why did you pierce your daughter's ears? Answers on when to pierce ears were varied and essentially boiled down to familiar and/or cultural traditions. Some examples of the answers on the question of timing: "at birth," "shortly after birth," "after her vaccines," "when she asked for it," "when she reached a certain age/school grade/maturity."
When I asked "why did you pierce your daughter's ears?" the most common answers included: "it's what my family does," "it's my culture," "it's sort of a rite of passage," "I feel she should want it," "I feel she should be ready for it," and "I felt she was responsible enough to take care of it." The conversations opened my eyes to different beliefs systems I had never thought of before. I felt all the arguments were valid, reasonable and came from a good place in their heart.
Are Ear Piercings Harmful for Babies?
I then reviewed the scientific evidence around earlobe piercing. There is no evidence to support one argument versus the other. Complications of earlobe piercing include bleeding, contact allergies, post-traumatic tearing, imbedded backings and infection. These can occur at any age. Aside from tetanus, vaccines don't cover the most common organisms associated with earlobe piercing related infections, and tetanus infections are not very common. With good local care of the pierced earlobe site, complications can be avoided. I was very diligent in taking care of both my daughters' piercings and they had no complications.
What's the Right Decision for My Family?
So, where does that leave us? For me, I am happy with my choice. My daughters love their earrings and love to change them to match their outfits. I've asked them if they would have liked to have waited until they were older or if they are mad I took the choice away from them. They both look at me like I am crazy and say no. So, that's good enough for me. Is it the right way? It's what was right for me and my cultural beliefs. Therefore, my advice is to do what feels right for you. There is no data to support one particular practice. Talk to your pediatrician about your concerns and make informed decisions. Most importantly, this exercise taught me to listen to other parents and respect their choices, whether they agree with mine or not.
The post Ear Piercings for Babies | A Cultural Controversy appeared first on ChildrensMD.
https://ift.tt/2n0atxv
Omalizumab for the treatment of chronic spontaneous urticaria in daily clinical practice in South Spain
Dermatologic Therapy, EarlyView.
https://ift.tt/2O0riUs
Is there a place for FDG-PET-CT in early oral cancer patients?
Publication date: Available online 31 July 2018
Source: Oral Oncology
Author(s): Remco de Bree, Bart de Keizer
https://ift.tt/2OyP4YT
Letter to the Editor in response to the article, “The epidemiology of oral human papillomavirus infection in healthy populations: A systematic review and meta-analysis”
Publication date: Available online 31 July 2018
Source: Oral Oncology
Author(s): Rama Jayaraj, Chellan Kumarasamy, Shanthi Sabarimurugan, Siddhartha Baxi
https://ift.tt/2vvfTED
Sweat allergy
Publication date: Available online 31 July 2018
Source: Allergology International
Author(s): Shunsuke Takahagi, Akio Tanaka, Michihiro Hide
Abstract
Sweat allergy is defined as a type I hypersensitivity against the contents of sweat, and is specifically observed in patients with atopic dermatitis (AD) and cholinergic urticaria (CholU). The allergic reaction is clinically revealed by positive reactions in the intradermal skin test and the basophil histamine release assay by sweat. A major histamine-releasing antigen in sweat, MGL_1304, has been identified. MGL_1304 is produced at a size of 29 kDa by Malassezia (M.) globosa and secreted into sweat after being processed and converted into the mature form of 17 kDa. It induces significant histamine release from basophils of patients with AD and/or CholU with MGL_1304-specific IgE, which is detected in their sera. Patients with AD also show cross-reactivity to MGL_1304-homologs in Malassezia restricta and Malassezia sympodialis, but MGL_1304 does not share cross antigenicity with human intrinsic proteins. Malassezia or its components may penetrate the damaged epidermis of AD lesions and interact with the skin immune system, resulting in the sensitization and reaction to the fungal antigen. As well as the improvement of impaired barrier functions by topical interventions, approaches such as anti-microbial treatment, the induction of tolerance and antibody/substance neutralizing the sweat antigen may be beneficial for the patients with intractable AD or CholU due to sweat allergy. The identification of antigens other than MGL_1304 in sweat should be the scope for future studies, which may lead to better understanding of sweat allergy and therapeutic innovations.
https://ift.tt/2O01veX
Observing carbon cycle-climate feedbacks from space [Earth, Atmospheric, and Planetary Sciences]
The impact of human emissions of carbon dioxide and methane on climate is an accepted central concern for current society. It is increasingly evident that atmospheric concentrations of carbon dioxide and methane are not simply a function of emissions but that there are myriad feedbacks forced by changes in climate...
https://ift.tt/2OALVaW
Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing [Medical Sciences]
The precise correction of genetic mutations at the nucleotide level is an attractive permanent therapeutic strategy for human disease. However, despite significant progress, challenges to efficient and accurate genome editing persist. Here, we report a genome editing platform based upon a class of hematopoietic stem cell (HSC)-derived clade F adeno-associated...
https://ift.tt/2Oyuxnh
Soft wetting: Models based on energy dissipation or on force balance are equivalent [Physical Sciences]
In Newtonian mechanics, an overdamped system at steady state is governed by a local balance of mechanical stress but also obeys a global balance between injected and dissipated energy. In the classical literature of purely viscous drop spreading, apparent differences in "dissipation" and "force" approaches have led to unnecessary debates,...
https://ift.tt/2OxGtFv
Direction of flagellum beat propagation is controlled by proximal/distal outer dynein arm asymmetry [Cell Biology]
The 9 + 2 axoneme structure of the motile flagellum/cilium is an iconic, apparently symmetrical cellular structure. Recently, asymmetries along the length of motile flagella have been identified in a number of organisms, typically in the inner and outer dynein arms. Flagellum-beat waveforms are adapted for different functions. They may...
https://ift.tt/2OyuCHB
Reply to Karpitschka et al.: The Neumann force balance does not hold in dynamical elastowetting [Physical Sciences]
In their letter, Karpitschka et al. (1) discuss our claim that the predictions of our theoretical description for the spreading of a droplet on a soft solid layer based on a global-dissipation approach (2) differ from the outcomes of Karpitschka et al.'s model based on a local-force-balance analysis (3). In...
https://ift.tt/2AvqDII
Time-resolved neural reinstatement and pattern separation during memory decisions in human hippocampus [Neuroscience]
Mnemonic decision-making has long been hypothesized to rely on hippocampal dynamics that bias memory processing toward the formation of new memories or the retrieval of old ones. Successful memory encoding may be best optimized by pattern separation, whereby two highly similar experiences can be represented by underlying neural populations in...
https://ift.tt/2mYuPac
Robert W. Kates (1929-2018): Grappled with problems of the human environment [Retrospectives]
Robert W. Kates died April 21, 2018, at age 89, a geographer who studied the relationship between society and environment and whose commitment to collaborative science kept his colleagues busy with big questions, big projects, and the challenge of fixing problems imbricated in the human use and transformation of the...
https://ift.tt/2Oys7oG
Cholesterol promotes Cytolysin A activity by stabilizing the intermediates during pore formation [Biophysics and Computational Biology]
Pore-forming toxins (PFTs) form nanoscale pores across target membranes causing cell death. Cytolysin A (ClyA) from Escherichia coli is a prototypical α-helical toxin that contributes to cytolytic phenotype of several pathogenic strains. It is produced as a monomer and, upon membrane exposure, undergoes conformational changes and finally oligomerizes to form...
https://ift.tt/2Oxubxa
Information utility in the human brain [Psychological and Cognitive Sciences]
A funding agency just made a decision about your grant application. The official letter should arrive tomorrow, announcing the outcome, but you can log in to the agency's website and find out today. Would you? Humans and other animals are intrinsically motivated to acquire information, even when this information is...
https://ift.tt/2n0VQtO
Role of carbon allocation efficiency in the temperature dependence of autotroph growth rates [Ecology]
Relating the temperature dependence of photosynthetic biomass production to underlying metabolic rates in autotrophs is crucial for predicting the effects of climatic temperature fluctuations on the carbon balance of ecosystems. We present a mathematical model that links thermal performance curves (TPCs) of photosynthesis, respiration, and carbon allocation efficiency to the...
https://ift.tt/2mYuWTa
Kv2 potassium channels meet VAP [Cell Biology]
A defining characteristic of eukaryotic cells is the presence of distinct intracellular membrane-bound compartments. Much research has focused on the functional interconnection of these organelles via membrane traffic. A flurry of recent studies, however, has brought to center stage the important role of interorganelle communication independent of vesicular transport and...
https://ift.tt/2AoTnD2
Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory [Neuroscience]
Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal...
https://ift.tt/2mVGOFE
When maternal periconceptional diet affects neurological development, it’s time to think [Neuroscience]
There is increasing awareness that the nutritional status of women at the onset of pregnancy can have a profound effect on the general health and well-being of children. However, recent analyses indicate that the majority of women from different socioeconomic backgrounds are ill prepared for the nutritional rigors of pregnancy,...
https://ift.tt/2mZqT98
Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome [Pharmacology]
Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contribute to human disease is unknown. We evaluated endosomal signaling of protease-activated receptor-2 (PAR2), which has been proposed to mediate pain in patients...
https://ift.tt/2OALZYe
Wafer-recyclable, environment-friendly transfer printing for large-scale thin-film nanoelectronics [Engineering]
Transfer printing of thin-film nanoelectronics from their fabrication wafer commonly requires chemical etching on the sacrifice of wafer but is also limited by defects with a low yield. Here, we introduce a wafer-recyclable, environment-friendly transfer printing process that enables the wafer-scale separation of high-performance thin-film nanoelectronics from their fabrication wafer...
https://ift.tt/2AoTmyY
Monovalent ions modulate the flux through multiple folding pathways of an RNA pseudoknot [Biophysics and Computational Biology]
The functions of RNA pseudoknots (PKs), which are minimal tertiary structural motifs and an integral part of several ribozymes and ribonucleoprotein complexes, are determined by their structure, stability, and dynamics. Therefore, it is important to elucidate the general principles governing their thermodynamics/folding mechanisms. Here, we combine laser temperature-jump experiments and...
https://ift.tt/2AtNJzi
Theoretical search for heterogeneously architected 2D structures [Engineering]
Architected 2D structures are of growing interest due to their unique mechanical and physical properties for applications in stretchable electronics, controllable phononic/photonic modulators, and switchable optical/electrical devices; however, the underpinning theory of understanding their elastic properties and enabling principles in search of emerging structures with well-defined arrangements and/or bonding connections...
https://ift.tt/2mZqPpU
Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB [Cell Biology]
Kv2.1 exhibits two distinct forms of localization patterns on the neuronal plasma membrane: One population is freely diffusive and regulates electrical activity via voltage-dependent K+ conductance while a second one localizes to micrometer-sized clusters that contain densely packed, but nonconducting, channels. We have previously established that these clusters represent endoplasmic...
https://ift.tt/2AqgFYW
Valuation of knowledge and ignorance in mesolimbic reward circuitry [Psychological and Cognitive Sciences]
The pursuit of knowledge is a basic feature of human nature. However, in domains ranging from health to finance people sometimes choose to remain ignorant. Here, we show that valence is central to the process by which the human brain evaluates the opportunity to gain information, explaining why knowledge may...
https://ift.tt/2AzfF58
Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma [Developmental Biology]
Neuroblastoma is a neural crest-derived childhood tumor of the peripheral nervous system in which MycN amplification is a hallmark of poor prognosis. Here we show that MycN is expressed together with phosphorylation-stabilizing factor CIP2A in regions of the neural plate destined to form the CNS, but MycN is excluded from...
https://ift.tt/2AtNgNy
Adenocarcinoma papilar de nasofaringe de bajo grado «thyroid-like». Caso clínico y revisión de la literatura
Publication date: Available online 31 July 2018
Source: Acta Otorrinolaringológica Española
Author(s): J. García-Gómez, F. Sánchez-González, V. Pérez-Holgado, I. Anguita-Sánchez, G. Fernández-Rodríguez
https://ift.tt/2AsClDJ
Kava to Reduce Tobacco Use in Head & Neck Cancer Survivors
Condition: Tobacco Use Cessation
Interventions: Drug: Kava; Other: Placebo
Sponsor: University of Florida
Not yet recruiting
https://ift.tt/2KiUovQ
Interventions: Drug: Kava; Other: Placebo
Sponsor: University of Florida
Not yet recruiting
https://ift.tt/2KiUovQ
Efficacy of Fluoroscopic Guided Atlantoaxial Joint Injection on Head and Neck Pain and Sleep Quality in RA Patients
Conditions: Pain, Head; Sleep Disturbance
Intervention: Drug: Steroids
Sponsor: Assiut University
Recruiting
https://ift.tt/2LPaUsy
Intervention: Drug: Steroids
Sponsor: Assiut University
Recruiting
https://ift.tt/2LPaUsy
Continous Popliteal Block for Microvascular Free Flap Reconstruction in Ear, Nose and Throat Surgery
Conditions: Head and Neck Cancer; Pain, Musculoskeletal
Interventions: Drug: Levobupivacaine; Drug: Saline Solution
Sponsor: Region Skane
Not yet recruiting
https://ift.tt/2KexLJf
Interventions: Drug: Levobupivacaine; Drug: Saline Solution
Sponsor: Region Skane
Not yet recruiting
https://ift.tt/2KexLJf
Oropharyngeal CSF Leak Secondary to Anterior Cervical Discectomy and Fusion
We present a case of an oropharyngeal cerebrospinal fluid (CSF) fistula in a patient that presented with headache, rhinorrhea, and pneumocephalus years after an anterior cervical discectomy and fusion. Imaging suggested a defect in the fovea ethmoidalis, but endoscopic surgery revealed the defect in the oropharynx. A second procedure was performed to remove the spinal hardware and repair the leak. This case is not only unique in the literature but also highlights the importance of maintaining a broad differential diagnosis to include rare complications and shows that despite dramatic improvements in imaging, locating CSF leaks still presents a challenge.
https://ift.tt/2ApIMHI
Turning Off Protein Could Boost Immunotherapy Effectiveness on Cancer Tumors
Researchers at the Bloomberg~Kimmel Institute for Cancer Immunotherapy in the Johns Hopkins Kimmel Cancer Center discovered inhibiting a previously known protein could reduce tumor burdens and enhance the effectiveness of immunotherapy treatments.
https://ift.tt/2NUB2zx
Sexism and Sexual Harassment: Considering the Impact on Medical Students, Residents, and Junior Faculty
The Laryngoscope, EarlyView.
https://ift.tt/2v5Fapb
Table of contents
The Laryngoscope, Volume 128, Issue 7, Page iii-vii, July 2018.
https://ift.tt/2vozvtR
Survey of Sexual Medicine Society Members Reveals Only Half Ask For Patients’ Sexual Orientation
Johns Hopkins Medicine researchers say their small survey of nearly 100 health care practitioners who are members of the Sexual Medicine Society of North America revealed that only half routinely ask their patients directly about their sexual orientation. In addition, the survey found, of those who do not ask, more than 40 percent say that sexual orientation is irrelevant to patients' care, a position contrary to longstanding clinical evidence.
https://ift.tt/2LDeiHw
Digital Technology and Mobile Health in Behavioral Migraine Therapy: a Narrative Review
Abstract
Purpose of Review
This article reviews the recent research and development of electronic health (eHealth) and, in particular, mobile health (mHealth) strategies to deliver behavioral treatment for migraine. Prospects for future development and research of mobile health in migraine are suggested.
Recent Findings
Advances in digital technology and mobile technology have led to an era where electronic and mobile approaches are applied to several aspects of healthcare. Electronic behavioral interventions for migraine seem to be acceptable and feasible, but efficacy measures are uncertain. Clinical trials on mHealth-based classical behavioral therapies, such as relaxation, biofeedback, and cognitive behavioral therapy are missing in the literature. Within mHealth, headache diaries are the most researched and scientifically developed. Still, there is a gap between commercially available apps and scientifically validated and developed apps.
Summary
Digital technology and mobile health has not yet lived out its potential in behavioral migraine therapy. Application of proper usability and functionality designs towards the right market, together with appraisal of medical and technological recommendations, may facilitate rapid development of eHealth and mHealth, while also establishing scientific evidence.
https://ift.tt/2vhZDGK
Serratus Plane Block: A Cadaveric Study to Evaluate Optimal Injectate Spread
Background and Objectives Although serratus plane block reportedly provides satisfactory analgesia for breast and thoracic surgeries, the optimal technique for consistent success has not been studied. The goal of this anatomical study was to evaluate the impact of volume, level, and site of injection on the extent of injectate spread that can influence anesthetic coverage. Methods Ultrasound-guided dye injection and subsequent dissection were performed in 39 cadaveric hemithoraces. Methylene blue was injected according to 1 of 4 injection protocols as follows: one 20-mL bolus, either superficial or deep to the serratus anterior muscle (SAM), at the fifth rib level (groups SUP-20 and DEEP-20, respectively), or two 20-mL boluses, either superior or deep to the SAM, one at the third rib and one at the fifth rib level (group SUP-40 and group DEEP-40, respectively). Following injection, dissection and 3-dimensional digitization were performed to map the area of dye spread. Results We found that the extent of dye spread was mostly influenced by the volume of injection rather than the plane of injection (superficial vs deep to SAM). Increasing the volume from 20 to 40 mL doubled the area of injectate spread and promoted dye spread preferentially to the anterior chest wall, with some impact on cephalad-to-caudad spread and no impact on posterior spread. Dye was found most consistently in the axilla when a separate injection was performed at the third rib level. Conclusions Our data showed that a high-volume double-injection technique provides extensive and consistent dye spread in the anterior chest wall and axilla, regardless of the plane of injection relative to the SAM. This technique likely provides more reliable analgesic coverage for breast procedures especially those that involve the axilla, pending confirmation in future clinical studies. Accepted for publication April 22, 2018. Address correspondence to: Vincent Chan, MD, FRCPC, FRCA, Department of Anesthesia, Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst St, MCL 2-405, Toronto, Ontario M5T 2S8, Canada (e-mail: vincent.chan@uhn.ca). V.C. has received honorarium from SonoSite, BBraun, and Aspen Pharma. He also sat on the Medical Advisory Board of Smiths Medical. A.P. has a research grant from Fisher and Pykel for an unrelated study. She is associate editor of Regional Anesthesia and Pain Medicine. A.A. is an anatomy faculty at Allergan Academy of Excellence. The other authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.
https://ift.tt/2vmDw22
https://ift.tt/2vmDw22
Pericapsular Nerve Group (PENG) Block for Hip Fracture
Fascia iliaca block or femoral nerve block is used frequently in hip fracture patients because of their opioid-sparing effects and reduction in opioid-related adverse effects. A recent anatomical study on hip innervation led to the identification of relevant landmarks to target the hip articular branches of femoral nerve and accessory obturator nerve. Using this information, we developed a novel ultrasound-guided approach for blockade of these articular branches to the hip, the PENG (PEricapsular Nerve Group) block. In this report, we describe the technique and its application in 5 consecutive patients. Accepted for publication April 14, 2018. Address correspondence to: Philip W.H. Peng, MBBS, FRCPC, Founder (Pain Med), Department of Anesthesia, McL 2-405, TWH, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8 (e-mail: philip.peng@uhn.ca). A.P. has a research grant from Fisher and Pykel. P.W.H.P. has equipment support from Fujifilm/Sonosite Canada. The other authors declare no conflict of interest. The authors have no sources of funding to declare for this article. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.
https://ift.tt/2v15bpK
https://ift.tt/2v15bpK
Comparison of the ED50 and ED95 of Intrathecal Bupivacaine in Parturients Undergoing Cesarean Delivery With or Without Prophylactic Phenylephrine Infusion: A Prospective, Double-Blind Study
Background and Objectives While prophylactic phenylephrine infusions during cesarean delivery are often used to counteract the sympathectomy associated with spinal anesthesia, their use has been associated with decreased rostral spread of local anesthetic. The purpose of this study was to determine the median effective dose (ED50) and 95% effective dose (ED95) of intrathecal hyperbaric bupivacaine for cesarean delivery in the presence and absence of prophylactic phenylephrine infusion. Methods One hundred healthy parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this randomized, double-blind, dose-finding study to determine ED50 and ED95. Subjects were randomly assigned to receive prophylactic phenylephrine or control (saline) infusion with injection of 6, 7.5, 9, 10.5, or 12 mg intrathecal hyperbaric bupivacaine. An effective dose was defined as achieving a T5 sensory level within 10 minutes of intrathecal drug administration without the need for epidural supplementation. Results The ED50 of intrathecal hyperbaric bupivacaine was 10.0 mg (95% confidence interval [CI], 5.9–11.4 mg) with prophylactic phenylephrine infusion and 7.9 mg (95% CI, 2.3–9.4 mg) in the control group. The ED95 of intrathecal hyperbaric bupivacaine was 14.1 mg (95% CI, 12.3–37.6 mg) with prophylactic phenylephrine infusion and 11.7 mg (95% CI, 9.9–22.8 mg) in the control group. Conclusions The administration of prophylactic phenylephrine infusion results in higher intrathecal hyperbaric bupivacaine dosing requirements in parturients undergoing cesarean delivery. Clinical Trial Registration This study was registered at the Chinese Clinical Trial Registry, identifier ChiCTR-TRC-16008938. Accepted for publication April 14, 2018. Address correspondence to: Xinzhong Chen, MD, Department of Anesthesia, Women's Hospital, School of Medicine, Zhejiang University, No. 1, Xueshi Road, 310006 Hangzhou, China (e-mail: chenxinz@zju.edu.cn). The authors declare no conflict of interest. This study was supported by the funds from National Natural Science Foundation of China (no. 81271237 and no. 81471126). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.
https://ift.tt/2vhX2N0
https://ift.tt/2vhX2N0
Topical Sphenopalatine Ganglion Block Compared With Epidural Blood Patch for Postdural Puncture Headache Management in Postpartum Patients: A Retrospective Review
Background and Objectives Postdural puncture headache (PDPH) is a severe and debilitating complication of unintentional dural puncture. The criterion-standard treatment for PDPH has been epidural blood patch (EBP), but it is an invasive intervention with the potential for severe complications, such as meningitis and paralysis. We believe this is the first ever 17-year retrospective chart review in which we compare the effectiveness of sphenopalatine ganglion block (SPGB) to EBP for PDPH treatment in postpartum patients. Methods We conducted a chart review of the first authors' obstetric patients who experienced PDPH from an unintentional dural puncture from a 17-gauge Tuohy needle for labor epidural from January 1997 to July 2014. Demographic characteristics, headache severity, and associated symptoms were collected prior to treatment. Forty-two patients who received SPGB and 39 patients who received EBP were identified. Residual headache, recovery from associated symptoms, and new treatment complications were compared between the 2 groups at 30 minutes, 1 hour, 24 hours, 48 hours, and 1 week posttreatment. Results A greater number of patients showed significant relief in their PDPH and associated symptoms at 30 and 60 minutes after treatment with SPGB than after treatment with EBP (P
https://ift.tt/2LRIEW7
https://ift.tt/2LRIEW7
Shared decision-making for postoperative analgesia: A semistructured qualitative study
BACKGROUND Shared decision-making (SDM) and decision-support tools have attracted broad support in healthcare as they improve medical decision-making. Experts disagree on how these can help patients evaluate their present situation and possible outcomes of therapy, and how they might reduce decisional conflict. Little is known about their implementation, especially in anaesthesiology. OBJECTIVE To obtain a more fundamental understanding of pre-operative SDM and evaluate the use of a decision-support tool for postoperative analgesia after major thoracic and abdominal surgery. DESIGN A qualitative study with semistructured, in-depth interviews of patients and professionals. SETTING Patient recruitment took place at the Radboud University Medical Centre in Nijmegen and the Canisius Wilhelmina Hospital in Nijmegen, a nonacademic teaching centre. Professionals of the Radboud University Medical Centre were invited to participate in the interviews. PARTICIPANTS Interviews were performed with 10 individual patients and two focus groups both consisting of eight different professionals. MAIN OUTCOME MEASURES To gain insight into the provision of pre-operative information, decision-making processes and the clarity and usability of a prototype decision-support tool. RESULTS Professionals seemed to provide their patients with information directed towards the application of epidural analgesia, providing little attention to its negative effects. For many patients, the information was not tailored to their needs. Patients' involvement in decision-making was minimal, but they did not feel a need for more involvement. They were positive about the decision-support tool, although they indicated that it would not have influenced their treatment decision. Professionals expressed their doubt about the capacity of their patients to fully understand the decisions involved and about the clinical usability of the decision-support tool, because patients might misinterpret the information provided. CONCLUSION The results of this study suggest that both patients and professionals did not adhere to some 'self-evident' principles of SDM when postoperative analgesia after major thoracic and abdominal surgery was discussed. Correspondence to Dr Martin J.L. Bucx, MD, PhD, Consultant, Anaesthesiologist and Clinical Epidemiologist, Department of Anaesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, Internal Postal Code 717, PO Box 9101, 6500 HB Nijmegen, The Netherlands Tel: +31 24 361 45 53; fax: +31 24 354 04 62; e-mail: Martin.Bucx@Radboudumc.nl Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology
https://ift.tt/2AutFwQ
https://ift.tt/2AutFwQ
Case of Wells’ syndrome: A rare association with the clinical course of chronic lymphocytic leukemia
The Journal of Dermatology, EarlyView.
https://ift.tt/2ArP3CQ
Informed consent for regional anesthesia
Purpose of review This narrative review describes the current framework for informed consent discussions for regional anesthesia practice from an ethical and medicolegal stand point as the cornerstone of the patient–physician relationship and the respect for patient autonomy. Recent guidelines and position statements from anesthesia societies have emphasized the importance of these discussions and their appropriate documentation. Recent findings Recent studies have shown that patients want to know more about both common and benign, as well as rare but serious adverse events, as it relates to their anesthetic care. Several strategies have been recently recommended as a means to facilitate a meaningful consent discussion and proper documentation in the perioperative environment. Summary Defining the material risks of ultrasound-guided regional anesthetic procedures remains challenging, due in part to the difficulty in quantifying incidence rates of relatively rare events. However, well informed discussions are of great importance to support patient autonomy and lay a strong foundation for the patient–anesthesiologist relationship. Correspondence to Anahi Perlas, MD, FRCPC, Staff Anesthesiologist, Toronto Western Hospital, University Health Network, Professor, Department of Anesthesia, University of Toronto, 399 Bathurst St, Toronto, ON M5T 2S8, USA. Tel: +1 416 603 5118; fax: +1 416 603 6494; e-mail: Anahi.perlas@uhn.ca Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2O0DDbh
https://ift.tt/2O0DDbh
Does islet size really influence graft function following clinical islet transplantation?
Background It has been proposed that islet transplants comprised primarily of small rather than large islets may provide better graft function, due to their lower susceptibility to hypoxic damage. Our aim was to determine whether islet size correlated with in vivo graft function in islet transplant recipients with C peptide negative type 1 diabetes when islets have undergone pretransplant islet culture. Methods Human pancreatic islets were isolated, cultured for 24hours and infused by standardised protocols. 90 min-stimulated C-peptide concentrations were determined during a standard meal tolerance test 3 months posttransplant. The islet isolation index (IEq/islet number) was determined immediately after isolation and again before transplantation (after tissue culture). This was correlated with patient insulin requirement or stimulated C-peptide. Results Changes in insulin requirement did not significantly correlate with islet isolation index. Stimulated C-peptide correlated weakly with IEq at isolation (p=0.40) and significantly with IEq at transplantation (p=0.018). Stimulated C-peptide correlated with islet number at isolation (p=0.013) and more strongly with the islet number at transplantation (p=0.001). In contrast, the correlation of stimulated C-peptide and islet isolation index was weaker (p=0.018) and this was poorer at transplantation (p=0.034). Using linear regression, the strongest association with graft function was islet number (r=0.722, p=0.001). Islet size was not related to graft function after adjusting for islet volume or number. Conclusion These data show no clear correlation between islet isolation index and graft function; both small and large islets are suitable for transplantation provided the islets have survived a short culture period postisolation. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding author: SJ Hughes; stephen.hughes@nds.ox.ac.uk (44 (0)1865 857507). Islet Lab, Nuffield Department of Surgical Sciences, OCDEM Building, Churchill Hospital, Headington Oxford OX3 7LE The authors declare no conflict of interest. Stephen J Hughes participated in research design, data analysis and manuscript preparation Paul A Bateman participated in data analysis and manuscript preparation Sarah E Cross participated in manuscript preparation Daniel Brandhorst participated in manuscript preparation Heide Brandhorst participated in manuscript preparation Ioannis Spiliotis participated in data analysis and manuscript preparation Chitra Ballav participated in manuscript preparation Miranda Rosenthal participated in manuscript preparation Martin K Rutter participated in data analysis and manuscript preparation James Shaw participated in manuscript preparation Stephen Gough participated in manuscript preparation Paul RV Johnson participated in research design and manuscript preparation Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2mUwqOi
https://ift.tt/2mUwqOi
Favorable Outcomes After Liver Transplantation With Normothermic Regional Perfusion From Donors After Circulatory Death: A Single-Center Experience
Background Controlled donation after circulatory death (cDCD) has been associated with a high incidence of ischemic cholangiopathy (IC) and other perioperative complications. In an attempt to avoid these complications, we implemented an active protocol of cDCD liver transplant (LT) with normothermic regional perfusion (NRP) preservation. Methods This is a descriptive analysis of data collected from a prospective date base of cDCD LT preserved with NRP, from January 2015 to June 2017 with a minimum follow up of 9 months. Results Fifty-seven potential cDCD donors were connected to the NRP system. Of these, 46 livers were transplanted over a 30-months period (80% liver recovery rate). The median posttransplant peak in alanine transaminase was 1136 U/L (220–6683 U/L). Seven patients (15%) presented postreperfusion syndrome and eleven (23%) showed early allograft dysfunction. No cases of ischemic cholangiopathy were diagnosed and no graft loss was observed over a medium follow-up period of 19 months. Of note, 13 donors were older than 65 years, achieving comparable perioperative and midterm results to younger donors. Conclusions As far as we know, this represents the largest published series of cDCD LT with NRP preservation. Our results demonstrate that cDCD liver grafts preserved with NRP appear far superior to those obtained by the conventional rapid recovery technique. CORRESPONDING AUTHOR CONTACT INFORMATION: Patricia Ruiz Ordorica, Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital., Plaza de Cruces s/n. 48903. Baracaldo. Vizcaya. Spain, Phone: +34946006372, Fax: +34946006590. E-mail: patruor@gmail.com AUTHORSHIP PAGE Patricia Ruiz MD • Participated in the writing of the paper • Participated in the performance of the research • Contributed new reagents or analytic tools • Participated in data analysis Mikel Gastaca MD* • Participated in the writing of the paper • Participated in the performance of the research Francisco Javier Bustamante, MD** • Participated in the writing of the paper • Participated in the performance of the research Alberto Ventoso MD* • Participated in the writing of the paper • Participated in the performance of the research Ibone Palomares MD* • Participated in the writing of the paper • Participated in the performance of the research Mikel Prieto MD* • Participated in the writing of the paper • Participated in the performance of the research Jose Ramón Fernández MD ** • Participated in the writing of the paper • Participated in the performance of the research Patricia Salvador MD** • Participated in the writing of the paper • Participated in the performance of the research Jose Ignacio Pijuan MD*** • Contributed new reagents or analytic tools • Participated in data analysis Andres Valdivieso MD* • Participated in the writing of the paper • Participated in the performance of the research DISCLOSURE The authors of this manuscript have no conflicts of interest to disclose as described by Transplantation. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2ArHCeT
https://ift.tt/2ArHCeT
EVALUATION OF OLFACTORY FUNCTION IN CHILDREN WITH SEASONAL ALLERGIC RHINITIS AND ITS CORRELATION WITH ACOUSTIC RHINOMETRY
Publication date: Available online 31 July 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Ceren Aksoy, Çağdaş Elsürer, Hasibe Artaç, Mete Kaan Bozkurt
Abstract
Objectives
Seasonal allergic rhinitis (SAR) is common in children and hyposmia is a major symptom affecting the quality of life. The aim of the present study is to assess olfactory dysfunction in pediatric patients with SAR and correlate the results with acoustic rhinometry measurements.
Methods
Forty children, diagnosed as moderate and severe SAR based on clinical findings, ARIA (Allergic rhinitis and it's impact on asthma) classification and prick test results were enrolled in the study. Endoscopic nasal examination, acoustic rhinometry, total nasal symptom score (TNSS) and Connecticut Chemosensory Clinical Research Center (CCCRC) tests were performed 'in season' (May-August) and 'out season' (November-February). Three patients who did not show up in 'out season' examinations were excluded from the study.
Results
The ages of the children ranged between 8 and 18 years with a hyposmia increased and odor identification decreased (p<0.005, p=0.003, respectively), whereas no differences were found between odor thresholds and the discrimination values (p>0.05). Mean CCCRC value was obstruction score (r=-0.340, p=0.04), subjective hyposmia (r=-0.44, p=0.007) and TNSS (r=-0.494, p=0.02). Although some of the acustic rhinometry parameters were lower during allergy season, there were no correlations between acoustic rhinometry parameters and CCCRS values.
Conclusion
Nearly half of the children with AR reported a mild to moderate hyposmia during pollen season and there was a decrease in odor identification, which can be easily shown using a CCCRC test.
https://ift.tt/2mYJK4p
Childhood asthma clusters reveal neutrophil‐predominant phenotype with distinct gene expression
Allergy, EarlyView.
https://ift.tt/2AtokpC
Antitumor virotherapy using syngeneic or allogeneic mesenchymal stem cell carriers induces systemic immune response and intratumoral leukocyte infiltration in mice
Abstract
Oncolytic virotherapy uses oncolytic viruses that selectively replicate in cancer cells. The use of cellular vehicles with migration ability to tumors has been considered to increase their delivery to target sites. Following this approach, the antitumor efficacy of the treatment Celyvir (mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5) has been demonstrated in patients with neuroblastoma. However, the better efficacy of syngeneic or allogeneic mesenchymal stem cells as cell carriers and the specific role of the immune system in this therapy are still unknown. In this study we use our virotherapy Celyvir with syngeneic and allogeneic mouse mesenchymal stem cells to determine their antitumor efficacy in a C57BL/6 murine adenocarcinoma model. Adoptive transfer of splenocytes from treated mice to new tumor-bearing mice followed by a secondary adoptive transfer to a third group was performed. Similar reduction of tumor growth and systemic activation of the innate and adaptive immune system was observed in groups treated with syngeneic or allogeneic mesenchymal stem cells loaded with ICOVIR-5. Moreover, a different pattern of infiltration was observed by immunofluorescence in Celyvir-treated groups. While non-treated tumors presented higher density of infiltrating immune cells in the periphery of the tumor, both syngeneic and allogeneic Celyvir-treated groups presented higher infiltration of CD45+ cells in the core of the tumor. Therefore, these results suggest that syngeneic and allogeneic Celyvir induce systemic activation of the immune system, similar antitumor effect and a higher intratumoral infiltration of leukocytes.
https://ift.tt/2vqwtFE
New Cartilage Slicer for Slicing Techniques in Tympanoplasty: Design and Applications
Abstract
Cartilage-perichondrium composite graft is used in middle ear surgery for tympanic membrane, ossicular and for soft wall reconstruction. The thickness of the cartilage is thought to interfere with the sound conduction. In our otology practice for tympanic membrane reconstruction, we prefer the sliced cartilage graft to achieve acoustic benefit. At times in the process of slicing, the cartilage gets wasted if not sliced with a precision slicing instrument. We have designed and developed a multi-purpose cartilage slicer for precise reduction of the thickness of the cartilage. To describe the design of our cartilage slicer and to report our preliminary experience with the cartilage slicer. Descriptive study. The technique of slicing with our new cartilage slicer and its usage has been described in detail. A total number of 689 cartilages in tympanoplasty and mastoidectomy have been sliced with it from 2013 to 2017. Our study reports the technique of slicing the tragal cartilage for tympanoplasty, highlighting its advantages and precision of the cartilages slices obtained. Our cartilage slicer is a good option for cartilage slicing in tympanoplasty.
Level of Evidence
Level 4.
https://ift.tt/2K8Vcn7
Endoscopic Removal of Intranasal Supernumerary Tooth: A Case Report
Abstract
The presence of an ectopic tooth into the nasal cavity is unusual. It can be supernumerary, deciduous or permanent. It is important to identify it early to prevent complications such as epistaxis, paranasal sinusitis, nasal septal deviation, nasal septal abscess, and oral-nasal fistula. The diagnosis of nasal teeth is mainly based on clinical and radiographic examination. Treatment is early extraction and endoscopy gives good illumination and helps in easy and precise dissection which is better than old morbid traditional techniques. We report a case of a female presenting with nasal obstruction and foul smell, diagnosed with nasal tooth and successfully removed with endoscopic approach.
https://ift.tt/2LPratm
New Cartilage Slicer for Slicing Techniques in Tympanoplasty: Design and Applications
Abstract
Cartilage-perichondrium composite graft is used in middle ear surgery for tympanic membrane, ossicular and for soft wall reconstruction. The thickness of the cartilage is thought to interfere with the sound conduction. In our otology practice for tympanic membrane reconstruction, we prefer the sliced cartilage graft to achieve acoustic benefit. At times in the process of slicing, the cartilage gets wasted if not sliced with a precision slicing instrument. We have designed and developed a multi-purpose cartilage slicer for precise reduction of the thickness of the cartilage. To describe the design of our cartilage slicer and to report our preliminary experience with the cartilage slicer. Descriptive study. The technique of slicing with our new cartilage slicer and its usage has been described in detail. A total number of 689 cartilages in tympanoplasty and mastoidectomy have been sliced with it from 2013 to 2017. Our study reports the technique of slicing the tragal cartilage for tympanoplasty, highlighting its advantages and precision of the cartilages slices obtained. Our cartilage slicer is a good option for cartilage slicing in tympanoplasty.
Level of Evidence
Level 4.
https://ift.tt/2K8Vcn7
Endoscopic Removal of Intranasal Supernumerary Tooth: A Case Report
Abstract
The presence of an ectopic tooth into the nasal cavity is unusual. It can be supernumerary, deciduous or permanent. It is important to identify it early to prevent complications such as epistaxis, paranasal sinusitis, nasal septal deviation, nasal septal abscess, and oral-nasal fistula. The diagnosis of nasal teeth is mainly based on clinical and radiographic examination. Treatment is early extraction and endoscopy gives good illumination and helps in easy and precise dissection which is better than old morbid traditional techniques. We report a case of a female presenting with nasal obstruction and foul smell, diagnosed with nasal tooth and successfully removed with endoscopic approach.
https://ift.tt/2LPratm
Concomitant Extramedullary Plasmacytoma in the Oropharynx and Hypopharyngeal Squamous Cell Carcinoma
We report a rare case of hypopharyngeal squamous cell carcinoma occurring synchronously with extramedullary plasmacytoma (EPM) of the oropharynx in which radiotherapy was used as the curative treatment. A 73-year-old man presented with a sore throat that had persisted for 6 months. Examination revealed a superficial, smooth tumorous lesion at the base of his tongue with a red hue in the oropharynx. In addition, a protruding tumor was observed on the mucosal surface in the right piriform recess of the hypopharynx, and computed tomography revealed thickening of the pharyngeal wall at the right tongue base and in the right piriform recess of the hypopharynx. Because no definitive diagnosis could be reached for the lesion at the base of the tongue, the entire tongue-base tumor was resected by transoral surgery under endoscopy. Proliferation of plasma cells in the tumor was detected, and a bone marrow puncture test ruled out multiple myeloma leading to a definitive diagnosis of Stage I (cT1N0M0) squamous cell carcinoma in the right piriform recess of the hypopharynx and primary extramedullary plasmacytoma in the oropharynx. Radiotherapy was selected for curative treatment with a complete response for both cancers. No recurrences have been observed as of 12 months postoperatively.
https://ift.tt/2vjR6TR
A new nonsense mutation in the POGLUT1 gene in two sisters with Dowling–Degos disease
Journal of the European Academy of Dermatology and Venereology, EarlyView.
https://ift.tt/2mX9u0U
Brucellosis in renal transplant recipients: a comparative review of 5 cases
Although brucellosis in renal transplant recipients is rare, we studied the clinical characteristics of this infection in this patient population due to the significantly increased number of renal transplantations performed over the past few decades. We report one case from our experience and undertake a review of the previously reported cases retrieved from the PubMed. A total of 5 cases of brucellosis in renal transplant recipients were found to date. The mean time from transplantation to diagnosis of brucellosis was 4.7 years (range, 4 months to 13 years). Blood culture and detection of anti-Brucella antibodies were frequently used diagnostic investigations. Treatment with appropriate antibiotic regimen led to a clinical cure and marked improvement in Brucella titre in all the patients. This review illustrates that clinicians should remain vigilant for this infectious aetiology following renal transplantation. Further studies are required to delineate the magnitude and scope of this association.
https://ift.tt/2M5t2ez
From carcinoma through lymphoma to myeloma: a gastric mass diagnostic rollercoaster ride
We describe a dramatic clinical presentation of extramedullary multiple myeloma (MM) in an elderly patient with known monoclonal gammopathy of unknown significance (MGUS). Gastrointestinal symptoms and a gastric mass on imaging studies suggested an advanced solid gastric malignancy. Pathological workup of gastric biopsies first suspected a lymphoma, a second opinion finally confirmed an extramedullary MM. Treatment with bortezomib, cyclophosphamide and dexamethasone induced rapid relief of symptoms and normalisation of renal function as well as serum MM markers. Our case highlights the diagnostic difficulties when MM presents with signs and symptoms of respective end-organ involvement rather than typical 'CRAB' criteria. It underlines the importance of actively considering MM in a patient with MGUS, regardless of the clinical presentation of a specific medical problem. Our report also impressively illustrates the rapid response of MM and its gastric extramedullary manifestation to guideline-adherent chemotherapy.
https://ift.tt/2mYSc3G
Mycobacterium bovis BCG spinal osteomyelitis in a patient with bladder cancer without a history of BCG instillation
BCG has been used as intravesical immunotherapy for the treatment of bladder carcinoma. However, this treatment is not harmless and may lead to complications, with a reported incidence of systemic BCG infection ranging from 3% to 7%. We report a case of culture-proven Mycobacterium bovis (BCG) vertebral osteomyelitis in a 72-year-old patient with bladder carcinoma who was treated with intravesical mitomycin C but did not receive BCG. Cultures from biopsy recovered isolate resembling Mycobacterium tuberculosis biochemically, but resistant to pyrazinamide (PZA). The patient was originally started on a four-drug antituberculous regimen of isoniazid, rifampin, ethambutol and PZA. After genotypic analysis identified the organism as M. bovis (BCG), the regimen was changed to isoniazid and rifampin for 12 months. The patient responded well to this treatment. This case is unique as the patient received only intravesical mitomycin and did not receive BCG, implying the possibility of transmission from contaminated equipment.
https://ift.tt/2M1Cv6E
Primary malignant melanoma of urethra mimicking as urethral caruncle
Description
A 50-year-old woman presented with dysuria and intermittent vaginal bleeding for last 6 months. On local examination, a 1x1 cm mass was seen protruding from anterior wall of urethral meatus. The mass was lobulated, firm, painless and tan coloured (figure 1). The local pelvic examination and general physical examination was normal. Cystourethroscopy revealed no abnormality in the urethra and urinary bladder. The mass was provisionally diagnosed as urethral caruncle and was excised under local anaesthesia. The histopathology came as a surprise to us as it revealed diffuse infilteration of large pleomorphic, epitheloid and spindle-shaped tumour cells with high nucleocytoplasmic ratio, vesicular chromatin, prominent nucleoli and scant amount of cytoplasm (figure 2). Melanin pigment was also seen within the cells. Further analysis with immunohistochemistry revealed positive immunostaining with HMB-45 and confirmed it to be primary malignant melanoma of urethra (figure 3). Further workup...
https://ift.tt/2mYueFH
Spontaneous pneumomediastinum in limited cutaneous systemic sclerosis and myositis overlap
A 58-year-old man with limited cutaneous systemic sclerosis and myositis overlap complicated by interstitial lung disease presented with several months of progressive dyspnoea and weakness. CT chest revealed extensive pneumomediastinum that was not present on imaging 6 months before this study and appeared to be spontaneous, with no preceding trauma, infection or invasive procedures.
https://ift.tt/2M1CkZ2
Acute kidney injury associated with hypercalcaemic crisis in a patient with primary hyperparathyroidism
Parathyroid or hypercalcaemic crisis is a rare presenting manifestation of primary hyperparathyroidism and usually seen in relation to parathyroid carcinoma and multiple myeloma. We present a middle-aged woman with extreme hypercalcaemia due to parathyroid adenoma presenting as acute kidney injury. This case highlights the need to consider primary hyperparathyroidism in differentials of a patient presenting with severe hypercalcaemia and renal dysfunction. Also this is the second reported case in literature of a patient surviving such extreme hypercalcaemia due to parathyroid adenoma.
https://ift.tt/2mUbln8
Solitary juvenile polyp as a cause of elevated faecal calprotectin in an adult
Faecal calprotectin (FCP) levels are commonly measured in both primary and secondary care as an adjunct to the diagnosis of inflammatory bowel disease (IBD). Juvenile polyps are a rare form of colonic polyp found in both adults and children. We present a case of an adult patient who presented with a very high FCP level, which subsequently normalised following removal of a solitary colonic juvenile polyp. There was no evidence of IBD. Elevation of FCP levels due to this type of colonic pathology have not previously been described in the literature.
https://ift.tt/2M5vB07
Multiorgan system structural malformations associated with Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS) type 2: avoiding pitfalls in diagnosis, counseling and treatment
An 18-year-old virginal woman was referred to the reproductive endocrinology clinic with primary amenorrhoea and secondary sexual development in the absence of pelvic pain. Additionally, she had significant congenital sensorineural hearing loss, autism, bipolar disorder and class III obesity. On physical examination, secondary sexual development was confirmed (Tanner 5 breasts and Tanner 4 pubic hair). She refused further pelvic examination following prior attempts by the referring physicians. Serum leutinizing hormone (LH), follicle sitmulating hormone (FSH). prolactin, estradiol and total testosterone values were within normal limits. Karyotype was 46,XX. MRI demonstrated complete uterine agenesis, short vagina, sacral dysgenesis with complete absence of the coccyx and a horseshoe kidney. Diagnosis of Mayer-Rokitansky-Küster-Hauser Syndrome type 2 was established based on clinical, laboratory and MRI findings. The patient and family were counselled regarding the disease process, techniques for vaginal elongation, sexual activity and future reproductive options.
https://ift.tt/2LDv9tZ
Unusual presentation of acute pulmonary embolus presenting with inferior ST elevation
Description
A 67-year-old woman presented with a 6-hour history of dull, inspiratory chest pain and shortness of breath that had subsided on arrival to hospital. She denied any history of coronary artery disease and had no veno-thromboembolic risk factors. Her semirecumbent blood pressure was 94/50 mm Hg, and oxygen saturations were 98% on room air. Chest X-ray was unremarkable. The initial ECG demonstrated sinus tachycardia only. She later developed further chest pain with dynamic 1 mm ST segment elevation in lead III (figure 1A). In addition, there was ECG evidence of S1Q3T3 pattern, and troponin was 3444 ng/mL. An urgent bedside transthoracic echocardiogram supported a diagnosis of acute pulmonary embolus (APE) as opposed to acute ST elevation myocardial infarction (figure 1B–D). It showed a D-shaped left ventricle in both phases of the cardiac cycle reflecting right ventricular volume and pressure overload and a dilated inferior vena cava. The patient was...
https://ift.tt/2KbVI3N
Rehabilitation of simultaneous bilateral epiphysial fracture of proximal tibia in adolescent
Simultaneous and bilateral epiphysial fracture of the proximal tibia is an extremely rare injury, with only 23 cases reported in the literature. In this paper, we present a 15-year-old adolescent with a simultaneous and bilateral epiphysial fracture of the proximal tibia in sport context (trampoline jump). He underwentsurgical repair with bilateral closed reduction and internal fixation, followed by outpatient rehabilitation programme during 4 months. There was a good functional outcome, without limitation in activities of daily living and with resumption of amateur sports activity. Since there are no guidelines described for this pathology, the authors suggest a rehabilitation protocol for bilateral epiphysial fractures of the proximal tibia that underwent surgical treatment previously and in which there were no complications in the acute phase.
https://ift.tt/2LDuUPB
Δευτέρα 30 Ιουλίου 2018
Speech audiometry in noise: Development of the French-language VRB (vocale rapide dans le bruit) test
Publication date: Available online 30 July 2018
Source: European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): F. Leclercq, C. Renard, C. Vincent
Abstract
Introduction
Understanding speech in noise is a major challenge for most hearing-impaired subjects, with or without hearing aids. To overcome the weaknesses of French-language speech-in-noise tests, we developed a new instrument, with a balanced mix of difficulty of the speech material.
Material and methods
The speech material comprised 127 sentences taken from the "Marginal Benefit from Acoustic Amplification" (MBAA) corpus, each including 3 keywords. The noise was created using the "onde vocale globale" (global vocal wave: OVG), described by Dodelé. The 127 speech/noise pairs were recorded individually after root-mean-square equalization. The first experiment, on 10 normal-hearing adults, determined the signal-to-noise ratio (SNR) associated with 50% correct keyword identification in each sentence (SNR-50), using an ascending method with noise level set at 73 dB SPL. Relative levels between sentences and noise were then adjusted sentence by sentence to achieve an SNR-50 of 0 dB. The second experiment, with 12 normal-hearing adults, validated the equalization of sentence difficulty.
Results
Mean SNR-50 was −6.64 dB (σ = 1.47). Mean adjusted SNR-50 was 0.08 dB (σ = 0.55). Mean psychometric curve slope was 19.3%/dB, with low standard deviations, testifying to the sensitivity of the speech material.
Conclusion
The VRB (vocale rapide dans le bruit: rapid speech in noise) test is based on sentences from the MBAA corpus with background noise based on the OVG at different signal-to-noise ratios. The test is feasible and able to detect slight variations in speech-in-noise performance between subjects.
https://ift.tt/2AxkCeK
Zinc deficiency and severe protein–energy malnutrition in a child with atopic eczema
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2mZF5z6
The Prognostic Impact of Tumor Size in Papillary Thyroid Carcinoma is Modified by Age
Thyroid, Ahead of Print.
https://ift.tt/2Kd00I3
Early Determinants of Thyroid Function Outcomes in Children with Congenital Hypothyroidism and a Normally Located Thyroid Gland: A Regional Cohort Study
Thyroid, Ahead of Print.
https://ift.tt/2LKefZR
Protective Effect of Ginseng on Salivary Dysfunction Following Radioiodine Therapy in a Mouse Model
Thyroid, Ahead of Print.
https://ift.tt/2KcjsEM
A Novel Mutation in NKX2-1 Shows Dominant-Negative Effects Only in the Presence of PAX8
Thyroid, Ahead of Print.
https://ift.tt/2LKefsP
Iron Deficiency May Predict Greater Risk for Hypothyroxinemia: A Retrospective Cohort Study of Pregnant Women in China
Thyroid, Ahead of Print.
https://ift.tt/2M2rmSN
Predicting Malignancy in Thyroid Nodules: Radiomics Score Versus 2017 American College of Radiology Thyroid Imaging, Reporting and Data System
Thyroid, Ahead of Print.
https://ift.tt/2vnfzHN
In Memoriam to the man behind the camera: David J LIM, MD November 27 1935–June 29, 2018
Publication date: Available online 30 July 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Bernd Fritzsch
https://ift.tt/2KcrugW
In vivo imaging reveals increased eosinophil uptake in the lungs of obese asthmatics
Publication date: Available online 30 July 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Neda Farahi, Chrystalla Loutsios, Nicola Tregay, Adam K.A. Wright, Rachid Berair, Laurence S.C. Lok, Daniel Gillett, Ian Cullum, Rosalind P. Simmonds, Charlotte Summers, Anna Wong, Chandra K. Solanki, John Buscombe, Pee Hwee Pang, Arthikkaa Thavakumar, A.Michael Peters, Christopher E. Brightling, Alison M. Condliffe, Edwin R. Chilvers
Capsule Summary
Using radiolabeled eosinophils coupled with SPECT/CT the authors quantify eosinophilic inflammation in the lungs of patients with asthma and focal pulmonary eosinophilic inflammation, revealing important differences in eosinophil kinetics between obese and non-obese asthmatics.
https://ift.tt/2NZCErU
Sulfide protects Staphylococcus aureus from aminoglycoside antibiotics but cannot be regarded as a general defense mechanism against antibiotics [PublishAheadOfPrint]
Sulfide production has been proposed to be a universal defense mechanism against antibiotics in bacteria (Shatalin K, Shatalina E, Mironov A and Nudler E. Science 334:986-90,2011, doi: 10.1126/science.1209855). To gain insight into the mechanism underlying sulfide protection, we systematically and comparatively addressed the interference of sulfide with antibiotic activity against Staphylococcus aureus as model organism. The impact of sulfide and sulfide precursors on the antibiotic susceptibility of S. aureus towards the most important classes of antibiotics was analyzed using modified disk diffusion assays, killing kinetics and drug uptake studies. In addition, sulfide production and the impact of exogenously added sulfide on the physiology of S. aureus was analyzed. Sulfide protection was found to be limited to aminoglycoside antibiotics, known to be taken up by bacterial cells in an energy dependent process. The protective mechanism was found to rely on an inhibitory effect of sulfide on the bacterial respiratory chain leading to reduced drug uptake. S. aureus was found to be incapable of producing substantial amounts of sulfide. We propose that bacterial sulfide production should not be regarded as a general defense mechanism against antibiotics since, (i) it is limited to aminoglycosides and (ii) production levels vary considerably among species and, as for S. aureus, may be too low for protection.
https://ift.tt/2Aqjjhh
Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis [PublishAheadOfPrint]
Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient's characteristics from adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using non-linear mixed effects modeling with first-order conditional estimation method. A two-compartment model with first-order elimination best-described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for CL and Vd, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volume, and inter-compartmental clearance were 3.06 L/h, 14.4 L, 17.1 L and 0.925 L/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ compared with individuals without cystic fibrosis. However, further investigations are needed to confirm these results, and thus the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.
https://ift.tt/2mWsfS5
Characterization of mutations conferring resistance to rifampicin in Mycobacterium tuberculosis clinical strains [PublishAheadOfPrint]
Resistance of Mycobacterium tuberculosis to rifampicin, mediated by mutations in the rpoB gene, coding for the beta-subunit of RNA polymerase, poses a serious threat to the efficacy of clinical management and thus control programs of TB. The contribution of many individual rpoB mutations to the development and level of RMP resistance remains elusive. In this study, the incidence of mutations throughout the rpoB gene among 115 Mycobacterium tuberculosis clinical isolates, both resistant and susceptible to RMP was determined. Of the newly-discovered rpoB mutations, the role of three substitutions in the causation of RMP resistance was empirically tested. The results from in vitro mutagenesis experiments were combined with the assessment of the prevalence of rpoB mutations, and their reciprocal co-occurrences, across global M. tuberculosis populations.
Twenty-two different types of mutations in the rpoB gene were identified and distributed among 59 (90.8%) RMP-resistant strains. The minimum inhibitory concentrations (MICs) of RMP were within the range of 40-800 mg/L, with MIC50 and MIC90 values of 400 and 800 mg/L, respectively. None of the mutations (Gln429His, Met434Ile, Arg827Cys) inspected for their role in the development of RMP resistance produced a RMP-resistant phenotype in isogenic M. tuberculosis H37Rb strain-derived mutants. These mutations are supposed to compensate for fitness impairment incurred by other mutations directly associated with drug resistance.
https://ift.tt/2AAEIEX
Impact of inducible blaDHA-1 on susceptibility of Klebsiella pneumoniae clinical isolates to LYS228 and identification of chromosomal mpl and ampD mutations mediating upregulation of plasmid borne blaDHA-1 expression [PublishAheadOfPrint]
Twenty three K. pneumoniae (blaDHA-1) clinical isolates exhibited a range of susceptibilities to LYS228, with MICs of ≥8 μg/mL for 9 of these. Mutants with decreased susceptibility to LYS228 and upregulated expression of blaDHA-1 were selected from representative isolates. These had mutations in the chromosomal peptidoglycan recycling genes mpl or ampD. Pre-existing mpl mutations were also found in some of the clinical isolates examined and these had strongly upregulated expression of blaDHA-1.
https://ift.tt/2OyVzLc
The monobactam LYS228: mode of action and mechanisms decreasing in vitro susceptibility of Escherichia coli and Klebsiella pneumoniae [PublishAheadOfPrint]
The monobactam scaffold is attractive for the development of new agents to treat infections caused by drug-resistant Gram-negative bacteria since it is stable to metallo-β-lactamases (MBLs). However, the clinically used monobactam aztreonam lacks stability to serine β-lactamases (SBLs) that are often co-expressed with MBLs. LYS228 is stable to MBLs and most SBLs. LYS228 bound purified Escherichia coli penicillin binding protein 3 (PBP3) similarly to aztreonam (k2/Kd = 367504 s-1M-1 and 409229 s-1M-1, respectively) according to stopped-flow fluorimetry. A gel-based assay showed that LYS228 bound mainly to E. coli PBP3, with weaker binding to PBP1a and PBP1b. Exposing E. coli cells to LYS228 caused filamentation, consistent with impaired cell division. No single-step mutants were selected from twelve Enterobacteriaceae strains expressing different classes of β-lactamases at 8X the minimum inhibitory concentration (MIC) of LYS228 (frequency <2.5x10-9). At 4X the MIC, mutants were selected from two of twelve strains at frequencies of 1.8x10-7 and 4.2x10-9. LYS228 MICs were ≤ 2 μg/mL against all mutants. These frequencies compared favorably to those for meropenem and tigecycline. Mutations decreasing LYS228 susceptibility occurred in ramR and cpxA (Klebsiella pneumoniae) and baeS (E. coli and K. pneumoniae). Susceptibility of E. coli ATCC 25922 to LYS228 decreased 256-fold (MIC 0.125 to 32 μg/mL) after 20 serial passages. Mutants accumulated mutations in ftsI (encoding the target, PBP3), baeR, acrD, envZ, sucB and rfaI. These results support the continued development of LYS228, which is currently undergoing Phase II clinical trials for complicated intraabdominal infection and complicated urinary tract infection (https://clinicaltrials.gov/ct2/show/NCT03377426; https://clinicaltrials.gov/ct2/show/NCT03354754).
https://ift.tt/2AnQFNQ
Absence of K13 Polymorphism in Plasmodium falciparum Parasites from Brazilian Endemic Areas. [PublishAheadOfPrint]
P. falciparum ART-resistant parasites can be evaluated examining polymorphisms in the Kelch (PfK13) domain. 69 samples from falciparum malaria patients were analyzed. All samples were from Brazilian endemic areas of the following states: Acre (n=14), Amapá (n=15), Amazonas (n=30) and Pará (n=10). After DNA alignment with the 3D7 reference sequence all samples were found to be wild-type. These data provide a baseline on PfK13 and reinforce the pertinence of ACTs treatment in Brazilian areas.
https://ift.tt/2mZ7vcA
Ceftazidime-Avibactam Susceptibility Breakpoints Against Enterobacteriaceae and Pseudomonas aeruginosa [PublishAheadOfPrint]
Clinical susceptibility breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa for the ceftazidime-avibactam dosage regimen of 2000-500 mg every 8 hours (q8h) by 2-h intravenous infusion (adjusted for renal function) have been established by the FDA, CLSI and EUCAST as susceptible, MIC ≤8 mg/L, and resistant, MIC >8 mg/L. The key supportive data from PK/PD analyses, in vitro surveillance including molecular understanding of relevant resistance mechanisms, and efficacy in regulatory clinical trials, are collated and analyzed here.
https://ift.tt/2AnQFxk
Past and Present Perspectives on {beta}-Lactamases [PublishAheadOfPrint]
β-Lactamases, the major resistance determinant for β-lactam antibiotics in Gram-negative bacteria, are ancient enzymes whose origins can be traced back millions of years. These well-studied enzymes, currently numbering almost 2800 unique proteins, initially emerged from environmental sources, most likely to protect a producing bacterium from attack by naturally-occurring β-lactams. Their ancestors were presumably penicillin-binding proteins that share sequence homology with β-lactamases possessing an active site serine. Metallo-β-lactamases also exist, with one, or two, catalytically functional zinc ions. Although penicillinases in Gram-positive bacteria were reported shortly after penicillin was introduced clinically, transmissible β-lactamases that could hydrolyze recently-approved cephalosporins, monobactams and carbapenems later became important in Gram-negative pathogens. Nomenclature is based on one of two major systems. Originally, functional classifications were used, based on substrate and inhibitor profiles. A later scheme classifies β-lactamases according to amino acid sequences, resulting in class A, B, C and D enzymes. A more recent nomenclature combines the molecular and biochemical classifications into 17 functional groups that describe most β-lactamases. Some of the most problematic enzymes in the clinical community include extended-spectrum β-lactamases (ESBLs) and the serine and metallo-carbapenemases, all of which are at least partially addressed with new β-lactamase inhibitor combinations. New enzyme variants continue to be described, partly because of the ease of obtaining sequence data from whole genome sequencing studies. Often these new enzymes are devoid of any phenotypic descriptions, making it more difficult for clinicians and antibiotic researchers to address new challenges that may be posed by unusual β-lactamases.
https://ift.tt/2OwAf8X
Antibiotic-induced dysbiosis predicts mortality in an animal model of Clostridium difficile infection [PublishAheadOfPrint]
Background
Antibiotic disruption of the intestinal microbiota favors colonization by Clostridium difficile. Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis, and quantified the link between this intensity and mortality.
Methods
We administered either moxifloxacin (n=70) or clindamycin (n=60) to hamsters by subcutaneous injection from day 1 (D1) to D5, and challenged them with a C. difficile toxigenic strain at D3. Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D0 and D3 using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D16. We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time of C. difficile challenge and studied their capacity to predict subsequent death of the animals.
Results
Increasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (p<10-5 for the change of Shannon index in moxifloxacin-treated animals and p<10-9 in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the ROC curve of 0.89 [95%CI, 0.82;0.95] and 0.95 [0.90;0.98], respectively.
Conclusions
Altogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency to the DAV131A dose; mortality after C. difficile challenge was related to the intensity of dysbiosis in a similar manner with the two antibiotics.
https://ift.tt/2AqiYev
Extensive Genetic Commonality among Wildlife, Wastewater, Community, and Nosocomial Isolates of Escherichia coli Sequence Type 131 (H30R1 and H30Rx Subclones) That Carry blaCTX-M-27 or blaCTX-M-15 [PublishAheadOfPrint]
Escherichia coli sequence type 131 (ST131) is currently one of the leading causes of multi-drug-resistant extraintestinal infections globally. Here we analyzed the phenotypic and genotypic characteristics of 169 ST131 isolates from various sources (wildlife, wastewater, companion animals, community, and hospitals) to determine whether wildlife and the environment share similar strains with humans, supporting transmission of ST131 between different ecological niches. Susceptibility to 32 antimicrobials was tested by disc diffusion and broth microdilution. Antibiotic resistance genes, integrons, plasmid replicons, 52 virulence genes, and, fimH-based subtypes were detected by PCR and DNA sequencing. Genomic relatedness was determined by pulsed-field gel electrophoresis (PFGE). The genetic context and plasmid vs. chromosomal location of extended-spectrum beta-lactamase (ESBL) genes was determined by PCR and probe hybridization, respectively. The 169 ST131 study isolates segregated predominantly into blaCTX-M-15H30Rx (60%) and blaCTX-M-27H30R1 (25%) subclones. Within each subclone, isolates from different source groups were categorized into distinct PFGE clusters; genotypic characteristics were fairly well conserved within each major PFGE cluster. Irrespective of source, the blaCTX-M-15H30Rx isolates typically exhibited virotype A (89%), an F2:A1:B- replicon (84%), and a 1.7 kb class 1 integron (92%), and had diverse structures upstream of the blaCTX-M region. In contrast, the blaCTX-M-27H30R1 isolates typically exhibited virotype C (86%), an F1:A2:B20 replicon (76%), and a conserved IS26-ISEcp1-blaCTX-M-like structure. Despite considerable overall genetic diversity, our data demonstrate significant commonality between E. coli ST131 isolates from diverse environments, supporting transmission between different sources, including humans, environment, and wildlife.
https://ift.tt/2OtV7hd
In Vitro Activity of Isavuconazole versus Opportunistic Fungal Pathogens from Two Mycology Reference Laboratories [PublishAheadOfPrint]
Monitoring antifungal susceptibility patterns for new and established antifungal agents seems prudent given the increasing prevalence of uncommon species associated with higher antifungal resistance. We evaluated the activity of isavuconazole against 4,856 invasive yeasts and moulds collected worldwide.
The 4,856 clinical fungal isolates, including 2351 Candida spp. isolates, 97 non-Candida yeasts, 1,972 Aspergillus spp. isolates, and 361 non-Aspergillus moulds, including 292 Mucorales isolates collected in 2015-2016, were tested using CLSI methods.
The MIC values for isavuconazole versus Aspergillus ranged from 0.06 μg/ml to ≥16 μg/ml. The modal MIC for isavuconazole was 0.5 μg/ml (range 0.25 μg/ml [A. nidulans and A. terreus species complex] to 4 μg/ml [A. calidoustus and A. tubingensis]). Eight A. fumigatus isolates had elevated isavuconazole MIC values at ≥8 μg/ml (non-wild type). Isavuconazole showed comparable activity to itraconazole against the Mucorales. The lowest modal isavuconazole MIC values were seen for Rhizopus spp., R. arrhizus var. arrhizus, and R. microsporus (all 1 μg/ml). Candida spp. isolates were inhibited by ≤0.25 μg/ml of isavuconazole (range 96.1% [C. lusitaniae] to 100.0% [C. albicans, C. dubliniensis, C. kefyr, and C. orthopsilosis]). MIC values were ≤1 μg/ml for 95.5% of C. glabrata and for 100.0% of C. krusei. Isavuconazole was active against the non-Candida yeasts, including C. neoformans (100.0% at ≤0.5 μg/ml).
Isavuconazole exhibited excellent activity against most species of Candida and Aspergillus. Isavuconazole was comparable to posaconazole and voriconazole against the less common yeasts and moulds. Isavuconazole was generally less active than posaconazole and more active than voriconazole against the 292 Mucorales isolates. We confirm the potentially useful activity of isavuconazole against species of Rhizopus as determined by CLSI methods.
https://ift.tt/2ArzDOU
Εγγραφή σε:
Αναρτήσεις (Atom)