Comorbidity of bipolar disorder and obsessive–compulsive disorder is common in adolescence. Obsessive–compulsive disorder symptoms may be episodic and secondary to alterations in mood, and display specific fea...
http://ift.tt/2z1RcST
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 11 Δεκεμβρίου 2017
Electroconvulsive therapy for manic state with mixed and psychotic features in a teenager with bipolar disorder and comorbid episodic obsessive–compulsive disorder: a case report
Radiofrequency-assisted subcision for postacne scars
Subcision is a commonly performed procedure for depressed rolling scars of acne.1 Breaking up the fibrotic strands mechanically with a blade or needle leads to neocollagenosis and hematoma formation, resulting in elevation of the depressed scars. However, the excessive mechanical force often leads to trauma to the surrounding tissue, excessive bleeding, and large hematoma formation and fibrosis.
http://ift.tt/2yguvXM
Trends in US sunscreen formulations: Impact of increasing spray usage
To the Editor: Sunscreen is an important component of sun protection. Almost all dermatologists believe that sunscreen is safe, effective, and can reduce the risk of skin cancer.1 In the United States, many different sunscreen formulations exist, including balms, sprays, lotions, sticks, creams, foams, gels, and oils.
http://ift.tt/2AvJNh2
Botulinum toxin type A for the treatment of localized recalcitrant chronic pruritus
To the Editor: Localized chronic pruritus is a common condition that significantly affects health-related quality of life. A variety of diseases result in localized chronic itch, which can be broadly classified as dermatologic, neuropathic, or psychogenic in nature. For patients with chronic pruritus that is refractory to conventional therapy, the burden of disease is substantial.
http://ift.tt/2yheUXT
Cantharidin for treatment of facial molluscum contagiosum: A retrospective review
To the Editor: Molluscum contagiosum (MC) papules are self-limited, resolving within months to years. Active nonintervention is a common management approach in children; caregivers, however, often seek treatment owing to the contagious nature of the virus, itch, embarrassment, pain, or other reasons (Fig 1). Cantharidin is a common treatment for pediatric MC, although some discourage its use on the face. We present caregiver-reported outcomes of cantharidin treatment for facial molluscum in our practice.
http://ift.tt/2AwvRni
Micromelanomas identified with time-lapse total body photography and dermoscopy
To the Editor: Secondary prevention efforts to detect malignant melanoma focus on lesions at an initial growth phase with diameters <6 mm; earlier detection correlates with improved survival rates.1 Two photographic approaches provide critical and complementary information in the differential diagnosis of malignant melanoma. Total body photography (TBP) traditionally provides baseline images from which macroscopic lesion changes can be detected, whereas digital epiluminescence (dermoscopic) microscopy reveals subtle changes in preexisting nevi.
http://ift.tt/2ygRIsC
Romance, love, and sex in the dermatology department and residency program
Many businesses and academic organizations have policies that address the issue of workplace amorous relationships. Virtually all such policies forbid relationships between supervisors and those whom they supervise, or between employees of significantly different rank. Some even go so far as to prohibit relationships between employees in different departments or those reporting to different supervisors. The basis for such policies is to prohibit relationships that may affect the work environment for other employees, the productivity of the company, and to prevent the company from becoming entangled in sexual harassment suits.
http://ift.tt/2AwvM2Y
Vitamin D deficiency in patients with alopecia areata: A systematic review and meta-analysis
Alopecia areata (AA) is a T cell–mediated autoimmune disease that causes nonscarring hair loss.1 Some autoimmune diseases are associated with a vitamin D deficiency, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and vitiligo.2,3 Previous studies that evaluated vitamin D levels in patients with AA have reached inconsistent conclusions. This study aimed to perform a systematic review and meta-analysis on the association between vitamin D levels and AA.
http://ift.tt/2yhafW1
Innovative modification of the USB dermatoscope for mucoscopy
There have been a number of technological advancements in dermoscopy of cutaneous lesions1; However, dermoscopy of mucosae remains a challenge, primarily because existing dermatoscopes are not well designed to explore them. Contact magnifying endoscopes and oral mucoscopes have been used in the past for contact and noncontact mucoscopy.2 But the lack of availability and versatility of these instruments and lack of expertise in handling them make them unsuitable for routine use by dermatologists in clinical practice.
http://ift.tt/2l244E6
Health care utilization for psoriasis in the United States differs by race: An analysis of the 2001-2013 Medical Expenditure Panel Surveys
To the Editor: Racial/ethnic differences in general health care utilization exist in the United States.1 Little is known about health care utilization among racial/ethnic groups for skin diseases, including for psoriasis, the most prevalent immune-mediated disease.2 We aimed to evaluate health care utilization for psoriasis by race/ethnicity using population-based data derived from the Medical Expenditure Panel Surveys, the most complete source of information on health care utilization, cost, and health insurance coverage in the United States.
http://ift.tt/2iVJVeI
Hidradenitis suppurativa burden of disease tool: Pilot testing of a disease-specific quality of life questionnaire
To the Editor: Hidradenitis suppurativa (HS) is a chronic inflammatory condition affecting intertriginous areas of the body that dramatically impairs quality of life (QoL) and has a substantial psychosocial burden.1,2 Full remission of HS is rare, making improvements in QoL a critical goal of therapy. Currently, when investigating the impact of HS, we are limited to generic QoL questionnaires, none of which are specific for HS. We propose a disease-specific tool that would better capture the unique burden of disease caused by HS, which is necessary to determine the impact of therapeutic interventions in clinical trials and in the clinical setting.
http://ift.tt/2kZ76sH
Andrews' diseases of the skin clinical atlas
Andrews' Diseases of the Skin Clinical Atlas by William James, Dirk Elston, and Patrick McMahon is the first published atlas from the writers of Andrews' Diseases of the Skin, a renowned comprehensive dermatological text. It not only serves as a wonderful accompaniment to the Andrews text but also is a strong standalone atlas benefitting any reader, from student to practicing clinician. For a specialty that relies heavily on the physical exam, this text provides wonderful depictions of thousands of entities that help the reader learn the morphology and distribution of each diagnosis.
http://ift.tt/2l1Ur8o
Cancer risks among patients with alopecia areata: A population-based case-control study in Korea
To the Editor: Studies have shown the reduced incidence of skin cancer in patients with autoimmune dermatologic diseases, including alopecia areata (AA) and vitiligo.1,2 The aim of this study was to investigate the association between AA and several types of cancer. This study was a retrospective case-control study from the National Health Insurance Service–National Sample Cohort.3 Age, sex, location, income, and diagnostic codes based on the International Classification of Diseases, 10th edition were retrieved.
http://ift.tt/2iRwMDk
Reply to: “Updated diagnostic criteria for frontal fibrosing alopecia”
To the Editor: We thank Vaño-Galvan et al for their letter regarding criteria for frontal fibrosing alopecia (FFA).1 The differential diagnosis of FFA is broad, and diagnostic criteria can aid in identifying this entity. We agree with many of the suggestions to our diagnostic criteria proposed in our article on the Mayo Clinic cohort of FFA patients.2
http://ift.tt/2B7aBDy
Decreased risk of vitiligo in organ transplant recipients: A population-based cohort study
To the Editor: Vitiligo remains a major challenge in dermatology because there is no definitive cure.1 The autoimmune nature of vitiligo has been described,2 and the involvement of T cells in pathogenesis of vitiligo has also been shown in previous reports.3 While the therapeutic potential of immunosuppressants has often been raised, their role has not been well examined.
http://ift.tt/2BD70xY
Vitiligo-like lesions in patients receiving anti–programmed cell death-1 therapies are distinct from spontaneously occurring active vitiligo
To the Editor: We would like to thank Fukuda and Harris for their interest in our manuscript.1 Clinically, we have voluntarily characterized vitiligo-like lesions induced by anti–programmed cell death-1 (PD-1) as "multiple flecked depigmented macules" to differ from the description reported for active lesions in spontaneously occurring vitiligo (referred to as vitiligo). Indeed, in vitiligo, active lesions are associated with hypomelanotic appearance and poorly defined borders2 (as shown in Fukuda et al, Fig 1), a clinical sign completely absent in vitiligo-like lesions under anti–PD-1.
http://ift.tt/2B7iBEt
Trends in Medicare spending on topical immunomodulators and chemotherapies
To the Editor: Actinic keratoses (AKs) and in situ/superficial carcinomas are common and costly dermatologic conditions that account for ≥5.2 million visits and $920 million in annual spending.1,2 Topical therapies are often used as field therapy for these conditions. In this study, we evaluate recent national trends in topical therapy use and costs for precancerous and in situ/superficial carcinomas in the Medicare population.
http://ift.tt/2BEjYM3
Acknowledging the pseudo “fringe sign” in frontal fibrosing alopecia has diagnostic and prognostic implications
To the Editor: A frontal band of scarring alopecia with eyebrow involvement in postmenopausal women (ie, frontal fibrosing alopecia [FFA]) evolved from a "recently described disease" to the status of "a growing epidemic" in less than 2 decades. Since the first report by Kossard,1 additional features and variants not contemplated in the original description have been incorporated into the clinical picture. For such, I read with great interest the paper by Rossi et al reporting 3 unusual clinical patterns of FFA.
http://ift.tt/2B7LC2P
High riding of brachiocephalic artery: A rare case of pulsatile anterior neck mass
Publication date: Available online 11 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Bao Ling Wong, Shashi Gopalan, Muhammad Nasri Abu Bakar, Ming Huei Wong
Anterior neck swellings are common presentations that are seen in otorhinolaryngology clinics. We presented a rare diagnosis of pulsatile anterior neck swelling where a high riding brachiocephalic artery needs to be considered as a differential diagnosis. This 54-year-old lady presented with anterior neck swelling for one year which appear to be pulsatile, soft and non-tender mass. Ultrasound and Doppler scan, contrast-enhanced computed tomography (CECT) scan revealed that the neck swelling corresponds to the high riding brachiocephalic artery. Hence, ultrasound scan is essential to detect any vascular lesion prior to biopsy or fine needle aspiration cytology as to avoid catastrophic hemorrhage.
http://ift.tt/2jzIne6
Placental abruption leading to hysterectomy
A 32-year-old multigravid patient at 21 weeks gestation presents with major concealed placental abruption and subsequent fetal demise. During an eventually failed misoprostol regime aiming for vaginal delivery she develops severe disseminated intravascular coagulopathy. Subsequent hysterotomy reveals Couvelaire uterus with major haemorrhage and requires subtotal hysterectomy for haemostasis. This case highlights the severity of the systemic response to abruption and fetal demise in utero and the multifactorial nature of its management.
http://ift.tt/2nPPuR5
A novel technique for superior-based pharyngeal flaps: 10-year results with formal speech outcomes assessment
Source:American Journal of Otolaryngology
Author(s): Ryan Winters, John Carter, J. Lindhe Guarisco
PurposeDescribe a novel technique for superior-based pharyngeal flaps allowing restoration of bulk to the soft palate and intraoperative fine-tuning of lateral port size, while avoiding midline palate-splitting. Validated speech assessment tools are employed for quantitative analysis.MethodsRetrospective review of all patients who underwent superior-based pharyngeal flap in a 10-year period by a single surgeon. Pittsburgh Weighted Values for Speech Symptoms Associated with VPI and the Goldman-Fristoe Test of Articulation were used for formal speech assessment.Results78 patients met inclusion criteria with clinical data up to 10years postoperatively. 31 patients had congenital velopharyngeal insufficiency (VPI), and the remainder acquired VPI after cleft palate repair or adenoidectomy. 37 patients had a recognized syndrome. All patients noted subjective improvement in nasality, and evaluation with the validated speech assessment tools demonstrated statistically significant improvement in speech. Only one flap takedown was required in a patient with severe midface hypoplasia who developed sleep apnea several years postoperatively.ConclusionsThis technique is successful in congenital and acquired VPI, and in patients with complex craniofacial syndromes. Customization of lateral ports based on preoperative nasopharyngoscopy, and avoidance of a midline palate splitting incision, make this an attractive option for superior-based flap surgery.
http://ift.tt/2jAx4lV
Gastro-pharyngeal reflux and total laryngectomy. Increasing knowledge about its management
Source:American Journal of Otolaryngology
Author(s): Giuditta Mannelli, Roberto Santoro, Francesco Segala, Elisabetta Surrenti, Oreste Gallo
PurposeInvestigate the incidence, the degree and the effect of gastro-pharyngeal reflux (GPR) in laryngectomised patients.Materials and methodsBehavioral and 24-hour pH- and impedance-monitoring data were prospectively analyzed for 25 laryngectomised patients with no previous history of GER in outpateints' setting. Reflux detected was characterized as either acid, weakly acidic or nonacid. Proximal reflux was found at 15cm above the LES.Results40% of patients presented a pathological number of reflux episodes in the upright position (p<0.0001); 9 of them presented a pathologic bolus exposure time. Bolus exposure at the proximal sphincter was one fourth-fold lower than 5cm above the LES (p=0.3593). There was a prevalence of acid reflux at both sphincters (p<0.0001); liquid reflux was prevalent at the LES (p=0.003) and mixed reflux at the UES (p=0.0001). Median REs was higher than time acid exposure (p=0.0013).ConclusionsPre- and post-surgical reflux investigation could identify preexisting reflux severity and screen potential high-risk cancer patients for postoperative complications. This might allow the early onset of acid suppressive therapy in presence of pathologic findings in high-complication risk cancer patients.
http://ift.tt/2Bg2mWp
Haploinsufficiency of A20 causes autoinflammatory and autoimmune disorders
Source:Journal of Allergy and Clinical Immunology
Author(s): Tomonori Kadowaki, Hidenori Ohnishi, Norio Kawamoto, Tomohiro Hori, Kenichi Nishimura, Chie Kobayashi, Tomonari Shigemura, Shohei Ogata, Yuzaburo Inoue, Tomoki Kawai, Eitaro Hiejima, Masatoshi Takagi, Kohsuke Imai, Ryuta Nishikomori, Shuichi Ito, Toshio Heike, Osamu Ohara, Tomohiro Morio, Toshiyuki Fukao, Hirokazu Kanegane
http://ift.tt/2jQkc8m
Long-term follow up of IPEX syndrome patients after different therapeutic strategies: an international multicenter retrospective study
Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Federica Barzaghi, Laura Cristina Amaya Hernandez, Benedicte Neven, Silvia Ricci, Zeynep Yesim Kucuk, Jack Bleesing, Zohreh Nademi, Mary Anne Slatter, Erlinda Rose Ulloa, Anna Shcherbina, Anna Roppelt, Austen Worth, Juliana Silva, Alessandro Aiuti, Luis Murguia-Favela, Carsten Speckmann, Magda Carneiro-Sampaio, Juliana Folloni Fernandes, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Ayca Kiykim, Ansgar Schulz, Sandra Steinmann, Lucia Dora Notarangelo, Eleonora Gambineri, Paolo Lionetti, William Thomas Shearer, Lisa Forbes, Caridad Martinez, Despina Moshous, Stephane Blanche, Alain Fisher, Frank M. Ruemmele, Come Tissandier, M. Ouachee-Chardin, Frédéric Rieux-Laucat, Marina Cavazzana, Waseem Qasim, Barbarella Lucarelli, Michael H. Albert, Ichiro Kobayashi, Laura Alonso, Cristina Diaz De Heredia, Hirokazu Kanegane, Anita Lawitschka, Jong Jin Seo, Marta Gonzalez-Vicent, Miguel Angel Diaz, Rakesh Kumar Goyal, Martin G. Sauer, Akif Yesilipek, Minsoo Kim, Yesim Yilmaz-Demirdag, Monica Bhatia, Julie Khlevner, Erick .J. Richmond Padilla, Silvana Martino, Davide Montin, Olaf Neth, Agueda Molinos-Quintana, Justo Valverde-Fernandez, Arnon Broides, Vered Pinsk, Antje Ballauf, Filomeen Haerynck, Victoria Bordon, Catharina Dhooge, Maria Laura Garcia-Lloret, Robbert G. Bredius, Krzysztof Kałwak, Elie Haddad, Markus Gerhard Seidel, Gregor Duckers, Sung-Yun Pai, Christopher C. Dvorak, Stephan Ehl, Franco Locatelli, Frederick Goldman, Andrew Richard Gennery, Mort J. Cowan, Maria Grazia Roncarolo, Rosa Bacchetta
BackgroundImmunedysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.ObjectiveTo evaluate disease onset, progression and long-term outcome of the two main treatments in long-term IPEX survivors.MethodsClinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed.ResultsWe confirm neonatal onset with enteropathy, type 1 diabetes (T1D), and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n=58) had a median follow-up of 2.7 years (range: 1 week - 15 years). Patients receiving chronic IS (n=34) had a median follow-up of 4 years (range: 2 months - 25 years). The overall survival (OS) after HSCT was 73.2% (95% confidence interval [CI], 59.4 to 83.0) and after IS was 65.1% (95 % CI, 62.8 to 95.8). The pre-treatment OI score was the only significant predictor of OS after transplant (p=0.035) but not under IS.ConclusionsPatients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source or conditioning regimen.
Graphical abstract
Teaser
This international retrospective multicenter study of patients with long-term IPEX syndrome (n=96) provides data on onset, disease progression, and outcomes after different treatments to inform future therapeutic choices.http://ift.tt/2kpynAJ
Efficacy of lentiviral mediated gene therapy in an Omenn syndrome Rag2 mouse model is not hindered by inflammation and immune dysregulation
Source:Journal of Allergy and Clinical Immunology
Author(s): Valentina Capo, Maria Carmina Castiello, Elena Fontana, Sara Penna, Marita Bosticardo, Elena Draghici, Luigi P. Poliani, Lucia Sergi Sergi, Rosita Rigoni, Barbara Cassani, Monica Zanussi, Paola Carrera, Paolo Uva, Kerry Dobbs, Nicolò Sacchetti, Luigi D. Notarangelo, Niek P. van Til, Gerard Wagemaker, Anna Villa
BackgroundOmenn syndrome (OS) is a rare severe combined immunodeficiency associated with autoimmunity, caused by defects of the lymphoid-specific V(D)J recombination. Most patients carry hypomorphic mutations in recombination activating genes (RAG) 1 or 2. Hematopoietic stem cell (HSC) transplantation is the standard treatment, however gene therapy (GT) may represent a valid alternative, especially for patients lacking a matched donor.ObjectiveTo determine the efficacy of lentiviral vector (LV) mediated GT in the murine model of OS (Rag2R229Q/R229Q) in correcting immunodeficiency and autoimmunity.MethodsOS Lin- cells were transduced with a LV encoding the human RAG2 gene and injected into irradiated OS recipients. Control mice were transplanted with wild-type or OS untransduced Lin- cells. Immunophenotype, T-dependent and independent antigen challenges, immune spectratyping, autoantibodies detection and detailed tissue immunohistochemical analyses were performed.ResultsLV-mediated GT allowed immunological reconstitution, although suboptimal as compared to wild type bone marrow transplanted OS mice, in peripheral blood and hematopoietic organs, such as bone marrow, thymus and spleen. We observed in vivo variability in the efficacy of GT correlating with the levels of transduction achieved. Immunoglobulin levels and T cell repertoire normalized and gene corrected mice properly responded to challenges in vivo. Autoimmune manifestations, such as skin infiltration and autoantibodies, dramatically improved in GT mice with a vector copy number/genome higher than 1 in the bone marrow and 2 in the thymus.ConclusionsOur data show that LV-mediated GT for Omenn Syndrome significantly ameliorates the immunodeficiency even in an inflammatory environment.
http://ift.tt/2kpymg9
An actin cytoskeletal barrier inhibits lytic granule release from Natural Killer cells in Chediak-Higashi syndrome
Source:Journal of Allergy and Clinical Immunology
Author(s): Aleksandra Gil-Krzewska, Mezida B. Saeed, Anna Oszmiana, Elizabeth R. Fischer, Kathryn Lagrue, William A. Gahl, Wendy J. Introne, John E. Coligan, Daniel M. Davis, Konrad Krzewski
BackgroundChediak-Higashi syndrome (CHS) is a rare disorder caused by biallelic mutations in the LYST gene, resulting in formation of giant lysosomes or lysosome-related organelles in several cell types. The disease is characterized by immunodeficiency and a fatal hemophagocytic lymphohistiocytosis due to impaired function of cytotoxic lymphocytes, mainly Natural Killer (NK) cells.ObjectiveWe sought to determine the underlying biochemical cause of the impaired cytotoxicity of NK cells in CHS.MethodsWe generated a human cell model of CHS, using CRISPR technology. We used a combination of classical techniques to evaluate lysosomal function and cell activity in the model system, and super-resolution microscopy to visualize filamentous (F-)actin and lytic granules in normal and LYST-deficient NK cells.ResultsLoss of LYST function in a human NK cell line, NK92mi, resulted in inhibition of NK cell cytotoxicity and reproduced other aspects of CHS cellular phenotype, including the presence of significantly enlarged lytic granules with defective exocytosis, and impaired integrity of endo-lysosomal compartments. The large granules had an acidic pH, normal activity of lysosomal enzymes, and were positive for the proteins essential for lytic granule exocytosis. Visualization of the actin meshwork openings at the immunological synapse revealed that the cortical actin acts as a barrier for secretion of such large granules at the cell-cell contact site. Decreasing the cortical actin density at the immunological synapse, or decreasing the lytic granule size, restored the ability of LYST-deficient NK cells to degranulate and kill target cells.ConclusionThe cortical actin and granule size play significant roles in NK cell cytotoxic function. The periodicity of sub-synaptic actin is an important factor limiting the release of large lytic granules from CHS NK cells, and could be a novel target for pharmaceutical intervention.
Teaser
The large lytic granules in Chediak-Higashi syndrome NK cells are functional, but the actin meshwork at the immunological synapse is a barrier to their exocytosis, resulting in defective CHS NK cell degranulation and cytotoxicity. Decreasing the cortical actin density, or lytic granule size, restores the ability of LYST-deficient NK cells to degranulate and kill target cells..http://ift.tt/2jQk7S6
Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting
Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Marie-Claire Arrieta, Andrea Arévalo, Leah Stiemsma, Pedro Dimitriu, Martha E. Chico, Sofia Loor, Maritza Vaca, Rozlyn C.T. Boutin, Evan Morien, Mingliang Jin, Stuart E. Turvey, Jens Walter, Laura Wegener Parfrey, Philip J. Cooper, Brett Finlay
BackgroundAsthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment.ObjectiveWe sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting.MethodsWe conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography.ResultsAs previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze.ConclusionsOur findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.
Graphical abstract
http://ift.tt/2jOEsqS
Plasmodium falciparum Recrudescence Two Years after a First Treated Uncomplicated Infection without Return in a Malaria Endemic Area [PublishAheadOfPrint]
We report here evidence, confirmed by the lack of travel activity outside of France and genetic diversity analysis using polymorphic microsatellite markers, that Plasmodium falciparum malaria infection effectively treated with an artemisinin-based combination can remain dormant and relapse during pregnancy at least 2 years after treatment.
http://ift.tt/2l0hfWb
Topical antibiotic use co-selects for the carriage of mobile genetic elements conferring resistance to unrelated antimicrobials in Staphylococcus aureus [PublishAheadOfPrint]
Topical antibiotics such as mupirocin and fusidic acid are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains.
New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences Single Molecule Real Time (SMRT) whole genome sequencing, Illumina short read sequencing and Bayesian phylogenomic modelling on 118 new multilocus sequence type 1 (ST1) community Staphylococcus aureus isolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1 S. aureus. We also provide in vitro experimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDR S. aureus isolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.
http://ift.tt/2iRy8xM
Adverse effects of intravenous vancomycin-based prophylaxis during therapy for pediatric acute myeloid leukemia [PublishAheadOfPrint]
Background Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infection, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk, but might increase risk of renal or liver toxicity, or Clostridium difficile infection (CDI).
Methods A retrospective review was conducted of patients treated for newly diagnosed AML at St. Jude Children's Research Hospital from 2002 to 2008. Nephrotoxicity was classified according to pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease (RIFLE) criteria, and hepatotoxicity according to Common Terminology Criteria for Adverse Events criteria. The risks of nephrotoxicity, hepatotoxicity and CDI were compared between patients receiving vancomycin-based prophylaxis, no intravenous prophylaxis, or other prophylaxis. Generalized linear mixed models were used to address potential confounding.
Results 392 chemotherapy courses (108 with no intravenous prophylaxis, 218 with vancomycin-based prophylaxis, and 66 with other prophylaxis) in 111 patients were included. Development of pRIFLE risk, injury, or failure occurred in 190, 44, and 2 courses, respectively. An increase in ≥1, 2, or 3 grades for hepatotoxicity occurred in 189, 52, and 19 courses, respectively. After adjusting for confounders, vancomycin-based prophylaxis was not associated with nephrotoxicity or hepatotoxicity, and reduced the risk of CDI compared to no intravenous prophylaxis (0.9% vs. 6.5%; P= 0.007) or other prophylaxis regimens (0.9% vs. 3.0%; P= 0.23).
Summary Despite concerns about vancomycin toxicity, vancomycin-based prophylaxis in pediatric patients with AML did not increase the risk of nephrotoxicity or hepatotoxicity and reduced CDI. Caution is advised to avoid contributing to antibiotic resistance.
http://ift.tt/2l0G0BI
Whole cell screen of fragment library identifies gut microbiota metabolite indole propionic acid as antitubercular [PublishAheadOfPrint]
Several key tuberculosis drugs including pyrazinamide, with a molecular weight of 123.1 g/mol, are smaller than the usual drug like molecules. Current drug discovery efforts focus on the screening of larger compounds with molecular weights centered around 400-500 g/mol. Fragment (molecular weight < 300 g/mol) libraries have not been systematically explored for antitubercular activity. Here we screened a collection of 1000 fragments, present in the Maybridge Ro3 library, for whole cell activity against Mycobacterium tuberculosis. Twenty-nine primary hits showed dose-dependent growth inhibition equal or better than pyrazinamide. The most potent hit, indole propionic acid (IPA, 3-(1H-indol-3-yl)propanoic acid), a metabolite produced by the gut microbiota, was profiled in vivo. The molecule was well tolerated in mice and showed adequate pharmacokinetic properties. In an acute mouse model of tuberculosis infection, IPA reduced the bacterial load in the spleen 7 fold. Our results suggest that IPA should be evaluated as an add-on to current regimens and that fragment libraries should be further explored to identify antimycobacterial lead candidates.
http://ift.tt/2iRy0yi
Genomic insights into Colistin Resistant Klebsiella pneumoniae from a Tunisian teaching hospital [PublishAheadOfPrint]
The emergence of colistin-resistant Klebsiella pneumoniae (CoRKp) is a public health concern since this antibiotic has become the last line of treatment for infections caused by multidrug-resistant (MDR) gram-negatives. In this study, we have investigated the molecular basis of colistin-resistance in 13 MDR Kp isolated from 12 patients in a teaching hospital in Sousse, Tunisia. Whole-genome sequencing (WGS) was used to decipher the molecular mechanism of colistin-resistance and to identify the resistome of these CoRKp. It revealed a genome of ca. 5,5 Mbp in size with a G+C content of 57% corresponding to that commonly observed for K. pneumoniae. These isolates belonged the 5 different STs (ST11, ST15, ST101, ST147, and ST392) and their resistome was composed of acquired β-lactamases including ESBLs and carbapenemases (blaCTX-M-15, blaOXA-204, blaOXA-48, blaNDM-1 genes), aminoglycoside resistance genes (aac(6')Ib-cr, aph(3' ')-Ib, aph(6)-Id, aac(3)-IIa), fosfomycin (fosA), fluoroquinolone (qnr-like), chloramphenicol, trimethoprim and tetracyclin resistance genes. All the isolates were identified as having a mutated mgrB gene. Mapping reads with reference sequences of the most common genes involved in colistin-resistance revealed several modifications in mgrB, pmr and pho operons (deletions, insertion, susbstitution, ..) likely affecting the function of these proteins. Noteworthy, among the 12 patients, 10 were treated with colistin before the isolation of CoRKp. No plasmid encoding mcr-1-5 genes were found in these isolates.
This study corresponds to the first molecular characterization of a collection of CoRKp in Tunisia, and highlights that the small transmembrane protein MgrB is a main mechanism for colistin resistance in K. pneumoniae.
http://ift.tt/2kXH7lo
Suppression of reactive-oxygen-species accumulation accounts for paradoxical bacterial survival at high quinolone concentration [PublishAheadOfPrint]
When bacterial cells are exposed to increasing concentrations of quinolone-class antibacterials, survival drops, reaches a minimum, and then recovers, sometimes to 100%. Despite decades of study, events underlying the paradoxical, high-concentration survival remain obscure. Since reactive oxygen species (ROS) have been implicated in antimicrobial lethality, conditions generating paradoxical survival were examined for diminished ROS accumulation. Escherichia coli cultures were treated with various concentrations of nalidixic acid, followed by measurement of survival, rate of protein synthesis, and ROS accumulation. The latter measurement used a dye (carboxy-H2DCFDA) that fluoresces in the presence of ROS; fluorescence was assessed by microscopy (individual cells) and flow cytometry (batch cultures). High, non-lethal concentrations of nalidixic acid induced lower levels of ROS than moderate, lethal concentrations. Sub-lethal doses of exogenous hydrogen peroxide became lethal and eliminated the nalidixic acid-associated paradoxical survival. Thus, quinolone-mediated lesions needed for ROS-executed killing persist at high, non-lethal quinolone concentrations, thereby implicating ROS as a key factor in cell death. Chloramphenicol suppressed nalidixic acid-induced ROS accumulation and blocked lethality, further supporting a role for ROS in killing. Nalidixic acid also inhibited protein synthesis, with extensive inhibition at high concentrations correlating with lower ROS accumulation and paradoxical survival. A catalase deficiency, which elevated ROS levels, overcame the inhibitory effect of chloramphenicol on nalidixic acid-mediated killing, emphasizing the importance of ROS. The data collectively indicate that ROS play a dominant role in the lethal action of first-generation, quinolone-class compounds; a drop in ROS levels accounted for the quinolone tolerance observed at very high concentrations.
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Cystatin 9 and C: A novel immunotherapy that protects against multi-drug resistant New Delhi metallo-beta-lactamase-1 producing Klebsiella pneumoniae [PublishAheadOfPrint]
Multidrug-resistant (MDR) bacterial pneumonia can induce dysregulated pulmonary and systemic inflammation leading to morbidity and mortality. Antibiotics to treat MDR pathogens do not function to modulate the extent and intensity of inflammation and can have serious side effects. Herein, we evaluate the efficacy of two human cysteine proteinase inhibitors, cystatin 9 and cystatin C, as a novel immunotherapeutic treatment to combat MDR New Delhi metallo-beta-lactamase-1 (NDM-1) producing Klebsiella pneumoniae (Kp). Our results showed mice intranasally (i.n.) infected with an LD90 challenge of NDM-1 Kp then treated with the combination of human recombinant (r) rCST9 and rCSTC (rCSTs; 50 pg of each i.n. 1h post-infection (PI) and/or 500 pg of each intraperitoneal [i.p.] 3d PI) significantly improved survival compared to infected mice alone or infected mice treated with individual rCSTs (p<0.05). Results showed that both of our optimal rCST treatment regimens modulated pulmonary and systemic pro-inflammatory cytokine secretion in the serum, lungs, livers and spleens of infected mice (p<0.05). Treatment also significantly decreased bacterial burden (p<0.05), while preserving lung integrity with reduced inflammatory cell accumulation compared to infected mice. Further, rCST treatment regimens reduced lipid peroxidation and cell apoptosis in the lungs of infected mice. Additionally, in vitro studies showed that rCSTs (50 or 500 pg of each) directly decreased the viability of NDM-1 Kp. In conclusion, these data showed that rCST9/rCSTC worked synergistically to modulate host inflammation against MDR NDM-1 Kp pneumonia, which significantly improved survival. Therefore, rCST9/rCSTC are a promising therapeutic candidate for the treatment of bacterial pneumonia.
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Elucidating the Pharmacokinetics/Pharmacodynamics of Aerosolized Colistin against Multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Mouse Lung Infection Model [PublishAheadOfPrint]
Pharmacokinetics/pharmacodynamics (PK/PD) of aerosolized colistin was investigated against Acinetobacter baumannii and Klebsiella pneumoniae over 24 h in a neutropenic mouse lung infection model. Dose fractionation studies were performed over 2.64 to 23.8 mg/kg/day, and the data were fitted to a sigmoid inhibitory model. AUC/MIC in the epithelial lining fluid was the most predictive PK/PD index for aerosolized colistin against both pathogens. Our study provides important pharmacological information for optimizing aerosolized colistin.
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Hyperbaric Oxygen Reduces Aspergillus fumigatus Proliferation In Vitro and Influences In Vivo Disease Outcomes [PublishAheadOfPrint]
Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, developing new clinical modalities as standalone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we test the in vitro and in vivo impact of hyperbaric oxygen (100% oxygen, >1 ATA) (HBO) on A. fumigatus proliferation and murine IPA outcomes. Our findings indicate that HBO reduces established fungal biofilm proliferation in vitro by over 50%. The effect of HBO under the treatment conditions was transient and fungistatic with A. fumigatus metabolic activity rebounding within six hours of HBO treatment being removed. In vivo, daily HBO provides a dose-dependent but modest improvement in murine IPA disease outcomes as measured by survival analysis. Intriguingly, no synergy was observed between sub-therapeutic voriconazole or amphotericin B and HBO in vitro or in vivo with daily HBO dosing, though loss of fungal superoxide dismutase genes enhanced HBO antifungal activity. Further studies are needed to optimize the HBO treatment regimen and better understand the effects of HBO on both the host and the pathogen during a pulmonary invasive fungal infection.
http://ift.tt/2AvHXNi
Sequencing of FKS Hot-Spot1 from Saprochaete capitata. Searching for a relationship with reduced echinocandin susceptibility. [PublishAheadOfPrint]
Saprochaete capitata, formerly known as Geotrichum capitatum, is an emerging fungal pathogen with low susceptibility to echinocandins. Here, we report the nucleotide sequence of the S. capitata Hot Spot 1 region of the FKS gene (FKS HS1) which codifies for the catalytic subunit of β-1,3-D-glucan synthase, the target of echinocandins. For that purpose, we firstly designed degenerated oligonucleotide primers derived from conserved flanking regions of the FKS1 HS1 segment of 12 different fungal species. Interestingly, the analysis of the translated FKS HS1 sequences of 12 isolates of S. capitata revealed that all of them exhibited the same substitution, F-to-L, in a position highly related to reduced echinocandins susceptibility.
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Decisional balance and self-efficacy mediate the association among provider advice, health literacy and cervical cancer screening
Publication date: February 2018
Source:European Journal of Oncology Nursing, Volume 32
Author(s): Kyounghae Kim, Qian-Li Xue, Benita Walton-Moss, Marie T. Nolan, Hae-Ra Han
PurposeHealth literacy has emerged as a potential determinant of cancer screening, yet limited literature has investigated the pathways which health literacy influences Pap tests among immigrant women who experience a higher incidence of cervical cancer. This study aimed to test a health literacy-focused sociocognitive model which proposes motivational (knowledge, decisional balance) and volitional (self-efficacy) factors mediating the association between health literacy and triennial Pap tests.MethodsUsing structural equation modeling, we conducted a secondary analysis of baseline data obtained from a randomized controlled trial to promote breast and cervical cancer screenings among 560 Korean American women 21–65 years of age. They were interviewed on demographics such as education and English proficiency, provider advice, health literacy, knowledge of cervical cancer, decisional balance for Pap tests, self-efficacy, and Pap test use.ResultsHigher health literacy predicted high level of knowledge and high decisional balance score, and greater self-efficacy and then only decisional balance and self-efficacy affected Pap tests. High level of knowledge predicted Pap tests through its impact on the decisional balance score. Receiving provider advice both directly and indirectly predicted Pap tests through high level of health literacy, high level of decisional balance and greater self-efficacy.ConclusionsFindings from this study suggest possible pathways through which provider advice and health literacy affect Pap tests. Interventions targeting immigrant women with limited English proficiency should consider skill-based approaches such as health literacy training, promoting patient-provider communications and emphasizing decisional balance and self-efficacy as potentially sustainable ways of promoting Pap tests.
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Mannitol and the blood-labyrinth barrier
Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically diffi...
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MicroRNA 143-5p regulates alpaca melanocyte migration, proliferation, and melanogenesis
Abstract
microRNAs (miRNAs) have been shown to be closely involved in the control of melanogenesis and hair colour in mammals. Previous data also indicate that miR-143 regulates cell growth in melanoma. Here, we aimed to investigate the role of miR-143-5p in alpaca melanocytes. We found that miR-143-5p was highly expressed in the cytoplasm of alpaca melanocytes as demonstrated by an in situ hybridization assay. Prediction analysis revealed that miR-143-5p could regulate TGF-β-activated kinase 1 (TAK1) expression, which we confirmed by luciferase reporter assay, indicating that miR-143-5p controls TAK1 expression by directly targeting its 3′ untranslated region (UTR). miR-143-5p overexpression decreased TAK1 expression, which led to increased melanocyte migration and proliferation, and downregulation of microphthalmia-associated transcription factor (MITF), which regulates melanin production. These results support a functional role for miR-143-5p in regulating alpaca melanocyte migration, proliferation, and melanogenesis through direct targeting of TAK1.
This article is protected by copyright. All rights reserved.
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Gastro-pharyngeal reflux and total laryngectomy. Increasing knowledge about its management
Investigate the incidence, the degree and the effect of gastro-pharyngeal reflux (GPR) in laryngectomised patients.
http://ift.tt/2AMAtSW
A novel technique for superior-based pharyngeal flaps: 10-year results with formal speech outcomes assessment
Describe a novel technique for superior-based pharyngeal flaps allowing restoration of bulk to the soft palate and intraoperative fine-tuning of lateral port size, while avoiding midline palate-splitting. Validated speech assessment tools are employed for quantitative analysis.
http://ift.tt/2BTYA1k
How to manage anaphylaxis in primary care
Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction characterized by rapidly developing airway and/or circulation problems. It presents with very different com...
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Postoperative thrombocytopenia: why you should consider antiplatelet therapy?
Purpose of review This review addresses the role of platelets in perioperative ischemic complications involving the brain, kidneys, and gastrointestinal tract, and long-term survival in patients undergoing coronary artery bypass grafting surgery. Importantly, findings of several recent clinical studies will be discussed with emphasis on platelet activation and leukocyte inflammatory responses as important mediators of vascular microthrombosis and ischemic injury. Recent findings Our recent findings suggest that in some patients, the hemostatic balance during and after surgery may shift toward a hypercoagulable state and contribute to acute organ failure. Summary For over 6 decades, major postoperative complications after cardiac surgery have remained unchanged. The potential influence of microthrombosis involving platelets has been underappreciated and use of perioperative antiplatelet therapy remains very limited – primarily because of a culture of fear of bleeding. Correspondence to Manuel L. Fontes, MD, Professor of Anesthesiology and Critical Care, Yale University School of Medicine, 333 Cedar Street, TMP-3, P.O. Box 208051, New Haven, CT 06520, USA. Tel: +1 203 785 2802; e-mail: manuel.fontes@yale.edu Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2BdAORm
http://ift.tt/2BdAORm
Perioperative steroid therapy: where's the evidence?
Purpose of review Review of historical and current evidence of adrenal suppression in patients on chronic glucocorticoid therapy during perioperative period, and discussion of current recommendations for perioperative stress dose steroid administration. Recent findings Evidence suggests low incidence of perioperative adrenal insufficiency in patients receiving chronic glucocorticoid therapy. Recent studies show no difference in survival or hemodynamic sequella by withholding perioperative stress steroids; however, these studies are limited in size and universal applicability. Summary Current recommendations for perioperative stress dose steroids for patients on chronic glucocorticoid therapy are based on duration and dose of maintenance steroids. All patients should take their regular daily dose of steroid preoperatively regardless of dose or chronicity of prior treatment. Additional, stress dose steroid dosing is based on patient risk of adrenal suppression and surgical complexity and stress. Correspondence to Leon Freudzon, MD, 333 Cedar Street, TMP 3, P.O. Box 208051, New Haven, CT 06520-8051, USA. Tel: +1 203 785 2802; e-mail: leon.freudzon@yale.edu Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2jx1m9m
http://ift.tt/2jx1m9m
Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery: A randomised controlled trial
BACKGROUND In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated. OBJECTIVES To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery. DESIGN Randomised controlled study. SETTING A tertiary hospital. PATIENTS Sixty women undergoing breast cancer surgery between April 2014 and February 2015. INTERVENTIONS The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery. MAIN OUTCOME MEASURES Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1. RESULTS PECS block combined with propofol–remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) μg ml−1; P
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http://ift.tt/2kmbGxr
Kevin Sowers is Named President of the Johns Hopkins Health System and Executive Vice President of Johns Hopkins Medicine
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When Forensic Odontology met Biochemistry: Multidisciplinary approach in Forensic Human Identification
Source:Archives of Oral Biology
Author(s): Joe Adserias-Garriga, Christian Thomas, Douglas H. Ubelaker, Sara C. Zapico
When human remains are found, the priority of the investigation is to ascertain the identity of the deceased. A positive identification is a key factor in providing closure for the family of the deceased; it is also required to issue the death certificate and therefore, to settle legal affairs. Moreover, it is difficult for any forensic investigation involving human remains to be solved without the determination of an identity. Therefore, personal identification is necessary for social, legal and forensic reasons.In the last thirty years forensic odontology has experienced an important transformation, from primarily involving occasional dental identification into a broader role, contributing to the determination of the biological profile. In the same way, "DNA fingerprinting" has evolved not only in terms of improving its technology, but also in its application beyond the "classical": helping with the estimation of sex, age and ancestry. As these two forensic disciplines have developed independently, their pathways have crossed several times through human identification operations, especially the ones that require a multidisciplinary approach. Thus, the aim of this review is to describe the contributions of both forensic odontology and molecular biology/biochemistry to human identification, demonstrating how a multidisciplinary approach can lead to a better and more efficient identification.
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ETosis-derived DNA trap production in middle ear effusion is a common feature of eosinophilic otitis media
Publication date: Available online 11 December 2017
Source:Allergology International
Author(s): Nobuo Ohta, Shigeharu Ueki, Yasunori Konno, Makoto Hirokawa, Toshinori Kubota, Sachiko Tomioka-Matsutani, Takahiro Suzuki, Yusuke Ishida, Tasuku Kawano, Tomomitsu Miyasaka, Tomoko Takahashi, Tatsutoshi Suzuki, Isao Ohno, Seiji Kakehata, Shigeharu Fujieda
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Recent advances in understanding the roles of blood platelets in the pathogenesis of allergic inflammation and bronchial asthma
Publication date: Available online 11 December 2017
Source:Allergology International
Author(s): Tomohiro Takeda, Hideaki Morita, Hirohisa Saito, Kenji Matsumoto, Akio Matsuda
Platelets play an essential role in hemostasis to minimize blood loss due to traumatic injury. In addition, they contain various immune-associated molecules and contribute to immunological barrier formation at sites of vascular injury, thereby protecting against invading pathogens. Platelets are also crucially involved in development of allergic diseases, including bronchial asthma. Platelets in asthmatics are more activated than those in healthy individuals. By using a murine asthma model, platelets were shown to be actively involved in progression of the disease, including in airway eosinophilia and airway remodeling. In the asthmatic airway, pathological microvascular angiogenesis, a component of airway remodeling, is commonly observed, and the degree of abnormality is significantly associated with disease severity. Therefore, in order to repair the newly formed and structurally fragile blood vessels under inflammatory conditions, platelets may be continuously activated in asthmatics. Importantly, platelets constitutively express IL-33 protein, an alarmin cytokine that is essential for development of bronchial asthma. Meanwhile, the concept of development of allergic diseases has recently changed dramatically, and allergy researchers now share a belief in the centrality of epithelial barrier functions. In particular, IL-33 released from epithelial barrier tissue at sites of eczema can activate the antigen-non-specific innate immune system as an alarmin that is believed to be necessary for subsequent antigen-specific acquired immunological responses. From this perspective, we propose in this review a possible mechanism for how activated platelets act as an alarmin in development of bronchial asthma.
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Molecular Testing for Oncogenic Gene Alterations in Pediatric Thyroid Lesions
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Mannitol and the blood-labyrinth barrier
Abstract
Background
Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically difficult to perform. In this report, we demonstrated a unique method of controlling the BLB, and established the pharmacokinetics of gentamicin in perilymph, cerebrospinal fluid (CSF) and blood with and without mannitol.
Study design
Controlled animal research project.
Methods
Permeability of the BLB and the blood brain barrier (BBB) to gentamicin with and without mannitol was studied by collecting 175 samples from 44 guinea pigs using concentrations relevant to human clinical situations. Samples were taken from two groups of 22 animals, with each animal undergoing sampling at a different time after administration of either 10 mg/ml gentamicin (4 mg/kg) (Gardena, CA) alone or gentamicin with 20% mannitol (250 mg/kg) (Mallinckrodt Inc., KY). The sample times varied from 0.5 to 17.5 h post-infusion. Samples were also taken from 4 animals as negative controls after administration of normal saline. Our goal was to simultaneously assess the pharmacokinetics of gentamicin in each of three different fluid samples in the same animal. Thus at the pre-determined post-infusion sampling time, each animal was sampled once for perilymph, CSF, and blood before being euthanized. Each animal contributed to a single time point on the subsequent pharmacokinetic curves with more than one animal per time point.
Results
Mannitol increased the rate of entry and egress of gentamicin through BLB significantly (p = 0.0044) but the effects on the BBB did not reach statistical significance (p = 0.581). Mannitol did not alter renal clearance of gentamicin from the blood (p = 0.433). The concentration of gentamicin in perilymph and CSF was always significantly lower than in blood.
Conclusions
Mannitol administration transiently increases the permeability of the BLB. Potential clinical benefits may accrue from selected timing of administration of osmotic agents such as mannitol augmenting the rate of entry and egress of compounds such as gentamicin into and out of perilymph.
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Comprehensive analysis of ectopic mandibular third molar: a rare clinical entity revisited
Abstract
Background
Ectopic mandibular third molar is a rare clinical entity with incompletely known etiology. Here, we sought to delineate its epidemiological, clinical and radiographic characteristics, and therapy by integrating and analyzing the cases treated in our institution together with previously reported cases.
Method
A new definition and classification for ectopic mandibular third molar was proposed based on its anatomic location on panoramic images. Thirty-eight ectopic mandibular third molars in 37 patients and 51 teeth in 49 patients were identified in our disease registry and from literature (1990–2016), respectively. These cases were further categorized and compared according to our classification protocol. The demographic, clinicopathological and radiographic data were collected and analyzed.
Results
These ectopic teeth were categorized into four levels, 33 in level I(upper ramus), 32 in level II (middle ramus), 15 in level III (mandibular angle) and 9 in level IV (mandibular body). The common clinical presentations included pain, swelling and limited mouth opening, although sometimes asymptomatic. Most teeth were associated with pathological lesions. Treatments included clinical monitor and surgical removal by intra- or extraoral approach with favorable outcomes. Clinical presentations and treatment options for these teeth were significantly associated with their ectopic locations as we classified.
Conclusions
Ectopic mandibular third molars are usually found in patients with middle ages and in upper and middle ramus of mandible. Surgery is preferred to remove these ectopic teeth and associated pathologies when possible.
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Challenges of Vaccine Development for Zika Virus
Viral Immunology , Vol. 0, No. 0.
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Increased histopathological yield for granulomatosis with polyangiitis based on nasal endoscopy of suspected active lesions
Abstract
Purpose
To present the results of an endoscopic and histopathologic evaluation of suspected nasal active granulomatosis with polyangiits (GPA) lesions, describe them as seen by the ENT specialist, and propose a guide for tissue sampling of the nasal cavity to improve the yield of confirmatory histology.
Methods
Randomly selected patients seen from December 1997–October 2007 had a thorough endoscopic nasal evaluation, preceded by careful cleansing of the nasal cavity. Endoscopic lesions were described; sensitivities, specificities, and predictive values of the composites of endoscopic and histological activity were determined.
Results
Six lesions, some not previously described in detail, were observed: white submucosal nodules, mucosal swelling, polypoid nodules, vascular submucosal dilatations, bloody submucosal patches, and ulcers. Of these, polypoid nodules (PPV 100%), persistent white submucosal nodules (PPV 81%), and bloody submucosal patches (PPV 93%) had the better diagnostic performance with confirmed histological diagnosis.
Conclusions
Careful nasal cavity preparation, observation, and description of the nasal mucosa can guide tissue sampling documenting active GPA. This can lead to a better histological yield when definitive proof of the disease is needed.
http://ift.tt/2B4pJBy
Expression and enzyme activity of Cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue engineered skin equivalents
Abstract
CYP3A4 and CYP4A5 share specificity for a wide range of xenobiotics with the CYP3 subfamily collectively involved in the biotransformation of approximately 30% of all drugs. CYP3A4/5 mRNA transcripts have been reported in the skin yet knowledge of their protein expression and function is lacking. In this study, we observed gene and protein expression of CYP3A4/5 in both human skin and tissue-engineered skin equivalents (TESE), and enzyme activity was detected using the model substrate benzyl-O-methyl-cyanocoumarin. Mass spectrometric analysis of TESE lysates following testosterone application revealed a time-dependent increase in metabolite production, confirming the functional expression of these enzymes in skin.
This article is protected by copyright. All rights reserved.
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Neck Dissection vs Radiotherapy for Cervical Metastases in Advanced Hypopharyngeal Cancer
Condition: Hypopharyngeal Carcinoma
Interventions: Procedure: Neck dissection followed by radiotherapy(50Gy) according to risk factors; Radiation: Definitive radiotherapy
Sponsors: Tianjin Medical University Cancer Institute and Hospital; Tianjin Medical University Second Hospital; Tianjin Medical University General Hospital
Not yet recruiting
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Interventions: Procedure: Neck dissection followed by radiotherapy(50Gy) according to risk factors; Radiation: Definitive radiotherapy
Sponsors: Tianjin Medical University Cancer Institute and Hospital; Tianjin Medical University Second Hospital; Tianjin Medical University General Hospital
Not yet recruiting
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Dose‐Effect Relation of Salivary Gland Irradiation
Condition: HNSCC
Intervention: Device: PSMA PET/CT-scan
Sponsor: The Netherlands Cancer Institute
Recruiting
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Intervention: Device: PSMA PET/CT-scan
Sponsor: The Netherlands Cancer Institute
Recruiting
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Bioethicists Call For Caution in Use of Rare Experimental Fetal Therapy
Citing uncertainties about the risks and benefits of an experimental therapy for fetuses whose kidneys do not develop, bioethicists at Johns Hopkins and a team of medical experts are calling for rigorous clinical trials in the use of a potential treatment, known as amnioinfusion.
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Lebensqualität und Schwindel bei bilateraler Cochleaimplantation
Zusammenfassung
Hintergrund
Persistierende Schwindelbeschwerden nach Cochleaimplantation sind bekannte Einflussfaktoren auf die Lebensqualität. Mit in diesen Patientenkollektiven bisher nur teilweise eingesetzten Fragebogeninstrumenten werden die Effekte einer bilateralen Versorgung mit einem Cochleaimplantat (CI) auf die Lebensqualität sowie subjektive Schwindelbeschwerden analysiert.
Ziel der Arbeit
Es sollte untersucht werden, ob Fragebogeninstrumente eine erfolgreiche Methode zur Dokumentation von Schwindelbeschwerden und der Lebensqualität im Rahmen der Qualitätssicherung darstellen.
Material und Methoden
Es wurden 32 bilateral versorgte CI-Patienten bezüglich ihrer Schwindelsymptomatik und Lebensqualität befragt. Dabei kam der Nijmegen-Cochlear-Implant-Fragebogen (NCIQ) zum Einsatz. Bei berichteten, regelmäßigen Schwindelbeschwerden wurden zusätzlich der Schwindel-Handicap-Fragebogen (VHQ) und der Vertigo-Symptom-Scale(VSS)-Fragebogen erhoben.
Ergebnisse
Acht von 32 Patienten zeigten persistierende Schwindelbeschwerden. Die Lebensqualität, gemessen mit dem NCIQ, verbesserte sich signifikant (p < 0,001) um 23,7 % durch eine Versorgung mit dem zweiten CI. Die Schwindelbeschwerden veränderten sich geringfügig (VHQ –11,2 %; VSS +16,4%) nach der zweiten Implantation.
Schlussfolgerung
Die Ergebnisse zeigen, dass mit den Fragebögen praktikable Instrumente vorliegen, mit denen sich Lebensqualität und Schwindelbeschwerden zur Qualitätssicherung dokumentieren lassen und die möglicherweise ergänzend oder alternativ zur apparativen Schwindeldiagnostik sinnvoll angewendet werden können.
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Prospective transfrontal sheep model of skull-base reconstruction using vascularized mucosa
Background
No high-fidelity animal model exists to examine prospective wound healing following vascularized reconstruction of the skull base. Such a model would require the ability to study the prospective behavior of vascularized mucosal repairs of large dural and arachnoid defects within the intranasal environment. The objective of this study was to therefore develop and validate a novel, in vivo, transfrontal sheep model of cranial base repair using vascularized sinonasal mucosa.
Methods
Twelve transfrontal craniotomy and 1.5-cm durotomy reconstructions were performed in 60-kg to 70-kg Dorset/Ovis Aries sheep using vascularized mucosa with or without an adjunctive Biodesign™ underlay graft (n = 6 per group). Histologic outcomes were graded (scale, 0 to 4) by a blinded veterinary histopathologist after 7, 14, and 28 days for a range of wound healing parameters.
Results
All sheep tolerated the surgery, which required 148 ± 33 minutes. By day 7, the mucosa was fully adherent with complete partitioning of the sinus and intracranial compartments. Fibroblast infiltration and flap neovascularization scores significantly increased between day 7 (0.3 ± 0.5 and 0.0 ± 0.0) and day 28 (4.0 ± 0.0, p = 0.01 and 2.0 ± 0.8, p = 0.01; respectively), while hemorrhage scores significantly decreased from 2.5 ± 0.6 to 0.0 ± 0.0 (p = 0.01). The inflammatory scores were not significantly different between the heterologous graft and control sides.
Conclusion
The described sheep model accurately reflects prospective intranasal wound healing following vascularized mucosal reconstruction of dural defects. This model can be used in future studies to examine novel reconstructive materials, tissue glues, and transmucosal drug delivery to the central nervous system.
http://ift.tt/2Atf5oM
The prevalence of Eustachian tube dysfunction symptoms in patients with chronic rhinosinusitis
Background
While Eustachian tube dysfunction (ETD) is a known comorbidity of chronic rhinosinusitis (CRS), the prevalence of ETD symptoms in the CRS population is poorly understood. We sought to determine the cross-sectional prevalence of ETD in patients with CRS using the validated Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and to correlate ETDQ-7 scores with 22-item Sino-Nasal Outcome Test (SNOT-22) scores, endoscopy scores, and computed tomography (CT) scores.
Methods
A total of 101 patients with confirmed CRS completed the ETDQ-7 and SNOT-22 at their initial visit to our rhinology clinic. Lund-Mackay CT and Lund-Kennedy endoscopy scores were also obtained. Spearman's correlation coefficient (ρ) was calculated.
Results
Among the 101 patients, 49 patients (48.5%) had an ETDQ-7 score of ≥14.5, signifying clinically significant ETD. The mean ± standard deviation (SD) ETDQ-7 score of the entire cohort was 17.8 ± 10.1. There was a moderately strong correlation between ETDQ-7 and the SNOT-22 ear subdomain (ρ = 0.691, p < 0.001). The correlation coefficient between ETDQ-7 and total SNOT-22 scores was ρ = 0.491 (p < 0.001), indicating moderate correlation. ETDQ-7 scores were poorly correlated to objective measures of sinonasal disease, including Lund-Mackay CT score (ρ = −0.055, p = 0.594) and Lund-Kennedy endoscopy score (ρ = −0.099, p = 0.334).
Conclusion
Symptoms of ETD are highly prevalent among patients with CRS as documented by patient-reported outcome measures. The correlation between ETDQ-7 scores and SNOT-22 ear subdomain scores is moderately strong, while the correlation between ETDQ-7 scores and SNOT-22 scores is moderate. ETD severity does not correlate with CT score or nasal endoscopy score.
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The association of air pollutants and allergic and nonallergic rhinitis in chronic rhinosinusitis
Background
There has been little investigation regarding air quality and rhinitis in the pathophysiology of upper airway disease. In this study, we assessed the impact of inhalant pollutants (particulate matter 2.5 [PM2.5] and black carbon [BC]) on allergic rhinitis and chronic rhinosinusitis (CRS) disease severity.
Methods
CRS patients with nasal polyps (CRSwNP) and without polyps (CRSsNP) were identified. Spatial modeling from pollutant monitoring sites was used to estimate exposures for patients meeting the inclusion criteria (total, n = 125; CRSsNP, n = 67; CRSsNP, n = 58). Skin-prick, intradermal dilutional, and in-vitro testing methods were utilized to determine aeroallergen sensitization. Disease severity indicators were measured by modified Lund-Mackay score (LMS), the 22-item Sino-Nasal Outcome Test (SNOT-22), systemic steroid therapy, and number of functional endoscopic sinus surgeries (FESS).
Results
Thirty-six percent (n = 45) of patients who described rhinitis symptoms demonstrated no reactivity to aeroallergen testing. Sixty-four percent (n = 80) tested positive for at least 1 allergen, with no differences found between CRSsNP and CRSwNP (62.1% vs 67.2%). There were significant differences in air pollutants between patients testing negative and positive for allergies (nonallergic vs allergic: PM2.5, 11.32 vs 11.07 μg/m3, p = 0.030; BC, 0.81 vs 0.76 absorbance, p =0.044). Nonallergic CRSwNP demonstrated higher PM2.5 compared with allergic counterparts (11.48 vs 11.09 μg/m3, p = 0.032). A similar pattern was observed with BC (0.82 vs 0.75 absorbance, p = 0.017). In CRSsNP, BC correlated significantly with SNOT-22 (r = 0.55, p = 0.042).
Conclusion
Our results suggest that small inhalant pollutants may contribute to nonallergic symptomatology in patients with and without nasal polyps. Regardless of allergy status, BC may play a role in CRS symptom severity.
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