Αρχειοθήκη ιστολογίου

Πέμπτη 12 Οκτωβρίου 2017

The nose as a predilection site of pemphigus



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A rare vulval manifestation of acrochordons in a young woman



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Schnitzler syndrome: A rare cause of chronic recalcitrant urticaria successfully treated with Anakinra



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Nuclear Magnetic Resonance-Assisted Metabolic Analysis of Plasma for Mild Gestational Diabetes Mellitus Patients

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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A concealed giant peritonsillolith masquerading as oropharyngeal tumor

Publication date: Available online 12 October 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Boon Chye Gan, Irfan Mohamad, Norhafiza Mat Lazim




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2017 ATA Annual Alliance for Patient Education Public Health Forum

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2017 ATA Annual Alliance for Patient Education Public Health Forum – Saturday, October 21, 2017

October 11, 2017– The public is invited to attend a free public health forum focused on thyroid disease, in which leading physicians will be present to discuss and answer questions about different types of thyroid disorders and symptoms. The informational forum is free and open to the public. Walk-in attendance is welcome although reservations are encouraged. The public forum is sponsored and organized by the American Thyroid Association (ATA) and will take place Saturday, October 21, 2017, 2:00-4:00pm at the The Fairmont Empress, Victoria, BC, Canada. Endocrinologists and Thyroid Patient Support Groups will be available to meet with thyroid patients during the forum.

Who Should Attend?

Anyone who has or cares for someone with an overactive or underactive thyroid, thyroiditis, a thyroid nodule, thyroid cancer, or a family history of thyroid problems or related disorders, including rheumatoid arthritis, juvenile diabetes, pernicious anemia, or prematurely gray hair (starting before age 30).

Do you have questions or concerns about thyroid disease? Have you experienced any of the following symptoms and wonder if they might be related to a thyroid disorder: low energy, memory loss, fatigue, depression, rapid heartbeat, restlessness, infertility, weight or hair changes, or a lump in your neck?

Anyone with questions, symptoms, or concerns about a thyroid problem should join ATA physician experts at the free public form on Saturday, October 21st. Free educational materials will be available.

Do I Need to Register?

Reservations are requested. To register or for more information, please e-mail: thyroid@thyroid.org

(Please indicate in your message the thyroid condition you are most concerned about.)

Walk-ins welcome! Please come if you have questions, symptoms, or concerns about a thyroid problem.  More information about thyroid disease and thyroid cancer is available at www.thyroid.org. Join Friends of the ATA and receive news of the latest thyroid research.

Flyer for Printing and Posting (PDF File 136 KB)

The post 2017 ATA Annual Alliance for Patient Education Public Health Forum appeared first on American Thyroid Association.



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Effect of various durations of smoking cessation on postoperative outcomes: A retrospective cohort analysis.

BACKGROUND: Preoperative smoking cessation is commonly advised in an effort to improve postoperative outcomes. However, it remains unclear for how long smoking cessation is necessary, and even whether a brief preoperative period of abstinence is helpful and well tolerated. OBJECTIVE: We evaluated associations between various periods of preoperative smoking cessation and major morbidity and death. DESIGN: Retrospective cohort analysis. SETTING: Adults who had noncardiac surgery at the Cleveland Clinic Main Campus between May 2007 and December 2013. PATIENTS: A total of 37 511 patients whose smoking history was identified from a preoperative Health Quest questionnaire. Of these patients, 26 269 (70%) were former smokers and 11 242 (30%) were current smokers. Of the current smokers, 9482 (84%) were propensity matched with 9482 former smokers (36%). We excluded patients with American Society of Anesthesiologists' physical status exceeding four, patients who did not have general anaesthesia, and patients with missing outcomes and/or covariables. When multiple procedures were performed within the study period, only the first operation for each patient was included in the analysis. MAIN OUTCOME MEASURES: The relationship between smoking cessation and in-hospital morbidity/mortality. RESULTS: The incidence of the primary composite of in-hospital morbidity/mortality was 6.9% (656/9482) for all former smokers; the incidence was 7.8% (152/1951) for patients who stopped smoking less than 1 year before surgery, 6.3% (118/1977) for 1 to 5 years, 7.2% (115/1596) for 5 to 10 years and 6.9% (271/3457) for more than 10 years. CONCLUSION: Smoking cessation was associated with reduced in-hospital morbidity and mortality which was independent of cessation interval. (C) 2017 European Society of Anaesthesiology

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Influence of the Polymorphism C-509T in the TGFB1 Gene Promoter on the Response to Montelukast

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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Hyperpigmentation cutanée induite par le méropénème et la lévofloxacine

Publication date: Available online 12 October 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): E. Garval, V. Vuiblet, A. Durlach, G. Perceau, D. Anuset, P. Bernard
IntroductionLe méropénème (carbapénème) est un antibiotique rarement prescrit. Des effets secondaires cutanés ont été rapportés à type d'exanthème, de prurit, d'urticaire et de syndromes de Lyell ou de Stevens–Johnson. La lévofloxacine (fluoroquinolone), antibiotique largement prescrit, partage les mêmes effets secondaires cutanés, auxquels s'ajoute une action photosensibilisante. Nous rapportons un cas d'hyperpigmentation cutanée noirâtre induite par l'association de méropénème et de lévofloxacine.ObservationUn homme de 67 ans était traité par méropénème (1g×4/j), lévofloxacine (500mg×2/j) et amikacine (500mg/j) pendant 2 semaines, puis méropénème, lévofloxacine et rifampicine (600mg×2/j) pendant 4 semaines, pour une ostéite du cinquième métatarsien. Trois semaines après le début de l'antibiothérapie, une pigmentation noirâtre apparaissait, prédominant à la face antérieure des jambes. La biopsie cutanée révélait un dépôt noirâtre du derme superficiel et moyen, périvasculaire et interstitiel, coloré par les colorations de Fontana et de Perls. L'étude en microspectroscopie infrarouge permettait d'identifier la molécule de méropénème dans le derme. Après arrêt des antibiotiques, la pigmentation régressait lentement.DiscussionDes cas similaires d'hyperpigmentation cutanée noirâtre ont été rapportés après utilisation de minocycline. Dans ces cas, l'analyse histologique montrait également des dépôts dermiques de fer et/ou de mélanine, mais la nature du pigment responsable restait incertaine. Dans notre cas, l'analyse en spectroscopie infrarouge a permis de localiser le méropénème dans le derme. Deux cas d'hyperpigmentation cutanée ont été rapportés après utilisation de la lévofloxacine, avec une analyse histologique similaire.BackgroundVarious cutaneous side–effects, including, exanthema, pruritus, urticaria and Lyell or Stevens–Johnson syndrome, have been reported with meropenem (carbapenem), a rarely-prescribed antibiotic. Levofloxacin (fluoroquinolone), a more frequently prescribed antibiotic, has similar cutaneous side–effects, as well as photosensitivity. We report a case of cutaneous hyperpigmentation induced by meropenem and levofloxacin.Patients and methodsA 67-year-old male was treated with meropenem (1g×4 daily), levofloxacin (500mg twice daily) and amikacin (500mg daily) for 2 weeks, followed by meropenem, levofloxacin and rifampicin (600mg twice daily) for 4 weeks for osteitis of the fifth metatarsal. Three weeks after initiation of antibiotic therapy, dark hyperpigmentation appeared on the lower limbs, predominantly on the anterior aspects of the legs. Histology revealed dark, perivascular and interstitial deposits throughout the dermis, which stained with both Fontana–Masson and Perls stains. Infrared microspectroscopy revealed meropenem in the dermis of involved skin. After withdrawal of the antibiotics, the pigmentation subsided slowly.DiscussionSimilar cases of cutaneous hyperpigmentation have been reported after use of minocycline. In these cases, histological examination also showed iron and/or melanin deposits within the dermis, but the nature of the causative pigment remains unclear. In our case, infrared spectroscopy enabled us to identify meropenem in the dermis. Two cases of cutaneous hyperpigmentation have been reported following use of levofloxacin, and the results of histological examination were similar. This is the first case of cutaneous hyperpigmentation induced by meropenem.



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Isolated sphenoid sinus opacifications: a systematic review and meta-analysis

Background

Isolated sphenoid sinus opacifications (ISSOs) represent a relatively uncommon disease with the potential for serious complications. To better understand this disease, we performed a systematic review to further characterize the underlying pathologies, associated symptoms, and treatment outcomes of patients with ISSOs.

Methods

A systematic review of ISSO case series was performed utilizing the Medline, Embase, Web of Science, and Cochrane databases in accordance with guidelines established by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Data of interest included disease pathology, associated symptoms, and treatment outcomes.

Results

Of the initial 1051 hits from the 4 databases, 17 articles, with a combined 1133 ISSO patients, were ultimately included in the review. On a weighted analysis, the underlying pathologies were classified as chronic rhinosinusitis without nasal polyps (CRSsNP) (28.3%), mucoceles (20.3%), fungal sinusitis (12.5%), malignant neoplasms (7.7%), intracranial lesions (7.0%), benign neoplasms (5.7%), chronic rhinosinusitis with nasal polyps (CRSwNP) (3.4%), and other lesions (4.7%). Cranial neuropathies were present in 16.3% (95% confidence interval [CI], 10.1-22.5%) of ISSO patients. A favorable surgical complication rate of 1.5% (95% CI, −0.1% to 3.2%) was found in patients undergoing surgery for an ISSO.

Conclusion

ISSOs are caused by diverse pathologies. Given the considerable rates of neoplastic disease and cranial neuropathies, patients affected by an ISSO should be monitored closely and treated aggressively. Prompt surgical intervention, with either diagnostic or therapeutic intent, is often indicated.



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In vitro safety evaluation of human nasal epithelial cell monolayers exposed to carrageenan sinus wash

Background

Carrageenans have shown to reduce the viral load in nasal secretions and lower the incidence of secondary infections in children with common cold. Despite the widespread use of carrageenans in topical applications, the effect of carrageenans on the sinonasal epithelial barrier has not been elucidated. We investigate the effect of different carrageenans on the sinonasal epithelial barrier and inflammatory response in vitro.

Methods

Iota and Kappa carrageenan delivered in saline irrigation solutions applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells from chronic rhinosinusitis patients and controls. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER) and immunolocalization of F actin. Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied.

Results

Kappa or Iota carrageenan in the different solutions was not toxic, did not have detrimental effects on epithelial barrier structure and CBF. Rather, application of Kappa carrageenan significantly increased TEER and suppressed interleukin 6 (IL-6) secretion in ALI cultures from CRS patients.

Conclusion

Kappa or Iota carrageenan solution was safe and did not negatively affect epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6 production in CRS patients, indicating positive effects on epithelial barrier function in vitro.



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Allergen immunotherapy: exploring areas for further inquiry

Background

Allergy-related illness impacts millions of individuals worldwide. Our objectives were to characterize current trends of clinical trials research relating to allergen immunotherapy and to describe the landscape of allergen immunotherapy in National Institutes of Health (NIH)-supported research inquiry.

Methods

On ClinicalTrials.gov, the following terms were searched: allergen immunotherapy OR allergy immunotherapy. Variables, including completion status, dates, design, study population, funder, location, and allergen were recorded. The NIH Research Portfolio Online Reporting Tools (RePORTER) system was also used to gather relevant variables.

Results

A total of 372 clinical trials met inclusion criteria. The proportion of industry-funded clinical trials has declined over 15 years. There has been a slow decline in pollen allergy immunotherapy research, with an increase in both food and animal allergy immunotherapy research. Otolaryngologists comprised only 6.4% of clinical trials principal investigators (PIs). There was a total adjusted NIH funding of $74,986,125 for the 118 total funding years.

Conclusion

Despite an immense interest in allergen immunotherapy, this analysis demonstrates that otolaryngologists represented a small proportion of PIs leading associated clinical trials and basic science inquiry. The proportion of trials with industry sponsorship has declined considerably in recent decades. These trends could help direct future resource allocation for allergen immunotherapy.



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Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment

Abstract

The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.



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Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment

Abstract

The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.



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Corrigendum to “Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma” [Oral Oncol. 73 (2017) 118–123]

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Publication date: Available online 12 October 2017
Source:Oral Oncology
Author(s): Mingyao Wu, Dan Ou, Xiayun He, Chaosu Hu
ObjectivesTo evaluate long-term results of a phase II study of induction and adjuvant gemcitabine and cisplatin (GP) chemotherapy with intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC).Materials and methodsOne hundred and twelve patients (Stage III: 65, IVA-B: 47) with locoregionally advanced NPC were enrolled in this study. All patients received induction chemotherapy consisting of 1000 mg/m2 gemcitabine on day 1 and 8, and cisplatin 25 mg/m2 on day 1–3, every 3 weeks for 2 cycles. Adjuvant chemotherapy for 2 cycles of the same regime was given 28 days after the end of IMRT. The IMRT technique was utilized for all patients.ResultsIn total, 97.3% patients completed 2 cycles of induction chemotherapy. The overall response rate (RR) of cervical lymph nodes was 89.0%. Acute toxicities were mainly grade 1–2 myleosuppression and vomiting. And 83.9% patients completed 2 cycles of adjuvant chemotherapy. All patients finished IMRT with RR at the end of IMRT for nasopharynx, lymph nodes of neck and retropharyngeal area being 99.1%, 97.9% and 97.7%, respectively. The 5-year local control, regional control, distant metastasis-free and overall survival rates were 93.2%, 92.3%, 89.0% and 82.1%, respectively. The 5-year overall survival of stage III and IVA-B were 87.0%, and 75.5%, respectively. The incidence of grade 3–4 acute radiotherapy-related mucositis was 28.6%. Severe late toxicities were uncommon.ConclusionIMRT combined with GP for locoregionally advanced NPC is well tolerated, effective, and convenient, and warrants further studies.



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Snail-mediated cancer stem cell-like phenotype in human CNE2 nasopharyngeal carcinoma cell

Abstract

Background

Cancer stem cell (CSC)-like phenotype, which has been proven to play a critical role in invasion and metastasis of many kinds of cancers, has also been reported to be associated with epithelial-mesenchymal transition. Snail, a potent repressor of E-cadherin expression, was found to have a function to regulate the aforementioned processes.

Methods

In the current study, expression of putative CSCs biomarkers and the ratio of CSC-like CNE2 (cancer cell line) in total CNE2 were measured, and CSC-like characteristics were analyzed with tumor-sphere self-renewal and colony-forming assays. Migration and invasion properties were determined by using transwell and wound healing assays. Xenograft tumor assays in vivo were done to evaluate the function of Snail and radiation in the tumor forming ability.

Results

In human nasopharyngeal carcinoma (NPC) cells, overexpression of Snail mediates a CSC-like phenotype, which enhances the initiation, invasion, and migration ability of cancer cells.

Conclusion

Thus, Snail is a potential therapeutic target in NPC.



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Study of Niraparib or Carboplatin-Paclitaxel in Combination With TSR-042

Conditions:   Metastatic Cancer;   Advanced Cancer;   Solid Tumor
Interventions:   Drug: Niraparib;   Drug: TSR-042;   Drug: Carboplatin-Paclitaxel
Sponsor:   Tesaro, Inc.
Not yet recruiting

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Assessment of Metabolic & Path Response w/ RCT & ImT Before Surgery in Locally Advanced Esoph and Gastro-esoph Jction CA

Conditions:   Adenocarcinoma of the Esophagus;   Adenocarcinoma of the Gastroesophageal Junction;   Squamous Cell Carcinoma of the Esophagus
Interventions:   Drug: Monalizumab;   Drug: Oxaliplatin;   Drug: 5-Fluorouracil;   Radiation: Metabolic;   Other: Metabolic;   Procedure: Surgery
Sponsors:   Jules Bordet Institute;   Innate Pharma
Recruiting

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Phase III Study of Simultaneous Integrated Boost Radiotherapy (SIB-IMRT) With or Without Concurrent Chemotherapy for Locally Advanced Esophageal Cancer - 3JECROG-P02

Condition:   Esophageal Neoplasms
Interventions:   Radiation: SIB-IMRT;   Drug: Paclitaxel;   Drug: Platinum-Based Drug
Sponsors:   Chinese Academy of Medical Sciences;   Hebei Medical University Fourth Hospital;   Tianjin Medical University Cancer Institute and Hospital;   Anyang Tumor Hospital;   The First Affiliated Hospital with Nanjing Medical University;   Affiliated Hospital of Hebei University;   Fujian Cancer Hospital;   Sichuan Cancer Hospital and Research Institute
Recruiting

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Thyroid Ultrasound Elasticity (TrUE) Imaging

Condition:   Cancer, Thyroid
Interventions:   Diagnostic Test: Ultrasound;   Diagnostic Test: Shear wave elasticity imaging;   Diagnostic Test: Multi-angle compound shear wave elasticity imaging
Sponsor:   Emory University
Not yet recruiting

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Paediatric anaesthesia for low-resource settings

1H022A033J02

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Endocrine problems in the critically ill 2: endocrine emergencies

1A012C013J02

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Intraoperative ventilation and postoperative respiratory assistance

1A013C01

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Endocrine problems in the critically ill 1: diabetes and glycaemic control

1A012C013J02

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Cardiomyopathy and anaesthesia

1A012A033J02

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Post-tonsillectomy dietary advice and haemorrhage risk: Systematic review

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Publication date: December 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 103
Author(s): Miles Bannister, Chris Thompson
ObjectivesTonsillectomy remains one of the commonest operations performed in children. Post-operative diet may affect post-tonsillectomy haemorrhage rate, although post-operative dietary advice varies. We undertook a systematic review of the published literature to assess if and how different post-operative diets were associated with differences in PTH rates following paediatric tonsillectomy, to provide an evidence base to inform individual otorhinolaryngologists' practice and for future guideline development.MethodsA systematic review of the published English literature of the PubMed, Medline and Cochrane Collaboration databases, using search terms used included 'post-tonsillectomy', 'diet', 'dietary advice', 'bleeding', 'haemorrhage', 'paediatric' &'children'.ResultsEight publications were included in the review, including 5 randomised controlled trials, 2 case-control studies and 1 cohort study. These involved 1039 patients with 545 patients following a restricted/non-additive diet after tonsillectomy and 494 patients following an unrestricted/additive diet. The average reported PTH rate of patients in the restricted diet groups was 2.3% and 0.8% in patients in the unrestricted diet groups, which is not statistically significant (p = 0.12, one tailed t-test).ConclusionPTH following paediatric surgery does not appear to be affected by different post-operative diets or regimes followed by patients. Clinicians should not change the advice provided regarding oral intake and diet following tonsillectomy surgery in children.



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Tonsillectomy or tonsillotomy? A systematic review for paediatric sleep-disordered breathing

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Publication date: December 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 103
Author(s): Lai-Ying Zhang, Laurie Zhong, Michael David, Anders Cervin
BackgroundRecent evidence has challenged the practice of tonsillectomy in children with sleep-disordered breathing. Tonsillotomy (subtotal/partial/intracapsular tonsillectomy) has been proposed as an alternative with equivalent effectiveness and decreased post-operative morbidity, thus improving cost-effectiveness.ObjectiveTo systematically review the literature comparing clinical efficacy, post-operative morbidity, and cost-effectiveness of tonsillotomy and tonsillectomy in paediatric (<16yo) patients with sleep-disordered breathing.Data sourcesA systematic search of MEDLINE, EMBASE, and CENTRAL (1984–July 2014) was conducted. Papers in English directly comparing post-operative outcomes in tonsillectomy and tonsillotomy in children undergoing surgery for sleep-disordered breathing were included.Review methodsTwo authors independently assessed abstracts for relevance, with disagreements resolved by a third author. Selected studies were independently assessed regarding inclusion and exclusion criteria.ResultsThirty-two studies satisfied inclusion and exclusion criteria (19 randomised, 13 non-randomised). Patient satisfaction, quality-of-life, and polysomnographic improvement post-surgery did not vary between tonsillotomy and tonsillectomy. Tonsillotomy reduced the odds of a secondary haemorrhage by 79% (OR 0.21, 95% CI 0.17–0.27, p < 0.01), decreased post-operative pain and reduced return to normal oral intake by 2.8 days (95% CI 1.08–4.52, p < 0.01). The odds of readmission were decreased by 62% (OR 0.38, 95% CI 0.23–0.60, p < 0.01). Tonsillotomy had a slightly higher rate of symptom recurrence (4.51%) than tonsillectomy (2.55%), the long-term impact of which was unclear.ConclusionCurrent evidence supports tonsillotomy in children with obstructive surgical indications. It is likely to reduce post-operative haemorrhage, pain, and facilitate a faster return to normal diet and activity. Healthcare burden is decreased due to fewer post-operative complications and reduced need for medical re-contact. More research is necessary to assess the risk of recurrence, and further classification of secondary haemorrhage severity is required to fully clarify the clinical benefit of tonsillotomy.



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Outcomes of tympanoplasty in children with down syndrome

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Publication date: December 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 103
Author(s): Saied Ghadersohi, Jonathan B. Ida, Bharat Bhushan, Kathleen R. Billings
IntroductionThe prevalence of chronic otitis media with effusion (COME), and Eustachian tube dysfunction (ETD) is high in Down syndrome (DS) patients. This often necessitates multiple tympanostomy tube (TT) placements resulting in a higher rate of persistent tympanic membrane (TM) perforation requiring tympanoplasty for repair.ObjectivesTo assess risk factors for persistent perforation and outcomes of tympanoplasty in DS patients.MethodsRetrospective case series of 91 ears in 69 DS patients with TM perforations, who were either observed or underwent tympanoplasty. Clinical features, surgical outcomes, and hearing outcomes were assessed.Results91 ears were evaluated. Sixty perforations were observed, and 31 perforations were repaired. The closure rate was 54.8% for primary surgery, and 70.9% after secondary surgical interventions in the Tympanoplasty Group, compared to 33.0% spontaneous closure rate in the Observation Group (p < 0.001). The only risk factor for failed tympanoplasty repair was persistent COME/ETD (OR 27.2, p = 0.001). In the Observation Group perforations diagnosed at an older age, with >3 TT insertions, and with persistent COME/ETD were less likely to close spontaneously. Patients undergoing tympanoplasty had worse preoperative pure tone averages than those being observed, but significant improvement in air-bone gaps were noted in the Tympanoplasty Group (p = 0.02) post-operatively. Patients were often rehabilitated with hearing aids regardless of intervention (53.3% Observation Group, 48.4% Tympanoplasty Group).ConclusionsPersistent TM perforation in children with Down syndrome was associated with a history of COME/ETD, and multiple prior TT insertions. Tympanoplasty was successful for repair in most patients who underwent surgical intervention, but residual hearing loss was common.



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Pre- and post-operative application of acoustic rhinometry in children with otitis media with effusion and with or without adenoid hypertrophy-a retrospective analysis

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Publication date: December 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 103
Author(s): Dan Lai, Gang Qin, Junmei Pu, Lu Liu, Yiying Yang
BackgroundThere is no standardized scheme for preoperative evaluation of adenoid hypertrophy or a consensus on surgical indications for adenoidectomy in children with otitis media with effusion (OME), especially for young children intolerant to nasal endoscopic assessment. The aim of this study was to evaluate the efficacy and reliability of acoustic rhinometry (AR) in evaluating benefits from adenoidectomy in children with OME.MethodChildren with OME who were scheduled for surgical intervention were reviewed and AR tests performed preoperatively and postoperatively. The patients were divided into two groups based on the surgical strategy (Group I: tympanostomy tube placement alone; Group II: tympanostomy tube placement plus adenoidectomy). Correlation and regression analyses were performed to assess the relationship between findings of AR and nasal endoscopy. AR parameters including minimal nasal cross-sectional area (MCA), and nasopharyngeal volume (NPV), as well as scores of subjective symptoms were obtained to evaluate the utility of AR pre- and post-surgery.ResultsSixty-five children aged 4–10 years who met the inclusion criteria were included. No significant differences in gender or age distribution were observed between Group I and Group II. MCA, as well as NPV significantly decreased in Group II when compared with Group I (p = 0.000). A significant inverse correlation was observed between NPV and choanal obstruction ratio in both groups I (r = -0.625, p < 0.001) and II (r = −0.570, p < 0.001). A significant difference between preoperative and postoperative NPV and subjective symptom scores was observed in group II after adenoidectomy (p = 0.000).ConclusionAR parameters showed a good clinical correlation with findings of nasal endoscopy and thus may be useful for evaluating candidacy for surgical adenoidectomy among children with OME, especially in whom preoperative nasal endoscopic examination is not feasible. Additionally, AR can reveal the changes occurring within the nasopharyngeal passage before and after adenoidectomy.



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Herpes Simplex Virus and Human Papillomavirus Coinfections in Hyperimmunoglobulin E Syndrome Presenting as a Conjunctival Mass Lesion

Hyperimmunoglobulin E syndrome (HIES) or Job's syndrome is a rare immunodeficiency disease with less than 200 cases reported worldwide, among which few cases are reported with lesions due to herpes simplex virus (HSV) or human papillomavirus (HPV). This case study presents a rare case of HIES with coinfection of HSV and HPV. A 12-year-old boy, previously diagnosed with HIES, presented with a large conjunctival mass lesion. The presence of HPV in the lesion was confirmed by biopsy and by using the line-probe assay method to detect the HPV genome. However, the mass lesion did not respond to anti-HPV therapy with topical interferon-α2b (IFN-α2b) and oral cimetidine but improved promptly after intravenous (IV) acyclovir, which is often administered for cutaneous herpetic lesions. This suggested the presence of HSV in the conjunctival mass. Review of pathology and HSV immunohistochemical staining confirmed the presence of HSV as a coinfection. The likelihood that the mass arose from an abnormal host response to HSV and HPV due to HIES was considered, but coexisting infection with these two viruses and HIES has not been reported in the literature; therefore, such cases require further investigation.

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Randomized controlled pilot study of the preoperative use of brimonidine 0.33%topical gel for hemostasis in Mohs micrographic surgery

Brimonidine topical gel may be useful in cutaneous surgical procedures because of its vasoconstricting properties.

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Lichen planus affecting the female genitalia: A retrospective review of patients at Mayo Clinic

Genital or vulval lichen planus (VLP) may have a disabling effect on a patient's quality of life. Evidence-based management guidelines are lacking for VLP.

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Validity of skin cancer malignancy reporting to the Organ Procurement Transplant Network: A cohort study

The Organ Procurement Transplant Network (OPTN) registry collects data on posttransplant malignancies in solid organ transplant recipients. Complete and accurate registry data on skin cancer is critical for research on epidemiology and interventions.

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Case 31-2017: A 19-Month-Old Girl with Failure to Thrive

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Presentation of Case. Dr. Rachelle E. Gupta (Pediatrics): A 19-month-old girl was admitted to this hospital because of failure to thrive. The patient had been born in Puerto Rico by induced vaginal delivery after 41 weeks of gestation. Her mother did not smoke, drink alcohol, or take any…

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Chronic active Epstein-Barr virus infection with cutaneous lymphoproliferation: haemophagocytosis in the skin and haemophagocytic syndrome

Abstract

Patients with chronic active Epstein-Barr virus (EBV) infections (CAEBV) present with cutaneous manifestations including hydroa vacciniforme-like eruptions.1 Haemophagocytic lymphohistiocytosis (HLH), a fatal complication, can occur in severe cases of CAEBV.2,3 We retrieved 25 cases of CAEBV treated in our hospital and histopathologically characterized the skin lesions of 3 of those cases, including one case with haemophagocytosis. This is a novel report of CAEBV with haemophagocytosis in the skin.

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A novel combination regimen with intense focused ultrasound and pressure- and dose-controlled transcutaneous pneumatic injection of hypertonic glucose solution for lifting and tightening of the aging face

Summary

Background

Intense focused ultrasound (IFUS) has demonstrated moderate efficacy for facial laxity of the aging face. Pressure- and dose-controlled transcutaneous pneumatic injections of hypertonic glucose solution (TPIG) are a minimally invasive way to deliver solution into the skin for therapeutic purposes. Recently, its application around temporal areas is known to exert early-onset lifting effects with facial contour rejuvenation.

Aims

We sought to evaluate the safety and efficacy of this novel combination regimen with IFUS and TPIG for lifting and tightening of aging face.

Patients and Methods

Twenty-two Korean subjects with mild-to-moderate facial skin laxity were evaluated after receiving a sequential single session of IFUS and TPIG treatments. Dermatologists' objective assessments for general appearance, and mid- and low faces based on photographic images were performed at 1- and 12-week post-treatment follow-ups. Patients' subjective assessments were also conducted. Skin biopsies were taken at baseline and the last visit.

Results

Among 22 subjects, twenty (91%) demonstrated improvement after 12-week follow-up. We also observed similarly improved state just after 1 week of treatments (82%: 18/22). Specifically, improvement of the mid-face was evident from the first week, while the progress of the low face improvement was observed at the twelve week. Subjective assessments paralleled these findings. No seriously adverse effect was observed during procedures. Histologic evaluation showed greater dermal collagen fibers throughout the dermis after treatments.

Conclusion

Combination treatment with IFUS and TPIG has beneficial effects for skin lifting and tightening with early-onset time.



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Table of Contents

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Cover



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Subscriptions

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In This Issue

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Improvement of Foxp3 stability through CNS2 demethylation by TET enzyme induction and activation

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Abstract
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine. TET-CD over-expression in iTregs resulted in partial demethylation of CNS2 and stable Foxp3 expression. We also discovered that TET expression was enhanced under low oxygen (5%) culture conditions, which facilitated CNS2 DNA demethylation and stabilization of Foxp3 expression in a TET2- and TET3-dependent manner. In combination with vitamin C treatment, which has been reported to enhance TET catalytic activity, iTregs generated under low oxygen conditions retained more stable Foxp3 expression in vitro and in vivo and exhibited stronger suppression activity in a colitis model compared with untreated iTregs. Our data indicate that the induction and activation of TET enzymes in iTregs would be an effective method for Treg-mediated adoptive immunotherapy.

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Autoimmunity associated with chemically induced thymic dysplasia

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Abstract
Autoimmune and inflammatory conditions are frequent complications in patients with reduced numbers of T cells. Here, we describe a mouse model of thymic stromal dysplasia resulting in peripheral T-cell lymphopenia. In Foxn1:CFP-NTR transgenic mice, the bacterial nitroreductase enzyme is expressed in thymic epithelial cells and converts the prodrug CB1954 into a cytotoxic agent. This strategy enables titratable and durable destruction of thymopoietic tissue in early embryogenesis. Our results indicate that the resulting low levels of thymic capacity for T-cell production create a predisposition for the development of a complex autoimmune syndrome, chiefly characterized by inflammatory bowel disease and lymphocytic organ infiltrations. We conclude that the Foxn1:CFP-NTR transgenic mouse strain represents a suitable animal model to optimize established clinical protocols, such as thymus transplantation, to correct various forms of thymic dysplasia and to explore novel treatment options.

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The human NAIP-NLRC4-inflammasome senses the Pseudomonas aeruginosa T3SS inner-rod protein

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Abstract
While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella enterica serovar typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different neuronal apoptosis inhibitory proteins (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P. aeruginosa T3SS. Surprisingly, only a single human NAIP (hNAIP) has been found. Moreover, there is no description of hNAIP-NLRC4 inflammasome recognition of T3SS inner-rod proteins in humans. Here, we show that the P. aeruginosa T3SS inner-rod protein PscI and needle protein PscF are both sensed by the hNAIP-NLRC4 inflammasome in human macrophages and PBMCs from healthy donors, allowing caspase-1 and IL-1β maturation and resulting in a robust inflammatory response. TLR4 and TLR2 are involved in redundantly sensing these two T3SS components.

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Requirement of glycosylation machinery in TLR responses revealed by CRISPR/Cas9 screening

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Abstract
The Toll family of receptors sense microbial products and activate a defense response. The molecular machinery required for the TLR response is not yet fully understood. In the present study, we used a clustered, regularly interspaced, short palindromic repeats (CRISPR)/CAS9 screening system to study TLR responses. We employed a cell line expressing TLR with an NF-κB-driven GFP reporter. The cell line was transduced with a guide RNA (gRNA) library and stimulated with TLR ligands. The cells impaired in GFP induction were sorted, and gRNAs were sequenced. Identified genes were ranked according to the count of sequence reads and the number of gRNA target sites. The screening system worked correctly, as molecules that were already known to be required for the TLR response were identified by the screening. Furthermore, this system revealed that the oligosaccharide transferase complex (OSTC) mediating co-translational glycosylation was required for TLR5, 7 and 9 responses. Protein expression of TLR5, but not an irrelevant molecule (CD44), was abolished by the lack of OSTC, suggesting the essential role of glycosylation in TLR5 protein stability. These results demonstrate that the screening system established here is able to reveal molecular mechanisms underlying the TLR response.

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Uromodulin–SlpA binding dictates Lactobacillus acidophilus uptake by intestinal epithelial M cells

Abstract
Bacterial access to the gut immune system is a crucial process to promote host immune responses. The probiotic L-92 strain of Lactobacillus acidophilus exerts anti-allergic immunomodulatory effects upon oral administration in mice. Here, we show that microfold cells (M cells) are responsible for L-92 internalization for evoking L-92-mediated immune responses. L-92 specifically bound to uromodulin, a glycosylphosphatidylinositol-anchored protein expressed exclusively on M cells among intestinal epithelial cells. Internalization of L-92 into M cells was significantly reduced in uromodulin-deficient (Umod−/−) mice compared to Umod+/+ mice. Furthermore, the binding of L-92 to uromodulin was significantly decreased after removal of surface layer protein A (SlpA) from the bacteria. Our study thus revealed a crucial role of uromodulin on the M-cell surface for the uptake of SlpA-positive lactic acid bacteria into M cells, possibly leading to subsequent delivery of the bacteria to dendritic cells closely associated with M cells for immunomodulation. Our study also shed light on the possibility that SlpA and uromodulin could be used as vehicle and target, respectively, for efficient mucosal vaccine delivery.

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A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer

Abstract

Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8+ T cells, as depletion of circulating CD8+ T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.



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Rosacea and subsequent diagnosis for Parkinson's Disease: a large, urban, single center, U.S. patient population retrospective study

Abstract

Rosacea is a chronic inflammatory, multifactorial disorder [1]. Parkinson Disease (PD), is a serious, neurodegenerative disorder, believed to be a manifestation of a complex interplay between genetic and environmental factors [2]. A recent study found an association between PD and rosacea [3].

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Autosomal recessive epidermolysis bullosa simplex due to KRT14 mutation: two large Palestinian families and literature review

Abstract

Inherited epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of skin fragility disorders characterized by trauma-induced blister formation. Four major EB types are distinguished based on the level of blister formation within the skin: EB simplex (EBS), junctional EB, dystrophic EB, and Kindler syndrome1. EBS represents the most common type and is defined by intraepidermal cleavage.

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Acrochordons on the neck; a remarkable clinical feature of tuberous sclerosis showing different patterns

Abstract

Sachs and Lipsker1 recently published a few patients diagnosed with tuberous sclerosis (TS) presenting with multiple loosely arranged acrochordons (molluscum pendulum) located on the posterior neck showing a lace-like distribution and they proposed the term "molluscum pendulum necklace sign" for these typically located lesions. They detected acrochordons in five cases (17%) in a retrospectively analysed consecutive series of 29 TS patients, of whom four (three adults and one child) remarkably showed this typical pattern. Whether that sign might be a new pathognomonic sign of this genodermatosis was also discussed by the authours..1

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First genetic analysis of atypical phenotype of pseudoxanthoma elasticum with ocular manifestations in the absence of characteristic skin lesions

Abstract

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease, characterized by mineralization and degeneration of the elastic fibers in the skin, retina, and cardiovascular system.1-4 PXE is caused by mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene, but it remains unknown how these mutations lead to the clinical phenotype.2-4 Although an association between mutations and phenotypes has been postulated, no definite correlation has been established.5 Patients with PXE usually exhibit typical skin lesions that are frequently the first diagnostic signs.1,6,7

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Paraneoplastic bullous pemphigoid associated with penile squamous cell carcinoma

Abstract

A 43-year-old farmer presented to us for evaluation of multiple, itchy, tense vesicles and bullae, containing clear to hemorrhagic fluid, surmounting an urticarial background on his thighs and inguinal area for 20-days (Figure 1a). He was also undergoing evaluation for bilateral metastatic inguinal lymphadenopathy detected 3 months back that had revealed squamous cell carcinoma on cytology. Search for primary was still on. Genital examination incidentally revealed a bright red, well-defined, verrucous plaque on glans penis (Figure 1b).

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Large plaque-type blue nevus with cellular nodules: a rare unrecognized melanocytic tumor

Abstract

A 24-year-old Caucasian woman referred to us due to the modification of a congenital skin lesion in her right scapular area over the past 10 months. Physical examination disclosed multiple blue/whitish nodules arising on a bluish oval plaque, 6 cm in maximum diameter (fig. 1). The patient's personal and family medical history were unremarkable and negative for melanoma and non-melanoma skin cancers. The entire lesion was totally excised. Microscopy revealed a multifocal dermal proliferation of fusiform and dendritic melanocytes arranged in irregular nodules characterized by many individual foci with the histologic appearance of common blue nevus involving the reticular dermis (fig. 2a-2b).

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