Lower proximal cup and outer root sheath cells regenerate hair bulbs during anagen hair follicle repair after chemotherapeutic injury

xlomafota13 shared this article with you from Inoreader Lower proximal cup and outer root sheath cells regenerate hair bulbs during anagen hair follicle repair after chemotherapeutic injury Via Experimental Dermatology Abstract The cell dynamics and cell origin for anagen hair follicle (HF) repair following chemotherapeutic injury are unclear. We first mapped the HF response to cyclophosphamide (CYP) at natural anagen VI in mice. We found that 30‐60 mg/kg of CYP leads to dose‐dependent HF dystrophy that was spontaneously repaired with anagen resumption, while 120 mg/kg of CYP prematurely induced catagen/telogen entry. To explore how anagen HF repair is achieved in the dystrophic anagen pathway, we analysed the cell dynamics at 30 mg/kg of CYP. Hair bulbs first shrunk due to matrix cell apoptosis associated with DNA double‐strand breaks. DNA damage was repaired, and ordered hair bulb structures were restored within 96 hours. Bulge stem cells did not undergo apoptosis nor proliferation. K5+ basal lower proximal cup cells and outer root sheath cells quickly replenished the cells in the germinative zone and regenerated the concentric layered structures of the lower HF seg ment. Therefore, anagen HFs are able to summon extra‐bulge progenitor cells in close proximity to the damaged matrix for quick repair after CYP injury. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Laser‐assisted epicutaneous immunization to target human skin dendritic cells

xlomafota13 shared this article with you from Inoreader Laser‐assisted epicutaneous immunization to target human skin dendritic cells Via Experimental Dermatology Abstract Dendritic cells (DC) are promising targets for immunotherapy of cancer. Clinically, immunization against cancer antigens by means of the most potent antigen‐presenting cells, i.e., DC, remains an important treatment option in combination with the modern immune checkpoint approaches. Instead of adoptively transferring in vitro monocyte‐derived DC, they can also be loaded in situ by antibody‐mediated targeting of antigen. Conventionally, these vaccines are delivered by classical intradermal injections. Here, we tested an alternative approach, namely laser‐assisted epicutaneous immunization. With an infrared laser ("Precise Laser Epidermal System" / P.L.E.A.S.E.® Laser System) we created micropores in human skin and applied antibodies against C‐type lectins, e.g. DEC‐205 / CD205 and Langerin / CD207. Optimal parameters for formation of pores in epidermis and dermis were determined. We could induce pores of defined depths without enhanced apoptosis aroun d them. Antibodies applied epicutaneously to the laser‐porated skin could be detected both in Langerhans cells (LC) in situ in the epidermis and in migratory skin DC subsets from short term human skin explant culture, demonstrating uptake and transport of Langerin and DEC‐205 mAbs. Efficacy of targeting was similar between the different laser treatments and pore depths. Thus, laser‐assisted epicutaneous immunization may be a valuable alternative to intradermal injection, yet the loading efficacy of DC needs to be further improved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comprehensive characterization of the structure and properties of human stratum corneum relating to barrier function and skin hydration: modulation by a moisturizer formulation

xlomafota13 shared this article with you from Inoreader Comprehensive characterization of the structure and properties of human stratum corneum relating to barrier function and skin hydration: modulation by a moisturizer formulation Via Experimental Dermatology Abstract The stratum corneum (SC) is key in the maintenance of the biomechanical barrier and hydration of skin. Our previous investigations showed beneficial effects of a combination of emollients on water capture and retention and protein and lipid organization, all of which are linked to dryness and dry skin damage. Here, we show how a formulation containing an emollient combination ("Trio") and its basal formulation (placebo) impacted the descriptors of SC hydration in SC layers. Only the Trio formulation—not its placebo formulation—modified SC biomechanical drying stress behaviour and imparted a high capacity to protect it from dehydration. This was in accordance with findings at the molecular level using Raman analyses and at the structural level using cryo‐scanning electron microscopy (SEM). After topical application, only the Trio formulation profoundly increased lateral packing of lipids and their compactness. Cryo‐SEM showed that, unlike the placebo formulation, the Tr io formulation prevented the water loss when applied before the dehydration process. In conclusion, these studies demonstrate that stresses in the SC due to dehydration can be alleviated using a formulation containing emollients that interact with the SC lipid components. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Complement Factor I upregulates expression of matrix metalloproteinase‐13 and ‐2 and promotes invasion of cutaneous squamous carcinoma cells

xlomafota13 shared this article with you from Inoreader Complement Factor I upregulates expression of matrix metalloproteinase‐13 and ‐2 and promotes invasion of cutaneous squamous carcinoma cells Via Experimental Dermatology ABSTRACT The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing globally. Here, we have studied the functional role of complement factor I (CFI) in the progression of cSCC. CFI was knocked down in cSCC cells and RNA‐seq analysis was performed. Significant down‐regulation of genes in IPA biofunction categories Proliferation of cells and Growth of malignant tumor, in Gene Ontology (GO) terms Metallopeptidase activity and Extracellular matrix component, as well as Reactome Degradation of extracellular matrix was detected after CFI knockdown. Further analysis of the latter three networks, revealed down‐regulation of several genes coding for invasion‐associated matrix metalloproteinases (MMPs) after CFI knockdown. The downregulation of MMP‐13 and MMP‐2 was confirmed at mRNA, protein and tissue levels by qRT‐qPCR, western blot and immunohistochemistry, respectively. Knockdown of CFI decreased the invasion of cSCC cells through typ e I collagen. Overexpression of CFI in cSCC cells resulted in enhanced production of MMP‐13 and MMP‐2 and increased invasion through type I collagen and Matrigel, and in increased ERK1/2 activation and cell proliferation. Altogether, these findings identify a novel mechanism of action of CFI in upregulation of MMP‐13 and MMP‐2 expression and cSCC invasion. These results identify CFI as a prospective molecular marker for invasion and metastasis of cSCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Novel predictive tools and therapeutic strategies for patients with initially diagnosed glottic cancer in the United States

xlomafota13 shared this article with you from Inoreader Novel predictive tools and therapeutic strategies for patients with initially diagnosed glottic cancer in the United States Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 Apr 5. doi: 10.1007/s00405-021-06788-4. Online ahead of print. ABSTRACT OBJECTIVE: The objective of this study is to identify valuable prognostic factors, build clinical prediction nomograms, and recommend the optimal therapeutic strategy for patients with initially diagnosed glottic cancer. METHODS: Patients were extracted from the SEER database. Cox regression analyses, survival analyses, an internal validation, the propensity score analysis, and the competing risk analysis were performed. RESULTS: Nine overlapped factors were considered as valuable prognostic factors. Furthermore, nomograms were established for clinical prediction models to assess the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS). C-indexes, receiver operating characteristic curves, calibration curves, and decision curve analyses proved that nomograms showed better predictive accuracy, ability , and prognostic value compared to the American Joint Committee on Cancer stage. For patients in stage I, primary site surgery alone would acquire best OS and CSS. For patients in stage II, primary site surgery and/or radiation would gain better OS and CSS. For patients in stage III, radiation plus chemotherapy or primary site surgery (alone or plus radiation) would acquire better OS and CSS. Moreover, for patients in stage IV, primary site surgery plus radiation would gain better OS and CSS. CONCLUSIONS: Nomograms could be useful for patients' counseling and guide therapeutic decision-making. Primary site surgery alone may likely be the optimal therapy for stage I glottic cancer, and primary site surgery and/or radiation may be the recommended therapy for stage II glottic cancer. The combination treatment would be the preferred choice for advanced-stage (stage III & IV) glottic cancer, and the role of chemotherapy needs to be further explored. PMID:33821328 | DOI:10.1007/s00405-021-06788-4 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Scapular Free Flap Reconstruction of Pharyngoesophageal Defects

xlomafota13 shared this article with you from Inoreader Scapular Free Flap Reconstruction of Pharyngoesophageal Defects Via Clinical Otolaryngology Abstract Scapular and parascapular free tissue transfer (SFTT) is a well described reconstructive option for the head and neck. The aim of this study is to describe SFTT for reconstruction of PE (pharyngoesophagyeal) defects. This study was a retrospective review of patients undergoing SFTT for PE defects between 2009 and 2014 at a tertiary center. Seventeen patients (13 male and 4 female) were evaluated for surgical outcomes, speech, voice outcomes, swallowing outcomes, enteral feeding and tracheoesophageal puncture (TEP) usage. Two of 17 patients developed pharyngocutaneous fistulas (PCF) as inpatients. There was one major medical complication (pulmonary embolism) and 7 minor complications. Mean hospital length of stay was 15.7 days (SD 8.2). In post‐operative setting, only one patient remained PEG‐dependent, 11 patients supplemented oral intake with PEG feeds and 5 patients took nutrition solely by mouth. Four patients utilized written communication exclusively, 6 patients pursued TEP placement and 7 utilized electrolarynx. The SFTT is a viable option for hypopharyngeal reconstruction. All scapula free tissue transfers remained viable for the duration of our review. Post‐operative PCF rate were comparable to that reported after laryngectomy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Utility of Intraoperative Frozen Sections of Thyroid Tissue in the Age of Molecular Testing

xlomafota13 shared this article with you from Inoreader Utility of Intraoperative Frozen Sections of Thyroid Tissue in the Age of Molecular Testing Via Clinical Otolaryngology Abstract Objectives Our study aims to examine the correlation between pre‐operative ultrasound guided fine needle aspiration and intraoperative frozen section, and examine the clinical benefit of frozen section in the context of the latest national guidelines on the management of differentiated thyroid cancer. Study Design A retrospective review of thyroid frozen section from 2012 – 2017 at one institution. Setting Tertiary care center Participants/Main Outcome Patient demographics, fine needle aspiration results, molecular testing results, frozen section diagnosis (classified as benign, indeterminate, or malignant), final pathologic diagnosis, initial planned surgery, actual surgery performed, need for additional surgery, and complications were recorded. Complications included hematoma formation, hypocalcemia (requiring readmission, symptomatic, or >24 hour stay post op), and recurrent or superior laryngeal nerve damage. Results 728 total patients had an intraoperative frozen section performed. A Thy 4/Bethesda V USGFNA diagnosis (n=55) significantly correlated with a clinically important intraoperative frozen section (n = 17, p <0.01). Intraoperative management was changed by the frozen section 53 times (7.2%). Molecular testing was sent on 92 USGFNA specimens, 80 of which were deemed "suspicious." Of the 49 patients whose management was upstaged intraoperatively, 29 (59%) would not necessitate a completion thyroidectomy under the latest UK and ATA guidelines based on final pathology. Conclusion Intraoperative frozen sections rarely alter the pre‐surgical plan, and indeed may result in expanded surgery that could have been avoided based on latest UK and US guidelines. Molecular testing of indeterminate fine needle aspiration results does not appear to predict meaningful intraoperative frozen section results. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Vocal cord paralysis secondary to vincristine treatment in children – A case series of seven children and literature review

xlomafota13 shared this article with you from Inoreader Vocal cord paralysis secondary to vincristine treatment in children – A case series of seven children and literature review Via Clinical Otolaryngology Abstract Vincristine is a vinca alkaloid chemotherapy agent used in the treatment haematological malignancies including acute lymphoblastic leukaemia (ALL) and some lymphomas. Common toxicity includes neuropathy which can be peripheral, autonomic or less commonly central1. Vincristine remains an essential chemotherapy agent in modern ALL protocols1,2,3. Its mechanism of action is by inhibiting the M phase of mitosis by binding with the protein component of microtubules. Axonal degeneration takes place when axonal transport and secretory functions are impaired thus leading to apoptosis and toxicity in neural tissue. This is typically seen within the extra‐ocular muscles and larynx in cranial neuropathy1. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anterior ethmoid artery septal flap for endoscopic reconstruction of frontal sinus Cerebrospinal Fluid leak

xlomafota13 shared this article with you from Inoreader Anterior ethmoid artery septal flap for endoscopic reconstruction of frontal sinus Cerebrospinal Fluid leak Via Clinical Otolaryngology Abstract ‐Surgical repair is required for persistent CSF leaks due to trauma or following endoscopic skull base resections ‐The endoscopic endonasal approach is associated with low morbidity and high success rates; 90% at first attempt and overall in 97% ‐A variety of materials are used for the reconstruction and closure of CSF leaks with no overall consensus; the multilayered approach to defect closure is currently deemed best practice ‐The anterior ethmoid septal flap can be successfully utilized for frontal CSF leak repair ‐Anterior ethmoid flap is conveniently located for frontal sinus defects; and so provides excellent final layer of multilayer reconstruction when septum is intact View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

British Rhinological Society Consensus Guidance on the use of biological therapies for Chronic Rhinosinusitis with Nasal Polyps

xlomafota13 shared this article with you from Inoreader British Rhinological Society Consensus Guidance on the use of biological therapies for Chronic Rhinosinusitis with Nasal Polyps Via Clinical Otolaryngology Abstract Objectives We set out to create Consensus Guidelines, based on current evidence and relative risks of adverse effects and the costs of different treatments, that reflect the views of the British Rhinological Society (BRS) Council on where the use of biologics should be positioned within treatment pathways for CRSwNP, specifically in the setting of the National Health Service (NHS). Design An expert panel of 16 members was assembled. A review of the literature and evidence synthesis was undertaken and circulated to the panel We used the RAND/UCLA methodology with a multi‐step process to make recommendations on the use of biologics. Setting N/A Participants N/A Results Recommendations were made, based on underlying disease severity, prior treatments and co‐morbidities. A group of patients for whom biologics were considered an appropriate treatment option for CRSwNP was defined. Conclusions Although biologics are not currently available for the treatment of CRSwNP, the BRS Council have defined a group of patients who have higher rates of 'failure' with current treatment pathways, higher resource use and are more likely to suffer with uncontrolled symptoms. We would urge NICE to consider approval of biologics for such indications without applying further restrictions on use. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Induction chemotherapy followed by intensity‐modulated radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma: A retrospective analysis

xlomafota13 shared this article with you from Inoreader Induction chemotherapy followed by intensity‐modulated radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma: A retrospective analysis Via Clinical Otolaryngology Abstract Objectives The optimal treatment strategy of combining systemic chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC) is controversial. This study aimed to compare the efficacy and toxicities of induction chemotherapy followed by intensity‐modulated radiotherapy (IC‐RT) versus concurrent chemoradiotherapy (CCRT) in NPC. Methods Of 448 stage II‐IVb NPC patients treated with IC‐RT or CCRT were retrospectively analysed. The primary outcome was overall survival, which was analysed by using Kaplan‐Meier curves and log‐rank (Mantel‐Cox) test. Results The median follow‐up was 66 months (interquartile range, 46‐84 months). There was no statistically significant difference in the estimated 5‐year overall survival (OS), progression‐free survival (PFS), distance metastasis‐free survival (DMFS) and locoregional relapse‐free survival (LRFS) between IC‐RT group and CCRT group (OS: 89.5% vs 91.7%, P = .568; PFS: 85.2% vs 87.5%, P = .615; DMFS: 90.9% vs 91.7%, P = .847; LRFS: 92.0% vs 96.9%, P = .104). In the multivariate analysis, the treatment group (IC‐RT vs CCRT) was not an independent prognostic factor for OS, PFS, DMFS and LRFS. Less advanced tumour stage and lymph node stage were predictive of higher OS. EBV‐DNA level was an independent prognostic factor that was only significantly associated with LRFS. Conclusions IC‐RT achieves similar survival outcomes and treatment‐related toxicities as CCRT in OS, PFS, DMFS and LRFS for patients with NPC. We need multicentre randomised controlled trials to reconfirm our data. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Deep periocular trauma with affection of the lacrimal ducts during Caesarean section

xlomafota13 shared this article with you from Inoreader Deep periocular trauma with affection of the lacrimal ducts during Caesarean section Via hno HNO. 2021 Apr 6. doi: 10.1007/s00106-021-01039-8. Online ahead of print. ABSTRACT Periocular injuries during a caesarean section are extremely rare. The case report of a five hour old newborn addresses the trauma management concerning diagnostics, therapy, and post-operative care of a deep periocular soft tissue injury. The pattern of injury consisted of full thickness wounds of the medial and lateral lid margins, opening of the superior conjunctival fornix, and penetration of Tenon's capsule. The reconstruction was performed layer by layer while an autostable monocanaliculonasal lacrimal intubation was inserted. PMID:33822270 | DOI:10.1007/s00106-021-01039-8 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.