Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation

xlomafota13 shared this article with you from Inoreader Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):222. doi: 10.3892/etm.2022.11146. Epub 2022 Jan 17. ABSTRACT Osteoarthritis (OA) is an age-related degenerative disease, and its incidence is increasing with the ageing of the population. Metformin, as the first-line medication for the treatment of diabetes, has received increasing attention for its role in OA. The purpose of the present study was to confirm the therapeutic effect of metformin in a mouse model of OA and to determine the mechanism underlying the resultant delay in OA progression. The right knees of 8-week-old C57BL/6 male mice were subjected to destabilization of the medial meniscus (DMM). Metformin (200 mg/kg) was then administered daily for 4 or 8 weeks. Safranin O-fast green staining, H&E staining and micro-CT were used to analyse the structure and morphological changes. Immunohistochemical staining was used to detect type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), NO D-like receptor protein 3 (NLRP3), caspase-1, gasdermin D (GSDMD) and IL-1β protein expression. Reverse transcription-quantitative PCR was used to detect the mRNA expression of NLRP3, caspase-1, GSDMD and IL-1β. Histomorphological staining showed that metformin delayed the progression of OA in the DMM model. With respect to cartilage, metformin decreased the Osteoarthritis Research Society International score, increased the thickness of hyaline cartilage and decreased the thickness of calcified cartilage. Regarding the mechanism, in cartilage, metformin increased the expression of Col II and decreased the expression of MMP-13, NLRP3, caspase-1, GSDMD and IL-1β. In addition, in subchondral bone, metformin inhibited osteophyte formation, increased the bone volume fraction (%) and the bone mineral density (g/cm3), decreased the trabecular separation (mm) in early stage of osteoarthritis (4 weeks) but the opposite in an advanced stage of osteoarthritis (8 weeks). Overall, metformin inhibited the activation of NLRP3 inflammasome, decreased cartilage degradation, reversed subchondral bone remodelling and inhibited chondrocyte pyroptosis. PMID:35222699 | PMC:PMC8812147 | DOI:10.3892/etm.2022.11146 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Managing Cachexia in Head and Neck Cancer: a Systematic Scoping Review

xlomafota13 shared this article with you from Inoreader Managing Cachexia in Head and Neck Cancer: a Systematic Scoping Review Via swallowing exercises Adv Ther. 2022 Feb 27. doi: 10.1007/s12325-022-02074-9. Online ahead of print. ABSTRACT INTRODUCTION: Patients with head and neck cancer (HNC) are usually confronted with functional changes due to the malignancy itself or its treatment. These factors typically affect important structures involved in speech, breathing, chewing, swallowing, and saliva production. Consequently, the intake of food will be limited, which further contributes to loss of body weight and muscle mass, anorex ia, malnutrition, fatigue, and anemia. This multifactorial condition can ultimately lead to cancer cachexia syndrome. This study aims to examine the treatment of cachexia in HNC patients. METHODS: We systematically searched OvidMedline, PubMed, Scopus, and Web of Science for articles examining the treatment of cachexia in HNC. RESULTS: A total of nine studies were found, and these suggested interventions including nutritional, pharmacologic, therapeutic exercise, and multimodal approaches. The nutritional intervention includes essential components such as dietary counseling, oral nutritional supplements, and medical nutritional support. Individualized nutritional interventions include oral, enteral (feeding tubes i.e., percutaneous endoscopic gastrostomy [PEG], nasogastric tube [NGT]) and parenteral nutrition. The pharmacologic interventions aim at increasing the appetite and weight of cachectic patients. Therapeutic exercise and increased physical activity can help to e nhance the synthesis of muscle protein, reducing inflammation and the catabolic effects of cachexia syndrome. CONCLUSION: Owing to the multifactorial nature of this syndrome, it is expected that the management approach should be multi-interventional. Early implementation of these interventions may help to improve survival and quality of health and life of cachectic HNC patients. PMID:35224702 | DOI:10.1007/s12325-022-02074-9 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Growth in fetuses of the constrictor pharyngis superior with special reference to its meeting with the buccinator: an embryological basis of adult variations in palatopharyngeal anatomy

xlomafota13 shared this article with you from Inoreader Growth in fetuses of the constrictor pharyngis superior with special reference to its meeting with the buccinator: an embryological basis of adult variations in palatopharyngeal anatomy Via radiol anat Surg Radiol Anat. 2022 Feb 28. doi: 10.1007/s00276-022-02907-w. Online ahead of print. ABSTRACT PURPOSE: The constrictor pharyngis superior (CPS) initially develops along the posterior wall of the pharyngeal mucosal tube, whereas, during the early phase, the buccinators (BC) are far anterolateral to the CPS. The process and timing of their meeting during fetal growth have not been determined. METHODS: The topographical relationship between the growing BC and CPS was as sessed in histological sections from 22 early- and mid-term fetuses of approximate gestational age (GA) 8-16 weeks, and eight late-term fetuses of approximate GA 31-39 weeks. RESULTS: At 8-9 weeks, the palatopharyngeus appeared to pull the CPS up and forward. Until 11 weeks, the CPS was attached to the hamulus of the pterygoid (pterygopharyngeal part). Until 13 weeks, the CPS extended anterolaterally beyond the hamulus to meet the BC. Some BC muscle fibers originated from the oral mucosa. Notably, by 30 weeks, the CPS-BC interface had become covered by or attached to the palatopharyngeus. Muscle fibers of the palatopharyngeus, however, were thinner than those of the CPS and BC. At and near the interface, BC muscle fibers tended to run along the left-right axis, whereas those of the CPS ran anteroposteriorly. A definite fascia (i.e., a future pterygomandibular raphe) was usually absent between these muscles in fetuses. CONCLUSIONS: The excess anterior growth of the CPS wi th its subsequent degeneration might cause individual anatomical variations in composite muscle bundles of the palatopharyngeus-CPS complex or palatopharyngeal sphincter. A tensile transduction from the BC to the CPS through the raphe seemed unnecessary for cooperative suckling and swallowing after birth. PMID:35226125 | DOI:10.1007/s00276-022-02907-w View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Quality of Life and Functionality of Head and Neck Cancer Patients Are Diminished As a Function of Sarcopenia and Obesity

xlomafota13 shared this article with you from Inoreader Quality of Life and Functionality of Head and Neck Cancer Patients Are Diminished As a Function of Sarcopenia and Obesity Via ear nose throat Ear Nose Throat J. 2022 Feb 28:1455613221076791. doi: 10.1177/01455613221076791. Online ahead of print. ABSTRACT BACKGROUND: Health-related quality of life (QoL) is a measure that allows us to know the patient's perception of well-being and how it is affected by their disease and treatments. In cancer patients, sarcopenia has been associated with low scores on various instruments used to assess the QoL; however, little information is available on the effects of sarcopenia an d sarcopenic obesity on the QoL of patients with head and neck cancer (H&NC). METHODS: In this cross-sectional study with 71 H&NC patients aged between 40 and 80 years, we describe the scores on the instruments EORTC QLQ C-30 and EORTC QLQ-H&N35 according to the sarcopenia phenotype (NSG, nonsarcopenic group; SG, sarcopenic group; and SOG, sarcopenic obesity group), hand-grip strength, gait speed, total lymphocyte count, albumin, cholesterol and C-reactive protein, and the relationships between these variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 48% and 28%, respectively. The QoL analysis showed that NSG had higher scores on the physical functioning scale [NSG 93 (83-100); SG 73 (52-88); SOG 83 (53-93), P = .009] and lower scores on the fatigue scale [NSG 11 (0-22); S 39 (30-67); SOG 44 (14-56); P = .004]. The NSG had a higher hand-grip strength (31.1 kg) than SG (24.1 kg, P = .007) and SOG (26.3 kg, P = .001), and a lower C-reac tive protein. The SG and SOG showed no differences between them. CONCLUSIONS: Patients with sarcopenia or sarcopenic obesity have lower physical performance and a higher level of fatigue than nonsarcopenic patients. This loss of function can maintain or worsen sarcopenia due to the patient's self-restraint in physical exertion that encourages an increase in muscle tissue. PMID:35226551 | DOI:10.1177/01455613221076791 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Conservative Management of Post-Operative Cerebrospinal Fluid Leak following Skull Base Surgery: A Pilot Study

xlomafota13 shared this article with you from Inoreader Conservative Management of Post-Operative Cerebrospinal Fluid Leak following Skull Base Surgery: A Pilot Study Via leak of cerebrospinal fluid Brain Sci. 2022 Jan 24;12(2):152. doi: 10.3390/brainsci12020152. ABSTRACT BACKGROUND/AIMS: Iatrogenic CSF leaks after endoscopic endonasal transsphenoidal surgery remain a challenging entity to manage, typically treated with CSF diversion via lumbar drainage. OBJECTIVE: To assess the safety and efficacy of high-volume lumbar puncture (LP) and acetazolamide therapy to manage iatrogenic CSF leaks. METHODS: We performed a prospective pilot study of four patients who developed iatrogenic postoperative CSF leaks after transsphenoidal surgery and analyzed their response to treatment with concomitant high-volume lumbar puncture followed by acetazolamide therapy for 10 days. Data collected included demographics, intra-operative findings, including methodology of skull base repair and type of CSF leak, time to presentation with CSF leak, complications associated with high-volume LP and acetazolamide treatment, and length of follow-up. < p>RESULTS: Mean patient age was 44.28 years, with an average BMI of 27.4. Mean time from surgery to onset of CSF leak was 7.71 days. All four patients had resolution of their CSF leak at two- and four-week follow-up. Mean overall follow-up time was 179 days, with a 100% CSF leak cure rate at the last clinic visit. No patient suffered perioperative complications or complications secondary to treatment. CONCLUSION: Although our pilot case series is small, we demonstrate that a high-volume LP, followed by acetazolamide therapy for 10 days, can be considered in the management of post-operative CSF leaks. PMID:35203915 | DOI:10.3390/brainsci12020152 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Precise fabrication of porous polymer frameworks using rigid polyisocyanides as building blocks: from structural regulation to efficient iodine capture

xlomafota13 shared this article with you from Inoreader Precise fabrication of porous polymer frameworks using rigid polyisocyanides as building blocks: from structural regulation to efficient iodine capture Via radioactive iodine Chem Sci. 2022 Jan 12;13(4):1111-1118. doi: 10.1039/d1sc05361b. eCollection 2022 Jan 26. ABSTRACT Porous materials have recently attracted much attention owing to their fascinating structures and broad applications. Moreover, exploring novel porous polymers affording the efficient capture of iodine is of significant interest. In contrast to the reported porous polymers fabricated with small molecular blocks, we herein report the preparation of porous polymer frameworks using rigid polyisocyanides as building blocks. First, tetrahedral four-arm star polyisocyanides with predictable molecular weight and low dispersity were synthesized; the chain-ends of the rigid polyisocyanide blocks were then crosslinked, yielding well-defined porous organic frameworks with a designed pore size and narrow distribution. Polymers of appropriate pore size were observed to efficiently capture radioactive iodine in both aqueous and vapor phases. More than 98% of iodine could be captured within 1 minute from a saturated aqueous solution (capacity of up to 3.2 g g-1), and an adsorption capacity of up to 574 wt% of iodine in vapor was measured within 4 hours. Moreover, the polymers could be recovered and recycled for iodine capture for at least six times, while maintaining high performance. PMID:35211277 | PMC:PMC8790772 | DOI:10.1039/d1sc05361b View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

PET/CT versus triple endoscopy in initial workup of HPV+ oropharyngeal squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader PET/CT versus triple endoscopy in initial workup of HPV+ oropharyngeal squamous cell carcinoma Via Head & Neck Abstract Background Synchronous primary tumors (SPTs) are detected via triple endoscopy or positron emission tomography/computed tomography (PET/CT). Patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) lack risk factors for SPTs. Methods We performed a single institution retrospective review of the efficacy of triple endoscopy and PET/CT in HPV+ OPSCC patients. Results Sixty-five HPV+ OPSCC patients underwent triple endoscopy and PET/CT. Patients were white (n = 48, 72.7%), male (n = 53, 81.5%), mean 58.7 ± 8.1 years old. SPT was detected in 1 (1.5%) patient via PET/CT. No SPTs were detected on triple endoscopy. PET/CT had 100% and 95.3% sensitivity and specificity, respectively. PET/CT positive predictive value (PPV) and negative predictive value (NPV) were 25.0% and 100%, respectively. Triple endoscopy specificity and NPV was 90.2% and 93.2%, respectively. Conclusions PET/CT is superior to triple endoscopy in ruling out SPTs. With negative PET/CT, only direct laryngoscopy with biopsy may be necessary. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The COVID-19 pandemic and upgrades of CI speech processors for children: part I-procedure of speech processor upgrade

xlomafota13 shared this article with you from Inoreader The COVID-19 pandemic and upgrades of CI speech processors for children: part I-procedure of speech processor upgrade 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. 2022 Feb 26. doi: 10.1007/s00405-022-07278-x. Online ahead of print. ABSTRACT PURPOSE: To demonstrate the feasibility of upgrading speech processors during the COVID-19 pandemic. METHODS: Adopting concepts from "lean thinking", we optimized hospital workflows to allow speech processors to be upgraded despite the obstacles arising from national guidelines for COVID-19 prevention. The study involved 297 children, aged from 7.3 to 18.0 years, whose processors were upgraded on five consecutive Saturdays during a time of peak COVID-19 in Poland. RESULTS: The optimized workflow allowed us to conduct speech processor upgrades during a time of peak COVID-19 in Poland. The upgrades were conducted as scheduled, patient flow was smooth, appropriate social distancing was kept, and no reports of COVID-19 infection in our patients in the 2 weeks after their visit were received. CONCLUSION: Upgrading of sp eech processors in children is still feasible under coronavirus conditions. PMID:35217905 | DOI:10.1007/s00405-022-07278-x View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dendritic cells in reflectance confocal microscopy is a clue for early melanoma diagnosis in extrafacial flat pigmented melanocytic lesions

xlomafota13 shared this article with you from Inoreader Dendritic cells in reflectance confocal microscopy is a clue for early melanoma diagnosis in extrafacial flat pigmented melanocytic lesions Via Experimental Dermatology Abstract Background Differential diagnosis of extrafacial flat pigmented lesions with dermoscopic reticular and/or homogeneous pattern is challenging. Dendritic cells upon reflectance confocal microscopy (RCM) still represent a pitfall. Objective To determine the role of dendritic cells upon RCM in the epidermis and dermo-epidermal junction (DEJ), together with common RCM features for melanoma and nevi, in dermoscopically equivocal extrafacial flat pigmented lesions. Methods A retrospective evaluation of RCM images of melanocytic extrafacial flat pigmented lesions with reticular and/or homogeneous dermoscopic pattern and with histopathological diagnosis, was performed. A multivariate model of RCM features was used to obtain a score of independent risk factors. Results A total of 698 lesions were included. Increasing patient age, epidermal dendritic cells, many dendritic cells in the DEJ (>30%), and many (>5/mm2) round atypical cells were independent risk factors for melanoma. Edged papillae and melanophages were indicative of nevus. A score based on these features was developed to assist in melanoma differential diagnosis. Conclusion The RCM observation of abundant (>30%) dendritic cells in the DEJ is highly suggestive of malignity. This independent risk factor should also be considered for improved differential diagnosis of extrafacial melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Can cystic lesions of the jaws be considered as the cause of mandibular asymmetry?

xlomafota13 shared this article with you from Inoreader Can cystic lesions of the jaws be considered as the cause of mandibular asymmetry? Via pubmed: "med oral patol oral... Med Oral Patol Oral Cir Bucal. 2022 Mar 1;27(2):e159-e163. doi: 10.4317/medoral.25134. ABSTRACT BACKGROUND: The aim of this study is to investigate the presence of condylar and ramal asymmetry in patients with a cyst larger than 10 mm in the maxilla or mandible. MATERIAL AND METHODS: Condylar and ramal asymmetry index measurements of 47 patients (mean age: 28.85 ± 15.348) in the study group and 40 patients in the control group (mean age: 33.73 ± 13.095) were performed using panoramic radiographs. The study group consists of patients with cysts larger than 10 mm in diameter in the maxilla or mandible. The control group consisted of patients with no radiolucent lesions and no history of trauma. The possible statistical difference between the groups was evaluated by the Mann-Whitney U test. RESULTS: No statistically significant difference was observed in asymmetry indices according to gender and the jaw (maxilla or mandible) in which the cyst was located. However, it was determined that CAI and RAI values were statistically significantly different between the study and control groups (p = 0.047 and p = 0.016, respectively). CONCLUSIONS: The presence of intraosseous cysts larger than 10 mm in the jaws was found to be associated with condylar and ramal asymmetry. PMID:35218644 | DOI:10.4317/medoral.25134 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study

xlomafota13 shared this article with you from Inoreader MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study Via pubmed: "med oral patol oral... Med Oral Patol Oral Cir Bucal. 2022 Mar 1;27(2):e164-e173. doi: 10.4317/medoral.25138. ABSTRACT BACKGROUND: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSβ (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. MATERIAL AND METHODS: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSβhigh based on hMSH2-hMSH6 and hMSH3- hMSH6 expression, respectively. RESULTS: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. CONCLUSIONS: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT. PMID:35218645 | DOI:10.4317/medoral.25138 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.