Machine learning directed sentinel lymph node biopsy in cutaneous head and neck melanoma

xlomafota13 shared this article with you from Inoreader Machine learning directed sentinel lymph node biopsy in cutaneous head and neck melanoma Via Head & Neck Abstract Background The specificity of sentinel lymph node biopsy (SLNB) for detecting lymph node metastasis in head and neck melanoma (HNM) is low under current National Comprehensive Cancer Network (NCCN) treatment guidelines. Methods Multiple machine learning (ML) algorithms were developed to identify HNM patients at very low risk of occult nodal metastasis using National Cancer Database (NCDB) data from 8466 clinically node negative HNM patients who underwent SLNB. SLNB performance under NCCN guidelines and ML algorithm recommendations was compared on independent test data from the NCDB (n = 2117) and an academic medical center (n = 96). Results The top-performing ML algorithm (AUC = 0.734) recommendations obtained significantly higher specificity compared to the NCCN guidelines in both internal (25.8% vs. 11.3%, p < 0.001) and external test populations (30.1% vs. 7.1%, p < 0.001), while achieving sensitivity >97%. Conclusion Machine learning can identify clinically node negative HNM patients at very low risk of nodal metastasis, who may not benefit from SLNB. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Wogonin reduces cardiomyocyte apoptosis from mitochondrial release of cytochrome c to improve doxorubicin-induced cardiotoxicity

xlomafota13 shared this article with you from Inoreader Wogonin reduces cardiomyocyte apoptosis from mitochondrial release of cytochrome <em>c</em> to improve doxorubicin-induced cardiotoxicity Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):205. doi: 10.3892/etm.2022.11128. Epub 2022 Jan 7. ABSTRACT Doxorubicin (DOX) has powerful anticancer properties, but its clinical application is affected by its serious cardiotoxicity. Wogonin (WG) has been shown to have marked cardiovascular protection potential. However, it is not known whether this potential can protect the heart from DOX damage. The aim of the present study was to investigate whether WG could ameliorate the cardiotoxicity of DOX. DOX and WG were used to establish a model of cardiac damage. Echocardiography, brain natriuretic peptide, creatine kinase MB and cardiac troponin T were used to detect the degree of cardiac damage. The levels of superoxide dismutase, malondialdehyde, glutathione and catalase in serum were measured to observed oxidative stress state. The mRNA levels of cyclophilin D, voltage-dependent anion-selective channel 1 and adenine nucleotide transporter 1 were detected by reverse transcription-quantitative PCR. Western blotting was used to detect the expression of cytochrome c in mitochondria and cytoplasm and cleaved-caspase-9 and pro/cleaved-caspase-3 in cytoplasm in cardiac tissue and primary cardiomyocytes to verify the related signaling pathways. DOX rats showed a series of cardiac damage. However, these damages were alleviated following WG treatment. Further studies showed that WG antagonized DOX cardiotoxicity through inhibiting the release of cytochrome c. WG protected rat heart from DOX damage. The mechanism may be closely related to inhibiting the release of cytochrome c from mitochondria and reducing cardiomyocyte apoptosis caused by caspase activation. PMID:3512 6708 | PMC:PMC8796616 | DOI:10.3892/etm.2022.11128 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Col9a2 gene deletion accelerates the degeneration of intervertebral discs

xlomafota13 shared this article with you from Inoreader Col9a2 gene deletion accelerates the degeneration of intervertebral discs Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):207. doi: 10.3892/etm.2022.11130. Epub 2022 Jan 7. ABSTRACT As an essential component of the extracellular matrix (ECM) in cartilage, the α2 chain of type IX collagen (Col9a2), has been implicated in human intervertebral disc degeneration (IVDD). However, the precise role of the Col9a2 gene in the pathogenesis of IVDD has remained elusive. In the present study, the spines of Col9a2-deficient (Col9a2-/-) mice were systematically analyzed and compared with wild-type control mice using micro-CT (µCT), histomorphology, immunofluorescence, immunohistochemistry and reverse transcription-quantitative PCR (RT-qPCR). µCT analysis revealed that endplate (EP) osteochondral remodeling in the Col9a2-/- group was accompanied by a significant increase in EP porosity. Likewise, histopathological staining at 12 weeks revealed that the Col9a2-/- mice exhibited a marked early-stage IVDD phe notype, including EP sclerosis, calcification and annulus fibrosus rupture. The immunofluorescence results indicated that Col9a2 was extensively expressed in the IVDs, whereas it was barely detectable in Col9a2-/- mice. Immunohistochemical and RT-qPCR analyses demonstrated that the expression levels of Col2a1 and Aggrecan in the IVDs of Col9a2-/- mice were significantly decreased. In addition, the levels of Mmp13, ADAM metallopeptidase with thrombospondin type 1 motif 5, Col10a1 and Runx family transcription factor 2 were significantly elevated. These results suggested that deletion of the Col9a2 gene led to osteochondral remodeling of cartilage EP and suppressed ECM synthesis, accelerating matrix degradation and chondrocyte hypertrophy in the IVD tissue. PMID:35126710 | PMC:PMC8796617 | DOI:10.3892/etm.2022.11130 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An original method of simulating the articular cartilage in the context of in vitro biomechanical studies investigating the proximal femur

xlomafota13 shared this article with you from Inoreader An original method of simulating the articular cartilage in the context of <em>in vitro</em> biomechanical studies investigating the proximal femur Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):202. doi: 10.3892/etm.2022.11125. Epub 2022 Jan 5. ABSTRACT Biomechanical testing is a necessity given the development of novel implants used in the osteosynthesis of hip fractures. The purpose of biomechanical testing is to recreate realistic conditions similar to the in vivo conditions. Although biomechanical testing of hip arthroplasty has been standardized since the 1970s, there is no consensus at present on testing methodology for osteosynthesis of hip fractures. Most biomechanical studies examining the fractures of the proximal femur in order to optimize implants opt for loading the bone-implant ensemble directly on the femoral head or using a metallic loading part. This loading technique fails to perform a mechanical stress distribution similar to in vivo conditions, which could alter the outcome. The present study aimed to design loading/unloading cups with mechanical properties that r esemble those of the cartilage at the hip level. Through the impression and scanning of the cast models obtained, a digital 3D model was created in STL format and this was processed in order to obtain the computer numerical control (CNC) trajectories of the printing head. For prototyping using additive manufacturing technology, a thermoplastic polymer with biochemical properties, such as tensile strength, that resemble those of the adult hip and a Stratasys FORTUS 250 mc CNC machine were used. Loading/unloading cups with similar anatomy and biomechanical forces compared with those of the adult hip were created, which allowed the experimental simulation of the conditions during walking. PMID:35126705 | PMC:PMC8794553 | DOI:10.3892/etm.2022.11125 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Benefits and adverse events of melatonin use in the elderly (Review)

xlomafota13 shared this article with you from Inoreader Benefits and adverse events of melatonin use in the elderly (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):219. doi: 10.3892/etm.2022.11142. Epub 2022 Jan 14. ABSTRACT Melatonin is a hormone secreted by the pineal gland in accordance with the circadian rhythm when the light level decreases. Reduction of melatonin secretion with age may be associated with physiological aging in neurodegenerative diseases by affecting the suprachiasmatic nucleus or of the neuronal pathways of transmission to the pineal gland. A significant decrease in melatonin synthesis has been reported in various disorders and diseases, including cardiovascular diseases, metabolic disorders (particularly diabetes type 2), cancer and endocrine diseases. In addition to the fact, that melatonin is a sleep inducer, it also exerts cytoprotective properties as an antioxidant and free radical scavenger. The therapeutic role of melatonin has been demonstrated in sleep disorders, eye damage and cardiovascular disease. The association between melatonin a nd β-blockers has had a positive impact on sleep disorders in clinical trials. Previous studies have reported the anti-inflammatory effect of melatonin by adjusting levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis factor-α. Melatonin treatment has been demonstrated to decrease IL-6 and IL-10 expression levels and efficiently attenuate T-cell proliferation. Currently, there is an inconsistency of scientific data regarding the lowest optimal dose and safety of melatonin for long-term use. The aim of the present review was to summarize the evidence on the role of melatonin in various clinical conditions and highlight the future research in this area. PMID:35126722 | PMC:PMC8796282 | DOI:10.3892/etm.2022.11142 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficiency of platelet-rich plasma therapy for healing sports injuries in young athletes

xlomafota13 shared this article with you from Inoreader Efficiency of platelet-rich plasma therapy for healing sports injuries in young athletes Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):215. doi: 10.3892/etm.2022.11139. Epub 2022 Jan 11. ABSTRACT In recent years, platelet-rich plasma (PRP) therapy has been a subject of controversy in orthopedics field. Our objective was to assess the efficiency of PRP therapy for patients who have suffered grade 2 meniscal lesions and grade 2 anterior cruciate ligament (ACL) lesions, graded by magnetic resonance imaging (MRI). A retrospective observational study was conducted, which included 72 young recreational athletes who had been diagnosed with grade 2 meniscal injury, graded using MRI, that benefited from PRP therapy as an enhancement of the primary treatment, after cast immobilization. The Lysholm score, the pain intensity and the resuming of the physical activity before the PRP treatment and one month after were analyzed. Our study revealed that patients had an improved subjective perception of pain after PRP therapy and an improvement of the Lysho lm score. Concurrently, 83.3% of patients could return to sports and daily physical activity. It can be concluded that PRP therapy is a safe, easy to manage treatment, efficient for pain relief and in resuming of sports activities for young recreational athletes who have sustained partial meniscal or ACL tears. In terms of pain relief, it appears that the PRP therapy could be more efficient for young patients with ACL injuries. PMID:35126718 | PMC:PMC8796279 | DOI:10.3892/etm.2022.11139 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats

xlomafota13 shared this article with you from Inoreader Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):216. doi: 10.3892/etm.2022.11140. Epub 2022 Jan 11. ABSTRACT Hypertension is associated with bladder symptoms. The present study investigated whether an angiotensin receptor blocker could improve the symptoms and pathological changes associated with a neurogenic bladder (NB). A Sprague-Dawley rat model of NB was constructed. Rats in the sham and model groups were gavaged with saline, and rats in the treatment group were gavaged with telmisartan. Urodynamic parameters, including maximum cystometric capacity, residual urine volume, bladder wet weight, bladder compliance and detrusor pressure, were detected. Masson and H&E staining were performed to assess bladder fibrosis and histopathological changes. The expression levels of basic fibroblast growth factor (bFGF), TGF-β1, Collagen I, Collagen III, and α-smooth muscle actin (α-SMA) were also measured by reverse transcription-quantitative PCR, western b lotting and immunohistochemistry. The model rats exhibited symptoms and pathological changes associated with NB. Treatment with telmisartan reduced maximum cystometric capacity, residual urine volume, bladder compliance and bladder wet weight, and increased detrusor pressure in model rats. The tissue staining results showed that telmisartan exerted an antifibrotic effect. In addition, telmisartan inhibited the expression of bFGF, TGF-β1, Collagen I, Collagen III and α-SMA in model rats. Therefore, the results of the present study indicated that telmisartan may serve as a potential therapeutic agent for NB. PMID:35126719 | PMC:PMC8796288 | DOI:10.3892/etm.2022.11140 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Identification of key pathways and genes in vestibular schwannoma using bioinformatics analysis

xlomafota13 shared this article with you from Inoreader Identification of key pathways and genes in vestibular schwannoma using bioinformatics analysis Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):217. doi: 10.3892/etm.2022.11141. Epub 2022 Jan 13. ABSTRACT The aim of the present study is to identify novel promising marks and targets of diagnosis, therapy and prognosis for patients with vestibular schwannoma at the molecular level. The gene expression profiles of GSE54934, GSE39645 and GSE56597 datasets were obtained respectively from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified by comparing between gene expression profiles of the vestibular schwannoma tissues and normal tissues. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were performed. The function and pathway enrichment analysis were performed for DEGs with DAVID. Reverse transcription-quantitative PCR were conducted to confirm the expression of BCL2, AGT, IL6 and ITGA2 in human Schwann cells and vestibular schwannoma cells. A total of 4,025, 1,1291 and 1,513 DEGs were identified from GSE54934, GSE56597 and GSE39645 datasets, respectively. GO and KEGG analysis showed that the mutual upregulated genes were mainly enriched in cell division, mitotic nuclear division, and transition of mitotic cell cycle, whilst mutual downregulated genes were enriched in chemical synaptic transmission, neurotransmitter transport, and synaptic vesicle membrane. Subsequently, 20 genes, including BCL2, AGT, IL6 and ITGA2 were selected as hub genes with high degrees after PPI network analysis. The significant differential expression of those genes were detected among vestibular schwannoma tissues compared with normal nerve tissues. In conclusion, BCL2, AGT, IL6 and ITGA2 are significantly higher expressed in vestibular schwannoma tissues compared with human Schwann tissues. The DEGs identified in the present study provide novel targets for the diagnosis and treatment of vestibular schwannoma. PMID:35126720 | PMC:PMC8796280 | DOI:10.3892/etm.2022.11141 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review)

xlomafota13 shared this article with you from Inoreader Role of antioxidants and oxidative stress in the evolution of acute pancreatitis (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):197. doi: 10.3892/etm.2022.11120. Epub 2022 Jan 5. ABSTRACT Acute pancreatitis (AP) is a severe disease with a high prevalence and 3 to 15% mortality worldwide, which can represent an important challenge for the physician. Oxidative stress and antioxidants are involved in AP progression. The mechanisms responsible for the onset and progression of AP are still poorly understood. Previous studies have highlighted the important contribution of antioxidants and oxidative stress in AP. The existence of a relationship between oxidative stress and antioxidants in AP is unquestionable, although a more accurate understanding of the mechanistic pathways involved is required to create a solid basis for potential prevention or treatment strategies. Further investigation is needed to clarify the role of antioxidant status and the severity of AP and to determine the association between oxidative stress and pancreatic enz yme activities. Antioxidant therapy may represent an interesting option for the management of patients with AP, although additional information about the effectiveness of this potential treatment is required. PMID:35126700 | PMC:PMC8794551 | DOI:10.3892/etm.2022.11120 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

From chronic pruritus to neuroendocrine tumor: A case report

xlomafota13 shared this article with you from Inoreader From chronic pruritus to neuroendocrine tumor: A case report Via Experimental and therapeutic medicine Exp Ther Med. 2022 Mar;23(3):189. doi: 10.3892/etm.2022.11112. Epub 2022 Jan 4. ABSTRACT Chronic pruritus is a major and distressing symptom of many diseases of dermatological, neurological, psychogenic or systemic origin. This chronic itch could be a presenting sign of malignancy; therefore, paraneoplastic pruritus has also been associated with neuroendocrine tumors (NETs). This article focuses on a patient presenting with chronic pruritus for the past 12 months and who received numerous treatment schemes with very poor clinical improvement, that presented in the hospital for worsening of the chronic pruritus associated with skin rash and significant weight loss (approximately 6 kg over a 2-month period). The laboratory tests showed iron deficiency anemia, eosinophilia and negative tumor markers. In order to investigate the hypoanabolic and anemic syndromes, upper gastrointestinal endoscopy and colonoscopy, which showed no lesions or tumors, were employed. Skin biopsy was performed and antihistaminic and local steroid treatment was initiated. The patient's status worsened within a week and the patient was started on systemic steroid treatment with poor results. Computer tomography was performed to identify any tumor(s) located either in the pelvis or abdomen. A lesion was found in the terminal ileum, identified as a hypervascularized associating bulky lymphadenopathy. The patient was transferred to the surgical ward where right hemicolectomy with manual ileotransverse anastomosis L-L was performed. The histopathological result confirmed NET G2. The patient clinically improved, the skin lesions resolved and the itchiness disappeared. The general status improved significantly. NET G2 diagnosing was possible due to the atypic paraneoplastic sign: chronic pruritus. This case study highlights the association between itch and malignancy and presents an atypical way of NET presentation when all tumor markers remain neg ative. PMID:35126692 | PMC:PMC8794552 | DOI:10.3892/etm.2022.11112 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cytokines and Inflammation in Meniere Disease

xlomafota13 shared this article with you from Inoreader Cytokines and Inflammation in Meniere Disease Via pubmed: "clin exp otorhinola... Clin Exp Otorhinolaryngol. 2022 Feb 8. doi: 10.21053/ceo.2021.00920. Online ahead of print. ABSTRACT Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evide nce to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials. PMID:35124944 | DOI:10.21053/ceo.2021.00920 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.