Objective: Systemic Sclerosis (SSc) is primarily characterized by autoimmunity, Microangiopathy, and tissue fi brosis. Hypoxia, a powerful stimulator of Vascular Endothelial Growth Factor (VEGF), may be responsible for excessive expression of chronic VEGF in SSc. The oxygen-regulated α-subunit of hypoxia-inducible transcription factor-1 (HIF-1α) plays an important role in transcriptional regulation of VEGF. The protein phosphatase and tension homolog (PTEN) is responsible for dephosphorylation of proteins and thereby promotes tissue repair.
The present study aimed to examine the expressions of HIF-1α, PTEN, and VEGF in patients with scleroderma in an attempt to
estimate prognosis and guide therapeutic decisions. We therefore studied the expressions of HIF-1 α, VEGF, and PTEN in skin samples exhibiting the features of scleroderma.
This double-blind, placebo-controlled trial explored the safety and potential efficacy of hyperimmune caprine serum (AIMSPRO) in 20 patients with established diffuse cutaneous systemic sclerosis (SSc) over 26 weeks. The trial found no safety concerns with AIMSPRO. Patients receiving AIMSPRO showed a mean decrease in modified Rodnan Skin Score compared to an increase in the placebo group. Levels of PIIINP, a biomarker of fibrosis, increased less in the AIMSPRO group. The results support the safety of AIMSPRO and suggest it may provide clinical benefit for skin disease in SSc.
This document describes a case report of a successful treatment of disseminated strongyloidiasis in an immunocompromised patient using subcutaneous ivermectin. A 56-year-old man being treated with corticosteroids developed sepsis and respiratory failure due to strongyloidiasis. Oral ivermectin treatment was ineffective, so the patient was treated with subcutaneous ivermectin, which successfully cured the infection. The patient was removed from life support and discharged from the hospital. While parenteral ivermectin treatment has not been approved, this case suggests it may be an effective salvage therapy for disseminated strongyloidiasis when oral treatment fails or cannot
Yayan T. Sundara, Dokter di Klinik Jejaring Padjadjaran dan Master of Bio Medical Science Research dari Leiden University Medical Centrum, juga staff Departemen Pelayanan PT Rumah Sakit Padjadjaran
This document summarizes a study on using maggot debridement therapy (MDT) to treat necrotizing fasciitis. 15 patients with necrotizing fasciitis were treated with surgical debridement, antibiotics, and MDT. MDT involved applying sterile maggots to wounds to remove dead tissue. Patients who started MDT within 9 days of diagnosis needed fewer surgical debridements than those treated later. The study concludes that early use of MDT may reduce surgical interventions and help wounds heal for patients with necrotizing fasciitis.
This document discusses treatment options for Legionnaires' disease, including macrolides versus fluoroquinolones. It summarizes several studies comparing these drug classes and finds azithromycin and levofloxacin to be equally effective with shorter treatment duration for fluoroquinolones. Severe Legionnaires' disease is associated with higher mortality, especially if initial appropriate treatment is delayed or inadequate. Prognostic factors for death include an APACHE score over 15, shock, immunosuppression, and acute renal failure.
Turn in version literature 5 years old (excluding seminal articlesSALU18
This meta-analysis reviewed 12 randomized controlled trials and 6 non-randomized controlled trials comparing outcomes of cadaver skin allograft and other skin substitutes for burn treatment. The studies generally had a high risk of bias. No significant differences were found between allografts and other substitutes for outcomes of wound healing, graft take percentage, scar appearance, or mortality. More high-quality research is still needed to determine the best treatment options.
This document summarizes a research study that investigated the role of long non-coding RNA H19, microRNA miR-29b, and the gene FOXO4 in the apoptosis of retinal Müller cells in diabetic retinopathy. The study found that H19 and FOXO4 expression were increased, while miR-29b expression was decreased, in retinal tissue from diabetic rats and in retinal Müller cells treated with high glucose. Overexpression of H19 promoted retinal Müller cell apoptosis. Knockdown of H19 reversed the effects of high glucose by decreasing cell apoptosis and FOXO4 upregulation. Further experiments indicated that H19 is a target of miR-29b and inhibition of miR-29b
This double-blind, placebo-controlled trial explored the safety and potential efficacy of hyperimmune caprine serum (AIMSPRO) in 20 patients with established diffuse cutaneous systemic sclerosis (SSc) over 26 weeks. The trial found no safety concerns with AIMSPRO. Patients receiving AIMSPRO showed a mean decrease in modified Rodnan Skin Score compared to an increase in the placebo group. Levels of PIIINP, a biomarker of fibrosis, increased less in the AIMSPRO group. The results support the safety of AIMSPRO and suggest it may provide clinical benefit for skin disease in SSc.
This document describes a case report of a successful treatment of disseminated strongyloidiasis in an immunocompromised patient using subcutaneous ivermectin. A 56-year-old man being treated with corticosteroids developed sepsis and respiratory failure due to strongyloidiasis. Oral ivermectin treatment was ineffective, so the patient was treated with subcutaneous ivermectin, which successfully cured the infection. The patient was removed from life support and discharged from the hospital. While parenteral ivermectin treatment has not been approved, this case suggests it may be an effective salvage therapy for disseminated strongyloidiasis when oral treatment fails or cannot
Yayan T. Sundara, Dokter di Klinik Jejaring Padjadjaran dan Master of Bio Medical Science Research dari Leiden University Medical Centrum, juga staff Departemen Pelayanan PT Rumah Sakit Padjadjaran
This document summarizes a study on using maggot debridement therapy (MDT) to treat necrotizing fasciitis. 15 patients with necrotizing fasciitis were treated with surgical debridement, antibiotics, and MDT. MDT involved applying sterile maggots to wounds to remove dead tissue. Patients who started MDT within 9 days of diagnosis needed fewer surgical debridements than those treated later. The study concludes that early use of MDT may reduce surgical interventions and help wounds heal for patients with necrotizing fasciitis.
This document discusses treatment options for Legionnaires' disease, including macrolides versus fluoroquinolones. It summarizes several studies comparing these drug classes and finds azithromycin and levofloxacin to be equally effective with shorter treatment duration for fluoroquinolones. Severe Legionnaires' disease is associated with higher mortality, especially if initial appropriate treatment is delayed or inadequate. Prognostic factors for death include an APACHE score over 15, shock, immunosuppression, and acute renal failure.
Turn in version literature 5 years old (excluding seminal articlesSALU18
This meta-analysis reviewed 12 randomized controlled trials and 6 non-randomized controlled trials comparing outcomes of cadaver skin allograft and other skin substitutes for burn treatment. The studies generally had a high risk of bias. No significant differences were found between allografts and other substitutes for outcomes of wound healing, graft take percentage, scar appearance, or mortality. More high-quality research is still needed to determine the best treatment options.
This document summarizes a research study that investigated the role of long non-coding RNA H19, microRNA miR-29b, and the gene FOXO4 in the apoptosis of retinal Müller cells in diabetic retinopathy. The study found that H19 and FOXO4 expression were increased, while miR-29b expression was decreased, in retinal tissue from diabetic rats and in retinal Müller cells treated with high glucose. Overexpression of H19 promoted retinal Müller cell apoptosis. Knockdown of H19 reversed the effects of high glucose by decreasing cell apoptosis and FOXO4 upregulation. Further experiments indicated that H19 is a target of miR-29b and inhibition of miR-29b
Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecu...Joshua Mangerel
This document summarizes the results of a study that integrated genomic data to identify molecular subgroups in diffuse intrinsic pontine glioma (DIPG), a deadly childhood brain cancer. The study found that DIPG comprises three distinct subgroups - MYCN, silent, and H3-K27M - with differences in mutations, gene expression, methylation, and clinical features. A novel recurrent mutation was discovered in the ACVR1 gene in 20% of DIPGs. The identification of distinct molecular subgroups highlights the heterogeneity of DIPG and could help guide more targeted treatment approaches for this incurable cancer.
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
Cefditoren pivoxil:a new antibiotic for the treatment of respiratory infectionsJordi Roig
Cefditoren pivoxil is a new oral cephalosporin antibiotic for the treatment of respiratory tract infections. It has high in vitro activity against common respiratory pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Clinical trials showed that cefditoren was as effective as other antibiotics like amoxicillin-clavulanate, cefuroxime, and clarithromycin in treating conditions like acute otitis media, acute sinusitis, acute pharyngotonsillitis, and acute exacerbations of chronic bronchitis. Cefditoren demonstrated bactericidal activity against penicillin-resistant S. pneumoniae strains
Recent Trends in Genomic Biomarkers - Pepgra HealthcarePEPGRA Healthcare
Cardiovascular disease is a significant health concern worldwide despite having many genomics developments providing valuable new candidates for better biomarkers and novel therapeutic targets. The main integration of new technologies promises the discovery and validation of better biomarkers of the presence of cardio disease, its progression, and the response to treatment in this blog. Some of the features are:
1. Analyzing the Gene expression
2. Genome-wide association studies
3. Linkage analysis
4. Wrapping up...
Continue Reading: http://bit.ly/3bqq3Np
Contact us:
UK: +44-1143520021
US/Canada: +1-972-502-9262
India: +91-9884350006
Email id: sales.cro@pepgra.com
Website: www.pepgra.com
Detection of Cystathionine, 2-Hydroxyglutarate and Citrate in Oligodendroglio...Uzay Emir
The semi-LASER sequence optimized for 2-HG detection with a TE of 110 ms successfullydemonstrated distinct cystathionine peaks in glioma patients with molecularly definedoligodendroglioma (IDH-mutant and 1p/19q codeleted) at 7T. While a prospective, betterpowered study is needed to confirm our observations, we propose that our method has thepotential to allow presurgical stratification of patients with IDH-mutant glioma into those witholigodendrogliomas and astrocytomas; which is of important prognostic significance.
(PDF) Detection of Cystathionine, 2-Hydroxyglutarate and Citrate in Oligodendrogliomas at 7T using Long-TE Semi-LASER. Available from: https://www.researchgate.net/publication/349575306_Detection_of_Cystathionine_2-Hydroxyglutarate_and_Citrate_in_Oligodendrogliomas_at_7T_using_Long-TE_Semi-LASER [accessed Mar 03 2021].
Newer management techniques for glioblastomaabhitux
Local therapies for brain tumors involve directly administering therapeutic agents into or near the tumor to produce an anti-tumor effect. Gliadel wafers, which slowly release the chemotherapy drug BCNU, have been shown in clinical trials to improve survival outcomes for patients with malignant glioma when implanted during surgery compared to placebo wafers. While Gliadel can cause side effects like edema and healing abnormalities, its benefits outweigh the risks. Convection-enhanced delivery is a method for directly infusing drugs into brain tumors that may help overcome issues like poor drug penetration and resistance.
The document summarizes research on using skin gene expression as a biomarker for systemic sclerosis (SSc) skin disease. It discusses how skin biopsies are currently used to measure gene expression and develop a 415-gene signature of SSc skin disease. This signature appears to correlate with and potentially predict future skin severity scores. The signature analysis also suggests the epidermal growth factor (EGF) pathway may be important in SSc skin disease. Future work aims to determine if targeting the EGF pathway could be a useful treatment approach.
This document provides an overview of gene therapy presented by Vishnu Kumar Dhakad. It discusses the history of gene therapy from its origins in 1960 to early clinical trials in 1990. The presentation covers approaches to gene therapy including gene modification, transfer methods using viral and non-viral vectors, and applications to specific cell lines. Examples of successful gene therapy treatments for blindness and Parkinson's disease are provided. The document also notes some advantages and disadvantages of gene therapy as well as ethical considerations surrounding the field.
This document discusses the diagnosis and treatment of primary central nervous system lymphoma (PCNSL). It begins by describing the typical clinical presentation of PCNSL, which most commonly involves focal neurological deficits, personality changes, and increased intracranial pressure. Magnetic resonance imaging is the preferred imaging modality, showing lesions that are often hypointense on T2-weighted imaging and demonstrate homogeneous enhancement with contrast. Stereotactic biopsy is the preferred method for diagnosis while avoiding gross tumor resection which has not shown survival benefits. The document goes on to discuss treatment approaches and challenges in managing this rare and aggressive malignancy of the central nervous system.
BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadi...UniversitasGadjahMada
1) The study investigated BRCA1 promoter methylation and its association with clinicopathological characteristics in 56 Indonesian breast cancer patients.
2) BRCA1 promoter methylation was detected in 48 of 56 (85%) patients. Lower BRCA1 mRNA expression was associated with higher methylation levels, suggesting epigenetic silencing of BRCA1.
3) However, no significant associations were found between methylation levels, BRCA1 expression, and clinicopathological factors like tumor stage or size. This study provides the first analysis of BRCA1 methylation in an Indonesian breast cancer population.
This study investigated the effects of cytokine adsorption therapy in patients with severe refractory septic shock. 48 patients received 3 sessions of cytokine adsorption therapy within 24 hours of shock onset, while 48 matched control patients received standard care without cytokine adsorption. Both groups saw similar decreases in interleukin-6 levels and vasopressor requirements. However, patients receiving cytokine adsorption therapy had higher intensive care mortality than the control group. The results suggest that indiscriminate removal of cytokines with adsorption therapy may be harmful for patients with severe septic shock.
This study examined the prevalence of cryptococcal meningitis (CM) among people living with HIV/AIDS (PLHAs) at a hospital in southern Odisha, India. Of 112 clinically diagnosed CM patients, 16 cases were confirmed via cerebrospinal fluid analysis, showing a prevalence of 14.3%. Males aged 21-40 were most commonly affected. The most common symptoms were fever, headache, altered sensorium, and neck stiffness. CD4 T-lymphocyte counts were below 100 cells/μl in 93.7% of confirmed cases. All patients responded initially to antifungal therapy but 2 died during hospitalization and 4 were lost to follow up. Early diagnosis and treatment of CM is
1. The study examines the mechanism by which gd T cells induce cytotoxicity of human oligodendrocytes, which are relevant to multiple sclerosis.
2. The results show that gd T cells from MS patients utilize both the Fas-mediated and perforin-based pathways to exert cytotoxic effects on oligodendrocytes.
3. Blocking perforin release completely inhibited killing of targets expressing high levels of heat shock proteins, but additional blocking of Fas ligand was required to fully inhibit killing of Fas-expressing targets and fresh oligodendrocytes.
This document provides an overview of glioblastoma, including its incidence, risk factors, prognosis, biomarkers, and molecular subtypes. Some key points:
- Glioblastoma accounts for 54% of new gliomas and 45% of primary malignant brain tumors. 5-year survival rates are below 5% worldwide.
- Risk factors include age, ionizing radiation exposure, and certain genetic syndromes. Prognostic factors associated with better outcomes include younger age, methylated MGMT status, and extent of surgical resection.
- Emerging biomarkers like IDH1/2 mutations and EGFR amplification/mutations show promise in predicting prognosis, though MGMT methylation status is currently the only validated predictive biomarker.
1) The study analyzed copy number variants (CNVs) in 60 cardiomyopathy-associated genes from over 2,000 individuals who underwent genetic testing.
2) They identified 35 unique CNVs in these individuals, 10 of which were classified as pathogenic and 24 as uncertain significance.
3) Pathogenic CNVs were found in 1.9% of individuals and included deletions in genes like DSP and PKP2 associated with arrhythmogenic right ventricular cardiomyopathy. The identification of pathogenic CNVs provides important clinical implications for affected families.
This document summarizes a study examining the expression of Thomsen-Friedenreich antigen (TF-antigen), a mucin-type glycoprotein, in human esophageal squamous cell carcinoma (ESCC) using peanut agglutinin (PNA) binding. The study found increased levels of TF-antigen in the serum and tissues of ESCC patients compared to normal individuals. TF-antigen levels did not differ between well, moderately, and poorly differentiated ESCC grades and did not decrease after therapy. Expression of TF-antigen increased with histological progression and was localized to the Golgi apparatus and cell membrane in ESCC tissues. The study establishes TF-antigen as a potential diagnostic marker for ES
This document describes a large Indian family with 18 individuals affected by distal arthrogryposis (DA). Whole exome sequencing was performed on 3 affected individuals and identified a heterozygous missense mutation (c.188G>A) in the TNNT3 gene in all 3 individuals. This mutation has previously been reported to cause DA. Detailed clinical descriptions are provided for 4 affected family members, demonstrating variable features including camptodactyly, brachydactyly, syndactyly, decreased flexion creases, ulnar deviation of hands, and club feet. This study identifies a causal mutation for DA in this family and highlights the phenotypic variability associated with mutations in the TNNT3 gene
Analysing Entity Type Variation across Biomedical SubdomainsClaudiu Mihăilă
This document discusses analyzing variation in entity types across biomedical subdomains. It presents a methodology that uses named entity annotations from three sources to generate feature vectors representing entity type distributions in documents. These feature vectors are used to calculate similarity between pairs of documents from different subdomains, using Chi-squared statistics and the Frobenius norm. A random forest classifier is able to distinguish between similar and dissimilar subdomain pairs based only on entity type distributions. The findings indicate significant semantic variation between biomedical sublanguages that can be leveraged to distinguish subdomains and inform adaptation of NLP tools.
A common rejection module (CRM) for acute rejection across multiple organsKevin Jaglinski
This document summarizes a study that identified a common rejection module (CRM) of genes that are overexpressed during acute rejection across multiple solid organ transplants (heart, kidney, liver, lung). Through meta-analysis of gene expression data from transplant biopsies, the study identified 11 genes that comprise the CRM. Validation in independent cohorts showed the CRM genes can diagnose acute rejection with high accuracy. The CRM genes also correlated with the extent of graft injury and predicted future injury. Based on known drug mechanisms, the study explored using FDA-approved drugs atorvastatin and dasatinib to target specific CRM genes, reducing graft-infiltrating cells and extending graft survival in a mouse model of cardiac transplant rejection
Study Demonstrates Effectiveness of combination therapy for breast cancer cel...emmanuel0915
The document discusses two studies: 1) A combination therapy for breast cancer cells that was shown to be effective in vitro, targeting genes that promote cancer cell growth. 2) A safer alternative gene therapy for HIV infection that uses zinc finger nucleases to eliminate the CCR5 receptor in T cells, making them resistant to HIV. The therapies show promise for treating cancers resistant to chemotherapy and providing an effective treatment for HIV infection.
A NOVEL STUDY OF LICHEN PLANOPILARIS AMONG DIFFERENT IRANIAN ETHNICITIES BASE...ijcsit
Introduction: Demographic studies of a disease can reveal the characteristics of that disease among a specific population and will help the physicians to achieve a more accurate perception about it.The demographic of Lichen PlanoPilaris (LPP) among the Iranian population is unknown. The aim of this study is to describe the clinical, demographic, and histopathologic findings of lichen planopilaris in the Iranian population.
Materials and Methods: In this cross-sectional study, all the patients with Lichen planopilaris were referred to the dermatology clinic of Imam Khomeini hospital from 2013 to 2015. Lichen planopilaris can be diagnosed by collecting histological evidence, dermatological examination, and clinical diagnosis. Their demographic characteristics, drug histories, onset of disease, and family histories were obtained by written questionnaire. Additionally, this study employed SPSS v.20 as the statistical analysis software.
Results: One hundred patients were enrolled in this study. With an average age of 47.11 years, 78% of the patients were female, and 50 of these were housewives. The patients included were often from Tehran with Fars ethnicity. Among these patients, 7 had alopecia areata skin disease, and 10 of them suffered from thyroid disease. Most of the histopathology samples collected from these biopsies revealed degeneration of the basal layer of the follicular structure, perifollicular fibrosis, inflammatory cells, and atrophy of the pilosebaceous structures.
Conclusion: Both the age spectrum and the disease distribution of LPP among the Iranian population were very diverse when compared to previous studies. Moreover, this study helps the physicians to have a brighter vision about the main reason and cause of LPP spread among diverse Iranian Ethnicities.
Demographic studies of a disease can reveal the characteristics of that disease among a specific population and will help the physicians to achieve a more accurate perception about it.The demographic of Lichen PlanoPilaris (LPP) among the Iranian population is unknown. The aim of this study is to describe the clinical, demographic, and histopathologic findings of lichen planopilaris in the Iranian population.
Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecu...Joshua Mangerel
This document summarizes the results of a study that integrated genomic data to identify molecular subgroups in diffuse intrinsic pontine glioma (DIPG), a deadly childhood brain cancer. The study found that DIPG comprises three distinct subgroups - MYCN, silent, and H3-K27M - with differences in mutations, gene expression, methylation, and clinical features. A novel recurrent mutation was discovered in the ACVR1 gene in 20% of DIPGs. The identification of distinct molecular subgroups highlights the heterogeneity of DIPG and could help guide more targeted treatment approaches for this incurable cancer.
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
Cefditoren pivoxil:a new antibiotic for the treatment of respiratory infectionsJordi Roig
Cefditoren pivoxil is a new oral cephalosporin antibiotic for the treatment of respiratory tract infections. It has high in vitro activity against common respiratory pathogens like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Clinical trials showed that cefditoren was as effective as other antibiotics like amoxicillin-clavulanate, cefuroxime, and clarithromycin in treating conditions like acute otitis media, acute sinusitis, acute pharyngotonsillitis, and acute exacerbations of chronic bronchitis. Cefditoren demonstrated bactericidal activity against penicillin-resistant S. pneumoniae strains
Recent Trends in Genomic Biomarkers - Pepgra HealthcarePEPGRA Healthcare
Cardiovascular disease is a significant health concern worldwide despite having many genomics developments providing valuable new candidates for better biomarkers and novel therapeutic targets. The main integration of new technologies promises the discovery and validation of better biomarkers of the presence of cardio disease, its progression, and the response to treatment in this blog. Some of the features are:
1. Analyzing the Gene expression
2. Genome-wide association studies
3. Linkage analysis
4. Wrapping up...
Continue Reading: http://bit.ly/3bqq3Np
Contact us:
UK: +44-1143520021
US/Canada: +1-972-502-9262
India: +91-9884350006
Email id: sales.cro@pepgra.com
Website: www.pepgra.com
Detection of Cystathionine, 2-Hydroxyglutarate and Citrate in Oligodendroglio...Uzay Emir
The semi-LASER sequence optimized for 2-HG detection with a TE of 110 ms successfullydemonstrated distinct cystathionine peaks in glioma patients with molecularly definedoligodendroglioma (IDH-mutant and 1p/19q codeleted) at 7T. While a prospective, betterpowered study is needed to confirm our observations, we propose that our method has thepotential to allow presurgical stratification of patients with IDH-mutant glioma into those witholigodendrogliomas and astrocytomas; which is of important prognostic significance.
(PDF) Detection of Cystathionine, 2-Hydroxyglutarate and Citrate in Oligodendrogliomas at 7T using Long-TE Semi-LASER. Available from: https://www.researchgate.net/publication/349575306_Detection_of_Cystathionine_2-Hydroxyglutarate_and_Citrate_in_Oligodendrogliomas_at_7T_using_Long-TE_Semi-LASER [accessed Mar 03 2021].
Newer management techniques for glioblastomaabhitux
Local therapies for brain tumors involve directly administering therapeutic agents into or near the tumor to produce an anti-tumor effect. Gliadel wafers, which slowly release the chemotherapy drug BCNU, have been shown in clinical trials to improve survival outcomes for patients with malignant glioma when implanted during surgery compared to placebo wafers. While Gliadel can cause side effects like edema and healing abnormalities, its benefits outweigh the risks. Convection-enhanced delivery is a method for directly infusing drugs into brain tumors that may help overcome issues like poor drug penetration and resistance.
The document summarizes research on using skin gene expression as a biomarker for systemic sclerosis (SSc) skin disease. It discusses how skin biopsies are currently used to measure gene expression and develop a 415-gene signature of SSc skin disease. This signature appears to correlate with and potentially predict future skin severity scores. The signature analysis also suggests the epidermal growth factor (EGF) pathway may be important in SSc skin disease. Future work aims to determine if targeting the EGF pathway could be a useful treatment approach.
This document provides an overview of gene therapy presented by Vishnu Kumar Dhakad. It discusses the history of gene therapy from its origins in 1960 to early clinical trials in 1990. The presentation covers approaches to gene therapy including gene modification, transfer methods using viral and non-viral vectors, and applications to specific cell lines. Examples of successful gene therapy treatments for blindness and Parkinson's disease are provided. The document also notes some advantages and disadvantages of gene therapy as well as ethical considerations surrounding the field.
This document discusses the diagnosis and treatment of primary central nervous system lymphoma (PCNSL). It begins by describing the typical clinical presentation of PCNSL, which most commonly involves focal neurological deficits, personality changes, and increased intracranial pressure. Magnetic resonance imaging is the preferred imaging modality, showing lesions that are often hypointense on T2-weighted imaging and demonstrate homogeneous enhancement with contrast. Stereotactic biopsy is the preferred method for diagnosis while avoiding gross tumor resection which has not shown survival benefits. The document goes on to discuss treatment approaches and challenges in managing this rare and aggressive malignancy of the central nervous system.
BRCA1 Promoter Methylation and Clinicopathological Characteristics in Sporadi...UniversitasGadjahMada
1) The study investigated BRCA1 promoter methylation and its association with clinicopathological characteristics in 56 Indonesian breast cancer patients.
2) BRCA1 promoter methylation was detected in 48 of 56 (85%) patients. Lower BRCA1 mRNA expression was associated with higher methylation levels, suggesting epigenetic silencing of BRCA1.
3) However, no significant associations were found between methylation levels, BRCA1 expression, and clinicopathological factors like tumor stage or size. This study provides the first analysis of BRCA1 methylation in an Indonesian breast cancer population.
This study investigated the effects of cytokine adsorption therapy in patients with severe refractory septic shock. 48 patients received 3 sessions of cytokine adsorption therapy within 24 hours of shock onset, while 48 matched control patients received standard care without cytokine adsorption. Both groups saw similar decreases in interleukin-6 levels and vasopressor requirements. However, patients receiving cytokine adsorption therapy had higher intensive care mortality than the control group. The results suggest that indiscriminate removal of cytokines with adsorption therapy may be harmful for patients with severe septic shock.
This study examined the prevalence of cryptococcal meningitis (CM) among people living with HIV/AIDS (PLHAs) at a hospital in southern Odisha, India. Of 112 clinically diagnosed CM patients, 16 cases were confirmed via cerebrospinal fluid analysis, showing a prevalence of 14.3%. Males aged 21-40 were most commonly affected. The most common symptoms were fever, headache, altered sensorium, and neck stiffness. CD4 T-lymphocyte counts were below 100 cells/μl in 93.7% of confirmed cases. All patients responded initially to antifungal therapy but 2 died during hospitalization and 4 were lost to follow up. Early diagnosis and treatment of CM is
1. The study examines the mechanism by which gd T cells induce cytotoxicity of human oligodendrocytes, which are relevant to multiple sclerosis.
2. The results show that gd T cells from MS patients utilize both the Fas-mediated and perforin-based pathways to exert cytotoxic effects on oligodendrocytes.
3. Blocking perforin release completely inhibited killing of targets expressing high levels of heat shock proteins, but additional blocking of Fas ligand was required to fully inhibit killing of Fas-expressing targets and fresh oligodendrocytes.
This document provides an overview of glioblastoma, including its incidence, risk factors, prognosis, biomarkers, and molecular subtypes. Some key points:
- Glioblastoma accounts for 54% of new gliomas and 45% of primary malignant brain tumors. 5-year survival rates are below 5% worldwide.
- Risk factors include age, ionizing radiation exposure, and certain genetic syndromes. Prognostic factors associated with better outcomes include younger age, methylated MGMT status, and extent of surgical resection.
- Emerging biomarkers like IDH1/2 mutations and EGFR amplification/mutations show promise in predicting prognosis, though MGMT methylation status is currently the only validated predictive biomarker.
1) The study analyzed copy number variants (CNVs) in 60 cardiomyopathy-associated genes from over 2,000 individuals who underwent genetic testing.
2) They identified 35 unique CNVs in these individuals, 10 of which were classified as pathogenic and 24 as uncertain significance.
3) Pathogenic CNVs were found in 1.9% of individuals and included deletions in genes like DSP and PKP2 associated with arrhythmogenic right ventricular cardiomyopathy. The identification of pathogenic CNVs provides important clinical implications for affected families.
This document summarizes a study examining the expression of Thomsen-Friedenreich antigen (TF-antigen), a mucin-type glycoprotein, in human esophageal squamous cell carcinoma (ESCC) using peanut agglutinin (PNA) binding. The study found increased levels of TF-antigen in the serum and tissues of ESCC patients compared to normal individuals. TF-antigen levels did not differ between well, moderately, and poorly differentiated ESCC grades and did not decrease after therapy. Expression of TF-antigen increased with histological progression and was localized to the Golgi apparatus and cell membrane in ESCC tissues. The study establishes TF-antigen as a potential diagnostic marker for ES
This document describes a large Indian family with 18 individuals affected by distal arthrogryposis (DA). Whole exome sequencing was performed on 3 affected individuals and identified a heterozygous missense mutation (c.188G>A) in the TNNT3 gene in all 3 individuals. This mutation has previously been reported to cause DA. Detailed clinical descriptions are provided for 4 affected family members, demonstrating variable features including camptodactyly, brachydactyly, syndactyly, decreased flexion creases, ulnar deviation of hands, and club feet. This study identifies a causal mutation for DA in this family and highlights the phenotypic variability associated with mutations in the TNNT3 gene
Analysing Entity Type Variation across Biomedical SubdomainsClaudiu Mihăilă
This document discusses analyzing variation in entity types across biomedical subdomains. It presents a methodology that uses named entity annotations from three sources to generate feature vectors representing entity type distributions in documents. These feature vectors are used to calculate similarity between pairs of documents from different subdomains, using Chi-squared statistics and the Frobenius norm. A random forest classifier is able to distinguish between similar and dissimilar subdomain pairs based only on entity type distributions. The findings indicate significant semantic variation between biomedical sublanguages that can be leveraged to distinguish subdomains and inform adaptation of NLP tools.
A common rejection module (CRM) for acute rejection across multiple organsKevin Jaglinski
This document summarizes a study that identified a common rejection module (CRM) of genes that are overexpressed during acute rejection across multiple solid organ transplants (heart, kidney, liver, lung). Through meta-analysis of gene expression data from transplant biopsies, the study identified 11 genes that comprise the CRM. Validation in independent cohorts showed the CRM genes can diagnose acute rejection with high accuracy. The CRM genes also correlated with the extent of graft injury and predicted future injury. Based on known drug mechanisms, the study explored using FDA-approved drugs atorvastatin and dasatinib to target specific CRM genes, reducing graft-infiltrating cells and extending graft survival in a mouse model of cardiac transplant rejection
Study Demonstrates Effectiveness of combination therapy for breast cancer cel...emmanuel0915
The document discusses two studies: 1) A combination therapy for breast cancer cells that was shown to be effective in vitro, targeting genes that promote cancer cell growth. 2) A safer alternative gene therapy for HIV infection that uses zinc finger nucleases to eliminate the CCR5 receptor in T cells, making them resistant to HIV. The therapies show promise for treating cancers resistant to chemotherapy and providing an effective treatment for HIV infection.
A NOVEL STUDY OF LICHEN PLANOPILARIS AMONG DIFFERENT IRANIAN ETHNICITIES BASE...ijcsit
Introduction: Demographic studies of a disease can reveal the characteristics of that disease among a specific population and will help the physicians to achieve a more accurate perception about it.The demographic of Lichen PlanoPilaris (LPP) among the Iranian population is unknown. The aim of this study is to describe the clinical, demographic, and histopathologic findings of lichen planopilaris in the Iranian population.
Materials and Methods: In this cross-sectional study, all the patients with Lichen planopilaris were referred to the dermatology clinic of Imam Khomeini hospital from 2013 to 2015. Lichen planopilaris can be diagnosed by collecting histological evidence, dermatological examination, and clinical diagnosis. Their demographic characteristics, drug histories, onset of disease, and family histories were obtained by written questionnaire. Additionally, this study employed SPSS v.20 as the statistical analysis software.
Results: One hundred patients were enrolled in this study. With an average age of 47.11 years, 78% of the patients were female, and 50 of these were housewives. The patients included were often from Tehran with Fars ethnicity. Among these patients, 7 had alopecia areata skin disease, and 10 of them suffered from thyroid disease. Most of the histopathology samples collected from these biopsies revealed degeneration of the basal layer of the follicular structure, perifollicular fibrosis, inflammatory cells, and atrophy of the pilosebaceous structures.
Conclusion: Both the age spectrum and the disease distribution of LPP among the Iranian population were very diverse when compared to previous studies. Moreover, this study helps the physicians to have a brighter vision about the main reason and cause of LPP spread among diverse Iranian Ethnicities.
Demographic studies of a disease can reveal the characteristics of that disease among a specific population and will help the physicians to achieve a more accurate perception about it.The demographic of Lichen PlanoPilaris (LPP) among the Iranian population is unknown. The aim of this study is to describe the clinical, demographic, and histopathologic findings of lichen planopilaris in the Iranian population.
HETEROGENEITY OF C ERB B FAMILY MEMBERS EXPRESSION IS RELATED TO CELL MORPHOL...ANCA MARIA CIMPEAN
This document summarizes a study examining the expression of HER2 and EGFR in pituitary adenomas and their relationship to hormone profiles. The study found that over one-third of pituitary adenomas expressed HER2, particularly prolactin-secreting adenomas. HER2 expression was also related to certain hormone co-expressions. Approximately half of adenomas expressed EGFR, which was correlated with GH-prolactin co-expression. The results suggest HER2 and EGFR expression may help define subclasses of pituitary adenomas and explain their clinical heterogeneity.
236 Understanding Systemic Lupus Erythematosus. A Qualitative Study Of Women ...Wendy Berg
This document describes a study that evaluated the effect of iberdomide, a drug that targets the transcription factors IKZF1 and IKZF3, on B cell differentiation and immunoglobulin production in systemic lupus erythematosus (SLE) B cells. The study found that iberdomide exposure early in cell culture significantly reduced the differentiation of SLE B cells into plasmablasts and decreased immunoglobulin production, but did not affect fully differentiated plasmablasts. RNA sequencing of B cell populations treated with iberdomide found significant differential expression of genes involved in B cell development and key pathways. This confirms the role of IKZF1 and IKZ
vascular insulin and IGF-1 in diabetic woundsSaeed Aghdam
This document summarizes a study examining the role of vascular endothelial insulin/IGF-1 signaling in skin wound healing. The study found that deleting the insulin receptor and IGF-1 receptor specifically in endothelial cells of mice (DKOIVE mice) did not significantly impact skin vessel homeostasis under normal conditions. However, when the skin was wounded, DKOIVE mice showed strongly reduced neovascularization during wound healing compared to controls, accompanied by reduced granulation tissue formation. This indicates that endothelial insulin/IGF signaling is essential for neovascularization during wound healing and implies its reduction directly contributes to impaired healing associated with diabetes.
This study investigated the expression of Caspase-12 and ADAMTS-5 in placental samples from 15 pregnant women with placenta previa and 15 healthy pregnant women. Histopathological examination found significant degeneration and apoptotic changes in the placenta previa group. Immunohistochemical analysis showed increased expression of ADAMTS-5 and Caspase-12 in the placenta previa group. The researchers concluded that increased expression of these proteins, which are involved in extracellular matrix development, inflammation, and angiogenesis, may negatively impact maternal function and fetal development in placenta previa.
Anti-Mullerian hormone (AMH) is a glycoprotein, a member of the transforming growth factor-B super family. This hormone is a sensitive marker of ovarian reserve. The present study aims to measure the Anti-Mullerian hormone in thalassemic females receiving the regular blood transfusion as well as patients of chronic idiopathic thrombocgtopenic purpura and age and sex matched controls. Serum Anti-Mullerian hormone was measured by ELISA and Ferritin were measured by RIA. Clinical evaluation was done for all patients including anthropometric measurements, pubertal staging and history taking. Results of the study were analyzed by appropriate statistical methods. Obtained results revealed that the values of Body Mass Index as well as Anti-Mullerian were significantly higher in controls than thalassemics and chronic idiopathic thrombocytopenic purpura and there was a negative correlation between serum Ferritin and Anti-Mullerian hormone. Moreover, Anti-Mullerian hormone was significantly higher in patients receiving Desferal than in those receiving Deferriprone. Reduced Anti-Mullerian hormone in thalassemics as well as chronic ITP patients are considered an important indicator declines in ovarian function which entail modification in the therapeutic plans for thalassemic and chronic ITP patients.
This study investigated the relationship between tumor characteristics and somatostatin receptor 2 (SSTR2) expression in 81 patients with meningioma. Univariate and multivariate analyses found that older age (>65), larger tumor size (>3 cm), and female sex were associated with poorer overall survival. However, there was no association found between SSTR2 expression levels (negative, weakly positive, strongly positive) and overall survival or other tumor characteristics. Therefore, further research is needed to understand the role of SSTR2 receptor expression in meningiomas beyond its diagnostic value.
This study examined the expression of HER-2 and LRP in tumor tissue samples from 65 gastric cancer patients and 32 non-gastric cancer patients. Immunohistochemical staining and Western blot analysis were used to test for HER-2 and LRP expression and phosphorylation levels. The results showed that HER-2 and LRP expression in gastric cancer tissues were positively correlated and higher than in non-gastric cancer tissues. HER-2 phosphorylation was highest in gastric cancer patients with lymphatic metastasis. This suggests that LRP may cause primary resistance in gastric cancer and that HER-2 activation may mediate gastric cancer resistance by influencing LRP expression.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...JohnJulie1
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...NainaAnon
1. The study found that IRF5 was upregulated in hepatocellular carcinoma (HCC) tissues compared to normal tissues based on mRNA and protein levels.
2. Overexpression of IRF5 promoted the growth and colony formation of HCC cells in vitro, while silencing IRF5 inhibited HCC cell growth and proliferation.
3. TRIM35 was found to interact with and promote the degradation of IRF5. TRIM35 expression was negatively correlated with IRF5 levels in HCC clinical samples.
AACR Immune Infiltration In ER, PR, HER2 IHC SubtypesRafael Casiano
This study used a multiplexed immunofluorescence assay to measure levels of immune cell infiltration in different breast cancer subtypes defined by estrogen receptor, progesterone receptor, and HER2 status. The results showed that ER-/PR-/HER2 overexpressed and triple negative subtypes had the highest percentages of CD4+ and CD8+ T cells as well as Ki67+ proliferating cells. However, in the ER-/PR-/HER2 overexpressed subtype, despite high levels of CD8+ cytotoxic T cells, many tumor cells were still Ki67+. This suggests that the presence of intratumoral T cells does not necessarily indicate an active anti-tumor immune response and that immunotherapy targeting immune checkpoints may provide benefit.
This document contains abstracts from presentations given at the 28th International Symposium on Pediatric Surgical Research held in Dublin, Ireland from September 24-26, 2015. The abstracts describe recent research on topics related to pediatric surgery, including analyses of enteric neural crest cell migration in mouse models of Hirschsprung's disease using 3D and 4D imaging, characterization of blood vessel formation by human adipose-derived endothelial cells in a 3D skin substitute, and the role of surfactant protein D in attenuating inflammation in an intestinal cell line with overexpression of toll-like receptor 4.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...daranisaha
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells. When studying the molecular mechanism, it was found that TRIM35 interacted with IRF5, promoting the ubiquitination and degradation of IRF5. In the clinical specimens of HCC, TRIM35 was negatively correlated with the expression of IRF5. These observations reveal the oncogenic function of IRF5 in the progression of HCC, suggesting that IRF5 is a promising target for the therapy of HCC.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...semualkaira
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells. When studying the molecular mechanism, it was found that TRIM35 interacted with IRF5, promoting the ubiquitination and degradation of IRF5. In the clinical specimens of HCC, TRIM35 was negatively correlated with the expression of IRF5. These observations reveal the oncogenic function of IRF5 in the progression of HCC, suggesting that IRF5 is a promising target for the therapy of HCC.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...eshaasini
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells. When studying the molecular mechanism, it was found that TRIM35 interacted with IRF5, promoting the ubiquitination and degradation of IRF5. In the clinical specimens of HCC, TRIM35 was negatively correlated with the expression of IRF5. These observations reveal the oncogenic function of IRF5 in the progression of HCC, suggesting that IRF5 is a promising target for the therapy of HCC.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...semualkaira
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells. When studying the molecular mechanism, it was found that TRIM35 interacted with IRF5, promoting the ubiquitination and degradation of IRF5. In the clinical specimens of HCC, TRIM35 was negatively correlated with the expression of IRF5. These observations reveal the oncogenic function of IRF5 in the progression of HCC, suggesting that IRF5 is a promising target for the therapy of HCC.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...semualkaira
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells. When studying the molecular mechanism, it was found that TRIM35 interacted with IRF5, promoting the ubiquitination and degradation of IRF5. In the clinical specimens of HCC, TRIM35 was negatively correlated with the expression of IRF5. These observations reveal the oncogenic function of IRF5 in the progression of HCC, suggesting that IRF5 is a promising target for the therapy of HCC.
This document describes a study comparing primary focal segmental glomerulosclerosis (FSGS) and minimal change nephrotic syndrome (MCNS). The study included 30 patients with biopsy-proven MCNS and 30 with FSGS. Histological and immunohistochemical analysis was performed on biopsy samples to examine differences between the two conditions. Immunohistochemical staining for CD44 was evaluated as a potential marker to distinguish FSGS from MCNS, as CD44 marks activated parietal epithelial cells that may be present in FSGS but not MCNS. The results were analyzed to compare demographic, clinical, laboratory, histopathological and immunohistochemical findings between MCNS and FSGS.
- Larval toxocarosis is a common parasitic infection that can cause a wide variety of clinical manifestations depending on the location and number of migrating larvae. It is a long-lasting infection with severe recurrent symptoms.
- The study examined 16 patients with various forms of larval toxocarosis who had not responded to previous standard anti-parasitic drug treatment. Many patients also had immunodeficiencies of varying degrees.
- Treatment with Citomix and low-dose Interleukin-5 resulted in significant clinical and laboratory improvements in most patients. It effectively treated symptoms, reduced liver abnormalities, and improved immune parameters. The treatment was well-tolerated with no adverse effects.
Similar to Scientifi c Journal of Clinical Research in Dermatology (20)
A 5-year old boy, with an established diagnosis of a topic
dermatitis, previously treated by topical corticosteroids and emollient cream with a good improvement, developed widespread papules on his legs, hands and forearm that appeared 5 months ago.
Methods: Retrospectively, the file records of the patients who underwent sleeve gastrectomy were examined. Demographic features, Body Mass Index (BMI), the mouth opening, Mallampati score, thyromental distance, sternomental distance, neck circumference measurements and videolaryngoscopic examination results were recorded Results: In a total of 140 consecutive patients (58 male, 82 female) were included in the study. The mean age of the study participants was 35.40 ± 9.78 and the mean BMI of the patients was 44.33 ± 7.52 kg/m2
. The mean mouth opening of the patients was 4.82 ± 0.54 cm
and the mean neck circumference was 43.52 ± 4.66 cm. The mean thyromental distance was 8.02 ± 1.00 cm and the mean sternomental distance was16.58 ± 1.53 cm. Difficult intubation was determined in 8 (5.7%) patients. In logistic regression analysis, age (p : 0.446), gender (p : 0.371), BMI (p : 0.947), snoring (p : 0.567), sleep apnea (p : 0.218), mouth opening (p : 0.687), thyromental distance (p :0.557), sternomental (p : 0.596) and neck circumference (p : 0.838) were not the independent predictors of difficult intubation. However, Mallampati score (p : 0.001) and preoperative direct laryngoscopy findings (p : 0.037) performed in outpatient clinic were the significant
predictors of difficult intubation. Interestingly, all patients with grade 4 laryngoscopy findings had difficult intubation.
Introduction: Laparoscopic surgery has been performed in Mexico since 1989, but no reports about training tendencies exist. We conducted a national survey in 2015, and here we report the results concerning training characteristics during the surgical residence of the respondents. Materials and Methods: A prospective study was conducted through a survey questioning demographic data, laparoscopic training during pre and post surgical residency and other of areas of laparoscopic practice. The sample was calculated and survey piloted before
application. Special interest in this report was placed on type and quality of training received. Data are reported in percentages.
Heterotopic Ossification (HO) is defined as pathological bone formation at locations where bone normally does not exist. The
presence of HO has been found to be a rare complication after stroke in several studies, whereas there are only sporadic references relating HO to Cerebral Palsy (CP) and few for CP and stroke. No effective treatment for HO has yet been found, whereas the cellular and molecular mechanisms have not been completely understood. Therefore, increased awareness among physicians is required, as a challenge for early diagnosis and treatment. A case of a male patient with CP, who developed HO on the paretichip joint following an ischemic stroke is presented.
Objectives: To assess the practice of food hygiene and safety, and its associated factors among street food vendors in urban areas of Shashemane, West Arsi Zone, Oromia Ethiopia, 2019.
Methods: Cross-sectional study design was applied from December 28, 2019 to January 27, 2020. Data was collected from 120 food handlers, which were selected by purposive sampling techniques. Information was gathered from interview and field observation by conducting food safety survey and using questionnaires via face to face interview. The collected data was entered using Epi Data 3.1 and finally, it was analyzed using SPSS VERSION 20.
A Division I football player experienced acute posterior leg pain while playing. An ultrasound examination revealed an unusual injury - a complete rupture of the plantaris tendon mid-substance. This type of isolated plantaris tendon injury has rarely been reported. Ultrasound was useful for diagnosis and guided rehabilitation by monitoring healing over time. The athlete was able to return to full competition within 3 weeks through a progressive rehabilitation program focused on restoring range of motion and strength. This case suggests isolated plantaris tendon injuries may allow for faster return to play than other potential causes of posterior leg pain.
Type 1 Diabetes (T1D), is a severe disease, representing 5-10% of all reported cases of diabetes worldwide. Fulminant Type 1 Diabetes Mellitus (FT1D) is a subtype of type 1 diabetes mellitus that is largely characterized by the abrupt onset of Diabetic Ketoacidosis (DKA) and severe hyperglycemia without insulin defi ciency. Viral infections have been hypothesized to play a major role in the pathogenesis of Fulminant Type 1 Diabetes Mellitus (FT1D) through the complete and rapid destruction of pancreatic beta cells. Coxsackie viral infection has been detected in islets of 50% of the pancreatic tissue recovered from recent-onset Type 1 Diabetes (T1D) patients. In this report we have highlighted a case where the patient developed a Group B Coxsackie virus infection culminating in the development of Fulminant Type 1 Diabetes Mellitus (FT1D).
Methods: Cercariae are released by infected water snails. To determine the occurrence of cercariae-emitting snails in SchleswigHolstein, 155 public bathing places were visited and searched for fresh water snails. Family and genus of the collected snails were determined and the snails were examined for the shedding of cercariae, using a standard method and a newly developed method.
Objective: To generate preliminary information about of enteroviruses and Enterovirus 71 (EV71) in patients with aseptic meningitis in Khartoum State, Sudan.
Method: Cerebrospinal fluid specimens were collected from 89 aseptic meningitis patients from different Khartoum Hospitals
(Mohammed Alamin Hamid Hospital, Soba Teaching Hospital, Omdurman Military Hospital, Alban Gadeed Teaching Hospital and Police Hospital) within February to May 2015. Among these 89 patients, 43 (48%) were males and 46 (52%) were females. The patient’s age ranged between 1 day and 30 years old. The collected specimens were assayed to detect enteroviruses and EV71 RNA using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique
Femoral hernias, comprise 2% to 4% of all hernias in the inguinal region, and occur most commonly in women. Th ey present typically with a mass below the level of the inguinal ligament. The sac may contain preperitoneal fat, omentum, small bowel, or other structures and have a high rate of incarceration and strangulation due to the small size of the hernia neck orifice, requiring emergency surgery. We present the case of a 54-year-old female patient with intestinal occlusion due to incarcerated femoral hernia, repaired by laparoscopic approach, that gave the patient the opportunity to attend her daughter’s wedding the same day.
Small Supernumerary Marker Chromosome (sSMC) is a rare genetic condition marked by the presence of an extra chromosome to the 46 human chromosomes. This case report describes a 4 year old child with SSMC on the 46th chromosome. The child presented with delayed speech and language development, seizures and mild developmental delay. Speech and Language evaluation was carried out and management options are discussed.
A catheter is a thin tube made from medical grade materials that serve a broad range of functions, but mainly catheters are medical devices that can be inserted in the body to treat disease or perform surgical procedures. Catheters have been inserted into body cavities, ducts, or vessels to allow for drainage, administration of therapeutic fluids or gases, operational access for surgery. Catheters help perform tasks in various systems such as cardiovascular, urological, gastrointestinal, neurovascular, and ophthalmic systems. A dataset of 12 patients with varying “weights” and “heights” was recorded along with the lengths of their catheter tubes. This data set was found from two revered statistical textbooks on linear regression and the Department of Scientific Computing at Florida State University. This data set was not able to be linked to any particular clinical or experimental research studies, but the data set can be used to help catheter manufacturers and medical professionals better decide on what particular catheter lengths to use for patients knowing only their height & weight. These research insights could be helpful to healthcare professionals that have patients with incomplete or no healthcare records
to decide what catheter length to use. The main investigative inquiry that needed to be answered was how does patient weight & height influence catheter length together and separately? We conducted linear regression and other statistical analysis procedures in R program & Microsoft Excel and discovered that this data exhibited a quality called multi collinearity. With multi collinearity, all predictors (2 or more
independent variables) are not significant in an all encompassing linear aggression, but the predictors might be significant in their own individual linear regressions. Individual linear regression analyses were conducted for both patient height & weight to see how much they both contribute to varying catheter length. Patient weight was found to be more impatful than patient height in relationship to catheter length, even though height and weight are a classical example of multi collinearity predictors.
Bovine mastitis has a negative impact through economic losses in the dairy sector across the globe. A cross sectional study was carried out from September 2015 to July 2016 to determine the prevalence of bovine mastitis, associated risk factors and isolation of major causative bacteria in lactating dairy cows in selected districts of central highland of Ethiopia. A total of 304 lactating cows selected randomly from five districts were screened by California Mastitis Test (CMT) for subclinical mastitis. Based on CMT result and clinical examination, over all prevalence of mastitis at cow level was 70.62% (214/304).
Two hundred fourteen milk samples collected from CMT positive cows were cultured for isolation of major causative bacteria. From 214 milk samples,187 were culture positive and the most prevalent isolates were Staphylococcus aureus 42.25% (79/187) followed by Streptococcus agalactiae 14.43%
(27/187). Other bacterial isolates were included Coagulase Negative Staphylococcus species 12.83% (24/187), Streptococcus dysgalactiae 5.88% (11/187), Escherichia coli 13.38% (25/187) and Entrococcus feacalis 11.23% (21/187) were also isolated. Moreover, age, parity number, visible teat abnormalities,husbandry practice, barn fl oor status and milking hygiene were considered as risk factors for the occurrence of bovine mastitis and they were found significantly associated with the occurrence of mastitis (p < 0.05). The findings of this study warrants the need for strategic approach including dairy extension that focus on enhancing dairy farmers’ awareness and practice of hygienic milking, regular screening for subclinical mastitis, dry cow therapy and culling of chronically infected cows.
A 36-year-old female developed right upper quadrant pain and nausea after taking the herbal supplement kratom for two weeks to manage back pain. Laboratory tests showed elevated liver enzymes. A liver biopsy ruled out other causes and determined she had drug-induced liver injury from kratom use. Her symptoms and liver enzymes gradually returned to normal over six weeks after stopping kratom. The case report discusses kratom's potential for hepatotoxicity and advises clinicians to consider its effects on patient health.
The assessment, diagnosis and treatment of critically ill patients is extremely challenging. Patients often deteriorate whilst being
reviewed and their rapidly changing pathophysiology barrages healthcare professionals with new data. Furthermore, comprehensive assessments must be postponed until the patient has been stabilised. So, important data and interventions are often missed in the heat of the moment. In emergency situations, suboptimal management decisions may cause signifi cant morbidity and mortality. Fortunately, standardisation and careful design of documentation (i.e. proformas and checklists) can enhance patient safety. So, I have developed a series of checklist proformas to guide the assessment of critically ill patients. These proformas also promote the systematic recording and presentation of information to facilitate the retrieval of the precise data required for the management for critically ill patients. The proformas have been modifi ed extensively over the last twenty years based on my personal experience and extensive consultation with colleagues in several world-renowned centres of excellence. The proformas were originally developed for use in the intensive therapy unit
or high dependency unit. However, they have been adapted for use by outreach teams reviewing patients admitted outside of critical care areas. The use of these tools can direct eff orts to provide appropriate organ support and provides a framework for diagnostic reasoning.
This review article discusses microvascular and macrovascular disease in systemic hypertension. It summarizes that:
1) Cardiac imaging plays a crucial role in risk stratifying hypertensive patients and identifying management strategies by properly diagnosing microvascular and coronary artery disease.
2) The nitric oxide synthase (eNOS) G298 gene allele may be a marker for microvascular angina in hypertensive patients, as studies have found it to be more prevalent in hypertensive patients with chest pain and reversible myocardial defects but normal coronary arteries.
3) Both structural changes like capillary rarefaction and functional changes like endothelial dysfunction can cause microvascular dysfunction and angina in hypertensive individuals in the absence of
This study characterized dengue infections in Pakistan by analyzing hematological and serological markers in 154 suspected dengue cases and 146 control patients with other febrile illnesses. NS1 antigen was detected in 55% of dengue cases, IgM antibodies in 30%, and both in 15%. Control groups primarily had malaria (71%) and enteric fever (20%). Hematological markers (platelet count, hematocrit, WBC) measured before and after treatment showed significant differences for platelet count and hematocrit but not WBC count between the groups. Analysis of clinical symptoms and serological/hematological markers helps diagnose dengue, assess prognosis, and inform prevention efforts to reduce morbidity, mortality and spread of the disease.
Researchers from Utrecht recently published yet another paper on the use of Magnetic Resonance Imaging (MRI)demonstrating an additional failed attempt to understand the importance of qualitative versus quantitative imaging, and anatomic versus physiologic imaging. Th e implications of this failure here cannot be overstated.
Introduction: Stroke is an even more dramatic major public health problem in young people. Goal of the study: Contribute to the knowledge of strokes in young people. Methodology: This was a retrospective study carried out over a period of 02 years (January 2017 to December 2018) including the files of patients aged 18 to 49 years hospitalized for any suspected case of stroke in the Neurology department of the University Hospital
Center of the Sino-Central African Friendship (CHUSCA) of Bangui.
Background: This report describes a unique case of a patient that developed psychotic symptoms believed to be secondary
to a tentorial meningioma with associated hydrocephalus. These psychotic symptoms subsequently abated with placement of a
ventriculoperitoneal shunt. Case description: 60-year-old female was admitted to an inpatient psychiatric facility on a psychiatric involuntary commitment petition due to progressive paranoia, homicidal ideation and psychosis. The work up showed a calcified six cm tentorial meningioma with associated hydrocephalus. The patient initially rejected treatment but later became amenable to placement of Ventriculoperitoneal Shunt
(VPS).
More from SciRes Literature LLC. | Open Access Journals (20)
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
low birth weight presentation. Low birth weight (LBW) infant is defined as the one whose birth weight is less than 2500g irrespective of their gestational age. Premature birth and low birth weight(LBW) is still a serious problem in newborn. Causing high morbidity and mortality rate worldwide. The nursing care provide to low birth weight babies is crucial in promoting their overall health and development. Through careful assessment, diagnosis,, planning, and evaluation plays a vital role in ensuring these vulnerable infants receive the specialize care they need. In India every third of the infant weight less than 2500g.
Birth period, socioeconomical status, nutritional and intrauterine environment are the factors influencing low birth weight
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Are you looking for a long-lasting solution to your missing tooth?
Dental implants are the most common type of method for replacing the missing tooth. Unlike dentures or bridges, implants are surgically placed in the jawbone. In layman’s terms, a dental implant is similar to the natural root of the tooth. It offers a stable foundation for the artificial tooth giving it the look, feel, and function similar to the natural tooth.
Lecture 6 -- Memory 2015.pptlearning occurs when a stimulus (unconditioned st...AyushGadhvi1
learning occurs when a stimulus (unconditioned stimulus) eliciting a response (unconditioned response) • is paired with another stimulus (conditioned stimulus)
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
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INTRODUCTION
Scleroderma or systemic sclerosis is a complex connective tissue
disease which is characterized by vasculopathy, autoimmunity and
progressive fibrosis in the skin and visceral organs [1-3]. It includes
diffuse and limited subgroups. These groups are separated from
each other by skin involvement [4]. Despite some characteristics
distinguishing the two types from each other, they share the common
feature of fibrosis involving excessive Extracellular Matrix (ECM)
production that impairs usual tissue characteristics to cause organ
failure late in the disease course [5]. Although a large body of
novel scientific knowledge has been acquired about the molecular
mechanisms of pathophysiology of SSc [6-8]we are far from stopping
or even slowing down the ongoing fibrotic process characterizing the
disease [9-11].
In this immunohistochemically study, we aimed to find new
markers to predict prognosis and guide therapy.
MATERIAL AND METHODS
Skin biopsies of 43 patients were obtained from the specimen
archives of Mersin University Medical School Pathology Department.
Twenty-seven patients were compatible with scleroderma in
histologically and clinically. We diagnosed systemic sclerosis 27
patients with skin thickening of the fingers of both hands extending
proximal to the metacarpophalangeal joints as clinically. Histological,
areas of cutaneous in duration are characterized by compactor
hyalinized collagen, excessive deposition of collagen, atrophic eccrine
and pilosebaceous glands, loss of intradermal fat, and, in patients with
early-stage disease, sparse mononuclear cell in filtrate in the dermis.
Sixteen cases with intact surgical margins of malignant melanomas
were used as a control group. It was paraffin embedding tissue. We
processed the skin tissue after fixing in formalin.
Immunohistochemical study was performed by avidine-biotin-
peroxidase complex method using 4 micrometer thick sections
embedded in paraffin. Gradual ethanol solutions were used for
deparaffinization and dehydration. The samples were treated with
0.3% hydrogen peroxidase and methanol for 20 minutes to block
endogenous peroxidase activity. Following three rinses in Phosphate
Buffered Saline (PBS), the samples were processed in a 0.01 M citrate
buffer (pH 6.0), stored in microwave for 20 minutes, and allowed to
cool down at room temperature. The sections were incubated with
the primary antibodies following PTEN (Santa Cruze, Sc- 133242,
1/100 dilution, Texas, U.S.A), VEGF (Santa Cruze, sc-152, 1/100
dilution, Texas, U.S.A), and HIF-1α (Santa Cruze, Sc-10790, 1/50
dilution, Texas, U.S.A) at 4°C followed by the secondary antibody.
AEC-substrate chromogen (Dako, k3464, Denmark) was used to
visualize the binding sites of peroxidase activity. The sections were
counterstained with hematoxylin. Light microscopy (Olympus,
Bx53, and Tokyo, Japan) was used to detect immunostaining by two
pathologists who were blind to the clinic pathological properties. Each
Immunohistochemistery staining was scored by the modified method
of Distler, et al. [12]. The immunostaining samples were graded in
varied grades ranging from no or weak expression to moderate-to-
severe expression by the cells including keratinocyte, fibroblast and
endothelial cells (cytoplasm staining for PTEN and VEGF, nuclear
staining for HIF-1α) on 5 High Power Fields (HPF). Accordingly,
1(+) staining equaled no or weak staining of a few cells (≤ 25%) and
2(+) staining equaled moderate or intense staining of the cells (25%).
If there was no staining, we used O and marked staining we used 3(+).
It was all membranous staining.
STATISTICAL ANALYSIS
Descriptive statistics were used to express study data. Inter -
group analyses were performed using Shapiro Wilk, Mann Whitney
U, and Kruskal Wallis tests. A p value less than 0.05 was considered
statistically significant. MedCalc ®
v.10.3.0 software (Medcalc Turkey,
Belgium) was used for all statistical analyses.
RESULTS
Demographic, clinical and pathological findings
In this study, there were 5 male and 22 female patients with
scleroderma. The histopathological properties of skin biopsy samples
from patients with SSc mainly included perivascular inflammatory
infiltrates, perivascular edema, and collagen accumulation of
ABSTRACT
Objective: Systemic Sclerosis (SSc) is primarily characterized by autoimmunity, Microangiopathy, and tissue fibrosis. Hypoxia, a
powerful stimulator of Vascular Endothelial Growth Factor (VEGF), may be responsible for excessive expression of chronic VEGF in SSc.
The oxygen-regulated α-subunit of hypoxia-inducible transcription factor-1 (HIF-1α) plays an important role in transcriptional regulation
of VEGF. The protein phosphatase and tension homolog (PTEN) is responsible for dephosphorylation of proteins and thereby promotes
tissue repair.
The present study aimed to examine the expressions of HIF-1α, PTEN, and VEGF in patients with scleroderma in an attempt to
estimate prognosis and guide therapeutic decisions. We therefore studied the expressions of HIF-1 α, VEGF, and PTEN in skin samples
exhibiting the features of scleroderma.
Methods: Skin biopsies of patients were obtained and samples were stained with primary antibodies following PTEN, VEGF and
HIF-1α, immunohistochemically.
Results: The SSc and the control group were compared with respect to staining of epidermal keratinocytes, fibroblasts, and the
endothelial cells for the antibodies. SSc patients displayed a reduced VEGF expression in endothelial cells. The lesion group showed a
significantly lower staining of epidermal cells and endothelial cells for PTEN. SSC group was also characterized by a significantly weaker
HIF-1α expression compared to the control group.
Conclusion: In scleroderma skin samples, manipulated expression of these molecules at varying stages of the disease may affect
the prognosis of scleroderma.
Keywords: HIF-1α; PTEN; Scleroderma; VEGF
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variable extent in papillary and reticular layers of dermis (Figure
1A). In addition, dermal papillary flattening prominently reduced
microvascular density, and severe fibrotic changes manifested by
collagen bundles that were densely stored and showed irregular
distribution were evident (Figure 1B). The SSc group, as compared to
the control group, was significantly younger than the control group
at the time of biopsy (42.63 ± 18.79 vs. 60.63 ± 12.53 years, p = 0.002),
and it contained significantly more females than males (81.5% vs.
31.3, %, p < 0.001). Nevertheless, the lesion thickness did not differ
significantly between the lesion and the control group (Table 1).
Immunohistochemical findings
The SSc and the control group were compared with respect to
staining of epidermal keratinocytes, fibroblasts, and the endothelial
cells for PTEN, HIF-1α, and VEGF. The control group exhibited
a variable PTEN expression in dermal vascular endothelial cells,
fibroblasts, and epidermal keratinocytes. The lesion group showed a
significantly lower staining of epidermal cells and endothelial cells for
PTENthanthecontrolgroup,respectively(81.5%vs.18.8%number/5
HPF and 74.1% vs. 18.8% number/ 5 HPF), (for both p < 0.0001). Both
epidermal and micro vascular expression were either undetectable or
absent. This contrasted the skin samples from the patients with SSc,
which showed significantly increased PTEN expression in fibroblasts
of dermis and had a significantly higher immune positivity (77.8%
vs. 18.8% number/ 5 HPF) (p < 0.0001) (Figure 2A–C). The patient
group had a significantly lower VEGF staining of endothelial cells
(74.1% vs. 6.3% number/ 5 HPF) (p < 0.001) than the control group.
SSc patients displayed a reduced VEGF expression in endothelial cells
(Figure 3A-C). The both groups, however, did not significantly differ
from each other with regard to epidermal cell and fibroblast staining
for VEGF. The both groups exhibited a weak and heterogeneous
immunostaining in keratinocytes and fibroblasts. The SSc group
was also characterized by a significantly weaker HIF-1α expression
compared to the control group (%77.8 vs. %18.8 number/5 HPF),
(p < 0.001). The control subjects had a more prominent HIF-1α
immunostaining in keratinocytes albeit to a lesser extent in some
fibroblasts and endothelial cells. Dermal micro vessels and fibroblasts
displayed a weak and similar HIF-1α expression in both groups. The
both groups were not significant with regard to HIF-1α expression
(Figure 4A-C; Table 2).
DISCUSSION
SScisprimarilycharacterizedbyautoimmunity,microangiopathy,
and tissue fibrosis. A reduced capillary density results in decreased
blood flow and tissue oxygenation. Initially, ECM accumulation
around blood vessels leads to reduced transport of oxygen and
nutrition to tissues. Severe hypoxia in turn may cause the disease to
progress by stimulating the production and release of ECM proteins
from fibroblasts in response to increased levels of transforming
growth factor-β the stimulation of increased production and release of
ECM proteins is mediated by hypoxia-inducible factor-1α-dependent
and independent pathways. It is also possible that vascular disease be
Figure 1: A: Histological features of Ssc including fibrosis of papillary and reticular dermis. B: Ssc represents flattening of dermal papilla and edema around the
microvessels (H-E, x100). C:. Normal skin sample (H-E, x100).
Table 1: Demographic data of the patient and control groups.
SD / n / % / p SSc Control p
Age 42.63 ± 18.79 60.63 ± 12.53 0.002
Sex
Male Female Male Female
0.001n % n % n % n %
5 (18.5) 22 (81.5) 11 (68.8) 5 (31.3)
Thickness 3cm (SD: 2- 5cm) 5.50cm (SD: 3- 8cm) 0.092
SSc: Scleroderma; SD: Standard Deviation; n: number of cases; p: significance; %: percentage
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Figure 2: A: Decreased expression of PTEN of the fibroblasts (arrow) (inset: increased expression of PTEN in control). B: Increased PTEN expression of
endothelial cells (arrow head) (inset: decreased expression of PTEN in endothelial cells in control). C: Increased PTEN expression of keratinocytes (arrow head)
(inset: decreased expression of PTEN in keratinocytes in control) (PTEN, x100).
Figure 3: A: Endothelial cells showing reduced expression of VEGF (arrow) (inset: increased expression of VEGF in endothelial cells in control). B: Moderate
staining of VEGF in keratinocytes (arrow) in Ssc and control group (inset) C: Similar staining of VEGF in fibroblasts in Ssc (arrowhead) and in control (inset) (VEGF,
x100).
Figure 4: A: Weak nuclear HIF-1α staining in keratinocytes (arrow) in Ssc in contrast to strong staining in control group (inset). B: Strong nuclear HIF-1α staining
only rarely occurs in normal endothelial cells in Ssc and control group (inset). C: Similar exhibition of HIF-1α in Ssc and control group (inset) in fibroblasts (arrow)
(HIF-1α, X100).
induced or worsened by hypoxia-induced VEGF receptor signaling
since hypoxia represents a strong inducer of VEGF production.
This leads to over-expression of VEGF in SSc, which causes to exert
some unwanted effects on angiogenesis owing to formation of a non-
uniform and chaotic vascular distribution and reduces blood flow.
These effects, by increasing vascular disease and augmenting tissue
fibrosis, jointly play a role in the pathogenesis of SSc [13]. SSc is
characterized by progressive dilatation of and leakage from the
skin capillaries, which in time coalesce to form extensive avascular
areas and ultimate formation of digital ulcers. VEGF is consistently
increased throughout the disease course and had negligible effects on
neovascularization. The central event in transcriptional regulation
of VEGF is the HIF-1α production regulated by oxygen [14]. VEGF
levels have been found increased in early-stage SSc and this finding
has been linked to pulmonary fibrosis and abnormal pulmonary
function. A high level of VEGF has also been correlated to a shorter
disease duration and rapidly progressive diffuse cutaneous SSc.
However, some studies have reported contradictory results [15].
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Table 2: Immunohistochemical findings of the patient and control groups.
Immunohistochemistery (n, %, p) Location Score
Control group Scleroderma group
p
n % n %
PTEN
Epidermis 1 3 18.8 22 81.5
< 0.001
2 13 81.3 5 18.5
Fibroblast 1 13 81.3 6 22.2
< 0.001
2 3 18.8 21 77.8
Endothelium
1 3 18.8 20 74.1
< 0.001
2 13 81.3 7 25.9
VEGF
Epidermis 1 15 93.8 20 74.1
0.087
2 1 6.3 7 25.9
Fibroblast 1 14 87.5 21 77.8
0.418
2 2 12.5 6 22.2
Endothelium
1 1 6.3 20 74.1
< 0.001
2 15 93.8 7 25.9
HIF-1α
Epidermis 1 3 18.8 21 77.8
< 0.001
2 13 81.3 6 22.2
Fibroblast 1 15 93.8 24 88.9
0.586
2 1 6.3 3 11.1
Endothelium
1 15 93.8 24 88.9
0.586
2 1 6.3 3 11.1
Our results showed a decreased VEGF expression in endothelial cells
obtainedfromskinsamplesofpatientswithscleroderma.Scleroderma
is characterized by vascular endothelial injury that is responsible for
pathological alterations of vascular tissue, resulting in adverse events
in physiology of many organ systems and culminating into chronic
tissue ischemia. The tissue response to the hypoxia includes complex
cellular and molecular mechanisms aimed to salvage endothelial
functions and tissue perfusion. Both progressive capillary loss and
progressive arteriolar vascular modeling lead to reduction of blood
supply with associated severe and chronic hypoxia. Our results
indicating reduced VEGF expression in endothelial cells may be
related to loss of skin capillaries [16].
One study reported that SSc patients had lower HIF-1α levels in
skin compared to healthy controls [12] Skin samples from SSc patients
were not characterized by increased HIF-1α expression as detected
by Immunohistochemistery. While healthy controls displayed a
moderate-to-high HIF-1α staining in epidermis, SSc patients showed
HIF-1α expression that was confined to single keratinocytes. Both SSc
patients and healthy individuals had no detectable HIF-1α protein
levels. Furthermore, SSc patients had no HIF1α expression pattern
that was correlated to upregulated VEGF levels, which are among the
main transcriptional targets of HIF-1α [12].
In SSc, decreased HIF-1α levels in fibrotic skin may be a result
of PHD-dependent HIF-1α negative feedback loops occurring in
chronic hypoxic conditions [13].Our results also showed a decreased
HIF-1α expression in epidermal keratinocytes. Hypoxia-inducible
factor-1 (HIF-1) mediates cellular responses to hypoxia. HIF-1
expression may be reduced in response to hypoxia in scleroderma.
The fate of stem cells, i.e., differentiation or proliferation, is highly
dependent on oxygen content that regulates expression of various
genes via Hypoxia-Inducible Factor-1 (HIF-1). Scleroderma may
benefit from hyperbaric oxygen therapy [17]. Marcus, et al. [18]
demonstrated that hyperbaric oxygen therapy well succeeded in
treatment of ischemic scleroderma lesions. Hyperbaric oxygen can
also be useful for treating Raynaud’s phenomenon in scleroderma.
It may boost hypoxia-inducible factor-1 expression, which may be a
useful marker for scleroderma activation in future. In many diseases,
fibrosis is a common process with no known effective therapy, which
ultimately causes organ failure and results in a high mortality rate.
The common elements of fibrotic process in any human tissue are
dysregulated repair and excessive scar formation. The PTEN has a
dephosphorylating action on proteins, and this effect is responsible
for tissue repair and, possibly, pathological fibrosis [19]. Overly
active and/or continuous tissue repair underlies fibrosis. A defect
in the production and/or activity of proteins that are responsible
for suppressing the fibrosing activity may be responsible for this
occurrence. PTEN may be one of those proteins [20]. However, it
is not entirely clear if a defective PTEN/Akt pathway is responsible
for chronic fibrosis of SSc. It is equally controversial that defective
PTEN expression is enough for emergence of a fibrotic phenotype
[19]. We found that PTEN expression was absent in epidermal
keratinocytes and endothelial cells despite an increase in fibroblasts
in SSc patients. It has been showed by some functional studies that
PTEN is critically important in suppressing skin cancer and loss
of its activity may lead to skin tumor development by a variety of
mechanisms including mutation, deletion, or reduced expression
[21]. Studies in humans and mice have demonstrated that PTEN is
of vital importance for skin homeostasis and it is critically important
for suppression and thus prevention of skin tumors. It has been
suggested that PTEN exerts its suppressing effects on skin tumors
by antagonizing PI3K/AKT pathways. Proliferation and balance
of epidermal cells, including keratinocytes and melanocytes, are
critically dependent on a normal PTEN function in order to suppress
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their transformation. A heightened PTEN expression in scleroderma
may actually reduce fibroblast spread and emigration. Moreover,
PTEN activity is suppressed by Ultraviolet (UV) radiation, suggesting
that skin carcinogenesis induced by UV radiation is highly dependent
on loss of PTEN activity. It is also interesting that UV phototherapy
benefits patients with scleroderma [22].It may be advocated that this
beneficial effect is a result of inhibition of PTEN expression.
A lower VEGF expression in endothelial cells, a lower HIF-
1α expression in keratinocytes, and a variable PTEN expression in
scleroderma skin samples (higher expression in fibroblasts and lower
in endothelial cells and keratinocytes) were demonstrated by our
study. Such a pattern of expression is of particular importance since
they have a critical role in emergence of scleroderma. Results of other
studies using some different methods for scleroderma therapy may
worth being compared with our results as they would offer a unique
insight into their ability to alter the expression of these molecules
and initiate certain molecular pathways that lead to scleroderma.
Furthermore, pathophysiology and cellular events in development
of scleroderma may be clarified by a more detailed analysis of these
mediators. Further studies on this topic will shed light on the question
if manipulated expression of these molecules at varying stages of the
disease is a direct effect of scleroderma or they result from the altered
number of skin cells responsible from production of these molecules.
We hope that our study will introduce some novel fibrosis markers
and their inhibitors that may be used in treatment of scleroderma.
There is no financial source. There is no conflict of interest.
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