A Comparative Study of Demographic and Clinical Criteria Between Male and Female Patients With Pemphigus Referred to a Referral Hospital in Iran.

Background: Pemphigus is a rare autoimmune disease characterized by the formation of blisters on the skin and mucous membranes, caused by autoantibodies against desmoglein, a key protein in cell adhesion. This study aims to compare demographic and clinical criteria between male and female patients with pemphigus referred to a referral hospital, utilizing data from the pemphigus diseases registry. Method: This retrospective cross-sectional analysis focused on several key aspects age at disease onset, severity (measured by the Pemphigus Disease Area Index [PDAI]), types of pemphigus, duration of disease, and diagnostic criteria including the presence of antidesmoglein antibodies and findings from direct immunofluorescence (DIF). By examining these variables among a cohort selected based on their diagnosis of pemphigus, the study aimed to identify significant gender differences in disease manifestation, diagnosis, and progression. This approach is crucial for tailoring more effective gender-specific management and treatment strategies for this rare autoimmune condition. Results: In a comprehensive analysis of 1218 pemphigus patients in the year 2021 from the hospital's registry, comprising 543 males (44.6%) and 675 females (55.4%), significant gender differences were identified in 9 out of 44 variables examined. The study revealed that males had a higher age at disease onset, more frequent clinical manifestations in the head, neck, and trunk areas, and greater severity of disease as measured by the PDAI score compared to females. Conversely, females exhibited higher instances of mucosal manifestations and a higher PDAI score for mucosal erosion blister of the lower gingiva. No significant gender differences were found in 21 variables, including the overall age of patients, specific clinical manifestations across various mucous membranes, types of pemphigus, and PDAI scores for mucosal erosions in particular locations, indicating a nuanced gender impact on the presentation and severity of pemphigus that necessitates tailored clinical approaches. Conclusion: The study highlights significant gender differences in the presentation and severity of pemphigus, underscoring the importance of gender-specific approaches in the diagnosis and management of this condition. The findings contribute valuable insights into the complex nature of pemphigus and underline the necessity for further research to understand the underlying mechanisms driving these differences.

Potential contribution of gut microbiota in the development of autoantibodies in T1D children carrying HLA-DRB1/DQB1 risk alleles: an experimental and in silico analysis.

This study aimed to investigate the prevalence of insulin autoantibody (IAA), glutamic acid decarboxylase antibody (GADA), and insulinoma-associated antigen-2 antibody (IA-2A) in type 1 diabetes (T1D) children based on the presence of predisposing HLA-II alleles. Additionally, to assess the sequence homology between autoantigens of islet cells and selected proteins derived from gut bacteria in terms of their binding capacities to HLA risk alleles, HLA-DRB1/DQB1 alleles were determined by PCR-SSOP in 111 T1D children (probands) along with 222 parents and 133 siblings. Autoantibodies were measured by ELISA, and in silico analysis was run as follows: protein extraction, homology and epitope prediction, peptide alignment, and HLA-peptide docking. Higher significant frequencies of DRB1*03:01, DQB1*02:01, and DQB1*03:02 alleles and DRB1*03:01 ~ DQB1*02:01 haplotype and lower frequencies of DRB1*11:01, DRB1*14:01, and DQB1*03:01 alleles were found in probands compared to parents and siblings. DRB1*11:01 ~ DQB1*03:01, DRB1*14:01 ~ DQB1*05:03, and DRB1*15:01-DQB1*06:02 haplotypes were significantly less frequent in the probands compared to parents. Out of 111 probands, 21 were seronegative, 90 tested positive for one autoantibody, and 15 showed the concurrent presence of three autoantibodies. Logistic regression analysis revealed that DRB1*04 ~ DQB1*03:02 haplotype was associated with the induction of GADA and IA-2A, while DRB1*11:01 ~ DQB1*03:01 was associated with seronegativity. Epitopes derived from GAD and gut bacteria showed strong binding capacities to HLA risk alleles. Due to the sequence similarities between gut bacteria-derived proteins and islet cell autoantigens and their potential for binding to HLA risk alleles, dysbiosis of gut microbiota can be considered another risk factor for the development of T1D, especially in genetically susceptible individuals.

Applications of mesenchymal stem cell-exosome components in wound infection healing: new insights.

The healing process at a wound is made up of many types of cells, growth factors, the extracellular matrix, nerves and blood vessels all interacting with each other in complex and changing ways. Microbial colonization and proliferation are possible at the place of injury, which makes infection more likely. Because of this, any cut has a chance of getting an infection. Researchers have found that wound infections make patients more upset and cost the healthcare system a lot of money. Surgical site infections happen a lot to people who have recently had surgery. This study shows that such surgical infection is linked to a high rate of illness and death. This is shown by the fact that 25% of patients get serious sepsis and need to be transferred to an intensive care unit. In both animal models and people, mesenchymal stem cells (MSCs) play an active role in all stages of wound healing and have positive effects. Exosomes are one of the main things MSCs release. They have effects that are similar to those of the parent MSCs. Various effector proteins, messenger RNA and microRNAs can be transported by extracellular vesicles to control the activity of target cells. This has a big impact on the healing process. These results suggest that using MSC-exosomes as a new type of cell-free therapy could be a better and safer option than whole cell therapy. This review is mostly about how to use parts of MSC-exosomes to help wound infections heal.

Hailey-Hailey Disease: Case Series and Review of Systemic Medications.

INTRODUCTION: Hailey-Hailey disease (HHD) is a rare inherited blistering skin disorder characterized by a chronic relapsing course. While it does not pose a serious threat to the patient's health, the quality of life can change. Unfortunately, there is currently no standard treatment for this condition. OBJECTIVES: In this observational retrospective cohort study, our aim was to discover the demographic characteristics and treatment strategies for managing HHD. METHODS: In this retrospective cohort study, we documented the demographic, clinical, and histopathological characteristics beside various treatment employed options of patients diagnosed with HHD at Razi Hospital over the past 14 years. RESULTS: A total of 32 patients with HHD were enrolled in the study (15 male and 17 female). The mean age of patients was 50.41 ± 13.15 (22-77) years. The average age of disease onset was 37.31 ± 11.88 (15-60) years. Among the participants, 16 individuals (50%) affirm a positive family history of some kind of pemphigoid blisters. The most common site of disease activity was the inguinal area, observed in 14 patients (33.33%). Histopathological examination discovered the existence of suprabasal acantholysis in all of the specimens. Worthily, direct immunofluorescence analysis showed negative results in all skin biopsies. All patients received topical steroids and either topical or systemic antimicrobial agents. In cases of flares, systemic steroids were the most popular and favorable treatment choice during flares. CONCLUSION: Indeed, Hailey-Hailey disease, characterized by its chronic inflammatory and rare nature with a relapsing and remitting course, poses a significant challenge for dermatologists. The treatment of HHD has been less than satisfactory and it often presents a challenge and could be misdiagnosed. Among the available treatment options, topical steroids and antimicrobial agents are the most administered therapies.

Comparative analysis of vision transformers and convolutional neural networks in osteoporosis detection from X-ray images.

Within the scope of this investigation, we carried out experiments to investigate the potential of the Vision Transformer (ViT) in the field of medical image analysis. The diagnosis of osteoporosis through inspection of X-ray radio-images is a substantial classification problem that we were able to address with the assistance of Vision Transformer models. In order to provide a basis for comparison, we conducted a parallel analysis in which we sought to solve the same problem by employing traditional convolutional neural networks (CNNs), which are well-known and commonly used techniques for the solution of image categorization issues. The findings of our research led us to conclude that ViT is capable of achieving superior outcomes compared to CNN. Furthermore, provided that methods have access to a sufficient quantity of training data, the probability increases that both methods arrive at more appropriate solutions to critical issues.

The Effects of Subcutaneous Rapid-Acting Insulin Aspart in the Treatment of Mild and Moderate Diabetic Ketoacidosis in Children: A Prospective Study.

Background and objectives The traditional treatment approach to diabetic ketoacidosis (DKA) involves the replacement of fluid and electrolyte deficits and a continuous intravenous infusion of regular insulin. Several clinical trials supported the administration of subcutaneous rapid-acting insulin analogs in the management of uncomplicated DKA. This study aimed to determine the effects/safety of subcutaneous rapid-acting insulin aspart injections in treating uncomplicated mild and moderate DKA in children. Methods In this prospective study in 2022, 25 children with mild/or moderate DKA were enrolled. The main outcome measure was median time (hours) for the resolution of ketoacidosis. Data recorded were as follows: clinical characteristics, severity of ketoacidosis and dehydration, blood glucose, sodium, potassium, creatinine, urine ketones, hospitalization's duration, and complications. Based on the degree of dehydration, fluid deficit was replaced by sodium chloride 0.45%. Insulin aspart 0.15 units/kg subcutaneous injections were given every 2 hours in the hospital outside ICU. Blood glucose was measured hourly and blood gases every 2 hours. Ketoacidosis was considered resolved when the patient did not have nausea/vomiting, was conscious, and could eat, and blood glucose was <250 mg/dL, pH was >7.30, and/or HCO3 was >15 mmol/L. Results Of 25 DKA patients (mean age 11.06±3.89, range 4-17 years, 60% girls), 16 cases (64%) had established type 1 diabetes. Overall, 13 (52%) cases had mild ketoacidosis (average pH=7.25), and 12 (48%) cases had moderate ketoacidosis (average pH=7.15). The mean time to resolution of ketoacidosis was 11.24 hours. All but one patient met DKA recovery criteria without complications. Mild cases compared to moderate cases of DKA had a shorter duration to resolution of DKA (p = 0.04). Mean duration of hospitalization was 2.3 days. No electrolyte disturbances, hypoglycemia events, readmission or mortality, or other adverse effects were observed. Conclusion In children with mild and moderate DKA, subcutaneous rapid-acting insulin aspart administration was an effective, safe, and convenient treatment.

The First Case of Eruptive Pyogenic Granuloma following COVID-19 Vaccination.

Introduction: Pyogenic granuloma presents clinically as a rapidly growing, friable, red papule of skin or mucosa, commonly measuring less than 10 mm with frequent bleeding due to ulceration. Angioproliferative diseases including pyogenic granuloma and cherry angioma have been reported during COVID-19 infection or following COVID-19 vaccination. Case Presentation: Here, we report a 52-year-old female patient who developed diffuse skin eruptions 3 weeks after the second dose of COVID-19 vaccination. Conclusion: As per our knowledge, this is the first case of eruptive PG following COVID-19 vaccination. Oral propranolol and PDL laser therapy were administered after obtaining inconvenient results from electro-cautery, and there was a good response within 6 weeks of starting therapy, defined by the cessation of new lesion formation and a decrease in the size of large lesions.

Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.

Chemotherapy and radiotherapy are widely used in clinical practice across the globe as cancer treatments. Intrinsic or acquired chemoresistance poses a significant problem for medical practitioners and researchers, causing tumor recurrence and metastasis. The most dangerous kind of malignant brain tumor is called glioblastoma multiforme (GBM) that often recurs following surgery. The most often used medication for treating GBM is temozolomide chemotherapy; however, most patients eventually become resistant. Researchers are studying preclinical models that accurately reflect human disease and can be used to speed up drug development to overcome chemoresistance in GBM. Non-coding RNAs (ncRNAs) have been shown to be substantial in regulating tumor development and facilitating treatment resistance in several cancers, such as GBM. In this work, we mentioned the mechanisms of how different ncRNAs (microRNAs, long non-coding RNAs, circular RNAs) can regulate temozolomide chemosensitivity in GBM. We also address the role of these ncRNAs encapsulated inside secreted exosomes.

Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective.

Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.

Key barriers to the provision and utilization of maternal health services in low-and lower-middle-income countries; a scoping review.

BACKGROUND: The preservation and promotion of maternal health (MH) emerge as vital global health objectives. Despite the considerable emphasis on MH, there are still serious challenges to equitable access to MH services in many countries. This review aimed to determine key barriers to the provision and utilization of MH services in low- and lower-middle-income countries (LLMICs). METHODS: In this scoping review, we comprehensively searched four online databases from January 2000 to September 2022. In this study, the approach proposed by Arksey and O'Malley was used to perform the review. Consequently, 117 studies were selected for final analysis. To determine eligibility, three criteria of scoping reviews (population, concept, and context) were assessed alongside the fulfillment of the STROBE and CASP checklist criteria. To synthesize and analyze the extracted data we used the qualitative content analysis method. RESULTS: The main challenges in the utilization of MH services in LLMICs are explained under four main themes including, knowledge barriers, barriers related to beliefs, attitudes and preferences, access barriers, and barriers related to family structure and power. Furthermore, the main barriers to the provision of MH services in these countries have been categorized into three main themes including, resource, equipment, and capital constraints, human resource barriers, and process defects in the provision of services. CONCLUSIONS: The evidence from this study suggests that many of the barriers to the provision and utilization of MH services in LLMICs are interrelated. Therefore, in the first step, it is necessary to prioritize these factors by determining their relative importance according to the specific conditions of each country. Consequently, comprehensive policies should be developed using system modeling approaches.

Family-based association of HLA-DRB1 and DQB1 alleles and haplotypes in a group of Iranian Type 1 diabetes children.

This family-based study was conducted in a group of Iranians with Type 1 diabetes (T1D) to investigate the transmission from parents of risk and non-risk HLA alleles and haplotypes, and to estimate the genetic risk score for this disease within this population. A total of 240 T1D subjects including 111 parent-child trios (111 children with T1D, 133 siblings, and 222 parents) and 330 ethnically matched healthy individuals were recruited. High-resolution HLA typing for DRB1/DQB1 loci was performed for all study subjects (n = 925) using polymerase chain reaction-sequence-specific oligonucleotide probe method. The highest predisposing effect on developing T1D was conferred by the following haplotypes both in all subjects and in probands compared to controls: DRB1*04:05-DQB1*03:02 (Pc = 2.97e-06 and Pc = 6.04e-10, respectively), DRB1*04:02-DQB1*03:02 (Pc = 5.94e-17 and Pc = 3.86e-09, respectively), and DRB1*03:01-DQB1*02:01 (Pc = 8.26e-29 and Pc = 6.56e-16, respectively). Conversely, the major protective haplotypes included DRB1*13:01-DQB1*06:03 (Pc = 6.99e-08), DRB1*15:01-DQB1*06:02 (Pc = 2.97e-06) in the cases versus controls. Also, DRB1*03:01-DQB1*02:01/DRB1*04:02|05-DQB1*03:02 and DRB1*03:01-DQB1*02:01/DRB1*03:01-DQB1*02:01 diplotypes conferred the highest predisposing effect in the cases (Pc = 8.65e-17 and Pc = 6.26e-08, respectively) and in probands (Pc = 5.4e-15 and Pc = 0.001, respectively) compared to controls. Transmission disequilibrium test showed that the highest risk was conferred by DRB1*04:02-DQB1*03:02 (Pc = 3.26e-05) and DRB1*03:01-DQB1*02:01 (Pc = 1.78e-12) haplotypes and the highest protection by DRB1*14:01-DQB1*05:03 (Pc = 8.66e-05), DRB1*15:01-DQB1*06:02 (Pc = 0.002), and DRB1*11:01-DQB1*03:01 (Pc = 0.0003) haplotypes. Based on logistic regression analysis, carriage of risk haplotypes increased the risk of T1D development 24.5 times in the Iranian population (p = 5.61e-13). Also, receiver operating characteristic curve analysis revealed a high predictive power of those risk haplotypes in discrimination of susceptible from healthy individuals (area under curve: 0.88, p = 5.5e-32). Our study highlights the potential utility of genetic risk assessment based on HLA diplotypes for predicting T1D risk in individuals, particularly among family members of affected children in our population.

Determination of HLA class II risk alleles and prediction of self/non-self-epitopes contributing Hashimoto's thyroiditis in a group of Iranian patients.

One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-II risk alleles for developing Hashimoto's thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (thyroid peroxidase, TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective alleles for HT disease. Then, in silico analysis was conducted to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacities to HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles and DRB1*13:01 as a potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002; OR, 3.97) and DRB1*03:01 ~ DQB1*02:01 (Pc = 0.004; OR, 2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles for discrimination of the susceptible from healthy individuals (AUC, 0.70; P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herpes virus and sequence 151-199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individuals carrying HLA risk alleles which can also be related to herpes virus infection.

A computational approach to design a multiepitope vaccine against H5N1 virus.

Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human ß-defensin-3 (HßD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.

Molecular mechanism of lncRNAs in pathogenesis and diagnosis of auto-immune diseases, with a special focus on lncRNA-based therapeutic approaches.

Autoimmune diseases are a diverse set of conditions defined by organ damage due to abnormal innate and acquired immune system responses. The pathophysiology of autoimmune disorders is exceedingly intricate and has yet to be fully understood. The study of long non-coding RNAs (lncRNAs), non-protein-coding RNAs with at least 200 nucleotides in length, has gained significant attention due to the completion of the human genome project and the advancement of high-throughput genomic approaches. Recent research has demonstrated how lncRNA alters disease development to different degrees. Although lncRNA research has made significant progress in cancer and generative disorders, autoimmune illnesses are a relatively new research area. Moreover, lncRNAs play crucial functions in differentiating various immune cells, and their potential relationships with autoimmune diseases have received growing attention. Because of the importance of Th17/Treg axis in auto-immune disease development, in this review, we discuss various molecular mechanisms by which lncRNAs regulate the differentiation of Th17/Treg cells. Also, we reviewed recent findings regarding the several approaches in the application of lncRNAs in the diagnosis and treatment of human autoimmune diseases, as well as current challenges in lncRNA-based therapeutic approaches to auto-immune diseases.

Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/ß-catenin signaling pathway in C26 colorectal cancer cells.

Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.

Is skin autofluorescence a novel non-invasive marker in diabetes? A systematic review and meta-analysis of case-control studies.

Background: The advanced glycation end product (AGE) is produced from the nonenzymatic reaction between glucose and macromolecules by aging. Accumulation of AGE causes functional and structural changes in body proteins that lead to impairment of tissue protein functions. We aimed to validate AGE measurement by skin autofluorescence (SAF) in diabetes mellitus (DM) compared to the nondiabetes population. Materials and Methods: We searched the PubMed, Cochrane, and Scopus databases from their inception till September 18, 2022, for casecontrol studies measuring AGE by SAF. Nonhuman studies, as well as review articles, study proposals, editorials, case reports, or congress posters, were excluded. We used a random effects model to assess the standard mean difference (MD) of age, body mass index (BMI), HbA1c, and SAF between diabetes and nondiabetes individuals. Results: Higher SAF in DM patients indicated more accumulation of AGE compared with the nondiabetic population. Furthermore, HbA1c was considerably higher in DM patients. The MD of age, male gender, and BMI were significantly different between the DM individuals, compared with nondiabetic subjects, which can lead to altered SAF level and AGE production. There was a remarkable heterogeneity between diabetes and nondiabetes when measuring age, gender, and BMI, as well as HbA1c and SAF level. Conclusion: This study could not confirm the validity of SAF as a surrogate marker in diabetes patients. Interestingly, metabolic load and high BMI can increase SAF, considerably. Altogether, SAF could be helpful in the future as a marker for metabolic syndrome or diabetes.

Two cases of neglected leishmaniasis with marked facial disfigurement: A diagnostic conundrum.

Key Clinical Message: There is a need to pay more attention to cutaneous leishmaniasis in endemic regions which may mimic other dermatoses and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy. Abstract: Leishmaniasis is a vector-borne disease with a variety of Clinical manifestations. Cutaneous leishmaniasis (CL) is the most common form of disease and can mimic other dermatoses. We describe two unusual cases of chronic leishmaniasis that remained undiagnosed for many years and led to superimposition of squamous cell carcinoma (SCC) on lesions of one patient. These reports showed that the leishmaniasis should be borne in mind by clinicians when encountering any infiltrated lesion in patients from endemic regions and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy.

Combined training in addition to cortisol reduction can improve the mental health of girls with precocious puberty and obesity.

Background: Obesity and central precocious puberty (CPP) are associated with increased anxiety, depression, and anger in girls. The contribution of exercise as an efficacious component in decreasing anxiety, depression, and anger has been increasingly recognized. Objectives: This study aims to evaluate the effects of combined training on cortisol, anxiety, depression, and anger in overweight and obese girls with CPP. Methods: The study involved 30 girls aged 7-9 years diagnosed with CPP (undergoing triptorelin treatment) and dealing with obesity. In addition, these girls scored higher than the cut-off line for anxiety, depression, and anger. The participants were divided into two groups, with 15 individuals in each group. The exercise group engaged in 60 min of combined aerobic and resistance training three times per week for a duration of 12 weeks. On the other hand, the control group did not receive any training. Throughout the study, the serum cortisol levels were measured in both groups. Anxiety, anger, and depression questionnaires were also completed at three different stages, namely, baseline, 12 weeks, and 16 weeks (after a 4-week period of detraining). Results: In the exercise group, there was a significant decrease (P < 0.05) in cortisol serum levels and anxiety, depression, and anger scores. These changes were observed consistently during detraining (P > 0.05). However, in the control group, only the depression score significantly decreased (P < 0.05). Conclusions: Based on the results, it can be concluded that combined training is a method to improve the mental health of CPP girls. Clinical Trial Registration: https://en.irct.ir/trial/61990, identifier IRCT20170411033378N10.

Molecular landscape of LncRNAs in bladder cancer: From drug resistance to novel LncRNA-based therapeutic strategies.

Bladder cancer (BC) is a common and serious type of cancer that ranks among the top ten most prevalent malignancies worldwide. Due to the high occurrence rate of BC, the aggressive nature of cancer cells, and their resistance to medication, managing this disease has become a growing challenge in clinical care. Long noncoding RNAs (lncRNAs) are a group of RNA transcripts that do not code for proteins and are more than 200 nucleotides in length. They play a significant role in controlling cellular pathways and molecular interactions during the onset, development and progression of different types of cancers. Recent advancements in high-throughput gene sequencing technology have led to the identification of various differentially expressed lncRNAs in BC, which indicate abnormal expression. In this review, we summarize that these lncRNAs have been found to impact several functions related to the development of BC, including proliferation, cell growth, migration, metastasis, apoptosis, epithelial-mesenchymal transition, and chemo- and radio-resistance. Additionally, lncRNAs may improve prognosis prediction for BC patients, indicating a future use for them as prognostic and diagnostic biomarkers for BC patients. This review highlights that genetic tools and anti-tumor agents, such as CRISPR/Cas systems, siRNA, shRNA, antisense oligonucleotides, and vectors, have been created for use in preclinical cancer models. This has led to a growing interest in using lncRNAs based on positive research findings.