Desmopressin enhances random-pattern skin flap survival in rats: Possible role of vasopressin Type-1a and 2 receptors.

BACKGROUND: Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process. MATERIALS AND METHODS: We randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 µg/rat). SR-49059, a selective V1a receptor antagonist, was given at 2µg/rat before providing the most effective dose of desmopressin (8µg/rat). Histopathological assessments, quantitative measurements of interleukin-1ß (IL-1ß), Tumor necrosis factor-alpha (TNF-α), and Nuclear Factor-κB (NF-κB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed. RESULTS: Desmopressin (8µg/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1ß, TNF-α, and NF-κB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group. CONCLUSIONS: Desmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect.

Metabolic risk factors attributed burden in Iran at national and subnational levels, 1990 to 2019.

Introduction: Metabolic risk factors (MRFs) predispose populations to a variety of chronic diseases with a huge burden globally. With the increasing burden of these risk factors in Iran, in this study, we aimed to report the estimated burden attributed to MRFs at national and subnational scales in Iran, from 1990 to 2019. Methods: Based on the comparative risk assessment method of the Global Burden of Disease (GBD) Study 2019, data of deaths and disability-adjusted life years (DALYs) attributable to four top MRFs in Iran including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body mass index (BMI), and high low-density lipoprotein (LDL) for the 1990-2019 period, were extracted. The socio-demographic index (SDI) was used to report the data based on the corresponding socio-economic stratifications. The results were reported in national and subnational 31 provinces of Iran to discover disparities regarding the attributable burden to MRFs. Furthermore, we reported the causes of diseases to which the attributable burden to MRFs was related. Results: Overall, the age-standardized high LDL, high SBP, high BMI, and high FPG-attributed death rate changed by -45.1, -35.6, +2.8, and +19.9% from 1990 to 2019, respectively. High SBP was the leading risk factor regarding attributed age-standardized death rates reaching 157.8 (95% uncertainty interval: 135.3-179.1) and DALY rates reaching 2973.4 (2652.2-3280.2) per 100,000 person-years, in 2019. All rates increased with aging, and men had higher rates except for the +70 years age group. At the subnational level, provinces in the middle SDI quintile had the highest death and DALY rates regarding all four MRFs. Total deaths, DALYs, YLLs and YLDs number by the causes of diseases linked to MRFs increased over the study period. Cardiovascular diseases, diabetes mellitus, and kidney diseases were the main causes of burden of disease attributable to MRFs. Conclusion: Herein, we found divergent patterns regarding the burden of MRFs as well as disparities in different regions, sex, and age groups for each risk factor and related causes. This could provide policymakers with a clearer vision toward more appropriate decision-making and resource allocation to prevent the burden of MRFs in Iran.

National and subnational burden of female and male breast cancer and risk factors in Iran from 1990 to 2019: results from the Global Burden of Disease study 2019.

BACKGROUND: Breast cancer (BC) is one of the most burdensome cancers worldwide. Despite advancements in diagnostic and treatment modalities, developing countries are still dealing with increasing burdens and existing disparities. This study provides estimates of BC burden and associated risk factors in Iran at the national and subnational levels over 30 years (1990-2019). METHODS: Data on BC burden for Iran were retrieved from the Global Burden of Disease (GBD) study from 1990 to 2019. GBD estimation methods were applied to explore BC incidence, prevalence, deaths, disability-adjusted life years (DALYs), and attributable burden to risk factors based on the GBD risk factors hierarchy. Moreover, decomposition analysis was performed to find the contribution of population growth, aging, and cause-specific incidence in the total incidence change. Age-standardized rates (per 100,000 population) and 95% uncertainty intervals (UI) were reported based on sex, age, and socio-demographic index (SDI). RESULTS: Age-standardized incidence rate (ASIR) increased from 18.8 (95% UI 15.3-24.1)/100,000 in 2019 to 34.0 (30.7-37.9)/100,000 in 2019 among females and from 0.2/100,000 (0.2-0.3) to 0.3/100,000 (0.3-0.4) among males. Age-standardized deaths rate (ASDR) increased slightly among females from 10.3 (8.2-13.6)/100,000 in 1990 to 11.9 (10.8-13.1)/100,000 in 2019 and remained almost the same among males-0.2/100,000 (0.1-0.2). Age-standardized DALYs rate also increased from 320.2 (265.4-405.4) to 368.7 (336.7-404.3) among females but decreased slightly in males from 4.5 (3.5-5.8) to 4.0 (3.5-4.5). Of the 417.6% increase in total incident cases from 1990-2019, 240.7% was related to cause-specific incidence. In both genders, the BC burden increased by age, including age groups under 50 before routine screening programs, and by SDI levels; the high and high-middle SDI regions had the highest BC burden in Iran. Based on the GBD risk factors hierarchy, high fasting plasma glucose (FPG) and alcohol were estimated to have the most and the least attributed DALYs for BC among females, respectively. CONCLUSIONS: BC burden increased from 1990 to 2019 in both genders, and considerable discrepancies were found among different provinces and SDI quintiles in Iran. These increasing trends appeared to be associated with social and economic developments and changes in demographic factors. Improvements in registry systems and diagnostic capacities were also probably responsible for these growing trends. Raising general awareness and improving screening programs, early detection measures, and equitable access to healthcare systems might be the initial steps to tackle the increasing trends.

High expression of Talin-1 is associated with tumor progression and recurrence in melanoma skin cancer patients.

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors. METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed. RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels for skin cancer samples. In addition, there was a statistically significant difference in Talin-1 expression in terms of intensity of staining, percentage of positive tumor cells, and H-score in melanoma tissues compared to NMSC (P = 0.001, P < 0.001, and P < 0.001, respectively). Moreover, high cytoplasmic expression of Talin-1 was found to be associated with significantly advanced stages (P = 0.024), lymphovascular invasion (P = 0.023), and recurrence (P = 0.006) in melanoma cancer tissues. Our results on NMSC showed a statistically significant association between high intensity of staining and the poor differentiation (P = 0.044). No significant associations were observed between Talin-1 expression levels and survival outcomes of melanoma and NMSC patients. CONCLUSION: Our observations showed that higher expression of Talin1 in protein level may be significantly associated with more aggressive tumor behavior and advanced disease in patients with skin cancer. However, further studies are required to find the mechanism of action of Talin-1 in skin cancers.

A case of C-ANCA-positive systematic lupus erythematous and ANCA-associated vasculitis overlap syndrome superimposed by COVID-19: a fatal trio.

Coronavirus disease 2019 (COVID-19) poses a substantial challenge for rheumatologists and rheumatologic patients. They are concerned about the reciprocal interaction between connective tissue diseases, such as systemic lupus erythematosus (SLE), and the virus. Here, we report a 21-year-old female SLE patient presented to the emergency department with gastrointestinal symptoms and kidney involvement evidence. Based on the pathology and laboratory assessments, she was suspected of C-antineutrophil cytoplasmic antibody (ANCA) positive SLE and ANCA-associated vasculitis overlap syndrome (SLE/AAV OS), and plasmapheresis was performed every other day due to this diagnosis alongside the high titer of C-ANCA. We also administered methylprednisolone [1 g/day, intravenous (IV)] for 3 days, followed by dexamethasone with the maintenance dosage (1 mg/kg/day, IV). Although the patient's general condition improved the next days, her condition deteriorated suddenly on the 7th day of hospitalisation. She got intubated and went to the intensive care unit. Despite taking possible measures to manage the patient's condition, she eventually passed away due to severe acute respiratory distress syndrome, triggered by COVID-19. The distinct role of C-ANCA in SLE/AAV vascular damage and activating neutrophil cytokine release accompanied by the impaired immune system while facing COVID-19 seems to lead to increased morbidity and mortality in such patients. This report is presented to bring into consideration the possible role of C-ANCA in the prognosis of COVID-19 in SLE/AAV OS patients.

Rapid Detection Test for COVID-19 among Healthcare Workers and the Role of Personal Protective Equipment.

BACKGROUND: In this study, we assessed the prevalence of positive rapid detection test (RDT) among healthcare workers (HCWs) and evaluated the role of personal protective equipment (PPE) and knowledge of the pandemic. METHODS: In a cross-sectional study conducted between August 2020 and October 2020 in a tertiary referral center (Tehran, Iran), we enrolled 117 physicians, nurses, and other HCWs (OHCWs)-aides, helpers, and medical waste handlers-regularly working in coronavirus disease 2019 (COVID-19) wards. The RDT kit was utilized to reveal recent infection; data on demographics, PPE use and availability, and knowledge of the pandemic was collected through pre-defined questionnaires. RESULTS: Overall, 24.8% (95% CI: 16.8-32.7%) of HCWs had positive RDTs. The more PPE was available and used, the less the chance of positive RDT was (OR: 0.63 [0.44-0.91], P = 0.014 and 0.63 [0.41-0.96], P = 0.030). The same was true for the knowledge of prevention and adhering to preventive rules (OR: 0.44 [0.24-0.81], P = 0.008 and 0.47 [0.25-0.89], P = 0.020). OHCWs had the highest prevalence of positive RDT, while they had more shifts per month, less accessibility to PPE, and less knowledge of the pandemic than physicians. CONCLUSION: The findings of this study suggest that HCWs should have a thorough knowledge of the pandemic along with using PPE properly and rationally. Furthermore, adhering to preventive regulations plays a crucial role in HCWs' safety. It is also noteworthy that shifts should be arranged logically to manage exposures, with a special attention being paid to OHCWs.

The Promising Effect of Colchicine on Random-Pattern Skin Flap Survival in Rats: Glutamate Pathway.

BACKGROUND: Random-pattern skin flap is a conventional procedure in reconstructive surgery, yet partial or complete flap necrosis has remained a major issue. Herein, we investigated the potential effects of colchicine on skin flap survival through the glutamate pathway and N-methyl-D-aspartate (NMDA) receptors. METHODS: Wistar male rats were injected multiple doses of colchicine intraperitoneally (0.02, 0.05, 0.1, and 0.4 mg/kg) before the surgery. MK-801 (a noncompetitive NMDA receptor antagonist) was administered in combination with colchicine to assess the role of glutamate. Histopathological evaluation; quantitative assessment of glutamate, IL-6, and TNF-α; and the expression of NR2A-type NMDA receptors were performed in the skin tissue. RESULTS: Colchicine 0.05 mg/kg could significantly promote flap survival compared to the control group (P < 0.001), while administration of MK-801 (0.05 mg/kg) reversed the effect of colchicine (0.05 mg/kg) (P < 0.001). Levels of IL-6 and TNF-α decreased, and the expression of NR2A-type NMDA receptors was enhanced in the flap tissue of colchicine 0.05 mg/kg group compared to the controls. Also, glutamate level significantly increased after the administration of colchicine 0.05 mg/kg compared to the controls (P < 0.05). CONCLUSIONS: We found that colchicine could improve skin flap survival remarkably in rats that have undergone skin flap surgery through the glutamate pathway and NMDA receptors.

Anti-inflammatory Effects of Ivermectin in the Treatment of Acetic Acid-Induced Colitis in Rats: Involvement of GABAB Receptors.

BACKGROUND: Recent investigations have proposed the potential role of gamma-aminobutyric acid (GABA) in regulating motility and immunity of the gastrointestinal system. AIMS: We aimed to investigate the anti-inflammatory effects of ivermectin (IVM) through GABAB receptors following acetic acid-induced colitis in rats. METHODS: In a controlled experimental study, we enrolled 78 male Wistar rats (13 groups; 6 rats/group). After colitis induction using acetic acid (4%), IVM, baclofen (a standard GABAB agonist) or the combination of both agents was delivered to rats orally (by gavage), with the same dosage continued for 5 days. The control group received the vehicle, and prednisolone (a standard anti-inflammatory agent) was administered in a separate group as the positive control. Colon samples were collected on the sixth day for histopathological evaluations and measurement of myeloperoxidase (MPO) activity, TNF-α levels, and p-NF-ĸB p65, COX-2 and iNOS expression levels. RESULTS: The greatest recovery was found after administering IVM 0.5, baclofen 0.5, or IVM 0.2 + baclofen 0.2 mg/kg/day (ulcer index [UI] = 1.4 ± 0.4, 1.7 ± 0.6, and 1.4 ± 0.3, respectively; p < 0.001 vs. the control [UI = 6.5 ± 0.7]). Histopathological evaluations revealed a significant decrease in the inflammation severity in the three above-mentioned groups. P-NF-ĸB p65, COX-2, and iNOS expression, MPO activity, and TNF-α levels also decreased dramatically following treatment with IVM 0.5, baclofen 0.5, or the combination therapy (p < 0.001 vs. the control). CONCLUSIONS: IVM exerted promising anti-inflammatory effects in treating acetic acid-induced colitis in rats. Its synergistic effect with baclofen also signified the possible involvement of GABAB receptors in this process.

The impact of air pollution on skin and related disorders: A comprehensive review.

As the largest organ in the body, human skin is constantly exposed to harmful compounds existing in the surrounding environment as the first-line barrier. Studies have indicated that exposure to high concentrations of many environmental factors, such as ultraviolet (UV) radiation, outdoor air pollutants, including polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), particulate matter (PM), heavy metals, gaseous pollutants, such as carbon monoxide (CO), nitric oxides (NOx ), sulfur oxide (SO2 ), ozone (O3 ), and indoor air pollutants (solid fuels consumption), might interrupt the skin's normal barrier function. Besides, the intensity of the pollutants and the length of exposure might be a contributing factor. Air pollutants are believed to induce or exacerbate a range of skin conditions, such as aging, inflammatory diseases (atopic dermatitis, cellulitis, and psoriasis), acne, hair loss, and even skin cancers (mainly melanoma and Squamous Cell Carcinoma) through various mechanisms. The interaction between pollutants and the skin might differ based on each agent's particular characteristics. Also, damaging the skin barrier seems to be closely related to the increased production of reactive oxygen species (ROS), induction of oxidative stress, activation of aryl hydrocarbon receptor (AhR), and inflammatory cytokines. This article reviews recent studies on the correlation between air pollutants and skin diseases, along with related mechanisms.