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1.
Proc Natl Acad Sci U S A ; 120(3): e2216458120, 2023 01 17.
Article in English | MEDLINE | ID: mdl-36626557

ABSTRACT

The lack of techniques for noninvasive imaging of inflammation has challenged precision medicine management of acute respiratory distress syndrome (ARDS). Here, we determined the potential of positron emission tomography (PET) of chemokine-like receptor-1 (CMKLR1) to monitor lung inflammation in a murine model of lipopolysaccharide-induced injury. Lung uptake of a CMKLR1-targeting radiotracer, [64Cu]NODAGA-CG34, was significantly increased in lipopolysaccharide-induced injury, correlated with the expression of multiple inflammatory markers, and reduced by dexamethasone treatment. Monocyte-derived macrophages, followed by interstitial macrophages and monocytes were the major CMKLR1-expressing leukocytes contributing to the increased tracer uptake throughout the first week of lipopolysaccharide-induced injury. The clinical relevance of CMKLR1 as a biomarker of lung inflammation in ARDS was confirmed using single-nuclei RNA-sequencing datasets which showed significant increases in CMKLR1 expression among transcriptionally distinct subsets of lung monocytes and macrophages in COVID-19 patients vs. controls. CMKLR1-targeted PET is a promising strategy to monitor the dynamics of lung inflammation and response to anti-inflammatory treatment in ARDS.


Subject(s)
Acute Lung Injury , COVID-19 , Respiratory Distress Syndrome , Humans , Mice , Animals , Lipopolysaccharides/toxicity , Acute Lung Injury/chemically induced , Acute Lung Injury/diagnostic imaging , Acute Lung Injury/metabolism , Lung/diagnostic imaging , Lung/metabolism , Chemokines/metabolism , Respiratory Distress Syndrome/diagnostic imaging , Molecular Imaging , Receptors, Chemokine
2.
J Infect Dis ; 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38271564

ABSTRACT

BACKGROUND: Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection. METHODS: We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct ELISA, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model. RESULTS: We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In five genetically-related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsono-phagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice. CONCLUSIONS: Loss of function in wcaJ led to increased complement resistance, complement binding, and opsono-phagocytosis, which may promote KPC-Kp persistence by enabling co-existence of increased bloodstream fitness and reduced tissue virulence.

3.
Am J Respir Cell Mol Biol ; 70(5): 379-391, 2024 May.
Article in English | MEDLINE | ID: mdl-38301257

ABSTRACT

GDF15 (growth differentiation factor 15) is a stress cytokine with several proposed roles, including support of stress erythropoiesis. Higher circulating GDF15 levels are prognostic of mortality during acute respiratory distress syndrome, but the cellular sources and downstream effects of GDF15 during pathogen-mediated lung injury are unclear. We quantified GDF15 in lower respiratory tract biospecimens and plasma from patients with acute respiratory failure. Publicly available data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reanalyzed. We used mouse models of hemorrhagic acute lung injury mediated by Pseudomonas aeruginosa exoproducts in wild-type mice and mice genetically deficient for Gdf15 or its putative receptor, Gfral. In critically ill humans, plasma levels of GDF15 correlated with lower respiratory tract levels and were higher in nonsurvivors. SARS-CoV-2 infection induced GDF15 expression in human lung epithelium, and lower respiratory tract GDF15 levels were higher in coronavirus disease (COVID-19) nonsurvivors. In mice, intratracheal P. aeruginosa type II secretion system exoproducts were sufficient to induce airspace and plasma release of GDF15, which was attenuated with epithelial-specific deletion of Gdf15. Mice with global Gdf15 deficiency had decreased airspace hemorrhage, an attenuated cytokine profile, and an altered lung transcriptional profile during injury induced by P. aeruginosa type II secretion system exoproducts, which was not recapitulated in mice deficient for Gfral. Airspace GDF15 reconstitution did not significantly modulate key lung cytokine levels but increased circulating erythrocyte counts. Lung epithelium releases GDF15 during pathogen injury, which is associated with plasma levels in humans and mice and can increase erythrocyte counts in mice, suggesting a novel lung-blood communication pathway.


Subject(s)
COVID-19 , Growth Differentiation Factor 15 , Lung , Pseudomonas aeruginosa , SARS-CoV-2 , Growth Differentiation Factor 15/genetics , Growth Differentiation Factor 15/metabolism , Animals , COVID-19/metabolism , COVID-19/virology , Humans , Mice , Lung/metabolism , Lung/pathology , Lung/virology , Male , Pseudomonas Infections/metabolism , Acute Lung Injury/pathology , Acute Lung Injury/metabolism , Female , Mice, Inbred C57BL , Mice, Knockout , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Disease Models, Animal
4.
Am J Physiol Lung Cell Mol Physiol ; 325(5): L604-L616, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37724373

ABSTRACT

Basic leucine zipper transcription factor ATF-like 2 (BATF2) is a transcription factor that is emerging as an important regulator of the innate immune system. BATF2 is among the top upregulated genes in human alveolar macrophages treated with LPS, but the signaling pathways that induce BATF2 expression in response to Gram-negative stimuli are incompletely understood. In addition, the role of BATF2 in the host response to pulmonary infection with a Gram-negative pathogen like Klebsiella pneumoniae (Kp) is not known. We show that induction of Batf2 gene expression in macrophages in response to Kp in vitro requires TRIF and type I interferon (IFN) signaling, but not MyD88 signaling. Analysis of the impact of BATF2 deficiency on macrophage effector functions in vitro showed that BATF2 does not directly impact macrophage phagocytic uptake and intracellular killing of Kp. However, BATF2 markedly enhanced macrophage proinflammatory gene expression and Kp-induced cytokine responses. In vivo, Batf2 gene expression was elevated in lung tissue of wild-type (WT) mice 24 h after pulmonary Kp infection, and Kp-infected BATF2-deficient (Batf2-/-) mice displayed an increase in bacterial burden in the lung, spleen, and liver compared with WT mice. WT and Batf2-/- mice showed similar recruitment of leukocytes following infection, but in line with in vitro observations, proinflammatory cytokine levels in the alveolar space were reduced in Batf2-/- mice. Altogether, these results suggest that BATF2 enhances proinflammatory cytokine responses in macrophages in response to Kp and contributes to the early host defense against pulmonary Kp infection.NEW & NOTEWORTHY This study investigates the signaling pathways that mediate induction of BATF2 expression downstream of TLR4 and also the impact of BATF2 on the host defense against pulmonary Kp infection. We demonstrate that Kp-induced upregulation of BATF2 in macrophages requires TRIF and type I IFN signaling. We also show that BATF2 enhances Kp-induced macrophage cytokine responses and that BATF2 contributes to the early host defense against pulmonary Kp infection.


Subject(s)
Klebsiella Infections , Pneumonia , Animals , Humans , Mice , Adaptor Proteins, Vesicular Transport/metabolism , Cytokines/metabolism , Klebsiella Infections/microbiology , Klebsiella pneumoniae , Macrophages/metabolism , Mice, Inbred C57BL , Pneumonia/metabolism
5.
Breast Cancer Res ; 25(1): 47, 2023 04 26.
Article in English | MEDLINE | ID: mdl-37101247

ABSTRACT

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.


Subject(s)
Breast Neoplasms, Male , Global Burden of Disease , Humans , Male , Female , Breast Neoplasms, Male/epidemiology , Iran/epidemiology , Risk Factors , Aging , Incidence
6.
Am J Physiol Cell Physiol ; 323(3): C857-C865, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35912991

ABSTRACT

Matricellular proteins comprise a diverse group of molecular entities secreted into the extracellular space. They interact with the extracellular matrix (ECM), integrins, and other cell-surface receptors, and can alter matrix strength, cell attachment to the matrix, and cell-cell adhesion. A founding member of this group is thrombospondin-1 (TSP-1), a high molecular-mass homotrimeric glycoprotein. Given the importance of the matrix and ECM remodeling in the lung following injury, TSP-1 has been implicated in a number of lung pathologies. This review examines the role of TSP-1 as a damage controller in the context of lung inflammation, injury resolution, and repair in noninfectious and infectious models. This review also discusses the potential role of TSP-1 in human diseases as it relates to lung inflammation and injury.


Subject(s)
Pneumonia , Thrombospondin 1 , Cell Adhesion , Extracellular Matrix/metabolism , Extracellular Matrix Proteins/metabolism , Humans , Pneumonia/metabolism , Thrombospondin 1/metabolism , Thrombospondins/metabolism
7.
Virol J ; 19(1): 132, 2022 08 08.
Article in English | MEDLINE | ID: mdl-35941646

ABSTRACT

BACKGROUND: Immunocompromised (IC) patients are at higher risk of more severe COVID-19 infections than the general population. Special considerations should be dedicated to such patients. We aimed to investigate the efficacy of COVID-19 vaccines based on the vaccine type and etiology as well as the necessity of booster dose in this high-risk population. MATERIALS AND METHODS: We searched PubMed, Web of Science, and Scopus databases for observational studies published between June 1st, 2020, and September 1st, 2021, which investigated the seroconversion after COVID-19 vaccine administration in adult patients with IC conditions. For investigation of sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. Statistical analysis was performed using R software. RESULTS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 81 articles in the meta-analysis. The overall crude prevalence of seroconversion after the first (n: 7460), second (n: 13,181), and third (n: 909, all population were transplant patients with mRNA vaccine administration) dose administration was 26.17% (95% CI 19.01%, 33.99%, I2 = 97.1%), 57.11% (95% CI: 49.22%, 64.83%, I2 = 98.4%), and 48.65% (95% CI: 34.63%, 62.79%, I2 = 94.4%). Despite the relatively same immunogenicity of mRNA and vector-based vaccines after the first dose, the mRNA vaccines induced higher immunity after the second dose. Regarding the etiologic factor, transplant patients were less likely to develop immunity after both first and second dose rather than patients with malignancy (17.0% vs 37.0% after first dose, P = 0.02; 38.3% vs 72.1% after second dose, P < 0.001) or autoimmune disease (17.0% vs 36.4%, P = 0.04; 38.3% vs 80.2%, P < 0.001). To evaluate the efficacy of the third dose, we observed an increasing trend in transplant patients after the first (17.0%), second (38.3%), and third (48.6%) dose. CONCLUSION: The rising pattern of seroconversion after boosting tends to be promising. In this case, more attention should be devoted to transplant patients who possess the lowest response rate.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Antibodies, Viral , COVID-19/prevention & control , Humans , SARS-CoV-2 , Seroconversion , Vaccination , Vaccines, Synthetic , mRNA Vaccines
8.
J Surg Res ; 275: 63-71, 2022 07.
Article in English | MEDLINE | ID: mdl-35220146

ABSTRACT

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.


Subject(s)
Dizocilpine Maleate , Glutamic Acid , Animals , Colchicine/pharmacology , Dizocilpine Maleate/pharmacology , Glutamic Acid/metabolism , Interleukin-6/metabolism , Male , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate , Tumor Necrosis Factor-alpha/metabolism
9.
Dig Dis Sci ; 67(8): 3672-3682, 2022 08.
Article in English | MEDLINE | ID: mdl-34674071

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents , Colitis , Ivermectin , Receptors, GABA , Acetic Acid , Animals , Anti-Inflammatory Agents/therapeutic use , Baclofen/pharmacology , Baclofen/therapeutic use , Colitis/chemically induced , Colitis/drug therapy , Colitis/pathology , Colon/pathology , Cyclooxygenase 2 , Ivermectin/therapeutic use , Male , NF-kappa B/metabolism , Peroxidase/metabolism , Rats , Rats, Wistar , Receptors, GABA/metabolism , Tumor Necrosis Factor-alpha/metabolism
10.
Pancreatology ; 21(8): 1443-1450, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34561167

ABSTRACT

BACKGROUND: Pancreatic cancer (PC) is among the most lethal cancers worldwide, and the quality of care provided to PC patients is a vital public health concern. We aimed to investigate the quality of care of PC globally and to report its current burden. METHODS: The Quality of Care Index (QCI) was achieved by performing a Principal Component Analysis utilizing the results of the GBD study 2017. The QCI was defined as a range between 0 and 100, in which higher QCIs show higher quality of care. Possible gender- and age-related inequalities in terms of QCI were explored based on WHO world regions and the sociodemographic index (SDI). RESULTS: In 2017, Japan had the highest QCI among all countries (QCI = 99/100), followed by Australia (QCI = 83/100) and the United States (QCI = 76/100). In Japan and Australia, males and females had almost the same QCIs in 2017, while in the United States, females had lower QCIs than males. In contrast to these high-QCI nations, African countries had the lowest QCIs in 2017. Besides, QCI increased by SDI, and high-SDI regions had the highest QCIs. Regarding patients' age, elderly cases had higher QCIs than younger patients globally and in high-SDI regions. CONCLUSION: This study provides clinicians and health authorities with a wider vision around the quality of care of PC worldwide and highlights the existing disparities. This could help them investigate possible effective strategies to improve the quality of care in regions with lower QCIs and higher gender- and age-related inequities.


Subject(s)
Global Burden of Disease , Pancreatic Neoplasms , Aged , Australia , Female , Global Health , Humans , Japan/epidemiology , Male , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/therapy , Quality of Health Care
11.
J Surg Res ; 268: 267-275, 2021 12.
Article in English | MEDLINE | ID: mdl-34392180

ABSTRACT

BACKGROUND: Oncoplastic breast surgery (OBS) is becoming an acceptable procedure for the surgical treatment of breast cancer; however, its safety and recurrence rate still need further clarification. This study evaluates the rate of local recurrence and its predictive factors after OBS in a large series of patients. MATERIALS AND METHODS: This study was conducted between January 2008 and June 2018 in two centers in Iran. Patients underwent OBS, and baseline characteristics were recorded. Patients underwent regular follow-up; local recurrence rate, median time, and the hazard ratio of predictive factors were calculated. Also, a multivariate analysis was performed. RESULTS: A total of 676 patients with a mean age of 48 ± 10.7 y were included. The median follow-up time was 26.4 (first, third IQR: 13.2, 45.6) mo, and 37 (5.5%) patients were diagnosed with local recurrence. The median time to local recurrence was 22.0 (first, third IQR: 16.0, 32.8) mo. Pathological N stage, neoadjuvant chemotherapy, overexpression of HER2, and one surgery technique was associated with a higher risk of recurrence, while the expression of estrogen receptor and progesterone receptor (PR) decreased the risk of recurrence. PR status, neoadjuvant chemotherapy, and pathological N stage remained significant in the final model for recurrence on multivariate analysis. CONCLUSION: OBS is a safe technique with an acceptable risk of local recurrence. PR status, neoadjuvant chemotherapy, and pathological N stage can predict recurrence in these patients with an acceptable power.


Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Adult , Breast/pathology , Breast/surgery , Breast Neoplasms/pathology , Female , Humans , Mastectomy/adverse effects , Mastectomy, Segmental/adverse effects , Mastectomy, Segmental/methods , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/surgery , Receptor, ErbB-2/metabolism , Retrospective Studies
12.
J Surg Res ; 259: 431-441, 2021 03.
Article in English | MEDLINE | ID: mdl-33069391

ABSTRACT

BACKGROUND: Ivermectin (IVM) was first used as an antiparasitic agent; however, the role of this drug evolved into a broad spectrum. Many mechanisms have been proposed, including interaction with the GABAergic system. Considering the presence of GABA receptor in the skin tissue and its role in ischemia-reperfusion I/R injury, we aimed to evaluate the effect of IVM through GABA receptors on random-pattern skin flap survival. METHODS: Sixty Wistar male rats were used. Multiple doses of IVM (0.01, 0.05, 0.2, and 0.5 mg/kg) were injected intraperitoneally before the surgery. Baclofen (selective GABAB agonist) and bicuculline (selective GABAA antagonist) were administered in combination with IVM to assess the role of the GABAergic system. Histopathological evaluations, immunohistochemical staining, quantitative assessment of IL-1ß and TNFα, and the expression of GABAA α1 subunit and GABAB R1 receptors were evaluated in the skin tissue. RESULTS: IVM 0.05 mg/kg could significantly increase flap survival compared with the control group (P < 0.001). Subeffective dose of baclofen (0.1 mg/kg) had synergistic effect with the subeffective dose of IVM (0.01 mg/kg) (P < 0.001), whereas bicuculline 1 mg/kg reversed the effect of IVM (0.05 mg/kg) (P < 0.001). IVM 0.05 mg/kg could also decrease the IL-1ß and TNFα levels and increase the expression of GABAA α1 subunit and GABAB R1 receptors in the flap tissue compared with the control group. CONCLUSIONS: IVM could improve skin flap survival, probably mediated by the GABAergic pathway. Both GABAA and GABAB receptors are involved in this process. This finding may repurpose the use of old drug, "Ivermectin."


Subject(s)
Graft Survival/drug effects , Ivermectin/administration & dosage , Surgical Flaps/transplantation , gamma-Aminobutyric Acid/metabolism , Animals , Baclofen/administration & dosage , Bicuculline/administration & dosage , Drug Repositioning , GABA Antagonists/administration & dosage , GABA-A Receptor Antagonists/administration & dosage , Humans , Male , Models, Animal , Rats , Receptors, GABA-A/metabolism , Receptors, GABA-B/metabolism , Skin/drug effects , Skin/metabolism , Surgical Flaps/adverse effects
13.
Dermatol Ther ; 34(2): e14840, 2021 03.
Article in English | MEDLINE | ID: mdl-33527709

ABSTRACT

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.


Subject(s)
Air Pollutants , Air Pollution , Polycyclic Aromatic Hydrocarbons , Air Pollutants/adverse effects , Air Pollution/adverse effects , Humans , Particulate Matter/adverse effects , Particulate Matter/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Skin
14.
Neurol Sci ; 42(2): 437-444, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33389228

ABSTRACT

Coronavirus disease 2019 (COVID-19) pandemic has struck many countries and caused a great number of infected cases and death. Healthcare system across all countries is dealing with the increasing medical, social, and legal issues caused by the COVID-19 pandemic, and the standards of care are being altered. Admittedly, neurology units have been influenced greatly since the first days, as aggressive policies adopted by many hospitals caused eventual shut down of numerous neurologic wards. Considering these drastic alterations, traditional ethical principles have to be integrated with state-of-the-art ethical considerations. This review will consider different ethical aspects of care in neurologic patients during COVID-19 and how this challenging situation has affected standards of care in these patients.


Subject(s)
COVID-19 , Endovascular Procedures/ethics , Nervous System Diseases/therapy , Neurology/ethics , Palliative Care/ethics , Psychosocial Support Systems , Respiration, Artificial/ethics , Triage/ethics , Humans
15.
Neurol Sci ; 42(10): 4063-4072, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34341860

ABSTRACT

Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating disorder of the central nervous system (CNS), leading to progressive functional impairments, and many intrinsic and acquired factors are believed to be associated with its development and relapse. In terms of environmental factors, air pollution has gained much attention during recent decades, as chronic exposure to ambient air pollution seems to increase the level of some pro-inflammatory markers in the human brain, which can lead to neuroinflammation, neurodegeneration, and blood-brain barrier (BBB) breakdown. These events may also be associated with the risk of MS development and relapse. In this review, we aimed to summarize recent findings around the impact of air pollutants, including particulate matter (PM10, PM2.5, and ultra-fine particles), gaseous pollutants (carbon monoxide [CO], nitrogen oxides [NOx], sulfur dioxide [SO2], and ozone [O3]), and heavy metals, on MS development and relapse.


Subject(s)
Air Pollutants , Air Pollution , Multiple Sclerosis , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Environmental Exposure/adverse effects , Humans , Multiple Sclerosis/epidemiology , Multiple Sclerosis/etiology , Particulate Matter/analysis , Particulate Matter/toxicity
16.
Echocardiography ; 37(1): 41-46, 2020 01.
Article in English | MEDLINE | ID: mdl-31944375

ABSTRACT

BACKGROUND: Cardiac involvement by sarcoidosis may affect any part of the heart such as the pericardium, atriums, ventricles, and papillary muscles. In this regard, the use of two-dimensional speckle-tracking strain has been reported to be valuable in detecting heart sarcoidosis and its distinction from cardiomyopathy. The aim of this study was to investigate subclinical cardiac involvement using 2D speckle tracking and its associated factors in patients with normal systolic function by 2D transthoracic echocardiography (TTE). METHODS: In this study, 55 patients with extra-cardiac sarcoidosis and 21 normal people were evaluated by 2D speckle tracking. The mean longitudinal global strain for the left ventricle was calculated as an average of 16 segments per patient. RESULTS: The comparison of the mean 2D speckle-tracking indices including GCS (global circumferential strain) SAXA, GCSSAXM, Average GCS, AP2LS, AP3LS, AP4LS, and also Average GLS (global longitudinal strain) showed a significant difference between the two groups. Also, the evaluation of each of the above indices with a specific cutoff point as well as a high sensitivity and acceptable specificity predicted the presence of sarcoidosis. The occurrence of changes in the above indices was independent of ventricular function by 2D echocardiography in these patients. CONCLUSIONS: The marked changes in the 2D speckle-tracking parameters in patients with extra-cardiac sarcoidosis can be of great value in the prediction of cardiac involvement. The occurrence of the abovementioned cardiac changes can be completely independent of the involvement of left ventricular function and is therefore predictable in patients with normal ventricular function.


Subject(s)
Sarcoidosis , Ventricular Dysfunction, Left , Echocardiography , Heart Ventricles/diagnostic imaging , Humans , Reproducibility of Results , Sarcoidosis/diagnosis , Sarcoidosis/diagnostic imaging , Systole , Ventricular Function, Left
17.
Ann Plast Surg ; 84(5): 512-517, 2020 05.
Article in English | MEDLINE | ID: mdl-31800564

ABSTRACT

BACKGROUND: Breast cancer, with an incidence of 33.2 per 100,000 in Iranian population, is considered as the most common cancer in Iranian women. Nowadays, with the increasing survival rates, breast reconstruction has been integrated into surgical techniques of breast cancer treatment. The aim of this study was to evaluate the current status of breast reconstruction in Iranian population. PATIENTS AND METHODS: This retrospective study was conducted in Imam Hospital between January 2008 and June 2018. All the patients underwent breast reconstruction surgery. The trend of reconstruction and complication rates were 2 major outcomes. Logistic regression model was used to predict complications. Student t test was used to compare means. RESULTS: Fifty-five patients underwent 60 autologous breast reconstruction surgeries and 152 patients underwent 193 prosthesis-based reconstruction surgeries. Most of cases were invasive ductal carcinoma ± ductal carcinoma in situ (126 cases, 68%). Among 253 surgeries in 207 patients, 98 cases (38.7%) were 2-stage implant, 91 (36.0%) were 1-stage implant, 3 (1.2%) were acellular dermal matrix + prosthesis, 31 (12.2%) were pedicled transverse rectus abdominis myocutaneous flap, 25 (9.8%) were latissimus dorsi flap ± prosthesis, and 4 (15.8%) were latissimus dorsi flap. Among prosthesis-based reconstructions, chemotherapy could predict the occurrence of complications (odds ratio, 2.87; 95% CI, 1.07-7.68), whereas none of these factors could predict the occurrence of complications in autologous reconstructions. The most prevalent complication was seroma formation (48.5% of all complications). Overall complication rates (including major and minor) were higher among autologous reconstructions compared with prosthesis-based reconstructions (45.8% and 21.1%, respectively, P < 0.001). CONCLUSIONS: The trend of breast reconstruction is changing in Islamic Republic of Iran as a developing country. Implant-based reconstruction has surpassed autologous reconstructions in recent years. In terms of complications, we observed higher rates among autologous reconstructions.


Subject(s)
Breast Neoplasms , Mammaplasty , Breast Neoplasms/surgery , Developing Countries , Female , Humans , Iran/epidemiology , Retrospective Studies , Surgical Flaps
20.
Eur Heart J ; 42(6): 559-560, 2021 02 11.
Article in English | MEDLINE | ID: mdl-33206948
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