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Coronavirus disease 2019 (COVID-19) pandemic is still a world-class challenge. Inflammation, especially its severe form with excess release of pro-inflammatory cytokines (cytokine storm) which is a life-threatening condition, is among the most important suspects involved in COVID-19 pathogenesis. It has been shown that cytokine storm could cause notable morbidities such as acute respiratory distress syndrome (ARDS) which leads to hypoxia which is significantly associated with mortality of patients with COVID-19. Hypoxia-inducible factor 1α (HIF-1α) which activates following ARDS-induced hypoxia plays a crucial role in pathogenesis of cytokine storm. The expression of tumor necrosis factor α (TNF-α), interleukin 1 β (IL-1β), and IL-6 which are key elements of cytokine storm are by nuclear factor κβ (NFκB). Interestingly, during the hypoxia, HIF-1α activates NFκB to induce expression of pro-angiogenic and pro-inflammatory factors. These released factors starts a autocrine/paracrine loop and causes deterioration of their etiological pathways of expression: cytokine storm and ARDS. To sum up, it seems HIF-1α is an important target to hit to ameliorate the mentioned pathways. Herein, we suggest perfluorocarbons (PFCs) which are among the organofluorine compounds as a possible co-treatment to reduce hypoxemia and then hypoxia. These substances are known for their high gas solving potential that make them able to be used as a synthetic artificial blood product. Due to the potential of PFCs to affect the fountain of important physiopathological pathway such as inflammation a hypoxia through affecting NFκB, they could be considered as multi-target co-treatment for ARD individuals with COVID-19. It is highly suggested to evaluate this hypothesis in following researches.

Regarding the risk of antibiotic therapy during pregnancy, any medication given to the mother should be according to the indications due to the risk of possible side effects. Antibiotics are one of the most important groups of these medications to be considered. Along with direct antibiotic-induced side effects, indirect pathways also affect the fetus through the maternal changes. According to the data, different cytokines including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) are involved in both term and preterm parturition. These cytokines could trigger expression of different substances such as prostaglandins (PGs), their receptors, and PGs synthetizing molecules with already proven roles in parturition. Moreover, IL-1, IL-6, and TNF-α knocked -out mice have delayed parturition and lower levels of PGs compared to the wild types. The earlier -mentioned cytokines are able to induce matrix metalloproteinases and are also involved in parturition. Certain antibiotics have been shown capable of inducing inflammation cascade directly. Both in -vivo and in -vitro studies in human have also demonstrated this inflammation as elevated levels of inflammatory cytokines especially IL-1, IL-6, and TNF-α. This increase has been observed both in the presence and the absence of lipopolysaccharide (LPS). Moreover, antibiotics can induce endotoxemia in healthy cases which finally leads to the pro-inflammatory cytokine release. Regarding the role of mentioned pro-inflammatory cytokines in both term and preterm parturition, it seems that non-indicated use of antibiotics during pregnancy may increase the risk of preterm labor.

Adhesive Capsulitis (AC) is a self-limiting disease of the shoulder joint characterized by progressive painful restriction of theshoulder’s motion. This study aimed to search the findings on AC in non-contrast MRI. Although AC is a clinical diagnosis,imaging can provide helpful data for earlier diagnosis and treatment. It seems that some findings are specific and sensitive foraccurate diagnosis and staging of AC such as coracohumeral ligament thickening, joint capsule edema, and rotator intervalinfiltration. Non-contrast MRI can provide an abundance of information on AC and help clinicians make a more definitivediagnosis, stage the disease, and choose better treatment plans.

Background Coronavirus disease 2019 (COVID-19) still is a global emergency. According to the studies, pregnant women are of the at risk populations and any underlying disease(s) might even worsen their condition. The aim of this study is reporting a complex case of immune thrombocytopenic purpura (ITP) during pregnancy who has been diagnosed with COVID-19 as well as suspicion of HELLP syndrome. Case presentation A 24-year-old woman with a platelet count of 6000/mL and resistance to conventional therapies was referred. A day after starting 0.5 g/day of methylprednisolone for her, fever and a decrease in SpO2 presented. According to the paraclinical investigations, COVID-19 was diagnosed and the conventional COVID-19 treatments started for her (the methylprednisolone pulse stopped). Due to the increased liver enzymes and low platelet count, with suspicion of HELLP syndrome, cesarean section surgery was performed which resulted in a healthy neonate. Then, the methylprednisolone pulse was restarted for and she developed an increase in the platelet count. Conclusion It is not clear how COVID-19 and pregnancy affected the patient’s condition and the underlying disease; however, it seems the delivery and/or restarting the methylprednisolone pulses caused improvement in her condition.

Purpose: To evaluate ocular movement disorders after scleral buckling surgery (SBS) for retinal detachment. Methods: In this prospective, observational, case series, 206 patients (206 eyes) with rhegmatogenous retinal detachment who underwent SBS and investigated at the strabismus ward of Farabi Eye Hospital in Iran between November 2011 and November 2014 were assessed. Patients were followed from 6 to 36 months after SBS to evaluate for strabismus. Logistic regression analysis test and SPSS software version 20 were used for statistical analysis. Results: From 206 patients, 56.8% were male, and 33.2% were female. For scleral buckle in 44.7% of patients, silicone band and tire (SBT) was used, and in 55.3%, a sponge. Among all patients, seven (3.39%) exhibited ocular movement disorder. There was no significant relation between type of buckle (P = 0.65) or the location of buckle (P = 0.56) and movement disorder. Conclusion: Ocular movement disorder is one of the main complications after SBS without specific association between the type and location of exoplanet. Keywords: Scleral buckling, Ocular movement disorders, Retinal detachment, Strabismus

The article's Abstract is not available.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been led to a pandemic emergency. So far, different pathological pathways for SARS-CoV-2 infection have been introduced in which the excess release of pro-inflammatory cytokines (such as interleukin 1 β [IL-1β], IL-6, and tumor necrosis factor α [TNFα]) has earned most of the attentions. However, recent studies have identified new pathways with at least the same level of importance as cytokine storm in which endothelial cell (EC) dysfunction is one of them. In COVID-19, two main pathologic phenomena have been seen as a result of EC dysfunction: hyper-coagulation state and pathologic angiogenesis. The EC dysfunction-induced hypercoagulation state seems to be caused by alteration in the levels of different factors such as plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF) antigen, soluble thrombomodulin, and tissue factor pathway inhibitor (TFPI). As data have shown, these thromboembolic events are associated with severity of disease severity or even death in COVID-19 patients. Other than thromboembolic events, pathologic angiogenesis is among the recent findings. Furthermore, over-expression/higher levels of different proangiogenic factors such as vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 α (HIF-1α), IL-6, TNF receptor super family 1A and 12, and angiotensin-converting enzyme 2 (ACE2) have been found in the lung biopsies/sera of both survived and non-survived COVID-19 patients. Also, there are some hypotheses regarding the role of nitric oxide in EC dysfunction and acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection. It has been demonstrated that different pathways involved in inflammation are generally common with EC dysfunction and angiogenesis. Altogether, considering the common possible upstream pathways in cytokine storm, pathologic angiogenesis, and EC dysfunction, it seems that targeting these molecules (such as nuclear factor κB) could be more effective in the management of patients with COVID-19., Graphical abstract Unlabelled Image

The aim of this study was to evaluate differences in clinical features and laboratory parameters in critically ill pregnant women with acute respiratory distress syndrome (ARDS) compared to moderate and severe pregnant women with coronavirus disease-2019 (COVID-19) but without ARDS. This was a retrospective multicenter study of all pregnant women with COVID-19 diagnosed with ARDS between February 15, and May 1, 2020 in nine level III maternity centers in Iran (ARDS group). The control COVID-19 pregnant women were selected from 3 of 9 level III maternity centers between March 15 and April 20, 2020. Univariate statistics were used to look at differences between groups. Cluster dendrograms were used to look at the correlations between clinical and laboratory findings in the groups. A value of p n = 26) 89.7% and severe: (n = 3)10.3%). The mean maternal age (35.6 vs. 29.4 years; p = .002) and diagnosis of chronic hypertension (20.0% vs. 0%, p = .034) were significantly higher in the ARDS group. There was no significant difference between the two groups in their presenting symptoms. The ARDS group had a significantly higher prevalence of tachypnea (66.6% vs. 10.3%, p = .042) and blood oxygen saturation (SpO2) p = .004) at presentation. Relative lymphopenia (lymphocyte ratio < 10.5%, 66.6% vs. 17.2%, p = .002), lymphocytes to leukocytes ratio (11.3% vs. 17.7%, p = .010), and neutrophils to lymphocytes ratio (NLR) >7.5 were significantly different between the two groups (all p < .05). Our data demonstrate that symptom-based strategies for identifying the critically ill pregnant women with SARS-CoV-2 are insufficient; however, vital signs and laboratory data might be helpful to predict ARDS in critically ill COVID-19 pregnant patients.

This study aimed to evaluate the primary symptoms, comorbidities, and outcomes of inpatients with confirmed reverse transcription–PCR (RT-PCR) for SARS-CoV-2 infection among 2077 suspected/diagnosed cases of COVID-19. Based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression, age, and suggestive chest X-ray (CXR) findings for SARS-CoV-2 infection, cardiovascular diseases, diabetes mellitus, chronic lung diseases, and intensive care units admission had significant associations with positive RT-PCR results for COVID-19 infection. Also, the highest area under the curve (AUC) was related to cough (AUC = 0.53, 95% CI: 0.51–0.56), dyspnea (AUC = 0.52, 95% CI: 0.50–0.54), and abnormal CXR (AUC = 0.52, 95% CI: 0.50–0.54), as significant predictors. This study showed that some symptoms including cough and dyspnea, as well as abnormal CXR, could be proper predictors of positive RT-PCR result for SARS-CoV-2 infection. It seems that patients with underlying disease(s), such as cardiovascular diseases, diabetes mellitus, and chronic lung diseases, had a higher probability to have positive RT-PCR for SARS-CoV-2 infection than those with no underlying disease(s).

The novel coronavirus (SARS-CoV-2) infection which has been known as Coronavirus diseases 2019 COVID-19 has become an endemic emergent situation by the World Health Organization. So far, no successful specific treatment has been found for this disease. As has been reported, most of non-survivor patients with COVID-19 (70%) had septic shock which was significantly higher than survived ones. Although the exact pathophysiology of septic shock in these patients is still unclear, it seems to be possible that part of it would be due to the administration of empiric antibiotics with inflammatory properties especially in the absence of bacterial infection. Herein, we have reviewed possible molecular pathways of septic shock in the patients who have received antibiotics with inflammatory properties which mainly is release of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF- α) through different routes. Altogether, we highly recommend clinicians to look after those antibiotics with anti-inflammatory activity for both empiric antibiotic therapy and reducing the inflammation to prevent septic shock in patients with diagnosed COVID-19.

Multiple evanescent white dot syndrome (MEWDS) is an inflammatory eye disease of the outer retina, retinal pigmented epithelium, choroid presenting with photopsia, loss of vision, and temporal scotoma. The patient was a 31-year-old female with a history of vision loss since 11 days ago (left eye). At presentation, best-corrected Snellen visual acuity was 20/140 in the Snellen chart. We decided to treat her with short time corticosteroid therapy (0.75 mg/kg/day prednisolone which was tapered in 3 weeks) for any possible rapid recovery of vision. The visual acuity of the involved eye was improved to 20/25 and 20/20, one week and three weeks after starting treatment respectively. Thus, it seems that short-term oral steroids might be an alternative method of management for patients with MEWDS.

The term ‘keratoconus (KC) suspect’ is used as a blanket term to refer to any deviation of virgin cornea shape toward KC features. We intend to subclassify such topographies in meaningful and informative designations. Pentacam corneal topographies of 199 consecutive refractive surgery candidates (398 eyes) are examined. Features of steepness, inferior–superior asymmetry, focal steepening, thinning, and bounded anterior or posterior elevations are observed in the quad map. Scissoring on retinoscopy, loss of best spectacle-corrected visual acuity, and iron ring deposition were looked for. Through iterative observation and refinement of classification criteria—partly taken from the literature—all eyes were designated a specific topographic diagnosis, i.e., circumventing the usage of the expression KC ‘suspect’. Topographies of 308, 48, 21, 13, 6, 1, and 1 (collectively 398 eyes) were designated: normal, ‘atypical normal,’ forme fruste KC, posterior KC, subclinical/mild KC, superior KC, and pseudo–KC, respectively. Current imaging modalities of the cornea and our accumulated experience in refractive science allow assignment of distinctive designations for abnormal corneal shapes along the topography spectrum. We devised and used the expressions: normal, atypical normal, forme fruste (arrested-incomplete) KC, posterior KC, subclinical (active latent) KC, superior KC, and pseudo-keratoconus. Identification of 1.5% (mild) KC highlights the importance of screening for ultraviolet cross-linkage candidacy in refractive surgery referrals.

The aim of the present study was to evaluate the effectiveness of using autologous platelet-rich plasma (PRP) gel for treatment of diabetic foot ulcer (DFU) during the first 4 weeks of the treatment. In this longitudinal and single-arm trial, 100 patients were randomly selected after meeting certain inclusion and exclusion criteria; of these 100 patients, 70 (70%) were enrolled in the trial. After the primary care actions such as wound debridement, the area of each wound was calculated and recorded. The PRP therapy (2mL/cm2 of ulcers) was performed weekly until the healing time for each patient. We used one sample T-test for healing wounds and Bootstrap resampling approach for reporting confidence interval with 1000 Bootstrap samples. The p-value 0.5). According to the results, PRP could be considered as a candidate treatment for non-healing DFUs as it may prevent future complications such as amputation or death in this pathological phenomenon.

The impact of infections and inflammation during pregnancy on the developing fetal brain remains incompletely defined with important clinical and research gaps. Though the classic infectious TORCH pathogens [i.e. Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus] are known to be directly teratogenic, emerging evidence suggests that these infections represent the most extreme end of a much larger spectrum of injury. We present the accumulating evidence that prenatal exposure to a wide variety of viral and bacterial infections – or simply inflammation – may subtly alter fetal brain development, leading to neuropsychiatric consequences for the child later in life. The link between influenza infections in pregnant women and an increased risk for development of schizophrenia in their children was first described more than 30 years ago. Since then, evidence suggests that a range of infections during pregnancy may also increase risk for autism spectrum disorder and depression in the child. Subsequent studies in animal models demonstrated that both pregnancy infections and inflammation can result in direct injury to neurons and neural progenitor cells or indirect injury through activation of microglia and astrocytes, which can trigger cytokine production and oxidative stress. Infectious exposures can also alter placental serotonin production, which can perturb neurotransmitter signaling in the developing brain. Clinically, detection of these subtle injuries to the fetal brain is difficult. As the neuropsychiatric impact of perinatal infections or inflammation may not be known for decades after birth, our construct for defining teratogenic infections in pregnancy (e.g. TORCH) based on congenital anomalies is insufficient to capture the full adverse impact on the child. We discuss the clinical implications of this body of evidence and how we might place greater emphasis on prevention of prenatal infections. For example, increasing uptake of the seasonal influenza vaccine is a key strategy to reduce perinatal infections and the risk for fetal brain injury. An important research gap exists in understanding how antibiotic therapy during pregnancy impacts the fetal inflammatory load and how to avoid inflammation-mediated injury to the fetal brain. In summary, we discuss the current evidence and mechanisms linking infections and inflammation with the increased lifelong risk of neuropsychiatric disorders in the child, and how we might improve prenatal care to protect the fetal brain.

Background: Testis-specific gene antigen (TSGA10) mainly involves in spermatogenesis and embryogenesis. In the new defined roles, being a tumor suppressor agent or a cancer/testis antigen (CTA) is still unclear for this protein. The current study aimed to examine exact role of TSGA10 as a tumor suppressor or CTA in breast cancer and evaluate the role of microenvironment on its expression. Methods: This study evaluated the expression of TSGA10 and hypoxia-inducible factor 1α (HIF-1α) in two different breast cancer cell lines (MCF-7 and MDA-MB23) as well as their control (MCF10A) using real-time PCR. Moreover, expression of the mentioned genes evaluated in samples obtained from tumoral tissues with two types of controls: paired (tumor-free margin) and unpaired (healthy individuals). Also, in order to asses TSGA10 levels in the tumoral tissues, western blotting was performed. Furthermore, to evaluate the role epigenetic changes on TSGA10 expression, breast cancer cell lines were treated with a histone deacetylase inhibitor (HDACI) as well as H2O2 for oxidative stress induction. Results: The current study evaluated 36 patients diagnosed with breast cancer as well as 10 healthy controls. According to the results, it was shown that 35 (97.7%) and 1 (2.8%) of patients were diagnosed with ductal and lobular carcinomas respectively. The TSGA10 levels in the tumoral samples showed 1.38±0.014-fold decrease and 1.41±0.127-fold increase compared with their paired (PTSGA10 expression in MCF-7 and MDA-MB23 cells had 4.9±0.283 and 4.21±0.163 folds of decrease in normoxic and 4.7±.0.283 and 7.1±0.141 folds of expression reduction in hypoxic condition respectively (all PHIF-1α expression was up-regulated in both normoxic (PTSGA10 expression increased up to 7.39±0.156 folds in MCF-7 cells after HDACI treatment (all PTSGA10 expression (all PConclusion: Results of current study showed that TSGA10 seems to be tumor suppressor, however, further studies are necessary.

The objective of this study was to compare the release of endotoxin and pro-inflammatory cytokines as well as pregnancy outcomes after antibiotic exposure in healthy and bacterial infected pregnant rats. Thirty female Wistar pregnant rats were divided into five groups. Group A considered as control and received intraperitoneal saline 0.9% on 17th day of gestation or DG) and groups B and C treated with 20 mg/kg/day intravenous ceftriaxone and ceftazidime, respectively (DG: 18-20). Groups D and E received intraperitoneal E. coli and LPS on 17th DG respectively. Also, groups F and G received the same treatment as group D but they treated with the exact antibiotics mentioned for groups B and C (same dose and duration). Pregnancy outcomes as well as maternal sera levels of endotoxin, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 were assessed using enzyme-linked immunosorbent assay. It was shown that group B had a higher IL-1β (P = 0.003) and TNF-α (P = 0.003) levels compared to the controls (CTC). Group C expressed a lower gestational duration (P = 0.007) as well as higher IL-6 (P = 0.025) and TNF-α (P < 0.001) levels CTC. Interestingly, both group B (P = 0.021) and C (P < 0.001) had a higher rate of endotoxin release CTC. Moreover, in group C, IL-6 (P < 0.0001 and r = -0.941) had a significant correlation with gestational duration. As the results showed, antibiotic administration in non-indication condition seems to be associated with significantly higher production of endotoxin and inflammatory cytokines which increase the risk of poor pregnancy outcomes.

Background Breast cancer is currently the most common neoplasm diagnosed in women globally. There is a growing body of evidence to suggest that human papillomavirus (HPV) infection may play a key role in invasiveness of breast cancer. The aim of this study was to determine the presence of HPV in patients with breast cancer and its possible association with cancer progression. Methods Breast specimens were collected from 72 patients with breast cancer and 31 healthy controls. The presence of HPV was investigated by polymerase chain reaction (PCR) and genotyping was performed for positive cases. We also evaluated the viral factors such as E6, E2, and E7 in HPV positive cases. Enzyme-linked immunosorbent assay (ELISA (and Real-time PCR techniques were used to measure the expression level of anti-carcinogenic genes, such as p53, retinoblastoma (RB), breast and ovarian cancer susceptibility gene (BRCA1, BRCA2) and inflammatory cytokines, including tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), nuclear factor-kB (NF-kB), and different interleukins [ILs] (IL-1,IL6, and IL-17). Results The HPV DNA was detected in 48.6% of breast cancer samples, whereas only 16.1% of controls were positive for HPV. We observed statistically significant differences between breast cancer patients and HPV presence (P = 0.003). HPV type 18 was the most prevalent virus genotype in patients. The expression of P53, RB, BRCA1, and BRCA2 were decreased in patients with HPV-positive breast cancer as compared to HPV-negative breast cancer and healthy controls. (All P-values were less than 0.05). The presence of the HPV was associated with increased inflammatory cytokines (IL-1, IL-6, IL-17, TGF-β, TNF-α, and NF-kB) and tumor progression. Conclusion The present study demonstrated that HPV infection may implicate in the development of some types of breast cancer.

This report highlights details on a pregnant case of COVID-19 who unfortunately did not survive. This 27-year-old woman at her 30 and 3/7 weeks’ gestation was referred to our center with fever, myalgia, and cough. The laboratory investigations showed leukopenia and lymphopenia as well as increased creatinine and CRP levels. The first chest X-ray (faint bilateral patchy opacities) and CT scan (some faint subpleural ground-glass opacities associated with pleural thickening) were not typical for initial COVID-19 pulmonary infection, however, the treatment for COVID-19 was started. Due to respiratory distress, she was intubated and put under mechanical ventilation. After a while, the fetus was born with Apgar score of 0 and did not react to the neonatal cardiopulmonary resuscitation protocol. Finally, due to deterioration in the clinical and imaging findings, the patient was expired as a result of multi-organ failure. Following the death, autopsy was performed and the histopathologic evaluations of the lungs showed evidence of viral pneumonia (viral cytopathic effect and a mild increase in alveolar wall thickness) and ARDS (hyaline membrane). Also, reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infection in the lungs. To our knowledge, this is the first report of maternal death with confirmed COVID-19 infection.

Hematopoietic stem cell transplantation is a curative treatment for many hematologic malignancies with its most important side effect being graft-versus-host disease (GVHD). Herein, we present a 3.5 year-old male with weight of 9.8 kg with acute GVHD (grade IV gastrointestinal and cutaneous) who did not respond to the first line therapies (corticosteroids). Thus, the patient was a candidate for extracorporeal photochemotherapy (ECP). Due to the hyperbilirubinemia, two sessions of ECP every week as well as one session of plasmapheresis 24 h before each ECP session were performed (Spectra ™ Optia ® apheresis system). The procedures were performed successfully without any side effects and the GVHD manifestations of skin and GI responded perfectly to the treatment after 12 and 14 sessions of ECP, respectively. According to the results, it seems that ECP could be successfully performed in even less than 10-kg patients.

Regardless of remarkable progresses in prevention and treatment approaches, graft versus host disease (GVHD) remains a major impediment for successful allogeneic hematopoietic stem cells transplantation (HSCT) and leads to morbidity and mortality in transplanted patients. Corticosteroids are the standard therapy for GVHD; however, a great number of patients will not respond sufficiently and others will be significantly affected by adverse effects of steroids. Extracorporeal photochemotherapy (ECP), as one of the numerous second line therapies, through modulation of immune cells may improves GVHD affected organ function in steroid-refractory forms. Considering to widespread utilization of ECP as a therapeutic strategy, we performed review on current literature of ECP, regarding the treatment strategies, monitoring protocols and technical aspects in chronic and acute GVHD.

Corneal neovascularization (CN) which is associated with angiogenesis and inflammation is seen in different pathological conditions. Among all these situations inflammation and angiogenesis factors such as vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), tumor necrosis factor-α (TNF-α) and other related factors are involved in CN regardless of the etiology. Thus inhibition of these agents that lead to suppression of angiogenesis and inflammation is one the most important strategies to treat CN. Tranilast (TR) is an anti-allergic medicine which has been used in Japan and South Korea in clinic. TR is able to inhibit VEGF, MMP-2 and MMP-9, TNF-α and some other angiogenic and inflammatory factors. According to the anti-angiogenic and anti-inflammatory activity of TR, we hypothesize on the probable efficacy of TR in treating CN. Also topical application of TR in human eye is reported to be safe, so it would be easier to have additional research on therapeutic potential of TR in clinic.