Rasool Akram Hospital

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of articular cartilage. As chondrocytes are the only cell type forming the articular cartilage, their gradual loss is the main cause of OA. There is a substantial body of published research that suggests reactive oxygen species (ROS) are major causative factors for chondrocyte damage and OA development. Oxidative stress elicited by ROS is capable of oxidizing and subsequently disrupting cartilage homeostasis, promoting catabolism via induction of cell death and damaging numerous components of the joint. IL-1β and TNF-α are crucial inflammatory factors that play pivotal roles in the pathogenesis of OA. In this process, the mitochondria are the major source of ROS production in cells, suggesting a role of mitochondrial dysfunction in this type of arthritis. This may also be promoted by inflammatory cytokines such as IL-1β and TNF-α which contribute to chondrocyte death. In patients with OA, the expression of endoplasmic reticulum (ER) stress-associated molecules is positively correlated with cartilage degeneration. Melatonin and its metabolites are broad-spectrum antioxidants and free radical scavengers which regulate a variety of molecular pathways such as inflammation, proliferation, apoptosis, and metastasis in different pathophysiological situations. Herein, we review the effects of melatonin on OA, focusing on its ability to regulate apoptotic processes and ER and mitochondrial activity. We also evaluate likely protective effects of melatonin on OA pathogenesis.

This study aimed to elucidate the genetic causes underlying early-onset Parkinsonism (EOP) in a consanguineous Iranian family. To attain this, homozygosity mapping and whole-exome sequencing were performed. As a result, a homozygous mutation (c.773G>A; p.Arg258Gln) lying within the NH2 -terminal Sac1-like inositol phosphatase domain of polyphosphoinositide phosphatase synaptojanin 1 (SYNJ1), which has been implicated in the regulation of endocytic traffic at synapses, was identified as the disease-segregating mutation. This mutation impaired the phosphatase activity of SYNJ1 against its Sac1 domain substrates in vitro. We concluded that the SYNJ1 mutation identified here is responsible for the EOP phenotype seen in our patients probably due to deficiencies in its phosphatase activity and consequent impairment of its synaptic functions. Our finding not only opens new avenues of investigation in the synaptic dysfunction mechanisms associated with Parkinsonism, but also suggests phosphoinositide metabolism as a novel therapeutic target for Parkinsonism.

Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome.

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

OBJECTIVE: Previous studies have shown that the bioflavonoid quercetin has anti-inflammatory and anti-nociceptive effects. We investigated the effect of quercetin supplementation on inflammation, disease severity, and clinical symptoms in women with rheumatoid arthritis (RA). METHODS: The present study was a randomized, double-blind, placebo-controlled clinical trial in which 50 women with RA were allocated into a quercetin (500 mg/day) or placebo group for 8 weeks. Plasma levels of high-sensitivity tumor necrosis factor-α (hs-TNFα), erythrocyte sedimentation rate (ESR), clinical symptoms including early morning stiffness (EMS), morning and after-activity pain, and tender (TSC) and swollen joint counts (SJC) were determined. Disease activity and functional disability were assessed by Disease Activity Score 28 (DAS-28), physician global assessment (PGA), and a health assessment questionnaire (HAQ) at the beginning and end of the study. RESULTS: Quercetin supplementation for 8 weeks significantly reduced EMS, morning pain, and after-activity pain (p < 0.05). DAS-28 and HAQ scores decreased in the quercetin group compared to placebo and the number of patients with active disease significantly decreased in the quercetin group. Plasma hs-TNFα level was significantly reduced in the quercetin group compared to placebo (p < 0.05). There were no significant differences in TJC and SJC between groups but TJC significantly decreased in the quercetin group after the intervention. Supplementation had an effect on ESR but it was not significant (p > 0.05). CONCLUSIONS: Five hundred milligrams per day quercetin supplementation for 8 weeks resulted in significant improvements in clinical symptoms, disease activity, hs-TNFα, and HAQ in women with RA.

Introduction: Deep brain stimulation is a safe and effective neurointerventional technique for the treatment of movement disorders. Electrical stimulation of subcortical structures may exert a control on seizure generators initiating epileptic activities. The aim of this review is to present the targets of the deep brain stimulation for the treatment of drug-resistant epilepsy. Methods: We performed a structured review of the literature from 1980 to 2018 using Medline and PubMed. Articles assessing the impact of deep brain stimulation on seizure frequency in patients with DRE were selected. Meta-analyses, randomized controlled trials, and observational studies were included. Results: To date, deep brain stimulation of various neural targets has been investigated in animal experiments and humans. This article presents the use of stimulation of the anterior and centromedian nucleus of the thalamus, hippocampus, basal ganglia, cerebellum and hypothalamus. Anterior thalamic stimulation has demonstrated efficacy and there is evidence to recommend it as the target of choice. Conclusion: Deep brain stimulation for seizures may be an option in patients with drug-resistant epilepsy. Anterior thalamic nucleus stimulation could be recommended over other targets.

PURPOSE: To describe optical coherence tomography angiography (OCTA) image artefacts in eyes with and without ocular pathologies. METHODS: The OCTA images of healthy subjects and patients with age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions were retrospectively reviewed. All OCTA images were obtained using a swept-source OCTA instrument (Triton, Topcon). The frequency of various image artefacts including segmentation, banding, motion, projection, masking, unmasking, doubling of the retinal vessels, blink, stretching, out-of-window and crisscross artefacts was assessed. The impact of the artefact on the grading of the images for the foveal avascular zone in deep and superficial retinal layers, capillary non-perfusion and choroidal neovascularisation (CNV) was evaluated. RESULTS: OCTA images of 57 eyes of 48 subjects including 23 eyes (40.3%) with CNV, 13 eyes (22.8%) with dry age-related macular degeneration, 9 eyes (15.7%) with cystoid macular oedema due to diabetic retinopathy or retinal vein occlusion and 12 normal eyes (21.1%) were available for evaluation. At least one type of artefact was present in the images from 51 eyes (89.4%). Banding artefact, segmentation, motion, unmasking, blink, vessel doubling, masking and out-of-window artefacts were found in 51 (89.4%), 35 (61.4%), 28 (49.1%), 9 (15.8%), 5 (8.8%), 1 (1.7%), 1 eye (1.7%) and 1 eye (1.7%), respectively. Projection artefact, stretch artefact or crisscross artefact was not observed. Banding, motion and segmentation artefacts were statistically significantly more frequent in eyes with ocular pathology compared with control eyes (all p<0.001). Eyes with choroidal diseases had significantly higher rate of segmentation error in the choriocapillaris slab compared with eyes with only retinal disease (p=0.02). In nine eyes (17.6%), the artefacts were deemed severe enough by the graders to preclude accurate grading of the image. CONCLUSIONS: Image artefacts occur frequently in OCTA images. The artefacts are more frequent in eyes with pathology.

Purpose: To evaluate the changes in foveal avascular zone (FAZ) area and the retinal capillary density after a single intravitreal anti-VEGF injection for macular edema secondary to diabetic retinopathy or retinal vein occlusion. Methods: In this prospective noncomparative case series, 18 eyes of 15 patients with diabetic macular edema (13 eyes) or macular edema secondary to central retinal vein occlusion (5 eyes) were included. Optical coherence tomography angiography (OCTA) images were obtained, and retinal capillary vessel density and FAZ area were measured in the foveal and parafoveal regions at the level of the superficial (SCP) and deep retinal capillary plexus (DCP) before and at the first visit after intravitreal injection. Results: The mean interval between baseline and follow up OCTA was 32.5 ± 9.4 (range, 21-50) days. Foveal and parafoveal vessel density in the SCP and DCP were not significantly different before and after intravitreal injection (all P > 0.1), nor was FAZ area (P = 0.48 and P = 0.42, respectively). No significant difference was found between eyes with diabetic macular edema and those with retinal vein occlusion with respect to the mean change of vessel density and FAZ area (all P > 0.05). Conclusions: In this pilot study, retinal capillary density and FAZ area remained statistically unchanged in the short-term after a single intravitreal injection of an anti-VEGF agent.

< 0.05). However, no differences in IL-1β were seen between groups. Elevated levels of the proinflammatory cytokine TNF-α were seen in the olfactory epithelium in patients with COVID-19. This suggests that direct inflammation of the olfactory epithelium could play a role in the acute olfactory loss described in many patients with COVID-19.

AIMS: To find the cure rate of late (second year of age) and very late (3-5 years of age) initial probing for congenital nasolacrimal duct obstruction (CNLDO) and to identify the factors contributing to the failure rate of the probing in older children. METHODS: In a prospective interventional case series study, 169 eyes of 125 consecutive patients (1-5 years old) with CNLDO underwent probing under general anaesthesia. Cure was defined as absence of tearing and discharge in the affected eye. RESULTS: 138 eyes of 101 patients aged 13-60 months (mean 23.4 (SD 10.2)) were included. Of 15 eyes (10.8%) with complex CNLDO, 80% presented after 24 months of age (p<0.0001). The cure rate was 89% in patients 13-24 months of age and 72% after the age of 24 months (p = 0.01). It was 90.2% in the membranous and 33.3% in the complex CNLDO in both late and very late probing (p<0.0001). There was a high correlation (r = 0.97) and no significant difference between the cure rate at 1 week and final follow up. CONCLUSION: Accumulation of the complex CNLDO is the main risk factor for failure of probing in the older children. The outcome of the nasolacrimal duct probing at 1 week follow up is highly indicative of the final outcome.

Desirable carbon allotropes such as graphene oxide (GO) have entered the field with several biomedical applications, owing to their exceptional physicochemical and biological features, including extreme strength, found to be 200 times stronger than steel; remarkable light weight; large surface-to-volume ratio; chemical stability; unparalleled thermal and electrical conductivity; and enhanced cell adhesion, proliferation, and differentiation properties. The presence of functional groups on graphene oxide (GO) enhances further interactions with other molecules. Therefore, recent studies have focused on GO-based materials (GOBMs) rather than graphene. The aim of this research was to highlight the physicochemical and biological properties of GOBMs, especially their significance to biomedical applications. The latest studies of GOBMs in biomedical applications are critically reviewed, and in vitro and preclinical studies are assessed. Furthermore, the challenges likely to be faced and prospective future potential are addressed. GOBMs, a high potential emerging material, will dominate the materials of choice in the repair and development of human organs and medical devices. There is already great interest among academics as well as in pharmaceutical and biomedical industries.

Combat or burn injuries are associated with a series of risks, such as microbial infection, an elevated level of inflammatory response, and pathologic scar tissue formation, which significantly postpone wound healing and also lead to impaired repair. Skin engineering for wound healing requires a biomimetic dressing substrate with ideal hydrophilicity, holding antioxidant and antimicrobial properties. In addition, available bioactive specification is required to reduce scar formation, stimulate angiogenesis, and improve wound repair. In this study, we successfully fabricated chitosan (Ch)-based hydrogel enriched with isolated exosome (EXO) from easy-accessible stem cells, which could promote fibroblast cell migration and proliferation in vitro. Full-thickness excisional wound model was used to investigate the in vivo dermal substitution ability of the fabricated hydrogel composed Ch and EXO substrates. Our finding confirmed that the wounds covered with Ch scaffold containing isolated EXO have nearly 83.6% wound closure ability with a high degree of re-epithelialization, whereas sterile gauze showed 51.5% of reduction in wound size. In summary, obtained results imply that Ch-glycerol-EXO hydrogel construct can be utilized at the full-thickness skin wound substitution and skin tissue engineering.

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents.

Acne is known as a chronic inflammatory skin disease with sever adverse effects on quality of life in the patients. The increasing resistance to antibiotics has decreased their effectiveness in treating acne. As viable microbial dietary supplements, probiotics provide health benefits through fighting pathogens and maintaining the homeostasis of the gut and skin microbiome. The present article reviewed the potential of probiotics as beneficial microorganisms for treating acne vulgaris. This review of literature was conducted through a bibliographic search of popular databases, including Science Direct, PubMed, Scielo and Medline, using keywords such as probiotics, prebiotics, synbiotics, microbiome, and acne vulgaris to determine potential applications of these beneficial microbiomes in treating acne vulgaris. Acne lesions are associated with increases in proportion of Propionibacterium acnes as a skin commensal bacterium. The environmental studies showed inhibitory effects of probiotics on P. acnes, mediating by antibacterial proteins and bacteriocin-like inhibitory substances, and their immunomodulatory effects onkeratinocytes and epithelial cells. Probiotics were also found to inhibit cytokine IL-8 in epithelial cells and keratinocytes, suggesting immunomodulatory activities. Moreover, glycerol fermentation by Staphylococcus epidermidis was found to be a natural skin defense against acne and an overgrowth inhibitor of P. acnes. As an antimicrobial agent in lotions and cosmetic formulations, Lactococcus sp. can decrease the inflammatory mediators that are produced by P. acnes and cause vasodilation, edema, mast cell degranulation and TNF-alpha release. Oral administration of probiotics was found to constitute an adjuvant therapy to conventional modalities for treating mild-to-moderate acne vulgaris.

Latent transforming growth factor (TGF) beta-binding protein 2 (LTBP2) is an extracellular matrix (ECM) protein that associates with fibrillin-1 containing microfibrils. Various factors prompted considering LTBP2 in the etiology of isolated ectopia lentis and associated conditions such as Weill-Marchesani syndrome (WMS) and Marfan syndrome (MFS). LTBP2 was screened in 30 unrelated Iranian patients. Mutations were found only in one WMS proband and one MFS proband. Homozygous c.3529G>A (p.Val1177Met) was shown to cause autosomal recessive WMS or WM-like syndrome by several approaches, including homozygosity mapping. Light, fluorescent, and electron microscopy evidenced disruptions of the microfibrillar network in the ECM of the proband's skin. In conjunction with recent findings regarding other ECM proteins, the results presented strongly support the contention that anomalies in WMS patients are due to disruptions in the ECM. Heterozygous c.1642C >T (p.Arg548*) possibly contributed to MFS-related phenotypes, including ocular manifestations, mitral valve prolapse, and pectus excavatum, but was not cause of MFS.

COVID-19 had a great impact on medical approaches among dermatologist. This systematic review focuses on all skin problems related to COVID-19, including primary and secondary COVID-related cutaneous presentations and the experts recommendations about dermatological managements especially immunomodulators usage issues. Search was performed on PubMed, Scopus, Embase and ScienceDirect. Other additional resources were searched included Cochrane, WHO, Medscape and coronavirus dermatology resource of Nottingham university. The search completed on May 3, 2020. Three hundred seventy-seven articles assigned to the inclusion and exclusion groups. Eighty-nine articles entered the review. Primary mucocutaneous and appendageal presentations could be the initial or evolving signs of COVID-19. It could be manifest most commonly as a maculopapular exanthamatous or morbiliform eruption, generalized urticaria or pseudo chilblains recognized as "COVID toes" (pernio-like acral lesions or vasculopathic rashes). During pandemic, Non-infected non-at risk patients with immune-medicated dermatologic disorders under treatment with immunosuppressive immunomodulators do not need to alter their regimen or discontinue their therapies. At-risk o suspected patients may need dose reduction, interval increase or temporary drug discontinuation (at least 2 weeks). Patients with an active COVID-19 infection should hold the biologic or non-biologic immunosuppressives until the complete recovery occur (at least 4 weeks).