Side effects of COVID-19 vaccines among Iranian healthcare workers: a retrospective cohort study.

INTRODUCTION: This study assessed the incidence and severity of side effects associated with coronavirus disease 2019 (COVID-19) vaccination among healthcare workers registered with the Medical Council of the Islamic Republic of Iran. METHODOLOGY: A retrospective cohort study was conducted on the healthcare workers focusing on the side-effects of COVID-19 vaccines from March to June 2021. Data were collected using online questionnaires. Multivariable logistic regression was used to assess the association between side effects of the vaccines and demographic variables, comorbidities, vaccine type, and history of COVID-19. RESULTS: Out of 42,018 people who were included, 55.85% reported at least one side effect after receiving the first vaccine dose. 4.59% of those with side effects sought diagnostic intervention or were referred to treatment centers. Multivariable logistic regression indicated that being a woman, higher education, having a history of COVID-19 infection, and having comorbidities increased the risk of side effects. The AstraZeneca vaccine significantly increased the risk of side effects compared to the Sputnik vaccine, while the Sinopharm vaccine decreased this risk. The risk of developing a side effect decreased with age. The risk of moderate and severe side effects was significantly associated with gender, younger age, comorbidities, and a history of COVID-19 infection. Moderate and severe side effects were less reported by those who received the Sinopharm vaccine. CONCLUSIONS: Clinical complications after COVID-19 vaccination, directly or indirectly caused by the vaccines, are common. However, the benefits of COVID-19 vaccines greatly outweigh the risk of reversible side effects, especially among the high-risk population.

Optimization of a recombinant BlaR-CTD protein formulation using the response surface methodology.

The sequence of a carboxy-terminal of the ß-lactam sensor-transducer protein (BlaR-CTD) from Bacillus licheniformis ATCC14580 was extracted from US7745193B2 patent and expressed in E. coli using pColdI vector as a soluble His-tag recombinant protein. In this study, several excipients were used to improve the stability of recombinant BlaR-CTD and obtain the optimal formulation for this protein using response surface methodology (RSM)/ Central Composite Design (CCD). Total protein concentration was measured by UV spectroscopy and the Bradford test. A total of 7 various factors were designed using four different excipients including Glycerol, Sucrose, Triton x-100, and Tween-20, and three different buffers like Tris, Borate, and PBS. By obtaining suitable excipients and buffer i.e. glycerol and sucrose, pH ranging from 7 to 9 were evaluated. The pH 7.62, glycerol 15.35%, and sucrose 152.52 mM were determined as the most suitable for improving the thermal stability of recombinant BlaR-CTD.

In-silico engineering of RNA nanoplatforms to promote the diabetic wound healing.

One of the most notable required features of wound healing is the enhancement of angiogenesis, which aids in the acceleration of regeneration. Poor angiogenesis during diabetic wound healing is linked to a shortage of pro-angiogenic or an increase in anti-angiogenic factors. As a result, a potential treatment method is to increase angiogenesis promoters and decrease suppressors. Incorporating microRNAs (miRNAs) and small interfering RNAs (siRNAs), two forms of quite small RNA molecules, is one way to make use of RNA interference. Several different types of antagomirs and siRNAs are now in the works to counteract the negative effects of miRNAs. The purpose of this research is to locate novel antagonists for miRNAs and siRNAs that target multiple genes to promote angiogenesis and wound healing in diabetic ulcers.In this context, we used gene ontology analysis by exploring across several datasets. Following data analysis, it was processed using a systems biology approach. The feasibility of incorporating the proposed siRNAs and miRNA antagomirs into polymeric bioresponsive nanocarriers for wound delivery was further investigated by means of a molecular dynamics (MD) simulation study. Among the three nanocarriers tested (Poly (lactic-co-glycolic acid) (PLGA), Polyethylenimine (PEI), and Chitosan (CTS), MD simulations show that the integration of PLGA/hsa-mir-422a is the most stable (total energy = -1202.62 KJ/mol, Gyration radius = 2.154 nm, and solvent-accessible surface area = 408.416 nm2). With values of -25.437 KJ/mol, 0.047 nm for the Gyration radius, and 204.563 nm2 for the SASA, the integration of the second siRNA/ Chitosan took the last place. The results of the systems biology and MD simulations show that the suggested RNA may be delivered through bioresponsive nanocarriers to speed up wound healing by boosting angiogenesis.

Domino protocol for the synthesis of diversely functionalized derivatives of a novel fused pentacyclic antioxidant/anticancer fluorescent scaffold: Pyrazolo[5'',1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxaline.

Rising to the challenge of formidable multi-step reaction needed for the synthesis of polycyclic compounds, an efficient one-pot two-step procedure for the synthesis of densely functionalized novel pyrazolo[5″,1'':2',3']pyrimido[4',5':5,6] [1,4]thiazino[2,3-b]quinoxalines from synthetically accessible starting materials 6-bromo-7-chloro-3-cyano-2-(ethylthio)-5-methylpyrazolo[1,5-a]pyrimidine, 3-aminoquinoxaline-2-thiol and some readily accessible alkyl halides was established. The domino reaction pathway involves cyclocondensation/N-alkylation sequence in K2CO3/N,N-dimethyl formamide under heating condition. DPPH free radical scavenging activity of all synthesized pyrazolo[5″,1'':2',3']pyrimido[4',5':5,6][1,4]thiazino[2,3-b]quinoxalines was evaluated to determine their antioxidant potentials. IC50 values were recorded in the range of 29-71 µM. N-benzyl substituted derivative represented the most effective antioxidant activity as well as antiproliferative activity against MCF-7 cells. Moreover, fluorescence in solution for these compounds exhibited strong red emission in the visible region (λflu. = 536-558 nm) with good to excellent quantum yields (61-95%). Due to their interesting fluorescence properties, these novel pentacyclic fluorophores can be used as fluorescent markers and probes for studies in biochemistry and pharmacology.

Stimulating olfactory epithelium mitigates mechanical ventilation-induced hippocampal inflammation and apoptosis.

Mechanical ventilation (MV), as a life-saving procedure in critical patients, is a risk factor to develop of neurocognitive dysfunction and triggers of inflammation and apoptosis in the brain. Since diversion of breathing route to the tracheal tube diminishes brain activity entrained by physiological nasal breathing, we hypothesized that simulating nasal breathing using rhythmic air-puff (AP) into the nasal cavity of mechanically ventilated rats can reduce hippocampal inflammation and apoptosis in association with restoring respiration-coupled oscillations. We found that stimulating olfactory epithelium through applying rhythmic nasal AP, in association with reviving respiration-coupled brain rhythm, mitigates MV-induced hippocampal apoptosis and inflammation involving microglia and astrocytes. The current translational study opens a window for a novel therapeutic approach to reduce neurological complications induced by MV.

Molecular study of feline dermatophytosis and Toll-like receptor 2 and 4 gene expression in their lesions.

BACKGROUND: Pattern recognition receptors (PRRs) as the recognition of pathogenic fungal structures induce the secretion of cytokines by immune systems. Toll-like receptors (TLRs) 2 and 4 are the main PRRs that recognize fungal components. AIM: The present study aimed to assess the presence of dermatophyte species in symptomatic cats in a region of Iran and to investigate the expression of TLR-2 and 4 in cat lesions with dermatophytosis. METHODS: A total of 105 cats suspected of dermatophytosis with skin lesions were examined. Samples were analysed by direct microscopy using potassium hydroxide (20%) and culture on Mycobiotic agar. Dermatophytes strains were confirmed by the polymerase chain reaction (PCR) amplification and then sequencing of the Internal Transcribed Spacer rDNA region. Also, for pathology and real-time PCR studies, skin biopsies were taken by sterile single-use biopsy punch from active ringworm lesions. RESULTS: Dermatophytes were found in 41 felines. Based on the sequencing of all strains, Microsporum canis (80.48%, p < 0.05), Microsporum gypseum (17.07%) and Trichophyton mentagrophytes (2.43%) were the dermatophytes isolated from cultures. Cats under 1 year (78.04%) revealed a statistically significantly higher prevalence of infection (p < 0.05). Gene expression by real-time PCR revealed the increased TLR-2 and 4 mRNA levels in skin biopsies of cats with dermatophytosis. CONCLUSIONS: M. canis is the most prevalent dermatophyte species isolated from feline dermatophytosis lesions. Increased expression of TLR-2 and TLR-4 mRNAs in cat skin biopsies suggests that these receptors are involved in the immune response by recognizing dermatophytosis.

Corticosteroid treatment attenuates anxiety and mPFC-amygdala circuit dysfunction in allergic asthma.

AIMS: Allergic asthma is associated with anxiety-related behaviors, leading to poor quality of life. Previous studies mainly described the neuropathophysiology of asthma-induced anxiety. However, the effects of corticosteroids, the most common anti-inflammatory agents for asthma treatment, on the neurophysiological foundations of allergic asthma-induced anxiety are unexplored. MAIN METHODS: Here, we evaluated lung and brain inflammation as well as anxiety in an animal model of allergic asthma pretreated with inhaled fluticasone propionate. Furthermore, to define the neurophysiological bases of these conditions, we studied the medial prefrontal cortex (mPFC)-amygdala circuit, which is previously shown to accompany asthma-induced anxiety. KEY FINDINGS: Our data showed that allergen induces anxiety, mPFC and amygdala inflammation, as well as disruptions in the local and long-range oscillatory activities within the mPFC-amygdala circuit. Interestingly, we observed a roughly consistent trend of changes with inhaled fluticasone pretreatment. Namely, the asthma-induced behavioral, inflammatory, and neurophysiological changes were partly, but not totally, prevented by inhaled fluticasone pretreatment. SIGNIFICANCE: We suggest that early treatment of asthmatic patients with inhaled corticosteroids improves mPFC-amygdala circuit function by attenuating neuroinflammation leading to reduced anxiety. These findings could lead clinical guidelines of asthma to consider the neuropsychiatric disorders of patients in treatment recommendations.

A Cost-effectiveness Analysis of Adding Cetuximab to the First-line Treatment of Metastatic Colorectal Carcinoma in Iran; Considering Genetic Screening for Precision Medicine.

PURPOSE: This study aimed to evaluate the cost-effectiveness of cetuximab in different genetic populations of metastatic colorectal carcinoma patients, including KRAS and RAS wild types and mutants, when added to FOLFIRI treatment regimens for evidence-based disease management in Iran. METHOD: A Markov decision model was designed in TreeAge software with the three states of stable, progress, and death. Clinical outcomes were extracted from published clinical studies, and costs were extracted from the Iranian local data. The primary outcome was an incremental cost-effectiveness ratio (ICER) in the simulated population. RESULTS: The cost-utility model from the perspective of the health system indicated that the average direct medical costs of a patient that has not been genetically screened are $56,985.27 and $20,767.74 in FOLFIRI + cetuximab and FOLFIRI regimens, respectively. However, costs per patient in the KRAS wild-type population were $21,845.52 in FOLFIRI and $78,321.22 in FOLFIRI + cetuximab. In RAS wild-type patients, FOLFIRI and FOLFIRI + cetuximab costs per patient were $23,111.62 and $84,976.39, respectively. Incremental QALYs for the above scenarios were 0.069, 0.193, and 0.285, respectively. Therefore, the ICER of add-on cetuximab in Iran compared to the treatment alternatives in the scenarios with and without KRAS screening was $520,771.55/QALY, $292,768.16/QALY, and $217,460.51/QALY. CONCLUSION: Although genetic screening in precision medicine reduces costs per outcome, according to the willingness-to-pay threshold of $4349.50 in the Iranian health system, add-on cetuximab to the FOLFIRI regimen is not a cost-effective strategy even with genetic screening and a 20% price reduction.

A review on the role of PRNCR1 in human disorders with an especial focus on cancer.

Prostate Cancer Associated Non-Coding RNA 1 (PRNCR1) is a long non-coding RNA (lncRNA) which is transcribed from chromosome 8, plus strand. This lncRNA has been reported to be an oncogenic transcript participating in the pathogenesis of several kinds of cancers. Some single nucleotide polymorphisms within this lncRNA affect cancer risk. Moreover, few studies have revealed its possible roles in some non-neoplastic conditions, such as cisplatin-induced acute kidney injury, osteolysis after hip replacement, preeclampsia and pulmonary disorders. In the present narrative review, we explain diverse roles of PRNCR1 in human disorders.

Asthma induces psychiatric impairments in association with default mode and salience networks alteration: A resting-state EEG study.

Asthma is a chronic inflammatory disease associated with a high prevalence of psychiatric disorders. There are specific brain networks responsible for emotional processes, including two important networks associated with psychiatric problems: the default mode network (DMN), which is more active in the resting state, and the salience network (SN), which is structurally connected to DMN. Although previous studies suggested that neuro-phenotypes of asthma may be recognizable by the neural activity of brain circuits, an association between the brain's functional alterations and psychiatric impairments induced by asthma remains unknown. We aimed to assess DMN and SN activity and its association with psychiatric indices and clinical parameters in asthmatic patients. Electroencephalography was recorded during the resting state with an awake and eyes-open condition in thirty-eight sex and age-matched subjects (19 atopic asthma patients and 19 healthy participants). Power spectrum and functional connectivity were computed for DMN and SN. We examined psychiatric disorders (including depression, anxiety, and stress) and pulmonary function using the DASS questionnaire and spirometry test, respectively. The results showed that DASS scores were significantly higher in asthmatic patients compared to healthy subjects. Asthmatic patients also demonstrate a significant enhancement in power and functional connectivity in the two networks. Notably, these power enhancements of the networks were correlated with psychiatric problems scores, pulmonary function, asthma duration, and poor asthma control. These results introduce new evidence for the association between altered brain activity, the existence of psychiatric disorders, and asthma-related features, including pulmonary function. Also, we provide new insights into asthma-induced inflammatory response and the importance of developing novel interventions and therapeutic strategies for managing allergic inflammation patients who suffer from concurrent psychiatric disorders.

Nasal Air Puff Promotes Default Mode Network Activity in Mechanically Ventilated Comatose Patients: A Noninvasive Brain Stimulation Approach.

OBJECTIVES: Coma state and loss of consciousness are associated with impaired brain activity, particularly gamma oscillations, that integrate functional connectivity in neural networks, including the default mode network (DMN). Mechanical ventilation (MV) in comatose patients can aggravate brain activity, which has decreased in coma, presumably because of diminished nasal airflow. Nasal airflow, known to drive functional neural oscillations, synchronizing distant brain networks activity, is eliminated by tracheal intubation and MV. Hence, we proposed that rhythmic nasal air puffing in mechanically ventilated comatose patients may promote brain activity and improve network connectivity. MATERIALS AND METHODS: We recorded electroencephalography (EEG) from 15 comatose patients (seven women) admitted to the intensive care unit because of opium poisoning and assessed the activity, complexity, and connectivity of the DMN before and during the nasal air-puff stimulation. Nasal cavity air puffing was done through a nasal cannula controlled by an electrical valve (open duration of 630 ms) with a frequency of 0.2 Hz (ie, 12 puff/min). RESULTS: Our analyses demonstrated that nasal air puffing enhanced the power of gamma oscillations (30-100 Hz) in the DMN. In addition, we found that the coherence and synchrony between DMN regions were increased during nasal air puffing. Recurrence quantification and fractal dimension analyses revealed that EEG global complexity and irregularity, typically seen in wakefulness and conscious state, increased during rhythmic nasal air puffing. CONCLUSIONS: Rhythmic nasal air puffing, as a noninvasive brain stimulation method, opens a new window to modifying the brain connectivity integration in comatose patients. This approach may potentially influence comatose patients' outcomes by increasing brain reactivity and network connectivity.

Stress and burnout in health care workers during COVID-19 pandemic: validation of a questionnaire.

Aim: To validate a questionnaire to assess stress and burnout in healthcare workers during COVID-19 pandemic. Subjects and methods: In this study, content validity, Cronbach's alpha, and test-retest reliability method were utilized among 60 HCWs to evaluate the validity, internal consistency, and reliability of the questionnaire respectively. The final questionnaire was composed of four parts asking for the background information, questions about the stress caused by the COVID-19, the Depression, Anxiety and Stress Scale - 21 (DASS-21), and six questions from the Copenhagen Burnout Inventory (CBI). Results: The CVR of 46 questions was equal to 1, making them acceptably valid (CVR > 0.78), so that the items could be arranged into a final questionnaire. Moreover, all items could successfully attain CVI values above 0.79, confirming the content validity of the questionnaire. The Cronbach's alpha was between 0.80-0.95 for different sections of questionaire, confirming the stable reliability and high repeatability of the questionnaire. Conclusion: The results of this study showed that the DASS-21 offers adequate levels of validity and reliability for assessing the stress, anxiety, and depression among the HCWs engaged with the COVID-19 pandemic. Moreover, the six items adapted from the Copenhagen burnout inventory (CBI) were found to provide a good instrument for investigating the job burnout among the HCWs at Masih Daneshvari Hospital during the outbreak of the COVID-19 epidemic.

Evaluation of NUF2 and GMNN Expression in Prostate Cancer: Potential Biomarkers for Prostate Cancer Screening.

BACKGROUND: Prostate cancer (PC) is one of the most abundant cancers among men, and In Iran, has been responsible for 6% of all deaths from cancer in men. NUF2 and GMNN genes are considered as loci of susceptibility to tumorigenesis in humans. Alterations in expression of these genes have been reported in various malignancies. The aim of our study was to test whether different NUF2 and GMNN expression levels are associated with PC incidence and hence, might be considered as new molecular tools for PC screening. METHODS: Biopsy samples from 40 PC patients and 41 healthy Iranian men were used to determine the relative gene expression. After RNA extraction and cDNA synthesis, samples were analyzed using TaqMan Quantitative Real time PCR. Patients' background information, included smoking habits and family histories of PC, were recorded. Stages and grades of their PC were classified by the TNM tumor, node, metastasis (TMN) staging system based on standard guidelines. RESULTS: NUF2 expression did not significantly differ between the groups, while GMNN expression was significantly greater in the PC specimens than in the controls. CONCLUSION: Regarding the significant role of GMNN in various tumor phenotypes, and its importance in PC progression, the alteration in GMNN expression in PC samples vs. controls indicate that the genetic profiling of this cancer might be considered to personalize therapy for each patient in the future.

Deep brain stimulation for multiple sclerosis tremor: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aims to evaluate efficacy of deep brain stimulation (DBS) in treating MS-related tremor. METHODS: We systematically searched PubMed, Web of Science, Embase, Scopus, Google Scholar, and gray literature using a search strategy including the MeSH and text words as (((Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Stimulations) OR (Deep Brain Brain Stimulation) OR (Deep Electrical Stimulation of the Brain)) AND (Multiple Sclerosis OR Sclerosis, Multiple) OR Sclerosis, Disseminated) OR Disseminated Sclerosis) OR MS (Multiple Sclerosis)) OR Multiple Sclerosis, Acute Fulminating). RESULTS: The literature search revealed 1663 articles, 1027 of which remained after removing duplicates. Seventeen articles, published between 1999-2018, were included for the meta-analysis, including overall 168 patients. Follow-up time ranged between 6-62 months. The pooled frequency of tremor improvement among the enrolled patients was 73%, (95% CI:64-83%) (I2=84.1%, p<0.001). The pooled standardized mean difference (SMD) (after -before) was -2.9, (95% CI:-4.8, -0.98) (I2=89.8%, p<0.001). CONCLUSION: The results of this systematic review and meta-analysis demonstrate MS-related tremor improvement after DBS.

The olfactory bulb modulates entorhinal cortex oscillations during spatial working memory.

Cognitive functions such as working memory require integrated activity among different brain regions. Notably, entorhinal cortex (EC) activity is associated with the successful working memory task. Olfactory bulb (OB) oscillations are known as rhythms that modulate rhythmic activity in widespread brain regions during cognitive tasks. Since the OB is structurally connected to the EC, we hypothesized that OB could modulate EC activity during working memory performance. Herein, we explored OB-EC functional connectivity during spatial working memory performance by simultaneous recording local field potentials when rats performed a Y-maze task. Our results showed that the coherence of delta, theta, and gamma-band oscillations between OB and EC was increased during correct trials compared to wrong trials. Cross-frequency coupling analyses revealed that the modulatory effect of OBs low-frequency phase on EC gamma power and phase was enhanced when animals correctly performed working memory task. The influx of information from OB to EC was also increased at delta and gamma bands within correct trials. These findings indicated that the modulatory influence of OB rhythms on EC oscillations might be necessary for successful working memory performance.

A review on the role of chemokines in the pathogenesis of systemic lupus erythematosus.

Chemokines are a group of cytokines with low molecular weight that principally direct chemotaxis of target cells. They have prominent roles in the pathogenesis systemic lupus erythematosus (SLE) and related complications particularly lupus nephritis. These molecules not only induce autoimmune responses in the organs of patients, but also can amplify the induced inflammatory responses. Although chemokine family has at least 46 identified members, the role of a number of these molecules have been more clarified in SLE patients or animal models of this disorder. In the current paper, we review the role of CCL2, CCL3, CCL4, CCL11, CCL20, CXCL1, CXCL2, CXCL8, CXCL10, CXCL12 and CXCL13 in the pathogenesis of SLE.

Emerging role of lncRNAs in the regulation of Rho GTPase pathway.

The Ras homolog (Rho) family of small GTPases comprise several proteins with prominent roles in regulation of cell cycle transition, cell migration, and remodeling of actin cytoskeleton. Expression of these proteins is regulated by several factors among them are long non-coding RNAs (lncRNAs). The impact of lncRNAs on Rho GTPases signaling can be exerted through direct modulation of expression of these proteins or influencing expression of miRNAs that negatively regulate Rho GTPases. LINC00974/miR-122/RhoA, MALAT1/miR-429/RhoA, ZFAS1/miR-3924/RhoA/ROCK2, PCAT6/miR-326/RhoA/ROCK, SMILR/miR-141/RhoA/ROCK, DAPK1/miR-182/RhoA, GAS5/miR663a/RhoB, H19/miR-15b/CDC42/PAK1, TDRG1/miR-93/RhoC, TUG1/miR-498/CDC42, UCA1/miR-18a/Cdc42 and UCA1/miR-182/Cdc42 are examples of lncRNAs/miRNAs axes that regulate Rho GTPases. In the present manuscript, we describe the role of lncRNAs on Rho GTPases.

Allergic rhinitis impairs working memory in association with drop of hippocampal - Prefrontal coupling.

Allergic rhinitis (AR) is a chronic inflammatory disease frequently associated with a deficit in learning and memory. Working memory is an important system for decision making and guidance, which depends on interactions between the ventral hippocampus (vHipp) and the prelimbic prefrontal cortex (plPFC). It is still unclear whether AR influences the activity and coupling of these brain areas, which consequently may impair working memory. The current study aimed to examine alterations of the vHipp-plPFC circuit in a rat model of AR. Our results show decreased working memory performance in AR animals, accompanied by a reduction of theta and gamma oscillations in plPFC. Also, AR reduces coherence between vHipp and plPFC in both theta and gamma frequency bands. Cross-frequency coupling analyses confirmed a reduced interaction between hippocampal theta and plPFC gamma oscillations. Granger causality analysis revealed a reduction in the causal effects of vHipp activity on plPFC oscillations and vice versa. A significant correlation was found between working memory performance with disruption of functional connectivity in AR animals. In summary, our data show that in AR, there is a deficit of functional coupling between hippocampal and prefrontal network, and suggest that this mechanism might contribute to working memory impairment in individuals with AR.