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Abstract Background In mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations. Objective This review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD. Results It is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T‐reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T‐regs, a subset of T‐cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T‐reg function, facilitates T‐reg differentiation through microbiota‐mediated degradation and the kynurenine pathway. Conclusion Therefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten‐free diet.

Background: Preoperative anxiety is a widespread phenomenon in anesthesia, a challenging issue for the caring team in evaluating and managing patients’ anxiety. This study aimed to determine the operating room (OR) healthcare providers’ point of view on the patients’ anxiety under regional anesthesia. Methods: This cross-sectional study was conducted on 203 OR healthcare providers in the adult public educational hospitals of Golestan University of Medical Sciences, Gorgan, Iran, from April to November 2021. Eligible OR healthcare providers, including nurse anesthetists (104), surgical technologists (82), and anesthesiologists (17), were recruited through the census method. Data were collected using anesthesiologists’ perception of patients’ anxiety under a regional anesthesia questionnaire developed by Jlala (2010). The impact score was determined to ensure the face validity of the Iranian version of the questionnaire, and ten healthcare providers checked it qualitatively. The average score of the content validity index (CVI=0.978) and content validity ratio (CVR=0.978) were acceptable. The instrument’s internal consistency was evaluated using Cronbach’s alpha coefficient (α =0.675). Data were analyzed in SPSS software version 18 using Fisher’s Exact, Chi-Square, and Kruskal-Wallis tests. Results: There were no differences in most questionnaire items between healthcare providers’ views based on their professional roles (P

Background: Self-care is an important concept in controlling COVID-19 disease and a simple and effective way to maintain and improve health. This study aimed to examine the role of general health and health literacy in predicting the self-care behaviors of patients with COVID-19. Methods: This research was a cross-sectional study with a predictive correlational design. The sample consisted of 385 patients with mild to moderate COVID-19 infection referring to the COVID-19 diagnosis and treatment center in Shahid Beheshti Hospital in Kashan City, Iran, from June to September 2021. The subjects were under quarantine at home and were recruited by convenience sampling. The data were collected by the general health questionnaire (GHQ-28), the Iranian health literacy questionnaire (IHLQ), and a researcher-made questionnaire on self-care behaviors in patients with COVID-19 (SCB-COVID-19). The Pearson correlation coefficient, t-test, and logistic regression were used for data analysis in SPSS software, version 19. The significance level was set at P

Objective: Epigenetic and genetic changes have important roles in stem cell achievements. Accordingly, the aim of thisstudy is the evaluation of the epigenetic and genetic alterations of different culture systems, considering their efficacy inpropagating human spermatogonial stem cells isolated by magnetic-activated cell sorting (MACS).Materials and Methods: In this experimental study, obstructive azoospermia (OA) patient-derived spermatogonial cells were divided into two groups. The MACS enriched and non-enriched spermatogonial stem cells (SSCs) were cultured in the control and treated groups; co-culture of SSCs with Sertoli cells of men with OA, co-culture of SSCs with healthy Sertoli cells of fertile men, the culture of SSCs on PLA nanofiber and culture of testicular cell suspension. Gene-specific methylation by MSP, expression of pluripotency (NANOG, C-MYC and OCT-4), and germ cells specific genes (Integrin α6, Integrin β1, PLZF) evaluated. Cultured SSCs from the optimized group were transplanted into the recipient azoospermic mouse.Results: The use of MACS for the purification of human stem cells was effective at about 69% with the culture of the testicular suspension, being the best culture system. Upon purification, the germ-specific gene expression was significantly higher in testicular cell suspension and treated groups (P≤0.05). During the culture time, gene-specific methylation patterns of the examined genes did not show any changes. Our data from transplantation indicated the homing of the donor-derived cells and the presence of human functional sperm.Conclusion: Our in vivo and in vitro results confirmed that culture of testicular cell suspension and selection ofspermatogonial cells could be effective ways for purification and enrichment of the functional human spermatogonial cells. The epigenetic patterns showed that the specific methylation of the evaluated genes at this stage remained constant with no alteration throughout the entire culture systems over time.

Streptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3−/− mice presented more severe invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin-deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 gene polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid-phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.

BackgroundEarly prognostic stratification of patients with sepsis is a difficult clinical challenge. Aim of this study was to evaluate novel molecules in association with clinical parameters as predictors of 90-days mortality in patients admitted with sepsis at Humanitas Research Hospital.MethodsPlasma samples were collected from 178 patients, diagnosed based on Sepsis-3 criteria, at admission to the Emergency Department and after 5 days of hospitalization. Levels of pentraxin 3 (PTX3), soluble IL-1 type 2 receptor (sIL-1R2), and of a panel of pro- and anti-inflammatory cytokines were measured by ELISA. Cox proportional-hazard models were used to evaluate predictors of 90-days mortality.ResultsCirculating levels of PTX3, sIL-1R2, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-1ra, TNF-α increased significantly in sepsis patients on admission, with the highest levels measured in shock patients, and correlated with SOFA score (PTX3: r=0.44, p

Background: The use of medicinal plants has been one of the most common treatments since ancient times. Various plants are used in traditional and modern medicine, due to their antioxidant, antimicrobial and anticancer properties, and other biological potentials. Objective: In this study, the aerial parts of four species of Salvia including two populations of S. reuteriana Boiss., two populations of S. limbata C.A.Mey. and one population of each S. syriaca L. and S. ceratophylla L. species from Kashan region have been investigated. Methods: The antioxidative activity of the methanol extracts of plant samples were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The total phenol and flavonoid contents were determined via the Folin-Ciocalteu and aluminum chloride methods, respectively. The cytotoxic effects of samples on HeLa cells were determined through MTT assay. Results: Based on the results of DPPH assay, IC50 levels of methanolic extracts were in the range of 39.08 ± 0.15 to 163.77 ± 0.63 μg/ml, and total phenol contents were in the range of42.7 ± 3.09 to 105.8 ± 1.15 μg/mg. In addition, the flavonoid contents ranged from 30.07 ± 2.52 to 82.46 ± 2.2 μg/mg. There was a direct relationship between antioxidant activity and phenol compound contents. According to our study, the methanolic extracts of Salvia species showed toxicity effects on HeLa cells. Conclusion: The extracts of two populations of S. reuteriana were associated with the highest cytotoxicity, compared to other species of Salvia. Furthermore, all examined extracts exhibited weak to moderate antioxidant activities. The S. ceratophylla extract was associated with the highest antioxidant activity.

In the present study, calcined melamine (CM) and magnetite nanoparticles (MNPs) were encapsulated in a calcium alginate (CA) matrix to effectively activate peroxymonosulfate (PMS) and generate free radical species for the degradation of ibuprofen (IBP) drug. According to the Langmuir isotherm model, the adsorption capacities of the as-prepared microcapsules and their components were insignificant. The CM/MNPs/CA/PMS process caused the maximum degradation of IBP (62.4%) in 30 min, with a synergy factor of 5.24. Increasing the PMS concentration from 1 to 2 mM improved the degradation efficiency from 62.4 to 68.0%, respectively, while an increase to 3 mM caused a negligible effect on the reactor effectiveness. The process performance was enhanced by ultrasound (77.6% in 30 min), UV irradiation (91.6% in 30 min), and electrochemical process (100% in 20 min). The roles of O•H and SO4•− in the decomposition of IBP by the CM/MNPs/CA/PMS process were 28.0 and 25.4%, respectively. No more than 8% reduction in the degradation efficiency of IBP was observed after four experimental runs, accompanied by negligible leachate of microcapsule components. The bio-assessment results showed a notable reduction in the bio-toxicity during the treatment process based on the specific oxygen uptake rate (SOUR).

Klebsiella pneumoniae is a common pathogen in human sepsis. The emergence of multidrug-resistant K. pneumoniae strains represents a major clinical challenge in nosocomial and community acquired infections. The long pentraxin PTX3, a key component of humoral innate immunity, is involved in resistance to selected pathogens by promoting opsonophagocytosis. We investigated the relevance of PTX3 in innate immunity against K. pneumoniae infections using Ptx3-/- mice and mouse models of severe K. pneumoniae infections. Local and systemic PTX3 expression was induced following K. pneumoniae pulmonary infection, in association with the up-regulation of TNF-α and IL-1β. PTX3 deficiency in mice was associated with higher bacterial burden and mortality, release of pro-inflammatory cytokines as well as IL-10 in the lung and systemically. The analysis of the mechanisms responsible of PTX3-dependent control of K. pneumoniae infection revealed that PTX3 did not interact with K. pneumoniae, or promote opsonophagocytosis. The comparison of susceptibility of wild-type, Ptx3-/-, C3-/- and Ptx3-/-/C3-/- mice to the infection showed that PTX3 acted in a complement-independent manner. Lung histopathological analysis showed more severe lesions in Ptx3-/- mice with fibrinosuppurative, necrotizing and haemorrhagic bronchopneumonia, associated with increased fibrin deposition in the lung and circulating fibrinogen consumption. These findings indicate that PTX3 contributes to the control of K. pneumoniae infection by modulating inflammatory responses and tissue damage. Thus, this study emphasizes the relevance of the role of PTX3 as regulator of inflammation and orchestrator of tissue repair in innate responses to infections.

Eco-criticism, a branch of modern literary criticism, nowadays everywhere in the world, from West to East, and in the form of a cultural and moral flow, through literature announces its message as an alarm, a concern for the environment. Among the writers of contemporary Italian Literature, Italo Calvino is the first ecologic story-teller, who beyond his short stories reveals the emergency situation of urban ecosystem. The first character of his stories, condemned to live in industrial cities, is looking at nature disappearing in his smoky hands. The present article, through the content analysis of some of these works, points out to the important role of Literature which serves in the cultivation for preserving the environment and awakening the minds of humen against a serious danger that threatens their lives.

The first line of defense in innate immunity is provided by cellular and humoral mediators. Pentraxins are a superfamily of phylogenetically conserved humoral mediators of innate immunity. PTX3, the first long pentraxin identified, is a soluble pattern recognition molecule rapidly produced by several cell types in response to primary pro-inflammatory signals and microbial recognition. PTX3 acts as an important mediator of innate immunity against pathogens of fungal, bacterial and viral origin, and as a regulator of inflammation, by modulating complement activation and cell extravasation, and facilitating pathogen recognition by myeloid cells. In sepsis, PTX3 plasma levels are associated with severity of the condition, patient survival, and response to therapy. In combination with other established biomarkers, PTX3 could improve stratification of sepsis patients and thus, complement the system of classification and monitoring of this disease.

Intracellular delivery of DNA is considered a challenge in biological research and treatment of diseases. The previously reported transfection rate by commercially available transfection reagents in cancer cell lines, such as the mouse lung tumor cell line (TC-1), is very low. The purpose of this study is to introduce and optimize an efficient gene transfection method by mechanical approaches. The combinatory transfection effect of mechanical treatments and conventional chemical carriers is also investigated on a formerly reported hard-to-transfect cell line (TC-1). To study the effect of mechanical loadings on transfection rate, TC-1 tumor cells are subjected to uniaxial cyclic stretch, equiaxial cyclic stretch, and shear stress. The TurboFect transfection reagent is exerted for chemical transfection purposes. The pEGFP-N1 vector encoding the green fluorescent protein (GFP) expression is utilized to determine gene delivery into the cells. The results show a significant DNA delivery rate (by ~30%) in mechanically transfected cells compared to the samples that were transfected with chemical carriers. Moreover, the simultaneous treatment of TC-1 tumor cells with chemical carriers and mechanical loadings significantly increases the gene transfection rate up to ~ 63% after 24 h post-transfection. Our results suggest that the simultaneous use of mechanical loading and chemical reagent can be a promising approach in delivering cargoes into cells with low transfection potentials and lead to efficient cancer treatments.

Background. Migraine-specific quality of life (MSQ) is a valid and reliable questionnaire. Linguistic validation of Persian MSQ questionnaire, analysis of psychometric properties between chronic and episodic migraine patients, and capability of MSQ to differentiate between chronic and episodic migraines were the aims of this study. Method. Participants were selected from four different neurology clinics that were diagnosed as chronic or episodic migraine patients. Baseline data included information from MSQ v. 2.1, MIGSEV, SF-36, and symptoms questionnaire. At the third week from the baseline, participants filled out MSQ and MIGSEV. Internal consistency (Cronbach alpha) and test-retest reproducibility (intraclass correlation coefficients) were used to assess reliability. Convergent and discriminant validities were also assessed. Results. A total of 106 participants were enrolled. Internal consistencies of MSQ among all patients, chronic and episodic migraines, were 0.92, 0.91, and 0.92, respectively. Test-retest correlation of MSQ dimensions between visits 1 and 2 varied from 0.41 to 0.50. Convergent, item discriminant, and discriminant validities were approved. In all visits MSQ scores were lower in chronic migraine than episodic migraine; however, the difference was not statistically significant. Conclusion. Persian translation of MSQ is consistent with original version of MSQ in terms of psychometric properties in both chronic and episodic migraine patients.

There is a growing interest in the early prediction of outcomes in ongoing business processes. Predictive process monitoring distills knowledge from the sequence of event data generated and stored during the execution of processes and trains models on this knowledge to predict outcomes of ongoing processes. However, most state-of-the-art methods require the training of complex and inefficient machine learning models and hyper-parameter optimization as well as numerous input data to achieve high performance. In this paper, we present a novel approach based on Hyperdimensional Computing (HDC) for predicting the outcome of ongoing processes before their completion. We highlight its simplicity, efficiency, and high performance while utilizing only a subset of the input data, which helps in achieving a lower memory demand and faster and more effective corrective measures. We evaluate our proposed method on four publicly available datasets with a total of 12 binary prediction tasks. Our proposed method achieves an average 6% higher area under the ROC curve (AUC) and up to a 14% higher F1-score, while yielding a 20× earlier prediction than state-of-the-art conventional machine learning- and neural network-based models.

Objectives: We will try to present cases of coinfection with COVID‑19 and mucormycosis in Kashan to increase the awareness of health‑care providers and reduce the number of forgotten and neglected cases.Methods: This is a descriptive cross‑sectional study that patients infected with COVID‑19 become vulnerable to a variety of opportunistic diseases. There are several studies of COVID‑19 and mucormycosis, but an effort has been made to provide a collection of cases in Kashan (the center of Iran) to reduce morbidity and mortality by increasing the awareness of health‑care providers.Results: A total of 31 patients with mucormycosis following COVID‑19 including 18 males and 13 females were included in the study. All reverse transcriptase‑polymerase chain reaction patients were positive for severe acute respiratory syndrome‑coronavirus‑2. Twenty had a history of diabetes, eight had a history of hypertension, and three had no record of any underlying disease. The maxillary sinuses were the most common site of involvement. The maximum length of hospital stay was 52 dayss.Conclusion: Patients with COVID‑19 vulnerable to comorbidities, any facial involvement, or severe glucocorticoid and antibiotic treatment should be closely examined and monitored at the first encounter and during hospitalization for any signs of mucormycosis and start standard care and antifungal treatment as soon as possible.

Traditional systems for indoor pressure sensing and human activity recognition (HAR) rely on costly, high-resolution mats and computationally intensive neural network-based (NN-based) models that are prone to noise. In contrast, we design a cost-effective and noise-resilient pressure mat system for HAR, leveraging Velostat for intelligent pressure sensing and a novel hyperdimensional computing (HDC) classifier that is lightweight and highly noise resilient. To measure the performance of our system, we collected two datasets, capturing the static and continuous nature of human movements. Our HDC-based classification algorithm shows an accuracy of 93.19%, improving the accuracy by 9.47% over state-of-the-art CNNs, along with an 85% reduction in energy consumption. We propose a new HDC noise-resilient algorithm and analyze the performance of our proposed method in the presence of three different kinds of noise, including memory and communication, input, and sensor noise. Our system is more resilient across all three noise types. Specifically, in the presence of Gaussian noise, we achieve an accuracy of 92.15% (97.51% for static data), representing a 13.19% (8.77%) improvement compared to state-of-the-art CNNs.

Background: Anopheles stephensi is a sub-tropical species and has been considered as one of the most important vector of human malaria throughout the Middle East and South Asian region including the malarious areas of southern Iran. Current reports confirmed An. stephensi resistance to temephos in Oman and India. However, there is no comprehensive research on mechanisms of temephos resistance in An. stephensi in the literature. This study was designed in order to clarify the enzymatic and molecular mechanisms of temephos resistance in this species. Methods: Profile activities of α- and ß-esterases, mixed function oxidase (MFO), glutathione-S-transferase (GST), insensitive acetylcholinesterase, and para-nitrophenyl acetate (PNPA)-esterase enzymes were tested for An. stephensi strain with resistance ratio of 15.82 to temephos in comparison with susceptible strain. Results: Results showed that the mean activity of α-EST, GST and AChE enzymes were classified as altered indicating metabolic mechanisms have considerable role in resistance of An. stephensi to temephos. Molecular study using PCR-RFLP method to trace the G119S mutation in ACE-1 gene showed lack of the mutation responsible for organophosphate insecticide resistance in the temephos-selected strain of An. stephensi. Conclusion: This study showed that the altered enzymes but not targets site insensitivity of ACE-1 are responsible for temephos resistance in An. stephensi in south of Iran.