Evaluation of the effectiveness of Tadalafil on improving pulmonary function and asthma severity in severe asthmatic patients: a randomized controlled trial study

Phosphodiesterase inhibitors elevate the levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, which have been associated with various anti-inflammatory effects that can help alleviate asthma symptoms. This study aims to assess the impact of Tadalafil, a selective phosphodiesterase inhibitor, on pulmonary function in patients with asthma. This study was a randomized, double-blind clinical trial conducted in 2021 at Imam Khomeini Hospital in Ahvaz, Iran. The study enrolled 44 patients with severe asthma, who were divided equally into a Tadalafil group and a placebo group. The Tadalafil group received 20 mg/day of Tadalafil, while the placebo group received a placebo at the same dose. The patients' spirometry tests, asthma quality of life questionnaire, 6-minute walk distance, and quality of life were measured at the beginning of the study and one month later. The study results indicated that there was no statistically significant difference between the Tadalafil group and the placebo group in terms of pulmonary parameters (p>0.05). Furthermore, the scores for patients' quality of life (p=0.167) and the 6-minute walk test (p=0.148) at the end of the study did not show any statistically significant improvement compared to the placebo group. Results showed that the use of Tadalafil (20 mg) once daily for one month in patients with severe asthma did not affect clinical and laboratory outcomes.

Epithelial cells/progenitor cells in developing human lower respiratory tract: Characterization and transplantation to rat model of pulmonary injury.

Introduction: For cell-based therapies of lung injury, several cell sources have been extensively studied. However, the potential of human fetal respiratory cells has not been systematically explored for this purpose. Here, we hypothesize that these cells could be one of the top sources and hence, we extensively updated the definition of their phenotype. Methods: Human fetal lower respiratory tissues from pseudoglandular and canalicular stages and their isolated epithelial cells were evaluated by immunostaining, electron microscopy, flow cytometry, organoid assay, and gene expression studies. The regenerative potential of the isolated cells has been evaluated in a rat model of bleomycin-induced pulmonary injury by tracheal instillation on days 0 and 14 after injury and harvest of the lungs on day 28. Results: We determined the relative and temporal, and spatial pattern of expression of markers of basal (KRT5, KRT14, TRP63), non-basal (AQP3 and pro-SFTPC), and early progenitor (NKX2.1, SOX2, SOX9) cells. Also, we showed the potential of respiratory-derived cells to contribute to in vitro formation of alveolar and airway-like structures in organoids. Cell therapy decreased fibrosis formation in rat lungs and improved the alveolar structures. It also upregulated the expression of IL-10 (up to 17.22 folds) and surfactant protein C (up to 2.71 folds) and downregulated the expression of TGF-ß (up to 5.89 folds) and AQP5 (up to 3.28 folds). Conclusion: We provide substantial evidence that human fetal respiratory tract cells can improve the regenerative process after lung injury. Also, our extensive characterization provides an updated phenotypic profile of these cells.

Oral Health Status and Salivary Properties among Children before and after Tonsillectomy.

Objectives: Enlarged adenoids can lead to obstruction of the nasopharyngeal airway and subsequent oral respiration. Oral breathing can cause dry mouth, dehydration in gingival tissue, and resistance to plaque accumulation. This study aimed to evaluate the impact of tonsillectomy on oral health status, salivary pH and flow rate, and common complications caused by tonsillar hypertrophy in children. Materials and Methods: An analytical before-and-after study was conducted on 60 children aged 5-12 years who required tonsillectomy. We gathered data through a questionnaire and collected unstimulated saliva using the spitting method for five minutes. Salivary pH was measured by a pH meter and its volume was determined with a calibrated test tube. The plaque index, bleeding index and modified gingival index were determined using a disclosing tablet, Williams' probe and observational examination, respectively. All measurements were repeated one month after tonsillectomy. Paired t-test was used for data analysis. Results: We found a significant increase in mean pH and salivary flow rate after tonsillectomy and observed a decrease in oral health indices among the children one month after surgery. Over half of the children who reported complications such as dry mouth, itchy nose and throat, snoring, night sweats, and sleep disturbances experienced complete recovery after tonsillectomy. Conclusion: Based on the results obtained in the present study, children with enlarged adenoids showed significant improvements in salivary pH, salivary flow rate, and oral health indices, one month after tonsillectomy.

Non-Pharmacologic Interventions in COVID-19 Pandemic Management; a Systematic Review.

Introduction: Different countries throughout the world have adopted non-pharmacologic interventions to reduce and control SARS - CoV-2. In this systematic approach, the impact of non-pharmacologic interventions in management of COVID-19 pandemic was assessed. Methods: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, systematic search was carried out on the basis of a search strategy on PubMed, Web of Science, Scopus, and WHO databases on COVID-19. The impact of travel ban, personal protective equipment, distancing, contact tracing, school closure, and social distancing and the combined effect of interventions on COVID-19 were assessed. Results: Of the 14,857 articles found, 44 were relevant. Studies in different countries have shown that various non-pharmacological interventions have been used during the COVID-19 pandemic. The travel ban, either locally or internationally in most of the countries, movement restriction, social distancing, lockdown, Personal Protective Equipment (PPE), quarantine, school closure, work place closure, and contact tracing had a significant impact on the reduction of mortality or morbidity of COVID-19. Conclusion: Evidence shows that the implementation of non-pharmacologic interventions (NPIs), for this study suggests that the effectiveness of any NPI alone is probably limited, thus, a combination of various actions, for example, social distancing, isolation, and quarantine, distancing in the workplace and use of personal protective equipment, is more effective in reducing COVID-19.

Detection of different variants of SARS-CoV-2 RNA (genome) on inanimate surfaces in high-touch public environmental surfaces.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease started in late 2019 and still continues as a global pandemic, spreading among people around the world. There is limited knowledge about the role of contaminated environmental surfaces, especially high-touch public surfaces, in the transmission of the disease. The objective of the present investigation was detection of different variants (Delta, UK, and Omicron) of SARS-CoV-2 RNA (genome) on inanimate surfaces in high-touch public environmental surfaces in different seasons. Automated teller machines of banks (ATM), point-of-sale (POS) machine, gas station pump nozzles, and escalator handrails of malls were selected as high-touch environmental surfaces in public places. Overall, 75 samples were collected from these places and examined for the presence of SARS-CoV-2 RNA (genome), and 21 samples (28%) were positive. Although the role of fomite transmission of COVID-19 is understood, more studies should be conducted to determine the virus survival rate as well as the required efforts to prevent the spread of SARS-CoV-2 such as frequent cleaning and the use of efficient disinfectants on environmental surfaces, especially high-touch public places. In conclusion, the results address the importance of touching contaminated inanimate objects as well as transmission through environmental surfaces, and they could be used to establish an effective protocol to prevent indirect environmental transmission of SARS-CoV-2, slow down the spread of the virus, and reduce the risk of infection.

Finite element analysis of biomechanical interactions of a subcutaneous suspension suture and human face soft-tissue: a cadaver study.

In order to study the local interactions between facial soft-tissues and a Silhouette Soft® suspension suture, a CE marked medical device designed for the repositioning of soft tissues in the face and the neck, Finite element simulations were run, in which a model of the suture was embedded in a three-layer Finite Element structure that accounts for the local mechanical organization of human facial soft tissues. A 2D axisymmetric model of the local interactions was designed in ANSYS, in which the geometry of the tissue, the boundary conditions and the applied loadings were considered to locally mimic those of human face soft tissue constrained by the suture in facial tissue repositioning. The Silhouette Soft suture is composed of a knotted thread and sliding cones that are anchored in the tissue. Hence, simulating these interactions requires special attention for an accurate modelling of contact mechanics. As tissue is modelled as a hyper-elastic material, the displacement of the facial soft tissue changes in a nonlinear way with the intensity of stress induced by the suture and the number of the cones. Our simulations show that for a 4-cone suture a displacement of 4.35 mm for a 2.0 N external loading and of 7.6 mm for 4.0 N. Increasing the number of cones led to the decrease in the equivalent local strain (around 20%) and stress (around 60%) applied to the tissue. The simulated displacements are in general agreement with experimental observations.

Mutational analysis of mechanosensitive ion channels in the carnivorous Venus flytrap plant.

How the Venus flytrap (Dionaea muscipula) evolved the remarkable ability to sense, capture, and digest animal prey for nutrients has long puzzled the scientific community.1 Recent genome and transcriptome sequencing studies have provided clues to the genes thought to play a role in these tasks.2,3,4,5 However, proving a causal link between these and any aspect of the plant's hunting behavior has been challenging due to the genetic intractability of this non-model organism. Here, we use CRISPR-Cas9 methods to generate targeted modifications in the Venus flytrap genome. The plant detects prey using touch-sensitive trigger hairs located on its bilobed leaves.6 Upon bending, these hairs convert mechanical touch signals into changes in the membrane potential of sensory cells, leading to rapid closure of the leaf lobes to ensnare the animal.7 Here, we generate mutations in trigger-hair-expressed MscS-like (MSL)-family mechanosensitive ion channel genes FLYCATCHER1 (FLYC1) and FLYCATCHER2 (FLYC2)5 and find that double-mutant plants have a reduced leaf-closing response to mechanical ultrasound stimulation. While we cannot exclude off-target effects of the CRISPR-Cas9 system, our genetic analysis is consistent with these and other functionally redundant mechanosensitive ion channels acting together to generate the sensory system necessary for prey detection.

Comparable Outcomes of Pre- Versus Post-Tyrosine Kinase Inhibitor Era Treatment in Chronic Myeloid Leukemia: A Retrospective Cohort Study With Long-term Follow-up.

Imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was introduced after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia (CML). However, the long-term effects of allo-HSCT in chronic phase CML patients are mostly unknown. We retrospectively analyzed the outcomes of 204 patients with sibling donors who received peripheral stem cells and underwent allo-HSCT of chronic phase I (CP1) in the pre- and post-TKI era at Shariati Hospital in Tehran, Iran, from 1998 to 2017 and followed up till the end of 2021. The median follow-up time for all patients was 8.7 (SD = 0.54) years. Fifteen-year overall survival (OS), disease-free survival (DFS), graft-versus-host disease-free relapse-free survival (GRFS), relapse, and non-relapse mortality (NRM) incidence were 65.70%, 57.83%, 17.56%, 13.17%, and 28.98%, respectively. Using multivariable analyses, the only risk factor increasing the hazard of death was the time between diagnosis to allo-HSCT greater than 1 year compared to this time less than 1 year by 74% [hazard ratio (HR) = 1.74, P = 0.039]. Also, age is a significant risk factor for DFS (HR = 1.03, P = 0.031). Our findings suggested that allo-HSCT is still an important treatment option for CP1 patients, especially those resistant to TKI treatment. TKI consumption can have a desirable effect on NRM after allo-HSCT for CP1 CML.

Bcl-2 expression in cell lines breast cancer and death program.

Breast cancer is a hormone-dependence and heterogenic disease. Drug resistance is the main reason for the failure of breast cancer treatment. Combinatory medications are methods for treatment but they are not sufficient in action. However, new approaches like molecular therapy reveal a new insight into cancer treatment. Studies show that Bcl-2 gene family inhibitors and ER blockers cause the improvement of recovery. Interfering molecules such as antisense ones can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Our team designed a new Antisense Oligonucleotide (ASO) based on Antisense oligo G3139. MCF-7 and MDA-MB-231 cell lines were used to evaluate cellular proliferation. Liposomes and cationic nano-complex (Niosome) are used to increase the cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO. The results indicated significant down-regulation of the Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all cell groups. The newly designed ASO reduced the expression of the Bcl-2 gene. It also had a synergistic effect with the Tamoxifen. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 in the cancer cells.

Variation in Platelet Activation State in Pre-Donation Whole Blood: Effect of Time of Day and ABO Blood Group.

Background: Whilst there has been investigation into the effect of time of the day on platelet activation and function in healthy individuals, there is a lack of studies in the literature to examine this relationship among platelet donors. Methods: We assessed the extent of platelet activation by percentage of platelets with surface-expressed P-selectin and flow cytometry in samples of whole blood from a group of qualified platelet donors (n = 84). Results: The mean (SD) percentage of activated platelets in the pre-donation blood samples was 1.85 ± 1.57% (range 0.2-7.5%). In univariate analyses, the percentage of activated platelets was significantly and inversely correlated with the collection time (ie, the time of day blood samples were collected) (r = -0.35, p = 0.001) and positively correlated to mean platelet volume (MPV) (r = 0.29, p = 0.008). A weaker positive correlation was also observed with ABO blood group (r = 0.228, p = 0.036). Analysis of the collection time as a categorical variable showed a greater degree of activated platelets in samples collected between 8:00 h and 10:00 h than in samples collected during the hours of >10:00 h ≤14:00 h (2.5 ± 1.8 versus 1.1 ± 0.74, p < 0.001). In the adjusted linear regression model, collection time was a significant independent predictor of platelet activation state in whole blood (ß = -0.26; p < 0.001), as did ABO blood group (ß = 0.55; p = 0.019). Conclusion: Our results show that collection time is the most important predictor of platelet activation state in pre-donation whole blood among platelet donors. This work may have implications for optimizing the timing of platelet donation.

Effects of supplementation of vitamins D, C and E on Idiopathic Pulmonary Fibrosis (IPF): A clinical trial.

BACKGROUND & AIMS: Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a growing prevalence. We aimed to evaluate the effects of co-supplementation with vitamins C, E, and D on respiratory, inflammatory, and oxidative stress outcomes in IPF patients. METHODS: Thirty-three patients participated in this quasi-experimental study and were supplemented with vitamins E, C, and D with 200 IU/daily, 250 mg/every other day and 50000 IU/Weekly, respectively for 12 weeks. Anthropometric indices, dietary recall, physical activity, Saint George questionnaire were assessed along with the biochemical measures of inflammation and oxidative stress, and respiratory parameters. Data were analyzed by SPSS version 21, and P-value ≤ 0.05 was considered significant. RESULTS: Results of spirometry and plethysmography tests showed a significant increase in FEV1 (P-value = 0.016), IRV (P-value = 0.001), RV (P-value = 0.002) and TLC (P-value = 0.003). But no significant change was observed in FVC, VC, FEV1/FVC, and ERV. We also found that ESR, hs-CRP, TGFß, and PrC remarkably reduced after the supplementation (P-value ≤ 0.05), while the GPx level remained unchanged. CONCLUSIONS: It is concluded that three months of supplementation with a combination of D, C, and E vitamins in IPF patients may positively affect the respiratory function and alleviate the inflammation and oxidative stress.

Radiation-free reduced-intensity hematopoietic stem cell transplantation with in vivo T-cell depletion from matched related and unrelated donors for Fanconi anemia: prognostic factor analysis.

Fanconi anemia (FA) is a rare and complex genetic disorder, clinically characterized by bone marrow failure, congenital defects, and cancer predisposition. Hematopoietic stem cell transplantation (HSCT) represents the only therapeutic option to restore normal hematopoiesis after the occurrence of marrow failure or clonal hematopoietic abnormality. However, radiation exposure during transplant may increase the risk of later malignancies. In this retrospective study, we analyzed the results of HSCT with a radiation-free, busulfan-based conditioning regimen in FA patients. A total of 122 patients (median age: 8 years, range: 2-18 years) with FA who underwent HSCT between January 2008 and January 2020 were enrolled in this study and followed up to the end of 2020. The preparative regimen included busulfan (0.2 mg/kg/day, days -9 to -6), cyclophosphamide (15 mg/kg/day, days -5 to -2), and in vivo T-cell depletion with rabbit anti-thymocyte globulin. All patients received graft-versus-host disease prophylaxis with cyclosporine combined with methotrexate. We used the Kaplan-Meier method, log-rank test, and Cox proportional hazards models to analyze patient survival. Peripheral blood, bone marrow and cord blood hematopoietic stem cells were used in 84 (68.9%), 31 (25.4%) and 7 (5.7%) patients, respectively. Donors were matched siblings in 48 (39.3%), matched other relatives in 56 (45.9%), and matched unrelated persons in 18 (14.8%) patients. With a median follow-up time of 24.25 months, graft rejection occurred in only one patient. The 1- and 5-year overall survival rates were 84.14% (95% confidence interval: 76.02-89.70) and 82.16% (95% confidence interval: 73.01-88.45), respectively. Of the patient characteristics documented before transplant, the presence of cardiopulmonary, genitourinary tract, central nervous system, and limb malformations significantly affected survival rates. Our results indicate excellent outcomes in patients with FA undergoing HSCT with a radiation-free, busulfan-based conditioning regimen. It would be desirable to aim at optimizing the outcome of HSCT in FA patients in future studies.

Diagnostic sensitivity of impulse oscillometry in early detection of patients exposed to risk factors chronic obstructive pulmonary diseases.

Background: Impulse oscillometry (IOS) is a method that does not depend on the cooperation of the patient and can detect small airway diseases with higher sensitivity than spirometry. However, the clinical application value of IOS in the screening of patients exposed to risk factors COPD and early diagnosis remains unclear. The aim of this study is to evaluate diagnostic sensitivity of IOS in the early detection of patients exposed to risk factors COPD. Methods: A prospective cross-sectional study was conducted in Rasoul Akram Hospital, Tehran, Iran, from 2013 to 2015. 28 patients with COPD risk factors and normal spirometry participated in the study. The IOS was performed. We obtained the respiratory resistance and impedance of 5 Hz (R5) and 20 Hz (R20) and 5 Hz (Z5), respectively. The data were analyzed using SPSS version 17 using Chi-square and two independent sample t-test. Spearman correlation test was used to measure the correlation of oscillometry parameters in the diagnosis of COPD. P-value <0.05 was considered significantfor all statistical analyses. Results: The mean patient age was 55.50±11.27 years. In this study, the sensitivity of Z5, R5, and R20 was respectively 28.5%, 25%, and 31.5%. All oscillometry parameters were significantly correlated with each other but none of the oscillometry parameters showed significant correlations with FEV1/FVC (rZ5=0.018, rR5=0.082, rR20=0.041 and PZ5=0.932, PR5=0.711, P R20=0.850). According to the results, only 9 patients (32.5%) with normal values of FEV1/FVC had abnormal values of oscillometry. Conclusion: IOS has a low sensitivity and cannot be used in the screening of early-stage chronic obstructive pulmonary disease.

Celiac disease in patients with systemic lupus erythematosus.

OBJECTIVES: Celiac disease (CD) is one of the most common chronic diseases. Celiac disease has been associated with several autoimmune disorders, but the association with systemic lupus erythematosus (SLE) as a systemic autoimmune disease is still controversial. In this study, we aimed to determine the prevalence of biopsy-proven CD in patients with SLE, and to determine the clinical symptoms and laboratory data in these patients. MATERIAL AND METHODS: In a cross-sectional study, SLE patients at a referral clinic were evaluated for gastrointestinal symptoms between March and December 2016. Patients were evaluated by a gastroenterologist, and upper gastrointestinal endoscopy with intestinal biopsy was performed if deemed necessary. The clinical symptoms, laboratory data, and endoscopy results were recorded and compared between groups. RESULTS: In total, 130 patients were evaluated in this study. Gastrointestinal symptoms were present in 40% of the patients. Endoscopy was performed in all SLE patients with gastrointestinal symptoms. Four patients (3%) were diagnosed as having CD based on biopsy results and response to a gluten-free diet. Anti-endomysium antibody (AEA) was found to be 100% sensitive and 99.2% specific for the diagnosis of CD in SLE patients, and anti-gliadin antibody (AGA) had a 50% sensitivity and 98% specificity. Patients with comorbid CD and SLE were significantly more likely to have diarrhea, abdominal pain, nausea/vomiting, recurrent oral aphthosis, and anemia. CONCLUSIONS: The results of this study suggest that a significant association is present between CD and SLE. We found a prevalence of 3% for biopsy-proven CD in patients with SLE, which is five times the prevalence of CD in the general population.

Health Behavior and Lifestyle Trends among Platelet Donors: Results from a Questionnaire-Based Survey in Norway.

BACKGROUND: Blood donors are on average healthier than the general population, a phenomenon known as the "healthy donor effect." Earlier studies have also pointed to healthier behaviors among whole blood donors than the general population. This study is aimed at assessing the prevalence of four healthy behaviors (sufficient physical activity, avoiding cigarette smoking, low to moderate alcohol use, and maintaining a healthy weight) among platelet donors and to compare the results with those in the general population of similar ages. METHODS: Eighty-six platelet donors were asked to complete a questionnaire designed to assess physical activity, smoking, and alcohol use. Sociodemographic information including gender, age, and education was also collected from all participants. Chi-square statistics and logistic regression were used in statistical analysis. RESULTS: The mean age of the study donors was 51 years, 56% were female. Most were employed (90%), and 48% hold a bachelor's or higher degree. The prevalence of healthy behaviors differed by education gradients but not by gender and age. About 49% of the donors met the weekly physical activity recommendations, less than 5% were daily smokers, and~26% were classified as more frequent drinkers (≥1 to ≤5 times per week). The corresponding percentages for the general population were, respectively, 33%, 13%, and 35%. The prevalence of overweight and obesity, as assessed by body mass index (BMI), among donors were 50% and 29%, respectively, much higher than the current prevalence of overweight and obesity of 37% and 19%, respectively, among adults in the general population. CONCLUSIONS: The individual health behaviors of the majority of the study population could be characterized by a relatively high level of physical activity, low prevalence of daily smoking, and moderate alcohol drinking. The above-average overweight/obesity prevalence among platelet donors in this cohort is of concern because of the potential serious health consequences and it warrants further reflection.

Stretch-activated ion channels identified in the touch-sensitive structures of carnivorous Droseraceae plants.

In response to touch, some carnivorous plants such as the Venus flytrap have evolved spectacular movements to capture animals for nutrient acquisition. However, the molecules that confer this sensitivity remain unknown. We used comparative transcriptomics to show that expression of three genes encoding homologs of the MscS-Like (MSL) and OSCA/TMEM63 family of mechanosensitive ion channels are localized to touch-sensitive trigger hairs of Venus flytrap. We focus here on the candidate with the most enriched expression in trigger hairs, the MSL homolog FLYCATCHER1 (FLYC1). We show that FLYC1 transcripts are localized to mechanosensory cells within the trigger hair, transfecting FLYC1 induces chloride-permeable stretch-activated currents in naïve cells, and transcripts coding for FLYC1 homologs are expressed in touch-sensing cells of Cape sundew, a related carnivorous plant of the Droseraceae family. Our data suggest that the mechanism of prey recognition in carnivorous Droseraceae evolved by co-opting ancestral mechanosensitive ion channels to sense touch.

CovidCTNet: an open-source deep learning approach to diagnose covid-19 using small cohort of CT images.

Coronavirus disease 2019 (Covid-19) is highly contagious with limited treatment options. Early and accurate diagnosis of Covid-19 is crucial in reducing the spread of the disease and its accompanied mortality. Currently, detection by reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard of outpatient and inpatient detection of Covid-19. RT-PCR is a rapid method; however, its accuracy in detection is only ~70-75%. Another approved strategy is computed tomography (CT) imaging. CT imaging has a much higher sensitivity of ~80-98%, but similar accuracy of 70%. To enhance the accuracy of CT imaging detection, we developed an open-source framework, CovidCTNet, composed of a set of deep learning algorithms that accurately differentiates Covid-19 from community-acquired pneumonia (CAP) and other lung diseases. CovidCTNet increases the accuracy of CT imaging detection to 95% compared to radiologists (70%). CovidCTNet is designed to work with heterogeneous and small sample sizes independent of the CT imaging hardware. To facilitate the detection of Covid-19 globally and assist radiologists and physicians in the screening process, we are releasing all algorithms and model parameter details as open-source. Open-source sharing of CovidCTNet enables developers to rapidly improve and optimize services while preserving user privacy and data ownership.

A role of PIEZO1 in iron metabolism in mice and humans.

Iron overload causes progressive organ damage and is associated with arthritis, liver damage, and heart failure. Elevated iron levels are present in 1%-5% of individuals; however, iron overload is undermonitored and underdiagnosed. Genetic factors affecting iron homeostasis are emerging. Individuals with hereditary xerocytosis, a rare disorder with gain-of-function (GOF) mutations in mechanosensitive PIEZO1 ion channel, develop age-onset iron overload. We show that constitutive or macrophage expression of a GOF Piezo1 allele in mice disrupts levels of the iron regulator hepcidin and causes iron overload. We further show that PIEZO1 is a key regulator of macrophage phagocytic activity and subsequent erythrocyte turnover. Strikingly, we find that E756del, a mild GOF PIEZO1 allele present in one-third of individuals of African descent, is strongly associated with increased plasma iron. Our study links macrophage mechanotransduction to iron metabolism and identifies a genetic risk factor for increased iron levels in African Americans.

Diagnosis of Behçet's disease: clinical characteristics, diagnostic criteria, and differential diagnoses.

BACKGROUND: The diagnosis of Behçet disease (BD) is challenging in many cases. The purpose of this study was to describe the clinical characteristics of patients at a referral BD clinic. METHODS: In a retrospective study, we collected data from patients at a national referral Behçet clinic from November 2018-August 2019. A BD diagnosis was confirmed (BD group) or ruled out (Non-BD group), and the two groups were compared for differences. RESULTS: A total of 238 patients satisfied the inclusion criteria. Forty patients (16.8%) were finally diagnosed with BD. Ocular and genital lesions were significantly more prevalent in the BD group. A positive pathergy test and HLA-B51 were also significantly more common in BD. However, oral lesions, articular involvement, and gastrointestinal manifestations were similar between groups. Also, patients with BD were significantly more likely to have multi-organ (≥2 organ systems) involvement. CONCLUSIONS: Being the first study to evaluate the clinical characteristics of patients who are visited at a referral BD clinic and are believed to have a high probability of Behçet, the results of this study are important from an epidemiological standpoint. Also, the findings of this study could be used by referral Behçet clinics, which evaluate and diagnose patients with a high pretest probability and atypical presentations of BD on a daily basis. The alternative diagnoses established in this study could be used as the list of the most common differential diagnoses for Behçet's disease.

Almond as a nutraceutical and therapeutic agent in Persian medicine and modern phytotherapy: A narrative review.

Sweet almond (Prunus dulcis (Mill.) D.A.Webb) is a known nut, which has long been used in several ethnomedical systems, especially in Persian medicine (PM) for its nutritional and therapeutic activities. In this study, we aimed to provide a summary on traditional uses, phytochemistry, and pharmacological activities of sweet almond. Thus, we reviewed textbooks of PM and electronic literature on traditional medicine. Moreover, the available data on the usage of sweet almond were searched in electronic databases to find articles on its pharmacological properties and phytochemistry. According to phytochemical investigations, this plant contains macronutrients, micronutrients, essential oils, various phenolic compounds, and phytosterols. Current pharmacological studies represent that Prunus dulcis has several biological activities including prebiotic, antimicrobial, antioxidant, antiinflammatory, anticancer, hepatoprotective, cardiometabolic protection, nootropic, anxiolytic, sedative-hypnotic, and nervous-improving effects. Further clinical trials and meta-analysis are required to draw a definitive conclusion on the efficacy and therapeutic activities of almond.