Inspiring a convergent engineering approach to measure and model the tissue microenvironment.

Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics of the TiME in unprecedented detail; however, many advances still occur in silos that rarely integrate information to study the TiME in its full detail. This review provides an integrative overview of the engineering principles underlying chemical, optical, electrical, mechanical, and computational science to probe, sense, model, and fabricate the TiME. In individual sections, we first summarize the underlying principles, capabilities, and scope of emerging technologies, the breakthrough discoveries enabled by each technology and recent, promising innovations. We provide perspectives on the potential of these advances in answering critical questions about the TiME and its role in various disease and developmental processes. Finally, we present an integrative view that appreciates the major scientific and educational aspects in the study of the TiME.

Poly[poly(ethylene glycol) methacrylate]-modified starch-based solid and gel polymer electrolytes for high performance Li-ion batteries.

The idea of replacing liquid electrolytes with polymer electrolytes has been successful and the development of these electrolytes has provided acceptable results. With the start of using natural polymers in the polymer industry, as well as starch, these materials can be one of the most important candidates for the polymer matrix in electrolytes. In this study, starch has been investigated as a polymer electrolyte, poly[poly(ethylene glycol) methacrylate] (PEGMA) is grafted to the starch by radical polymerization, and synthesized copolymers are used as solid polymer electrolytes (SPEs). Furthermore, by adding N,N'-methylenebisacrylamide (MBA) as a cross-linking agent, gel polymer electrolytes (GPEs) are produced after swelling in the liquid electrolyte. After characterization, the synthesized polymer electrolytes are investigated in terms of electrochemical properties. The best ionic conductivity of 3.8 × 10-5 S cm-1 is obtained for SPEs whereas it is obtained 4.3 × 10-3 S cm-1 for GPEs at room temperature. The ion transfer number in the range of 0.47-0.91 confirms the compatibility between the electrolytes and electrode. Also, the prepared polymer electrolytes present excellent electrochemical properties, including, a wide electrochemical stability window above 4.7 V, good specific capacities in the range of 170-200 mAh g-1 with a storage capacity of more than 92 %, and Coulombic efficiency of about 98 % after 100 cycles at 0.2 C.

Desmosomal Cadherin Tension Loss in Pemphigus Vulgaris Mediated by the Inhibition of Active RhoA at Cell-Cell Adhesions.

Binding of autoantibodies to keratinocyte surface antigens, primarily desmoglein 3 (Dsg3) of the desmosomal complex, leads to the dissociation of cell-cell adhesion in the blistering disorder pemphigus vulgaris (PV). After the initial disassembly of desmosomes, cell-cell adhesions actively remodel in association with the cytoskeleton and focal adhesions. Growing evidence highlights the role of adhesion mechanics and mechanotransduction at cell-cell adhesions in this remodeling process, as their active participation may direct autoimmune pathogenicity. However, a large part of the biophysical transformations after antibody binding remains underexplored. Specifically, it is unclear how tension in desmosomes and cell-cell adhesions changes in response to antibodies, and how the altered tensional states translate to cellular responses. Here, we showed a tension loss at Dsg3 using fluorescence resonance energy transfer (FRET)-based tension sensors, a tension loss at the entire cell-cell adhesion, and a potentially compensatory increase in junctional traction force at cell-extracellular matrix adhesions after PV antibody binding. Further, our data indicate that this tension loss is mediated by the inhibition of RhoA at cell-cell contacts, and the extent of RhoA inhibition may be crucial in determining the severity of pathogenicity among different PV antibodies. More importantly, this tension loss can be partially restored by altering actomyosin based cell contractility. Collectively, these findings provide previously unattainable details in our understanding of the mechanisms that govern cell-cell interactions under physiological and autoimmune conditions, which may open the window to entirely new therapeutics aimed at restoring physiological balance to tension dynamics that regulates the maintenance of cell-cell adhesion.

Synthesis and evaluation of cellulose/polypyrrole composites as polymer electrolytes for lithium-ion battery application.

Natural polymers as battery components have a number of advantages, including availability, biodegradability, unleakage, stable form, superior process, electrochemical stability, and low cost. In other sides, conductive polymers can improve the electrochemical properties of the battery, such as charge/discharge rates, cycling stability, and overall energy storage capacity. Therefore, the combination of these two materials can provide acceptable features. In this study, polymer electrolytes based on cellulose have been synthesized by solution casting method to prepare a thin polymer film. Then, polypyrrole (PPy) was blended with cellulose in different weight ratios. To prevent electrical conductivity of blends, PPy was used <10 wt%. The electrochemical properties of prepared electrolytes have been investigated by different methods. The results showed that ionic conductivity was increased by addition of PPy to cellulose due to the creation of pores and also due to the high dielectric constant of conductive polymers. All synthesized electrolytes had suitable ionic conductivity (in the range of 10-3 S cm-1), significant charge capacity, stable cyclic performance, excellent electrochemical stability (above 4.8 V), and high cation transfer number (between 0.38 and 0.66 for pure cellulose and the sample containing 10 wt% PPy).

Fluorescent cellulosic composites based on carbon dots: Recent advances, developments, and applications.

Cellulose and its derivatives are highly applicable in advanced applications on the basis of fluorescence phenomena. Carbon dots (CDs) have also appealing properties, such as high photoluminescence, easy synthesis pathway, cheap source materials, chemical stability, and easy functionalization. In this regard, combination of luminescent CDs with natural cellulosic materials could adjust or expand its desirable properties and have advanced applications. This review summarizes chemical and physical incorporation of CDs and graphene quantum dots into different types of cellulosic materials to yield smart fluorescent materials with applications in films, catalysts, bioimaging, drug delivery, anticounterfeiting, and fluorescence chemosensors for sensing pH, temperature, cations, anions, glucose, and aromatic amines. The challenges and future directions in fluorescent materials based on CDs are also briefly discussed. We hope that these studies will provide more consideration and curiosity for chemists, biologists, and materials scientists working in the field of fluorescent and CDs-containing cellulosic materials.

Investigating the effect of magnesium supplement in patients with major depressive disorder under selective serotonin reuptake inhibitor treatment.

Background: Major depression disorder (MDD) is a mental disorder that affects millions of people worldwide. This disease has negative impacts on quality of life and psychological-related functions. This is a multifactorial disorder; both genetic background and environmental factors have their role. Antidepressants are prescribed as the first line of treatment for patients with depressive disorders. Selective serotonin reuptake inhibitor (SSRI) antidepressants are used to treat MDD and anxiety; however, some patients do not respond to them. Regarding that, magnesium plays a major role in mood regulation; therefore, this study aimed to investigate the role of magnesium supplement in patients with MDD and under an SSRI treatment regimen. Methods: In this randomized, double-blind controlled trial, 60 patients with major depressive disorders based on the DSM-V diagnosis referred to Golestan Hospital in Ahvaz, Iran, were included. The eligible patients were categorized randomly into two thirty-people groups receiving magnesium (intervention) and placebo (control) along with SSRI for 6 weeks. To evaluate the depression status, the Beck II test was applied. Subjects were examined before and after the intervention. Results: There was no statistically significant difference between the two groups in terms of demographic characteristics (P > 0.05). The mean Beck scores at the beginning of the study and the second week after the intervention were not different between the two groups (P = 0.97, P = 0.56), whereas the mean Beck scores were lower in the intervention group than in the control group in the fourth and sixth weeks after the intervention (P = 0.02 and P = 0.001, respectively). Conclusion: Administration of Mg supplement for at least 6 weeks might improve depression symptoms. It can also be considered as a potential adjunct treatment option for MDD patients who are under SSRI treatment.

Adipose-derived mesenchymal stem cells ameliorate lung epithelial injury through mitigating of oxidative stress in mustard lung.

Aim: We investigated potential efficacy of autologous adipose-derived mesenchymal stem cell (MSC) on oxidative stress (OS) and airway remodeling in patients with chronic mustard lung. Patients & methods: Ten patients received 100 × 106 cells every 20 days for 4 injections over a 2-month period. Results: A gradual improvement was observed for 6 min walk test scores, pulmonary function tests and respiratory quality after MSCs therapy. A significant decrease was found for the mean levels of Mucin-1 protein (KL-6; p = 0.022) and Clara cell protein 16 (CC16; p = 0.005). Antioxidants had a tendency to be higher after each injection. Conclusion: Our findings revealed that MSCs therapy can be safely used for improvement of lung injury and regeneration in these patients without adverse effects. Trial registration number: NCT02749448 (ClinicalTrials.gov).

Quantitative Classification of 3D Collagen Fiber Organization From Volumetric Images.

Collagen fibers in biological tissues have a complex 3D organization containing rich information linked to tissue mechanical properties and are affected by mutations that lead to diseases. Quantitative assessment of this 3D collagen fiber organization could help to develop reliable biomechanical models and understand tissue structure-function relationships, which impact diagnosis and treatment of diseases or injuries. While there are advanced techniques for imaging collagen fibers, published methods for quantifying 3D collagen fiber organization have been sparse and give limited structural information which cannot distinguish a wide range of 3D organizations. In this article, we demonstrate an algorithm for quantitative classification of 3D collagen fiber organization. The algorithm first simulates five groups, or classifications, of fiber organization: unidirectional, crimped, disordered, two-fiber family, and helical. These five groups are widespread in natural tissues and are known to affect the tissue's mechanical properties. We use quantitative metrics based on features such as preferred 3D fiber orientation and spherical variance to differentiate each classification in a repeatable manner. We validate our algorithm by applying it to second-harmonic generation images of collagen fibers in tendon and cervix tissue that has been sectioned in specified orientations, and we find strong agreement between classification from simulated data and the physical fiber organization. Our approach provides insight for interpreting 3D fiber organization directly from volumetric images. This algorithm could be applied to other fiber-like structures that are not necessarily made of collagen.

The Eurasian lactase persistence variant LCT-13910 C/T is associated with vitamin D levels in individuals living at high latitude, more so than exposure to sunlight.

Rapid selection of a genetic variant that confers continuous life-long lactase production in Europeans (LCT-13910 C/T) has been attributed to the advantages of acquiring nutrients from consuming milk without the disadvantages of lactose malabsorption. Individuals with this genetic lactase persistence (LP) variant generally consume more milk and have been shown to have higher levels of serum vitamin D. Vitamin D is the principal regulator of Ca absorption and its synthesis in skin is dependent on UVB exposure. The primary aim of the present study was to compare serum vitamin D concentrations with LP variant and to control for UVB exposure. Data from over 100 000 individuals living in Norway, a country with low UVB exposure, was retrospectively retrieved for comparison of genetic LP variant, serum 25-hydroxyvitamin D (25(OH)D) concentration and the time of year when serum samples were taken. For comparison, a similar analysis was performed with a natural dairy micronutrient, namely vitamin B12. It was found that individuals with the genetic LP variant had considerably higher levels of serum 25(OH)D (P < 2 × 10-16, Cohen's d = 0·73) but lower levels of vitamin B12 (P < 2 × 10-16, Cohen's d = 0·11), compared with genetic lactase non-persistent individuals, even when controlled for seasonality, age and sex. The difference in serum 25(OH)D levels did not diminish in summer months, showing the role of vitamin D in LP variant selection in areas of low UVB irradiation. LP variant selection advantage through acquiring another dairy micronutrient, vitamin B12, was not observed.

An indentation-based approach to determine the elastic constants of soft anisotropic tissues.

Characterization of the mechanical properties of tissue can help to understand tissue mechanobiology, including disease diagnosis and progression. Indentation is increasingly used to measure the local mechanical properties of tissue, but it has not been fully adapted to capture anisotropic properties. This paper presents an indentation-based method to measure elastic constants of soft anisotropic tissues without additional mechanical tests. The approach uses measurement of the indentation modulus and the aspect ratio of the elliptical contact introduced by anisotropic mechanical properties of tissue to determine the elastic constants from finite element analysis. The imprinted area imparted by a fluorescent bead-coated spherical indenter showed the aspect ratio of the contact area, giving a generalized sense of the level of anisotropy, and instrumented indentation determined the indentation modulus. A parametric study using finite element simulation of the indentation tests established the relationship between the aspect ratio of contact and the non-dimensional ratios, Ex/Ey and Gxy/Ey; here, Ex and Ey are the Young's moduli (Ex > Ey) and Gxy is the shear modulus in the xy plane. For strongly anisotropic materials (Ex/Ey > 150), aspect ratio and indentation modulus are sufficient to determine Gxy and Ey. For weakly anisotropic materials, indentation modulus in the transverse direction, Ey, and the aspect ratio of contact in the anisotropic plane can be used to determine the elastic constants. The proposed approach improves the elastic characterization of soft, anisotropic biological materials from indentation and helps to elucidate the complex mechanical behavior of soft anisotropic tissues.

The relationship between IFNL4 genotype and the rate of fibrosis in hepatitis C patients.

Introduction: IFNL4 rs12979860 genotype CC is associated with increased ALT activity and liver stiffness in hepatitis C virus (HCV) genotype (G) 3 infection but not in G1. The primary aim of this study is to assess an interaction between IFNL4 genotype, viral genotype and the stage of liver fibrosis. Secondary aims are to study the potential interactions between IFNL4 genotype, viral genotype and viral load as well as ALT levels. Methods: We performed a cross sectional study of patients with untreated chronic hepatitis C. Inflammation and liver fibrosis were scored using METAVIR. DNA was extracted from serum samples and the rs12979860 was genotyped using a custom made Taqman assay. Results: About 304 consecutive patients with chronic Hepatitis C were included. 52% had G1 infection and 48% had G3. Among patients with G3, advanced fibrosis or cirrhosis (F3F4) was present in 35% of the patients with IFNL4 CC and 28% with CT/TT (p = 0.24). Among patients with G1, F3F4 was present in 20% of the patients with IFNL4 CC and 19% with CT/TT (p = 0.52). IFNL4 CC was associated with higher mean value of normalized (n)ALT both in HCV G1 and G3 infection. Conclusions: IFNL4 genotype was not a predictor of advanced liver fibrosis in G3 or G1 infected patients. IFNL4 CC predicted a higher mean value of ALT among both G1 and G3 infected patients.

Lactase persistence may explain the paradoxical findings of high vitamin D concentrations in Europeans living in areas of low UV-B irradiation.

BACKGROUND/OBJECTIVES: Vitamin D has a critical role in skeletal health and maintaining serum calcium levels. Calcium is needed for a variety of cellular and metabolic processes in the body. Large amounts of vitamin D can be produced in the skin when exposed to UV-B radiation. It is therefore a paradox that in Europe, Caucasians living in higher latitude countries, such as Scandinavia and Iceland, have higher serum vitamin D compared with those living in lower latitude. In a recent study of adult-type lactase persistence (LP), it was shown that Caucasian of European descent, who carried the C-13910T LP allele, had higher levels of total serum 25-hydroxyvitamin D compared with those who were lactase non-persistent. This was attributed to higher consumption of dairy. We postulated that the distribution of the LP C-13910T allele in Caucasian populations may explain the vitamin D concentration pattern seen in Europe. SUBJECTS/METHODS: Baseline mean total serum 25 hydroxyvitamin D concentration from a clinical trial of post-menopausal women with osteoporosis was correlated to published LP frequencies in European populations. RESULTS: In multiple regression analysis, mean total serum 25 hydroxyvitamin D concentrations in both winter and summer were in turn correlated to LP phenotype frequency (winter: r2 = 0.51, p < 0.05; summer: r2 = 0.4, p < 0.05). CONCLUSIONS: High frequency of LP in northern Europe may explain high mean total serum 25 hydroxyvitamin D concentrations despite low UV-B radiation exposure.

Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis.

Multiple sclerosis (MS) is a multifocal inflammatory disease that involves the central nervous system and associated with limbs paralysis and serious problems in sensation, limbs, visual and sphincter. This disease is a result of autoimmune mechanism in which autoantibodies target the self-myelin antigens and cause demyelination. Because of the myelin dysfunction, MS is clinically identified with neurological disabilities. Furthermore, it can be entered into the progressive phase because of irreversible neurodegeneration and axons damage. Unfortunately, there is no effective therapeutic method for this disease and current medications have been focused on amelioration of symptoms and chronic inflammation. Although current immunotherapies ameliorate the reactivity of autoimmune anti-myelin and MS relapse rate, there is no approved method for improvement of the disease progression and repairing of the damaged myelin. Therefore, finding an appropriate clinical treatment for improvement of neurological damages in MS patients is essential. Mesenchymal stem cells (MSCs) are multipotent cells with high proliferative and self-renewal capacities, as well as immunomodulatory and neuroregenerative effects. Bone marrow and adipose tissues derived MSCs have been considered for the treatment of different diseases because not only they can be easily isolated from these tissues, but also a patient can be served as a donor for himself without the risk of rejection. More importantly, autologous MSCs carry a safer pattern without the risk of malignant transformation. Here, we will discuss the effectiveness of MSCs therapy for MS patients by reviewing of clinical trials.

Effects of a 12-week aerobic exercise on markers of hypertension in men.

Introduction: This study was aimed at determining the effects of a 12-week aerobic exercise program on markers of hypertension in men. Methods: The study was of a semi-experimental design featuring repeated measurements. A total of 40 men (age range=37.9 ± 2.68) with primary hypertension were divided into two groups, namely, the exercise group (n=20) and the control group (n=20) (systolic blood pressure [SBP]: 140.531 ± 0.23, diastolic blood pressure [DBP]: 90.71 ± 0.05). The exercise group participated in a 12-week aerobic exercise program (55% to 70% of HRmax). Blood samples were taken from both groups at the baseline and at the 4th, 8th, and 12th weeks of the training program for the assessment of adiponectin, paraoxonase-1 (PON-1), and hydrogen peroxide (H2 O2 ) levels as the markers for investigation. A linear mixed model was also used to evaluate the association among the markers. Results: In the exercise group, exercise reduced the SBP and DBP at week 12 (P=0.031 and 0.023, respectively), and adiponectin increased at weeks 8 and 12 (P=0.014 and 0.001, respectively). The plasma PON-1 level showed a significant increase in all the three stages of measurement (P=0.007, 0.004, and 0.002 at weeks 4, 8, and 12, respectively), whereas the H2 O2 levels showed a significant decrease at weeks 8 and 12 (P=0.013 and 0.011, respectively). The control group exhibited significantly decreased PON-1 (P=0.003) and adiponectin (P=0.025) levels but significantly increased SBP at week 12 (P=0.032). Conclusion: The exercise-induced reduction of oxidative stress exerts a considerable effect on the reduction of blood pressure in hypertensive patients. According to our results increase in oxidative stress has the great impact on the of blood pressure.

Stem cells therapy: a review on approaches that can be used for treatment of respiratory failures in sulfur mustard-injured patients.

Sulfur mustard (SM) is a toxic agent which causes severe abnormalities in an airway system such as necrosis and inflammation, oxidative stress, chronic bronchitis, shortness of breath, and chronic obstructive pulmonary disease. Although possible mechanisms of SM toxicity have been extensively considered, there is still need to find an appropriate clinical treatment to decrease chronic lung injuries caused by SM. Due to extensive progresses and achievement in tissue repairing through stem cells therapy, the importance of cell therapy for the treatment of lung injuries has been increased. However, several factors such as types of stem cells, necessary conditions for growth and proliferation of stem cells, and their homing into the target tissues are considered as the most important problems in this issue. Mesenchymal stem cells (MSCs) are a class of multipotent stem cells with proliferative and self-renewal capacity which are able to differentiate into different cell lines such as lung epithelial cells. They have a potential repairing and immune modulatory properties which make them as a good candidate for the regeneration of bronchioles tract in SM-exposed patients. Unlike chemical drugs, the differentiation and high-level safety properties of MSCs can be considered as a new strategy for the treatment of SM-injured patients with pulmonary complications. This review aims to consider the therapeutic effects of MSCs in the treatment of SM-induced pulmonary injuries in both animals and humans.

The Role of Polymorphonuclear Leukocyte Counts from Urethra, Cervix, and Vaginal Wet Mount in Diagnosis of Nongonococcal Lower Genital Tract Infection.

Objective: The aim of this study was to evaluate whether the polymorphonuclear leukocyte (PMNL) inflammatory response in women with nongonococcal lower genital tract infection (LGTI) can be used to optimize criteria for syndromic treatment. Methods: A cross-sectional study of 375 women attending the STI clinic in Oslo. Urethral, cervical, and vaginal specimens underwent microscopy for PMNLs. Chlamydia trachomatis (Ct) and other STIs were detected in the cervical/vaginal swabs and urine, using nucleic acid amplification test (NAAT). After excluding vulvovaginal candidiasis, genital herpes, and trichomoniasis, we correlated clinical and microscopic signs of inflammation with positive NAAT for Ct, mycoplasma genitalium (Mg), and Ureaplasma urealyticum (Uu) in a subgroup of 293 women. Results: To predict a positive Ct, the combination of high cut-off urethritis (≥10 PMNLs/HPF) and microscopic cervicitis had a high specificity of 0.93, a PPV of 0.37, and a sensitivity of 0.35. LGTI criteria had low predicting values for Mg and Uu. Conclusion: Including microscopic criteria for the diagnosis of LGTI gives better indication for presumptive antibiotic treatment than anamnestic and clinical diagnosis alone.

Bone Remodeling under Vibration: A Computational Model of Bone Remodeling Incorporating the Modal Behavior of Bone.

Developing precise computational models of bone remodeling can lead to more successful types of orthopedic treatments and deeper understanding of the phenomenon. Empirical evidence has shown that bone adaptation to mechanical loading is frequency dependent and the modal behavior of bone under vibration can play a significant role in remodeling process, particularly in the resonance region. The objective of this study is to develop a bone remodeling algorithm that takes into account the effects of bone vibrational behavior. An extended/modified model is presented based on conventional FE remodeling models. Frequency domain analysis is used to introduce appropriate correction coefficients to incorporate the effect of bone's frequency response into the model. The method is implemented on a bovine bone with known modal/vibration characteristics. The rate and locations of new bone formation depend on the loading frequency and are consistently correlated with the bone modal behavior. The proposed method can successfully integrate the bone vibration conditions and characteristics with the remodeling process. The results obtained support experimental observations in the literature.

Administration of zinc against arsenic-induced nephrotoxicity during gestation and lactation in rat model.

BACKGROUND: Free radicals production by toxicity of arsenic (Ar) is most important in the nephrotoxicity. There is accumulating evidence that zinc (Zn), has anti-oxidant properties. OBJECTIVES: The aim of present study was to evaluate protective and ameliorative effects of Zn against Ar-induced nephrotoxicity in rat pups during gestation and lactation. MATERIALS AND METHODS: Twenty-four adult pregnant wistar rats were randomly divided into four groups (n = 6). Group one was given vehicle only. Group two received Zn (ZnSO4) at 20 mg/kg/d. Group three received Ar at 5 mg/kg/d as sodium meta-arsenite. Group four received Ar + Zn at the same dose that mentioned in groups of two and three. At the end of the study, 24 hours after the last treatment, samples were killed with overdose of sodium pentobarbital and kidneys were harvested for measuring malondialdehyde (MDA), glutathione (GSH) and histopathological assessment. RESULTS: The MDA level in kidney was increased in the Ar group, which was decreased after Zn administration in the Ar + Zn group. The GSH level in kidney was decreased in the Ar group, which were increased after Zn administration in the Ar + Zn group. Also, the histopathological changes which were detected in the Ar group attenuated after Zn consumption. CONCLUSIONS: Our findings suggested that administration of Zn during gestation and lactation could have protective and prevent effect in Ar-induced oxidative stress in kidney tissue.

Adipose-Derived Mesenchymal Stem Cells for Treatment of Airway Injuries in A Patient after Long-Term Exposure to Sulfur Mustard.

OBJECTIVE: Sulfur mustard (SM) is a potent mutagenic agent that targets several organs, particularly lung tissue. Changes in morphological structure of the airway system are associated with chronic obstructive pulmonary deficiency following exposure to SM. Although numerous studies have demonstrated pathological effects of SM on respiratory organs, unfortunately there is no effective treatment to inhibit further respiratory injuries or induce repair in these patients. Due to the extensive progress and achievements in stem cell therapy, we have aimed to evaluate safety and potential efficacy of systemic mesenchymal stem cell (MSC) administration on a SM-exposed patient with chronic lung injuries. MATERIALS AND METHODS: In this clinical trial study, our patient received 100×106cells every 20 days for 4 injections over a 2-month period. After each injection we evaluated the safety, pulmonary function tests (PFT), chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Borg Scale Dyspnea Assessment (BSDA), and 6 Minute Walk Test (6MWT). One-way ANOVA test was used in this study which was not significant (P>0.05). RESULTS: There were no infusion toxicities or serious adverse events caused by MSC administration. Although there was no significant difference in PFTs, we found a significant improvement for 6MWT, as well as BSDA, SGRQ, and CAT scores after each injection. CONCLUSION: Systemic MSC administration appears to be safe in SM-exposed patients with moderate to severe injuries and provides a basis for subsequent cell therapy investigations in other patients with this disorder (Registration Number: IRCT2015110524890N1).

Microscopy of Stained Urethral Smear in Male Urethritis; Which Cutoff Should be Used?

BACKGROUND: The microscopical diagnosis of male urethritis was recently questioned by Rietmeijer and Mettenbrink, lowering the diagnostic criteria of the diagnosis to ≥2 polymorphonuclear leucocytes (PMNL) per high power field (HPF), and adopted by Centers for Disease Control and Prevention in their 2015 STD Treatment Guidelines. The European Non-Gonococcal Urethritis Guideline advocates a limit of ≥5 PMNL/HPF. OBJECTIVE: To determine if syndromic treatment of urethritis should be considered with a cutoff value of ≥2 PMNL/HPF in urethral smear. METHODS: The design was a cross-sectional study investigating the presence and degree of urethritis relative to specific infections in men attending an STI clinic as drop-in patients. RESULTS: The material included 2 cohorts: a retrospective study of 13,295 men and a prospective controlled study including 356 men. We observed a mean chlamydia prevalence of 2.3% in the 0-9 stratum, and a 12-fold higher prevalence (27.3%) in the strata above 9. Of the chlamydia cases, 89.8% were diagnosed in strata above 9. For Mycoplasma genitalium, the prevalence was 1.4% in the 0-9 stratum and 11.2% in the stratum ≥10, and 83.6% were diagnosed in strata above 9. For gonorrhea, a significant increase in the prevalence occurred between the 0-30 strata and >30 strata from 0.2% to 20.7%. The results of the prospective study were similar. CONCLUSIONS: Our data do not support lowering the cutoff to ≥2 PMNL/HPF. However, a standardization of urethral smear microscopy seems to be impossible. The cutoff value should discriminate between low and high prevalence of chlamydia, mycoplasma, and gonorrhea to include as many as possible with a specific infection in syndromic treatment, without overtreating those with few PMNL/HPF and high possibility of having nonspecific or no urethritis.