The Effect of Multilayered Electrospun PLLA Nanofibers Coated with Human Amnion or Bladder ECM Proteins on Epithelialization and Smooth Muscle Regeneration in the Rabbit Bladder.

Nanofibrous scaffolds have attracted much attention in bladder reconstruction approaches due to their excellent mechanical properties. In addition, their biological properties can be improved by combination with biological materials. Taking into account the advantages of nanofibrous scaffolds and decellularized extracellular matrix (dECM) in tissue engineering, scaffolds of poly-L-lactic acid (PLLA) coated with decellularized human amnion membrane (hAM) or sheep bladder (SB)-derived ECM proteins are developed (amECM-coated PLLA and sbECM-coated PLLA, respectively). The bladder regenerative potential of modified electrospun PLLA scaffolds is investigated in rabbits. The presence of ECM proteins is confirmed on the nanofibers' surface. Coating the surface of the PLLA nanofibers improves cell adhesion and proliferation. Histological and immunohistochemical evaluations show that rabbits subjected to cystoplasty with a multilayered PLLA scaffold show de novo formation and maturation of the multilayered urothelial layer. However, smooth muscle bundles (myosin heavy chain [MHC] and α-smooth muscle actin [α-SMA] positive) are detected only in ECM-coated PLLA groups. All groups show no evidence of a diverticulumor fistula in the urinary bladder. These results suggest that the biofunctionalization of electrospun PLLA nanofibers with ECM proteins can be a promising option for bladder tissue engineering. Furthermore, hAM can also replace animal-sourced ECM proteins in bladder tissue regeneration approaches.

Immunological Evaluation of Pediatric Patients with Polyautoimmunity.

BACKGROUND: Autoimmunity can be the first or predominant manifestation in patients with primary immunodeficiency disorder, also referred to as inborn errors of immunity (IEI). This study aims to evaluate the immune status of pediatric patients with polyautoimmunity to identify those with underlying immune defects. METHODS: In this cross-sectional study, pediatric patients with polyautoimmunity including at least one confirmed autoimmune endocrine disease were enrolled. Demographic and clinical data were collected using a questionnaire based on medical records and direct family interviews. For each patient, a basic immunologic evaluation was performed. The clinical diagnosis was established according to the criteria of the European Society for Immunodeficiencies (ESID). Based on the presence or absence of a history of severe and/or recurrent infections, patients were divided into two groups for comparison. RESULTS: Thirty-nine patients, 18 males (46.2%) and 21 females (53.8%), were included. Fourteen patients (35.9%) had consanguineous parents. Fifteen patients (38.5%) had a history of severe and/or recurrent infections. The median (interquartile range: IQR) age of our patients at the time of evaluation was 11.1 (9-16) years. The median (IQR) age at the onset of infections and autoimmunities were 3 (1-10.8) and 5 (2.6-8) years, respectively. The most common infectious complications reported were pneumonia and candidiasis, each in 12.8% of the patients. The most prevalent autoimmune disorders were type 1 diabetes (74.3%) and autoimmune thyroiditis (58.9%). IEI was diagnosed in six patients (15.38%), five of which were from the group with severe or recurrent infections: three with selective IgA deficiency, two with common variable immunodeficiency (CVID), and one with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX), but without a history of infections. CONCLUSION: The occurrence of early onset polyautoimmunity in association with severe and/or recurrent infections or in patients with a positive family history should be a warning sign for physicians to initiate an evaluation for possible immunodeficiency disorders to prevent complications through early treatment.

Enhanced bone tissue regeneration using a 3D-printed poly(lactic acid)/Ti6Al4V composite scaffold with plasma treatment modification.

The mechanical and biological properties of polylactic acid (PLA) need to be further improved in order to be used for bone tissue engineering (BTE). Utilizing a material extrusion technique, three-dimensional (3D) PLA-Ti6Al4V (Ti64) scaffolds with open pores and interconnected channels were successfully fabricated. In spite of the fact that the glass transition temperature of PLA increased with the addition of Ti64, the melting and crystallization temperatures as well as the thermal stability of filaments decreased slightly. However, the addition of 3-6 wt% Ti64 enhanced the mechanical properties of PLA, increasing the ultimate compressive strength and compressive modulus of PLA-3Ti64 to 49.9 MPa and 1.9 GPa, respectively. Additionally, the flowability evaluations revealed that all composite filaments met the print requirements. During the plasma treatment of scaffolds, not only was the root-mean-square (Rq) of PLA (1.8 nm) increased to 60 nm, but also its contact angle (90.4°) significantly decreased to (46.9°). FTIR analysis confirmed the higher hydrophilicity as oxygen-containing groups became more intense. By virtue of the outstanding role of plasma treatment as well as Ti64 addition, a marked improvement was observed in Wharton's jelly mesenchymal stem cell attachment, proliferation (4',6-diamidino-2-phenylindole staining), and differentiation (Alkaline phosphatase and Alizarin Red S staining). Based on these results, it appears that the fabricated scaffolds have potential applications in BTE.

Junk food consumption and psychological distress in children and adolescents: a systematic review and meta-analysis.

Background: Available evidence indicates that junk foods, defined as unhealthy foods with high-calorie and low-nutrient value, negatively affect mental and metabolic health of children. This study aimed to conduct a meta-analysis to clarify the association between junk food consumption and psychological distress in children and adolescents.Methods: A systematic literature search of relevant documents published in PubMed, Web of Science, and SCOPUS was conducted up to 2022. All observation studies which assessed association of junk foods and psychological distress in children and adolescents were included. Random-effect model was used to pool odds ratio (OR) and 95% confidence interval (CI) from individual studies. Subgroup meta-analysis was performed based on junk foods categories (sweet drinks, sweet snacks and snacks).Results: Data of 17 included articles on junk foods consumption in relation to depression, stress, anxiety, sleep dissatisfaction and happiness in children and adolescents were included in this systematic review. According to random effect model, the pooled OR in the highest vs. the lowest category of junk foods was 1.62 (95% CI: 1.35-1.95) for depression, 1.34 (95% CI: 1.16-1.54) for stress, 1.24 (95% CI: 1.03-1.50) for anxiety, 1.17 (95% CI: 1.05-1.30) for sleep dissatisfaction and 0.83 (95% CI: 0.75-0.92) for happiness. In subgroup meta-analysis, there were significant associations between different types of junk foods and psychological distress (P < 0.05).Conclusion: This meta-analysis showed that junk foods consumption was associated with increased odds of psychological distress in children and adolescents. These findings support the current recommendation of decreasing junk foods intake.

NiFe2O4/ZnO-coated Poly(L-Lactide) nanofibrous scaffold enhances osteogenic differentiation of human mesenchymal stem cells.

Background: A combination of bioceramics and polymeric materials has attracted the research community's interest in bone tissue engineering. These composites are essential to support cell attachment, proliferation, and osteogenesis differentiation, which are vital as a classic strategy in bone tissue engineering. In this study, NiFe2O4/ZnO-coated poly L-Lactide (PLLA) was employed as a scaffold to evaluate the osteogenic differentiation capability of human adipose tissue derived mesenchymal stem cells (hAMSCs). Material and methods: The electrospun PLLA nanofibers were fabricated, coated with nanocomposite (NiFe2O4/ZnO), and evaluated by the water contact angle (WCA), tensile test, attenuated total reflectance fourier-transform infrared (ATR-FTIR) and scanning electron microscopy (SEM). Then, the osteogenic differentiation potential of hAMSCs was assessed using NiFe2O4/ZnO-coated PLLA compared to tissue culture plastic (TCP) and a simple scaffold (PLLA) in vitro conditions. Results: The adhesion, proliferation, and differentiation of hAMSCs were supported by the mechanical and biological properties of the NiFe2O4/ZnO-coated PLLA scaffold, according to SEM and 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining patterns. During bone differentiation, Alkaline phosphatase (ALP) enzyme activity, biomineralization, calcium content, and osteogenic gene expression (ALP, Osteonectin, Osteocalcin, Collagen type I, and Runx2) were higher on NiFe2O4/ZnO-coated PLLA scaffold than on PLLA scaffold and TCP. Conclusion: Based on our results, the osteogenic differentiation of hAMSCs on the improved biological scaffold (PLLA coated with NiFe2O4/ZnO) could accelerate due to the stimulating effect of this nanocomposite.

Ocular Toxocariasis Associated with Blurred Vision and Visual Impairment: Report of Four Cases.

Ocular toxocariasis in humans is caused by infection with larvae of Toxocara species, which are common ascarid roundworms of mammals, kept in close proximity to human. Four cases with a history of contact with dogs and cats and blurred vision and visual impairment over periods of variable duration were examined. We screened patients diagnosed with ocular larva migrans syndrome between March and June 2021 at the Ophthalmology clinics affiliated with Alborz University of Medical Sciences, Karaj, Iran. Detailed demographics, clinical characteristics, and fundus photography were recorded. Anti-Toxocara antibodies in the sera and vitreous fluid detected by ELIZA. Complete recovery in all four patients was achieved following treatment with oral albendazole. The diagnosis of ocular toxocariasis can be challenging, because both the condition is relatively uncommon and its presentation varies from patient to patient. There are lots of differential diagnoses like retinoblastoma, therefore correct, quick diagnosis, and treatment is very important.

X-linked SCID with a rare mutation.

BACKGROUND: Severe combined immunodeficiency (SCID) is a group of relatively rare primary immunodeficiency disorders (PIDs), characterized by disturbed development of T cells and B cells, caused by several genetic mutations that bring on different clinical presentations. SCID may be inherited as an autosomal recessive or an X-linked genetic trait. CASE PRESENTATION: A 6-year-old male presented with a history of food allergy, productive coughs, and recurrent purulent rhinitis, poor weight gain and hypothyroidism. The total count of CD4+ T lymphocytes, along with their naïve and central memory subpopulations, as well as central memory CD8+ T cells were decreased in flow cytometry. A nucleotide substitution in exon one of interleukin 2 receptor gamma chain (IL-2RG) gene (c.115 G>A, p.D39N, ChrX: 70,331,275) was reported, based on which the diagnosis of X-liked SCID was confirmed. Antiviral and antibiotic prophylaxis, along with monthly IVIG (intravenous immunoglobulin) was started and the patient was subsequently referred for hematopoietic stem cell transplantation. CONCLUSION: PIDs should be considered as the differential diagnosis in any patient with unexplained and bizarre symptoms associated with recurrent infections, allergic and autoimmune manifestations. Clinicians should also bear X-SCID in mind in case of approach to any patient with poor weight gain, unusual allergic or endocrine manifestations, even in the case of a normal or increased level of serum immunoglobulins or T and B cells numbers.

Lumbosacral polyradiculitis associated with brucellosis.

INTRODUCTION: Brucellosis is a bacterial disease caused by different species of Brucella. Neurobrucellosis is one of the complications of brucellosis and polyradiculopathy is an uncommon manifestation. CASE REPORT: In this article we report a 29-year-old male patient diagnosed with neurobrucellosis who presented with subacute lower limbs weakness and inability to walk in the last 50 days. The patient declared usage of non-pasteurized dairy products in his past medical history. Diagnosis was confirmed by the LP of CSF and serological tests. Although PCR for Brucella was negative, Wright, Coombs Wright and 2ME tests were reported positive in both CSF and serum. MRI and EMG were also performed that highlighted polyradiculopathy. After six months treatment, complete clinical recovery along with elimination of nerve root enhancement in MRI by injection in the lumbosacral region was seen. CONCLUSION: Neurobrucellosis is a serious manifestation of Brucellosis that can have many side effects. Therefore, clinicians must pay attention to the neurological manifestations of this disease, but also reduce the effects of this disease by accelerating the start of treatment.

Nanofibrous Scaffolds Containing Hydroxyapatite and Microfluidic-Prepared Polyamidoamin/BMP-2 Plasmid Dendriplexes for Bone Tissue Engineering Applications.

OBJECTIVE: The aim of this study is to fabricate functional scaffolds to gene delivery bone morphogenetic protein-2 (BMP-2) plasmid for bone formation in bone tissue engineering. METHODS: Dendriplexes (DPs) of generation 4 polyamidoamin (G4-PAMAM)/BMP-2 plasmid were prepared through microfluidic (MF) platform. The physiochemical properties and toxicity of DPs were evaluated by DLS, AFM, FESEM and MTT assay. In order to create a suitable environment for stem cell growth and differentiation, poly-l-lactic acid (PLLA) and poly-l-lactic acid/poly (ethylene oxide) (PLLA/PEO) scaffolds containing hydroxyapatite nanoparticles (HA) and DPs were fabricated by the electrospinning method. The osteogenic potency of the scaffolds on human adipose tissue-derived mesenchymal stem cells (hASCs) was investigated. RESULTS: The results revealed that tuning the physical properties of DPs by adjusting flow parameters in microfluidic platform can easily improve the cell viability compared to conventional bulk mixing method. Also, the result showed that the presence of HA and DPs in PLLA/PEO scaffold enhanced alkaline phosphatase (ALP) activity and increased the amount of deposited Ca, as well as, related to osteogenesis gen markers. CONCLUSION: This study indicated that on using the MF platform in preparation of DPs and loading them along with HA in PLLA/PEO scaffold, the osteogenic differentiation of hASCs could be tuned.

Paratubal endosalpingiosis: a case report.

INTRODUCTION: Endosalpingiosis is a rare condition and its pathogenesis and clinical significance are not fully understood. The unfamiliar presentation of this disease can misguide health care professionals. The reports available on this matter describe it as a disease of older age. In the majority of the cases it is an incidental finding in those with other concurrent gynecologic conditions. PRESENTATION OF CASE: Here we report the case of a 14-year-old female who presented with abdominal pain and no specific past medical history. Imaging and physical examination were highly suggestive of appendicitis. With the initial diagnosis of acute abdomen, she underwent surgery. During the surgery gastrointestinal tract organs were found to be normal and in gynecological examination, the ovaries were normal, however the fallopian tube revealed a twisted paratubal cyst which was removed and sent to the laboratory for further investigation. On the basis of the cellular pathology, tubal like epithelium in the cyst was found and patient diagnosed with endosalpingiosis. DISCUSSION: We suggest that in our case, the lesion possibly originated from the metaplasia of coelomic membrane into tubal cells. There are studies suggesting that co-occuring diseases should be considered when the diagnosis of endosalpingiosis is established and further studies are needed in regard to this matter. CONCLUSION: Endosalpingiosis, although being a rare condition, should be included in our differential diagnosis since co-existing comorbidities are a possibility in patients with endosalpingiosis and can be of great importance.

Therapeutic and Preventive Effects of Olea europaea Extract on Indomethacin-Induced Small Intestinal Injury Model in Rats.

BACKGROUND: Olea europaea (known as olive fruit) has anti-inflammatory and antioxidant activities and many potential health benefits including gastric inflammation reduction has been shown previously. This study aimed to investigate the preventive and therapeutic effects of O. europaea extract on the early histological changes in indomethacin-induced small intestinal injury model with the plasma D-lactate concentration being measured as a tool for determination of intestinal permeability. METHODS: In this experimental study, two separate protective and therapeutic protocols were designed. In both experiments, male Wistar rats were randomly divided into 4 groups and either pretreated with 0, 100, 200, or 400 mg/kg/day of O. europaea extract or received the treatment after administration of indomethacin. Their small intestines were examined to compare the histological changes. The intestinal injury severity was evaluated according to the presence of eosinophils, plasma cell infiltration, edema, congestion, and hyperplasia of the crypt using a histological scoring system. Also, measured were the presence of neutrophils, decreased villus length-to-crypt depth ratio, and destructed villus architecture. The plasma concentration of D-lactate was measured as well. RESULTS: The therapeutic use of O. europaea decreased the eosinophil, edema, congestion, and crypt hyperplasia scores compared to the control group. Although no significant difference was seen between groups of the preventive experiment in plasma cell infiltration score, villus length-to-crypt depth ratio, neutrophil infiltration, and percentage of destructed villus architecture, treatment with O. europaea caused a reduction in edema, eosinophil, congestion, and crypt hyperplasia score. In both experiments, no significant difference was seen between groups for villus length-to-crypt depth ratio, neutrophil infiltration, and percentage of destructed villus architecture. Plasma D-lactate concentration was decreased in all O. europaea-treated groups compared to the control group in the therapeutic and preventive experiments (p < 0.01, one-way ANOVA followed by the Dunnett test). CONCLUSION: O. europaea extract can be used to decrease some side effects of indomethacin on intestinal tissue and enhances the gastrointestinal function. O. europaea extract could be considered as a potential herbal supplement in the treatment of intestinal morphological injuries.

Diagnostic Approach to the Patients with Suspected Primary Immunodeficiency.

BACKGROUND AND OBJECTIVE: Primary immunodeficiency diseases (PIDs) are a group of more than 350 disorders affecting distinct components of the innate and adaptive immune systems. In this review, the classic and advanced stepwise approach towards the diagnosis of PIDs are simplified and explained in detail. RESULTS: Susceptibility to recurrent infections is the main hallmark of almost all PIDs. However, noninfectious complications attributable to immune dysregulation presenting with lymphoproliferative and/or autoimmune disorders are not uncommon. Moreover, PIDs could be associated with misleading presentations including allergic manifestations, enteropathies, and malignancies. CONCLUSION: Timely diagnosis is the most essential element in improving outcome and reducing the morbidity and mortality in PIDs. This wouldn't be possible unless the physicians keep the diagnosis of PID in mind and be sufficiently aware of the approach to these patients.

Baghdadite nanoparticle-coated poly l-lactic acid (PLLA) ceramics scaffold improved osteogenic differentiation of adipose tissue-derived mesenchymal stem cells.

Bone repair has been a new approach in regenerative medicine especially by application of stem cells. Discovering a suitable combination of scaffolds to stimulate osteogenesis is one of the major concerns in this issue. Porous polymeric scaffolds such as poly l-lactic acid (PLLA) have been attracted a lot of attention because of their biodegradability. In the present study, we have been coated Baghdadite on the plasma-treated surface of PLLA and evaluated osteogenic potential of mesenchymal stem cells (MSCs). Adipose tissue-derived mesenchymal stem cells (AD-MSCs) were cultured on PLLA and PLLA-Baghdadite scaffolds, and cell properties were characterized by MTT assay, scanning electron microscope, and FTIR analysis. Then, osteogenic differentiation potential of AD-MSCs has been investigated, such as alkaline phosphatase (ALP) activity, calcium mineral deposition, and the expression of bone-related genes (RUNX2, ALP, and OCN). The results have been indicated that calcium content and ALP activity of cells cultured on PLLA-Baghdadite nanofibers were higher than that of tissue culture polystyrenes (TCPs). Gene expression analysis showed that PLLA-Baghdadite had effectively induced osteogenesis-related genes. Taken together, these results suggest that porous nanofiber scaffolds which coated with Baghdadite can enhance osteogenic differentiation of AD-MSC, and PLLA-Baghdadite can be used as a new biodegradable scaffold for bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1284-1293, 2019.

Chitosan-Coated Alginate Microcapsules Loaded with Herbal galactagogue Extract: Formulation Optimization and Characterization.

Many herbs and spices have been recommended traditionally as galactagogues and several commercial formulations prepared using herbs. Due to the presence of various compounds such as polyphenols, flavonoids, isoflavones, and terpenes, bitter and stringent taste is elicited that make the consumption of these herbal preparations unpleasant. Moreover, these compounds are unstable when exposed to environmental conditions. In this regard, different approaches are used for taste masking such as microencapsulation. In the present study, microcapsules containing herbal galactagogue extract were developed through emulsification/external gelation and Box-Behnken design was used to investigate the effects of independent variables (sodium alginate: 1-1.5%, calcium chloride: 0.2-1% and extract concentrations: 1-5%) on encapsulation efficiency (EE%). Following evaluation of the model, the optimum condition of encapsulation process was selected as 1.49% sodium alginate, 0.84 CaCl2, and 1.58% extract with EE% of 77.97%. Microcapsules had an acceptable spherical morphology and the results of Fourier transform-infrared spectroscopy (FTIR) revealed the presence of the extract within the microcapsules. The mean diameters of the uncoated and chitosan-coated microcapsules were 52 and 123 µm and encapsulation yield was 50.21 and 69.7%, respectively. The polydispersity index of 0.45 and 0.48 were an indicative of polydisperse nature of the microcapsules. The loss of flavonoids in microcapsules stored at two different temperatures was insignificant. The in-vitro release in simulated gastric fluid (SGF; pH 1.2) and simulated intestinal fluid (SIF; pH 7.4) were 48.1% and 80.11%, respectively during 24 h. The prepared extract-loaded microcapsules have potential to be used in matrices with neutral pH.

Bioactive glass ceramic nanoparticles-coated poly(l-lactic acid) scaffold improved osteogenic differentiation of adipose stem cells in equine.

Horses with big bone fractures have low chance to live mainly due to the lake of a proper treatment strategy. We believe that further attempts in equine bone tissue engineering will probably be required to meet all the needs for the lesion therapies. Therefore in this study we aimed to investigate the osteogenic differentiation capacity of equine adipose-derived stem cells (e-ASCs) on nano-bioactive glass (nBGs) coated poly(l-lactic acid) (PLLA) nanofibers scaffold (nBG-PLLA). Using electrospinning technique, PLLA scaffold was prepared successfully and coated with nBGs. Fabricated nanofibers were characterized by MTT, SEM, and FTIR analyses, and then osteogenic differentiation potential of isolated e-ASCs was investigated by the most key osteogenic markers, namely Alizarin red-S, ALP, calcium content and bone related (RUNX2, Collagen I, Osteonectin, and ALP) gene markers. Our results indicated that nBGs was successfully coated on PLLA scaffold and this scaffold had no negative (p>0.05) effect on cell growth rate as indicated by MTT assay. Moreover, e-ASCs that differentiated on nBGs-PLLA scaffold showed a higher (p<0.05) ALP activity, more (p<0.05) calcium content, and higher (p<0.05) expression of bone-related genes than that on uncoated PLLA scaffold and TCPS. According to the results, a combination of bioceramics and biopolymeric nanofibers hold valuable promising potentials to use for bone tissue engineering application and regenerative medicine.