Development and evaluation of a novel methotrexate-loaded electrospun patch to alleviate psoriasis plaques.

OBJECTIVE: To achieve an effective topical formulation of Methotrexate (MTX) as a first-line treatment of psoriasis, we formulated three MTX-loaded electrospun nanofibrous patches composed of polycaprolactone (PCL), Eudragit L100, and a mixture of them. SIGNIFICANCE: Topical delivery of MTX provides an appropriate therapeutic performance while circumventing the life-threatening side effects of systemic administration. METHODS: Three MTX-loaded electrospun nanofibrous patches were prepared and characterized in terms of size and morphology (using SEM), thermal behavior (by TGA and DSC), and crystalline structure (using XRD). Furthermore, the wettability and mechanical strength of samples were investigated through water contact angle and tensile strength tests. Also, the encapsulation efficiency of MTX was calculated. Subsequently, in vitro drug release profile of each formulation was obtained and different kinetic models were fitted to achieve the best-matched model. Accordingly, the ex vivo skin permeation of MTX was studied for the optimum formulation. RESULTS: All samples showed appropriate morphology, thermal behavior, and encapsulation efficiency. Also, XRD results showed that MTX is dispersed within the polymeric matrices in the amorphous state (with no crystalline region). Release studies demonstrated that MTX-loaded Eudragit L100-PCL formulation outperformed in terms of mechanical behavior and in vitro drug release. This formulation also exhibited better skin permeation. CONCLUSION: The obtained controlled-release MTX-loaded electrospun patches seem promising to provide a long-acting topical treatment of psoriatic plaques with minimized systemic side effects.

Fabrication, in Vitro, and in Vivo Characterization of Mucoadhesive Berberine-Loaded Blended Wafers for Treatment of Chemotherapy-Induced Oral Mucositis.

This study aims to design and characterize berberine-loaded wafers for the treatment of chemotherapy-induced oral mucositis. Wafers were prepared by lyophilization of hydrogels of various ratios of chitosan (CS)/sodium alginate (SA) as well as CS/hydroxypropyl methylcellulose (HPMC). In vitro release, in vitro mucoadhesion, porosity, and swelling studies were conducted to select the optimized formulations. Moreover, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and mechanical properties studies were also performed for further characterization. The efficacy of optimized berberine-loaded wafers in the treatment of oral mucositis was investigated in a 5FU-induced oral mucositis rat model. F2-CS-SA and F6-CS-HPMC wafers exhibited sustained release profile and excellent mucoadhesion strength. Therefore, these wafers were selected as the optimized formulations. SEM confirmed the porous structure of these wafers and is in agreement with the results of porosity and swelling studies. XRD and FTIR studies indicated that berberine was incorporated into the wafer matrix in the amorphous form. In vivo studies demonstrated that topical application of berberine-loaded optimized wafers reduced significantly the severity of 5FU-induced oral mucositis and decreased the expression of inflammatory markers (TNF-α and IL-1ß). The results of in vitro and in vivo studies revealed that berberine-loaded F2-CS-SA and F6-CS-HPMC wafers can be effective in the treatment of chemotherapy-related oral mucositis.

Optimization of a dry powder inhaler of ciprofloxacin-loaded polymeric nanomicelles by spray drying process.

Ciprofloxacin is a commonly prescribed antibiotic for treatment of pulmonary infections. Nanocarriers such as nanomicelles can increase the drug residence time in the lungs and enhance their antibacterial effects. Dry powder inhalers (DPIs) are the preferred pulmonary drug delivery system and preparation of an optimum nanoaggregate from nanomicelles by means of spray drying would be valuable. The two-level full factorial design was performed in 16 runs. The effects of carrier type, anti-adhesion agent type, carrier to nanoparticle ratio and anti-adhesion agent to carrier ratio on the size of the microparticles, their in vitro pulmonary deposition, and redispersibility were investigated. Its antibacterial effects against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae also were investigated. All independent variables were fitted into two-factorial interaction models. The optimum nanoaggregate was prepared using mannitol and L-phenylalanine with a D0.5 of 1.7 µm and 60% fine particles. The process had no negative effect on the stability or drug release profile of the nanomicelles. The antibacterial effects of ciprofloxacin against microorganisms increased significantly. This spray drying process could be used for preparation of an optimum DPI from polymeric nanomicelles. This formulation could increase the efficacy of ciprofloxacin for treatment of pulmonary infections.

Evaluation of the toxicity effects of silk fibroin on human lymphocytes and monocytes.

Silk fibroin nanoparticles (SFNPs) as a natural polymer have been utilized in biomedical applications such as suture, tissue engineering-based scaffolds, and drug delivery carriers. Since there is little data regarding the toxicity effects on different cells and tissues, we aimed to determine the toxicity mechanisms of SFNPs on human lymphocytes and monocytes based on reliable methods. Our results showed that SFNPs (0.5, 1, and 2 mg/mL) induced oxidative stress via increasing reactive oxygen species production, mitochondrial membrane potential (∆Ψ) collapse, which was correlated to cytochrome c release and Adenosine diphosphate (ADP)/Adenosine tri phosphate (ATP) ratio increase as well as lysosomal as another toxicity mechanism, which led to cytosolic release of lysosomal digestive proteases, phosphor lipases, and apoptosis signaling. Taken together, these data suggested that SFNPs toxicity was associated with mutual mitochondrial/lysosomal cross-talk and oxidative stress on human lymphocytes and monocytes with activated apoptosis signaling.

Evaluation of Ion-pair Formation of Adefovir to Improve Permeation across Artificial and Biological Membranes.

PURPOSE: Adefovir is an antiviral drug that exhibits high hydrophilic properties and negligible bioavailability (less than 12%). It is only applied in the form of the ester prodrug adefovir dipivoxil (ADV). The oral bioavailability of ADV is limited (32% to 45%) by its low permeability (Class 3) and biological conversion of the prodrug to adefovir. Ion-pair formation is considered as an alternative approach to a covalent prodrug (ADV) to enhance intestinal permeation of adefovir. METHODS: The effect of various counter-ions (anionic, cationic and two quaternary ammonium salts) on the lipophilicity of adefovir was investigated by means of the n-octanol/buffer partitioning system, an in vitro transport model (PAMPA) and a biological membrane (everted gut sac). RESULTS: Quaternary ammonium salts, cetylpyridinium chloride (CPC) and cetrimide enhanced the lipophilicity of adefovir 136- and 87-fold, respectively. The apparent permeability of adefovir in combination with CPC (counter-ion) was 2.5-fold greater than ADV permeability in the PAMPA model. The apparent permeability of adefovir-CPC (counter-ion) was 1.3-fold greater than that of adefovir dipivoxil permeability in a biologic membrane (everted gut sac). CONCLUSION: These results suggest that the adefovir-CPC ion-paired system has potential for improving the permeation of adefovir across the intestinal membrane. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Preparation of an optimized ciprofloxacin-loaded chitosan nanomicelle with enhanced antibacterial activity.

OBJECTIVE: The objective of this study was to evaluate the effect of lipid structure on physicochemical properties of chitosan-fatty acid nanomicelles and prepare an optimum ciprofloxacin-loaded formulation from these conjugates which could enhance the antibacterial effects of drug against some important pathogens like P. aeruginosa. SIGNIFICANCE: Nowadays, resistance in infectious diseases is a growing worldwide concern. Nanocarriers can increase the therapeutic index and consequently reduce the antibiotic resistance. By site-specific delivery of drug, the adverse effects of broad-spectrum antibiotics such as ciprofloxacin would be reduced. METHODS: Fatty acid grafted chitosan conjugates were synthetized in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The effects of fatty acid type (stearic acid, palmitic acid, and linoleic acid) on physicochemical properties of conjugates were investigated. Ciprofloxacin was encapsulated in nanomicelles by thin film hydration method. Also, the preparation process was optimized with a central composite design. The antibacterial effect of optimum formulation against P. aeruginosa, K. pneumoniae, and S. pneumoniae species was determined. RESULTS: All conjugates were synthetized with high yield values and the substitution degrees ranged between 2.13 and 35.46%. Ciprofloxacin was successfully encapsulated in nanomicelles. The optimum formulation showed high drug loading (≈ 19%), with particle size of about 260 nm and a sustained release profile of ciprofloxacin. The minimum inhibitory concentrations of ciprofloxacin in optimum formulation against P. aeruginosa and K. pneumoniae species were 4 and 2 times lower in comparison with the free drug, respectively. CONCLUSIONS: The antibacterial effect of ciprofloxacin was improved by encapsulation of drug in chitosan nanomicelles.

The role of work- related physical and psychological factors on prevalence of neck/shoulder complaints among nurses: A multicentric study.

Background: Identifying the predisposing factors of neck and shoulder complaints and finding solutions to avoid them could improve the occupational health condition of the nurses. In this study, we aimed at determining the role of psychological and physical occupational factors in developing neck and shoulder complaints among the participants. Methods: This analytic cross-sectional study was conducted on the nurses of main hospitals of Tehran. To study the prevalence of neck and shoulder pain, the Nordic questionnaire was used, and job content questionnaire was used to assess the psychological and physical occupational factors. Data were analyzed using SPSS and statistical methods. Independent sample t-test was used to compare the qualitative variables, and chi-square test was utilized for the statistical analysis of the qualitative variables. Results: Prevalence of neck and shoulder complaints among the nurses with high physical workload was significantly higher than in those nurses with low physical workload. Unlike physical workload, the prevalence of neck and shoulder complaints was not significantly different between the nurses with low or high psychological workload. Prevalence of neck and shoulder complaints among the female nurses was significantly higher than in the male nurses. In our study, only female nurses with high physical workload had been known as independent predictors of neck and shoulder complaints. Conclusion: Those nurses who had more workload, especially physical workload, had a higher prevalence of neck and shoulder complaints, and this fact could affect their work tasks.

The effect of work- related stress on development of neck and shoulder complaints among nurses in one tertiary hospital in Iran.

Background: There are some challenges about the role of work- related stress on development of musculoskeletal complaints. The present prospective study was conducted on nurses of Milad hospital in Tehran (Iran) to assess the role of work- related stress on development of neck and shoulder pain among nurses. Methods: From the 1,900 nurses who completed the registry forms, 1,450 nurses met the inclusion criteria. We divided the participants into exposed and unexposed groups according to their DASS-21 scores. We collected the data of neck and shoulder pain among the nurses at two points of the first and the second year after the study, using the Nordic Questionnaire. Qualitative and quantitative variables were compared between the exposed and unexposed variables with chi-square and independent sample t-test, respectively. Results: One year after the commencement of the study, 62 (9.1%) nurses in the exposed group and 36 (4.7%) in the unexposed group had been reported as new cases of neck and shoulder pain, respectively. The incidence of the new cases of neck and shoulder pain was significantly higher in the exposed group compared to the unexposed group (p= 0.001). Two years after the start of the study, at the second follow-up point, 135 (19.8%) nurses in the exposed group and 76 (9.9%) in the unexposed group had been reported as new cases of neck and shoulder pain, respectively. The incidence of new cases of neck and shoulder pain was significantly higher in the exposed group compared to the unexposed group (p<0.001). Conclusions: The incidence of neck and shoulder pain was higher in those nurses with high level of workrelated stress. According to our results, more attention should be paid to mental health as well as physical symptoms and limitations of the healthcare workers when they refer to occupational health services with musculoskeletal pain complaints.

The effect of physical and psychosocial occupational factors on the chronicity of low back pain in the workers of Iranian metal industry: a cohort study.

BACKGROUND: Low back pain (LBP) is one of the most common problems among the workers of different industries. The role of occupational factors in causing the LBP has been indicated previously. LBP has great socio-economic costs and most of its costs are related to the chronic LBP. The aim of this study was to identify the occupational risk factors that are related to the progression of the LBP from acute to chronic phase. METHODS: This cohort study has been conducted on 185 workers with acute LBP. Information related to their occupational exposure at baseline has been measured with a valid questionnaire using the self-report approach. Patients follow up was done monthly for three months after the start of the pain. Those workers whose occupational exposure had not changed during the follow up were divided into two groups of chronic LBP (n = 49) and cured (n = 136) according to the duration of the pain period (more or less than 3 months), and their job exposures were compared. RESULTS: Among the physical and psychosocial risk factors, social support (OR= 0.466, CI= 0.231- 0.940) and job satisfaction (OR= 0.455, CI= 0.232-0.891), and lifting weights more than 15kg (OR=2.482, CI= 1.274-4.834) indicated a significant relationship with the chronicity of the LBP. After putting the variables into the regression model, only lifting>15kg remained statistically significant. CONCLUSION: According to the observed relationship between these occupational risk factors (social support, job satisfaction, lifting>15kg) and the chronicity of the LBP, there is hope that eliminating these factors in the workers with acute LBP will prevent its progression to the chronic phase.

An investigation into the drug release from ibuprofen matrix tablets with ethylcellulose and some poly-acrylate polymers.

This study was performed to achieve sustained-release Ibuprofen matrix tablets with a zero-order release kinetic while most of the previous formulations have shown Higuchi release kinetic. Considering the results from previous studies, ethyl cellulose, Carbopol 934P, Carbopol 974P, and Pemulen TR-1 were used at different amounts for preparation of the tablets by direct compression. The release profiles were studied in a two-stage release test using non-linear regression analysis. Carbopols 934P and 974P could not sustain the release adequately while Pemulen TR-1 had too strong sustaining effect. Therefore, combination formulations were considered and studied. The release profiles of ethyl cellulose formulation and the combination formulation consisting Carbopol 934P and Pemulen TR-1 best fitted in Higuchi model, although the zero-order model was not completely rejected. However, the kinetic model of release from the combination formulation consisting Carbopol 974P and Pemulen TR-1 changed to zero-order indicating the most constant release rate among formulations. This was speculated to be due to some erosion of the gel, as well as some interaction of the hydrophobic chain of Pemulen TR-1 with Ibuprofen. Therefore, this formulation is suggested for directly compressed sustained-release matrix tablets of Ibuprofen with a more constant release rate.

The impact of positive psychology counseling on sexual and marital satisfaction and anxiety among reproductive-aged women during the COVID-19 pandemic: a randomized controlled clinical trial.

BACKGROUND: Sexual and marital satisfaction is considered one of the important factors in happiness and life satisfaction of couples. COVID-19 pandemic results in psychological effects, such as increased anxiety levels which can affect sexual and marital satisfaction. This study aimed to investigate the impact of positive psychology on women's sexual and marital satisfaction. METHODS: A randomized controlled trial was conducted on 72 married women of reproductive age in Tabriz, Iran between February 2021 and May 2022. The participants were randomly divided into the intervention and control groups. There was no significant difference between the control and intervention groups in terms of the socio-demographic characteristics (p < 0.05). The mean age of the participants in the intervention and control groups was 31.8 ± 6.92 and 30.97 ± 5.09 years, respectively. The intervention group attended seven 60-90 min counseling sessions at weekly intervals. The Spielberger anxiety, sexual satisfaction and marital satisfaction questionnaires were completed before and four weeks after the intervention. RESULTS: The results of this study indicated that after counseling, the average overall score of marital satisfaction [MD: 15.46, 95% CI: 7.47 to 23.41, p = 0.034] and sexual satisfaction [MD: 7.83, 95% CI: 6.25 to 9.41, p = 0.001] significantly increased in the intervention group compared to the control group. Also, the mean score of state anxiety [MD: -2.50, 95% CI: -4.19 to -0.80, p = 0.001] and trait anxiety [MD: -1.03, 95% CI: -2.46 to -0.09, p = 0.032] significantly decreased after counseling in the intervention group compared to the control group. CONCLUSIONS: Using counseling based on a positive psychology approach can improve anxiety, sexual and marital satisfaction, and anxiety of women of reproductive age during the COVID-19 pandemic. However, further randomized clinical trials are needed before making a definitive conclusion. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20171007036615N8. Date of registration: 11/28/21. Date of first registration: 11/28/21. URL: https://www.irct.ir/user/trial/58680/view ; Date of recruitment start date: 12/01/21.

Corticosteroid-loaded chitosan-based in-situ forming gel combined with microneedle technology for improvement of burn eschar wound healing.

Burn is one of the most common skin injuries and accounts for 300,000 deaths annually. Debridement and antibiotic therapy are major burn treatments, however, as debridement is not always possible and many drugs have poor penetration into necrotic tissue, permeation enhancement is acquired. Another challenge is the short duration of topically applied drugs. This study aims to address both problems by combining in-situ forming gels and microneedles. A chitosan-based in-situ forming gel of hydrocortisone was applied to human burn eschar using microneedles. The formulation was optimized using Design-Expert software. Formulation characterization was done in terms of gelling time and temperature, thermal analysis, release phenomenon, rheology, texture analysis, and stability. Finally, animal studies on mice burn wound treatment were conducted. Results showed that optimized formulation controlled the drug release, and wherever microneedle was used, drug permeation and flux increased (P-value < 0.05). In all ex-vivo and in-vivo stages, gel plus microneedle (length of 1.5 mm and application mode of 2) produced the best results concerning increased flux and faster recovery of burn eschar. In conclusion, the in-situ forming gel with appropriate texture, quality, and stability in combination with microneedle can be a good candidate for the controlled release of drugs in third-degree burn eschars.

Stephen Hawking's Warning on Contacting Aliens: A Physics Perspective on the Intelligence Trap.

The search for extraterrestrial intelligence is a fascinating and important endeavor, but it raises significant ethical and safety concerns. In the search for extraterrestrial intelligence, scientists use knowledge of physics to identify potential communication methods and signals that may be used by extraterrestrial civilizations. One of the most notable scientists to highlight these concerns was the late physicist Stephen Hawking, who cautioned that actively attempting to communicate with extraterrestrial civilizations could harm humanity. While it is true that we cannot predict the intentions of any potential extraterrestrial civilizations, some scientists argue that the potential advantages of seeking contact outweigh the potential risks. Deciding to initiate contact with extraterrestrial civilizations is a complex issue that requires balancing scientific curiosity with concerns for our own safety. The "Intelligence Trap" is a concept in psychology that suggests that highly intelligent people are more susceptible to cognitive biases and flawed thinking than less intelligent people. It can be argued that Hawking's warnings may be an example of the so-called intelligence trap, as some evidence from the field of physics suggests. Nonetheless, Hawking emphasized that it is crucial for scientists and policymakers to carefully weigh the potential risks and benefits of such efforts and proceed with caution.

Exploring the Disparity in Indoor/Outdoor Time and Radon Exposure as Possible Factors Contributing to the Unexpected Increase in Lung Cancer Risk among Non-Smoking Women.

According to a NIH study, Lung cancer among individuals who have never smoked is more prevalent in women and occurs at an earlier age than in smokers. The rise in lung cancer rates among female non-smokers might be linked to radon inhalation and should be further investigated. Our theory is based on the differences in radon exposure between males and females, which can be attributed to the variations in time spent indoors versus outdoors. Over the past few years, the smoking rates have shown a steady decline in the United States and other developed countries. This decrease in smoking prevalence has led to a new shift in the primary risk factors associated with lung cancer. Although tobacco smoke historically served as the primary cause of lung cancer, the reduction in smoking rates has allowed other risk factors, such as radon exposure, to come to the forefront. Given that women in certain countries, on average, might spend more time indoors compared to men, they are potentially exposed to higher levels of radon. This increased exposure could explain the rising rates of lung cancer among female non-smokers. The theory is still in its nascent stages and requires further research and validation. However, if proven correct, it could significantly alter our understanding of lung cancer risk factors and lead to new prevention. It is therefore crucial to expedite the review and publication of this theory, given its potential implications for public health.

Liposomal factor VIII as an efficient pharmaceutical system for the treatment of hemophilia.

Objectives: Currently, the most important treatment approach for hemophilia type A is recombinant Factor VIII. However, due to its low retention time in the blood, the patients usually need successive injections. In addition, neutralization of injected proteins by antibodies complicates treatment. We examined the prolongation of the persistence time of injectable FVIII in the blood and the potential effects on survival using promising PEGylated liposomes (PEGLip) utilizing hydrogenated soy phosphatidylcholine (HSPC, Tm= 54.5 ºC) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC, Tm= - 2 ºC). Materials and Methods: Nanoliposomes with different percentages of PEG (3% and 5%) were obtained via the thin film hydration procedure and extrusion. Liposomal FVIII formulation was prepared and characterization was done. Results: The results revealed that the formulations are in the 80-120 nm range with uniform dispersion, which was confirmed using transmission electron microscopy (TEM) imaging. The phase transition temperature (Tm) of the liposomes was obtained by differential scanning calorimetry (DSC). With an attachment efficacy of approximately 87%, proteins bind non-covalently yet with a strong affinity to the exterior of PEGLip. The final formulations underwent additional examination. No significant change was observed in size, charge, and PDI between the FVIII-conjugated liposomal formulations and their liposomal nanoparticles. The selected formulations were injected into BALB/c mice. The circulation time and potential clotting effectiveness of PEGLip-FVIII are vastly improved over free protein, in non-hemophilic mice. Conclusion: The obtained results showed that using phospholipids with high Tm (HSPC) can improve the hemostatic efficiency of liposomes more than phospholipids with low Tm (POPC).

Blue Light and Digital Screens Revisited: A New Look at Blue Light from the Vision Quality, Circadian Rhythm and Cognitive Functions Perspective.

Research conducted over the years has established that artificial light at night (ALAN), particularly short wavelengths in the blue region (~400-500 nm), can disrupt the circadian rhythm, cause sleep disturbances, and lead to metabolic dysregulation. With the increasing number of people spending considerable amounts of time at home or work staring at digital screens such as smartphones, tablets, and laptops, the negative impacts of blue light are becoming more apparent. While blue wavelengths during the day can enhance attention and reaction times, they are disruptive at night and are associated with a wide range of health problems such as poor sleep quality, mental health problems, and increased risk of some cancers. The growing global concern over the detrimental effects of ALAN on human health is supported by epidemiological and experimental studies, which suggest that exposure to ALAN is associated with disorders like type 2 diabetes, obesity, and increased risk of breast and prostate cancer. Moreover, several studies have reported a connection between ALAN, night-shift work, reduced cognitive performance, and a higher likelihood of human errors. The purpose of this paper is to review the biological impacts of blue light exposure on human cognitive functions and vision quality. Additionally, studies indicating a potential link between exposure to blue light from digital screens and increased risk of breast cancer are also reviewed. However, more research is needed to fully comprehend the relationship between blue light exposure and adverse health effects, such as the risk of breast cancer.

Synthesis and functionalization of mucoadhesive mesoporous silica particles containing diphenhydramine for treatment of aphthous ulcers.

Introduction: Medications used to treat oral ulcers include corticosteroids, anesthetics, and antihistamines. These can be used as gels, mouthwashes, pastes, ointments, etc. Diphenhydramine hydrochloride (DPH) has local anesthetic properties that can help treat the aphthae. One of the drawbacks of the delivery to the transmucosal is the quick turnaround time of the gel, a mucous form that is located on the epithelial film surface. Methods: Therefore, it seems that the preparation of a carrier that has the characteristics of adhesive mucus can increase the duration of drug retention on the mucous surface. To solve this problem, mesoporous silica nanoparticles (MSNPs) were synthesized and functionalized with amino and thiol groups and suggested as a system of drug delivery. The properties and structure of MSNPs were investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and nitrogen adsorption-desorption isotherms (BET). Results: Our outcomes indicated that the average sizes of bare MSNPs (MSN), amino modified MSNPs (MSN-NH2), and thiol modified MSNPs (MSN-SH) were obtained to be 611, 655, and 655 nm respectively and the average pore size of MSN, MSN-NH2, and MSN-SH were about 2.42 nm, 2.42 nm, and 2.44 nm, respectively, according to the BJH (Barrett-Joyner-Halenda) pore size distribution. The release kinetics and release of DPH from mesoporous silica carriers were evaluated. Conclusion: Eventually, the mucoadhesive study and DPH-loaded particles were investigated. Also, the MSN-SH exhibited a high mucoadhesive capacity for buccal mucosa compared with MSN-NH2 and MSN.

Thiolated chitosan hydrogel-embedded niosomes: A promising crocin delivery system toward the management of aphthous stomatitis.

Aphthous stomatitis is a common inflammatory oral disease with challenging management. Crocin is a natural carotenoid that has shown great anti-inflammatory properties. The aim of this study was to develop thiolated chitosan (TCS)-based hydrogels containing niosomes to serve as a mucoadhesive crocin delivery system for aphthous stomatitis. Crocin-loaded niosomes were prepared and the impact of surfactant type, cholesterol content, and lipid to drug ratio on the characteristics of niosomes was evaluated. TCS was synthesized and the success of thiolation was investigated. The optimum niosomal formulation was loaded into the hydrogel and the hybrid system was characterized regarding the morphology, mucoadhesive properties, viscosity, chemical structure, in vitro drug release, and in vivo efficacy. The optimized niosome formulation showed 77% crocin entrapment, a particle diameter of 59 nm, and a zeta potential of -18 mV. The niosome-containing hydrogel exhibited pseudoplastic rheological behavior, mucoadhesive properties, suitable swelling, and sustained release of crocin. In vivo study revealed that the niosome-containing hydrogel improved ulcer healing and decreased the expression of tumor necrosis factor-alpha (TNF-α) and p53 while increasing the expression of vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA). Collectively, TCS hydrogel-embedded crocin-loaded niosomes is a promising therapeutic option for aphthous stomatitis. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Crocin (PubChem CID: 5281233) Chitosan (PubChem CID: 71853) Thioglycolic acid (PubChem CID: 1133) 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (PubChem CID: 2723939) 5,5'-dithiobis (2-nitrobenzoic acid) (PubChem CID: 6254) Cholesterol (PubChem CID: 5997).

The Effect of Psychological Interventions on Sexual and Marital Satisfaction: A Systematic Review and Meta-Analysis.

Background: Sexual and marital satisfaction play an important role in the stability of couples' relationships, so it is necessary to take a proper approach to promote them. This study aimed to identify and categorize psychological interventions affecting sexual satisfaction and marital satisfaction of women in Iran. Methods: An electronic systematic review search was conducted using the Persian and English databases of SID, Embase, PubMed, Scopus, Web of Science, Medline, Cochran library, and Google Scholar motor engine until 2021 to identify all relevant clinical trials and experimental and quasi-experimental studies assessing the effect of psychological interventions on sexual and marital satisfaction. Results: Totally, we retrieved 528 studies from the previously mentioned databases, of which, 38 met the eligibility criteria. The subgroup meta-analysis of 4 studies conducted showed that interventions based on individual consultations increase sexual satisfaction (MD: 2.94, 95% CI: -0.36 to 6.24, P= .23), (I 2 =30.83%). The subgroup meta-analysis of 10 studies conducted revealed that couple-based consultations increase marital satisfaction (MD: 5.93, 95% CI: -2.59 to 9.27, P=.95), (I 2 = 0%). Conclusion: The results of meta-analysis demonstrated the effect of counseling-based psychological interventions on increasing sexual and marital satisfaction of couples. However, further clinical trials are required before making a definitive conclusion.

How Reactivation of SARS-CoV-2 in Astronauts with Dysregulated Immune Systems Can Negatively Affect the Odds of Success in Future Space Missions.

We have previously reported that during future space missions the risk of severe COVID-19 infection will be a cardinal issue that needs careful attention. Our studies show that even with the most reliable pre-mission screening and quarantine strategies, astronauts with a latent (hidden, inactive, or dormant) SARS-CoV-2 infection might be sent to space. Given this consideration, an asymptomatic individual with dormant SARS-CoV-2 infection may successfully pass all the pre-launch medical tests. Then during a space mission such as a journey to Mars or beyond, when the immune system of these astronauts starts to weaken, the dormant infection may progress to a severe infection that possibly affects the chance of the mission's success. The effects of microgravity and the elevated space radiation are two key factors that should be evaluated. Furthermore, the limited size of the spacecraft, the proximity of crew members during flight operations, spacecraft atmospheric composition, limited exercise capability, effects of viral response to space radiation, and uncertainty in the likelihood of the virus to mutate and evolve during a space mission merit additional study.