Metal-Organic Frameworks for Cisplatin Delivery to Cancer Cells: A Molecular Dynamics Simulation.

Metal-organic frameworks (MOFs) are utilized as nanocarriers to enhance the efficiency of chemotherapy drugs, including cisplatin, which exhibit limitations such as side effects and resistance mechanisms. To evaluate the role of MOFs, we employed a molecular dynamics simulation, which, unlike other experiments, is cost-effective, less dangerous, and provides accurate results. Furthermore, we conducted molecular docking simulations to understand the interaction between cisplatin and MOF, as well as their internal interactions and how they bind to each other. Cisplatin and MOF molecules were parametrized using the Avogadro software and x2top command in GROMACS 5.1.2 and optimized by CP2K software; the Charmm-GUI site parametrized the cell cancer membrane. Three molecular dynamics simulations were conducted in four stages at various pHs, followed by simulated umbrella sampling. The simulations analyzed the pH responsiveness, total energy, Gibbs free energy, gyration radius, radial distribution function (RDF), solvent accessible surface area, and nanoparticles' toxicity. Results demonstrated that a neutral pH level (7.4) has greater adsorption and interaction compared to acidic pH values (6.4 and 5.4) because it displays the highest total energy (-17.1 kJ/mol), the highest RDF value (6.66), and the shortest distance (0.51 nm). Furthermore, the combination of cisplatin and MOFs displayed increased penetration compared to that of their individual forms. This study highlights the suitability of MOFs as nanocarriers and identifies the optimal pH values for desirable outcomes. Thus, it provides future studies with appropriate data to conduct their experiments in assessing MOFs.

Physical and psychosocial challenges of people with gender dysphoria: a content analysis study.

BACKGROUND: The mismatch between the gender experienced by a person and the gender attributed to him/her leads to gender dysphoria. It seems that people's perception of gender dysphoria is affected by individual, cultural, and sociological factors and these factors affect different aspects of their biological, psychological, and social health. To this end, this qualitative study aimed to identify the physical, psychological, and social challenges of people with gender dysphoria referring to the Department of forensic medicine in Iran. METHODS: This qualitative study was conducted using conventional content analysis on 9 individuals who were selected through purposive sampling. A total of 16 interviews were conducted with 9 participants. Each interview lasted 60-90 min. The participants' gender dysphoria was confirmed by the Department of forensic medicine. The data were collected through face-to-face semi-structured interviews with the participants. RESULTS: The data revealed 3 main categories and 10 subcategories. The main categories were living in agony, confusion, and social concerns. The subcategories were annoying physical characteristics, mental suffering, disturbing sexual changes, concerns about public reaction, helplessness, surrender, the final solution, retreating to isolation, stressful family conditions, and lack of public recognition. CONCLUSION: The findings showed that people with gender dysphoria suffer from some problems including living in agony, confusion, and social concerns. Each of these problems is associated with several challenges. It seems that most of the challenges faced by people with gender dysphoria are caused by unawareness of their conditions by the family and the public, which in turn is caused by the failure of related organizations and experts in this field to provide adequate information about the conditions of these people. Thus, the findings of the present study can have some implications for resolving the challenges faced by people with gender dysphoria.

Parenting styles, maladaptive coping styles, and disturbed eating attitudes and behaviors: a multiple mediation analysis in patients with feeding and eating disorders.

Background: Although preliminary studies support the roles of unhealthy parenting styles and maladaptive coping styles in increasing rates of disturbed eating attitudes and behaviors (EAB) and clinically significant feeding and eating disorders (FED), underlying mechanisms have not been well-recognized. This study aims to investigate the factors associated with disturbed EAB and the mediating roles of overcompensation and avoidance coping styles in the relationship between different types of parenting styles and disturbed EAB among patients with FED. Methods: A total of 102 patients with FED in Zahedan, Iran, participating in this cross-sectional study (from April to March 2022) completed a sociodemographic information form and self-report measures of parenting styles, maladaptive coping styles, and EAB. Model 4 of Hayes' PROCESS macro in SPSS was employed to identify and explain the mechanism or process that underlies an observed relationship between study variables. Results: The results showed that authoritarian parenting style, overcompensation and avoidance coping styles, and female gender might be related to disturbed EAB. The overall hypothesis that overcompensation and avoidance coping styles mediated the effect of fathers' and mothers' authoritarian parenting styles on disturbed EAB was also supported. Conclusions: Our findings highlighted the necessity of evaluating particular unhealthy parenting styles and maladaptive coping styles as the important possible risk factors in the development and maintenance of higher level of disturbance in EAB among patients with FED. However, more research is needed to explore individual, family, and peer risk factors for disturbed EAB among these patients.

Prevalence of Domestic Violence Against Women Undergoing Methadone Maintenance Therapy Programs and its Related Risk Factors.

Background: This study aimed to investigate the prevalence of domestic violence (DV) against women who are undergoing methadone maintenance therapy (MMT) and its related risk factors. Methods: This case-control study was conducted on 195 women who were under MMT and a control group consisting of 195 women who were not under it in the city of Zahedan from 22 May to 1 December 2019. Data were collected using a questionnaire for the measurement of violence against women and a sociodemographic questionnaire. In order to analyze the data, the t test, analysis of variance (ANOVA), Pearson's correlation, and multiple regression analysis were used. Findings: In the case group, 67.2% of participants had experienced DV during the past year. In the control group, the prevalence was 78.5%. The rate of more than one occasion of DV was significantly higher in the group who were under MMT (P<0.05). The most common type of violence was mental abuse. Physical, sexual, and economic abuses were in the next ranks. Important predictors of DV, in order of importance, were: the women's low educational level, smoking, income level, and polygamy (P<0.05). Conclusion: MMT is not a risk factor for DV. It seems that the rate of DV against women in Zahedan is very high. The prevalence of recurrent DV in women under MMT was higher than in the general population.

Promethazine hydrochloride reduces children's agitation during ocular examination for trauma.

Examination and intervention are always the causes of agitation, anxiety, and fear in children's lives. This study aimed to investigate the effectiveness of promethazine hydrochloride in reducing children's agitation during the ocular examination for trauma. In this interventional-clinical trial study, a total of 62 children referred to Al-Zahra Ophthalmology Hospital in Zahedan, Iran, were evaluated in two matched groups (case (n = 31) and control (n = 31)) for an initial examination of ocular trauma. Finally, the intervention was performed (giving placebo or promethazine hydrochloride cough syrup 20 minutes before the initial ocular examination at 0.5 mg/kg), and the demographic information form and researcher-made questionnaire modeled on the Cohen-Mansfield Agitation Inventory (CMAI) were completed. The obtained results revealed that the mean scores of physical/aggressive behaviors (p ˂ 0.001), physical/nonaggressive behaviors (p = 0.013), verbal/aggressive behaviors (p ˂ 0.001), and hiding behaviors (p ˂ 0.001) were significantly lower in the promethazine hydrochloride-receiving group than the placebo group. These findings demonstrated that promethazine hydrochloride cough syrup facilitated the examination among the pediatric patients who suffered from traumatic ocular injuries. However, further studies in this field need to be carried out through randomized controlled trials.

The Persian version of the Calgary Depression Scale for Schizophrenia (CDSS-P).

Determining depression symptoms in schizophrenic patients is a challenging process because of a degree of similarity between depression symptoms and negative symptoms and the extrapyramidal side effects of neuroleptic drugs, but it is crucial to evaluate and measure depression among patients with schizophrenia for a better clinical outcome. The Calgary Depression Scale for Schizophrenia (CDSS) is a valid and reliable instrument used for the evaluation of depression in schizophrenia. This study aimed to determine the psychometric properties of the Persian version of CDSS in a sample of people with schizophrenia. Clinical interviews were conducted with 95 schizophrenic patients (40 inpatients and 55 outpatients), who were assessed with the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HDRS-17 and HDRS-24 items), and the Calgary Depression Rating Scale (CDSS). Then an exploratory factor analysis was conducted to determine correlations between scales, Cronbach's alpha, and cutoff scores. The factor analysis led to the extraction of a unifactorial solution. The CDSS had significant relationships with PANSS Negative and PANSS General. However, it had no significant relationship with PANSS Positive and the PANSS Total. The CDSS also had significant relationships with HDRS-17 and HDRS-24. In addition, Cronbach's alpha of total score, test-retest reliability, and cutoff score were estimated at 0.86, 0.82, and 8 (sensitivity = 0.79 and specificity = 0.84), respectively. The findings support the CDSS unifactorial approach. Results also showed that the CDSS Persian version had acceptable psychometric properties; thus, it could be employed to evaluate depression among schizophrenic patients.

Enhancing analgesic and anti-inflammatory effects of capsaicin when loaded into olive oil nanoemulsion: An in vivo study.

Topical preparations of capsaicin, the major pungent ingredient of hot pepper, are being used for management of pain and inflammatory disorders. Purpose of this study was to use nanoemulsion as an effective topical drug carrier for in vivo delivery of capsaicin. An oil-in-water nanoemulsion containing capsaicin was prepared by spontaneous emulsification method. Optimized formulation showed a median droplet diameter (d50) of 13-14 nm and was stable for more than 8 months in room and harsh temperature (i.e. 4 and 45 °C). The nanoemulsion was then formulated into topical cream and gel to compare its efficacy and safety profiles with conventional cream of capsaicin. Skin irritation study showed that topical application of capsaicin nanoemulsion was safe and no sign of edema and erythema was observed. The preparation significantly decreased inflammation of rats paw edema compared to the commercial cream and control group, especially in 2nd and 3rd hours of the test. Also, pretreated rats with capsaicin nanoemulsion gel showed very good resistance to the pain caused by heat stimulus. In total, the selected nanoemulsion showed great potential as carrier for topical delivery of capsaicin for improving its analgesic and anti-inflammatory effects. It was also found that the topical gel outperforms the topical cream as dosage form for the nanoemulsion.

The Effect of Topical Substance-P Plus Insulin-like Growth Factor-1 (IGF-1) on Epithelial Healing After Photorefractive Keratectomy in Rabbits.

PURPOSE: To determine whether topical Substance-P (SP) plus insulin-like growth factor-1 (IGF-1) can improve corneal healing after photorefractive surface ablation in a rabbit. METHODS: After a 9.0-mm corneal de-epithelialization using a combination of chemical (18% alcohol) and mechanical debridement, excimer photorefractive surface ablation was performed bilaterally in eight rabbits (16 eyes) with an 8.0-mm ablation zone and 70-µm depth. The right eye was treated with SP (250 µg/mL) and IGF-1 (25 ng/mL) in hyaluronic acid, one drop twice a day, and the other eye treated with only hyaluronic acid. The epithelial healing process was documented photographically twice a day until healing was complete. Six rabbits were sacrificed 6 weeks after photorefractive keratectomy (PRK) and corneas examined histologically. RESULTS: Seven of eight rabbit eyes treated with SP/IGF-1 healed in a shorter time than the untreated eye. For rabbit #6, both eyes healed at the same time. The average healing time (total time until wound closure) for the treated eyes was 99 hours, while the average healing time for the untreated eyes was 170 hours (P = 0.0490). A persistent epithelial defect was found in two of the nontreated eyes but none in the treated eyes. Corneal pathology showed some degree of epithelial separation in the central corneal wound in three out of six nontreated eyes and in just the treated eye of rabbit #6. CONCLUSION: Topical SP plus IGF-1 increases the epithelial healing rate after PRK. There may have been beneficial effects upon cell adhesion as well. TRANSLATIONAL RELEVANCE: Better and faster healing.

L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: A randomized double-blind study.

BACKGROUND: Dysregulation of glutamate is implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Consistently, glutamate-modulating agents, such as riluzole and memantine have been used in OCD treatment. Previous research has identified some neuroprotective role for L-carnosine potentially via its modulatory effect on glutamate. Here, we assessed the efficacy of L-carnosine as adjuvant to fluvoxamine in OCD treatment. METHODS: Forty-four patients diagnosed with moderate to severe OCD were recruited in a randomized double-blind trial. Patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10 weeks. The Yale- Brown Obsessive Compulsive Scale (Y-BOCS) was used for assessing the severity of symptoms at baseline and at weeks 4, 8, and 10. RESULTS: General linear model repeated measure showed significant effects for Time × Treatment interaction on total Y-BOCS [F (2.10, 88.42) = 8.66, p < 0.001], obsession [F (1.88, 79.34) = 4.96, p = 0.01] and compulsion [F (1.88, 79.11) = 4.57, p = 0.01]. At week 10, the change from baseline in Y-BOCS scores was 8.86 ± 2.89 (mean ± SD) in the L-carnosine group compared to 5.86 ± 2.88 in the placebo group. CONCLUSION: L-carnosine results in significant reduction of obsessive-compulsive symptoms when used as an adjuvant to fluvoxamine.