Shiraz University of Medical Sciences

The skin microbiome, encompassing a variety of microorganisms, plays a critical role in skin health and function. Acne vulgaris, affecting approximately 9.4% of the global population, is a prevalent skin condition primarily targeting pilosebaceous units rich in sebaceous glands. The condition is influenced by factors such as hormonal changes, sebaceous gland dysfunction, and the activity of Cutibacterium acnes, a gram-positive bacterium linked to acne development. The skin’s immune system, particularly keratinocytes with pattern recognition receptors like Toll-like receptors (TLRs), plays a crucial role in recognizing and responding to bacterial presence. The onset of acne is often linked to adolescence, marked by significant hormonal fluctuations. Genetics also plays a role, with family history being a notable risk factor. Acne is characterized by distinct alterations in the C. acnes composition, with specific phylotypes associated with either commensal or pathogenic behavior. Traditional treatments include antibiotics, but the rise of antibiotic resistance has led to exploring alternative therapies, such as bacteriophage therapy. Bacteriophages offer a targeted approach to treating acne by targeting C. acnes strains, potentially reducing antibiotic resistance and enhancing treatment efficacy. Phage therapy shows promise, but further research is needed to fully understand its effectiveness and potential in clinical applications. Additionally, combining phages with antibiotics may offer a synergistic approach to overcoming antibiotic resistance and managing acne.

Despite the importance of finding replacements for fetal bovine serum (FBS), very few studies have focused on this subject. Historically, the use of animals and their derivatives in growth, reproduction, and physiological studies has raised several concerns. The supplementation of culture media with FBS, also known as fetal calf serum, continues to be widespread, despite its limitations in quality, reproducibility, and implications for animal welfare. Moreover, the presence of counterfeit and illegal products can adversely affect cell cultures and treatments, prompting the search for alternative solutions. To reduce reliance on FBS, various substitutes have been introduced, such as plant-derived proteins, bovine eye fluid, sericin protein, human platelet lysate, and inactivated coelomic fluid, which can provide roles similar to that of FBS. Therefore, it is essential to develop serum-free and animal supplement-free environments suitable for therapeutic and clinical applications, tailored to the specific needs of different cell types. Among the alternatives, plant-based options have gained attention as sustainable and ethical solutions. These include plant-derived peptones from sources like soy and wheat, which are rich in amino acids and peptides essential for mammalian cell growth, as well as plant protein hydrolysates from beans and peas that serve as sources of amino acids and growth factors. Plant extracts, especially from soy and various seeds, contain necessary proteins and growth factors, while phytohormones such as cytokinins and plant polysaccharides can help regulate cell growth. While these alternatives offer benefits like reduced costs and lower risks of disease transmission, further research is necessary to refine and align them with the specific requirements of diverse cell types. Graphical abstract

Alzheimer’s disease (AD) remains a formidable challenge in the field of neurodegenerative disorders, necessitating innovative therapeutic strategies. Nanomedicine, leveraging nanomaterials, has emerged as a promising avenue for AD treatment, with a key emphasis on overcoming the blood-brain barrier (BBB) to enhance drug delivery efficiency. This review provides a comprehensive analysis of recent advancements in the application of nanomaterials for AD therapy, highlighting their unique properties and functions. The blood-brain barrier, a complex physiological barrier, poses a significant hurdle for traditional drug delivery to the brain. Nanomedicine addresses this challenge by utilizing various nanomaterials such as liposomes, polymeric nanoparticles, and metal nanoparticles. These nanocarriers enable improved drug bioavailability, sustained release, and targeted delivery to specific brain regions affected by AD pathology. The review discusses the diverse range of nanomaterials employed in AD treatment, exploring their capacity to encapsulate therapeutic agents, modulate drug release kinetics, and enhance drug stability. Additionally, the multifunctionality of nanomaterials allows for simultaneous imaging and therapy, facilitating early diagnosis and intervention. Key aspects covered include the interaction of nanomaterials with Aβ aggregates, the role of antioxidants in mitigating oxidative stress, and the potential of nanomedicine in alleviating neuroinflammation associated with AD. Furthermore, the safety, biocompatibility, and toxicity profiles of various nanomaterials are scrutinized to ensure their clinical applicability. In conclusion, this review underscores the pivotal role of nanomedicine and nanomaterials in revolutionizing AD treatment strategies. By specifically addressing BBB challenges, these innovative approaches offer new avenues for targeted drug delivery and improved therapeutic outcomes in the complex landscape of Alzheimer’s disease.

Introduction This study aimed to explore the predictive and prognostic value of tumor-stromal ratio (TSR) and tumor budding (TB) in the recurrence and outcome of patients with Oral tongue squamous cell carcinoma (OTSCC). Methods All patients with OTSCC who underwent glossectomy with or without neck dissection in a tertiary center between 2010 and 2020 were included. The pathology slides of all patients were reviewed by a consulting pathologist. All pathologic features including tumor size, tumor grade, tumor thickness, surgical margin status, lymphovascular- and perineural invasion, T-stage, number of dissected, TB, TSR, and involved, tumor budding and tumor-stromal ratio were defined, we categorized the tumors as stroma-rich (low TSR) and stroma-poor (high TSR); as well as TB as low (0–4 buds) and high (≥ 5 buds). The inter-observer reliability of TB and TSR was assessed using the Kappa statistics analysis. Results A total of 109 patients, with a median age of 62 (range 19–88) years, were included. There was a significant correlation between TSR and tumor budding with other adverse pathologic features and prognostic factors. In univariate analysis, both stromal-rich tumors and tumor budding were poor prognostic factors for disease-free survival (DFS) and overall survival (OS). However, on multivariate analysis, N-stage, adjuvant radiotherapy, tumor size, depth of invasion (DOI) and tumor budding emerged as independent prognostic factors for DFS. Likewise, N-stage, and DOI were recognized as independent prognostic factors for OS. Conclusion Both TSR and TB are important histopathological parameters strongly linked to other pathologic prognostic indicators. Additionally, they play key roles in predicting tumor behavior, recurrence, and patient survival.

Oral cancer commonly affects various parts of the oral cavity, including the lips, tongue, gums, palate, and inner cheeks. Oral rehabilitation involves multiple approaches aimed at restoring and improving oral function, esthetics, and overall well-being. This study assessed the functional outcomes and quality of life in patients who underwent rehabilitation following an oral cancer diagnosis. A comprehensive literature search was performed across PubMed, Cochrane Library, Dimensions, ScienceDirect, CINAHL, and Google Scholar databases. The study included patients diagnosed with oral cancer who had undergone oral rehabilitation. Functional outcomes and quality of life were key selection criteria. The methodological quality of the included studies was assessed, and data were systematically extracted and analyzed. A significant relationship was observed between the type of maxillectomy and quality of life, with obturator retention and stability being critical factors. Radiotherapy was found to adversely impact oral function and implant survival rates, with a strong correlation between radiation treatment and reduced implant survival (p < 0.00001). Additionally, dentition and the timing of implant placement were associated with recurrence rates and adverse effects. The findings highlight the crucial role of oral rehabilitation in improving both functional outcomes and quality of life in oral cancer patients. This study underscores the importance of incorporating oral rehabilitation into oral cancer treatment to enhance patient recovery and overall health.

Overt hepatic encephalopathy (OHE) is a common complication of decompensated cirrhosis. This study aimed to assess the effects of probiotic, alone and in combination with zinc, on OHE recurrence, Model for End‐stage Liver Disease (MELD) score, ammonia level, health‐related quality of life (HRQoL), and sleep quality in patients with cirrhosis. We performed an open‐label randomized controlled trial on patients with decompensated cirrhosis with a previous history of OHE. Eligible patients (n = 45) were divided randomly into three equal groups to receive 30–45 mL lactulose syrup (2–4 times/day), lactulose and probiotic (4.5 × 10¹¹ CFU of bacteria, 2 times/day), or a combination of lactulose, probiotic, and zinc (25 mg) for 3 months. In this study, probiotic, alone or in combination with zinc, had no effect on OHE recurrence, ammonia levels, and MELD score. Mental aspects and total score of HRQoL were improved following probiotic and its combination with zinc, even after adjustment for baseline values, age, and sex. However, physical aspects of HRQoL and sleep quality were only improved by probiotic and zinc combination compared to the lactulose alone. Our findings showed improved HRQoL after treatment with probiotic, alone or in combination with zinc. However, sleep quality was influenced only by probiotic and zinc combination. Trail Registration: This study has been registered in the Iranian registry of clinical trials (IRCT20170609034406N9).

Background Road traffic collisions (RTCs) are the primary cause of death, which usually occur during the most crucial years of life, resulting in significant damage to health, society, and the economy. A wide variety of strategies and policies have been implemented around the world to minimize injuries and fatalities resulting from RTCs. This study aimed to systematically evaluate the effectiveness of interventions to reduce road traffic injuries (RTIs) in low-, middle-, and high-income countries. Methods The researchers looked for articles in many databases (PubMed, Web of Science, Google Scholar, Scopus, Embase, PsycInfo, OpenGrey, EconLit, IMEMR, AIM, Cochrane Injuries Group’s specialized register, Transport Research International Documentation (TRID), Transportation Research Information Services (TRIS) Database and the OECD’s Joint Transport Research Centre’s International Transport Research Documentation (ITRD)) about ways to reduce RTIs and included articles published up to December 2023. The study area did not matter; only RTI reduction methods were considered. Two people checked the articles to ensure being relevant and qualified and summarized what they found in the articles. Results A total of 852 articles were included in this systematic review. Most interventions were related to legislation (26.4%) and enforcement (17.0%), and the minor interventions were related to social marketing (4.9%) and traffic user safety (2.2%). Regarding income level (based on the latest classification of the World Bank—2020), more than half of the interventions (83.7%) took place in developed and high-income countries. Regarding intervention types, legislative and road safety interventions effectively reduced road traffic crashes by 26% and 16.7%, respectively. The results indicated that interventions in high-income countries were more likely to minimize RTCs than other countries. However, this difference was not statistically significant (p-value = 0.982). Most effective interventions (36.1%) were reported during the Decade of Action for Road Safety (2011–2020). Conclusion Current road safety efforts prioritize changing how people behave on the roads (training, laws, enforcement) over making the roads safer. Focusing on fixing the entire system rather than blaming drivers ("system repair") is necessary for a complete picture.

Background The co-occurrence of deep vein thrombosis with vascular aneurysms, whether venous or arterial, seems to be uncommon. This case report details a patient who experienced an isolated rupture of the right common iliac aneurysm 1 year after a deep vein thrombosis episode. Case presentation A 20-year-old Iranian female with a history of deep vein thrombosis DVT was treated with rivaroxaban but later presented with a ruptured right common iliac aneurysm. Surgical intervention was successful, but she developed persistent abdominal pain, small bowel obstruction, and a large pancreatic pseudocyst requiring drainage. Despite continued anticoagulant therapy, a thrombosed graft was observed, although the patient remains asymptomatic for organ ischemia or blood supply disorders. Conclusion The association of deep vein thrombosis with vascular aneurysms is a rare occurrence. It is important to consider aneurysm-related flow disturbances and compression effects on veins when evaluating patients with concurrent deep vein thrombosis and aneurysms. Behçet’s disease, Hughes–Stovin syndrome, chronic traumatic arteriovenous fistula, and recurrent nontyphoidal Salmonella bacteremia can also contribute to this association.

Placenta percreta, a rare variant of placenta accreta spectrum (PAS) disorders, poses a significant risk of life‐threatening hemorrhage associated with the adherent placenta. Bladder involvement signifies an even rarer incidence and may sometimes present solely with gross hematuria. Therefore, it is imperative to consider both microscopic and gross hematuria during pregnancy as alarming signs. Among 342 cases of PAS admitted to our hospital between 2016 and 2023, 48 patients were diagnosed with placenta percreta. Two patients, one at 18 weeks and the other at 25 weeks of pregnancy, were referred to our tertiary care center due to severe gross hematuria. Following thorough preoperative evaluation, both pregnancies were terminated due to their unstable conditions. The first case underwent an elective supracervical cesarean hysterectomy at the 19th week of gestation, while the second case underwent an emergency total cesarean hysterectomy due to lack of response to blood transfusions. Both procedures included bilateral internal iliac artery ligation. Postoperatively, patients recovered without any complications; however, the fetuses did not survive. Placenta percreta, protruding into the bladder, can lead to severe hematuria at any stage of pregnancy, increasing the risk of life‐threatening hemorrhage. Therefore, both microscopic and macroscopic hematuria during pregnancy should be considered alarming signs that require immediate attention. Early involvement of a urologist and a multidisciplinary medical team is also essential in suspected or confirmed cases of placenta percreta, as immediate surgical intervention may be necessary to ensure patient safety.

Objective Methylmalonic acidemia (MMAs) is known as a severe, complex, and lethal disorder of methylmalonate and cobalamin. The patients with MMA may have developmental, neurological, and metabolic disorders such as liver disease. Here, we aim to evaluate 6 Iranian patients suspected to MMA disorder. Study design We will provide genetic results, biochemical analysis and treatment for these patients. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) and variant screening in probands by whole exome sequencing (WES) were performed. Results A total of six homozygous variants were identified, including five previously identified variants and one novel variant, in the two MMA-causing genes as follows: c.577G > C, c.290 + 69G > T, c.662T > A, c.290 + 69G > T of MMAB, and c.100dupA, c.394 C > T of MMACHC. Sanger sequencing confirmed the identified variants. Additionally, metabolomics data analysis reliably identified elevated C3 and MMA levels, as well as abnormalities in the amino acid profile, indicating the presence of pathogenic variants. Conclusions Our findings expand the global spectrum of genotypes in MMA. While WES, combined with metabolomics and biochemical analysis, offers valuable insights for accurate diagnosis and subtyping of MMA, it is most beneficial in complex cases where clinical findings are unclear.

Background When utilized as an adjunct with antidepressants, antipsychotics, and other psychopharmacological drugs, certain amino acids, such as L-Theanine (LT), have shown potential effectiveness in enhancing the symptomatic outcomes of patients with mental disorders. Despite this, there is a lack of previous systematic reviews examining these associations. Therefore, we conducted a systematic review of randomized controlled trials examining these relationships. Methods A comprehensive systematic review was conducted, scouring six electronic databases (PubMed, Scopus, PsycINFO, Web of Science, CINAHL Complete, and Cochrane) from their inception up to June 2023, specifically focusing on randomized controlled trials that investigated the effects of LT supplementation on the outcomes of patients with mental health disorders. The Cochrane Risk of Bias Tool for Randomized Trials was employed to assess the quality of the included studies. Results Among the 419 publications identified, 11 studies from six countries — Israel, Iran, the USA, Japan, Australia, and Italy — were included in the final analysis. These studies covered a range of mental disorders, including schizophrenia, Attention-Deficit/Hyperactivity Disorder (ADHD), Obsessive-Compulsive Disorder (OCD), Major Depressive Disorder (MDD), sleep disorders, Generalized Anxiety Disorder (GAD), and Tourette syndrome. The findings demonstrated that LT supplementation reduced psychiatric symptoms more effectively than control conditions in individuals with schizophrenia, anxiety disorders, and ADHD. Conclusions The findings from this systematic review suggest that LT supplementation significantly reduced psychiatric symptoms more effectively than control conditions in individuals with schizophrenia, anxiety disorders, and ADHD. However, further studies are essential to validate these findings, deepen the understanding of the observed effects, and explore the mechanisms underlying these associations.

Introduction The study aimed to investigate the impact of an information-based preparation program on the psychological safety of adolescents admitted to pediatric wards, emphasizing the importance of enhancing patient safety. Methods This quasi-experimental study was conducted among 98 adolescents admitted to pediatric wards at Namazi Hospital, managed by Shiraz University of Medical Sciences, in 2021. The participants were randomly assigned to either an intervention group or a control group using an electronic randomization table. The intervention group received an information-based preparation program, while the control group followed routine care. Adolescents completed the Psychological Safety Questionnaire after admission and at discharge. Data were analyzed using SPSS (Version 22), with a significance level of 0.05. Results The mean psychological safety scores before the intervention were 136.73 ± 17.30 in the control group and 141.03 ± 16.34 in the intervention group, with no significant difference between the two groups (p = 0.20). After the intervention, the mean scores were 136.65 ± 19.01 in the control group and 145.50 ± 14.05 in the intervention group. A comparison of the mean psychological safety scores showed a significant difference between the two groups after the intervention (p = 0.01). Conclusions The findings of this study indicate that the information-based preparation program positively affected the psychological safety of hospitalized adolescents. Therefore, it is recommended that nurses incorporate this method into therapeutic programs for hospitalized adolescents to enhance their psychological safety effectively.

This study investigated the potential of MET kinase inhibitors, cabozantinib, crizotinib, and PHA665752, in reversing multidrug resistance (MDR) mediated by ABCB1 in cancer cells. The accumulation of the fluorescent probe, Rhodamine 123, was assessed using flow cytometry and fluorescence microscopy in MDR MES-SA/DX5 and parental cells. The growth inhibitory activity of MET inhibitors as monotherapies and in combination with chemotherapeutic drugs was evaluated by MTT assay. CalcuSyn software was used to analyze the combination index (CI) as an index of drug-drug interaction in combination treatments. Results showed that at concentrations of 5, and 25 μM, c-MET inhibitors significantly increased Rhodamine 123 accumulation in MDR cells, with ratios up to 17.8 compared to control cells, while exhibiting no effect in parental cells. Additionally, the combination of c-MET inhibitors with the chemotherapeutic agent doxorubicin synergistically enhanced cytotoxicity in MDR cells, as evidenced by combination index (CI) values of 0.54 ± 0.08, 0.69 ± 0.1, and 0.85 ± 0.07 for cabozantinib, crizotinib, and PHA665752, respectively. While all three c-MET inhibitors stimulated ABCB1 ATPase activity in different manners at certain concentrations, PHA-665752 suppressed it at high concentration. In silico analysis also suggested that the transmembrane domains (TMD) of ABCB1 transporters could be considered potential target for these agents. Our results suggest that c-MET inhibitors can serve as promising MDR reversal agents in ABCB1-medicated drug-resistant cancer cells.

We report the case of a 68-year-old man with sclerocornea with corneal plana who presented with progressive pseudophakic bullous keratopathy. He underwent Descemet stripping automated endothelial keratoplasty. Although a single air bubble was needed for the initial lenticule detachment, there was notable improvement in corneal clarity and visual acuity over the course of a year.