Search

Abstract Background Diurnal and nocturnal mammals have evolved distinct pathways to optimize survival for their chronotype-specific lifestyles. Conventional rodent models, being nocturnal, may not sufficiently recapitulate the biology of diurnal humans in health and disease. Although diurnal rodents are potentially advantageous for translational research, until recently, they have not been genetically tractable. The present study aims to address this major limitation by developing experimental procedures necessary for genome editing in a well-established diurnal rodent model, the Nile grass rat (Arvicanthis niloticus). Results A superovulation protocol was established, which yielded nearly 30 eggs per female grass rat. Fertilized eggs were cultured in a modified rat 1-cell embryo culture medium (mR1ECM), in which grass rat embryos developed from the 1-cell stage into blastocysts. A CRISPR-based approach was then used for gene editing in vivo and in vitro, targeting Retinoic acid-induced 1 (Rai1), the causal gene for Smith-Magenis Syndrome, a neurodevelopmental disorder. The CRISPR reagents were delivered in vivo by electroporation using an improved Genome-editing via Oviductal Nucleic Acids Delivery (i-GONAD) method. The in vivo approach produced several edited founder grass rats with Rai1 null mutations, which showed stable transmission of the targeted allele to the next generation. CRISPR reagents were also microinjected into 2-cell embryos in vitro. Large deletion of the Rai1 gene was confirmed in 70% of the embryos injected, demonstrating high-efficiency genome editing in vitro. Conclusion We have established a set of methods that enabled the first successful CRISPR-based genome editing in Nile grass rats. The methods developed will guide future genome editing of this and other diurnal rodent species, which will promote greater utility of these models in basic and translational research.

Abstract Purpose An elevated number of circulating neutrophils is a poor prognostic factor for breast cancer, where evidence of bone marrow cancer-dependent priming is found. However, how early this priming is detectable remains unclear. Patients and methods Here, we investigate changes in circulating neutrophils from newly diagnosed breast cancer patients before any therapeutic interventions. To do this, we assessed their lifespan and their broader intracellular kinase network activation states by using the Pamgene Kinome assay which measures the activity of neutrophil kinases. Results We found sub-type specific L-selectin (CD62L) changes in circulating neutrophils as well as perturbations in their overall global kinase activity. Strikingly, breast cancer patients of different subtypes (HR+, HER2+, triple negative) exhibited distinct neutrophil kinase activity patterns indicating that quantifiable perturbations can be detected in circulating neutrophils from early breast cancer patients, that are sensitive to both hormonal and HER-2 status. We also detected an increase in neutrophils lifespan in cancer patients, independently of tumour subtype. Conclusions Our results suggest that the tumour-specific kinase activation patterns in circulating neutrophils may be used in conjunction with other markers to identify patients with cancer from those harbouring only benign lesions of the breast. Given the important role neutrophil in breast cancer progression, the significance of this sub-type of specific priming warrants further investigation.

Abstract Background Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge. Results Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients. Conclusions These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of “dysbiosis” that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

Abstract Background Recent studies show an increase in the prevalence of iron deficiency anemia (IDA) worldwide and a concomitant rise in the number of revision total knee arthroplasty (RTKA). The literature evaluating the association between IDA and perioperative outcomes following RTKA are limited. Therefore, the purpose of this study was to determine whether IDA patients undergoing RTKA have higher rates of (1) in-hospital lengths of stay (LOS), (2) complications; and (3) costs. Methods Using International Classification of Disease, Ninth Revision (ICD-9) and Current Procedural Terminology (CPT), a retrospective query was performed from January 1st, 2005 to March 31st, 2014. The inclusion criteria consisted of those patients who have IDA undergoing RTKA. Study group patients were 1:5 ratio matched to a comparison cohort by age, sex, and various comorbidities: coronary artery disease, chronic obstructive pulmonary disease, diabetes mellitus, hyperlipidemia, hypertension, obesity, and tobacco use, yielding a total of 106,534 patients within the study (n = 17,784) and control (n = 88,750) cohorts. Outcomes assessed included: in-hospital LOS, costs of care, and medical complications. Multivariate Logistic regression analyses were used to calculate the odds-ratios (OR) and respective 95% confidence intervals (95%CI). Welch’s t-tests were used to compare in-hospital LOS and costs of care. Following Bonferroni-correction, a P-value less than 0.001 was considered statistically significant. Results IDA patients undergoing RTKA were found to have significantly higher in-hospital LOS (4-days vs. 3-days, P

Abstract Background Dependent adults have been shown to have a greater experience of oral health deterioration and orofacial pain. This is partly because their non-dental caregivers may not easily identify oral health problems and orofacial pain experienced by them. Thus, this systematic review aimed to investigate measurement properties, interpretability and feasibility of instruments assessing oral health and orofacial pain in dependent adults, which can be used by the non-dental caregivers to establish oral care plans for those who are dependent upon them. Methods Seven bibliographic databases were searched: MEDLINE, Embase, CINAHL, CENTRAL, HTA, OATD and OpenGrey. Citations and reference lists of the included studies were also manually searched. Two authors independently screened titles and abstracts, and then full texts. A quality assessment of included studies was conducted independently by two authors using the COSMIN Risk of Bias checklist. The best evidence synthesis method was used to synthesise results from different studies for each measurement property per measurement instrument by integrating the overall rating for each measurement property per measurement instrument with its quality level of evidence. Results Nineteen eligible studies were included, which reported the development, measurement properties’ evaluation, interpretability and feasibility of nine oral health and three orofacial pain measurement instruments. Methodological quality of the included studies ranged from very good to inadequate. None of the identified measurement instruments has been adequately and comprehensively tested. Conclusions While several measurement instruments were identified in this systematic review, more evidence is needed to be able to more comprehensively evaluate these instruments. Among those identified, the OPS-NVI demonstrated sufficient construct validity, while the OHAT and the THROAT demonstrated sufficient reliability. These instruments therefore have potential for future use with more confidence once other measurement properties, interpretability and feasibility have been sufficiently tested and evaluated.

Abstract Objective This study aims to assess the economic burden of prostate cancer in Iran by analyzing direct medical costs, direct non-medical costs, and indirect costs. We conducted a cross-sectional cost-of-illness study in Khorramabad, located in western Iran, during 2023, using a prevalence-based, bottom-up approach. Data were collected from 285 prostate cancer patients using questionnaires, interviews, and patient records. Results Our study estimated the economic burden of prostate cancer at $744,990. Direct medical costs accounted for 63.50% of this, totaling $153,330, with therapy being the largest component. Direct non-medical costs were $62,130, and indirect costs from productivity losses were $209,760. The calculated overall cost per patient was $2,614.88. Extrapolating from the 2021 Global Burden of Disease data, which reported approximately 83,000 prostate cancer patients in Iran, the national economic burden is estimated at $217,034,040. This substantial burden highlights the need for improved insurance coverage and early detection. The findings suggest that policymakers and healthcare providers in Iran should develop standardized cost analysis methods and enhance financial protection to alleviate economic strain and improve healthcare outcomes and sustainability.

Abstract Background Antibiotics are widely used in the pediatric population, and their inappropriate use contributes to antibiotic resistance, which is a growing concern in developing countries. Therefore, this national cross-sectional study aimed to assess community pharmacists’ knowledge, attitudes and practices regarding appropriate antibiotic use and dosing in pediatric patients and to explore the barriers to such use in Palestine. Methods A questionnaire-based survey was conducted among community pharmacists on the West Bank, Palestine, from September 2022 to March 2023. The survey assessed the pharmacists’ sociodemographic characteristics; knowledge, practices, and attitudes toward antibiotic use; and understanding of antibiotic dosing. The data were analyzed using descriptive statistics, and the factors affecting pharmacists’ knowledge were evaluated. Results The study included 301 community pharmacists, with an average age of 30.06 years, who were primarily female (75.1%). The majority of the pharmacists (80.1%) correctly believed that antibiotics are effective against bacterial infections. However, 18.3% believed that antibiotics are effective against viruses. While 61.8% knew that antibiotics kill germs, 32.0% were unaware that not all antibiotics require refrigeration. Furthermore, 67.8% were aware that antibiotics do not speed up recovery from diarrhea. Over 99% of the participants recognized that antibiotic resistance developed due to various resistant mechanisms. The majority (78.7%) believed that each infection needed a different antibiotic. Pharmacists demonstrated reasonable knowledge of antibiotic dosing in case scenarios. Knowledge was positively correlated with years of experience (P = 0.001). Conclusions This study revealed that community pharmacy professionals have a good understanding of antibiotic usage in pediatric patients. The findings suggest that professional expertise and quality training improve healthcare services. However, the results may not be universally applicable, as identifying knowledge gaps is necessary to help with the development of focused interventions. Therefore, ongoing educational initiatives, awareness campaigns and antibiotic stewardship programs are recommended.

Abstract Background Fluoroquinolones are the most commonly prescribed antibiotics. Because of their known tendency to drive antimicrobial resistance, their prescribing patterns need to be more restricted. This study aimed to describe the clinical practice of fluoroquinolone prescription, dose adjustments for renal impairment patients and bacterial resistance profiles, eventually providing evidence-based recommendations to optimize antibiotic prescribing practices in the local population. Methods This retrospective, cross-sectional study was conducted at An-Najah National University Hospital in Palestine. The data were collected from admitted patients who were given ciprofloxacin or levofloxacin from July 2021 to June 2023. Data from 692 inpatients across various hospital departments were examined (409 for levofloxacin and 283 for ciprofloxacin). Statistical analysis was performed via IBM SPSS version 23.0 to summarize the demographic, clinical, and epidemiological data. Results The sociodemographic profile revealed diverse age distributions, with 25.4% and 39% older than 50 years for ciprofloxacin and levofloxacin, respectively. Ciprofloxacin was predominantly used in the oncology department (28.2%), with surgical prophylaxis (22.6%) and febrile or afebrile neutropenia (21.1%) being the most common indications. Levofloxacin was predominantly used in the medical ward (45.7%), mainly for lower respiratory tract infection (58.8%) and prophylaxis for bone marrow transplantation (16.5%). Enterococcus and methicillin-resistant Staphylococcus aureus were the most commonly isolated pathogens, with 62.5% of the isolates demonstrating resistance to ciprofloxacin. Moreover, extended-spectrum beta-lactamase-producing Enterobacterales were the most common pathogen isolated, with 33.3% being resistant to levofloxacin. Statistical analysis revealed a significant association between the choice of antibiotic and the approach to therapy. Levofloxacin was significantly more likely than ciprofloxacin to be used as empiric therapy (p

Background The quality of the learning environment significantly impacts student engagement and professional identity formation in health professions education. Despite global recognition of its importance, research on student perceptions of learning environments across different health education programs is scarce. This study aimed to explore how health professional students perceive their learning environment and its influence on their professional identity development. Methods An explanatory mixed-methods approach was employed. In the quantitative phase, the Dundee Ready Education Environment Measure [Minimum–Maximum possible scores = 0–200] and Macleod Clark Professional Identity Scale [Minimum–Maximum possible scores = 1–45] were administered to Qatar University-Health students (N = 908), with a minimum required sample size of 271 students. Data were analyzed using SPSS, including descriptive statistics and inferential analysis. In the qualitative phase, seven focus groups (FGs) were conducted online via Microsoft Teams. FGs were guided by a topic guide developed from the quantitative results and the framework proposed by Gruppen et al. (Acad Med 94:969-74, 2019), transcribed verbatim, and thematically analyzed using NVIVO®. Results The questionnaire response rate was 57.8% (525 responses out of 908), with a usability rate of 74.3% (390 responses out of 525) after excluding students who only completed the demographic section. The study indicated a “more positive than negative” perception of the learning environment (Median [IQR] = 132 [116–174], Minimum–Maximum obtained scores = 43–185), and a “good” perception of their professional identity (Median [IQR] = 24 [22–27], Minimum–Maximum obtained scores = 3–36). Qualitative data confirmed that the learning environment was supportive in developing competence, interpersonal skills, and professional identity, though opinions on emotional support adequacy were mixed. Key attributes of an ideal learning environment included mentorship programs, a reward system, and measures to address fatigue and boredom. Conclusions The learning environment at QU-Health was effective in developing competence and interpersonal skills. Students' perceptions of their learning environment positively correlated with their professional identity. Ideal environments should include mentorship programs, a reward system, and strategies to address fatigue and boredom, emphasizing the need for ongoing improvements in learning environments to enhance student satisfaction, professional identity development, and high-quality patient care.

Abstract Bioactive agents have demonstrated regenerative potential for cell-free bone tissue engineering. Nevertheless, certain challenges persist, including ineffective delivery methods and confined therapeutic potency. Here, we demonstrated that the biomimetic calcium phosphate coating system (BioCaP) could effectively uptake and slowly release the incorporated bioactive agents compared to the surface absorption system via osteoclast-mediated degradation of BioCaP coatings. The release kinetics were determined as a function of time. The release rate was stable without remarkable burst release during the first 1 day, followed by a sustained release from day 7 to day 19. Then, we developed the bi-functional BioCaP-coated silk fibroin scaffolds enabling the effective co-delivery of TGF-β3 and BMP-2 (SFI-T/SFI-B) and the corresponding slow release of TGF-β3 and BMP-2 exhibited superior potential in promoting chondrogenesis and osteogenesis without impairing cell vitality in vitro. The SFI-T/SFI-B scaffolds could improve cartilage and bone regeneration in 5 × 4 mm rabbit osteochondral (OC) defect. These findings indicate that the biomimetic calcium-phosphate coated silk fibroin scaffolds with slowly co-released TGF-β3 and BMP-2 effectively promote the repair of OC defects, hence facilitating the future clinical translation of controlled drug delivery in tissue engineering. Graphic Abstract

Abstract Background Premenstrual dysphoric disorder (PMDD) is a debilitating condition, affecting women of reproductive age. It is characterized by severe periodic physical and psychological symptoms, which end after the onset of menstruation. This study aimed to evaluate the effectiveness of emotion-focused therapy (EFT) for PMDD patients. Methods A total of 48 PMDD women, in the age range of 18–44 years, were randomly assigned to two intervention and control groups. The intervention group participated in 16 weeks of EFT treatment, while the control group was selected based on the waiting list (waitlist control group) and followed-up after three months. Forty-four patients finally completed this study. The participants completed the Premenstrual Syndrome Screening Tool (PSST), Difficulties in Emotion Regulation Scale (DERS), and Depression Anxiety Stress Scale-21 (DASS-21) in the first premenstrual period before treatment, the first premenstrual period after treatment, and the premenstrual period three months after treatment. Results Based on the repeated measure analysis of variances, the total score of DERS and the total score of PSST decreased significantly (P 0.05). Conclusion Based on the present results, EFT can be an effective treatment for alleviating the symptoms of PMDD. This treatment can reduce the emotion regulation difficulties of women with PMDD and alleviate the symptoms of depression and stress. Trial registration Iranian Registry of Clinical Trials, IRCT ID: IRCT20220920055998N1, Registered on: 12/2/2023.

Abstract Background Endometriosis affects 10–15% of women of reproductive age and is considered a critical gynecological problem. Endometriosis causes pain and infertility, both of which can impair the patient’s quality of life. Sleep disorders account for the most bothersome presentation of impaired quality of life. This study investigated the frequency and severity of sleep disorders in women with endometriosis. Methods In this analytical cross-sectional study, 665 women referred to three hospitals in Tehran, Rasool-e-Akram, Pars, and Nikan, were included (463 patients with endometriosis and 202 women without endometriosis). All of them were informed about the study design and the aim of the research, and then they were asked to sign the consent form and complete the Pittsburgh Sleep Quality Index (PSQI). After data gathering and entering, they were analyzed by SPSS version 22 and were considered significant with P

Abstract Background Standardized patients are considered a significant educational method in medical sciences and have been successfully employed for many years. This study was conducted with the aim of explaining the experience of standardized patients participating in the education of medical student. Method A qualitative content analysis approach was used. This study was conducted at Standardized Patient Center, Tehran University of Medical Sciences, Tehran, Iran, May to February 2022. Fifteen standard patients were selected through purposive sampling with maximum variation. Semi-structured, in-depth, face-to-face interviews were conducted with standard patients. The average duration of the interviews was 60 to 90 min. Data were transcribed and analyzed using the Graneheim and Lundman approach. Results A passport for the future and duality of feelings were the two main themes identified in this study with six subthemes. One of the main themes was passport for the future with subthemes creative, participation in educating future generation, reflection and another theme was duality of feeling with subthemes feeling of value, guilty conscience, and fear of judgment by others. Conclusion The participants expressed having mixed feelings about their role as standard patients. They felt conflicted because they were compensated for their participation, which made them worry about being judged by others and feel guilty about taking the fee. Therefore, it is recommended to conduct further studies in this area.

Abstract Background Nursing students are faced with a variety of challenges that demand effective cognitive and emotional resources. The physical and psychological well-being of the students plays a key part in the public health of the community. Despite the special lifestyle of nursing students, few studies have addressed chronic pain in this population. Accordingly, the present study aims to identify the predictors of chronic pain among nursing students. Methods This cross-sectional study was conducted on 1,719 nursing students aged 18–42 years, between February and November 2019. Sampling was carried out in several stages. Data were collected using seven instruments, namely a demographics survey, the characteristics of chronic pain form, Spielberger State-Trait Anxiety Inventory (STAI), the Patient Health Questionnaire-9 (PHQ-9), the Bar-on Emotional Quotient Inventory, Academic Satisfaction Scale, and Procidano and Heller Social Support Scale. Descriptive statistics, multinomial logistic regression, and regression models were used to describe the characteristics of the pain and its predictive factors. Results The average age of the participants was 22.4 ± 2.96 years. The results of univariate analysis showed that gender (P = 0.506), mother’s education (P = 0.056, P = 0.278, P = 0.278), father’s education (P = 0.817, P = 0.597, P = 0.41), place of residence (P = 0.215), depression (P = 0.501), grade point average (P = 0.488), academic satisfaction (P = 0.183) and chronic pain weren’t significantly correlated with chronic pain in nursing students. The results of the multiple logistic regression models showed that chronic pain was positively correlated with age, social support, state anxiety, and trait anxiety (OR = 1.07, 95% CI: 1.02–1.12; OR = 0.95, 95% CI: 0.93–0.97; OR = 1.03, 95% CI: 1.02–1.05; and OR = 1.97, 95% CI: 0.95–1.99; respectively). Conclusion The prevalence of chronic pain was relatively high in these students. In addition, age, social support, and anxiety could be important factors in the development or persistence of chronic pain in nursing students. The results also provided basic and essential information about the contributing factors in this area. However, consideration of factors such as referral for treatment, home medications for pain relief, and outcomes of chronic pain are suggested in future longitudinal studies.

Abstract Background The variation in breast cancer incidence rates across different regions may reflect disparities in breast cancer screening (BCS) practices. Understanding the factors associated with these screening behaviors is crucial for identifying modifiable elements amenable to intervention. This systematic review aims to identify common factors influencing BCS behaviors among women globally. Methods Relevant papers were sourced from PubMed, Scopus, Embase, and Google Scholar. The included studies were published in English in peer-reviewed journals from January 2000 to March 2023 and investigated factors associated with BCS behaviors. Results From an initial pool of 625 articles, 34 studies (comprising 29 observational and 5 qualitative studies) with 36,043 participants were included. Factors influencing BCS behaviors were categorized into nine groups: socio-demographic factors, health status history, knowledge, perceptions, cultural factors, cues to action, motivation, self-efficacy, and social support. The quality appraisal scores of the studies ranged from average to high. Conclusions This systematic review highlights factors pivotal for policy-making at various levels of breast cancer prevention and assists health promotion professionals in designing more effective interventions to enhance BCS practices among women.

Abstract Background Human Immunodeficiency Virus (HIV) remains a significant global health burden, particularly affecting vulnerable populations residing in slum areas which is characterized by overcrowding, poverty, and limited access to healthcare services, create an environment conducive to the transmission and spread of HIV. Despite the recognition of this issue, there is a lack of comprehensive understanding regarding the prevalence of HIV in slums. The aim of this study was to systematically synthesize the existing global evidence on HIV prevalence in slum populations. Methods A rigorous systematic literature review was conducted by searching multiple electronic databases, including Medline via PubMed, Scopus, Embase, Web of Sciences, and Directory of Open Access Journals (DOAJ), covering the period from January 1, 1990, to March 31, 2023. The quality and risk of bias for each included study were assessed using the Newcastle–Ottawa Scale. The pooled prevalence with its corresponding 95% confidence interval (CI) was calculated using a random-effects model with the Freeman-Tukey double arcsine transformation. The degree of heterogeneity among the studies was evaluated using the I2 test. Publication bias was also assessed using Egger's test. Additionally, subgroup analysis was performed to explore potential factors contributing to the observed heterogeneity. Results A systematic examination of the relevant literature resulted in the inclusion of a total of 22 studies for the purpose of this meta-analysis. These studies collectively assessed a sizable cohort consisting of 52,802 participants. Utilizing a random-effects model, an estimation of the overall prevalence of HIV in the slum area was determined to be 10% (95% CI: 7–13%). Further delineation through subgroup analysis based on the gender revealed a higher prevalence of HIV among women, standing at 13% (95% CI: 8–19%, 18 studies: I2 = 98%), as opposed to men, where the prevalence was found to be 8% (95% CI: 6–12%, 16 studies: I2 = 95%). A geographical breakdown of the included studies revealed that Africa exhibited the highest prevalence, with a figure of 11% (95% CI: 9–13%, 18 studies: I2 = 98%). Subsequently, studies conducted in the American continent reported a prevalence of 9% (95% CI: 7–11%, 2 studies: I2 = 57%). The Asian continent, on the other hand, displayed the lowest prevalence of 1% (95% CI: 0–3%, 2 studies: I2 = 94%). Notably, studies employing rapid tests indicated a prevalence of 13% (95% CI: 9–17%, 6 studies: I2 = 94%), while those relying on self-reported data reported a lower prevalence of 8% (95% CI: 5–11%, 6 studies: I2 = 99%). Moreover, studies utilizing ELISA reported a prevalence of 9% (95% CI: 6–12%, 10 studies: I2 = 96%). Finally, it was determined that studies conducted in upper-middle-income countries reported a higher prevalence of 20% (95% CI: 16–24%, 5 studies: I2 = 45%), whereas studies conducted in lower- and middle-income countries reported a prevalence of 8% (95% CI: 6–10%, 12 studies: I2 = 98%). Conclusion The current study elucidates the troublingly high prevalence of HIV infection within slums area. Also, this finding underscores the urgent necessity for targeted and tailored interventions specifically aimed at curtailing the spread of HIV within slums. Policymakers must take cognizance of these results and devote their efforts towards the implementation of effective strategies to mitigate gender disparities, address poverty alleviation, and empower the inhabitants of these marginalized areas.

Abstract Background Compassionate care is the main indicator of the quality regarding nursing care. The importance of this care in the recovery process for the elderly hospitalized for COVID-19 has been under-researched in studies. Therefore, this study aimed to determine the compassionate care level of nurses to the elderly hospitalized in the COVID-19 wards of teaching hospitals in the south of Iran. Methods This descriptive-analytical study was conducted on 212 nurses working in the COVID-19 wards of teaching hospitals in the south of Iran, who were selected through census in a cross-sectional study. The data were collected using the Tehranineshat et al. nurses’ compassionate care questionnaire and then the data were analyzed using descriptive and analytical statistics along with SPSS software version 22. Results The mean score of nurses’ compassionate care was 130.18 ± 9.42, which was at a high level. The highest and lowest scores were related to professional performance (43.17 ± 2.799) and empathic communication dimension (27.76 ± 2.970). No significant relationship was found between variables such as gender, marital status, education, work experience, and job position with the compassionate care score (P > 0.05). Conclusion Nurses providing care for hospitalized elderly are recommended to consider all aspects of compassionate care, especially empathic communication, in their educational planning.

Abstract Background The evaluation of health technologies plays a crucial role in the allocation of resources and the promotion of equitable healthcare access, known as health technology assessment (HTA). This study focuses on Iran’s efforts to integrate HTA and aims to gain insights into stakeholder perspectives regarding capacity needs, demand and implementation. Methods In this study, we employed the HTA introduction status analysis questionnaire developed by the International Decision Support Initiative (iDSI), which has been utilized in various countries. The questionnaire consisted of 12 questions divided into three sections: HTA need, demand and supply. To identify key informants, we conducted a literature review and consulted with the Ministry of Health and Medical Education (MOHME), as well we experts in policy-making, health service provision and HTA. We selected stakeholders who held decision-making positions in the healthcare domain. A modified Persian version of the questionnaire was administered online from September 2022 to January 2023 and was pretested for clarity. The analysis of the collected data involved quantitative methods for descriptive analysis and qualitative methods for thematic analysis. Results In this study, a total of 103 questionnaires were distributed, resulting in a favourable response rate of 61% from 63 participants, of whom 68% identified as male. The participants, when assessing the needs of HTA, rated allocative efficiency as the highest priority, with a mean rating of 8.53, thereby highlighting its crucial role in optimizing resource allocation. Furthermore, healthcare quality, with a mean rating of 8.17, and transparent decision-making, with a mean rating of 7.92, were highly valued for their impact on treatment outcomes and accountability. The importance of budget control (mean rating 7.58) and equity (mean rating 7.25) were also acknowledged, as they contribute to maintaining sustainability and promoting social justice. In terms of HTA demand, safety concerns were identified as the top priority, closely followed by effectiveness and cost-effectiveness, with an expanded perspective on the economy. However, limited access to local data was reported, which arose from various factors including data collection practices, system fragmentation and privacy concerns. The priorities of HTA users encompassed coverage, payment reform, benefits design, guidelines, service delivery and technology registration. Evidence generation involved the participation of medical universities, research centres and government bodies, albeit with ongoing challenges in research quality, data access and funding. The study highlights government support and medical education as notable strengths in this context. Conclusions This study provides a comprehensive evaluation of Iran’s HTA landscape, considering its capacity, demand and implementation aspects. It underlines the vital role of HTA in optimizing resources, improving healthcare quality and promoting equity. The study also sheds light on the strengths of evidence generation in the country, while simultaneously identifying challenges related to data access and system fragmentation. In terms of policy priorities, evidence-based decision-making emerges as crucial for enhancing healthcare access and integrating technology. The study stresses the need for evidence-based practices, a robust HTA infrastructure and collaboration among stakeholders to achieve better healthcare outcomes in Iran.

Abstract Background Pseudomonas infections are among the most common infections encountered in hospitalized patients, especially those with chronic illnesses or an immunocompromised state. Management of these infections has become challenging due to increased antibiotic resistance. Therefore, this study examines the antibiotic resistance profiles of Pseudomonas spp. and the associated factors among patients admitted to a large tertiary hospital in a developing country. Methods This retrospective observational chart review study assessed patients admitted to a large tertiary hospital in a developing country with a positive culture growth of Pseudomonas from anybody site. Antibiotic susceptibility of the isolated Pseudomonas and patient characteristics were studied from the start of 2021 to the end of 2022. The study ground consisted of 185 patients. Results The study included 185 patients with positive Pseudomonas isolates. Males constituted 54.6% of the sample, while 45.4% were females. The median age of the patients was 53 years. Patient comorbidities and risk factors for Pseudomonas infection and multidrug resistance were assessed. Antibiotic resistance to the Pseudomonas regimens showed the highest resistance to meropenem and ciprofloxacin (23.4%, similarly) among isolates of Pseudomonas aeruginosa. Multidrug resistance (MDR) was found in 108 (58.4%) isolates. The most commonly used antibiotic for treatment was piperacillin-tazobactam, accounting for 33.3% of cases, followed by aminoglycosides at 26.6%. Conclusions Pseudomonas aeruginosa isolates were resistant to meropenem and ciprofloxacin. Over half of the isolates were multidrug-resistant, which was worrying. Piperacillin-tazobactam and aminoglycosides were the most often utilized antibiotics, highlighting the significance of susceptibility testing. Implementing antimicrobial stewardship programs and infection control measures can help reduce drug resistance and improve outcomes in Pseudomonas infections.

Abstract Objective Equity in the delivery of health services, including diagnostic imaging, is crucial to achieving universal health coverage. The Health Transformation Plan (HTP), launched in 2014, represents a major healthcare policy to improve the quality and accessibility of healthcare services. This study aimed to explore the impact of the HTP on equity in the access to medical imaging in Lorestan province, located in west Iran, from 2014 to 2023. Annual growth rates (AGR) of imaging devices were calculated, whilst equity assessment of medical imaging distribution was carried out by means of the Gini coefficient and the Lorenz curve per 100,000 population. The latter was generated using the cumulative distribution of imaging devices, as well as the cumulative population ratio. Results Between 2014 and 2023, the number of imaging devices has increased threefold. The AGR of installing CT and MRI scanners in Lorestan province increased between 2014 and 2023. The Gini coefficients increased from 0.12 for CT and 0.16 for MRI in 2014 to 0.33 in 2023 for both devices. This indicates a decrease in equity in access to these fundamental health technologies despite the increase in their figures. Policymakers should better allocate medical equipment based on the specific health needs of different regions throughout Iran.

Abstract Background Advanced glycation end products (AGEs) have been linked to cardiovascular disease (CVD), especially coronary heart disease (CHD), but their role in CVD pathogenesis remains unclear. Therefore, we investigated cross-sectional associations of skin AGEs with subclinical atherosclerosis, arterial stiffness, and hypertension after confirming their relation with CHD. Methods In the population-based Rotterdam Study, skin AGEs were measured as skin autofluorescence (SAF). Prevalent MI was obtained from digital medical records. Carotid plaques, carotid intima-media thickness (IMT), coronary artery calcification (CAC), pulse wave velocity (PWV), and hypertension were assessed. Associations of SAF with endophenotypes were investigated in logistic and linear regression models adjusting for common cardiovascular risk factors. Effect modification by sex, diabetes mellitus, and chronic kidney disease (CKD) was tested. Results 3001 participants were included (mean age 73 (SD 9) years, 57% women). One unit higher SAF was associated with the presence of carotid plaques (OR 1.2 (0.92, 1.57)), a higher max IMT (0.08 SD (0.01, 0.15)), higher CAC (OR 2.2 (1.39, 3.48)), and PWV (0.09 SD (0.01, 0.16)), but not with hypertension (OR 0.99 (0.81, 1.21)). The associations with endophenotypes were more pronounced in men and participants with diabetes or CKD with significant interactions. Conclusions Previously documented associations between SAF and CVD, also found in our study, may be explained by the endophenotypes atherosclerosis and arterial stiffness, especially in men and individuals with diabetes or CKD, but not by hypertension. Longitudinal studies are needed to replicate these findings and to test if SAF is an independent risk factor or biomarker of CVD. Trial registration: The Rotterdam Study has been entered into the Netherlands National Trial Register (NTR; www.trialregister.nl ) and the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/ ) under shared catalogue number NTR6831.

Abstract Background Psychological distress (PD) is a significant issue during pregnancy and postpartum, adversely affecting both children and mothers. This study aims to determine PD's prevalence and risk factors in a large Iranian population sample during pregnancy and postpartum. Methods A cross-sectional study was conducted using data from the Babol Pregnancy Mental Health Registry (located in the north of Iran) between June 2020 and March 2021. A total of 2305 women were included, with 1639 during pregnancy and 666 during postpartum. Psychological distress was assessed using the Brief Symptoms Inventory (BSI-18), and data were analyzed using independent t-tests and multiple logistic regressions. Results The prevalence of psychological distress, defined by a cut-off score of BSI ≥ 13, was 19% during pregnancy and 15% during postpartum. Multivariate logistic analysis revealed that high-risk pregnancy was the leading risk factor for psychological distress during the antenatal period (β = 1.776, P

Abstract Background Septic pulmonary embolism (SPE), deep vein thrombophlebitis (DVT), and acute osteomyelitis (AOM) form a triad that is rarely seen in children and is usually associated with a history of trauma on long bones. Unfortunately, a delay in diagnosis is frequently observed in this syndrome, which places the patient at risk of life-threatening complications. This delay can largely be attributed to the failure to consider osteomyelitis as a potential underlying cause of DVT. Case presentation In this case report, we present the case of a 16-year-old Arabian male who presented with limb trauma and fever. The patient had a delayed diagnosis of osteomyelitis, which resulted in the formation of an abscess and subsequent joint destruction. Surgical drainage and joint replacement surgery were deemed necessary for treatment. Conclusions persistent fever along with a history of trauma on a long bone with signs of DVT of the limb in a child should raise concern for osteomyelitis and an MRI evaluation of the limb should be obtained.

Abstract Background Nosocomial infections or hospital-acquired infections are a growing public health threat that increases patient morbidity and mortality. Patients at the highest risk are those in intensive care units. Therefore, our objective was to provide a pattern analysis of nosocomial infections that occurred in an adult surgical intensive care unit (ICU). Methods This study was a retrospective observational study conducted in a 6-bed surgical intensive care unit (SICU) at An-Najah National University Hospital (NNUH) to detect the incidence of nosocomial infections from January 2020 until December 2021. The study group included 157 patients who received antibiotics during their stay in the SICU. Results The incidence of nosocomial infections, either suspected or confirmed, in the SICU was 26.9% (95 out of 352 admitted patients). Pneumonia (36.8%) followed by skin and soft tissue infections (35.8%) were the most common causes. The most common causative microorganisms were in the following order: Pseudomonas aeruginosa (26.3%), Acinetobacter baumannii (25.3%), extended-spectrum beta lactamase (ESBL)-Escherichia coli (23.2%) and Klebsiella pneumonia (15.8%). The average hospital stay of patients with nosocomial infections in the SICU was 18.5 days. Conclusions The incidence of nosocomial infections is progressively increasing despite the current infection control measures, which accounts for an increased mortality rate among critically ill patients. The findings of this study may be beneficial in raising awareness to implement new strategies for the surveillance and prevention of hospital-acquired infections in Palestinian hospitals and health care centers.

Abstract Background Carbapenem-resistant Enterobacterales (CREs) are a significant source of healthcare-associated infections. These bacteria are difficult to treat and have a high mortality rate due to high rates of antibiotic resistance. These pathogens are also linked to major outbreaks in healthcare institutions especially those with limited resources in infection prevention and control (IPC). Therefore, our study aimed to describe the epidemiology and clinical characteristics of patients with carbapenem-resistant Enterobacteriaceae in a referral hospital in a developing country. Methods This was a retrospective cross-sectional study that included 218 patients admitted to An-Najah National University Hospital between January 1, 2021, and May 31, 2022. The target population was all patients with CRE infection or colonization in the hospital setting. Results Of the 218 patients, 135 had CR-Klebsiella pneumoniae (61.9%), and 83 had CR-Escherichia coli (38.1%). Of these, 135 were male (61.9%) and 83 were female (38.1%), with a median age of 51 years (interquartile range 24–64). Malignancy was a common comorbidity in 36.7% of the patients. Approximately 18.3% of CRE patients were obtained from patients upon admission to the emergency department, the largest percentage among departments. Most CRE pathogens were isolated from rectal swabs, accounting for 61.3%. Among the 218 patients, colistin was the most widely used antimicrobial agent (13.3%). CR- E. coli showed resistance to amikacin in 23.8% of the pathogens tested and 85.7% for trimethoprim/sulfamethoxazole compared to CR- K. pneumonia, for which the resistance to trimethoprim/sulfamethoxazole was 74.1%, while for amikacin it was 64.2%. Regarding meropenem minimum inhibitory concentration, 85.7% of CR- E. coli were greater than 16 µg/mL compared to 84% of CR- K. pneumonia isolates. Conclusion This study found that CRE is frequently reported in this tertiary care setting, implying the presence of selective pressure and transmission associated with healthcare setting. The antibiotics tested showed a variety of resistance rates, with CR-K. pneumoniae being more prevalent than CR-E. coli, and exhibiting an extremely high resistance pattern to the available therapeutic options.

Abstract Background Antiphospholipid syndrome (APS), defined by thrombotic events or obstetric complications in the presence of persistently high antiphospholipid antibodies, is characterized by a wide variety of clinical presentations and the effects of vascular occlusion can impact almost any organ system or tissue. Since adult-onset APS classification criteria are not well verified in pediatrics (where pregnancy-related problems are rare), estimating childhood prevalence is challenging. Stroke and pulmonary embolism are thromboembolic events occurring in children that can cause considerable long-term morbidity. Children with APS are more prone to recurrent thromboembolism than adults. Cutaneous symptoms are prominent and typically represent the first clue of APS. Although dermatologic findings are exceedingly heterogeneous, it is essential to consider which dermatological symptoms justify the investigation of antiphospholipid syndrome and the required further management. Case presentation We describe a seven-year-old Iranian boy with retiform purpura and acral cutaneous ischemic lesions as the first clinical presentation of antiphospholipid syndrome in the setting of systemic lupus erythematous. Conclusion APS in pediatrics, is associated with a variety of neurologic, dermatologic, and hematologic symptoms. Therefore, it is essential for pediatricians to be aware of the rare appearance of Catastrophic APS as an initial indication of APS.

Abstract Background As crises occur, attention to physical health usually becomes more than mental health, neglecting mental health, especially in some vulnerable groups such as pregnant women and new mothers, can have adverse consequences. Therefore, it is imperative to recognize and comprehend their mental health needs, particularly during critical situations such as the recent COVID-19 pandemic. The aim of this study was to explain the understanding and experience of mental health concerns faced by pregnant and postpartum women during this pandemic. Methods This qualitative study was conducted from March 2021 to November 2021 in Iran. Data were collected using semi-structured in-depth interviews to understand mental health concerns in pregnancy and the postpartum period during the COVID-19 pandemic. Twenty-five purposefully retrieved and participated in the study. Due to the prevalence of coronavirus, most of the participants preferred tele interviews. When data saturation was achieved, the data were codified manually and analyzed using Graneheim and Lundman’s approach 2004. Results Based on the content analysis of the interviews, 2 main themes, 8 categories 23 subcategories were identified. The identified themes were as follows: (1) Maternal mental health threats and (2) Inadequate access to the required information. Conclusion The results of this study showed that the main concern and fear of pregnant and postpartum women in the COVID-19 pandemic was the fear of the possibility of death for themselves and/or their fetus/infant. The knowledge that was obtained from the understanding of pregnant women and new mothers about the mental health concerns during the COVID-19 pandemic can help managers in planning to improve and promote women's mental health, especially in critical situations.

Abstract Background Bloodstream infections (BSI) are a leading cause of morbidity and mortality in hospitalized patients worldwide. A blood culture is the primary tool for determining whether a patient has BSI and requires antimicrobial therapy, but it can result in an inappropriate outcome if the isolated microorganisms are deemed contaminants from the skin. Despite the development of medical equipment and technology, there is still a percentage of blood culture contamination. The aims of this study were to detect the blood culture contamination (BCC) rate in a tertiary care hospital in Palestine and to identify the departments with the highest rates along with the microorganisms isolated from the contaminated blood samples. Method Blood cultures that were taken at An-Najah National University Hospital between January 2019 and December 2021 were evaluated retrospectively. Positive blood cultures were classified as either true positives or false positives based on laboratory results and clinical pictures. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 21. A p-value of less than 0.05 was considered statistically significant for all analyses. Results Out of 10,930 blood cultures performed in the microbiology laboratory from 2019 to 2021, 1479 (13.6%) were identified as positive blood cultures that showed microbial growth. Of these, 453 were blood culture contaminations, representing 4.17% of total blood cultures and 30.63% of the positive blood culture samples. The highest rate of contamination was in the hemodialysis unit (26.49%), followed by the emergency department (15.89%). Staphylococcus epidermidis was the most prevalent (49.2%), followed by Staphylococcus hominis (20.8%) and Staphylococcus haemolyticus (13.2%). The highest annual contamination rate was observed in 2019 (4.78%) followed by 2020 (3.95%) and the lowest was in 2021 (3.79%). The rate of BCC was decreasing, although it did not reach statistically significant levels (P value = 0.085). Conclusion The rate of BCC is higher than recommended. The rates of BCC are different in different wards and over time. Continuous monitoring and performance improvement projects are needed to minimize blood culture contamination and unnecessary antibiotic use.

Abstract The transient receptor potential melastatin subfamily member 2 (TRPM2), a thermo and reactive oxygen species (ROS) sensitive Ca2+-permeable cation channel has a vital role in surviving the cell as well as defending the adaptability of various cell groups during and after oxidative stress. It shows higher expression in several cancers involving breast, pancreatic, prostate, melanoma, leukemia, and neuroblastoma, indicating it raises the survivability of cancerous cells. In various cancers including gastric cancers, and neuroblastoma, TRPM2 is known to conserve viability, and several underlying mechanisms of action have been proposed. Transcription factors are thought to activate TRPM2 channels, which is essential for cell proliferation and survival. In normal physiological conditions with an optimal expression of TRPM2, mitochondrial ROS is produced in optimal amounts while regulation of antioxidant expression is carried on. Depletion of TRPM2 overexpression or activity has been shown to improve ischemia–reperfusion injury in organ levels, reduce tumor growth and/or viability of various malignant cancers like breast, gastric, pancreatic, prostate, head and neck cancers, melanoma, neuroblastoma, T-cell and acute myelogenous leukemia. This updated and comprehensive review also analyzes the mechanisms by which TRPM2-mediated Ca2+ signaling can regulate the growth and survival of different types of cancer cells. Based on the discussion of the available data, it can be concluded that TRPM2 may be a unique therapeutic target in the treatment of several types of cancer. Video Abstract

Abstract Background Nitrogen is very important for crop yield and quality. Crop producers face the challenge of reducing the use of mineral nitrogen while maintaining food security and other ecosystem services. The first step towards understanding the metabolic responses that could be used to improve nitrogen use efficiency is to identify the genes that are up- or downregulated under treatment with different forms and rates of nitrogen. We conducted a transcriptome analysis of barley (Hordeum vulgare L.) cv. Anni grown in a field experiment in 2019. The objective was to compare the effects of organic (cattle manure) and mineral nitrogen (NH4NO3; 0, 40, 80 kg N ha−1) fertilizers on gene activity at anthesis (BBCH60) and to associate the genes that were differentially expressed between treatment groups with metabolic pathways and biological functions. Results The highest number of differentially expressed genes (8071) was found for the treatment with the highest mineral nitrogen rate. This number was 2.6 times higher than that for the group treated with a low nitrogen rate. The lowest number (500) was for the manure treatment group. Upregulated pathways in the mineral fertilizer treatment groups included biosynthesis of amino acids and ribosomal pathways. Downregulated pathways included starch and sucrose metabolism when mineral nitrogen was supplied at lower rates and carotenoid biosynthesis and phosphatidylinositol signaling at higher mineral nitrogen rates. The organic treatment group had the highest number of downregulated genes, with phenylpropanoid biosynthesis being the most significantly enriched pathway for these genes. Genes involved in starch and sucrose metabolism and plant-pathogen interaction pathways were enriched in the organic treatment group compared with the control treatment group receiving no nitrogen input. Conclusion These findings indicate stronger responses of genes to mineral fertilizers, probably because the slow and gradual decomposition of organic fertilizers means that less nitrogen is provided. These data contribute to our understanding of the genetic regulation of barley growth under field conditions. Identification of pathways affected by different nitrogen rates and forms under field conditions could help in the development of more sustainable cropping practices and guide breeders to create varieties with low nitrogen input requirements.

Abstract Background Peptidyl arginine deiminase 4 (PADI4) has been implicated in Rheumatoid arthritis (RA) pathogenesis. Here we aimed to evaluate the association of PADI4 gene rs11203367 and rs1748033 single nucleotide polymorphisms (SNPs) with RA proneness. Methods The mRNA expression of PADI4 was determined in the whole blood samples. The genotyping of PADI4 polymorphisms was conducted using allelic discrimination TaqMan genotyping Real-time PCR. Results The alleles and genotypes of rs11203367 polymorphism were not associated with susceptibility to RA risk. The T allele (OR = 1.58, 95%CI: 1.21–2.04, P = 0.0005), TT genotype (OR = 2.79, 95%CI: 1.53–5.06, P = 0.0007), TC genotype (OR = 1.52, 95%CI: 1.04–2.23, P = 0.0291), dominant (OR = 1.72, 95%CI: 1.19–2.47, P = 0.0034) and recessive (OR = 2.19, 95%CI: 1.25–3.82, P = 0.0057) models of rs1748033 SNP were associated with higher risk of RA. There was a significant upregulation of PADI4 mRNA in the RA patients compared to controls. mRNA expression of PADI4 had significantly positive correlation with anti-CCP level (r = 0.37, P = 0.041), RF level (r = 0.39, P = 0.037), and CRP level (r = 0.39, P = 0.024). Conclusion PADI4 gene rs1748033 SNP was associated with increased RA risk. This polymorphism might affect the RA pathogenesis regardless of impressing the levels of PADI-4 in serum.

Abstract Background Febrile neutropenia (FN) is a life-threatening complication that predisposes cancer patients to serious infections. This study aims to describe the epidemiology and source of infection in cancer patients with FN in a tertiary care hospital. Methods A hospital-based retrospective study was conducted in a large tertiary care hospital from January 2020 to December 2021. Data on cancer patients with FN were collected from the hospital information system. Results 150 cancer patients with FN were identified during the study period. Most patients were males (98; 65.3%), and the mean age of participants was 42.2 ± 16.0 years. Most patients (127; 84.7%) had hematologic malignancies, and acute myeloid leukemia was the most common diagnosis (42; 28%), followed by acute lymphocytic leukemia (28; 18.7%) and Hodgkin’s lymphoma (20; 13.3%). Fifty-four (36%) patients had a median Multinational Association for Supportive Care in Cancer (MASCC) scores greater than 21. Regarding the outcome, nine (6%) died, and 141(94%) were discharged. The focus of fever was unknown in most patients (108; 72%). Among the known origins of fever were colitis (12; 8%), pneumonia (8; 5.3%), cellulitis (6; 4%), bloodstream infections (7; 4.6%), perianal abscess (2; 1.3%) and others. The median duration of fever was two days, and the median duration of neutropenia was seven days. Sixty-three (42%) patients had infections: 56 (73.3%) were bacterial, four (2.6%) were viral, two (1%) were fungal and 1 (0.7%) was parasitic. Among the bacterial causes, 50 cases (89.2%) were culture-positive. Among the culture-positive cases, 34 (68%) were gram-positive and 22 (44%) were gram-negative. The most frequent gram-positive bacteria were E. faecalis (9; 18% of culture-positive cases), and the most frequent gram-negative organisms were Klebsiella pneumoniae (5; 10%). Levofloxacin was the most commonly used prophylactic antibiotic (23; 15.33%), followed by acyclovir (1610.7%) and fluconazole in 15 patients (10%). Amikacin was the most popular empiric therapy, followed by piperacillin/tazobactam (74; 49.3%), ceftazidime (70; 46.7%), and vancomycin (63; 42%). One-third of E. faecalis isolates were resistant to ampicillin. Approximately two-thirds of Klebsiella pneumoniae isolates were resistant to piperacillin/tazobactam and ceftazidime. Amikacin resistance was proven in 20% of isolates. Conclusions The majority of patients suffered from hematologic malignancies. Less than half of the patients had infections, and the majority were bacterial. Gram-positive bacteria comprised two-thirds of cases. Therefore, empiric therapy was appropriate and in accordance with the antibiogram of the isolated bacteria.

Abstract Background Coronavirus disease 2019 (COVID–19) is currently one of the world's most critical health issues so far. Given the importance of appropriate treatment in pregnancy and the controversies about Remdesivir effectiveness and complications, the present study aimed to evaluate the impact of Remdesivir on maternal, fetal, and perinatal outcomes in pregnant women with COVID–19 diseases. Methods A total of 189 pregnant women with positive polymerase chain reaction (PCR) results for SARS–COV–2, and oxygen saturation [SpO2] of

Abstract Background For the first time, we aimed to determine the epidemiology and associated factors of obesity and hypertension among children of military families in our region. Methods In this multi-centered study, children between the ages of 5 to 12 years old, entered the study. Data on baseline and clinical characteristics, history of disease and anthropometric measurements, were collected. Results Among 504 children, 44.2% were males. Mean (SD) age of participants was 7.9 ± 1.9 years. Overall, 5% were obese and 9.9% were overweight. In total, 16.3% had elevated BP, 12.5% had stage one and 0.2% had stage two hypertension. Age (beta = 0.306, OR = 1.35, 95% CI:1.14—1.61), obesity/overweight (OR = 5.58, 95% CI:2.59—12.0), history of hypertension in mother (OR = 43.24, 95% CI:5.99—312.11), low birth weight (OR = 7.96, 95% CI:2.59—12.0), physical activity (OR = 0.27, 95% CI:0.10—0.72), and consumption of fast food more than once a week (OR = 3.36, 95% CI:1.82—6.19), were associated with risk of hypertension. Furthermore, age (beta = 0.346, OR = 1.41, 95% CI:1.21—1.64), history of childhood obesity in the father (OR = 3.78, 95% CI: 1.77—8.06) and mother (OR = 2.44, 95% CI:1.07—5.56), and physical activity (OR = 0.27, 95% CI:0.11—0.66), were associated with obesity. Conclusion Age, obesity/overweight, history of hypertension in the mother, birth weight, physical activity, and consumption of fast food, were associated with risk of hypertension. Moreover, age, history of childhood obesity in parents, and physical activity, were associated with obesity. Furthermore, we found that school-age children in military families have higher rates of hypertension and overweight compared to other reports from our region.

Abstract Background Infertility has been considered as a critical health problem for couples and society. Given the worldwide exponential rise of infertility, mobile phone-based applications are drastic ways to deliver nutrition educational content to women with infertility. The present study aimed to prepare the required educational content for designing a mobile phone-based nutrition educational application for women with infertility. Methods Educational contents were initially determined based on the literature review and library studies. As a result, a researcher-made questionnaire was designed containing 28 items in six dimensions. To ensure about the questionnaire’s validity, a panel of experts (15 nutritionists and 5 infertility specialists) was asked to review the items, make revisions (if necessary), and confirm the final contents. The questionnaire reliability was also corroborated using the KR-20 coefficient (0.89). Results While the amount of consumed calories per meal and between meals were not significantly effective on fertility, factors such as main definitions, disease and treatment instructions, personal activities and habits, and menstruation were deemed necessary by the respondents. Participants also suggested adding sections entailing introductions to different types of diets, users' suggestions and opinions, and of the address and contact information of senior nutrition centers to the questionnaire. Conclusions Followed by obtaining the required valid and reliable contents, a mobile phone- based nutrition education application can be designed to improve the patients' knowledge and facilitate their treatment process.

Abstract Background The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial. Methods In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vitamin D3 or placebo. The co-primary outcomes were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75 nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented. Results Thirty-four (19 intervention, 15 control) subjects were randomized, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95% CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95% CI:1.6, 22.9). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported. Conclusion The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation. Trial registration This trial was registered at https://clinicaltrials.gov on July 23, 2020 (# NCT04483635 ).

Abstract The PI3K-Akt-mechanistic (formerly mammalian) target of the rapamycin (mTOR) signaling pathway is important in a variety of biological activities, including cellular proliferation, survival, metabolism, autophagy, and immunity. Abnormal PI3K-Akt-mTOR signalling activation can promote transformation by creating a cellular environment conducive to it. Deregulation of such a system in terms of genetic mutations and amplification has been related to several human cancers. Consequently, mTOR has been recognized as a key target for the treatment of cancer, especially for treating cancers with elevated mTOR signaling due to genetic or metabolic disorders. In vitro and in vivo, rapamycin which is an immunosuppressant agent actively suppresses the activity of mTOR and reduces cancer cell growth. As a result, various sirolimus-derived compounds have now been established as therapies for cancer, and now these medications are being investigated in clinical studies. In this updated review, we discuss the usage of sirolimus-derived compounds and other drugs in several preclinical or clinical studies as well as explain some of the challenges involved in targeting mTOR for treating various human cancers.

Abstract Melatonin is an important naturally occurring hormone in mammals. Melatonin-mediated biological effects include the regulation of circadian rhythms, which is important for optimal human health. Also, melatonin has a broad range of immunoenhancing actions. Moreover, its oncostatic properties, especially regarding breast cancer, involve a variety cancer-inhibitory processes and are well documented. Due to their promising effects on the prognosis of cancer patients, anti-cancer drugs with epigenetic actions have attracted a significant amount of attention in recent years. Epigenetic modifications of cancers are categorized into three major processes including non-coding RNAs, histone modification, and DNA methylation. Hence, the modification of the latter epigenetic event is currently considered an effective strategy for treatment of cancer patients. Thereby, this report summarizes the available evidence that investigated melatonin-induced effects in altering the status of DNA methylation in different cancer cells and models, e.g., malignant glioma and breast carcinoma. Also, we discuss the role of artificial light at night (ALAN)-mediated inhibitory effects on melatonin secretion and subsequent impact on global DNA methylation of cancer cells.

Abstract Background Fibromyalgia (FM) as a prototypical nociplastic pain condition displays a difficult therapeutic situation in many cases. Given the promising data on the effect of vitamin B12 in improving pain and cognitive functions in various nociplastic pain conditions, we aimed to determine the efficacy of 1000 mcg daily dose of oral vitamin B12 on the symptom severity and psychological profile of FM patients. Methods This open-label, pre-post study was performed on FM patients whose diagnoses were confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). Patients were instructed to take a daily dose of 1000mcg vitamin B12 for fifty days. Outcome measures including the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item Short-Form health survey (SF-12), and pain Visual Analog Scale (pain-VAS) were fulfilled by patients before and after the treatment. Results Of 30 eligible patients, 28 patients completed the study protocol. Patients were female with a mean age of 47.50 ± 8.47 years. FIQR scores in all domains improved significantly after treatment (total FIQR: 49.8 ± 21.86 vs 40.00 ± 18.36, p value

Abstract Purpose The quantifiable description of PPARγ expression pattern beside mechanistic in-vitro evidence will provide insights into the involvement of this mediator in tumor pathogenesis. This study is focused on illuminating the PPARγ gene and protein expression pattern, its association with tumor deterioration and its diagnostic value in different types of primary bone tumors. Methods The expression pattern of PPARγ was investigated in the 180 bone tissues including 90 bone tumor tissues and 90 non-cancerous bone tissues. The local PPARγ expression level was assessed using real-time qRT-PCR and the PPARγ protein expression pattern was measured using immunohistochemistry. The correlation of PPARγ expression level with patients’ clinic-pathological features, also the value of the variables in predicting PPARγ expression level in tumors and the value of PPARγ to discriminate tumor subtypes were assessed. Results The mean PPARγ mRNA expression was significantly higher in bone tumors compared to healthy bone tissues, also the malignant tumors including osteosarcoma and Ewing sarcoma had the elevated level of PPARγ mRNA compared to GCT tumors. Consistently, the protein expression of PPARγ in the tumor site was significantly higher in the bone tumors and malignant tumors compared to non-cancerous and benign tumors, respectively. The PPARγ protein could predict malignant tumor features including tumor grade, metastasis and recurrence significantly. Moreover, PPARγ could potentially discriminate the patients from the controls also malignant tumors from benign tumors with significant sensitivity and specificity. Conclusions PPARγ might be involved in primary bone tumor pathogenesis and determining its molecular mechanism regarding bone cancer pathogenesis is of grave importance.

Abstract MAPK (mitogen-activated protein kinase) or ERK (extracellular-signal-regulated kinase) pathway is an important link in the transition from extracellular signals to intracellular responses. Because of genetic and epigenetic changes, signaling cascades are altered in a variety of diseases, including cancer. Extant studies on the homeostatic and pathologic behavior of MAPK signaling have been conducted; however, much remains to be explored in preclinical and clinical research in terms of regulation and action models. MAPK has implications for cancer therapy response, more specifically in response to experimental MAPK suppression, compensatory mechanisms are activated. The current study investigates MAPK as a very complex cell signaling pathway that plays roles in cancer treatment response, cellular normal conduit maintenance, and compensatory pathway activation. Most MAPK inhibitors, unfortunately, cause resistance by activating compensatory feedback loops in tumor cells and tumor microenvironment components. As a result, innovative combinatorial treatments for cancer management must be applied to limit the likelihood of alternate pathway initiation as a possibility for generating novel therapeutics based on incorporation in translational research. We summarize current knowledge about the implications of ERK (MAPK) in cancer, as well as bioactive products from plants, microbial organisms or marine organisms, as well as the correlation with their chemical structures, which modulate this pathway for the treatment of different types of cancer.

Abstract Background Given the role of vitamin B6 on pronociceptive/antinociceptive neurotransmitters balance, metabolic reactions, and inflammation, it is important to clarify the effect of vitamin B6 on pain and psychological disturbance in fibromyalgia (FM). This study aimed to evaluate whether an 80-mg daily dose of vitamin B6 improves pain, disease severity and psychological symptoms of FM compared to a placebo. Methods This randomized, double-blinded, placebo-controlled trial was performed on the FM patients whose diagnosis was confirmed by a rheumatologist based on the 2016 American College of Rheumatology (ACR). 90 Patients were randomized to receive either vitamin B6 (80 mg daily) or placebo in a 1:1 ratio, with a permuted block size of 30 stratified by disease severity. Primary outcomes included the Revised Fibromyalgia Impact Questionnaire (FIQR), Hospital Anxiety and Depression Scale (HADS), 12-item short-form health survey (SF-12), and pain visual analog scale (pain-VAS)). The mean differences in outcomes (before and after treatment) were compared between the vitamin B6 and placebo groups using an independent T-test. An ANCOVA model adjusted for baseline outcome value was also provided to compare the outcomes between the two groups. Results Of 90 eligible patients, 60 patients (31 patients in vitamin B6 and 29 in the placebo group) completed the trial. Overall, the FIQR, pain-VAS, and HADS-anxiety scores improved after treatment in both vitamin B6 and placebo groups; However, there was no statistically significant intergroup difference regarding primary outcomes. ANCOVA model also showed no difference in the treatment effects. Conclusions Our results showed no priority for vitamin B6 over placebo in FM patients. Considering the potential ameliorating role of vitamin B6 on pain and psychological symptoms, acknowledgment of vitamin B6 as a relatively safe adjuvant treatment needs larger future studies. Trial registration Iranian Registry of Clinical Trials: IRCT20200920048782N2 on 2021/10/04.

Abstract Background Food addiction is one of the behavioral factors that play an important role in the pathogenesis of obesity. Much evidence is available suggesting intestinal microbiomes can play a role in eating behavior, body composition, and BDNF levels, and they can be modified by time-restricted feeding (TRF). So, this study will aim to evaluate the effect of TRF on anthropometric measures, eating behavior, stress, and serum BDNF and LBP levels in women with overweight/obesity and food addiction. Methods We will carry out a randomized clinical trial for 8 weeks to evaluate the effect of a TRF on anthropometric measures, eating behavior, stress level, serum BDNF and LBP levels in women with overweight/obesity and food addiction. Discussion Given the effect of BDNF on regulating eating behavior and body weight and the effect of dietary restrictions on BDNF and the gut microbiome, the TRF diet could possibly be a new way to successfully manage weight through modifying BDNF in people with eating disorders, including food addiction. Trial registration Iranian Registry of Clinical Trials IRCT20131228015968N7 . Registered on 25 October 2020.

Abstract Background The Invalidation Illness Inventory (3*I) is an instrument that assesses invalidation (including discounting and lack of understanding dimensions) experienced by patients with rheumatic disorders. This study aimed to translate and validate the 3*I in Iran. Methods Following translation of the 3*I into the Iranian language (Persian), a cross-sectional study was conducted. A consecutive sample of females with chronic non-inflammatory rheumatic painful diseases completed the questionnaire. Patients also completed the Revised Symptom Impact Questionnaire (SIQR) and the Short Form Health Survey-12 (SF-12). To examine convergent validity, the correlation between the 3*I, the SIQR, and the SF-12 was assessed. The reliability of the 3*I was examined by internal consistency (the Cronbach's alpha coefficient) and intraclass correlation coefficient (ICC). Results In all 196 patients participated in the study. The mean (SD) age of patients was 45.62 ± 10.70 years. Several significant correlations between the Invalidation Illness Inventory (discounting/lack of understanding) with the symptom impact (SIQR) and the short form health survey (SF-12) were observed lending support to the convergent validity of the 3*I. The Cronbach’s alpha coefficients were acceptable for most dimensions and sources, ranging from 0.52 to 0.88. Most ICC values for the dimensions of 3*I were above 0.75. Conclusions The findings indicated that the Persian version of Illness Invalidation Inventory (3*I) is a valid instrument for invalidation assessment in patients with chronic pain. Given the high frequency of perceived invalidation among patients with rheumatic painful disorders, serious attention is needed to the issue in clinical and research settings.

Abstract Background The primary objective was to compare the serum brain-derived neurotrophic factor (BDNF) level in the patients with two types of pain: fibromyalgia (FM) and non-FM nociceptive pain (non-FM NP). The secondary objective was to investigate the effect of duloxetine on serum BDNF in FM patients and assess the direction of BDNF changes’ relation to clinical parameters’ alterations. Methods: This is a study on 73 patients (50 FM and 23 non-FM chronic non-inflammatory pain patients). Serum BDNF was first compared between both groups. Patients with FM, then prospectively, underwent standardized FM treatment with duloxetine maximized to 60 mg/day. The Revised Fibromyalgia Impact Questionnaire (FIQR), Short-Form Health Survey (SF-12), pain visualized analog scale (pain VAS), Beck Depression Inventory-II (BDI-II), polysymptomatic distress scale (PSD) and serum BDNF were measured and compared at baseline and 4 weeks after treatment in FM group. Results The mean of adjusted BDNF level in the FM group had no significant difference than the non-FM NP group ((5293.5 ± 2676.3 vs. 6136.3 ± 4037.6; P value = 0.77). Using linear mixed model, we showed that duloxetine reduced BDNF level significantly in FM patients, even after adjusting for depression, pain and severity of the disease (P