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Purpose: To assess oral hygiene, gingivitis, and the association between them for adolescents with cystic fibrosis (CF) compared to nonCF controls. Methods: This was a cross-sectional study of adolescents with CF aged 12 to 17 years (n=27), compared to two non-CF control groups: Medicaid-enrolled adolescents with special health care needs (ASHCN; n=60) and healthy Medicaid-enrolled adolescents (n=185). Dental plaque was a proxy for oral hygiene, and gingival bleeding was a proxy for gingivitis. This study employed confounder-adjusted binomial logistic regression to compare outcomes between adolescents with CF and controls. Results: After adjusting for confounders, adolescents with CF had significantly poorer oral hygiene than controls (CF versus ASHCN odds ratio [OR] = 2.9, 95 percent confidence interval [95% CI] = 2.0 to 4.4, P<0.001; CF versus healthy OR = 1.7, 95% CI=1.3 to 2.2, P<0.001), but there was no significant difference in gingivitis (CF versus ASHCN OR=1.3, 95% CI=0.87 to 1.9, P=0.21; CF versus healthy OR = 0.80, 95% CI=0.60 to 0.99, P=0.04). Poor oral hygiene was significantly associated with gingivitis for all adolescents (CF OR=1.2, 95% CI=1.1 to 1.4, P<0.001; ASHCN OR = 1.8, 95% CI=1.6 to 2.0, P<0.001; healthy OR = 1.2, 95% CI=1.1 to 1.3, P<0.001). Conclusions: Adolescents with CF had poorer oral hygiene than non-CF controls but similar levels of gingivitis. Future efforts should identify factors that protect adolescents with CF from gingivitis.

Background: Pediatric Sleep Questionnaire (PSQ) is a valid, reliable tool for screening for sleep-related breathing disorders (SRBDs) translated into several languages since 2000. The diagnostic accuracy of an Arabic version of the PSQ has never been tested. Our aim was to translate the original version of PSQ into Arabic (Arabic-PSQ), validate it as a reliable screening tool, and compare it to the gold standard diagnostic method for SRBDs., Materials and Methods: This was a prospective longitudinal study of 54 children (2-14 years) who were to undergo polysomnography (PSG). SRBD was assessed by administering the Arabic version of PSQ to the parents of these children. The validity and reliability of the Arabic-PSQ were assessed. Data were analyzed using Stata 16. Correlation between with polysomnographic indices and PSQ scores, as well as measurement of the diagnostic accuracy were determined. Receiver operating characteristic analysis between the mean PSQ scores and binary PSG results was done and the area under curve (AUC) value was calculated., Results: Thirty-four (63%) children were diagnosed with obstructive sleep apnea by PSG (Apnea-Hypopnea Index [AHI] ≥1), 26 of whom were accurately identified with the Arabic-PSQ (76.5%). Arabic-PSQ showed comparable validity and reliability. Using a cutoff of 0.33, the score showed a significant correlation with AHI: Rs: 0.30 ( P = 0.029). The sensitivity was 76.5%, the specificity was 50%, the positive predictive was 72.2%, the negative predictive value was 55.6%, the positive likelihood ratio was 1.63, and the negative likelihood ratio was 0.37., Conclusions: The Arabic-PSQ is a valid tool for the screening of Arabic-speaking populations for SRBD. It is valuable for directing the diagnostic approach in a timely and cost-effective manner., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family and Community Medicine.)

Objectives: Periodontitis is a highly prevalent complication of diabetes. However, the association between cystic fibrosis-related diabetes (CFRD) and periodontitis has not yet been evaluated. The objective of this study was to assess if: 1) CFRD is associated with periodontitis among adults with CF, and 2) periodontitis prevalence differs by CF and diabetes status., Methods: This was a pilot cross-sectional study of the association between CFRD and periodontitis in adults with cystic fibrosis (CF) (N = 32). Historical non-CF controls (N = 57) from the U.S. National Health and Nutrition Examination Survey (NHANES) dataset were frequency matched to participants with CF on age, sex, diabetes status, and insulin use. We defined periodontitis using the U.S. Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition, as the presence of two or more interproximal sites with CAL ≥3 mm and two or more interproximal sites with PD ≥4 mm (not on the same tooth) or one site with PD ≥5 mm. Because NHANES periodontal data were only available for adults ages ≥30 years, our analysis that included non-CF controls focused on this age group (CF N = 19, non-CF N = 57). Based on CF and diabetes status, we formed four groups: CFRD, CF and no diabetes, non-CF with diabetes, and non-CF and no diabetes (healthy). We used the Fisher's exact test for hypotheses testing., Results: There was no association between CFRD and periodontitis for participants with CF ages 22-63 years (CFRD 67% vs. CF no diabetes 53%, P = 0.49), this was also true for those ages ≥30 years (CFRD 78% vs. CF no diabetes 60%, P = 0.63). For the two CF groups, the prevalence of periodontitis was significantly higher than for healthy controls (CFRD 78% vs. healthy 7%, P<0.001; CF no diabetes 60% vs. healthy 7%, P = 0.001) and not significantly different than the prevalence for non-CF controls with diabetes (CFRD 78% vs. non-CF with diabetes 56%, P = 0.43; CF no diabetes 60% vs. non-CF with diabetes 56%, P = 0.99)., Conclusion: Among participants with CF, CFRD was not associated with periodontitis. However, regardless of diabetes status, participants with CF had increased prevalence of periodontitis compared to healthy controls., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alkhateeb et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Saliva is a readily accessible and inexpensive biological specimen that enables investigation of the oral microbiome, which can serve as a biomarker of oral and systemic health. There are two routine approaches to collect saliva, stimulated and unstimulated; however, there is no consensus on how sampling method influences oral microbiome metrics. In this study, we analyzed paired saliva samples (unstimulated and stimulated) from 88 individuals, aged 7-18 years. Using 16S rRNA gene sequencing, we investigated the differences in bacterial microbiome composition between sample types and determined how sampling method affects the distribution of taxa associated with untreated dental caries and gingivitis. Our analyses indicated significant differences in microbiome composition between the sample types. Both sampling methods were able to detect significant differences in microbiome composition between healthy subjects and subjects with untreated caries. However, only stimulated saliva revealed a significant association between microbiome diversity and composition in individuals with diagnosed gingivitis. Furthermore, taxa previously associated with dental caries and gingivitis were preferentially enriched in individuals with each respective disease only in stimulated saliva. Our study suggests that stimulated saliva provides a more nuanced readout of microbiome composition and taxa distribution associated with untreated dental caries and gingivitis compared to unstimulated saliva., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Roca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper explores the application of Set-based Design (SBD) in the design of a dates harvesting machine. Dates are a popular fruit with significant economic importance, especially in Saudi Arabia. However, the process of harvesting them is highly labour-intensive, and there is a need for an automated solution to improve efficiency and reduce costs. The study begins with a comprehensive review of the literature on other fruit-harvesting machines. The research then proposes an architectural design of a dates harvesting machine based on the understanding of the typical fruit harvesting machines. The dates harvesting machine design proposed in this study consists of several sub-assemblies. Each sub-assembly is designed as a set of alternatives, with different configurations of components, mechanisms and materials. The understanding of the customer requirements of typical date farms helped to identify the list of values that are essential to design the dates harvesting machine. These values were filtered and analysed using an analytical hierarchy process to define three key value attributes of 'design performance', 'safety' and 'cost'. The SBD approach helped to evaluate all the possible combinations of subsystems to identify the optimal solution that meets the customer's requirements and constraints. The SBD methodology resulted in the generation of 576 alternative design configurations which were aggressively narrowed down to 48 design solutions and then into 4 solutions where the final optimized design was selected using the PUGH matrix. The narrowing down is based on the combination of trade-off curves, solution performance and the identified key-value attributes. The proposed dates harvesting machine design shows great promise in improving the efficiency and sustainability of harvesting dates, and it can be adapted for use in agricultural applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Purpose Individuals with cystic fibrosis (CF) present with multiple condition-specific risk factors for periodontitis including CF-related diabetes, chronic inhaled treatments that induce xerostomia, and increased systemic inflammation because of frequent lung infections. General factors like age, oral hygiene, and diet may also contribute to the risk of periodontitis. However the relative importance of these specific risk factors and periodontitis in individuals with CF has not yet been evaluated. The purpose of this pilot study was to assess the associations between CF condition-specific and general risk factors and the prevalence of periodontitis in adults with CF. Methods This cross-sectional pilot study was designed to assess a multifactorial model of periodontitis risk factors in a population in adults with CF who were recruited from the University of Washington Adult CF center. Periodontitis was defined using the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition. Risk factors included condition-specific and general factors. Differences between participants with moderate/severe periodontitis and those with no/mild periodontitis was assessed using the Mann-Whitney test, the Fisher's exact test, and the exact chi-square test (α=0.05). Results Thirty-two participants were enrolled. Twenty-eight percent of the participants had moderate periodontitis, 72% had no/mild periodontitis; none of the participants had severe periodontitis. There were no significant differences in condition-specific factors between between the two study groups. Participants with moderate periodontitis were older ( p =0.028) and reported daily flossing in higher proportions than those with no/mild periodontitis ( p =0.023). Conclusions The findings from this pilot study suggest that future research is needed to determine whether sociodemographic and other general risk factors are more important contributors to periodontitis risk than CF-specific factors., (Copyright © 2023 The American Dental Hygienists’ Association.)

Objectives: To determine the microvascular complications prevalence in patients with type 2 diabetes mellitus (DM) in the eastern province of the Kingdom of Saudi Arabia., Methods: The participants in this retrospective, cross-sectional study included patients with type 2 DM who visited the diabetes clinics of primary health care centers of 2 National Guard Hospitals, Eastern Province, Saudi Arabia., Results: This study included 935 patients with type 2 diabetes (54.1% women versus 45.9% men). Oral hypoglycemic medication was the most common treatment (90.3%). Overall, 55.1% of patients visited the ophthalmology clinic for retinopathy screening. The last glycated hemoglobin A1c result (mean: 8.04%) was higher than the second-to-last result (mean: 8.03%), or the third-to-last result (mean: 7.99%). The prevalence of microvascular complications of DM was 55.1%. Independent significant factors linked with a higher risk of microvascular issues of DM were higher age, visits to an ophthalmology clinic, and the use of injection therapy. The most typical complications that our patients experienced was nephropathy (80.2%), followed by retinopathy (32.7%), and neuropathy (8.4%)., Conclusion: Microvascular complications were extremely common in type 2 DM patients in our region. Being older, regularly visiting an ophthalmologist, and using injection therapy were predictive factors correlated with a higher chance of experiencing these complications., (Copyright: © Saudi Medical Journal.)

Globally, it is known that smoking can cause a variety of diseases. Studies have shown that smoking not only causes heart and lung diseases but is also strongly related to ocular diseases which could lead to blindness. This study aims to assess the level of awareness of blindness related to smoking in young people in Saudi Arabia. This is a descriptive cross-sectional study conducted among the young population in Saudi Arabia. A self-administered questionnaire was distributed using an online platform that includes socio-demographic data, education level, smoking status, and knowledge of the harmful effect of smoking like lung and cardiac diseases, including blindness. The data were analyzed using Statistical Packages for Social Sciences (SPSS) version 26 (IBM Corp., Armonk, NY). A total of 655 young individuals responded to the survey. Among our subjects, the prevalence of smoking participants was (18.7%) more common among the age group 21-25 years, males, bachelor, or higher degrees and those living in the Central region (p<0.001). Participants were definitely or probably more aware that the most common condition associated with excessive smoking was lung cancer (99.5%), followed by heart disease (98.1%) and stroke (93%) while the least of them was melanoma (91.3%) and blindness (81%). This is the first study in Saudi Arabia to assess the level of awareness of the risks of blindness related to smoking in young people and disclosed limited knowledge of the effect of smoking on their vision. The effects of smoking on lung cancer, heart disease, stroke, and even melanoma received higher ratings than blindness. Smokers may be able to quit smoking and enhance their quality of life by better understanding the link between smoking and blindness, which suggests that appropriate action is required to enhance their awareness., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alarfaj et al.)

Introduction: Diabetic ketoacidosis (DKA) is one of the most serious consequences of diabetes. This serious issue occurs when the body cannot use the glucose as a source of energy because of a lack in the level of insulin which as consequence will lead to an increased level of glucose resulting in DKA., Aim: The goal of this study was to increase diabetic patients' and caregivers' awareness and practice of DKA at the community level in Hail City, Saudi Arabia, in 2022. The assessment of people's awareness and knowledge on DKA is importance to support any subsequent actions. Subjects and Methods . This is a cross-sectional study conducted in Hail City, Saudi Arabia, among diabetic patients and carers. A self-administered questionnaire in Arabic was given to the target demographic via an internet survey. The questionnaire includes basic demographic data (i.e., age, gender, and marital status), clinical characteristics of the diabetic patients, and a set of questionnaires to assess the awareness and practice of the subjects regarding DKA., Results: 348 surveys were received (51.1% males vs. 48.9% females). A total of 29.9% of patients have been diagnosed with DKA. Out of a possible 14 points, the average awareness score was 5.22 (SD 3.39). Poor awareness levels had been found in nearly 70% of the subjects, 23.6% were moderate, and only 8.6% were considered good. Factors associated with increased awareness were being younger, female gender, unmarried, students, type 1 DM, DKA diagnosis, and having good information about DKA., Conclusion: The awareness of diabetic patients and their caregivers toward DKA was unsatisfactory. Younger female patients who were single and who had been diagnosed with DKA tend to be more aware of DKA as compared to other subjects. There is a compelling reason to bridge the gaps in the awareness of DKA among the diabetic population and their caregivers in our region., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Nahlah Fahad Alreshidi et al.)

Introduction Acne vulgaris is considered one of the most common dermatological issues that affect approximately 9.4% of the world's population, and the most affected group is adolescents. Acne can vary among adolescents and adults of different ethnicities and countries. Aim This study aimed to assess the psychological impact of acne vulgaris among female adults in the Eastern province of Saudi Arabia. Subjects and methods This is a cross-sectional study conducted among young females aged 15 to 25 years old. A self-administered validated questionnaire translated into Arabic was distributed among the female respondents with acne vulgaris using an online survey. The questionnaire includes basic demographic data and the Dermatology Life Quality Index (DLQI) questionnaire to assess the psychological impact of acne vulgaris. Results Four hundred seventy-six female participants aged 15-25 years took part. The majority were single (86.3%) and of Saudi nationality (92.4%). The prevalence of psychological impact affecting acne patients was 85.5% (ranging from low effect to severe effect). A significant relationship was observed between psychological impact according to marital status (p=0.034) and educational level (p=0.023). In a multivariate regression model, patients who had never been married and were more educated were the independent significant factors associated with increased rates of psychological impairment. Conclusion The quality of life of young females has been greatly affected by acne vulgaris. The severity of psychological impairment associated with acne vulgaris can be significantly predicted among educated and single females. Psychological counseling is necessary to decrease the burden caused by the dermatologic condition affecting young females in the region., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Khan et al.)

To explore the effects of triacontanol (TR) on drought tolerance of strawberry plants (cv Fertona), two field experiments were carried out to study the effects of three supplementary foliar TR rates (0, 0.5, and 1 ppm) under the following three levels of water irrigation: 11 m 3 /hectare (40% of water holding capacity (WHC) severe as a drought treatment, 22 m 3 /hectare (80% of WHC) as moderate drought stress, and normal irrigation with 27 m 3 /hectare (100% of WHC) server as a control treatment. TR treatments were applied five times after 30 days from transplanting and with 15-day intervals. The results showed that drought stress (40% and 80%) markedly decreased the growth, fruit yield, and chlorophyll reading, as well as the gas exchange parameters (net photosynthetic rate, stomatal conductance, and transpiration rate). Meanwhile, drought stress at a high rate obviously increased antioxidant enzyme activities such as superoxide dismutase (SOD), peroxidase (POX), and catalase (CAT) contents in the leaves of the strawberry plants. The moderate and high drought stress rates enhanced some strawberry fruit quality parameters such as total soluble solids (TSS), vitamin C, and anthocyanin content compared to the control. Additionally, TR increased the activities of SOD, POX, and CAT. TR treatment significantly increased the chlorophyll contents, gas exchange parameters (photosynthetic rate and stomatal conductance), and water use efficiency (WUE). Plant height, fruit weight, and total biomass were increased also via TR application. Total yield per plant was increased 12.7% using 1 ppm of TR compared with the control. In conclusion, our results suggested that TR application could relieve the adverse effects of drought stress on the growth of strawberry plants by enhancing the antioxidant enzymes, photosynthesis rate, and WUE of the leaves.

Aims: Dental clearance is typically part of the evaluation process prior to placement on the lung transplant waiting list. Individuals with cystic fibrosis (CF) are thought to be at low risk for dental disease. We hypothesized that individuals with CF in need of lung transplantation would have lower dental disease prevalence and shorter waitlist evaluation time than individuals with non-CF lung diseases., Methods and Results: We conducted a retrospective study of individuals who received a lung transplant between 2011 and 2017 at the University of Washington (Seattle, WA, USA) (N = 280). Untreated dental disease was assessed by the individual's dentist. Waitlist evaluation time was defined as the time, in days, from the initial evaluation by a transplant pulmonologist to placement on the lung transplant waiting list. We used logistic and linear regression models for hypothesis testing. The prevalence of untreated dental disease did not differ by CF status (p = 0.99). There was no difference in waitlist evaluation time for transplant recipients by CF status (p = 0.78) or by dental disease status (p = 0.93)., Conclusions: Our findings provide further evidence that individuals with CF are not at low risk for dental disease. Ensuring optimal oral health is important for all individuals with lung diseases., (© 2021 Special Care Dentistry Association and Wiley Periodicals LLC.)

Background: Objective structured clinical examination (OSCE) is being increasingly used as an assessment tool for undergraduate dermatology courses. One of the practical difficulties in conducting OSCEs in dermatology is getting patients with typical skin lesions which can be used for the whole group to ensure uniformity of assessment. We present a study on the use of simple moulage techniques to create uniform and standardized skin lesions for OSCEs in dermatology., Methods: As a first step, the dermatology faculty in our department chose the clinical conditions which could be covered by using moulages. The main criteria considered were the importance of the condition to the exam blueprint, ease of making and resistance to handling (should not require frequent retouching). Moulages were created on volunteers after taking consent and the same were used in OSCEs s for a group of 5 th -year students (N = 102). Difficulty and discrimination indices were compared between the stations using the moulage and the other stations. Qualitative feedback was obtained regarding the same from both the faculty and the students., Results: There was consensus among the faculty and the majority of the students that the lesions were clearly recognizable. As far as other psychometrics were concerned, average difficulty and discrimination of the stations using the moulage were good (average difficulty index-0.78 and average discrimination index-0.68) and compared favorably with the other stations (average difficulty index-0.77 and average discrimination index-0.57)., Limitations: Limited number of stations included, lack of detailed item analysis and lack of feedback from the simulated patients were the main limitations in this study., Conclusion: For most common skin conditions creating moulages to simulate the corresponding lesions is an easy procedure and can be an effective tool to standardize dermatology OSCEs for undergraduates, especially in resource-poor settings., Competing Interests: None

Salivary flow rate, pH, and buffering capacity are associated with dental caries, but studies from the cystic fibrosis (CF) literature are inconclusive regarding these salivary factors and caries. The aim of this study was to evaluate these factors and their associations with dental caries in individuals with CF. Unstimulated whole saliva was collected from individuals aged 6-20 years at Seattle Children's Hospital CF Clinic, USA (n = 83). Salivary flow rate was measured in milliliters per minute. Salivary pH was assessed using a laboratory pH meter. Buffering capacity was assessed by titration with HCl. The outcome measure was caries prevalence, defined as the number of decayed, missing, or filled primary and permanent tooth surfaces. Spearman's rank correlation coefficient and the t test were used to test for bivariate associations. Multiple variable linear regression models were used to (1) run confounder-adjusted analyses and (2) assess for potential interactions. There was no significant association between salivary flow rate or buffering capacity and caries prevalence. There was a significant negative association between salivary pH and caries prevalence, but this association was no longer significant after adjusting for age. There was no significant interaction between salivary flow rate and buffering capacity or between antibiotic use and the 3 salivary factors. Our results indicate that unstimulated salivary factors are not associated with dental caries prevalence in individuals with CF. Future studies should investigate other potential saliva-related caries risk factors in individuals with CF such as cariogenic bacteria levels, salivary host defense peptide levels, and medication use., (© 2016 S. Karger AG, Basel.)

Background: Salinity is a serious factor limiting the productivity of agricultural plants. One of the potential problems for plants growing under saline conditions is the inability to up take enough K(+). The addition of K(+) may considerably improve the salt tolerance of plants grown under salinity. It is assumed that increasing the K(+) supply at the root zone can ameliorate the reduction in growth imposed by high salinity. The present study aims to determine whether an increase in the K/Na ratio in the external media would enhance the growth of date palm seedlings under in vitro saline conditions., Methods: Date palm plants were grown at four concentrations of Na + K/Cl (mol/m(3)) with three different K/Na ratios. The 12 salt treatments were added to modified MS medium. The modified MS medium was further supplemented with sucrose at 30 g/l., Results: Growth decreased substantially with increasing salinity. Growth expressed as shoot and root weight, enhanced significantly with certain K/Na ratios, and higher weight was maintained in the presence of equal K and Na. It is the leaf length, leaf thickness and root thickness that had significant contribution on total dry weight. Na(+) contents in leaf and root increased significantly increased with increasing salinity but substantial decreases in Na(+) contents were observed in the leaf and root with certain K/Na ratios. This could be attributed to the presence of a high K(+) concentration in the media. The internal Na(+) concentration was higher in the roots in all treatments, which might indicate a mechanism excluding Na(+) from the leaves and its retention in the roots. K/Na ratios up to one significantly increased the leaf and root K(+) concentration, and it was most pronounced in leaves. The K(+) contents in leaf and root was not proportional to the K(+) increase in the media, showing a high affinity for K(+) uptake at lower external K(+) concentrations, but this mechanism continues to operate even with high external Na(+) concentrations., Conclusion: Increasing K/Na ratios in the growing media of date plam significantly reduced the absorption of Na(+) less than 200 mM and also balance ions compartmentalization.

Previous studies have shown that administration of ferristatin II to rats is associated with decreased serum iron, reduced transferrin saturation, and increased hepatic hepcidin expression. BMP and IL-6 signaling act via Smad and Stat3 transcription factors, respectively, to increase expression of hepcidin, the master regulator of iron metabolism. In this study, we aimed to explore the underlying mechanism of ferristatin II action on hepcidin production. We found that ferristatin II greatly increased hepcidin expression both in vivo and in vitro. In the rat liver, ferristatin II treatment decreased expression of Smad downstream targets Smad7 and Id1 and increased expression of Stat3 downstream targets α-2-macroglobulin, α-1-acid glycoprotein, and C-reactive peptide. Ferristatin II also increased Stat3 phosphorylation in the rat liver without affecting serum or hepatic IL-6 levels. It is unclear whether the Stat3 activation observed in vivo is a cause or a consequence to hepcidin induction. Reporter gene expression studies demonstrated that ferristatin II synergized with BMP6 and IL-6 to enhance hepcidin expression in vitro. However, this synergy was not due to activation of either Smad or Stat3 signaling, raising the possibility that ferristatin II may activate a novel pathway for hepcidin regulation., (Copyright © 2015 the American Physiological Society.)

The iron storage protein ferritin has been continuously studied for over 70years and its function as the primary iron storage protein in cells is well established. Although the intracellular functions of ferritin are for the most part well-characterized, the significance of serum (extracellular) ferritin in human biology is poorly understood. Recently, several lines of evidence have demonstrated that ferritin is a multi-functional protein with possible roles in proliferation, angiogenesis, immunosuppression, and iron delivery. In the context of cancer, ferritin is detected at higher levels in the sera of many cancer patients, and the higher levels correlate with aggressive disease and poor clinical outcome. Furthermore, ferritin is highly expressed in tumor-associated macrophages which have been recently recognized as having critical roles in tumor progression and therapy resistance. These characteristics suggest ferritin could be an attractive target for cancer therapy because its down-regulation could disrupt the supportive tumor microenvironment, kill cancer cells, and increase sensitivity to chemotherapy. In this review, we provide an overview of the current knowledge on the function and regulation of ferritin. Moreover, we examine the literature on ferritin's contributions to tumor progression and therapy resistance, in addition to its therapeutic potential., (© 2013.)

Two young Egyptian women with homozygous familial hypercholesterolemia (HoFH) were diagnosed after the appearance of vascular complications despite the presence of family history and suggestive clinical features. The first patient was treated by repeated surgical excisions of disfiguring tendon xanthomas diagnosed as "lipomas". The second patient, presenting with embolic ischemia, had an amputation of the forearm and repeated reconstructive surgical procedures. Each patient was diagnosed as HoFH after presenting with typical angina to a cardiologist. The first patient had severe aortic stenosis, left main and multi-vessel coronary artery disease, and died at age 21 years. The second patient had multivessel coronary artery disease that was treated by Percutaneous Coronary Intervention (PCI) with drug-eluting stents. These cases demonstrate that the delayed diagnosis of xanthomas and familial inheritance characteristic of HoFH leads to atherosclerosis and aortic stenosis early in life., (Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Tumor-associated macrophages play a critical role in breast tumor progression; however, it is still unclear what effector molecular mechanisms they employ to impact tumorigenesis. Ferritin is the primary intracellular iron storage protein and is also abundant in circulation. In breast cancer patients, ferritin is detected at higher levels in both serum and tumor lysates, and its increase correlates with poor clinical outcome. In this study, we comprehensively examined the distribution of ferritin in normal and malignant breast tissue at different stages in tumor development. Decreased ferritin expression in cancer cells but increased infiltration of ferritin-rich CD68-positive macrophages was observed with increased tumor histological grade. Interestingly, ferritin stained within the stroma surrounding tumors suggesting local release within the breast. In cell culture, macrophages, but not breast cancer cells, were capable of ferritin secretion, and this secretion was further increased in response to pro-inflammatory cytokines. We next examined the possible functional significance of extracellular ferritin in a breast cancer cell culture model. Ferritin stimulated the proliferation of the epithelial breast cancer cell lines MCF7 and T47D. Moreover, this proliferative effect was independent of the iron content of ferritin and did not increase intracellular iron levels in cancer cells indicating a novel iron-independent function for this protein. Together, these findings suggest that the release of ferritin by infiltrating macrophages in breast tumors may represent an inflammatory effector mechanism by which ferritin directly stimulates tumorigenesis.

Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP) in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml) or CRP (>7.25 mg/l) was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

Background: Ferritin has been traditionally considered a cytoplasmic iron storage protein. However, several studies over the last two decades have reported the nuclear localization of ferritin, specifically H-ferritin, in developing neurons, hepatocytes, corneal epithelial cells, and some cancer cells. These observations encouraged a new perspective on ferritin beyond iron storage, such as a role in the regulation of iron accessibility to nuclear components, DNA protection from iron-induced oxidative damage, and transcriptional regulation., Scope of Review: This review will address the translocation and functional significance of nuclear ferritin in the context of human development and disease., Major Conclusions: The nuclear translocation of ferritin is a selective energy-dependent process that does not seem to require a consensus nuclear localization signal. It is still unclear what regulates the nuclear import/export of ferritin. Some reports have implicated the phosphorylation and O-glycosylation of the ferritin protein in nuclear transport; others suggested the existence of a specific nuclear chaperone for ferritin. The data argue strongly for nuclear ferritin as a factor in human development and disease. Ferritin can bind and protect DNA from oxidative damage. It also has the potential of playing a regulatory role in transcription., General Significance: Nuclear ferritin represents a novel new outlook on ferritin functionality beyond its classical role as an iron storage molecule., (Copyright 2010 Elsevier B.V. All rights reserved.)