Noncommunicable Disease and Health Care-Seeking Behavior Among Urban Camp-Dwelling Syrian Refugees in Lebanon: A Preliminary Investigation.

Purpose: Syrian refugees (SRs) in Lebanon are often relegated to informal camps with poor living conditions and substandard access to health care. This study examined the unique condition of urban camp-dwelling SRs in Lebanon. This population is rarely studied as they are marginalized and difficult to access. We sought to assess the prevalence of noncommunicable diseases (NCDs) and health care-seeking behaviors within this population. Methods: A randomized group of urban camp-dwelling SR participants completed a survey on disease burden, health care-seeking patterns, and attitudes toward care. A second group completed interviews regarding health care experiences. We present descriptive population and epidemiologic measures to quantify NCD burden and health care-seeking behaviors. Results: Of 101 participants, 39% reported arthritis, 25% skin infection, 24% high blood pressure, 16% chronic lung conditions, 16% eye disease, and 15% diabetes. Major themes from interviews with SRs included poor living conditions, high cost of health care services, and perceived discrimination by health care workers (HCWs). The major theme from interviews with HCWs was a perception that SRs received health care services similar to members of surrounding communities. Discussion: In this population, we found a higher prevalence of NCDs at younger ages than in the general SR population. We described perceived barriers to accessing health care, including the noteworthy finding of perceived discrimination by HCWs in a linguistically and culturally related host community. We discussed social determinants of health within the camp and refugees' ability to access health care services.

Healthcare professionals' views and perceptions of analgesic and antipyretic use in paediatric patients in four major Saudi hospitals.

BACKGROUND: Antipyretics and analgesics, including non-steroidal anti-inflammatory drugs, are medications commonly used in the Kingdom of Saudi Arabia (KSA) and elsewhere to manage fever and pain in the paediatric age group.Research work investigating misuse of these medications in paediatric populations and pertinent healthcare professionals' (HCPs) perceptions as a major determinant of the severity of these errors is scarce. OBJECTIVES: The aim of this study was to explore the perceptions of HCPs about analgesic and antipyretic use in paediatric patients at four major hospitals in Jeddah, KSA. The study also sought to explore factors believed by HCPs to be associated with occurrence of medication errors and adverse drug reactions (ADRs) due to analgesic and antipyretic use. METHODS: A cross-sectional survey employing a pre-piloted online questionnaire with an information sheet was delivered to HCPs in four hospitals in the western region of KSA. The questionnaire comprised a mix of a tick list and open and closed questions with Likert scales for attitudinal statements, and it also comprised items including demographics, healthcare professions and the respondents' work experience, HCPs' views and perceptions relating to occurrence of ADRs and medication errors in children who attended the hospital in the preceding three months and the severity and outcomes of the ADRs. RESULTS: Two-hundred seventy-four HCPs were approached, and 200 agreed to participate, yielding a response rate of 73%, including physicians (50%), nurses (24.5%), and pharmacists (16.5%).The majority of HCPs reported that ADRs could be minimized with appropriate actions. They believed that their lack of experience may have contributed to ADRs. Most HCPs (81%) reported that parental knowledge was a key factor contributing to the decreased occurrence of ADRs in children. They also believed that other factors contributed to the occurrence of ADRs, such as lack of reconciliation (65%), parents' anxiety leading to overmedication (69%) and the easy availability of these medications at home (77%).Twenty-nine respondents (n = 29, 14.5%) reported medication errors related to the use of analgesics or antipyretics. Specifically, they reported that possible contributing factors included poor communication of information (69.5%); interruptions (67.5%) and work pressure (66.0%). CONCLUSION: HCPs reported that ADRs and medication errors related to using analgesics and antipyretics in paediatric patients are not uncommon. In their opinion, several factors were associated with occurrence of these events, including parental knowledge about medications and insufficient training of HCPs.

GC-MS analysis of polycyclic aromatic hydrocarbons in bottled olive oil marketed in Lebanon.

Lebanon has witnessed elevated levels of pollution over the last few years due to increased waste incineration, emissions from vehicles and electricity generators, and mass demonstrations involving the burning of tires. The resultant generation of polycyclic aromatic hydrocarbons (PAHs) from the incomplete combustion of organic materials present in these sources may contaminate various foods including olive oil. Lebanon has a sizeable olive oil industry that is a main pillar of its agricultural sector. In this study, we investigated the occurrence of 16 semi-volatile lipophilic organic pollutants in 25 bottled olive oil brands, marketed in Lebanon, using a solid phase extraction (SPE) method followed by gas chromatography mass spectrometry (GC-MS). PAHs were detected in 60% of brands (41% of samples) where 12% of brands contained traces of probably carcinogenic (Class 2A) compounds and 56% of brands contained traces of possibly carcinogenic (Class 2B) compounds. One brand revealed levels of benzo[a]pyrene of 9.45 µg/kg and 11.9 µg/kg in batches collected over two production dates which are higher than the limit set by the European Commission for benzo[a]pyrene in food (2 µg/kg). The same batches contained a total of 19.3 µg/kg and 26.7 µg/kg of the four PAHs: benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, and chrysene which also exceeded the limit set by the EC for the combination of these four PAHs in olive oil (10 µg/kg). This study is the first-of-its-kind in Lebanon and emphasizes the need to perform adequate cleanup steps in the manufacturing process in order to reduce the content of carcinogenic PAHs in olive oil.

Parental Experience of Potential Adverse Drug Reactions Related to Their Oral Administration of Antipyretic Analgesic Medicines in Children in Saudi Arabia.

BACKGROUND: Oral antipyretic analgesic medicines are commonly used in children and have the potential for adverse drug reactions (ADRs). OBJECTIVE: The aim of this study was to explore parental experiences of potential ADRs related to their oral administration of antipyretic analgesics in children in the Kingdom of Saudi Arabia. METHODS: For this cross-sectional survey, a paper-based questionnaire, consent form and information sheet were handed out to 1000 parents who had administered an oral antipyretic analgesic medicine to their children during the previous 3 months. Data were entered and analyzed using SPSS version 21.0 (IBM-SPSS Inc, Armonk, NY). Simple descriptive and inferential statistics were used. Management and ethical approvals were attained. RESULTS: During March to April 2017, 661 parents agreed to participate, giving a response rate of 66.1%. Of the surveyed sample, 208 parents had observed 1 or more potential ADRs (31.5%, n = 208 out of 661). Parents' (n = 208) most commonly reported potential ADRs (n = 523) were loss of appetite (23%, n = 120 out of 523), stomachache (20.3%, n = 106 out of 523), abdominal colic (13%, n = 68 out of 523), and diarrhea (10.3%, n = 54 out of 523). Parents described severity of the ADRs as slight (71.8%, n = 342 out of 476), annoying to the child (7.9%, n = 85 to of 476), significant and affecting daily tasks (3.6%, n = 17 out of 476) and significant and led to the hospital (6.7%, n = 32 out of 476). Fever was the top-ranked reason for using antipyretic analgesic medicines (41.0%, n = 271 out of 661), followed by toothache (25.0%, n = 165 out of 661) and tonsillitis/laryngitis (24.7%, n = 163 out of 661). Among parents, 34.7% (n = 165 out of 476) did not seek medical attention when a potential ADR occurred, whereas 26.3% (n = 125 out of 476) of parents took their children to hospital clinics. CONCLUSIONS: Although the majority of parentally reported (but not proven) ADRs were mild, a number of significant ADRs were reported. Future research should consider whether there is a role for physicians and pharmacists in educating parents in Saudi Arabia, and perhaps more widely, about the optimal use of oral antipyretic and analgesic medicines in children. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX)© 2020 Elsevier HS Journals, Inc.

Determination of Ochratoxin A (OTA), Ochratoxin B (OTB), T-2, and HT-2 Toxins in Wheat Grains, Wheat Flour, and Bread in Lebanon by LC-MS/MS.

Cereals are prone to fungal infection during growth, harvesting, transportation, and/or storage. As a result, cereals such as wheat grains and wheat-derived products may be contaminated with mycotoxins leading to acute and chronic health exposure. The current study investigated the presence of the mycotoxins: ochratoxin A (OTA), ochratoxin B (OTB), T-2, and HT-2 toxins in samples of wheat grains (n = 50), wheat flour (n = 50), and bread (n = 37) from the main mills in Lebanon using LC-MS/MS. Accuracy ranged from 98-100%, recoveries from 93-105%, and intraday and interday precision were 5-7% and 9-12%, respectively. The tested wheat grains, wheat flour, and bread samples did not contain detectable levels of T-2 and HT-2 toxins and OTB. Four wheat flour samples (8% of flour samples) showed positive OTA levels ranging from 0.6-3.4 µg·kg-1 with an arithmetic mean of 1.9 ± 0.2 µg·kg-1. Only one sample contained an OTA concentration greater than the limit set by the European Union (3 µg·kg-1) for wheat-derived products. This study suggests that mycotoxin contamination of wheat grains, wheat flour, and bread in Lebanon is currently not a serious public health concern. However, surveillance strategies and monitoring programs must be routinely implemented to ensure minimal mycotoxin contamination of wheat-based products.

The Influence of Emerging Markets on the Pharmaceutical Industry.

Emerging markets represent an exceptional opportunity for the pharmaceutical industry. Although a precise definition is not yet available, economists define emerging markets as developing prosperous countries in which investment is expected to result in higher income despite high risks. Qualifying a market as emerging is not merely based on the economic status of the country, but also on several criteria that render the definition applicable to each country. Jim O'Neil, retired chairman of asset management at Goldman Sachs, identified leading economies of emerging markets: Brazil, Russia, India, and China (BRIC) and later Brazil, Russia, India, China, and South Africa (BRICS) and then Mexico, Indonesia, South Korea, and Turkey (MIST), which followed years later as the second tier of nations. Sales of the pharmaceutical markets in BRICS and MIST countries doubled in 5 years, reaching a market share of approximately 20%. The shift toward these new markets has been attributed to the large populations, growing prosperity, and increasing life expectancy in BRICS and MIST countries. In addition, companies are experiencing flattened growth of developed markets, expiration of patents leading to the up-selling of less expensive generic drugs, and tight regulations enforced in mature markets. Particular attention must therefore be given to these emerging markets. The strategies adopted by pharmaceutical companies that want to expand in these markets must be tailored to the pace of development of each country. These countries need drugs against infectious diseases and communicable diseases such as sexually transmitted diseases. They are readily exploitable territories for the innovative products of pharmaceuticals. Nevertheless, with the increase in wealth and longevity, a change of lifestyle is occurring. These changes accompany a shift in disease patterns. A disproportionally fast rise in the incidence of noncommunicable diseases such as cardiovascular illnesses, diabetes, and oncologic diseases has been observed in emerging markets, mimicking their Western counterparts. The incidence of diabetes and oncologic diseases is expected to grow by 20% or more by 2030. This shows that pharmaceutical industries will also be able to market their global products in these new countries. Conquering emerging markets can be challenging for industries. These challenges can be grouped into 3 categories: infrastructure development, cost-containment policies, and value-driven drug evaluation. Top strategies considered to overcome these challenges include adequate tailoring and a gain in market.

Experimental Diabetes Mellitus in Different Animal Models.

Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.

Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells.

While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO(4)) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a cellular compartment in close proximity but not overlapping with the basolateral surface. Surface biotinylation studies indicate that hephaestin in the peri-basolateral location is accessible to the extra-cellular environment. These results support the hypothesis that hephaestin is involved in iron mobilization of iron from the intestine to circulation.

Identification of zyklopen, a new member of the vertebrate multicopper ferroxidase family, and characterization in rodents and human cells.

We previously detected a membrane-bound, copper-containing oxidase that may be involved in iron efflux in BeWo cells, a human placental cell line. We have now identified a gene encoding a predicted multicopper ferroxidase (MCF) with a putative C-terminal membrane-spanning sequence and high sequence identity to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate MCF. Molecular modeling revealed conservation of all type I, II, and III copper-binding sites as well as a putative iron-binding site. Protein expression was observed in multiple diverse mouse tissues, including placenta and mammary gland, and the expression pattern was distinct from that of Cp and Heph. The protein possessed ferroxidase activity, and protein levels decreased in cellular copper deficiency. Knockdown with small interfering RNA in BeWo cells indicates that this gene represents the previously detected oxidase. We propose calling this new member of the MCF family "zyklopen."

Decreased hephaestin expression and activity leads to decreased iron efflux from differentiated Caco2 cells.

Iron is transported across intestinal brush border cells into the circulation in at least two distinct steps. Iron can enter the enterocyte via the apical surface through several paths. However, iron egress from the basolateral side of enterocytes converges on a single export pathway requiring the iron transporter, ferroportin1, and hephaestin, a ferroxidase. Copper deficiency leads to reduced hephaestin protein expression and activity in mouse enterocytes and intestinal cell lines. We tested the effect of copper deficiency on differentiated Caco2 cells grown in transwells and found decreased hephaestin protein expression and activity as well as reduced ferroportin1 protein levels. Furthermore, the decrease in hephaestin levels correlates with a decrease of (55)Fe release from the basolateral side of Caco2 cells. Presence of ceruloplasmin, apo-transferrin or holo-transferrin did not significantly alter the results observed. Repletion of copper in Caco2 cells leads to reconstitution of hephaestin protein expression, activity, and transepithelial iron transport.

Age-related changes in iron homeostasis in mouse ferroxidase mutants.

Disorders of iron metabolism are a significant problem primarily in young and old populations. In this study, We compared 1-year-old C57BL6/J mice on iron deficient, iron overload, or iron sufficient diets with two similarly aged genetic models of disturbed iron homeostasis, the sla (sex-linked anemia), and the ceruloplasmin knockout mice (Cp(-/-)) on iron sufficient diet. We found tissue specific changes in sla and nutritional iron deficiency including decreased liver Hamp1 expression and increased protein expression of the enterocyte basolateral iron transport components, hephaestin and ferroportin. In contrast, the Cp(-/-) mice did not show significantly increased Hamp1 expression despite increased liver iron suggesting that regulation is independent of liver iron levels. Together, these results suggest that older mice have a distinct response to alterations in iron metabolism and that age must be considered in future studies of iron metabolism.

Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency.

Copper and iron metabolism intersect in mammals. Copper deficiency simultaneously leads to decreased iron levels in some tissues and iron deficiency anemia, whereas it results in iron overload in other tissues such as the intestine and liver. The copper requirement of the multicopper ferroxidases hephaestin and ceruloplasmin likely explains this link between copper and iron homeostasis in mammals. We investigated the effect of in vivo and in vitro copper deficiency on hephaestin (Heph) expression and activity. C57BL/6J mice were separated into 2 groups on the day of parturition. One group was fed a copper-deficient diet and another was fed a control diet for 6 wk. Copper-deficient mice had significantly lower hephaestin and ceruloplasmin (approximately 50% of controls) ferroxidase activity. Liver hepcidin expression was significantly downregulated by copper deficiency (approximately 60% of controls), and enterocyte mRNA and protein levels of ferroportin1 were increased to 2.5 and 10 times, respectively, relative to controls, by copper deficiency, indicating a systemic iron deficiency in the copper-deficient mice. Interestingly, hephaestin protein levels were significantly decreased to approximately 40% of control, suggesting that decreased enterocyte copper content leads to decreased hephaestin synthesis and/or stability. We also examined the effect of copper deficiency on hephaestin in vitro in the HT29 cell line and found dramatically decreased hephaestin synthesis and activity. Both in vivo and in vitro studies indicate that copper is required for the proper processing and/or stability of hephaestin.

Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice.

Hephaestin (Hp) plays an important role in intestinal iron absorption and is predicted to be a ferroxidase based on significant sequence identity to the serum multicopper ferroxidase ceruloplasmin. Here, we demonstrate that Hp has both amine oxidase and ferroxidase activity in cultured cells and primary intestinal enterocytes with the use of both gel and solution assays. The specificity of the activity is shown by immunoblotting, immunoprecipitation, and immunodepletion experiments. Surprisingly, the truncated hephaestin expressed in sex-linked anemia (sla) mice still has measurable, but decreased, oxidase activity. Molecular modeling of the truncated hephaestin suggests retention of a minimum catalytic core required for enzymatic activity. We suggest that hephaestin, by way of its ferroxidase activity, facilitates iron export from intestinal enterocytes, most likely in cooperation with the basolateral iron transporter, Ireg1.

Systemic regulation of Hephaestin and Ireg1 revealed in studies of genetic and nutritional iron deficiency.

Hephaestin is a membrane-bound multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation. Mice with sex-linked anemia (sla) have a mutant form of Hephaestin and a defect in intestinal basolateral iron transport, which results in iron deficiency and anemia. Ireg1 (SLC11A3, also known as Ferroportin1 or Mtp1) is the putative intestinal basolateral iron transporter. We compared iron levels and expression of genes involved in iron uptake and storage in sla mice and C57BL/6J mice fed iron-deficient, iron-overload, or control diets. Both iron-deficient wild-type mice and sla mice showed increased expression of Heph and Ireg1 mRNA, compared to controls, whereas only iron-deficient wild-type mice had increased expression of the brush border transporter Dmt1. Unlike iron-deficient mice, sla mouse enterocytes accumulated nonheme iron and ferritin. These results indicate that Dmt1 can be modulated by the enterocyte iron level, whereas Hephaestin and Ireg1 expression respond to systemic rather than local signals of iron status. Thus, the basolateral transport step appears to be the primary site at which the small intestine responds to alterations in body iron requirements.