Assessment of Perceptions and Predictors Towards Consanguinity: A Cross-Sectional Study from Palestine.

Background/Aim: Consanguinity represents a biological relationship between two individuals. In clinical genetics, it specifically refers to the marriage between individuals who are second cousins or closer. The aim of the study is to assess perceptions and their predictors among the Palestinian population towards consanguinity. Methods: A survey-based cross-sectional study was conducted. The sample was collected using convenience and snowball sampling methods, yielding a sample of 1008 participants. The perceptions towards consanguinity and its predictors were assessed using Chi-square test. Results: The prevalence of consanguinity among married participants was 18.7% (N = 81/432), while it was 28.8% among their parents. Consanguinity rate was significantly low among the young age group (ie, <47 years old) and among participants whose mothers have undergraduate educational levels (P < 0.05). Other factors like parental consanguinity, educational level of participants, their father's educational level, and residency place showed no significant associations (P > 0.05). Rejection of consanguinity was significantly noted among young age participants, absence of parental consanguinity, the presence of children or family members with genetic disorders and female gender (P < 0.001). Furthermore, participants who indicated that they are governmental employees, those with 2000-5000 ILS monthly income, those who are married (P < 0.01), and those who indicated that their mothers are holders of postgraduate degree were significantly more likely to reject the idea of consanguinity (P < 0.05). Also, medical and/or scientific reasons were significantly associated with rejecting the idea of consanguinity (P < 0.001). Conclusion: Consanguinity prevalence has decreased among recent generations in Palestine, but it remains a significant challenge in Palestine. Therefore, educational and awareness programs about consanguinity and its health effects are effective strategies for reducing the consanguinity rate, especially for persons who are at the age of marriage.

Lack of exposure to pharmacogenomics education among the health care providing students in the West Bank of Palestine.

OBJECTIVES: Evaluating the knowledge in pharmacogenomics (PGx) is the first step toward the implementation of PGx testing in clinical practice. This survey aimed to evaluate the knowledge of PGx testing among healthcare providing students at the top-ranked university in the West Bank of Palestine. METHODS: First an online questionnaire consisting of 30 questions regarding the demographic, knowledge, and attitude toward pharmacogenomics testing was structured and validated. Then the questionnaire was distributed to 1,000 current students from different fields. RESULTS: 696 responses was received. The results showed that almost half of the participants (n=355, 51.1%) have never took any courses about PGx during their university training. Only 81 (11.7%) of the students who took the PGx course stated that it helped them understanding how genetic variations affect drug response. The majority of the students were uncertain (n=352, 50.6%) or disagreed (n=143, 20.6%) that the lectures during university education described the effects of genetic variants on drug response. Although most of the students (70-80%) answered that genetic variants can indeed affect the drug's response, only 162 students (23.3%) responded that VKORC1 and CYP2C9 genotypes influence the response to warfarin. In addition, only 94 (13.5%) students were aware that many medicine labels include clinical information about PGx testing provided by the FDA. CONCLUSIONS: It is concluded from the results of this survey that there is a lack of exposure to PGx education associated with poor knowledge of PGx testing among the healthcare providing students in the West Bank of Palestine. It is recommended to include and improve the lectures and courses regarding PGx as this will have a major impact on precision medicine.

Prevalence and associated risk factors of tinnitus among adult Palestinians: a cross-sectional study.

Tinnitus is a common complaint with potentially negative impact on quality of life. Prevalence of tinnitus ranges from 5 to 43% worldwide. This variation could be due to the heterogeneity of tinnitus assessment. This has limited the progress in understanding tinnitus. Therefore, we employed a standardized and a validated assessment method to determine the prevalence and related risk factors of tinnitus among Palestinians for the first time. This is a cross-sectional study in which we questioned a representative sample of 618 subjects in one-to-one interviews. The prevalence of any tinnitus was 30.6% among adult Palestinians. Participants from the oldest age group were almost five times more likely to have tinnitus. Moreover, participants with head and neck pain syndrome, severe hearing impairment, sleeping disorders or frequent complaints of vertigo were approximately two times more likely to have tinnitus. Our study provides novel information regarding tinnitus in Palestine and improves our understanding of tinnitus. This will improve the diagnosis and consequently will contribute in reducing the prevalence and perhaps in preventing tinnitus. As tinnitus still has no known cure, further investigations of modifiable risk factors and causes of tinnitus are crucial to prevent it in the future.

Gundelia tournefortii inhibits hepatocellular carcinoma progression by lowering gene expression of the cell cycle and hepatocyte proliferation in immunodeficient mice.

Gundelia (G.) tournefortii has antibacterial, anti-inflammatory, and hypolipemic effects. We evaluated the anticancer effect of G. tournefortii in an hepatocellular carcinoma (HCC) mouse model of an HCC cell line (Hep3B) injected into NOD.CB17-Prkdc-SCID/NCrHsD male mice. Tumorigenicity was assessed by tumor size, histology, serum α-fetoprotein (αFP), and glypican 3 (GPC3). HCC-related gene expression of the cell cycle (Cyclin-dependent kinase inhibitor 2A (CDNK2A)), proliferation (MKI67), and platelet-derived growth factor receptor α (PDGFA) were measured. HCC cell cycle alterations, apoptosis, and antioxidant markers in serum and liver following treatment with G. tournefortii were determined. Signaling pathways of liver p53 and phosphorylated PI3K, AKT, and mTOR were also evaluated. Results indicate a significant increase in tumor size in HCC animals associated with elevated αFP, GPC3, and MKI67. Tumor markers of p53 and phosphorylated AKT/PI3K/mTOR signaling pathway were diminished, with less proliferating cells and reduced PDGFRA gene expression following G. tournefortii infection. H&E staining showed a remarkable reduction in inflammatory lesions in HCC mice treated with G. tournefortii. This result was in line with a significant delay in the G2/M phase of HCC-primary hepatocytes by 1.39- to 2.4-fold and reduced HCC necrosis associated with inhibited CDNK2A gene expression. Antioxidant activity was significantly lower in the HCC mice than in the control group. Moreover, G. tournefortii inhibited the HCC formation of 3D MCTS spheroids. G. tournefortii treatment markedly restored antioxidant levels and displayed anticancer and antiproliferative effects and could be a promising cancer therapy.

Nutritional status and quality of life in diabetic patients on hemodialysis: a cross-sectional study from Palestine.

BACKGROUND: End-stage renal disease (ESRD) is a leading cause of death and morbidity worldwide. Malnutrition is a common problem among hemodialysis (HD) patients that negatively impacts their prognosis and is linked to an increase in morbidity and mortality in these patients, as well as a decrease in their quality of life (QOL). In this study, we aimed to evaluate the QOL and to investigate factors that can influence it, including nutritional status, as well as socio-demographic factors, among Palestinian diabetic patients on HD therapy. METHODS: This was a cross-sectional study that occurred at a large hemodialysis center in Palestine. Malnutrition was assessed by the malnutrition-inflammation scale (MIS), and the quality of life was evaluated by using the EuroQoL five-dimensional instrument (EQ-5D). Multivariable linear regression analysis was carried out to look at the effect of multiple variables on QOL. RESULTS: A total of 118 diabetic patients on HD were included. Of these, 66.9% were male, and 60.2% were aged 60 years or higher. Having multiple comorbid diseases (p=0.004) and having been on HD for >4 years (p=0.003) were significantly associated with a higher MIS score, whereas living alone (p=0.037) and having been on HD for >4 years (p=0.002) was significantly associated with lower EQ-5D score. We also observed a significant association between the MIS score and the EQ-5D score(r=-0.616, p<0.001). Multiple linear regression analysis demonstrated that diabetic hemodialysis patients who lived within a family household were positively correlated with the QOL score (standardized coefficient, 0.178; 95% confidence interval (CI), 0.042 to 0.372; p = 0.015), and MIS score was significantly and negatively correlated with QOL scores (standardized coefficient, -0.587; 95% CI, -0.047 to -0.028; p < 0.001). CONCLUSIONS: We found that malnutrition was associated with a lower QOL score among diabetic patients on HD. We recommend general practitioners, dietitians, nephrologists, and nurses to make plans that pay more attention to this group of patients who show evidence of malnutrition. Patients on dialysis for ≥ 4 years, patients who live alone, and those suffering from multiple co-morbid diseases should receive special care due to their higher risk of being impacted by this problem.

Prevalence of underweight, overweight and obesity among Palestinian school-age children and the associated risk factors: a cross sectional study.

BACKGROUND: Childhood obesity is rising in developed and developing countries, while childhood underweight is rising mainly in developing countries. Childhood underweight has been shown to increase a child's risk of rapid weight gain. Overweight and obese children are more likely to become obese adults, which increases the risk of type-II diabetes and cardiovascular diseases. Studies concerning obesity among Palestinian children are scarce. The prevalence of obesity among Palestinian children has increased from 3 to 6% within 5 years in comparison to the worldwide rise from 1 to 7%, within 41 years. We aim to determine the current prevalence of underweight, overweight and obesity among Palestinian school-age children and to assess the role of dietary and sociodemographic factors. METHODOLOGY: A cross sectional study was conducted in Palestine in 2017. A total of 1320 school-age children and their 2640 corresponding parents were recruited. A written questionnaire was filled out by the parents. Anthropometric indices were measured and categorized according to the Center for Disease Control and prevention (CDC). RESULTS: The mean ± SD age of the children was 9.5 ± 1.5 years and 48.8% were females. The prevalence of underweight, overweight and obesity among the children was approximately 7.3% (95% CI = 5.9-8.8%), 14.5% (95% CI = 12.7-16.6%) and 15.7% (95% CI = 13.8-17.8%) respectively. Multinomial logistic regression analysis demonstrated a significant correlation of waist circumference, age, gender and living place with the body mass indexes of the students. CONCLUSION: Our findings highlighted the accelerated increase in the prevalence of underweight, overweight and obesity (37.5%) among Palestinian children within a very short time in comparison to the globe. Therefore, Interventions aiming to prevent obesity and underweight at an early stage might be vital to avoid obesity later in life and its health-related co-morbidities, e.g. type-II diabetes and cardiovascular diseases.

Ethnopharmacological survey of medicinal plants practiced by traditional healers and herbalists for treatment of some urological diseases in the West Bank/Palestine.

BACKGROUND: Throughout history, every civilization in the world used plants or their derivatives for treatment or prevention of diseases. In Palestine as in many other countries, herbal medicines are broadly used in the treatment of wide range of diseases including urological diseases. The main objective of this research is to study the use of herbal remedies by herbalists and traditional healers for treatment of various urological diseases in the West Bank regions of Palestine and to assess their efficacy and safety through the literature review of the most cited plants. METHOD: The study included a survey part, plant identification and a review study. The first part was a cross-sectional descriptive study. Face to face questionnaires were distributed to 150 traditional healers and herbalist in all regions of the West Bank of Palestine. The literature review part was to assess the most cited plants for their efficacy and toxicity. RESULTS: One hundred forty four herbalists and traditional healers accepted to participate in this study which was conducted between March and April, 2016. The results showed that 57 plant species belonging to 30 families were used by herbalists and traditional healers for treatment of various urinary tract diseases in Palestine. Of these, Apiaceae family was the most prevalent. Paronychia argentea, Plantago ovata, Punica granatum, Taraxacum syriacum, Morus alba and Foeniculum vulgare were the most commonly used plant species in the treatment of kidney stones, while Capsella bursa-pastoris, Ammi visnaga and Ammi majus were the most recommended species for treatment of urinary tract infections and Portulaca oleracea used for renal failure. In addition Curcuma longa and Crocus sativus were used for enuresis while Juglans regia, Quercus infectoria, Sambucus ebulus and Zea mays were used for treatment symptoms of benign prostate hyperplasia. Fruits were the most common parts used, and a decoction was the most commonly used method of preparation. Through literature review, it was found that Paronychia argentea has a low hemolytic effect and contains oxalic acid and nitrate. Therefore, it could be harmful to renal failure patients, also Juglans regia, Quercus infectoria and, Sambucus ebulus are harmful plants and cannot be used for treatment of any disease. CONCLUSIONS: Our data provided that ethnopharmacological flora in the West Bank regions of Palestine can be quite wealthy and diverse in the treatments of urinary tract diseases. Clinical trials and pharmacological tests are required evaluate safety and efficacy of these herbal remedies.

Global methaemoglobinaemia research output (1940-2013): a bibliometric analysis.

Bibliometric studies, which involve the use of statistical methods, are increasingly being used for research assessment. A bibliometric analysis was conducted to evaluate the publication pattern of methaemoglobinaemia research output at the global level based on the Scopus database. We analysed selected documents with "methemoglobinemia", or "methaemoglobinaemia" as a part of the title and reported the following parameters: trends of publication output, country of publication, journal pattern, collaborative measures, citations pattern, and institute productivity. A total of 1770 articles were published worldwide. The time trend for the number of articles showed an increase after 2000. The highest number of articles related to methaemoglobinaemia was from the USA (24.8 %), followed distantly by the UK (4.5 %), India (3.7 %), and France (3.7 %). No data related to methaemoglobinaemia were published from 152 countries. The total number of citations at the date of data collection was 10,080, with an average of 5.7 citations per document. The USA and UK had the highest h-index of 31 and 14, respectively, and six countries had an h-index of 9-14. It is notable that Canada was ranked eighth in the number of publications but fourth in h-index and India was ranked third in the number of publications but eighth in h-index. Furthermore, Canada produced the most internationally collaborated papers out of the total number of publications for each country (16.1 %), followed by the UK (13.9 %). This bibliometric analysis provides data contributing to a better understanding of the methaemoglobinaemia research field. The number of publications on methaemoglobinaemia increased significantly after 2000. The USA was the most productive country as measured by total publications. The USA and UK achieved the highest h-index in the field of methaemoglobinaemia research, signifying a higher quality of research than other countries.

The transcription factor HNF-4α: a key factor of the intestinal uptake of fatty acids in mouse.

With an excessive postprandial accumulation of intestine-derived, triglyceride-rich lipoproteins being a risk factor of cardiovascular diseases, it is essential to characterize the mechanisms controlling the intestinal absorption of dietary lipids. Our aim was to investigate the role of the transcription factor hepatocyte nuclear factor (HNF)-4α in this process. We used transgenic mice with a specific and inducible intestinal knockout of Hnf-4α gene. One hour after a lipid bolus, in the presence of the lipase inhibitor tyloxapol, lower amounts of triglycerides were found in both plasma and intestinal epithelium of the intestine-specific Hnf-4α knockout (Hnf-4α(intΔ)) mice compared with the Hnf-4α(loxP/loxP) control mice. These discrepancies were due to a net decrease of the intestinal uptake of fatty acid in Hnf-4α(intΔ) mice compared with Hnf-4α(loxP/loxP) mice, as assessed by the amount of radioactivity that was recovered in intestine and plasma after gavage with labeled triolein or oleic acid, or in intestinal epithelial cells isolated from jejunum after a supply of labeled oleic acid-containing micelles. This decreased fatty acid uptake was associated with significant lower levels of the fatty acid transport protein-4 mRNA and protein along the intestinal tract and with a lower acyl-CoA synthetase activity in Hnf-4α(intΔ) mice compared with the control mice. We conclude that the transcription factor HNF-4α is a key factor of the intestinal absorption of dietary lipids, which controls this process as early as in the initial step of fatty acid uptake by enterocytes.

The proteome of cytosolic lipid droplets isolated from differentiated Caco-2/TC7 enterocytes reveals cell-specific characteristics.

BACKGROUND INFORMATION: Intestinal absorption of alimentary lipids is a complex process ensured by enterocytes and leading to TRL [TAG (triacylglycerol)-rich lipoprotein] assembly and secretion. The accumulation of circulating intestine-derived TRL is associated with atherosclerosis, stressing the importance of the control of postprandial hypertriglyceridaemia. During the postprandial period, TAGs are also transiently stored as CLDs (cytosolic lipid droplets) in enterocytes. As a first step for determining whether CLDs could play a role in the control of enterocyte TRL secretion, we analysed the protein endowment of CLDs isolated by sucrose-gradient centrifugation from differentiated Caco-2/TC7 enterocytes, the only human model able to secrete TRL in culture and to store transiently TAGs as CLDs when supplied with lipids. Cells were analysed after a 24 h incubation with lipid micelles and thus in a state of CLD-associated TAG mobilization. RESULTS: Among the 105 proteins identified in the CLD fraction by LC-MS/MS (liquid chromatography coupled with tandem MS), 27 were directly involved in lipid metabolism pathways potentially relevant to enterocyte-specific functions. The transient feature of CLDs was consistent with the presence of proteins necessary for fatty acid activation (acyl-CoA synthetases) and for TAG hydrolysis. In differentiated Caco-2/TC7 enterocytes, we identified for the first time LPCAT2 (lysophosphatidylcholine acyltransferase 2), involved in PC (phosphatidylcholine) synthesis, and 3BHS1 (3-ß-hydroxysteroid dehydrogenase 1), involved in steroid metabolism, and confirmed their partial CLD localization by immunofluorescence. In enterocytes, LPCAT2 may provide an economical source of PC, necessary for membrane synthesis and lipoprotein assembly, from the lysoPC present in the intestinal lumen. We also identified proteins involved in lipoprotein metabolism, such as ApoA-IV (apolipoprotein A-IV), which is specifically expressed by enterocytes and has been proposed to play many functions in vivo, including the formation of lipoproteins and the control of their size. The association of ApoA-IV with CLD was confirmed by confocal and immunoelectron microscopy and validated in vivo in the jejunum of mice fed with a high-fat diet. CONCLUSIONS: We report for the first time the protein endowment of Caco-2/TC7 enterocyte CLDs. Our results suggest that their formation and mobilization may participate in the control of enterocyte TRL secretion in a cell-specific manner.

Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet.

Western diet is characterized by a hypercaloric and hyperlipidic intake, enriched in saturated fats, that is associated with the increased occurrence of metabolic diseases. To cope with this overload of dietary lipids, the intestine, which delivers dietary lipids to the body, has to adapt its capacity in lipid absorption and lipoprotein synthesis. We have studied the early effects of a high-fat diet (HFD) on intestinal lipid metabolism in mice. After 7 days of HFD, mice displayed normal fasting triglyceridemia but postprandial hypertriglyceridemia. HFD induced a decreased number of secreted chylomicrons with increased associated triglycerides. Secretion of larger chylomicrons was correlated with increased intestinal microsomal triglyceride transfer protein (MTP) content and activity. Seven days of HFD induced a repression of genes involved in fatty acid synthesis (FAS, ACC) and an increased expression of genes involved in lipoprotein assembly (apoB, MTP, and apoA-IV), suggesting a coordinated control of intestinal lipid metabolism to manage a high-fat loading. Of note, the mature form of the transcription factor SREBP-1c was increased and translocated to the nucleus, suggesting that it could be involved in the coordinated control of gene transcription. Activation of SREBP-1c was partly independent of LXR. Moreover, HFD induced hepatic insulin resistance whereas intestine remained insulin sensitive. Altogether, these results demonstrate that a short-term HFD is sufficient to impact intestinal lipid metabolism, which might participate in the development of dyslipidemia and metabolic diseases.