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Objective: Increased oxidative stress and immune dysfunction are implicated in preeclampsia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 diabetes. Prospective measures of fat-soluble vitamins in diabetic pregnancy are therefore of interest.Research Design and Methods: Maternal serum carotenoids (α- and β-carotene, lycopene, and lutein) and vitamins A, D, and E (α- and γ-tocopherols) were measured at first (12.2 ± 1.9 weeks [mean ± SD], visit 1), second (21.6 ± 1.5 weeks, visit 2), and third (31.5 ± 1.7 weeks, visit 3) trimesters of pregnancy in 23 women with type 1 diabetes who subsequently developed PE (DM PE+) and 24 women with type 1 diabetes, matched for age, diabetes duration, HbA(1c), and parity, who did not develop PE (DM PE-). Data were analyzed without and with adjustment for baseline differences in BMI, HDL cholesterol, and prandial status.Results: In unadjusted analysis, in DM PE+ versus DM PE-, α-carotene and β-carotene were 45 and 53% lower, respectively, at visit 3 (P < 0.05), before PE onset. In adjusted analyses, the difference in β-carotene at visit 3 remained significant. Most participants were vitamin D deficient (<20 ng/mL), and vitamin D levels were lower in DM PE+ versus DM PE- throughout the pregnancy, although this did not reach statistical significance.Conclusions: In pregnant women with type 1 diabetes, low serum α- and β-carotene were associated with subsequent development of PE, and vitamin D deficiency may also be implicated. [ABSTRACT FROM AUTHOR]

Background: Clear and trustworthy information is crucial to improving public acceptance of COVID-19 vaccinations, especially among pregnant women. Given the increased risk of severe viral pneumonia in pregnant women, it is critical to foster confidence in the vaccine's safety and understand any potential adverse events (AEs). So, we did this study in Jeddah, Saudi Arabia (SA), from March to May 2022 to compare women who did not get any doses of the COVID-19 vaccine during pregnancy (Group A) to women who did get at least one dose during pregnancy (Group B) regarding (1) the frequency, types, AEs, and management of its AEs of the COVID-19 vaccination; and (2) exploring pregnancy, delivery, and fetus-related complications (e.g., miscarriage, birth defects, and preterm labor)., Methods: A cross-sectional study targeted 438 women who gave birth or were pregnant within the previous 8 weeks. Data was collected through face-to-face interviews with skilled nurses in 13 randomly selected primary healthcare facilities, using a validated, well-structured questionnaire that included the Centers for Disease Control (CDC) COVID-19 vaccination-related AEs. We analyzed the collected data using SPSS version 27., Results: Most participants were aged 25 to less than 35 (58.8%), and 287 (61.3%) were university graduates. There was no statistically significant difference among the studied groups regarding demographics. However, women in Group B had a significantly higher rate of abortions, oligohydramnios (24.4%), abnormal placentas (size and location), 103 (42.7%) abnormal fetal growth, 122 (53.7%) problems breastfeeding, blood pressure problems, and more cases of malaise, headaches, chest pain, breathing problems, and sleep problems than women in Group A. After the second and third doses, the confirmed post-vaccination COVID-19 rates in Group B were lower than those in Group A., Conclusion: The COVID-19 vaccine significantly reduces post-vaccination COVID-19. Although COVID-19 vaccine-related AES are prevalent, analgesics and antipyretics effectively treat most of them., (© The Author(s), 2024.)

This study aimed to investigate the effects of adding Nano-Selenium (NSe) and Nano-clay (NC) as feed supplements on European Sea Bass (Dicentrarchus labrax). Two separate experiments were conducted, one with NC and the other with NSe. Each experiment consisted of four sub-groups with varying concentrations of NC or NSe. The expression levels of five immune-related genes (TNF-α, TNF-β, IL-2, IL-6 and IL-12) were measured using Real-time Quantitative PCR (Rt-PCR) Assay. The results showed an increase in the expression of interleukins (IL-2, IL-6 and IL-12) and pro-inflammatory cytokines (TNF-α and TNF-β) after exposure to NC and NSe. TNF-α gene expression was significantly higher with both 1 mg and 10 mg concentrations of NC and NSe. TNF-β gene expression was highest with the 5 mg concentration of NC. The concentrations of 1 mg and 10 mg for NC, and 1 mg, 5 mg, and 10 mg for NSe, led to the highest (p < 0.05) levels of IL-2 expression compared to the control. Similar trends were observed for IL-6 and IL-12 gene expression. Understanding the impact of these concentrations on gene expression, growth rate, biochemical indices, and antioxidant status can provide valuable insights into the potential applications of NC and NSe supplements on European Sea Bass., (© 2024. The Author(s).)

Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease.

Sphingolipids play an important role in the development of diabetes, both type 1 and type 2 diabetes, as well as in the development of both micro- and macro-vascular complications. Several reviews have been published concerning the role of sphingolipids in diabetes but most of the emphasis has been on the possible mechanisms by which sphingolipids, mainly ceramides, contribute to the development of diabetes. Research on circulating levels of the different classes of sphingolipids in serum and in lipoproteins and their importance as biomarkers to predict not only the development of diabetes but also of its complications has only recently emerged and it is still in its infancy. This review summarizes the previously published literature concerning sphingolipid-mediated mechanisms involved in the development of diabetes and its complications, focusing on how circulating plasma sphingolipid levels and the relative content carried by the different lipoproteins may impact their role as possible biomarkers both in the development of diabetes and mainly in the development of diabetic complications. Further studies in this field may open new therapeutic avenues to prevent or arrest/reduce both the development of diabetes and progression of its complications.

Aims: We aimed to determine whether plasma advanced glycation end products or oxidation products (AGE/oxidation-P) predict altered renal function and/or preeclampsia (PE) in pregnant women with type 1 diabetes., Methods: Prospectively, using a nested case-control design, we studied 47 pregnant women with type 1 diabetes, of whom 23 developed PE and 24 did not. Nineteen nondiabetic, normotensive pregnant women provided reference values. In plasma obtained at ~12, 22, and 32 weeks' gestation (visits 1, 2, and 3; V1-V3), we measured five AGE products (carboxymethyllysine (CML), carboxyethyl-lysine (CEL), methylglyoxal-hydroimidazolone (MGH1), 3-deoxyglucosone hydroimidazolone (3DGH), and glyoxal-hydroimidazolone (GH1)) and four oxidation products (methionine sulfoxide (MetSO), 2-aminoadipic acid (2-AAA), 3-nitrotyrosine (3NT), and dityrosine (DT)), by liquid chromatography/mass spectroscopy. Clinical outcomes were "estimated glomerular filtration rate" (eGFR) at each visit and onset of PE., Results: In diabetic women, associations between AGE/oxidation-P and eGFR were found only in those who developed PE. In this group, CEL, MGH1, and GH1 at V2 and CML, CEL, MGH1, and GH1 at V3 were inversely associated with contemporaneous eGFR, while CEL, MGH1, 3DGH, and GH1 at V2 were inversely associated with eGFR at V3 (all p < 0.05). There were no associations of plasma AGE or oxidation-P with pregnancy-related development of proteinuria or PE., Conclusions: Inverse associations of second and early third trimester plasma AGE with eGFR among type 1 diabetic women who developed PE suggest that these patients constitute a subset susceptible to AGE-mediated injury and thus to cardiorenal complications later in life. However, AGE/oxidation-P did not predict PE in type 1 diabetic women., Competing Interests: The authors have declared that no conflict of interest exists., (Copyright © 2023 Clare B. Kelly et al.)

Apolipoprotein M (apoM), primarily carried by HDL, has been associated with several conditions, including cardiovascular disease and diabetic nephropathy. This study proposes to examine whether plasma apoM levels are associated with the development of diabetic kidney disease, assessed as progression to macroalbuminuria (MA) and chronic kidney disease (CKD). Plasma apoM was measured using an enzyme immunoassay in 386 subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort at DCCT entry and closeout and the concentrations used to determine the association with risk of progression to kidney dysfunction from the time of measurement through 18 years of EDIC follow-up. apoM levels, at DCCT baseline, were higher in patients who developed CKD than in those who retained normal renal function. At DCCT closeout, participants who progressed to MA, CKD, or both MA and CKD also had significantly higher apoM levels than those who remained normal, and increased levels of apoM were associated with increased risk of progression to both MA (risk ratio [RR] 1.30 [95% CI 1.01, 1.66]) and CKD (RR 1.69 [95% CI 1.18, 2.44]). Our results strongly suggest that alterations in apoM and therefore in the composition and function of HDL in type 1 diabetes are present early in the disease process and are associated with the development of nephropathy., (© 2022 by the American Diabetes Association.)

Background: We have previously shown that very long ceramides/lactosylceramides predicted the development of macroalbuminuria (MA) in type 1 diabetes and expanded our studies into type 2 diabetes., Objective: This study proposes comparing the levels of plasma sphingolipids and their distribution in circulating lipoproteins (VLDL/IDL, LDL, HDL2 and HDL3) between a healthy control group and two groups of subjects with type 2 diabetes, one with and other without MA., Methods: Plasma and lipoprotein sphingolipids/glycosphingolipids were measured using HPLC-MS/MS in 114 subjects (40 controls; 74 type 2 diabetes, 40 without MA; and 34 with MA) and the levels were compared between controls and the two groups of diabetes. Group effect sizes were calculated using Cohen's d., Results: Sphingomyelin species carried by LDL are significantly higher in diabetic patients with MA than in those with normal albumin excretion rate (AER). Compared to controls, significant decreases in the levels of sphingolipids carried by HDL in patients with diabetes with normal AER or MA were observed for all sphingolipid classes except for hexosylceramide, which was normal in diabetic patients without MA. Although lower than in controls, the levels of lactosylceramides carried by HDL2/HDL3 were significantly higher in diabetes with MA., Conclusions: Considering the critical role sphingolipids play in major cell biological responses and cell signaling pathways, the consequences for disease development of changes in the distribution of sphingolipids/glycosphingolipids carried by lipoproteins could be considerable. Our work is just a first step to address a considerable gap in our present knowledge in this important field., Competing Interests: Conflict of interest None of the authors has any conflict of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background. The present study aimed to assess the stress and strain distribution on mini-screws and the surrounding bone in cases of different cortical bone thicknesses (CBTs), mini-screw insertion angles, and force directions using finite element analysis (FEA). Methods. Inventor professional version 8 software was used to construct 24 three-dimensional assemblies of mini-screws inserted with different insertion angles (30º, 60º, and 90º) in alveolar bone blocks with different CBTs (0.5, 1, 1.5, and 2 mm). The models simulated mini-screws inserted in bones with different CBTs and different insertion angles. A 2-N load was applied in two directions to mini-screw heads. The resultant stresses of the applied load were collected from the output of the ANSYS program. Results. The results indicated that force direction affected bone strains as the horizontal force generated more strains on cortical bone than the oblique one. Force applied to 60º inserted mini-screws generated much more strains on cortical bone than 90º and 30º inserted mini-screws. In a 60º inserted mini-screw, the horizontal force generated about 45% more strains on cortical bone than the oblique one. The exerted microstrain on bone decreased as CBT increased. Conclusion. It can be concluded that inserting mini-screws at 60º to the bone surface should be avoided as it generates much more strains on cortical bone than 90º and 30º, especially when a force parallel to the bone surface is applied., (© 2021 The Author(s).)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects females more than males, with African Americans developing more severe manifestation of the disease. SLE patients are at increased risk for cardiovascular disease (CVD), and SLE women 35-44 years old have 50 fold the incidence rate of CVD. Because SLE patients do not follow the typical age and gender pattern for CVD, but instead an accelerated disease course, the traditional biomarkers of elevated LDL and total cholesterol levels do not accurately assess their CVD risk. Recently, we have reported that African American SLE patients had higher ceramide, hexosylceramide, sphingosine and dihydrosphingosine 1-phosphate levels compared to their healthy controls, and those with atherosclerosis had higher sphingomyelin and sphingoid bases levels than those without (PLoS One. 2019; e0224496). In the current study, we sought to identify sphingolipid species that correlate with and pose the potential to predict atherosclerosis severity in African American SLE patients. Plasma samples from a group of African American predominantly female SLE patients with well-defined carotid atherosclerotic plaque burden were analyzed for sphingolipidomics using targeted mass spectroscopy. The data demonstrated that at baseline, plaque area and C3 values correlated inversely with most lactoceramide species. After one-year follow-up visit, values of the change of plaque area correlated positively with the lactoceramide species. There was no correlation between LDL-C concentrations and lactoceramide species. Taken together, lactocylcermide levels may have a 'predictive' value and sphingolipidomics have an added benefit to currently available tools in early diagnosis and prognosis of African American SLE patients with CVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hammad, Harden, Wilson, Twal, Nietert and Oates.)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves multiple organs and disproportionality affects females, especially African Americans from 15 to 44 years of age. SLE can lead to end organ damage including kidneys, lungs, cardiovascular and neuropsychiatric systems, with cardiovascular complications being the primary cause of death. Usually, SLE is diagnosed and its activity is assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics Damage Index (SLICC/ACR), and British Isles Lupus Assessment Group (BILAG) Scales, which unfortunately often occurs after a certain degree of systemic involvements, disease activity or organ damage already exists. There is certainly a need for the identification of early biomarkers to diagnose and assess disease activity as well as to evaluate disease prognosis and response to treatment earlier in the course of the disease. Here we review advancements made in the area of sphingolipidomics as a diagnostic/prognostic tool for SLE and its co-morbidities. We also discuss recent reports on differential sphingolipid metabolism and blood sphingolipid profiles in SLE-prone animal models as well as in diverse cohorts of SLE patients. In addition, we address targeting sphingolipids and their metabolism as a method of treating SLE and some of its complications. Although such treatments have already shown promise in preventing organ-specific pathology caused by SLE, further investigational studies and clinical trials are warranted., (Copyright © 2020 Harden and Hammad.)

The risk for preeclampsia (PE) is enhanced ~4-fold by the presence of maternal type 1 diabetes (T1DM). Vitamin D is essential for healthy pregnancy. We assessed the total, bioavailable, and free concentrations of plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH) 2 D), and vitamin D binding protein (VDBP) at ~12, ~22, and ~32 weeks' gestation ("Visits" (V) 1, 2, and 3, respectively) in 23 T1DM women who developed PE, 24 who remained normotensive, and 19 non-diabetic, normotensive women (reference controls). 25(OH)D deficiency was more frequent in diabetic than non-diabetic women (69% vs. 22%, p < 0.05), but no measure of 25(OH)D predicted PE. By contrast, higher 1,25(OH) 2 D concentrations at V2 (total, bioavailable, and free: p < 0.01) and V3 (bioavailable: p < 0.05; free: p < 0.01), lower concentrations of VDBP at V3 ( p < 0.05), and elevated ratios of 1,25(OH) 2 D/VDBP (V2, V3: p < 0.01) and 1,25(OH) 2 D/25(OH)D (V3, p < 0.05) were all associated with PE, and significance persisted in multivariate analyses. In summary, in women with T1DM, concentrations of 1,25(OH) 2 D were higher, and VDBP lower, in the second and third trimesters in women who later developed PE than in those who did not. 1,25(OH) 2 D may serve as a new marker for PE risk and could be implicated in pathogenesis.

Objective: To investigate the effect of ZnO nanocoating on mechanical properties of NiTi orthodontic wires and antibacterial activity., Methods: 0.016 x 0.022-in NiTi orthodontic wires were coated with ZnO nanoparticles using an electrochemical deposition method with three electrodes system in 0.1M Zn(NO3)2. Mechanical properties and frictional resistance of the coated wires were investigated using an universal testing machine. Antibacterial effect of ZnO coating was also investigated., Results: A stable adhered ZnO nanocoating on NiTi wires was obtained. The coated wires have a significant antibacterial activity against S. aureus, S. pyogens and E. coli, and a reduction of frictional forces by 34%., Conclusion: ZnO nanocoating may improve the antibacterial effects of NiTi wires and reduce the frictional resistance. Coating may be implanted in orthodontic practice for faster and safer treatment.

Background: Depression is a common comorbidity in type-II diabetic patients, which if undiagnosed leads to poor clinical outcomes., Objectives: To determine the prevalence and risk factors of depression among type-II diabetic patients attending the National Guard Diabetic Clinic in Arar city. Subjects and methods . This cross-sectional study included every third type-II diabetic patient attending the National Guard Primary Health Care Center between the 1 st of January and 31 st of March 2019. Participants were interviewed using the Patient Health Questionnaire 9 (PHQ-9). Patients who scored ≥5 were considered to have depression. Chi-square test ( χ 2 ) was used to compare differences between categorical variables. P ≤ 0.05 was considered statistically significant., Results: Of the total 422 diabetic patients approached for this study, 397 provided complete responses (94% response rate). Of these, 37% had depression: 23% mild, 9% moderate, and 5% severe. Diabetic patients with low education, poor income, and long duration of diabetes mellitus were found to be at higher risk of depression. Poor compliance with physical activities, diet regimen, family history of DM, and the presence of complications was also significantly associated with depression. On logistic regression analysis, low family income, duration of DM, poor compliance to physical activity, and presence of complications as neuropathy or libido were the main predictors of depression in diabetic patients., Conclusion: More than one-third of type-II diabetic patients had depression. Regular screening of type-II diabetic patients for depression is a necessity, as it can affect the clinical outcome., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Norah Muqbil Alhunayni et al.)

Background: Violence against health-care workers (HCWs) showed increasing worldwide concern. No previous studies addressed violence against HCWs in the Northern region, Saudi Arabia., Objectives: To determine the prevalence of violence against HCWs in public hospitals and primary health-care centers in Arar city, KSA, and to identify its associated factors., Methods: A cross-sectional study was conducted on 352 HCWs in the Ministry of Health (MOH) facilities in Arar city from 1 st October to 31 st December 2018. Consented HCWs completed a structured self-administered questionnaire which was modified from the WHO questionnaire for violence., Results: Out of 352 health-care workers, 171 (48.6%) reported exposure to violence during work in the past year. The verbal violence was the most common form experienced (83%). Physicians were the main exposed group (59%). Being non-Saudi HCWs, older with longer duration of experience, working in hospitals, working in the emergency room, and working in evening or night shifts were significantly associated with more exposure to violence. The unmet demand for the patient and deficient staff number were the leading reasons for aggression. Only 16.4% of assaulted HCWs reported the violent acts to the higher health affairs authority with the most frequent reasons for nonreporting were their perception that it was useless and their fear of negative consequences., Conclusions: Violence against HCWs in Arar city, KSA, is a prevalent problem. Improving health security system and increasing staffing and their training on proper dealing with violence are highly recommended. Also, enforcing rules and regulations is an important demand to control and prevent violence against HCWs., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Ruqayyah B. Al Anazi et al.)

Objective: This study was conducted to evaluate the clinical effectiveness treatment effects of a simple buccal technique for maxillary molar distalization using direct buccal skeletal anchorage., Materials and Methods: After sample size calculation, fourteen female patients with bilateral Class II molar relationship (age 11-14 years) were selected from the clinic of the Department of Orthodontics, Faculty of Dentistry, Mansoura University, Egypt. After the application of the eligibility criteria, only eleven patients remained to final evaluation. The criteria included: erupted second maxillary molars, mild to moderate maxillary crowding not exceeding 6mm with/without increased overjet and non-extraction treatment in the lower arch. After alignment and levelling, a miniscrew (1. 8mm diameter - 0. 8mm long) was placed buccally between the maxillary second premolar and the first molar in each side. The maxillary molar distalization was done using 250 grams of force produced from NiTi closed coil spring stretched to a buccal miniscrew. Records including cephalometric x-rays and study casts were taken for all patients before and after molar distalization. Statistical evaluation was performed for the data obtained from analysis of cephalometric tracing and cast photocopies., Results: The maxillary first molars were distalized with a rate of 0. 89±0. 30mm (95% CI 0.76-1.02) (P<0.001) and distalization amount of 4.09±0. 92mm (CI 3.68-4.50) (P<0.001). They were distally tipped by 2.48°±6. 16 (CI -0.26-5.21) (P=0.073) and rotated distopalatally by 11.89°±5.86 with negligible change in their vertical position about 0.11±0.63mm (CI -0.40-0.17) (P=0.411). There was no anchorage loss evident by the distal movement of all the maxillary teeth (P<0.001). Overjet significantly reduced by 0. 86±0. 50 (CI 0.52-1.20) (P=0.004)., Conclusions: Maxillary molar distalization using a closed coil and buccal miniscrew is an effective and non-compliance dependent technique in a relatively short time., (Copyright © 2019 CEO. Published by Elsevier Masson SAS. All rights reserved.)

Sphingolipids are bioactive lipids associated with cellular membranes and plasma lipoproteins, and their synthesis and degradation are tightly regulated. We have previously determined that low plasma concentrations of certain ceramide species predict the development of nephropathy in diabetes patients with normal albumin excretion rates at baseline. Herein, we tested the hypothesis that altering the sphingolipid content of circulating lipoproteins can alter the metabolic and signaling pathways in podocytes, whose dysfunction leads to an impairment of glomerular filtration. Cultured human podocytes were treated with lipoproteins from healthy subjects enriched in vitro with C16 ceramide, or D-erythro 2-hydroxy C16 ceramide, a ceramide naturally found in skin. The RNA-Seq data demonstrated differential expression of genes regulating sphingolipid metabolism, sphingolipid signaling, and mTOR signaling pathways. A multiplex analysis of mTOR signaling pathway intermediates showed that the majority (eight) of the pathway phosphorylated proteins measured (eleven) were significantly downregulated in response to C16 ceramide-enriched HDL2 compared to HDL2 alone and hydroxy ceramide-enriched HDL2. In contrast, C16 ceramide-enriched HDL3 upregulated the phosphorylation of four intermediates in the mTOR pathway. These findings highlight a possible role for lipoprotein-associated sphingolipids in regulating metabolic and signaling pathways in podocytes and could lead to novel therapeutic targets in glomerular kidney diseases.

Objective: To qualitatively and quantitatively assess the color changes effect and the color stability of the resin infiltrant on white spot lesions (WSLs), in comparison with nano-hydroxyapatite (nano-HA) toothpaste and microabrasion., Methods: WSLs were artificially created on sixty human premolars enamel surfaces and randomly assigned to equal four groups (n = 15 each): nano-HA toothpaste, microabrasion (Opalusture), resin infiltrant (Icon) treatment, or artificial saliva (control group). The color change (ΔE) of each specimen was measured by dental spectrophotometer (Vita Easyshade) at different time points: baseline, after WSLs' creation, after application of treatments, one month, three and six months after treatments application., Results: The ΔE value did not differ significantly for the four groups at baseline measurement before treatment (p> 0.05). Icon resin infiltrant improved the color of WSLs significantly immediately after its application, giving the lowest ΔE value (3.00 ± 0.59), when compared to other treatments (p< 0.001). There were no significant changes in ΔE (p> 0.05) for all groups during the follow up intervals (one month, three and six months after treatments application)., Conclusion: Resin infiltrant can improve the color of WSLs and restore the natural appearance of enamel better than nano-HA toothpaste and microabrasion.

Background: The quality of life (QOL) of the families of children with autism is lower than that of families of normal children or children with other disabilities. The study's aim was to describe the severity of effect on the domains of the QOL of caregivers of autistic children and to identify the characteristics of caregivers and children associated with impaired QOL., Materials and Methods: This cross-sectional study included 84 parents of autistic children attending developmental abnormalities clinic in Arar city during January 1 to March 31, 2019. Parents of autistic children were interviewed using an Arabic version of the short-form 36 to assess their QOL. A mean score of <50 was considered to indicate poor QOL. Collected data were analyzed using the Statistical Package for the Social Sciences (SPSS, version 20.0). A Chi-square test was used for comparison between categorical variables., Results: Of 84 caregivers, 63.1% had impaired QOL. The main domains affected were energy/fatigue and role limitations resulting from emotional problems. Female gender, unemployment, and low income of caregivers were significant factors associated with poor QOL. Autistic children of the first birth order and with long duration of the disease were more likely to be associated with poor parental QOL. Gender, income, occupation, and duration of illness were associated with poor quality of life, but this was not statstically significant., Conclusion: Slightly less than two-thirds of the caregivers had impaired QOL. Caregivers of autistic children need social and emotional support to help them to cope with this disability., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family and Community Medicine.)

Objective: To compare the effectiveness of dual task specific training and conventional physical therapy in ambulation of patients with chronic stroke., Methods: The randomised controlled trial was conducted at the Habib Physiotherapy Complex, Peshawar, Pakistan, from January to August 2017, and comprised patients with chronic stroke. The patients were randomly assigned to two treatment groups. Group A received dual task training, while Group B received conventional physiotherapy. Dual task training included activities such as slowlywalking backward, sideways, and forward on a smooth surface while holding a 100gm sandbag. The conventional physiotherapy included mat activities, stretching and strengthening exercises and gait training. Pre-test and post-test data was taken for both spatial and temporal variables for both groups using Time Up and Go Test and 10-meter walk test. Step length, stride length, cycle time and cadence were also calculated before and after treatment. SPSS 23 was used to analyse the data., Results: Of the 64 patients, there were 32(50%) in each of the two groups that both had 17(53%) males and 15(47%) females. Mean age in Group A was 58.28 ± 7.13 years, while in Group B it was 58.87 ± 6.13 years. Baseline parameters had no significant differences between the groups (p>0.05). Post-treatments scores revealed significant improvement of spatial and temporal variable of gait, 10-meter walk, cadence, step length, stride and cycle time in Group A compared to Group B (p<0.05 each)., Conclusions: Conventional physical therapy and dual task training effectively improved gait ability of chronic stroke patients, and the latter showed significant improvement in all spatial and temporal gait variables compared to former.

Systemic lupus erythematous (SLE) is a chronic multi-organ autoimmune disease. Genetic and environmental factors contribute to disease onset and severity. Sphingolipids are signaling molecules involved in regulating cell functions and have been associated with multiple genetic disease processes. African-Americans are more likely to suffer from SLE morbidity than Whites. The Medical University of South Carolina has banked plasma samples from a well-characterized lupus cohort that includes African-Americans and Whites. This study examined the influence of race on plasma sphingolipid profiles in SLE patients and association of sphingolipid levels with comorbid atherosclerosis and SLE disease activity. Mass spectrometry revealed that healthy African-Americans had higher sphingomyelin levels and lower lactosylcermide levels compared to healthy Whites. SLE patients, irrespective of race, had higher levels of ceramides, and sphingoid bases (sphingosine and dihydrosphingosine) and their phosphates compared to healthy subjects. Compared to African-American controls, African-American SLE patients had higher levels of ceramides, hexosylceramides, sphingosine and dihydrosphingosine 1-phosphate. Compared to White controls, White SLE patients exhibited higher levels of sphingoid bases and their phosphates, but lower ratios of C16:0 ceramide/sphingosine 1-phosphate and C24:1 ceramide/sphingosine 1-phosphate. White SLE patients with atherosclerosis exhibited lower levels of sphingoid bases compared to White SLE patients without atherosclerosis. In contrast, African-American SLE patients with atherosclerosis had higher levels of sphingoid bases and sphingomyelins compared to African-American SLE patients without atherosclerosis. Compared to White SLE patients with atherosclerosis, African-American SLE patients with atherosclerosis had higher levels of select sphingolipids. Plasma levels of sphingosine, C16:0 ceramide/sphingosine 1-phosphate ratio and C24:1 ceramide/sphingosine 1-phosphate ratio significantly correlated with SLEDAI in the African-American but not White SLE patients. The C16:0 ceramide/sphingosine 1-phosphate ratio in SLE patients, and levels of C18:1 and C26:1 lactosylcermides, C20:0 hexosylceramide, and sphingoid bases in SLE patients with atherosclerosis could be dependent on race. Further ethnic studies in SLE cohorts are necessary to verify use of sphingolipidomics as complementary diagnostic tool., Competing Interests: The authors have declared that no competing interests exist.

Context: The incidence of preeclampsia (PE) is increased in women with diabetes (∼20% vs ∼5% in the general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, the Hp 2-2 phenotype is associated with cardiorenal disease., Objective: To investigate whether Hp phenotype is associated with PE in type 1 diabetes mellitus (T1DM) and/or modulates lipoprotein-associated risks., Design and Setting: Multicenter prospective study of T1DM pregnancy., Patients: Pregnant women with T1DM (normal albuminuria, normotensive at enrolment, n = 47) studied at three visits, all preceding PE onset: 12.3 ± 1.9, 21.8 ± 1.5, and 31.5 ± 1.6 weeks' gestation (mean ± SD)., Main Outcome Measures: Hp phenotype and lipoprotein profiles in women with (n = 23) vs without (n = 24) subsequent PE., Results: Hp phenotype did not predict PE, but lipoprotein associations with subsequent PE were confined to women with Hp 2-2, in whom the following associations with PE were observed: increased low-density lipoprotein (LDL) cholesterol, LDL particle concentration, apolipoprotein B (APOB), triacylglycerol/high-density lipoprotein (HDL) cholesterol ratio, and APOB/apolipoprotein AI (APOA1) ratio; decreased HDL cholesterol, APOA1, large HDL particle concentration, and peripheral lipoprotein lipolysis (all P < 0.05). In women with one or two Hp-1 alleles, no such associations were observed., Conclusions: In women with T1DM, although Hp phenotype did not predict PE risk, lipoprotein-related risks for PE were limited to those with the Hp 2-2 phenotype. Hp phenotype may modulate PE risk in diabetes., (Copyright © 2019 Endocrine Society.)

Objective: To compare the effectiveness of Kaltenborn mobilization combined with thermotherapy versus Kaltenborn mobilization alone in patients with adhesive capsulitis., Methods: The randomised controlled trial was conducted at the Hayatabad Medical Complex and Habib Physiotherapy Complex, Peshawar, Pakistan, from January to June 2017, and comprised patients with adhesive capsulitis. The subjects were randomised into two groups. Group A received Kaltenborn mobilisation with thermotherapy, while group B received Kaltenborn mobilisation alone. Shoulder pain and disability index was used to assess the effectiveness of the intervention. SPSS 20 was used for data analysis., Results: Of the 30 patients, 15(50%) were in each of the two groups. Baseline characteristics were not significantly different between the groups (p>0.05). Pre- and post-treatment Shoulder pain and disability index score of group A was 75.27}5.738 and 12.33}1.988 respectively (p<0.05). Corresponding scores in group B were 73.67}6.137 and 64.13}5 (p<0.05). Group A showed greater reduction in disability compared to group B (p<0.05)., Conclusions: Kaltenborn mobilisation combined with thermotherapy was found to be more effective than Kaltenborn mobilisation alone in patients with adhesive capsulitis.

Tomato mosaic disease, caused by Tomato Mosaic Virus (ToMV), is one of the most destructive diseases which results in serious crop losses. Research investigations dealing with the biocontrol activity of arbuscular mycorrhizal fungi (AMF) against this viral disease are limited. In this study, the biocontrol activity of AMF on tomato plants infected with ToMV was evaluated in the greenhouse. In addition, their impacts on the transcriptional expression levels of thirteen genes controlling the phenylpropanoid, flavonoid and chlorogenic acid biosynthetic pathways were also investigated using quantitative real-time PCR. Transcriptional expressions of the majority of the studied genes were up-regulated by mycorrhizal colonization in the presence of ToMV, particularly PAL1 and HQT, suggesting their pathogen-dependent inducing effect. Under greenhouse conditions, a significant reduction in the disease severity and incidence, as well as the viral accumulation level was observed as a response to the mycorrhizal colonization of the infected plants. Moreover, the evaluated growth parameters, photosynthetic pigments, and flavonoid content were significantly enhanced by AMF colonization. The obtained results demonstrated the protective role of AMF in triggering the plant immunity against ToMV in a pathogen-dependent manner. Beside their protective and growth-promotion activities, AMF are characterized by low-cost and environment-friendly properties which support their possible use for control of tomato mosaic disease.

Objective: To investigate the ability of resin infiltration to protect demineralized enamel against acidic challenge., Materials and Methods: Forty-five extracted healthy premolars were selected for the study, each of which was sectioned vertically into 2 halves, giving 90 specimens. Specimens were then divided into three groups, where specimens of group A were not decalcified (control), while those of groups B and C were either subjected to decalcification only, or decalcification followed by Icon resin infiltration, respectively. Each group was further divided into three subgroups, according to the type of storage medium (water, Coca-Cola, or Redbull). Evaluation parameters included color difference and surface roughness. Scanning electron microscope was used to evaluate enamel surface topography. Statistical analysis was performed by ANOVA followed by least significant difference test., Results: Although Coca-Cola caused the highest color change and surface roughness among the studied specimens, yet, the resin-infiltrated enamel was more resistant to surface changes than the nonresin infiltrated enamel, even under acid attack., Conclusion: Resin infiltration has the ability to provide and maintain protection to the demineralized enamel against acidic attack., Clinical Significance: Resin infiltration may be considered as a promising solution to restore esthetic of demineralized enamel following orthodontic treatment and to protect it against acidic beverages., (© 2019 Wiley Periodicals, Inc.)

Background: Population-wide reductions in cardiovascular disease (CVD) have not been equally shared in the African American community due to a higher burden of CVD risk factors such as metabolic disorders and obesity. Differential concentrations of sphingolipids such as ceramide, sphingosine, and sphingosine 1-phosphate (S1P) has been associated with the development of CVD, metabolic disorders (MetD), and obesity. Whether African Americans have disparate expression levels of sphingolipids that explain higher burdens of CVD remains unknown., Methods: A cross sectional analysis of plasma concentrations of ceramides, sphingosine, and S1P were measured from 8 whites and 7 African Americans without metabolic disorders and 7 whites and 8 African Americans with metabolic disorders using high performance liquid chromatography/tandem mass spectrometry methodology (HPLC/MS-MS). Subjects were stratified by both race and metabolic status. Subjects with one or more of the following physician confirmed diagnosis: diabetes, hypertension, hypercholesterolemia, or dyslipidemia were classified as having metabolic disease (MetD). Data was analyzed using a Two-Way ANOVA and Tukey's post hoc test., Results: Total ceramide levels were increased in African Americans compared to African Americans with MetD. Ceramide C16 levels were higher in whites with MetD compared to African Americans with MetD (p<0.05). Ceramide C20 levels were higher in whites with MetD compared to whites. Ceramide C20 levels were higher in African Americans compared to African Americans with MetD. Furthermore, whites with MetD had higher levels of C20 compared to African Americans with MetD (p<0.0001). Ceramide C24:0 and C24:1 in African Americans was higher compared to African Americans with MetD (p<0.05). The plasma concentration of Sph-1P ceramide was higher in African Americans vs whites (p = 0.01). Lastly, ceramide C20 negatively correlated with hemoglobin A1c (HbA1c) levels in our study cohort., Conclusions: Plasma ceramide concentration patterns are distinct in African Americans with MetD. Further research with larger samples sizes are needed to confirm these findings and to understand whether racial disparities in sphingolipid concentrations have potential therapeutic implications for CVD-related health outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Glycosphingolipids are important components of cell membranes, modulators of cell-cell interactions and cell recognition, and have recently emerged as bioactive molecules and important players in nearly all cell biological processes. We previously have shown that decreased plasma levels of long and very long species of ceramides were able to predict the development of macroalbuminuria (MA) in type 1 diabetes., Objective: This study proposed to examine whether plasma glycosphingolipids could predict development of diabetic nephropathy, assessed as MA or chronic kidney disease (CKD)., Methods: Measurement of plasma hexosylceramides (H) and lactosylceramides (L) were conducted in the Lipidomics Core Facility of our Institution in a subcohort of 432 patients from the DCCT/Epidemiology of Diabetes Interventions and Complications cohort in plasma collected at entry into the study. Inverse probability weighted Cox proportional hazards regression models were used to assess the effect of glycosphingolipids levels on the risk of developing MA (albumin excretion rate ≥300 mg/24 hours) or CKD (glomerular filtration rate <60 mL/min) over a period of 21 to 28 years., Results: Decreases of several long and very long chain lactosylceramides were significantly associated with increased risk of progression to MA but not CKD. Among the hexosylceramides, the only significant association observed was between one of its minor species C18:1-H and CKD., Conclusion: Our findings showed that decreased levels of long and very long lactosylceramides were able to predict the development of MA in type 1 diabetes. This finding is similar to previous findings showing that low levels of long and very long ceramides were also able to predict development of MA in the same cohort. Further studies are needed to determine the changes in sphingolipid metabolism leading to the development of complications., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Tobacco is one of the leading preventable cause of death worldwide. Tobacco consumption among teenagers is a major public health problem, especially in developing countries. Younger smokers are more liable to smoking complications. The objectives were to evaluate the prevalence of smoking among male secondary school students in the Northern Borders region, KSA., Methods: A cross-sectional study was conducted in Arar city. Four schools were chosen randomly from 21 secondary schools. A total of 240 students responded to the pre-designed questionnaire. The questionnaire included questions on demographic factors, smoking behavior and knowledge about smoking hazards., Results: Prevalence of current smoking among male secondary school students is 40.8%. Cigarette smoking was the most common type (67.3%) followed by Shish smoking (22.4%). Few students (2.1%) reported other forms of smoking, example (Hashish). Of the studied group, 39.8% smoke on a daily basis with 29.6% of them smoke more than five cigarettes per day., Conclusion: Smoking is a prevalent habit among teenagers. Special concern should be directed to smoking cessation campaigns with behavioral, legal and economic interventions., Competing Interests: The authors declare no competing interests.

3-ketodihydrosphingosine reductase (KDSR) is the key enzyme in the de novo sphingolipid synthesis. We identified a novel missense kdsr I105R mutation in zebrafish that led to a loss of function, and resulted in progression of hepatomegaly to steatosis, then hepatic injury phenotype. Lipidomics analysis of the kdsr I105R mutant revealed compensatory activation of the sphingolipid salvage pathway, resulting in significant accumulation of sphingolipids including ceramides, sphingosine and sphingosine 1-phosphate (S1P). Ultrastructural analysis revealed swollen mitochondria with cristae damage in the kdsr I105R mutant hepatocytes, which can be a cause of hepatic injury in the mutant. We found elevated sphingosine kinase 2 (sphk2) expression in the kdsr I105R mutant. Genetic interaction analysis with the kdsr I105R and the sphk2 wc1 mutants showed that sphk2 depletion suppressed liver defects observed in the kdsr I105R mutant, suggesting that liver defects were mediated by S1P accumulation. Further, both oxidative stress and ER stress were completely suppressed by deletion of sphk2 in kdsr I105R mutants, linking these two processes mechanistically to hepatic injury in the kdsr I105R mutants. Importantly, we found that the heterozygous mutation in kdsr induced predisposed liver injury in adult zebrafish. These data point to kdsr as a novel genetic risk factor for hepatic injury.

Objectives: To determine type 2 diabetic patients' satisfaction with the services provided by the Diabetic Center, Arar, Saudi Arabia, and to assess the relationship between patients' satisfaction and their diabetic control. Methods: An observational cross-sectional study, carried out in 322 patients at the Arar Diabetic Center, Arar, Kingdom of Saudi Arabia between January and April 2018. A systematic random sampling technique was applied to include every second type 2 diabetic patient attending the center. We interviewed the type 2 diabetic patients using a predesigned questionnaire tested for validity and reliability. Results: The mean age of the studied population was 48.5±13.05. The overall satisfaction rate was 65.8%. There was a significant association between patient satisfaction to both self-reported health status (p=0.001) and mode of treatment (p=0.02). Regarding service related factors: 78% of patients were satisfied with the time spent during consultation; 58.7% were satisfied with information given regarding the disease; 58.7% were dissatisfied with dietary advice; and 44.7% were dissatisfied with information given regarding medications. Hemoglobin A1c (HbA1c) was controlled in 64% of patients. There was a statistically significant association between patients' dissatisfaction and poor diabetic control. Conclusion: Two-thirds of the patients were satisfied with the services provided by the Diabetic Centres of Arar city, Saudi Arabia. The study recommends emphasis on patient education and addressing patient needs and worries.

Despite the advancements in modern medicine, there are still difficulties in diagnosing common illnesses. The invasiveness and price of the tests used to follow up certain diseases can be a barrier to proper patient follow-up. Sphingolipids are a diverse category of lipids. They are structural molecules in cell membranes and signaling molecules involved in the regulation of crucial cell functions, including cell growth, differentiation, proliferation and apoptosis. Recent research has shown that abnormal sphingolipid metabolism is associated with genetic and metabolic disease processes. Given their crucial role to maintain homeostasis within the body, sphingolipids have been investigated as potential biomarkers to predict disease in the population. Here we discuss how sphingolipids levels are altered in different diseases, thus illustrating their possible use as diagnostic and prognostic biomarkers for disease.

Sphingolipids, including ceramide, SM, and hexosylceramide (HxCer), are carried in the plasma by lipoproteins. They are possible markers of metabolic diseases, but little is known about their control. We previously showed that microsomal triglyceride transfer protein (MTP) is critical to determine plasma ceramide and SM, but not HxCer, levels. In human plasma and mouse models, we examined possible HxCer-modulating pathways, including the role of ABCA1 in determining sphingolipid plasma concentrations. Compared with control samples, plasma from patients with Tangier disease (deficient in ABCA1) had significantly lower HxCer (-69%) and SM (-40%) levels. Similarly, mice deficient in hepatic and intestinal ABCA1 had significantly reduced HxCer (-79%) and SM (-85%) levels. Tissue-specific ablation studies revealed that hepatic ABCA1 determines plasma HxCer and SM levels; that ablation of MTP and ABCA1 in the liver and intestine reduces plasma HxCer, SM, and ceramide levels; and that hepatic and intestinal MTP contribute to plasma ceramide levels, whereas only hepatic MTP modulates plasma SM levels. These results identify the contribution of ABCA1 to plasma SM and HxCer levels and suggest that MTP and ABCA1 are critical determinants of plasma sphingolipid levels.

Background: Influenza outbreaks occur annually and have significant ramifications on the wellbeing of the population. Influenza is given high priority in Saudi Arabia where numerous reports of different types of influenza outbreaks have occurred in recent years., Objective: The study aimed to determine the prevalence of influenza vaccination among healthcare providers., Methods: The study employed a cross-sectional design, and data was collected using a predesigned questionnaire which was validated by a panel of experts and tested for reliability (Cronbach's alpha =0.8). All primary healthcare workers in Arar city (Saudi Arabia) were taken as a comprehensive sample between January and March 2018. The questionnaire used a Likert scale that assessed the reasons for embracing or rejecting the influenza vaccines. A p-value of ≤0.05 was considered statistically significant., Results: In total, 204 health professionals (72 physicians, 102 nurses and 30 other staff members) filled the questionnaire. The mean age of the healthcare professionals was 31.9±8.7 years. Self-report of seasonal influenza vaccination uptake was 55.9% (65.3% for physicians, 55.9% for nurses and 33.3% for other staff). Perceived risk of severity of influenza was 2.5 times more in the compliant group than that of the non-compliant group (p<0.001, 95% CI: 1.4-4.4)., Conclusion: Utilization of influenza vaccine is 55% in both nurses and physicians despite 89% of them being aware of influenza vaccination guidelines and MOH recommendations. It is needed to ensure the intensive education of healthcare providers to understand the protective value of influenza vaccine., Competing Interests: Conflict of Interest: There is no conflict of interest to be declared.

Background: Acne vulgaris is a common heath problem affecting adolescents with considerable impact on their quality of life., Objective: To determine the prevalence of Acne vulgaris and its psychological impact among female secondary school students., Methods: A cross-sectional study was conducted during the period from January to March 2018, among all female secondary school students in 3 randomly selected schools, in Arar city (Saudi Arabia). The participants were clinically examined by a dermatologist to identify acne cases. Dermatological quality of life of acne cases were assessed using an Arabic version of Dermatology Life Quality Index (DLQI). Data collected were analyzed by IBM-SPSS version 20, using Chi-square, Fisher's Exact test, Mann-Whitney U, and Kruskal Wallis test. P-value ≤0.05 was considered statically significant., Results: The overall prevalence of Acne vulgaris was 14.3%. It was not significantly affected by age, marital status or nationality of participants. Post inflammatory hyper-pigmentation and scarring were detected in 11.6% and 8.7% respectively. Twenty nine percent of the cases had no impact; 56.3% had small to moderate impact and 14.5% had large effect. The psychological impact was significantly increased with increased severity, presence of acne lesions on face and other sites, presence of hyper pigmentation and scarring (p=0.001)., Conclusion: Acne vulgaris had large impact on quality of life in 14.5% of cases. Students should be counseled and educated on how to deal with this dermatological problem., Competing Interests: Conflict of Interest: There is no conflict of interest to be declared.

Immune complexes (IC) containing predominantly malondialdehyde-LDL and the corresponding autoantibodies (MDA-LDL IC) predict acute cardiovascular events, while IC rich in oxidized LDL (oxLDL IC) predict cardiovascular disease progression. Our objective was to determine mechanisms that could explain these prognostic differences. We compared the effects of the interaction of oxLDL, MDA-LDL and the corresponding IC with human macrophages focusing on apoptosis, metalloproteinases, and proinflammatory cytokines. MDA-LDL IC induced higher degrees of apoptosis, higher levels of caspase-3 expression, and increased expression and release of MMP-1 and TNF compared to MDA-LDL, oxLDL, and oxLDL IC. The pro-apoptotic effects of MDA-LDL IC were inhibited by blocking TNFR 1 or FcγRI. Blocking FcγRI abrogated the induction and expression of MMPs and proinflammatory cytokines by MDA-LDL IC. In conclusion, the interaction of MDA-LDL IC with FcγRI triggers macrophage apoptosis and increased expression and release of TNF and MMP-1, which can lead to the rupture of unstable plaques., (Copyright © 2017. Published by Elsevier Inc.)

Objective: This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester., Research Design and Methods: This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL, urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks' gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE-), and, for reference, in 19 normotensive pregnant women without diabetes (DM-). The groups with diabetes were matched for age, diabetes duration, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE., Results: Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ vs. DM+PE- women ( P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE-) ( P = 0.02). Accounting for BMI, HbA 1c , and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE ( P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ vs. DM+PE- ( P = 0.04)., Conclusions: Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE., (© 2017 by the American Diabetes Association.)

Aims/hypothesis: The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia., Methods: From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1- Visit 3) at different gestational ages (mean ± SD): Visit 1, 12.4 ± 1.8 weeks; Visit 2, 21.7 ± 1.4 weeks; and Visit 3, 31.4 ± 1.5 weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia., Results: In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1: (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p < 0.05), while total adiponectin was decreased (p < 0.05); and (2) in normotensive diabetic vs non-diabetic women, total adiponectin was elevated (p < 0.05). At Visits 2 and 3: (1) the primary findings in the two diabetic groups persisted, and FABP4 also increased in women with subsequent pre-eclampsia (p < 0.05); and (2) there were no differences between the two normotensive groups. By logistic regression analyses after covariate adjustment (HbA 1c , insulin kg -1  day -1 and gestational age), the best predictive models for pre-eclampsia were as follows: Visit 1, doubling of leptin, OR 9.0 (p < 0.01); Visit 2, doubling of the leptin:total adiponectin ratio, OR 3.7 (p < 0.05); and Visit 3, doubling of FABP4 concentration, OR 25.1 (p < 0.01). The associations were independent of BMI., Conclusions/interpretation: As early as the first trimester in type 1 diabetic women, adipokine profiles that suggest insulin resistance are associated with subsequent pre-eclampsia, possibly reflecting maternal characteristics that precede pregnancy. These associations persist in the second and third trimesters, and are independent of BMI. Insulin resistance may predispose women with type 1 diabetes to pre-eclampsia.

Sphingolipids are structurally and functionally diverse molecules with significant physiologic functions and are found associated with cellular membranes and plasma lipoproteins. The cellular and plasma concentrations of sphingolipids are altered in several metabolic disorders and may serve as prognostic and diagnostic markers. Here we discuss various sphingolipid transport mechanisms and highlight how changes in cellular and plasma sphingolipid levels contribute to cardiovascular disease, obesity, diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). Understanding of the mechanisms involved in intracellular transport, secretion, and extracellular transport may provide novel information that might be amenable to therapeutic targeting for the treatment of various metabolic disorders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Adolescence is an unpredictable stage of life with varied and rapid changes. In Jordan, health-related quality of life (HRQoL) has been examined among diabetic and obese children and adolescents. The purpose of this study was to assess the HRQoL of Jordanian healthy adolescents. Three hundred fifty-four male and female adolescents whose ages ranged from 12 to 19 participated in the study. A descriptive comparative design was employed to investigate adolescents' HRQoL. The results revealed statistically significant differences in physical well-being, psychosocial well-being, and autonomy in favor of male adolescents. In addition, statistically significant differences were observed in favor of nonsmoker adolescents in psychosocial well-being, self-perception, parent relations and home life, financial resources, social relations and peers and school environment. In conclusion, the creation of a school health nurse role in Jordanian schools is crucial for helping adolescents improve their health.

Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80), with and without symptoms of neuropathy, were investigated. Patient-determined neuropathy was based on 15-item self-administered questionnaire (Michigan Neuropathy Screening Instrument) developed to assess distal symmetrical peripheral neuropathy in diabetes. Patients who scored ≥4, or reported inability to sense their feet during walking or to distinguish hot from cold water while bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin, hexosyl- and lactosylceramide species, and amino acids were measured and analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24- and C26-ceramide were higher in patients with neuropathy than those without neuropathy. Cysteine was higher in patients with neuropathy. No differences in other sphingolipids or amino acids were detected. The covariate-adjusted Odds Ratios of positive patient-reported neuropathy was associated with increased levels of deoxy-C24-, and deoxy-C24:1-ceramide; C22-, C24-, and C26-ceramide; and cysteine. Plasma deoxy-ceramide and ceramide species may have potential diagnostic and prognostic significance in diabetic neuropathy.

HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

Objective: To evaluate the effect of silica dioxide (SiO2) nanofillers in different bonding systems on shear bond strength (SBS) and mode of failure of orthodontic brackets at two experimental times., Methods: Ninety-six intact premolars were divided into four groups: A) Conventional acid-etch and primer Transbond XT; B) Transbond Plus self-etch primer; and two self-etch bonding systems reinforced with silica dioxide nanofiller at different concentrations: C) Futurabond DC at 1%; D) Optibond All-in-One at 7%. Each group was allocated into two subgroups (n = 12) according to experimental time (12 and 24 hours). SBS test was performed using a universal testing machine. ARI scores were determined under a stereomicroscope. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to determine the size and distribution of nanofillers. One-way ANOVA was used to compare SBS followed by the post-hoc Tukey test. The chi-square test was used to evaluate ARI scores., Results: Mean SBS of Futurabond DC and Optibond All-in-One were significantly lower than conventional system, and there were no significant differences between means SBS obtained with all self-etch bonding systems used in the study. Lower ARI scores were found for Futurabond DC and Optibond All-in-One. There was no significant difference of SBS and ARI obtained at either time points for all bonding systems. Relative homogeneous distribution of the fillers was observed with the bonding systems., Conclusion: Two nanofilled systems revealed the lowest bond strengths, but still clinically acceptable and less adhesive was left on enamel. It is advisable not to load the brackets immediately to the maximum.

Background and Objective: White spot lesions (WSLs) are an undesirable side effect of fixed orthodontic appliance therapy and are reported to occur in 2-96 % of orthodontic patients. In this study, the efficacy of a new sealant to prevent WSLs during fixed orthodontic treatment was compared to a control group that did not receive sealant., Patients and Methods: For this 2-arm parallel-group randomized trial, 50 subjects aged 12-18 years (mean age 14.57 ± 2.04 years) were recruited from the orthodontics department at Mansoura University, Egypt. Eligibility criteria were no restorations, no active WSLs or caries, and adequate oral hygiene. Subjects were randomized in a 1:1 ratio to one of the two arms prior to undergoing fixed orthodontic treatment, namely a single application of SeLECT Defense™ sealant during the bracketing appointment or no sealant (control arm). Instructions and dentifrices for local home fluoridation regimen were identical in both groups. Oral hygiene was assessed using the Approximal Plaque Index (API) at specified time intervals. Dental photographs were taken for blinded WSLs assessment; inter- and intra-operator error were also calculated. Categorical data were tested using the χ 2 test, and a logistic regression model was adopted to detect associations between decalcification (WSLs), sealant application, and oral hygiene status., Results: Only excellent or good oral hygiene were independent prognostic factors for preventing severe WSLs (p = 0.035). No significant effect on caries incidence was observed for the sealant., Conclusions: In combination with adequate oral hygiene SeLECT Defense™ helps to reduced the frequency of WSLs. However, the sealat showed no significant effect as sole preventive strategy.