bluuebunny/crossref_metadata_2025_split huggingface dataset:
525-P: Impact of Extracellular-to-Intracellular Fluid Volume Ratio on Albuminuria in People with Type 2 Diabetes: A Cross-Sectional and Retrospective Cohort Study
Authors: NAKAJIMA HANAKO , HASHIMOTO YOSHITAKA , SENMARU TAKAFUMI , OKADA HIROSHI , HAMAGUCHI MASAHIDE , FUKUI MICHIAKI 
Published: June 2020

Body fluid volume imbalance is common in patients with kidney failure and is associated with all-cause mortality. We hypothesized that fluid volume imbalance occurs in diabetic patients without kidney failure and is associated with albuminuria. This study aimed to investigate the association between fluid volume imbalance and albuminuria in patients with type 2 diabetes without kidney failure. Body fluid imbalance was determined by measuring the extracellular water to intracellular water ratio (ECW/ICW) using bioelectrical impedance analysis. In the cross-sectional study of 432 participants, ECW/ICW increased with level of albuminuria (0.634 ± 0.002 in normo-, 0.645 ± 0.003 in micro- and 0.656 ± 0.004 in macroalbuminuria, all p &lt;0.001 by Tukey’s HSD test). The log-transformed urinary ACR was associated with elevated ECW/ICW ratio (r =0.313, p &lt;0.001) (Figure). In addition, there was an association between ECW/ICW ratio and logarithms urinary ACR after adjusting for covariates (β = 0.217, p &lt;0.001) by multiple regression analysis. Moreover, in the retrospective studies of 368 participants, ECW/ICW was associated with change in the urinary ACR after adjusting for covariates (β = 0.171, p = 0.005) by multiple regression analysis. This reinforces the importance of monitoring fluid balance in diabetic patients.

Disclosure
H. Nakajima: None. Y. Hashimoto: None. T. Senmaru: None. H. Okada: None. M. Hamaguchi: None. M. Fukui: None.
530-P: Longitudinal Characterization of Peripheral Neuropathy in a Cafeteria Diet and Low-Dose Streptozotocin Rat Model of Type 2 Diabetes
Authors: HOSSAIN MD JAKIR , KENDIG MICHAEL D. , WILD BRANDON M. , MORRIS MARGARET J. , ARNOLD RIA 
Published: June 2020

Diabetic peripheral neuropathy is a major complication of diabetes with complex and incompletely understood pathophysiology. We utilised a cafeteria-style diet (Caf) and low dose streptozotocin (STZ) to model varying degrees of hyperglycemia. Adult male Sprague-Dawley rats were divided into four groups: control (chow diet), prediabetic (Caf diet for 21 weeks), diet reversal (13 weeks Caf diet then 8 weeks chow; all n=12) and type 2 diabetic (T2D - Caf+STZ 25mg/kg i.p, n=24). STZ was administered after 5 weeks of diet; one week later, non-fasted blood glucose was 16.09 ± 1.19 [SEM] and 78% of T2D rats had glucose levels ≥10mmol/L. Metabolic phenotyping revealed significantly increased body weight, fat mass, fasting blood HDL cholesterol, plasma insulin and impaired glucose tolerance in both prediabetic and T2D rats compared to controls; fasting glucose and HbA1c were significantly elevated only in T2D. Neuropathy phenotyping included sensory behavioural testing (thermal and mechanical nociceptive sensibility) and electrophysiology (nerve conduction studies and nerve excitability) which were assessed at two timepoints, early (8-11 weeks of diet) and late (17-19 weeks of diet). Nerve excitability abnormalities were present in prediabetes and T2D groups at the early stage (superexcitability p&lt;0.05) while changes in nerve conduction velocity and amplitude emerged later. Mechanical and thermal hypoalgesia was observed in prediabetic and T2D rats only at the late stage. Diet reversal improved body weight, fat mass, HDL, HbA1c, glucose clearance and mechanical nociception response, with no changes in nerve conduction and excitability. Together these data suggest that Caf diet combined with low dose STZ could be utilized to investigate the onset of neuropathological changes in T2D and assessment of subsequent peripheral neuropathy.

Disclosure
M. Hossain: None. M.D. Kendig: None. B.M. Wild: None. M.J. Morris: None. R. Arnold: None.

Funding
National Health and Medical Research Council of Australia (1126929, 1091006); Rebecca L. Cooper Foundation (RG160627)
534-P: The Association between Glycemic Variability and Cardiovascular Autonomic Neuropathy in Patients with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy
Authors: NATTERO-CHÁVEZ LÍA , SILVA JHONATAN QUIÑONES , BENGOA NURIA , ARGÜESO MARÍA FERNÁNDEZ , MONTANEZ LAURA , DURÁN ELENA FERNÁNDEZ , DORADO BEATRIZ , ZAMORANO BELÉN ARIAS , LECUMBERRI EDURNE , RAMÍREZ MANUEL LUQUE 
Published: June 2020

Aim: Describe the relationships between cardiovascular autonomic neuropathy (CAN) and glucose variability (GV) in patients with DM1 on continuous subcutaneous insulin infusion therapy (CSII).
Methods Observational retrospective study (n=89). CAN was assessed by heart rate variability (HRV) in response to deep breathing, standing, Valsalva’s maneuver, and the amplitude of the low (LFa) and high (HFa) frequency of HRV. The standard deviation (SD), the coefficient of variation (CV) and time in range (TIR) were calculated from the capillary blood measurements downloaded of CSII (the mean of glucose capillary assessments was 5.8/day).
Results The mean age was 38±13 and their average duration of DM1 was 22±10 years. The prevalence of CAN was 36% (95%CI: 27-46). The population characteristics according to the presence of CAN are summarized in Table 1. The age and the duration of diabetes correlated negatively with LFa (r= -0.496, P &lt; 0.001) and HFa (r= -0.510, P &lt; 0.001). Separate multivariate binary logistic models were constructed for clinical and GV parameters introducing CAN as dependent variable. Only the age (expB 1.1; CI 1.04-1.15. P &lt; 0.001) was associated with CAN in the fully adjusted model.
Conclusions Age and duration of diabetes, but not GV parameters, appear to be associated with CAN in our cohort of patients with DM1 on CSII.

Disclosure
L. Nattero-Chávez: None. J. Quiñones Silva: None. N. Bengoa: None. M. Fernández Argüeso: None. L. Montanez: None. E. Fernández Durán: None. B. Dorado: None. B. Arias Zamorano: None. E. Lecumberri: None. M. Luque Ramírez: None.

Funding
Menarini Group
536-P: Protein Tyrosine Phosphatase 1B Inhibitor MSI-1436 Promotes M2 Macrophage Polarization and Decreases Oxidative Stress in Human Monocytes under High-Glucose Conditions
Authors: FIGUEIREDO ANA , LEAL ERMELINDO C. , SANTOS DIANA , GASIUNAITE GERDA , DELIBEGOVIC MIRELA , CARVALHO EUGENIA 
Published: June 2020

Peripheral neuropathy plays a role in chronic diabetic foot ulcers (DFUs), also leading to an imbalance in inflammation, as pro-inflammatory macrophages (M1) have difficulty switching to an anti-inflammatory phenotype (M2) contributing to a chronic inflammatory phase and healing impairment. Protein tyrosine phosphatase 1B (PTP1B), in the skin, is over expressed in diabetes and DFUs. We aimed to evaluate the role of PTP1B inhibition in macrophage under high glucose conditions. THP-1 monocytic cells were differentiated into macrophages, treated with the PTP1B inhibitor MSI-1436 (1 µM) and stimulated with LPS for 24h, under high glucose (25 mM) or normoglycemic conditions (5.5 mM). Cell viability was measured by MTT assay. The numbers of M1 and M2 macrophages were evaluated by immunocytochemistry by double staining with CD68 and TNF-α for M1 macrophages, and CD68 and CD163 for M2 macrophages. In addition, pro-inflammatory cytokine expression was analyzed by qRT-PCR. Oxidative stress was assessed by the DCFH-DA assay, heme oxygenase-1 (HO-1) enzyme levels were also measured by immunocytochemistry and Western blot. The treatment with MSI-1436 did not alter THP-1 cell viability. In inflammatory conditions (LPS), THP-1 cells grown under HG and treated with MSI-1436 showed an increase in M2 macrophages and a reduction in M1 macrophages (246 ± 26% and 102 ± 9%, p&lt;0.05, of LPS treated cells, respectively). In addition, PTP1B inhibition induced a decrease in pro-inflammatory cytokine expression, IL-6, IL-1β and MCP-1, a decrease in ROS levels (78 ± 10% of LPS treated cells) and an increase in HO-1 expression (290 ± 23%, p&lt;0.05, of LPS treated cells). Inhibition of PTP1B in macrophages, under high glucose conditions, promotes a significant reduction in the inflammatory environment and oxidative stress via increase of HO-1 expression, suggesting that PTP1B is a potential therapeutic target for the treatment of chronic DFUs.

Disclosure
A. Figueiredo: None. E.C. Leal: None. D. Santos: None. G. Gasiunaite: None. M. Delibegovic: None. E. Carvalho: None.

Funding
Diabetes UK; Portuguese Foundation for Science and Technology; European Foundation for the Study of Diabetes; Portuguese Society of Diabetology
54-LB: Control Yourself: Impact of Self-Regulation on Diabetes Management in Adolescents
Authors: ALBRIGHT DANA , RILEY HURLEY O. , FREDERICKS EMILY , STURZA JULIE , LO SHARON , CLARK KATY M. , LEE JOYCE M. , MILLER ALISON L. 
Published: June 2020

Adolescents have the poorest blood sugar control compared to other age groups (Foster et al., 2019). Adolescence is also a period of developing self-regulation (SR) abilities, defined as the ability to manage thoughts, emotions, and actions to achieve a desired outcome (Eisenberg, 2019). The attention, planning, and decision making required for optimal T1D management is both cognitively and emotionally draining on the developing system of adolescents, which may be contributing to difficultly with diabetes management and glycemic control (Duke & Harris, 2014). This project examines the relationship between specific aspects of SR, including executive functions and affect; and T1D outcomes, including diabetes management behaviors and HbA1c. As part of an ongoing clinical trial (NCT03688919), adolescents (13-17 yo) diagnosed with T1D for ≥ 6 months with HbA1c ≥ 7.0 were recruited from diabetes clinics (n = 56). They completed baselines measures of self-regulation including the Behavior Rating Inventory of Executive Functioning, Positive and Negative Affect Schedule for Children, and self-reported diabetes management behaviors. HbA1c was also collected.
Parent reported cognitive aspects of SR were negatively related to number of insulin boluses per day, specifically attentional shift, task completion and planning, (r(47)= -.36, -.31, -.33 respectively, all p &lt; .05); however, no association was found between inhibition, self-monitoring, and working memory and diabetes outcomes (p &gt;.05). With regard to emotional aspects of SR, positive affect, including excitement, enthusiasm, pride, determination, and activation (r(47)= .34, .33, .36, .31, .29 respectively, all p &lt; .05) were positively related to number of insulin boluses per day. No aspects of SR were related to blood glucose testing behaviors or HbA1c. SR in adolescents may be an important factor in successful T1D management. With evidence-based approaches, SR may be an optimal target for intervention.

Disclosure
D. Albright: None. H.O. Riley: None. E. Fredericks: None. J. Sturza: None. S. Lo: None. K.M. Clark: None. J.M. Lee: Advisory Panel; Self; Goodrx. Consultant; Self; T1D Exchange. Research Support; Self; Lenovo. A.L. Miller: None.

Funding
National Institutes of Health (NCT03688919)
543-P: A Randomised Control Trial to Evaluate the Efficacy of Chinese Traditional Medicine for the Treatment of Diabetic Peripheral Neuropathy
Authors: GUANJIE FAN , LIN YUPING , PAUL SANJOY K. , HUANG HAOYUE , XIANYU TANG , YUEHONG ZHOU , ZHAOHUI FANG , XIAOTANG QIU , FANG DAI , WANG SHI-DONG , WANG MEI , WEI HUA , LING ZHAO , ZHENJIE LIU , FU YU , WU MINGHUI , ANXIANG LI , JINZHU HUANG , LI QINGBO 
Published: June 2020

Background: Diabetic peripheral neuropathy (DPN) is a common complication in patients (pts) with diabetes. However, multinational data do not support any convincing efficacy of the current therapies for treating DPN. This necessitated the evaluation of safety and efficacy of alternative medicine to tackle DPN.
Methods: A double-blinded RCT was conducted in 8 Chinese medicine hospitals in China, evaluating the safety and efficacy of 190 g Tangbi Waixi decoction (TW, intervention (Int)) compared with 19 g TW (control (Cont)). Change in Toronto Clinical Scoring System - Total Score (TCSS-TS) at 12 and 24 weeks follow-up was the primary outcome, with treatment ceasing at 12 weeks. Secondary outcomes included change in bilateral motor velocity (BMV) and sensory nerve conduction velocity (SNCV) of the common peroneal nerve (CPN). All pts received standard care for glycaemic management. The pts in the Int (n=317) and Cont (n=315) groups were analysed on ITT principle. All adverse events (AEs) were recorded.
Results: The pts were mean 60 years old with median 10 yrs and 2 yrs of diabetes and DPN duration respectively at randomisation. With median TCSS-TS of 10 at randomisation in both groups, the median (95% CI) reduction in Int and Cont: at 12 weeks 2 (1.7, 2.3) and 3 (2.7, 3.3) respectively (median between group difference (MBGD): 1.0, p=0.011); at 24 weeks 3 (2.6, 3.4) in both groups. At 12 weeks, median (95% CI) CPN velocity increased in both Int and Cont - BMV Int vs. Cont: 2.7 (1.9, 4.9) m/s vs. 4.9 (2.7, 5.5) m/s, MBGD - 2.5 m/s (p=0.044); SNCV Int vs. Cont: 1.4 (0, 2) m/s vs. 2.7 (1.9, 4.9) m/s, MBGD - 0.7 m/s (p=0.26). Similar increase in CPN velocity was observed at 24 weeks in both groups. Overall 12% pts experienced at least one AE, with no difference between groups.
Conclusion: Treatment of DPN with TW decoction significantly benefitted the pts and is safe, while lower dose of TW appears to be more effective than the higher does.

Disclosure
F. Guanjie: None. Y. Lin: None. S.K. Paul: Advisory Panel; Self; Sanofi. Research Support; Self; AstraZeneca, Genentech, Inc. H. Huang: None. T. Xianyu: None. Z. Yuehong: None. F. Zhaohui: None. Q. Xiaotang: None. D. Fang: None. S. Wang: None. M. Wang: None. H. Wei: None. Z. Ling: None. L. Zhenjie: None. Y. Fu: None. M. Wu: None. L. Anxiang: None. H. Jinzhu: None. Q. Li: None.

Funding
National Science and Technology Support Program (2015BAI04B09)
547-P: Associations between Bladder Symptoms and Diabetic Neuropathy in a Romanian Cohort of Patients with Diabetes
Authors: VONICA CAMELIA L. , BONDOR COSMINA I. , SIMA DIANA , COSMA DANIEL T. , VERESIU IOAN ANDREI , GAVAN NORINA , POP-BUSUI RODICA , SARMA ARUNA V. 
Published: June 2020

Lower urinary tract symptoms (LUTS) are commonly reported by men and women with diabetes and may share a common pathogenic mechanism with diabetic peripheral neuropathy (DPN). We aimed to evaluate associations between DPN and self-reported LUTS in a cohort of Romanian patients with diabetes phenotyped for DPN with the Michigan Neuropathy Screening Instrument (MNSI). Clinical DPN was defined as MNSI exam score of &gt;2; symptomatic DPN as MNSI questionnaire score of ≥4. LUTS was assessed with the validated American Urological Association Symptom Index and defined as 0-7 none/mild and ≥8 moderate/severe. Preliminary data is shown for 174 participants [51% men, mean age 67 years, 95% type 2 diabetes, mean diabetes duration 16 years, mean hemoglobin A1c (HbA1c 8%)]. Sixty% and 64% met the criteria for clinical and symptomatic neuropathy, respectively and 53% of men and 47% of women reported moderate/severe LUTS. MNSI questionnaire scores were significantly associated with LUTS in both men (p&lt;0.001) and women (p&lt;0.001) after adjusting for age and HbA1c. These data demonstrate that patients with symptomatic neuropathy are more likely to present with bladder dysfunction.

Disclosure
C.L. Vonica: Other Relationship; Self; AstraZeneca. C.I. Bondor: Consultant; Self; Wörwag Pharma. D. Sima: None. D.T. Cosma: Other Relationship; Self; Wörwag Pharma. I. Veresiu: None. N. Gavan: None. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association. A.V. Sarma: None.

Funding
Woerwag Pharma GmbH & Co. KG
553-P: Brain Microstructural Tissue Changes in Patients with Controlled and Uncontrolled Type 2 Diabetes
Authors: CHOI SARAH E. , ROY BHASWATI , FREEBY MATTHEW , WOO MARY A. , KUMAR RAJESH 
Published: June 2020

Patients with type 2 diabetes mellitus (T2DM) show brain tissue changes in mood and cognitive control sites. However, it is unclear whether brain microstructural tissue changes differ between patients with controlled (hemoglobin A1c [A1C] &lt;7%) and uncontrolled (A1C ≥ 7%) T2DM. Diffusion tensor imaging (DTI) based mean diffusivity (MD) measures water molecular motion within tissue and shows microstructural changes by values reduced in acute and increased in chronic pathological conditions. Methods: We collected DTI and A1C data from 37 T2DM patients (15 controlled; age 56.4±6.8 years, BMI 29.2±6.2 kg/m2, diabetes duration 6.0±4.8 years, A1C 6.2±0.4%, 7 female; 22 uncontrolled; age 57.2±7.4 years, BMI 30.5±5.1 kg/m2, diabetes duration 15.0±9.0 years, A1C 8.2±1.3%, 14 female) and 12 healthy controls (age 54.3±8.2 years, BMI 25.9±4.6 kg/m2, A1C 5.2±0.4%, 5 male) using a 3.0-Tesla magnetic resonance imaging scanner and point-of-care A1C testing. Whole-brain MD maps were calculated, normalized to a common space, smoothed, and compared between groups (controlled T2DM patients vs. healthy controls; uncontrolled T2DM patients vs. healthy controls) using ANCOVA (SPM12; covariates, age and sex; uncorrected threshold, p&lt;0.005).
Results: No significant differences appeared between groups in age or sex. Mean duration of diabetes was significantly different between controlled and uncontrolled T2DM patients (p &lt;0.001). Uncontrolled T2DM patients showed increased MD values in multiple brain areas, including the cingulate, insula, para-hippocampal, hippocampus, cerebellum, basal-forebrain, prefrontal, frontal, and temporal cortices over controlled T2DM patients and healthy controls.
Conclusion: Uncontrolled T2DM patients show widespread chronic brain microstructural changes in areas that are involved in mood and cognition regulation. The findings support tight glycemic control to prevent further brain tissue damages in patients with T2DM.

Disclosure
S.E. Choi: None. B. Roy: None. M. Freeby: Research Support; Self; Abbott, Novo Nordisk Inc. M.A. Woo: None. R. Kumar: None.

Funding
National Institutes of Health (R01NR017190)
558-P: Poor Oral Health Predicts Progression of Diabetic Neuropathy
Authors: JIVANESCU ANCA , BONDOR COSMINA I. , SIMA DIANA , VONICA CAMELIA L. , COSMA DANIEL T. , STEIGMANN LARISSA , VERESIU IOAN ANDREI , GAVAN NORINA , SARMA ARUNA V. , POP-BUSUI RODICA 
Published: June 2020

Poor oral health (OH) manifested mainly as gingivitis/periodontitis is emerging as a serious diabetes complication. Recent reports suggest that poor OH may share pathogenic mechanisms with diabetic neuropathy (DN). We previously reported a high prevalence of poor OH in a large Romanian cohort of &gt;1300 participants with diabetes phenotyped for OH and DN in 2016, particularly among participants with DN. This follow-up study aimed to further evaluate associations between DN and OH in this cohort over time. DN was assessed with the Michigan Neuropathy Scoring Instrument (MNSI), questionnaire (MNSIq) and clinical examination (MNSIe). Clinical DN was defined as MNSIe score of &gt;2; symptomatic DN as MNSIq score of ≥4. OH was assessed using a validated questionnaire that includes questions about gingival pain, bleeding and complete dentures. OH was defined as good (no symptoms/signs), poor (symptoms/signs often/very often) or very poor (edentulous patients wearing complete dentures). Preliminary data is presented for 104 participants who completed a second evaluation in 2018/2019, median age (25th-75th percentile) 63 (59-70) years, 53% male, median diabetes duration 13 (8-17) years, mean A1c 7.8±1.5%. Among them 62 % presented with MNSIe&gt;2 and 44 % with MNSIq&gt;4. Poor and very poor OH at baseline (2016) were significantly correlated with MNSIe at follow-up (2018) (r = 0.20, p = 0.04). After adjusting for age and duration, there was a significant positive correlation between worsening in OH and DN (r = 0.26, p = 0.037) at follow-up. In multivariate analysis, after controlling for age and diabetes duration, there was a significantly higher change in the overall MNSI scores during follow-up in those with poor and very poor OH (0.97 +/- 1.9 vs. 0.16 +/- 1.8 p = 0.036). These data show that in this longitudinal cohort with diabetes DN worsened over time particularly in those with poor OH, suggesting that OH may directly affect risk of DN and other complications.

Disclosure
A. Jivanescu: None. C.I. Bondor: Consultant; Self; Wörwag Pharma. D. Sima: None. C.L. Vonica: Other Relationship; Self; AstraZeneca. D.T. Cosma: Other Relationship; Self; Wörwag Pharma. L. Steigmann: None. I. Veresiu: None. N. Gavan: None. A.V. Sarma: None. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association.

Funding
Woerwag Pharma GmbH & Co. KG
563-P: Differentially Expressed Plasma miRNAs Are Closely Associated with the Presence of Microvascular Complications in Type 2 Diabetes: The 1000 Qatar-Omics Study Cohort
Authors: AKIL AMMIRA S. , PADMAJEYA SUJITHA SUBASH , JERMAN LAILA A. , AL-KURBI ALYA , HUSSEIN AMAL M. , HARDIKAR ANAND , JOGLEKAR MUGDHA , HABIB TANWIR , ANBARI MOHAMMED EL , FAKHRO KHALID 
Published: June 2020

Background: In the light of growing global epidemic of T2D and related microvascular complications, it is important to find early detection marker for the disease. Circulating miRNAs serve as a potential biomarker for monitering the progression to DR in diabetic individuals.
Hypothesis and Aims: miRNAs play a substantial role in metabolic homeostasis through regulation of multiple genes, and could serve as a prognostic biomarker in DR. This study aims to assess a functional role of selected miRNAs in the Qatari population recruited for the Qatar Genome Project through Qatar BioBank.
Methods: Plasma samples from 470 T2D subjects with and without DR and 500 matched-healthy controls has been included in this study. Total RNA was extracted and the expression profiling of 56 miRNA that previously reported as a player in the pathogenesis of DR was performed using custom open array panel. The miRNA expression data were normalized using ath-mir159a. Statistical analysis was performed to study the association between the phenotypes (HbA1c, C-peptide, age, BMI) and miRNA.
Results: The patients and controls phenotypic and miRNA expression data were analyzed to interepret the differential expression of the miRNA in DR subjects. Initial analysis by applying the generalized additive model reveals that six miRNA (hsa-miR-27a, hsa-miR-376c, hsa-miR-92a, hsa-miR-1 hsa-miR-223, and mmu-miR-451) were found to be significantly associated with DR (p&gt;0.05). Furthermore, two differentially expressed miRNAs, (hsa-miR-1274A and hsa-miR-24) found to be associated with higher level of C-peptide in DR patients, which suggest the correlation of these miRNAs with the glucose hemostasis and DR.
Conclusion: The etiology of DR is unclear, and present treatments have limited effectiveness. The biomarkers and downstream functional studies are required to deepen the understanding of this chronic diseases and its complications.

Disclosure
A.S. Akil: None. S. Subash Padmajeya: None. L.A. Jerman: None. A. Al-Kurbi: None. A.M. Hussein: None. A. Hardikar: None. M. Joglekar: None. T. Habib: None. M. El Anbari: None. K. Fakhro: None.