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Assim A Alfadda,1– 3 Khalid Siddiqui,2 Mohamed Rafiullah,2 Mohammad AlKhowaiter,1 Naif Alotaibi,4 Musa Alzahrani,5 Khalifa Binkhamis,6 Amira M Youssef,2 Haifa Altalhi,7 Ibrahim Almaghlouth,8 Mohammed Alarifi,9 Saleh Albanyan,1 Mohammed F Alosaimi,10 Arthur Isnani,3 Shaik S Nawaz,2 Khalid Alayed5 1Department of Internal Medicine, College of Medicine, and King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 2Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 5Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 7Infection Control Department, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 8Rheumatology Unit, Department of Internal Medicine, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 9Intensive Care Department, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 10Pediatric Department, King Khalid University Hospital, King Saud University Medical City, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Assim A Alfadda, Department of Internal Medicine and the Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925(98), Riyadh, 11461, Saudi Arabia, Tel + 966 11 467 1315, Email aalfadda@ksu.edu.saBackground: The severe manifestation of coronavirus disease 2019 (COVID-19) is known to be mediated by several cytokines and chemokines. The study aimed to compare the early cytokine profile of mild and severe COVID-19 patients to that with COVID-19-like symptoms and tested negative for Severe Acute Respiratory Syndrome Coronavirus-2 in the Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) test.Methods: This was a prospective, observational study on COVID-19 patients admitted to King Khalid University Hospital, King Saud University Medical City from June to November 2020. Clinical and biochemical data were collected from hospital charts. Blood samples were collected at the time of hospital admission to measure cytokines. A Cytokine and Growth Factor High-Sensitivity Array was used to quantitatively measure cytokines.Results: The study included 202 RT-PCR-positive individuals and 61 RT-PCR-negative individuals. C-Reactive protein (CRP) and Interleukin-10 (IL-10) levels were found significantly elevated in the RT-PCR positive group compared to the RT-PCR negative group (p=0.001). Patients with severe COVID-19 had significantly longer median hospital stays than those with mild COVID-19 cases (7 vs 6 days). They also had higher CRP and Vascular Endothelial Growth Factor (VEGF) levels and lower Interleukin-4 (IL-4) levels compared to the mild cases. CRP, interleukin-6, IL-10, VEGF, and Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly elevated in men and IL-10 was significantly higher and interleukin-8 was significantly lower in women compared to negative controls. Elevated Interferon-ɣ (IFN-γ) and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.Conclusion: CRP and IL-10 levels were elevated in the RT-PCR positive group. People with severe COVID-19 had higher CRP and VEGF levels and lower IL-4 levels. Elevated IFN-γ and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.Keywords: SARS-CoV-2, early inflammation, asymptomatic patient, proinflammatory cytokines, regulatory cytokines

Khalid Siddiqui,1 Shaik Sarfaraz Nawaz,1 Assim A Alfadda,1– 3 Muhammad Mujammami1,2,4 1Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Khalid Siddiqui, Strategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh, 11411, Saudi Arabia, Tel +966 114724179 Ext.3106, Fax +966 114725682, Email ksiddiqui@ksu.edu.saBackground: Diabetic Nephropathy (DN) is one of the most typical causes of end-stage renal disease and thyroid hormone exerts effects on the kidney. There are few reports on the role of thyroid hormone in the progression of DN. We aimed to assess the relationship between thyroid hormone and DN.Methods: In this cross-sectional study, 400 patients with type 2 diabetes (T2D) (aged between 35 and 70 years) were divided into two groups T2D control and DN group according to albumin creatinine ratio (ACR). Clinical biochemistry parameters were measured using the Rx Daytona chemistry analyzer and thyroid hormone levels (TT4, TT3, TSH, FT4, and FT3) using the Evidence Biochip analyzer. To assess the relationship between thyroid hormone and DN, multiple logistic regression models were developed.Results: Serum FT4 and FT3 levels were significantly lower in DN compared to T2D controls (p< 0.05). Thyroid hormone levels tend to decrease with the progression of DN. In unadjusted and adjusted logistic regression models, FT3 levels were negatively associated with odds of having DN (OR=0.28, CI=0.128– 0.616, p=0.002).Conclusion: The free triiodothyronine level was negatively associated with the progression of DN. Further longitudinal studies are required to assess the cause of thyroid hormone differences.Keywords: diabetic nephropathy, type 2 diabetes, thyroid hormone

Nawaf A Alshammari,1,2,&ast; Abdulaziz A Alodhayani,3,&ast; Salini S Joy,4 Arthur Isnani,5 Muhammad Mujammami,1,4,6 Assim A Alfadda,4– 6 Khalid Siddiqui4 1University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 2King Salman Specialist Hospital, Diabetes and Endocrine Center, Hail Health Cluster, Hail, Hail Region, Saudi Arabia; 3Department of Family and Community Medicine College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 5Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Khalid Siddiqui, Strategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh, 11411, Saudi Arabia, Email ksiddiqui@ksu.edu.saBackground: Neuropathy is the most common microvascular complications among diabetic patients. Diabetic peripheral neuropathy (DPN) is the predominant variety which may associate with increased in mortality and morbidity among type 2 diabetes mellitus (T2DM).Objective: To assess the prevalence of diabetic peripheral neuropathy and its correlation with risk factors among T2DM.Methods: This was a cross-sectional retrospective study, data was collected from a previous cohort study conducted at the University Diabetes Center, King Saud University Medical City (KSUMC), King Saud University, Riyadh, Saudi Arabia. The data of T2DM patients were collected from case report form, included demographic data, history of chronic diabetes neuropathy, and laboratory reports. Statistical analysis includes Student`s t test, chi square test, and Pearson correlation and logistic regression were performed.Results: A total of 430 patients with T2DM data was collected and analyzed, and of them 54% were females, with the mean age of 55.88 years. The prevalence of diabetic neuropathy among study participants were 40.2%, and 73.3% of them having the subtype polyneuropathy. The mean BMI; p = 0.006, FBS; p < 0.001, HbA1c; p < 0.001, cholesterol p = 0.001, LDL; p < 0.001, and triglyceride; p < 0.001 levels were a significantly higher among participants with diabetic neuropathy than without neuropathy. The male gender (Risk Ratio: 1.294, 95% CI:1.090, 1.536) p = 0.003, fasting blood glucose (Risk Ratio: 1.157, 95% CI:1.051, 1.273) p = 0.003 Cholesterol (Risk Ratio: 1.588, 95% CI:1.174, 2.147) p = 0.003, triglyceride (Risk Ratio: 1.290, 95% CI:1.086, 1.538), p = 0.004, and LDL (Risk Ratio: 1.299, 95% CI:1.073, 1.574), p = 0.007) were found to be significant risk factors for DPN.Conclusion: DPN is highly prevalent among T2DM patients in Saudi Arabia. Poor glycemic control and hyperlipidemia were associated with significantly higher risk for DPN patients among T2DM.Keywords: diabetic peripheral neuropathy, hyperlipidemia, glycemic control, type 2 diabetes

Rasha A Almubark,1 Saleh Alqahtani,2,3 Arthur C Isnani,4 Ali Alqarni,5 Mahmoud Shams,6 Moataz Yahia,6 Assim A Alfadda4,7,8 1Sharik Association for Health Research, Riyadh, Saudi Arabia; 2Liver Transplant Unit, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; 3Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA; 4Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 5King Abdulaziz Hospital and King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Ahsa, Eastern Region, Saudi Arabia; 6Novo Nordisk, Riyadh, Saudi Arabia; 7Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 8Obesity, Endocrine, and Metabolism Center, King Fahad Medical City, Riyadh, Saudi ArabiaCorrespondence: Assim A Alfadda, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Tel + 966 11 4671315, Email aalfadda@ksu.edu.saPurpose: Several studies have investigated gender differences in various obesity-related outcomes. Females were found to have more accurate weight perception and reported more frequency of attempted weight loss. The objective of this study was to assess gender differences in the attitudes and management of people with obesity (PwO) in Saudi Arabia using data from the ACTION-IO study.Patients and Methods: A survey was conducted in Saudi Arabia in June and July 2018 on adults with obesity (based on self-reported body mass index of ≥ 30 kg/m2).Results: A total of 1000 people with obesity completed the survey; 565 (56.5%) were male (mean age of 36.9 years and mean BMI of 33.5 kg/m2) and 435 (43.5%) were female (mean age of 36.3 years and mean BMI of 34.5 kg/m2). The two most reported motivations for wanting to lose weight for both groups were to improve appearance (38%) and to have more energy (35%). Females were more likely to trust their health-care provider (HCP) advice about weight management when compared to males (87% females, 82% males, p = 0.059) and were more likely to have concerns regarding long-term safety associated with prescription weight loss medications (65% female versus 59% males, p = 0.043). On the other hand, males were more likely to seek their physician to prescribe weight loss medication if they hear of a new medication (55% males versus 46% females, p = 0.014), and more to believe that there are good options available for weight loss medications (74% males versus 67% females, p = 0.040). Also, more males prefer to take weight loss medications than to have a weight loss surgery (65% males, 59% females, p = 0.054).Conclusion: Overall, this study increases our understanding on the attitudes of both females and males towards the management of weight loss and opens the discussion for gender-specific weight loss interventions.Keywords: obesity, gender, management, Saudi Arabia, ACTION-IO

Aishah Ekhzaimy,1 Shadin Alkatari,1 Mohamed AlMaatouq,1 Daad Alotaibi,1 Sarah Aljasser,1 Amal Aseeri,1 Anwar Jammah,1 Muhammad Mujammami,1– 3 Mona Fouda,1 Assim A Alfadda,1,2,4 Riad Sulaimani1 1Division of Endocrinology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia; 3University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia; 4Obesity Research Center, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi ArabiaCorrespondence: Aishah Ekhzaimy, Division of Endocrinology, Department of Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Kingdom of Saudi Arabia, Email aishahekhzaimy@hotmail.comPurpose: Impact of ramadan fasting on healthy and women with diabetes is already known. However, there is a scarcity of data on impact of fasting on pregnant women with diabetes. Moreover, religious and medical recommendations advise pregnant women against fasting as it is unsafe. Despite being exempted, many pregnant Muslim women with diabetes still choose to fast during ramadan. This study investigated different glycemic marker as an indicator for diabetes control in fasting pregnant women.Patients and Methods: This is a prospective observational study. A total of 89 pregnant diabetes women were recruited. Blood glucose was self-monitored in all the pregnant women using glucose monitoring device at home. We measure the fructosamine, HbA1c levels before, during and after ramadan.Results: Pregnant women with type 1 diabetes were 14 (25%), type 2 diabetes were 21 (37.5%), and gestational diabetes were 21 (37.5%). The mean fructosamine level decreased during and after ramadan in gestation diabetes pregnant women compared to type 2 diabetes and type 1 diabetes pregnant women subjects (p = 0.009).Conclusion: The present study indicates that pregnant women with diabetes were able to fast during ramadan and there fructosamine level reduced during fasting. Utilization of fructosamine for short-term monitoring of glycemic control in addition to home glucose monitoring in pregnant women with diabetes will provide a good index of glycemic control.Recommendation: Religious and medical recommendations advise pregnant women against fasting as it is unsafe, and they are under high risk. However, if they insist to do fast, they must do under strict medical supervision and fructosamine can be used as a glycemic control marker.Keywords: ramadan fasting, gestational diabetes, type 2 diabetes, type 1 diabetes, pregnant women, fructosamine

Khalid Siddiqui,1 Salini Scaria Joy,1 Teena Puthiyaparampil George,1 Muhammad Mujammami,1– 3 Assim A Alfadda1,3,4 1Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 4Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Khalid SiddiquiStrategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh 11411, Kingdom of Saudi ArabiaTel +966 114724179 ext.1340Email ksiddiqui@ksu.edu.saBackground: Analyzing urinary biomarkers may provide better insight into pathophysiological mechanisms of diabetic kidney diseases. The study aimed to analyze the pattern of selected excreted urinary biomarkers and its correlation with albuminuria and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.Methods: A total of 185 patients with type 2 diabetes were categorized according to KDIGO guideline based on albuminuria and eGFR. The urinary markers (transferrin, KIM-1, RBP, MCP-1 and NGAL) were measured by ELISA.Results: The urinary markers were associated with eGFR (total protein/Cr, p=0.001; RBP/Cr, p=0.007; MCP-1/Cr, p=0.023; NGAL/Cr, p=0.011) and albuminuria (total protein/Cr, p< 0.001; transferrin, p< 0.001; RBP/Cr, p< 0.001; MCP-1/Cr, p< 0.001; NGAL/Cr, p=0.002).Conclusion: The urinary marker levels (total protein, RBP, MCP-1, and NGAL) are elevated with severity of kidney damage and expressed more in progressive renal impairment.Keywords: diabetic kidney disease, urinary markers, albuminuria, transferrin, kidney injury molecule-1, retinol-binding protein, monocyte chemoattractant protein-1, neutrophil gelatinase-associated lipocalin

Helalah Alenizy,1 Nouran Aleyeidi,2 Reema Almutairi,3 Leen Khosyfan,3 Raghad Bedaiwi,3 Leen Alowaidah,3 Hissah Alrushud,3 Khawla Alfadda,3 Lujain A Alshamekh,3 Najd Al Anazi,3 Shuruq Alshammari,3 Amal Alzahrani,3 Hanin Alomar3 1Obstetrics and Gynecology, Department of Obstetrics and Gynecology, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 2Community Medicine, Department of Family and Community Medicine, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 3College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaCorrespondence: Nouran Aleyeidi, Department of Family and Community Medicine, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia, Tel +966 504304577, Email naaleyeidi@pnu.edu.saBackground: Menstruation is a natural process that occurs monthly in women. Although menstruation is a fundamental aspect of women’s lives, their readiness for and beliefs about menstruation vary. Moreover, their practices during menstruation can be influenced by various factors, including age, education level, mother’s education, and field of specialty. This study aimed to explore menstruation-related readiness, beliefs, and practices among women who had experienced menstruation in Saudi Arabia. In addition, the study aimed to evaluate the factors affecting these women’s readiness, beliefs, and practices regarding menstruation.Patients and Methods: This cross-sectional online questionnaire-based study included 3471 women of different ages who had experienced menstruation. The participants were selected using convenience sampling from all regions of Saudi Arabia. The questionnaire was distributed between late December 2022 and March 2023 and included questions on demographics and menstruation-related readiness, beliefs, and practices.Results: Of the 3471 participants, 1627 (46.8%) were well prepared for menstruation. In addition, most of the study participants (80.2%) had positive beliefs about menstruation. However, the participants’ menstrual practices varied. Over half of the participants (63%) used painkillers and approximately half (54.4%) used herbal medicine during menstruation.Conclusion: This study found that less than half of the participants were ready for menarche. In contrast, most participants displayed positive beliefs concerning menstruation. In terms of practices, the women exhibited certain dietary restrictions during their menstrual period and predominantly favored herbal remedies for pain relief over conventional painkillers. Implementing awareness campaigns and incorporating school education on menstrual readiness and hygiene is needed.Keywords: women’s health, gynecology, menarche, hygiene, herbal medicine, menstrual pain

Background and Aim The prevalence of obesity is increasing and people with obesity (PwO) continue to struggle with their weight. We aimed to describe the experiences of people who struggled with their weight at an early age (EAO) or at a later age (LAO), their discussions with their healthcare practitioners (HCPs) and episodes of depression and anxiety. Methods We gathered information from 1,000 adults PwO, categorized them into EAO and LAO and analyzed their responses regarding weight loss attempts, discussions with their HCP, perceptions about obesity and episodes of depression/anxiety. Results Mean age was 36.6 years old, and 73.0% were AAO. EAO had significantly fewer weight loss attempts and had fewer interactions with their HCP. EAO reported less HCP support for weight management, were less motivated to lose weight, and experienced more episodes of anxiety/depression. Significant association between greater obesity class with longer duration of weight problems, and depression and anxiety. EAO PwOs were less likely to discuss weight problems with their HCP. Conclusion It is fundamental that HCPs recognize and address weight issues in PwO who are at risk of obesity in adulthood as early as adolescence. They should also take the lead in addressing these psychophysiological concerns by involving the parents in the decision-making process and facilitating shared planning. These may enhance their motivation to lose weight, boost self-confidence, and reduce the complications of obesity.

The mastery of vocabulary is a fundamental step when learning a language but for many learners, it seems difficult and boring. English as Foreign Language (EFL) learners find some difficulties in learning new words. The aim of this study was to examine the effect of using the hologram application in learning medical English terminology for EFL learners. The study involved 109 EFL learners studying at a medical college to determine if a holographic tool affected their learning. They were divided into three groups: a control group using traditional methods to learn new medical terms (no technology was used), and two experimental groups. One experimental group was taught using PowerPoint without the holographic application, while the other experimental group was taught using the holographic application. The data were collected using the pre-, post-, and delayed post-test design. The findings of the study indicated that learners who were taught using the holographic application outscored other groups and remembered more medical English terms after three weeks. Moreover, the learners felt the hologram application had a positive impact on learning medical terms.

Liraglutide, a type2 diabetes mellitus (T2DM)-related treatment, improves glycemic control and reduces the risks of adverse cardiovascular events in T2DM patients. However, the underlying mechanisms of the above-mentioned beneficial effects of Liraglutide are not well understood. To have better understanding of these mechanisms, we aimed to study the metabolic impacts of Liraglutide on the metabolome and corresponding pathways in T2DM patients, especially metabolism plays a very fundamental role in health and diseases and is influenced by drugs. In this study, plasma samples collected from T2DM patients (n = 20) and taken pre- and post-Liraglutide treatment were used for untargeted metabolomics analyses, including metabolome profiling and metabolic pathway/network analyses. The metabolome profiling analyses identified 93 endogenous metabolites that were significantly affected by Liraglutide treatment where 49 and 44 metabolites were up and down regulated, respectively. Liraglutide caused metabolic alterations impacting metabolic pathways such as pentose and glucuronate interconversion and alanine, aspartate and glutamate metabolism in T2DM patients. Since the last-mentioned pathways are affected by Liraglutide, it could explain partially the overall beneficial effects of Liraglutide in T2DM, especially that glucuronate interconversion pathway is known by its important roles in eliminating toxic and undesirable substances from the human body to maintain good health status. In addition, the metabolism of amino acids induced by Liraglutide could improve the function of immune cells, strengthening the immunity of T2DM patients. Also, Liraglutide induced the level of other metabolites that help in the defense mechanism against oxidative events. Overall, the findings of this study provide a deeper understanding of the underlying mechanisms involved in the beneficial effects of Liraglutide in T2DM from the metabolic aspect.

IntroductionTreatment and management of obesity is clinically challenging. The inclusion of GLP-1 receptor agonists (GLP1RA) in the medical management of obesity has proven to be efficacious. However, mechanisms underlying the molecular changes arising from GLP1RA treatment in patients with obesity remain to be elucidated.MethodsA single-center, prospective study was undertaken to evaluate the changes in the plasma proteins after liraglutide 3 mg therapy in twenty patients (M/F: 7/13) with obesity (mean BMI 40.65 ± 3.7 kg/m2). Anthropometric and laboratory parameters were measured, and blood samples were collected at two time points: baseline, before initiating treatment (pretreatment group, PT), and after three months of receiving the full dose liraglutide 3 mg (posttreatment group, PoT). An untargeted label-free LC MSMS mass spectrometric approach combined with bioinformatics and network pathway analysis was used to determine changes in the proteomic profiles.ResultsThe mean age of the study participants was 36.0 ± 11.1 years. A statistically significant change was observed in weight, BMI and HbA1c levels between the PT and PoT groups (paired t-test, P < 0.001). A significant dysregulation was noted in the abundances of 151 proteins (31 up and 120 downregulated) between the two groups. The potential biomarkers were evaluated using receiver operating characteristic (ROC) curves. The top ten proteins (area under the curve (AUC) of 0.999 (95% CI)) were identified as potential biomarkers between PT and PoT groups and included Cystatin-B, major vault protein, and plastin-3, which were upregulated, whereas multimerin-2, large ribosomal P2, and proline–rich acidic protein 1 were downregulated in the PoT group compared with the PT group. The top network pathway identified using ingenuity pathway analysis (IPA), centered around dysregulation of MAPK, AKT, and PKc signaling pathways and related to cell-to-cell signaling and interaction, cellular assembly and organization, cellular compromise and a score of 46 with 25 focus proteins.DiscussionThrough label-free quantitative proteomic analysis, our study revealed significant dysregulation of plasma proteins after liraglutide 3 mg treatment in patients with obesity. The alterations in the proteomic profile between the PT and PoT groups demonstrated a decrease in levels of proteins involved in inflammation and oxidative stress pathways. On the other hand proteins involved in the glycolytic and lipolytic metabolic pathways as well as those participating in cytoskeletal and endothelial reorganization were observed to be increased. Understanding actions of liraglutide at a molecular and proteomic levels provides a holistic look into how liraglutide impacts metabolism, induces weight loss and improves overall metabolic health.

After the exceptional circumstances the whole world has experienced due to the COVID-19 pandemic, students have become digital natives who seek learning that overcomes the barriers of place and time. This mixed-methods study aimed at investigating EFL learners' perceptions regarding the application of Busuu in language learning, by applying the Technology Acceptance Model (TAM). The participants were 58 first secondary stage students in a Saudi private school. An online survey and a semi-structured interview were used to collect data. The results revealed that EFL learners have a positive attitude towards Mobile Assisted Language Learning (MALL). Additionally, according to the TAM, the participants found the language application Busuu useful and easy to use. They also thought of Busuu as a valuable resource for language learning, which increases their motivation to be autonomous learners. However, in addition to the TAM components, the results also showed that affordance and joyfulness could be strong indicators of learners' acceptance of a particular technology. Moreover, the results revealed that mobile applications might be more helpful for beginner learners than advanced ones. On the other hand, the findings also showed that Busuu might distract learners from doing their homework. Besides, the regular use of Busuu might be harmful to their eyes due to the small mobile screen size. For further research, the recommendation includes a large sample size in addition to a long-term study of EFL learners' perception towards Busuu in normal classroom circumstances.

The Sheltered Instructional Observation Protocol SIOP is a model designed to assist teachers in organizing and planning the lessons delivery through different stages. This model is also useful in enhancing the students' achievement and minimizing any chance of educational failure. However, EFL teachers need to be trained in order to guarantee successful implementation of this model. This study examined the implementation of the SIOP model from teachers' perspectives after they attended an introductory workshop in a private school in Riyadh city, Saudi Arabia. The study adopted the qualitative approach for collecting and analyzing the data. The sample of the study consisted of seven English language teachers (4 females & 3 males). Two data collection instruments were used, namely, observational sessions and a semi-structured interview. Most of the researcher interaction with the sample was done online due to the outbreak of COVID-19 pandemic. The workshop and the interviews were done through Zoom video communication. The central findings of this study reveal that the majority of the teachers have covered all SIOP components during their lessons. Moreover, it was found that there is a relationship between the implementation of the SIOP model and the students' learning motivation. Furthermore, the results showed that the SIOP implementation might help in enhancing the teachers' proficiency. Besides, it was revealed that most of the teachers had a positive attitude towards the implementation of the SIOP model. However, they claimed that time and place might hinder any future implementation of the SIOP model. This study recommends a larger sample size, longtime study application and a life sample workshop to guarantee better results. It also provides significant implications which might be useful for EFL teachers, policy makers and interested researchers.

This paper investigates the various roles found in the EFL classroom, such as native English-speaking teachers, learners' parents, and study habits outside of the classroom. During the study, the development of learners' reading comprehension, vocabulary, and writing ability was measured over the course of one semester in a weekly 2-hour English class taught by a native English speaker. Results of the change in the twenty learners' performance on reading comprehension, vocabulary, and writing ability, are drawn from pre-tests and post-tests. In both the pre and post-tests, the frequently occurring errors included articles, spelling errors, the use of fragments and run-on sentences, as well as a lack of overall coherence in the writing portion of the pre and post-tests. The study finds the learner's struggled to express their ideas properly in and academic way in both the pre and post-tests writing ability section. Based on the findings in the pre and post-tests performance of the learners, it is concluded that the role of a native English-speaking teacher in the development of learners' reading comprehension, vocabulary, and writing skills may not be as important a factor as perceived by students and parents of English language in China.

Here, we, for the first time, compared the cardioprotective effects of third-generation vasodilating beta-blocker nebivolol (Neb) and conventional beta-blocker metoprolol (Met) on LPS-induced injury in H9c2 cardiomyoblasts. Our findings denoted that Neb and Met pretreatment diminish LPS-mediated cytotoxicity and oxidative stress. Concomitantly, LPS-triggered inflammatory cytokines activation was significantly suppressed by Neb but not by Met. Pretreatment with either Neb or Met alleviated LPS-mediated mitochondrial impairment by enhancing the expression of genes related to its biogenesis such as PGC-1α, NRF1, and TFAM. On the contrary, Neb but not Met-upregulated mitochondrial fusion-related genes such as OPA, and MFN2. In summary, our findings suggest that Neb and Met treatment significantly ameliorated the LPS-induced cytotoxicity and oxidative stress. Additionally, these findings suggest that Neb but not Met significantly down-regulates LPS-induced proinflammatory factors, probably by enhancing mitochondrial biogenesis and fusion.

Background: Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP1RA), is a well-established anti-diabetic drug, has also been approved for the treatment of obesity at a dose of 3 mg. There are a limited number of studies in the literature that have looked at changes in metabolite levels before and after liraglutide treatment in patients with obesity. To this end, in the present study we aimed to explore the changes in the plasma metabolomic profile, using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in patients with obesity. Methods: A single-center prospective study was undertaken to evaluate the effectiveness of 3 mg liraglutide therapy in twenty-three patients (M/F: 8/15) with obesity, mean BMI 40.81 ± 5.04 kg/m2, and mean age of 36 ± 10.9 years, in two groups: at baseline (pre-treatment) and after 12 weeks of treatment (post-treatment). An untargeted metabolomic profiling was conducted in plasma from the pre-treatment and post-treatment groups using LC-HRMS, along with bioinformatics analysis using ingenuity pathway analysis (IPA). Results: The metabolomics analysis revealed a significant (FDR p-value ≤ 0.05, FC 1.5) dysregulation of 161 endogenous metabolites (97 upregulated and 64 downregulated) with distinct separation between the two groups. Among the significantly dysregulated metabolites, the majority of them were identified as belonging to the class of oxidized lipids (oxylipins) that includes arachidonic acid and its derivatives, phosphorglycerophosphates, N-acylated amino acids, steroid hormones, and bile acids. The biomarker analysis conducted using MetaboAnalyst showed PGP (a21:0/PG/F1alpha), an oxidized lipid, as the first metabolite among the list of the top 15 biomarkers, followed by cysteine and estrone. The IPA analysis showed that the dysregulated metabolites impacted the pathway related to cell signaling, free radical scavenging, and molecular transport, and were focused around the dysregulation of NF-κB, ERK, MAPK, PKc, VEGF, insulin, and pro-inflammatory cytokine signaling pathways. Conclusions: The findings suggest that liraglutide treatment reduces inflammation and modulates lipid metabolism and oxidative stress. Our study contributes to a better understanding of the drug’s multifaceted impact on overall metabolism in patients with obesity.

Abstract Background Telomere length, an indicator of ageing and longevity, has been correlated with several biomarkers of cardiometabolic disease in both Arab children and adults. It is not known, however, whether or not telomere length is a highly conserved inheritable trait in this homogeneous cohort, where age-related diseases are highly prevalent. As such, the aim of this study was to address the inheritability of telomere length in Saudi families and the impact of cardiometabolic disease biomarkers on telomere length. Methods A total of 119 randomly selected Saudi families (123 adults and 131 children) were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for routine analyses of fasting glucose and lipid profile. Leukocyte telomere length was determined using quantitative real time PCR. Results Telomere length was highly heritable as assessed by a parent-offspring regression [h2 = 0.64 (p = 0.0006)]. Telomere length was modestly associated with BMI (R2 0.07; p-value 0.0087), total cholesterol (R2 0.08; p-value 0.0033), and LDL-cholesterol (R2 0.15; p-value 3 x 10-5) after adjustments for gender, age and age within generation. Conclusion The high heritability of telomere length in Arab families, and the associations of telomere length with various cardiometabolic parameters suggest heritable genetic fetal and/or epigenetic influences on the early predisposition of Arab children to age-related diseases and accelerated ageing.

The application of biosensors in neurolinguistics has significantly advanced the detection and mapping of language areas in the brain, particularly for individuals with brain trauma. This study explores the role of biosensors in this domain and proposes a conceptual model to guide their use in research and clinical practice. The researchers explored the integration of biosensors in language and brain function studies, identified trends in research, and developed a conceptual model based on cluster and thematic analyses. Using a mixed-methods approach, we conducted cluster and thematic analyses on data curated from Web of Science, Scopus, and SciSpace, encompassing 392 articles. This dual analysis facilitated the identification of research trends and thematic insights within the field. The cluster analysis highlighted Functional Magnetic Resonance Imaging (fMRI) dominance and the importance of neuroplasticity in language recovery. Biosensors such as the Magnes 2500 watt-hour (WH) neuromagnetometer and microwire-based sensors are reliable for real-time monitoring, despite methodological challenges. The proposed model synthesizes these findings, emphasizing biosensors’ potential in preoperative assessments and therapeutic customization. Biosensors are vital for non-invasive, precise mapping of language areas, with fMRI and repetitive Transcranial Magnetic Stimulation (rTMS) playing pivotal roles. The conceptual model serves as a strategic framework for employing biosensors and improving neurolinguistic interventions. This research may enhance surgical planning, optimize recovery therapies, and encourage technological advancements in biosensor precision and application protocols.

In recent decades, Saudi Arabia has experienced a significant surge in energy consumption as a result of population growth and economic expansion. This has presented utility companies with the formidable challenge of upgrading their facilities and expanding their capacity to keep pace with future energy demands. In order to address this issue, there is an urgent need to implement energy-saving solutions such as energy storage systems (ESSs) and renewable energy sources, which can help to reduce demand during peak hours. To ensure optimal use of ESSs, it is crucial to integrate a load forecasting model with the ESS in order to control charging and discharging rates and schedules. The irregular load profile is a particularly significant consumer of energy, consuming approximately 2.5 GWh annually at the cost of USD 3 billion in Saudi Arabia. In light of this, this paper develops a load forecasting model for the irregular load profile with a high degree of accuracy: achieving 95%. One of the key applications of this model is load peak shaving. Given the region’s abundance of solar irradiation, the paper propose an integration of a solar PV system with a battery energy storage system (BESS) and analyzes various scenarios to determine the efficacy of the proposed approach. The results demonstrate significant savings when the proposed forecasting model is integrated with a BESS and PV system, with the potential to reduce monthly imported power by more than 22% during the summer season.

The neuropsychological diagnosis and assessment of alexia remain formidable due to its multifaceted presentations and the intricate neural underpinnings involved. The current study employed a mixed-method design, incorporating cluster and thematic analyses, to illuminate the complexities of alexia assessment. We used the Web of Science and Scopus to retrieve articles spanning from 1985 to February 2024. Our selection was based on identified keywords in relation to the assessment and diagnosis of alexia. The analysis of 449 articles using CiteSpace (Version 6.3.R1) and VOSviewer (Version 1.6.19) software identified ten key clusters such as ‘pure alexia’ and ‘posterior cortical atrophy’, highlighting the breadth of research within this field. The thematic analysis of the most cited and recent studies led to eight essential categories. These categories were synthesized into a conceptual model that illustrates the interaction between neural, cognitive, and diagnostic aspects, in accordance with the International Classification of Functioning, Disability, and Health (ICFDH) framework. This model emphasizes the need for comprehensive diagnostic approaches extending beyond traditional reading assessments to include specific tasks like character identification, broader visual processing, and numerical tasks. Future diagnostic models should incorporate a diverse array of alexia types and support the creation of advanced assessment tools, ultimately improving clinical practice and research.

Childhood apraxia of speech (CAS) represents a significant diagnostic and therapeutic challenge within the field of clinical neuropsychology, characterized by its nuanced presentation and multifactorial nature. The aim of this study was to distil and synthesize the broad spectrum of research into a coherent model for the assessment and diagnosis of CAS. Through a mixed-method design, the quantitative phase analyzed 290 studies, unveiling 10 clusters: developmental apraxia, tabby talk, intellectual disabilities, underlying speech processes, breakpoint localization, speech characteristics, functional characteristics, clinical practice, and treatment outcome. The qualitative phase conducted a thematic analysis on the most cited and recent literature, identifying 10 categories: neurobiological markers, speech motor control, perceptual speech features, auditory processing, prosody and stress patterns, parent- and self-report measures, intervention response, motor learning and generalization, comorbidity analysis, and cultural and linguistic considerations. Integrating these findings, a descriptive and prescriptive model was developed, encapsulating the complexities of CAS and providing a structured approach for clinicians. This model advances the understanding of CAS and supports the development of targeted interventions. This study concludes with a call for evidence-based personalized treatment plans that account for the diverse neurobiological and cultural backgrounds of children with CAS. Its implications for practice include the integration of cutting-edge assessment tools that embrace the heterogeneity of CAS presentations, ensuring that interventions are as unique as the children they aim to support.

Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (p < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, p ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide.

The study uses technology acceptance model (TAM) to gain insights into user reactions to the technology adopted for language learning. The study aims to analyze the correlation between the variables of TAM on using Zoom application in language learning, in addition to examining how gender and experience influence the use of technology. The participants of this study comprise of 75 undergraduate English-as-Foreign-Language learners who have studied for their courses online during the COVID-19 pandemic. The results of the study reveal a strong positive correlation between the actual use of Zoom and the students' attitudes and behavioral intention. In addition, there is a positive correlation between computer self-efficacy and other variables (i.e. PU, actual use, PEU, attitude and behavioral intention). Further, while the results reveal that there is no correlation between the gender and any variables of the model, it has been found that experience is positively correlated with the variables of TAM.

Uterine cancer is the most prevalent gynecologic malignancy in women worldwide. Endometrial cancer (EC) has an 81% five-year survival rate, depending on disease stage and time of diagnosis. While endometrial cancer is largely treatable when detected early, no established screening techniques are available in clinical practice. As a result, one of the most significant issues in the medical field is the development of novel ways for early cancer identification, which could boost treatment success rates. Liquid chromatography–high-resolution mass spectrometry (LC-HRMS)-based metabolomics was employed to explore the metabolomic markers and pathways unique to this cancer type and link them to the benign endometrial hyperplasia that may progress to cancer in 5% to 25% of patients. The study involved 59 postmenopausal participants, 20 with EC type 1, 20 with benign hyperplasia, and 19 healthy participants. Metabolite distribution changes were analyzed, and 338 of these features were dysregulated and significant. The first two main components, PC1 and PC2, were responsible for 11.5% and 12.2% of the total metabolites, respectively. Compared with the control group (CO), EC samples had 203 differentially expressed metabolites (180 upregulated and 23 downregulated); in hyperplasia (HP), 157 metabolites were dysregulated (127 upregulated and 30 downregulated) compared to the CO group while 21 metabolites exhibited differential regulation (16 upregulated and 5 downregulated) in EC plasma samples compared to the HP group. Hyperplasia samples exhibited similar metabolic changes to those reported in cancer, except for alterations in triglyceride levels, 7a,12 b-dihydroxy-5b-Cholan-24-oic acid, and Hept-2-enedioyl carnitine levels. The metabolites N-heptanoyl glycine and -(Methylthio)-2,3-isopentyl phosphate and formimino glutamic acid can be specific markers for hyperplasia conditions and dimethyl phosphatidyl ethanolamine and 8-isoprostaglandin E2 can be specific markers for EC conditions. Metabolic activities rely on mitochondrial oxidative phosphorylation for energy generation. The changes in metabolites identified in our study indicate that endometrial cancer cells adopt alternative strategies to increase energy production to meet the energy demand, thereby supporting proliferation.

We have recently illustrated that nebivolol can inhibit angiotensin II (Ang II)-mediated signaling in cardiomyoblasts; however, to date, the detailed mechanism for the beneficial effects of nebivolol has not been studied. Here, we investigated whether the inhibition of NO bioavailability by blocking eNOS (endothelial nitric oxide synthase) using L-NG-nitroarginine methyl ester (L-NAME) would attenuate nebivolol-mediated favorable effects on Ang II-evoked signaling in H9c2 cardiomyoblasts. Our data reveal that the nebivolol-mediated antagonistic effects on Ang II-induced oxidative stress were retreated by concurrent pretreatment with L-NAME and nebivolol. Similarly, the expressions of pro-inflammatory markers TNF-α and iNOS stimulated by Ang II were not decreased with the combination of nebivolol plus L-NAME. In contrast, the nebivolol-induced reduction in the Ang II-triggered mTORC1 pathway and the mRNA levels of hypertrophic markers ANP, BNP, and β-MHC were not reversed with the addition of L-NAME to nebivolol. In compliance with these data, the inhibition of eNOS by L-N⁵-(1-Iminoethyl) ornithine (LNIO) and its upstream regulator AMP-activated kinase (AMPK) with compound C in the presence of nebivolol showed effects similar to those of the L-NAME plus nebivolol combination on Ang II-mediated signaling. Pretreatment with either compound C plus nebivolol or LNIO plus nebivolol showed similar effects to those of the L-NAME plus nebivolol combination on Ang II-mediated signaling. In conclusion, our data indicate that the rise in NO bioavailability caused by nebivolol via the stimulation of AMPK/eNOS signaling is key for its anti-inflammatory and antioxidant properties but not for its antihypertrophic response upon Ang II stimulation.

Simple Summary: This study aimed to identify proteins associated with chronic rhinosinusitis with nasal polyps (CRSwNP) using label-free quantitative proteomic analysis. Samples of nasal lavage fluid from CRSwNP patients and controls were analyzed and revealed a significant difference in protein expression: a total of 234 proteins, 151 up- and 83 down-regulated in the CRSwNP group. Dysregulated proteins were linked to airway inflammation, immune response, and oxidative stress. Several proteins, including EMILIN-3, RAB11-binding protein RELCH, Macrophage migration inhibitory factor, and deoxyribonuclease-1, were identified as potential biomarkers for CRSwNP. The findings suggest that these proteins play a crucial role in the pathogenesis of the disease and may be valuable for future research and clinical applications. (1) Background: Chronic rhinosinusitis (CRS) is a common chronic inflammation of the nasal mucosa and the paranasal sinuses. The pathogenesis of chronic rhinosinusitis (CRS) is multifactorial and, as of yet, not well understood. (2) Methods: Nasal lavage fluid samples were collected from patients diagnosed with chronic sinusitis with nasal polyposis (CRSwNP) (n = 10) and individuals without sinusitis (control group) (n = 10) who had no nasal complaints. In the present study, we used an untargeted label-free LC-MS/MS mass spectrometric approach combined with bioinformatics and network pathway analysis to compare the changes in the proteomic profiles of the CRSwNP group and the control group. Data from LC-MS/MS underwent univariate and multivariate analyses. (3) Results: The proteomic analyses revealed distinct differences in the abundances of nasal lavage fluid proteins between the CRSwNP and control groups: a total of 234 proteins, 151 up- and 83 down-regulated in CRSwNP. Functional Gene Ontology (GO) analysis showed that dysregulated proteins were involved in airway inflammatory reaction, immune response, and oxidative stress. The biomarkers were evaluated using the Receiver Operating Characteristic (ROC) curve; an Area Under the Curve (AUC) of 0.999 (95% CI) identified potential biomarkers between the CRSwNP and control group. EMILIN-3 and RAB11-binding protein RELCH were down-regulated, and Macrophage migration inhibitory factor and deoxyribonuclease-1 were up-regulated, in CRSwNP compared to the control group. (4) Conclusions: These differentially expressed proteins identified in CRSwNP are involved in airway inflammatory reaction, immune response, and oxidative stress. In particular, the identification of increased interleukin-36 gamma (IL-36γ), which contributes to inflammatory response, and a decrease in SOD, in this group are notable findings. In the future, several of these proteins may prove useful for exploring the pathogenesis of nasal polyps and chronic sinusitis or as objective biomarkers for quantitatively monitoring disease progression or response to therapy. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is one of the most common problems encountered in outpatient general medicine and gastroenterology clinics. GERD may present with classic esophageal symptoms, extraesophageal symptoms, or mixed symptoms. The diagnosis and treatment of GERD are challenging due to the variety of symptoms and multifactorial pathophysiology. Since there is no consensus on the diagnosis and treatment of GERD in Saudi Arabia, the Saudi Gastroenterology Association established an expert group to formulate a consensus on the clinical care pathway for the diagnosis and treatment of GERD to update health-care providers in Saudi Arabia. The expert group reviewed the literature including recently published international guidelines, clinical trials, and expert opinion and conducted virtual and in-person meetings. A total of 22 statements on the definition, diagnosis, and treatment of GERD were formulated, and three algorithms for the clinical care of GERD were developed with a detailed description for each step. The expert group endorsed the new definition of GERD, the practical principles of interpretation of the diagnostic GERD evaluation, and the practical guidance for GERD treatment including medical, surgical, and endoscopic therapy. The expert group recommends further studies to investigate local data on the diagnosis and treatment of GERD. [ABSTRACT FROM AUTHOR]

Spelling is an essential literacy skill and an important language component that can have a significant effect on L2 students' future education and occupational status. However, many students struggle to master this skill, and most L2 teachers are limited to traditional approaches when teaching spelling. Therefore, this study aims to investigate both the effect of using visualisation strategies to improve the L2 students' spelling skills and student's attitudes towards the use of those strategies. I adopted an experimental approach, whereby the experimental group was trained to use visualisation strategies to study the spelling of new words, while the control group received no special tuition and was required to study the spelling of new words using the methods they normally use. The sample for the study consisted of 42 female sixth graders from Al-Manahej Private Elementary School in Riyadh; they were divided into two groups: 21 students in the experimental group and 21 students in the control group. In order to collect data and achieve the goal of the study, three tools were used: pre-achievement and post-achievement tests to measure the differences between the experimental and control groups' scores. The students undertook five weekly tests to measure the effectiveness of the visualisation strategies to improve their spelling skills, and a social validity questionnaire to assess their attitudes towards the strategies. The findings were anticipated to promote the use of visualisation strategies in the field of education, to encourage curriculum designers, decision makers, and language teachers to employ them when teaching spelling.