Deciphering the role of MicroRNAs in diabetic nephropathy: Regulatory mechanisms and molecular insights.

A serious consequence of diabetes mellitus, diabetic nephropathy (DN) which causes gradual damage to the kidneys. Dietary changes, blood pressure control, glucose control, and hyperlipidemia are all important components of DN management. New research, however, points to microRNAs (miRNAs) as having a pivotal role in DN pathogenesis. Miniature non-coding RNA molecules such as miRNAs control gene expression and impact several biological processes. The canonical and non-canonical routes of miRNA biogenesis are discussed in this article. In addition, several important signaling pathways are examined in the study of miRNA regulation in DN. A deeper knowledge of these regulatory mechanisms would allow for a better understanding of the molecular basis of DN and the development of innovative therapeutic strategies. Finally, miRNAs show tremendous potential as DN diagnostic biomarkers and treatment targets, opening up promising avenues for further study and potential clinical use.

Photobiomodulation versus corticosteroid in the management of erosive oral lichen planus: a randomized controlled clinical trial.

BACKGROUND: Oral lichen planus (OLP) is a chronic illness of immune origin that is typically treated with corticosteroids as a gold standard therapy. Photobiomodulation (PBM) may represent an alternative remedy that has the potential to treat a variety of pathological conditions by alleviating pain, reducing inflammation, and promoting tissue healing without the drawbacks of steroid therapies. Thus, the aim of the current study was to compare the effect of photobiomodulation to topical 0.1% triamcinolone acetonide on erosive oral lichen planus. METHODS: This randomized controlled clinical trial involved 44 patients complaining of erosive oral lichen planus. Patients were assigned to one of two groups: control group (n = 22) received 0.1% topical triamcinolone acetonide three times daily with miconazole oral gel once daily for 4 weeks, and photobiomodulation group (n = 22) received laser therapy by 980 nm diode laser utilizing output power 300 mW twice weekly for 5 weeks (a total of 10 sessions). The evaluation of patients was performed at baseline, 6 weeks, and 12 weeks postoperatively in terms of pain, clinical scores, and biochemical evaluation of salivary malondialdehyde levels. All recorded data were analyzed using Mann-Whitney test to compare the two studied groups regarding pain, lesion size, and salivary levels of malondialdehyde. Friedman test, followed by post hoc test, was used for comparison of the data within the same group along the 3 periods at baseline, 6 weeks, and 12 weeks. RESULTS: Both groups showed significant improvement in pain and clinical scores, with no statistical difference between them. Moreover, there was a significant improvement in salivary malondialdehyde levels for both groups, with no significant difference between them. CONCLUSIONS: Photobiomodulation could be a promising therapeutic modality for management of erosive oral lichen planus without the side effects of steroid therapy. The salivary malondialdehyde level could be used as a biomarker to evaluate the disease severity and its response to the treatment. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov (NCT05951361) (19/07/2023).

Assessment of anosmia/hyposmia in post-COVID-19 patients: a cross-sectional study in an eastern province of Saudi Arabia.

Background and aim It has been shown that olfactory dysfunction is one of Coronavirus disease-2019 (COVID-19)common and puzzling symptoms that may persist weeks after the infection. This study aimed for the objective assessment of persisting olfactory dysfunction in post-COVID-19 patients. It also investigated the factors associated with the development of such symptoms in the Eastern Province of Saudi Arabia. METHODS: A cross-sectional study that was conducted in the Department of Physiology, College of Medicine, Imam Abdulrahman bin Faisal University, Khobar, Saudi Arabia. One hundred and forty-seven participants were included in this study, and sixty of them agreed  to participate in the objective testing using the Connecticut Chemosensory Clinical Research Center (CCCRC) olfaction test. RESULTS: There was a significant correlation between the following factors: (1) Persistence of anosmia/hyposmia and the time of onset of anosmia/hyposmia (P=0.015). (2) Persistence of anosmia/hyposmia and the duration of anosmia/hyposmia (P=0.012). (3) Duration of anosmia/hyposmia and the duration of COVID-19 symptoms (P=0.010). Interestingly, there was a significant association between the subjective participants' claim of anosmia/hyposmia and the score of their objective assessment (P=0.026). CONCLUSION: The current study demonstrated that post-COVID-19 participants with delayed onset of anosmia/hyposmia and/or longer duration of either anosmia/hyposmia or COVID-19 symptoms were prone to have persistent olfactory dysfunction. Further studies are necessary to uncover the underlying pathophysiology and management of this olfactory dysfunction in COVID-19 patients.

Effect of Prebiotic Dietary Supplement Acacia senegal on Hormonal and Metabolic Markers in Polycystic Ovary Syndrome Patients: A Pilot Study.

Background The most prevalent endocrine condition affecting women of reproductive age is polycystic ovarian syndrome (PCOS), which is linked to a variety of metabolic abnormalities. Although the pathogenesis of PCOS is not fully understood, it is known that oxidative stress, altered gut microbiome, and increased gonadotrophin-releasing hormone play a significant role. Gum arabic (GA) is an edible, dried, gummy exudate from the Acacia senegal tree, well-known for its prebiotic and antioxidant effects. The main objective of the study was to assess the changes in hormonal and metabolic profiles in PCOS patients after the ingestion of gum arabic. Method This was a clinical trial conducted on fifteen patients suffering from PCOS, with a mean age of 27.8 years (20-39 years). All patients experienced irregular cycles. Hormonal and metabolic markers (follicular stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), fasting insulin, total cholesterol (TC), and glycosylated hemoglobin (HBA1c) were measured before and after the ingestion of gum arabic (30 g/day of GA dissolved in 250 ml water for eight weeks) on the second day of the menstrual cycle after granting ethical approval from the National Medicine and Poisons Board and from the participants of the study. Results The study demonstrated a significant decrease in the luteinizing hormone level, FSH/LH ratio, and cholesterol pre- and post-gum arabic ingestion (p-values 0.001, 0.013, and 0.007, respectively). Follicular stimulating hormone slightly reduced post-ingestion with no significant difference (p-value 0.414). No significant changes were seen in the testosterone, insulin, or HBA1c levels. Conclusion The study concluded that gum arabic ingestion for eight weeks decreases the luteinizing hormone and LH/FSH ratio and improves the metabolic profile by reducing the cholesterol level in PCOS patients.

Uro-protective role of chrysin against cyclophosphamide-induced hemorrhagic cystitis in rats involving the turning-off NF-κB/P38-MAPK, NO/PARP-1 and STAT-3 signaling cascades.

BACKGROUND: Chemotherapeutic agents are used to treat a wide range of cancer types, but they cause serious side effects which must be managed after treatment. Cyclophosphamide (CYP) is one of chemotherapeutic drugs that causes hemorrhagic cystitis (HC) induced by acrolein. OBJECTIVE: The current investigation intended to uncover the role of chrysin (CHR) in CYP-induced HC in rats and explore the signaling pathway beyond this effect. ANALYSIS: process: A single dose of CYP (200 mg/kg/IP) was injected, meanwhile CHR (25, 50 and 100 mg/kg, P.O) was administered respectively for 7 days prior to CYP administration and resume for 7 days afterwards. Urinary bladder tissue was then isolated from all rats to assess oxidative stress and inflammatory biomarkers. Moreover, histopathological examinations were performed. RESULTS: Treatment with CHR showed a marked alleviation in oxidative stress biomarkers induced by CYP. Furthermore, CHR treatment presented a dose-dependent boost in the anti-inflammatory; IL-10 levels and a drop in the pro-inflammatory biomarkers; IL-1ß, IL-6, and TNF-α. Additionally, stabilization of the PARP-1 protein expression was also detected thus preventing DNA damage. Similarly, CHR restored the urinary bladder cGMP levels. Notably, CHR treatment was accompanied with inhibition in NF-κB/p38-MAPK, NO/PARP-1 and STAT-3 signaling pathways inflammatory cascades. All these findings conformed with the histopathological examinations as well as iNOS immunostaining in the urinary bladder tissue. CONCLUSION: Co-administration of CHR and CYP attained uro-protective therapeutic potential to guard against HC as well as spot the tangled mechanism of CHR in attenuating the HC induced by CYP.

Comparable detection of nasopharyngeal swabs and induced sputum specimens for viral nucleic acid detection of suspected novel coronavirus (SARS-Cov-2) patients in Fayoum governorate, Egypt.

Background: The most commonly utilized samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) are nasopharyngeal swabs (NPS) and oropharyngeal swabs. However, there are some drawbacks. For SARS-CoV-2 detection, induced sputum might be analyzed and may be equivalent to pharyngeal swabs. This study was done to assess the potential superiority of induced sputum over NPS for SARS-CoV-2 detection. Sixty symptomatic COVID-19 patients who attended Fayoum University Hospitals in Fayoum Governorate, Egypt, were included in this cross-sectional descriptive study. Paired NPS and induced sputum samples were collected from each subject on the third and tenth days after symptoms began for RT-qPCR SARS-COV2 diagnosis. Results: At day 3, 52 (86.7%) of NPS and 48 (80.00%) of induced sputum specimens had positive RT-qPCR results with a significant statistical difference (P = 0.001). At day 10, 41 induced sputum samples (68.3%) were negative, while 19 (31.7%) were positive. Only three (5.0%) of the 19 positive induced sputum samples tested positive for NPS. NPS samples had a higher viral load than induced sputum samples at day 3 [25 (41.7%) vs. 23 (38.3%)]. At day 10, induced sputum samples had a higher viral load than NPS [9 (15.0%) vs. 6 (10.0%)]. A statistically significant positive correlation between the viral load value of the NPS and the induced sputum sample at day 3 (r = 0.497, p = 0.00) denoting similarity in the results of the two types of samples. By ROC analysis, the highest area under the curve for the overall CT value of the induced sputum was (0.604), with a statistically significant difference (p value = 0.0418). Conclusion: In the early stages of the disease, induced sputum and NPS tests had comparable results, but NPS yielded more false negative results later in the disease course than an induced sputum sample, which yielded higher sample positivity and viral load than NPS. Furthermore, induced sputum collection is a straightforward, non-invasive, and risk-free method. As a result, induced sputum could be useful for COVID-19 confirmation in patients with radiologically or epidemiologically suspected COVID-19 who have a negative NPS or in difficult-to-diagnose COVID-19 patients.

Morin post-treatment surpassed calpeptin in ameliorating 3-NP-induced cortical neurotoxicity via modulation of glutamate/calpain axis, Kidins220, and BDNF/TrkB/AKT/CREB trajectory.

The neuroprotective capacity of morin hydrate (MH), a potent antioxidant flavonoid, and calpeptin (CP), a calpain inhibitor, was documented against different insults but not Huntington's disease (HD). Accordingly, we aim to assess the neuroprotective potential of MH and/or CP in a 3-nitropropionic acid (3-NP)-induced HD model. The 3-NP-treated rats were post-treated with saline, MH, CP, or MH + CP for a week. Post-treatment with MH and/or CP amended motor function (beam walking test) and short-/ long-term spatial memory (novel object recognition test) and improved cortical microscopic architecture. On the molecular level, MH, and to a lesser extent CP, inhibited the cortical content/expression of glutamate, calpain, and Kidins220 and abated the inflammatory molecules, nuclear factor (NF)-κB, tumor necrosis factor-α, and interleukin-1ß, as well as lipid peroxidation. However, MH, but barely CP, activated the molecules of the neuroprotective trajectory; viz., brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (TrkB), protein kinase B (AKT), and cAMP response element-binding protein (CREB). Compared to the single treatments, the combination regimen mediated further reductions in the cortical contents of glutamate, calpain, and Kidins220, effects that extended to entail the anti-inflammatory/anti-oxidant potentials of MH and to a greater extent CP. However, the combination of MH strengthened the fair effect of CP on the survival signaling pathway BDNF/TrkB/AKT/CREB. In conclusion, MH, CP, and especially their combination, afforded neuroprotection against HD through curbing the glutamate/calpain axis, Kidins220, as well as NF-κB-mediated neuroinflammation/oxidative stress, besides activating the BDNF/TrkB/AKT/CREB hub that was partly dependent on calpain inhibition.

A breakthrough effect of gene replacement therapy on respiratory outcomes in children with spinal muscular atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) is an inherited progressive neuromuscular disorder characterized by generalized hypotonia, respiratory failure and early death. The introduction of gene replacement therapy (GRT) modified the natural history of the disease. However, more data is needed to understand the long-term effect of GRT on measurable respiratory outcomes. We report the respiratory outcomes in our cohort of patients with SMA post-GRT in 2-year period. METHODS: A retrospective chart-review of genetically confirmed children with SMA who received GRT between 2019 and 2021 in Qatar. The evaluated respiratory outcomes were chronic respiratory support, respiratory hospitalizations, escalation of respiratory support and polysomnography results before and after GRT. Nonrespiratory outcomes; nutritional status, swallowing, and motor functions; were also assessed. RESULTS: A total of 11 patients (9 patients with SMA-1 and 2 patients with SMA-2) received GRT at a median age of 12 months and 22 months in patients with SMA-1 and SMA-2, respectively. All patients were successfully weaned off Noninvasive ventilation (NIV) except one patient who remained on mechanical ventilation through tracheostomy tube. The annualized hospitalization rate dropped by half after GRT. The average length of stay (LOS) in intensive care unit (ICU) decreased by 17.32 days/patient/year after GRT. Duration of required escalation of respiratory support during acute hospitalizations has dropped by 18.56 days/patient/year post-GRT. CONCLUSION: We report favorable respiratory outcomes of GRT in our cohort. GRT resulted in discontinuation of chronic respiratory support in majority of ventilated patients. GRT also resulted in decreased respiratory hospitalization rate, hospital-LOS, ICU-LOS, and need for escalation of ventilatory support.

Antitumor and Protective Activity of TVLE against CdCl2-Induced Renal Damage in Rats.

<b>Background and Objective:</b> Cadmium is a heavy metal that has a wide range of applications in human existence. Cadmium may bind to the protein metallothionein and decrease kidney function once it enters the body. The purpose of this study was to investigate the renal protective activity of TVLE against CdCl₂-induced renal toxicity in rats. <b>Materials and Methods:</b> TVLE was prepared and characterized using instrumental analysis and spectral data. Furthermore, the IC₅₀ of TVLE against the Vero renal carcinoma cell line was calculated. Adult albino rats were used to assess the renal protective activity of TVLE (150 and 300 mg kg¹ b.wt.) in CdCl₂-treated rats. <b>Results:</b> IC₅₀of TVLE against Vero cell line equals 148.25 µg mL¹. The daily oral administration of TVLE at concentrations of 150 and 300 mg kg¹ b.wt. for 21 days to CdCl₂-treated rates resulted in a significant improvement in tumour volume and tumour weight, urea, creatinine, uric acid, TNF-α, NOx, TBARs, GSH, CAT, SOD, GPx and VEGF-C gene expression in CdCl₂-treated rats. Furthermore, TVLE almost normalized these effects in renal histoarchitecture. <b>Conclusion:</b> The biochemical, histological and MRI examinations of the current study suggested that TVLE have renal protective activity against CdCl₂-induced renal toxicity in rats.

Parents attitudes toward the human papilloma virus (HPV) vaccine: A new concept in the State of Qatar.

BACKGROUND: Human papillomavirus (HPV) is one of the leading causes of cervical and genital cancer in both genders. PURPOSE: To delineate parental attitude regarding HPV in Qatar. METHODS: A cross-sectional study using a questionnaire was conducted at Sidra Medicine, Qatar. RESULTS: A total of 334 questioners were completed. More than 60% of the parents were not aware that HPV can cause cervical and genital cancer. When asked about the level of comfort in giving their children a vaccine that would prevent them from getting genital cancer, 77% of the participants answered "very comfortable." Interestingly, less than 4% of the parents stated that their children's primary care physicians ever mentioned that such a vaccine exists. When asked about the most preferable mode of receiving information regarding the HPV vaccine, 54% preferred the clinician's office, followed by 34% of whom preferred social media. In terms of the preferred age to receive the vaccine, 45% of the participants preferred to administer the vaccine to their children before they were mature enough to understand sexual relations, while 22% recommended vaccination right before marriage and 15% preferred to wait till they were grown up and decide for themselves. Furthermore, only 42% of the caregivers agreed that it is important to explain to their children that the vaccine can protect against some of the sexually transmitted infections. Finally, approximately 20% of the participants were not convinced about the HPV vaccine. CONCLUSION: A large proportion of parents residing in Qatar have a positive perception regarding the HPV vaccine. TheParents' attitudes and perceptions are considered indispensable targets for community health intervention. We will share the result of our study with the ministry of public health in Qatar with a goal to incorporate the HPV vaccine in the National Immunization Schedule.

Optimization of nanovesicular carriers of a poorly soluble drug using factorial design methodology and artificial neural network by applying quality by design approach.

The current work aims to utilize a quality by design (QbD) approach to develop and optimize nanovesicular carriers of a hydrophobic drug. Rosuvastatin calcium was used as a model drug, which suffers poor bioavailability. Several tools were used in the risk assessment study as Ishikawa diagrams. The critical process parameters (CPP) were found to be the particle size, polydispersity index, zeta potential, and entrapment efficiency. A factorial design was used in risk analysis, which was complemented with an artificial neural network (ANN); to assure its accuracy. A design space was established, with an optimized nanostructured lipid carrier formula containing 3.2% total lipid content, 0.139% surfactant, and 0.1197 mg % drug. The optimized formula showed a sustained drug release up to 72 h. It successfully lowered each of the total cholesterol, low-density lipoprotein, and triglycerides and elevated the high-density lipoprotein levels, as compared to the standard drug. Thus, the concurrent use of the factorial design with ANN using the QbD approach permitted the exploration of the experimental regions for a successful nanovesicular carrier formulation and could be used as a reference for many nanostructured drug delivery studies during their pharmaceutical development and product manufacturing.

Students' and Faculty Perspectives Toward the Role and Value of the Hidden Curriculum in Undergraduate Medical Education: a Qualitative Study from Saudi Arabia.

A hidden medical curriculum is defined as the unwritten, unofficial, and unintended learning that students experience in medical school along with more formal aspects of education. This term describes the behaviours, attitudes, assumptions and beliefs conveyed by teachers, peers and the surrounding environment. However, more research is needed to evaluate its impact on student and faculty interactions in this context. We conducted this qualitative study utilizing focus group and semi-structured interviews of students and faculty to evaluate the perspectives of medical students and faculty toward the role and impact of the hidden medical curriculum in medical education at Alfaisal University, Riyadh, Saudi Arabia. Data was analysed using open-, axial- and selective-coding using thematic framework analysis. Interviewees consisted of 24 students in years 1-3 during the spring semester 2018-2019, 8 faculty members and 4 teaching assistants. We identified six core themes of hidden curriculum at Alfaisal University (Appendix). Role and behavioural modelling, value-based teaching, interpersonal faculty-student interactions, effects of diversity and socialization, teaching methodologies and hidden curriculum, mentoring and student support systems. Although some of the themes identified in these focus group interviews were similar to previously published studies, the novel themes that we identified were diversity, socialization and interpersonal faculty-student interactions. We conclude that identifying the issues pertaining to hidden curriculum is important for the development of medical students and for nurturing and upholding the values that we want to instil in our future physicians.

Palonosetron/Methyllycaconitine Deactivate Hippocampal Microglia 1, Inflammasome Assembly and Pyroptosis to Enhance Cognition in a Novel Model of Neuroinflammation.

Since westernized diet-induced insulin resistance is a risk factor in Alzheimer's disease (AD) development, and lipopolysaccharide (LPS) coexists with amyloid ß (Aß)1-42 in these patients, our AD novel model was developed to resemble sporadic AD by injecting LPS into high fat/fructose diet (HFFD)-fed rats. The neuroprotective potential of palonosetron and/or methyllycaconitine, 5-HT3 receptor and α7 nAChR blockers, respectively, was evaluated after 8 days of daily administration in HFFD/LPS rats. All regimens improved histopathological findings and enhanced spatial memory (Morris Water Maze); however, palonosetron alone or with methyllycaconitine promoted animal performance during novel object recognition tests. In the hippocampus, all regimens reduced the expression of glial fibrillary acidic protein and skewed microglia M1 to M2 phenotype, indicated by the decreased M1 markers and the enhanced M2 related parameters. Additionally, palonosetron and its combination regimen downregulated the expression of ASC/TMS1, as well as levels of inflammasome downstream molecules and abated cleaved caspase-1, interleukin (IL)-1ß, IL-18 and caspase-11. Furthermore, ACh and 5-HT were augmented after being hampered by the insult. Our study speculates that blocking 5-HT3 receptor using palonosetron overrides methyllycaconitine to combat AD-induced neuroinflammation and inflammasome cascade, as well as to restore microglial function in a HFFD/LPS novel model for sporadic AD.

Gene therapy for spinal muscular atrophy: the Qatari experience.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by hypotonia, progressive muscle weakness, and wasting. Onasemnogene abeparvovec (Zolgensma®) is a novel gene therapy medicine, FDA-approved in May 2019 for the treatment of SMA. This study aimed to describe Qatari experience with onasemnogene abeparvovec by reviewing the clinical outcomes of 9 SMA children (7 SMA type 1 and 2 with SMA type 2) aged 4‒23 months treated between November 2019 and July 2020. Children <2 years with 5q SMA with a bi-allelic mutation in the SMN1 gene were eligible for gene therapy. Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin), platelet count, coagulation profile, troponin-I levels, and motor scores (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]), were regularly monitored following gene therapy. All patients experienced elevated AST or ALT, two experienced high prothrombin time, and one experienced elevated bilirubin; all of these patients were asymptomatic. Furthermore, one event of vomiting after infusion was reported in one patient. Significant improvements in CHOP INTEND scores were observed following therapy. This study describes the short-term outcomes and safety of onasemnogene abeparvovec, which is well tolerated and shows promise for early efficacy.

Pharmaceutical and Pharmacological Evaluation of the Effect of Nano-Formulated Spironolactone and Progesterone on Inflammation and Hormonal Levels for Managing Hirsutism Experimentally Induced in Rats.

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.

Clinical and genomic characteristics of LAMA2 related congenital muscular dystrophy in a patients' cohort from Qatar. A population specific founder variant.

Congenital LAMA2 related muscular dystrophy (LAMA2-RD), the most commonly recognized type of congenital muscular dystrophies, has been described in patients' cohorts from Europe and the UK but not from Middle-Eastern. This study aimed to reveal the prevalence, clinical and genomic characteristics of congenital LAMA2-RD in a patient's cohort of 17 families (21 patients) from the Gulf and Middle East. Affected subjects exhibited the classic phenotype of generalized hypotonia, developmental delay, and progressive muscular weakness. Despite the homogeneous background of most of our patients, clinical variability was evident; however, none of our patients was able to achieve independent ambulation. The associated features of nephrocalcinosis, infantile-onset osteopenia, and cardiac arrest were first described in this study. LAMA2 mutations constituted 48% of the genetic causes underlying congenital muscular dystrophies (CMDs) in our patients. We estimated a point prevalence of 0.8 in 100.000 for LAMA2-RD in Qatar, relatively higher compared to that described in Europe's studies. The founder mutation and high rate of consanguinity are potential contributors. This study identified five LAMA2 truncating variants, two novel and three recurrent, of which the c.6488delA-frameshift that was found in 12 unrelated Qatari families, highlighting a founder mutation in Qatari patients. The two novel variants involved an acceptor splice site and N-terminus deletion that removes the LAMA2 promoter, exon1, and part of intron1. The "residual" expression of LAMA2 transcript and protein associated with this large N-terminus deletion suggested an alternative promoter that, while seems to be activated, acts less efficiently.

Barriers, Facilitators, and Potential Solutions to Advancing Interoperable Clinical Decision Support: Multi-Stakeholder Consensus Recommendations for the Opioid Use Case.

With the advent of interoperability standards such as FHIR, SMART, CDS Hooks, and CQL, interoperable clinical decision support (CDS) holds great promise for improving healthcare. In 2018, the Agency for Healthcare Research and Quality (AHRQ)-sponsored Patient-Centered CDS Learning Network (PCCDS LN) chartered a Technical Framework Working Group (TechFWG) to identify barriers, facilitators, and potential solutions for interoperable CDS, with a specific focus on addressing the opioid epidemic. Through an open, multi-stakeholder process that engaged 54 representatives from healthcare, industry, and academia, the TechFWG identified barriers in 6 categories: regulatory environment, data integration, scalability, business case, effective and useful CDS, and care planning and coordination. Facilitators and key recommendations were also identified for overcoming these barriers. The key insights were also extrapolated to CDS-facilitated care improvement outside of the specific opioid use case. If applied broadly, the recommendations should help advance the availability and impact of interoperable CDS delivered at scale.

Tropisetron modulates peripheral and central serotonin/insulin levels via insulin and nuclear factor kappa B/receptor for advanced glycation end products signalling to regulate type-2 diabetes in rats.

Despite its known central effect, 5% of serotonin is found centrally, while around 95% is found peripherally. Serotonin is stored and co-released with insulin upon pancreatic islets stimulation by glucose. This fact raises the curiosity regarding its possible role in diabetes. Hence, in this study, we assessed the possible modulatory effects of tropisetron, a 5-HT3 receptor antagonist, on type 2 diabetes mellitus models in rats. The rats were allocated into two groups: normal and diabetic. The latter group was treated with metformin (500 mg kg-1, p.o.), tropisetron (1 and 2 mg kg-1, i.p.), and a combination of metformin and tropisetron (1 mg kg-1). The different treatment regimens corrected glucose and lipid homeostasis manifested by the decrease in serum levels of glucose, fructosamine, homeostasis model of insulin resistance, triglycerides, total cholesterol, free fatty acid, as well as receptor for advanced glycation end products. Additionally, the treatments elevated levels of insulin, serotonin, and homeostasis model of ß-cell function. On the molecular level, treatments corrected the altered insulin signaling cascade (phosphorylated insulin receptor substrate 1, phosphorylated protein kinase B, and glucose transporter 4), and inhibited ß-catenin and phosphorylated nuclear factor kappa B p65 in the assessed soleus skeletal muscle. A similar pattern was duplicated in the hippocampus. This study provided evidence for the role of tropisetron on type 2 diabetes mellitus via modulating the insulin signaling cascade (insulin, phosphorylated insulin receptor substrate 1, phosphorylated protein kinase B, and glucose transporter 4), improving lipid/glucose profile, decreasing inflammatory markers (receptor for advanced glycation end products, and phosphorylated nuclear factor kappa B p65), as well as increasing 5-HT and reducing ß-catenin.

Impact of serology and molecular methods on improving the microbiologic diagnosis of infective endocarditis in Egypt.

BACKGROUND: Conventional diagnosis of infective endocarditis (IE) is based mainly on culture-dependent methods that may fail because of antibiotic therapy or fastidious microorganisms. OBJECTIVES: We aimed to evaluate the added values of serological and molecular methods for diagnosis of infective endocarditis. PATIENTS AND METHODS: One hundred and fifty-six cases of suspected endocarditis were enrolled in the study. For each patient, three sets of blood culture were withdrawn and serum sample was collected for Brucella, Bartonella and Coxiella burnetii antibody testing. Galactomannan antigen was added if fungal endocarditis was suspected. Broad range PCR targeting bacterial and fungal pathogens were done on blood culture bottles followed by sequencing. Culture and molecular studies were done on excised valve tissue when available. RESULTS: One hundred and thirty-two cases were diagnosed as definite IE. Causative organisms were detected by blood cultures in 40 (30.3 %) of cases. Blood culture-negative endocarditis (BCNE) represented 69.7 %. Of these cases, PCR followed by sequencing on blood and valvular tissue could diagnose five cases of Aspergillus flavus. Eleven patients with BCNE (8.3 %) were diagnosed as zoonotic endocarditis by serology and PCR including five cases of Brucella spp, four cases of Bartonella spp and two cases of Coxiella burnetii. PCR detected three cases of Brucella spp and two cases of Bartonella spp, while cases of Coxiella burnetii were PCR negative. The results of all diagnostic tools decreased the percentage of non-identified cases of BCNE from 69.7 to 49.2 %. CONCLUSION: Our data underline the role of serologic and molecular tools for the diagnosis of blood culture-negative endocarditis.

Pattern of glomerular diseases in Sudanese children: a clinico-pathological study.

Glomerular diseases are a common cause of chronic kidney disease (CKD) in many countries. The pattern of glomerular diseases has been reported in adult Sudanese patients but there has been no previous study on Sudanese children. The aim of this study is to describe the pattern of glomerular diseases in Sudanese children from a clinico-pathological perspective. We retrospectively reviewed the clinical records of 321 children seen with nephritis/nephrosis at the Pediatric Nephrology Unit, Soba University Hospital and Dr. Salma Dialysis and Kidney Transplantation Centre, Khartoum, Sudan during the period from 2002 to 2007. Biopsies were studied with light microscopy and immuno-histochemistry with electron microscopy performed abroad in selected patients (predominantly Alport's). The mean age of the 321 study children was 8.71 years (range 2 months-16 yrs) of whom, 188 were males (60.2%). The most common presentation was with the nephrotic syndrome, seen in 202 patients (62.9%). The most common glomerular disease encountered was minimal change disease, seen in 96 children (29.9%), followed by post-infectious GN in 78 (24.3%) and focal and segmental glomerulosclerosis, seen in 44 patients (13.7%). Membranoproliferative GN (MPGN) was seen in 43 patients (13.4%) while mesangioproliferative GN was seen in 24 (7.5%). Systemic lupus erythematosus (SLE) was the most common secondary glomerular disease accounting for 16 patients (4.9%). HBsAg was positive in 10 patients and the most common associated lesion was MPGN (60%). Histopathology enabled us to change the therapy in 55.3% of the patients. Our study suggests that the pattern of GN in our cohort of patients is comparable with reports from other parts of the world with a high prevalence of post-infectious GN. Renal biopsies have an important part in planning therapy and management. Also, the importance of establishing a Sudanese renal registry including pediatric patients is stressed.