Assessment of Albumin Usage Patterns and Appropriateness in a Comprehensive Cancer Centre: A retrospective study in Jordan.

Objectives: Albumin is commonly used for various indications; however, there is conflicting data regarding its appropriate use in different clinical cases. This study aimed to determine the pattern and appropriateness of albumin use among cancer patients at the King Hussein Cancer Center in Jordan. Methods: A retrospective analysis was conducted on adult cancer patients who were prescribed albumin between January 2019 and July 2020 in both outpatient and inpatient settings. Data collected included demographics, prescribing services, indications and dosing regimens. A literature review was performed using PubMed to assess the appropriateness of albumin indications and dosing regimens against current guidelines, drug information resources and the package insert. Results: Albumin was prescribed to 1,361 patients during the study period. Each patient received an average of 74.4 ± 89 g of albumin for an average of 2.6 ± 1.8 days. Albumin use was deemed appropriate in 69% of the patients. The critical care service accounted for the highest albumin consumption, with 37% of prescriptions for septic shock. Inappropriate use of albumin was most prevalent in the medical solid tumour services (40.8% of prescriptions), primarily for edema (28%). Conclusion: To the best of the author's knowledge, this study is the first to evaluate albumin use in a large cohort of oncology patients. Approximately one-third of the albumin prescriptions were considered inappropriate. Continuous education on appropriate usage and regular evaluations of guideline adherence are essential to ensure proper utilisation of albumin in cancer care.

Evaluating the effectiveness of nicotine replacement therapy in critically ill smokers: A meta-analysis of randomized controlled trials.

INTRODUCTION: The effectiveness of nicotine replacement therapy (NRT) in critically ill patients remains uncertain, as conflicting research results have been reported. Despite potential side effects and inconsistent data on safety and efficacy, NRT is still prescribed in intensive care units (ICUs) to prevent withdrawal symptoms and manage agitation in patients who are smokers. This meta-analysis aimed to assess the effectiveness of nicotine replacement therapy in critically ill smoking patients. METHODS: A systematic review and meta-analysis of randomized controlled trials investigated the outcomes of smokers admitted to ICUs and were randomized either to receive or not receive nicotine replacement therapy (NRT) during their ICU stay. The MEDLINE and Embase databases were searched from inception through 13 February 2023 using OVID. The primary outcome was ICU length of stay (LOS) for this systematic review and meta-analysis. Meta-analysis was conducted using both random-effects and fixed-effect models; the latter is recommended when meta-analysis is restricted to just a few studies. The study was registered in the Prospective International Register of Systematic Reviews (PROSPERO) under reference number CRD42023407804. RESULTS: Of 28 studies initially identified, three, with 67 patients on NRT and 72 controls, were deemed eligible for pooled analysis. Patients who received NRT experienced a shorter LOS (mean difference, MD= -3.06; 95% CI: -5.88 - -0.25, p=0.0, I2=0%). The mechanical ventilation (MV) duration was also shorter in the NRT group, but this difference was not statistically significant (MD= -1.24; 95% CI: -3.21-0.72, p=0.22, I2=12.69%). Delirium duration was reported by two studies, from which pooled analysis revealed an MD of -0.50 (95% CI: -1.63-0.62, I2=0%). The vasopressor duration was assessed in two studies, and the overall MD for vasopressor duration was not statistically different between NRT patients and controls in the fixed-effects model (MD=0.11; 95% CI: -0.75-0.96, I2=0%). CONCLUSIONS: Critically ill smoker patients who received NRT experienced a significantly shorter ICU LOS but no significant differences in the durations of MV, vasopressor use, or delirium.

An activatable NIR turn-on fluorescent probe for copper (II) ion and live cell imaging.

Herein we have reported a fluorescent probe (MB-M) based on MB derivative for Cu2+ ions detection. The probe was well characterized by 1H NMR, 13C NMR and HR-MS spectrum. Probe MB-M showed naked-eyes recognition to Cu2+ as color change from colorless to indigo. The probe exhibited promising features such as high fluorescence and UV-vis selectivity, fast response (5 mint), workable at pH 2-7, and low limit of detection (LOD = 0.33 µM). Probe MB-M was also used for Cu2+ ions imaging in HepG-2 cells and detection in daily life (Test Strip and lake water). Moreover, non-covalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analysis were used to study the interaction between MB-M and Cu2+ ions. By examining the electronic characteristics of the complex using natural bond orbital (NBO), electron density difference (EDD), and frontier molecular orbital (FMO) analysis, the sensitivity of MB-M towards Cu2+ ions were investigated. The results illustrated that the interactions between MB-M and Cu2+ ions involved chemisorption.

Evaluation of colour change, marginal adaptation, fracture strength, and failure type in maxillary and mandibular premolar zirconia endo-crowns.

OBJECTIVES: The objective of this in vitro study was to evaluate the effects of different preparation designs on the mean colour change (ΔE*), marginal adaptation, fracture resistance, and fracture types of maxillary and mandibular premolar endocrowns (ECs). METHODOLOGY: A total of 40 extracted maxillary and mandibular premolars were treated endodontically, and each type was subdivided according to the remaining axial height (remaining walls on all surfaces; 2-4 mm) and 2 mm inside the pulp chamber. Specimens were immersed in coffee for 14 days, ΔE* was determined, marginal adaptation was observed, fracture forces test was conducted, and the samples were examined visually at 10× magnification to evaluate failure type and identify fracture origin. The data were entered and analyzed using Statistical Package for Social Sciences, and significance between and within groups was evaluated through ANOVA. The p-value ≤ 0.05 was considered statistically significant. RESULTS: The ΔE* values of the maxillary premolar with 2 mm axial height were the highest (6.8 ± 0.89 units), whereas the lowest value was observed in the mandibular premolar with 4 mm axial height (2.9 ± 0.53 units). Significant differences (p < 0.05) in teeth and design were observed. The marginal adaptation of the mandibular premolar with 4 mm axial height was the highest (30.20 ± 1.53 µm), whereas the lowest marginal adaptation was observed in the maxillary premolar with 2 mm axial height (14.38 ± 0.99 µm), and the difference was statistically significant (p < 0.05). The maximum fracture force was observed in maxillary premolars with 2 mm axial height (2248.15 ± 134.74 N), and no statistically significant difference (p = 0.07) was observed between maxillary and mandibular premolars at 4 mm axial height. CONCLUSION: The recorded ΔE* values of the ECs were within clinically acceptable values or slightly higher, and the marginal adaption values were within acceptable and recommended clinical values in µm. EC preparation with 2 mm axial height in both arches recorded the highest fracture forces. Type III (split fracture) failure was recorded as the highest in the maxillary and mandibular premolar ECs with different axial wall heights.

Enhanced delivery of CRISPR/Cas9 system based on biomimetic nanoparticles for hepatitis B virus therapy.

The persistent presence of covalently closed circular DNA (cccDNA) in hepatocyte nuclei poses a significant obstacle to achieving a comprehensive cure for hepatitis B virus (HBV). Current applications of CRISPR/Cas9 for targeting and eliminating cccDNA have been confined to in vitro studies due to challenges in stable cccDNA expression in animal models and the limited non-immunogenicity of delivery systems. This study addresses these limitations by introducing a novel non-viral gene delivery system utilizing Gemini Surfactant (GS). The developed system creates stable and targeted CRISPR/Cas9 nanodrugs with a negatively charged surface through modification with red blood cell membranes (RBCM) or hepatocyte membranes (HCM), resulting in GS-pDNA@Cas9-CMs complexes. These GS-pDNA complexes demonstrated complete formation at a 4:1 w/w ratio. The in vitro transfection efficiency of GS-pDNA-HCM reached 54.61%, showing homotypic targeting and excellent safety. Additionally, the study identified the most effective single-guide RNA (sgRNA) from six sequences delivered by GS-pDNA@Cas9-HCM. Using GS-pDNA@Cas9-HCM, a significant reduction of 96.47% in in vitro HBV cccDNA and a 52.34% reduction in in vivo HBV cccDNA were observed, along with a notable decrease in other HBV-related markers. The investigation of GS complex uptake by AML-12 cells under varied time and temperature conditions revealed clathrin-mediated endocytosis (CME) for GS-pDNA and caveolin-mediated endocytosis (CVME) for GS-pDNA-HCM and GS-pDNA-RBCM. In summary, this research presents biomimetic gene-editing nanovectors based on GS (GS-pDNA@Cas9-CMs) and explores their precise and targeted clearance of cccDNA using CRISPR/Cas9, demonstrating good biocompatibility both in vitro and in vivo. This innovative approach provides a promising therapeutic strategy for advancing the cure of HBV.

Ultraviolet-enhanced detoxification of chromate and protection of Brassica napus by Aspergillus sojae SH 20.

The pervasive issue of heavy metal contamination in agricultural lands poses significant concerns and has wide-ranging implications for ecosystems. However, an encouraging solution lies in exploiting the potential of fungal endophytes to alleviate these detrimental effects. This study emphasized on improving the growth-promoting and chromium-alleviating capabilities of fungal endophytes, particularly Aspergillus sojae strain SH20, through ultraviolet (UV) irradiation. Following UV treatment, SH20 exhibited significantly enhanced growth-promoting and chromium-alleviating capabilities in comparison to its non-irradiated counterpart. Distinctly, the UV-treated SH20 strain demonstrated an improved ability to accumulate and reduce toxic chromate in the soil, effectively addressing the growth constraints imposed by elevated chromium levels in Brassica napus L. The UV-irradiated SH20 variant boosted shoot length up to 3 times that of the control. Similarly, this fungal strain displayed a remarkable increase in the total fresh weight of the seedlings, recording nearly 17 times greater than the control. The isolate treated with UV light reduced the absorption of chromium by about 3 times in the roots, helping the young plants to grow well even when exposed to chromate stress. A drop in root colonization by the UV-treated strain further resulted in reduced chromate absorption by the roots. Also, the strain showed great skill in boosting the host's antioxidant defenses by reducing the buildup of harmful reactive oxygen species (ROS), increasing the removal of ROS, and improving the plant's antioxidant levels, including phenols and flavonoids. When the host plants were exposed to 25 ppm of Cr stress, the UV-irradiated variant SH 20 stimulated the production of flavonoids (246 µg/ml) and phenols (952 µg/ml) in comparison to the control (with 220 µg/ml of flavonoids and 919 µg/ml of phenols). In conclusion, this report highlights how exposing the A. sojae strain SH20 to UV light has the potential to enhance its abilities to promote growth and bioremediate. This suggests a promising solution for addressing heavy metal contamination in agricultural lands.

Evaluating diabetic foot care knowledge and practices at education level.

Diabetic foot is one of the complications in type 2 diabetes mellitus. Adequate knowledge and practice are an important aspect to control further deteriorating conditions such as ulcers and amputations. Thus, the objective of this cross-sectional study was to investigate the impact of the education levels of diabetic patients on diabetic foot care knowledge and practice. This cross-sectional study with a convenient sampling technique was conducted on 534 patients with diabetes mellitus from public and private care hospitals. The data was collected using a validated, pretested and structured bilingual (Arabic, English) questionnaire. There were 534 patients interviewed, 39.1% of whom were males and 60.9% of whom were females and 61.4% of the patients had had T2DM for over 10 years. There was a significant difference in education levels between the male and female patients (53.8% and 46.2%, P = .001). Furthermore, 83.9% patients were married. The difference in education between the married and the single, divorced, and widowed patients was significant (P = .007). Patients with uncontrolled HbA1c were 2.43 times more likely to have hypertension (RR = 2.43, P = .03), while patients with highly uncontrolled diabetes had 3.1 times more chances of hypertension (RR = 3.1, P = .009). Heart disease prevalence was 3.27 times higher in diabetes patients with uncontrolled HbA1c and 3.37 times higher in patients with highly uncontrolled HbA1c. Patients with diabetes who have been diabetic for more than 10 years have a greater risk of heart disease (RR = 2.1; P = .03). Patients with lower education levels exhibited more diabetic complications compared to patients with higher education levels (P < .05). The present study highlights the importance of education and awareness campaigns targeting diabetic patients, especially those with lower education levels, to improve diabetes control and prevent, or manage, comorbidities. Healthcare providers should also prioritize patient education and medication adherence to improve diabetes management and reduce the risk of complications.

Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat.

Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100 µg/kg/day) for 5 days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated (p < 0.05) mRNA and protein of AT1R within the PVN and lowered (p < 0.05) circulating angiotensin II in rats. RUPP increased neural and microglial activation. Cellular localization assessment revealed that AT1R was primarily expressed in neurons and slightly in microglia and astrocytes. Infusion of 100 ng/kg as bolus increased the mean arterial pressure (MAP in mmHg) in both RUPP and Sham. ICV losartan infusion attenuated RUPP-increased MAP (113.6 ± 6.22 in RUPP vs. 92.16 ± 5.30 in RUPP + Los, p = 0.021) and the expression of nuclear transcription factor NF-κB, tyrosine hydroxylase (TH), NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) in the PVN. Our data suggest that centrally expressed AT1R, within the PVN, contributes to placental ischemia-induced hypertension in RUPP rats highlighting its therapeutic potential in PE.

Incorporating Technology Adoption in Medical Education: A Qualitative Study of Medical Students' Perspectives.

Introduction: The integration of technology into medical education has witnessed significant growth in recent years, with tools such as virtual reality, artificial intelligence, and telemedicine gaining prominence. These tool in medical education, offering immersive, experiential learning experiences. Methods: We approached medical students currently enrolled in medical education programs and who are familiar with and actively use AI in medical education. Initially, we invited 21 random students to participate in the study; however, only 13 agreed to interviews. Some students cited their busy exam schedules as the reason for not participating. The participants were informed of the objective of the study before the commencement of the recorded interviews. Semi-structured interviews were used to guide the record interviews. Audio recordings were transcribed and analyzed using Atlas.ti, a qualitative data analysis software. Results: Participants exhibited a diverse range of perceptions and levels of awareness regarding VR, AI, and telemedicine technologies. Learning with virtual reality was considered to be fun, memorable, inclusive, and engaging by participants. The use of virtual reality technology is seen as complementing current teaching and learning approaches, helping to build learners' confidence, as well as providing medical students with a safe environment for problem-solving and trial-and-error learning. The students reported that AI was seen as a potential game-changer in the healthcare sector. Participants hoped that telemedicine would provide healthcare services to remote and underserved populations. Conclusion: The study conducted focus group discussions with medical students and residents in Saudi Arabia to explore their views on integrating VR, AI, and telemedicine in medical education and practice. Their insights highlight the need for informed decision-making and strategic development to optimize the benefits and address challenges like initial investments, technical issues, ethics, and regulations. These considerations are crucial for fully realizing the potential benefits of technology in medical education globally.

Modified ILM flap techniques versus classical inverted ILM flap technique for large macular holes: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Macular holes (MHs) constitute a vitreoretinal interface disorder that occurs when structural abnormalities in the fovea lead to impaired central vision. The standard treatment for MHs is mainly surgical. Using an inverted internal limiting membrane (ILM) flap has enhanced the success rates of MH surgeries. This systematic review and meta-analysis aimed to compare the classical inverted ILM flap technique to modified ILM flap techniques for managing large MHs. METHODS: We searched Medline, Embase, and CENTRAL. We included randomized controlled trials (RCTs) that compared the classic inverted ILM flap technique to modified ILM flap techniques as initial surgical treatment of eyes with large MHs of more than 400 microns. We sought to evaluate the following outcomes: (1) MH closure. (2) Best-corrected visual acuity (BCVA). (3) Foveal closure type (4) Rate of ellipsoid zone (EZ) defects and external limiting membrane (ELM) defects. The standardized mean difference (SMD) was used to represent continuous outcomes, while the risk ratio (RR) was used to represent dichotomous outcomes. RESULTS: Four RCTs that enrolled 220 participants were deemed eligible. The analysis revealed no statistically significant differences in MH closure between both groups (95% CI: 0.20, 7.96; P = 0.81). No statistically significant differences in mean BCVA were found at 1 and 3 months between both groups (SMD: 0.04; 95% CI: -0.16, 0.23; P = 0.70 and SMD: -0.167; 95%CI: -1.240, 0.906; P = 0.760, respectively). In addition, there were no significant differences between the two groups in the pattern of foveal closure, namely U-shape, V-shape, and flap open at 3, 6, and 12 months (RR: 0.87; 95% CI: 0.67, 1.12; P = 0.28, RR: 0.96; 95% CI: 0.58, 1.61; P = 0.89, and RR: 1.95, 95% CI: 0.26, 14.50; P = 0.51, respectively). Finally, the analysis showed no statistically significant difference in both groups' EZ and ELM defect rates at 3, 6, and 12 months (RR: 1; 95% CI: 0.85; 1.18: P = 1 and RR: 1.14; 95% CI: 0.90, 1.45; P = 0.27). CONCLUSION: Macular holes (MHs) constitute a vitreoretinal interface disorder that occurs when structural abnormalities in the fovea lead to impaired central vision. The standard treatment for MHs is mainly surgical. Using an inverted internal limiting membrane (ILM) flap has enhanced the success rates of MH surgeries. This systematic review and meta-analysis aimed to compare the classical inverted ILM flap technique to modified ILM flap techniques for managing large MHs.

Mesenchymal stem cells and their potential therapeutic benefits and challenges in the treatment and pathogenesis of gastric cancer.

Mesenchymal stem/stromal cells (MSCs) are acknowledged for their remarkable ability to undergo differentiation into various cell types. In addition, they exhibit anti-tumor characteristics, prompting endeavors to modify MSCs for employment in cancer therapies. On the contrary, it is imperative to recognize that MSCs have been extensively linked to pathways that facilitate the advancement of tumors. Numerous research studies have sought to modify MSCs for clinical application; however, the outcomes have been ambiguous, potentially due to the heterogeneity of MSC populations. Furthermore, the conflicting roles of MSCs in suppressing and promoting tumor growth present a challenge to the appropriateness of their use in anti-cancer therapies. Currently, there exists a lack of comprehensive comprehension concerning the anti-tumor and pro-tumor characteristics of MSCs for gastric cancer (GC). This article discusses the influence of MSCs on GC, the underlying mechanisms, the origins of MSCs, and their effects. This review article also elucidates how MSCs exhibit dual characteristics of promoting and inhibiting tumor growth. Hence, it is of utmost importance that clinical inquiries aimed at utilizing MSCs as a therapeutic intervention for cancer consider the potentiality of MSCs to accelerate the progression of GC. It is crucial to exercise caution throughout the process of developing MSC-based cellular therapies to enhance their anti-cancer attributes while simultaneously eliminating their tumor-promoting impacts.

Improving sunflower growth and arsenic bioremediation in polluted environments: Insights from ecotoxicology and sustainable mitigation approaches.

The issue of arsenic (As) contamination in the environment has become a critical concern, impacting both human health and ecological equilibrium. Addressing this challenge requires a comprehensive strategy encompassing water treatment technologies, regulatory measures for industrial effluents, and the implementation of sustainable agricultural practices. In this study, diverse strategies were explored to enhance As accumulation in the presence of Acinetobacter bouvetii while safeguarding the host from the toxic effects of arsenate exposure. The sunflower seedlings associated with A. bouvetii demonstrated a favorable relative growth rate (RGR) and net assimilation rate (NAR) even less than 100 ppm of As stress. Remarkably, the NAR and RGR of A. bouvetii-associated seedlings outperformed those of control seedlings cultivated without A. bouvetii in As-free conditions. Additionally, a markedly greater buildup of bio-transformed As was observed in A. bouvetii-associated seedlings (P = 0.05). An intriguing observation was the normal levels of reactive oxygen species (ROS) in A. bouvetii-associated seedlings, along with elevated activities of key enzymatic antioxidants like catalases (CAT), ascorbate peroxidase (APX), superoxide dismutase (SOD), and peroxidases (POD), along with non-enzymatic antioxidants (phenols and flavonoids). This coordinated antioxidant defense system likely contributed to the improved survival and growth of the host plant species amidst As stress. A. bouvetii not only augmented the growth of the host plants but also facilitated the uptake of bio-transformed As in the contaminated medium. The rhizobacterium's modulation of various biochemical and physiological parameters indicates its role in ensuring the better survival and progression of the host plants under As stress.

The role of mesenchymal stem cells in the treatment and pathogenesis of psoriasis.

Psoriasis, a prevalent inflammatory skin condition impacting millions globally, continues to pose treatment challenges, despite the availability of multiple therapies. This underscores the demand for innovative treatments. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their capacity to modulate the immune system and facilitate tissue healing. Recent research indicates that MSCs don't just work through direct cell-to-cell interactions but also release extracellular vesicles (EVs), containing various bioactive substances like proteins, lipids, and nucleic acids. This article explores our current knowledge of psoriasis's origins and the potential utilization of MSCs and their EVs, particularly exosomes, in managing the condition. Additionally, we delve into how MSCs and EVs function in therapy, including their roles in regulating immune responses and promoting tissue repair. Lastly, we discuss the obstacles and opportunities associated with translating MSC-based treatments for psoriasis into clinical practice.

Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly.

Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles in cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, and synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the NAV3 gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues. In mouse brain, Nav3 is expressed throughout the nervous system, with more prominent signatures in postmitotic, excitatory, inhibiting, and sensory neurons. When overexpressed in HEK293T and COS7 cells, pathogenic variants impaired NAV3 ability to stabilize microtubules. Further, knocking-down nav3 in zebrafish led to severe morphological defects, microcephaly, impaired neuronal growth, and behavioral impairment, which were rescued with co-injection of WT NAV3 mRNA and not by transcripts encoding the pathogenic variants. Our findings establish the role of NAV3 in neurodevelopmental disorders, and reveal its involvement in neuronal morphogenesis, and neuromuscular responses.

The role of miR-765 in human cancers.

MicroRNAs, a collection of short noncoding RNAs, are promising biomarkers for identifying cancer in its early stages and tracking the effectiveness of treatment. This is due to their critical role in regulating gene expression and other vital biological functions via cell-level epigenetic mechanisms. This review brings together data on the molecular and clinical effects of miR-765 on different types of cancer. Significant variation in miR-765 levels has been observed in a variety of cancer types, suggesting that it could have an oncogene or tumor suppressor role. A number of pathways, including PLP2/Notch, VEGFA/Akt1, PDX1, KLK4, RUNX2, DPF3, EMP3, APE1, ERK/EMT axis, and others, are impacted by the inclusion of miR-765 in their analysis. MiR-765 is an essential biomarker that shows promise as a diagnostic tool for various types of cancer. The latest research has identified them as reliable predictive markers for detecting tumor development at an early stage. Based on our study, miR-765 shows promising potential as a biomarker for prognosis in multiple types of cancer. Specifically, we suggest that miR-765 could be an early detection marker for tumor development, progression, and metastasis.

Genome-wide association study and polygenic score assessment of insulin resistance.

Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly conducted in European populations, while Middle Eastern populations remain largely underrepresented. We conducted a GWAS on the indices of IR (HOMA2-IR) and beta cell function (HOMA2-%B) in 6,217 non-diabetic individuals from the Qatar Biobank (QBB; Discovery cohort; n = 2170, Replication cohort; n = 4047) with and without body mass index (BMI) adjustment. We also developed polygenic scores (PGS) for HOMA2-IR and compared their performance with a previously derived PGS for HOMA-IR (PGS003470). We replicated 11 loci that have been previously associated with HOMA-IR and 24 loci that have been associated with HOMA-%B, at nominal statistical significance. We also identified a novel locus associated with beta cell function near VEGFC gene, tagged by rs61552983 (P = 4.38 × 10-8). Moreover, our best performing PGS (Q-PGS4; Adj R2 = 0.233 ± 0.014; P = 1.55 x 10-3) performed better than PGS003470 (Adj R2 = 0.194 ± 0.014; P = 5.45 x 10-2) in predicting HOMA2-IR in our dataset. This is the first GWAS on HOMA2 and the first GWAS conducted in the Middle East focusing on IR and beta cell function. Herein, we report a novel locus in VEGFC that is implicated in beta cell dysfunction. Inclusion of under-represented populations in GWAS has potentials to provide important insights into the genetic architecture of IR and beta cell function.

Application of mesenchymal stem cells derived from the umbilical cord or Wharton's jelly and their extracellular vesicles in the treatment of various diseases.

Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.