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.

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.

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.

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.

Interleukin-6 serves as a critical factor in various cancer progression and therapy.

Interleukin-6 (IL-6), a pro-inflammatory cytokine, plays a crucial role in host immune defense and acute stress responses. Moreover, it modulates various cellular processes, including proliferation, apoptosis, angiogenesis, and differentiation. These effects are facilitated by various signaling pathways, particularly the signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). However, excessive IL-6 production and dysregulated signaling are associated with various cancers, promoting tumorigenesis by influencing all cancer hallmarks, such as apoptosis, survival, proliferation, angiogenesis, invasiveness, metastasis, and notably, metabolism. Emerging evidence indicates that selective inhibition of the IL-6 signaling pathway yields therapeutic benefits across diverse malignancies, such as multiple myeloma, prostate, colorectal, renal, ovarian, and lung cancers. Targeting key components of IL-6 signaling, such as IL-6Rs, gp130, STAT3, and JAK via monoclonal antibodies (mAbs) or small molecules, is a heavily researched approach in preclinical cancer studies. The purpose of this study is to offer an overview of the role of IL-6 and its signaling pathway in various cancer types. Furthermore, we discussed current preclinical and clinical studies focusing on targeting IL-6 signaling as a therapeutic strategy for various types of cancer.

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.

Genetic Association Between Polycystic Ovary Syndrome and the APOA5 rs662799 and PLIN1 rs894160 Metabolic Variants in the Western Saudi Population: A Case-Control Study.

Background: Polycystic ovary syndrome (PCOS) is a common endocrinological condition affecting women of reproductive age, associated with insulin resistance and obesity. PCOS pathogenesis is complex and multifactorial, involving genetic and environmental factors. Objectives: This study aimed to determine and compare genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (APOA5; rs662799) and perilipin 1 (PLIN1; rs894160, rs1052700 and rs6496589) genes in Western Saudi women to investigate their association with PCOS and its clinical characteristics. Design and methods: This was a case-control study conducted on women with (n = 104) and without (n = 87) PCOS. The SNPs were genotyped using TaqMan genotyping assays. Results: Significant and direct associations were detected between PCOS susceptibility and APOA5 SNP rs662799 and PLIN1 SNP rs894160 (P < .001). For APOA5 SNP rs662799, women with the A allele were more likely to have PCOS (relative risk [RR] = 1.348, odds ratio [OR] = 2.313, P < .001) and hypertriglyceridaemia (OR = 17.0, P = .5) than women with the G allele. For PLIN1 SNP rs894160, women with the T allele were more likely to have PCOS than women with the C allele (RR = 8.043, OR = 7.427, P < .001). For PLIN1 SNP rs1052700, women with the TT genotype were more likely to have hyperandrogenism (OR = 29.75, P = .02) and an irregular period (OR = 0.07, P = .040) than women with the AT genotype. Conclusion: We identified novel alleles and genotypes contributing to the genetic risk of PCOS in the Western Saudi population.

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.

Evaluation of Apixaban standard dosing in underweight patients with non-valvular atrial fibrillation: a retrospective cohort study.

BACKGROUND: Recent guidelines recommend using direct oral anticoagulants (DOACs) as first-line agents in patients with non-valvular atrial fibrillation (NVAF). Research is currently investigating the use of Apixaban in underweight patients, with some results suggesting altered pharmacokinetics, decreased drug absorption, and potential overdosing in this population. This study examined the effectiveness and safety of standard Apixaban dosing in adult patients with atrial NVAF weighing less than 50 kg. METHODS: This is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC); adult patients with a body mass index (BMI) below 25 who received a standard dose of Apixaban (5 mg twice daily) were categorized into two sub-cohorts based on their weight at the time of Apixaban initiation. Underweight was defined as patients weighing ≤ 50 kg, while the control group (Normal weight) comprised patients weighing > 50 kg. We followed the patients for at least one year after Apixaban initiation. The study's primary outcome was the incidence of stroke events, while secondary outcomes included bleeding (major or minor), thrombosis, and venous thromboembolism (VTE). Propensity score (PS) matching with a 1:1 ratio was used based on predefined criteria and regression model was utilized as appropriate. RESULTS: A total of 1,433 patients were screened; of those, 277 were included according to the eligibility criteria. The incidence of stroke events was lower in the underweight than in the normal weight group at crude analysis (0% vs. 9.1%) p-value = 0.06), as well in regression analysis (OR (95%CI): 0.08 (0.001, 0.76), p-value = 0.002). On the other hand, there were no statistically significant differences between the two groups in the odds of major and minor bleeding (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40, respectively). CONCLUSION: This exploratory study revealed that underweight patients with NVAF who received standard doses of Apixaban had fewer stroke events compared to normal-weight patients, without statistically significant differences in bleeding events. To confirm these findings, further randomized controlled trials with larger sample sizes and longer observation durations are required.

Azolla filiculoides extract improved salt tolerance in wheat (Triticum aestivum L.) is associated with prompting osmostasis, antioxidant potential and stress-interrelated genes.

The growth and productivity of crop plants are negatively affected by salinity-induced ionic and oxidative stresses. This study aimed to provide insight into the interaction of NaCl-induced salinity with Azolla aqueous extract (AAE) regarding growth, antioxidant balance, and stress-responsive genes expression in wheat seedlings. In a pot experiment, wheat kernels were primed for 21 h with either deionized water or 0.1% AAE. Water-primed seedlings received either tap water, 250 mM NaCl, AAE spray, or AAE spray + NaCl. The AAE-primed seedlings received either tap water or 250 mM NaCl. Salinity lowered growth rate, chlorophyll level, and protein and amino acids pool. However, carotenoids, stress indicators (EL, MDA, and H2O2), osmomodulators (sugars, and proline), antioxidant enzymes (CAT, POD, APX, and PPO), and the expression of some stress-responsive genes (POD, PPO and PAL, PCS, and TLP) were significantly increased. However, administering AAE contributed to increased growth, balanced leaf pigments and assimilation efficacy, diminished stress indicators, rebalanced osmomodulators and antioxidant enzymes, and down-regulation of stress-induced genes in NaCl-stressed plants, with priming surpassing spray in most cases. In conclusion, AAE can be used as a green approach for sustaining regular growth and metabolism and remodelling the physio-chemical status of wheat seedlings thriving in salt-affected soils.

Endoscopic management of intraprocedural bleeding during endoscopic interventions.

Endoscopic resection techniques have evolved over time, allowing effective and safe resection of the majority of pre-malignant and early cancerous lesions in the gastrointestinal tract. Bleeding is one of the most commonly encountered complications during endoscopic resection, which can interfere with the procedure and result in serious adverse events. Intraprocedural bleeding is relatively common during endoscopic resection and, in most cases, is a mild and self-limiting event. However, it can interfere with the completion of the resection and may result in negative patient-related outcomes in severe cases, including the need for hospitalization and blood transfusion as well as the requirement for radiological or surgical interventions. Appropriate management of intraprocedural bleeding can improve the safety and efficacy of endoscopic resection, and it can be readily achieved with the use of several endoscopic hemostatic tools. In this review, we discuss the recent advances in the approach to intraprocedural bleeding complicating endoscopic resection, with a focus on the various endoscopic hemostatic tools available to manage such events safely and effectively.

Elicitation of salicylic acid and methyl jasmonate provides molecular and physiological evidence for potato susceptibility to infection by Erwinia carotovora subsp. carotovora.

Among the range of severe plant diseases, bacterial soft rot caused by Erwinia carotovora is a significant threat to crops. This study aimed to examine the varying response patterns of distinct potato cultivars to the influence of E. carotovora. Furthermore, it seeks to highlight the potential role of salicylic acid (SA) and methyl jasmonate (MeJA) in stimulating the antioxidant defence system. We collected eight bacterial isolates from diseased and rotted tubers which were morphologically and physiologically identified as E. carotovora subsp. carotovora. We conducted a greenhouse experiment to analyse the antioxidant responses of three different potato cultivars (Diamont, Kara, and Karros) at various time intervals (2, 4, 6, 8, 12, and 24 h) after bacterial infection (hpi). We assessed the extent of disease damage by applying a foliar spray of 0.9 mM salicylic acid (SA) and 70 µM methyl jasmonate (MeJA). Inoculating with Ecc led to an increase in total phenolic levels, as well as the activities and gene expression of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POX) as time progressed. Additionally, the application of SA and MeJA resulted in a further increase relative to the diseased treatments. The Karros cultivar, unlike the Diamont and Kara cultivars, demonstrated the highest expression levels of PAL, PPO and POX through inoculation, reflecting its higher levels of activity and resistance. Furthermore, the genetic response of potato cultivars to infection at 0 hpi varied depending on their susceptibility. The examination of the rate of PAL activity upregulation following SA or MeJA stimulation clarifies the cultivars' susceptibility over time. In conclusion, the study identified E. carotovora subsp. carotovora as the most virulent isolate causing soft rot disease in potato tubers. It further revealed that the Karros cultivar displayed superior resistance with high activities and gene expression of PAL, PPO and POX, while the cv. Diamont exhibited sensitivity. Additionally, foliar exposure to SA and MeJA induced antioxidant responses, enhancing the potato plants' resistance against Ecc pathogenesis and overall plant defence.

A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred.

Intellectual disability (ID), which affects around 2% to 3% of the population, accounts for 0.63% of the overall prevalence of neurodevelopmental disorders (NDD). ID is characterized by limitations in a person's intellectual and adaptive functioning, and is caused by pathogenic variants in more than 1000 genes. Here, we report a rare missense variant (c.350T>C; p.(Leu117Ser)) in HACE1 segregating with NDD syndrome with clinical features including ID, epilepsy, spasticity, global developmental delay, and psychomotor impairment in two siblings of a consanguineous Pakistani kindred. HACE1 encodes a HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), which is involved in protein ubiquitination, localization, and cell division. HACE1 is also predicted to interact with several proteins that have been previously implicated in the ID phenotype in humans. The p.(Leu117Ser) variant replaces an evolutionarily conserved residue of HACE1 and is predicted to be deleterious by various in silico algorithms. Previously, eleven protein truncating variants of HACE1 have been reported in individuals with NDD. However, to our knowledge, p.(Leu117Ser) is the second missense variant in HACE1 found in an individual with NDD.

Cross-cultural adaptation and validation of the Arabic version of the Multiple Sclerosis Impact Scale-29.

PURPOSE: The Multiple Sclerosis Impact Scale-29 (MSIS-29) is a patient self-reported outcome (PRO) that measures patients' quality of life, and it is divided into two sub-scales for the physical (PHYS) and psychological (PSYCH) domains. This study aimed to translate the MSIS-29 into Arabic, cross-culturally adapt it, and examine its psychometric properties. MATERIALS AND METHODS: One hundred fifty patients with MS completed the MSIS-29-Ar, the Functional Assessment of Multiple Sclerosis (FAMS), and the Short-Form Health Survey (SF-36). After one week, 60 participants were asked to complete the MSIS-29-Ar again to examine test-retest reliability. RESULTS: The MSIS-29-Ar was clear and understandable among patients with MS in Saudi Arabia. The internal consistency for the MSIS-29-Ar-PHYS was excellent, with a Cronbach's alpha of 0.955, and was good for the MSIS-29-Ar-PSYCH, with a Cronbach's alpha of 0.891. The test-retest reliability for MSIS-29-Ar-PHYS was ICC2,1 = 0.97; 95% confidence interval (0.93, 0.99) and ICC2,1 = 0.95.; 95% confidence interval (0.897, 0.976) for MSIS-29-Ar-PSYCH domains. The minimal detectable change with 95% confidence (MDC95) was 10.28 and 13.37 for the MSIS-29-Ar-PHYS and MSIS-29-Ar-PSYCH, respectively. No floor and ceiling effects were observed. Convergent and divergent validity was supported by 75% of the predefined hypotheses and correlated with the other health-related quality-of-life measures, SF-36 and FAMS. CONCLUSION: The MSIS-29-Ar questionnaire is a valid and reliable outcome measure among Saudi patients with MS.IMPLICATION FOR REHABILITATIONRehabilitation specialists can confidently interpret patient scores in the MSIS-29-Ar to measure physical and psychological factors impacting patients' quality of life with Multiple Sclerosis (MS).Patients with unchanged clinical status will have similar scores in the MSIS-29-Ar with repeated scale administrations over time.The MSIS-29-Ar can be used in clinical practice and research studies to measure factors that impact the quality of life in Arabic-speaking patients with MS.

Genome-wide association study and trans-ethnic meta-analysis identify novel susceptibility loci for type 2 diabetes mellitus.

BACKGROUND: The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar. METHODS: Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment. RESULTS: We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel. CONCLUSION: Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis.