Exploring factors influencing sustainable human capital development: Insights from Saudi Arabia.

This study investigates the critical factors influencing Saudi Arabia's sustainable human capital development. It primarily aims to explore the correlations among the postulated variables and how each variable influences the development of a skilled, adaptable, and socially conscious workforce, in alignment with the objectives of the Saudi Vision 2030. This study utilizes a quantitative approach, employing partial least squares structural equation modeling to analyze the data collected from 203 public personnel in Saudi Arabia through an online questionnaire. The findings reveal that training, community engagement, institutional support, and technology integration are essential in sustainable human capital development. However, learning, education, and access to resources were not statistically significant and did not improve sustainable human capital development in Saudi Arabia. The findings underscore the significance of an educational framework that transcends traditional perspectives, focusing on not only academic preparation but also the holistic development of individuals. This study contributes to understanding how training, community engagement, institutional support, and technology integration are transformative in shaping the future of Saudi Arabia by nurturing a skilled, adaptable, and socially responsible citizenry.

Loop Diuretics: An Overview of Its History and Evolution.

The loop of Henle plays a key role in kidney function, especially in retaining solutes and concentrating urine. Diuretic agents, crucial for managing fluid overload and related conditions like hypertension and heart failure (HF), enhance water and electrolyte excretion. The history of diuretics dates back to 1775 with the discovery of Digitalis, evolving significantly with the introduction of chlorothiazide in 1957, which revolutionized diuretic therapy. Loop diuretics, developed in the 1950s and including drugs like torsemide, furosemide, and ethacrynic acid, are potent agents acting on the loop of Henle. They are vital for treating severe fluid overload conditions and require careful monitoring to manage potential side effects.

Cortisol affects macrophage polarization by inducing miR-143/145 cluster to reprogram glucose metabolism and by promoting TCA cycle anaplerosis.

Chronic stress can have adverse consequences on human health by disrupting the hormonal balance in our body. Earlier, we observed elevated levels of cortisol, a primary stress hormone, and some exosomal microRNAs in the serum of patients with breast cancer. Here, we investigated the role of cortisol in microRNA induction and its functional consequences. We found that cortisol induced the expression of miR-143/145 cluster in human monocyte (THP1 and U937)-derived macrophages but not in breast cancer cells. In silico analysis identified glucocorticoid-response element in the upstream CARMN promoter utilized by the miR-143/145 cluster. Enhanced binding of glucocorticoid-receptor (GR) upon cortisol exposure and its regulatory significance was confirmed by chromatin-immunoprecipitation and promoter-reporter assays. Further, cortisol inhibited IFNγ-induced M1 polarization and promoted M2 polarization, and these effects were suppressed by miR-143-3p and miR-145-5p inhibitors pretreatment. Cortisol-treated macrophages exhibited increased oxygen-consumption rate (OCR) to extracellular-acidification rate (ECAR) ratio, and this change was neutralized by functional inhibition of miR-143-3p and miR-145-5p. HK2 and ADPGK were confirmed as the direct targets of miR-143-3p and miR-145-5p, respectively. Interestingly, silencing of HK2 and ADPGK inhibited IFNγ-induced M1 polarization but failed to induce M2 polarization, since it suppressed both ECAR and OCR, while OCR was largely sustained in cortisol-treated M2-polarized macrophages. We found that cortisol treatment sustained OCR by enhancing fatty acid and glutamine metabolism through upregulation of CPT2 and GLS, respectively, to support M2 polarization. Thus, our findings unfold a novel mechanism of immune suppression by cortisol and open avenues for preventive and therapeutic interventions.

circRNAs as Epigenetic Regulators of Integrity in Blood-Brain Barrier Architecture: Mechanisms and Therapeutic Strategies in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease leading to progressive demyelination and neuronal loss, with extensive neurological symptoms. As one of the most widespread neurodegenerative disorders, with an age onset of about 30 years, it turns out to be a socio-health and economic issue, thus necessitating therapeutic interventions currently unavailable. Loss of integrity in the blood-brain barrier (BBB) is one of the distinct MS hallmarks. Brain homeostasis is ensured by an endothelial cell-based monolayer at the interface between the central nervous system (CNS) and systemic bloodstream, acting as a selective barrier. MS results in enhanced barrier permeability, mainly due to the breakdown of tight (TJs) and adherens junctions (AJs) between endothelial cells. Specifically, proinflammatory mediator release causes failure in cytoplasmic exposure of junctions, resulting in compromised BBB integrity that enables blood cells to cross the barrier, establishing iron deposition and neuronal impairment. Cells with a compromised cytoskeletal protein network, fiber reorganization, and discontinuous junction structure can occur, resulting in BBB dysfunction. Recent investigations on spatial transcriptomics have proven circularRNAs (circRNAs) to be powerful multi-functional molecules able to epigenetically regulate transcription and structurally support proteins. In the present review, we provide an overview of the recent role ascribed to circRNAs in maintaining BBB integrity/permeability via cytoskeletal stability. Increased knowledge of the mechanisms responsible for impairment and circRNA's role in driving BBB damage and dysfunction might be helpful for the recognition of novel therapeutic targets to overcome BBB damage and unrestrained neurodegeneration.

Value addition to dietetic frozen yoghurt through use of fruit peel solids.

The study pertains to preparing value added frozen yoghurt through use of orange peel powder (OPP). The quality aspects of medium-fat (6.0% fat) frozen yoghurt prepared using OPP at three levels (1.5, 2.5, 3.5% as T1, T2 and T3 respectively) was studied. Frozen yoghurt was prepared by freezing blend of fermented yoghurt base with ice cream mix (25:75 w/w); other ingredients were sugar, stabilizer-emulsifier and orange crush. Inclusion of OPP in frozen yoghurt impacted the orange flavour favorably and enriched product with ß-carotene and dietary fiber. The control product (TC) was prepared in similar manner, avoiding OPP. As the level of OPP was raised in formulation, there was a marked increase in the protein, carbohydrate, ash and total solids when compared with TC. Presence of OPP markedly affected the acidity, viscosity, overrun and melting resistance of the product; maximum overrun was associated with TC. Product T3 had the maximum acidity and viscosity; T2 had maximum total sensory score. It is recommended to prepare medium-fat frozen yoghurt utilizing 2.5% OPP along with orange crush as flavouring. Such inclusion of peel solids enriched the product with ß-carotene and dietary fiber, contributed to stabilization of product and enhanced the products sensory acceptance.

Geospatial Analysis of Lumpy Skin Disease Outbreaks among Cattle in Uttar Pradesh, India, 2021-2022.

The emergence of lumpy skin disease (LSD) among cattle in India is concerning. District-level data on LSD cases in Uttar Pradesh between 2021 and 2022 were analyzed. A stepwise spatial analytical approach was followed by first constructing yearly and monthly disease maps for LSD incidence rates (IRs), then spatially interpolating the LSD IRs, followed by evaluating the global and local clustering of LSD IRs and finally conducting spatial regression modeling. Overall, 5784 LSD cases from 6 districts and 112,226 cases from 33 districts were detected in 2021 and 2022, respectively. In the incremental spatial autocorrelation analysis, the highest global clustering of LSD IRs for the 2022 outbreak was detected at 196.49 km. For the 2021 LSD outbreak, one district with high-low and nine districts with low-high LSD IRs were identified in the eastern region of the state. For the 2022 LSD outbreak, 13 districts with high-high and 7 districts with low-high LSD IRs were identified in the western part of the state. A geographically weighted regression model identified the impact of climate (temperature and humidity) and land cover (pasture, fallow, and non-agricultural land) on LSD IRs. The study results can aid animal health authorities in developing LSD prevention and control programs.

Nanoprimers in sustainable seed treatment: Molecular insights into abiotic-biotic stress tolerance mechanisms for enhancing germination and improved crop productivity.

Abiotic and biotic stresses during seed germination are typically managed with conventional agrochemicals, known to harm the environment and reduce crop yields. Seeking sustainable alternatives, nanotechnology-based agrochemicals leverage unique physical and chemical properties to boost seed health and alleviate stress during germination. Nanoprimers in seed priming treatment are advanced nanoscale materials designed to enhance seed germination, growth, and stress tolerance by delivering bioactive compounds and nutrients directly to seeds. Present review aims to explores the revolutionary potential of nanoprimers in sustainable seed treatment, focusing on their ability to enhance crop productivity by improving tolerance to abiotic and biotic stresses. Key objectives include understanding the mechanisms by which nanoprimers confer resistance to stresses such as drought, salinity, pests, and diseases, and assessing their impact on plant physiological and biochemical pathways. Key findings reveal that nanoprimers significantly enhance seedling vigor and stress resilience, leading to improved crop yields. These advancements are attributed to the precise delivery of nanomaterials that optimize plant growth conditions and activate stress tolerance mechanisms. However, the study also highlights the importance of comprehensive toxicity and risk assessments. Current review presents a novel contribution, highlighting both the advantages and potential risks of nanoprimers by offering a comprehensive overview of advancements in seed priming with metal and metal oxide nanomaterials, addressing a significant gap in the existing literature. By delivering advanced molecular insights, the study underscores the transformative potential of nanoprimers in fostering sustainable agricultural practices and responsibly meeting global food demands.

Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.

Objective: Dysregulated glucagon secretion and inadequate functional beta cell mass are hallmark features of diabetes. While glucagon receptor (GCGR) antagonism ameliorates hyperglycemia and elicits beta cell regeneration in pre-clinical models of diabetes, it also promotes alpha and delta cell hyperplasia. We sought to investigate the mechanism by which loss of glucagon action impacts pancreatic islet non-alpha cells, and the relevance of these observations in a human islet context. Methods: We used zebrafish, rodents, and transplanted human islets comprising six different models of interrupted glucagon signaling to examine their impact on delta and beta cell proliferation and mass. We also used models with global deficiency of the cationic amino acid transporter, SLC7A2, and mTORC1 inhibition via rapamycin, to determine whether amino acid-dependent nutrient sensing was required for islet non-alpha cell growth. Results: Inhibition of glucagon signaling stimulated delta cell proliferation in mouse and transplanted human islets, and in mouse islets. This was rapamycin-sensitive and required SLC7A2. Likewise, gcgr deficiency augmented beta cell proliferation via SLC7A2- and mTORC1-dependent mechanisms in zebrafish and promoted cell cycle engagement in rodent beta cells but was insufficient to drive a significant increase in beta cell mass in mice. Conclusion: Our findings demonstrate that interruption of glucagon signaling augments islet non-alpha cell proliferation in zebrafish, rodents, and transplanted human islets in a manner requiring SLC7A2 and mTORC1 activation. An increase in delta cell mass may be leveraged for future beta cell regeneration therapies relying upon delta cell reprogramming.

Suicide and Suicidal Ideation in Medical Students: A Systematic Review.

The incidence of suicide and its ideation among medical students is increasingly recognized as a significant issue, influenced by the demanding nature of medical education and the various associated psychological stressors. This systematic review aims to elucidate the risk factors and prevalence of suicide and suicidal ideation within this group, with a focus on the implications for mental health interventions. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this review analyzed 11 studies selected from major databases such as Scopus-Elsevier, Google Scholar, PubMed, and others, focusing on publications between 2015 and 2023. Studies were predominantly observational and cross-sectional, examining suicide rates and suicidal ideation among medical students. The review found that medical students experience higher rates of suicide and suicidal ideation compared to the general population, with significant stressors including academic pressure, personal relationship challenges, and professional expectations. Notably, female respondents displayed a higher prevalence of suicidal ideation than males. Key warning signs identified include changes in mood or behavior and previous attempts of suicide. Despite varying findings regarding the role of medical training duration on suicidal ideation, all studies highlight the critical need for targeted mental health support. The findings underscore the urgent need for integrated mental health services and the incorporation of mental health education within the medical curriculum. A multidimensional approach involving enhancements to both curricular and support structures is crucial for mitigating the risk of suicide among medical students. Future research should focus on developing and evaluating interventions to reduce educational stress and promote psychological well-being in medical educational settings.

A review on green synthesis, biological applications of carbon dots in the field of drug delivery, biosensors, and bioimaging.

Since the beginning of nanoscience and nanotechnology, carbon dots (CDs) have been the foundational idea and have dominated the growth of the nano-field. CDs are an intriguing platform for utilization in biology, technology, catalysis, and other fields thanks to their numerous distinctive structural, physicochemical, and photochemical characteristics. Since several carbon dots have already been created, they have been assessed based on their synthesis process, and luminescence characteristics. Due to their biocompatibility, less toxic effects, and most significantly their fluorescent features in contrast to other carbon nanostructures, CDs have several benefits. This review focuses on the most recent advancements in the characterization, applications, and synthesis techniques used for CDs made from natural sources. It will also direct scientists in the creation of a synthesis technique for adjustable carbon dots that is more practical, effective, and environmentally benign. With low toxicity and low cost, CDs are meeting the new era's requirements for more selectivity and sensitivity in the detection and sensing of various things, such as biomaterial sensing, enzymes, chemical contamination, and temperature sensing. Its variety of properties, such as optical properties, chemiluminescence, and morphological analysis, make it a good option to use in bioimaging, drug delivery, biosensors, and cancer diagnosis.

Hydrothermal liquefaction for biochar production from finger millet waste: its valorisation, process optimization, and characterization.

In this study, the potential of finger millet waste biomass (FMWB) as a source of biochar production through hydrothermal liquefaction (HTL) was investigated. The HTL process was designed using Box-Behnken design (BBD) and carried out with process variables, i.e., temperature (250 °C, 350 °C, and 450 °C), time (30 min, 45 min, and 60 min), and solid-to-water ratio (1 : 6, 1 : 8, and 1 : 10). The responses, i.e., biochar yield (%), bulk density (g cm-3), pH, and high heating value (HHV), were analysed. Optimisation was done using design expert software (version 13.0.1). The optimized finger millet waste biochar (O-FMWBC) was produced at optimum values (450 °C, 1 : 10, and 33.5 min). The results of proximate and elemental analysis revealed that moisture, ash, and volatile content, H, and O of O-FMWBC decreased while fixed carbon, thermal stability, and C content increased compared to FMWB. FT-IR, SEM-EDX, and XRD analyses were performed for O-FMWBC. The results of FT-IR showed the presence of O-H, C-H, C[double bond, length as m-dash]O, and C[double bond, length as m-dash]C functional groups. The SEM image revealed the rough surface of O-FMWBC, and XRD confirmed the production of a broad range of inorganic compounds and minerals. This study provides the full exploitation of FMWBC as a source of solid fuel.

Deciphering desiccation tolerance in wild eggplant species: insights from chlorophyll fluorescence dynamics.

BACKGROUND: Climate change exacerbates abiotic stresses, which are expected to intensify their impact on crop plants. Drought, the most prevalent abiotic stress, significantly affects agricultural production worldwide. Improving eggplant varieties to withstand abiotic stress is vital due to rising drought from climate change. Despite the diversity of wild eggplant species that thrive under harsh conditions, the understanding of their drought tolerance mechanisms remains limited. In the present study, we used chlorophyll fluorescence (ChlaF) imaging, which reveals a plant's photosynthetic health, to investigate desiccation tolerance in eggplant and its wild relatives. Conventional fluorescence measurements lack spatial heterogeneity, whereas ChlaF imaging offers comprehensive insights into plant responses to environmental stresses. Hence, employing noninvasive imaging techniques is essential for understanding this heterogeneity. RESULTS: Desiccation significantly reduced the leaf tissue moisture content (TMC) across species. ChlaF and TMC displayed greater photosystem II (PSII) efficiency after 54 h of desiccation in S. macrocarpum, S. torvum, and S. indicum, with S. macrocarpum demonstrating superior efficiency due to sustained fluorescence. PSII functions declined gradually in S. macrocarpum and S. torvum, unlike those in other species, which exhibited abrupt declines after 54 h of desiccation. However, after 54 h, PSII efficiency remained above 50% of its initial quantum yield in S. macrocarpum at 35% leaf RWC (relative water content), while S. torvum and S. indicum displayed 50% decreases at 31% and 33% RWC, respectively. Conversely, the susceptible species S. gilo and S. sisymbriifolium exhibited a 50% reduction in PSII function at an early stage of 50% RWC, whereas in S. melongena, this reduction occurred at 40% RWC. CONCLUSION: Overall, our study revealed notably greater leaf desiccation tolerance, especially in S. macrocarpum, S. torvum, and S. indicum, attributed to sustained PSII efficiency at low TMC levels, indicating that these species are promising sources of drought tolerance.

Combinative workflow for mRNA vaccine development.

Recently, mRNA has gained a lot of attention in the field of vaccines, gene therapy, and protein replacement therapies. Herein, we are demonstrating a comprehensive approach to designing, cloning, and characterizing an antigenic cassette for the development of mRNA vaccine for COVID-19. The gene encoding the antigenic spike protein of the SARS-CoV-2 Omicron variant (B.1.1.529) was designed using the databases, characterized by in-silico tools, and assembled using overlapping oligonucleotide-based assembly by PCR. Next, the gene was cloned, mRNA was synthesized, and characterized using orthogonal approaches (Capillary electrophoresis, Sanger DNA sequencing, Next-generation sequencing, HPLC, qPCR, etc.). Furthermore, the antigen expression was monitored in-vitro using an animal cell model by western blot, flow cytometer, and surface plasmon resonance. The demonstrated approach has also been followed for developing the mRNA vaccines for various other indications such as Malaria, Herpes, Dengue, HPV, etc.

Obesity and Early-Onset Breast Cancer and Specific Molecular Subtype Diagnosis in Black and White Women: NIMHD Social Epigenomics Program.

Importance: Epidemiologic data suggest an association of obesity with breast cancer (BC); however, obesity's contribution to early onset and risk of diagnosis with specific molecular subtypes by race is uncertain. Objective: To examine the race-specific association of body mass index with early onset and diagnosis of specific molecular subtypes. Design, Setting, and Participants: This retrospective cohort study included patients with BC diagnosed between October 1, 2017, and March 31, 2022, at 3 University of South Alabama Mitchell Cancer Institute clinics. Participants were also prospectively enrolled for serum leptin measurement. Main Outcomes and Measures: The primary outcome was age at BC onset and specific subtype diagnosis. The secondary outcome was race-specific differences. Odds ratios (ORs) for associations of body mass index with age at onset and subtype were estimated using the Fisher exact test. Race was self-reported. Results: Of the 1085 study patients, 332 (30.6%) were Black with a median age of 58 (IQR, 50-66) years, and 753 (69.4%) were White with a median age of 63 (IQR, 53-71) years. A total of 499 patients (46.0%) had obesity, with Black women with obesity receiving more frequent BC diagnosis than their White counterparts (OR, 2.40; 95% CI, 1.87-3.15; P < .001). In addition, Black women had a significantly higher incidence of early-onset disease (OR, 1.95; 95% CI, 1.33-2.86; P = .001) than White women, and obesity increased this risk significantly in Black women (OR, 2.92; 95% CI, 1.35-6.22; P = .006). Black women with obesity also had a significantly higher risk of luminal A BC (OR, 2.53; 95% CI, 1.81-3.56; P < .001) and triple-negative BC (TNBC) (OR, 2.48; 95% CI, 1.43-4.22; P = .002) diagnosis than White counterparts. Black women, with or without BC, had significantly higher serum leptin levels (median [IQR], 55.3 [40.3-66.2] ng/mL and 29.1 [21.1-46.5] ng/mL, respectively, P < .001) than White women (median [IQR], 33.4 [18.9-47.7] ng/mL and 16.5 [10.0-22.9] ng/mL, respectively), which was associated with higher odds of luminal A disease (OR, 5.25; 95% CI, 1.69-14.32, P = .003). Higher odds of early-onset disease (OR, 3.50; 95% CI, 0.43-23.15; P = .33 for trend), and TNBC diagnosis (OR, 6.00; 95% CI, 0.83-37.27; P = .14 for trend) were also seen, although these outcomes were not statistically significant. Conclusions and Relevance: In this cohort study of patients with BC, obesity and high serum leptin levels were associated with an enhanced risk of early-onset BC and diagnosis of luminal A and TNBC subtypes in Black women. These findings should help in developing strategies to narrow the existing disparity gaps.

Evaluation of Bone Markers in Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) has affected over 387 million patients globally, expected to reach 592 million by the end of 2035. It is a metabolic disorder characterized by chronic hyperglycemia caused by either insulin deficiency, insulin resistance, or both. MATERIALS AND METHODS: The present study was designed to estimate the levels of different bone markers; serum Vitamin D, alkaline phosphatase, phosphorus, and calcium in patients with type 2 DM (T2DM). The study was conducted on patients aged 20-50 years diagnosed with T2DM, who were attending the outpatient/inpatient department of internal medicine. RESULTS: The levels of calcium were decreased in the patients with diabetes and also the study proved a negative correlation between calcium and random plasma glucose (RPG). There was a significant negative correlation between RPG and serum 25(OH)D3. CONCLUSION: We conclude that Vitamin D insufficiency is frequent in Moradabad, Uttar Pradesh. Sunshine exposure daily for 15 min on the face and hands is necessary to elevate the sunlight Vitamin D levels.

Résumé Contexte:Le diabète sucré (DM) a touché plus de 387 millions de patients dans le monde et devrait atteindre 592 millions d'ici la fin de l'année. 2035. Il s'agit d'un trouble métabolique caractérisé par une hyperglycémie chronique provoquée soit par un déficit en insuline, soit par une résistance à l'insuline, ou les deux.Matériels et méthodes:La présente étude a été conçue pour estimer les niveaux de différents marqueurs osseux; sérum Vitamine D, alkaline.Résultats:Les niveaux de calcium ont diminuéles patients diabétiques ainsi que l'étude ont prouvé une corrélation négative entre le calcium et le glucose plasmatique aléatoire (RPG). Il y avaitune corrélation négative significative entre le RPG et le sérum 25(OH)D3 phosphatase, phosphore et calcium chez les patients atteints de diabète de type 2 (DT2). L'étude a été menée sur des patients âgés de 20 à 50 ansdiagnostiqués atteints de DT2, qui fréquentaient le service de médecine interneambulatoire/hospitalisé.Conclusion:Nous concluons que l'insuffisance en vitamine D est fréquente chez Moradabad, Uttar Pradesh. Une exposition quotidienne au soleil pendant 15 minutes sur le visage et les mains est nécessaire pour élever les niveaux de vitamine D du soleil.

Canniprene B, a new prenylated dihydrostilbene with cytotoxic activities from the leaves of Cannabis sativa.

A new, canniprene B (4), along with five known (1-3 and 5-6) dihydrostilbenes were isolated from the leaves of Cannabis sativa collected at CSIR - IIIM, Jammu, India. Structures of all isolated compounds were elucidated by spectroscopic data analysis, including 1D and 2D NMR, and HR-ESI-MS. Canniprene B is a new prenylated dihydrostilbenes, a positional isomer of the known compound canniprene (5). The cytotoxic activities of these compounds (1-6) were evaluated using the SRB assay against a panel of five human cancer cell lines. Notably, canniprene B (4) exhibited varying levels of cytotoxicity with IC50 values ranging from 2.5 to 33.52 µM, demonstrating the most potent activity against pancreatic cancer cells.

Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

Clinical trial designs of emerging therapies for diabetic kidney disease (DKD).

Current evidence for medical therapies for diabetic kidney disease (DKD) is largely based on large-scale clinical trials. These trials, however, often exhibit heterogeneity in participant characteristics and baseline kidney function. These differences may lead to misinterpretation in clinical practice, such that treatment effects from different trials are directly compared and generalized to broader populations beyond the population in which each trial was conducted. This is particularly relevant if comparisons on efficacy and safety are made when the underlying study populations are distinctly different. Indeed, key clinical trials evaluating sodium-glucose transport protein-2 inhibitors (SGLT2i), non-steroidal mineralocorticoid receptor antagonist (nsMRA), and glucagon-like peptide-1 receptor agonist (GLP-1RA) differed in recruitment requirements (inclusion/exclusion criteria), resulting in differences in the severity of the underlying kidney disease as well as risk factor profiles. Moreover, these trials defined their primary and secondary outcomes differently. Collectively, these factors lead to distinct study populations with different baseline risks for DKD progression in the placebo arm in each clinical trial. Consequently, a direct head-to-head comparison of the treatment effect between treatments using relative risk measures from placebo-controlled clinical trials alone is not recommended. In addition, healthcare professionals should be equipped to understand the specific target population of clinical trials to avoid over-generalization when drawing conclusions from these trials.

The medicines approved to help people with compromised kidney function were developed based on clinical trials that differed in many ways. There is a risk that clinical trials may be incorrectly compared and generalized by healthcare providers. In this review, the authors highlight the importance of interpreting clinical trial results cautiously while being mindful of the study population features. Key clinical trials for the treatment of diabetic kidney disease had different recruitment requirements for participants, a wide range of kidney disease severity, and different risks of disease progression in the comparison arm that did not receive the treatment during the trial. The conclusion of this review is to highlight the inappropriateness of comparing these medicines with each other using the results of clinical trials alone. It is important for the medical community to understand the specific types of patients that were involved in the clinical trials, to avoid unjustified conclusions.