Medicine and Pharmacology

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Review
Pharmacology and Toxicology
Medicine and Pharmacology

Ipeleng Kopano Kgosiemang,

Relebohile Lefojane,

Ayodeji Mathias Adegoke,

Oludare Ogunyemi,

Samson Sitheni Mashele,

Mamello Patience Sekhoacha

Abstract: This study documents Euphorbiaceae plants in Southern Africa, focusing on their traditional medicinal uses, pharmacological properties, toxicity, and active secondary metabolites. Literature from scientific journals, books, dis-sertations, and conference papers from 1962 to 2023 was reviewed for 15 Euphorbia species. Recent findings indicate that certain compounds in Eu-phorbia plants have significant biological and pharmacological properties. However, the white sticky latex sap they contain is highly toxic yet can also have medicinal applications. Phytochemical analysis has shown these plants exhibit beneficial effects, including antibacterial, antioxidant, antiprolifera-tive, anticancer, anti-inflammatory, antiviral, antifungal, and anti-HIV activ-ities. Key phytochemicals such as euphol, cycloartenol, tirucallol, and triterpenoids contribute to their therapeutic efficacy, along with various proteins like lectin and lysozyme. Despite some Euphorbiaceae species being screened for medicinal compounds, many have not been thoroughly exam-ined, highlighting a critical gap. Given their historical usage, further research is essential to evaluate the medicinal significance of Euphorbia species through detailed studies of isolated compounds and their pharmacokinetics and pharmacodynamics. This research will serve as a valuable resource for future inquiries into the benefits of lesser-studied Euphorbia species.
Communication
Oncology and Oncogenics
Medicine and Pharmacology

Ram Patel,

John Mathews,

Caroline Hamm,

Swati Kulkarni,

Rasna Gupta,

Tarquin Opperman,

John Dean Chiong,

Abdullah Nasser

Abstract: Introduction: CDK4/6 inhibitors in combination with aromatase inhibitors (AI) are the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer. Landmark trials have demonstrated comparable progression-free survival (PFS) across CDK4/6 inhibitors, but overall survival (OS) outcomes have varied. This study aimed to evaluate real-world PFS and OS for palbociclib and ribociclib when combined with AI in patients with HR+/HER2- advanced breast cancer. Materials and Methods: This was a retrospective chart review of adult patients with HR+/HER2- metastatic breast cancer treated at a single academic center between January 1, 2015, and December 1, 2022. Baseline demographics, clinical characteristics, and treatment details were extracted. Kaplan-Meier analysis was used to estimate PFS and OS, and differences between treatment groups were assessed using the log-rank test. Cox proportional hazards models were constructed to adjust for confounding factors. Results: Seventy-five patients were included in the final analysis. The cohort was predominantly female (98.7%) and postmenopausal (77.3%), with 52.0% having de novo stage IV disease. Palbociclib was prescribed to 74.7% of patients, and ribociclib to 25.3%. Patients receiving ribociclib were significantly younger (57.6 vs. 67.5 years, p= 0.013) and more likely to be premenopausal (42.1% vs. 5.4%, p< 0.001). The real-world median PFS and OS for palbociclib were 20.3 months (95% CI: 14.8–46) and 37.2 months (95% CI: 20.3–not reached [NR]), respectively. For ribociclib, the median PFS and OS were not reached. Cox proportional hazards models adjusting for age and menopausal status found no significant differences between ribociclib and palbociclib for PFS (HR = 0.92 , p= 0.86) or OS (HR= 0.95 , p= 0.92). Conclusion: In this real-world analysis, palbociclib demonstrated a median progression-free survival consistent with results from landmark trials, although the observed overall survival was shorter. Ribociclib-treated patients had numerically longer PFS and OS compared with those treated with palbociclib, but the differences were not statistically significant. Discontinuation rates were similar between the two groups.
Article
Epidemiology and Infectious Diseases
Medicine and Pharmacology

Charles Afriye Agyapong,

Ali Davod Parsa,

Richard Hayhoe,

Russell Kabir,

Mark Cortnage

Abstract: Background: Ghana has seen a notable rise in Tuberculosis cases with mired treatment outcomes. However, evidence suggests disparities in the incidence of Tuberculosis and its treatment outcomes across the country. Nzema East Municipal specifically reported a 62.34% increase in TB incidence in 2023 compared to 2022. The study, therefore, aims to determine the geospatial distribution of TB incidence and predictors of TB treatment outcomes in Nzema East Municipal.Methods: The study used a retrospective cohort with a quantitative approach, utilising health records of 545 TB cases from 2018 to 2023 in Nzema East. Data was processed with Microsoft Excel and analysed using ArcGIS Pro version 3.3.2, Joinpoint Regression Programme 5.2.0, and STATA MP version 17.Results: The Moran’s index was 0.03 (p=0.00). All the subdistricts had at least one settlement with 2 to 26 TB cases per squared kilometre. Significant TB hotspots were identified in the population-dense communities and mining communities. Overall, successful TB treatment outcome was 76.70%. There was a significant decline in successful TB treatment outcomes from 2018 to the end of 2020 and through 2023 (p=0.03 and p=0.00, respectively). Having at least one follow-up lab (aOR= 0.25, 95% CI = 0.15, 0.42) and having a treatment supporter (aOR=0.43, 95% CI = 0.23, 0.80) lessens the chances of having an unsuccessful TB treatment outcome. Having started the TB treatment in 2020 increases the chances of having an unsuccessful outcome (aOR = 2.97 95% CI = 1.30, 6.81),Conclusion: TB incidence in Nzema East was spatially dependent, with a higher incidence in the highly populated and mining communities. The overall successful treatment outcome is suboptimal, which demands targeted intervention to mitigate these menaces.
Review
Oncology and Oncogenics
Medicine and Pharmacology

Hengrui Liu

Abstract: Cancer research has been significantly advanced by the integration of transcriptomic data through high-throughput sequencing technologies like RNA sequencing (RNA-seq). This paper reviews the transformative impact of transcriptomics on understanding cancer biology, focusing on the use of extensive datasets such as The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). While transcriptomic data provides crucial insights into gene expression patterns and disease mechanisms, the analysis is fraught with technical and biological biases. Technical biases include issues related to microarray, RNA-seq, and nanopore sequencing methods, while biological biases arise from factors like tumor heterogeneity and sample purity. Additionally, misinterpretations often occur when correlational data is erroneously assumed to imply causality or when bulk data is misattributed to specific cell types. This review emphasizes the need for researchers to understand and mitigate these biases to ensure accurate data interpretation and reliable clinical outcomes. By addressing these challenges, the paper aims to enhance the robustness of cancer research and improve the application of transcriptomic data in developing effective therapies and diagnostic tools.
Article
Dermatology
Medicine and Pharmacology

Hanny Nilasari,

Eliza Miranda,

Melani Marissa,

Ani Ruspitawati,

Dwi O.T.L. Handayani,

Ngabila Salama,

Budi Setiawan,

Supriadi Supriadi,

Tiranti Vindhagita Aisyah,

Inggariwati Inggariwati

+15 authors
Abstract:

Background/Objective: This study is to identify the epidemiology and clinical features of Mpox in Jakarta that just reemerged in Indonesia. Methods: This study used a cross-sectional study design to describe the epidemiological data, clinical features, and mortality of Mpox patients from August 2022 to December 2023. In addition, this study also aims to identify the differences in both epidemiology and the clinical features of Mpox in HIV (PLHIV) and non-HIV patients (non-PLHIV). Results: Our study shows that as of the end of December 2023, 59 Mpox cases were treated in Jakarta. Mpox in Indonesia were mainly diagnosed in male, MSM, and HIV patients. Most patients would manifest with fever, rash, and skin lesions. Syphilis was found as a concomitant infection in this group. Severe manifestations were found among PLHIV without ART. Conclusions: Mpox in Jakarta were found mainly in MSM, especially in PLHIV. There are various manifestations of Mpox, however, the clinical features were more severe in PLHIV without ART. Therefore, a strong surveillance system and spreading awareness regarding vaccination programme is needed to prevent the spread of Mpox. A cautious management was needed especially on PLHIV.

Article
Clinical Medicine
Medicine and Pharmacology

Marek Kowalski,

Danuta Domżał-Magrowska,

Ewa Malecka-Wojciesko

Abstract:

Background: Celiac disease (CD) is defined as a systemic autoimmune disorder induced by gluten and other prolamins, which leads to gradual histopathological damage of the duodenum mucosa, intestinal villous atrophy, in particular. The brush border of enterocytes produces disaccharidases, including lactase. Lactase deficiency may be primary - genetically determined or secondary- due to damage to the intestinal villi. To exclude the primary cause of lactase deficiency, LCT gene polymorphism is necessary to evaluate. Objective: In patients diagnosed with CD, the intestinal villi should recover after strict adherence to the gluten-free diet, and therefore no lactase enzyme deficiency secondary to the underlying disease should be observed. Methods: The study group consisted of 38 patients, 30 women and 8 men (Group 1), who presented symptoms suggesting CD at the time of diagnosis, histology of duodenal mucosa samples revealed Marsh grade 3 and had confirmed the presence of HLA-DQ2 or DQ8 genes and had the gluten-free diet recommended. The control group consisted of 31 healthy volunteers, 18 women and 13 men. A hydrogen breath test (HBT) was performed in all groups with 50 g of lactose dissolved in 250 ml of water. Among patients with a positive HBT in all groups, a blood sample was collected to determine the C/T (-13910) and G/A (-22018) polymorphism in the promoter of the LCT gene responsible for the synthesis of the lactase enzyme. Among patients with lactase deficiency confirmed in HBT, LCT gene analysis was performed by assessing the C/T (-13910) and G/A (-22018) polymorphisms.Results: A significantly higher incidence of lactase enzyme deficiency was found in Group 1 (n=27, 71.1%) compared to the control group (n=10, 32.3%) (p<0.01). Severe lactase deficiency was observed more frequently in the group 1 than in the control group (n=19 (50%) vs. n=5 (16.1%); p<0.01), while mild and moderate lactase enzyme deficiency was observed with similar prevalence. Severe deficiency of the lactase enzyme was found significantly more frequently in the group of patient who did not strictly follow the diet than in the group declaring a strict adherence to a gluten-free diet (n=13 (65%) vs. n=6 (33%); p<0.05). No significant difference was found in the frequency of the C/T (-13910) and G/A (-22018) polymorphism in the promoter of the LCT between the analyzed groups with previously positive HBT test. Only in group 1, in 5 (18.5%) patients presence of LCT gene variants responsible for lactase enzyme deficiency was not detected. Conclusions: Among patients with CD, lactase deficiency was confirmed in the majority of the study participants, of whom only about half had primary lactase deficiency. In the study group, a correlation was demonstrated between severe deficiency of the lactase enzyme and non-adherence to gluten- free diet.

Review
Neuroscience and Neurology
Medicine and Pharmacology

Elisa Navarro,

Noemí Esteras

Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of cellular defence mechanisms essential for maintaining brain’s health. Nrf2 supports mitochondrial function and protects against oxidative damage, which is vital for meeting the brain's substantial energy and antioxidant demands. Furthermore, Nrf2 modulates glial inflammatory responses, playing a pivotal role in preventing neuroinflammation. This review explores these multifaceted functions of Nrf2 within the central nervous system, focusing on its activity across various brain cell types, including neurons, astrocytes, microglia, and oligodendrocytes. Due to the brain's vulnerability to oxidative stress and metabolic challenges, Nrf2 is emerging as a key therapeutic target to enhance resilience against oxidative stress, inflammation, mitochondrial dysfunction, and demyelination, which are central to many neurodegenerative diseases.
Article
Clinical Medicine
Medicine and Pharmacology

Congwen Bian,

Hanfei Huang,

Zhong Zeng

Abstract: AbstractBackground: The increasing prevalence of fibrosis in donor livers raises concerns about its impact on post-transplantation outcomes, though this relationship remains unclear. This study aims to assess the effect of donor liver fibrosis on patient and graft survival following liver transplantation.Methods: Data from the UNOS-STAR registry (1987–2024) were analyzed, focusing on patients who received liver transplants with biopsy-proven fibrosis. The cohort was stratified based on fibrosis grade, and outcomes were compared using Cox regression and Kaplan-Meier survival analysis. Competing risk models were applied to assess specific mortality causes, and subgroup analyses explored the sensitivity of fibrosis on transplant outcomes.Results: Of the 22,897 patients, 17,926 received non-fibrotic grafts, and 4,971 had grafts with varying fibrosis grades. Donor fibrosis was associated with donor age, steatosis, and portal infiltrate, generally affecting those in better overall condition. Significant differences were observed in patient survival (p=0.001) and graft survival (p=0.002) between the fibrosis and non-fibrosis groups. Further analysis revealed that fibrosis increased the risk of malignancy (p=0.028), cardiovascular disease (p=0.017), and respiratory failure (p=0.033), but showed lower rejection rates at six months and one year. Sensitivity analyses confirmed fibrosis as an independent risk factor, with varying effects in subgroups.Conclusion: Donor liver fibrosis significantly impacts post-transplant outcomes, notably increasing the risk of all-cause mortality and graft failure. Specific causes of death, such as malignancy and cardiovascular disease, were more prevalent in recipients of fibrotic grafts, highlighting the need for further research to refine donor selection criteria.
Article
Pediatrics, Perinatology and Child Health
Medicine and Pharmacology

Amani H Elgadal,

Asim Ahmed Elnour,

Rofaida Mahmoud Mohamed,

Yasssmien Abdu Alrhaman Omer,

Ali Awadallah Saeed,

Khalid Awad Al-Kubaisi,

Nadia Al Mazrouei,

Semira Abdi Beshir,

Vineetha Menon,

Abdulla Al Amoodi

+4 authors
Abstract: Background Child development is multifaceted and depends on various elements including diet, genetic makeup, environmental conditions, and exposure to infections. Proper nutrition significantly impacts a child’s capacity to manage and recover from illness. Thus, evaluating nutritional health is a fundamental aspect of pediatric healthcare. Objective The current study assesses the nutritional status of hospitalized children and adolescents by analyzing growth parameters related to age, weight, height, and gender, identifying disparities , and determining influencing risk factors. Methods A single-center cross-sectional study was conducted at Mohamed El-Alamin Hamed Hospital for children in Khartoum-Sudan. The study focused on children and adolescents aged six months to 16 years who were hospitalized for over 24 hours, excluding those in critical conditions, selected by purposive sampling. Caregivers were interviewed after consent was obtained, with data collected through detailed medical histories, physical examination, and a specialized questionnaire. Results Two hundred sixty-eight subjects were enrolled in this study. Among them, males accounted for 146 (54.5%), with a male-to-female ratio of 1.2:1. A total of 199 (74.2%) of the subjects had a height/length for age >-2 z-score (normal), 49 (18.3%) had a +3 SD (obese). Regarding nutrition status, 161 (60%) had normal malnutrition, 32 (11.9%) had moderate wasting, and 45 (16.8%) had severe wasting. Grade 2 edema was observed in four (8.9%) children, and only three (9.4%) had grade 3 edema. Malnutrition risk factors significantly correlated with the female gender, hospital admission rate, and the absence of exclusive breastfeeding (p
Review
Clinical Medicine
Medicine and Pharmacology

Rahul Kumar,

Ethan Waisberg,

Joshua Ong,

Phani Paladugu,

Dylan Amiri,

Jeremy Saintyl,

Jahnavi Yelamanchi,

Robert Nahouraii,

Ram Jagadeesan,

Alireza Tavakkoli

Abstract: Advancements in neuroimaging, particularly diffusion MRI techniques and molecular imaging via PET, have significantly improved our ability to detect early biomarkers of both neurodegenerative and neuro-ophthalmic disorders, such as Alzheimer's, Parkinson's, multiple sclerosis (MS), neuromyelitis optica (NMO), and myelin oligodendrocyte glycoprotein (MOG) antibody disease. Despite these breakthroughs, the integration of AI-driven models has become crucial in harnessing the full potential of these technologies for clinical decision-making. This paper explores the role of advanced diffusion MRI techniques—specifically Neurite Orientation Dispersion and Density Imaging (NODDI) and Diffusion Kurtosis Imaging (DKI)—in revealing microstructural changes in brain and visual pathway tissues that precede clinical symptoms. These techniques, when paired with AI algorithms, enhance diagnostic precision, enabling the detection of early-stage degeneration and inflammatory processes with unprecedented accuracy. Additionally, the emergence of next-generation PET tracers targeting misfolded proteins, such as tau and alpha-synuclein, and inflammatory markers, further augments our ability to visualize and quantify pathological processes in vivo. The integration of AI, particularly deep learning models like convolutional neural networks (CNNs) and multimodal transformers, has demonstrated remarkable success in improving diagnostic accuracy, combining data from multiple imaging modalities, and providing predictive insights into disease progression. This review also examines the challenges associated with integrating AI into clinical practice, including technical variability, data privacy concerns, and regulatory hurdles. While these technologies promise to revolutionize early diagnosis and personalized treatment approaches, significant efforts in model validation, standardization, and clinical implementation remain crucial. The ongoing development of AI-enhanced neuroimaging holds great potential for advancing the precision of diagnosis and the effectiveness of therapeutic interventions in both neurodegenerative and neuro-ophthalmic disorders.

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