by Nour Aboalhaija, Hala Abulawi, Rania Hamed, Mohammad Alwahsh, Fatma Afifi, Heba Syaj, Elham Abusharieh, Ismail Abaza
Chiliadenus montanus (Vahl) Boiss. (Asteraceae) is a pharmacologically significant plant with different potent pharmacological properties. This study aimed to evaluate the phytochemical and anticancer activity of C. montanus, and to develop nanoemulsions (NEs) to enhance pulmonary delivery for lung carcinoma treatment. For that ethanol and water extracts, along with petroleum ether, chloroform, ethyl acetate, and methanol fractions, were assessed for total phenol and flavonoid contents, antioxidant activity, and cytotoxicity against H1299 and A549 lung cancer cell lines. The results showed that ethyl acetate fraction exhibited the highest phenol (47.94 ± 0.32 mg GAE/g of DW) and flavonoid (20.34 ± 1.48 mg rutin/g of DW) contents, while the ethanol extract showed the most potent antioxidant activity (IC₅₀ = 322.1 µg/mL) and selective cytotoxicity (IC₅₀ = 641.2 µg/mL) against H1299 cells. Nevadensin, chlorogenic acid, and sorbifolin were identified as the major constituents of the ethanol extract using liquid chromatography-mass spectrometry (LC-MS) analysis. Gas chromatography-mass spectrometry (GC-MS) analysis revealed α-phellandrene, 1,8-cineole, and α-cadinol as the lead volatile constituents. The major volatile compound of the aroma profile of the aerial parts, determined by solid phase micro extraction (SPME) was 1,8-cineole. Spontaneous emulsification was used to formulate ethanolic NE (S1-S4 NEs) with varying concentrations of ethanol extract, surfactant, cosurfactant, and oil phase. The optimal S4 NE demonstrated thermodynamic stability, appropriate pulmonary pH, and droplet sizes below 100 nm. These findings highlight the promising potential of C. montanus NE as a stable pulmonary drug delivery system for lung carcinoma therapy.Multiple sclerosis (MS) is a chronic neurological condition that affects approximately 150 000 people in the UK and presents a significant healthcare burden, including the high costs of disease-modifying treatments (DMTs). DMTs have substantially reduced the risk of relapse and moderately reduced disability progression. Patients exhibit a wide range of responses to available DMTs. The Predicting Optimal INdividualised Treatment response in MS (POINT-MS) cohort was established to predict the individual treatment response by integrating comprehensive clinical phenotyping with imaging, serum and genetic biomarkers of disease activity and progression. Here, we present the baseline characteristics of the cohort and provide an overview of the study design, laying the groundwork for future analyses.
POINT-MS is a prospective, observational research cohort and biobank of 781 adult participants with a diagnosis of MS who consented to study enrolment on initiation of a DMT at the Queen Square MS Centre (National Hospital of Neurology and Neurosurgery, University College London Hospital NHS Trust, London) between 01/07/2019 and 31/07/2024. All patients were invited for clinical assessments, including the expanded disability status scale (EDSS) score, brief international cognitive assessment for MS and various patient-reported outcome measures (PROMs). They additionally underwent MRI at 3T, optical coherence tomography and blood tests (for genotyping and serum biomarkers quantification), at baseline (i.e., within 3 months from commencing a DMT), and between 6–12 (re-baseline), 18–24, 30–36, 42–48 and 54–60 months after DMT initiation.
748 participants provided baseline data. They were mostly female (68%) and White (75%) participants, with relapsing–remitting MS (94.3%), and with an average age of 40.8 (±10.9) years and a mean disease duration of 7.9 (±7.4) years since symptom onset. Despite low disability (median EDSS 2.0), cognitive impairment was observed in 40% of participants. Most patients (98.4%) had at least one comorbidity. At study entry, 59.2% were treatment naïve, and 83.2% initiated a high-efficacy DMT. Most patients (76.4%) were in either full- or part-time employment. PROMs indicated heterogeneous impairments in physical and mental health, with a greater psychological than physical impact and with low levels of fatigue. When baseline MRI scans were compared with previous scans (available in 668 (89%) patients; mean time since last scan 9±8 months), 26% and 8.5% of patients had at least one new brain or spinal cord lesion at study entry, respectively. Patients showed a median volume of brain lesions of 6.14 cm3, with significant variability among patients (CI 1.1 to 34.1). When brain tissue volumes z-scores were obtained using healthy subjects (N=113, (mean age 42.3 (± 11.8) years, 61.9% female)) from a local MRI database, patients showed a slight reduction in the volumes of the whole grey matter (–0.16 (–0.22 to –0.09)), driven by the deep grey matter (–0.47 (–0.55 to –0.40)), and of the whole white matter (–0.18 (–0.28 to –0.09)), but normal cortical grey matter volumes (0.10 (0.05 to 0.15)). The mean upper cervical spinal cord cross-sectional area (CSA), as measured from volumetric brain scans, was 62.3 (SD 7.5) mm2. When CSA z-scores were obtained from the same healthy subjects used for brain measures, patients showed a slight reduction in CSA (–0.15 (–0.24 to –0.10)).
Modelling with both standard statistics and machine learning approaches is currently planned to predict individualised treatment response by integrating all the demographic, socioeconomic, clinical data with imaging, genetic and serum biomarkers. The long-term output of this research is a stratification tool that will guide the selection of DMTs in clinical practice on the basis of the individual prognostic profile. We will complete long-term follow-up data in 4 years (January 2029). The biobank and MRI repository will be used for collaborative research on the mechanisms of disability in MS.
This study aimed to determine the association between diabetes mellitus (DM) medication use and glycaemic control.
This was a retrospective diabetes registry-based cohort study.
Singapore.
Patients aged 18 and above with incident DM in the SingHealth Diabetes Registry from 2013 to 2020 were included. The entire study period included a 1 year baseline period, a 1 year observation period and a 3 month outcome period.
Drug use was measured using the proportion of days covered (PDC), and the changes in glycated haemoglobin (HbA1c) between the outcome and baseline periods were assessed. The associations between baseline HbA1c and PDC ≥0.80 and between PDC and change in HbA1c were analysed using logistic regression and the Kruskal–Wallis test, respectively.
Of 184 646 unique patients in the registry from 2013 to 2020, 36 314 met the inclusion and exclusion criteria and were included in the analysis. The median PDC for any DM drug, oral DM drugs and insulin during the observation period was 20.3%, 16.8% and 0%, respectively. Those who had good glycaemic control at baseline were less likely to receive DM drugs and those with poor baseline glycaemic control or missing baseline HbA1c were more likely to be consistent users (PDC >80%) (px 10-16).
The relationship between DM drug use and glycaemic control is complex and non-monotonic. Higher PDC for any DM drug and oral DM drugs during the observation period was significantly associated with clinically relevant HbA1c improvements.
Heart failure clinics (HFCs) are associated with increased survival rates, lower hospitalisation and improved quality of life. This study investigated factors influencing patient access to multidisciplinary outpatient HFCs from the perspective of patients and cardiologists.
This was a qualitative study. A trained researcher conducted semistructured face-to-face interviews with patients and online interviews with cardiologists. Interviews, conducted between March and October 2023, were audio-recorded. Transcripts were cleaned (deidentification, translation verification) and analysed by two trained researchers independently using systematic text condensation in NVivo v12. Codes were derived from the transcripts and grouped and organised into themes. Two authors independently coded data, reconciling disagreements with the senior author, followed by respondent validation. Member checking ensued.
Outpatient multidisciplinary HFCs in Qatar.
A purposive sample of patients diagnosed with heart failure who had attended at least one HFC appointment at Qatar’s Heart Hospital were approached in person or via phone, and cardiologists with the authority to make referrals to these clinics via the electronic medical record system were emailed; interviews ensued until theme saturation was achieved.
26 individuals (14 patients and 12 cardiologists) participated in the interviews. Four major themes were identified: health system organisation (subthemes: benefits, HFC triage criteria, need/capacity), HFC referral processes (subthemes: electronic record system, patient communication and education), care continuity and communication (subthemes: patient navigators, clinician preferences) and access challenges (subthemes: transportation, costs).
Resources are needed to expand HFC capacity and coverage, leverage electronic medical record tools as well as telehealth, educate physicians and patients on referral guidelines and processes and engage primary care to ultimately improve patient outcomes.
Sepsis is a major cause of death both globally and in the United States. Early identification and treatment of sepsis are crucial for improving patient outcomes. International guidelines recommend hospital sepsis screening programmes, which are commonly implemented in the electronic health record (EHR) as an interruptive sepsis screening alert based on systemic inflammatory response syndrome (SIRS) criteria. Despite widespread use, it is unknown whether these sepsis screening and alert tools improve the delivery of high-quality sepsis care.
The Sepsis Electronic Prompting for Timely Intervention and Care (SEPTIC) master protocol will study two distinct populations in separate trials: emergency department (ED) patients (SEPTIC-ED) and inpatients (SEPTIC-IP). The SEPTIC trials are pragmatic, multicentre, blinded, randomised controlled trials, with equal allocation to compare four SIRS-based sepsis screening alert groups: no alerts (control), nurse alerts only, prescribing clinician alerts only, or nurse and prescribing clinician alerts. Randomisation will be at the patient level. SEPTIC will be performed at eight acute-care hospitals in the greater New York City area and enrol patients at least 18 years old. The primary outcome is the percentage of patients with completion of a modified Surviving Sepsis Campaign (SSC) hour-1 bundle within 3 hours of the first SIRS alert. Secondary outcomes include time from first alert to completion of a modified SSC hour-1 bundle, time from first alert to individual bundle component order and completion, intensive care unit (ICU) transfer, hospital discharge disposition, inpatient mortality at 90 days, positive blood cultures (bacteraemia), adverse antibiotic events, sepsis diagnoses and septic shock diagnoses.
Ethics approval was obtained from the Columbia University Institutional Review Board (IRB) serving as a single IRB. Results will be disseminated in peer-reviewed journal(s), scientific meeting(s) and via social media.
ClinicalTrials.gov: NCT06117605 and
by Muhammad Hafiz Mohamed Pauzi, Azidah Abdul Kadir, Rosediani Muhamad, Zainab Mat Yudin
BackgroundCOVID-19 vaccination is crucial for pregnant women to protect against severe complications during pregnancy. However, vaccine hesitancy and refusal can affect acceptance rates among this vulnerable group, posing risks to both maternal and fetal health. This research was conducted to explore the barriers and facilitators influencing COVID-19 vaccination among Malaysian pregnant women.
MethodsThis qualitative study adopted a hermeneutic phenomenological design. Nineteen pregnant women receiving antenatal care at three clinics in Kelantan between February 2024 and June 2024 were purposively selected to participate in in-depth interviews. The interviews were audio-recorded, transcribed verbatim, and analyzed using NVivo software alongside manual coding. Thematic analysis, incorporating both inductive and deductive approaches, was conducted to identify key themes.
ResultsMost pregnant women expressed hesitancy toward COVID-19 vaccination during pregnancy due to various concerns. Our findings identified four key themes as barriers to vaccination: (i) Fear of side effects, (ii) Negative social influences, (iii) Perception of returning to normalcy, and (iv) Vaccine scepticism and prejudice. Conversely, three themes emerged as facilitators of vaccine acceptance: (i) Concerns about the effects of COVID-19 infection, (ii) Trust in the vaccine, and (iii) Personal and shared vaccination experiences.
ConclusionThis study identified key factors influencing COVID-19 vaccine hesitancy. These findings highlight the importance of addressing both personal and social dimensions of vaccine hesitancy. Public health interventions should focus on building trust, countering misinformation, and leveraging positive community experiences to encourage vaccine uptake, particularly in populations where hesitancy remains a concern.
by Lucie Ancel, Jules Gueguen, Guillaume Thoër, Jules Marçais, Aïda Chemloul, Bernard Le Guen, Marc Benderitter, Radia Tamarat, Maâmar Souidi, Mohamed Amine Benadjaoud, Stéphane Flamant
The threat of nuclear or radiological events requires early diagnostic tools for radiation induced health effects. Localized radiation injuries (LRI) are severe outcomes of such events, characterized by a latent presymptomatic phase followed by symptom onset ranging from erythema and edema to ulceration and tissue necrosis. Early diagnosis is crucial for effective triage and adapted treatment, potentially through minimally invasive biomarkers including circulating microRNAs (miRNAs), which have been correlated with tissue injuries and radiation exposure, suggesting their potential in diagnosing LRI. In this study, we sought to identify early miRNA signatures for LRI severity prognosis before clinical symptoms appear. Using a mouse model of hindlimb irradiation at 0, 20, 40, or 80 Gy previously shown to lead to localized injuries of different severities, we performed broad-spectrum plasma miRNA profiling at two latency stages (day 1 and 7 post-irradiation). The identified candidate miRNAs were then challenged using two independent mouse cohorts to refine miRNA signatures. Through sparse partial least square discriminant analysis (sPLS-DA), signatures of 14 and 16 plasma miRNAs segregated animals according to dose groups at day 1 and day 7, respectively. Interestingly, these signatures shared 9 miRNAs, including miR-19a-3p, miR-93-5p, miR-140-3p, previously associated with inflammation, radiation response and tissue damage. In addition, the Bayesian latent variable modeling confirmed significant correlations between these prognostic miRNA signatures and day 14 clinical and functional outcomes from unrelated mice. This study identified plasma miRNA signatures that might be used throughout the latency phase for the prognosis of LRI severity. These results suggest miRNA profiling could be a powerful tool for early LRI diagnosis, thereby improving patient management and treatment outcomes in radiological emergency situations.by Badrul Akmal Hisham Md Yusoff, Muhammad Ikmal Hazli, Norlelawati Mohamad, Muhamad Karbela Reza Ramlan, Nik Kamarul Arif Bin Nik Kamrulzaman, Mohamed Razzan Rameez, Mohamad Azwan Aziz
IntroductionThis study aims to determine the clinical outcomes of a new technique of cartilage repair surgery, using calcified cartilage zone debridement coupled with Hyalofast and bone marrow aspirate concentrate, in terms of pain and functional outcomes.
MethodsThis was a retrospective case series in 19 patients with cartilage injuries, ICRS 3 and 4. Using arthroscopic examination, cartilage defects were identified and debrided. Then, the calcified cartilage zone was identified and scrapped, until punctate bleeding occurred. Hyalofast was fixed into the defect and bone marrow aspirate concentrate was injected into the Hyalofast. Patients were followed up at baseline, 1, 6, and 18 months post-operative, using visual analog scale, KOOS, IKDC, and Lysholm Score.
ResultsThe mean age was 45.33 ± 9.68 years, with the mean cartilage defects of 10.21 ± 11.10 X 9.43 ± 10.85 mm2. Among the cohort, seven patients (36.8%) underwent three chondral repair procedures, five (26.4%) received two procedures, and the remaining seven (36.8%) were treated with a single procedure. In the KOOS subscale, there was a steady improvement; symptoms (mean difference: −23.87, CI: −43.97 – −3.77, p-value = 0.015), pain (mean difference: −28.39, CI: −43.94 – −12.83, p-value = 0.001), activity of daily living (mean difference: −26.23, CI: −40.95 – −10.14, p-value = 0.001), and sports subscale (mean difference: −57.36, CI: −80.76 – −33.97, p-value Conclusion
The calcified cartilage zone debridement technique served as a novel technique to preserve subchondral plate allowing better outcomes for cartilage repair.
To assess predictors of timely transition to adult diabetes care among individuals diagnosed with type 1 diabetes during childhood and adolescence. We hypothesised that older age at the last paediatric visit and urban residency would be predictors of timely transition.
Retrospective cohort study using healthcare administrative data in a jurisdiction with a universal healthcare system.
2045 adolescents and young adults diagnosed with type 1 diabetes between the ages of 0.5 and 18 years.
We ascertained age at the last paediatric diabetes visit (LPDV), age at the first adult diabetes visit (FADV) and transition duration, defined as the time between LPDV and FADV. Timely transition was defined as a transition duration of
Only 31.3% of individuals saw an adult provider within 1 year of their LPDV. Each 1-year increase in the age at LPDV was associated with increased odds of timely transition (adjusted OR 1.82, 95% CI 1.71 to 1.93, p0.05).
Older age at the LPDV and urban residency are associated with increased odds of timely transition. Interventions should be developed to help keep adolescents engaged in paediatric care until an older age before referring them to adult diabetes care. Limitations of this study include unmeasured confounding and limited generalisability to non-universal healthcare systems.
by Weam Mohamed Meargni Ahmed, Malaz M. Abdalmotalib, Mohamed H. Elbadawi, Galia Tajelsir Fadulelmula Mohammed, Waad Mohamed Ibrahim Mohamed, Fatima Salih Babiker Mohammed, Hajar Saad Salih, Hiba Omer Yousif Mohamed
BackgroundArtificial intelligence (AI) is revolutionizing education globally, yet its adoption in medical education remains inadequately understood. ChatGPT, a generative AI tool, offers promising yet doubtful potential for enhancing academic and clinical training.
MethodsThis study employed an analytical cross-sectional design, involving 1,443 Sudanese medical students who participated through an online, structured questionnaire. The questionnaire was designed to assess ChatGPT awareness, usage, and associated factors. Statistical analysis was performed using SPSS software to identify key determinants influencing ChatGPT awareness and usage among the participants.
ObjectiveThis study investigates the levels of awareness, attitude, and usage of ChatGPT among Sudanese medical students, identifying key socio-demographic, economic, and institutional factors influencing its adoption.
ResultsAmong the participants, 65.8% were aware of ChatGPT, yet only 41.9% reported using it. Gender differences were statistically significant, with males demonstrating higher usage rates (p 300,000 SDGs) showed significantly greater usage (p Conclusions
The findings underscore the urgent need for targeted interventions, including curriculum reform to integrate AI literacy, enhanced digital infrastructure, and gender-equity initiatives. Addressing these systemic gaps will scale up AI adoption in medical education. This study provides actionable insights for educators and policymakers, emphasizing the urgency of bridging socio-economic and institutional inequities to foster equitable access to AI tools in medical training.
Environmental tobacco smoke (ETS) is generally known as secondhand smoke. Assessing the magnitude of children’s exposure to ETS from early infancy is essential for public health and research endeavours. Urinary cotinine is now widely recognised as the primary indicator for assessing exposure to ETS across all age groups. This systematic review and meta-analysis aim to synthesise all the published evidence on the urinary cotinine cut-off concentrations used to categorise children under 5 years as being exposed to ETS.
We will conduct a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A comprehensive search will be conducted from various databases including PubMed, EMBASE, Scopus and Cochrane Library. This search will be performed from the earliest published articles up to the latest available studies until February 2025. We will include all the experimental and observational studies, such as cohort, case–control and cross-sectional, that measure urinary cotinine concentrations in children under 5 years old. Data extraction will be conducted using a standardised data extraction form, and the study quality will be evaluated according to the guidelines specified by the Newcastle-Ottawa Scale. The extracted data will be pooled and combined for meta-analysis. Two reviewers will independently screen, select and assess the quality of the included study. The result will be tabulated in a table of characteristics of the included study, which consists of the cut-off cotinine concentrations, analytical technique, method referred, study design, study area and respondents’ characteristics.
Ethics approval is not required as this is a review of collected published data. Findings will be disseminated in peer-reviewed publications and conference presentations, as well as with key stakeholders, health policymakers and healthcare professionals.
CRD42024556969.
by Nehal Mohamed Eisa, Mohamed A. M. El-Tabakh, Nourhan M. Kamal, Sara M. Gharbia, Mahmoud M. Samir, Wajid Syed, Mahmood Basil A. Al-Rawi, Ahmed Essam Abou Warda, Abdelrahman S. H. Refaee
IntroductionThe phenomenon of burnout and the lifestyle of physicians significantly influence the delivery of healthcare. Over time, burnout intensifies, negatively impacting professional performance, which in turn leads to decreased quality of treatment, patient satisfaction, and productivity. Additionally, it increases the occurrence of medical mistakes and turnover among physicians. In addition to the direct influence of lifestyle on those components.
Aim of the studyThe purpose of this study is to assess burnout syndrome among Egyptian physicians, as well as to investigate factors that contribute to burnout, especially demographic characteristics, lifestyle patterns, and health habits.
MethodsA cross-sectional study examined burnout prevalence and determinants among 502 Egyptian physicians in different governorates. An electronic questionnaire was used to collect data for the study. Questionnaire covered socio-demographics, The abbreviated Maslach Burnout Inventory (aMBI), and The Health Lifestyle and Personal Control Questionnaire (HLPCQ).
ResultsYounger physicians under 30 showed higher burnout on emotional exhaustion and depersonalization scales, with significant findings (P = 0.047), (P Conclusion
These findings highlight the intricate relationship between burnout and lifestyle among physicians. A healthy lifestyle, including diet, routines, social support, and physical activity was linked to reduced burnout, while dietary harm avoidance was negatively correlated. This suggests opportunities to enhance the well-being of medical professionals through lifestyle interventions.
The burden of non-communicable diseases is rising in low-and-middle-income countries, with diet being a key risk factor. This study aimed to assess the patterns, socioeconomic inequalities and determinants of eating healthy in Kenya. The study is the first in Kenya to use a healthy diet index to assess dietary patterns.
We analysed cross-sectional data from the 2015/16 Kenya Integrated Household Budget Survey. The study’s outcome variable was a continuous healthy diet index (HDI) constructed using principal component analysis from nine WHO/Food and Agriculture Organization (FAO) healthy diet recommendations. The HDI score and WHO/FAO healthy diet recommendations met were summarised for Kenyan households. Using the concentration index, we examined the socioeconomic disparities in healthy eating. In addition, multivariable linear regression was used to determine factors that influence healthy eating in Kenya.
A total of 21 512 households in Kenya were included, of which 60% were rural and about two-thirds headed by males. The HDI score ranged between –1.13 and 1.70, with a higher value indicating healthier eating. Overall, the average HDI score was 0.24 (95% CI: 0.24 to 0.25), interpreted as moderate. We identified key determinants including socioeconomic status and urban–rural residency differences. Healthy eating was concentrated among higher socioeconomic households, regardless of gender or location. Higher socioeconomic status (β=0.28, 95% CI 0.26 to 0.30), rural residence (β=0.18, 95% CI 0.15 to 0.20), household head being in union (β=0.04, 95% CI 0.02 to 0.06) or employed (β=0.05, 95% CI 0.02 to 0.08) were significantly associated with increased HDI scores, whereas male-headed households and lack of education were associated with significant decreases in HDI scores on average.
Most Kenyan households do not meet all the healthy dietary recommendations, and socioeconomic inequalities exist in eating healthy. Targeted interventions that promote healthy eating based on key determinants in Kenya are required.
Blood flow restriction therapy (BFRT) has gained attention for its capacity to induce substantial muscle hypertrophy and strength gains even when employing relatively minimal loads. Strength training is of significant importance in the rehabilitation of patients experiencing shoulder pain, which may arise from a multitude of sources, including rotator cuff injuries, tendinopathies or postsurgical recovery. However, traditional resistance training can be challenging for these individuals due to the presence of pain and functional limitations. In this regard, BFRT in conjunction with low-load strength training may prove an efficacious alternative. The integration of BFRT into rehabilitation protocols for shoulder pain could provide a viable pathway to improving muscle strength and facilitating recovery while minimising the risk of exacerbating pain or injury. The primary objective of this study is to conduct a systematic review of the effects of training with BFRT of the upper limb on shoulder strength.
A comprehensive database search will be conducted across multiple platforms, including PubMed, Scopus, Ovid, Web of Science, EBSCO, Cochrane Central, PEDro and Google Scholar, using predefined key terms without any language restriction. The particular focus of the study will be clinical trials with a controlled group that assess the impact of BFRT on upper extremity, neck and trunk muscles in both healthy individuals and patients. The primary outcome measure will be shoulder strength and power in different directions. The Cochrane Collaboration’s Risk of Bias 2 tool will be employed for the purpose of evaluating the risk of bias inherent to the studies in question. A meta-analysis will be conducted using Stata software. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be employed to evaluate the quality of evidence for the primary outcomes.
The previously published papers will be used for all analyses in this study. Results will be disseminated through professional networks, presentations at conferences and publication in a peer-reviewed journal. No ethics approval is required.
CRD42024605189.
by Abdeta Muktar Ahmed, Ayanle Suleiman Ahmed, Mohamed Mussa Abdilahi, Abdulkadir Mohamed Nuh
BackgroundMetabolic syndrome (met-s) is a medical condition that includes abdominal obesity, hyperlipidemia, high blood glucose, and high blood pressure. It is associated with a high risk of developing cardiovascular diseases and type 2 diabetes mellitus. The condition was believed to be a challenge mostly faced by developed nations. A few studies conducted showed that met-s is increasing and becoming more common in Africa, where it was considered rare. The study aimed to assess the determinants and prevalence of met-s among the adult population in Hargeisa town, Somaliland, in 2023.
MethodsA community-based cross-sectional study among 498 adults living in all eight districts of Hargeisa, was carried out from August to September 2023. The sample size was divided proportionally by the number of households in selected sub-districts. Systematic random sampling was employed to select the households in the sub-districts. One adult from each household was selected and assessed. Data were collected using the STEPwise approach of the World Health Organization. The data were analysed using International Diabetic Federation (IDF) criteria for metabolic syndrome with SPSS version 25. Bivariate and multivariate analyses using logistic regression were performed.
ResultIn total, 498 adults participated in the study. The prevalence of met-s was 26.7% in IDF (males 11% vs. females 38.9%). Being of an advanced age of 45–54 years (AOR = 3.6, CI 1.17–11.27), 55–64 years (AOR = 6.1, CI 1.88–19.83), >64 (AOR = 9.1 CI 2.41–34.92), being a woman (AOR = 10.8, CI 5.3–21.8), being overweight or obese (AOR = 4.5, CI 2.5–8), sedentary behavior (AOR = 3.5, CI 1.6–7.5), and lack of physical exercise (AOR = 0.39, CI 0.17–0.88) were significantly associated with met-s.
ConclusionThe met-s was predominant in our findings. Community-based prevention strategies and actions are necessary if the met-s and its potential consequences are needed to be mitigated.
by Mahmoud A. A. Ibrahim, Doaa G. M. Mahmoud, Alaa H. M. Abdelrahman, Khlood A. A. Abdeljawaad, Gamal A. H. Mekhemer, Tamer Shoeib, Mohamed A. El-Tayeb, Peter A. Sidhom, Paul W. Paré, Mohamed-Elamir F. Hegazy
Mycobacterium tuberculosis is a lethal human pathogen, with the key flavoenzyme for catalyzing bacterial cell-wall biosynthesis, decaprenylphosphoryl-D-ribose oxidase (DprE1), considered an Achilles heal for tuberculosis (TB) progression. Inhibition of DprE1 blocks cell wall biosynthesis and is a highly promising antitubercular target. Macozinone (PBTZ169, a benzothiazinone (BTZ) derivative) is an irreversible DprE1 inhibitor that has attracted considerable attention because it exhibits an additive activity when combined with other anti-TB drugs. Herein, 754 BTZ analogs were assembled in a virtual library and evaluated against the DprE1 target using a covalent docking approach. After validation of the employed covalent docking approach, BTZ analogs were screened. Analogs with a docking score less than –9.0 kcal/mol were advanced for molecular dynamics (MD) simulations, followed by binding energy evaluations utilizing the MM-GBSA approach. Three BTZ analogs–namely, PubChem-155-924-621, PubChem-127-032-794, and PubChem-155-923-972– exhibited higher binding affinities against DprE1 compared to PBTZ169 with ΔGbinding values of –77.2, –74.3, and –65.4 kcal/mol, versus –49.8 kcal/mol, respectively. Structural and energetical analyses were performed for the identified analogs against DprE1 throughout the 100 ns MD simulations, and the results demonstrated the great stability of the identified BTZ analogs. Physicochemical and ADMET characteristics indicated the oral bioavailability of the identified BTZ analogs. The obtained in-silico results provide promising anti-TB inhibitors that are worth being subjected to in-vitro and in-vivo investigations.by Unwaniah Abdull Rahim, Marami Mustapa, Nik Noorul Shakira Mohamed Shakrin, Armania Nurdin, Nursiati Mohamad Taridi, Yasmin Anum Mohd Yusof, Mariam Firdhaus Mad Nordin, Nur Aishah Che Roos
Cervical cancer ranked fourth most common malignancy among women worldwide despite the establishment of vaccination programmes. This systematic review evaluates the anti-cancer properties of turmeric and ginger bioactive compounds, specifically curcumin, 6/10-gingerol, and 6/10-shogaol, and their combination in cervical cancer through in-vitro and in-vivo models. A comprehensive electronic search was performed using Science Direct, PubMed, and Scopus from inception until the second week of June 2024 for studies published in English. Only studies investigating the effects of curcumin, gingerol, shogaol, and/or their combination in human cervical cancer cell lines and/or rodent animal models implanted with cervical cancer xenografts were included. Altogether, 27 studies were included in this review. The evidence gathered indicated that curcumin, 6/10-gingerol and 6-shogaol exert their anticancer action through modulation of cell signalling pathways, including AMPK, WNT, PI3K/AKT, and NF‐κB pathway, and mediators including Bax/Bcl2, TNF‐α, EGFR, COX‐2, caspases‐3, ‐9, p53, and pRb. However, the synergistic effect of these bioactive compounds is not known due to lack of evidence. In conclusion, curcumin, 6/10-gingerols, and 6-shogaols hold promise as therapeutic agents for cervical cancer. Yet, further research is essential to understand their combined efficacy, emphasising the need for additional studies exploring the synergistic anticancer effects of these bioactive compounds. Additional factors to explore include long-term effects and susceptibility of chemoresistant cervical cancer cells towards curcumin, shogaols, and gingerols.by Mahmoud A. A. Ibrahim, Maggie N. S. Hanna, Al-shimaa S. M. Rady, Peter A. Sidhom, Shaban R. M. Sayed, Mohamed A. El-Tayeb, Ahmed M. Awad, Hatem Tallima, Tamer Shoeib
The study of the interactions between biomolecules and nanostructures is quite fascinating. Herein, the adsorption propensity of beryllium oxide (Be12O12) nanocarrier toward nucleobases (NBs) was investigated. In terms of DFT calculations, the adsorption tendency of Be12O12 toward NBs, including cytosine (NB-C), guanine (NB-G), adenine (NB-A), thymine (NB-T), and uracil (NB-U), was unveiled through various configurations. Geometrical, electronic, and energetic features for Be12O12, NBs, and their associated complexes were thoroughly evaluated at M06-2X/6-311+G** level of theory. The potent adsorption process within NBs∙∙∙Be12O12 complexes was noticed through favorable interaction (Eint) and adsorption (Eads) energies with values up to –53.04 and –38.30 kcal/mol, respectively. Generally, a significant adsorption process was observed for all studied complexes, and the favorability followed the order: NB-C∙∙∙ > NB-G∙∙∙ > NB-A∙∙∙ > NB-T∙∙∙ > NB-U∙∙∙Be12O12 complexes. Out of all studied complexes, the most potent adsorption was found for NB-C∙∙∙Be12O12 complex within configuration A (Eint = –53.04 kcal/mol). In terms of energy decomposition, SAPT analysis revealed electrostatic (Eelst) forces to be dominant within the studied adsorption process with values up to –99.88 kcal/mol. Analyzing QTAIM and NCI, attractive intermolecular interactions within the studied complexes were affirmed. From negative values of thermodynamic parameters, the nature of the considered adsorption process was revealed to be spontaneous and exothermic. Regarding density of state, IR, and Raman analyses, the occurrence of the adsorption process within NBs∙∙∙Be12O12 complexes was confirmed. Noticeable short recovery time values were observed for all studied complexes, confirming the occurrence of the desorption process. The findings provided fundamental insights into the potential application of Be12O12 nanocarrier in drug and gene delivery processes.by Lianyu Shan, Mojdeh Matloubi, Ifeoma Okwor, Sam Kung, Mohamed Sadek Almiski, Sujata Basu, Andrew Halayko, Latifa Koussih, Abdelilah S. Gounni
Dendritic cells (DCs) are pivotal in regulating allergic asthma. Our research has shown that the absence of Sema3E worsens asthma symptoms in acute and chronic asthma models. However, the specific role of PlexinD1 in these processes, particularly in DCs, remains unclear. This study investigates the role of PlexinD1 in CD11c+ DCs using a house dust mite (HDM) model of asthma. We generated CD11c+ DC-specific PlexinD1 knockout (CD11cPLXND1 KO) mice and subjected them, alongside wild-type controls (PLXND1fl/fl), to an HDM allergen protocol. Airway hyperresponsiveness (AHR) was measured using FlexiVent, and immune cell populations were analyzed via flow cytometry. Cytokine levels and immunoglobulin concentrations were assessed using mesoscale and ELISA, while collagen deposition and mucus production were examined through Sirius-red and periodic acid Schiff (PAS) staining respectively. Our results indicate that CD11cPLXND1 KO mice exhibit significantly exacerbated AHR, characterized by increased airway resistance and tissue elastance. Enhanced mucus production and collagen gene expression were observed in these mice compared to wild-type counterparts. Flow cytometry revealed higher CD11c+ MHCIIhigh CD11b+ cell recruitment into the lungs, and elevated total and HDM-specific serum IgE levels in CD11cPLXND1 KO mice. Mechanistically, co-cultures of B cells with DCs from CD11cPLXND1 KO mice showed significantly increased IgE production compared to wild-type mice.These findings highlight the critical regulatory role of the plexinD1 signaling pathway in CD11c+ DCs in modulating asthma features.Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.