Categories
Nevin Manimala Statistics

Thiosemicarbazone Complexes and 6-MP Suppress Acute Lymphoblastic Leukemia via the NOTCH Signaling Pathway and Regulation of LUNAR1 and NALT1 lncRNA

Asian Pac J Cancer Prev. 2025 Jan 1;26(1):59-66. doi: 10.31557/APJCP.2025.26.1.59.

ABSTRACT

BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is the most common type of leukemia among children. There are several types of drugs that are common in treating and controlling leukemia, including 6-M. Moreover, the anti-cancer effects of the Thiosemicarbazone-Ni complex were surveyed as well as 6-MP. The current study aimed to evaluate the effect of the Thiosemicarbazone-Ni complex in comparison with 6-MP on the expression of NALT1 and LUNAR1 LncRNAs and their target gene, NOTCH1, in the Jurkat E6.1 cell line.

MATERIALS AND METHODS: Jurkat E6.1 cell was treated with 6-MP with the concentrations of 1, 5, 10, and 25μM and 0.5, 1, 2, and 5μM of Ni-nanoparticles, loaded with Thiosemicarbazone complexes for 24, 48, and 72 h. Subsequently, the RNA extraction and cDNA synthesis were performed and the expression of NALT1, LUNAR1, NOTCH1, and GAPDH genes was surveyed by Real-time PCR. Finally, the results were analyzed by statistical analysis.

RESULTS: The highest significant reduction in the expression of LUNAR1 was observed at 6-MP at 10μM for the first 72 h and the Thiosemicarbazone-Ni complex showed its effective dose at 5μM for 48 h. The highest decrease in NOTCH1 expression was observed in 6-MP treatment at 10μM concentration for 24h and Ni-Thiosemicarbazone treatment, the significant decrease was at 0.5μM for 72h. The most significant reduction in NALT1 expression was observed in treatment with Ni-Thiosemicarbazone complex and 6-MP at the concentrations of 2 and 10μM respectively for 24h.

CONCLUSION: Given the association between the aforementioned genes and the positive effects of the drugs at achieved concentrations and times, it can be concluded that Thiosemicarbazone-Ni complex and 6-MP can show putative roles in regulating the expression of studied genes.

PMID:39873986 | DOI:10.31557/APJCP.2025.26.1.59

Categories
Nevin Manimala Statistics

Medical indemnity knowledge and awareness among international medical graduates in Ireland

Ir J Med Sci. 2025 Jan 28. doi: 10.1007/s11845-025-03887-7. Online ahead of print.

ABSTRACT

BACKGROUND: Medical indemnity (MI) has become an important topic in the era of increasing number of medico-legal cases in Ireland. However, there is a sensible difference in understanding and usage of medical indemnity between Irish and international medical graduates.

AIM: This study aimed to investigate the knowledge and awareness of medical indemnity among international medical graduates in Ireland.

METHODS: This was a descriptive study with an anonymous online survey including 19 questions about various aspects of MI. Analysis of the data was done using Microsoft Excel statistical analysis pack.

RESULTS: One hundred eighty-six doctors participated in the study, 34 (18.2%) consultants, 74 (39.8%) registrars, 72 (38.7%) Senior House Officers (SHOs) and 6 (3.2%) General Practitioners (GPs). Their knowledge and insurance coverage were deficient before working in Ireland. The majority did not have any educational session about clinical indemnity insurance when starting work in Ireland. While most consultants (88.2%) had supplemental MI (SMI) at the time of the study, only 41.9% of registrars and 38.9% of SHOs had SMI. In addition, there was a difference between consultants and Non-consultant Hospital Doctors (NCHDs) involvement in medico-legal cases. 32.2% of consultants were involved in medico-legal cases compared to 19% of registrars and 18% of SHOs.

CONCLUSION: There is a need to address clinical indemnity and supplemental clinical indemnity topics on induction days for international medical graduates working in Ireland, including clear information about professional protection arrangements with refresher meetings every six months especially during rotational placements.

PMID:39873966 | DOI:10.1007/s11845-025-03887-7

Categories
Nevin Manimala Statistics

The relationship between fatigue levels and psychosocial adjustment in elderly individuals with chronic obstructive pulmonary disease: A descriptive study

Ir J Med Sci. 2025 Jan 28. doi: 10.1007/s11845-025-03882-y. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with physical limitations and significant social, psychological, and behavioral challenges. This study investigates the relationship between fatigue levels and psychosocial adjustment in COPD patients, considering their sociodemographic characteristics.

METHODS: A descriptive study was conducted with 160 COPD patients hospitalized in the Pulmonology Department of a university hospital. Data were collected via face-to-face interviews using a patient information form, the COPD and Asthma Fatigue Scale (CAFS), and the Psychosocial Adjustment to Illness Scale-Self-Report (PAIS-SR). Statistical analyses included Independent Sample t-test, One-Way ANOVA, Mann-Whitney U test, Kruskal-Wallis test, and Spearman correlation analysis, with significance set at p < 0.05.

RESULTS: The mean age of participants was 68.70 ± 9.41 years; 71.9% were male, and 67.9% had COPD for over six years. Most participants (74.4%) reported limitations in daily living activities due to the disease, and 91.9% reported having social support. Mean scores were 58.03 ± 15.80 on the CAFS and 64.19 ± 6.41 on the PAIS-SR. Significant differences were observed in fatigue and psychosocial adjustment scores based on gender, social support, and disease impact on daily activities (p < 0.05). A weak positive correlation was found between fatigue levels and psychosocial adjustment (p < 0.05).

CONCLUSIONS: COPD patients experience moderate-to-high fatigue levels and challenges in psychosocial adjustment, with fatigue negatively influencing adjustment. Interventions should focus on enhancing coping strategies, addressing psychosocial needs, and leveraging social support systems to improve patient outcomes.

PMID:39873964 | DOI:10.1007/s11845-025-03882-y

Categories
Nevin Manimala Statistics

Efficacy and Safety of Proactive Therapy with 2% Crisaborole Ointment in Children with Mild-to-Moderate Atopic Dermatitis: A Randomized Controlled Study

Paediatr Drugs. 2025 Jan 28. doi: 10.1007/s40272-025-00682-w. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness of crisaborole for proactive treatment of atopic dermatitis (AD) is not well established.

OBJECTIVES: This study aims to investigate the efficacy and safety of a proactive treatment strategy with 2% crisaborole ointment for managing mild-to-moderate AD in children.

PATIENTS AND METHODS: In this 16-week randomized-controlled trial, children aged 2-17 years with mild-to-moderate AD were enrolled. All participants received treatment with 0.1% mometasone furoate cream for 2 weeks. Those with an IGA score of ≤ 1 were randomly assigned in a 1:1 ratio to either the proactive treatment group, which received crisaborole combined with emollient twice daily, or the reactive treatment group, which received emollients alone, and in the event of disease relapse, both groups received 0.1% mometasone furoate cream as rescue treatment.

RESULTS: Of the 153 patients screened, 142 were randomized; 73 to the proactive treatment group and 69 to the reactive treatment group. At the end of the 16-week trial, the proactive treatment group had a relapse rate of 43.84%, significantly lower than the 71.01% relapse rate in the reactive group (P = 0.001). Additionally, the proactive treatment group demonstrated a significant reduction in the need for mometasone furoate prescriptions at weeks 4, 8, 12, and 16 (P < 0.05). Improvements were also observed in IGA, EASI, PP-NRS, and POEM scores at 12 weeks (P < 0.05). No significant differences in adverse events were found between the groups (χ2 = 2.237, P = 0.135).

CONCLUSIONS: Proactive treatment with crisaborole ointment for children older than 2 years with mild-to-moderate AD effectively reduces flare-ups and reliance on topical corticosteroids, demonstrating good tolerability and safety.

CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2100054340 (Date of Trial Registration: 14 December 2021).

PMID:39873962 | DOI:10.1007/s40272-025-00682-w

Categories
Nevin Manimala Statistics

Self-perceived and measured visual function, the impact of eye-disease, wellbeing, social determinants, and personality traits in Swedish 70-year-olds-results from the Gothenburg H70 Study

Acta Ophthalmol. 2025 Jan 28. doi: 10.1111/aos.17440. Online ahead of print.

ABSTRACT

PURPOSE: To explore the potential correlation between subjective and measured visual function, as well as to analyse the influence of eye disease, socioeconomic factors and emotional dimensions.

METHODS: Semi-structured interviews, physical examinations and functional tests (n = 1203). Demographics covered sex, marital status, education, household economy, smoking and alcohol. Participants (born in 1944) rated their visual function (n = 533); those misjudging (n = 48) were studied. Group A (n = 18) had low presenting visual acuity (PVA) but reported good vision; Group B (n = 30) had normal PVA but reported low vision. Control group (n = 485) matched subjective and measured visual function. Ophthalmic examination tested visual acuity (VA), visual field and contrast sensitivity (CS). Psychometric tests: NEO-FFI, sense of coherence (SOC) and Montgomery-Åsberg Depression Rating Scale (MADRS).

STATISTICAL TESTS: chi-square, t-tests, Mann-Whitney U test and logistic regression.

RESULTS: Of the population, 91% made correct assumptions about their vision. The 9% who made incorrect assumptions about their vision ability (combining groups A + B) were more likely to live alone (p = 0.02) and had lower household incomes compared to the control group (p = 0.04). Additionally, the exhibited significantly lower PVA and BCVA, a higher prevalence of visual field defects (p = 0.02) and lower CS, mean 1.63 (p = 0.005). Group A (3.4%) were women (p = 0.002) with the personality of extraversion, mean 40.0 (p = 0.01). Group B (5.6%) had more self-reported eye diseases (p = 0.01), lower CS (p = 0.01), lower educational level (p = 0.03) and border significantly lower SOC (p = 0.06).

CONCLUSIONS: The perception of visual function is shaped by awareness of an eye disease but is additionally influenced by sex, socioeconomic factors and emotional parameters.

PMID:39873951 | DOI:10.1111/aos.17440

Categories
Nevin Manimala Statistics

Safety and Efficacy of Lotilaner Ophthalmic Solution (0.25%) in Treating Demodex Blepharitis: Pooled Analysis of Two Pivotal Trials

Ophthalmol Ther. 2025 Jan 28. doi: 10.1007/s40123-024-01089-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Lotilaner ophthalmic solution (0.25%) is the first United States Food and Drug Administration (US FDA)-approved drug for treating Demodex blepharitis. In pivotal trials, it was found to be well tolerated and demonstrated a significant reduction in collarettes and mite density after a 6-week treatment regimen. This study aimed to report the safety and efficacy profile of lotilaner ophthalmic solution (0.25%) from a pooled analysis of two pivotal trials in patients with Demodex blepharitis.

METHODS: Pooled data were analyzed from two randomized, double-masked, vehicle-controlled clinical trials [phase 2b/3 Saturn-1 (NCT04475432) and phase 3 Saturn-2 (NCT04784091)] in which patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution (0.25%) (study group) or the vehicle formulation without lotilaner (control group), twice daily for 6 weeks. The outcome measures were the proportion of patients with 0-2 collarettes (grade 0 collarettes), mite eradication, erythema cure, and the proportion of patients with ≤ 10 collarettes (grade 0 or 1 collarettes) at day 43.

RESULTS: Overall, 833 participants were randomized to receive either the study drug (N = 415) or vehicle (N = 418). On day 43, 49.8% of patients in the study group vs. 9.9% in the control group (p < 0.0001) had collarette grade 0 (0-2 collarettes). A reduction to ≤ 10 collarettes (grade 0 or 1 collarettes) was achieved in 85.1% of patients in study group vs. 28.0% in control group (p < 0.0001). The proportion of patients achieving mite eradication (60.2% vs. 16.1%, p < 0.0001) and erythema cure (24.9% vs. 7.9%, p < 0.0001) were also statistically significantly higher in the study group compared to the control group. The rates of adverse events were low in both studies, with no serious drug-related ocular adverse events reported. As many as 92% of patients rated the study drop as neutral to very comfortable.

CONCLUSIONS: Twice-daily treatment with lotilaner ophthalmic solution (0.25%) for 6 weeks demonstrated statistical significance for all outcome measures compared to the vehicle control, with low rates of adverse events and a high rate of drop comfort.

PMID:39873946 | DOI:10.1007/s40123-024-01089-5

Categories
Nevin Manimala Statistics

Synergistic antimicrobial activity of essential oils mixture of Moringa oleifera, Cinnamomum verum and Nigella sativa against Staphylococcus aureus using L-optimal mixture design

AMB Express. 2025 Jan 28;15(1):15. doi: 10.1186/s13568-024-01797-y.

ABSTRACT

The urgent need to address the growing problem of antimicrobial resistance in multidrug-resistant bacteria requires the development of pioneering approaches to treatment. The present study aims to evaluate the antimicrobial potential of the essential oils (EOs) of Moringa oleifera (moringa), Cinnamomum verum (cinnamon), and Nigella sativa (black seed) and the synergistic effect of the mixture of these oils against Staphylococcus aureus MCC 1351. Statistical modeling revealed cinnamon oil had the highest individual antimicrobial potency, followed by black seed oil. The combination of the three EOs exhibited significant synergistic effects compared to the individual oils, with a Fractional Inhibitory Concentration (∑FIC) index of 0.27. L-Optimal mixture design of response surface methodology (RSM) identified the optimal mixture as moringa: cinnamon: black seed oils by the ratio of (1:1:1) in run 15 (0.338:0.307:0.355 mL) (v/v). This mixture exhibited significant antibacterial efficacy, outperforming individual oils and conventional antibiotics like tetracycline. Specifically, the combination reduced the MIC values from 3.12, 0.78, and 6.25 to 0.25, 0.06, and 0.78 μg/mL for moringa, cinnamon, and black seed oil, respectively. Synergistic interactions between oils further boosted efficacy, with moringa-cinnamon and cinnamon-black seed pairings exhibiting the strongest synergies. The developed predictive models for IZD and MIC showed excellent fit, with R2 values of 0.9843 and 0.9958, respectively. Pareto chart analysis highlighted the predominant individual and synergistic effects, with the Moringa-Cinnamon interaction exhibiting the highest positive synergy. Notably, the oil mixture of run 15 demonstrated excellent biocompatibility, maintaining 97.6% viability of normal human skin fibroblasts (HSF) after 24 h exposure to 200 μL EOs of the mixture per mL. Gas chromatography mass spectrometry (GC/MS) identified abundant bioactive phytochemicals like cinnamaldehyde, linoleic acid, and palmitic acid methyl esters underlying the observed antimicrobial effects. This rationally designed, synergistic phytochemical combination presents a promising natural therapeutic against antibiotic-resistant S. aureus while exhibiting minimal cytotoxicity. The results underscore how combining essential oils could help address the issue of antibiotic resistance in S. aureus.

PMID:39873942 | DOI:10.1186/s13568-024-01797-y

Categories
Nevin Manimala Statistics

Bridging Classrooms and Communities: The Transformative Impact of Community-Based Dental Education on the Learning Experiences of Undergraduate Students

Eur J Dent Educ. 2025 Jan 27. doi: 10.1111/eje.13076. Online ahead of print.

ABSTRACT

AIMS: This study aimed to evaluate the impact of community-based dental education (CBDE) on the learning experiences of undergraduate dental students and recent dental graduates from two diverse geographical regions.

METHODS: The study followed a cross-sectional design, conducted online using Google Forms, with ethical approval from Qatar University. A non-probability purposive sampling method was used to recruit dental students and recent graduates from three institutions in India and one in Qatar. A questionnaire based on 20 closed-ended items and two open-ended questions, developed by a team of dental academics, was used for data collection. Data analysis involved descriptive statistics, analysis of variance (ANOVA) and thematic analysis for open-ended responses.

RESULTS: The study included 148 participants, with 116 female (78.37%) and 32 male (21.62%) students, mostly from India (75%) and the rest from Qatar (25%). ANOVA revealed significant differences based on age, country and stage of education (p < 0.001). Dental interns had the highest mean score (1.12 ± 0.8), while Year 2 students had the lowest (0.75 ± 1.08). Female participants had a slightly higher mean score (1.05 ± 0.77) than male participants (0.92 ± 0.98), although this difference was not statistically significant (p = 0.127). Key challenges included inadequate support and cultural barriers in India, and conflicts with religious obligations and didactic workload in Qatar. Recommendations focused on enhancing field activities, logistical support and mentorship programmes.

CONCLUSIONS: The study shows that dental students value CBDE for developing essential skills for community engagement. However, challenges differ across socio-cultural contexts, highlighting the need for more localised and supportive frameworks to improve CBDE experiences. The variation in student perceptions by age, education stage and country suggests that CBDE strategies should be flexible and adaptable to address the diverse learning needs of students.

PMID:39871109 | DOI:10.1111/eje.13076

Categories
Nevin Manimala Statistics

Where does the tether break in vertebral body tethering cases? Clinical insights from revision cases after tether breakage

Spine Deform. 2025 Jan 27. doi: 10.1007/s43390-025-01048-5. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the sites where the tether breaks in vertebral body tethering (VBT) cases.

METHODS: Intraoperative evaluation of broken tethers in patients who had anterior revision.

INCLUSION CRITERIA: anterior revision of VBT cases with explantation of the full implant and photo documentation. Eight patients met the inclusion criteria. The primary variable of interest was the location of tether breakage in relation to the vertebral curve and the tether-screw interface. Another variable of interest was to evaluate the difference in breakage rates between anterior and posterior tethers in double tether cases.

RESULTS: Sixty tethers bridging the intervertebral disc within this cohort of eight patients were found. Seven implants were removed from thoracolumbar curves and one implant from a thoracic curve. We identified 32 tether breakages. Double tethers were used in six patients. In these six cases, 15 breakages were found in the posterior tether and 13 in the anterior tether. Four cases (50%) exhibited breakages at the apex, eight cases (100%) at the lowest instrumented vertebra (LIV), and five cases (63%) at the uppermost-instrumented vertebra (UIV). Five tether breakages (in three cases with double tether) were observed at the screw sites, while the remaining 27 exhibited cord breakages near the intervertebral discs. In double tether systems, statistical analysis did not reveal any significant difference in breakage rates between anterior and posterior tethers.

CONCLUSIONS: In VBT cases, the tether breaks mostly at the level of the intervertebral disc, adjacent to the lowest instrumented vertebra.

LEVEL OF EVIDENCE: Level IV (Case series with no comparison group).

PMID:39871083 | DOI:10.1007/s43390-025-01048-5

Categories
Nevin Manimala Statistics

Age determination by measurement of pulp volume of canine teeth in patients with cleft lip and palate: a retrospective study

Oral Radiol. 2025 Jan 27. doi: 10.1007/s11282-025-00802-9. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluates the potential of pulp volume/total tooth-volume measurements of canine teeth in relation to chronologic age in patients with cleft lip and palate (CLP). The significance of this study lies in its exploration of the usability of these measurements for age determination in CLP patients, providing a novel perspective to the existing literature.

METHODS: Cone beam computed tomography images of 33 patients (16 females, 17 males) with unilateral CLP aged 14-45 years and 33 age- and sex-matched healthy individuals (16 females, 17 males) were retrospectively evaluated. Using ITK-SNAP software, pulp and whole tooth volumes of canine teeth on the non-defect side of CLP patients and the corresponding side of healthy individuals were measured. Their relationship with chronologic age was evaluated, and comparisons were made between the CLP and control groups.

RESULTS: No statistically significant difference was observed between the whole tooth volume, pulp volume, and pulp volume/total tooth-volume ratios of the control and CLP groups. A paired t test comparing chronologic age and calculated mean age of both groups found no significant difference.

CONCLUSIONS: The results show that the pulp and total tooth-volume ratios of canine teeth in the non-defect areas of individuals with unilateral CLP correlate with chronologic age and can be used reliably for age determination. This indicates that individuals with CLP can be evaluated similarly to healthy individuals, allowing accurate age estimation based on dental measurements.

PMID:39871068 | DOI:10.1007/s11282-025-00802-9