Categories
Nevin Manimala Statistics

Suppressing the progression of bladder cancer using cyclovirobuxine D based on network pharmacology and bioinformatics approaches

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 11. doi: 10.1007/s00210-024-03754-9. Online ahead of print.

ABSTRACT

Limited treatment options are available for bladder cancer (BCa) resulting in extremely high mortality rates. Cyclovirobuxine D (CVB-D), a naturally alkaloid, reportedly exhibits notable antitumor activity against diverse tumor types. However, its impact on CVB-D on BCa and its precise molecular targets remain unexplored. This study conducts CCK8 assay, colony formation assay, and flow cytometry experiments to demonstrate that CVB-D inhibits long-term proliferation and viability of BCa cell lines, thereby inducing apoptosis in vitro. It employs PPI networks and the CytoHubba algorithm to identify COL1A1, COL6A1, COL6A2, COL5A2, COL5A1, COL12A1, COL18A1, ITGA5, VCL, FLNA, and GSN as crucial therapeutic targets for CVB-D that can halt the malignant progression of BCa. GO and KEGG analyses indicate that the PI3K/AKT signaling pathway potentially may play a pivotal role in mediating the anti-BCa growth effects of CVB-D. The ROC curve and K-M survival analyses reveal the significant clinical value of all the 11 identified therapeutic targets, with GSN as the most effective target of CVB-D in combating BCa. This study also uncovers a potential interaction between GSN and CVB-D through molecular docking and molecular dynamics simulations. RT-qPCR and Western blotting experiments provide further evidence that CVB-D effectively suppresses GSN mRNA and protein expression in a concentration-dependent fashion. Our comprehensive study is the first report on the molecular mechanism of CVB-D against BCa, identifying GSN as a pivotal target in CVB-D-based anti-BCa therapy. We believe that our study results may help establish a theoretical basis for the possible utilization of CVB-D in cancer therapeutics.

PMID:39797986 | DOI:10.1007/s00210-024-03754-9

Categories
Nevin Manimala Statistics

Human Brucellosis in the Rural and Urban Population of Pakistan: Seroprevalence, Risk Factors, and Clinical Manifestations

Curr Microbiol. 2025 Jan 11;82(2):80. doi: 10.1007/s00284-025-04063-x.

ABSTRACT

Brucella spp. is the bacterium responsible for brucellosis, a zoonotic infection that affects humans. This disease poses significant health challenges and contributes to poverty, particularly in developing countries. This study aimed to assess the seroprevalence, risk factors, and clinical symptoms of human brucellosis within the general population of Multan and Muzaffargarh, Pakistan. A total of 307 blood samples were collected from patients visiting local hospitals in Multan and Muzaffargarh between August 2015 and January 2016. Demographic information, risk factors, and clinical outcomes were documented. Serum samples were initially screened for anti-Brucella antibodies using the Rose Bengal Plate Test, and positive cases were subsequently confirmed through RT-PCR. The chi-square test assessed the link between Brucella positivity and the identified risk factors. The study recorded an overall seroprevalence of 6.8%, with 8.9% in Multan and 4.3% in Muzaffargarh. Genus-specific Brucella detection through RT-PCR confirmed that 20 out of 21 samples were positive. Significant associations with human brucellosis were found for contact with aborted animals (p = 0.032) and consumption of raw milk (p = 0.031), while factors such as age, gender, occupation, urbanicity, and geographical region did not show a significant impact on seropositivity (p > 0.05). Non-specific clinical symptoms were commonly observed among seropositive patients. The findings highlight the significance of close human interaction with infected animals, especially concerning livestock practices and dairy product consumption. The results also emphasize the importance of focusing efforts on raising awareness in risky occupations and developing control programs by healthcare authorities.

PMID:39797980 | DOI:10.1007/s00284-025-04063-x

Categories
Nevin Manimala Statistics

Functional outcomes after ankle fracture-dislocation: a systematic review

Arch Orthop Trauma Surg. 2025 Jan 11;145(1):117. doi: 10.1007/s00402-024-05643-5.

ABSTRACT

INTRODUCTION: Ankle fractures represent a significant portion of orthopedic injuries, with fracture dislocations tending to have worse outcomes. Logsplitter fractures represent a subset of fracture dislocations in which the talus is axially wedged in the tibiofibular joint. We aim to comprehensively investigate and report on the complications and functional outcomes associated with ankle fracture-dislocations.

MATERIALS AND METHODS: Following PRISMA guidelines, a medical librarian conducted a literature search in Embase, Ovid Medline, Scopus, Cochrane Central Register of Controlled Trials, and The Cochrane Database of Systematic Reviews. Studies examining ankle fracture-dislocations and reporting on functional or employment outcomes were included. Excluded were non-English studies, abstracts, conference proceedings, letters, perspective pieces, reviews, editorials, and case reports or series with fewer than five patients. Data on functional outcomes were extracted and reported using descriptive statistics. A comparative analysis of AOFAS scores between Logsplitter and ankle fracture-dislocations was conducted using pooled means and independent t-tests.

RESULTS: A total of 21 studies involving 810 cases of ankle fracture-dislocations were included. The pooled mean AOFAS score across 13 studies was 81.5, indicating “good” outcomes, while Logsplitter injuries had a significantly lower mean score of 75.8 compared to 82.9 for other ankle fracture-dislocations (p = 0.016). Complications included wound infection (7.3%), posttraumatic osteoarthritis (29.2%), nonunion/malunion (12.6%), and malunion. No studies reported on employment outcomes.

CONCLUSIONS: Ankle fracture-dislocations are high-energy injuries that affect a younger population compared to non-dislocated ankle fractures. Their functional outcomes resemble those of pilon fractures more than common ankle fractures. Logsplitter injuries are a subset of fracture dislocations that occur in even younger patients, with worse functional outcomes. This information can guide perioperative discussion and expectations for functional recovery. Additional studies are needed to evaluate the impact of these injuries on return to employment.

PMID:39797975 | DOI:10.1007/s00402-024-05643-5

Categories
Nevin Manimala Statistics

Ethnic disparities in survival and progression among EGFR-mutated adenocarcinoma of lung cancer patients treated with tyrosine kinase inhibitors: a systematic review and meta-analysis

Clin Transl Oncol. 2025 Jan 11. doi: 10.1007/s12094-024-03843-4. Online ahead of print.

ABSTRACT

BACKGROUND: The benefit of treatment with tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR-TKI) for lung adenocarcinoma (ADC), stratified by ethnicity, has not yet been fully elucidated.

METHODS: We searched PubMed, Embase, and Cochrane databases for studies that investigated EGFR-TKI for lung ADC. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses.

RESULTS: A total of 18 studies, comprising 4,497 patients with lung ADC randomized to TKIs or chemotherapy alone. TKIs significantly improved OS (HR 0.91; 95% CI 0.88-0.95), PFS (HR 0.60; 95% CI 0.38-0.97), and ORR (HR 0.34; 95% CI 0.25-0.48) in Asian patients, compared with the chemotherapy alone. In Caucasian patients, TKIs significantly improved PFS compared with chemotherapy alone (HR 0.34; 95% CI 0.25-0.48) and ORR(RR 2.35; 95% CI: 1.05-5.28). TKIs significantly reduced any adverse events of any grade in patients with mixed ethnicity (RR 0.86; 95% CI 0.76-0.98) and any adverse events of grade ≥ 3 in Caucasian patients (RR 0.67; 95% CI 0.51-0.89).

CONCLUSIONS: This is the first meta-analysis to reveal the ethnic influence on the outcomes of oncologic treatments for patients with lung ADC. In collaboration with in-depth molecular characterization, these data will allow the creation of a clinical-pathological predictive model to increase the magnitude of the expected benefit for patients from different ethnic groups.

PMID:39797945 | DOI:10.1007/s12094-024-03843-4

Categories
Nevin Manimala Statistics

The Oxford hip score demonstrates moderate ceiling effects at one and two years after total hip arthroplasty: which patients are at risk and does it matter?

Eur J Orthop Surg Traumatol. 2025 Jan 11;35(1):54. doi: 10.1007/s00590-024-04155-7.

ABSTRACT

BACKGROUND: The aim was to assess whether the postoperative Oxford Hip Score (OHS) demonstrated a ceiling effect at 1 or 2 years after total hip arthroplasty (THA) and to identify which patients are more likely to achieve a ceiling score and whether this limits assessment of their outcome.

METHODS: A retrospective cohort of 7871 patients undergoing primary THA was identified from an established arthroplasty database. Patient demographics, ASA grade, socioeconomic status, OHS and EuroQol questionnaire were collected preoperatively and at 1 and 2 years postoperatively. Regression analysis was used to identify independent preoperative factors associated with achieving a ceiling score. Receiver operating characteristic curves were used to identify preoperative OHS’s that predicted a postoperative ceiling score.

RESULTS: The ceiling effect (proportion achieving the maximal score) at 1 year was 21.8% (n = 1372) which increased significantly (p < 0.001) to 26.6% (n = 1569) at 2 years. Female gender (p ≤ 0.028), younger age (p < 0.001), decreasing socioeconomic deprivation (only for 2-year OHS), a better preoperative OHS (p < 0.001) or EQ-VAS (p < 0.001) were independently associated with a ceiling OHS postoperatively. The preoperative OHS was demonstrated to be a poor discriminator of achieving postoperative ceiling score at 1 year (AUC 62.4%, 95% CI 60.7 to 64.1, p < 0.001) and 2 years (AUC 61.5%, 95% CI 60.0 to 63.2). Those achieving a postoperative ceiling OHS at 1 and 2 years had statistically significant (p < 0.001) greater improvements in their OHS, EQ-5D and EQ-VAS and were more likely to have achieved a minimal important change in their OHS relative to their preoperative baseline and a postoperative patient acceptable symptom state.

CONCLUSION: The OHS demonstrated moderate ceiling effects at both 1 and 2 years following THA, and the preoperative score was a predictor of achieving a ceiling score. However, it would seem the ceiling effect did not limit the potential for improvements relative to baseline and achieving clinically meaningful values in the OHS.

PMID:39797938 | DOI:10.1007/s00590-024-04155-7

Categories
Nevin Manimala Statistics

The role of the Mediterranean diet in reducing the risk of cognitive impairement, dementia, and Alzheimer’s disease: a meta-analysis

Geroscience. 2025 Jan 11. doi: 10.1007/s11357-024-01488-3. Online ahead of print.

ABSTRACT

Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer’s disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet-characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil-has been widely recognized for its cardiovascular benefits and may also reduce the risk of cognitive decline and dementia. To investigate the protective effects of the Mediterranean diet on cognitive health, we conducted a systematic literature review using PubMed, Web of Science, and Google Scholar, focusing on studies published between 2000 and 2024. The studies included in the meta-nalysis examined the adherence to the Mediterranean diet and the incidence of dementia and AD. We applied a random-effects model to calculate pooled hazard ratios (HRs) with 95% confidence intervals (CIs) and assessed heterogeneity through I-square statistics. Forest plots, funnel plots, and Z-score plots were used to visualize study outcomes. Of the 324 full-text records reviewed, 23 studies met the inclusion criteria. The combined HR for cognitive impairment among those adhering to the Mediterranean diet was 0.82 (95% CI 0.75-0.89); for dementia, the HR was 0.89 (95% CI 0.83-0.95); and for AD, the HR was 0.70 (95% CI 0.60-0.82), indicating substantial protective effects. Significant heterogeneity was observed across studies, though Z-score plots suggested sufficient sample sizes to support reliable conclusions for each condition. In conclusion, this meta-analysis confirms that adherence to the Mediterranean diet is associated with an 11-30% reduction in the risk of age-related cognitive disorders, including cognitive impairment, dementia, and AD. These findings underscore the Mediterranean diet’s potential as a central element in neuroprotective public health strategies to mitigate the global impact of cognitive decline and dementia and to promote healthier cognitive aging.

PMID:39797935 | DOI:10.1007/s11357-024-01488-3

Categories
Nevin Manimala Statistics

Evaluating the Real-World Safety of Icosapent Ethyl Versus Omega-3 Polyunsaturated Fatty Acid in Nationwide US Veterans Cohort: Examining Atrial Fibrillation and Bleeding Endpoints

Clin Drug Investig. 2025 Jan 11. doi: 10.1007/s40261-024-01417-4. Online ahead of print.

ABSTRACT

PURPOSE: The REDUCE-IT randomized trial demonstrated a cardiovascular benefit of icosapent ethyl (IPE) but also raised potential safety signals for atrial fibrillation (AF) and serious bleeding. We aimed to evaluate the real-world safety of IPE versus mixed omega-3 polyunsaturated fatty acid (OM-3) formulations.

METHODS: This retrospective active comparator new-user cohort study compared rates of new-onset AF and major bleeding (MB) among adult new users of IPE versus OM-3 in 2020-2024 US Veterans Affairs data. Daily drug exposure was determined via prescription dispensing dates. AF and MB outcomes were identified via validated algorithms based on the International Statistical Classification of Diseases and Related Health Problems, 10th revision, clinical modification. Confounding was accounted for via nearest-neighbor pairwise propensity score (PS) matching. The PS, constructed via logistic regression, was informed by expert-identified variables meeting the disjunctive cause criterion. Cox regression was used to estimate adjusted hazard ratios (aHRs), interpretable as average treatment effects for the treated.

RESULTS: Cohorts for analyses of AF and MB endpoints included 1927 and 2015 people, respectively, in each of the IPE and OM-3 exposure groups. The median age was 70 years, and the groups exhibited a predominance of white (80%) males (93%). The median follow-up time was 1.29 years per person. Baseline covariates were well balanced by treatment arm after PS matching. Incidence rates for AF were 7.29 versus 7.48 per 100 person-years among new users of IPE versus OM-3. The aHR for AF was 1.15 (95% confidence interval 0.82-1.63). Incidence rates for MB were 3.27 versus 3.35 per 100 person-years among new users of IPE versus OM-3. The aHR for MB was 1.22 (95% confidence interval 0.87-3.02).

CONCLUSIONS: Our measures of association were consistent with the null, but we were unable to rule out harms from IPE (vs. OM-3) more modest than a 63% increased rate of AF and threefold increased rate of MB.

PMID:39797933 | DOI:10.1007/s40261-024-01417-4

Categories
Nevin Manimala Statistics

Volumetric and tridimensional root resorption and alveolar bone changes in Class II malocclusion extraction protocol treated with clear aligners and fixed orthodontic appliances: A comparative study

Am J Orthod Dentofacial Orthop. 2025 Jan 9:S0889-5406(24)00526-2. doi: 10.1016/j.ajodo.2024.11.012. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to assess the root resorption and alveolar bone changes of maxillary incisors volumetrically and 3-dimensionally in patients with Class II Division 1 malocclusion who underwent treatments involving the extraction of 4 first premolars with conventional fixed appliances (FAs) vs clear aligners (CAs).

METHODS: A total of 320 maxillary incisors from 80 patients were assessed and divided into 2 groups (FAs and CAs), each possessing similar baseline characteristics. Pretreatment and posttreatment cone-beam computed tomography scans were used to analyze linear and volumetric orthodontically induced inflammatory root resorption, alveolar bone thickness (ABT), alveolar bone height (ABH), as well as anteroposterior and vertical movements of maxillary incisors.

RESULTS: Both groups revealed a significant reduction in palatal ABT and an increase in labial ABT in both the central and lateral incisors. The total ABT reduction was more pronounced in the FAs group than in the CAs group (P <0.005). In terms of ABH, FAs treatment resulted in more labial and palatal marginal alveolar bone resorption around the maxillary incisors. The root length and volume losses in the CAs group were significantly less than those in the FAs group: 0.90 ± 0.97 vs 1.85 ± 1.18 mm and 19.59 ± 8.75 vs 24.28 ± 10.05 mm3, respectively. The axial inclination was significantly less in the CAs group than in the FAs group: 8.83 ± 8.73 vs 2.64 ± 12.31°.

CONCLUSIONS: Treatments of Class II Division 1 malocclusion with FAs and CAs appeared to cause a statistically significant palatal ABT reduction and maxillary incisors root resorptions, with the FAs treatment causing a more significant effect. Both treatment modalities significantly reduced the ABH, with the greatest reduction found on the lateral incisors’ palatal side in the FAs group. The CAs treatment resulted in a more significant incisor lingual tipping.

PMID:39797866 | DOI:10.1016/j.ajodo.2024.11.012

Categories
Nevin Manimala Statistics

Dietary Salt-Related Knowledge, Attitudes, and Behaviors of New Zealand Adults Aged 18-65 Years

J Nutr Educ Behav. 2025 Jan 10:S1499-4046(24)00529-3. doi: 10.1016/j.jneb.2024.12.001. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore dietary salt-related knowledge, attitudes, and behaviors of New Zealand (NZ) adults aged 18-65 years and assess differences by demographic subgroups.

DESIGN: Cross-sectional online survey conducted between June 1, 2018 and August 31, 2018.

SETTING: Participants were recruited in shopping malls, via social media, and a market research panel.

PARTICIPANTS: English-speaking adults residing in NZ.

VARIABLES MEASURED: An amended version of The Pan American and World Health Organization Knowledge, Attitudes, and Behaviors standardized survey tool was used. Demographic data (age, sex, ethnicity, and educational attainment) were also collected.

ANALYSIS: Descriptive statistics reported. Chi-square test for independence to assess differences by demographics.

RESULTS: The survey was completed by 1,131 adults (mean age 36 ± 15 years; n = 876 [78%] female; n = 661 [78%] NZ European/other; n = 210 [19%] Asian; n =164 [15%] Māori). In addition, 865 participants (83%) knew the primary dietary source of salt; 406 (40%) knew the recommended salt intake; 946 (95%) believed food manufacturers are responsible for sodium reduction; 563 (55%) supported government regulations; and 259 (26%) used food labels. Females and NZ European/other participants reported more favorable salt-reducing behaviors, such as avoiding fast-food and packaged, ready-to-eat foods (P < 0.001).

CONCLUSIONS AND IMPLICATIONS: Improving salt-related knowledge, attitudes, and behaviors in NZ is particularly important for men, underserved populations, and adults aged 45-65 years. A multicomponent, national NZ salt reduction program based on research addressing engagement and effectiveness for at-risk groups is warranted.

PMID:39797828 | DOI:10.1016/j.jneb.2024.12.001

Categories
Nevin Manimala Statistics

Effects of adjuvant hyperbaric oxygen therapy and real-time fluorescent imaging on deep sternal wound infection: a retrospective study

J Wound Care. 2025 Jan 2;34(1):48-58. doi: 10.12968/jowc.2022.0095.

ABSTRACT

OBJECTIVE: Deep sternal wound infection (DSWI) is a rare but devastating complication that is estimated to occur in 1-2% of patients after median sternotomy. Current standard of care (SoC) comprises antibiotics, debridement and negative pressure wound therapy (NPWT). Hyperbaric oxygen therapy (HBOT) appears to be an effective adjuvant therapy for osteomyelitis. The aim of this study was to determine the effectiveness of HBOT and real-time fluorescence imaging (RTFI) in a DSWI treatment protocol and their benefits on infection control.

METHOD: A retrospective analysis of DSWI management was performed. Enrolled patients were divided into two groups: HBOT group and RTFI group. Patients in the HBOT group received SoC, HBOT, NPWT and reconstructive flap surgery. Patients in the RTFI group received the same therapeutic plan as well as treatment with a RTFI device (MolecuLight i:X (MolecuLight, Inc., Canada) to achieve high-quality debridement. Infection status and short-term outcomes within three months were measured. Long-term outcomes were analysed at a 12-month follow-up.

RESULTS: Of the 55 patients enrolled: 22 in the HBOT group and 33 in the RTFI group. Infection control status, evaluated in terms of white blood cell counts and C-reactive protein levels, antibiotic use duration, antibiotic costs, reinfection rate and osteomyelitis recurrence rate, were statistically significantly improved in the RTFI group (<0.001, <0.001, 0.042, 0.022, 0.049 and 0.022, respectively). Length of total intensive care unit stay and duration of complete healing were statistically significantly decreased in the RTFI group (<0.001 and 0.046, respectively).

CONCLUSION: Patients with DSWI can benefit from HBOT, especially in terms of in-hospital mortality. RTFI can be used to eliminate bacterial burden and achieve high-quality debridement, which considerably improves infection control and clinical outcomes.

PMID:39797755 | DOI:10.12968/jowc.2022.0095