Tag: pubmed

Turk Neurosurg. 2024 May 21. doi: 10.5137/1019-5149.JTN.46503-24.2. Online ahead of print.

ABSTRACT

AIM: This study was conducted to evaluate the in vitro effects of hydroxychloroquine (HCQ) on histone deacetylase (HDAC) enzyme activity and interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) expression. HDAC enzyme activity and the expression of inflammation markers were tested, with the presence of the HDAC inhibitor valproic acid, in human primary cell cultures prepared from two different tissues.

MATERIAL AND METHODS: Primary cell cultures were prepared. Samples that did not receive any medication constituted the control group, while culture samples treated with HCQ served as the study group. The surface morphology of cells and the extracellular matrix (ECM) were evaluated by Giemsa staining and inverted light microscopy. Cell viability, proliferation, and cytotoxicity were determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium-bromide (MTT) analysis. The cultures were simultaneously stained with acridine orange (AO)/propidium iodide (PI) and viewed under fluorescence microscopy. HDAC enzyme activity and IL-6, IL-10, and TNF-α expression were evaluated using commercial enzyme-linked immunosorbent assay kits. The obtained data were analyzed using statistical methods. The alpha significance level was accepted as p 0.05.

RESULTS: HCQ applied to cell cultures at the tested doses and durations showed cytotoxic effects on cell viability, proliferation, and cell or ECM morphology. It increased HDAC activity in chondrocytes and caused a proinflammatory response, indicated by an increase in TNF-α in the cells (p 0.05).

CONCLUSION: Taken together, the results emphasized that the cytotoxic effect of HCQ increased HDAC activity; therefore, this proinflammatory response should be taken into consideration in the clinical use of HCQ.

PMID:39840570 | DOI:10.5137/1019-5149.JTN.46503-24.2

Turk Neurosurg. 2024 May 4. doi: 10.5137/1019-5149.JTN.46011-23.3. Online ahead of print.

ABSTRACT

AIM: The aim of the study is to determine sac volume based on radiological examinations in patients undergoing surgery for myelomeningocele (MMC) and to investigate the relationship of sac volume with hydrocephalus and Chiari malformation type 2 (CM) with a view to determining the optimum length of follow-up and recommend a treatment plan.

MATERIAL AND METHODS: The present study involved the retrospective review of radiologic examinations and medical files of 81 patients who underwent surgery for myelomeningocele between 2015 and 2022 in the neurosurgery clinic of Ankara Training and Research Hospital. Then, MMC sac volumes were measured and the statistical relationship of these measurements with the Evans Index, progressive enlargement of the ventricles after sac repair and CM was investigated.

RESULTS: Of the 81 patients, 41(50.6%) were boys and 40(49.4%) were girls. The median MMC sac volume was 11,005.28 mm³ and the mean Evans index (EI) based on brain tomography performed on postnatal day1was 0.405 ± 0.146. Analysis of the relationship between the EI and MMC sac volume yielded r=0.622, p 0.001 and showed a strong positive correlation between the two parameters at a statistical significance level of 5%. Evans Indexes based on brain tomography scans performed on postnatal day 1 showed that ventriculomegaly was present in 49(60.5%) patients and absent in 32(39.5%) patients. Of the 81 patients, 48(59.3%) underwent shunting and the remaining 33(40.7%) patients did not require shunting. 28 patients underwent shunting simultaneously with the sac repair, i.e., on day 12 on average, while 20 patients exhibited a progressive increase in their EI after sac repair and required a second surgery for shunting on day 28 on average. The mean MMC sac volume was 11,511.214 mm³ in 20 patients who subsequently developed hydrocephalus versus 3,066.9997 mm³ in patients who did not require shunting before or after sac repair. In patients who developed hydrocephalus after sac repair, there was no correlation between the day of intervention and sac volume. Mean sac volume was 28,297.36 mm³ in 28 patients with comorbid CM versus 7,600.32mm³ in patients without CM. All children with CM required shunting.

CONCLUSION: Patients with larger myelomeningocele sac volume have higher risk of concomitant hydrocephalus or subsequent development of hydrocephalus after sac repair compared to patients with a smaller sac volume. These patients should definitely be evaluated for same-session intervention. Patients with a larger sac volume and/or comorbid CM should be followed up more frequently and for a longer period of time.

PMID:39840569 | DOI:10.5137/1019-5149.JTN.46011-23.3

Turk Neurosurg. 2024 Mar 20. doi: 10.5137/1019-5149.JTN.45958-23.3. Online ahead of print.

ABSTRACT

AIM: St. John’s Wort Oil (JWO) has a sedative property and it is used traditionally for the treatment of depression, neuralgia and excitability. JWO has been shown to have anticancer activity via apoptosis in glioblastoma cells. However, information on whether JWO is effective on the autophagy mechanism in glioblastoma is still not known. So, the current study was the first to search the autophagy mechanism T98 glioma cells.

MATERIAL AND METHODS: Three groups were created with T98 human glioblastoma cells; Group 1: T98 glioma cells with no treated (Control group). Group 2: T98 glioma cells treated with 3 µl/ml JWO. Group 3: T98 glioma cells treated with 6 µl/ml JWO. The cell proliferation, oxidative stress, types of cell death were studied at IC50 dose of JWO.

RESULTS: The proliferation of glioma cells was inhibited in 5.296 µl/ml dose. JWO induced apoptosis in T98 glioma cells in comparison with the control and there was statistically significant difference (p 0.001). Apoptosis was analyzed via TUNEL method and results were checked by flow cytometry. We also investigated the effects of JWO on autophagy in T98 glioma cells by immunostaining LC3-II and MDC fluorescent stainings. The differences between JWO treated and control group were notably significant (p 0.001). The immunofluorescence staining resultsof LC3-II was confirmed by Western blotting analysis.

CONCLUSION: JWO seems to be an effective treatment agent for glioblastoma. Not only does it induce apoptosis via oxidative stress but also affects the autophagy. The use of JWO in combination with other treatment options may increase the efficacy of treatment.

PMID:39840562 | DOI:10.5137/1019-5149.JTN.45958-23.3

Turk Neurosurg. 2024 Jan 11. doi: 10.5137/1019-5149.JTN.43568-23.2. Online ahead of print.

ABSTRACT

AIM: This study aims to assess the clinicopathological and prognostic significance of Tim-3, an immune checkpoint molecule, and Rel-B, an NF-κB subunit, in grade 4 diffuse glioma samples and their relationship with each other.

MATERIAL AND METHODS: The demographic, radiologic, prognostic, and treatment data of patients diagnosed with grade 4 diffuse glioma between 2016 and 2019 were reviewed and recorded. Tim-3 and Rel-B were applied to the paraffin-embedded tissues by immunohistochemistry method. Tim-3 expression was grouped as immunoreactivity density score (IDS) (Low, High) and expression percentage ( 12%, 12%), while Rel-B expression was divided into positive and negative groups.

RESULTS: 99 grade 4 diffuse glioma samples were detected, 8 of which were IDH-1 positive. Tim-3 was expressed only in immune cells around and inside the tumoral tissue, and expression was detected only in tumoral cells with Rel-B. Tim-3 IDS was found at lower levels (median 31.8) in IDH-1 positive cases and higher (median 158) in IDH-1 negative ones (p=0.020). A significant correlation was found between the Tim-3 IDS high group and Rel-B positivity (p=0.007). In the IDH-1 negative cohort, the univariate analysis revealed higher Tim-3 expression percentage and higher IDS were associated with better overall survival (OS) (p=0.041 and p=0.042 respectively) and progression-free survival (PFS) (p=0.023 and p=0.029 respectively), while in the multivariate analysis higher Tim-3 expression percentage was found to be an independent predictor for better OS (p=0.008) and PFS (p=0.022). Rel-B positive cases exhibited longer OS and PFS but the result was not statistically significant (p 0.05).

CONCLUSION: Tim-3 can be a good prognostic predictor and treatment candidate, especially in patients with IDH-1 negative grade 4 diffuse gliomas however, further studies with more cases are needed for Rel-B. The significant relationship between Tim-3 and Rel-B expressions supported the interaction between NF-κB and immune checkpoint pathways.

PMID:39840558 | DOI:10.5137/1019-5149.JTN.43568-23.2

BJU Int. 2025 Jan 22. doi: 10.1111/bju.16641. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the association between prostate-specific antigen (PSA) density (PSAD) and prostate cancer mortality after a benign result on systematic transrectal ultrasonography (TRUS)-guided prostate biopsy.

PATIENTS AND METHODS: This retrospective study used data from the Finnish Randomised Study of Screening for Prostate Cancer (FinRSPC) collected between 1996 and 2020. We identified men aged 55-71 years randomised to the screening arm with PSA ≥4.0 ng/mL and a benign systematic TRUS-guided biopsy result. The cumulative prostate cancer mortality of men stratified by a PSAD cutoff of 0.15 ng/mL/cm³ was modelled with competing risk functions. The ability of PSAD, PSA, and base variables (age at biopsy, DRE result, socioeconomic status, 5α-reductase inhibitor usage, family history, and Charlson Comorbidity Index (CCI)) to predict prostate cancer death was compared using c-statistics and a likelihood ratio test.

RESULTS: After excluding 10 men without PSA data within 2 years of the biopsy and 65 without prostate volume data, 2276 men were eligible for inclusion in the study. A total of 50 men died from prostate cancer and 1028 from other causes during a median (interquartile range) follow-up of 17.4 (13.2-20.9) years. The cumulative prostate cancer mortality of men with PSAD <0.15 ng/mL/cm³ was significantly lower than that of men with PSAD ≥0.15 ng/mL/cm³: 0.5% (95% confidence interval [CI] 0.2%-1.1%) vs 2.0% (95% CI 1.2%-3.1%) at 15 years (Grey’s test, P = 0.001). The model consisting of PSAD, PSA and the base variables predicted prostate cancer mortality (c-statistic 0.781) significantly better than either the base variables alone (c-statistic 0.737; likelihood-ratio test, P = 0.003) or the base variables and PSA (c-statistic 0.765; likelihood-ratio test, P = 0.039).

CONCLUSION: Prostate cancer mortality after a benign systematic TRUS-guided biopsy is low. In these patients, PSAD predicts prostate cancer mortality and provides additional value to other clinical variables. PSAD-based stratification can be used to guide follow-up strategy.

PMID:39840544 | DOI:10.1111/bju.16641

J Clin Pharmacol. 2025 Jan 22. doi: 10.1002/jcph.6192. Online ahead of print.

ABSTRACT

Obesity significantly influences drug pharmacokinetics (PK), which challenges optimal dosing. This study examines the effects of diet-and-exercise-induced weight loss on key drug-metabolizing enzymes and gastric emptying in patients with obesity, who frequently require medications for comorbidities. Participants followed a structured weight management program promoting weight loss over 3-6 months and were not concomitantly on potential CYP inducers or inhibitors. Using a drug cocktail of acetaminophen, caffeine, omeprazole, and midazolam, we assessed UGT1A1, CYP1A2, CYP2C19, and CYP3A4 enzyme activities before and after weight loss, respectively, by measuring parent and metabolite concentrations. The time to maximum acetaminophen plasma concentrations reflected the gastric emptying time. PK profiles were compared across two phases: baseline (Phase 1) and post-weight loss (Phase 2). Twenty-four participants enrolled, 21 completed Phase 1 and 12 completed both phases. Statistically significant (N = 12, P < .05) gains in CYP2C19 and CYP3A4 activity were observed after weight loss of 7.6% to 26.2%, with a median [25th, 75th percentile] increase in activity of 90.5 [15.0, 194.3] % and 43.0 [7.5, 68.0] %, respectively. A 2- or 3-h single plasma sample-based ratio of the metabolite to parent concentration strongly correlated with the respective AUC ratio for the drug metabolism phenotype (N = 21). Our findings provide provisional data for evaluation of the effects of non-pharmacologically and non-surgically induced weight loss on gastric emptying and drug metabolism for future physiologically based PK models. Development of mechanistic models to optimize drug dosing in obesity are necessary since weight and body composition shifts are expected with emerging new treatments.

PMID:39840538 | DOI:10.1002/jcph.6192

J Endovasc Ther. 2025 Jan 22:15266028241312356. doi: 10.1177/15266028241312356. Online ahead of print.

ABSTRACT

OBJECTIVE: There is a lack of consensus regarding the optimal antithrombotic therapy (ATT) after popliteal and infrapopliteal (PIP) endovascular therapy (EVT). Currently, dual antiplatelet therapy (DAPT) for 3 months and single antiplatelet therapy (SAPT) are the most prescribed regimens in the Netherlands. Thus far, no randomized comparison has been performed on the optimal ATT approach. Therefore, this study compared the efficacy and safety of 3-month DAPT with SAPT following PIP EVT.

DESIGN: Retrospective analysis of prospectively collected data from a multicenter registry.

METHODS: The Dutch chronic lower limb-threatening ischemia registry (THRILLER) collected prospective data on patients enrolled between January 2021 and October 2023. As for ATT, only patients prescribed antiplatelet therapy (APT), were included in this analysis. The primary efficacy outcome was a composite of 3-month major adverse cardiovascular events (MACEs, ie, myocardial infarction, cerebrovascular event, cardiovascular death), major adverse limb events (MALEs, ie, major amputation, reintervention), and non-cardiovascular death. Secondary efficacy outcomes were 3-month MACE, MALE, and all-cause mortality. The primary safety outcome was major bleeding according to the ‘Thrombolysis In Myocardial Infarction’ (TIMI) classification. Descriptive statistics and Cox proportional hazard models were applied.

RESULTS: In total, 460 of 840 THRILLER patients used DAPT or SAPT as ATT and were therefore included in the analysis. Of these, 322 (70%) received DAPT and 138 (30%) received SAPT. In total, 73 (15.9%) primary efficacy outcomes were observed of which 21 (15.2%) events in the SAPT group and 52 (16.1%) events in the DAPT group. No significant differences were observed between SAPT and DAPT for the primary efficacy outcomes or any of the secondary efficacy outcomes. In both groups, one case of major bleeding was observed.

CONCLUSION: The findings suggest that 3 months of DAPT is not superior to SAPT. A well-powered randomized trial is warranted to assess the efficacy and safety of post-procedural DAPT in chronic limb-threatening ischemia (CLTI) patients undergoing PIP EVT.

CLINICAL IMPACT: This manuscript reports on the efficacy and safety outcomes of 3 months of DAPT versus SAPT, which are commonly chosen therapies following popliteal and infrapopliteal endovascular therapy. No significant difference was found between the two groups regarding major adverse cardiovascular events, all-cause death, major amputation, or major bleeding. Therefore, 3 months of DAPT does not seem superior to SAPT. These results suggest that SAPT appears to be a sufficient alternative when considering 3 months of DAPT. Further research should verify these outcomes and focus on the efficacy and safety of prolonged DAPT suppletion after endovascular therapy.

PMID:39840536 | DOI:10.1177/15266028241312356

J Clin Pharmacol. 2025 Jan 22. doi: 10.1002/jcph.6191. Online ahead of print.

ABSTRACT

Albuvirtide (ABT) is a novel long-acting fusion inhibitor for human immunodeficiency virus type 1 (HIV-1), and may be co-administered with rifampicin (RIF) in patients concurrent with tubercle bacillus and HIV-1. This study was conducted to investigate the pharmacokinetic effect of co-administration of the two drugs. In the study, 24 healthy volunteers were randomized to receive ABT alone or with RIF. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry for RIF and competitive enzyme-linked immunosorbent assay for ABT. Co-administration with RIF increased the maximum concentration (C_max) of ABT by 6.93%, and the area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC_0-t) by 21.31%; the geometric mean ratio values (GMRs) for C_max and AUC_0-t of ABT when co-administered with RIF, relative to administered alone, were 106.93% (90% confidence interval [CI] 97.53%-117.23%) and 121.31% (90% CI 108.68%-135.40%), respectively. Co-administration with ABT decreased the steady-state C_max (C_max,ss) of RIF by 10.19%, and the steady-state AUC from time 0 to 24 h (AUC_{0-24 h,ss}) by 19.93%; the GMRs for C_max,ss and AUC_{0-24 h,ss} of RIF when co-administered with ABT, relative to administered alone, were 89.81% (90% CI, 79.97%-104.79%) and 80.07% (90% CI 75.68%-84.72%), respectively. The time to reach Cmax (Tmax) of both ABT and RIF demonstrated no statistically significant difference, whether administered alone or concurrently. The pharmacokinetics profiles of both RIF and ABT changed to some extent when co-administered, while no clinically significant impact on these two drugs was observed, indicating that ABT and RIF can be used together without necessitating dose adjustments.

PMID:39840531 | DOI:10.1002/jcph.6191

J Anat. 2025 Jan 22. doi: 10.1111/joa.14195. Online ahead of print.

ABSTRACT

The fibula, despite being traditionally overlooked compared to the femur and the tibia, has recently received attention in primate functional morphology due to its correlation with the degree of arboreality (DOA). Highlighting further fibular features that are associated with arboreal habits would be key to improving palaeobiological inferences in fossil specimens. Here we present the first investigation on the trabecular bone structure of the primate fibula, focusing on the distal epiphysis, across a vast array of species. We collected μCT data on the distal fibula for 21 species of primates, with representatives from most of the orders, and we employed a recently developed approach implemented in the R package ‘indianaBones’ to isolate the entire trabecular bone underlying an epiphysis or articular facet. After extracting both traditional trabecular parameters and novel topological indices, we tested for the posited relationship between trabecular bone and DOA. To disentangle this effect from others related to body size and phylogenetic relationship, we included a body mass proxy as covariate and employed phylogenetic comparative methods. We ran univariate/multivariate and exploratory/inferential statistical analyses. The trabecular structure of the fibular distal epiphysis in primates does not appear to be associated with the DOA. Instead, it is strongly affected by body mass and phylogenetic relationships. Although we identified some minor trends related to human bipedalism, our findings overall discourage, at this stage, the study of distal fibula trabecular bone to infer arboreal behaviors in extinct primates. We further found that body size distribution is strongly related to phylogeny, an issue preventing us from unravelling the influence of the two factors and that we believe can potentially affect future comparative analyses of primates. Overall, our results add to previous evidence of how trabecular traits show variable correlation with locomotor aspects, size and phylogenetic history across the primate skeleton, thus outlining a complex scenario in which a network of interconnected factors affects the morphological evolution of primates. This work may represent a starting point for future studies, for example, focusing on the effect of human bipedalism on distal fibula trabecular bone, or aiming to better understand the effects of body size and phylogenetic history on primate morphological evolution.

PMID:39840527 | DOI:10.1111/joa.14195

Sci Prog. 2025 Jan-Mar;108(1):368504241307719. doi: 10.1177/00368504241307719.

ABSTRACT

BACKGROUND: Retail involves directly delivering goods and services to end consumers. Natural disasters and epidemics/pandemics have significant potential to disrupt supply chains, leading to shortages, forecasting errors, price increases, and substantial financial strains on retailers. The COVID-19 pandemic highlighted the need for retail sectors to prepare for crisis impacts on sales forecasts by regularly assessing and adjusting sales volumes, consumer behavior, and forecasting models to adapt to changing conditions.

METHODS: This study explores strategies for adapting sales forecasts and retail approaches in response to such crises. By employing different machine learning (ML) methods, we analyze consumer behavior changes and sales impacts across various product categories, including bottom wear, top wear, one piece, accessories, outwear, and shoes during the COVID-19 pandemic.

RESULTS: The gradient boosting and CatBoost algorithms excelled in product groups with significant sales changes during the pandemic. The Multi-Layer Perceptron (MLP) algorithm performed well in low-volume categories like accessories and footwear. Meanwhile, MLP, LightGBM, and XGBoost were effective in medium-volume categories such as outerwear and underwear.

CONCLUSION: The findings highlight the efficacy of these models in adapting sales forecasts to crisis conditions, offering a practical approach to enhancing retail resilience against future disruptions. This study offers an effective approach for adapting sales forecasting to shifting consumer behaviors during crises.

PMID:39840498 | DOI:10.1177/00368504241307719