Nevin Manimala

Curr Issues Mol Biol. 2025 Mar 26;47(4):228. doi: 10.3390/cimb47040228.

ABSTRACT

The aim of this research was to provide a comparative analysis of the major parameters of the blood lipid spectrum found both in the case of brain tumors and in atherosclerosis, as well as to assess the correlation of these indicators with the proliferative activity index Ki-67 in cells. Blood analyses were conducted on samples from 50 patients with brain tumors and 50 patients with cerebral atherosclerosis. Blood plasma from 50 essentially healthy people was used for controls. Significant differences were found in the parameter values between the atherosclerosis sufferers and the control group only for their ratios of neutral lipids to cholesterol. Of the short-chain fatty acids, butyric acid is of greatest interest due to the significant differences of its levels from the control group in the blood of both patients with meningiomas and of those with gliomas. Statistically significant correlation coefficients between the levels of the Ki-67 cell proliferation marker and, in particular, butyric acid were found when compared with the neutral lipids to cholesterol ratios. These identified parameters of the blood plasma lipid spectrum can be used for preoperative diagnostics of brain tumors. However, these ratios cannot be used as preoperative noninvasive predictors of the level of the Ki-67 mitotic index, as no significant differences corresponding to this were found for low-grade or for high-grade anaplasia of brain tumors.

PMID:40699627 | DOI:10.3390/cimb47040228

Curr Issues Mol Biol. 2025 Mar 21;47(4):216. doi: 10.3390/cimb47040216.

ABSTRACT

High heterogeneity of breast cancer is due to a large variety of cancer cell characteristics at the genomic, epigenomic, transcriptome, and proteomic levels. One of the difficulties is the separation of molecular biological subtypes based on the expression of tumor markers. Another problem is the difficulty of venipuncture in cancer patients when taking blood at different stages of patient care. Objectives: To identify statistically significant changes in the level of salivary tumor markers depending on the molecular biological subtype of breast cancer in order to improve understanding of the individual properties of each of its subtypes, 140 volunteers (breast cancer-110; healthy control-30) took part in the case-control study. Saliva was collected strictly before the start of treatment, and the content of ten tumor markers was determined by ELISA: EGFR2, CA15-3, CA27.29, MCA, CEA, CA125, CA19-9, CYFRA 21-1, ferritin, and CRP. The content of MUC1 antigens (CA15-3, CA27.29, and MCA) statistically significantly decreased in the luminal B(+) subtype of breast cancer. The CA19-9 antigen showed high sensitivity to low HER2 expression. A reliable increase in the level of CYFRA 21-1 in saliva was shown in luminal A and luminal B(-) breast cancer. The work demonstrates the diagnostic capabilities of saliva in measuring tumor markers in patients with breast cancer. It was also found that there are reliable differences in the expression level and set of tumor markers in saliva depending on the molecular biological subtype of breast cancer. Thus, CYFRA 21-1 significantly increases with luminal A and luminal B(-), but CRP only increases with luminal A. CA15-3, CA27.29, MCA, and CA19-9 significantly decrease with luminal B(+) breast cancer.

PMID:40699615 | DOI:10.3390/cimb47040216

Int J Oral Maxillofac Implants. 2025 Jul 23;0(0):1-26. doi: 10.11607/jomi.11144. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to compare the peri-implant bone surrounding a new abutment free tissue-level implant design with classic tissue-level implants restored with titanium-base abutments.

MATERIALS AND METHODS: A retrospective cohort study was conducted between 2018 and 2022 in patients requiring dental implants. A total of 53 patients received either a novel abutment-free tissue-level implant (n₁ = 50 sites) or a conventional tissue-level implant (n₂ = 50 sites). Patients were monitored for one year after prosthetic loading, with the primary endpoint being any change in hard tissue around the implant. Bone resorption was evaluated using cone beam computed tomography (CBCT). Statistical analyses included Fisher’s exact test for categorical variables and Student’s t-test for continuous variables. Longitudinal outcomes were assessed using linear mixed models to account for within patient correlations over time. The models incorporated treatment group, time, and their interaction, with statistical significance evaluated using Wald tests. Non-inferiority was assessed with one-sided p-values <0.025, while two-sided p-values <0.05 indicated statistical significance.

RESULTS: No significant differences in patient demographics or complications were found between abutment-free and conventional implants. However, abutment-free implants exhibited less buccal bone loss than traditional implants. The abutment-free implant group had significantly lower buccal bone loss (p-values of 0.025 and 0.024 for oral palatal/lingual bone and alveolar ridge width, respectively).

CONCLUSION: The results of this study suggest that abutment-free dental implants offer advantages in reducing buccal bone loss compared to conventional implants, potentially due to their ability to mitigate risks to peri-implant tissues. Further research is warranted to evaluate their long-term efficacy and safety.

PMID:40699608 | DOI:10.11607/jomi.11144

JAMA. 2025 Jul 23. doi: 10.1001/jama.2025.11178. Online ahead of print.

ABSTRACT

IMPORTANCE: Cognitive behavioral therapy (CBT) skills training interventions are recommended first-line nonpharmacologic treatment for chronic pain, yet they are not widely accessible.

OBJECTIVE: To examine effectiveness of remote, scalable CBT-based chronic pain (CBT-CP) treatments (telehealth and self-completed online) for individuals with high-impact chronic pain, compared with usual care.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness, 3-group, phase 3 randomized clinical trial enrolled 2331 eligible patients with high-impact chronic musculoskeletal pain from 4 geographically diverse health care systems in the US from January 2021 through February 2023. Follow-up concluded in April 2024.

INTERVENTIONS: Participants were randomized 1:1:1 to 1 of 2 remote, 8-session, CBT-based skills training treatments: health coach-led via telephone/videoconferencing (health coach; n = 778) or online self-completed program (painTRAINER; n = 776); or to usual care plus a resource guide (n = 777).

MAIN OUTCOMES AND MEASURES: The primary outcome was attaining or exceeding the minimal clinically important difference (MCID) in pain severity score (≥30% decrease; score range, 0-10) on the 11-item Brief Pain Inventory-Short Form from baseline to 3 months; 6 and 12 months from baseline were secondary time points. Secondary outcomes at 3, 6, and 12 months included pain intensity, pain-related interference, PROMIS (Patient-Reported Outcomes Measurement Information System) social role and physical functioning; and patient global impression of change.

RESULTS: Among 2331 eligible randomized individuals (mean age, 58.8 [SD, 14.3] years; 1712 [74%] women; 1030 [44%] rural/medically underserved), 2210 (94.8%) completed the trial. At 3 months, the adjusted percentage of participants achieving 30% or greater decrease in pain severity score was 32.0 (95% CI, 29.3-35.0) in the health coach group, 26.6 (95% CI, 23.4-30.2) in the painTRAINER group, and 20.8 (95% CI, 18.0-24.0) in the usual care group. Both intervention groups were significantly more likely to attain an MCID in pain severity compared with control (health coach vs usual care: relative risk [RR], 1.54 [95% CI, 1.30-1.82]; painTRAINER vs usual care: RR, 1.28 [95% CI, 1.06-1.55]), and the health coach program was more effective than the online self-completed painTRAINER program (health coach vs painTRAINER: RR, 1.20 [95% CI, 1.03-1.40]). Statistically significant benefits were observed for both intervention groups vs usual care at 6 and 12 months after randomization for the pain severity outcomes and for other secondary pain and functioning outcomes.

CONCLUSIONS AND RELEVANCE: Remote, scalable CBT-CP treatments (delivered either via telehealth or self-completed modules online) resulted in modest improvements in pain and related functional/quality-of-life outcomes compared with usual care among individuals with high-impact chronic pain. These lower-resource CBT-CP treatments could improve availability of evidence-based nonpharmacologic pain treatments within health care systems.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04523714.

PMID:40699570 | DOI:10.1001/jama.2025.11178

Expert Rev Hematol. 2025 Jul 23. doi: 10.1080/17474086.2025.2535422. Online ahead of print.

ABSTRACT

BACKGROUND: Mesenchymal stromal cells (MSCs) have emergedas a potential alternative therapeutic strategy for the prophylaxisof graft-versus-host disease (GVHD) in patients undergoinghematopoietic stem cell transplantation (HSCT).

RESEARCH DESIGN AND METHODS: This meta-analysis included eight randomizedcontrolled trials (RCTs) involving 570 patients. The primary outcomesassessed were overall survival (OS), the development of acute GVHD(aGVHD), and chronic GVHD (cGVHD). Secondary outcomes includedprimary disease relapse and adverse events. The statistical analysiswas performed using Review Manager (RevMan 5.4) with a random-effectsmodel.

RESULTS: The meta-analysis showed a significantimprovement in overall survival in the MSC group compared to thecontrol group (RR 1.12; 95% CI: 1.02-1.23), with no evidence ofheterogeneity (I² = 0%). MSC prophylaxis was associated with asignificant reduction in the incidence of aGVHD (RR 0.67; 95% CI:0.40-0.83, I² = 33%) and cGVHD (RR 0.65; 95% CI: 0.49-0.87, I² = 0%).However, no significant difference was found between the MSC andcontrol groups regarding primary disease relapse (RR 1.00; 95% CI:0.73-1.38, I² = 0%) or the incidence of infections (RR 0.80; 95% CI:0.57-1.11, I² = 0%). In terms of patients with at least one adverseevent, no statistically significant difference was observed betweenthe two groups (RR 1.10; 95% CI: 0.74-1.63, I² = 34%).

CONCLUSIONS: MSC prophylaxis significantly improves overallsurvival and reduces the incidence of both aGVHD and cGVHD in HSCTpatients, without increasing the risk of relapse, infections, oradverse events, indicating its potential as a safe and effectiveintervention for GVHD management. Further large-scale, multicenterRCTs are needed to validate or refute the current findings.

REGISTRATION: This review has been registered with theInternational Prospective Register of Systematic Reviews (PROSPERO)(CRD42024569358).

PMID:40699555 | DOI:10.1080/17474086.2025.2535422

Alzheimers Dement. 2025 Jul;21(7):e70513. doi: 10.1002/alz.70513.

ABSTRACT

INTRODUCTION: South Africa faces growing dementia challenges, worsened by limited medical resources and low education. Modifiable risk factors like hearing and vision impairments remain understudied despite their high prevalence.

METHODS: We analyzed data from 567 participants in a rural South African cohort to examine the associations between vision and hearing impairment, and dementia outcomes. Multinomial logistic regression assessed associations between sensory impairments (distance vision, near vision, hearing) and mild cognitive impairment (MCI) or dementia. Linear regression examined sensory impairment and predicted dementia probability score 2 years later.

RESULTS: Half of the participants were over 70, with no formal education. Sensory impairments were common, especially in dementia cases. Distance vision impairment was linked to both MCI and dementia, while near vision and hearing impairments were associated with dementia. Hearing impairment also predicted higher dementia probability after 2 years.

DISCUSSION: Addressing sensory impairments is key to dementia prevention in rural South Africa.

HIGHLIGHTS: Among rural older South Africans, 65% had near vision impairment and 47% had hearing impairment. Distance or near vision and hearing impairments are linked to an increased risk of dementia. Distance vision impairment is also associated with a higher risk of mild cognitive impairment (MCI). Dementia risk was seven times higher with distance vision, near vision and hearing impairment. Hearing impairment increased the probability of dementia 2 years later in initially non-demented individuals.

PMID:40693440 | DOI:10.1002/alz.70513

Biomed Chromatogr. 2025 Sep;39(9):e70173. doi: 10.1002/bmc.70173.

ABSTRACT

In the present study, it was aimed to optimize the extraction of fumaric acid from Fumaria officinalis L. by response surface methodology and its quantification by a newly developed and validated reverse phase high performance liquid chromatography method. Chromatographic separations were performed at 40°C with a C18 column. Aqueous o-phosphoric acid solution and methanol were used as the mobile phase by gradient elution. The flow rate was set at 1.0 mL/min, and the injection volume was 20 μL. Fumaric acid was detected at 215 nm with a UV detector. The method was linear in the range of 10.00-200.00 μg/mL. The limits of detection and quantification were 3.02 μg/mL and 9.15 μg/mL, respectively. The relative mean errors were ≤ 3.77%, whereas the relative standard deviation values were calculated as ≤ 0.48%. The conditions to obtain an extract with high fumaric acid content were optimized by central composite design, a type of response surface methodology. The independent variables were extraction time, solvent volume, and temperature for the maceration procedure, where fumaric acid concentration was the response. The experimental model was evaluated statistically and found to fit well, considering the lack-of-fit p value of 0.211 and coefficient of determination 0.9862 at a confidence level of 95%.

PMID:40693429 | DOI:10.1002/bmc.70173

Clin Exp Rheumatol. 2025 Jul 21. doi: 10.55563/clinexprheumatol/t0xgtk. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess risk factors for rethrombosis, the intensity and maintenance of anticoagulation in primary antiphospholipid syndrome (APS).

METHODS: We retrospectively included 81 patients with thrombotic APS under VKAs with ≥4 INR determinations per year in at least 1 year. We defined an index period as the time between the first available INR value and the next thrombotic event, or the time between the first and last available INR if rethrombosis-free. We recorded demographic and clinical/serologic variables, mean INR, mean INR-AUC, and anticoagulation intensity (INR<2.5, INR 2.5-3.5, and INR>3.5). For the statistical analysis we used Cox survival analysis, hazard function (H(t)) curves and AUC.

RESULTS: The median follow-up time was 6.4 years. 64 patients had no rethrombosis, whereas 17 did (15 arterial, 2 venous). The risk factors for rethrombosis were number of previous rethrombosis (RR 7.3 95% CI 2.3-322.7, p=0.007) and INR intensity (RR 0.03, 95% CI 0.002-0.367, p=0.001). Results were similar when only arterial events were analysed. At the H(t) curves, the cumulative risk was higher in patients with an INR <2.5 than those in an INR of 2.5-3.5. A mean INR of 2.2 identified patients at risk of rethrombosis (SE=0.82, SP=0.20, AUC=0.42).

CONCLUSIONS: The number of previous thrombotic events and the intensity of anticoagulation are rethrombosis risk factors. An INR ranging 2.5-3.5 protects against re-thrombosis, including arterial events.

PMID:40693427 | DOI:10.55563/clinexprheumatol/t0xgtk

J Exp Biol. 2025 Aug 1;228(15):jeb250537. doi: 10.1242/jeb.250537. Epub 2025 Jul 22.

ABSTRACT

Visual ecology, the study of how animals acquire and respond to visual information in nature, has grown rapidly over the past few decades. Research in this field has transformed our understanding of fundamental processes, such as the neurobiological basis of behavior and the diversification of species through sensory drive. The recent growth in the field has been accompanied by leaps in our understanding of the diversity of visual systems and in the development of novel technologies and techniques (for example, those allowing us to measure scenes and signals). With such growth, however, it is more important than ever to integrate wide perspectives and expertise to move the field forward in the most productive way. To that end, in summer 2024, 30 visual ecologists from around the world – spanning all career stages – met to discuss the state of the field. From that meeting, we identified two broad emerging themes in the study of visual ecology. (1) Can we further ‘step inside’ the perceptual experience of a non-human animal? (2) Can foundational ‘rules’ of vision and visual stimuli be identified? Although large questions such as these can feel unanswerable, this is where some of the most exciting discoveries in visual ecology remain to be made. Here, we outline eight relevant areas of research and identify ways in which researchers can bring us closer to answering these complex questions.

PMID:40693401 | DOI:10.1242/jeb.250537

Insect Sci. 2025 Jul 22. doi: 10.1111/1744-7917.70123. Online ahead of print.

ABSTRACT

Galleria mellonella is becoming increasingly used as a model organism for studying human pathogen infection disease. Therefore, all factors affecting the level of immune response of G. mellonella should be evaluated. One of these factors is DNA methylation, among the most important epigenetic modifications. Firstly, we investigated the presence of CpG dinucleotides and their methylation status of eggs, last instars, pupae, and adults using HpaII, MspI, and ScrFI methylation-sensitive restriction endonucleases. The gel analysis of the restriction pattern of HpaII, MspI, ScrFI, and MspI+ScrFI on G. mellonella genomic DNA showed that all enzymes produced a wide range of smears. The digestion of DNA samples of egg, pupa, and adult resulted in a smear at higher molecular weight for MspI+ScrFI, and these differences were statistically significant. These results confirm the presence of CpG dinucleotides and methylation at the internal and outer cytosines in different developmental stages of G. mellonella. Presence of global DNA methylation, which was by 3%-5% was investigated in various developmental stages of G. mellonella. Then, different levels of DNA methylation in the last instars of G. mellonella were created with the hypomethylation agent, zebularine (0.25-32 mg/mL), and immunity responses were examined. The most effective doses of zebularine, to create a global hypomethylation status in G. mellonella larvae, were 0.25 and 1 mg/mL. The humoral/cellular immune response of G. mellonella larvae became weak at high hypomethylation. These results present the level of DNA methylation during all developmental stages of G. mellonella and how zebularine treatment affects physiological processes.

PMID:40693385 | DOI:10.1111/1744-7917.70123