Nevin Manimala

Clin Epigenetics. 2025 Jan 29;17(1):16. doi: 10.1186/s13148-025-01822-2.

ABSTRACT

BACKGROUND: Glioblastoma is the commonest malignant brain tumor and has a very poor prognosis. Reduced expression of the MGMT gene (10q26.3), influenced primarily by the methylation of two differentially methylated regions (DMR1 and DMR2), is associated with a good response to temozolomide treatment. However, suitable methods for detecting the methylation of the MGMT gene promoter and setting appropriate cutoff values are debated.

RESULTS: A cohort of 108 patients with histologically and genetically defined glioblastoma was retrospectively examined with methylation-specific Sanger sequencing (sSeq) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methods. The DMR2 region was methylated in 29% of samples, whereas DMR1 was methylated in 12% of samples. Methylation detected with the MS-MLPA method using probes MGMT_215, MGMT_190, and MGMT_124 from the ME012-A1 kit (located in DMR1 and DMR2) correlated with the methylation of the corresponding CpG dinucleotides detected with sSeq (p = 0.005 for probe MGMT_215; p < 0.001 for probe MGMT_190; p = 0.016 for probe MGMT_124). The threshold for methylation detection with the MS-MLPA method was calculated with a ROC curve analysis and principal components analysis of the data obtained with the MS-MLPA and sSeq methods, yielding a weighted value of 0.362. Thus, methylation of the MGMT gene promoter was confirmed in 36% of samples. These patients had statistically significantly better overall survival (p = 0.003).

CONCLUSIONS: Our results show that the threshold for methylation detection with the MS-MLPA method determined here is useful from a diagnostic perspective because it allows the stratification of patients who will benefit from specific treatment protocols, including temozolomide. Detailed analysis of the MGMT gene promoter enables the more-precise and personalized treatment of patients with glioblastoma.

PMID:39881389 | DOI:10.1186/s13148-025-01822-2

BMC Nurs. 2025 Jan 29;24(1):110. doi: 10.1186/s12912-024-02657-7.

ABSTRACT

BACKGROUND: One of the best ways to impart important skills to trainees is through simulation-based training, which is more reliable than the conventional clinical examination method. It is used in pediatric nursing training to allow nurses to practice and improve their clinical and conversational skills during an actual child encounter. A heel-prick is a complex psychomotor task that requires skill and knowledge from the pediatric nurse performing the procedure while applying for the National Newborn Screening Program.

AIM: This study aimed to assess the impact of simulation-based training on pediatric nurses’ knowledge and performance regarding the heel-prick technique used during newborn blood screening tests in select hospitals in Saudi Arabia and Egypt.

METHODS: This study utilized an experimental pre-test and post-test design. The G*Power Program^® Version 3.1.9.4 was employed to determine the sample size to fulfil the study’s objectives. The sample consisted of 50 nurses recruited from the Maternity & Children Hospital Bisha, Al-Namas General Hospital in the Kingdom of Saudi Arabia, and Pediatric Assiut University Hospital in Egypt; they were randomly divided into two groups of 25 nurses, intervention and control. The sample size was calculated assuming α level of 0.05, a β level of 0.20, and a desired power of 80%. The study was conducted from June 1st to August 30th, 2023. Two data collection instruments were used: a structured questionnaire and an observational checklist for the heel-prick technique in newborn bloodspot screening sample collection. Before the training intervention, a pre-test assessing knowledge and performance was administered. Intervention and control groups received two hours of instruction every 5 days. The researcher utilized PowerPoint presentations, videos, and interactive learning session intervention to deliver the instructional content to increase nurses’ knowledge and also employed mannequins for a newborn blood spot test simulator to train participants on performance. A post-test 1 was administered immediately after the training sessions. Additionally, post-test 2 was conducted 20 days after the study and followed up after 40 days of intervention (post-test 3).

RESULTS: The study participants ranged in age from 25 to 30 years, with the majority being female. A statistically significant difference was observed in the knowledge and performance of pediatric nurses following simulation-based training. The majority of nurses demonstrated correct responses after the simulation-based learning intervention. However, the nurses’ knowledge varied, as evidenced by the mean scores of their total knowledge regarding the heel-prick for the newborn bloodspot screening test. Immediately after the learning intervention session, the mean scores were 37.86 ± 1.28 and 34.84 ± 1.22 in the experimental and control groups, respectively. At 20 days post-training, the mean scores were 40.16 ± 1.11 and 33.55 ± 1.18 in the experimental and control groups, respectively, with a highly statistically significant difference (P-value = 0.0001). Moreover, at 40 days post-training, the mean scores were 39.54 ± 1.09 and 29.66 ± 1.32 in the experimental and control groups, respectively, and a statistically significant difference was found (P-value = 0.0001). Conversely, the level of nurses’ performance before training was below average, with 52% and 56% in the experimental and control groups, respectively. Immediately after the simulation-based learning, the majority of nurses in the experimental group demonstrated a good level of performance in post-test 1, post-test 2, and post-test 3, with a statistically significant difference compared to the nurses in the control group (P-value = 0.001).

CONCLUSION: The use of newborn blood spot test simulators is useful during simulation-based training in raising the overall level of the pediatric nurses’ knowledge and performance, especially through 1, 2, & 3 post-training tests. The findings have several practical implications, and one is that pediatric nurses’ performance and knowledge concerning newborn blood screening tests should be prioritized to guarantee patient safety and quality of care in pediatric patient scenarios. It is essential for nursing trainers to effectively train pediatric nurses’ by using simulators to improve their caring knowledge and performance in educational settings. By improving nurses’ knowledge and performance, we can reduce the dangers caused by their training on real neonates; also, it can be an attractive way to train nurses when trained by simulators and ultimately enhance the overall quality of nursing services in the hospital.

CLINICAL TRIAL NUMBER: This study was registered by Clinical Trials.gov Identifier: (NCT06685471|| https://www.

CLINICALTRIALS: gov/ ) with the clinical Trail registry (12-11-2024).

PMID:39881378 | DOI:10.1186/s12912-024-02657-7

J Orthop Surg Res. 2025 Jan 30;20(1):111. doi: 10.1186/s13018-025-05475-y.

ABSTRACT

BACKGROUND: The use of intravenous tranexamic acid (TXA), an antifibrinolytic agent, has been shown to effectively reduce total blood loss and transfusion rates in total knee arthroplasty (TKA). The aim of this paper is to evaluate the implementation lag and clinical uptake of the use of TXA for primary TKA after publication of two landmark studies. Additionally, it assessed the efficacy of TXA use in TKA in reducing post-operative blood transfusions and hospital length of stay (LOS).

METHODS: A total of 763 patients aged over 18 years of age underwent primary TKA at a level 4 metropolitan hospital in Australia between January 2011 and December 2017. Primary outcome measure was use of TXA at operative induction. Secondary outcome measures were post-operative blood transfusion, haemoglobin levels and in-hospital length of stay.

RESULTS: The rate of TXA uptake was ≥ 50% by April-June 2013, 1.5 years following landmark paper publication. TXA use was ≥ 90% by April-June 2015, equating to 3.5 years after landmark publication. For each additional year since publication, the odds that TXA was used in a TKA surgery increased by 254.3%, 95% CI (confidence interval) [195.2%, 334.1%]. There was a negative association between TXA use and blood transfusion rate (p < 0.001), while controlling for other variables. TXA use reduced the odds of blood transfusions occurring by 73.5%, 95% CI [35.8% and 89.8%]. Analysis showed that reduced LOS was seen even after controlling for post-operative blood transfusion (p < 0.05).

CONCLUSION: The implementation lag from research to clinical practice, using ≥ 90% TXA use in TKA as a proxy, was 3.5 years. The use of TXA reduced LOS and blood transfusion rate in TKA patients.

PMID:39881376 | DOI:10.1186/s13018-025-05475-y

J Orthop Surg Res. 2025 Jan 29;20(1):108. doi: 10.1186/s13018-025-05541-5.

ABSTRACT

BACKGROUND: The endoplasmic reticulum stress (ER stress) has been involved in various musculoskeletal disorders including non-traumatic osteonecrosis of femoral head (NT-ONFH).

OBJECTIVE: The current study aimed to investigate the association of glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) expressions in serum and femoral head (FH) tissues with NT-ONFH’s severity.

METHODS: We enrolled NT-ONFH patients (n = 150) alongside healthy controls (HCs, n = 150). Meanwhile, 49 patients with femoral neck fracture (FNF) were also enrolled. Serum CHOP and GRP78 levels were determined through enzyme linked immunosorbent assay (ELISA). Local CHOP and GRP78 expressions were detected by immunohistochemistry, western blot, alongside real-time polymerase chain reaction (RT-PCR). Radiographic severity was assessed by FICAT grading system. The visual analogue scale (VAS) together with Harris hip score (HHS) were utilized to determine symptomatic severity.

RESULTS: Serum CHOP and GRP78 levels were markedly increased in NT-ONFH patients than HCs. NT-ONFH patients at FICAT stage 4 showed significant higher serum CHOP and GRP78 levels in contrast with those at stage 3. Furthermore, patients at stage 3 demonstrated higher serum CHOP and GRP78 levels than those at stage 2. There was a positive correlation observed between the serum CHOP and GRP78 levels and the severity of the FICAT stages. A total of 42 ONFH patients at FICAT stage 3, 40 patients at FICAT stage 4, and 49 FNF patients received total hip replacement (THR). The mRNA and protein levels of CHOP and GRP78 were elevated in necrotic area compared to the non-necrotic area of ONFH patients and the FH tissues of FNF patients with statistical significance. The expression levels of CHOP and GRP78 within the local tissues were significantly elevated in patients at FICAT stage 4 as opposed to those at stage 3. Besides, ROC curve analysis indicated that serum and local CHOP and GRP78 expressions may act as indicators of disease progression. The levels of CHOP and GRP78, both in serum and at the local site, were in a positive correlation with VAS scores but an inverse relationship with HHS.

CONCLUSIONS: Serum and local GRP78 as well as CHOP expressions were positively linked with disease progression in NT-ONFH patients. Potential therapeutics targeting ER stress related protein may serve as a method for alleviating NT-ONFH.

PMID:39881366 | DOI:10.1186/s13018-025-05541-5

BMC Sports Sci Med Rehabil. 2025 Jan 29;17(1):14. doi: 10.1186/s13102-025-01061-1.

ABSTRACT

BACKGROUND: Isokinetic dynamometry is a common tool for evaluating muscle function and is used across various disciplines. Technical advancements have shifted focus towards multi-joint exercises such as the leg press, offering insights into practical human movement dynamics. However, previous reproducibility studies have focused predominantly on single-joint exercises, warranting investigations into the reliability of multi-joint exercises. This study aimed to assess the reproducibility of peak force (PF) during multi-joint leg press exercises using the IsoMed 2000 dynamometer.

METHODS: Thirty physically active subjects (mean: stature 179.4 cm; body mass 76.0 kg; age 30.6 years) participated in three testing sessions. Each session consisted of isometric and isokinetic leg press exercises. Knee angles for isometric exercises included 100° and 140°; velocities for isokinetic exercise included 30 mm/s and 600 mm/s. The first session served as the familiarization session. Statistical analysis included paired sample t-tests, Cohen’s d effect sizes, intraclass correlation coefficients (ICC), standard errors of measurement (SEM), and Bland-Altman calculations, including corresponding plots.

RESULTS: Descriptive data revealed consistent PF across sessions, with a significant between-sessions difference observed only for isometric (100°) leg extension in the right leg (p < 0.001; d = 0.13). ICC calculations showed high relative reproducibility (ICC > 0.911), with SEM ranging from 37.6 to 294.7 N (SEM% 2.3-6.3%, respectively). Bland-Altman plots depicted minimal intersession disparities (-141.8-68.3 N, respectively – 3.02-1.26%), supporting high reliability.

CONCLUSIONS: This study highlights the reliability of assessing peak force during isometric and isokinetic leg press exercises using the IsoMed 2000 after a single familiarization session. These findings support its utility in muscular performance evaluation, urging practitioners to incorporate familiarization trials for accurate assessments.

PMID:39881349 | DOI:10.1186/s13102-025-01061-1

World J Surg Oncol. 2025 Jan 29;23(1):30. doi: 10.1186/s12957-025-03675-8.

ABSTRACT

OBJECTIVE: This study aimed to compare the expression of lymphoid enhancer factor 1 (LEF1) and β-catenin in basal cell adenoma (BA), desmoid-type fibromatosis (DF), and pancreatic solid pseudopapillary neoplasm (SPN) to evaluate their diagnostic utility in tumors associated with the WNT/β-catenin signaling pathway harboring the mutation of CTNNB1 gene 3 exon.

METHODS: Eighty tumor patients, including 26 BAs, 30 DFs, and 24 SPNs, were analyzed. Immunohistochemical staining was identified positive (nuclear staining of LEF1 and β-catenin in > 50% of tumor cells). The diagnostic rate of LEF1 alone, β-catenin alone, and their combination were compared for each tumor type and all patients.

RESULTS: Compared to β-catenin, when LEF1 alone was used for diagnosis, the diagnostic rate increased by 46.16% for BA, 16.67% for SPN, and 11.25% for all patients, but decreased by 23.34% for DF. The combined use of β-catenin and LEF1 significantly increased the diagnostic ratio in BA (46.16%), SPN (16.67%), and all patients (21.25%), but only marginally in DF (3.33%). In terms of all WNT pathway tumors with CTNNB1 gene mutation encompassed by our study, statistical analysis revealed no significant difference between LEF1 alone and β-catenin alone. However, their combined application was highly significant (P = 0.001) .

CONCLUSION: While β-catenin is commonly used as a marker for WNT pathway tumors, its variable expression and localization can be challenging for diagnosis. Our study emphasizes the importance of LEF1 as a complementary marker to β-catenin in diagnosing BA, DF, SPN, and other WNT pathway tumors activated by exon 3 CTNNB1 gene mutation. The combined use of LEF1 and β-catenin enhances diagnostic accuracy and may help the identification of these tumor types.

PMID:39881334 | DOI:10.1186/s12957-025-03675-8

Trials. 2025 Jan 30;26(1):32. doi: 10.1186/s13063-025-08734-9.

ABSTRACT

BACKGROUND: The aim of the SURECAN trial is to evaluate a person-centred intervention, based on Acceptance and Commitment Therapy (ACT Plus ( +)), for people who have completed treatment for cancer with curative intent, but are experiencing poor quality of life. We present the statistical analysis plan for assessing the effectiveness and cost-effectiveness of the intervention in improving quality of life 1 year post randomisation.

METHODS AND DESIGN: SURECAN is a multi-centre, pragmatic, two-arm, partially clustered randomised controlled superiority trial comparing the effectiveness of ACT + added to usual care with usual aftercare. The target sample size is 344 (172 per arm), randomised centrally in a 1:1 ratio.

RESULTS: The primary outcome is the total score of the Functional Assessment of Cancer Therapy scale-General (FACT-G) at 52 weeks, analysed using a partially nested mixed-effects model with heteroskedastic error terms. Secondary outcomes include scores at 16 and 52 weeks: FACT-G subscales; Fear of Cancer Recurrence Inventory (FCR4); positive and negative Impact of Cancer scales (IOCv2); Hospital Anxiety and Depression scale (HADS); Chalder Fatigue Scale (CFQ); and physical activity, measured on a modified version of the Godin scale. Health economic analyses will determine the incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life years (QALYs) derived from the Euroqol 5-Dimension 5-Level (EQ-5D-5L) compared to usual care at 52 weeks.

DISCUSSION: This manuscript is the statistical analysis plan (SAP) and economic evaluation for the SURECAN trial. Any exploratory or post hoc analyses will be identified as such in the respective analysis report.

TRIAL REGISTRATION: The trial was prospectively registered.

ISRCTN: ISRCTN67900293. Registered on 09 December 2019.

PMID:39881331 | DOI:10.1186/s13063-025-08734-9

BMC Med Ethics. 2025 Jan 29;26(1):15. doi: 10.1186/s12910-025-01164-x.

ABSTRACT

INTRODUCTION: Despite the existing reports on mistreatment and disrespectful maternal care, few studies have investigated interventions to mitigate this issue. The present study aims to assess the impact of consulting midwives on maternal rights charter on perception of respectful maternity care and postpartum blues among postpartum women in two hospitals in southern Iran.

METHODOLOGY: This quasi-experimental study was conducted on 437 postpartum women (217 mothers before the intervention and 220 mothers after the intervention) and 44 midwives working in the maternity ward of two hospitals affiliated to Bushehr University of Medical Sciences in 2023-2024. The hospitals were randomly divided into control and intervention groups. The mothers and midwives were selected using convenience and census sampling methods, respectively. Initially, the first sampling phase of postpartum women was conducted. Then, midwives in the intervention group received consultation on patient rights charter in groups of 3-4 individuals over three sessions. After the intervention, the second phase of sampling of postpartum women was conducted. Data collection tools included questionnaires assessing women’s perception of respectful maternity care and postpartum blues. The data were analyzed using descriptive and analytical statistical tests in SPSS 20.0.

RESULTS: After performing the intervention on midwives, the mean score of postpartum respectful maternity care from the perspectives of the mothers in the intervention and control hospitals were 91.08 ± 5.51 and 68.34 ± 10.81 respectively (P < 0.001). Also, the mean scores of postpartum blues in the intervention and control hospitals were 12.88 ± 4.66 and 14.85 ± 5.94 respectively (P = 0.007). Multivariable linear regression analysis revealed that consulting with midwives regarding the Maternal Rights Charter, led to an increase in respectful maternity care (β coefficient = 0.780, 95% C.I. = 19.796). ~ 24.541) and decreased postpartum blues (β coefficient = -0.172, 95% C.I. = -3.318 ~ -0.390) from the perspectives of the mothers.

CONCLUSION: Consulting midwives on patient rights charter was positively correlated with mothers’ perception of respectful maternity care and negatively correlated with postpartum blues, indicating the positive effect of intervention on increasing women’s satisfaction and reducing postpartum blues. It is recommended that this consultation be included in midwives’ continuing education programs.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:39881329 | DOI:10.1186/s12910-025-01164-x

BMC Oral Health. 2025 Jan 29;25(1):156. doi: 10.1186/s12903-025-05545-x.

ABSTRACT

BACKGROUND: To compare the effects of first premolar extraction, molar distalization, and non-extraction treatments on the angulation and vertical positions of maxillary second molars (MxM2s) and maxillary third molars (MxM3s). To our knowledge, this is the first study to compare the effects of three different treatment types on MxM3 simultaneously.

METHODS: Initial (T0) and final (T1) panoramic radiographs of three different patient groups were analyzed: first premolar extraction group (n = 26 patients, 52 MxM2, 52 MxM3), molar distalization group (n = 20 patients, 40 MxM2, 40 MxM3), and non-extraction group (n = 31 patients, 62 MxM2, 62 MxM3). Descriptive data, including growth pattern, crowding, overjet, overbite, and maxillary incisor inclination, were recorded. Angular changes of maxillary third molars (MxM3) relative to the Interorbital Plane (IOP) and Palatal Plane (PP), as well as changes in inclination and vertical position according to Archer’s classification, were also documented. Differences between T0 and T1 within the same group were assessed using the paired sample t-test and Wilcoxon signed-rank test. Comparisons between groups were evaluated with one-way analysis of variance (ANOVA) and Kruskal-Wallis H test. The threshold for statistical significance was set at p < .05.

RESULTS: IOP and PP values of MxM2 and MxM3 showed significant improvement in the extraction group (EG)(p < .001). The improvement in MxM3 IOP and PP values was not significant in the distalization group (DG)(p = .196 and p = .544, respectively). According to Archer’s classification, within-group comparisons revealed that the inclination and vertical position of MxM3 showed significant improvement in the EG, DG, and non-extraction groups (NEG)(inclination: p < .001 in EG, p = .032 in DG, p = .024 in NEG; vertical position: p < .001 in EG, p = .048 in DG, p < .001 in NEG). In between-group comparisons, the most significant improvement was observed in the EG. The number of MxM3 with vertical positions in Stages 1 and 2 at T1 were 19 in EG, 3 in DG, and 10 in NEG.

CONCLUSION: Premolar extraction has a positive effect on the angular and positional changes of MxM2 and MxM3. The changes in the inclination and vertical position of MxM3 between NEG and DG were not statistically significant.

PMID:39881326 | DOI:10.1186/s12903-025-05545-x

Nutr J. 2025 Jan 29;24(1):19. doi: 10.1186/s12937-024-01063-8.

ABSTRACT

BACKGROUND: A better understanding of correlates of sugary drink consumption is essential to inform public health interventions. This study examined differences in perceived healthiness of sugary drinks and related social norms between countries, over time, and sociodemographic groups and associations with sugary drink intake.

METHODS: This study used annual cross-sectional data from the International Food Policy Study from 2018 to 2021 in Australia, Canada, the United Kingdom, the United States, and Mexico. Analyses examined perceived healthiness of eight beverage types and two types of perceived social norms (descriptive, injunctive) that discourage sugary drink consumption. The 24-item Beverage Frequency Questionnaire was used to estimate beverage intake in the past 7 days. Logistic regression models examined trends over time in odds of perceiving each beverage type as unhealthy and agreeing with social norms discouraging sugary drink consumption, across countries and sociodemographic characteristics. Negative binomial regressions examined associations between perceived healthiness, social norms and consumption.

RESULTS: Energy drinks, regular soft drinks, and diet soft drinks were most frequently perceived as unhealthy in all countries, while water and 100% juice were least frequently perceived as unhealthy. Participants in Mexico had higher odds of perceiving 100% juice, chocolate milk, and iced tea as unhealthy in 2021 compared to 2018 (AOR = 1.71 99%CI 1.10-2.64; AOR = 2.69, 99%CI 1.70-4.26; AOR = 1.79, 99%CI 1.15-2.76; respectively), with little change in other countries. Agreement with social norms discouraging consumption of sugary drinks was higher in Mexico than in other countries. Trends in social norms over time were mostly stable, except in Mexico where participants had higher odds of agreeing with both norms in 2020 compared to 2018 (AOR = 1.27, 99%CI 1.09-1.48 for a descriptive norm and AOR = 1.27 99%CI 1.09-1.49 for an injunctive norm). In most countries, perceiving a beverage as unhealthy and agreeing with social norms discouraging consumption of sugary drink were associated with lower sugary drink consumption, with varying strength of associations across countries and beverage types.

CONCLUSIONS: Shifts over time in social norms and perceived healthiness observed in Mexico and associations with intake of sugary drinks in most countries suggest that targeted interventions to change norms and perceptions could help reduce sugary drink consumption.

PMID:39881318 | DOI:10.1186/s12937-024-01063-8