Nevin Manimala

Brain Commun. 2025 Dec 16;7(6):fcaf476. doi: 10.1093/braincomms/fcaf476. eCollection 2025.

ABSTRACT

Despite a decline in severe neonatal brain injury in preterm infants, neurodevelopmental impairment remains prevalent. Identifying early biomarkers for neurodevelopmental impairment, particularly in infants without severe neonatal brain injury, is crucial for intervention. This study explores whether brain dysmaturation, indicated by functional connectivity alterations at term-equivalent age, predicts neurodevelopmental impairment severity at 24 months corrected age in preterm infants without severe neonatal brain injury. In this observational cohort study, preterm infants born < 31 weeks’ gestation without severe neonatal brain injury underwent resting-state functional MRI at term-equivalent age. Neurodevelopmental outcomes at corrected age 24 months were assessed using Bayley-III cognitive and motor composite scores, cerebral palsy severity, and neurosensory impairments. Functional connectivity alterations were analyzed in relation to cognitive, language, and motor outcomes. Machine learning models were applied to assess the predictive value of functional connectivity features alongside neonatal exposures for neurodevelopmental impairment severity. Among the 122 preterm infants, 89 (73%) infants had no/mild neurodevelopmental impairment, 27 (22%) had moderate neurodevelopmental impairment, and 6 (5%) showed severe neurodevelopmental impairment. Compared with the no/mild neurodevelopmental impairment group, the moderate/severe neurodevelopmental impairment group was significantly lower in gestational age, and required longer durations of invasive mechanical ventilation, oxygen therapy, vasopressors, and total parenteral nutrition during admission. Compared with term-born controls, a clear trend emerged across neurodevelopmental impairment severity levels: as impairment increased from the no/mild group to the moderate and severe groups, the clustering coefficient increased, whereas the global efficiency decreased. Statistical comparisons between the no/mild and moderate/severe groups, relative to term-born controls, confirmed these patterns (clustering coefficient: t = -4.38, P < 0.001; global efficiency: t = 3.44, P < 0.001). Infants with no/mild neurodevelopmental impairment exhibited enhanced connectivity in the limbic system (t = -5.21, P < 0.001) and between the thalamus and basal ganglia (t = -5.9, P < 0.001), but this compensatory connectivity weakened with increasing neurodevelopmental impairment severity. The thalamo-cortical (frontal lobe, limbic system), thalamo-basal ganglia, and thalamo-cerebellar connectivity were strongly associated with cognitive, language, and motor performance at follow-up. A predictive model incorporating these functional connectivity features and neonatal adverse exposure parameters achieved 82% accuracy. Distinct disruptions in functional connectivity at term-equivalent age in very preterm infants without severe neonatal brain injury may predict the severity of later neurodevelopmental impairment. Early functional connectivity assessment holds promise as a biomarker for identifying high-risk infants who may benefit from timely neurodevelopmental interventions.

PMID:41404526 | PMC:PMC12704428 | DOI:10.1093/braincomms/fcaf476

Brain Commun. 2025 Dec 9;7(6):fcaf478. doi: 10.1093/braincomms/fcaf478. eCollection 2025.

ABSTRACT

In Alzheimer’s disease (AD), accelerated long-term forgetting (ALF), where information is retained normally over 10-30 min but lost at an accelerated rate over subsequent days to weeks, develops several years before symptom onset. However, the neuroanatomical changes underpinning ALF remain undetermined. Eighteen presymptomatic autosomal dominant AD mutation carriers and 12 non-carriers underwent ALF assessment with a list, a story, and visual figure, testing 30-min and 7-day recall of each, separately. T₁ and diffusion-weighted MRI were acquired. Cortical thickness was estimated for 13 pre-defined grey matter regions, with streamline tractography assessing associated structural connectivity. In mutation carriers, lower verbal ALF performance (list and story) was strongly associated with thinner prefrontal cortex (PFC) across four contiguous regions bilaterally. This association was absent in non-carriers. No associations were found between ALF and the thickness/volume of medial temporal lobe (MTL) structures. The association between ALF and PFC connectivity was weaker than for cortical thickness. Our results suggest that early subtle pathological change in PFC underpins ALF development, highlighting the central role of PFC dysfunction in very early AD-related cognitive decline. ALF may represent a qualitatively different (non-MTL driven) form of forgetting compared with the short interval forgetting that develops at later disease stages.

PMID:41404525 | PMC:PMC12704326 | DOI:10.1093/braincomms/fcaf478

Brain Commun. 2025 Dec 4;7(6):fcaf477. doi: 10.1093/braincomms/fcaf477. eCollection 2025.

ABSTRACT

Patients with acute hemispheric stroke exhibit various visuospatial impairments. While many recover rapidly, others remain impaired. Better defining which symptoms characterize the acute and chronic phases and which brain areas and connections are implicated could help to improve diagnostic and rehabilitation tools and inform effective rehabilitation strategies. Here, we report a systematic anatomo-functional study of two populations of acute and chronic hemispheric stroke patients (cross-sectional design). Patients were examined by a series of neuropsychological tests assessing different post-stroke clinical manifestations in the visuospatial domain. We first performed a statistical factorial analysis of patients’ behavioural performance across tests to break down symptoms into coherent profiles of co-varying deficits and determine whether any factors may be specific to each post-stroke phase. We then conducted voxel- and atlas-based lesion-symptom mapping, as well as disconnection-symptom mapping in the two populations. We found different patterns of behavioural impairment across groups, with acute symptoms mostly characterized by lateralized attentional deficits and chronic symptoms manifesting as constructional spatial impairments. Lesions to and/or disconnections of frontal and precentral gyri correlated with lateralized visuospatial symptoms in the acute but not chronic phase, whereas lesions to and/or disconnections of temporoparietal areas correlated with constructional deficits in the chronic phase. Our results indicate that constructional spatial deficits and damage/disconnection of dorsoventral higher-order visual areas most pervasively impair stroke patients in the long term. Such deficits might be overlooked or disregarded by rehabilitation strategies focusing on the (mainly acute) lateralized component of their visuospatial deficits and ignoring concomitant, more object-based deficits. This work may help design more specific diagnostic tests and guide future rehabilitation strategies, ultimately promoting better and more extensive recovery beyond lateralized deficits in attention and spatial awareness.

PMID:41404524 | PMC:PMC12704327 | DOI:10.1093/braincomms/fcaf477

G3 (Bethesda). 2025 Dec 16:jkaf304. doi: 10.1093/g3journal/jkaf304. Online ahead of print.

ABSTRACT

Gene-environment interactions (G×E) have been shown to explain a non-negligible proportion of variance for a plethora of complex traits in different species, including livestock, plants, and humans. While several studies have shown that including G×E can improve prediction accuracy in agricultural species, no increase in accuracy has been observed in human studies. In this work, we sought to investigate the scenarios in which accounting for G×E is expected to improve prediction accuracy. Model organisms are useful for studying G×E, since environments can be defined precisely, and genotypes can be replicated across environments, which are ideal conditions to minimize confounding in G×E analyses. Thus, we used data from an experiment in Drosophila melanogaster, where researchers measured lifespan in different environments for unrelated inbred lines (i.e., genotypes). We used three different cross-validation (CV) scenarios that mimic different relationships between reference and test populations, and fitted a few statistical models with and without including G×E. The results showed that G×E explained 8% of lifespan variance. Despite that, models accounting for G×E improved prediction accuracy only in CV scenarios where the same genotypes are observed in both the reference and test populations. While these scenarios are common in agriculture, where individuals of the same family or variety appear in both populations, they are not commonly encountered in human studies, where individuals are unrelated. Thus, our work shows in which prediction scenarios we can expect improvements by accounting for G×E, and may provide a potential reason (among others) for results of human studies.

PMID:41402999 | DOI:10.1093/g3journal/jkaf304

Ital J Pediatr. 2025 Dec 16;51(1):320. doi: 10.1186/s13052-025-02156-8.

NO ABSTRACT

PMID:41402982 | DOI:10.1186/s13052-025-02156-8

BMC Oral Health. 2025 Dec 16. doi: 10.1186/s12903-025-07315-1. Online ahead of print.

ABSTRACT

BACKGROUND: Sickle cell disease is a major public health issue that is associated with caries and oral health problems. This study aimed to assess the association between dental caries experience and sickle cell anaemia.

METHODS: This was a case-control study that recruited children aged 4 to 16 years old with sickle cell anaemia (SCA) and those with normal haemoglobin genotype attending the Paediatric outpatient clinic of the Obafemi Awolowo University Teaching Hospitals’ Complex. Data collected included confounders (age, sex, socio-economic status, frequency of toothbrushing, use of fluoridated toothpaste, frequency of consumption of refined carbohydrate in-between-meals daily, history of dental service utilization, and oral hygiene status), dependent (dental caries experience), and independent (SCD status) variables. Multiple logistic regression was conducted to determine the association between sickle cell disease and dental caries experience after adjusting for the confounding factors.

RESULTS: There were 264 participants with a mean age of 9.41 ± 3.35 years. Thirty-nine children (14.8%) had dental caries: twenty-eight (13.5%) in the primary dentition and eleven (5.0%) in the permanent dentition. Although the differences were not statistically significant, the caries experience of children with sickle-cell anaemia was twice those without with normal haemoglobin genotype, both in the primary (17.9% vs. 8.9%, p = 0.058) and permanent (6.6% vs. 3.5%, p = 0.361) dentition. The presence of SCA and dental service utilization were significantly associated with dental caries (p = 0.04 and 0.001, respectively).

CONCLUSION: Sickle cell anaemia and dental service utilization were significantly associated with caries in the children. Children with SCA should be screened early for caries and preventive measures instituted.

PMID:41402964 | DOI:10.1186/s12903-025-07315-1

BMC Oral Health. 2025 Dec 16. doi: 10.1186/s12903-025-07511-z. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the clinical, radiographic, and histopathological characteristics of simple bone cysts and to investigate the relationships among these parameters.

METHODS: A total of 46 cases diagnosed with SBC were included in this retrospective study, analyzing clinical, radiological, histopathological, and treatment data, as well as recurrence. Radiographic evaluations were performed using panoramic imaging and/or cone-beam computed tomography. Associations among clinical, radiological, and histopathological variables were analyzed using chi-square and Fisher’s exact tests.

RESULTS: The results showed a slight female predilection and a predominant occurrence in the second decade of life. All lesions were located in the mandible, most commonly in the posterior region. Radiographically, lesions were typically unilocular radiolucencies, often with scalloped borders (63.1%) and pseudosepta (56.5%). Histopathologically, fragmented normal bone and fibrous septa were the most frequent findings. Curettage was the most common treatment, and no recurrences were observed. Correlation analyses demonstrated significant associations between multilocular appearance and vascular connective tissue (66.7% vs. 5.9%, p = 0.008), and between lesion size and age, with larger lesions predominantly seen in patients under 20 years, while all patients over 20 years had small lesions (p = 0.002). Although other associations did not reach statistical significance, inflammatory changes were more frequent in symptomatic cases (28.6% vs. 9.4%), and both hemosiderin deposition (25% vs. 10.9%) and vascular connective tissue (21.4% vs. 6.3%) tended to be more common in trauma-associated cases.

CONCLUSIONS: SBCs most often present as well-defined, unilocular radiolucencies in the posterior mandible; however, internal variations such as pseudosepta and radiopaque areas may complicate their appearance and highlight the need for careful differential diagnosis from more aggressive lesions. Correlation analyses indicated that multilocular radiographic appearance was linked to vascular connective tissue and lesion size was age-dependent, suggesting that clinical, radiological, and histopathological features are interrelated and should be evaluated together.

PMID:41402962 | DOI:10.1186/s12903-025-07511-z

Diabetol Metab Syndr. 2025 Dec 16. doi: 10.1186/s13098-025-02058-z. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the separate, joint, as well as interactive associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and oxidative balance score (OBS) with mortality among individuals with metabolic syndrome (MetS).

METHODS: The analysis included 12,078 participants with MetS from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Mortality was ascertained by linkage to National Death Index records through 31 December 2019.

RESULTS: During 99,690 person-years of follow-up, 2357 deaths were documented, including 654 cardiovascular disease (CVD) deaths and 518 cancer deaths. A pronounced “L-shaped” nonlinear relationship was observed between 25(OH)D and mortality; the hazard ratio (HR) [95% confidence interval (CI)] for 25(OH)D ≥ 75.0 vs. < 50.0 nmol/L (reference) were 0.71 (0.61, 0.82), 0.65 (0.48, 0.86), and 0.77 (0.57, 1.05) for all-cause, CVD, and cancer mortality, respectively. A reverse linear relationship was demonstrated between OBS and mortality; the HRs (95% CI) for high OBS vs. low OBS (reference) were 0.76 (0.68, 0.86), 0.70 (0.58, 0.85), and 0.75 (0.60, 0.94) for all-cause, CVD, and cancer mortality, respectively. In the joint analyses, the combination of 25(OH)D ≥ 75.0 nmol/L and high OBS was associated with the lowest risk of all-cause (HR 0.57, 0.46-0.70) and CVD mortality (HR 0.48, 0.34-0.69). In contrast, participants with 25(OH)D levels of 50.0-74.9 nmol/L and high OBS presented the lowest risk of cancer mortality (HR 0.52, 0.34-0.81). A significant synergistic additive interaction between OBS and sufficient 25(OH)D levels on CVD mortality was observed [relative excess risk due to interaction (RERI) = 0.29, 95% CI: 0.02-0.57], with 47% of the total protective effect attributable to their interaction.

CONCLUSIONS: Adequate 25(OH)D and higher OBS are significantly associated with lower risk of mortality and exhibit enhanced protective effects on CVD mortality risk.

PMID:41402956 | DOI:10.1186/s13098-025-02058-z

Pilot Feasibility Stud. 2025 Dec 16. doi: 10.1186/s40814-025-01751-0. Online ahead of print.

ABSTRACT

BACKGROUND: Muscle-strengthening activity (MSA) is beneficial for school-aged children, but most school-based MSA interventions have been delivered by external specialists or research staff, limiting scalability. We aimed to assess the feasibility of a teacher-delivered MSA intervention for children in advance of a future efficacy trial.

METHODS: We conducted a single-group feasibility trial with two Stage 2 (i.e. grade 3-4) classes from one primary school in New South Wales, Australia. The 6-week Muscle Movers intervention included (i) enhanced PE lessons focused on foundational MSA skills (1 × 45 min/week), (ii) classroom energiser breaks (2 × 5 min/week), and (iii) active homework tasks (1 × 10 min/week). We assessed acceptability, implementation, adaptation, and practicality using survey and interview methods. We also assessed pre-post change in children’s perceived strength, upper-body muscular endurance, and lower-body muscular power. Data were analysed in SPSS (V.25) using descriptive statistics and paired-samples t-tests, with Cohen’s d as a measure of effect size.

RESULTS: Two female teachers (31 and 59 years) and 30 students (mean [SD] = 9.8 [0.6] years; 40% female) were enrolled. Acceptability was high for teachers (mean [SD] = 5.0 [0.0] out of 5) and students (mean [SD] = 4.1 [1.0] out of 5). Teachers implemented all PE lessons and more than double the intended energiser breaks (mean [SD] = 5.5 [2.1] per week). Conversely, homework task assignment (mean [SD] = 5.0 [1.4]) and completion (mean [SD] = 2.5 [0.7]) were lower than intended. Teachers reported high confidence to deliver the program and viewed it as practical and adaptable. We found a moderate increase in children’s push-up performance (mean [95%CI] = 2.2 repetitions [0.7 to 3.8]; d = 0.61), but no meaningful changes in perceived strength (mean [95%CI] = 0.1 units [- 0.1 to 0.4]; d = 0.22) or standing long jump (mean [95%CI] = – 1.4 cm [- 7.4 to 4.7]; d = – 0.09).

CONCLUSIONS: Muscle Movers was feasible for classroom teachers to implement in a primary school setting. The observed improvement in students’ upper-body muscular endurance should be confirmed using an appropriately powered randomised controlled trial.

TRIAL REGISTRATION: Retrospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12625000703404).

PMID:41402953 | DOI:10.1186/s40814-025-01751-0

Adv Rheumatol. 2025 Dec 17. doi: 10.1186/s42358-025-00510-2. Online ahead of print.

ABSTRACT

BACKGROUND: Oxidative stress and inflammation contribute to telomere length (TL) attrition, a hallmark of cellular senescence. Systemic lupus erythematosus (SLE) is associated with premature cellular aging; however, the clinical relevance of TL shortening remains unclear. This study aimed to compare the relative TL of SLE patients and healthy controls and explore its association with clinical features and disease burden.

METHODS: We conducted a cross-sectional study including adult SLE patients and age- and sex-matched healthy controls (18-60 years). Demographic and clinical data were collected, and TL was measured using quantitative polymerase chain reaction (qPCR). Among SLE patients, disease activity, cumulative damage, fatigue, depression, anxiety, stress, and physical activity were also assessed. Statistical analyses included descriptive statistics, Student’s t-test or Mann-Whitney test for group comparisons, Spearman’s correlation, and multiple linear regression models selected based on the lowest Akaike information criterion (AIC).

RESULTS: Sixty SLE patients (37 years ± 11.5) and 55 controls (38 years ± 10.5) were enrolled. SLE patients exhibited significantly shorter TL [median (IQR): 0.80 (0.29-2.94)] compared to controls [1.07 (0.38-2.32); p = 0.005]. In multivariate analysis, moderate anxiety was associated with shorter TL compared to none/low anxiety [β= -0.353 (95%CI: -0.645; -0.061); p = 0.019]. An alternative model indicated that moderate stress was also associated with reduced TL [β= -0.411 (95%CI: -0.771; -0.050); p = 0.026]. No significant associations were found between TL and disease activity or cumulative damage.

CONCLUSIONS: SLE patients presented significantly shorter telomeres than healthy controls, with anxiety and stress symptoms contributing to TL attrition. Longitudinal studies are warranted to elucidate the clinical implications of TL shortening in SLE.

PMID:41402941 | DOI:10.1186/s42358-025-00510-2