Nevin Manimala

Orphanet J Rare Dis. 2025 Jun 16;20(1):309. doi: 10.1186/s13023-025-03750-z.

ABSTRACT

Precision treatments for monogenic epilepsies, i.e. treatments that can at least partially reverse the biochemical consequences of a pathogenic gene variant, have been gradually emerging over the years. To date, however, information on the efficacy of these treatments is mostly based on case-reports and retrospective studies. As a result, utilisation of precision treatments often lack consistency and a pre-defined outcome monitoring plan. N-of-1 strategies in clinical care are pre-defined, individually tailored, repeated challenge-withdrawal therapeutic trials designed to assess the value of a treatment of interest for an individual. Despite their potential to improve clinical decision-making, N-of-1 strategies have been hampered by limited guidance on their implementation and lack of consensus on oversight procedures. To improve treatment selection for rare monogenic epilepsies, the PINPOINT initiative (Precision Treatments In MoNogenic EPilepsies: Observational Registry And N-of-1 Trial Recommendations) was set up as a collaborative effort within the European Reference Network for Rare and Complex Epilepsies. PINPOINT aims to develop recommendations for the design of N-of-1 strategies with off-label precision treatments for monogenic epilepsies. Using available N-of-1 trial manuals, different components of N-of-1 design were tailored to the context of epilepsy and oversight procedures were outlined. These efforts resulted in this guidance document-or blueprint for N-of-1 strategies for monogenic epilepsies in clinical care. This blueprint defines the characteristics of treatments and patients that would be suitable for N-of-1 strategies. Key principles for outcome measure selection, period duration and statistical analysis are defined. Consideration is given to interim assessment rules, which establish whether proceeding onto an additional treatment cycle is likely to provide significant advantages. Procedures for ethical oversight are proposed. This blueprint for N-of-1 strategies can be used as a basis for master protocols to optimise individualised clinical care in a standardised and consistent manner. We are confident that this document will provide physicians with the building blocks needed to elevate precision treatments for rare monogenic epilepsies out of their current landscape of inadequate evidence.

PMID:40524218 | DOI:10.1186/s13023-025-03750-z

Biol Sex Differ. 2025 Jun 16;16(1):42. doi: 10.1186/s13293-025-00729-0.

ABSTRACT

BACKGROUND: Takotsubo Syndrome (TTS) is an acute form of heart failure that disproportionately impacts post-menopausal women. The brain-heart connection is considered a pathway for TTS pathophysiology leading to investigations of the role of psychological, psychosocial, and personality factors in TTS.

OBJECTIVES: We compare psychosocial characteristics among a subset of individuals with confirmed TTS and those who had symptoms adjudicated as non-TTS in our online Takotsubo registry (n = 104). We also evaluate differences in TTS clinical characteristics among those with and without symptoms of PTSD and depression.

METHODS: The Smidt Heart Institute Takotsubo registry enrolls individuals with a history of TTS sourced through physician referrals, medical records review, peer- and self-referrals. Psychosocial characteristics were assessed using questionnaires validated in acute coronary syndrome populations. Hedge’s g effect sizes were computed to compare differences in perceived stress, depression symptoms, and post-traumatic stress disorder (PTSD) symptoms relative to TTS status.

RESULTS: Compared to participants confirmed to be non-TTS, those with adjudication-confirmed TTS had worse mean psychosocial scores (indicative of worse psychosocial characteristics). After adjusting for age at event, BMI, race, and smoking status, the Hedge’s g effect size for depressive symptoms was moderate [0.60 (-0.03, 1.22)] while effect sizes for other psychosocial measures were minimal (Trait anxiety: [0.01 (-0.58, 0.60)], PTSD symptoms [0.13 (-0.46, 0.73)], perceived stress [0.06 (-0.53, 0.65)]. Effect sizes were relatively lower following adjustment, largely driven by participants’ age at first event. Individuals with elevated PTSD symptoms were significantly younger at their first TTS event compared to those with minimal or no symptoms (54 ± 8 vs. 61 ± 10; p = 0.005). QTc was relatively longer among individuals with elevated PTSD symptoms (483 ± 40 msec vs. 465 ± 32 msec; p = 0.08) and elevated depressive symptoms (481 ± 33 msec vs. 464 ± 36 msec; p = 0.07), although the differences were not statistically significant.

CONCLUSIONS: Psychosocial characteristics including PTSD, depression, and stress are common among women with TTS, and age at the time of TTS event is a potentially important moderator of this relationship. We did not find Trait-anxiety or early childhood trauma to be associated with TTS in our cohort.

PMID:40524204 | DOI:10.1186/s13293-025-00729-0

Thromb J. 2025 Jun 16;23(1):65. doi: 10.1186/s12959-025-00756-2.

ABSTRACT

BACKGROUND: Worldwide, the diagnosis and treatment of immune thrombocytopenia (ITP) and Henoch-Schönlein purpura (HSP) remain a major and ongoing challenge in hematology. Emerging clinical evidences suggest serum mineral elements are associated with ITP or HSP, but the causal relationship between them is still unclear.

AIMS: Conducting a two-sample, bidirectional Mendelian randomization (MR) study to evaluate the causal association between serum mineral elements including zinc, copper, magnesium, iron and calcium with ITP and HSP.

METHODS: In this two-sample, bidirectional MR study, summary statistics data of genome-wide association studies (GWAS) on exposures including zinc, copper, iron, magnesium and calcium were extracted from the MRC-Integrative Epidemiology Unit (MRC-IEU). The GWAS data on study outcomes, including ITP and HSP, were obtained from the FinnGen consortium. MR-Egger intercept and MR-PRESSO global test were utilized to assess the heterogeneity and horizontal pleiotropic of instrumental variables (IVs) between the exposures and outcomes, respectively. Inverse variance weighted (IVW) test was used as the primary analysis method to evaluate the causal between serum mineral elements with the risk of ITP and HSP, and weighted-median, weighted model, MR steiger, MR-PRESSO and radial MR were used as auxiliary analysis methods, moreover, the odds ratio (OR) and 95% confidence interval (CI) were calculated. Reverse MR analysis was also conducted. Leave-one-out test was further to conduct whether the association between serum mineral elements and the risk of ITP and HSP remain robust.

RESULTS: No significant horizontal pleiotropy and heterogeneity between individuals IVs was found after MR-Egger and MR-PRESSO global test. Genetically predicted that high copper (OR = 0.768, 95%CI: 0.628-0.937) and magnesium (OR = 0.314, 95%CI: 0.112-0.884) concentrations may reduce the risk of ITP and HSP, respectively. High calcium concentration may increase the risk of HSP (OR = 1.823, 95%CI: 1.226-2.712). There was no significant evidence to support a causal association between iron, zinc, magnesium, and calcium with the risk of ITP, or between iron, copper, and zinc and the risk of HSP (all P > 0.005). Moreover, no reverse causal associations between five serum mineral elements with the risk of ITP and HSP were found (all P > 0.05), suggesting the causal associations between serum mineral elements with ITP and HSP were not bidirectional. In addition, consistent results were obtained by multiple sensitivity analyses, indicating the associations of serum mineral elements with the risk of ITP and HSP relatively robust.

CONCLUSION: In this MR study, we discovered genetically predicted that elevated serum levels of copper and magnesium decreased the risk of ITP and HSP, respectively, and elevated levels of serum calcium increased the risk of HSP. However, no reverse causal association was found between serum mineral elements with the risk of ITP and HSP.

PMID:40524203 | DOI:10.1186/s12959-025-00756-2

Nutr J. 2025 Jun 16;24(1):91. doi: 10.1186/s12937-025-01159-9.

ABSTRACT

BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide, with acute coronary syndrome (ACS) being particularly fatal. Percutaneous coronary intervention (PCI) is a key treatment for ACS; however, major adverse cardiovascular events (MACE) frequently occur postoperatively. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been proposed as an emerging risk factor for cardiovascular disease. This study aims to systematically evaluate TMAO’s predictive value for MACE post-PCI and explore its dose-response relationship.

METHODS: A comprehensive literature search was conducted in four databases (PubMed, Web of Science, Embase, and the Cochrane Library), including retrospective or prospective cohort studies involving patients undergoing PCI. The primary outcome was MACE, and the secondary outcome was all-cause mortality. A dose-response analysis was conducted using a restricted cubic spline model to explore potential nonlinear associations between TMAO levels and outcomes. Heterogeneity was assessed using the Cochrane Q test and the I² statistic. Subgroup analysis and meta-regression were performed to identify sources of heterogeneity.

RESULTS: Eleven studies (comprising 13 independent cohorts) with 11,279 participants were included. Pooled analysis showed a significant association between elevated plasma TMAO levels and an increased risk of MACE after PCI (HR: 1.99, 95%CI: 1.68-2.35, 95%PI: 1.64-2.40, I² = 0%, p < 0.00001). Similarly, elevated plasma TMAO levels were significantly associated with an increased risk of all-cause mortality after PCI (HR: 1.76, 95%CI: 1.32-2.35, 95%PI: 0.79-3.90, I² = 65.1%, p < 0.00001). The dose-response analysis did not reveal a nonlinear relationship between TMAO and MACE or all-cause mortality. The linear model showed that each 1 µmol/L increase in plasma TMAO was associated with an 8.95% increased hazard of MACE (HR = 1.0895, 95%CI: 1.03-1.15), while all-cause mortality increased by 4% (HR = 1.04, 95%CI: 0.99-1.09).

CONCLUSIONS: This study demonstrates that elevated plasma TMAO levels are significantly associated with an increased risk of MACE and all-cause mortality after PCI, with a dose-dependent effect on MACE risk. As a potential biomarker, TMAO may be used to predict the risk of adverse cardiovascular events after PCI, and future studies should further validate its clinical utility.

REGISTRATION: PROSPERO CRD42024557486.

PMID:40524200 | DOI:10.1186/s12937-025-01159-9

J Orthop Surg Res. 2025 Jun 16;20(1):589. doi: 10.1186/s13018-025-06004-7.

ABSTRACT

BACKGROUND: While venous thromboembolism (VTE) prophylaxis is crucial following major orthopaedic surgeries including total knee arthroplasty (TKA), the impact of different prophylactic agents on postoperative hemoglobin (Hb) levels remains inadequately studied. The aim of this study was to compare the effects of aspirin, rivaroxaban, and low-molecular-weight heparin (LMWH) on early postoperative Hb changes following TKA.

METHODS: In this single-center retrospective cohort study, 655 primary TKAs were finally included using data from the hospital information system. Patients received either aspirin, rivaroxaban, or LMWH for VTE prophylaxis. The primary outcome was the magnitude of Hb reduction, calculated as the difference between the Hb level on the first postoperative day and the minimum postoperative Hb level before discharge. The secondary outcome was the trajectory of postoperative Hb changes within the first week.

RESULTS: Postoperative Hb levels clearly declined within the first week, with a mean of 13.9 g/L (SD, 8.5) from postoperative day 1 in the entire cohort. In the fully adjusted linear regression model, both rivaroxaban (β = 1.5, [95%CI, 0.0 to 3.0]) and low-molecular-weight heparin (LMWH) (β = 3.3, [95%CI, 1.5 to 5.2]) were associated with a greater reduction in Hb compared to aspirin. Regarding the trajectory of postoperative Hb changes, the generalized additive mixed model revealed no statistically significant difference between rivaroxaban and aspirin (β = -0.2, [95%CI, -0.6 to 0.2]). LMWH was associated with a greater daily reduction in Hb levels relative to aspirin, averaging 0.8 g/L per day (β = -0.8, [95%CI, -1.3 to -0.3]). Despite these observed differences, the effect sizes were small, suggesting a lack of clinical significance.

CONCLUSIONS: Hemoglobin levels declined significantly following TKA within the first week after surgery. However, no clinically meaningful distinction is discernible between the three most frequently used pharmacological agents, aspirin, rivaroxaban and LMWH.

LEVEL OF EVIDENCE: III, A retrospective cohort study.

PMID:40524197 | DOI:10.1186/s13018-025-06004-7

Chiropr Man Therap. 2025 Jun 16;33(1):26. doi: 10.1186/s12998-025-00588-x.

ABSTRACT

PURPOSE: Chronic non-specific low back pain (CNLBP) is a complex and heterogeneous condition, and it is necessary to explore new treatment approaches. We evaluated whether the addition of dry cupping therapy to guideline‑based conventional therapy would further improve clinical outcomes in CNLBP.

METHODS: Thirty-six patients with CNLBP were recruitedand randomly divided into two groups: the control group and the intervention group. The intervention group received cupping therapy in addition to the control group (core stabilization exercises, spinal manipulation and education) for 4 weeks. The primary outcome was the visual analog scale (VAS) for pain intensity. Secondary outcomes were the Roland Morris disability questionnaire (RMDQ), and pressure pain thresholds (PPT) at bilateral Shenshu (BL23), Qihaishu (BL24), and Dachangshu (BL25) acupuncture points.

RESULTS: At week 4 the between‑group difference in resting pain was trivial (median difference 0.0 cm, 95% CI – 1.0 to 1.0). Neither clinically important nor statistically significant differences were detected in disability or PPTs. Both groups improved substantially from baseline.

CONCLUSION: In this randomized trial, adding dry cupping to conventional therapy offered no additional benefit over conventional therapy alone for pain, disability or PPT in CNLBP. Larger, multicentre trials with longer follow‑up and standardized negative pressures are warranted.

TRIAL REGISTRATION: ChiCTR2300069398, http://www.chictr.org.cn , Registration Date: March 15, 2023.

PMID:40524196 | DOI:10.1186/s12998-025-00588-x

J Orthop Surg Res. 2025 Jun 16;20(1):590. doi: 10.1186/s13018-025-06008-3.

ABSTRACT

INTRODUCTION: The Both Column Fixation Corridor (BCFC) and Both Column Screws (BCS) represent innovative concepts in orthopedic surgery, yet they have not been extensively studied in the literature. This study aims to validate the BCFC as a consistent fixation pathway across genders, evaluate its axial fluoroscopic visualization, and investigate gender-specific anatomical variations for surgical planning.

MATERIALS AND METHODS: In this study, pelvic CT data from 400 adults (200 males, 200 females) were analyzed using Fujifilm-Synapse 3D software. In the initial step, axial fluoroscopic visualization of the corridor was simulated, and the optimal antegrade entry point (OAEP) was identified. Subsequently, virtual placement of anterior and posterior screws (aBCS, pBCS) was performed radiologically within the corridor. Measurements included screw thickness (R), length (L), distances to the spina iliaca anterior superior (SIAS-aBCS, SIAS-pBCS), and the caudo-cranial (CCT) and centro-lateral (CLT) fluoroscopic tilts required for axial visualization of the BCFC and its OAEP.

RESULTS: Fluoroscopic axial visualization of the BCFC and identification of the OAEP were successfully achieved in all models, enabling the placement of both anterior and posterior screws across genders. Measurements revealed the following average values for female and male pelvises, respectively: aBCS thicknesses were 6.5 ± 0.8 mm and 7.9 ± 0.9 mm (p < 0.001); lengths were 131.6 ± 8.8 mm and 146.8 ± 9.9 mm (p < 0.001); pBCS thicknesses were 6.5 ± 0.8 mm and 7.5 ± 0.7 mm (p < 0.001); lengths were 132.6 ± 9.7 mm and 148.3 ± 9.6 mm (p < 0.001); caudo-cranial tilts were 42.8°± 5.4 and 39.5°± 5.2 (p < 0.001); and centro-lateral tilts were 43.1°± 4.3 and 40.0°± 5.3 (p < 0.001). SIAS-pBCS distances were 38.5 ± 6.9 mm and 40.7 ± 7.5 mm (p = 0.003), while SIAS-aBCS distances were 29.7 ± 6.9 mm and 30.2 ± 6.7 mm (p = 0.467). All parameters, except for the SIAS-aBCS distance, exhibited statistically significant gender-specific differences.

CONCLUSION: The Both Column Fixation Corridor is a universally valid and consistent osseous fixation pathway present in both genders. It is suitable for the placement of two screws in pelvic and acetabular surgery, with careful consideration of gender-specific anatomical differences to optimize its application.

PMID:40524194 | DOI:10.1186/s13018-025-06008-3

ACS Appl Bio Mater. 2025 Jun 16. doi: 10.1021/acsabm.5c00697. Online ahead of print.

ABSTRACT

Advancements in cell-instructive biomaterials hinge on the precise design of their nanoscale topography, a critical factor in controlling cell-surface interactions. Nanofabrication techniques such as e-beam and nanoimprint lithography enable accurate nanopatterning on a wide range of materials. However, their limited applicability and scalability to medically relevant metals such as titanium, hinder the creation and modulation of precisely designed nanotopographies on metallic substrates to investigate structure-function relationships and clinical translation of nanotopographical surfaces for biomedical implants. In this context, anodization is a cost-effective, scalable method to nanopattern titanium and its alloys, producing arrays of TiO₂ nanotubes with precisely controlled diameters. Despite the significant advances in the understanding of how cells sense and respond to nanotubular surfaces, traditional diameter-focused research reliant on single-sized nanostructures restricts analysis to a narrow set of geometrical parameters and often overlook the spatial arrangement of nanotubes. To address these limitations, this study capitalizes on anodization to create scalable nanotubular gradients on titanium, introducing a high-throughput platform to explore the cellular response to a wide range of nanotopographical configurations within a single sample. Utilizing spatial metrics such as lacunarity, entropy, and fractal dimension, we characterized the structural complexity of the nanotubular surfaces, emphasizing geometrical considerations beyond the nanotube diameter in evaluating cellular response. In vitro assays with human MG63 osteoblastic cells revealed that more disordered, high-entropy regions significantly enhance cellular spreading and proliferation while promoting early osteogenic differentiation, evidenced by elevated RUNX2 and osteocalcin (OCN) expression. In contrast, mitochondrial activation and longer-term mineral deposition are elicited by more ordered nanotubular arrays. By streamlining the screening of nanotopographical features and enabling reproduction of user-selected designs as homogeneous surfaces, this gradient-based approach deepens mechanistic insights into structure-function relationships governing MG63 cell response to anodized titanium and offers a translatable framework for designing and evaluating nanotubular surfaces, shortening the gap between in vitro research and clinical applications.

PMID:40524179 | DOI:10.1021/acsabm.5c00697

Popul Health Metr. 2025 Jun 16;23(1):25. doi: 10.1186/s12963-025-00393-x.

ABSTRACT

BACKGROUND: Single-child families represent an expanded phenomenon in recent years due to prevailing socio-economic challenges. The single childbirth phenomenon can potentially cause negative population growth and undesirable effects on families. Thus, this study aimed to determine the prevalence (percent) of single-child families with an emphasis on interfering associated factors.

METHODS: For paper collection, valid databases of PubMed, Embase, ScienceDirect, Web of Science, Scopus, and Google Scholar search engine were systematically searched. All relevant studies were transferred to EndNote software (v.8) for duplicate detection. Primary and secondary screenings were applied and eligible studies enrolled for meta-analysis (CMA v.2). In this regard, the random effect model was employed and the I² index was used for heterogeneity assessment.

RESULTS: Following the examination of 33 studies, the prevalence (percent) of single-child families was found 41.3% (95% CI:33.1-49.9%). Meta-regression analysis revealed that following the acceleration in sample size and year of paper publication, the prevalence (percent) of single-child family increases and decreases (p < 0.05). Additionally, various influential factors effective on single-child families were listed as income status, financial difficulties, religious beliefs, educational level, and employment status.

CONCLUSION: According to the relatively high prevalence (percent) of single-child families and the influential impacts on families and communities, the findings of this study can provide valuable insights for policymakers to design appropriate policies and achieve demographic balance.

PMID:40524173 | DOI:10.1186/s12963-025-00393-x

BMC Pediatr. 2025 May 9;25(1):367. doi: 10.1186/s12887-025-05495-x.

ABSTRACT

BACKGROUND: Giving any things other than breast milk during the first 3 days after birth is a prelacteal feeding. Thus, providing anything other than breast milk to newborns has an impact on the prompt initiation and exclusive breastfeeding but a major issue in the developing countries. Therefore, the aimed to assess the determinants both individual and community level factors of given anything other than breast milk for neonates in Ethiopia.

METHODS: This study was a multilevel population-based cross-sectional conducted with total of weighted sample of 24,252 participants. The Ethiopian Demographic and Health Survey 2019 data were the source of secondary data analysis used in the study. The data was hierarchical; therefore we performed a multilevel analysis. In the multivariable analysis, variables with p-value < 0.05 were deemed substantially correlated with given anything other than breast milk for neonates.

RESULTS: In this study, respondents with Catholic religion followers [adjusted odds ratio (AOR) = 0.05; 95%CI: 0.12, 0.28] timely initiation of breast feeding [AOR = 4.44; 95%CI: 2.91, 6.74], Cesarean delivery usage [AOR = 3.94; 95%CI: 2.13, 7.13], and being in communities with pastoralist region [AOR = 6.39; 95%CI: 3.03, 11.62] were significant predictors of given anything other than breast milk for neonates.

CONCLUSION: This study found that giving anything other than breast milk to newborns was associated with both individual and community level characteristics, particularly among members of the Catholic Church, prompt commencement of breastfeeding, use of cesarean section delivery, and contextual region categories. Therefore, improving maternal health and early breastfeeding services should be strengthen. Furthermore, it is preferable to fairly distribute maternal services among regions and to focus on people living in pastoralist regions.

PMID:40524156 | DOI:10.1186/s12887-025-05495-x