Due to widespread availability and familiarity, unfractionated heparin (UFH) is the most used intravenous anticoagulant for many indications in hospitalised patients. UFH, however, is a high-risk medication with complex pharmacokinetics and pharmacodynamics that are highly variable between different patients and within the same patients over time. The traditional titration and monitoring approach uses a clot-based assay, the activated partial thromboplastin time (aPTT), titrated to one and a half to two and a half times the upper limit of the normal range. Alternate assays indirectly measuring the anti-Xa level have not been compared with the aPTT for the monitoring of heparin in a prospective study. The optimal laboratory test for monitoring and adjusting heparin is not known. Our pragmatic study developed within the learning healthcare infrastructure is designed to answer this clinical question by comparing two established protocols for monitoring heparin in our hospital through a pragmatic randomised clinical trial. The Comparison of Heparin Assay Monitoring Protocols (CHAMP) Trial is a single-centre, pragmatic, randomised trial conducted at Vanderbilt University Medical Centre (VUMC) beginning 26 June 2024. The CHAMP trial compares the aPTT protocol to the anti-Xa protocol for monitoring and titration of intravenous UFH for systemic anticoagulation in hospitalised adult patients. Admitted patients initiated on UFH protocols are assigned to either the aPTT or anti-Xa protocol in a randomised fashion. The primary outcome is time to reach the therapeutic anticoagulation range by coagulation assay. Secondary outcomes include the percent of measurements in the therapeutic range, the number of coagulation laboratory measurements over time, frequency of heparin rate changes while on the protocol and the incidence of thrombotic and clinically relevant bleeding events. The CHAMP trial is an ongoing pragmatic trial embedded into the current existing clinical workflow for heparin administration. The two protocols are considered clinically equivalent and already used in clinical practice, allowing for a waiver of consent approval (VUMC Institutional Review Board #232192). This waiver is critical to the implementation of the study due to the nature of scenarios and time constraints in which UFH is typically initiated. Partnering with nursing, pharmacy and clinical providers has been key to launching this study, which provides the first prospective, randomised, direct comparison of the two heparin laboratory protocols available for the monitoring and titration of intravenous UFH in hospitalised patients. After trial completion and data analysis, the findings of the CHAMP trial will be submitted to a peer-reviewed journal for consideration of publication for distribution to a broad clinical audience. The CHAMP study was registered on ClinicalTrials.gov (NCT identifier: NCT06329921) on 19 March 2024. The first patient was enrolled in the study on 26 June 2024, with enrolment of the planned 700 participants expected to occur over two years.
Prospective protocol registration is widely regarded as the preferred standard in systematic reviews. It promotes transparency from the outset of the research process, supports the prespecification of methods, contributes to reducing the risk of selective reporting and unnecessary duplication of effort, and is associated with improved methodological quality and reporting standards. However, despite these well-recognized advantages, not all systematic reviews are prospectively registered. In practice, retrospectively registered protocols continue to occur despite widespread recommendations for prospective registration. This raises an important question: how should retrospectively registered protocols be interpreted in systematic reviews? Within this context, the present commentary does not seek to position retrospective registration as equivalent to prospective registration. Rather, it aims to examine how retrospectively registered protocols may be interpreted in a transparent and methodologically informed manner, acknowledging that retrospective registration alone cannot demonstrate that methodological decisions were prespecified before the review process commenced. We propose that retrospectively registered protocols may be more appropriately interpreted through a transparency-oriented appraisal rather than a strictly timing-based judgment. Such an appraisal may consider whether the retrospective nature of registration is clearly reported, whether the reasons for delayed registration are explicitly described, whether deviations from the initial plan are transparently documented and justified, and whether overall methodological rigor and completeness of reporting are preserved in accordance with established guidance. Retrospective registration has inherent limitations, particularly its inability to prevent undisclosed methodological changes or reduce duplication of effort. Nevertheless, when clearly labeled, sufficiently detailed, and transparently reported, it may still contribute to the interpretability of the review process. Emphasizing transparency, consistency between planned and reported methods, and clarity of methodological decisions may support more robust critical appraisal and informed editorial decision-making in systematic reviews.
The safety of peripherally inserted central catheters (PICCs) in critically ill patients remains controversial, particularly regarding the risk of thrombosis and infection compared with centrally inserted central venous catheters (CVCs). With the adoption of contemporary vascular access techniques and standardized insertion protocols, the complication profile of these devices may have changed. We conducted a retrospective cohort study including adult ICU patients who underwent PICC or CVC placement between January 2023 and December 2024. All insertions followed standardized protocols (Safe Insertion of PICCs and Safe Insertion of Central Venous Catheters). Propensity score matching (1:2) was performed to balance baseline characteristics. Primary outcomes were symptomatic deep vein thrombosis (DVT) and central line-associated bloodstream infection (CLABSI). Secondary outcomes included catheter dislodgement and occlusion. A total of 250 patients were included, and 214 remained after propensity score matching (81 PICC vs. 133 CVC). Symptomatic DVT occurred in 2.5% of PICC patients and 3.0% of CVC patients. The corresponding incidence rates were 2.16 and 2.68 events per 1,000 catheter-days, respectively. CLABSI occurred in 2.5% and 2.3% of patients, corresponding to 2.16 and 2.01 events per 1,000 catheter-days, respectively. Because the number of outcome events was small, these estimates were associated with substantial statistical uncertainty. In this single-center matched cohort, no statistically significant differences in symptomatic DVT or CLABSI were observed between PICCs and CVCs. However, the small number of outcome events limited statistical power. These findings should be interpreted as exploratory and hypothesis-generating rather than as evidence of equivalence between catheter types.
A new n-type conjugated polymer is prepared using aldol polycondensation. The backbone is designed to be linear, coplanar and to have a low LUMO energy level. A bisisatin monomer is made in four steps only under metal-free and ambient conditions. Key to the linear and coplanar structure is the bridging of two isatin motifs by a thiazolothiazole unit. Aldol copolymers with benzodifuranone afford polymers with low LUMO energy levels of ∼ -4.2 eV without using halogens. Defect formation during aldol polycondensation is studied quantitatively using monofunctional model compounds. Besides known defects such as homocouplings, fused analogs are observed along with other defects. Zinc stearate is identified as a superior catalyst, with defects being mostly absent in model reactions. This is in contrast to all other catalytic conditions used, including common literature protocols. Importantly, water must be continuously removed from the reaction to prevent the formation of defects. From these results, protocols are selected that lead to different defect densities in aldol copolymers. Spectroscopic methods confirm the defective nature of aldol polymers but offer limited structural insight into their nature and abundance. Electrospray deposition scanning tunneling microscopy enables direct identification and quantification of defect structures, revealing both similar trends and notable differences in their relative frequencies between small-molecule model systems and full polymers, rationalized by differences in reaction equilibria and chain mobility. Alongside introducing a new low LUMO n-type polymer synthesized via a metal-free route, this study opens pathways toward defect-free aldol polymers, which are otherwise intrinsically prone to defect formation.
This study aimed to evaluate the performance of LUS aeration score in predicting extubation failure among mechanically ventilated neonates. This review was conducted in accordance with PRISMA-DTA 2018. Electronic searches were performed in PubMed, ScienceDirect, Wiley, Nature, and Springer. Methodological quality was assessed using QUADAS-3. Diagnostic meta-analysis was performed in Stata 17.0 using MIDAS, while univariable bivariate meta-regression was conducted in R using the mada package. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), log diagnostic odds ratio (logDOR), and area under the curve (AUC) were calculated. Clinical applicability was assessed using Fagan nomograms, while sensitivity analysis, subgroup analysis, and Deeks' funnel plot asymmetry test were conducted to evaluate robustness, heterogeneity, and publication bias. Ten studies involving 859 neonates were included. LUS aeration score showed high diagnostic accuracy, with a pooled sensitivity of 0.87, specificity of 0.86, PLR of 6.13, NLR of 0.15, logDOR of 3.71, and AUC of 0.93. Heterogeneity was moderate for sensitivity and substantial for specificity. Anatomical scanning coverage was the only significant moderator in meta-regression (p = 0.049), with posterior-inclusive protocols associated with a lower false-positive rate. Deeks' test showed no significant publication bias. LUS aeration score demonstrates good diagnostic performance for predicting neonatal extubation failure and may support clinical decision-making as an adjunct to conventional extubation readiness assessment. Standardized, validated scoring protocols and age-specific external validation are required before a universal cutoff can be recommended. What is Known: • Extubation failure remains a clinically important complication in mechanically ventilated neonates and is associated with increased morbidity. • Lung ultrasound (LUS) is a bedside, radiation-free imaging method, whereas the LUS aeration score is a quantitative measure of regional aeration loss; reported accuracy for predicting extubation failure varies across studies. What is New: • This updated diagnostic meta-analysis of 10 studies involving 859 neonates found strong pooled diagnostic performance of the LUS aeration score for predicting extubation failure, with a sensitivity of 0.87, specificity of 0.86, and AUC of 0.93. • Exploratory univariable bivariate meta-regression identified anatomical scanning coverage as the only significant overall moderator, with posterior-inclusive protocols associated with a lower false-positive rate.
The SH-SY5Y human neuroblastoma cell line is widely used as an in vitro model of β-amyloid (Aβ) neurotoxicity in Alzheimer's disease (AD). However, the lack of standardized protocols for assessing Aβ toxicity-including differentiation strategies for SH-SY5Y cells-limits the comparability of results across studies. To address these issues, we conducted a systematic review and meta-analysis to evaluate how methodological factors influence Aβ-induced toxicity in SH-SY5Y cells. We included 359 eligible studies encompassing 1192 MTT-based comparisons of cell viability between Aβ-treated and control SH-SY5Y cells. A three-level meta-analysis estimated mean cell viability after Aβ exposure at 63% of control levels (95% CI [61.6; 64.3]), with very high heterogeneity (I2 = 99.6%). Meta-regression identified significant associations between increased toxicity and higher Aβ concentrations, longer exposure durations, and the use of peptide preparations described as fibrils. Conversely, differentiation protocols, duration, and cell density did not significantly influence toxicity outcomes. Reporting quality was often poor, with frequent omissions regarding cell line origin, authentication, contamination testing, Aβ preparation details, and nature of the experimental unit. Overall, our findings show robust Aβ toxicity in SH-SY5Y cells, primarily driven by dose, exposure time, and Aβ aggregation state, but not cell differentiation status. Our conclusions highlight the critical need for better reporting of Aβ exposure parameters to enhance reproducibility and translational potential in AD research.
Alchemical free energy (AFE) calculations are a useful tool in computational drug discovery. However, they typically involve relatively short (<10 ns) simulations, meaning that the initial coordinates and, more generally, the setup of the system have a significant effect on the obtained free energy values. To remedy this, we recently developed a fully adaptive version of the simulated tempering algorithm (FAST) and applied it in the context of sampling. In this work, we extend FAST to AFE calculations with and without enhanced sampling of a particular degree of freedom of interest (FAST/MBAR). We show that enhanced sampling significantly increases the mobility of the targeted degree of freedom at the cost of reduced sampling efficiency over λ space. On the other hand, the free energy calculations without explicit targeting of certain degrees of freedom retain initial-coordinate bias over longer time scales. Despite this, both protocols readily explore nanosecond-time-scale events, such as torsional rotation, due to the single-trajectory nature of FAST, making them less sensitive to the system preparation. It is shown that the robust automated nature of FAST/MBAR makes it a competitive alternative to conventional AFE methods.
This narrative review evaluates the current evidence on the efficacy of probiotic interventions for Attention Deficit Hyperactivity Disorder (ADHD) symptoms in both medicated and drug-naïve paediatric and adult populations and assesses the implications for clinical dietetic practice. A narrative review synthesizing randomized controlled trials and observational microbiome studies in paediatric and adult populations, specifically distinguishing between probiotic monotherapy and adjunctive protocols. Observational data confirm gut microbiome alterations in ADHD populations, although specific bacterial signatures vary across studies. Evidence from treatment trials demonstrates that the efficacy of probiotics as monotherapy for core ADHD symptoms remains inconclusive. However, specific adjunctive trials combining probiotics with conventional medication have reported preliminary positive findings on symptom reduction, though results remain heterogeneous. Adult evidence is sparse but indicates potential benefits for emotional dysregulation in specific contexts. This review concludes that current data do not support universal probiotic supplementation or routine clinical recommendation. However, when families inquire about complementary approaches, the existing literature enables evidence informed guidance within a shared decision-making framework that acknowledges the preliminary nature of current findings and sets realistic expectations.
The presence of a pleural effusion in any oncological patient (patient with known underlying current or previous malignancy) tends to be classified as advanced disease with few curative measures. To establish the aetiology of pleural effusions in oncological patients in our subpopulation. The primary objective was to determine the percentage of proven malignant pleural effusions (MPEs). Secondary objectives were to determine the causes of proven MPEs and proven benign (non-malignant) pleural effusions (non-MPEs), and to determine whether proven non-MPEs change the initial cancer staging of patients. This was a retrospective record review of oncological patients admitted with suspected MPE to the Steve Biko Academic Hospital Cardiothoracic Surgery Unit during the period January 2018 - June 2020. Ninety-one patients met the inclusion criteria. The median (interquartile range) age was 56 (41 - 66) years, and there were 54 females (59.3%) and 37 males (40.7%). Pleural biopsy results confirmed MPE in 80.2% (95% confidence interval 70.6 - 87.8) of cases (n=73/91) and non-MPE in 19.8% (n=18/91). The aetiologies of MPEs in descending order were breast (42.5%), lung (24.7%), genitourinary tract (15.1%), lymphoma (9.6%), other (6.8%) and gastrointestinal tract (1.4%) carcinomas. The aetiologies of the non-MPEs were inflammatory (88.9%) and infective (11.1%) in nature. Among the proven non-MPEs, the results led to a possible cancer downstaging in 6/18 patients (33.3%). Among oncological patients with pleural effusions referred to our unit, a statistically significant proportion (80.2%) had MPE by pleural tissue confirmation, with breast carcinoma being the most common cause. Of those with proven non-MPE, only a third had a possible cancer downstaging. What the study adds. This study adds to the growing local evidence-based research by various authors that can be compared with other local and international literature. It also adds to the information needed when establishing or revising protocols in oncological patients with pleural effusions.Implications of the findings. In our population subgroup, the pleural effusions in oncological patients were mostly malignant in nature. The most common cause was breast carcinoma. This is not just a reflection of local referrals, as our unit also receives referrals from other provinces such as Mpumalanga, and sometimes Limpopo.
This exploratory secondary analysis of a randomized controlled trial - originally powered for medication adherence - investigated associations of a nurse-led Phase I cardiac rehabilitation pathway, integrated with narrative nursing, with anxiety and autonomy following percutaneous coronary intervention (PCI). All psychological analyses are exploratory and intended for hypothesis generation, not causal inference. Findings were interpreted within the transactional model of stress and coping, complemented by narrative nursing theory, focusing on how narrative engagement may help patients reconstruct a sense of control, confidence, and active participation during recovery-addressing narrative foreclosure and supporting autonomy beyond symptom alleviation. Phase I cardiac rehabilitation is essential for percutaneous coronary intervention patient, yet standardized nurse-led protocols are lacking and psychological effects remain incompletely understood. Routine care typically delivers didactic education without attending to patients' fears and self-doubt, potentially trapping them in narrative foreclosure. Narrative medicine suggests that providers acting as story witnesses may help transform stagnant trauma narratives into open recovery narratives, reducing threat perception and fostering engagement. A 6-month, parallel-group, assessor-blinded randomized controlled trial. This exploratory analysis enrolled 162 post-PCI patients, who were randomized to an intervention group (n = 81) or a control group (n = 81). The intervention group received a nurse-led, structured Phase I cardiac rehabilitation pathway developed from evidence-based principles and adapted to local practice, supplemented with narrative nursing modules targeting the relief of narrative foreclosure. The control group received conventional care. Outcomes were assessed using the Cardiac Rehabilitation Inventory at baseline, 7 days post-discharge, and at 1, 3, and 6 months, and were analyzed using repeated-measures analysis of variance (ANOVA), with ANCOVA applied for outcomes with baseline imbalances. All analyses of psychological outcomes were exploratory. After baseline adjustment, the intervention group showed significantly lower process anxiety at all follow-ups (F = 7.323, P = 0.008). For outcome anxiety, neither the group main effect (F = 2.088, P = 0.151) nor group × time interaction (F = 0.439, P = 0.725) reached significance, though the intervention group maintained numerically lower scores. For autonomy, significant main effects of time (F = 90.900, P < 0.001) and group (F = 36.843, P < 0.001), and a significant time × group interaction (F = 27.814, P < 0.001) were observed, with between-group differences widening over six months. In this exploratory analysis, a nurse-led pathway incorporating narrative components was associated with improvements in process anxiety and autonomy, though its association with outcome anxiety remained unclear after adjustment. These patterns are consistent with the possibility that structured narrative engagement may help disrupt closed situational trauma narratives, with the progressive widening of the autonomy gap suggesting a gradual reconstruction toward more agentic self-management. Interpreted within the integrated stress-coping and narrative framework, these hypothesis-generating results suggest that inpatient narrative intervention may be more relevant to alleviating proximal rehabilitation uncertainties than long-term fears. Confirmatory trials powered for psychological endpoints are warranted. This structured pathway offers a practical framework for systematizing inpatient cardiac rehabilitation and addressing narrative needs. The sustained reduction in process anxiety suggests combining protocols with narrative engagement may help establish a lower threat baseline early in recovery. The widening autonomy gap over follow-up raises the possibility that narrative reconstruction continues post-discharge, empowering self-management. Given the exploratory, single-center nature, findings should be interpreted as preliminary and hypothesis-generating. ChiCTR2500114277 (retrospectively registered on December 10, 2025), https://www.chictr.org.cn.
Post‑stroke cognitive impairment (PSCI) affects 64%-75% of stroke survivors, severely limiting daily independence and rehabilitation engagement. Conventional interventions often yield suboptimal outcomes due to poor patient psychological engagement. To review the therapeutic effects of horticultural therapy (HT) on cognition, mood, activities of daily living (ADL), and social participation in PSCI patients, and to explore the potential of combined regimens to shorten treatment duration. A narrative review of randomized controlled trials, systematic reviews, and meta‑analyses on HT for PSCI was conducted. HT protocols were categorized into five types based on activity content. HT significantly improves memory, executive function, and orientation through sequential horticultural tasks, while alleviating anxiety and depression via nature contact. It enhances upper‑limb coordination and directly translates to improved ADL. Group‑based HT promotes social reintegration. Plant cultivation and comprehensive programs show the largest effect sizes. Notably, HT combined with cognitive behavioral therapy or intelligent feedback training can achieve significant gains within 4 weeks, suggesting that combined approaches may shorten overall treatment duration. HT is a feasible, low‑cost adjunctive intervention for PSCI. However, protocol heterogeneity and limited long‑term follow‑up constrain current evidence. Standardized, large‑scale RCTs with extended follow‑up are needed to validate optimal standalone and combined protocols.
Cutaneous leishmaniasis (CL) is a zoonotic disease with wide geographic distribution and significant public health impact. In Brazil, the main etiological agents are Leishmania braziliensis and Leishmania amazonensis. In animals, the disease usually presents as a chronic condition characterized by poorly healing skin lesions, oral and ocular involvement, and cutaneous nodules, most commonly affecting the head and neck regions. Diagnosis may be achieved using molecular techniques, immunohistochemistry, cytology, histopathology, and culture. Despite the endemic nature of CL in several regions, histopathological descriptions of the disease in felines remain scarce. This study aimed to describe the histopathological features of cutaneous nodular tissue parasitized by amastigote forms of Leishmania amazonensis in a domestic cat, using different histological staining protocols to compare the performance of different histological staining protocols in this case. A fragment of cutaneous nodular tissue was subjected to routine histological processing and stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), fast green, Fontana-Masson, and Mallory's trichrome. Histological evaluation was performed using photomicrographs obtained from five microscopic fields. Among the evaluated staining techniques, hematoxylin and eosin appeared to provide the best visualization and differentiation of amastigote forms from surrounding tissue structures in the evaluated tissue. The evaluated sections showed moderate lymphoplasmacytic dermal infiltrates and numerous macrophages with cytoplasm filled with amastigotes. Special stains yielded variable contrast, with fast green and Mallory's trichrome allowing reasonable differentiation, while Fontana-Masson showed limited diagnostic utility.
Citizen science (CS) is often characterized as involving inherent trade-offs between scientific validity and public engagement. While existing literature has documented these competing imperatives, less is known about the concrete organizational mechanisms that enable their coexistence. Based on ethnographic fieldwork at the Israel Center for Citizen Science (ICCS), this article examines how hybrid knowledge production is sustained not by resolving this tension, but by structuring it. ICCS functions as a unique scientific site where the primary 'instruments' are communities of human participants. Through analysis of validation processes (mechanical objectivity, standardized protocols) and engagement practices (role-switching, boundary work), I demonstrate that the validity-engagement tension acts as a mechanism rather than a hurdle. The analysis reveals a structure of 'fractal biopower'-nested power/knowledge relations where the division between subject and object repeats at every scale: Nature is subject to participants' observation, participants to institutional management, and institutions to scientific evaluation. This recursive structure allows contradictory logics to operate simultaneously, suggesting that contemporary science increasingly functions through the management, rather than the purification, of hybrid tensions.
Familial DCM (FDCM) is identified when two or more firstdegree relatives have idiopathic dilated cardiomyopathy (DCM) or unexplained death at a young age. This report aims to highlight the clinical manifestations of FDCM in a Nigerian family, emphasizing the importance of genetics while addressing the paucity of local data. This report describes a 22-year-old male with DCM whose elder sibling died from DCM, and a younger one had similar echocardiographic features as the index patient, highlighting the hereditary nature of the disease within his family The patient, initially asymptomatic, reported easy fatigability, breathlessness, and cough, which worsened over three months. Clinical examinations revealed signs of advanced heart failure, including elevated jugular venous pressure and fine bibasal crepitations. Echocardiography confirmed DCM. Despite initial treatment, the patient developed an intracardiac clot and required an extensive medication regimen. Family history indicated an autosomal dominant inheritance pattern, with a younger sibling also showing features of DCM. This case underscores the importance of genetic factors in the pathogenesis of FDCM and highlights the challenges of managing the disease, particularly in resource-limited settings. Early family screening, patient education, and adherence to treatment protocols are crucial for improving outcomes. There is a need for accessible genetic testing to facilitate early diagnosis and intervention in at-risk populations.
Rush immunotherapy (RIT) accelerates the induction phase of allergen-specific immunotherapy treatment (ASIT) by administering incrementally increasing allergen doses over a single day. This approach reduces the time required to maintenance dosing. Safety information in cats with atopic skin syndrome (FASS) remains limited. The objective of the study was to evaluate the safety of RIT in cats with hypersensitivity disease compatible with FASS and to describe the frequency and nature of adverse events. Forty-seven client-owned cats that underwent RIT. A multicentre medical record review from 2019 to 2024 was performed to identify cats that met at least six of 10 criteria for non-flea-induced hypersensitivity dermatitis and were therefore considered consistent with a diagnosis of FASS. All included cats received documented flea prevention and underwent elimination diet trials. Data collected included signalment, medical history, concurrent medications, RIT protocol details, monitoring findings and follow-up communication. Adverse events (AEs) were recorded. In three of 47 cats (6.4%), AEs were observed including tachypnoea, behavioural distress and increased pruritus. In one cat, RIT was discontinued before protocol completion. All affected cats transitioned to maintenance ASIT without recurrence of AEs. Rush immunotherapy appears to be safe in cats with FASS when performed with clinical monitoring. Adverse events were infrequent, mild and self-limiting, supporting use of accelerated induction protocols in appropriately selected patients.
Trauma-informed care continues to follow the 4R principles (realize the widespread nature of trauma, recognize what unresolved trauma looks like, respond by changing practices and protocols, and resist retraumatization) but has expanded to include 6 core guiding principles that include safety, trust, peer support, mutuality, empowerment, and the understanding of an individual's cultural context. Additionally, it is now recommended that trauma-informed practices be offered as universal precautions to all individuals, regardless of trauma history, focusing on trauma prevention. Obstetric anesthesia providers play an important role in minimizing and eliminating preventable trauma and mitigating psychological harm.
Preeclampsia (PE) is a multifactorial hypertensive disorder specific to pregnancy that significantly contributes to maternal and perinatal morbidity and mortality worldwide. According to hospital-based studies, its prevalence in India ranges from 5% to 15%. Despite advances in obstetric care, the early identification of women at risk remains a major clinical challenge. Ophthalmic artery Doppler (OAD), a noninvasive and reproducible imaging technique, provides important information on cerebral autoregulation and maternal vascular resistance with potential exploratory utility in the early detection of PE. To evaluate the predictive value of maternal OAD indices measured during the second trimester (17-23 weeks of gestation) for the subsequent development of PE in a cohort of initially normotensive pregnant women. This prospective observational study, conducted from March 2024 to February 2025, enrolled 90 antenatal women in their second trimester with no prior history of hypertension or renal disease. OAD evaluation was performed using the transorbital approach with the Alpinion E-CUBE 8 ultrasound system, and key Doppler indices were recorded. Participants were subsequently followed through the third trimester to assess the development of PE. Statistical analysis was performed using the independent samples t-test for continuous variables, Fisher's exact test for categorical variables, and receiver operating characteristic curve analysis to assess the predictive performance of Doppler parameters. Out of the 90 participants, 8 (8.89%) developed PE during follow-up. The resistive index (P = 0.004), pulsatility index (P = 0.0003), and most notably, the peak ratio (PR) (P < 0.0001) showed statistically significant differences between the normotensive and preeclamptic groups. Among the Doppler parameters, PR demonstrated the best diagnostic performance, with a diagnostic accuracy of 91.11%, sensitivity of 100%, specificity of 90.24%, and area under the receiver operating characteristic curve of 0.90. Elevated PR values were strongly associated with the subsequent development of PE, indicating potential predictive value that requires further validation in larger studies. Maternal OAD measurements, particularly PR, demonstrated significant associations with the subsequent development of PE in this study cohort. Its noninvasive nature, ease of application, and observed diagnostic performance suggest that it may warrant further evaluation as an adjunctive risk stratification tool in antenatal screening protocols, particularly in resource-limited settings. The early detection and management of high-risk pregnancies could be greatly improved by incorporating OAD into standard obstetric care, potentially improving maternal and perinatal outcomes.
Oral squamous-cell carcinoma (OSCC) is a prevalent malignancy of the head and neck region. A delay in the diagnosis of OSCC often results in a high metastatic tendency, which is the main reason for the high patient mortality. Dynamic monitoring and management of the onset and progression of OSCC are critical for improving patient survival rates. Liquid biopsy technology-characterized by its non-invasive nature, procedural convenience, and capacity for longitudinal monitoring-is a promising adjunct to histopathological examination for the early diagnosis of OSCC. Epigenetic alterations, characterized by reversibility and long-term stability in physiological fluids, are critical enablers of liquid biopsy and its clinical utility. Advances in detection technologies, including quantitative polymerase chain reaction (qPCR), digital droplet PCR (ddPCR), next-generation sequencing (NGS), and electrochemical biosensors, have significantly facilitated the research and clinical translation of epigenetic biomarkers in oral liquid biopsies. However, translating epigenetic biomarkers from research discovery to clinical practice for OSCC remains hindered by several critical challenges: the scarcity of large-scale, rigorously designed cohort studies, limited multicenter validation, inconsistent preprocessing protocols, and a lack of harmonized analytical platforms. Finally, we propose a conceptual framework to outline potential clinical application models for these biomarkers.
To evaluate the prevalence and nature of hearing dysfunction in children with idiopathic nephrotic syndrome (INS) using objective audiological modalities, and to correlate findings with disease status, cumulative corticosteroid dose, and relapse frequency. Prospective cross-sectional study. Department of ENT and Head and Neck Surgery and Department of Pediatric Nephrology, Kasturba Medical College, MAHE, Manipal, India. Twenty-one children aged 2-18 years with confirmed INS were enrolled between March 2024 and March 2026. All participants underwent distortion product otoacoustic emissions (DP-OAE) testing and, where cooperation permitted, auditory brainstem response (ABR) testing. Patients were stratified into three disease groups: newly diagnosed (n = 3), in relapse (n = 7), and in remission (n = 11). Hearing outcomes were compared across groups and correlated with cumulative corticosteroid dose (in milligrams) and relapse frequency using Spearman's rank correlation coefficient. Two of 21 children (9.52%) demonstrated hearing abnormalities. Both were in the remission group (18.2% within this subgroup). DP-OAE revealed subclinical cochlear dysfunction in 2 of 21 children (9.52%). ABR confirmed abnormalities in the same 2 children (2/18, 11.11%) with 100% inter-modality concordance. Both abnormal cases were in the remission group, had multiple relapses (4 and 6 lifetime relapses), and high cumulative corticosteroid exposure (5200 mg and 24,456 mg). Neither child nor parent reported hearing difficulty; otological examination was normal in both. ABR confirmed cochlear origin with no retrocochlear pathology. Relapse frequency strongly correlated with cumulative steroid dose (Spearman ρ = 0.896, p < 0.001). Subclinical cochlear dysfunction is present in a subset of children with INS and is undetectable by routine clinical examination. The findings are consistent with shared renal-cochlear vulnerability and cumulative corticosteroid-associated cochlear toxicity. Objective hearing screening should be integrated into standard follow-up protocols for pediatric nephrotic syndrome.
Carbon nanopipettes (CNPs) have emerged as powerful tools to track intracellular redox processes with high spatial resolution. Their implementation for robust H2O2 sensing, however, is still limited by stability and mechanistic constraints largely attributed to the surface chemistry of the electrode under nanoconfinement. To address this challenge, we report for the first time a combination of Prussian Blue-Nickel hexacyanoferrate (PB-NiHCF) modified carbon nanopipettes for the electrochemical detection of H2O2 under nanoconfined conditions. Electrodeposition strategies and stabilization protocols for the growth of PB-NiHCF thin films are thoroughly inspected. Cyclic voltammetry and double-potential step chronoamperometry (DPSC) are used to rationalize the thin-layer regime established within the nanometric inner tip of the CNPs. Attention is devoted to the nature and catalytic properties of the electrodeposited materials, which are key factors governing the sensing performance. Notably, both the open-circuit potential of the modified nanopipette and the management of the applied potential at the working electrode prove crucial for the detection mechanism. The analytical performance of the system is evaluated by DPSC, demonstrating stable sensing and a linear response up to 500 μM H2O2 (R2 = 0.996), with a limit of detection of 28.9 μM at physiological pH, supporting further in vivo single-cell analysis. Overall, this work provides an analytical framework for H2O2 detection in thin-layer electrochemical cells, opening new perspectives for nanoscale electroanalysis in confined environments and coulometric sensor development.