Illinois is an abortion hub serving a high volume of patients who travel from midwestern and southern states for abortion care. To sustain access to quality services and reduce health care barriers, research is needed to understand the experiences of abortion travelers. To explore the experiences of out-of-state individuals who travel to central and southern Illinois to receive abortion care. This qualitative study used purposeful sampling to recruit 208 participants at 2 abortion clinics between November 2024 and August 2025. Participants completed the study at the time of recruitment. Participants traveled for abortion care based on their state of residence. Using reflexive thematic analysis, both the experiences of out-of-state abortion travelers in central and southern Illinois and the need for reduction in access barriers for those traveling for abortion were examined. In this qualitative study of 208 abortion seekers who successfully traveled to Illinois, 128 (61.54%) self-identified as Black, 50 (24.03%) non-Hispanic White, and 30 (14.42%) as women from additional minoritized racial and ethnic groups. Participants' age ranged from 18 to 45 years. All lived in midwestern or southern states. Participants were interviewed in a private room at the clinic between November 2024 and August 2025. Participants discussed structural, logistical, and emotional challenges. Yet, they described abortion traveling as necessary because of the abortion ban and misinformation, which contributed to increased medical distrust. Medical distrust was already rooted in some participants' previous experiences of receiving biased reproductive care, and for Black women, it worsened because of historical mistreatment and discrimination. Increased medical distrust likely drove people to travel for abortion care. These findings call for enhanced coordination of care with centralized trusted resources, equitable distribution of funding, mental health support, and attention to reduce biased care for Black women. The results also highlight the need to develop strategies to combat misinformation and increase advocacy efforts to reduce abortion stigma.
Understanding how children's spontaneous language behavior relates to standardized metrics of speech and language remains a crucial challenge in studies of language acquisition and clinical assessment. Traditional lab- and clinic-based paradigms are time- and resource-intensive and may not fully capture a child's underlying language competencies. This study aimed to investigate whether automated analysis of naturalistic, child-centered audio recordings can index the developmental trajectory of speech-language abilities from 2 to 5 years of age. A longitudinal design was employed with N = 155 preschoolers, who were followed from 2 to 5 years of age. Deep learning speech classification methods were used to compute canonical proportion-the proportion of a child's speech that is produced as canonical syllables (well-formed syllables with a consonant-vowel transition, such as "ba"), a key marker of speech motor control development and phonological representation building-from child-centered audio recordings collected at 2-4 years of age. Standardized lab-based assessments of speech and language development were administered concurrently and 1 year later at 2-5 years of age. Canonical proportion measures significantly predicted multiple dimensions of later speech-language development. The strongest longitudinal associations were observed for consonant articulation skill and vocabulary size. Weaker, although still significant, relationships were found for metaphonological skills, including phonological awareness and phonological working memory. Findings suggest that children's spontaneous, everyday speech production patterns provide moderate indices of subsequent language development across multiple domains. Automated measures such as canonical proportion hold promise for expanding and diversifying approaches to studying language acquisition and for complementing traditional lab-based assessments.
This year marks the 50th anniversary of the Ebola virus identification, but the 2026 outbreak of Bundibugyo ebolavirus disease has exposed important limitations in Ebola preparedness strategies that remain largely focused on Zaire ebolavirus. Although major advances in diagnostics, vaccines, and therapeutics have followed the 2014-2016 West African Ebola epidemic, most licensed countermeasures were developed against Zaire ebolavirus and may provide limited protection against other ebolavirus species, including Bundibugyo ebolavirus. Herein, we examine the epidemiological significance of Bundibugyo ebolavirus and review current and emerging diagnostics, vaccines, antibody therapies, and antiviral strategies, with emphasis on their species coverage and limitations. We further discuss how diagnostic blind spots and limited species-inclusive countermeasures contributed to challenges during the current outbreak. Future Ebola preparedness should adopt a broader framework encompassing multiple ebolavirus species with epidemic potential.
Monochromator phototesting is a specialist investigation to assess abnormal skin response to defined ultraviolet and visible wavebands in patients with suspected photodermatoses. Monochromator phototesting spans ultraviolet B (UVB), ultraviolet A (UVA) and visible light (VL) and is used in specialist UK photodiagnostic centres. Abnormal-response yield varies between individuals and diagnostic groups. However, the procedure is time- and resource-intensive and limited to specialist centres. To identify the wavebands and waveband combinations that captured the greatest proportion of abnormal monochromator responses, and to explore whether these findings could inform future evaluation of limited-waveband approaches within specialist phototesting pathways. This retrospective single-centre analysis included 668 phototesting results from 552 individuals collected between 2020 and 2025 at the Scottish Photobiology Service, NHS Tayside, Dundee, UK. Records prior to 2020 were reviewed in some selected patients to distinguish persistently negative monochromator tests from previously documented abnormal responses that had resolved before the study period. Assessed wavebands were 305 ± 5 nm (UVB), 335 ± 27 nm (UVB + UVA), 365 ± 27 nm (UVA), 400 ± 27 nm (UVA + VL) and 430 ± 27 nm (VL). Of 552 individuals, 353 received a final clinical diagnosis of photodermatosis and 199 did not. Across individuals with photodermatoses, 335 nm showed the highest single-wavelength abnormal-response yield (203/353, 57.5%), followed by 365 nm (194/353, 55.0%), 305 nm (169/353, 47.9%), 400 nm (108/353, 30.6%) and 430 nm (46/353, 13.0%). Selected two- and three-waveband combinations increased abnormal-response yield, with 305 + 365 nm showing the highest two-waveband yield (239/353, 67.7%) and 305 + 365+400 nm showing the highest selected three-waveband yield (259/353, 73.4%). In complete-case paired analysis, abnormal-response rates differed significantly across wavelengths (Cochran's Q = 200.4, df = 4, p < 0.001). Exploratory subgroup analyses showed distinct wavelength-response profiles across CAD, PLE and SU: CAD showed high yields at 305 and 335 nm, PLE showed lower monochromator abnormal-response yields across selected wavelengths and combinations, and SU showed greater longer-wavelength involvement. In this exploratory single-centre study, around one quarter of individuals with a final photodermatosis diagnosis in our service did not demonstrate abnormal responses on narrow-waveband monochromator phototesting. Limited waveband monochromator combinations showed differing abnormal response yields across photodermatoses, capturing most abnormal responses in chronic actinic dermatitis and many in solar urticaria, but under-detecting polymorphic light eruption. These findings support waveband phototesting across the ultraviolet and visible spectrum in specialist phototesting services. Broadband and provocation-based photodiagnostic approaches remain important, particularly for conditions such as polymorphic light eruption.
Adaptive therapy is an evolution-based treatment paradigm that has been shown to delay resistance in prostate cancer through treatment breaks that control, rather than minimize, tumor burden. However, patient responses are highly heterogeneous, and there is a significant unmet clinical need for biomarkers to personalize treatment scheduling. To develop and retrospectively validate mathematical biomarkers that predict time to progression (TTP), mean daily dose, and overall survival (OS) under adaptive therapy from first-cycle prostate-specific antigen (PSA) dynamics. This retrospective modeling and validation study used longitudinal, nonrandomized clinical trial data from 2 independent cohorts: 40 patients with castrate-sensitive prostate cancer (CSPC) (June 1996 to September 2006) and 13 patients with metastatic castrate-resistant prostate cancer (mCRPC) (April 2015 to January 2022). A 2-population differential equation model was used to describe the overall tumor growth through the competing dynamics of drug-sensitive and drug-resistant cells. The statistical analysis was conducted from January 2025 to May 2026. Patients received either intermittent androgen deprivation therapy (for CSPC) or adaptive abiraterone acetate (for mCRPC). The initial treatment cycle served as the exposure period to extract longitudinal PSA kinetics. Mechanism-based mathematical biomarkers (adaptive therapy score, expected TTP, and expected mean daily dose) were derived from first-cycle PSA kinetics. Outcomes included in silico benchmarking experiments and retrospective validation against clinical TTP and OS. Performance was benchmarked against standard phenomenological PSA metrics (eg, PSA nadir, time to nadir, and doubling time). Overall, data from 53 patients across 2 clinical trials were included. In the CSPC cohort of 40 patients, the adaptive therapy score derived from first-cycle data was highly prognostic for prolonged clinical TTP (univariable hazard ratio [HR], 0.49; 95% CI, 0.31-0.76; P = .002). In the mCRPC cohort of 13 patients, the adaptive therapy score exhibited a strong rank correlation with clinical TTP (Spearman ρ = 0.76; P = .002) and was associated with prolonged TTP (HR, 0.41; 95% CI, 0.16-1.07; P = .07). Analysis of long-term survival data in the mCRPC cohort demonstrated that both the adaptive therapy score and expected TTP were significantly associated with prolonged OS, whereas standard empirical PSA metrics displayed no association with OS. In this modeling and validation study, mechanism-based mathematical biomarkers derived from the initial-cycle PSA dynamics accurately predicted patient-specific outcomes and survival, outperforming traditional phenomenological PSA monitoring. These accessible metrics could act as a mathematically informed decision support framework to stratify patients into personalized treatment protocols.
National evidence on the long-term burden of Clostridioides difficile infection (CDI) in China remains limited. We assessed CDI-related burden from 1990 to 2021 and projected rates to 2030. China-specific estimates of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) were obtained from the Global Burden of Disease Study 2021 (GBD 2021). Temporal trends were evaluated using joinpoint regression, decomposition analysis, and autoregressive integrated moving average models. From 1990 to 2021, CDI-related DALYs increased from 6,645.59 to 15,759.24, and GBD-estimated CDI-attributable deaths increased from 215 to 721. YLLs accounted for more than 99% of DALYs within the GBD estimation framework. In 2021, DALY rates were higher in males than females and increased markedly with age. The death rate had the highest average annual percentage change. Population aging contributed 57.1% of the increase in DALYs, exceeding the contributions of population growth and epidemiological change. Historical-trend-based projections suggested that all-age burden rates may continue to rise through 2030; YLD projections require additional caution because of possible residual autocorrelation. GBD-estimated CDI-related burden in China increased substantially, and age-specific DALY rates were highest among older adults. These model-based findings support strengthened CDI surveillance, diagnostic capacity, antimicrobial stewardship, infection control, and prevention among high-risk older populations.
Electronic patient-reported outcome (PRO) monitoring has shown benefits in advanced cancer, but data specific to metastatic breast cancer (mBC) remain limited. Fatigue is a common, clinically important, and functionally impairing symptom in mBC, making it a patient-centered target for electronic PRO monitoring. To determine whether digital PRO monitoring with alert-based responses reduces fatigue in patients with mBC. This multicenter randomized clinical trial was conducted from May 2021 to February 2024, with 12 months of follow-up, at 52 breast cancer centers in Germany and included women aged 18 years or older with mBC who were receiving systemic therapy at any point in the metastatic disease course, had a life expectancy of longer than 3 months, were able to read German, and had smartphone access. Data analysis started in February 2024 and lasted 6 months. The intervention group completed weekly PRO questionnaires via a smartphone using validated short forms from the European Organization for Research and Treatment of Cancer computerized adaptive testing core item bank. Automated alerts based on predefined PRO deterioration were emailed to trained local nurses or physicians, who contacted patients by telephone within 48 hours. The control group received usual care with quarterly PRO questionnaires and no alerts. The primary outcome was fatigue at 6 months. Secondary outcomes included fatigue, physical functioning, and quality of life over 12 months. PROs were reported as standardized T scores. Of 2008 patients screened, 924 (46.0%) were randomized, and 909 (45.3%) were included in the primary analysis (median age, 50 years [range, 19-83 years]). Baseline mean (SD) fatigue T scores were 57.6 (9.5) in the intervention group and 60.2 (9.0) in the control group (P < .001), with baseline PROs assessed after randomization but before group-specific follow-up began. At 6 months, adjusted mean fatigue was 54.5 (95% CI, 53.7- 55.4) vs 59.9 (95% CI, 59.0-60.8), yielding a mean difference of -5.4 points (95% CI, -6.6 to -4.1; P < .001), exceeding the minimal clinically important difference (MCID) of 3.3 points. At 6 months, physical functioning was higher in the intervention group (mean difference, 4.0; 95% CI, 2.6-5.4), exceeding its MCID (3.2), whereas the between-group difference in quality of life was 0.8 points (95% CI, 0.02-1.5), which was less than the MCID of 2.9. This randomized clinical trial found that digital PRO monitoring was associated with clinically meaningful reductions in fatigue and improved physical functioning. These findings support further evaluation of alert-based PRO monitoring in routine oncology care. German Clinical Trials Register: DRKS00024015.
The World Health Organization recommends universal preventive iron interventions for young children in anemia-prevalent areas to alleviate the effects of anemia on child neurodevelopment and other outcomes. However, the functional benefits have not been confirmed in randomized clinical trials and there are concerns that iron interventions may increase infection risk. To determine whether universal iron interventions administered with malaria chemoprevention improve child functional outcomes and are safe regarding infection risk. This randomized clinical trial enrolled 6-month-old infants at 4 centers in southern Malawi, which is a rural, malaria-endemic setting. Enrollment occurred between April 2020 and October 2021. The final assessment was completed in October 2022. Six months of (1) iron syrup and malaria chemoprevention (n = 542), (2) iron-containing micronutrient powders and malaria chemoprevention (n = 543), (3) malaria chemoprevention alone (n = 541), or (4) placebo alone (n = 542). Children were assessed after the 6-month intervention period and after 6-month follow-up. The primary outcome was the Cognitive Scale composite score at the end of the intervention period using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). The secondary outcomes included Bayley-III Language Scale and Motor Scale composite scores, anemia prevalence, and concentrations of hemoglobin and ferritin. The primary and secondary outcomes were measured when children were 1 year of age and when they were 18 months of age. The safety outcomes included incidence of infection (including malaria). A total of 2168 infants (mean age, 5.7 months; 49% were female; and 71% had anemia) were recruited to participate. Compared with malaria chemoprevention alone, there was no between-group difference in the Bayley-III Cognitive Scale composite score for iron syrup and malaria chemoprevention (mean difference [MD], -0.52 [95% CI, -2.52 to 1.48]). Compared with malaria chemoprevention alone, there was no between-group difference in the Bayley-III Cognitive Scale composite score for iron-containing micronutrient powders and malaria chemoprevention (MD, -0.85 [95% CI, -2.80 to 1.09]). Compared with placebo alone, there was no between-group difference in the Bayley-III Cognitive Scale composite score for malaria chemoprevention alone (MD, 1.62 [95% CI, -0.31 to 3.55]). Although the 2 iron interventions increased ferritin concentration, neither reduced anemia prevalence compared with malaria chemoprevention alone. Compared with malaria chemoprevention alone, neither iron syrup and malaria chemoprevention nor iron-containing micronutrient powders and malaria chemoprevention increased malaria risk. Compared with placebo alone, malaria chemoprevention alone reduced the incidence of malaria. Two universal, 6-month iron interventions with malaria chemoprevention did not improve cognitive outcomes among children in Malawi. anzctr.org.au Identifier: ACTRN12620000386932.
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Decapod iridovirus 1 (DIV1) is a highly lethal pathogen that infects decapod crustaceans including Litopenaeus vannamei, causing mass mortality in cultured shrimp and severe economic losses worldwide. The ATPase gene is a highly conserved region within the DIV1 genome, plays a critical role in viral replication and represents an ideal target for molecular diagnostic development. In this study, we established a rapid, sensitive and field-adaptable detection platform for DIV1 by integrating recombinase polymerase amplification (RPA) with the CRISPR/Cas12a system. RPA enables efficient isothermal amplification of target nucleic acids, achieving exponential enrichment of the target nucleic acids and exerting the function of signal amplification. While the CRISPR/Cas12a system upon crRNA-guided specific recognition of the amplicon, triggers robust trans-cleavage activity against reporter probes for signal generation and readout. After systematic optimization, the RPA reaction was performed at 38°C for 10 min and the CRISPR-Cas12a reaction was conducted at 37°C for 20 min. The integrated two-step workflow completed detection within 40 min, with a limit of detection of 2.3 × 101 copies/μL. Specificity evaluation confirmed that the RPA-CRISPR/Cas12a assay exclusively recognised DIV1 without cross-reaction with other major shrimp pathogens. Further validation using clinical shrimp samples demonstrated stable and reliable performance, supporting its practical utility in aquaculture settings. In conclusion, the established CRISPR/Cas12a-based detection platform provides a robust technical tool for early warning and on-site rapid screening of DIV1, facilitating timely disease control and risk management in shrimp farming.
Antibiotic resistance and biofilm-associated infections represent persistent barriers to effective tissue healing, particularly in chronic and implant-associated wounds. Despite substantial advances in material design, most antibacterial wound dressings remain passive, empirically developed, and poorly adapted to the dynamic biological microenvironment of infection. Nanocellulose (NC), offers exceptional mechanical strength, high surface area, and excellent biocompatibility, positioning it as a versatile matrix for advanced therapeutic applications. Recent innovations focus on engineering NC composites through functionalization with bioactive moieties that enable the activation or localized release of antimicrobial agents selectively within pathological microenvironments. These advanced NC systems are specifically designed to overcome biofilm penetration barriers while minimizing systemic toxicity through site-specific intervention. This review delineates the evolution from fundamental material design principles, such as NC morphology control and surface chemistry modulation, to the development of NC-based platforms capable of disrupting mature biofilms and eliminating pathogenic bacteria. We highlight the breadth, versatility, and long-term potential of NC derivatives and composites as adaptable platforms for antibacterial and antibiofilm applications across multiple infected tissues, including skin, bone, diabetic foot ulcers, and dental infections. Furthermore, we emphasize the translational significance of NC-based hydrogels and scaffolds in future healthcare, positioning them as next-generation, clinically relevant platforms.
Bacterial infections, particularly those caused by multidrug-resistant pathogens and biofilm formation, have significantly undermined the efficacy of conventional antibiotics, highlighting the urgent need for novel antibacterial strategies. NIR-driven photothermal (PTT) and photodynamic therapies (PDT) have emerged as promising non-antibiotic approaches due to their noninvasive nature and precise spatiotemporal controllability. However, single-modality NIR treatments remain constrained by potential thermal damage to healthy tissues and reduced efficacy within the infection microenvironment. To address these limitations, researchers have developed NIR-mediated multimodal strategies that integrate complementary mechanisms for synergistic antimicrobial effects. Despite increasing studies, a systematic overview of NIR-based synergistic antibacterial strategies remains lacking. This review provides the first comprehensive focus on the combined application of NIR-mediated PTT/PDT with gas therapy (GT), chemodynamic therapy (CDT), immunotherapy, antibiotic adjuvants, and sonodynamic therapy (SDT). We summarize recent advances, discuss how these approaches overcome resistance, disrupt biofilm barriers, enhance antibacterial efficiency, and promote wound healing, and highlight the current challenges and prospects for clinical translation in this rapidly evolving field.
Intravenous thrombolysis (IVT) is an established therapy for acute ischemic stroke when administered within 4.5 hours of symptom onset. However, many patients present beyond this window or with unknown onset, and recent randomized clinical trials (RCTs) have evaluated whether imaging-selected patients may benefit from thrombolysis in the extended window. To evaluate the functional and safety outcomes associated with IVT administered 4.5 hours or more after stroke onset. PubMed, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from database inception through March 3, 2026. RCTs enrolling adults with acute ischemic stroke treated with IVT 4.5 hours or more after symptom onset were included. Trials comparing thrombolysis with placebo or standard medical care and reporting functional or safety outcomes were eligible. Data were extracted independently by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk ratios (RRs) and mean differences with 95% CIs were pooled using random-effects models. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Primary outcomes were excellent functional outcome (modified Rankin scale scores of 0-1 at 90 days), good functional outcome (modified Rankin scale scores of 0-2 at 90 days), all-cause 90-day mortality, and symptomatic intracerebral hemorrhage (ICH). Fourteen RCTs including 4174 patients (2102 in the thrombolysis group and 2072 in the control group) were analyzed, 9 of which were published within the past 5 years. IVT was associated with a higher likelihood of excellent functional outcome (RR, 1.22; 95% CI, 1.14-1.31) and good functional outcome (RR, 1.12; 95% CI, 1.06-1.18) at 90 days. Mortality did not differ between groups (RR, 1.13; 95% CI, 0.93-1.38), but thrombolysis was associated with an increased the risk of symptomatic ICH (RR, 2.44; 95% CI, 1.45-4.09). Absolute treatment effects corresponded to a number needed to treat of 12 to 16 for an additional favorable outcome and a number needed to harm of 62 for symptomatic ICH. In this systematic review and meta-analysis of 14 RCTs, IVT administered beyond 4.5 hours after stroke onset was associated with improved functional outcomes despite an increased risk of symptomatic ICH, supporting extension of thrombolytic therapy beyond the conventional treatment window in appropriately imaging-selected patients.
Saliva-based point-of-care testing (POCT) is critical for the early diagnosis of periodontal disease. However, current wearable platforms, such as smart mouthguards, are predominantly limited to monitoring small metabolites (e.g., glucose) and cannot detect specific macromolecular proteins essential for disease characterization. To enable precise early diagnosis, we demonstrate a novel biosensor that integrates microfluidics with organic electrochemical transistors (OECTs). Functionally, this integration enables the simultaneous, multiplexed detection of a complementary biomarker combination: interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8). In terms of performance, the device leverages the high transconductance of OECTs to ensure high precision even at trace levels, achieving exceptional sensitivity with distinct dynamic ranges tailored for early-stage detection (IL-6: 1-80 pg/mL; MMP-8: 10-500 ng/mL). Validating its diagnostic utility, the sensor showed precise quantification (R2 > 0.97) correlated with gold-standard laboratory measurements in a rat model. By delivering clinical-grade precision for complex biomacromolecules, this platform overcomes the limitations of existing wearables and offers a viable path for translating advanced bioelectronics into practical periodontal healthcare.
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Infection is a common and potentially fatal complication during the treatment of hematological diseases, particularly in the context of chemotherapy-induced immunosuppression. The nonselective use of antibiotic prophylaxis in patients with neutropenia in China has persistently accelerated antimicrobial resistance. Early identification of patients at high risk for infection before clinical symptom onset could enable targeted preventive strategies; however, reliable and biologically informed screening approaches remain limited. We developed a prediction model for infection risk stratification in newly diagnosed patients with hematological conditions. Plasma metagenomic next-generation sequencing was performed in a prospective cohort of 230 patients. Among them, 116 patients provided prechemotherapy, non-neutropenic plasma samples (cohort A), and 114 patients provided postchemotherapy, neutropenic samples (cohort B). Microbial community profiles were analyzed, and machine learning approaches were applied to construct classifiers for neutropenia status and subsequent infection risk. Plasma metagenomic profiling revealed a complex microecological landscape in patients with hematological conditions and identified distinct microbial features associated with neutropenia. A trained random forest classifier successfully distinguished patients without neutropenia from patients with neutropenia, achieving an area under the receiver operating characteristic curve of 0.8324. Importantly, a microorganism-based random forest model was established to predict patients at high risk of infection, yielding an area under the curve of 0.942. Nested cross-validation demonstrated high classification accuracy, correctly identifying 99.1% of patients who subsequently developed infections and 72.7% of patients who remained infection-free. Furthermore, integration of microbial features with clinical metrics improved predictive performance, resulting in an area under the curve of 0.953. This microorganism-based prediction model provides an effective tool for infection risk stratification in patients with hematological conditions. By enabling early identification of high-risk individuals, the model has potential clinical utility for guiding precise preventive interventions and optimizing infection management strategies, which can significantly reduce the use of prophylactic antibiotics, thereby mitigating the development of resistance. ChiCTR2100042992.
Heart rate variability (HRV) has remained a relatively finite and niche tool in cardiology despite decades of research supporting its physiological and clinical relevance. This limited adoption may resemble the early history of electrocardiography (ECG), which was initially regarded by many physicians as a laboratory instrument rather than a routine clinical tool. The delayed acceptance of ECG reflected technological limitations, cultural resistance and the need for clinicians to master unfamiliar concepts derived from physics and electrophysiology. HRV faces comparable barriers today. Although derived from ECG RR intervals, HRV requires interpretation of time-domain, frequency-domain, geometric and nonlinear indices that may appear mathematically complex and distant from conventional bedside reasoning. We argue that HRV should not be viewed as a replacement for ECG, but as an extension of ECG from electrical morphology to physiological dynamics. Lessons from ECG history were examined and compared with the current state of HRV adoption in clinical practice. The complementary diagnostic roles of ECG morphology and HRV analysis were considered, together with the potential contribution of wearable sensors, remote monitoring, artificial intelligence and large language models to facilitate HRV interpretation, education and clinical integration. Whereas conventional ECG morphology identifies arrhythmias, conduction disturbances, ischemic alterations and overt electrical abnormalities, HRV provides insight into autonomic modulation, cardiovascular adaptability and systemic physiological regulation. The emergence of wearable sensors, remote monitoring, artificial intelligence and large language models creates an opportunity to overcome barriers that have limited HRV adoption. Artificial intelligence may serve as an educational and interpretive bridge, translating complex HRV metrics into clinically meaningful concepts while supporting medical training, artefact awareness, case-based learning and workflow integration. HRV faces barriers comparable to those encountered during the early adoption of ECG, including technological limitations, educational challenges and resistance to incorporating unfamiliar physiological concepts into routine clinical practice. Lessons from ECG history suggest that HRV adoption will depend not only on evidence but also on standardization, education, clinical interpretation and cultural acceptance within cardiology.
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Exercise is an important non-pharmacological strategy for the management of sarcopenia. However, the relative effects of different exercise modalities and dose parameters remain unclear. We conducted a systematic review and network meta-analysis of randomized controlled trials. The analysis comprehensively evaluated the effects of different exercise interventions and prescription parameters on sarcopenia-related outcomes. Nineteen randomized controlled trials involving 1,267 participants were included. Compared with routine control, moderate-intensity resistance training (MRT) showed the clearest improvement in handgrip strength (mean difference [MD] = 2.37, 95% confidence interval [CI] 0.76-3.98). It also ranked highly for skeletal muscle mass index (SMI) and gait speed, but the related evidence remained uncertain. The findings for SMI were affected by local inconsistency. For gait speed, no intervention showed a significant advantage over routine control. Exploratory analyses suggested that training intensity, frequency, and intervention duration may jointly shape treatment responses across different outcomes. MRT may be considered a reasonable option for improving handgrip strength in older adults with sarcopenia. However, the current evidence does not support identifying a single best exercise approach across all outcomes. Exercise prescription for sarcopenia should therefore be guided by the target outcome and clinical relevance. CRD42024603850.
Mitochondrial diseases are common inherited neurometabolic disorders and frequently involve the nervous system, yet their multisystem nature often necessitates complex pharmacological management. Many commonly prescribed medications have off-target effects on mitochondrial function, and patients with mitochondrial disease may be particularly vulnerable to such effects due to impaired energy metabolism. However, systematic data on medication safety in this patient group remain scarce. In this retrospective, single-centre, cohort-based study at Turku University Hospital (Turku, Finland), we reviewed the medication data from all hospital stays and outpatient prescriptions of 44 mostly adult (20 women; mean age 50 years, range 12-83 years) patients with genetically and clinically confirmed mitochondrial disease for years 2010-2022. We used the Anatomical Therapeutic Chemical system for drug classification. Potential drug-drug interactions and potential adverse drug reactions were investigated. Special focus was on potential mitochondrial toxicity of drugs and clinically relevant drug-drug interactions. Altogether ~ 1000 individual medication entries were reviewed. We identified several common drugs with potentially adverse effects on mitochondria, including metformin, beta-blockers, statins, ciprofloxacin, fluoxetine, ibuprofen, and certain anti-seizure drugs. Medications generally considered contraindicated in mitochondrial disease were not observed. No high-risk drug interactions were detected. Additional finding of clinical relevance was the frequent use of analgesics. Further research regarding mitochondrial safety of several drug classes is needed for more evidence-based safety evaluations. Pain in the context of mitochondrial disease merits increased attention.