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Emergence of Babesia naoakii infection in Indonesian domestic cattle, a new host record in water buffaloes, and characterization of complete mitochondrial protein-coding genes.

Babesia (B.) naoakii, previously referred to as Babesia sp. Mymensingh, is a recently characterized tick-borne haemoprotozoan parasite of cattle. In Indonesia, we first reported its presence in 2022 from clinically affected cattle in Central Java. To investigate the wider epidemiology of this neglected ruminant-associated Babesia species, we surveyed apparently healthy cattle (Bos indicus) and water buffaloes (Bubalus bubalis) across three districts of Java, Indonesia. A PCR assay targeting the B. naoakii-specific apical membrane antigen 1 (ama1) gene detected the parasite occurrence in 34.39% of assessed cattle (87/253; 95% CI: 28.80-40.44%) and 30.77% of water buffaloes (12/39; 95% CI: 18.47-46.52%). These results represent the first record of B. naoakii infection in water buffaloes in the country and confirm that the parasite circulates in subclinically infected bovine hosts. To characterise this apicomplexan parasite further at the molecular level, we assembled in full length the three mitochondrial protein-coding genes (PCGs): cytochrome c oxidase subunits 1 (cox1) and 3 (cox3), as well as cytochrome b (cytb). These genes were reconstructed by next-generation sequencing of blood DNA collected during the acute haemolytic-phase of B. naoakii infection, from calves that subsequently succumbed to the disease in the endemic area. Phylogenetic analyses of the concatenated amino-acid sequences of cox1, cox3, and cytb placed the Indonesian isolates within a well-supported monophyletic clade, distinct from all previously characterised ruminant-associated Babesia species and sister to the Babesia bigemina/Babesia ovata lineage. This placement confirmed species identity and reinforced the genetic distinctiveness of B. naoakii in Indonesia. Notably, although B. naoakii circulates in peripheral blood and mirrors the diagnostic behaviour of the mild pathogen B. bigemina, its clinical impact more closely resembles that of the severe pathogenic B. bovis, particularly in young animals. This diagnostic-clinical discordance highlights the need for B. naoakii-specific molecular surveillance and species-level differentiation in regions of co-endemicity. Given the high prevalence in subclinically B. naoakii-infected adults, the documented severity of babesiosis in calves, and the potential for substantial economic losses, broader epidemiological investigations and species-specific control measures for B. naoakii are urgently performed. The same holds true for future epizootiological investigations of underdiagnosed B. naoakii-infections possibly circulating in Indonesian endemic ruminant bovids such as the banteng (Bos javanicus), the lowland anoa (Bubalus depressicornis) and the tamaraw (Bubalus mindorensis).

Animals

Effects of passive blood flow restriction on muscle function following exercise-induced muscle damage in recreationally active males.

This investigation examined the effects of passive blood flow restriction (pBFR) on indices of exercise-induced muscle damage (EIMD) in recreationally active males. Fifteen males completed six consecutive visits (&#xb1;2&#x2009;hours). Participants completed 3&#x2009;&#xd7;&#x2009;25 maximal, unilateral, isokinetic (60&#xb0;&#xb7;s-1), concentric-eccentric leg extensions on both legs. Each leg was randomly assigned to receive pBFR (80% arterial occlusion pressure) or sham (20&#x2009;mmHg) at 0, 24, 48, 72, and 96&#x2009;hours post-EIMD. Perceived muscle soreness, range of motion (ROM), pain pressure threshold (PPT), concentric peak torque (CPT), and maximal voluntary isometric contraction (MVIC) torque were assessed and analyzed using separate linear mixed-effects models. Perceived muscle soreness increased at 24&#x2009;hours (mean difference [meandiff] = 4.9 au; p&#x2009;<&#x2009;0.001) and recovered by 96&#x2009;hours (p&#x2009;=&#x2009;0.482), with no differences between conditions (p&#x2009;=&#x2009;0.450). ROM (meandiff&#x2009;=&#x2009;-3.1&#xb0;; p&#x2009;=&#x2009;0.040), PPT (meandiff&#x2009;=&#x2009;-1.63 kgf; p&#x2009;<&#x2009;0.001), CPT (meandiff&#x2009;=&#x2009;-27.7&#x2009;Nm; p&#x2009;<&#x2009;0.001), and MVIC torque (meandiff&#x2009;=&#x2009;-30.8&#x2009;Nm; p&#x2009;<&#x2009;0.001) decreased at 24&#x2009;hours, with recovery occurring between 48-96&#x2009;hours. Condition-specific differences were observed for ROM (meandiff&#x2009;=&#x2009;2.5&#xb0;; p&#x2009;<&#x2009;0.001), PPT (meandiff&#x2009;=&#x2009;0.49 kgf; p&#x2009;=&#x2009;0.005), CPT (meandiff&#x2009;=&#x2009;6.2&#x2009;Nm; p&#x2009;=&#x2009;0.020), and MVIC torque (meandiff&#x2009;=&#x2009;7.1&#x2009;Nm; p&#x2009;=&#x2009;0.044), which were greater in pBFR than sham. These findings suggested that pBFR may reduce impairments in ROM, PPT, CPT, and MVIC torque following EIMD, despite a similar recovery trajectory between conditions.

Humans

CanDo (Canadian Donor Milk) randomised controlled trial: pasteurised human donor milk supplementation in the well-baby unit - protocol.

INTRODUCTION: Mother's milk is the gold standard for feeding newborns. Despite lactation support while in hospital, supplementation rates remain high in Canadian well-baby units at 35-50%. When supplementation is needed, the choice between formula milk and pasteurised human donor milk (donor milk) remains uncertain with a lack of clinical trials to inform this practice. This study aims to compare the effect of supplementing mother's milk with donor milk versus formula in infants at higher risk for supplementation (infants of diabetic mothers, infants born small for gestational age or with a birth weight less than 2.5&#x2009;kg and late preterm infants born between 350/7 and 366/7 weeks gestation). METHODS AND ANALYSIS: This is an ongoing, open-label, single-centre, randomised controlled trial conducted at Mount Sinai Hospital, Toronto, Canada. A total of 112 infants (56 per group) will be randomised to receive donor milk or infant formula as a supplement to mother's milk during their initial hospital stay, when supplementation is deemed necessary by the family and/or healthcare team. The primary outcome is exclusive human milk feeding at 4 months of age. Secondary outcomes include any or exclusive human milk feeding at 1, 2 and 3 months; infant growth and health indicators and breastfeeding self-efficacy. Exploratory outcomes encompass infant temperament; parental mental health (assessed using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale); milk cortisol concentrations; and informal milk sharing comparing donor milk and formula supplementation. Follow-up includes monthly telephone assessments and a virtual or in-person visit at 4 months post partum. Data will be analysed using intention-to-treat principles. ETHICS AND DISSEMINATION: The CanDo trial has received ethics approval from the Mount Sinai Hospital Research Ethics Board and the University of Toronto. Results will be disseminated through peer-reviewed journals, conference presentations and stakeholder engagement with hospital and public health decision-makers. Findings will address a critical evidence gap regarding the use of donor milk supplementation in well-baby units and may inform future clinical practice and policy in newborn feeding. TRIAL REGISTRATION NUMBER: NCT06315127.

Humans

[Efficacy and safety of thoracic paravertebral block combined with thoracic nerve block for acute herpes zoster neuralgia involving upper thoracic dermatomes in middle-aged and elderly patients].

To investigate the clinical efficacy and safety of ultrasound-guided thoracic paravertebral block (TPVB) combined with pectoral nerve block (Pecs) in the treatment of acute herpetic neuralgia (AHN) involving the upper thoracic segments in middle-aged and elderly patients, a prospective study was conducted. A total of 70 middle-aged and elderly patients with upper thoracic AHN who visited the Department of Pain Medicine at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, from June to December 2023, were enrolled and randomly divided into a control group and an experimental group using a random number table, with 35 patients in each group. The control group received TPVB once weekly for a total of 3 sessions, while the experimental group received TPVB combined with Pecs block using the same regimen. Outcome measures included the Visual Analogue Scale (VAS) for pain, Pittsburgh Sleep Quality Index (PSQI), 7-item Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), treatment satisfaction score, incidence of postherpetic neuralgia (PHN), rescue analgesia, and adverse events. Assessments were conducted at 1, 4, 8, and 12 weeks post-treatment, and between-group differences were compared. Ultimately, 33 patients in the experimental group and 31 in the control group completed the follow-up and were included in the final analysis. The results showed that both groups demonstrated significant improvements in VAS scores, PSQI, GAD-7, PHQ-9, and satisfaction scores compared with baseline (all P<0.05). Compared with the control group, the experimental group exhibited significantly lower VAS scores and higher satisfaction scores at 1, 4, and 8 weeks post-treatment (P<0.05), as well as significantly lower PSQI, GAD-7, and PHQ-9 scores at 4 and 8 weeks (P<0.05). There were no statistically significant differences between the two groups in the incidence of PHN, rescue analgesia, or adverse events (all P>0.05). This study demonstrates that compared with TPVB alone, the combination of TPVB and Pecs block provides better pain relief, improves sleep quality, and alleviates anxiety and depression in middle-aged and elderly patients with upper thoracic AHN, with a favorable safety profile.

Humans

Transformation of antibiotics mediated by iron-bearing minerals: A review.

Iron-bearing minerals are ubiquitous in water, sediments and soil, where their surface chemical properties and redox activity can play an important role in degradation of trace antibiotics. This review systematically summarizes the roles of various iron-bearing minerals in chemical transformation and microbial degradation of antibiotics and reaction mechanisms involved, and refines the critical idea for iron-driven control of antibiotics with trace level in natural environment. Overall, antibiotics removal in the presence of iron-bearing minerals involves combination of adsorption, surface oxidative degradation, photo-induced degradation, Fenton-like reaction and microbial degradation. Adsorption of antibiotics by Fe(III)-minerals involves electrostatic interaction, complexation, H-bonding, &#x3c0;-&#x3c0; interaction and hydrophobic interaction. Adsorbed antibiotics form complexes with Fe(III)-minerals, undergoing electron transfer to generate radical intermediates, subsequently generating final products through hydroxylation, dealkylation, and deamination. Additionally, Fe(III)-minerals can be excited to produce electrons and holes under sunlight and to produce antibiotics-degrading hydroxyl radical through O2 reduction, H2O oxidation and ligand-to-metal charge transfer. Reduced iron minerals can activate oxygen to participate in Fenton-like degradation reactions. Finally, antibiotics are mainly removed by bio-driven Fenton reaction and direct enzyme biodegradation. The presence of iron-bearing minerals can promote antibiotics microbial degradation by providing nutrients for microorganisms or by changing microbial activity and microbial community structure. Existing problems and future research directions are identified. New insights for application of iron-bearing minerals in transformation of antibiotics are proposed. The work aims to suggest new methods and insights for pollution control and remediation of emerging contaminants including trace antibiotics in the natural environment.

Anti-Bacterial Agents

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145&#xa0;particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI&#xa0;=&#xa0;10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals

Patient and hospital factors associated with disparities in acute stroke treatment in community and academic hospitals.

BACKGROUND: Systemic barriers may affect identification, emergency transportation (EMS), and care coordination for people with stroke. We assessed patient- and hospital-level factors for associations with pre-hospital and emergency department care. We compared trends for patients presenting to an academic medical center (AMC) versus community hospitals (CHs). METHODS: We conducted a retrospective cohort study at an AMC (Tufts Medical Center) with 542 patients aged &#x2265;18&#xa0;years hospitalized with acute ischemic stroke or transient ischemic attack between 1/1/2018-12/31/2020 who presented directly to AMC or presented to AMC as a transfer from initial contact CHs. Primary outcomes were EMS use, stroke code activation, door-to-CT time, and door-to-needle time. RESULTS: AMC patients identifying as non-Hispanic Asian (odds ratio (OR)&#xa0;=&#xa0;0.25; 95% confidence interval (CI)&#xa0;=&#xa0;0.13-0.47) and Hispanic (OR&#xa0;=&#xa0;0.19; 95% CI&#xa0;=&#xa0;0.05-0.72) and CH non-Hispanic Black/African-American patients (OR&#xa0;=&#xa0;0.17; 95% CI&#xa0;=&#xa0;0.05-0.62) were less likely to use EMS compared to non-Hispanic white patients. Patients with non-English primary language were less likely to use EMS (OR&#xa0;=&#xa0;0.38; 95% CI&#xa0;=&#xa0;0.23-0.63) compared to English-speaking patients in both hospital settings. CH Hispanic patients were less likely to have stroke code activation (OR&#xa0;=&#xa0;0.24; 95% CI&#xa0;=&#xa0;0.05-0.86) compared to non-Hispanic white patients. CH patients were less likely to have stroke code activation (OR&#xa0;=&#xa0;0.12; 95% CI&#xa0;=&#xa0;0.07-0.19), had 31% shorter door-to-CT time (95% CI&#xa0;=&#xa0;15-43% shorter), and had 29% longer door-to-needle time (95% CI&#xa0;=&#xa0;5-58% longer). CONCLUSION: Patient-level factors and hospital setting were associated with differences in acute care suggesting opportunities for community outreach on EMS use, interventions to alleviate language barriers, and a need to address systemic biases.

Humans

Endovascular intervention for acute stroke in the very late window: A meta-analysis of 90-day mRS and procedural outcomes.

OBJECTIVE: This study investigates the effectiveness of Endovascular Therapy (EVT) in very late windows (beyond 24&#xa0;h) for patients with ischemic stroke, focusing on 90-day mortality, functional outcomes, and procedural success. METHODS: This systematic review and meta-analysis followed Cochrane and PRISMA guidelines to evaluate the effectiveness of endovascular therapy (EVT) in acute ischemic stroke patients. Literature from PubMed, Embase, Web of Science, and Scopus was reviewed using specific keywords. Studies included those after 2000 with outcomes such as functional independence (mRS 0-2), mortality, TICI scores, and neurological improvements. RESULTS: The data findings reveal mixed outcomes across studies on EVT beyond 24&#xa0;h. Sarraj et al. (2023) found a significant improvement in functional independence with EVT (38% vs. 10%, p&#xa0;<&#xa0;0.05), despite an increased risk of sICH. The forest plots for mRS and procedural outcomes show some significant results, such as Sarraj (2023) for mortality (p&#xa0;<&#xa0;0.05), but most other studies indicated no statistically significant differences (p&#xa0;>&#xa0;0.05). CONCLUSION: The study has concluded that Endovascular Therapy (EVT) beyond 24&#xa0;h can improve functional outcomes and reduce mortality in selected ischemic stroke patients, though patient selection remains crucial.

Humans

Triacylglycerol metabolism is a novel target to combat West Nile virus infection.

West Nile virus (WNV) is a zoonotic Orthoflavivirus transmitted by mosquitoes that is responsible for outbreaks of meningitis and encephalitis worldwide. Driven by climate change, WNV has expanded as a global public health concern, particularly in temperate regions. However, there are still no specific approved therapies, reinforcing the need for antiviral development. Previous works have documented that WNV multiplication strictly depends on certain cellular lipids. To identify novel lipid-related therapeutic targets, we analyzed the infection driven alterations in the CNS lipidome, the primary tissue supporting WNV replication. Our results indicated that the major alterations in the brain lipid content of WNV-infected mice corresponded to triacylglycerols (TAGs). Moreover, transcriptomic analysis showed that infected brains underwent changes in the expression of TAG metabolism. Supplementation with exogenous fatty acids increased lipid droplets (LD) content and promoted viral replication in cell culture models. On the contrary, pharmacological intervention in TAG metabolism using diacylglycerol acyltransferase inhibitors (DGATi) suppressed WNV multiplication in cell culture models. As a proof-of-concept of the therapeutic potential of DGATi, treatment of mice with A922500 reduced viral burden in the brain and proinflammatory cytokine production. Overall, our results unveil the importance of LDs and glycerolipid metabolism for WNV and highlight the potential of therapeutic interventions targeting this pathway to control viral replication and neuroinflammation.

West Nile virus; lipid

Orchard netting impacts on biodiversity leading to cascading effects at the ecosystem level.

Agriculture must ensure food production without further compromising the ecosystem functions upon which it depends. Agricultural practices should therefore avoid harming farmland biodiversity, especially of taxa that supply the key ecosystem services (e.g. pollination, pest control and nutrient uptake) that ultimately support crop production. Orchards are among the largest permanent plantations worldwide and are increasingly characterised by the spread of plastic nets used to protect fruits/nuts from either abiotic (anti-hail, anti-rain, shade nets) or biotic (exclusion nets) hazards. Despite having received little attention to date, these nets may impact natural communities, acting both as physical barriers and as drivers of habitat changes to which biota must respond. Species-level responses to netting depend on the organism's ability to enter the netted environment and successfully exploit available resources. Net-mediated ecological filtering and plastic behavioural responses may alter species interactions, leading to cascading ecological impacts that may create species-poorer 'netted communities' with simplified ecological networks. Such changes may erode biological control potential, other ecosystem functions, and overall system stability. We conducted a systematic review on the effects of protection nets on biota, and reported novel empirical evidence on anti-hail nets' impacts on communities of orchard-dwelling birds, flower-visiting insects, and rodents. In total, we identified 48 studies from the literature, however this literature was strongly biased towards apple orchards, western countries, and pest taxa. Net deployment was highly effective in deterring target pest species, in some cases regardless of their original function, as even weather-protection nets limited pest populations. Side effects on non-target taxa were also often reported, such as decreases in pollinators and natural enemies, and/or increases in secondary pests or microbial diseases. However, most assessments largely disregarded non-pest taxa and the broader ecological consequences of netting. The few studies that addressed the effects of nets at the guild/community level, including our empirical study, confirmed that orchard netting resulted in species-poor assemblages, with possible ecosystem-level consequences. We propose that future assessments should pay more attention to the indirect effects of netting on non-target taxa, and on the supply of crop-supporting ecosystem services mediated by wild species occurring in agroecosystems. Due to the trade-offs between these services and net-mediated crop protection, integrated alternatives should be tested to improve the environmental sustainability of food production and biodiversity conservation in farmed landscapes.

Biodiversity

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27&#x202f;&#xb1;&#x202f;7&#x202f;y) and 24 older adults (12M/12F, age 67&#x202f;&#xb1;&#x202f;8&#x202f;y) were randomized to receive either placebo or PB125 (200&#x202f;mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8&#x202f;&#xb1;&#x202f;1.5 to 3.8&#x202f;&#xb1;&#x202f;1.3%, p&#x202f;<&#x202f;0.0001) and popliteal FMD (PB125: 1.5&#x202f;&#xb1;&#x202f;1.5 to 2.3&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.033) in older, but not younger adults (both, p&#x202f;>&#x202f;0.27). During bed rest, PB125 preserved brachial (3.8&#x202f;&#xb1;&#x202f;1.3 to 3.6&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.543) and popliteal FMD (2.3&#x202f;&#xb1;&#x202f;1.4 to 2.7&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.269), LVC (1.1&#x202f;&#xb1;&#x202f;0.8 to 1.1&#x202f;&#xb1;&#x202f;1.5 AUC, p&#x202f;=&#x202f;0.530) and circulating SOD concentrations (28.3&#x202f;&#xb1;&#x202f;7.2 to 28.6&#x202f;&#xb1;&#x202f;8.6 U/mL, p&#x202f;=&#x202f;0.888) in older adults compared to placebo (all, p&#x202f;<&#x202f;0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4&#x202f;&#xb1;&#x202f;2.8 to 3.4&#x202f;&#xb1;&#x202f;1.8%, p&#x202f;=&#x202f;0.302) in younger adults compared to placebo (p&#x202f;<&#x202f;0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans

Dissemination of blaKPC-3-harbouring Klebsiella pneumoniae across ST48 and ST628 in multiple healthcare facilities in the Republic of Korea.

Klebsiella pneumoniae carbapenemase-3 (KPC-3) remains rare in South Korea, where KPC-2 is the dominant carbapenemase, making the repeated detection of a concentrated blaKPC-3 signal over five years notable. We performed genomic analyses of blaKPC-3-harbouring K. pneumoniae from a regional healthcare network. Two chromosomally distinct lineages with concordant capsule loci (ST628/KL15 and ST48/KL62) presented multidrug-resistant phenotypes, and the virulence-associated loci were confined to ST48. Single-nucleotide polymorphism (SNP) analyses revealed near-clonal relatedness within lineages, with 0-38 pairwise SNPs among ST628 isolates and 8 SNPs between the two ST48 isolates. Core-genome multilocus sequence typing (cgMLST) supported this structure, as ST628 isolates were assigned to complex type 19149 with 0-7 allelic differences, and ST48 isolates were assigned to complex type 19150 with 5 allelic differences. These patterns support vertical spread via clonal expansion across multiple facilities. Despite substantial chromosomal separation, most isolates carried the same IncFII(K) plasmid backbone and blaKPC-3, and they were nearly indistinguishable from a plasmid previously reported in South Korea. One isolate carried blaKPC-3 on a distinct multireplicon IncFIB(K)/IncFII(K) plasmid, indicating that the signal was not confined to a single plasmid backbone. In both plasmids, blaKPC-3 was embedded within Tn4401b. These findings indicate that a rare blaKPC-3 genotype can persist regionally through sustained clonal dissemination and that cross-lineage linkage is compatible with past horizontal transfer involving a conserved plasmid. These findings underscore the need for subtype-resolved, regionally coordinated genomic surveillance in connected healthcare networks to detect uncommon carbapenemase variants early.

Klebsiella pneumoniae

Effect of intraoperative 40-hz gamma-frequency auditory stimulation on postoperative delirium in older adults undergoing major surgery: a randomized clinical trial protocol.

INTRODUCTION: Postoperative delirium (POD) is a common and clinically significant complication among older adults undergoing major surgery under general anesthesia. Gamma-frequency (40-Hz) auditory stimulation has demonstrated potential neuroprotective and cognition-enhancing effects, suggesting a plausible role in perioperative delirium prevention. However, direct clinical evidence supporting intraoperative 40-Hz auditory stimulation in reducing POD remains limited, warranting rigorous evaluation in a randomized trial. PATIENTS AND METHODS: This prospective, parallel-group, randomized controlled trial will enroll 550 older adults scheduled for major noncardiac, nonneurosurgical surgery under general anesthesia. Participants will be randomized in a 1:1 ratio to either the active stimulation group, receiving intraoperative 40-Hz gamma-frequency auditory stimulation delivered via headphones for 2&#x2009;h following successful anesthesia induction, or the sham stimulation group, wearing headphones without active auditory output. The primary outcome is the incidence of POD on postoperative day 1 though 3, assessed using the Confusion Assessment Method (CAM) or the CAM for the ICU (CAM-ICU). Secondary outcomes include POD severity, sleep quality, pain scores, analgesic consumption, the incidence of postoperative nausea and vomiting (PONV), rescue antiemetic use, duration of post-anesthesia care unit (PACU) stay, length of hospital stay, quality of postoperative recovery, incidence of perioperative adverse events; postoperative morbidity, health-related quality of life, and all-cause 30-day mortality. DISCUSSION: This trial will determine whether intraoperative 40-Hz gamma-frequency auditory stimulation reduces the incidence of POD among older adults undergoing major surgery under general anesthesia. If efficacious, this noninvasive intervention could constitute a feasible perioperative strategy to mitigate delirium risk and enhance postoperative recovery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500115156).

Humans

Repeated scoring with the adult appendicitis score improves the sensitivity and the specificity of appendicitis diagnosis in patients with early equivocal signs of appendicitis: a secondary analysis.

PURPOSE: The utilization of computed tomography in the early stage of acute appendicitis may result in overdiagnosis and unnecessarily expose patients to ionising radiation. The Adult Appendicitis Score (AAS) can be used to select patients for imaging. Observation and re-scoring in the DIAMOND trial reduced the need for imaging. Now, we wanted to determine if the change in AAS (&#x2206;AAS) can serve as a diagnostic tool to select patients for imaging even more precisely. METHODS: Eighty-eight patients with early equivocal appendicitis participated in the observation arm of the DIAMOND trial. The data for these patients were reanalysed, and &#x2206;AAS during the observation was calculated. The baseline AAS, final AAS, and the change in C-reactive protein (&#x2206;CRP) were selected as reference standards. RESULTS: Eighty-three patients with complete data were included in the analysis. The AUROC (Area Under the Receiver Operating Characteristic) values are as follows: &#x2206;AAS, 0.932 (95% CI 0.868-0.996); baseline AAS, 0.629 (95% CI 0.498-0.760); final AAS, 0.936 (95% CI 0.886-0.987); and &#x2206;CRP, 0.796 (95% CI 0.696-0.897). Using receiver operating characteristic curves, we established the thresholds for low (AAS&#x2009;&#x2264;&#x2009;-2), intermediate (AAS -1 to 0), and high (AAS&#x2009;&#x2265;&#x2009;1) probability of appendicitis. The negative predictive value for the low-probability group and the positive predictive value for the high-probability group concerning acute appendicitis were 97% and 94%, respectively. CONCLUSION: Patients with equivocal signs of appendicitis may benefit from short observation and the calculation of &#x2206;AAS to reduce overdiagnosis and exposure to excessive imaging. REGISTRATION: The DIAMOND trial was officially registered on ClinicalTrials.gov (NCT02742402) on April 13, 2016.

Adult

The voice clone intelligibility benefit in noise in middle-aged listeners.

Research with younger adults showed that cloned voices are more intelligible than human voices in noise, with a benefit of 13.4%. This study tested whether this benefit extends to 40 middle-aged listeners (45-65&#x2009;years), as this population may show emerging difficulties with speech-in-noise. Participants recognised sentences by ten human voices and ten voice clones in four noise levels. Cloned voices were 11.8% more intelligible, with benefits enhanced at the two most severe noise levels (15.9% at -6 dB and 17.5% at -3 dB), suggesting cloned speech enhanced perception in middle-aged listeners, potentially by reducing listening effort and compensating for emerging age-related auditory-cognitive decline.

Humans

Type, severity, frequency and management of adverse reactions associated with ultrasound contrast agents: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis are aimed at evaluating the incidence of adverse drug reactions (ADRs) following administration of clinically approved ultrasound contrast agents (UCAs) in adults and children, to assess risks in patients with cardiovascular disease and in pregnancy, and to evaluate the effectiveness of emergency management of severe ADRs. MATERIALS AND METHODS: A PRISMA 2020 systematic review was conducted searching PubMed, Scopus, and Embase. Two reviewers independently screened, extracted data, and assessed quality. Incidence estimates were pooled when feasible, stratified by age group, contrast agent, and administration route. RESULTS: Seventy-four studies encompassing >&#x2009;1 million adults and >&#x2009;36,000 children were included, contributing multiple analytic cohorts to the quantitative synthesis. Severe acute ADRs were extremely rare (6 and 16 cases per 100,000 in adults and children, respectively) and absent following endocavitary administration in children. Non-severe acute ADRs occurred in 11 and 8 cases per 10,000 adults and children, respectively. Delayed reactions were very rare (<&#x2009;1 case per million in adults). No significant safety differences emerged between UCA products. The incidence of ADRs in patients with cardiovascular disease was analogous to the general population. No ADRs were reported in pregnant women. Standard emergency management was effective in almost all serious cases, though rare fatalities occurred. CONCLUSION: UCAs show an excellent safety profile in adults and children, with very rare severe ADRs and few non-severe, typically self-limiting reactions. Strict adherence to recommended emergency management protocols mitigates the remaining risks, supporting safe use across a broad range of clinical indications. PROSPERO REGISTRATION: CRD42023432668. KEY POINTS: Question What is the incidence, type, and severity of acute and delayed ADRs associated with clinically approved UCAs across different patient populations? Findings Severe acute adverse reactions are very rare, and non-severe reactions are rare and self-limiting, with no significant safety differences between adults, children, or patients with cardiovascular disease. Clinical relevant UCAs show an excellent safety profile across populations. These findings support their safe clinical use as reliable alternatives to iodine-based and gadolinium-based contrast agents in routine diagnostic imaging.

Contrast Media

Safety of early discharge and abbreviated nimodipine course in patients with good-grade aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular emergency associated with substantial morbidity and mortality. Current guidelines recommend 14-21&#xa0;days of inpatient monitoring and a 21-day course of nimodipine following aSAH. This retrospective study evaluates early outcomes early discharge (&#x2264;14&#xa0;days post-ictus) and an abbreviated nimodipine course in highly selected patients with good-grade aSAH managed under a standardized institutional protocol. Consecutive patients enrolled in the Vancouver Ruptured Aneurysm Database (VRAD) at Vancouver General Hospital between 2022 and 2025 were included. Inclusion criteria were good-grade aSAH (WFNS Grade I-III) and discharge home within 14&#xa0;days of ictus. The primary outcome was re-presentation to emergency care within 30&#xa0;days of discharge; secondary outcomes included hospital readmission and need for additional treatment. Of 333 total patients in VRAD, 49 patients met inclusion criteria. All patients received&#xa0;&#x2264;&#xa0;14&#xa0;days of nimodipine therapy. Forty-two patients (85.7%) were WFNS Grade I on presentation, 3 (6.1%) were WFNS Grade II, and 4 (8.2%) were WFNS Grade III. Radiographic vasospasm was reported in 18 cases (36.7%). No patients developed DCI or clinical vasospasm. Four patients (8.2%) re-presented to emergency care within 30&#xa0;days of discharge, and only one patient (2%) required hospital re-admission within 30&#xa0;days. While radiographic vasospasm was seen in over one third of patients, none developed clinical sequelae, supporting the premise that radiographic vasospasm alone may be insufficient to preclude early discharge in select good-grade patients.

Humans

Colorimetric gold nanosensors for monitoring protein aggregation: implications for Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It remains a major public health challenge due to the lack of early diagnostic tools and effective disease-modifying therapies. Molecularly, AD is characterized by extracellular amyloid-&#x3b2; (A&#x3b2;) plaques and intracellular Tau tangles, as well as soluble oligomers that are likely the neurotoxic species. However, the transient and heterogeneous nature of these oligomers makes them difficult to detect using conventional biosensing approaches. Nanomaterial-based colorimetric biosensors have emerged as promising platforms for detecting protein aggregates and discovering aggregation inhibitors. Specifically, the localized surface plasmon resonance properties of metallic nanomaterials can enable rapid, label-free, and visually detectable colorimetric sensing of molecular interactions. These features can be leveraged to monitor protein aggregation processes in real time and achieve high-throughput screening of aggregation inhibitors, which may collectively enable early detection and timely intervention of AD progression. This Review Article presents the design and engineering of gold-nanomaterial-based colorimetric biosensors for monitoring protein aggregation and highlights the current challenges and emerging opportunities for applying these nanosensors to combat AD.

Journal Article