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Endoscopic Ultrasound-Guided Versus Transjugular Portal Pressure Measurements: Systematic Review and Meta-Analysis.

PURPOSE: Published reviews of endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) have emphasized feasibility and safety. We performed a systematic review and meta-analysis specifically to evaluate how closely EUS-based portal pressure measurements track invasive comparator measurements in prospective paired studies and to summarize agreement, technical success, and adverse events. METHODS: We searched major databases through January 2026 for prospective cohorts reporting same-patient EUS-based portal pressure measurement and invasive hemodynamic measurements. Correlations were pooled with random-effects models and analyzed separately for studies comparing EUS-PPG with hepatic venous pressure gradient (HVPG) and studies comparing EUS-based portal measurements with direct portal venous pressure. Agreement and threshold discordance were summarized descriptively. RESULTS: Six prospective cohorts (127 attempted procedures) were included. In studies using HVPG as the comparator, the pooled correlation was 0.82 (95% CI, 0.72-0.89; I2 = 0%). In studies comparing EUS-based portal measurements with direct portal venous pressure, the pooled correlation was 0.86 (95% CI, 0.72-0.93; I2 = 16.9%). Technical success was 95.3%. EUS-PPG-attributed adverse events occurred in 2.4% of procedures, with no procedure-related deaths. Agreement data were limited. Reported limits of agreement were wide (approximately - 6 to + 7 mmHg), and discrepancies of 5 mmHg or greater occurred in 4 of 30 paired measurements. CONCLUSIONS: EUS-based portal pressure measurement is feasible and shows a strong association with invasive hemodynamic comparators, but the evidence base remains small (six cohorts, 127 attempted procedures). Further study will be necessary to establish patient-level agreement, procedural reproducibility, EUS-specific clinically significant portal hypertension thresholds, and whether HVPG-based decision thresholds can be transferred to EUS-derived measurements.

Humans

Correlative analysis of endogenous miRNA expression profiles underlying brown planthopper adaptation to resistant rice.

The brown planthopper (Nilaparvata lugens Stål, BPH) is a major insect pest threatening global rice production. However, the molecular mechanisms underlying the adaptation of BPH populations with different virulence levels to resistant rice cultivars remain poorly understood. MicroRNAs (miRNAs), as key post-transcriptional regulators, play critical roles in host adaptation in herbivorous insects. In this study, we analyzed the miRNA expression profiles of a high-virulent population (IR56p) and a low-virulence population (TN1p) after feeding on susceptible (TN1) and resistant (IR56) rice cultivars. Our findings reveal distinct miRNA-mediated regulatory strategies employed by the two populations. The IR56p population showed downregulation of miRNAs including miR-10, miR-124, and miR-316, showing an inverse correlation with increased expression of predicted target genes involved in detoxification (carboxylesterase, UDP-glycosyltransferase) and effector function (calmodulin). In contrast, several miRNAs highly expressed in IR56p, including miR-307, miR-317, and miR-275, were predicted to target rice genes associated with hormone signaling, cell wall biosynthesis, and oxidative homeostasis, suggesting a possible but unproven inter-species regulatory role that requires functional validation. Collectively, these descriptive and correlative findings provide hypothesis generating insights into insect-plant coevolution and identifies candidate molecular targets for future functional validation and RNA interference-based pest management strategies.

Animals

Effect of urinary catheter securement band on meatal pressure injury in male intensive care patients: A randomized controlled trial.

OBJECTIVES: To investigate the effectiveness of a urinary catheter securement band in preventing meatal pressure injury (meatal-PI) in male ICU patients, and to identify associated risk factors and the timing of injury development. METHODS: A total of 248 adult male ICU patients were randomly allocated to an intervention group (n&#xa0;=&#xa0;124) or a control group (n&#xa0;=&#xa0;124) between December 2024 and April 2025. The intervention group received a catheter securement band in addition to standard care, while the control group received standard care alone. Meatal-PI was evaluated daily using a structured monitoring form and a validated staging system. RESULTS: The incidence of meatal-PI was significantly lower in the intervention group (6.5%) compared with the control group (16.1%) (p&#xa0;=&#xa0;0.016). Multivariate analysis identified catheter securement, use of silicone catheters, higher Braden Scale scores, and shorter ICU length of stay as independent protective factors, while advanced age was associated with increased risk. Additional factors significantly associated with meatal-PI included comorbidities, higher device burden, latex catheter use, dry skin, lower Glasgow Coma Scale and Braden scores, sedation, and perineal oedema (p&#xa0;<&#xa0;0.001). CONCLUSIONS: The use of a catheter securement band significantly reduces the incidence of meatal-PI in male ICU patients. Incorporating catheter securement devices into routine nursing care, prioritising silicone catheter use, and performing regular meatal assessments may enhance patient safety by reducing the risk of device-related pressure injuries. Further research comparing different catheter securement methods across diverse patient populations is warranted. IMPLICATIONS FOR CLINICAL PRACTICE: The use of catheter securement bands may reduce the incidence of meatal-PI in male ICU patients. Incorporating standardized catheter stabilization strategies into routine intensive care nursing practice may enhance patient safety and support pressure injury prevention efforts.

Humans

Dynamics and virulence of Enterobacteriaceae reservoirs harboring blaCTX-M group 1 in community wastewater.

UNLABELLED: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are ubiquitous and can cause serious infections. Here, we examined untreated community wastewater influent as a reservoir for blaCTX-M group 1 organisms and their virulence potential. Raw influent samples (n = 268) were collected from four wastewater treatment plants (WWTPs) representing dense urban populations. We observed that blaCTX-M group 1 levels were high at all WWTPs and only ~1-2 log10 lower and not correlated to common human-specific microbiome fecal markers, Lachno3 and HF183, indicating a lack of connection to human fecal inputs. Concentrations of blaCTX-M group 1 genes and markers for presumptive host organisms Escherichia coli and Klebsiella pneumoniae were influenced by travel time and season. Amplicon sequencing revealed high diversity of blaCTX-M group 1-9 genes, with 63% belonging to group 1. Selective culture and 16S rRNA gene sequencing showed blaCTX-M group 1 isolates were 26% E. coli, 26% K. pneumoniae, 40% other Enterobacteriaceae, and 8% Aeromonas. Overall, E. coli averaged 3.6E7 cells/L, with 3% of all E. coli found to contain blaCTX-M group 1. Whole-genome sequencing of blaCTX-M group 1 E. coli from wastewater revealed resistance and virulence gene profiles similar to clinical isolates and distinct from other wastewater ESBL-resistant and non-resistant E. coli. Interpretation of wastewater data needs to consider both the existence of environmental reservoirs that contain potentially pathogenic organisms and the strong influence the dynamics of the conveyance system can have on final concentrations measured at the WWTP. IMPORTANCE: The CTX-M enzyme family is highly abundant in nosocomial, community, and environmental settings and is leading to treatment of infections with carbapenem antibiotics, a last-line therapeutic option. The progressive increase of the clinically relevant blaCTX-M group 1 resistance genes in the human population warrants investigation, particularly to understand the establishment and dynamics of environmental reservoirs. This study utilized molecular and culture methods to gain insight into the possible origin, abundance, and dynamics of blaCTX-M group 1 genes in untreated wastewater influent samples. We found extremely high levels of these genes, with Escherichia coli as a major host organism that closely resembled clinical strains, suggesting they are seeded and propagate in sewer pipe systems. The significance of our research is in developing approaches to monitor antimicrobial resistance reservoirs in community wastewater, which could shed light on global burdens and potential transmission cycles and indicate increasing inputs of clinically relevant strains originating from human populations.

E. coli

Illicium verum polysaccharide targets fimbriae and flagella to disrupt biofilm and inhibit multidrug-resistant Escherichia coli proliferation.

The widespread dissemination of multidrug-resistant (MDR) E. coli has led to a decrease in the efficacy of antibiotics, posing severe challenges to clinical anti-infective therapy. Owing to their safety, multitarget activities, and low risk of inducing drug resistance, plant polysaccharides represent a promising alternative strategy. In this study, an acidic polysaccharide (IVP-3) was isolated and purified from the medicinal and edible plant Illicium verum, and it was found to inhibit MDR E. coli colonization by disrupting its biofilm. The Mw of IVP-3 was determined to be 35.566&#xa0;kDa. Its backbone consists of &#x2192;4)-&#x3b1;-D-GalpA-6-OMe-(1&#x2192;, &#x2192;4)-&#x3b1;-D-GalpA-(1&#x2192;, &#x2192;4)-&#x3b2;-D-Galp-(1&#x2192;, and &#x2192;3,4)-&#x3b1;-D-GalpA-(1&#xa0;&#x2192;&#xa0;residues, whereas the branched chain is composed of &#x3b1;-L-Araf-(1&#xa0;&#x2192;&#xa0;5)-&#x3b1;-L-Araf-(1&#xa0;&#x2192;&#xa0;attached to the O-5 position of &#x2192;2,5)-&#x3b1;-L-Araf-(1&#x2192;, which is further linked to the O-3 position of the backbone. Mechanistically, IVP-3 disrupts the structure of fimbriae and flagella, inhibits bacterial motility, effectively prevents initial biofilm adhesion, and eradicates preformed mature biofilms. Additionally, IVP-3 damages cell membrane integrity, disrupts the proton motive force, and induces energy metabolism disorder, efflux pump inhibition, and oxidative stress, ultimately leading to bacterial lysis. This study provides a theoretical basis for the development of natural antibacterial agents targeting MDR E. coli biofilms and for the high-value utilization of Illicium verum.

Biofilms

Contribution of the Arg-33-His replacement in the histidine kinase CpxA to carbapenem and cefiderocol resistance in Serratia marcescens.

OBJECTIVE: The Serratia marcescens ROT_R clinical isolate, which was resistant to almost all &#x3b2;-lactams, including cefiderocol (4 mg/L), was recovered from a neonate 2 months after the isolation of the S. marcescens ROT_S strain that was susceptible to extended-spectrum cephalosporins (ESCs). In this study, we attempted to decipher the mechanism of resistance displayed by the ROT_R isolate. METHODS: The genomes of ROT_S and ROT_R were sequenced using the Illumina and the Oxford Nanopore Technologies. Long and short reads were assembled together, giving rise to a circularized hybrid genome. RESULTS: Genomic comparison between ROT_S and ROT_R disclosed only one mutation (G98A) in the cpxA gene of ROT_R, which led to the Arg-33-His substitution in the histidine kinase of the two-component system CpxA/CpxR. The cpxA alleles of ROT_S and ROT_R were amplified and cloned, thus giving rise to the pCpxA_WT and pCpxA_R33H recombinant plasmids, respectively, which were subsequently introduced into the S. marcescens HatR recipient strain, which lacks functional CpxA. The S. marcescens HatR (pCpxA_R33H) recombinant clone, which produced the altered CpxA_R33H variant, differed from the S. marcescens HatR (pCpxA_WT) recombinant clone, which produced the wild-type CpxA, by enhanced MICs of carbapenems and ESCs, including cefiderocol (1 mg/L). CONCLUSIONS: This study demonstrates that CpxA alteration, such as Arg-33-His substitution, can contribute to cefiderocol resistance. Although it increases slightly the MIC of cefiderocol without resulting per se in clinical resistance, it can contribute, in combination with other additional mechanisms, to achieve a high level of resistance to this siderophore cephalosporin.

Cefiderocol

Elucidating the evolution of meat quality, water distribution, microstructure, and protein structure during sous-vide and micro-pressure cooking.

This study investigated the evolution of eating quality (colour, texture and volatile flavour compounds), water status, microstructure and protein structure of pork meat under different cooking methods. The methods analysed included traditional cooking (TC: 10, 20, 30 and 40&#xa0;min, 100&#xa0;&#xb0;C), sous-vide cooking (SV: 1, 2, 3 and 4&#xa0;h, 60&#xa0;&#xb0;C) and micro-pressure cooking (MC: 10, 20, 30 and 40&#xa0;min, 120&#xa0;&#xb0;C). Across the three cooking processes, as cooking time increased, cooking loss, lightness, yellowness, P23, &#x3b2;-sheet, random coil and surface hydrophobicity of the meat samples increased. By contrast, redness, P22, hydrogen proton density, esters content, &#x3b1;-helix, &#x3b2;-turn and sulfhydryl group content decreased. Moreover, the Warner-Bratzler shear force (WBSF), adhesiveness, hardness, springiness, gumminess, chewiness, alcohols, aldehydes, ketones and fluorescence intensity of the meat samples, initially increased and then decreased as cooking progressed. SV resulted in higher water-holding capacity (WHC), improved redness and increased alcohol and ester levels, whereas MC produced softer meat and greater water mobility. Furthermore, MC enhanced the degree of microstructural damage and protein structural unfolding in the meat. MC requires less time to achieve textures and flavours similar to those obtained using the TC and SV methods. Thus, MC is an efficient cooking method for the catering industry to obtain desired meat quality rapidly.

Cooking

Association Between 24-Hour Blood Pressure and Rates of Retinal Nerve Fiber Layer Progression in Glaucoma: The Vascular Imaging in Glaucoma Study.

PURPOSE: Low systemic blood pressure (BP) has been implicated as a risk factor for glaucoma progression. The purpose of this study was to investigate the association between 24-hour BP and rates of retinal nerve fiber layer (RNFL) loss in eyes with primary open-angle glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-nine eyes from 42 subjects with glaucoma (mean age, 68.5 &#xb1; 7.6 years) enrolled in the Vascular Imaging in Glaucoma Study at the Bascom Palmer Eye Institute. METHODS: Participants underwent 24-hour ambulatory BP monitoring at baseline. Follow-up evaluations were conducted at 4-month intervals and included ophthalmic examination, BP measurement, and peripapillary RNFL thickness measurement with spectral-domain optical coherence tomography. The association between BP and RNFL loss over time was assessed using linear mixed-effects models adjusted for age, sex, race, baseline RNFL thickness, central corneal thickness, and intraocular pressure. MAIN OUTCOME MEASURES: The effect of baseline 24-hour mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) on the rate of average RNFL loss over time. RESULTS: Eyes underwent an average of 13 &#xb1; 3 optical coherence tomography exams over 43 &#xb1; 10 months of follow-up. The mean rate of RNFL loss was -0.34 &#xb1; 0.64 &#xb5;m/y (median: -0.32; interquartile range: -0.66 to -0.04 &#xb5;m/y). After adjusting for confounding factors, every 10 mm Hg lower in 24-hour minimum MAP, SBP, and DBP was associated with -0.542 &#xb5;m/y (P < .001), -0.360 &#xb5;m/y (P = .003), and -0.458 &#xb5;m/y (P = .008) faster RNFL loss, respectively. Eyes in the lowest quartile of average 24-hour MAP (81-90 mm Hg) and minimum 24-hour DBP (35-47 mm Hg) experienced significantly faster progression compared to those in the highest quartile, with differences of -0.68 &#xb5;m/y (P = .017) and -0.63 &#xb5;m/y (P = .030), respectively. CONCLUSIONS: Lower systemic BP, especially minimum MAP, SBP, and DBP measured by 24-hour ambulatory BP monitoring, is associated with faster rates of RNFL loss in primary open-angle glaucoma eyes. 24-hour BP monitoring may help predict glaucoma patients at greater risk of progression.

Humans

Telmisartan-based monotherapy and combination regimens for blood pressure control in adults with hypertension: a systematic review, meta-analysis, and GRADE assessment.

PURPOSE: To evaluate the efficacy, safety, and certainty of evidence for telmisartan-based antihypertensive regimens in adults with hypertension. METHODS: This systematic review and meta-analysis followed PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception to 2026. Eligible studies enrolled adults with hypertension and compared telmisartan monotherapy or telmisartan-containing combinations with placebo, usual care, non-telmisartan antihypertensive agents, or alternative telmisartan-based regimens. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs), using random-effects models, with additional subgroup analyses conducted by comparator type. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE. RESULTS: Twenty-five included reports (24 unique trials, since two reports present secondary outcomes from the same underlying trial) involving 6,521 participants were included, spanning placebo-controlled, usual-care-controlled, active-comparator, and telmisartan-combination-versus-telmisartan-monotherapy designs. Telmisartan-based therapy significantly reduced office systolic blood pressure (MD&#x2009;-&#x2009;6.39&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;7.86 to&#x2009;-&#x2009;4.93; low certainty) and office diastolic blood pressure (MD&#x2009;-&#x2009;4.88&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;6.67 to&#x2009;-&#x2009;3.09; low certainty), although the magnitude of effect was comparator-dependent. Based on only two trials, 24-h ambulatory systolic blood pressure (MD&#x2009;-&#x2009;7.16&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;10.61 to&#x2009;-&#x2009;3.72) and ambulatory diastolic blood pressure (MD&#x2009;-&#x2009;4.42&#xa0;mm Hg; 95% CI&#x2009;-&#x2009;6.36 to&#x2009;-&#x2009;2.48) were reduced with moderate certainty. Telmisartan-based regimens improved blood pressure response (RR 1.68; 95% CI 1.31 to 2.16; moderate certainty) but not blood pressure control achievement (RR 1.44; 95% CI 0.92 to 2.24; very low certainty). Overall adverse events, dizziness, and headache were comparable (very low to low certainty), while edema was less frequent with telmisartan-based therapy (RR 0.33; 95% CI 0.15 to 0.73; moderate certainty). CONCLUSION: Telmisartan-based regimens, particularly fixed-dose and multidrug combinations, effectively reduce office and ambulatory blood pressure and improve blood pressure response, with broadly comparable short-term safety and less edema. These effect sizes are comparator-dependent, and certainty of evidence for absolute blood pressure control achievement and for major adverse events is very low; heterogeneity, limited long-term data, and a predominance of Asian-population trials warrant cautious interpretation pending larger, higher-quality, and more geographically diverse confirmatory studies.

Humans

Blood pressure management after endovascular thrombectomy in acute ischemic stroke: association with symptomatic intracranial hemorrhage and functional outcome at 3&#xa0;months.

BACKGROUND: No clear consensus exists on ideal systolic blood pressure (SBP) targets after endovascular thrombectomy (EVT) following an acute ischemic stroke (AIS). This study investigated the association between SBP parameters within the first 24&#xa0;h after EVT and 3-month functional outcomes and the risk of symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively collected and prospectively followed clinical, and radiological data for patients undergoing EVT for AIS from 2016 to 2024, including 2-hourly BP measurements during the first 24&#xa0;h and SBP variability assessed by standard deviation (SD) and coefficient of variation (CV). Outcomes included 3-month functional status and sICH, and their associations with post-EVT BP metrics were analyzed. RESULTS: A total of 268 post EVT patients were included with a median age of 61&#xa0;years (IQR, 51-69). Mean SBP was 129.67&#xa0;&#xb1;&#xa0;17.17&#xa0;mm Hg, with SBP variability (SD 12.6&#xa0;&#xb1;&#xa0;5.4&#xa0;mm Hg; CV 9.6&#xa0;&#xb1;&#xa0;3.8&#xa0;%), while good functional outcome and sICH occurred in 39.7&#xa0;% and 4.9&#xa0;% of patients, respectively. Multivariate regression showed that higher admission NIHSS&#xa0;(>15) [0.90 (95&#xa0;%CI, [0.86, 0.95], p&#xa0;=&#xa0;0.000)], recanalization status [1.88 (95&#xa0;%CI, [1.43, 2.48], p&#xa0;=&#xa0;0.00)], and SBP-CV&#xa0;&#x2265;&#xa0;10 [0.44 (95&#xa0;%CI, [0.2, 0.94], p&#xa0;=&#xa0;0.036)] was independently associated with poor 3-month functional outcome, while higher admission NIHSS (>15) [0.87 (95&#xa0;%CI, [0.77,0.98], p&#xa0;=&#xa0;0.02)] and diabetes [0.12 (95&#xa0;%CI, [0.03, 0.54], p&#xa0;=&#xa0;0.006)] predicted increased risk of sICH. CONCLUSIONS: The study showed that reduced BP variability during the first 24&#xa0;h post-EVT was associated with better 3-month functional outcomes. A clear association between SBP and sICH risk was not demonstrated.

Humans

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

BACKGROUND: Acquired resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). Although circular RNAs (circRNAs) have been increasingly implicated in drug resistance, most studies have focused on their canonical role as microRNA sponges, while their capacity to encode functional micropeptides remains largely unexplored. This study aimed to identify novel circRNAs involved in osimertinib resistance and to characterize their regulatory functions at the protein level. METHODS: Osimertinib-resistant (OR) NSCLC cell lines were established and validated. High-throughput RNA sequencing was performed to compare the circRNA expression profiles between parental and OR cells. The function of the candidate circRNA was assessed through a series of in vitro and in vivo experiments, including cell viability assays, apoptosis analysis, and xenograft mouse models. Mechanistic investigations involved mass spectrometry, co-immunoprecipitation and western blotting to explore its protein-coding potential and downstream signaling pathways. RESULTS: We identified a novel circRNA, termed circTLL1, that was stably and significantly upregulated in OR-NSCLC cells. Functionally, overexpression of circTLL1 promoted osimertinib resistance, whereas its knockdown restored drug sensitivity both in vitro and in vivo. Mechanistically, we discovered that circTLL1 harbors an open reading frame (ORF) that is translated into a novel 90-amino-acid protein, which we designated circTLL1-90aa. Further investigation revealed that circTLL1-90aa directly interacts with and promotes the degradation of 5'-nucleotidase, cytosolic II (NT5C2), thereby uncoupling nucleotide metabolism from its normal regulatory constraints. The consequent downregulation of NT5C2 leads to elevated GTP levels and leading to the sustained activation of the downstream Ras/PI3K/AKT signaling pathway. CONCLUSION: Our findings unveil a previously unrecognized circRNA/micropeptide/metabolism cascade underlying osimertinib resistance. The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance. Given its selective upregulation in resistant cells, circTLL1-90aa holds promise both as a predictive biomarker for treatment stratification and as an actionable therapeutic target, offering a novel strategy to overcome osimertinib resistance in NSCLC patients.

Pyrimidines

Comparison of the Effects of Spinal Versus General Anesthesia on the Perioperative Intraocular Pressure: A prospective, randomized clinical trial.

OBJECTIVES: To evaluate the effects of spinal and general anesthesia on the intraocular pressure (IOP) in patients, who had lumbar spine and lower extremity orthopedic surgeries. METHODS: Sixty adult were randomly classified into Group spinal anesthesia (SA) and Group general anesthesia (GA). The IOP, mean systemic arterial pressure, and heart rhythm were measured at 6 pre-determined timepoints (T0: Baseline, T1: Before spinal procedure or anesthesia induction, T2: After injection with intrathecal or anesthesia induction, T3: 5th minutes (min) after spinal procedure or tracheal intubation, T4: 30th min intraoperative, T5: At the end of surgery, T6: 5th min after surgery or tracheal extubation in the operation room. RESULTS: The baseline IOP and IOP1 measurements during were not significantly different between the groups (SA = 14.28 &#xb1; 0.8 mmHg; GA = 14.62 &#xb1; 0.9 mmHg, p = 0.923; and IOP1: SA = 15.83 &#xb1; 0.9 mmHg; GA = 15.88 &#xb1; 0.9 mmHg, p = 0.929). The most significant decrease in IOP in both groups was recorded at T2 (SA: 12.37 &#xb1; 0.6. GA: 12.24 &#xb1; 0.4, p < 0.001). The decrease in IOP2 was more significant in the GA group. The IOP3 was significantly higher in GA group after intubation (GA: 19.82 &#xb1; 1.2, SA: 12.86 &#xb1; 1.0)(p < 0.05). The IOP4 and IOP5 in the SA group were lower than those in the GA group. The IOP6 in both groups was higher (SA: 15.20 &#xb1; 0.8, GA: 16.50 &#xb1; 1.0) than the baseline IOP values, albeit not significant (p > 0.05). In prone position, IOP at the T4 and T5 timepoints were significantly higher than the initial values in both the SA and the GA groups; however, the increase in the GA group was more higher than that of the SA group. CONCLUSION: In intraoperative period, intraocular pressure may increase in both management of anesthesia, but this increase is higher in the general anesthesia group.

Humans

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/&#x3b2;-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans

Influence of endodontic access on the fracture resistance, retention and microleakage of full-coverage restorations in vitro: A systematic review and meta-analysis.

BACKGROUND: Endodontic access through retained full-coverage restorations (FCRs) is a preferred option for patients because of its high cost-effectiveness. However, the clinical performance of FCRs after repaired access cavity remains insufficiently characterized. This systematic review investigates the effects of endodontic access cavity preparation through retained FCRs on fracture resistance, retention, and microleakage based on in vitro studies. METHODS: A comprehensive search was performed in PubMed, Web of Science, and Scopus databases. Studies investigating the influence of endodontic access on the fracture resistance, retention, and microleakage of FCRs were included. Two independent reviewers conducted study selection, data extraction, and risk-of-bias assessment using the QUIN tool. Meta-analysis was employed to estimate fracture resistance and retention, with sensitivity analysis and subgroup evaluation also performed. Microleakage was summarized qualitatively. RESULTS: Twentythree studies were included: fracture resistance (n = 15), retention (n = 5), and microleakage (n = 3). Endodontic access significantly reduced fracture resistance for zirconia (p = 0.0002) and lithium disilicate (LD) restorations (p = 0.007), but not for resin-matrix ceramic (RMC) restorations (p = 0.25). Abutment tooth type contributed to heterogeneity within the LD and RMC subgroups. Retention was significantly reduced when access cavities were left unrepaired (p = 0.03), whereas appropriate repair protocols restored or enhanced retention relative to baseline. Accelerated aging increased microleakage in retained FCRs. Surface pretreatments and flowable resin liners tended to reduce microleakage, but findings were inconsistent. CONCLUSIONS: Endodontic access significantly reduces fracture resistance of zirconia and LD FCRs, whereas RMC restorations show no significant change. Appropriate repair protocols can restore or improve retention, potentially exceeding original values. Limited evidence suggests that effective sealing is achievable with appropriate materials. However, well-designed and in-vivo researches are needed to provide more detailed clinical guidance. CLINICAL SIGNIFICANCE: When performing endodontic access through retained FCRs, reduced fracture resistance must be carefully considered for zirconia and LD restorations, while RMC restorations may be exempt from this concern. Loss of retention with access can be restored after repair. Surface pretreatment and flowable resin liners help decrease microleakage.

Humans

MIC-based tuberculosis drug susceptibility testing using Sensititre MYCOTB: a diagnostic accuracy meta-analysis.

Accurate drug susceptibility testing (DST) is crucial for designing effective regimens for multidrug-resistant (MDR) and pre-extensively drug-resistant tuberculosis (pre-XDR TB). Sensititre MYCOTB enables simultaneous determination of minimum inhibitory concentrations (MICs) for multiple drugs, but its diagnostic performance varies across studies. This meta-analysis evaluated the diagnostic performance of Sensititre MYCOTB for key MDR and pre-XDR TB drugs. The protocol was registered in PROSPERO (CRD420251230599). PubMed, Cochrane, Google Scholar, Scopus, ONOS, Web of Science, ScienceDirect, and registries were systematically searched for studies published between 2010 and 2025. Studies comparing the Sensititre MYCOTB with reference DST for Mycobacterium tuberculosis complex (MTBC) were included. Bias assessment and pooled diagnostic accuracy estimates were generated. Fourteen studies, including 1,728 isolates, were analyzed. Rifampicin and isoniazid demonstrated high sensitivity (0.976 [95% CI: 0.94-0.99] and 0.977 [95% CI: 0.95-0.99]) and specificity (0.958 [95% CI: 0.84-0.98] and 0.957 [95% CI: 0.83-0.99], respectively) with low heterogeneity. Amikacin, kanamycin, and ofloxacin demonstrate good diagnostic accuracy, with high specificity (>0.98 [95% CI]). Moderate diagnostic accuracy was observed for ethambutol, streptomycin, ethionamide, and rifabutin. Cycloserine, moxifloxacin, and para-aminosalicylic acid showed inconsistent performance despite excellent specificity (>0.97 [95% CI]). Sensitivity analysis partially improved pooled sensitivity for moxifloxacin 0.801 (95% CI: 0.585-0.924) and para-aminosalicylic acid 0.76 (95% CI: 0.518-0.894), whereas cycloserine remained at 0.436 (95% CI: 0.190-0.725), although heterogeneity persisted. Sensititre MYCOTB DST demonstrates high diagnostic accuracy for MDR-TB and pre-XDR-TB drugs, while caution is required with cycloserine, moxifloxacin, and para-aminosalicylic acid. These findings support the integration of MIC-based testing into clinical decision-making.

Microbial Sensitivity Tests

Effects of acute resistance exercise on prefrontal oxygenation and task-switching performance: Considerations of loading strategies and blood flow restriction.

Although acute resistance exercise (RE) has been proposed to influence cognitive flexibility and underlying neural mechanisms, it remains unclear whether these effects vary across loading strategies and whether exercise-induced prefrontal hemodynamic responses translate into cognitive outcomes. The present study examined (1) prefrontal cortex (PFC) oxygenated hemoglobin (O2Hb) responses across exercise sets and conditions, (2) the effects of low-load (LL), LL with blood flow restriction (BFR), and high-load (HL) RE on task-switching performance, and (3) whether exercise-related PFC O2Hb responses were associated with pre- to post-exercise changes in task-switching performance. Thirty physically active adults completed three randomized, counterbalanced RE conditions consisting of four sets of barbell squats. LL was performed at 30% one-repetition maximum (1RM) with and without BFR, whereas HL was performed at 70% 1RM. Cognitive flexibility was assessed pre- and post-exercise using a modified Stroop task, indexed by switch-cost reaction time (RT) and accuracy. PFC O2Hb was assessed using functional near-infrared spectroscopy during exercise and expressed as changes from the resting baseline for each set (Sets 1-4). PFC O2Hb increased across sets, rising from Set 1 to Set 3 before plateauing, with no differences observed across conditions. Switch cost RT and accuracy did not improve from pre- to post-exercise, and no differences across conditions were detected. PFC O2Hb during the final set was not associated with changes in switch cost. These findings suggest that although acute RE elicits robust increases in prefrontal hemodynamic activity, such responses may not translate into acute improvements in cognitive flexibility.

Humans

Higher versus Routine Intraoperative Blood Pressure Targets in Noncardiac Surgery: A Systematic Review and Meta-analysis with Trial Sequential Analysis of Randomized Trials.

BACKGROUND: Observational studies consistently link intraoperative hypotension to adverse postoperative outcomes, leading guidelines to recommend maintaining mean arterial pressure 60 to 65 mmHg or greater during noncardiac surgery. Whether targeting higher intraoperative blood pressure values improves clinical outcomes remains uncertain. METHODS: The authors conducted a Preferred Reporting Items for Systematic Reviews and Meta-analyses-guided search on PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Embase from inception to April 2026. Randomized trials comparing higher intraoperative blood pressure targets, either as fixed absolute thresholds or personalized to preoperative baseline, versus routine blood pressure management in adults undergoing elective noncardiac surgery with general anesthesia were included. Outcomes included in-hospital or 30-day mortality, postoperative delirium, acute kidney injury (AKI), 30-day major cardiovascular events, acute myocardial injury, stroke, length of stay, and intraoperative hypotension. RESULTS: Fifteen trials (15,603 patients) were included. Higher targets did not reduce AKI (risk ratio [RR], 0.95; 95% CI, 0.85 to 1.06; P = 0.36; I 2 = 16%) or acute myocardial injury (RR, 1.02; 95% CI, 0.94 to 1.12; P = 0.59; I 2 = 0%) compared with routine targets, with firm evidence from trial sequential analysis. Higher targets were associated with a significant reduction in postoperative delirium (RR, 0.73; 95% CI, 0.54 to 0.98; P = 0.04; I 2 = 26%), although trial sequential analysis indicated the cumulative evidence remained insufficient to draw firm conclusions. No significant effect was observed on in-hospital or 30-day mortality (RR, 1.00; 95% CI, 0.75 to 1.34; P = 1.00; I 2 = 0%); evidence on 30-day major cardiovascular events, stroke, and length of stay was similarly insufficient to draw firm conclusions. CONCLUSION: In adults undergoing elective noncardiac surgery, targeting higher intraoperative blood pressure values does not improve major postoperative outcomes compared with routine management. A potential reduction in postoperative delirium warrants confirmation in adequately powered trials.

Humans

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n&#x202f;=&#x202f;2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120&#x202f;Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5&#x202f;mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans