Search Results (445)

Citrus aurantium L. is a citrus-derived functional food rich in various phenolic compounds, including flavonoids. However, the bioavailability of its phytochemicals and sensory quality remain limited. This study investigated the effects of ultrasound-assisted fermentation by Lactiplantibacillus plantarum on microbial growth, phytochemical transformation, antioxidant activity, and metabolic profiles of C. aurantium. Ultrasound treatments were applied at different fermentation stages and power levels, among which treatment at 100 W during the exponential growth phase (ULP4) exhibited the best overall performance. Compared with conventional fermentation by L. plantarum (LP), ULP4 significantly promoted microbial growth, accelerated acidification, enhanced carbohydrate utilization, and stimulated β-glucosidase activity compared with conventional fermentation. Consequently, total phenolic content, total flavonoid content, and antioxidant capacities were markedly improved. Untargeted full-MS/MS metabolomic analysis revealed extensive metabolic alterations following ultrasound treatment, with 335 metabolites significantly altered between LP and ULP4. Differential metabolites were mainly associated with flavone and flavonol biosynthesis, secondary metabolite biosynthesis, amino acid metabolism, and lipid metabolism. These metabolic changes were closely associated with improved antioxidant properties and functional quality. Overall, ultrasound treatment during the exponential growth phase effectively enhanced microbial metabolism and phytochemical transformation, offering a promising strategy to improve the functional value of fermented C. aurantium products. Full article

Ionic liquid-assisted extraction can improve the recovery of monoterpene glycosides from Radix Paeoniae Alba, whereas post-extraction purification and ionic-liquid-associated marker-level quality control remain necessary before further bioactivity evaluation. In this study, a macroporous resin-based purification process was developed for monoterpene glycoside-enriched extracts obtained by conventional reflux extraction and ionic liquid-assisted microwave–ultrasound extraction. Among the five tested resins, AB-8 resin showed the best adsorption performance and was selected for further process optimization. The optimized purification conditions were a loading concentration of 13 mg/mL, loading pH of 7, elution with 70% ethanol, loading volume of 6 BV and elution volume of 9 BV. After purification, the total quantified monoterpene glycoside content increased from 6.59% to 51.68% in the conventional extract and from 15.30% to 75.30% in the ionic liquid-assisted extract. The ionic-liquid-associated elemental marker content in the ionic liquid-assisted extract decreased from 5.593% to 0.072% after purification, corresponding to an approximately 98.7% reduction at the elemental-marker level. Stability evaluation indicated that Na₂SO₃, Fe³⁺, ascorbic acid, sucrose and light exposure affected the detected monoterpene glycoside content to different extents, whereas short-term heating within 20–80 °C caused only slight fluctuations. The purified extracts showed stronger DPPH and ABTS radical scavenging activities and reducing power than the crude extracts. In LPS-stimulated RAW264.7 cells, the purified extracts reduced NO production and downregulated the mRNA expression of IL-6, IL-1β, TNF-α, iNOS and COX-2, suggesting anti-inflammatory potential at the NO and gene-expression levels. AB-8 resin purification enriched the monitored monoterpene glycosides, reduced the selected ionic-liquid-associated elemental marker, and generated purified fractions suitable for subsequent stability and bioactivity evaluation. Full article

Approximately 30% of patients with tremor-dominant Parkinson’s disease (PD) have rest tremor that persists despite optimal dopaminergic therapy. When deep brain stimulation and focused ultrasound are unavailable or declined, the therapeutic options narrow. Botulinum toxin (BoNT) offers a targeted, titratable, reversible approach, but whether a peripheral neuromuscular blocking agent makes sense for a centrally generated tremor is a legitimate question that deserves a direct answer. This narrative critical review appraises what is currently known across PD and non-PD tremor conditions, defines the technical requirements for safe and effective injection, and provides a practical framework for patient selection and clinical management. The PD-specific literature rests on a single positive double-blind randomized controlled trial of 30 patients; all remaining data are open-label or extrapolated from other tremor conditions, and this narrative synthesis combines heterogeneous conditions, outcome scales, and toxin protocols. A recurring technical observation is that, in the available trials, individualized, EMG-guided injection has been associated with substantially lower rates of hand weakness than fixed-dose injection (reported reductions from roughly 30–70% to below 15%) while maintaining tremor reduction, although the degree of benefit and weakness risk vary with the tremor syndrome, injected muscles, baseline impairment, dose, and guidance method. The careful patient selection this approach requires helps the individual clinician and patient achieve tremor relief, but it departs from the unselected real-world PD population and introduces selection bias that makes a large, statistically representative cohort difficult to assemble. In well-selected patients at centers with the appropriate expertise, BoNT may be a clinically useful option, but routine adoption is not yet supported. Full article

Background: Stress urinary incontinence (SUI) is defined as involuntary urine loss during activities that increase intra-abdominal pressure. It is highly prevalent among women and significantly affects physical, emotional, and social well-being. Pelvic floor muscle training (PFMT) is the gold-standard conservative therapy. Second-generation radiofrequency (RF) therapy has shown promise as an alternative. It stimulates collagen synthesis and promotes tissue remodeling. This study will compare the effects of PFMT, RF, and their combination on pelvic floor function, urethral stability, and health-related quality of life (HRQoL) in women with SUI due to urethral hypermobility. Methods/Design: This will be a single-blinded, three-arm, randomized controlled trial conducted at Clínica Traña (San José, Costa Rica). Women aged ≥18 years with clinically confirmed SUI and a retrovesical (β) angle ≥ 140° during the Valsalva maneuver on functional transperineal ultrasound will be randomized (1:1:1) to PFMT (16 weeks, twice-weekly supervised sessions), RF (5 weekly sessions using Capenergy^® C500 Urogyne), or combined RF + PFMT (39 per arm; total N = 117 accounting for 30% attrition). The primary outcome is the change from baseline in pelvic floor muscle strength at 12 months post-intervention, measured by the modified Oxford scale and vaginal manometry. Secondary outcomes will include urethral stability (retrovesical β angle and bladder neck descent on ultrasound), incontinence severity (Sandvik Severity Index), and HRQoL (ICIQ-UI SF and King’s Health Questionnaire). All outcomes will be assessed at baseline, immediately post-intervention, 15 days, 3 months, 6 months, and 12 months follow-up. Assessments will be performed by blinded evaluators. Analysis will follow intention-to-treat principles using repeated-measures ANOVA or non-parametric equivalents (SPSS v.29; p < 0.05). The trial was prospectively registered on ClinicalTrials.gov (NCT07095283, registered on 24 July 2025), prior to the recruitment of the first participant. Expected outcomes: This study will provide comparative effectiveness data on whether the addition of RF to PFMT offers additional benefits over PFMT alone in the management of SUI. Full article

Objectives: Distraction osteogenesis (DO) is an established technique for bone regeneration but is associated with prolonged consolidation time and extended external fixation. Biophysical and biologic adjuncts have been proposed to accelerate regenerative maturation. This systematic review aimed to comparatively evaluate the available clinical evidence regarding low-intensity pulsed ultrasound (LIPUS) and biologic augmentation strategies in distraction osteogenesis. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251125456). MEDLINE, Embase, Scopus, and Google Scholar were searched from inception to October 2025. Randomized controlled trials and cohort studies evaluating LIPUS, platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), culture-expanded mesenchymal stem cells, or hyperbaric oxygen therapy in distraction osteogenesis were included. Risk of bias was assessed using RoB 2 for randomized trials and structured domain-based criteria for observational studies. Due to substantial clinical and methodological heterogeneity, findings were synthesized narratively. Results: Nine studies involving 304 participants met the inclusion criteria, including randomized controlled trials and cohort studies across multiple anatomical sites and fixation techniques. Randomized trials evaluating LIPUS demonstrated inconsistent reductions in healing index and consolidation time, with no consistent effect on complication rates. Biologic adjuncts such as PRP, BMAC, and cell-based therapies showed signals of improved consolidation parameters in selected studies; however, evidence was limited by small sample sizes and methodological heterogeneity. Hyperbaric oxygen therapy lacked sufficient high-quality evidence to support routine use. Overall, the certainty of evidence was constrained by variability in study design, outcome definitions, and risk of bias. Conclusions: Although both biophysical and biologic adjuncts demonstrate compelling biological rationale, current clinical evidence in distraction osteogenesis remains heterogeneous and inconclusive. Biologic strategies may offer theoretical advantages through direct cellular and growth factor supplementation, whereas LIPUS provides non-invasive mechanotransductive stimulation; however, neither approach can currently be recommended for routine clinical use. High-quality, adequately powered trials with standardized outcome reporting are required to define their true clinical role. Level of Evidence: Level III (Systematic review of Level I–III studies). Full article

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BrCa), owing to its lack of targetable receptors and resistance to chemical and molecularly targeted therapeutic approaches. While chemotherapy and surgical resection remain the standard of care, these interventions have significant side effects and varying patient outcomes. Thermally ablative focused ultrasound (T-FUS)—a non-invasive and non-ionizing therapy that utilizes targeted acoustic energy to debulk tumors—has displayed immunomodulatory effects in BrCa. However, T-FUS as a monotherapy has had limited clinical efficacy in TNBC due to the presence of anti-inflammatory immunosuppressive myeloid cells (isMCs). We hypothesized that the elimination of isMCs or initiating tumoricidal activity from them would lead to augmented activity of T-FUS. Thus, we interrogated the ability of myeloablative chemotherapies and antibodies; myeloid recruiting chemokine receptor blockade; and TLR agonists to remodel the tumor myeloid populations. Consistent with our previous studies, we found that while myeloablative chemotherapies decreased circulating isMCs, they had little impact on intratumoral isMCs. In contrast, antibodies targeting Ly6C and Ly6G ablated intratumoral isMCs and systemic isMCs, yet their effect was transient and was accompanied by a surprising depletion of T cells. While targeting CCR2, the dominant chemokine receptor for intratumoral isMC diminished a large subset of immunosuppressive cells within the TME; it also depleted T cells and dendritic cells. Contrary to previous studies, TLR stimulation failed to repolarize myeloid cells into a pro-inflammatory, tumoricidal phenotype but did lead to their depletion from the tumor microenvironment (TME) and mobilization of conventional dendritic cells to the draining lymph nodes. We therefore hypothesized that combining isMC depletion and TLR-driven immune activation would enhance FUS efficacy; however, this combinatorial regimen did not enhance overall survival or control tumor volume after T-FUS treatment. Thus, the BrCa TME is highly resistant to approaches intended to remodel the myeloid cell component which fail to synergize with T-FUS-mediated tumor ablation. Full article

Caffeine and chlorogenic acid are among the most extensively investigated bioactive compounds in coffee, tea, and other plant-derived products due to their noteworthy physical, nutritional, and industrial relevance. Caffeine is primarily acknowledged for its central nervous system stimulant activity, whereas chlorogenic acid, a phenolic ester, contributes antioxidant, anti-inflammatory, and metabolic health benefits. This review was conducted according to the PRISMA guidelines in order to systematically compile and summarize the extraction and analytical conditions reported for caffeine and CGAs in different matrices and to provide a structured comparison among the reported studies. All studies focusing on the extraction and/or quantification of caffeine and chlorogenic acids in several matrices were considered eligible. Three independent electronic searches were performed using PubMed, Science.gov, and BASE to identify relevant articles. Extraction of data was conducted independently by four authors based on consistent selection and extraction criteria. One hundred and twenty-five studies were identified. The results were summarized in tables including several parameters. Conventional extraction techniques, including aqueous and organic solvent-based methods, have formed the foundation for separating caffeine and chlorogenic acids. However, rising interest in green and sustainable technologies has shifted attention towards advanced approaches such as ultrasound-assisted extraction and microwave-assisted extraction. These methods not only enhance extraction yields and reduce processing times but also align with environmental and safety concerns in the modern food and pharmaceutical industries. For quantification, high-performance liquid chromatography equipped with ultraviolet or mass spectrometric detection remains the benchmark, offering precision and reproducibility in different matrices. This review sheds light on recent advances and ongoing research in the extraction and quantification of caffeine and chlorogenic acid in different types of matrices. Continued innovation in green extraction technologies and robust quantification methods is essential for supporting scientific research applications. Full article

Background/Objectives: Vagus Nerve Stimulation (VNS) has been suggested as a treatment for tinnitus, but its effect on the condition remains unclear. Ultrasonic Vagus Nerve Stimulation (U-VNS) involves non-invasive stimulation of the auricular branch of the vagus nerve, potentially providing an alternative to traditional VNS. To pre-emptively address some of the methodological challenges of future trials investigating U-VNS, a highly blindable sham device is needed. This study aimed to (1) investigate the effectiveness of blinding of a U-VNS device and (2) record any adverse effects, including any negative effects on tinnitus loudness, alongside their onset and duration. Methods: In this single-blind randomized controlled study, 20 volunteers with chronic tinnitus received two 29 min sessions of true U-VNS followed by sham U-VNS, or vice versa. Sessions were a week apart, and in a randomized order. The effectiveness of blinding and adverse effects, including changes in tinnitus loudness, were measured using self-report questionnaires. Results: James’ Blinding Index revealed that blinding was highly effective in both the real U-VNS condition, BI = 0.79, 95% CI (0.61–0.92), and the sham condition, BI = 0.76, 95% CI (0.60–0.89). Adverse effects were uncommon and mild, primarily consisting of sensations on the skin beneath the transducer. For most participants, tinnitus loudness either decreased or stayed the same in both conditions. Conclusions: A high level of blinding was achieved, suggesting that the ZenBud sham device may be suitable as an effective placebo control in future trials. Adverse effects were uncommon and mild. These findings will help inform the design of future clinical trials to evaluate the safety and efficacy of U-VNS. Full article

Background/Objectives: Alzheimer’s disease (AD) remains a significant global health challenge, characterised by a persistent resistance to traditional pharmacological interventions. While non-invasive brain stimulation (NIBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) show therapeutic promise, their limited depth of penetration restricts their efficacy in targeting deep-brain AD pathology. Transcranial focused ultrasound stimulation (tFUS) has emerged as a novel, non-invasive neuromodulatory tool capable of precise deep-brain targeting. This scoping review aims to systematically map the current evidence base regarding the neuromodulatory application of tFUS in AD. Methods: Following PRISMA-ScR guidelines, a scoping search was conducted across four major databases (Ovid MEDLINE, Embase, Web of Science, and CENTRAL). Studies were included if they investigated focused ultrasound stimulation (FUS) as a neuromodulatory intervention for AD, excluding applications involving blood–brain-barrier disruption via microbubbles. Two independent reviewers performed screening and data extraction, with inter-rater reliability assessed via Cohen’s kappa. Results: Our analysis indicates that tFUS represents a safe and potent multi-modal intervention for AD that addresses both pathological protein aggregation and electrophysiological network failure. Its ability to modulate neuroplasticity and metabolic recovery suggests a promising therapeutic trajectory. Conclusions: Future research should prioritise the standardisation of acoustic protocols and the pursuit of longitudinal clinical cohorts to establish the long-term efficacy of this non-invasive technology. Full article

Background/Objectives: Arthroscopic shoulder surgery is associated with postoperative pain and loss of function. Percutaneous electrical nerve stimulation (PENS) may serve as an effective adjunct to postoperative rehabilitation. This randomized clinical trial examined whether adding ultrasound-guided PENS to a multimodal rehabilitation program improves pain, disability, pressure pain sensitivity, shoulder range of motion, and muscle strength in individuals with postoperative pain following shoulder arthroscopy. Methods: A randomized, parallel-group clinical trial (registry: NCT06331871) was conducted. Seventy patients who had undergone shoulder arthroscopy were randomized to receive manual therapy/exercise alone (n = 35) or manual therapy/exercise/PENS (n = 35). All participants received the multimodal program including manual therapy and exercises four weeks after surgery for a duration of 12 weeks (five sessions/week). Those allocated to the PENS group also received two sessions (once per week) of ultrasound-guided PENS targeting the suprascapular and axillary nerves. Pain intensity (Numeric Pain Rating Scale (NPRS)) and disability (Disabilities of the Arm, Shoulder and Hand (DASH)) were the primary outcomes, whereas function (Shoulder Pain and Disability Index (SPADI)), pressure pain threshold (PPT), isometric strength, and shoulder range of motion (ROM) were secondary outcomes. Pain, PPT, strength, and ROM were assessed before and after treatment, and at 1 and 3 months. Disability and function were assessed at baseline and 3 months after treatment. Results: Patients receiving PENS showed greater improvements in shoulder pain (F_{2.72, 182.32} = 7.76, p = 0.007, η²p = 0.10), disability (F_{1, 68} = 5.63, p = 0.020, η²p = 0.08), function (F_{1, 68} = 4.15, p = 0.046, η²p = 0.02) and PPT over the infraspinatus muscle (F_{3.20, 217.28} = 2.93, p = 0.032, η²p = 0.04) than those receiving manual therapy/exercise alone. No between-group differences were observed for PPT at the deltoid or tibialis anterior muscles. The PENS group also showed greater improvements in some, but not all, measures of shoulder strength and range of motion; however, the effect sizes were small and the clinical relevance of these differences remains uncertain. Conclusions: Adding ultrasound-guided PENS targeting the suprascapular and axillary nerves to a multimodal physical therapy program resulted in greater improvements in pain, disability, and shoulder-specific function, with limited additional benefits for some measures of strength and range of motion, compared with physical therapy alone, in individuals with postoperative shoulder pain. However, many of the lower-bound estimates of the 95% confidence interval did not surpass the minimal clinically important difference. Therefore, the clinical relevance of the results should be considered with caution. Full article

Geothermal energy extraction, hydrocarbon recovery, and CO₂ geological sequestration are frequently hindered by interfacial barriers and slow mass transfer. While high-power ultrasound offers a sustainable, purely physical method for reservoir stimulation, its field effectiveness remains debated because traditional macroscopic experiments fail to isolate mechanisms like acoustic streaming and cavitation. This review systematically examines acoustic mechanisms in porous media via microfluidic visualization, focusing on pore-scale fluid dynamics during enhanced oil recovery, hydrate dissociation, and CO₂ sequestration. Microscopic evidence reveals that fluid transport mechanisms depend heavily on pore geometry and local acoustic intensity. In wider channels, nonlinear acoustic flow provides sustained, directed convection to strip away concentration boundary layers; in narrow throats, microjets and pulsed stresses generated by transient cavitation are responsible for physically breaking capillary barriers. The spatiotemporal synergy of these mechanisms is critical for multiphase fluid transport in tight porous networks. Pore geometry serves not only as the application context but also as a core physical variable. To translate microfluidic results into reservoir-scale applications, future research must address two-dimensional simplifications, thermodynamic discrepancies under high-temperature and high-pressure conditions, and bubble cluster interactions, alongside the development of adaptive frequency-modulated control and multiscale computational models. Full article

Background: Thyroid nodules are common, yet only a small proportion are malignant. The independent role of nodule size in malignancy risk remains debated, particularly after adjustment for clinical, biochemical, and sonographic features. Methods: A retrospective cohort study was conducted on adult patients with thyroid nodules evaluated between 2018 and 2025 at a tertiary care center. Clinical, laboratory, ultrasound, cytology, and histopathology data were extracted. Thyroid-stimulating hormone (TSH), free thyroxine (free T4), and sonographic characteristics were analyzed. Univariable and multivariable logistic regression were performed. Missing ultrasound data were addressed using multiple imputation (m = 20), with pooled estimates derived using Rubin’s rules. The final multivariable model included 446 patients. Results: A total of 446 patients were included, of whom 91 (20.4%) had thyroid malignancy. Malignant nodules were significantly larger than benign nodules (2.30 [1.80] cm vs. 1.80 [1.13] cm; p = 0.015). In univariable analysis, TSH, free T4, and multiple ultrasound features were associated with malignancy. In multivariable analysis, nodule size remained the strongest independent predictor of malignancy (adjusted odds ratio [aOR] 1.51; p < 0.001). Hypoechogenicity (aOR 2.07; p = 0.020) and microcalcifications (aOR 1.86; p = 0.047) also remained independently significant, whereas thyroid function parameters were not associated with malignancy after adjustment. Conclusions: Thyroid nodule size is the strongest independent predictor of malignancy, with select ultrasound features retaining additional predictive value. These findings support incorporating nodule size more prominently into thyroid cancer risk stratification while maintaining key sonographic features. Full article

Background/Objectives: The growing aging population is susceptible to cognitive and memory impairment, most commonly due to Alzheimer’s disease, with no cures currently available. Noninvasive brain stimulation (NIBS) techniques may serve to improve cognition and delay catastrophic memory loss. Methods: A systematic review of NIBS research on cognitive impairment was carried out using PubMed, with additional backward citation searching. A total of 81 studies using NIBS were included. Conclusions: The reviewed studies show that NIBS holds promise in improving memory deficits in patients with cognitive impairment. While the longevity of benefits from transcranial electrical stimulation appears limited, its short-term effects may provide benefits when used consistently. Transcranial magnetic stimulation appears to provide longer-lasting benefits. Transcranial focused ultrasound stimulation may also provide further benefits through more precise targeting of deeper brain structures compared to other NIBS techniques. Together, these results suggest that NIBS shows promise for the treatment of symptoms related to cognitive and memory impairment, and may help to alleviate some of the growing issues associated with the increasing level of Alzheimer’s disease in an aging population. Full article

Probiotics and prebiotics in dairy products have gained increasing attention due to their potential health benefits and functional properties. Probiotics are beneficial microorganisms that help maintain intestinal microbiota balance, while prebiotics are non-digestible compounds that stimulate the growth of beneficial gut bacteria. Their incorporation into dairy foods has been associated with improved digestive health, nutrient absorption, and product functionality. However, challenges related to microbial survival during processing and storage, interactions with the dairy matrix, and strain-specific limitations remain significant. This review presents a bibliometric analysis of recent scientific advances involving probiotics and prebiotics in dairy products. The bibliometric analysis revealed a marked increase in publications over the last decade, with research concentrated on gut microbiota modulation, functional dairy foods, fermentation technologies, and health-promoting effects. The results also indicate the relevance of bacterial groups such as lactic acid bacilli and Bifidobacterium, as well as the growing interest in synbiotics and bioactive compounds. Additionally, emerging technologies, including microencapsulation, ohmic heating, and ultrasound, are discussed as promising strategies to improve probiotic stability, functionality, and industrial application in dairy systems. Overall, the findings highlight that the successful development of probiotic and prebiotic dairy products depends on the integration of strain selection, matrix compatibility, and emerging technologies to ensure stability, functionality, and industrial applicability. Full article

Objectives: To investigate current Canadian physicians’ practice patterns of treating upper limb post-stroke spasticity (PSS) and hemiplegic shoulder pain (HSP) acutely after a stroke. In addition, by examining Canadian physicians’ diagnostic capabilities, time till treatment, minimum criteria to begin treatment, mechanisms of treatment, targeting of muscles, and benefits and adverse effects of treatment, we aim to learn about areas of improvement to optimize PSS management for Canadians. Design: The present study was a cross-sectional survey, polling practicing Canadian physicians. Results: A total of 17 physicians completed the survey, all PM&R specialists, save one neurologist. Four provinces were represented in the responses. Participants had, on average, over ten years of experience managing post-stroke spasticity in outpatient and inpatient clinics. All 17 perform botulinum neurotoxin A (BoNT-A) injections for HSP associated with PSS. Most participants reported that they will begin BoNT-A treatments 2–3 weeks post-stroke, most commonly targeting the pectoralis major, subscapularis, and latissimus dorsi. Participants reported the mean median dosage they use as onabotulinum toxin A (169.12 units, SD = 73.70), incobotulinum toxin A (178.13 units, SD = 65.75), and abobotulinum toxin A (470.83 units, SD = 171.17). For injection guidance, participants responded that they use ultrasound for the largest percentage of their caseload, followed by electromyography, then electrical stimulation, then palpation. Very seldom did participants use palpation alone. Conclusions: From the limited sample included in analyses, the Canadian physicians respondents seem to be treating HSP and associated PSS with variable strategies. Further research is required to align dosages, targets, and guidance strategies as they vary considerably. Full article