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16 pages, 1269 KB  
Review
Mobile Health Interventions Across the Stroke Care Continuum: A Scoping Review
by Dahyeon Koo, Seunggyun Jeong, Kyumin Jang, Younghwan Jang, Seo Yeong Bae, Soonmi Kwon and Dougho Park
J. Clin. Med. 2026, 15(11), 4121; https://doi.org/10.3390/jcm15114121 (registering DOI) - 26 May 2026
Abstract
Stroke causes approximately 12.2 million new cases and 6.5 million deaths annually, with survivors requiring coordinated care across pre-hospital, acute, rehabilitative, and preventive phases. Mobile health (mHealth) technologies, including smartphone applications, wearable sensors, and tablet-based platforms, have shown clinical potential across these contexts, [...] Read more.
Stroke causes approximately 12.2 million new cases and 6.5 million deaths annually, with survivors requiring coordinated care across pre-hospital, acute, rehabilitative, and preventive phases. Mobile health (mHealth) technologies, including smartphone applications, wearable sensors, and tablet-based platforms, have shown clinical potential across these contexts, yet a structured mapping of their distribution across the full stroke care continuum is lacking. We searched PubMed, Scopus, and Web of Science for publications from January 2019 to March 2025. Studies evaluated mHealth interventions in which the mobile platform directly performed diagnostic, therapeutic, or rehabilitative functions in stroke populations. Of 4524 records identified, 17 met the inclusion criteria. Studies originated from eight countries and used heterogeneous designs: five randomized controlled trials, five non-randomized studies, four cohort studies, and three diagnostic accuracy studies. Median sample size was 37 participants (range 10–2249). Evidence concentrated at two poles: six studies addressed acute diagnosis and ten addressed rehabilitation, predominantly in the chronic phase. One study addressed secondary prevention; two targeted early rehabilitation, the period of maximum neuroplasticity after discharge. All seventeen studies covered a single care phase. Smartphone platforms dominated acute contexts; wearable and mixed-modality systems were confined to rehabilitation. The mHealth stroke landscape is fragmented and phase-specific, exhibiting a silo effect in which interventions operate as isolated tools rather than components of an integrated care system. An important gap is the near-absence of research in early rehabilitation. Future priorities include cross-continuum design, expansion into cognitive and secondary prevention domains, and progression toward adequately powered trials. Full article
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19 pages, 608 KB  
Article
Fermented Noni Polysaccharides and Immune-Related Biomarkers in Adults with Recurrent URTIs: A Randomized, Double-Blind, Placebo-Controlled Trial
by Seon-Mi Shin, Seong-Hwan Park, Seon-Gyu Bae, Eun-Young Park, Jae-Yeon Lee, Hee-Yeon Kwon, Im-Joung La, Sang-Jun Youn, Yong Choi, Yeong-Eun Choi, Do-Hee Kim, Sun-Young Park, Cheol Moon and Tae-Yeon Kim
Nutrients 2026, 18(11), 1691; https://doi.org/10.3390/nu18111691 - 26 May 2026
Abstract
Background: Fermented polysaccharides derived from Morinda citrifolia (noni) have been suggested to modulate innate immune responses, but clinical evidence remains limited. Objectives: This randomized, double-blind, placebo-controlled trial evaluated the effects of fermented noni polysaccharides on natural killer (NK) cell activity and immune-related biomarkers [...] Read more.
Background: Fermented polysaccharides derived from Morinda citrifolia (noni) have been suggested to modulate innate immune responses, but clinical evidence remains limited. Objectives: This randomized, double-blind, placebo-controlled trial evaluated the effects of fermented noni polysaccharides on natural killer (NK) cell activity and immune-related biomarkers in adults with recurrent upper respiratory tract infections (URTIs). Methods: A total of 100 adults aged 40 to <75 years with a documented history of ≥2 episodes of upper respiratory tract infection in the prior 12 months were randomly assigned to receive fermented noni polysaccharides (487.5 mg/tablet, two tablets once daily; 975 mg/day of FNP extract) or a matched placebo for 8 weeks. The primary endpoint was the change in NK cell activity at effector-to-target (E:T) ratios of 50:1, 25:1, and 12.5:1, assessed using K562 NK-sensitive target cells. Secondary endpoints included circulating cytokines (IFN-γ, TNF-α, IL-2, IL-6, IL-10, IL-12, IL-1β) and immunoglobulin G (IgG). Eighty-four participants (43 treatment, 41 placebo) were included in the modified intention-to-treat/full analysis set (mITT/FAS); 81 participants (41/40) constituted the per-protocol set (PPS). Primary efficacy was analyzed in the mITT/FAS. This trial was retrospectively registered at CRiS (KCT0011316) after trial completion; the IRB-approved protocol was finalised before enrolment and remained unchanged thereafter. Results: NK cell activity in the treatment group increased from baseline at all three E:T ratios, whereas it slightly decreased in the placebo group. Adjusted between-group LS mean differences (95% CI) were +8.94 (−0.61, 18.50; p = 0.066) at E:T 50:1, +7.68 (−1.14, 16.50; p = 0.087) at 25:1, and +3.29 (−2.95, 9.54; p = 0.145) at 12.5:1, all favouring treatment but not reaching the conventional threshold for significance in the mITT/FAS. Prespecified PPS sensitivity analyses reached significance at E:T 50:1 (+11.03; p = 0.025) and 25:1 (+9.94; p = 0.028). Selected cytokines (IFN-γ, IL-2, IL-6, IL-10, IL-1β) increased to a greater extent in the treatment group than in the placebo group, whereas TNF-α, IL-12, and IgG were unchanged. URTI incidence at week 4, week 8, and cumulatively did not differ significantly between groups. The intervention was well tolerated, with no serious adverse events and no treatment-related discontinuations. Conclusions: Compared with placebo, fermented noni polysaccharide supplementation showed numerically greater increases in NK cell activity at all three E:T ratios (50:1, 25:1, and 12.5:1) in the primary mITT/FAS analysis, although these between-group differences did not reach statistical significance. Prespecified per-protocol set (PPS) sensitivity analyses showed significant between-group differences at E:T ratios of 50:1 and 25:1. The treatment group also showed greater increases in selected cytokines (IFN-γ, IL-2, IL-6, IL-10) relative to placebo. No significant between-group differences were observed in URTI incidence, IgG, GARS, WBC, or leukocyte subset proportions. These exploratory biomarker findings, in the absence of safety signals, suggest a possible immunomodulatory profile but do not establish clinical efficacy. Confirmation in larger, prospectively registered trials with clinically adjudicated infection-related endpoints is warranted. Full article
(This article belongs to the Special Issue Fermented Foods and Health Modulation)
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21 pages, 9026 KB  
Article
A Video-Based Measurement Framework for Chewing-Event Detection Using 3D Facial Landmark Dynamics and sEMG-Based Reference Annotation
by Nicola Giulietti, Carlotta Massotti and Hermes Giberti
Sensors 2026, 26(11), 3351; https://doi.org/10.3390/s26113351 - 25 May 2026
Abstract
Accurate measurement of chewing events in natural eating conditions is important for unobtrusive monitoring of feeding behavior and masticatory function. Yet, existing methods often rely on contact sensors, dedicated wearables, or manual annotation. This work presents a non-contact, video-based framework for chewing-event detection [...] Read more.
Accurate measurement of chewing events in natural eating conditions is important for unobtrusive monitoring of feeding behavior and masticatory function. Yet, existing methods often rely on contact sensors, dedicated wearables, or manual annotation. This work presents a non-contact, video-based framework for chewing-event detection using frontal facial video, normalized 3D facial landmark dynamics, and recurrent temporal modeling. To obtain physiologically grounded reference labels, synchronized bilateral anterior temporalis surface electromyography was acquired during real-meal sessions and used to derive chewing-event annotations during dataset construction, whereas inference relied exclusively on video. Facial motion was represented from frame-wise 3D landmarks and processed by recurrent neural networks, with model selection performed through Bayesian hyperparameter optimization. On an independent hold-out test set comprising five sessions and 18,836 frames, the proposed method detected 577 chewing events versus 589 ground truth events, corresponding to a mean absolute error of 4.4 chews/session and a mean absolute percentage error of 4.32%. A comparison with a related rule-based video method from the literature showed substantially larger counting errors (MAE = 39.4, MAPE = 30.39%), particularly in sessions that included concurrent activities such as speaking, suggesting that the proposed approach can reduce counting errors relative to the considered rule-based baseline under the specific meal conditions tested in this feasibility study. The effect of landmark-localization uncertainty on the predicted chewing probability was assessed through Monte Carlo propagation, showing limited impact for most prediction instants and greater sensitivity for intermediate probability values. Finally, the ONNX implementation achieved a mean latency of 8.96 ± 5.74 ms on CPU and 6.89 ± 3.58 ms with CUDA execution on the test workstation, supporting real-time applicability. To support practical deployment, the pipeline was also implemented as a native Kotlin Android application and tested on a commercial tablet, achieving real-time operation at 20 fps. Full article
12 pages, 1831 KB  
Article
Cu-MOFs Nanozymes with Ascorbate Oxidase and Peroxidase-like Activity for Sensitive Fluorometric Detection of Total Antioxidant Capacity in Fruits
by Yanyan Huang, Jing Chen, Ai Nasi, Yiming Zhao, Xin Ding, Dan Xu, Fengzhi Lyu, Donghui Xu, Meng Zhang, Ge Chen and Guangyang Liu
Nanomaterials 2026, 16(11), 665; https://doi.org/10.3390/nano16110665 - 25 May 2026
Abstract
In this work, two-dimensional copper-based metal–organic frameworks (Cu-MOFs) nanozymes, including cuprous oxide-tetrakis (4-carboxyphenyl) porphyrin (Cu2O-TCPP) and copper-cuprous oxide-tetrakis (4-carboxyphenyl) porphyrin (Cu-Cu2O-TCPP), were synthesized, which exhibit dual ascorbate oxidase (AO) and peroxidase (POD)-like activities. The reductants, such as ascorbic acid [...] Read more.
In this work, two-dimensional copper-based metal–organic frameworks (Cu-MOFs) nanozymes, including cuprous oxide-tetrakis (4-carboxyphenyl) porphyrin (Cu2O-TCPP) and copper-cuprous oxide-tetrakis (4-carboxyphenyl) porphyrin (Cu-Cu2O-TCPP), were synthesized, which exhibit dual ascorbate oxidase (AO) and peroxidase (POD)-like activities. The reductants, such as ascorbic acid (AA), can be oxidized by the cascade AO and POD catalysis on Cu-MOFs to oxidize p-phthalic acid (PTA) and generate fluorescence. Consequently, a fluorescence sensing platform for AA and other reducing substances was established. This platform offers potential for efficient and selective monitoring of reductive species and related antioxidant levels in food systems. The results showed that the two Cu-MOFs displayed favorable linear relationships (R2 ≥ 0.99) for the detection of AA, glutathione (GSH) and L-cysteine (L-Cys). Their limits of detection (LOD) were 5.3 μM for Cu2O-TCPP and 92.5 μM for Cu-Cu2O-TCPP. Finally, by detecting real samples of vitamin C tablets and fruits, the accuracy of the two Cu-MOFs nanos enzymes was validated, with Cu2O-TCPP showing higher accuracy. Full article
(This article belongs to the Section Nanoelectronics, Nanosensors and Devices)
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11 pages, 2794 KB  
Case Report
Subcutaneous Thrombotic Vasculopathy with Features of Leukocytoclastic Vasculitis Following Intravenous Injection of Crushed Oxycodone and Methylphenidate Tablets: A Case Report with Literature Review
by Nina Łabędź, Maksymilian Markwitz, Paweł Głuszak, Monika Bowszyc-Dmochowska, Marian Dmochowski, Adriana Polańska and Aleksandra Dańczak-Pazdrowska
J. Clin. Med. 2026, 15(11), 4044; https://doi.org/10.3390/jcm15114044 - 23 May 2026
Viewed by 115
Abstract
Subcutaneous thrombotic vasculopathy (STV) is a rare, non-inflammatory occlusive disorder of the cutaneous microvasculature that predominantly involves the subcutaneous tissue and may closely mimic inflammatory vasculitis. We describe a case of STV with overlapping features of leukocytoclastic vasculitis (LCV) in a 23-year-old woman [...] Read more.
Subcutaneous thrombotic vasculopathy (STV) is a rare, non-inflammatory occlusive disorder of the cutaneous microvasculature that predominantly involves the subcutaneous tissue and may closely mimic inflammatory vasculitis. We describe a case of STV with overlapping features of leukocytoclastic vasculitis (LCV) in a 23-year-old woman presenting with rapidly progressive, painful purpuric skin lesions. The patient had a history of polysubstance use disorder and reported intravenous injection of crushed oral oxycodone and methylphenidate tablets. Histopathological examination of a deep skin biopsy revealed fibrin-rich thrombi occluding small vessels of the dermis and subcutaneous tissue. Fine granular IgA deposits in the walls of numerous superficial dermal blood vessels shown using direct immunofluorescence suggested LCV. Overall, the findings supported a mixed thrombotic-inflammatory vasculopathy with predominant features of STV. This case highlights the diagnostic complexity of STV and may suggest intravenous injection of crushed oral medications as a potential trigger through particle-induced microvascular obstruction and secondary thrombosis. In addition, we conducted a literature review indicating that STV remains a rare and likely underrecognized entity, with only a limited number of reported cases. Full article
(This article belongs to the Section Dermatology)
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21 pages, 14302 KB  
Article
Audio-Based Device for Automated Surgical Counting, ToolSafe
by Michael R. Gardner, Latifa A. Aladdal, Lama Alshammari, Fatima Aldalgan, Maram A. Alomair, Shahad Alomair and Amani Alrashed
Appl. Sci. 2026, 16(11), 5181; https://doi.org/10.3390/app16115181 - 22 May 2026
Viewed by 128
Abstract
Manual counting of surgical tools, known as surgical counting, is a time-consuming and error-prone task that increases the risk of retained surgical instruments and extends operating room (OR) time. Presently, in hospitals around the world, surgical counting is often performed manually with paper [...] Read more.
Manual counting of surgical tools, known as surgical counting, is a time-consuming and error-prone task that increases the risk of retained surgical instruments and extends operating room (OR) time. Presently, in hospitals around the world, surgical counting is often performed manually with paper or tablet checklists, often leading to delays, increased infection risk, and financial cost. RFID, barcode-based, and computer vision solutions exist but are expensive and have challenges with sterilization and signal interference. This paper presents ToolSafe, a low-cost, portable system that classifies surgical tools by their acoustic signatures when dropped into a detection box. A pilot dataset of 4004 audio samples from four tool types (n = 996, tissue forceps; n = 1005, iris scissors; n = 1006, scalpel handle; n = 997, testing needle) was collected using ToolSafe. A convolutional neural network (CNN) was evaluated using stratified five-fold cross-validation on the laboratory dataset, with a k-nearest neighbors (KNN) classifier implemented as a control model. In each fold, both models were trained on 80% of the data and tested on the remaining 20%, ensuring that all samples were used for both training and evaluation. The CNN achieved a mean (±standard deviation) classification accuracy of 99.55% (±0.19%) across the validation folds, outperforming the KNN model, which achieved a mean accuracy of 97.28% (±0.50%). The difference was statistically significant according to a paired t-test across folds (p = 0.0003), indicating CNN’s superior performance on the dataset. For a run of 100 additional samples using the Raspberry Pi-based system, spectrogram generation averaged 0.121 s (±0.025 s), CNN inference averaged 0.180 s (±0.033 s), and total end-to-end latency averaged 1.851 s (±0.253 s) per tool. This pilot study proposes a possible technological solution for surgical counting that reduces human error and enhances patient safety. ToolSafe may be subsequently improved by increasing the number of surgical tools used in the training dataset, testing under more robust OR-like environments, and comparing to other classification algorithms. Further refinement and incorporation of ToolSafe in operating room workflows have the potential to reduce patient risks from extended surgical times and retained surgical instruments. Full article
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12 pages, 5084 KB  
Article
A Randomized Intercept Survey Trial to Test the Effectiveness of Multiple Traffic Light Labels on Online Grocery Shopping Behaviors in Bahrain
by Soye Shin, Ali Shubbar Jawad, Buthaina Yusuf Ajlan, Fatema Ahmed Mohammed Isa, Amna Ghassan Alawadhi, Reem Alsukait and Eric A. Finkelstein
Nutrients 2026, 18(10), 1645; https://doi.org/10.3390/nu18101645 - 21 May 2026
Viewed by 192
Abstract
Background/Objectives: Multiple Traffic Light (MTL) front-of-pack (FOP) labels are being considered in Bahrain. We tested whether an adapted MTL label improves the nutritional quality of grocery purchases. Methods: In a two-arm randomized controlled intercept trial (January–May 2025), adults (≥21 years) responsible for household [...] Read more.
Background/Objectives: Multiple Traffic Light (MTL) front-of-pack (FOP) labels are being considered in Bahrain. We tested whether an adapted MTL label improves the nutritional quality of grocery purchases. Methods: In a two-arm randomized controlled intercept trial (January–May 2025), adults (≥21 years) responsible for household grocery shopping were recruited in high-footfall public venues and asked to complete a one-time shop on a tablet-based, purpose-built online grocery platform. The MTL label was adapted for Arabic reading direction and displayed per-serving nutrients and % recommended daily intake. Treatment effects were estimated using ordinary least squares regressions with robust standard errors and covariate adjustment. Results: Of 395 randomized participants, 360 were included in primary analyses (control n = 183; MTL n = 177). MTL exposure was not associated with a significant change in the primary outcome (basket weighted average MTL score per serving; β = 0.037; p = 0.64) or in per-serving calories and nutrients of concern (all p > 0.17). In the post-shop assessment, only 47.2% of participants correctly interpreted MTL labels, indicating modest objective label comprehension under the study conditions. Conclusions: These findings suggest that the impact of front-of-pack labels likely depends on both implementation features and consumer understanding, and that pairing labels with public communication and nutrition literacy initiatives may be necessary to maximize the effectiveness of labels in Bahrain and the wider Gulf region. Full article
(This article belongs to the Special Issue The Impact of Food Labeling on Food Choices and Eating Behaviors)
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13 pages, 896 KB  
Article
Accuracy and Agreement of a 45 mg Versus a 75 mg 13C-Urea Breath Test for the Diagnosis of Helicobacter pylori Infection in Adults: A Randomized Crossover Trial
by Jun Huang, Yaohong Xie, Jian Huang, Bingyun Lu and Ye Chen
Diagnostics 2026, 16(10), 1567; https://doi.org/10.3390/diagnostics16101567 - 21 May 2026
Viewed by 178
Abstract
Background: The optimal 13C-urea breath test (UBT) dosage for diagnosing Helicobacter pylori remains debated. We compared the accuracy and agreement of a low-dose 45 mg tablet (without citric acid) versus the standard 75 mg granule (with citric acid) protocol. Methods: In this [...] Read more.
Background: The optimal 13C-urea breath test (UBT) dosage for diagnosing Helicobacter pylori remains debated. We compared the accuracy and agreement of a low-dose 45 mg tablet (without citric acid) versus the standard 75 mg granule (with citric acid) protocol. Methods: In this prospective, randomized crossover trial, adults underwent both a 45 mg and a 75 mg 13C-UBT on the same day. Breath samples were collected at 15 and 30 min. The primary outcome was diagnostic agreement at 30 min. Secondary outcomes included diagnostic performance against a composite reference standard, wherein concordant 45 mg and 75 mg UBT results were presumed to represent true H. pylori status, while discordant cases underwent endoscopic reference testing (rapid urease test and histology, with immunohistochemistry where required), stratified by age and BMI. Results: For the 431 participants included, the 45 mg and 75 mg tests showed substantial agreement at 30 min (90.3%; κ = 0.766). The 30 min sampling time yielded significantly better accuracy than 15 min for both doses. The 45 mg protocol achieved excellent accuracy (AUC 0.953), statistically non-inferior to the 75 mg protocol (AUC 0.966; p = 0.50). Notably, in participants aged <40 years or with BMI < 25.0 kg/m2, the 45 mg protocol demonstrated robust performance (AUC 0.977 and 0.966, respectively), comparable to the 75 mg standard (p > 0.05). No adverse events occurred. Conclusions: The low-dose 45 mg 13C-UBT provides high diagnostic agreement and comparable clinical performance to the standard 75 mg protocol without requiring citric acid acidification. Its robust performance in younger, lower-BMI individuals shows clinical promise. However, because diagnostic accuracy analyses partly relied on a composite reference assumption, further externally validated studies are required before broad screening-policy claims can be made. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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12 pages, 1178 KB  
Article
Consumption Patterns and Product Format Preferences of Inner Beauty Functional Foods Among Korean Adults
by Eunjeong Park and Ki Han Kwon
Foods 2026, 15(10), 1820; https://doi.org/10.3390/foods15101820 - 21 May 2026
Viewed by 231
Abstract
The inner beauty functional food sector has grown rapidly in South Korea. These products are orally consumed bioactive formulations designed to improve skin health, hair vitality, and overall wellness. However, empirical evidence on consumption patterns and product format preferences across different demographic groups [...] Read more.
The inner beauty functional food sector has grown rapidly in South Korea. These products are orally consumed bioactive formulations designed to improve skin health, hair vitality, and overall wellness. However, empirical evidence on consumption patterns and product format preferences across different demographic groups remains limited. This cross-sectional study examined consumption patterns, purchase channels, and product format preferences among 502 Korean adults who had experience with inner beauty functional foods. Chi-square analysis was used to examine differences in consumption reasons, duration of use, purchase channels, and product format preferences according to socio-demographic characteristics. Results showed that skin health was the dominant consumption motivation (47.6%), particularly among younger and female consumers, while weight management and hair and nail health were more prevalent among older adults. Online purchasing dominated (57.8%), with significant age- and education-based variation; consumers in their 20s purchased online at 67.5%, declining to 44.4% among those aged 40 and above. Capsule and tablet formats were most prevalent overall (41.6%), with males, married consumers, and graduate-degree holders showing significantly stronger preference for this format, whereas gummy and chewable formats were more frequently preferred by female consumers. These findings provide practical implications for inner beauty producers, food distributors, and nutrition educators seeking to align product development and communication strategies with the heterogeneous preferences of Korean inner beauty consumers. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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9 pages, 747 KB  
Brief Report
Does the Short-Term Use of Continuous Glucose Monitoring Detect Favorable Effects of Vinegar Ingestion at Mealtime in Adults with Prediabetes? A Pilot Trial
by Novia Shin Ying Chiew, Emily Dow, Hassan Ghasemzadeh and Carol S. Johnston
Dietetics 2026, 5(2), 31; https://doi.org/10.3390/dietetics5020031 - 21 May 2026
Viewed by 126
Abstract
Clinical trials suggest that daily vinegar ingestion improves fasting blood glucose concentrations, postprandial glucose excursions, and hemoglobin A1c levels in patients with prediabetes and type 2 diabetes. With the recent commercialization of continuous glucose monitoring (CGM) technologies, diabetes patients as well as other [...] Read more.
Clinical trials suggest that daily vinegar ingestion improves fasting blood glucose concentrations, postprandial glucose excursions, and hemoglobin A1c levels in patients with prediabetes and type 2 diabetes. With the recent commercialization of continuous glucose monitoring (CGM) technologies, diabetes patients as well as other health-conscious individuals can evaluate the impact of food choices in real-time and make data-driven decisions to improve dietary behaviors. This 9-day, randomized crossover study documented CGM-derived glycemic patterns during vinegar ingestion in adults with prediabetes. Participants consumed two tablespoons of vinegar twice daily with meals for four days or a control tablet each morning for four days in random order. For each phase, fasting blood glucose on day four, average blood glucose across three days, and peak glucose excursion across three days were calculated. Fasting glucose concentrations of participants (n = 10 women; 36.6 ± 15.6 y; 33.9 ± 6.5 kg/m2) averaged 105.8 ± 20.6 mg/dL at baseline. Vinegar ingestion was associated with significant reductions in the mean glucose concentration (−4.4 mg/dL) and the frequency of blood glucose excursions > 140 mg/dL (−10%) in comparison to the control treatment, but fasting glucose concentrations were unaffected. These data suggest that vinegar-induced improvements in blood glucose can be observed in real-time using a CGM device in adults with prediabetes. Full article
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19 pages, 4386 KB  
Article
Nanosuspension and Microenvironmental pH Modification to Enhance Atorvastatin Dissolution in Fixed-Dose Combination Ezetimibe/Atorvastatin Tablets
by Deny Puriyani Azhary, Yuda Prasetya Nugraha and Rachmat Mauludin
Biophysica 2026, 6(3), 44; https://doi.org/10.3390/biophysica6030044 - 19 May 2026
Viewed by 110
Abstract
A Fixed-dose combination (FDC) therapy of ezetimibe (EZT) and atorvastatin (ATV) is increasingly prescribed for high-risk hyperlipidemic patients with cardiovascular disease. However, the pharmaceutical production of FDC EZT/ATV tablets often results in poor ATV dissolution under acidic conditions, failing to meet regulatory requirements. [...] Read more.
A Fixed-dose combination (FDC) therapy of ezetimibe (EZT) and atorvastatin (ATV) is increasingly prescribed for high-risk hyperlipidemic patients with cardiovascular disease. However, the pharmaceutical production of FDC EZT/ATV tablets often results in poor ATV dissolution under acidic conditions, failing to meet regulatory requirements. This study aimed to improve ATV dissolution in acidic media through nanosuspension (NS) technology and microenvironmental pH modification. The experimental stages included preparation and characterization of ATV-NS, optimization of FDC EZT/ATV-nanocrystal tablets with pH modifiers, and evaluation of dissolution similarity (f2) against the innovator product Atozet®. ATV-NS was prepared via sonication and high-pressure homogenization using different stabilizers. Poloxamer 188-stabilized ATV-NS demonstrated optimal stability (particle size: 466.6 ± 8.9 nm; polydispersity index: 0.12 ± 0.10; zeta potential: −44.20 ± 0.06 mV) and significantly enhanced solubility (p < 0.05) compared with pure ATV. FDC EZT/ATV-nanocrystal tablets incorporating pH modifiers achieved f2 values for ATV of 52.36, 51.31, and 51.09 in NaCl/HCl pH 1.2, acetate buffer pH 4.5, and phosphate buffer pH 6.8, respectively. In contrast, EZT exhibited f2 values of 18.18, 16.72, and 14.66 (acceptable range: 50–100). Although complete profile similarity was not obtained for EZT, ATV dissolution in acidic media improved significantly (p < 0.05), supporting the feasibility of developing a bioequivalent generic FDC EZT/ATV tablet. Full article
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29 pages, 3759 KB  
Article
Assessing the Safety of Carbon Dioxide Extracts of Acorus calamus Rhizomes and Calendula officinalis Flowers and the Antitussive Activity of the Tablet Dosage Form ‘Exkair’ and Granules ‘Zerp-Ak-Broncho’ Developed on Their Basis
by Galiya Ibadullayeva, Maigul Kizatova, Karlygash Raganina, Meruyert Tleubayeva, Aliya Mamatova, Rauan Botabayeva, Aigerim Karaubaeva, Aktolkyn Ibadullayeva, Aruzhan Darbassova, Lashyn Kiyekbayeva and Rizvangul Ayupova
Pharmaceuticals 2026, 19(5), 789; https://doi.org/10.3390/ph19050789 - 18 May 2026
Viewed by 240
Abstract
Background: The growing demand for safe and effective phytopharmaceuticals underscores the importance of studying regionally available medicinal plants. Acorus calamus L. and Calendula officinalis L., widely distributed in the Republic of Kazakhstan, are promising sources of biologically active compounds with significant pharmacological potential. [...] Read more.
Background: The growing demand for safe and effective phytopharmaceuticals underscores the importance of studying regionally available medicinal plants. Acorus calamus L. and Calendula officinalis L., widely distributed in the Republic of Kazakhstan, are promising sources of biologically active compounds with significant pharmacological potential. However, the combined use of their CO2 extracts remains insufficiently characterised, particularly regarding possible synergistic interactions. Therefore, the development of new dosage forms and their comprehensive pharmacological and toxicological evaluation is a priority in modern pharmaceutical research. Methods: Concentrated extracts from Acorus calamus rhizomes and Calendula officinalis flowers were obtained using precritical CO2 extraction. Safety was assessed through acute and chronic toxicity studies in laboratory animals according to standard non-clinical guidelines. Animals received graded doses of the extracts and developed formulations (‘Exkair’ tablets and ‘Zerp-Ak-Broncho’ granules). Clinical condition, mortality, body weight, and behaviour were monitored. Biochemical, haematological, and histopathological analyses were performed. Antitussive activity was evaluated in vivo by measuring oedema inhibition relative to reference drugs. Results: The CO2 extracts and formulations demonstrated low toxicity and good tolerability, with no mortality or significant adverse effects observed even at high doses. Biochemical and haematological parameters remained within physiological ranges, and histopathological examination revealed no structural alterations in internal organs. Both ‘Exkair’ and ‘Zerp-Ak-Broncho’ exhibited pronounced antitussive activity, confirmed by significant suppression of oedema. This effect is likely associated with the synergistic action of flavonoids, terpenoids, and phenolic compounds. Conclusions: The findings indicate that CO2 extracts of Acorus calamus L. and Calendula officinalis L., as well as the developed formulations, possess a favourable safety profile and significant antitussive activity. These results support their further development as phytotherapeutic agents in Kazakhstan. Full article
(This article belongs to the Section Pharmacology)
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29 pages, 754 KB  
Review
Emerging Perspectives in the Formulation of Lyophilized Orally Disintegrating Tablets: From Lyoc to Self-Nanoemulsifying Lyophilized Tablets (SNELTs) and Beyond into Hybrid Platforms
by Eliza Grațiela Popa, Liliana Mititelu Tartau, Alina Diana Panainte, Larisa Păduraru and Andreea Crețeanu
Pharmaceutics 2026, 18(5), 615; https://doi.org/10.3390/pharmaceutics18050615 - 18 May 2026
Viewed by 408
Abstract
Four decades have elapsed since orally disintegrating tablets (ODTs) were first formulated as the emulsion/type Lyoc tablet, a porous mass intended to rapidly disperse in saliva. Following the lyophilization process, new formulations of ODTs were designed, intending to make a simpler and more [...] Read more.
Four decades have elapsed since orally disintegrating tablets (ODTs) were first formulated as the emulsion/type Lyoc tablet, a porous mass intended to rapidly disperse in saliva. Following the lyophilization process, new formulations of ODTs were designed, intending to make a simpler and more reproducible formulationZydis, LBL-Flash, Quicksolv, and, more recently, Zydis Ultra. Lyophilization is widely recognized as an effective technique for the development of ODTs, due to its ability to produce highly porous structures that enable rapid disintegration and improved patient compliance. However, its advantages should be considered in relation to other manufacturing methods, as each technology presents specific trade-offs in terms of cost, scalability, mechanical strength, drug loading capacity, and process robustness. In line with the modern sustainable and green pharmacy trend, new raw materials have gained attention as excipients for lyophilized ODTs; these materials include certain plant derivatives, but also performant excipients with newly discovered functionalities. At present, a new generation of ODTs is available in the form of Self-Nanoemulsifying Lyophilized Tablets (SNELTs), which bring the advantages of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) into ODTs via the lyophilization method. The technique is mostly applicable to low-solubility drugs formulated as nanoemulsions, which are absorbed onto solid carriers and further lyophilized, forming the final ODT. Despite its limitations (expensive, time-consuming, and high product friability), lyophilization is being continuously developed nowadays, in combination with other techniques (3D printing, mucoadhesion, or electrospinning), building hybrid platforms for the modern ODTs of the future. Full article
(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)
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18 pages, 1684 KB  
Article
Evaluation of the Impact of a Novel Visual Training Video Game on Oculomotor Function and Visual Symptoms in Subjects with Parkinson’s Disease and Convergence Insufficiency: A Pilot Study
by David P. Piñero, Carla Pérez-Casas, Alba Pina-Balofer, Carmen Bilbao, Carlo Cavaliere-Ballesta, Laurent Bataille and Rafael J. Pérez-Cambrodí
Life 2026, 16(5), 825; https://doi.org/10.3390/life16050825 - 15 May 2026
Viewed by 163
Abstract
Rationale and objectives: Parkinson’s disease (PD) significantly affects visual function, especially convergence and eye movements, impacting tasks such as reading. The objective was to investigate preliminarily the impact of the use of digital visual training in PD patients with associated convergence insufficiency (CI). [...] Read more.
Rationale and objectives: Parkinson’s disease (PD) significantly affects visual function, especially convergence and eye movements, impacting tasks such as reading. The objective was to investigate preliminarily the impact of the use of digital visual training in PD patients with associated convergence insufficiency (CI). Materials and methods: Pre–post pseudo-experimental pilot study to evaluate the impact of a novel digital therapy system (video game for use on a mobile phone or tablet) in 13 patients with PD and CI, with a mean age of 67 years. A comprehensive visual assessment was performed before and after a 6-week home-based visual rehabilitation, including measurement of near point of convergence (NPC), near positive fusional vergence (PFV), oculomotor tests (NSUCO and King-Devick tests), and symptom assessments with two validated questionnaires (CISS and SQVD). Results: Treatment adherence was variable, ranging from 0.8% to 124.7%. Despite this, significant improvements were found after therapy in break (p = 0.022) and recovery points of the NPC (p = 0.007), as well as break (p = 0.003) and recovery points in near PFV (p < 0.001). In the NSUCO test, the total score improved significantly from 23.9 ± 4.2 to 26.2 ± 3.7 after therapy (p = 0.003). Furthermore, a significant reduction in the total King-Devick test time was observed, decreasing from 79.4 ± 28.8 s to 69.0 ± 21.5 s with therapy (p = 0.034). Finally, symptom questionnaire scores also decreased significantly with therapy (CISS p = 0.037, SQVD p < 0.001). Conclusions: The digital vision therapy system evaluated seems to improve oculomotor control and reduce visual symptoms associated with CI in PD patients. Studies with larger sample sizes and a control group are needed to fully validate the therapeutic effectiveness of this tool. Full article
(This article belongs to the Special Issue Eye Diseases: Diagnosis and Treatment, 3rd Edition)
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23 pages, 1695 KB  
Review
Experimental Design in Pharmaceutical Formulation Development: Achievements, Limitations and the Transition Toward Intelligent Optimization
by Ayşe Türkdoğan, Tarek Alloush and Burcu Demiralp
Sci. Pharm. 2026, 94(2), 38; https://doi.org/10.3390/scipharm94020038 - 13 May 2026
Viewed by 591
Abstract
Historically, pharmaceutical formulation development relied heavily on trial-and-error experimentation, which was useful for empirical progress but often provided limited mechanistic understanding and insufficient efficiency for increasingly complex drug products. The introduction of Design of Experiments (DoE) and Quality by Design (QbD) established a [...] Read more.
Historically, pharmaceutical formulation development relied heavily on trial-and-error experimentation, which was useful for empirical progress but often provided limited mechanistic understanding and insufficient efficiency for increasingly complex drug products. The introduction of Design of Experiments (DoE) and Quality by Design (QbD) established a more systematic framework for studying formulation variables, manufacturing parameters, and Critical Quality Attributes (CQAs). Approaches such as factorial designs, response-surface methodology, and mixture designs have therefore become central to modern pharmaceutical development because they improve experimental efficiency and support the definition of design space. However, as formulations become more nonlinear, high-dimensional, and multi-objective, these classical approaches may no longer be sufficient on their own. This review examines the evolution of experimental design in pharmaceutical research, from one-factor-at-a-time experimentation to structured DoE/QbD strategies, and then to emerging intelligent optimization methods. Its central objective is to clarify when conventional DoE/QbD remains appropriate and when it should be complemented by machine learning, Bayesian optimization, digital twins, and closed-loop experimental systems. The review first summarizes the foundations and strengths of classical experimental design; then, it discusses its practical limitations in complex formulation settings, and finally evaluates how data-driven and hybrid approaches can extend pharmaceutical development. Evidence from tablets, capsules, nanocarriers, transdermal patches, and biotherapeutic systems suggests that intelligent optimization can improve predictive performance and experimental efficiency when used alongside, rather than instead of, established pharmaceutical development principles. Full article
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