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Search Results (1,828)

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16 pages, 1239 KB  
Article
Beyond the Scale: Changes in Pain, Physical Function (WOMAC), and Low-Grade Inflammation Following Semaglutide Treatment in Patients with Knee Osteoarthritis—Results from a Six-Month Real-World Cohort
by Alessandro Conforti, Linda Lucchetti, Francesca Ciampa, Marco Bonifacio, Marco Giuseppe Musorrofiti, Valerio Cipolloni and Filippo Messina
J. Clin. Med. 2026, 15(15), 5876; https://doi.org/10.3390/jcm15155876 - 27 Jul 2026
Abstract
Background: Knee osteoarthritis (KOA) in people with overweight or obesity is clinically heterogeneous, reflecting mechanical loading, synovial and systemic inflammation, metabolic dysfunction, structural severity, and pain-related factors. We evaluated multidomain outcomes after semaglutide initiation and characterized clinically relevant response patterns. Methods: [...] Read more.
Background: Knee osteoarthritis (KOA) in people with overweight or obesity is clinically heterogeneous, reflecting mechanical loading, synovial and systemic inflammation, metabolic dysfunction, structural severity, and pain-related factors. We evaluated multidomain outcomes after semaglutide initiation and characterized clinically relevant response patterns. Methods: This retrospective, self-controlled cohort included 93 adults treated in routine rheumatology care; 88 completed a six-month follow-up. There was no untreated concurrent comparator; within-patient changes and exposure–outcome associations were therefore interpreted as non-causal. Changes in pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, anthropometry, inflammatory markers, glycated hemoglobin (HbA1c), lipids, dose exposure, and safety were evaluated. Joint multivariable models included percentage weight loss and maximum achieved dose. Exploratory K-means phenotyping integrated dose, weight loss, body mass index (BMI) decrease, visual analog scale (VAS) and WOMAC improvement, and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and HbA1c reductions, with candidate solutions and resampling stability examined. Results: At six months, mean weight decreased by 10.88 kg, VAS pain score by 2.47 points, WOMAC total by 22.50 points, CRP by 2.67 mg/L, ESR by 7.62 mm/h, and HbA1c by 0.51 percentage points (all p < 0.001). Weight loss remained independently associated with WOMAC improvement, while achieved dose retained positive adjusted associations with pain, function, inflammatory, and metabolic changes. Exploratory clustering identified five clinically interpretable patterns along a broader response-intensity gradient, including high-burden multidomain response, high-dose concordant response, dose-modified intermediate response, inflammation-preserved response despite moderate weight loss, and dose-limited graded response. These observational coefficients and clusters cannot distinguish treatment-related effects from residual confounding or co-interventions. Conclusions: Substantial within-patient improvements were observed, but the uncontrolled design precludes causal attribution. The exploratory patterns may be compatible with contributions from baseline disease burden, dose exposure, mechanical unloading, and residual inflammatory variation; they do not establish weight-independent pharmacologic effects or validated patient subtypes. Prospective controlled, multicenter validation is required. Full article
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14 pages, 6876 KB  
Article
Structural Insights into the Photoactivatable CO Release from Mn-CO and Re-CO Complexes for CO Delivery
by Tao Wu, Chaoyang Shi, Chenyang Liu, Chenjie Qin, Jiangshan Wang, Yating Pang, Wenjun Gong, Wenming Wang and Hongfei Wang
Int. J. Mol. Sci. 2026, 27(15), 6704; https://doi.org/10.3390/ijms27156704 - 27 Jul 2026
Abstract
Two tri-carbonyl complexes, [Mn(CO)3(5cpa)Br] (1) and [Re(CO)3(5cqn)(OCH3)] (2), were synthesized, where 5cpa is 5-Cl-2-picolinic acid and 5cqn is 5-Cl-8-Hydroxyquinoline. Their structures were determined using X-ray diffraction techniques. The electronic absorption and IR spectra [...] Read more.
Two tri-carbonyl complexes, [Mn(CO)3(5cpa)Br] (1) and [Re(CO)3(5cqn)(OCH3)] (2), were synthesized, where 5cpa is 5-Cl-2-picolinic acid and 5cqn is 5-Cl-8-Hydroxyquinoline. Their structures were determined using X-ray diffraction techniques. The electronic absorption and IR spectra of the complexes were experimentally measured and theoretically assigned through density functional theory (DFT) calculations. The photo-induced CO release was verified using time-resolved infrared spectroscopy, and the transfer of CO to hemoglobin (Hb) was monitored by UV-vis spectroscopy. The rate of CO release and transfer from Mn complex 1 is significantly faster than that from Re complex 2. Complex 2 exhibits higher cytotoxicity against HeLa cells than complex 1, with IC50 values of 40.1 μM and 10.6 μM for 1 and 2, respectively, which decrease to 16.2 μM and 4.9 μM after photo irradiation. Moreover, 1 exhibited a stronger binding constant (Kb) with human serum albumin (HSA) than 2, with values of 1.6 × 106 and 7.0 × 105 M−1, respectively. The structures of HSA complex adducts revealed that both the resulting [Mn(CO)3(5cpa)] and [Re(CO)3(5cqn)] group coordinate with the N atom of His146, while four additional dissociated Mn-CO groups were observed to bind to HSA for complex 1. This study provides insights into the stability, possible metabolic pathways, and potential applications of these carbonyl complexes. Full article
(This article belongs to the Special Issue Current Trends in Organometallic Chemistry and Its Applications)
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15 pages, 577 KB  
Article
Interpretable Machine Learning Analysis of Factors Associated with Postoperative Hemoglobin Reduction After Total Knee Arthroplasty: A Standardized-Protocol Cohort Study in Non-Transfused Patients
by Jae Bum Kwon, Seung Jae Yoo, Junhee Lee, Sang Gyu Kwak and Won Kee Choi
J. Clin. Med. 2026, 15(15), 5862; https://doi.org/10.3390/jcm15155862 - 27 Jul 2026
Abstract
Background: Postoperative hemoglobin (Hb) reduction reflects the physiologic extent of perioperative blood loss after total knee arthroplasty (TKA). Whereas previous studies have relied on transfusion as a binary endpoint, transfusion decisions are highly variable across institutions, obscuring the underlying hematologic trajectory. This study [...] Read more.
Background: Postoperative hemoglobin (Hb) reduction reflects the physiologic extent of perioperative blood loss after total knee arthroplasty (TKA). Whereas previous studies have relied on transfusion as a binary endpoint, transfusion decisions are highly variable across institutions, obscuring the underlying hematologic trajectory. This study aimed to develop and interpret machine learning (ML) models to characterize and quantify the determinants of postoperative Hb reduction in a standardized cohort of non-transfused TKA patients. Methods: A retrospective cohort of 866 patients who underwent primary TKA under a standardized operative protocol—with identical cemented posterior-stabilized implants and uniform cementing technique—was analyzed (1 January 2014–31 March 2024). During the study period, a consistent 1 g intra-articular tranexamic acid (TXA) regimen administered through the drain was introduced and applied to a subset of patients, allowing TXA use to be modeled as a binary predictor. Four ML algorithms (Linear Regression, Random Forest, XGBoost, and Stacking Regressor) were trained using preoperative, demographic, and perioperative variables. Fivefold cross-validation assessed model performance, and SHapley Additive exPlanations (SHAP) values were used to identify influential predictors and enhance interpretability. Results: Across all ML models, preoperative Hb emerged as the strongest determinant of postoperative Hb reduction, followed by TXA use, body mass index (BMI), and platelet count. Ensemble models captured non-linear and interacting effects more effectively than linear regression. Test-set performance was modest (best R2 = 0.330), consistent with the influence of unmeasured physiologic factors such as hidden blood loss, fluid dynamics, and inflammatory responses. Accordingly, the primary value of the framework lies in the exploratory and transparent assessment of determinant importance rather than in individual-level prediction. Conclusions: This study provides an interpretable, exploratory ML framework for identifying factors associated with percentage Hb reduction after TKA. Preoperative Hb was the dominant determinant, while TXA use and higher BMI were recurrently associated with smaller predicted percentage reductions. Given the modest test-set performance and the absence of external validation and clinical utility assessment, the models should not be interpreted as tools for individual-level prediction or clinical decision making. Full article
(This article belongs to the Section Orthopedics)
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22 pages, 1580 KB  
Review
Oxygen Timing as Therapy: Molecular Rationale and Clinical Imperative for Early Oxygen Administration in the Sickle Cell Disease Vaso-Occlusive Crisis—A Structured Narrative Review with Implications for Resource-Constrained Health Systems
by Kanwarjot Singh, Dervens Michaud, Tal Parness, Odinaka Mgbeke, Henry Okodaso, Kwami Jones, Bawo Teddy Ikolo, Shellon Thomas and Felicia Ikolo
Biomedicines 2026, 14(8), 1682; https://doi.org/10.3390/biomedicines14081682 - 27 Jul 2026
Abstract
Sickle cell disease (SCD) is a monogenic hemoglobinopathy in which hemoglobin S (HbS) polymerizes on deoxygenation, leading to sickling of red blood cells (RBCs) and driving the acute vaso-occlusive crisis (VOC). With curative (transformative) therapies inaccessible to most patients in sub-Saharan Africa and [...] Read more.
Sickle cell disease (SCD) is a monogenic hemoglobinopathy in which hemoglobin S (HbS) polymerizes on deoxygenation, leading to sickling of red blood cells (RBCs) and driving the acute vaso-occlusive crisis (VOC). With curative (transformative) therapies inaccessible to most patients in sub-Saharan Africa and the Caribbean, where burden is highest, optimizing acute VOC care is a priority; yet oxygen is given reactively, after hypoxemia is documented, not at symptom onset when polymerization is most interruptible. We conducted a structured narrative review integrating HbS polymerization kinetics, clinical studies of oxygen-based therapies, trial protocols, and home-care implementation evidence (PubMed, Scopus, Google Scholar; 1974–2026). When RBCs release oxygen, HbS does not solidify at once: a brief pause, the nucleation delay phase (tD), precedes polymerization and sickling. Because tD falls steeply as deoxygenated hemoglobin rises (inversely, to its ~30th–50th power), a small early gain in oxygen saturation (~5–10%) lengthens it many-fold, opening a short window, roughly 30 min from onset, during which oxygen may abort a crisis. The clinical message is that timing, not dose, is decisive: oxygen at the first symptoms may prevent a crisis that the same oxygen, given later, cannot. Standard, high-flow, hyperbaric, and inhaled nitric-oxide modalities help in selected hospital settings, and the DREPADOM model shows community delivery before hospital arrival is feasible and safe. The central argument is precision in timing, not quantity: starting oxygen at symptom onset could turn a low-cost, universally available treatment into a crisis-aborting one for patients beyond the reach of curative therapy. We advance this as a mechanistically grounded but clinically untested hypothesis; regional implementation trials in the Caribbean and sub-Saharan Africa are urgently warranted. Full article
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13 pages, 309 KB  
Article
Blood Transfusion and ABO Blood Groups in Sickle Cell Disease
by Mortadah Alsalman, Muthana AlSahlawi, Naushad Abid, Khaled Elzorkany, Eman Abdallah, Alaa AlQuraini, Hussain Abduljaleel Alkhalifa, Marwa Shafey and Zaenb Alsalman
Medicina 2026, 62(8), 1449; https://doi.org/10.3390/medicina62081449 - 26 Jul 2026
Abstract
Background and Objectives: Blood transfusion is a key component of sickle cell disease (SCD) management, and ABO and Rh compatibility is essential to minimize transfusion-related complications. This study investigated factors associated with blood transfusion history and examined the relationships of ABO and [...] Read more.
Background and Objectives: Blood transfusion is a key component of sickle cell disease (SCD) management, and ABO and Rh compatibility is essential to minimize transfusion-related complications. This study investigated factors associated with blood transfusion history and examined the relationships of ABO and Rh blood groups with clinical and laboratory markers of disease severity. Materials and Methods: A cross-sectional study was conducted among 309 patients attending a hematology outpatient clinic in Saudi Arabia between October and December 2025. Clinical data were collected through patient interviews, and laboratory results were obtained from medical records. Results: Overall, 89.9% of patients had a history of blood transfusion. Older age, chronic disease, higher platelet count, MCV, MCH, and HbA2 levels were associated with blood transfusion history. In contrast, higher hemoglobin and HbF levels were associated with fewer transfusions. Patients with blood group O had lower odds of transfusion than those with non-O blood groups (OR = 0.340, 95% CI: 0.135–0.856; p = 0.022). Hydroxyurea use was associated with lower LDH levels, while G6PD deficiency and higher MCV were independently associated with higher LDH levels. ABO and Rh blood groups were not associated with acute chest syndrome or LDH levels. Conclusions: Blood transfusion history in SCD was associated with several clinical and hematological factors. These findings support further investigation of G6PD status and reinforce the known benefits of hydroxyurea. Further studies are needed to clarify the role of ABO and Rh blood groups in disease progression and transfusion practices. Full article
(This article belongs to the Section Hematology and Immunology)
12 pages, 1329 KB  
Article
Kinetics of Blood Volume and Hemoglobin Mass Adaptation in Sea-Level Newcomers Relocating to Moderate Altitude: A Six-Month Prospective Study
by Mohammed A. Alshehri and Husain Y. Alkhaldy
J. Clin. Med. 2026, 15(15), 5833; https://doi.org/10.3390/jcm15155833 - 26 Jul 2026
Abstract
Background/Objectives: The kinetics of blood volume and hemoglobin mass (Hbmass) adaptation in newcomers to moderate altitude and the time required to reach the hematological phenotype of long-term residents remain poorly defined. We aimed to characterize this trajectory over six months and to compare [...] Read more.
Background/Objectives: The kinetics of blood volume and hemoglobin mass (Hbmass) adaptation in newcomers to moderate altitude and the time required to reach the hematological phenotype of long-term residents remain poorly defined. We aimed to characterize this trajectory over six months and to compare newcomers with established altitude residents. Methods: Thirty-seven healthy male sea-level newcomers were prospectively followed at baseline (within 48 h of arrival), two months, and six months after relocation to Abha, Saudi Arabia (2250 m). Hbmass, blood volume (BV), plasma volume (PV), and red blood cell volume (RBCV) were measured by CO rebreathing; lean body mass (LBM) was assessed by DXA. Six-month values were compared with 107 long-term male altitude residents. Linear mixed-effects models with Holm–Bonferroni correction were used. Results: Adaptation followed a biphasic trajectory. At two months, RBCV and Hbmass rose significantly from baseline (RBCV + 186 mL, Hbmass + 65 g; both p ≤ 0.005), confirmed by LBM-adjusted analysis. These gains partially regressed by six months, after which no volume parameter differed significantly from baseline. Hemoglobin (Hb) and hematocrit (Hct) remained persistently elevated (+6 g/L, +1.9%; both p < 0.001) due to sustained PV contraction. Compared with long-term residents, six-month newcomers had significantly lower LBM-adjusted Hbmass (15.7 vs. 18.0 g/kg), RBCV (48.0 vs. 54.2 mL/kg), and BV (98.9 vs. 109.8 mL/kg; all p < 0.001), yet Hb and Hct were not significantly different. Conclusions: Moderate altitude acclimatization follows a transient two-month erythropoietic increase, then partial regression. Six months is insufficient to attain the oxygen-carrying capacity of long-term residents’ deficit entirely masked by Hb and Hct. Direct Hbmass measurement normalized to LBM is required for accurate assessment of altitude adaptation. Full article
(This article belongs to the Topic Advances in Hemodynamic Monitoring)
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11 pages, 707 KB  
Article
The Association Between the HALP Score and Glycemic Control in Older Adults with Type 2 Diabetes Mellitus Receiving Home Health Care
by Safiye Kübra Çetindağ Karatlı, Münevver Yıldız, Ebru Uğraş, Erhan Şimşek and Ahmet Keskin
Healthcare 2026, 14(15), 2272; https://doi.org/10.3390/healthcare14152272 - 25 Jul 2026
Viewed by 53
Abstract
Background: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a simple inflammation–nutrition index that has been associated with adverse outcomes in patients with type 2 diabetes mellitus (T2DM). This study investigated the association between the HALP score and poor glycemic control in [...] Read more.
Background: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a simple inflammation–nutrition index that has been associated with adverse outcomes in patients with type 2 diabetes mellitus (T2DM). This study investigated the association between the HALP score and poor glycemic control in older adults with T2DM receiving home health care after excluding patients with malnutrition. Methods: This retrospective, cross-sectional study included 201 patients aged ≥65 years with T2DM whose routinely collected home health care records between 15 December 2025 and 15 March 2026 were retrospectively reviewed after ethics committee approval. Poor glycemic control was defined as HbA1c ≥ 8.0%. Logistic regression analyses were performed to identify factors associated with elevated HbA1c levels. A sensitivity analysis including clinically relevant variables was additionally conducted. The discriminative performance of HALP was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The median age was 83 years, 52.2% were male, and 51 patients (25.4%) had elevated HbA1c levels (≥8.0%). In univariate analysis, high HALP was significantly associated with lower odds of elevated HbA1c levels (OR: 0.27; 95% CI: 0.14–0.52; p < 0.001), whereas dementia showed a borderline association (OR: 0.36; 95% CI: 0.12–1.06; p = 0.065). In multivariable analysis, high HALP remained independently associated with lower odds of poor glycemic control (OR: 0.28; 95% CI: 0.14–0.54; p < 0.001). In a sensitivity analysis adjusted for age, sex, Barthel group, and dementia, high HALP maintained its independent association with lower odds of elevated HbA1c levels (OR: 0.30; 95% CI: 0.15–0.59; p = 0.001). The HALP score demonstrated weak to modest discriminative ability for predicting HbA1c ≥ 8.0% (AUC: 0.645; 95% CI: 0.552–0.739; p = 0.002), with 75.3% sensitivity and 45.1% specificity at a cut-off value of 29.24. Conclusions: High HALP was independently associated with better glycemic control in older adults with T2DM receiving home health care. However, given its weak to modest discriminative ability, HALP should be interpreted alongside clinical assessment and routine metabolic parameters rather than as a standalone diagnostic or predictive criterion. Full article
(This article belongs to the Section Chronic Care)
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12 pages, 332 KB  
Review
The Influence of Reliable Microbiota Consortia in Probiotic Yogurt on Improving Insulin Sensitivity in Type 2 Diabetes Mellitus Patients
by Lovita Adriani, Diding Latipudin, Andi Mushawwir and Khairunnisa Mohd Paad
Appl. Microbiol. 2026, 6(8), 86; https://doi.org/10.3390/applmicrobiol6080086 - 24 Jul 2026
Viewed by 65
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive insulin resistance, impaired glucose regulation, and elevated cardiometabolic risk. Despite the availability of pharmacological therapies, long-term glycemic control remains suboptimal in many patients, highlighting the need for effective adjunctive nutritional [...] Read more.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive insulin resistance, impaired glucose regulation, and elevated cardiometabolic risk. Despite the availability of pharmacological therapies, long-term glycemic control remains suboptimal in many patients, highlighting the need for effective adjunctive nutritional strategies. Probiotic yogurt containing well-characterized bacterial consortia has been proposed as one such approach, given its potential to modulate gut microbiota composition, increase short-chain fatty acid (SCFA) production, improve intestinal barrier integrity, and attenuate low-grade systemic inflammation. A narrative review was conducted by searching PubMed, Scopus, and Google Scholar databases using terms related to probiotic yogurt, synbiotic yogurt, insulin sensitivity, T2DM, gut microbiota, Lactobacillus, and Bifidobacterium. Priority was given to randomized controlled trials (RCTs), meta-analyses, and systematic reviews, supplemented by mechanistically relevant preclinical studies. The reviewed evidence indicates that probiotic yogurt generally produces more consistent improvements in long-term metabolic markers, particularly glycated hemoglobin (HbA1c) and lipid profile, than in acute fasting glucose responses. Several trials also report reductions in fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), combined with improvement in the quantitative insulin sensitivity check index (QUICKI), particularly when yogurt is enriched with prebiotic substrates such as inulin and konjac glucomannan. Probiotic yogurt formulated with well-selected microbial consortia may serve as a safe complementary intervention for improving insulin sensitivity and overall metabolic control in T2DM patients. Full article
(This article belongs to the Special Issue Applied Microbiology of Foods, 3rd Edition)
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19 pages, 3214 KB  
Article
The Host Tissue Repair Vulnerability Index (HTRVI): A Composite Biomarker for Predicting Osteoradionecrosis in Locally Advanced Nasopharyngeal Carcinoma
by Efsun Somay, Erkan Topkan, Sibel Bascil and Ugur Selek
Med. Sci. 2026, 14(4), 427; https://doi.org/10.3390/medsci14040427 - 24 Jul 2026
Viewed by 131
Abstract
Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related [...] Read more.
Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related parameters, to estimate biological susceptibility to ORNJ in locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × hemoglobin). HTRVI was compared with hemoglobin (Hb) and the Global Immune-Nutrition-Inflammation Index (GINI) using receiver operating characteristic analysis. Multivariable logistic regression, restricted cubic spline analysis (RCS), and bootstrap resampling assessed independent association, continuous risk relationship, and internal validation. Results: During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769–0.932) compared with Hb (AUC, 0.785; p = 0.001) and GINI (AUC, 0.759; p = 0.045). HTRVI remained independently associated with ORNJ after adjustment for mandibular mean dose and post-CCRT tooth extraction burden (OR per standard deviation increase, 4.81; 95% CI, 1.10–20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (Poverall < 0.001) without nonlinearity (Pnonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993). Conclusions: HTRVI was independently associated with ORNJ and provided additional predictive information beyond established clinical and dosimetric factors in this single-center cohort. The continuous HTRVI–ORNJ association supports a biological continuum model of host tissue repair vulnerability. However, HTRVI should currently be regarded as an investigational biomarker requiring independent external and prospective validation before clinical implementation. Full article
(This article belongs to the Special Issue Insights into the Modern Landscape of Cancer Therapeutics)
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19 pages, 3326 KB  
Article
A Pilot Study of Salmon Protein Hydrolysate (ProGo®) Supplementation to Assess Its Impact on Hematologic, Integumentary and Metabolic Health
by Crawford Currie, Tor Åge Myklebust, Christian Bjerknes and Bomi Framroze
Biomedicines 2026, 14(8), 1663; https://doi.org/10.3390/biomedicines14081663 - 24 Jul 2026
Viewed by 209
Abstract
Background: Healthy ageing depends on the maintenance of several interconnected biological processes including adequate oxygen-carrying capacity, control of systemic inflammation, and preservation of lean body mass. ProGo® is a salmon protein hydrolysate (SPH) with prior evidence of benefits on iron metabolism, inflammation, [...] Read more.
Background: Healthy ageing depends on the maintenance of several interconnected biological processes including adequate oxygen-carrying capacity, control of systemic inflammation, and preservation of lean body mass. ProGo® is a salmon protein hydrolysate (SPH) with prior evidence of benefits on iron metabolism, inflammation, and metabolic health. Methods: This randomized, double-blind, active-controlled pilot study examined whether 56 days of daily ProGo® supplementation could enhance key biological drivers of healthy ageing in overweight adults, compared with an iso-nitrogenous whey protein isolate (WPI). Primary outcomes were hematological parameters and a composite integumentary (hair, nail, and skin) score, assessed with Holm–Bonferroni multiplicity adjustment. Secondary outcomes included change in body composition, inflammatory biomarkers and glucose metabolism. Results: ProGo® showed significant improvements in hemoglobin, RBC count, and ferritin, and in the integumentary composite score. Secondary analyses showed reductions in percent body fat and BMI, with preservation of lean body mass (LBM), alongside reductions in pro-inflammatory cytokines, HbA1c, and fasting blood glucose. WPI had minimal impact on any of these outcomes. Conclusions: ProGo® supplementation improved multiple key biological drivers of healthy ageing: erythropoietic function, systemic inflammation, glycemic control, and body composition. These findings are consistent with a bioactive rather than a purely nutritional effect and are hypothesis-generating with respect to a multi-domain profile relevant to healthy ageing and the maintenance of intrinsic capacity. Confirmation in larger studies is warranted. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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19 pages, 3582 KB  
Article
Aqueous Artemisia herba-alba Asso Preparation as a Botanical Adjunct to Dapagliflozin: Enhanced Glycemic Control in Streptozotocin-Induced Diabetic Rats
by Mohammad M. Hailat, Mustafa M. Al-Karkhi, Nisreen T. Al-Qaisi, Marwan Shalash, Wael Abu Dayyih, Wafa Hourani, Mohammad Abu Assab, Ahmed Bassam Farhan, Abdul Rahman Abu Dayyih, Shorouq B. Talalah and Afnan B. Talalah
Pharmaceutics 2026, 18(7), 900; https://doi.org/10.3390/pharmaceutics18070900 - 22 Jul 2026
Viewed by 220
Abstract
Background/Objectives: optimization of the therapeutic efficacy of antidiabetic agents is still a great challenge in the management of type 2 diabetes mellitus (T2DM), and attention is becoming more and more focused on the use of adjunctive agents that help target the drug [...] Read more.
Background/Objectives: optimization of the therapeutic efficacy of antidiabetic agents is still a great challenge in the management of type 2 diabetes mellitus (T2DM), and attention is becoming more and more focused on the use of adjunctive agents that help target the drug action beyond the classic glycemic target. This study examined the effect of co-administration of an Artemisia herba-alba Asso (Asteraceae) aqueous extract on the glucose-lowering effect of dapagliflozin, a sodium–glucose cotransporter-2 (SGLT2) inhibitor. Methods: qualitative phytochemical screening and total phenolic and total flavonoid content were used to characterize the aqueous preparation. Male Wistar albino rats were divided into eight groups (10 rats each): four healthy and four diabetic rats induced with streptozotocin (STZ). Vehicle control, oral administration of an aqueous A. herba-alba preparation (0.39 g/kg twice daily), dapagliflozin (0.143 mg/kg/day), or a combination of both was given for 30 days. At baseline and days 7, 14, 21, and 30, glycated hemoglobin (HbA1c) was measured by nephelometry. Parallel fasting blood glucose (FBG) was monitored. Results: the diabetic animals treated with the combination regimen showed the greatest and most sustained decrease in HbA1c (from 4.42 ± 0.40% at baseline to 3.44 ± 0.17% at day 30; p < 0.001) and the greatest decrease in FBG (from 186.0 to 122.2 mg/dL). A. herba-alba monotherapy had little effect on HbA1c and had minimal effect on FBG (214.9 to 217.6 mg/dL); dapagliflozin monotherapy had a modest effect on HbA1c. The untreated diabetic controls (n = 10) showed a progressive increase in HbA1c from 4.45 ± 0.60% at 72 h post-induction to 11.90 ± 0.99% by day 30 (p < 0.001), consistent with delayed hemoglobin glycation relative to the rise in blood glucose. The repeated-measures ANOVA showed a highly significant interaction between time and treatment (p < 0.001). Conclusions: this study showed that the phytochemically defined aqueous A. herba-alba preparation is a beneficial adjunct to SGLT2 inhibitor therapy, an effect not observed with either treatment alone. Full article
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23 pages, 1390 KB  
Review
Diabetes Mellitus and Endo-Periodontal Lesions: An HbA1c-Guided Framework for Clinical Decision-Making
by Adrian Stan, Mihaela Moisei, Liliana-Lăcrămioara Pavel, Liliana Mititelu-Tarțău, Beatrice Rozalina Buca and Mioara Decusară
Medicina 2026, 62(7), 1420; https://doi.org/10.3390/medicina62071420 - 22 Jul 2026
Viewed by 248
Abstract
Background and Objectives: Diabetes mellitus is a major systemic modifier of oral infection, periodontal inflammation, and tissue healing. Persistent hyperglycemia may intensify oxidative stress, immune dysfunction, dysbiotic biofilm activity, and advanced glycation end-product/receptor signaling, thereby reducing the predictability of periapical and periodontal [...] Read more.
Background and Objectives: Diabetes mellitus is a major systemic modifier of oral infection, periodontal inflammation, and tissue healing. Persistent hyperglycemia may intensify oxidative stress, immune dysfunction, dysbiotic biofilm activity, and advanced glycation end-product/receptor signaling, thereby reducing the predictability of periapical and periodontal healing. In patients with endo-periodontal lesions, these mechanisms may interact with pulpal infection and periodontal breakdown, complicating diagnosis, prognosis, and therapeutic sequencing. This review summarizes current evidence on diabetes, glycated hemoglobin (HbA1c), and endo-periodontal outcomes and proposes an HbA1c-guided clinical framework for risk stratification and treatment planning. Materials and Methods: A structured narrative review with an expert-informed clinical framework was conducted using the literature published between January 2016 and December 2025. Eligible sources included consensus reports, clinical practice guidelines, systematic reviews, meta-analyses, umbrella reviews, randomized and non-randomized clinical studies, observational studies, and selected mechanistic studies or contemporary narrative reviews with direct relevance to the framework. Case reports, animal studies, and in vitro investigations without direct relevance to the clinical framework were excluded from the main synthesis. Results: Diabetes is associated with increased periodontal severity, impaired periodontal treatment response, a higher prevalence of radiolucent periapical lesions in root-filled teeth, delayed periapical healing, and increased non-retention of endodontically treated teeth. Periodontal therapy is safe in diabetic patients and may be associated with modest reductions in HbA1c, especially when baseline metabolic control is poor. Conclusions: HbA1c should complement, not replace, pulpal testing, periodontal charting, and radiographic assessment. The proposed framework prioritizes endodontic infection control when pulpal necrosis or active intracanal infection is present, adapts periodontal intervention to metabolic risk, and postpones elective surgical or regenerative procedures in poorly controlled diabetes until medical stabilization is achieved. Full article
(This article belongs to the Collection New Concepts for Dental Treatments and Evaluations)
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16 pages, 293 KB  
Review
Sickle Cell Disease: From Ancient Origins to Modern Breakthroughs in Gene Therapy
by Bawo Ikolo, Mathew Oyelami, Odinaka Mgbeke, Kwami Jones, Shellon Thomas and Felicia Ikolo
Biomedicines 2026, 14(7), 1649; https://doi.org/10.3390/biomedicines14071649 - 22 Jul 2026
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Abstract
Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy arising from a single-nucleotide transversion (GAG → GTG) at codon six of the HBB gene on chromosome 11, substituting glutamic acid with valine in the β-globin chain and producing hemoglobin S (HbS). Under hypoxic conditions, [...] Read more.
Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy arising from a single-nucleotide transversion (GAG → GTG) at codon six of the HBB gene on chromosome 11, substituting glutamic acid with valine in the β-globin chain and producing hemoglobin S (HbS). Under hypoxic conditions, HbS polymerizes and distorts erythrocytes into the characteristic sickle shape, initiating a cascade of vaso-occlusion, chronic hemolytic anemia, and progressive multi-organ damage that defines the clinical burden of this disease. Although SCD has ancient origins in sub-Saharan Africa, the Indian subcontinent, the Middle East, and the Mediterranean, regions where it conferred heterozygous resistance to malaria, the ease of human migration has long since made it a global health concern, affecting an estimated 300,000–400,000 newborns annually. Advances in molecular and genomic research have deepened our understanding of SCD pathophysiology, revealing the central contributions of hemoglobin polymerization, oxidative stress, endothelial inflammation, and nitric oxide depletion to disease progression. Current management rests on supportive pharmacological interventions, including hydroxyurea, chronic transfusion therapy, L-glutamine, and multimodal pain management, complemented by lifestyle modifications. Curative approaches have advanced substantially: hematopoietic stem cell transplantation (HSCT) remains the established standard of cure, while the regulatory approvals in late 2023 of the CRISPR/Cas9-based exagamglogene autotemcel (Casgevy) and the lentiviral vector-based lovotibeglogene autotemcel (Lyfgenia) represent the most transformative development in the history of SCD therapeutics. This review traces the disease from its ancient origins and molecular characterization through to its clinical manifestations, inheritance patterns, screening strategies, and the full spectrum of current and emerging therapies. Persistent challenges, prohibitive treatment costs, healthcare inequities, the ethical dimensions of genome editing, and the urgent need for long-term safety data, are examined critically, with a view to informing the research and policy agenda that must accompany these remarkable scientific advances. Full article
13 pages, 2866 KB  
Article
Development of a Deep Learning Model to Estimate Anemia from Palpebral Conjunctiva Taken with a Portable Slit-Lamp Microscope
by Yo Nakahara, Eisuke Shimizu, Takahiro Mizukami, Hiroki Nishimura, Shintaro Nakayama, Tetsuo Ishikawa, Masatoshi Hirayama, Risa Hokama, Kazuhiro Sakurada and Kazuno Negishi
Bioengineering 2026, 13(7), 824; https://doi.org/10.3390/bioengineering13070824 - 17 Jul 2026
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Abstract
Background: Anemia is a common systemic condition associated with adverse maternal, perioperative, and cardiovascular outcomes. Although timely screening is clinically important, diagnosis still relies on invasive blood testing. Palpebral conjunctival pallor has traditionally been used as a noninvasive indicator of anemia, but its [...] Read more.
Background: Anemia is a common systemic condition associated with adverse maternal, perioperative, and cardiovascular outcomes. Although timely screening is clinically important, diagnosis still relies on invasive blood testing. Palpebral conjunctival pallor has traditionally been used as a noninvasive indicator of anemia, but its diagnostic accuracy remains limited. This study aimed to develop and validate a deep learning system to estimate hemoglobin (Hb) concentration and screen for anemia using palpebral conjunctiva images captured with a smartphone-compatible slit-lamp microscope. Methods: In this prospective observational study, 225 Japanese participants (20–92 years) underwent conjunctival imaging and blood testing. Palpebral conjunctiva videos were obtained using the Smart Eye Camera. Video frames were processed using automated anterior-segment segmentation and conjunctiva extraction. A ConvNeXt-based regression model was trained to predict Hb values. Anemia was defined using sex-specific Hb thresholds. Results: From 225 videos, 53,776 frames were extracted, yielding 9903 quality-filtered conjunctiva images (training: 8082; test: 1821). Video-level predicted Hb values moderately correlated with measured Hb (r = 0.42). For anemia screening, frame-level analysis achieved an AUC of 0.75, with accuracy of 0.76, sensitivity of 0.71, and specificity of 0.79. Video-level aggregation achieved 69% accuracy. Conclusions: Deep learning analysis of palpebral conjunctiva images acquired with a portable slit-lamp microscope demonstrated the feasibility of non-invasive hemoglobin estimation and anemia screening. Although the proposed approach achieved moderate performance, further improvements in model accuracy and prospective multi-center validation are required before clinical implementation. Full article
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21 pages, 923 KB  
Article
Determinants of Health Status in Adult Diabetic Patients: From Anthropometric and Biological Indicators to Individual Perception
by Lăcrămioara Aurelia Brîndușe, Corina Vicol, Maria Alexandra Cucu and Eugenia Claudia Bratu
Diabetology 2026, 7(7), 138; https://doi.org/10.3390/diabetology7070138 - 17 Jul 2026
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Abstract
Background/Objectives: In Romania, diabetes mellitus remains a significant public health challenge, characterized by high prevalence and significant undiagnosed cases. This study assessed the prevalence of elevated glycated hemoglobin (HbA1c) levels within the adult population participating in the European Health Examination Survey (EHES) [...] Read more.
Background/Objectives: In Romania, diabetes mellitus remains a significant public health challenge, characterized by high prevalence and significant undiagnosed cases. This study assessed the prevalence of elevated glycated hemoglobin (HbA1c) levels within the adult population participating in the European Health Examination Survey (EHES) and examined their associations with major cardiometabolic risk factors, subjective health perception, and patient awareness of previously diagnosed chronic conditions. Methods: This cross-sectional study analyzed data from the EHES in Romania, including systematic, population-weighted sample of adults aged 25–64 years. Data were analyzed using the Complex Samples module in SPSS, version 29.0 (IBM Corp., Armonk, NY, USA). HbA1c levels were measured through standardized clinical examination, with values of 5.7–6.4% classified as at risk for diabetes mellitus, and values ≥6.5% as diabetes mellitus. Results: Among 5380 representative adults, the prevalence of elevated HbA1c (≥6.5%) was 7.1%, while prediabetes (HbA1c 5.7–6.4%) affected 35.4% of participants; both conditions were significantly more prevalent in men than in women. Elevated HbA1c and prediabetes were substantially more frequent among individuals with hypertension and hypercholesterolemia, and glycemic control among participants with previously diagnosed diabetes was generally poor (all p ≤ 0.05). Individuals who are aware of having a chronic health condition appear to engage more actively in self-care practices, including increased physical activity and more frequent monitoring of key biological parameters. Conclusions: Elevated HbA1c and prediabetes were more prevalent than estimates reported in other studies using HbA1c-based diagnostic criteria. These observations highlight the importance of early detection and timely diagnosis, as awareness of one’s health status may facilitate healthier behaviors that mitigate metabolic complications. Full article
(This article belongs to the Section Epidemiology and Risk Factors of Diabetes)
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