Search Results (72)

With the growing interest in personalized medicine, alternative biological matrices to blood are increasingly explored as sources of diagnostic information. Saliva has emerged as a promising diagnostic matrix due to its non-invasive collection, suitability for home sampling, and minimal requirements for personnel training. Numerous studies have demonstrated the presence of metabolites in saliva that enable disease diagnosis and monitoring. However, the influence of pre-analytical and analytical factors on salivary metabolomics outcomes remains insufficiently characterized. In this study, we investigated factors potentially affecting the number and abundance of detected metabolites in untargeted salivary metabolomics using liquid chromatography coupled with mass spectrometry (LC–MS). The impact of chromatographic column type, extraction protocol, and saliva type (stimulated versus resting) was evaluated. Additionally, the effect of swab type on analyte recovery was assessed. The use of a synthetic swab for saliva collection yielded results most comparable to those obtained without swabs, for both resting and stimulated saliva samples, indicating minimal pre-analytical interference. The greatest metabolite coverage was obtained using ACN:MeOH (1:1, v/v), with a ZIC-HILIC column for polar metabolites and a C18 column for non-polar metabolite separation. These findings demonstrate that swab type, chromatographic column, extraction solvent, and saliva type critically shape metabolite coverage in untargeted salivary metabolomics. Importantly, the distinct metabolic profiles of resting and stimulated saliva suggest that these matrices may provide complementary clinical insights, underscoring the need for saliva type selection tailored to specific diagnostic and biomarker discovery objectives. Full article

Despite the high prevalence of low back pain (LBP), evidence supporting the clinical effects of repetitive peripheral magnetic stimulation (rPMS) remains limited. A combined double-coil and handheld rPMS approach may enhance the therapeutic potential of this technology. This observational case series analyzed prospectively collected routine clinical data from 37 patients treated with a combined protocol of static double-coil lumbar rPMS and dynamic handheld lower-limb rPMS. Pain intensity, disability, and quality of life were assessed at baseline, post-treatment, and 1-month follow-up. Statistical analyses were complemented by an evaluation of clinical relevance using established minimal clinically important difference (MCID) thresholds. Significant improvements were observed across all outcomes. Pain decreased by 62.5% post-treatment and by 87.5% at follow-up, while disability was reduced by 86.8% and 92.1%, respectively. Quality of life scores approximately doubled. High MCID responder rates and consistent within-group changes were observed; however, given the single-arm design without a control group, these findings should be interpreted as exploratory and hypothesis-generating rather than confirmatory evidence of treatment effectiveness. This combined rPMS approach was feasible and well tolerated in routine clinical practice and was associated with clinically meaningful within-group improvements in pain, function, and quality of life. Further controlled studies are warranted. Full article

Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105⁺ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies Full article

Hair loss, or alopecia, constitutes a significant and prevalent concern affecting individuals worldwide. Despite the availability of numerous commercial solutions, many individuals continue to experience substantial psychological distress, leading to adverse impact on personal relationships, social interactions, and occupational performance. The limitations of conventional treatments, such as oral medication with potential systemic side effects and topical applications with localized adverse events, have driven the exploration of alternative therapies. Emerging localized injectable treatments for hair regrowth (PRP, stem cells, exosomes) offer a promising avenue for addressing this persistent issue. These injectable therapies hold the potential to minimize the systemic side effects often associated with oral medications, while also mitigating the localized adverse events that can arise from topical applications. This narrative review provides a comprehensive overview of the medical state-of-the-art in off-label injectable hair regrowth treatments, delving into the diverse range of available options. A critical component of this narrative review involves a thorough evaluation of relevant clinical studies, assessing the efficacy and safety profiles of these emerging therapies. Furthermore, detailed attention is given to injection techniques and administration protocols, crucial factors in optimizing treatment outcomes. These evolving therapies represent a significant advancement in the field of scalp regenerative medicine. By stimulating hair follicle reactivation, these treatments aim to promote sustained and natural hair growth, providing individuals with more effective and durable solutions. The enhanced safety profiles of these injectable therapies, compared to conventional systemic pharmacological treatments (minoxidil, finasteride), offer a substantial improvement in patient care, addressing a widespread clinical need. Full article

Background: Optimizing pregnancy outcomes while minimizing gonadotropin exposure and treatment burden remains a major goal in ovulation induction for intrauterine insemination (IUI), particularly for patients with polycystic ovary syndrome (PCOS) or high ovarian reserve. Sequential protocols combining early letrozole with late-onset recombinant FSH (rFSH) have been proposed to enhance efficiency while reducing medication requirements. However, real-world comparative data adjusting for baseline differences are limited. Methods: This retrospective comparative cohort study included 764 IUI cycles performed between January 2022 and October 2025. Cycles were stimulated either with conventional rFSH (n = 372) or letrozole plus late-onset rFSH (n = 392). The primary outcome was pregnancy per cycle, defined by a positive serum β-hCG. Secondary outcomes included clinical pregnancy, total gonadotropin dose, endometrial thickness, cycle cancelation, and obstetric outcomes. Confounding was addressed using multivariable logistic regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and doubly robust estimation. Results: The crude pregnancy rate was higher in the letrozole plus late rFSH group compared with conventional rFSH (14.8% vs. 9.9%, p = 0.042). Women in the sequential stimulation group had higher AMH levels, higher antral follicle counts, and a higher prevalence of PCOS (32.4% vs. 16.3%, p = 0.001). After adjustment for age, ovarian reserve, and other baseline characteristics using regression, PSM, and IPTW, the stimulation protocol was not independently associated with pregnancy (adjusted OR 1.09, 95% CI 0.68–1.74; p = 0.657). Female age remained the strongest predictor of pregnancy (adjusted OR 0.70 per year increase; p < 0.001). The sequential protocol required a significantly lower total gonadotropin dose (median 375 IU vs. 750 IU; p < 0.001) while maintaining comparable cycle cancellation and safety outcomes. Conclusions: Sequential stimulation with letrozole plus late-onset rFSH achieves pregnancy outcomes comparable to conventional rFSH stimulation while significantly reducing gonadotropin requirements. After adjustment for PCOS status and ovarian reserve, the protocol itself did not independently influence pregnancy, suggesting that crude differences reflected baseline imbalances rather than true treatment effects. This approach represents a clinically efficient, gonadotropin-sparing option for IUI, particularly in patients at risk for excessive ovarian response. Full article

Maintaining cardiovascular stability during anesthesia is essential, yet the routine use of atropine to prevent vagally induced low heart rate may impose additional stress on the heart. This randomized, controlled, observer-blinded, clinical study aimed to evaluate whether ondansetron, a selective 5-HT₃ receptor antagonist, could serve as an alternative anesthetic adjuvant to modulate autonomic activity while maintaining cardiovascular stability in dogs. A total of 66 female dogs, with a mean age of 1.5 years and a mean weight of 16–18 kg ASA I, undergoing elective surgery were assigned to three study groups to receive atropine, ondansetron, or no autonomic-modulating drug. Heart rate, arterial pressure, respiratory rate, and NT-proBNP were recorded before, during, and after anesthesia. Dogs treated with ondansetron maintained stable cardiovascular values throughout the procedure, with no episodes of low heart rate or excessive increases in heart rate. In contrast, atropine induced marked and sustained elevation in heart rate and higher arterial pressures. Concentrations of the cardiac biomarker NT-proBNP increased significantly 48 h after surgery in the atropine group but remained unchanged in the ondansetron group, indicating the absence of additional myocardial stress. These findings suggest that ondansetron may help preserve autonomic balance during anesthesia while minimizing myocardial stress. Ondansetron could represent a useful component of multimodal anesthetic protocols, particularly in dogs in which excessive cardiac stimulation should be avoided. Full article

Background: The success of in vitro fertilization (IVF) is influenced by multiple patient- and laboratory-related factors, including maternal age, body mass index (BMI), ovarian stimulation, and embryo quality. Laboratory illumination may induce photo-oxidative stress, potentially impairing embryo development and implantation. This study evaluated the clinical impact of introducing a light-protection protocol in an IVF laboratory. Methods: We retrospectively analyzed 2125 IVF cycles with fresh embryo transfer performed at the Assisted Reproduction Centre of the University of Pécs between 1 March 2016 and 30 November 2020. A light-protection protocol was implemented on 1 March 2017, while all other laboratory and clinical parameters remained unchanged. Pregnancy outcomes before and after implementation were compared, with additional subgroup analyses focusing on cycles with low blastocyst-formation rates. Results: After implementation of light protection, overall pregnancy rates increased by approximately 5%; however, this difference was not statistically significant. In contrast, subgroup analyses demonstrated a markedly greater improvement in pregnancy outcomes—up to 37%—in cycles characterized by low blastocyst-formation rates. Conclusions: Although light protection did not significantly improve overall pregnancy rates, the findings suggest a clinically relevant benefit in selected cases with reduced embryonic developmental competence. Minimizing photo-oxidative stress may therefore represent a targeted laboratory intervention to improve IVF outcomes in vulnerable embryo populations. Full article

Background: Rate-dependent depression of the Hoffmann reflex (RDD-HR) is a neurophysiological marker of spinal inhibition altered in several neurological conditions, yet no consensus exists on optimal stimulation frequency, number of stimuli, or the feasibility of upper limb recordings. This study aimed to define practical, standardized parameters for reliable RDD-HR assessment in upper and lower limbs of healthy adults, as a first step toward clinical application. Methods: In this observational study, bilateral Hoffmann reflexes were recorded from the flexor carpi radialis and soleus muscles in 21 healthy adults. Stimulation was delivered using three 10-pulse trains at seven frequencies (0.1–5 Hz). RDD-HR was quantified as the median H-reflex area, expressed as a percentage of the first response (lower values indicate greater depression). Optimal frequencies and minimal stimuli were identified by sigmoid fitting and confidence analyses, with train and stimulus effects tested by two-way ANOVA. Results: RDD-HR displayed a sigmoidal frequency–response across all limbs. Maximal depression occurred at 1–5 Hz, with no significant differences between these frequencies, supporting 1 Hz as optimal. Depression was greater in lower limbs (~30%) than upper limbs (~47%). Reliable estimates were obtained using a single train of seven stimuli, with no benefit from averaging across trains. Upper limb recordings required lower stimulation intensities. Conclusions: RDD-HR can be reliably assessed using a simplified protocol based on a single seven-pulse train at two key frequencies. This standardized approach provides a methodological foundation for future clinical validation of RDD-HR as a biomarker of spinal inhibitory dysfunction. Full article

Facial asymmetry significantly affects aesthetic appearance, essential functions such as mastication and speech, and psychological well-being. While traditional surgical interventions effectively address significant facial asymmetry, they are often associated with considerable morbidity, prolonged recovery periods, and potential complications. Consequently, interest in minimally invasive, non-surgical techniques has substantially increased, driven by advantages including reduced downtime, rapid recovery, and immediate aesthetic results. This narrative review critically evaluates contemporary non-surgical techniques for correcting facial asymmetry, focusing specifically on dermal fillers, collagen stimulators (polydioxanone powder), polydioxanone thread lifting, energy-based non-invasive devices (radiofrequency, ultrasound, and laser therapies), and extracorporeal shockwave therapy. The review is based on a structured literature search of PubMed/MEDLINE, Embase, and Google Scholar up to October 2025, focusing on human clinical studies and review articles on non-surgical correction of facial asymmetry and related facial contouring. We provide a detailed analysis of each treatment modality’s underlying mechanisms, clinical efficacy, advantages, limitations, and safety profiles. Current evidence suggests that these non-surgical methods effectively enhance facial symmetry by offering immediate visible improvements and progressive enhancements through natural collagen regeneration, thereby significantly improving patient satisfaction and overall quality of life. Clinicians are encouraged to incorporate these versatile, minimally invasive interventions into clinical practice, carefully tailoring treatments according to individual patient characteristics and specific aesthetic goals. Further research should aim to refine existing treatment protocols, evaluate long-term efficacy and safety, and establish standardized guidelines to optimize outcomes in facial asymmetry correction. Full article

Background/Objectives: Anterior cruciate ligament (ACL) injuries frequently lead to long-term quadriceps impairments despite surgical repair. There is growing evidence that these deficits are caused in part by alterations in the central nervous system. Thus, transcranial neuromodulation (TNM) could be valuable in ACL rehabilitation. To systematically review randomized controlled trials (RCTs) assessing the effects of TNM on neurophysiological, functional, and safety outcomes in patients with ACL injury or reconstruction. Methods: We conducted searches on PubMed, Scopus, Web of Science, and Cochrane. We considered all original studies evaluating TNM, including transcranial current stimulation (tCS) and transcranial magnetic stimulation (TMS), in patients with ACL reconstruction or injury. Measures of corticospinal excitability, safety, balance, and muscle strength were assessed. We employed the Cochrane RoB 2 method to assess the risk of bias. Results: Seven studies comprising 129 participants (64 TNM, 65 controls) were included. Most studies applied transcranial direct current stimulation (tDCS) over the primary motor cortex contralateral to the ACL injury in conjunction with physical rehabilitation. Single-session protocols demonstrated minimal effects, whereas repeated sessions resulted in improvements in corticospinal excitability, quadriceps strength, and balance. No serious adverse events were reported; minor effects included transient headache or scalp tingling. The risk of bias was assessed as low to moderate across the studies. Conclusions: TNM appears to be safe and may enhance functional recovery in individuals with ACL injuries when administered in multiple sessions alongside standard rehabilitation. Further high-quality trials are necessary to determine optimal protocols and long-term outcomes. Full article

Background: Melasma is a chronic hyperpigmentation disorder, often therapy-resistant. Minimally invasive combinations of chemical stimulators and serums show promise. This study evaluated trichloroacetic acid stabilized with hydrogen peroxide and kojic acid, plus a serum with niacinamide, tranexamic acid, lactoferrin, ferulic acid, alpha-lipoic acid, and physic acid. Methods: Ten female volunteers with clinically diagnosed melasma underwent six treatment sessions. Each procedure involved application of the chemical stimulator followed by the serum, with strict photoprotection advised. Clinical improvement was assessed using the modified Melasma Area and Severity Index (mMASI) by three independent experts. Objective analysis of pigmentation and texture was performed with photographic documentation processed by the Grey Level Co-Occurrence Matrix (GLCM), measuring contrast and homogeneity in selected facial regions. Results: After six treatments, significant improvement was observed. Mean mMASI scores decreased by 62.3% after 2 weeks and 62.9% after 8 weeks. GLCM confirmed pigmentation reduction, showing decreased contrast and increased homogeneity across all regions, with the chin responding best. Correlation analysis indicated a positive trend between mMASI reduction and contrast changes. No serious adverse events or post-inflammatory hyperpigmentation were reported. Conclusions: The combined protocol significantly reduced melasma hyperpigmentation both clinically and objectively. GLCM analysis complements traditional scales and may provide a valuable quantitative tool for future research. Full article

Background/Objectives: Tinnitus lateralization, a perceptual characteristic often neglected in clinical assessment, may reflect underlying auditory plasticity. This study aimed to investigate whether changes in tinnitus lateralization following a multimodal neuromodulation protocol are associated with improved clinical outcomes, particularly regarding tinnitus severity and discomfort. Methods: A retrospective interventional study was conducted with 104 adults diagnosed with chronic tinnitus. All participants underwent a combined protocol involving transcutaneous auricular vagus nerve stimulation (taVNS), cervical transcutaneous electrical nerve stimulation (TENS), and photobiomodulation (PBM) targeting auditory pathways. Clinical assessments included the Tinnitus Handicap Inventory (THI), Visual Analog Scales (VAS) for loudness and discomfort, and lateralization reports before and after treatment. Lateralization patterns were categorized and compared using ANOVA and Kruskal–Wallis tests. Linear models explored demographic and clinical predictors of symptom change. Results: Substantial changes in lateralization were observed post-treatment. Participants who shifted from bilateral to unilateral tinnitus or from unilateral to non-perception showed the greatest symptom reductions (p < 0.001). The Bilateral → Unilateral group presented the most marked THI reduction (−20.82 ± 7.12), while minimal changes were observed in the Bilateral → Bilateral group. Loudness and discomfort improvements followed similar trends. No significant influence of age or sex on clinical response was identified, whereas longer tinnitus duration showed a modest positive association with symptom improvement. Conclusions: Perceptual reorganization of tinnitus lateralization may serve as a clinical marker of response to neuromodulation. Tracking lateralization could provide a simple, cost-effective adjunct to outcome monitoring in tinnitus management. Full article

Background. Orthodontic extrusion (OE), or forced eruption, is a conservative technique used to recover teeth affected by coronal fractures, traumatic intrusions, or severe caries. It involves applying light, continuous forces to induce vertical tooth movement, promoting tissue remodeling through periodontal ligament stimulation. Materials and Methods. This narrative review included studies investigating OE as a therapeutic approach for the management of deep or subgingival carious lesions, traumatic dental injuries (such as intrusion or fracture), or for alveolar ridge augmentation in implant site development. OE is typically performed using fixed appliances such as the straight-wire system or, in selected cases, clear aligners. Forces between 30 and 100 g per tooth are applied, depending on the clinical situation. In some protocols, OE is combined with fiberotomy to minimize gingival and bone migration. Results. Studies show that OE leads to significant vertical movement and increases in buccal bone height and interproximal septa. It enhances bone volume in targeted sites, making it valuable in implant site development. Compared to surgical crown lengthening, OE better preserves periodontal tissues and improves esthetics. Conclusions. In this narrative review is analized how OE is effective for managing traumatic intrusions and compromised periodontal sites, particularly when paired with early endodontic treatment. It reduces the risks of ankylosis and root resorption while avoiding invasive procedures like grafting. Although clear aligners may limit axial tooth movement, OE remains a minimally invasive, cost-effective alternative in both restorative and implant dentistry. Full article

Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article

Carboxytherapy is a non-invasive therapeutic method involving the transcutaneous or subcutaneous administration of carbon dioxide (CO₂), which stimulates microcirculation, neoangiogenesis, and collagen production. This narrative review summarizes the latest scientific findings (2020–2025) on the effectiveness of carboxytherapy in treating selected dermatological and aesthetic skin conditions, including periorbital dark circles, stretch marks, scars, and signs of skin aging. The article discusses both monotherapies and combination protocols, particularly with laser therapies and chemical peels. Numerous clinical studies confirm that carboxytherapy significantly improves skin elasticity, tone, hydration, and structure through mechanisms such as improved oxygenation, stimulation of fibroblasts, and controlled inflammation. Moreover, combination therapies frequently offer superior outcomes, especially in scar and stretch mark reduction. Carboxytherapy demonstrates high safety, minimal side effects, and broad applicability, making it a valuable tool in both medical and cosmetic dermatology. Full article