Search Results (2,211)

Photobiomodulation (PBM) has emerged as a noninvasive therapeutic tool with promising clinical applications in veterinary clinical surgery. Its mechanism of action is based on the stimulation of cellular processes through low-intensity light, promoting adenosine triphosphate production, inflammatory modulation, and tissue regeneration. This narrative review examines the current state of knowledge on the use of PBM in veterinary surgical contexts, with an emphasis on its clinical application in wound healing, postoperative pain control, and functional recovery. The physiological foundations of the technique, the main technical parameters that determine its effectiveness (wavelength, dose, frequency, and mode of application), and the available clinical evidence from different specialties such as soft tissue surgery, orthopedics, dentistry, and neurosurgery are analyzed. Current limitations, such as the lack of standardized protocols and their limited inclusion in clinical guidelines, are also addressed, as are future opportunities related to treatment personalization, the development of specific veterinary devices, and integration with emerging technologies. PBM represents a safe and effective adjuvant therapeutic strategy with the potential to become an integral part of veterinary postoperative management. Full article

Purpose: Breast cancer (BC) incidence has been increasing rapidly in North Africa, including Morocco, yet evidence regarding modifiable lifestyle factors remains limited. This study aimed to assess the associations between physical activity, sedentary behavior, daily work habits, and BC risk among Moroccan women, addressing an important gap in regional data. Methods: We conducted a case–control study between 2019 and 2023, including 1400 histologically confirmed incident BC cases and 1400 matched controls. Physical activity was assessed across the lifespan, considering type, intensity, and duration. Associations with BC risk were estimated using adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Moderate physical activity was inversely associated with BC risk, showing a clear dose–response relationship. Compared with the lowest physical activity level, the highest quartile showed significantly lower odds of BC (aOR = 0.37 (95% CI: 0.29–0.47). Vigorous physical activity during young adulthood and mid-adulthood was similarly linked to reduced risk. Active daily habits, such as walking and regular stair climbing, were associated with lower odds, whereas frequent occupational fatigue and sweating were linked to increased risk. Conclusions: Our findings highlight a significant inverse association between physical activity and BC risk among Moroccan women. Notably, moderate PA and active daily habits like brisk walking are linked to lower odds of the disease. While these findings support the role of physical activity as an important factor associated with breast cancer prevention, the retrospective design of the study limits causal inference. Full article

The blood–brain barrier (BBB) is a major obstacle to the development of brain-targeted drug delivery systems, restricting greater than 98% of small molecules (<500 Da) and virtually all large-molecule drugs from entering the brain tissues from the bloodstream, resulting in suboptimal drug doses and therapeutic failure in the treatment of Alzheimer’s disease (AD). However, the advent of nanotechnology has provided significant solutions to the BBB challenges, enabling particle size reduction, enhanced drug solubility, reduced premature drug degradation, extended and sustained drug release, enhanced drug transport across the BBB, increased drug target specificity and enhanced therapeutic efficacy. In corollary, a library of brain-targeted surface-functionalized nanotherapeutics has been widely reported in the current literature. These promising in vitro, in vivo and pre-clinical results from the existing literature provide quantitative evidence for the relative clinical utility of each of the techniques, indicating remarkable capacity for brain-targeted carrier systems; many of them are still being tested in human clinical trials. However, despite the recorded research successes in drug transport across the BBB, there are currently no clinically proven medications that can slow or reverse the progression of AD because most of the novel therapeutics have not been successful during the clinical trials. Therefore, the main option for the treatment of AD is symptomatic treatment using cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Although these therapies help to alleviate symptoms of AD and improve patients’ quality of life, they neither slow the progression of disease nor cure it. Thus, an effective disease-modifying therapy for the treatment of AD is an unmet clinical need. It is apparent that a deeper understanding of the structural complexity and controlling dynamic functions of the BBB in tandem with a comprehensive elucidation of AD pathogenesis are crucial to the development of novel nanocarriers for the effective treatment of AD. Therefore, this narrative review describes the contextual analysis of several promising strategies that enhance brain-targeted drug delivery across the BBB in AD treatment and recent research efforts on two major AD biomarkers that have revolutionized AD diagnosis, amyloid-beta plaques and phosphorylated tau protein tangle, as potential targets in AD drug development. This has led to the Food and Drug Administration (FDA)’s approval of two intravenous (IV) anti-amyloid monoclonal antibodies, Lecanemab (Leqembi^®) and Donanemab (Kisunla^®), which were developed based on the Aβ cascade hypothesis for the treatment of early AD. This review also discusses the recent shift in the Aβ cascade hypothesis to Aβ oligomer (conformer), a soluble intermediate of Aβ, which is the most toxic mediator of AD and could be the most potent drug target in the future for a more accurate and effective drug development model for the treatment of AD. Furthermore, various promising nanoparticle-based drug carriers (therapeutic nanoparticles) that were developed from intensive research are discussed, including their clinical utility, challenges and prospects in the treatment of AD. Overall, it suffices to state that the advent of nanotechnology provided several innovative techniques for overcoming the BBB and improving drug delivery to the brain; however, their long-term biosafety is a relevant concern. Full article

Sliding mode control (SMC) is a robust nonlinear control framework that enforces system trajectories onto predefined manifolds, providing strong robustness guarantees against uncertainties. However, SMC inherently introduces unwanted transients or chattering in system state trajectories, which may cause issues especially for sensitive applications such as regulation of drug administration. This paper proposes a multi-input smooth sliding mode control (MISSMC) strategy that combines radiotherapy and chemotherapy for a nonlinear tumor–immune dynamical system described by ordinary differential equations. The closed-loop system is first analyzed to establish key qualitative properties: all state variables remain positive and bounded, the sliding surfaces exhibit asymptotic convergence, and explicit analytical upper bounds on the cumulative therapy doses are derived under clinically motivated constraints. On this basis, a smooth hyperbolic-tangent sliding manifold and associated control law are designed to regulate the radiation and drug infusion rates. While the use of a hyperbolic-tangent smoothing function effectively suppresses chattering, it introduces a small steady-state error due to the presence of a boundary layer. To address this limitation, integral action is incorporated into the sliding surfaces, ensuring asymptotic convergence of tumor state and reducing residual steady-state error, while enhancing robustness against model uncertainties and parameter variations. Numerical simulations, based on a brain-tumor case study, show that the proposed smooth SMC markedly suppresses transient overshoots in both states and control inputs, while preserving effective tumor reduction. Compared with a conventional (non-smooth) SMC scheme, the MISSMC controller reduces baseline radiation and chemotherapy intensities on average by roughly 70%. Similarly, MISSMC lowers the overall cumulative doses on average by about 40%, without degrading the therapeutic outcome. The resulting integral smooth SMC framework therefore offers a rigorous nonlinear-systems approach to designing combined radio-chemotherapy protocols with guaranteed positivity, boundedness, and asymptotic stabilization of the closed-loop system, together with explicit bounds on the control inputs. Full article

Background/Objectives: Septic shock involves severe circulatory and microcirculatory dysfunction and often requires vasopressors to maintain adequate mean arterial pressure (MAP). Conventional monitoring mainly reflects macrocirculation and may not capture changes in vascular tone or microcirculation. Remote photoplethysmography (rPPG) is a contactless optical method that analyzes peripheral pulse waveforms and may offer additional physiological insight during vasopressor therapy. The aim of this study was to assess the feasibility of rPPG for detecting pulse waveform changes associated with norepinephrine administration in septic shock. Methods: Prospective case series included three adult patients (n = 3) with septic shock admitted to the intensive care unit at Pauls Stradins Clinical University Hospital, Riga, Latvia. All patients received standard sepsis treatment, including fluid resuscitation and titrated norepinephrine to maintain MAP ≥ 65 mmHg. Continuous invasive arterial pressure monitoring was performed alongside rPPG signal acquisition from the palmar skin surface under controlled lighting. From averaged rPPG waveforms, perfusion index (PI), dicrotic notch amplitude (c-wave), and diastolic wave amplitude (d-wave) were extracted. Correlations between norepinephrine dose, MAP, and rPPG parameters were explored. Results: Increasing norepinephrine doses were associated with higher MAP and PI in all patients. Dicrotic notch and diastolic wave amplitude decreased consistently. These changes occurred alongside macrocirculatory stabilization and are consistent with increased vascular tone and altered arterial compliance. Conclusions: rPPG demonstrated feasibility for detecting pulse waveform changes during norepinephrine therapy in septic shock; however, larger controlled studies are required for validation. Full article

Neuroblastoma is the most common extracranial solid tumor of childhood and remains a leading cause of cancer-related mortality in pediatric patients. Characterized by marked clinical and biological heterogeneity, the disease ranges from spontaneously regressing tumors in infants to highly aggressive, treatment-resistant malignancies in older children. Advances in molecular biology and genomics have significantly improved understanding of neuroblastoma pathogenesis, revealing the critical role of genetic and epigenetic alterations—such as MYCN amplification, ALK mutations, and chromosomal aberrations—in disease behavior and prognosis. Contemporary risk stratification systems now integrate clinical, biological, and molecular features to guide therapy more precisely. Management strategies have evolved toward risk-adapted, multimodal approaches. Low- and intermediate-risk patients often achieve excellent outcomes with surgery alone or limited chemotherapy, whereas high-risk neuroblastoma requires intensive multimodal treatment including induction chemotherapy, surgical resection, high-dose chemotherapy with autologous stem cell rescue, radiotherapy, and maintenance therapy. The incorporation of immunotherapeutic approaches, particularly anti-GD2 monoclonal antibodies, has significantly improved survival in high-risk disease. Emerging therapies such as targeted agents, radiopharmaceuticals, and cellular immunotherapies are further expanding the therapeutic landscape. Despite these advances, high-risk and relapsed neuroblastoma remain associated with substantial morbidity and mortality. Ongoing challenges include treatment resistance, long-term toxicity, and disparities in access to advanced therapies. Continued progress will depend on integrating molecular profiling into clinical decision-making, refining risk-adapted treatment strategies, and expanding international collaborative research efforts. This narrative review summarizes current knowledge on neuroblastoma epidemiology, biology, staging, and treatment, highlighting recent advances and future directions aimed at improving outcomes for affected children. Full article

Physicians performing cardiac angiography are exposed to scattered radiation originating from the patient, and visualizing scattered radiation sources could help optimize radiation protection strategies. In this study, an existing scattered radiation source visualization system comprising a high-sensitivity CMOS camera, thallium-activated cesium iodide scintillator, and pinhole collimator was extended to incorporate a depth camera and employed to visualize scattered radiation sources in three dimensions under conditions simulating clinical cardiac angiography. Scattered radiation source images were captured using a patient phantom under multiple irradiation directions of a biplane angiography system, and changes in the images and dose rate reaching the system were evaluated with and without radiation protection equipment and for various ceiling-mounted radiation shielding positions. The scattered radiation source was visualized on the patient phantom surface for a 5-s exposure in three-dimensional images and was observed around the X-ray tube in one direction. Radiation protection equipment reduced both the scattered radiation source intensity and dose rate. The greatest reduction occurred when the ceiling-mounted radiation shielding was positioned near the physician. Irradiation at caudal angles caused the highest increase in scattered radiation source intensity and dose rate. These findings suggest that this system can support the optimization of radiation protection practices and education. Full article

Objectives: To synthesize current evidence and emerging data on systemic treatment strategies for early-stage and locally advanced human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), with emphasis on treatment de-escalation and the integration of immunotherapy. Data Sources: We searched PubMed/MEDLINE, Scopus, and EMBASE for English-language studies published from 2010 to 2025 using terms related to HPV-positive disease, oropharyngeal carcinoma, de-escalation, chemoradiation, and immunotherapy. Review Methods: Peer-reviewed clinical trials, meta-analyses, and key translational studies addressing systemic therapy, biomarkers, and immunotherapeutic strategies in HPV-positive OPSCC were included. Emphasis was placed on phase II–III trials evaluating cisplatin-sparing regimens, cetuximab substitution, radiation dose reduction, and early-phase immunotherapy combinations. Evidence was synthesized qualitatively. Results: Cisplatin-based concurrent chemoradiation remains the standard of care for locally advanced HPV-positive OPSCC. De-intensification trials suggest that reduced-intensity regimens may be feasible in carefully selected low-risk patients; however, replacing cisplatin with cetuximab results in inferior survival. PD-1 inhibitors (e.g., pembrolizumab, nivolumab) provide durable responses in recurrent/metastatic disease and are under active evaluation in earlier stages and in combination with therapeutic vaccines, bispecific antibodies, and viral-vector platforms. Conclusions: Systemic therapy for HPV-positive OPSCC is moving toward biomarker-informed personalization. Cisplatin-based chemoradiation remains the curative backbone, while rational de-escalation and immunotherapy integration may preserve high cure rates while reducing long-term toxicity. Ongoing phase III trials will clarify which patient subsets are most suitable for de-intensified or immunotherapeutic approaches, guiding future standards of care. Full article

This study evaluated the effectiveness and safety of mechanical debridement (MD) in treating experimental peri-implantitis (EPI) in rats with osseointegrated implants, specifically those treated with high-dose zoledronate. Senescent Wistar rats underwent the extraction of their upper incisor, followed by immediate implant placement. After 8 weeks, the implants were exposed, and a transmucosal component was placed. The animals were divided into four groups: Control (C), ZOL, ZOL-EPI, and ZOL-EPI-MD. In the 9th week, drug treatment commenced, consisting of the administration of 0.45 mL of a vehicle (for group C) or zoledronate (for groups ZOL, ZOL-EPI, and ZOL-EPI-MD) every 4 days over 10 weeks. After 5 weeks of drug treatment, a cotton bandage was placed around the implants to induce EPI in the ZOL-EPI and ZOL-EPI-MD groups. In the ZOL-EPI-MD group, the ligature was removed at week 16, and local treatment was performed using MD. Euthanasia was conducted at week 19. Histological sections were obtained and stained with hematoxylin–eosin for histopathological and histometric analyses, such as the percentage of total bone tissue (B.Ar/T.Ar) and the percentage of non-vital bone tissue (NVB.Ar/B.Ar). Immunohistochemical reactions were performed to detect TNFα, IL-1β, VEGF, OCN, and TRAP. In the peri-implant connective tissue, mild, intense, and moderate inflammatory infiltrates were observed in the ZOL, ZOL-EPI, and ZOL-EPI-MD groups, respectively. Immunolabeling for TNFα and IL-1β correlated with these histopathological findings. The ZOL and ZOL-EPI-MD groups showed lower immunolabeling for VEGF compared to the control group. There was a reduction in TRAP-positive cells and lower immunolabeling for OCN in the groups treated with zoledronate, with the ZOL-EPI-MD group displaying even lower levels of OCN compared to the ZOL group. While there was no significant difference in B.Ar/T.Ar across the groups, both the ZOL, ZOL-EPI, and ZOL-EPI-MD groups exhibited higher levels of NVB.Ar/B.Ar, with the ZOL-EPI-MD group showing the highest NVB.Ar/B.Ar compared to ZOL and the other groups. In conclusion, MD, as a standalone treatment, showed neither effectiveness nor safety in the management of EPI in rats that received high doses of zoledronate. Full article

Background/Objectives: Head and neck paragangliomas (HNPGs) are rare, typically benign, hypervascular tumors arising from neural crest cells. Although surgery is known as the primary treatment, radiotherapy (RT) is preferred for large and inoperable tumors. This study evaluated the results and safety of RT. Methods: Fifteen patients with radiologically or histologically confirmed HNPG treated with RT between 2001 and 2024 were retrospectively analyzed. Most patients received intensity-modulated radiotherapy (IMRT) with a median dose of 45 Gy. Treatment-related toxicities were graded according to CTCAE criteria. Local control (LC) was estimated with using Wilson score method. Results: With a median follow-up of 96 months, all patients achieved stable or improved symptomes, without local recurrence, resulting in a 100% LC rate. RT was well tolerated, with no acute or late toxicities ≥ grade 2. Conclusions: RT, particularly IMRT, provides excellent long-term LC with minimal toxicity in patients with HNPG. RT represents an effective and well-tolerated treatment option, especially for patients with unresectable disease or high surgical risk. Full article

Background: Pain management in patients with severe burns remains one of the most complex challenges in perioperative care. Burn-related pain is multifactorial, resulting from tissue destruction, intense inflammation, surgical procedures, and repeated dressing changes. Opioids remain the cornerstone of analgesia; however, prolonged use is associated with tolerance, dependence, adverse effects, and prolonged hospitalization. Multimodal and opioid-sparing strategies, including regional anesthesia, may improve postoperative outcomes by enhancing analgesia while reducing systemic drug exposure. This study aimed to evaluate the effectiveness of a standardized regional anesthesia protocol in reducing postoperative pain and opioid requirements in burn patients undergoing lower-limb escharectomy and autologous skin grafting. Methods: We conducted a retrospective, single-center analysis of 25 adult patients with deep thermal burns of the lower limbs who underwent escharectomy and split-thickness skin grafting. All patients received a combined ultrasound-guided sciatic popliteal block and adductor canal block on both the burned limb and the donor site. Ropivacaine 0.375% with clonidine was administered without exceeding a total dose of 3.0 mg/kg. Postoperative pain was assessed using the Numerical Rating Scale (NRS), and opioid consumption was recorded as rescue doses in intravenous morphine equivalents. Secondary outcomes included perioperative complications and 30-day hospital readmission. Results: Regional anesthesia provided effective postoperative pain control. Thirty-two percent of patients reported no pain (NRS 0), 52% reported mild pain (NRS 1–3), and 16% reported moderate pain (NRS 4–6). No patient reported severe pain (NRS 7–10). Only four patients (16%) required rescue opioids. No perioperative complications or block-related adverse events occurred, and no patient required hospital readmission within 30 days. Conclusions: In this cohort, regional anesthesia was associated with satisfactory postoperative analgesia and minimal opioid requirements. By reducing opioid exposure, this approach may help improve patient comfort and potentially limit opioid-related adverse effects. Larger prospective studies are needed to confirm these findings and to assess long-term outcomes. Full article

Background/Objectives: Infection prevention and control (IPC) programs combine pathogen-targeted measures (e.g., admission screening) with hospital-wide standard precautions (e.g., hand hygiene, HH). We assessed temporal associations between screening, HH, antimicrobial stewardship (AMS), and hospital-level outcomes in a tertiary paediatric hospital. Methods: This study was a retrospective hospital-wide ecological time-series at the Children’s Memorial Health Institute. Annual aggregate data: 2011–2024 for screening, colonisation, and healthcare-associated infections (HAIs) with alert pathogens; 2016–2024 for antibiotic consumption (ATC J01, systemic antibacterials). Process indicators: number of screening tests and alcohol-based hand rub (ABHR) consumption per 1000 patient-days (PD). Outcomes: colonisations/HAIs per 1000 PD and defined daily doses (DDD) per 1000 PD overall and by class. Trends used linear regression and Spearman’s rank correlation. Results: Screening intensity increased from 39 to 150/1000 PD (slope +8.3/year; R² = 0.90; p < 0.001). Detected colonisation rose (2.5 → peak 8.05/1000 PD in 2023; slope +0.39; R² = 0.81; p < 0.001), while multidrug-resistant-organism (MDRO)-attributable HAIs remained low/stable (0.27–0.62/1000 PD; slope −0.014; p = 0.023). ABHR consumption increased from 26.1 to 78.0 L/1000 PD in 2020 (p < 0.001) and partially normalised to 60.0 in 2024 (>2 × baseline). Overall ATC J01 showed no long-term linear trend (~278–356 DDD/1000 PD; +2.57/year; p = 0.46), but class mix shifted: carbapenems, fluoroquinolones, and amoxicillin–clavulanate decreased; third/fourth-generation cephalosporins, piperacillin/tazobactam, and glycopeptides increased. Conclusions: In this tertiary paediatric setting, expansion of risk-based admission screening and sustained implementation of horizontal IPC measures were accompanied by increased detection of colonisation with alert pathogens, while MDRO-attributable HAIs remained low and stable at the hospital level. Over the same period, AMS activity coincided with a redistribution in antibiotic class use without a clear long-term reduction in total antibiotic consumption. These hospital-level findings are descriptive and hypothesis-generating; causal inference is limited by the ecological study design, and the heterogeneous, multispecialty structure of a tertiary paediatric centre. Full article

Acute respiratory distress syndrome (ARDS) is a common condition among intensive care unit patients and is associated with high mortality. Currently, there are no unified therapeutic strategies, including for the use of systemic glucocorticosteroid (GCS) therapy, in the management of ARDS of various etiologies. Using our previously developed non-surgical and reproducible model of unilateral total diffuse alveolar damage (ARDS/DAD) in the left lung of ICR mice, we investigated the effects of GCS with different durations of action and administration regimens on lung function recovery. Our data show that repeated-course administration of dexamethasone promoted complete normalization of respiratory function, as well as restoration of aeration and perfusion of the left lung in mice following ARDS/DAD induction. In contrast, a single administration of the same drug or the use of a prolonged-release formulation, despite exhibiting anti-inflammatory effects, did not provide adequate lung tissue recovery and, in some cases, even exacerbated injury. These results underscore that in ARDS therapy, not just the use but the specific dosing regimen of glucocorticoids is critically important for driving complete functional and structural lung repair. Full article

Background: Plants represent an important source of photoprotective compounds that are capable of protecting human skin from solar-induced damage. In this study we investigated the suitability of a murine model for estimating the Erythema Protection Efficacy (EPE) of natural compound. Methods: UVB-induced skin erythema in albino BALB/c mice was quantified using a Mexameter MX18 MDD colorimeter. The ARRIVE principle was followed. The Minimum Erythema Dose (MED) was determined based on Log₁₀ dose–erythema response curves. EPE values for UV filters (e.g., titanium dioxide or zinc oxide) and selected plant-derived compounds (apigenin, caffeic acid, epigallocatechin gallate, kaempferol, and pinocembrin) were calculated as the ratio between the MED of protected skin and that of unprotected skin. Results: The UVB-induced erythema in both female and male mouse skin followed a linear response. Erythema intensity varied by sex and by the dorsal skin area examined. MED values ranged from 39 to 57 mJ/cm² in female mice and from 71 to 80 mJ/cm² in male mice. In both sexes, MED increased linearly with the logarithm of the radiation dose. All tested compounds (apigenin, caffeic acid, epigallocatechin gallate, kaempferol, and pinocembrin) provided protection against UV-radiation-induced erythema in mouse skin. Among them, apigenin, caffeic acid, and kaempferol exhibited the highest EPE values, indicating strong potential for incorporation into sunscreen formulations. Conclusions: The murine EPE metric proved to be a useful tool for identifying plant-derived compounds with potential relevance for the photoprotection of human skin. Full article

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that relies on the activation of photosensitizers (PS) by specific wavelengths of light to generate reactive oxygen species (ROS), resulting in localized cytotoxicity with relative sparing of healthy tissues. Depending on the PS properties, light dose, and intrinsic cellular features, PDT can elicit multiple cell death pathways, including apoptosis, necrosis, and autophagy. Increasing evidence indicates that PDT is also a potent inducer of ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation (LPO), glutathione (GSH) depletion, and inactivation of glutathione peroxidase 4 (GPX4). PDT-derived ROS promote ferroptosis both indirectly by exhausting antioxidant defenses and directly by peroxidizing PUFAs within membrane phospholipids. At the same time, intense oxidative stress generated by PDT can activate adaptive responses such as mitophagy, a selective autophagic process that removes damaged mitochondria to limit ROS production and preserve redox homeostasis. Ferroptosis and mitophagy are therefore tightly interconnected, functioning as opposing yet complementary regulators of cell fate. PDT emerges as a key upstream modulator of the ferroptosis–mitophagy balance, as spatially and temporally confined oxidative stress can shift cellular responses from adaptive mitochondrial quality control to irreversible ferroptotic injury. Despite growing interest in both PDT and ferroptosis, their mechanistic interplay, particularly in relation to mitophagy, remains underexplored. This narrative review provides an integrated overview of current knowledge on how PDT influences ferroptosis and mitophagy, highlighting the molecular mechanisms that connect these pathways and discussing their implications for improving therapeutic efficacy and overcoming resistance. Full article