Search Results (2,288)

This study aimed to evaluate the accuracy of the accelerometer-equipped collar RUMI to detect estrus in dairy cows, establish a recommendation for the optimal timing for artificial insemination (AI) when using this device, and characterize the blood flow of the dominant follicle (F) and the corpus luteum (CL) as ovulation approaches. Forty-seven cycling cows were monitored following synchronization with a modified G6G protocol, allowing for spontaneous ovulation. Ultrasound examinations were conducted every 12 h, starting 48 h after the second PGF2α dose, to monitor uterine and ovarian changes. Blood samples were also collected to determine serum progesterone (P4) levels. Each cow was fitted with a RUMI collar, which continuously monitored behavioral changes to identify the onset, offset, and peak of activity of estrus. One-way ANOVA assessed the relationship between physiological parameters and time before ovulation. Results showed that the RUMI collar demonstrated high specificity (100%), sensitivity (90.90%), and accuracy (93.62%) for estrus detection. The optimal AI window was identified as between 11.4 and 15.5 h after heat onset. Increased blood flow to the F and reduced luteal activity were observed in the 48 h prior to ovulation. Further research is needed to assess the influence of this AI window on conception rates, and if it should be modified considering external factors. Full article

The aim of this study was to refine the lipopolysaccharide (LPS)-induced synovitis model in normal carpal joints of Thoroughbred horses by comparing two low LPS doses. A further aim was to investigate the relationship between the induced synovitis and lameness. The study design consisted of two phases using nine horses with a unilateral crossover design and a within-animal saline control. Synoviocentesis was performed at post-injection hour (PIH) 0, 8, 24, 72 and 168, allowing for synovial fluid cytology and biomarker analysis. Objective gait and thermographic analysis were used to objectively measure clinical effects. The results demonstrate that injection of either a 0.125 ng or 0.25 ng dose of LPS induces a comparable degree of synovitis in terms of TP, WBC, PGE₂ and MMP activity at peak values. Statistically significant changes in baseline lameness values were not detected with the 0.125 ng dose, a novel and valuable finding suggesting a comparable degree of synovitis is achieved without significant lameness. All measured parameters had returned to baseline by PIH 168. In conclusion, the findings of this study confirm that this LPS model produces a consistent and reliable synovitis at 0.25 ng and 0.125 ng doses. The reduction in lameness evident at the 0.125 ng dose offers enhanced animal welfare while delivering measurable synovitis. The authors believe that a further reduction in the LPS dose is possible with continued development of a repeated low-dose/slow-release model to better mimic clinical disease. Full article

Ionizing radiation is a well-known environmental stressor capable of generating excessive reactive oxygen species (ROS), leading to oxidative damage in sensitive tissues, including the reproductive system. While oxidative stress is increasingly implicated in male reproductive dysfunction, the long-term effects of low-dose-rate (LDR) radiation on testicular structure and oxidative status remain underexplored. In this study, mice were exposed to continuous LDR radiation (0.39, 1.29, and 3.46 mGy/h) for 21 days to assess testicular histopathology and oxidative status. Although testis weight did not significantly differ among groups, histological analysis revealed basal membrane disruption and reduced spermatogenic cell populations in irradiated groups. Masson’s Trichrome and Sirius Red staining demonstrated dose-dependent collagen deposition, indicating progressive testicular fibrosis. TUNEL assays confirmed increased germ cell apoptosis in the mid- and high-dose-rate groups. ROS levels were significantly elevated only in the highest-dose group, suggesting a threshold-dependent oxidative stress response. These findings indicate that chronic LDR radiation induces testicular damage primarily through apoptosis and fibrosis, with oxidative stress potentially contributing at higher exposure levels. Full article

The time spent indoors under artificial (electric) lighting has continued to increase and currently amounts to up to 90% of the day. Light is the most important stimulus for the circadian rhythm and has, besides long-term effects, also a direct impact on emotional and physiological aspects such as sleepiness, alertness, or performance. This article presents the results of two studies investigating the acute effects of light during morning and early afternoon on people in a controlled office environment. Melanopically optimized lighting conditions, and a dose–response dependency are investigated, measuring cognitive performance, subjective sleepiness, and user preferences of the lighting scenarios as well as cardiac effort. The results show a dependency in subjective sleepiness ratings depending on light conditions and time of day. Further parameters did not show any statistical differences. The presented studies extend the findings of acute light effects during the day but are limited due to relatively small sample sizes. Full article

Background/Objectives: DTP3 (diphtheria–tetanus–pertussis vaccine, third dose) coverage is a key indicator of the strength and continuity of routine immunization programs, which demonstrably reduces the burden of infectious diseases globally. This study aims to assess trends in DTP3 vaccination coverage across Asian regions and countries from 2012 to 2023, focusing on changes associated with the COVID-19 pandemic. Methods: DTP3 vaccination data were obtained from official WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) and analyzed using Joinpoint regression to detect statistically significant changes in vaccination trends. Data were grouped by five Asian subregions based on the UN geoscheme (Central, Eastern, Southeastern, Southern, and Western Asia), and trends were weighted using birth cohort sizes. The presence of joinpoints and annual percentage changes (APCs) was calculated, and potential pandemic-related disruptions were contextualized. Results: At the continental level, Asia experienced a modest 0.4% annual increase in DTP3 coverage between 2012 and 2023, with a significant joinpoint detected in 2018. Following this, Southeast Asia’s coverage declined at an annual rate of −4.32% before beginning to recover in 2021, while South Asia showed a similar pattern. Country-level analysis revealed significant heterogeneity, with a comparison between 2019 and 2023 showing profound post-pandemic declines in some nations, such as Lebanon (–21%) and Myanmar (–9.4%), while others, like Iraq and the Philippines, achieved substantial recoveries with coverage increasing by over 6 percentage points. These trends contrasted with persistent declines in fragile states (e.g., Afghanistan, Yemen) and sustained high coverage in others (e.g., Bangladesh, Israel). The pandemic, systemic weaknesses, emerging vaccine hesitancy, and misinformation were identified as key influences. Conclusions: There is progress in DTP3 coverage across Asia. There were pandemic-related disruptions, particularly in regions with fragile health systems. Strategies to address zero-dose and dropout children, improve service continuity, and counter misinformation are essential to meet immunization targets under the Immunization Agenda 2030. Full article

This study aimed to develop and characterise novel hydrogels based on natural bioactive compounds for topical antimicrobial applications. Four gel systems were formulated using different polymers, namely polyacrylic acid (Carbopol 940, CBP-G), chitosan with high and medium molecular weights (CTH-G and CTM-G), and sodium alginate (ALG-G), incorporating tinctures of Verbena officinalis and Aloysia triphylla, Laurus nobilis essential oil, and a β-cyclodextrin–clove essential oil complex. All gels displayed a homogeneous macroscopic appearance and maintained stability for over 90 days. Rheological studies demonstrated gel-like behaviour for CBP-G and ALG-G, with well-defined linear viscoelastic regions and distinct yield points, while CTM-G exhibited viscoelastic liquid-like properties. SEM imaging confirmed uniform and continuous matrices, supporting controlled active compound distribution. Thermogravimetric analysis (TG-DTA) revealed a two-step degradation profile for all gels, characterised by high thermal stability up to 230 °C and near-total decomposition by 500 °C. FTIR spectra confirmed the incorporation of bioactive compounds and products and highlighted varying interaction strengths with polymer matrices, which were stronger in CBP-G and CTH-G. Antimicrobial evaluation demonstrated that chitosan-based gels exhibited the most potent inhibitory and antibiofilm effects (MIC = 2.34 mg/mL) and a cytocompatibility assessment on HaCaT keratinocytes showed enhanced cell viability for chitosan gels and dose-dependent cytotoxicity for alginate formulations at high concentrations. Overall, chitosan-based gels displayed the most favourable combination of stability, antimicrobial activity, and biocompatibility, suggesting their potential for topical pharmaceutical use. Full article

Background/Objectives: Systemic arterial hypertension is a prevalent condition associated with adverse cardiac remodeling. Echocardiography plays a crucial role in assessing cardiac structure and function in hypertensive patients. This study aimed to evaluate the changes in echocardiographic parameters in hypertensive patients over a 3-year follow-up period and assess the impact of blood pressure control and antihypertensive medication use on these changes. Methods: This observational cohort study included 131 adult patients with systemic arterial hypertension who underwent annual echocardiographic assessments. Statistical analyses included paired and unpaired comparisons, regression modeling, and subgroup analyses by BP control and lifestyle behavior. Results: Over the 3-year follow-up, mean left ventricular mass (LVM) increased significantly from 173.99 ± 59.33 g to 183.26 ± 64.19 g (p = 0.018), and the prevalence of LV hypertrophy rose from 29.0% to 40.5% (p = 0.021). Patients with uncontrolled blood pressure at the final visit had significantly greater interventricular septum and posterior wall thicknesses (p = 0.009 and p = 0.012, respectively), but no statistically significant difference in ΔLVM. Those who adopted more healthy lifestyle behaviors showed a dose-dependent reduction in LVM progression, with each additional lifestyle improvement associated with a −3.25 g change in ΔLVM (p = 0.01). Multivariable linear regression identified baseline LVM, sex, and lifestyle score as independent predictors of 3-year LVM change (model R² = 0.318). Conclusions: Our findings indicate that long-term cardiac remodeling may continue in hypertensive patients despite treatment, particularly in the presence of suboptimal BP control. Sustained lifestyle improvements were independently associated with attenuation of LVM progression. These results underscore the importance of integrating behavioral interventions alongside pharmacologic therapy in routine hypertension management. Full article

Background/Objectives: Intravenous patient-controlled analgesia (IV-PCA) is commonly used for pain control following arthroscopic rotator cuff repair (ARCR), but its use is limited by adverse effects such as nausea and vomiting. The suprascapular nerve block (SSNB) has emerged as an effective regional analgesic alternative. This retrospective cohort study aimed to compare the analgesic efficacy and safety of continuous intra-operative suprascapular nerve block (CI-SSNB) alone versus CI-SSNB combined with fentanyl-based IV-PCA (CI-SSNB + IV-PCA). Methods: A total of 40 patients undergoing ARCR under general anesthesia with a single-shot interscalene block (ISB) were allocated to either CI-SSNB alone (n = 20) or CI-SSNB + IV-PCA (n = 20). Pain scores were assessed using a 0–10 visual analog scale from 0 to 72 h postoperatively at predetermined intervals, along with opioid consumption and adverse events. Results: At post-operative day 0 (POD 0, 10 p.m.), mean pain scores were 5.75 ± 2.59 in the CI-SSNB + IV-PCA group vs. 3.95 ± 3.00 in the CI-SSNB group (p = 0.050). The total number of rescue pethidine doses up to post-operative day 3 was 1.80 ± 2.02 vs. 0.95 ± 1.10, respectively (p = 0.108). However, adverse effects such as nausea and vomiting occurred only in the CI-SSNB + IV-PCA group. Conclusions: CI-SSNB provides comparable analgesia to CI-SSNB + IV-PCA, while avoiding IV-PCA-related side effects, suggesting that IV-PCA may not be necessary when CI-SSNB is employed for post-operative analgesia following ARCR. Full article

Background/Objectives: Chemotherapy is an aggressive form of oncological treatment often accompanied by numerous adverse effects. A patient’s baseline status significantly influences the course of therapy, its efficacy, quality of life, and overall survival. This review aims to analyze the published peer-reviewed studies in this area and to assess whether they permit the formulation of preliminary recommendations for future prehabilitation protocols. Methods: An integrative review was conducted due to the limited number of relevant studies. Four databases—MEDLINE/PubMed (Medical Literature Analysis and Retrieval System Online/National Library of Medicine), Scopus, Cochrane, and Web of Science—were systematically searched for English-language articles published between 2010 and 13 January 2025, using the terms “prehabilitation,” “chemotherapy,” “drug therapy,” and “neoadjuvant.” A total of 162 records were retrieved. After duplicate removal, titles and abstracts were screened. The remaining papers were subjected to detailed analysis, resulting in ten studies with diverse methodologies being included. Results: We reviewed ten (n = 10) studies, most of which were reviews focused on breast cancer, indicating variation in the state of knowledge across different cancer types. A protein intake of 1.4 g/kg body mass helps preserve fat-free mass, with whey being more effective than casein. Omega-3 fatty acid supplementation at a dose of 2.2 g/kg may prevent chemotherapy-related neurotoxicity and support appetite and weight maintenance. Physical activity, especially when it includes strength training, improves VO₂max, preserves fat-free mass, and may reduce stress and anxiety. We identified one randomized controlled trial in which a single exercise session before the first dose of doxorubicin resulted in a smaller reduction in cardiac function. Continuous psychological support should be available. A combined behavioural and pharmacological approach appears to be the most effective strategy for smoking cessation. Conclusions: No official guidelines exist for prehabilitation before chemotherapy, and the availability of studies on this topic is very limited. The pre-treatment period represents a critical window for interventions. Further research is needed to evaluate the effectiveness and applicability of particularly single-component interventions. Full article

Chordomas are primary tumors of the skull base and vertebral column typically derived from the notochord. Treatment options consist of surgical resection, radiotherapy, and chemotherapy. This study reviews clinical trials focused on radiotherapy techniques, such as photon therapy and carbon ion radiotherapy, as well as the concomitant use of radia-tion sensitizers. We completed a literature review on all published clinical trials on the usage of photon, proton, and carbon ion radiotherapy (CIRT) for chordoma in adults and all published literature on radiation sensitizers used for treatment in chordoma from 2000 to 2025. We reviewed all nine current clinical trials on radiotherapy for chordoma in adults. All clinical trials were able to achieve an overall survival rate above 50% at 3-year follow-up. Seven publications were found on the use of radiation sensitizers for chordomas, both in vitro and in vivo. The completed clinical trials evaluate the effectiveness of proton, photon, and CIRT for treatment of the skull base, spine, and sacral chordoma. Current trials continue these efforts and compare the different radiotherapies and determine appropriate doses. Research on radiation sensitizers for chordomas shows various therapies, ranging from hyperthermia to pharmaceutical options, that require further study. Full article

We describe the first use of phage therapy in Canada for the treatment of a life-threatening periprosthetic joint infection (PJI), with successful outcome. PJI is a devastating complication of joint replacement surgery, with high morbidity and mortality. Our patient presented with early sepsis from a chronic recalcitrant multidrug-resistant (MDR) Staphylococcus epidermidis hip PJI which had repeatedly failed standard therapy. She had previously undergone 10 operations of the right hip, and only three weeks after completing a prolonged course of daptomycin following her most recent hip revision, she developed a draining sinus tract. Given the high burden of disease, inability to achieve surgical source control, and lack of antibiotic treatment options for long-term suppressive therapy, bacteriophage (phage) therapy was pursued. The patient underwent irrigation and debridement with complex flap reconstruction: intraoperative tissue cultures again yielded MDR S. epidermidis. We developed a novel phage therapy protocol for this patient, with twice daily, intra-articular and intravenous (7 × 10⁹ PFU/dose) phage delivery over a planned 14-day course. Complete healing of the wound with cessation of drainage occurred within one month after treatment. A marked improvement in right hip pain and mobility occurred within three months after treatment. Twelve months following phage treatment, there is normalization of serum inflammatory markers with diminished pain, increased mobility, and no recurrent surgery. Our patient continues to improve and is currently living independently at home, with sustained clinical control of infection. Full article

Background/Objectives: Controlled release systems, such as polymeric microparticles (MPs), have emerged as a promising solution to extend the bioavailability and reduce dosing frequency for biologic drugs; however, the formulation of these systems to encapsulate highly sensitive, hydrophilic biologic drugs within hydrophobic polymers remains a nontrivial task. Although scalable manufacturing and FDA approval of single emulsion processes encapsulating small molecules has been achieved, scaling more complex double emulsion processes to encapsulate hydrophilic biologics remains more challenging. Methods: Here, we demonstrate that two hydrophilic, low-molecular-weight, recombinant chemokines, CCL22 and CCL2, can be encapsulated in poly(lactic-co-glycolic acid) (PLGA) MPs using a single emulsion method where the proteins are dissolved in an organic solvent during formulation. Results: As expected, we observed some differences in release kinetics from single emulsion MPs compared to double emulsion MPs, which traditionally have been used to encapsulate proteins. Single emulsion MPs exhibited a substantially reduced initial burst. Importantly, protein released from single emulsion CCL22-MPs also retained biological activity, as determined by a cell-based functional assay. Decreasing particle size or changing the polymer end group from PLGA-COOH to PLGA-OH increased the initial burst from single emulsion MPs, demonstrating tunability of release kinetics for protein-loaded, single emulsion MPs. Finally, to improve scalability and enable more precise control over MP formulations, the single emulsion process was adapted to a microfluidic, continuous manufacturing system, and the resulting MPs were evaluated similarly. Conclusions: Altogether, this study demonstrates the feasibility of using a single emulsion encapsulation method for at least some protein biologics. Full article

Background: Adherence to current clinical guidelines is crucial for ensuring optimal therapy in patients with heart failure (HF). This study aims to explore how cardiologists, as specialists in heart failure, approach the clinical scenarios encountered in the management of HF patients, in line with the recommended guidelines. A heart failure-focused meeting was organized, during which participating cardiologists engaged actively. During HF meetings in which cardiologists participated, 108 questionnaires were distributed electronically. In total, 57 men and 51 women expressed their opinions regarding the Delphi analysis. Results: A strong consensus on the benefits of beta-blockers in improving prognoses for, and reducing mortality in, patients with HF and reduced systolic function emerged. The majority of cardiologists continue to prefer intravenous therapy with continuous loop-diuretic administration in combination with thiazide diuretics. The use of metolazone elicits fewer preferences, probably due to concerns about side effects. Certainly, SGLT2i is useful in reducing hospitalizations and reducing congestion; however, there is no full consensus on whether MRAi should be discontinued in favor of SGLT2i alone. The majority of participants would discontinue MRAs in the presence of hyperkalemia and worsening renal function, maintaining sacubitril/valsartan, and indicating a priority for renal safety. There was near-unanimous agreement on the early initiation of sacubitril/valsartan after the stabilization of patients hospitalized for heart failure. Conclusions: A significant majority (97%) of cardiologists expressed a preference for utilizing all of the guideline-recommended drug classes in the management of heart failure, even if this meant not always reaching the maximum tolerated dose for each medication. This approach underscores the importance of comprehensive therapy, targeting multiple pathophysiological mechanisms in heart failure. Cardiologists emphasized that while achieving optimal dosing is ideal, flexibility in treatment regimens is often necessary to accommodate individual patient characteristics, tolerance, and clinical status. The findings highlight the need for personalized treatment strategies that align with current guidelines, while also recognizing the challenges and variability in patient responses to therapy. Full article

mRNA-LNP-based COVID-19 vaccines, namely Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax, were successfully deployed to help control the SARS-CoV-2 pandemic, and their updated formulations continue to be recommended, albeit only for high-risk populations. One widely discussed aspect of these vaccines is their uniquely broad spectrum and increased incidence of adverse events (AEs), collectively referred to as post-vaccination syndrome (PVS). Although the reported PVS rate is low, the high number of administered doses among healthy individuals has resulted in a substantial number of reported vaccine-related injuries. A prominent manifestation of PVS is multisystem inflammation, hypothesized to result from the systemic transfection of organ cells with genetic instructions for a toxin, the spike protein, delivered with lipid nanoparticles (LNPs). In this narrative review, we focus on endothelial cells in the microcirculatory networks of various organs as primary sites of transfection with mRNA-LNP and consequent PVS. We outline the anatomical variations in the microcirculation contributing to the individual variability of symptoms and examine the molecular and cellular responses to vaccine nanoparticle exposure at the endothelial cell level with a focus on the pathways of a sustained cascade of toxic and autoimmune processes. A deeper understanding of the mechanisms underlying mRNA-LNP-induced AEs and PVS at the organ and cellular levels is critical for improving the safety of future vaccines and other therapeutic applications of this groundbreaking technology. Full article

Central nervous system (CNS) involvement is an extremely rare manifestation in eosinophilic granulomatosis with polyangiitis (EGPA), associated with a poor prognosis. Here we present a case of 50-year-old female patient with long-term asthma treatment who presented initially with extreme eosinophilia (56%) and severe progressive ascending paresis, similar to Guillain–Barré syndrome, leading to tetraplegia. After navigating through diagnostic mazes, the diagnosis of EGPA was established based on eosinophilia, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) positivity, asthma, eosinophil granulomatosis in the gastrointestinal tract, and severe peripheral nervous system involvement, complicated with rare central nervous granulomas and ischemia. With combined immunosuppressive and immunomodulatory treatment including high-dose corticosteroids, rituximab and intravenous immunoglobulin along with symptomatic treatment and planned rehabilitation over 6 months, our patient recovered gradually from tetraplegia and adverse events such as severe infections and osteoporotic fractures. Now, from a 2-year perspective, we can conclude a successful treatment leading to decrease in all of her symptoms. Due to persistent eosinophilia after steroid tapering, she was switched to mepolizumab maintenance treatment and demonstrated continuous improvement of motor and sensory functions. Thanks to periodically repeated rehabilitation, she became self-sufficient and returned to her previous job. Our case highlights that EGPA patients should be treated in a center of expertise due to the rarity of the disease and complexity of diagnosis and treatment. Careful multidisciplinary cooperation, the huge effort of the patient, and a supportive environment can show a way back from immune-mediated tetraplegia. Full article