In neuroendocrine neoplasms (NENs), the use of new radiopharmaceuticals has improved the accuracy of diagnosis and staging, refined surveillance approaches, and introduced specific and personalized radiation therapies. Nuclear medicine has therefore acquired a crucial role in the management of NENs patients by improving their risk stratification and personalized therapies. Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both di-agnostic and therapeutic settings by improving the prediction of tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art on AI and radiomics applications in molecular imaging of NENs.

Procedural Sedation and Analgesia (PSA) in the Emergency Department (ED) presents a crucial aspect of emergency medicine, enabling the execution of painful or distressing procedures with minimal patient discomfort. This narrative review delineates the pharmacological framework, methodologies, and clinical considerations integral to optimizing PSA, with a particular focus on pediatric and geriatric populations. Through a comprehensive review and analysis of current practices, this work evaluates the pharmacokinetics and pharmacodynamics of widely utilized sedatives and analgesics, including propofol, ketamine, dexmedetomidine, fentanyl, midazolam, etomidate, nitrous oxide, and remimazolam. Special attention is dedicated to the selection criteria based on patient-specific risk factors, procedural requirements, and the management of potential adverse effects. The manuscript also explores innovative sedation techniques and the integration of new pharmacological agents, emphasizing evidence-based approaches to enhance patient safety and outcome. Results underscore the significance of tailored sedation strategies, especially for vulnerable groups such as pediatric and geriatric patients, highlighting the need for meticulous pre-procedural assessment and monitoring to mitigate risks. Conclusions drawn advocate for a nuanced application of PSA, guided by current evidence and clinical guidelines, to improve the quality of care in emergency settings. This research reinforces the imperative for ongoing education, skill development, and adaptation of new evidence into clinical practice to advance procedural sedation and analgesia in the ED.

There is a significant risk of injury in sports and intense competition due to the demanding physical and psychological requirements. Hamstring strain injuries (HSI) are the most prevalent type of injury among professional soccer players and are the leading cause of missed days in the sport. These injuries stem from a combination of factors, making it challenging to pinpoint the most crucial risk factors and their interactions, let alone find effective prevention strategies. Recently, there has been a growing recognition of the potential of tools provided by artificial intelligence (AI). However, current studies primarily concentrate on enhancing the performance of complex machine learning models, often overlooking their explanatory capabilities. Consequently, medical teams encounter difficulty interpreting these models and are hesitant to trust them fully. In light of this, there is an increasing need for advanced injury detection and prediction models that can aid doctors in diagnosing or detecting injuries earlier and with greater accuracy. Accordingly, this study aims to identify biomarkers of muscle injuries in professional soccer players through a biomechanical analysis, employing several ML algorithms, such as Decision tree (DT) methods, Discriminant methods, Logistic regression, Naive Bayes, Support vector machine (SVM), K-nearest neighbor (KNN), Ensemble methods, Boosted and bagged trees, Artificial Neural Networks (ANN), and XGBoost. In particular, XGBoost was also used to obtain the most important features. The findings highlight that the variables that most effectively differentiate the groups and could serve as reliable predictors for injury prevention are the maximum muscle strength of the hamstrings and the stiffness of the same muscle. With regards to the 35 techniques employed, a precision of up to 78% was achieved with XGBoost, indicating that by considering scientific evidence, suggestions based on various data sources, and expert opinions, it is possible to attain good precision, thus enhancing the reliability of the results for doctors and trainers. Furthermore, the obtained results strongly align with the existing literature, although further specific studies about this sport are necessary to draw a definitive conclusion.

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

Through a partnership with three Federally Qualified Health Centers (FQHCs), the local health department in Los Angeles County implemented a produce prescription program (PPR) to increase fresh fruit and vegetable purchases among patients with diabetes or prediabetes. The PPR, which began in 2020, provided eligible patients with a $40 voucher every month for 6 months to promote the purchase of fresh produce at large chain grocery stores. This qualitative assessment describes staff experiences with the PPR, documenting the facilitators and barriers they encountered while implementing the program. Fifteen clinic staff (i.e., PPR implementers) were interviewed for this assessment. Thematic analysis and coding were conducted using the ATLAS.ti software; the coding was carried out by two separate coders. Interviewees discussed the importance of having preexisting partnerships and programs to support the PPR at their clinic site. Hidden costs related to implementing the program included a large and unexpected amount of staff time devoted to enrolling patients into the program. Collecting quality data and having limited expertise to rigorously evaluate the program were other challenges. Because patients often share their food with their family, the monthly $40 incentive was generally not enough to support their needs; interviewees suggested giving a higher inventive amount to those with a larger household. Future PPR efforts and similar food incentive programs should consider these and other facilitators and barriers to implementation and sustainability, especially when making adjustments to these programs to improve services and access to food resources.

Due to the success of artificial intelligence (AI) applications in the medical field over the past decade, concerns about the explainability of these systems have increased. The reliability requirements of black-box led algorithms for making decisions affecting patients pose a challenge even beyond their accuracy. Recent advances in AI increasingly underscore the need to incorporate explainability into these systems. While most traditional AI methods and expert systems are inherently interpretable, recent literature has focused primarily on explainability techniques for more complex models such as deep learning. This scoping review analyzes the existing literature on explainability and interpretability of AI methods in the medical and clinical field, providing an overview of past and current research trends, and limitations that might impede the development of Explainable Artificial Intelligence (XAI) in medicine, challenges, and possible research directions. In addition, this review discusses possible alternatives for leveraging medical knowledge to improve interpretability in clinical settings, while taking into account the needs of users.

Antisense oligonucleotide (ASO)-mediated exon skipping has emerged as a powerful tool for examining the function of genes and exons in basic research, as well as gene therapy. Computational methods, such as eSkip-Finder, have been developed to predict the efficacy of ASOs via exon skipping using machine learning. However, these methods can be computationally demanding and the prediction accuracy of the tool is not yet optimal. In this study, we propose an approach to reduce computational burden and improve prediction performance by utilizing feature selection within machine learning algorithms and employing ensemble learning techniques. The method was evaluated using a dataset of genes with experimentally validated exon skipping events. The dataset was divided into training and testing sets to assess the accuracy of the algorithm. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. These findings suggest that this approach has the potential to enhance the efficiency and accuracy of predicting ASO efficacy via exon skipping, facilitating the development of novel therapeutic strategies.

Escherichia coli causes several infections like intestinal diarrhea, urinary tract infections, and pneumonia, which are difficult to treat due to the emergence of antimicrobial resistance. The World Health Organisation (WHO) declared carbapenem-resistant E. coli a critical pathogen and called for the development of new antimicrobial agents. Phage therapy, a century-old technique, has been revitalised recently with many successful applications against multi-drug resistant infections. As such, phage therapy is considered one of the most effective alternatives or adjuvants to antibiotics and is also effective in treating multidrug-resistant (MDR) bacterial infections. However, few phages that can kill pathogenic E. coli strains from Southeast Asia have been studied at a molecular level, although the burden of MDR, particularly carbapenem resistance, is high in this region. In this study, three closely related obligately virulent Escherichia phages (øEc_Makalu_001, øEc_Makalu_002, and øEc_Makalu_003) that could infect uropathogenic E. coli were isolated from sewage samples and characterized using morphological as well as sequence-based analysis. Further, a comparative genomic and phylogenetic analysis was done to predict the functional genes and evolutionary relationships. Electron microscopy and genome-based classification revealed that all three phages belonged Krischvirus genus of Straboviridae family. One-step growth curve showed that the latent period of the phages ranged from 15-20 min, the outbreak period was about 50 min, and the burst size ranged between 74-127 PFU/bacterium. Moreover, the phages could tolerate a pH range of 6 to 9 and a temperature range of 25-37°C for up to 180 minutes without significant loss of phage viability. Spotting the purified phages in different clinical isolates showed a broad host-range of isolated Escherichia phages and could lyse up to 30% of the tested pathogenic clinical isolates, including an intra-genus isolate of Klebsiella pneumoniae. The genome organization of all three phages was almost identical and similar to T4-like phage with a full-length genome of ~163 kb. Around 284 coding sequences (CDS) were predicted in each phage, of which only 40% were functional with an average gene length of 951 bp. The coding density in all phages was approximately 95%, while the gene density was 1.73 gene/kbp. Putative lysin, holin, endolysin, and spanin genes were found in the genomes of all three phages, resembling that of T4-like phages implying their phylogenetic relatedness. Furthermore, various in silico sequence analysis tools confirmed that all three phages were strictly virulent with functional lysis modules but devoid of any known virulence or toxin genes, integron-associated genes and antimicrobial-resistance (AMR) genes. In summary, pre-clinical experimental analysis and exploration of genomic features suggest that all three phages may be suitable candidates for therapeutic applications against uropathogenic E. coli.

Breast cancer (BC) is the most common malignancy and the second cause of cancer specific death in women from high-income countries. More than 70% of all breast cancer are hormone receptor-positive BC, and elevated estrogen circulating in blood has been proved to be a strong risk for BC development. This is due to its contribution to enhance proliferation of cancerous cells, angiogenesis and metastasis stimulation and therapy resistance. The estrogen (E) metabolism–gut microbiome axis is functional with underlying individual variations in E levels. It is reasonable that the estrobolome (bacterial genes whose products are capable of metabolizing E) could contribute to the risk of hormone-driven malignancies including BC and may serve as a potential biomarker and target. Gut microbial β -glucuronidase (GUS) enzymes have been suggested to be involved in the estrobolome. Furthermore, bacterial GUS enzymes within the gastrointestinal tract have been postulated to contribute to hormone breast cancer. In this review, we discuss the recent knowledge about the role of GUS enzyme in the pathogenesis of breast cancer. We focus on the role of GUS in (i)-the microbioma and estrogen metabolism, (ii) diet, estrobolome, and the BC development, (iii) other activities of the bacterial β-glucuronidase, and (iv) the new molecular target for BC therapeutic application.

Palmitoylethanolamide (PEA) has been prescribed for neuropathic pain for several years. This study is mainly addressed to summarize what has been published on the topic in the last decades, and how appropriate the numerous prescriptions are. Among others, it examines the innovative EquiPEA^® patent, which aims to address obstacles encountered with conventional PEA formulations. EquiPEA^® seems to partially ameliorate the bioavailability and the targeted distribution. It seems to introduce novel advancements that have the potential to enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of this innovative formulation, in the context of several pathological conditions that may benefit from this molecule. In particular, it investigates the potential enhanced bioavailability and targeted delivery system of EquiPEA^®. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of EquiPEA^® on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that EquiPEA^® has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. This narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.

Evidence-based data for endometriosis management are limited. Experiments are excluded without adequate animal models. Data are limited to symptomatic women and occasional observations. Hormonal medical therapy cannot be blinded if recognised by the patient. Randomised controlled trials are not realistic for surgery since a variable disease with low numbers. Each diagnosis and treatment is an experiment with an outcome and experience is Bayesian updating from the past. If the experience of many is similar, this has more value than an opinion. The combined experience of a group of endometriosis surgeons was used to discuss problems in the management of endometriosis. Considering endometriosis as several genetically/epigenetically different diseases is important for medical therapy. Imaging cannot exclude endometriosis and diagnostic accuracy is limited for superficial lesions, deep lesions, and cystic corpora lutea. Surgery should not be avoided for emotional reasons. Shifting infertility treatment to IVF without considering fertility surgery is questionable. The concept of complete excision should be reconsidered. Surgeons should introduce quality control and teaching should move to explain why it is done. The perception of information has a personal bias. These are the major problems in the management of endometriosis identified by the combined experience of endometriosis surgeons.

The use of medicinal plants for the therapy of diseases of the digestive system; where the Andean peoples developed various forms of administration. The objective being the identification of medicinal plants used in the therapy of ailments of the digestive system by the Andean inhabitants of Pampas, Tayacaja, Huancavelica, Peru. Methods, non-probabilistic sampling, using the “snowball” technique, carrying out semi-structured surveys, allowing information to be collected on the prevalence of ailments or diseases of the digestive system treated with medicinal plants, with inhabitants over 20 years of age participating and using the medicinal plants in the therapy of your digestive system ailments; and, exclude those inhabitants who do not comply with it. Results, 16 families, 33 genera and 34 species are reported; where the families that present the greatest abundance of species are Asteraceae, Lamiaceae; Likewise, the widely used species are Minthostachys mollis (11.9%), Aloe vera (10.4%), Clinopodium bolivianum (9%), Artemisia absinthium (9%) and Matricaria chamomilla (8.2%). Concluding with the identification of a diversity of medicinal flora, used in the therapy of diseases of the digestive system, such as stomach pain, constipation, gallbladder ailments, gastritis, gastrointestinal and liver diseases.

A detailed review of the scientific literature was undertaken to examine the most recent developments in plasma processing in the field of medicine. The first part of the review includes a detailed breakdown of the different types of coatings that can be applied onto medical devices using plasma, with a specific focus on antimicrobial surfaces. The developments during 2023 in plasma deposited biocompatible, drug delivery and adhesive coatings are described and specific applications in additive manufacturing are highlighted. The use of plasma and plasma activated liquids as standalone therapeutics continues to evolve and pertinent advances in this field are described. In addition, the combination of plasma medicine with conventional pharmaceutical interventions was reviewed and key emerging trends were highlighted, including the use of plasma to enhance drug delivery directly into tissue. The potential synergies between plasma medicine and chemotherapeutics for oncology and infection treatment is a growing area and recent advancements are noted. Finally, the use of plasma to control excess antibiotics and to intentionally degrade such materials in waste streams is described.

Background: Falls risk assessment tools are used in hospital inpatient settings to identify pa-tients at increased risk of falls (which may be related to muscle loss/sarcopenia) to guide and target interventions for falls prevention. In 2022, Western Health, Melbourne, Australia, intro-duced a new falls risk assessment tool, the Western Health St. Thomas’ Risk Assessment Tool (WH-STRATIFY), a modified version of The Northern Hospital’s risk tool (TNH-STRATIFY), which replaced the Peninsula Health Risk Screening Tool (PH-FRAT). Aims: To determine the predictive accuracy of three falls risk assessment tools (PH-FRAT, TNH-STRATIFY and WH-STRATIFY) on admission to Geriatric Evaluation Management (GEM) units. Method: A retrospective observational study was conducted on four GEM units. Data was col-lected on 54 consecutive patients who fell during admission and 62 randomly sampled patients who did not fall between December 2020 and June 2021. Participants were scored against three falls risk assessment tools. The event rate Youden (Youden IndexER) indices were calculated and compared using default and optimal cut points to determine which tool was most accurate for predicting falls. Results: Using default cut points to compare falls assessment tools, TNH-STRATIFY had the highest predictive accuracy (Youden IndexER = 0.20, 95% confidence interval CI = 0.07, 0.34). The PH-FRAT (Youden IndexER = 0.01 and 95% CI = -0.04, 0.05) and WH-STRATIFY (Youden IndexER = 0.00 and 95% CI = -0.04, 0.03) were statistically equivalent and not predictive of falls compared to TNH-STRATIFY. When calculated optimal cut points were applied, predictive accuracy im-proved for PH-FRAT (Cut point 17, Youden IndexER = 0.14 and 95% CI = 0.01, 0.29) and WH-STRATIFY (Cut point 7, Youden IndexER = 0.18 and 95% CI = 0.00, 0.35). Overall, all tools had low predictive accuracy for falls. Conclusion: TNH-STRATIFY had the highest predictive accuracy for falls. The predictive accu-racy of WH-STRATIFY improved and was significant when the calculated optimal cut point was applied. The optimal cut points of falls risk assessment tools should be determined and validated in different clinical settings to optimise local predictive accuracy, enabling targeted falls risk mitigation strategies and resource allocation.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, and polyacrylamides, to the promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies emerge as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

This paper aims to list the current challenges in the study of Sports Medicine in Brazil based on a review of the literature and the author's experience as a member of a transdisciplinary team in this field, as well as to discuss methods for establishing an appropriate and organized course of health activities in this context. The authors identified four significant contemporary difficulties in the field of sports medicine in Brazil that, while minor, are complicated. There is a need to publish a greater number of national studies, generate integrated knowledge through transdisciplinary research, propose sports and movement as a tool for the prevention of degenerative conditions, and research and develop better therapeutic options through transdisciplinary research. It is expected that a transdisciplinary approach will reduce divergences between the real world and science, putting an end to dogmatism, prejudice, and theoretical thinking, increasing the scientificity of sports, bringing competitive advantages, improving training, performance, and athlete health management, and contributing to the advancement of sports medicine.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

Background: Covid-19 patients with any pre-existing cardio-vascular disease (CVD) are at highest risk for viral infection and for developing of severe disease. Pathophysiological mechanism is characterized by the viral link to Angioten-sin-Converting Enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and direct damage on myocardium, micro throm-bosis, and alterations of oxygen diffusion. Aim of the study is to analyze clinical course, treatment and outcome in patients (gender stratified) with pre-existing CVD. Methods: Out of the 1299 (700 M/599 F) patients admitted to Internal Medicine COVID Unit of “Castelli Hospital”, Lazio, Italy, from 01/01/2021 to 31/12/2021, 278 patients (167 M/111 F), mean age 76 (76 M/ 75 F) had previous CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated. Results: Most common CVD pathologies were Hearth Failure (HF): 131 (72 M/59 F), Atrial Fibrillation (AF): 45 (25 M/20 F), Myocardial Infarction (MI): 26 (19 M/7 F) and associations among them. 100% of CVD COVID patients under-went Non-Invasive Ventilation (NIV) and were treated with more than 5 drugs. HF was linked with increased LOS (23 days) compared to AF (21 days), MI (18 days) and no CVD (16 days). Overall mean LOS was 16,5 days. 21,4% of total pa-tients had CVD. Conclusions: Timely identification and evaluation of patients with pre-existing CVD are fundamental for adequate treatment based on gender, severity and state of illness and for risk reduction. Keywords: polypharmacy, gender medicine; COVID 19; Sars CoV 2; cardiovas-cular disease.

The first reports of the acute and often fatal illness known as the “English Sweat” are from 1485 and its last known outbreak was in 1551. During this period, the Sweat produced only five epidemic waves. Except for one outbreak which spread to the northern part of the continent of Europe in 1529, the Sweat was confined almost exclusively to England, with only anecdotal reports of isolated infections in other parts of the British Isles. The Sweat was thus only a minor component in the panorama of infectious disease affecting mediaeval and early modern Europe. Nevertheless, it continues to fascinate both medical historians and modern infectious disease biologists – the latter group now often engaged in competing exercises in retrospective diagnosis. This paper seeks to explore the reasons for such enduring interest, using the Early English Books Online (EEBO) text corpus to analyse the various contexts in which the Sweat was discussed up to 1700. EEBO shows that references to the Sweat occur repeatedly in astrological and religious discourses, especially from the mid-17^th century onwards. Four salient examples are examined in detail. It is proposed that the cultural memory of the Sweat, in the 150 years following its disappearance, was kept disproportionately alive not so much by accounts of its alarming symptoms but more due to its metaphorical and illustrative utility in non-medical discourse.

Caused by age or trauma, collapsed connective tissue can cause nerve entrapment and damage within the tarsal tunnel. Tarsal tunnel syndrome is relatively underdiagnosed. This study presents an intervention targeting damaged tissues surrounding the nerves and replacing the structural cushioning with a Wharton’s jelly tissue allograft. The eight selected patients from four clinical sites had tarsal tunnel-related defects. Patient outcomes were tracked on a 90-day calendar utilizing the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster University Arthritis Index (WOMAC). All patients had failed standard care practices for at least six weeks. Each patient received a Wharton’s jelly tissue allograft to sites around the affected tarsal tunnel. No patients experienced adverse reactions. Percent change calculated from the initial application to the 90-day follow-up showed an improvement of 59.43% in NPRS and a 37.58% improvement in WOMAC. This study provides evidence that WJ allograft applications are safe, minimally invasive, and efficacious for patients who have failed standard care treatments for tissue defects associated with Tarsal Tunnel syndrome. Limitations include the small cohort size and nonblinded nature. The results of this study warrant further research to confirm the efficacy, optimal dose, protocol, and durability of Wharton's jelly.

The employment of PRP in regenerative medicine has not generated the promised grandiose outcomes. Nonetheless, it currently remains the gold standard strategy for tissue regeneration. Therefore, scientific research has focused on identifying other matrices rich in growth factors and cytokines to improve the efficacy of PRP. In the present study, a new technology called AMPLEX PLUS -compound derived from colostrum enriched with exosomes- was applied in combination with PRP to evaluate the concentration trend of 20 bioactive molecules. The results show that the concentration of all the compounds analyzed increased significantly in PRP samples with AMPLEX PLUS technology compared with samples containing only plasma or PRP, suggesting how this new strategy could improve the performance of PRP and make significant advances in regenerative medicine.

Medicinal plants for bone grafts are promising because they are free from infecting microorganisms and biocompatible. We report a novel study evaluating osteoregeneration of bone grafts from extracts of Alternanthera brasiliana and Fridericia platyphylla after bone injury induced by radius fracture in rats. Grafts were obtained using 2% chitosan gel and 0.5% hydroalcoholic extract. The rats were randomly divided into four experimental groups (N= 12): Negative control (NC) - Chitosan gel; Positive control (PC) - bovine mineral bone graft (Lumina Bone®, fine powder 0.5); F. platyphylla Graft (FRID) - 0.5% bone graft; A. brasiliana Graft (ABRA) - 0.5% bone graft. The animals were evaluated for three periods, 30, 60, and 90 days after fracture induction. Bone alkaline phosphatase (BSAP) and radiographic and histological evaluations were followed. After 90 days, there was an increase in BSAP for the ABRA group on the newly formed bone matrix but not for FRID, indicating the presence of active osteoblasts. Additionally, mature bone tissue and bone remodeling were observed, and a conspicuous presence of type I collagen for both FRID and ABRA. We demonstrated that FRID and ABRA grafts produced early bone neoformation. New perspectives for these species as a graft are suggested.

Artificial Intelligence (AI) is becoming increasingly important, especially in the medical field. While AI has been used in medicine for some time, its growth in the last decade has been remarkable. Specifically, Machine Learning (ML) and Deep Learning (DL) techniques in medicine have been increasingly adopted thanks to the growing abundance of health-related data, improved suitability of such techniques for managing large data-sets, and more computational power. The Italian scientific community has been instrumental in advancing this research area. This article aims to conduct a comprehensive investigation of the ML and DL methodologies and applications used in medicine by the Italian research community in the last five years.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

Diabetes and mental disorders have been recognized as two significant public health concerns globally. Recent research indicates that there is a bidirectional relationship between these two conditions, with each influencing the other's course and outcomes. Nutrition plays an essential role in the prevention and treatment of both mental disorders and diabetes. A comprehensive review of existing literature was conducted to examine the impact of anxiety and depression on the development of diabetes and the influence of diabetes on the occurrence of mental health disorders such as anxiety and depression. Additionally, the effects of nutrition on the prevention and management of mental disorders, diabetes, and related complications in at risk individuals were assessed. Our findings show that mental disorders, such as depression and anxiety increase the risk of developing type 2 diabetes and are associated with poorer glycemic control, increased diabetes-related complications, and higher mortality rates. Conversely, diabetes is also linked with an increased risk of developing mental health disorders, including depression, anxiety, and cognitive decline. The biological, psychological, and social factors that contribute to the comorbidity between these two conditions are complex and multifaceted. Therefore, an integrated approach to the management of both conditions is critical for improving patient outcomes and reducing the overall burden of disease. Nutritional interventions should be utilized to reduce the risk of diabetes in patients with anxiety and depression as well as enhance mental health in patients with diabetes.

The enteric nervous system (ENS) is a neural network referred to as "the brain in the gut" because of its similarities to the central nervous system (CNS). The ENS consists of numerous types of neurons and glial cells distributed in two intramuscular plexuses that span the length of the intestine and control coordinated smooth muscle contractile activity and other intestinal functions. It is well-established that reciprocal communication exists between the brain and the gastrointestinal tract. Although the ENS can function independently, it is connected to the CNS through the afferent and efferent pathways of the parasympathetic and sympathetic nervous systems. In addition to regulating ENS function by the CNS, these connections are likely to be critically involved in the pathophysiology of Parkinson's disease (PD). PD is a common neurodegenerative disorder that presents with non-motor and motor symptoms. Surprisingly, ENS lesions have been shown to occur very early in the disease, even before CNS involvement. This has led to the postulation that the ENS may be central to the pathophysiology of PD. Autopsy studies have shown that α-synuclein (αS) aggregates in PD patients are found both in the substantia nigra (SN) and the ENS. Therefore, it has been hypothesized that the pathological process leading to PD may initially occur in the ENS years before the appearance of motor features. This process induces misfolding and aggregation of αS in specific subtypes of neurons in the CNS. Finally, it spreads retrogradely in the CNS through preganglionic vagal fibers to the dorsal motor nucleus of this nerve and to other central nervous structures. In addition to the presumed role in the spread of the disease process, it has also been suggested that pathological changes in the ENS might be involved in the gastrointestinal dysfunction frequently seen in Pd patients. Starting from the evidence in animal models and using a translational point of view, in this review, we aim to summarize the role of the ENS in the pathogenesis of PD and how this system could be modulated for a novel therapeutic approach. While acknowledging the presumed role of the microbiome in the gut-brain axis, we will shift the focus from this point of view to focus more on the neurons of the ENS.

Cancer theragnostics is a novel approach that combines diagnostic imaging and radionuclide therapy. It is based on the use of a pair of radiopharmaceuticals, one optimized for positron emission tomography imaging, through linkage to a proper radionuclide, and the other bearing a beta-emitter isotope that can induce significant damage to cancer cells. In recent years, the use of theragnostics in nuclear medicine clinical practice has increased considerably, and thus investigation has focused on the identification of novel radionuclides that can bind to molecular targets which are typically dysregulated in different cancers. The major advantages of the theragnostic approach include elimination of multi-step procedures, reduced adverse effects to normal tissues, early diagnosis, better predicting responses and personalized patient care. This review aims to discuss emerging theragnostic molecules that have been investigated in a series of human malignancies, including gliomas, thyroid cancer, neuroendocrine tumors, cholangiocarcinoma and prostate cancer, as well as potent and recently introduced molecular targets, like cell-surface receptors, kinases, and cell adhesion proteins. Furthermore, special reference has been made to copper radionuclides as theragnostic agents, and their radiopharmaceutical applications since they present promising alternatives to the well-studied gallium-68 and lutetium-177.

Bioactive plant compounds, also known as phytochemicals, are essential for plant resistance, growth, and development. These chemicals often possess therapeutic properties that have been used in traditional medicine for centuries as herbal remedies for a variety of diseases. As a member of the Lamiaceae family, Rydingia (Syn: Otostegia) is found in Asia and northeastern Africa. R. michauxii, is a unique shrub that grows in the Southern region of Iran, Fars province. Rydingia species have been used as traditional herbal medicine in Iran for many years. It seems that R. michauxii offers great potential for in-depth research on its diverse biological properties, especially its antioxidant and lipid-lowering effects. Nevertheless, no clinical investigation has been carried out on the phytochemical characteristics of this plant to date. Therefore, this study aims to contribute to the scientific knowledge on the pharmacological properties of R. michauxii and its phytochemical compounds and encourage researchers to evaluate its biological properties in animal models. In this study, all available scientific literature was compiled and all phytochemical and pharmacological properties of the R. michauxii plant were investigated, including antibacterial, antifungal, antiviral, antioxidant, antimalarial, cytotoxic, and lipid-lowering effects, which may prove useful in developing novel formulations with greater therapeutic benefits in clinical applications.

The elderly present age-related morphological and histological changes of the oral cavity; Literature displays many studies regarding the specific pathologies of the oral cavity in elderly patients, but no etiologically based classification is available. The aim of this study was to analyze the series of patients over 65 who were treated by our Unit of Pathology between 2020 and 2022 for a suspicion of oral lesion or for preventive dental evaluation (in anticipation of cardiac surgery, anti-resorptive drugs intake, chemotherapy, radiotherapy of the head-neck district or transplantation). The analysis was conducted by dividing oral lesions into 5 groups depending on the etiology: reactive, immunological, traumatic, benign and malignant degenerative. The sixth group consisted of patients undergoing preventive dental evaluation. The study included 435 patients; 91 of them were diagnosed with a reactive origin pathology, 174 with immunological origin pathology, 48 with traumatic pathology and 86 with degenerative pathology (42 benign and 44 malignant). 36 patients went to our Unit for preventive specialist evaluation. Oral health has a major impact on the daily life of the elderly; The examination of oral mucosa in geriatric patients is a fundamental diagnostic moment to report lesions early, thus allowing easier prevention and treatment.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

BACKGROUND: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics. OBJECTIVES: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic. METHODS: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety net hospital system was conducted between September 1, 2015 and December 31, 2020. We collected longitudinal data on patient demographics, UDT findings, and potential predictors of aberrant results. RESULTS: Of the 913 patients in the study, 500 (55%) underwent UDT testing, with 455 (50%) having the testing within the first three visits. Among those tested within the first three visits, 125 (27%) had aberrant UDT results; 44 (35%) of these 125 patients were positive for cocaine. In a multivariable regression model analysis of predictors for aberrant UDT within the first 3 visits, non-Hispanic White race (odds ratio [OR]=2.13; 95% confidence interval [CI]: 1.03-4.38; p=0.04), history of illicit drug use (OR=3.57; CI: 1.78-7.13; p< 0.001), and history of marijuana use (OR=7.05; CI: 3.85-12.91; p< 0.001) were independent predictors of an aberrant UDT finding. CONCLUSION: Despite limitations of immunoassay UDT, it was able to detect aberrant drug taking behaviors in a significant number of patients seen at a safety net hospital palliative care clinic, including cocaine use. These findings support universal UDT monitoring and utility of immunoassay-based UDT in resource limited settings.

Uncultured, unmodified, autologous, adipose-derived regenerative cells (UA-ADRCs) are a safe and effective treatment option for various musculoskeletal pathologies. However, it is unknown whether the composition of the final cell suspension systematically varies with the subject's individual age, sex, body mass index and ethnicity. UA-ADRCs were isolated from lipoaspirate from n=232 subjects undergoing elective lipoplasty using the Transpose RT system (InGeneron, Inc.; Houston, TX, USA). The UA-ADRCs were assessed for the number of nucleated cells, cell viability and the number of viable nucleated cells per gram of adipose tissue harvested. Cells from n=37 subjects were further characterized using four-channel flow cytometry. The present study shows, for the first time, that key characteristics of UA-ADRCs can be independent of the subject's age, sex, BMI and ethnicity. This result has important implications for the general applicability of UA-ADRCs in regeneration of musculoskeletal tissue. Future studies must determine whether in-dependence of key characteristics of UA-ADRCs of the subject's individual age, sex, BMI and eth-nicity only applies to the system used in the present study, or also to others of the more than 25 different experimental methods and commercially available systems used to isolate UA-ADRCs from lipoaspirate that have been described in the literature.

The current review comprehensively explores the multifaceted landscape of anaplastic lymphoma kinase (ALK) and its pivotal role, specifically within non-small cell lung cancer (NSCLC). It traces the trajectory of ALK's discovery, notably its fusion with nucleolar phosphoprotein (NPM)-1 in anaplastic large cell non-Hodgkin's lymphoma (ALCL) in 1994. It unfolds the subsequent impact of ALK gene alterations across various malignancies, including inflammatory myofibroblastoma (IMT) and NSCLC. The prevalence of intricate ALK rearrangements affecting roughly 3–5% of NSCLC patients prompted the approval of six ALK-tyrosine kinase inhibitors (TKIs) by 2022, revolutionizing the treatment landscape for advanced metastatic ALK+ NSCLC. Second-generation TKIs like alectinib, ceritinib, and brigatinib have notably emerged to combat resistance issues initially associated with crizotinib, the pioneer ALK-TKI approval. Moreover, this review delves into the intersection of ALK and immunotherapy, exploring the potential of immune checkpoint inhibitors in ALK-altered NSCLC tumors. Despite promising preclinical data, challenges encountered in trials evaluating combinations like nivolumab-crizotinib, primarily due to severe hepatic toxicity, underscore the need for cautious exploration of these novel approaches. Additionally, the review delves into innovative avenues such as ALK vaccines and biosensors, shedding light on their promising potential within ALK-driven cancers. This comprehensive analysis encompasses molecular mechanisms, therapeutic strategies, and immune interactions associated with ALK-rearranged NSCLC. Ultimately, the review is a pivotal resource guiding future research and therapeutic interventions in ALK-targeted therapy for NSCLC.

Despite recent advances in optimizing reliever, controller and maintenance therapy in asthma, a large subgroup of asthmatic patients continues to suffer from severe asthma, affecting their psychosociological status, their quality of life and even their life expectancy. Identifying and recognizing the specific phenotypic and endotypic characteristics in asthma has provided the medical community to drive the development of targeted therapies that are proved to benefit patients in terms of symptom control, exacerbation rate, quality of life and lung function. Adopting a more tailored and targeted approach is proving to be the key factor in reforming severe asthma treatment, minimizing the patients’ burden, as well as the socioeconomical impact worldwide. In this review, we are going to describe the different phenotypes and endotypes of asthma, the currently approved targeted therapies in severe asthma as imprinted in Global Initiative for Asthma (GINA) 2023, as well as other potential pharmacological agents and strategies investigated or currently under investigation for the treatment of severe asthma.

Targeted radionuclide therapy is become increasingly prominent as a nuclear medicine subspe-cialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being de-veloped. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mecha-nisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears as particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in severals types of tumors and have been or will soon be approved and authorized for clinical use.

The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and the process of aging. Analyzing these disease states is possible with GWAS and PheWAS methodology, and through our analysis, we aimed to explore the relationships between polymorphisms in the compendium of ECM genes (i.e., matrisome genes) in various disease states. A significant contribution on the part of the ECM polymorphisms is evident in many varying types of diseases, particularly those in the core matrisome genes. Our results confirm previous links to connective tissue disorders, but also unearth new and underexplored relationships with neurological, psychiatric, and age-related disease states. Upon analysis of drug indications for gene-disease relationships, we identified numerous targets that may be repurposed for age-related pathology. The identification of ECM polymorphisms and their contribution to disease plays an integral role in future therapeutic developments, drug repurposing, precision medicine, and personalized care.

Musculoskeletal disorders are increasingly prevalent worldwide, causing significant socioeconomic burdens and diminished quality of life. Notably, patellar chondropathy (PC) is among the most widespread conditions affecting the joint structures, resulting in profound pain and disability. Hyaluronic acid (HA) and platelet-rich plasma (PRP) have emerged as reliable, effective, and minimally invasive alternatives. Continuous research spanning from laboratory settings to clinical applications demonstrate the numerous advantages of both products. These encompass lubrication, anti-inflammation, and stimulation of cellular behaviors linked to proliferation, differentiation, migration, and the release of essential growth factors. Cumulatively, these benefits support the rejuvenation of bone and cartilaginous tissues, which are otherwise compromised due to the prevailing degenerative and inflammatory responses characteristic of tissue damage. While existing literature delves into the physical, mechanical, and biological facets of these products, as well as their commercial variants and distinct clinical uses, there is limited discussion on their interconnected roles. We explore basic science concepts, product variations, and clinical strategies. This comprehensive examination provides physicians with an alternative insight into the pathophysiology of PC as well as biological mechanisms stimulated by both HA and PRP that contribute to tissue restoration.

Neurocutaneous disorders, also known as phakomatoses, are congenital and acquired syndromes resulting in simultaneous neurologic and cutaneous involvement. In several of these conditions, the genetic phenomenon is understood, providing a pivotal role in the development of therapeutic options. This review encompasses the discussion of the genetic and clinical involvement of neurocutaneous disorders and examines clinical management and treatment options. With the current advances in genetics, the role of precision medicine and targeted therapy plays a substantial role in addressing management of these conditions. The interconnectedness between therapeutic options highlights the importance of precision medicine in treating each disorder’s unique molecular pathway. This review provides an extensive synthesis of ongoing and current therapeutics in the management of such clinically unique and challenging conditions.

Skin wounds and their infections by antibiotic resistant bacteria (ARB)are very common in small animals, posing the risk of acquiring ARB by pet owners or antibiotic resistance gene (ARG) transfer to the owners’ microbiota. The aim of this study was to identify the most common pathogens infecting wounds of companion animals, assess their antibiotic resistance and determine the ARGs using culture-based, molecular and proteomic methods. A total of 136 bacterial strains were isolated from wound swabs. Their species was identified using chromogenic media, followed by MALDI-TOF spectrometry. Disk diffusion was used to test the antibiotic resistance and twelve ARGs were detected using PCRs. The dominant species included Staphylococcus pseudintermedius (9.56%), E. coli and E. faecalis (both n=11, 8.09%). Enterobacterales were mostly resistant to amoxicillin/clavulanic acid (68.3% strains), all Pseudomonas were resistant to ceftazidime, piperacillin/tazobactam, imipenem and tylosin, Acinetobacter was mostly resistant to tylosin (55.5%), all Enterococcus were resistant to imipenem, 39.2% of Staphylococci were resistant to clindamycin. Among ARGs, strA (streptomycin resistance), sul3 (sulfonamide resistance) and blaTEM, an ESBL determinant, were the most frequent. The risk of ARB and ARD transfer between animals and humans causes the need to search for new antimicrobial therapies in the future veterinary medicine.

Abstract Peripartum depression (PPD) is a major complication of pregnancy and many risk factors have been associated with its development, including dysfunctional coping strategies and insecure attachment styles, both during pregnancy and postpartum. The aim of our study was to investigate the role of coping strategies in mediating the relationship between women’s attachment style and PPD in pregnancy, and one week after childbirth, in a large cohort of women. We hypothesized that the relationship between anxious and avoidant attachment and PPD would be mediated by use of maladaptive coping strategies. The assessment instruments were Edinburgh Postnatal Depression Scale (EPDS), Brief Coping Orientation for Problem Experiences (COPE), Experiences in Close Relationship Scale (ECR). The results indicated that the effect of insecure attachment styles (anxious and avoidant attachment) on antepartum depressive symptomatology was partially mediated by dysfunctional coping styles. Anxious attachment has also an indirect significant effect on postpartum depression through emotional coping; however, avoidant attachment does not seem to be significantly related to postpartum depression. Our findings revealed that not only it is important to consider attachment in understanding PPD but also that coping plays an important role in these relationships. These findings would help a preventive coping-based intervention strategy to enhance the capacity of women with insecure attachment styles to use more adaptive coping during and after pregnancy.

Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ^9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome-cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.

Asthma is a prevalent disease that around 300 million worldwide, resulting in substantial morbidity, mortality, and economic burden on a global scale. New clinical and laboratory research has shed light on the immunology causing asthma. Asthma is now recognized as a heterogeneous disease. A personalized medicine is based on the classification of asthma by endotype by linking observable characteristics to immunological mechanisms. Identifying endotype mechanisms is essential for better characterizing patients and personalizing therapeutic approaches with novel biological agents that target specific immune pathways. This article provides a summary of the major immunological mechanisms involved in the pathogenesis and emergence of the disease's phenotypic features, as well as the individualized treatment for severe asthma subtypes

The fresh bulbs of Stenomesson miniatum, a plant belonging to Amaryllidaceae family with a poorly investigated phytochemical profile, were traditionally employed by Andean healers to treat tumors and abscesses. The aims of this study were to characterize the alkaloid extract from the bulbs of S. miniatum and test its cytotoxic and antibacterial potential. The alkaloid extract was characterized by dereplication using various techniques (CPC, NMR, UPLC-HRMS) and referring to in-home or online databases for spectroscopic data matching. Cytotoxic activities were evaluated on A431 human epidermoid carcinoma cells through a metabolic assay, and on Jurkat human acute T-leukemia cells through a cell-impermeant fluorescent nuclear probe. Antibacterial assays were carried out against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes by using a standardized microdilution broth method 96-well plate. Eleven known Amaryllidaceae alkaloids were identified together with another compound determined as being an extraction artefact. The alkaloid extract showed good cytotoxic activity against both the tumor cell lines, reaching an IC50 of 3.3 µg/mL against A431 cells and of 10.9 µg/mL against Jurkat cells. The analysis of the fractions allowed the activity to be attributed to the presence of pretazettine and haemathamine. Conversely, no antibacterial activities were recorded for any of the samples.

The G protein-coupled receptor (GPCR) Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations of Smo have been identified in various other tumours, although their oncogenic effect remains unknown in these tissues. Drug resistance is a common challenge in cancer therapies targeting Smo, and data analysis shows that healthy individuals also harbour resistance mutations. Based on the importance of Smo in cancer progression and the high incidence of resistance towards Smo inhibitors, this review suggests that detection of Smo variants through tumour profiling could lead to increased precision and improved outcomes of anti-cancer treatments.

The aim of this systematic review is to describe and to identify prospect of β-Tricalcium Phosphate (β-TCP) as Alveolar Bone Grafting (ABG) in Cleft Lip/Palate (CL/P) or alveolar bone cleft defect. A systematic review protocol based on Preferred Reporting Items for Systematic Reviews and Meta Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted with MEDLINE/PubMed, Web of Science/ ISI-Web of Knowledge, Scopus and Cochrane Library with English language and no publication year limits. The keywords yielded a total of 5824 publications. There are 3196 suitable articles to evaluate after removing duplicates and languages. Afterward, 1315 studies left after doing title and abstract reading. In addition, 85 full-articles were assessed for eligibility. The read the complete texts of those papers and eventually chose 20 that matched the inclusion requirements. Thirteen of the twenty studies included in this systematic review had a low risk of bias, one had a high risk of bias, and six had moderate bias which not report the randomization. β-TCP as ABG is biocompatible, visible and practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. β-TCP as synthetic ABG can be the alternative to autologous bone grafts with several terms and conditions. Improvement of β-TCP efficacy for ABG in CL/P or alveolar bone cleft defects can be done by a tissue engineering approach combining β-TCP with growth factor, mesenchymal stem cells, or other graft materials and modification of β-TCP physical properties.

Precision cancer medicine primarily aims to identify individual patient genomic variations and exploit vulnerabilities in cancer cells to select suitable patients for specific drugs. These genomic features are commonly determined by gene sequencing prior to therapy, to identify individuals who would be most responsive. This precision approach in cancer therapeutics remains a powerful tool that benefits a smaller pool of patients, sparing others from unnecessary treatments. A limitation of this approach is that proteins, not genes, are the ultimate effectors of biological functions, and therefore the targets of therapeutics. An additional dimension in precision medicine that considers an individual’s cytokine response to cancer therapeutics is proposed. Cytokine responses to therapy are multifactorial and vary among individuals. Thus, precision is dictated by the nature and magnitude of cytokine responses in the tumor microenvironment exposed to therapy. This review highlights cytokine responses as modules for precision medicine in cancer therapy, including potential challenges. For solid tumors, both detectability of cytokines in tissue fluids and their being amenable to routine sensitive analyses could address the difficulty of specimen collection for diagnosis and monitoring. Therefore, in precision cancer medicine, cytokines offer rational targets that can be utilized to enhance the efficacy of cancer therapy.

It is well known that dietary choices impact both individual and global health. However, there are numerous challenges at the personal and systemic level to fostering sustainable healthy eating patterns. These barriers have emphasized the need for innovative approaches within minority communities, particularly those facing food insecurity, to help translate dietary recommenda-tions into practice. Food as Medicine is an approach that recognizes the potential to alleviate the burden of chronic diseases through a healthy diet that is customized to meet the needs of the indi-vidual. Key to implementing this approach are teaching kitchens, which offer an interactive envi-ronment for learning nutrition and cooking skills. Their curriculums are often rooted in Food as Medicine as well as Culinary Medicine, a similar approach. We have found that motivational in-terviewing (MI) techniques, which are primarily used to facilitate behavior change, are well-suited for implementing and maintaining dietary modification. In this commentary, we show how this has been done in a community-based teaching kitchen to empower individuals to make informed and sustainable dietary choices. In demonstrating the application of MI principles in this setting, we hope to offer an inclusive and sustainable way to help address the urgent need for healthier eating and its role in building healthier communities.

The first half of the 20th century was noteworthy for the introduction of a unique group of drugs – antibiotics. It drastically changed concepts of infectious diseases treatment, which for centuries remained a scourge of the human population. With improvement of the antibiotic treatment efficacy, humanity has faced the problem of a dramatic increase in antibiotic resistance in bacteria. The COVID-19 pandemic has only exacerbated the problem and posed a new challenge to the medical community in finding solutions, both clinical and organizational and methodological, to fight antibiotic resistance widespread all over the globe. This publication covers some aspects of evolutionary processes in either pathogens or diseases, including ethical perspective.

Cancer is second leading cause of death, worldwide. Lung cancer is the leading cause of cancer-related mortality. Plant-based therapeutics and herbal medicine have played a vital role in the development of several anti-cancerous agents, and has been used to reduce the severe side effects of chemotherapy as well. Since the anti-lung cancer properties of the plant Medicago. orbicularis are not explored yet, we identified its phytochemical composition and investigated the anti-oxidant, anti-hemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. Results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable anti-oxidant and hemolytic activities. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells; with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts activated Caspase-3 and PARPP-1, and reduced the ratio of anti-apoptotic BCL-2/ pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. M. orbicularis may be a potential source of anti-cancerous agents to manage progression of lung cancer and its resistance to therapy.

According to traditional Chinese medicine, Qi and Blood circulate through the human body via pathways known as 'channels and collaterals'. This process supports the normal function of internal organs and the whole body. Pathological conditions can be attributed to abnormal circulation of Qi and Blood, which results in excess or deficiency of organs and channels. Therapeutic methods used in traditional Chinese medicine restore the balance of Qi and Blood.Since acupuncture was introduced in Europe, discussion and debate about the nature of 'acupoints,' 'channels,' and 'collaterals' has continued. Currently, opposing views exist on this subject, ranging from complete denial of the existence of the channels to uncovering the previously unknown system of intra-tissue gaps and microscopic vessels. The author offers an original hypothesis that regards the theory of channels and collaterals as the description of the physiology and pathology of intercellular space and the theory of organs as a description of the physiology and pathology of cells.

This study assessed the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed (assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis-testing), and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed, stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics, with no genome-wide associations detected for periodontitis severity or Mets components at p&lt;10-7. Severe periodontitis was associated with pathogenetic genera and species. Some SNPs correlated with specific bacterial genera, as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. This is the first study exploring the role of host genotype variation in subgingival microbial dysbiosis in patients with MetS and periodontitis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and microbiome.

Anemia is a well-developed discipline where the concepts of precision medicine have, in part and being studied extensively. This review discusses the treatment of EPO-deficient anemia and resistance in Chronic Kidney Disease (CKD). Traditionally, erythropoietin-stimulating agents (ESA) and iron supplementation have been used to manage anemia in CKD. However, these treatments have potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron, and erythropoietin-iron combination therapy. Another novel approach is using hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). This review highlights the need for precision medicine targeting genetic components of EPO-deficient anemia in CKD and discusses individual variability of genes such as the erythropoietin gene (EPO), Interleukin-β gene (IL-β), and hypoxia-inducible factor gene (HIF). Pharmacogenomics testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, optimizing treatment outcomes and minimizing resistance and adverse effects. The article concludes by suggesting the potential of receptor modification to revolutionize treatment outcome of erythropoietin deficiency anemia through integration of the mentioned approach.

Nanofiber-based systems have emerged as a groundbreaking approach in the field of regenerative medicine, offering immense potential for tissue engineering and regenerative therapies. These systems, composed of nanoscale fibers, provide a unique platform for mimicking/bio-mimicking the complex structures and functionalities of native tissues, enabling the regeneration of injured tissues. This letter aims to provide a brief overview of nanofiber-based systems in regenerative medicine, discovering their importance, design, and fabrication techniques, characterization, biocompatibility, applications, challenges, and future directions as well as discussing key concepts and techniques involved in the development of this innovative tool.

Telemedicine has been increasingly considered an effective strategy to support patients with several diagnosis and therapies, avoiding the on-site visit and drastically reducing the risks to share infections. In the recent years, a number of different technologies have been developed and applied to clinical studies, with the aim to investigate new ways for increase the early diagnoses and monitor the clinical evolution of the most predictable diseases directly from the patients’ home. Telemedicine refers to all those technological interfaces used to remotely perform clinical procedures. Telemedicine applications could be useful in several medical fields, such as preventive medicine, home patient care, education for healthcare professionals and patients, research, public health, and health management. On the other hand, the synergy of these different technologies has a significant impact on the clinical risks analysis, particularly useful in frail patients. Although Telemedicine shows to have important advantages, undoubtedly important issues still remain. The present work aims to shed light on the main advantages and disadvantages related to of each application’s features, which may serve as a useful tool for researchers.

Nurses and paramedics play a pivotal role when Mass Casualty Incidents (MCI) occur, yet they often feel unprepared for such events. Implementation strategies for training activities, including Virtual Reality (VR) and Augmented Reality (AR) simulations, offer realistic and immersive learning experiences, enhancing skills and competencies for nursing students. The aim of this work was to investigate the adopted tools in studies on VR&amp;AR simulations for training nursing and paramedic students in managing MCI. A scoping review was performed following the PRISMA-ScR statement, and the search strategy was conducted through five electronic databases from December 2022 to March 2023. Of 162 records identified, 27 full-text were screened and, six studies were included in this review. These studies involved students who were assigned to different training methods, including immersive VR simulation, written instruction, and traditional lecture. VR&amp;AR and immersive simulation generally show promising evidences in enhancing practical skills and knowledge in MCI management. VR&amp;AR showed to be promising in disaster education and preparedness training, offering different levels of immersiveness and engagement, encouraging active and experential learning. Further research is needed to determine their long-term effectiveness. The choice of training method should consider program goals, target population, and available resources.

Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease's intricate molecular mechanisms, AML have not yet identified effective treatments or expanded diagnostic or prognostic markers. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSC) consist of hematopoietic stem cells (HSC) and cancer cells transformed by the complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSC dormancy, its diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML were discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSC, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveals that microRNAs are a unique factor for LSC. Furthermore, multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSC, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predicted that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes enabled achievable by Network Pharmacology research.

The Sakha people have a long history of use of medicinal plants in traditional medicine and healing practices. This article explores the use and naming practices found with 10 plants that grow in far northeastern Russia, in the Arctic and Subarctic zones of the Republic of Sakha (Yakutia). A field survey of 2500 participants was used to identify the most widely used medicinal plants, their names, and uses. Findings were double-checked with published resources. A small set of criteria are used in naming practices. These practices are based on the plant’s appearance, its habit, or in some way are related to their use, indexing the disease, or the diseased organ, or the result of healing. We find robust knowledge and practice of traditional medicine across the Sakha population, and deep knowledge of plants among Sakha herbalists, healers and shamans.

This study aimed to investigate the characteristics of composite scaffolds in combination of fibroin and carboxymethyl cellulose (CMC) in bone tissue engineering. Fibroin is a useful biomaterial and is a major component of silk yarns composed of fibrous proteins. Improving for binding efficiency in bone formation after implanted scaffold, CMC was added to fibroin. CMC could improve injectable characters in bone substitutes by adding in scaffold material, fibroin. The porous shapes, porosity, surface wettability, water absorption, and thermal properties of the CMC added fibroin scaffold were better than fibroin only scaffold. For tissue engineering of bone marrow mesenchymal stem cells (BMSCs), BMSCs isolated from mice were seeded onto the scaffold, and the cell proliferation rate was measured. alkaline phosphatase activity in BMSCs was higher in the scaffold containing CMC than that in the scaffold containing fibroin alone. The expression levels of osteocyte marker genes and proteins were increased in the CMC scaffold. The biocompatibility and hydrophilicity of CMC scaffolds play important roles in the growth and proliferation of osteocytes. Furthermore, the CMC scaffold design proposed in this study could play an important role in facilitating cartilage, ossification, and nerve differentiation of BMSCs.

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

Metabolomics is an advanced technology, still under development, with multiple research applications, especially in the field of health. Individual metabolic profiles, the functionality of the body, as well as its interaction with the environment can be established using this technology. The body's response to various external factors, including the food consumed and the nutrients it contains, has increased researchers' interest in nutrimetabolomics. Establishing correlations between diet and the occurrence of various diseases or even the development of personalized nutrition plans, could contribute to advances in precision medicine. The interdependence between humans, animals and the environment are of particular importance today, with the dramatic emergence and spread of zoonotic diseases, food, water and soil contamination, and the degradation of resources and habitats. All these events have led to an increase of risk factors for functional diseases, burdening global health. Thus, this study aimed to highlight the importance of metabolomics, in particular of nutrimetabolomics, as a technical solution for a holistic, collaborative, and precise approach for the advancement of the One Health strategy.

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs, and able to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials: they exhibit good features in terms of impermeability, deformability and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration: however, this kind of materials lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these mate-rials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields: in the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance and patency will be herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance will be been disclosed.

Cell-based therapy in regenerative medicine is a powerful tool that can be used both to restore various cell lost in a wide range of human disorders, and in renewal processes. Stem cells show promise for universal use in clinical medicine, potentially enabling the regeneration of numerous organs and tissues in the human body. This is possible due to their self-renewal capacity, and their ability to differentiate into various cell types. To date, pluripotent stem cells seem to be the most promising regeneration tool. Recently, a novel stem cell niche, called multilineage-differentiating stress-enduring (Muse) cells, is emerging. These cells are of particular interest because they are pluripotent and are found in adult human mesenchymal tissues. One of their most significant features is that they can produce cells representative of all the three germ layers. Furthermore, they can be easily harvested from fat, and isolated from the mesenchymal stem cells. This makes them very promising, allowing autologous treatments and avoiding the problems of rejection, typical of transplants. Muse cells have recently been employed, with encouraging results, in numerous preclinical studies, performed to test their efficacy in the treatment of various pathologies, exploiting their regenerative potential in different tissues. This systematic review aimed to 1) highlight the specific potential of Muse cells, and provide a better understanding of this niche, and 2) originate the first organized review of already tested applications of Muse cells in regenerative medicine. The obtained results could be useful to extend the possible therapeutic applications of Muse cells.

The gas molecules O2, NO, H2S, CO, CH4 , have been increasingly used for medical purposes. Beside these gas molecules, H2, the smallest diatomic molecule in nature, has become a rising star in gas medicine in the past few decades. As a non-toxic and easily accessible gas, H2 has shown preventive and therapeutic effects on various diseases of the respiratory, cardiovascular, central nervous and other systems, but the mechanisms are still unclear and even controversial, especially the mechanism of H2 as a selective radical scavenger. Mitochondria are the main organelles regulating energy metabolism in living organisms, as well as the main organelle of reactive oxygen species generation and target. We propose that the protective role of H2 may be mainly dependent on its unique penetrating ability to everywhere of the cells to regulate mitochondrial homeostasis by activating the Keap1-Nrf2 phase II antioxidant system, rather than its direct free radical scavenging activity. In this review, we summarize the protective effects and focus on the mechanism of H2 as a mitochondria-targeting nutrient by activating the Keap1-Nrf2 system in different disease models, and wish to provide a more rational theoretical support for the medical applications of hydrogen.

histology, the processing and staining of cells, tissues and organs to highlight contrast, visualize and analyze their microstructure under microscopy, encompasses a vast array of techniques used to confirm, refine, or refute the macroscopic findings in forensic investigations, for example in the case of autopsies. This review presents several applications of histological protocols, staining methods and techniques to case studies, with the aim of illustrating the established, current and potential applications of histological investigations to forensic sciences. The list of disciplines include anthropology, cytology, dendrochronology, diatomology, entomology, fiber analysis, palynology,human and veterinary pathology, taphonomy and thanatology.

Cyperus rotundus L. exhibits promising potential for the development of functional foods due to its documented pharmacological and biological activities. This study investigated the antioxidant and anti-diabetic properties of C. rotundus kombucha. The results demonstrated potent antioxidant activity with an IC50 value of 76.7±9.6 uL/mL for the DPPH assay and 314.2±16.9 uL/mL for the ABTS assay. Additionally, the kombucha demonstrated alpha-glucosidase inhibitory with an IC50 value of 142.7±5.2 µL/mL. This in vitro antioxidant potential was further validated in vivo using Drosophila. Drosophila fed a high-sugar diet and supplemented with pure kombucha revealed significant increases in DPPH and ABTS free radical scavenging activity. Drosophila on a high-sugar diet supplemented with varying kombucha concentrations manifested enhanced resistance to oxidative stresses induced by H2O2 and paraquat. Concurrently, there was a notable decline in lipid peroxidation levels. Additionally, significant upregulations in CAT, SOD1, and SOD2 activities were observed when the high-sugar diet was supplemented with kombucha. Furthermore, in vivo assessments using Drosophila demonstrated significant reductions in alpha-glucosidase activity when fed with kombucha. A comprehensive GC-MS and HPLC analysis of C. rotundus kombucha detected the presence of antioxidative and anti-glucosidase compounds. In conclusion, C. rotundus kombucha exhibits considerable antioxidant and anti-diabetic properties, demonstrating its potential as a beneficial beverage for health promotion.

According to the International Agency for Research on Cancer (IARC) of the World Health Organization (data of year 2020), Breast Cancer (BC) is one of the most common cancer types worldwide, with large geographical variations occurring between countries and world regions and highest incidence rates in countries that have undergone economic transition. The risk factors for BC include women ageing, genetic mutations, reproductive history, dense breast tissues, personal history of BC or specific non-cancerous breast diseases, family history of breast or ovarian cancer, previous treatment using radiation therapy, and exposure to hormone-like drugs such as diethylstilbestrol (DES). Additional risk factors include being overweight or having obesity after menopause, and taking hormones. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. In the last years, the knowledge about miRNAs role in BC has significantly improved, and complex interactions among coding and non-coding RNA has been elucidated. In this context, an increasing number of papers had been published regarding the role of miR-125 in BC. In this review, we summarize the state-of-the-art about this research topic in addition to elaborating on the need to set novel ethical and legal standards for the governance of such innovations in healthcare.

Diabetes and diabetes-induced micro and macrovascular complications are major causes of healthcare problems. The extracellular vesicles are produced by all cells from all organisms. They are shown to have properties of the producer cells and also reflect the host physiology and pathology. Since the EVs represent the cellular state they are excellent biomarkers. In this review, we will focus on the EVs produced by the Neuro Vascular Unit cells of the eye as well as the extraocular cells in the onset and progression of diabetic retinopathy. A brief account of the use of these nanovesicles in personalised medicine is also given.

For several millennia, doctors and healers used therapeutic ingredients extracted from minerals, plants, and animals. Among the active remedies derived from animals, the placenta was among the most popular ones. The use of placenta-based remedies has retained its significance in our time. The placenta-based therapeutics are indicated for stimulating immunity, wound healing, reduction of skin pigmentation, treatment of various patients suffering from gynecological disorders, etc. By the beginning of the 21st century, the majority of specific functions and chemical ingredients of the placenta were identified and described. However, only now active proteins and peptides with molecular weight of about ten kDa were revealed. Presumably, they play an essential role during the therapeutic application of placental extract. Hopefully, this discovery will start a new era in the research and clinical application of organotherapeutic remedies, including placenta.

(1) Background: the use of force by Public and Private Security Forces is currently an issue of great relevance because of the potential injuries that any excessive use of force by either the active or passive subjects or a deficit in the real mastery of the appropriate Physical Intervention Techniques (PIT) may cause. For this reason, certain traditionally used Physical Intervention Techniques have been questioned by scientific research studies and punished by justice. On the other hand, certain media have dealt with this matter in a biased and unfair manner by broadcasting videos where the use of force by police officer is displayed out of context. As a consequence, this problem has been brought under the spotlight, causing general uneasiness of the communities and rapidly spreading over social networks while favoring all sorts of parallel judgments. (2) Research method: A suit equipped with 19 Inertial Measurement Units (IMU) and a Biomechanics of Bodies software application for the Marras’ analysis of the data collected on trajectory, trunk twisting velocity, its sagittal angle, load, nature and severity of the injuries associated to the different intervention techniques that have been examined. (3) Results: according to the data registered, the implementation of Operational Tactical Procedures (OTP) reduces the probability of injuries and leads to a more satisfactory outcome. (4) Conclusions: the implementation of Operational Tactical Procedures, to-gether with the awareness on the risks associated to the excessive use of force by Public and Private Security Forces and Bodies, could reduce the risk of injuries suffered by both officers and citizens.

Background: Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether sex of the newborn affects the lymphocyte subpopulations in cord blood. Methods: 9 B and 21 T cell subpopulations were characterized by flow cytometry in human cord blood from 16 male and 21 female newborns, respectively. Results: Except for marginal zone B cells and transitional B cells, B cell count in all subsets was higher in cord blood of male newborns than in female newborns. Frequency of naive thymus negative Th cells was significantly higher in male cord blood whereas the remaining T cell subpopulations showed a higher count in cord blood of female newborns. Conclusion: Our study is the first revealing sex differences in B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system urging the need to expand research in this area.

Best practices in global health training prioritize leadership and engagement from investigators from low- and middle-income countries (LMICs), along with more conscientious community consultation and research that benefits local participants and autochthonous communities. However, well into the 20th century, international research and clinical care were rife with paternalism, extractive practices, and racist ideation, with race presumed to explain both vulnerability or protection from various diseases despite scientific evidence for more precise mechanisms for infectious disease. We highlight experiences in global research on health and illness among indigenous populations in LMICs, seeking to clarify what is both scientifically essential and ethically desirable in research with human subjects; we apply a critical view towards race and racism as historically distorting elements that must be acknowledged and overcome.

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT), obtained by mechanical fragmentation, on radiographic bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration while the NT group underwent TPLO alone. The adipose tissue was collected from the thigh region and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray exam preoperatively, immediately postoperatively (T0) and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12= complete remodelling) was used at T0, T1 and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76%–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

Platelet and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects in multiple conditions. PRP and its derivatives, including PRF, have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as OA. Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells and molecular components in these orthobiologic products stimulate numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by regulating proteolytic activity and promoting the recruitment of inflammatory cells and MSCs in areas of tissue regeneration, such as bone, cartilage, and muscle. PRP acts as a potent signaling agent; however, it diffuses easily, while the fibrin from PRF offers a durable scaffolding effect that promotes cell activity. The combination of fibrin with hyaluronic acid, another well-studied orthobiologic product, has been shown to improve its scaffolding properties, leading to more robust fibrin polymerization. This supports cell survival, attachment, migration, and proliferation. Therefore, the administration of the "power mix" containing HA and autologous PRP + PRF may prove to be a safe and cost-effective approach in regenerative medicine.

Telemedicine, telehealth, e-Health, and other related terms refer to the exchange of medical information or medical care from one site to another through electronic communication between a patient and healthcare provider. As telemedicine infrastructure has changed since the COVID-19 pandemic, this review provides an overview of telemedicine use and effectiveness in cardiology, with emphasis on the post-pandemic context. Pre-pandemic studies tend to report statistically insignificant or modest improvements in cardiovascular disease outcome from telemedicine use to usual care. By contrast, post-pandemic studies tend to report positive outcomes or comparable acceptance of telemedicine use to usual care. Today, telemedicine can effectively replace in person follow-ups to produce comparable (but not necessarily superior) outcomes in cardiovascular disease management. A major benefit of telemedicine is the significant reduction in follow-up time or time-to-intervention which may lead to earlier detection and prevention of adverse events. Nonetheless, there remain barriers to effective telemedicine implementation in the post-pandemic context. Providing accuracy and ease-of-use of telemedicine devices, ensuring adherence to remote rehabilitation procedures, and implementing widespread telemedicine infrastructure are such examples. Current knowledge gaps include the true economic cost of telemedicine infrastructure, feasibility of use in specific cardiology contexts, and sex/gender differences of health outcomes through telemedicine use. Future telemedicine developments will need to address these concerns to achieve widespread acceptance as the new standard of care.

The advancements achieved in Tissue Engineering are based on a careful and in-depth study of cell-tissue interaction. The choice of a certain biomaterial in Tissue Engineering is fundamental as it represents an interface for adherent cells in the creation of a microenvironment suitable for cell growth and differentiation. The knowledge of the biochemical and biophysical properties of the extracellular matrix is a useful tool for the optimization of polymeric scaffolds. The aim of this re-view is to analyse the chemical, physical and biological parameters on which it is possible to act in Tissue Engineering for the optimization of polymeric scaffolds. Understanding the scaffold impact on cell fate is of paramount importance for the successful advancement of Tissue Engineering.

Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we positively report the release of PL proteins and relate it to the degradation profile of the gels and the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and bioactive materials.

Background: Sensor usage in the classical scientific process has allowed new experimentation in medicine. We report on the design process of a MEMS sensor being used for muscle trauma evaluation in diagnosing acute compartment syndrome (ACS), a medical ailment costing society billions of dollars per year. Objectives: Modeling the disease with scientific process allows a more complete under-standing of the disease. The goal was to formulate a hypothesis that could be tested to aid in making the diagnosis of ACS accurately. Methods: Scientific process was observed throughout the disease modelling process. Background information was improved and clarified, new pre-clinical models were de-signed and verified, a hypothesis built on pressure measurement with MEMS sensors was carried out, and the testing of the model as verified against previous clinical data was accomplished. Results: Scientific process resulted in hypothesis generation around the relationship of intracompartmental pressure measurement and the disease process and therapy. This resulted in new understanding of ACS, accurate modelling, and sensor design resulting in a MEMS device that has an extremely high sensitivity and specificity (over 99%) in treating and diagnosing the disease. Conclusion: MEMS sensor technology defines the new gold standard of implanting a sensor in a muscle compartment that allows accurate diagnosis of ACS with continuous trends in pressure.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

Background: biophysical stimulation therapy, and in particular Pulsed Electromagnetic Fields (PEMFs) and capacitively coupled electric fields (CCEFs) has significantly increased in the last twenty years. For this, it is necessary to have clear information regarding the efficacy, the therapeutic indication and the expected objectives. Methods: we conducted a narrative review taking into consideration different types of studies with different areas of application. The objective was to take into consideration and analyze the different fields of use and the relevant information present in the literature. Results: There is unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue healing process and the symptoms associated with this situation. Differently, but no less importantly, in the joint compartment positive opinions were observed mainly on the inflammatory and catabolic process, however, at present,we did not report evidence regarding cartilaginous tissue regeneration. Conclusion: the effectiveness of PEMFs and CCEFs on the bone healing process in the Orthopedic and Traumatology fields is consolidated evidence in the literature. We have also found positive results on symptoms and patient compliance with rehabilitation therapies. Therefore, notable application can be envisaged in the fields of Prosthetic Surgery and Sports Medicine.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with GWAS studies showing that many psoriasis risk genes lie along the IL23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. The pathogenesis of psoriasis is complex and focusing on the IL23/Th17 axis can provide insight into key cell types, cytokines and intracellular signaling pathways involved. Examination of currently available biological treatments, time to relapse post drug withdrawal and rates of drug primary/secondary drug failure show the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely reduce dis-ease burden for the longest period possible.

On April 17, 2019, a coach with tourists from Germany crashed in Madeira requiring repatriation by the German Air Force. The Advance Trauma Life Support (ATLS) concept was the central component of patient care. Data in Madeira were collected through a structured interview. The analysis of the Aeromedical Evacuation was based on intensive care transport records. In Germany all available were reviewed for data collection. Quality of life (HRQoL) was evaluated by the 12-item Short-Form Health Survey (SF-12). Twenty-eight prehospital patients were transported to the Level III Trauma Center in Funchal (Madeira). Five operative procedures were performed. Fifteen patients were eligible for Aeromedical Evacuation (AE). In the second hospital phase in Germany in total 82 radiological images and nine operations were performed. Hospital stay lasted 11 days (median, IQR 10–18). Median Follow-up (14 of 15 patients) was 16 months (IQR 16–21). 80% (8 out of 10) showed an increased risk for post-traumatic stress disorder (PTSD). Six key findings were identified in this study: divergent injury classification, impact of AE mission on health status, lack of communication, need of PTSD prophylaxis, patient identification, media coverage. Those findings may improve AE missions in the future e.g. required after armed conflicts.

In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for the introduction and establishment of these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed by these emergent infections.

Nonsense mutations cause several genetic diseases such as Cystic fibrosis, Duchenne muscular dystrophy, β-thalassemia, and Shwachman-Diamond syndrome. These mutations induce the formation of a premature termination codon (PTC) inside the mRNA sequence that leads to the aberrant translation, resulting in the synthesis of truncated polypeptides. Nonsense suppression therapy mediated by translational readthrough-inducing drugs (TRIDs) is a promising approach to correct these genetic defects. TRIDs generate a ribosome miscoding of the PTC named “translational readthrough” and restore the synthesis of full-length and potentially functional protein. The new oxadiazole-core TRIDs NV848, NV914, and NV930 showed translational readthrough activity in nonsense-related in vitro systems. In this work, the possible off-target effect of NV molecules on natural termination codons (NTCs) was investigated. Two different in vitro approaches were used to assess if the NV molecules treatment induce NTCs readthrough: 1) A study of translational induced p53 molecular weight and functionality; 2) the evaluation of two housekeeping proteins (Cys-C and β2M) molecular weights. Our results showed that the treatment with NV848, NV914, or NV930 do not induce any translation alterations in both experimental systems. Data suggested that NV molecules have a specific action for the PTCs and an undetectable effect on the NTCs.

The growing dependence on large language models (LLM)s highlights the urgent need to deepen trust in these technologies. Regular, rigorous validation of their expertise, especially in nuanced and intricate scenarios, is essential to ensure their readiness for clinical applications. Our study pioneers the exploration of LLM utility in the field of cardiology. We stand at the cusp of a transformative era where mature AI and LLMs, notably ChatGPT, GPT-4, and Google Bard, are poised to influence healthcare significantly. Recently, we put three available LLMs, OpenAI's ChatGPT-3.5, GPT-4.0, and Google's Bard, to the test against a significant Polish medical special-ization licensing exam (PES). The exams cover the scope of completed specialist training, focusing on diagnostic and therapeutic procedures, excluding invasive medical procedures and interven-tions. In our analysis, GPT-4 consistently outperformed the others, ranking first, with and Google Bard and ChatGPT- 3.5 following, respectively. The performance metrics underscore GPT-4's no-table potential in medical applications. Given a score improvement of over 23.5 % between two AI models released just four months apart, clinicians must stay informed and up-to-date about these rapidly evolving tools and their potential applications to clinical practice. Our results provide a snapshot of the current capabilities of these models, highlighting the nuanced performance dif-ferences when confronted with identical questions

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC; some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and im-proved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years with histologi-cally confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP. Results: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 [18%]), HER2 (5 [18%]), MTAP (5 [18%]), and FGFR (3 [11%]). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n=12 [11.8%]), 14 months in patients with actionable GAs treated with standard therapies (n=17 [16.7%]), and 17 months in patients without actionable GAs treated with standard therapies (n=73 [71.5%]; p=0.26). The absence of liver metastases was associated with better OS (HR=0.471, p=0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. Interpretation: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.

Background: Patients with bipolar disorder (BD) receive traditional Chinese Medicine (TCM) for unmet clinical needs with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD. Methods: 12,113 patients with BD were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000) between 1996 and 2013. Chi-squared test for categorical variables and independent t-test for continuous variables. A p-value less than 0.05 indicated significance. Results: One-thousand and three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group (N= 1,053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herb and herbal formulas. Conclusions: Physicians need to be aware of the use of TCM in Patients with BD.

Infectious diabetic wounds can result in severe injuries or even death. Biocompatible wound dressings offer one of the best ways to treat these wounds, but creating a dressing with suitable hydrophilicity and biodegradation rate can be challenging. To address this issue, we used the electrospinning method to create a wound dressing composed of poly(glycerol sebacate) (PGS) and gelatin (Gel). We dissolved the PGS and Gel in acetic acid (75 v/v%) and added EDC/NHS solution as a crosslinking agent. Our measurements revealed that the scaffolds' fiber diameter ranged from 180.2 to 370.6 nm, and all the scaffolds had porosity percentages above 70%, making them suitable for wound healing applications. Additionally, we observed a significant decrease (p &lt; 0.05) in the contact angle from 110.8° ± 4.3° for PGS to 54.9° ± 2.1° for PGS/Gel scaffolds, indicating an improvement in hydrophilicity of the blend scaffold. Furthermore, our cell viability evaluations demonstrated a significant increase (p &lt; 0.05) in cultured cell growth and proliferation on the scaffolds during the culture time. Our findings suggest that the PGS/Gel scaffold has potential for wound healing applications.

(1) Background: The COVID-19 pandemic has affected healthcare utilization rates on a global scale. This study aimed to analyze whether the COVID-19 pandemic affected the characteristics of first-visit patients with peripheral facial palsy visiting a Korean Medicine hospital and to observe characteristics changes in them. (2) Methods: This study analyzed the electronic medical records of 2,310 first-visit patients with peripheral facial palsy who visited the Facial Palsy Center, Korean Medicine Hospital, Kyung Hee University Medical Center from January 1, 2019 to December 31, 2021 in terms of demographic characteristics, disease phase, residence locations, hospital visit route, and patient care type. (3) Results: There were significant relationships between the presence of the COVID-19 pandemic (i.e., before and during) and the number of patients by disease phase (p=0.043), residence locations (p=0.003), residence locations in Seoul (p=0.003), and patient care types (p=0.003). (4) Conclusions: There were several differences in characteristics of first-visit patients with peripheral facial palsy visiting a Korean Medicine hospital during COVID-19 pandemic in terms of demographic characteristics, disease phase, residence locations, residence locations in Seoul, and patient care types.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

There are several Amazonian plant species with potential pharmacological validation for the treatment of acute kidney injury, a condition in which the kidneys are unable to adequately filter the blood, resulting in the accumulation of toxins and waste in the body. Scientific production on plant compounds capable of preventing or attenuating acute kidney injury, caused by several factors, including ischemia, toxins and inflammation, has shown promising results in animal models of acute kidney injury and some preliminary studies in humans. Despite the popular use of Amazonian plant species for kidney disorders, further pharmacological studies are needed to identify active compounds and subsequently conduct more complex preclinical trials. Thus, this review aimed to describe the pharmacological properties of phytocompounds from Amazonian plant species and their effectiveness in the prevention and treatment of Acute Kidney Injury. (AKI). The classes of Amazonian plant compounds with significant biological activities most evident in the consulted literature were alkaloids, flavonoids, tannins, steroids and terpenoids. An expressive phytochemical and pharmacological relevance of the studied species was identified, although many of them with insufficiently explored potential, mainly in face of AKI, a clinical condition with high morbidity and mortality.

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that involve in regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result downstream activation of tyrosine kinases leading to tumor development. Targeting those FGFR alterations has shown to be effective in cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments of multiple agents targeting FGFR pathway including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody drug conjugates. However, most of these agents have variable and low responses with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments of agents targeting FGFR pathway and discuss future directions of FGFR targeting agents.

The purpose of this study was to explore and develop high-resolution infrared thermal (HRIT) imaging for screening toddler’s fracture. A Toddler’s fracture is a common tibial fracture of children younger than 6 years old. Initial x-ray radiographs may not show the fracture and another x-ray during a follow-on visit is usually required. The study included 39 participants admitted to an emergency department with a suspected toddler’s fracture. X-ray confirmed 8 cases with a toddler’s fracture (20.5%). Infrared images of participants were recorded on their index visit, focusing on region-of-interests on the injured and the contralateral (uninjured) legs. The uninjured leg acted as a thermal reference. Nine statistical measures were extracted from the images: maximum, mini-mum, mean, standard deviation, median, mode, interquartile range, skewness, and kurtosis. Wilcoxon rank sum test indicated that maximum, mean, standard deviation, median, and inter quartile range temperature measures were significantly different (p<0.05) when comparing fractured and non-fractured legs. Principal component analysis of these measures highlighted distinct separation of toddler’s fracture and non-fracture cases. Similarly, plots of the statistical measures further confirmed clustering of toddler’s fracture cases. The study demonstrated that HRIT imaging can be a valuable tool for screening for toddler’s fracture.

Preliminary clinical data suggest pain reduction through fasting in different diagnoses. This uncontrolled observational clinical study examined the effects of prolonged modified fasting on pain and functional parameters in hip and knee osteoarthritis. Patients admitted to the inpatient department of Internal Medicine and Nature-based Therapies of the Immanuel Hospital Berlin between February 2018 and March 2020, answered questionnaires at the beginning and end of inpatient treatment, as well as 3, 6 and 12 months after discharge. Additionally, selected blood and anthropometric parameters were routinely assessed during the inpatient stay. Fasting was performed as part of a multimodal integrative treatment program, with daily caloric intake of <600 kcal for 7.7 ± 1.7 days. N=125 consecutive patients were included. Results revealed an amelioration of overall symptomatology (WOMAC Index score: -14.8±13.31; p<0.001; d=0.78), and pain alleviation (NRS Pain: -2.7±1.98, p<0.001, d=1.48). Pain medication was reduced, stopped, or replaced by herbal remedies in 36% of patients. Improvements were also observed in secondary outcome parameters, including increased quality of life (WHO-5: +4.5±4.94, p<0.001, d=0.94), reduced anxiety (HADS-A: -2.1±2.91, p<0001, d=0.55) and depression (HADS-D: -2.3±3.01, p<0.001, d=0.65), decreases in body weight (-3.6 kg ± 1.65, p< 0.001, d=0.21), and blood pressure (systolic: -6.2±15.93, p<0.001, d= 0.43; diastolic: -3.7±10.55, p<0.001, d=0.43). Results suggest that patients with osteoarthritis of the lower extremities may profit from a prolonged fast embedded in a multimodal integrative treatment regarding quality of life, pain, and disease-specific functional parameters. Confirmatory RCTs are warranted to further investigate these hypotheses.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines, and 3D tumor models. To address this goal, a well characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G > T (p.(Gly12Val)) was used. Fluorescently labelled tumor cells were injected into the perivitelline space of 2 days post fertilization zebrafish embryos. At 1 day post-injection xenografts were as-sessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib, and trametinib + luminespib. Subsequently xenografts were euthanized and analysed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n=84) in vivo and with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.

Novel therapies for treatment of familial dilated cardiomyopathy (DCM) are lacking. Triggers for the progression of the disorder commonly occur due to specific gene variants that affect the production of sarcomeric/cytoskeletal proteins. Generally these variants cause a decrease in tension by the myofilaments, resulting in signaling abnormalities within the micro-environment which over time result in structural and functional maladaptations leading to heart failure (HF). Current concepts support the hypothesis that the mutant sarcomere proteins induce a causal depression in the tension time integral (TTI) of linear preparations of cardiac muscle. However, molecular mechanisms underlying tension generation particularly in relation to mutant proteins and their impact on sarcomere molecular signaling, are currently the subject of controversy. Thus, there is a need for clarification as to how mutant proteins affect sarcomere molecular signaling in the etiology and progression of DCM. A main topic in this controversy is the control of the number of tension generating myosin heads reacting with the thin filament. One line of investigation proposes that this number is determined by changes in the ratio of myosin heads in a sequestered super-relaxed state (SRX) or in a disordered relaxed state (DRX) poised for force generation upon Ca-activation of the thin filament. Contrasting evidence from nanometer–micrometer-scale x-ray diffraction in intact trabeculae indicates that the SRX/DRX states may have a lesser role. Instead, the proposal is that myosin heads are in a basal OFF state in relaxation then transfer to an ON state through a mechano-sensing mechanism induced during early thin filament activation and increasing thick filament strain. Recent evidence about the modulation of these mechanisms by protein phosphorylation has also introduced a need for reconsidering control of tension. We discuss these mechanisms that lead to different ideas related to how tension is controlled and disturbed by mutant sarcomere proteins linked to DCM including cardiac myosin, myosin-binding protein C, titin filaments, and thin filaments. Resolving the various mechanisms and incorporating them into a unified concept is crucial for gaining a comprehensive understanding of DCM. This deeper understanding is not only important for diagnosis and treatment strategies with small molecules, but also for understanding the reciprocal signaling processes that occur between cardiac myocytes and their micro-environment. By unraveling these complexities, we can pave the way for improved therapeutic interventions for managing DCM.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

This study aimed to investigate the prevalence, location, and characteristics of new-onset chronic pain by using a new definition in long-term survivors after discharge from a tertiary emergency center. We conducted a single-center ambidirectional cohort study from January to May 2022. A survey of patients was conducted by postal mail 2-2.5 years since their discharge from a tertiary emergency center. We used the Brief Pain Inventory to investigate chronic pain parameters, and the painDETECT questionnaire to investigate neuropathic pain. Patient information during hospitalization was collected retrospectively from medical records. The survey was sent to 78 patients, 63 (81%) of whom responded and were included in the analysis. Nine of the 63 patients (14%) had new-onset chronic pain. Of these, six (67%) had chronic pain of moderate or severe intensity which interfered with daily life. The most frequent location of chronic pain was the ankle/foot (n=4, 44%). Neuropathic pain was present in four (44%) patients with new-onset chronic pain. New-onset chronic pain may occur for up to 2-2.5 years after discharge from a tertiary emergency center, and this may interfere with daily life. Therefore, a follow-up system for chronic pain is warranted.

Modern anesthesia continues to be impacted in new and unforeseen ways by digital technology. Combining portability and versatility, mobile applications or “apps” provide a multitude of ways to enhance anesthetic and peri-operative care. Research suggests that uptake of apps into anesthetic practice is becoming increasingly routine, especially amongst younger anesthetists brought up in the digital age. Despite this enthusiasm, there remains no consensus in how apps are safely and efficiently integrated into anesthetic practice. This review summarizes the most popular forms of app usage in anesthesia currently and explores the challenges and opportunities inherent in implementing app use in anesthesia, with an emphasis on a practical approach for the modern anesthetist.

ABSTRACT(1) Background:. Because of the numerous debates about the training on the use of force provided to police officers, this study intends to evaluate several parameters (Police Ergonomic Parameters, PEP) in connection with such training. (2) Research method: : A smartsuit equipped with a set of 19 wireless sensors including triaxial accelerometers, Inertial Measurement Units (IMU), gyroscopes and geomagnetic sensors has been used. Biomechanics of Body (BoB) software application allowed to evaluate the risks associated to the basic technique number 1 of the Operational Tactical Procedures (OTP) with regard to the established parameters (PEP). The OTP basic technique number 1 was performed by 4 novice police officers. (3) Results: According to the evaluation of a number of specific parameters such as Rapid Entire Body Assessment (REBA), asymmetry over the sagittal plane, compression force at the L5-pelvic junction, shear force at the L5-pelvic junction and total muscle power, it was observed that the measured values clearly varied depending on each individual's performance, although they remained consistent with the values established by Police Ergonomic Parameters, and were significantly different from the values measured when a police officer used a traditional physical intervention procedure, in which case, the values measured were indicative of higher risks. (4) Conclusions: In order to achieve lower and more uniform values in terms of risk, we believe that it is necessary to employ a greater number of hours to the training of police officers on the use of force and also the convenience of conducting further studies on a larger and more representative sample of officers.