Given the long-standing debate about the nature of the concept of disease, the objective of this study was to understand how doctors categorize a condition as a disease or not and what kind of information they use. A survey with a set of clinical vignettes was designed, and a group of physicians were asked to interpret those situations as a disease or not and to motivate their choice with a short written text. Thematic analysis of the answers resulted in four themes: the temporal dimension of a disease, reification of disease, disease as an existential condition, and disease as a motivation to action. The respondents’ interpretations were very heterogeneous, supporting the idea that physicians do not share a common prototypical concept of disease. An interpretation of these results according to a critical realist and systemic approach suggested that the doctor-patient relationship is the context able to influence the interpretation of a condition as a disease or not as the final outcome of a process in which both objective, subjective, and socially mediated elements are taken into consideration.

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

Arguably the most important parameter in treating cognitive decline associated with Alzheimer’s disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups {Kennedy, 2018 #535}. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy [2], resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvement in patients with cognitive decline [3]; [4]; [5], but long-term follow-up (>5 years) has not been reported previously. Therefore, we report here sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol—something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

Background/Objectives: Community-acquired pneumonia (CAP) is a common emergency presentation in Australia, with the choice of admitting specialty unit often influenced by pneumonia severity and comorbidities. However, it remains unclear whether there are between-specialty differences in patient characteristics and outcomes. We sought to address this issue by investigating the characteristics and outcomes of CAP patients admitted to General Medicine (GM) versus Respiratory units.Methods: This retrospective observational study utilised data from the two largest metropolitan hospitals in South Australia, encompassing all non-COVID-19-related CAP admissions throughout 2021 to 2023. Hospital length of stay (LOS), in-patient and 30-day mortality, and 30-day readmission rates were assessed by propensity-score-matching (PSM) with using 14 variables.Results: Of the 3,004 cases of non-COVID-19 CAP admitted across the two hospitals during the study period, 2,673 (71.8%) were admitted under GM units and 331 (9.1%) under Respiratory units. GM patients were, on average, a decade older, presented with a significantly higher burden of comorbidities, exhibited a greater prevalence of frailty and had higher pneumonia severity compared to those admitted under a Respiratory unit, (P

The dawn of Artificial Intelligence (AI) in healthcare stands as a milestone in medical innovation. A plethora of different medical fields are heavily involved and pediatric emergency medicine is no exception. These new tools do not merely provide more advanced and efficient systems for patients’ diagnosis, management and treatment. They rather concern a strict shift from traditional methods based upon broad categories towards a more personalized healthcare. AI offers many promises in pediatric emergency medicine with a wide range of applications involving clinical decision making, patients’ flows management and prioritization. Main barriers to a widespread diffusion involve technological challenges but also ethical issues and the paucity of extensive datasets in pediatric contexts. We conducted a narrative review structured in two parts. The first part explores the theoretical principles of AI, providing all the necessary background to feel confident with these new state-of-the-art tools. The second part presents an informative analysis of AI models in pediatric emergencies, pointing out the actual applications and challenges until future feasible research perspectives.

The literature study delves into novel therapeutic strategies in transplantation medicine, highlighting unique approaches that could revolutionize current practices. It emphasizes novel patterns that have the potential to transform the current landscape. Commencing with a thorough examination of the historical environment, it traces crucial advances and changes in transplantation. The focus is on traditional techniques, emphasizing their limitations and challenges. An extensive examination of contemporary transplantation therapies offers valuable insights into the most recent progress in organ, cellular, and tissue transplantation. This analysis examines the immunological obstacles and outlines the current advancements and constraints. The exploration further navigates into novel models and concepts such as immunomodulation, developments in organ preservation techniques, gene editing, biomaterials, scaffold-based solutions, and the integration of precision medicine, artificial intelligence, and machine learning applications. Each section analyzes the potential for change and current progress in various areas, backed by relevant scientific sources up to 2023. The subsequent sections delve into innovative cellular therapies, biotechnological progress, current clinical trials, and case studies demonstrating effective applications. This examination delves into the ethical and regulatory considerations of innovative therapeutic procedures, emphasizing ethical implications, regulatory frameworks, and the importance of balancing innovation with patient welfare. The literature review concludes by offering a forward-looking perspective, emphasizing potential progress, anticipated challenges, and advocating for collaboration and interdisciplinary approaches to overcome limitations in the field of transplantation medicine.

This article evaluates the reliability and consistency of nutrition- and supplementation-related advice for pregnant women provided by ten selected health-related Internet portals. The portals were chosen based on their perceived reliability and prominence in Google searches, with representation from both English and Polish language sources. The evaluation criteria included the adherence of the presented information to official recommendations and its evidence-based character based on specific items representing dietary aspects important in pregnancy. While the overall reliability was deemed acceptable, significant variations existed both among the portals and specific evaluated items. Notably, HealthLine, Medline Plus, and NCEZ emerged as the most evidence-based, while WebMD and Medycyna Praktyczna were identified as less reliable. Despite a number of issues, the analysed portals remain valuable sources of nutritional information for pregnant women, offering user-friendly accessibility superior to alternatives such as social media, on the one hand, and scientific articles, on the other. Improved consistency and attention to detail, especially in relation to vitamin intake and supplementation, would improve the overall quality of health portals.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Same-day desensitization (SDD) is a procedure in which desensitization to the drug suspected of causing the hypersensitivity reaction (HR) is performed on the same day as the patient's reaction. In rapid drug desensitization (RDD), desensitization to the suspected drug is performed after an allergological study. The aim of the study was to analyze the diagnostic capacity of the allergist in Oncology Day Hospital (ODH) to establish the phenotype of the HR, in the context of SDD, based exclusively on clinical biomarkers. This is a study of patients treated with desensitization on the same day they had a HR. Later an allergological study (clinical history, skin test, risk assessment, serological biomarkers, drug provocation test if applicable) was performed prior to the following administrations. A total of 35 successful SDDs were performed. A high concordance (91.5% of patients) was found between the phenotype suspected by the allergist after the initial assessment of the patient prior to SDD and the final phenotype after subsequent allergological study performed in the Allergy Department. The presence of the allergist at the ODH allows, in addition to initial treatment according to phenotype, desensitization on the day of the reaction. This will lead to personalized and precision allergology.

The shift towards Personalized Cancer Medicine (PCM) represents a significant transformation in cancer care, emphasizing tailored treatments based on genetic understanding of cancer at the cellular level. This review draws on recent literature to explore key factors influencing PCM implementation, highlighting the role of innovative leadership, interdisciplinary collaboration, and coordinated funding and regulatory strategies. Success in PCM relies on overcoming challenges such as integrating diverse medical disciplines, securing sustainable investment for shared infrastructures, and navigating complex regulatory landscapes. Effective leadership is crucial for fostering a culture of innovation and teamwork, essential for translating complex biological insights into personalized treatment strategies. The transition to PCM necessitates not only organizational adaptation but also the development of new professional roles and training programs, underscoring the need for a multidisciplinary approach and the importance of team science in overcoming the limitations of traditional medical paradigms. The conclusion underscores that PCM's success hinges on creating collaborative environments that support innovation, adaptability, and shared vision among all stakeholders involved in cancer care.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Throughout the COVID-19 pandemic, masks have been promoted as an important tool for reducing SARS-CoV-2 transmission. However, even though masks are plausible experimental interventions, their mechanistic effectiveness has not been validated by randomized clinical trials (RCTs), with reduction risks of just 1.1-fold (11%) or less. Several meta-analyses have suggested that masks effectively reduce viral transmission, but all of them rely heavily or exclusively on observational data. Indeed, there is a strong inverse correlation between the effectiveness of masks and the number of RCTs included in the meta-analysis. RCTs on alternative therapies often show similar low levels of effectiveness. Thus, masks can be compared with potential new drugs or therapies that failed clinical trials despite showing mechanistic evidence.

The artificial intelligence (AI) refers to the science and engineering of creating intelligent machines for imitating and expanding human intelligence. Given the ongoing evolution of the multidisciplinary integration trend in modern medicine, numerous studies have investigated the power of AI to address orthopaedic-specific problems. One particular area of investigation focuses on the shoulder pathology, which is a range of disorders or abnormalities of shoulder joint, causing pain, inflammation, stiffness, weakness, and reduced range of motion. There has not yet been a comprehensive review of the recent advancements in this field. Therefore, the purpose of this review is to evaluate the current AI applications in the shoulder pathology. This review mainly summarizes several crucial stages of the clinical practice, including predictive models and prognosis, diagnosis, treatment, and physical therapy. In addition, the challenges and future development of AI are also discussed.

Background: Renal cancers are among the top ten causes of cancer-specific mortality, of which the ccRCC subtype is responsible for most cases. The grading of ccRCC is important in determining tumour aggressiveness and clinical management. Objectives: The objectives of this research were to predict the WHO/ISUP grade of ccRCC pre-operatively and characterise the heterogeneity of tumour sub-regions using radiomics and ML models, including comparison with pre-operative biopsy-determined grading in a sub-group. Methods: Data were obtained from multiple institutions across two countries, including 391 patients with pathologically proven ccRCC. For analysis, the data were separated into four cohorts. Cohorts 1 and 2 included data from the respective institutions from the two countries, cohort 3 was the combined data from both cohort 1 and 2, and cohort 4 was a subset of cohort 1, for which both the biopsy and subsequent histology from resection (partial or total nephrectomy) were available. 3D image segmentation was carried out to derive a voxel of interest (VOI) mask. Radiomics features were then extracted from the contrast-enhanced images, and the data were normalised. The Pearson correlation coefficient and the XGBoost model were used to reduce the dimensionality of the features. Thereafter, 11 ML algorithms were implemented for the purpose of predicting the ccRCC grade and characterising the heterogeneity of sub-regions in the tumours. Results: For cohort 1, the 50% tumour core and 25% tumour periphery exhibited the best performance, with an average AUC of 77.9% and 78.6%, respectively. The 50% tumour core presented the highest performance in cohorts 2 and 3, with average AUC values of 87.6% and 76.9%, respectively. With the 25% periphery, cohort 4 showed AUC values of 95.0% and 80.0% for grade prediction when using internal and external validation, respectively, while biopsy histology had an AUC of 31.0% for the classification with the final grade of resection histology as a reference standard. The CatBoost classifier was the best for each of the four cohorts with an average AUC of 80.0%, 86.5%, 77.0% and 90.3% for cohorts 1, 2, 3 and 4 respectively. Conclusion: Radiomics signatures combined with ML have the potential to predict the WHO/ISUP grade of ccRCC with superior performance, when compared to pre-operative biopsy. Moreover, tumour sub-regions contain useful information that should be analysed independently when determining the tumour grade. Therefore, it is possible to distinguish the grade of ccRCC pre-operatively to improve patient care and management.

Abstract: MicroRNAs can interfere with a protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The function of brain-derived neurotrophic factor (BDNF) is essential to the proper formation and function of the nervous system and is seen to be regulated by many microRNAs. However, understanding how microRNAs influence BDNF actions within cells requires a wider comprehension of their integrative regulatory mechanisms. Aim: In this literature review, we have synthesized the evidence of microRNA regulation on BDNF in cells and tissues, and provided an analytical discussion about direct and indirect mechanisms that appeared involved in BDNF regulation by microRNAs. Methods: Searches were conducted on PubMed.gov using the terms “BDNF” AND “MicroRNA” and “brain-derived neurotrophic factor” AND “MicroRNA”, updated on September 1st, 2023. Papers without open access were requested from the authors. One hundred and seventy-one papers were included for review and discussion. Results and Discussion: The local regulation of BDNF by microRNAs involves a complex interaction between a series of microRNAs with target proteins that can either inhibit or enhance BDNF expression, at the core of cell metabolism. Therefore, understanding this homeostatic balance provides resources for the future development of vector-delivery-based therapies for the neuroprotective effects of BDNF.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS>50%; n=10) or low (TPS<1%; n=10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and low PD-L1 expression. After analyzing the correlation between methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with low PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.

The proliferation of SARS-COV-2 through enhanced viral replication and its subsequent triggering of cytokine storm, are some of the hallmark phenotypes in severe COVID-19 patient cases. Cyclosporine, an immunosuppressant drug and Selinexor, an inhibitor of nuclear transporter protein, both have been successfully demonstrated to be effective against SARS-COV-2 infection by targeting those functions individually. However, the highly multifactorial pathology of SARS-COV-2 infection hinders any mono-therapeutic strategy to become an optimal option. In this study, we assess the potential efficacy of the Cyclosporine-Selinexor combination on an integrated interactome by adopting a network-medicine-based repositioning technique, where disease proximity, functional proximity and their topological separation are evaluated, followed by a robust statistical significance test. Results have shown that both drug target modules are highly proximal to the SARS-COV-2 disease modules in terms of network topology and functional associations, in a statistically significant manner, individually. Functional enrichment of both drug modules and SARS-COV-2 infected modules has shown that two drugs target the functions related to viral replication and cytokine storm during infection. Moreover, a high degree of network separation been those two drug target modules has been observed, revealing ``complementary exposure`` patterns, rendering this drug combination as an effective one against SARS-COV-2 infection. We hope that our results will encourage researchers to further investigate the potency of Cyclosporine and Selinexor combination in vivo or in vitro, and ultimately lead that up to clinical trials to treat SARS-COV-2 patients.

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.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

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.

Background Praziquantel is the commonly used conventional treatment recommended for schistosomiasis in the mainstream healthcare system. Although Praziquantel may be free in healthcare facilities, many individuals may resort to the use of traditional medicine. This study aimed to assess perceptions of participants on the availability of Praziquantel and to ascertain whether individuals infected with schistosomiasis used concurrently African traditional medicines with this treatment. Methods A cross–sectional descriptive study, using face-to-face interviews, was conducted from January to April 2023 among healthcare workers (HCWs) and patients. A review of medical chart records of patients was further carried out to triangulate the information from interviews. Ddescriptive statistics including frequency and percentage were used; categorical data were represented as tables. Chi-squared tests were performed for the association between continuous variables. A p value ≤ 0.05 was estimated as statistically significant. Results Most of HCWs (114/124; 91.9%) reported that Praziquantel was available in healthcare facilities. Majority of HCWs (76/124; 61.3%) did not know whether patients seen by them used concurrently traditional medicine and Praziquantel for schistosomiasis. There was no significant relationship between the availability of Praziquantel and the concurrent use of TM by patients for schistosomiasis (X2 = 3.042, p = 0.551). Patients seen by THPs (8/20, 40%) did not use Praziquantel for schistosomiasis. Those patients (8/15, 53.3%) who crossed from TM to the mainstream healthcare system did not disclose their use of TM to HCWs. Their main reason was that concurrent use of TM and Praziquantel could destroy organs or make Praziquantel not to work properly. None of the medical chart records analysed documented the concurrent use of TM and Praziquantel. Conclusion Most of HCWs were not aware of the concurrent use of TM and Praziquantel by patients for the treatment of schistosomiasis. Patients seen by THPs relied solely on TM for schistosomiasis. Although patients indicated crossing from TM to the mainstream healthcare system, there was no evidence of documented use of TM in medical chart records of patients. Further studies are needed to contribute to the knowledge of medicinal plants used by THPs for schistosomiasis.

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.

Background: Schistosomiasis is the third most important Neglected Tropical Disease, with more than 4 million South Africans being infected. Cases of re-infection with schistosomiasis after being treated using modern medication has opened ways to seeking alternative treatment modalities using medicinal plants. This study aims to explore and understand the way traditional healers diagnose schistosomiasis, the types of traditional medicines they use to treat it in communities with a high prevalence of infection, and to establish whether the unavailability of prescribed anti-schistosomal medicines leads to the use of traditional medicine. Methods: A qualitative exploratory study was conducted using a questionnaire from December 2022 to March 2023 in the iLembe District, KwaZulu-Natal Province, South Africa. In-depth individual interviews were carried out among traditional health practitioners (THPs) involved in managing female urogenital schistosomiasis (FUS). Recorded narrative data was transcribed verbatim, read through thoroughly and coded, and analysed using thematic or content analysis Results: Traditional Health Practitioners provide services to many women who did not want to be treated in the mainstream health care system for their FUS. The disease was perceived and understood the same way by most of the respondents, that being caused by use of fresh water. Various plants species, either alone or in combination, were used to manage bilharzia in women. Senecio serratuloides (Asteraceae) and Hypoxis hemerocallidea (Hypoxidaceae) were prominently used by THPs in FUS management. Conclusion: Traditional Health Practitioners are playing a key role in managing bilharzia in women in rural areas of the iLembe District, this study reported that THPs can diagnose schistosomiasis symptoms based on their knowledge and experience. Respondents indicated that modern conventional treatment was readily available and free in public sector healthcare facilities; however, they consulted patients suffering from FUS. Various traditional herbal medicines are reportedly used by THPs to manage bilharzia in women. Further studies are needed to investigate the views and experiences of clients regarding the success of the treatments used and why they seek care from THPs.

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.

Food insecurity is an economic and social condition that involves individuals having limited or uncertain access to healthy food. Despite the well-intentioned efforts of both governmental and not-for-profit organizations in addressing food insecurity, well over one-in-ten households in the U.S., the wealthiest nation in the world, experience food insecurity every year. This literature review covered several government programs and research interventions designed to address food insecurity. Results from the review highlight how the Supplemental Nutrition Assistance Program (SNAP), The Emergency Food Assistance Program (TEFAP), and not-for profit food banks have demonstrated success in improving food insecurity. However, the prevalence of food insecurity among U.S. households has fluctuated without any sustained decreases that achieve a food insecurity rate that remains below 10 percent of the population. Food waste, which refers to food that is edible yet discarded at the retail or consumption phases, is rampant in the U.S., as approximately 30 percent (66.5 million tons) of edible food is wasted after leaving the farm every year. Food waste prevention efforts that involve rescuing edible, nutritious food and redistributing it to individuals who are food insecure can promote both environmental- and public health through simultaneous reductions in food waste and food insecurity.

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.

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.

Studies on Medical Geology have up till recently tended to emphasise the harmful effects of geological material and processes. This is perhaps justifiable, given the realisation that many environmental diseases could have causal links with some geo-environmental variables as co-factors, making such studies extremely valuable in the improvement of diagnoses and therapy. However, this review aims to show that in addition to the high value of such research, studies conducted on the beneficial properties of Earth materials also have considerable merit, given their enormous potential for assuaging a wide range of environmental health disorders. For instance, certain geological materials including clay minerals contain active substances that show considerable promise in various applications such as pharmaceutical formulations, aesthetic medicine, and indigenous medicine. This review synthesises current knowledge of how certain geological materials can be exploited in formulating remedies for some human health problems. Reports of the therapeutic uses of clay minerals, zinc oxide (zincite), zeolite, and kaolin are appraised. The review shows that ancient and contemporary use of geological materials such as clay minerals have played crucial roles in the treatment of several human diseases, with recent and ongoing research revealing further development in these applications. Well strategised clinical trials using available resources could give impetus to further research in elucidating the potential of various geomaterials as innovative clinical remedies for some human diseases and infections as well as aid the proper scientific documentation of their natural uses.

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.

Adherence is vital for medicine to have an effect, yet adherence is considered to be low. However, research into adherence tends to focus on quantitative analysis of performance, something which fails to perceive how people are adherent in their many different environments. As a contribution to gaining a deeper understanding, interviews were held with 30 individuals in UK, Egypt, Kazakhstan and 6 countries in sub-Saharan Africa to understand their perceptions on adherence for a range of drugs, and these were compared with an existing well-regarded list. New reasons for non-adherence were discovered, and a new viewpoint on adherence derived which considers adherence to be a single act and therefore as an individual opportunity to be adherent, permitting greater focus on the enablers and inhibitors of adherence at a point in time.

SARS-CoV-2 Omicron variant spike RBD epitopes in complex with spike (S) -protein D614G mutations now predominate globally and increase infectivity by assembling more functional S proteins into the virion. On average, homeopathic medicine contains less than one molecule per dose on average. Single variable SphericalHarmonicY, LaguerreL, WhittakerM, SphericalBesselJ, LegendreP, LegendreQ, LaguerreL, ChebyshevT, and Hypergeometric1F1 Functions pFqarise in connection with the power series solution of the Schrodinger equation or in the summation of perturbation expansions in quantum mechanics. A quantum interpretation of the homeopathic method is presented here through a novel algebraic topology approach to supersymmetry and symmetry breaking in quantum fields and quantum gravity theory with the aim of developing a wide range of physical-based drug design applications in a Small Molecule Quantized Water Memory Network suggesting that the Hidden Black Hole Paradox of Information Loss might be solved under suitable conditions.

Recent advancements in molecular diagnostics have highlighted the potential of circulating cell-free DNA (ccfDNA) as a biomarker in various diseases. This study aims to explore the role of ccfDNA in the early diagnosis, prognosis, and therapeutic monitoring of diseases, with a focus on oncology. We conducted a comprehensive review and analysis of current literature, combined with experimental approaches involving advanced genomic sequencing and bioinformatics techniques. Our research systematically characterizes the molecular composition of ccfDNA, including its origins, size distribution, and methylation patterns, across different disease states. Furthermore, we investigate the dynamics of ccfDNA release and clearance in the bloodstream, elucidating mechanisms that could influence its diagnostic accuracy. In the context of cancer, we analyze the correlation between tumor-derived ccfDNA and disease progression, response to therapy, and overall survival. Our findings indicate that ccfDNA holds promise as a non-invasive biomarker for early disease detection, real-time monitoring of treatment efficacy, and potentially, predicting relapse. This study contributes to the growing field of liquid biopsies and opens new avenues for personalized medicine, emphasizing the need for standardized protocols in ccfDNA analysis to maximize its clinical utility. The implications of our findings extend beyond oncology, suggesting potential applications of ccfDNA in other pathological conditions.

This review study, delves into the groundbreaking potential of quantum dots in revolutionizing the field of stem cell tracking for regenerative medicine. Beginning with an introduction that underscores the pivotal role of stem cell tracking in regenerative medicine, this review introduces quantum dots as promising tools for this purpose. It proceeds to explore the fundamental properties of quantum dots, including the quantum confinement effect, size-dependent emission, and exceptional brightness, which render them ideal candidates for stem cell tracking. The historical evolution and recent advancements of quantum dot technology in biomedicine are discussed, emphasizing their growing importance in terms of biocompatibility and safety. Furthermore, various labeling strategies for stem cells using quantum dots are detailed, encompassing surface modification and internalization techniques, with a comparison of their respective advantages and drawbacks. A comprehensive exploration of the wide range of imaging modalities that synergize with quantum dots for stem cell tracking is presented, accompanied by an evaluation of their strengths and limitations. Real-world applications of quantum dot-based stem cell tracking in regenerative medicine, spanning tissue regeneration to disease modeling, are showcased, with illuminating case studies. Current challenges and limitations in quantum dot-based stem cell tracking, including long-term stability and regulatory considerations, are addressed, and innovative directions and emerging trends in quantum dot technology are proposed. Safety considerations and strategies to enhance quantum dot biocompatibility within biological systems are discussed, while ethical and regulatory implications related to their use in stem cell tracking are explored, promoting responsible research and development practices. Finally, the review concludes by summarizing key insights and takeaways, reaffirming the transformative potential of quantum dots in advancing stem cell tracking and the field of regenerative medicine.

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.

Cancer diagnosis stands at the cusp of a profound transformation, driven by the burgeoning capabilities of Artificial Intelligence (AI) and Machine Learning (ML). This comprehensive review illuminates the extraordinary impact of AI and ML in the field, unraveling their multifaceted roles in the realm of oncology. In the arena of cancer diagnosis, AI and ML serve as invaluable allies, empowering healthcare professionals with unparalleled tools for precision and efficiency. Notably, AI's prowess in analyzing medical images, including radiological scans and pathology slides, elevates the early detection of malignancies to new heights. Coupled with its ability to dissect genomic data, AI tailors therapeutic strategies to the individual, promising optimized treatment outcomes. However, the incorporation of AI and ML into clinical practice necessitates a careful navigation of ethical considerations, data privacy, and regulatory landscapes. Safeguarding patient data, ensuring transparency, and addressing algorithmic biases emerge as pivotal challenges that require vigilant attention. Yet, the future of AI and ML in cancer diagnosis is brimming with promise. The integration of multi-modal data, real-time monitoring, and Explainable AI (XAI) methods holds the potential to enrich diagnostic capabilities and engender patient trust. Global collaboration and data sharing initiatives are fostering the development of robust AI models. Furthermore, AI's role in cancer prevention, identifying high-risk individuals and enabling targeted preventive strategies, is poised to revolutionize healthcare. AI and ML are forging a path toward an era of unparalleled accuracy, efficiency, and personalization in cancer diagnosis. Challenges notwithstanding, these technologies bear the promise of fundamentally reshaping patient care, elevating outcomes, and advancing the fight against cancer. The ongoing exploration and responsible implementation of AI and ML in oncology will be pivotal in harnessing their full potential and paving the way for a brighter future for cancer patients.

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.

This review article offers an in-depth look at DNA, its discovery, structure, functions, and the significant role it plays in modern biomedical research. It begins by revisiting the landmark discovery of the DNA double helix by scientists Watson and Crick, a structure resembling a twisted ladder that forms the blueprint of life. The review explains the basic processes of DNA replication (copying DNA), transcription (converting DNA to RNA), and translation (turning RNA into proteins), which are fundamental to understanding how genetic information is passed on and used by living organisms. The article then explores gene regulation and epigenetics, which involve how genes are turned on or off and how environmental factors can affect gene expression without changing the DNA sequence itself. It examines how DNA interacts with various proteins and modifiers, which play crucial roles in these processes. A major focus is on the advancements in DNA sequencing technologies. From the initial Sanger sequencing method, which was labor-intensive and time-consuming, to the highly efficient next-generation sequencing (NGS) and the latest single-molecule sequencing techniques, the review covers how these technologies have revolutionized genomics and personalized medicine. It also highlights the importance of computational genomics and bioinformatics, fields that deal with analyzing and interpreting the vast amounts of data generated by DNA sequencing. The review discusses DNA's crucial role in understanding human diseases. It covers DNA-based research in cancer, rare genetic disorders, infectious diseases, and pharmacogenomics (how genes affect a person's response to drugs). It emphasizes studies that have led to new ways of diagnosing and treating diseases. The article looks at the future of DNA research. It talks about emerging technologies like CRISPR-Cas9, a revolutionary gene-editing tool that allows scientists to modify DNA with high precision. Synthetic biology, an interdisciplinary field that combines biology and engineering for designing and constructing new biological parts and systems, is also discussed. Furthermore, DNA nanotechnology, which involves designing DNA molecules for technological uses, is explored. Finally, the review addresses ethical issues in DNA research, such as privacy concerns and debates over genome editing.

Circulating tumor cells (CTCs) are cells released from the primary tumor and intravasate into the blood or lymphatic vessels, where they are transported to distant sites and act as seeds that initiate cancer metastases. Recent advances in CTC research have shown their relevance as prognostic markers for early and metastatic disease detection, predictive biomarkers for relapse, and response to medical intervention or therapy. The rapidly evolving landscape of CTC biology has opened new avenues for understanding cancer progression, metastasis, and treatment response. Additionally, translating these findings into clinical applications holds promise for improving cancer diagnostics, prognosis, and personalized therapeutic strategies. This review discusses the significance of CTCs in cancer research and their associated challenges. We explore recent developments in the detection and characterization of CTCs and their implications in cancer research and clinical practice.

Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects: antioxidant, anti-inflammatory and immunomodulatory, which involves inhibiting molec-ular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential, analysis of cyto-kine, protein and gene expression were investigated in the head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified mor-phology, inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in G2/M and S. A decrease in cell migration was also observed, and decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IF-y and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anti-cancer effects on tumor cells, and could be a promising natural treatment by regulating signaling pathways associated with head and neck cancer.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Biliary tract cancers, including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a heterogeneous group of cancers with distinct molecular characteristics in each anatomic and pathological subtype. The pathological classification of BTC includes grossly classifiable growth patterns, such as mass-forming, periductal infiltrating, and intraductal growing. The small duct and large duct types of intrahepatic cholangiocarcinoma have been recently introduced in the WHO classification. Typical clinical presentations and various radiological, endoscopic, and molecular modalities for diagnosis are described in detail. To overcome the limitations of traditional tissue acquisition, new diagnostic modalities are being investigated. In fact, the treatment landscape is evolving rapidly owing to the emergence of distinct subgroups harboring unique molecular alterations with corresponding targeted therapies. In addition, we highlight the key points in the diagnostic process in real-world clinical practice for biliary tract cancer.

Antidepressants are among the most used medications in the US, with significant deleterious effects on people’s well-being. At any given time, depression impacts approximately 1 in 10 Americans, causing wide and broad societal costs. Interest is developing for non-pharmacological treatments and preventative measures. We summarize the literature on non-invasive dietary and lifestyle approaches for treating depression, including recent work with the psychedelic treatment of depression. This review aims to inform future research and treatment programs for depression. This review provides an evidentiary summary of integrative therapeutic approaches for depression.

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.

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. 2cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning Electron Microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails.

Burning mouth syndrome (BMS) is a chronic oral pain disorder. There is a theory that BMS is nociplastic pain. Standard treatment for BMS has not yet been established. Kampo medicine is a traditional oriental medicine. The purpose of this study is to evaluate the effectiveness of rikkosan—a traditional Japanese herbal medicine (Kampo)—in the treatment of BMS. A single-center retrospective study was conducted in 20 patients who were diagnosed with BMS and treated with rikkosan alone (7.5 g) three times daily for approximately 4 weeks. They were treated with rikkosan alone approximately 4 weeks (29.5 ± 6.5 days) for the initial treatment. They had an average age of 63 years and 90% were being treated for other illnesses, but their medication status was the same during this study period, except for rikkosan. No side effects were observed in patients. Numerical rating scale (NRS) or visual analogue scale (VAS)/10 scores decreased significantly between the time of the initiation of rikkosan and the one-month after (-2.1 ± 1.2, p < 0.05). Rikkosan has a short-term effect of reducing NRS by two levels in BMS patients.

Myelodysplastic neoplasm (MDS) is a heterogenous clonal disorder of hemopoietic stem cells charac-terized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of pro-gression to Acute Myeloid Leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently prognostication and treatment are determined by cytogenetic and molecular data. Specific genetic abnormalities such as 5q deletion (del 5q), TP53 inactivation and SF3B1 mutation, are increasingly associated with disease phenotype and outcomes, as reflected in the recently updated 5th edition of the World Health Organization Classification of Hematolymphoid Tumors (WHO5) and International Consensus Classification 2022 (ICC 2022) classifications. Treatments are in-creasingly being tailored for patient specific phenotypes, and trials exploring the efficacy of targeted treatments are ongoing in this era of precision medicine.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Blocking the interaction of the SARS-CoV-2 spike protein with the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim in this study was to explore the efficacy of TCM treatments for SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. The antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis was found to be effective against SARS-CoV-2 infection through affecting the interaction of viral spike protein with the hACE2 protein. The active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside, respectively, found in S. baicalensis, exhibited strong inhibitory activities, targeting the viral spike protein or hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors of the interaction of the Omicron spike protein and hACE2 receptor from S. baicalensis. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

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.

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.

Vaccination represents the historical milestone in medical sciences, which has been saving millions of lives. Nonetheless, continued outbreaks of emergent infectious diseases are swamping from every coast to every border all over the world. Modern vaccines are our most powerful arsenals to defend the public health of a global population ever since 1796. As unexpected, modern vaccination approaches have brought out all sorts of unwelcome pathogenic disorders to varying extents. Pathogenic viruses have also continued to evolve to defeat elaborate arsenals devised by human intelligence. In this review, we have covered a variety of vaccination approaches along with their sophisticated materials from the past to the most recent development. Furthermore, we discuss varied serious pathogenic outcomes elicited by contemporary vaccination programmes involving novel materials in real clinical trials. The complex immune mediators will be discussed in the context to tackle the complication of vaccine-induced pathogenesis. We will offer the insight into the intractable discrepancy of vaccine-associated pathology. The precision approach bestowed with evolutionary concepts will be considered as a feasible option to confront various issues of pathogenic complicacy.

Foot pain related to the plantar fascia is common in adults regardless of athletic background. Many pathologies can lead to the diagnosis of plantar enthesopathy, but the most relevant to this case study is related to structural defects within the plantar fascia. Due to the variety and sometimes unclear etiology of plantar fasciosis, no single standard of care treatment protocol is recognized. Often, patients receive NSAIDs, night splints, taping, physical therapy, foot orthosis, and extracorporeal shock wave therapies. This study presents Wharton Jelly (WJ) tissue allografts as an additional intervention for patients who fail standard-care treatments. WJ allografts are applied to supplement connective tissue defects directly, unlike other therapies, which aim to reduce swelling and symptomatic pain. This retrospective study includes seven patients who have previously failed standard-of-care treatment. Each received extracorporeal pulse-activated therapy (EPAT), WJ, laser therapy, and an orthotic. Patient progress was tracked using a visual analog scale, 0-10 scoring, reported by the patient at the initial visit and approximately thirteen weeks following, reporting an average improvement of 50%. The study's limitations include a small cohort size and a non-blinded retrospective design. These promising results provide evidence for a more extensive, randomized study to define dosage protocols further and confirm safety and efficacy.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

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.

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.

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.

OBJECTIVE: Analyzing the effects of different physical exercise programs on the anthropometric, cardiovascular, metabolic, and strength variables of the elderly participating in health care programs. METHODS: Controlled clinical trial, with 60 elderly participants from health care groups, allocated into four groups: Group of resistance exercises in open-air gyms – GT1 (n = 17); Group of aerobic and localized exercises - GT2 (n = 11); Group of resistance exercises at GT3 gym (n = 17); Control group: non-exercise practitioners - CG (n = 15). Anthropometric (BMI, % body fat, and waist circumference), cardiovascular (SBP, DBP, HR, and DP), metabolic (total cholesterol, triglycerides, and glycemia), and strength variables were evaluated before and after 16 weeks of intervention. Descriptive statistics, Shapiro-Wilk and Kolmogorov-Smirnov normality test, equal variance test, T-Student test, non-parametric Mann-Witney test, ANOVA One Way, multivariate data analysis using data mining and machine learning techniques, Pearson and Spearman correlation tests, Classical Clustering (Agglomerative Hierarchical Method); Principal Component Analysis (PCA), Z score, Fruchterman-Reingold algorithm, Euclidian Similarity Index and, Cohen’s equations were applied. RESULTS: To observe effect size, morphofunctional variables for the GT1 group show a small effect for fat percentage, WHR, and ULS and a medium effect for LLS. For the GT2 group, there was a small effect for fat percentage, WHR, and ULS and a large effect for LLS. For the GT3 group, there was a small effect for the percentage of fat and HC, a medium effect for ULS, and a large effect for LLS. A small effect for glycemia in GT1, a medium effect for glycemia and triglycerides for GT2, a small effect for total cholesterol for GT3, and a large effect for glycemia in CG, with this effect being an increase in this analyte. For the cardiovascular variables, there is a small effect for SBP and HR in GT1, a small effect for DBP, HR, and DP, and a large effect for SBP in GT2, a small effect for SBP, DBP, and HR in GT3 and small effects for SBP and HR in CG. The correlation between BMI (P = 0.0007) and Body Fat% (P = 0.007) with ULS. The variables TG, LLS, and ULS were the ones that differed most in each type of stimulus chosen as an intervention in the present study. CONCLUSIONS: The results of this study indicate that GT2 caused more significant percentage reductions in body mass and BMI. However, GT3 caused greater fat percentage reduction. The GT2 caused the greatest decrease in waist circumference, while the GT3 caused the largest decline in hip circumference. The three groups induced an increase in strength (ULS and LLS). However, in ascending order, GT1 caused the smallest increase, GT2 an intermediate increase, and GT3 the greatest increase in strength, with considerable effects in GT2 and GT3. Finally, GT2 caused a greater percentage reduction in systolic blood pressure (large effect) and double product (small effect) than the other groups. The three methods proved to be efficient, but with particularities that may reflect the choice of one over another due to health conditions, objectives to be achieved, or characteristics of the patient at the time of their choice by the prescriber.

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.

: A comprehensive analysis was performed, considering blockchain technology (BT) proprieties in digital health, addressing medico-legal, privacy, and regulatory considerations. Adherence to personal data protection and healthcare regulatory guidelines were analyzed and compared for GDPR (Europe), HIPAA (United States), CCPA (California), PIPEDA (Canada), Privacy Act of 1988 (Australia), APPI (Japan), and LGPD (Brazil). Issues such as Health Systems, Strengthening and aligning policy orientations and initiatives, and emphasizing the role of data analysis in shaping health policies were explored. The study addressed conflicts between the legal frameworks and blockchain, comparing and suggesting solutions like revision of laws and integration of com-pliance mechanisms. Additionally, it sought to enhance IT-health literacy by integrating healthcare and legal domains. Ongoing collaboration between legal, health, and IT experts is essential for designing systems that effectively balance privacy rights and data protection while maximizing the benefits of disruptive technologies like blockchain.

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.

Abstract: This review addresses the complexities of type 1 diabetes (T1D)and its associated complications, with a par-ticular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of the review is devoted to technological advances in diabetes management, particu-larly the use of Hybrid Closed Loop systems (HCLS) and to the potential of open-source HCLS systems, which could be easily adapted to different patiens’needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient outcomes.

Abstract: The use of IVF and related procedures has offered opportunities for couples to conceive who otherwise would remain childless. This technology is often viewed as the only option but is very expensive and not highly effective. ln an effort to improve access to care, governments are attempting to provide funding. In Ireland for example the Health Service Executive (HSE) has recently made IVF funding available through Regional Fertility Hubs. for couples who qualify. However, this policy has threatened a less invasive approach available in Ireland that can help many couples before IVF is employed. We propose that a newly emerging “medical treatment process” called Restorative Reproductive Medicine (RRM), combined with methods or apps that track biomarkers of the menstrual cycle as a prerequisite option for appropriate patients. To illustrate the effectiveness, we compared live birth rates from an established Irish RRM clinic that uses the ChartNeo app to HFEA (Human Fertilization and Embryology Authority) data, both from 2019. RRM treatment had a live birth rate of 40.4% compared to 24.4% per treatment cycle for IVF (P>0.0001). RRM twin pregnancy rate was 2.5% compared to 7% for IVF. RRM babies were usually full term and normal birth weight. Therefore, RRM is less expensive, less invasive, and more effective than IVF for most patients. This merits further evaluation and support by the HSE and other global authorities guiding health policy.

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.

The incidence of chronic enteropathies (CE), in particular food-responsive enteropathies (FRE) in dogs, is on the rise in veterinary practice. The symptoms of these digestive disorders cannot be alleviated with the use of commercial hypoallergenic feeds. The applicability of novel substrates in hypoallergenic dog feeds is limited, and edible insects could pose a viable alternative. Insects have a high nutritional value, and their potential can be harnessed to design personalized nutrition strategies. However, the use of insects in animal feeds should be rigorously tested. The aim of this study was to analyze the applicability of edible insects as a source of dietary protein for companion animals, including the current and future prospects. Canine food formulas should be evaluated in a clinical setting. The role edible insects in pet diets and the efficacy of this substrate in animal nutrition should be examined in advanced clinical trials in gastroenterology, histology, immunology, and microbiology. These efforts are required to guarantee the safety and efficacy of innovative insect-based feeds and to increase their popularity among veterinary practitioners, pet food producers, and animal owners.

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.

Introduction: In an era of increasing public awareness regarding the pivotal role of nutrition in the onset and progression of chronic degenerative diseases, there is a growing demand for information and assistance pertaining to the intricate relationship between diet and disease. Nutritional practices, therefore, emerge as a fundamental element in the prevention and management of these maladies, necessitating a proactive response from healthcare professionals (HCP). This study sought to evaluate the impact of participation in a Culinary Medicine (CM) program on Mediterranean diet adherence, food management skills, culinary proficiency, and counseling confidence among HCP. Methods: A mixed-methods pilot implementation program (PIP) was meticulously designed and executed, engaging a cohort of 20 HCP recruited from Hospital Clinic Barcelona. The program unfolded at the Alícia Foundation kitchen-lab and encompassed a series of interactive, hands-on sessions that delved into the realms of gastronomy, food management, culinary skills, and culinary diet therapy, with a specific focus on prevalent diseases and their prevention, treatment, and care. Tailored questionnaires were administered to all participants both before and after the PIP. Results: Of the 20 participants, 14 successfully completed the study, comprising 86% women, 86% aged above 40, 71% nurses, and 7% medical doctors. Interestingly, 86% of the participants had previously received nutrition training, whereas only 14% had received culinary training. Following the completion of the program, there was a remarkable improvement in adherence to the Mediterranean diet (p < 0.01). However, no statistically significant improvements were observed in food management and culinary skills or counseling confidence (p > 0.5). Despite the absence of statistical significance, there was a noteworthy trend towards greater advocacy for dietary changes before resorting to medication, along with enhanced confidence in providing nutritional and culinary guidance to patients. Conclusion: The findings from this study underscore the potential of hands-on CM training as a vital component of nutrition education for HCP. While statistically significant improvements in certain domains were not observed, the program did demonstrate its ability to influence attitudes, knowledge, and behaviors related to healthy cooking and eating for both HCP themselves and their patients. Given these promising trends, future studies with a larger sample size must be performed to further elucidate the impact of CM training on HCP and its potential benefits for public health.

Adipose stem cells (ASCs) have multilineage differentiation capacity and hold great potential for regenerative medicine. Compared to bone-marrow-derived mesenchymal stem cells (bmMSCs), ASCs are easier to isolate from abundant sources with significantly higher yields. It is generally accepted that bmMSCs show age-related changes in their proliferation and differentiation potentials, whereas this aspect is still controversial in the case of ASCs. In this review, we evaluated the existing data on the effect of donor age on the osteogenic potential of human ASCs. Overall, a poor agreement has been achieved because of inconsistent findings in the previous studies. Finally, we attempted to delineate the possible reasons behind the lack of agreements reported in the literature. ASCs represent a heterogeneous cell population and the osteogenic potential of ASCs can be influenced by donor-related factors such as age, but also gender, lifestyle, and the underlying health and metabolic state of donors. Furthermore, future studies should consider experimental factors in in-vitro conditions, including passaging, cryopreservation, culture conditions, variations in differentiation protocols, and readout methods.

In the realm of artificial intelligence, knowledge graphs have become a fascinating area of research. Relationships between entities are depicted through a structural framework in knowledge graphs. In this paper, we propose to build a domain-specific medicine dictionary (DSMD) based on the principles of knowledge graphs. Our dictionary is composed of structured triples, where each entity is defined as a concept, and these concepts are interconnected through relationships. This comprehensive dictionary boasts more than 348,000 triples, encompassing over 20,000 medicine brands and 1,500 generic medicines. It offers a groundbreaking approach to storing and accessing medical data. Our dictionary facilitates various functionalities, including medicine brand information extraction, brand-specific queries, as well as queries involving two words or question answering. We anticipate that our dictionary will serve a broad spectrum of users, catering to both human users, such as diverse range of healthcare professionals as well as AI applications.

Abstract：To investigate the effects of feeding the Lincomycin and faecal bacterial on weaning stress in Tibetan piglets, we divided the weaned Tibetan piglets at 30 days of age into four groups. We measured growth performance, blood physiological indexes, and metabolomics. The results showed that the Ant, Tib, and Fec groups significantly reduced the ratio of diarrhoea to feed/weight (F/G) and increased the average daily gain (ADG) compared to the Nor group (p < 0.01). The Nor group had significantly lower leukocyte counts, hemoglobin levels, and erythrocyte counts compared to the other three groups on 21d (p < 0.05). These physiological indexes tended to stabilize on 42d. We found that there were beneficial metabolites and metabolic pathways for gastrointestinal function. Specifically, the porphyrin metabolic pathway was elevated in the Ant group, and the tryptophan metabolic pathway was significantly elevated in the Tib and Fec groups compared to the Nor group (p < 0.05). In conclusion, adding faecal bacterial supernatant and fifteen-flavour black pills of Tibetan medicine to the feed reduced the rate of diarrhoea and improved the growth performance of piglets. Moreover, it had an effect on microorganisms and their metabolites and pathways in the gastrointestinal tract of the animals, which might be the main reason for influencing the diarrhoea rate of weaned Tibetan piglets and the growth and development of the piglets. This study provides a new approach for anti-stress applications in weaned Tibetan piglets and the development of substitute anti-products.

Background: COVID-19 was initially identified as a respiratory system disorder, but it has been discovered to interact with and influence the cardiovascular system. COVID-19-associated cardiovascular (CV) complications are common, resulting in high acute phase mortality and a large number of morbidities in the chronic phase, thus severely impacting patients' quality of life and health outcomes. Nevertheless, clinical, cellular, and molecular biological factors underlying the pathophysiology of cardiovascular complications associated with COVID-19 are poorly understood. Objective: This review investigates putative underlying clinical factors as well as cellular and molecular biological mechanisms by which COVID-19 leads to acute CV complications, including state-of-the-art genomic sequencing-based findings, assessing the long-term CV consequences of COVID-19, and aiming to shed light on developing strategies for differential diagnosis, risk prognostic stratification, prevention, and clinical management of CV sequlea in COVID-19 patients. Methods: For this purpose, a through review of literature and published data was carried out from first report of COVID-19 till October 2023 to find out a comprehensive account of clinical, cellular and molecular genetic factors underlying COVID-19-associated cardiovascular diseases. Results: We found that the relationship between COVID-19 and CV risk is complex and multifaceted. In addition to acute COVID-19 detertriuos effects, COVID-19 survivors may experience long-term CV effects. We provide a detailed account of the involvement of a large number of genomic alterations, microRNAs, and novel viral as well as host proteins in CVDs associated with COVID-19, which has helped identify some novel drug targets to treat COVID-19-related cardiovascular complications. Conclusions: The relationship between COVID-19 and CV risk is complex and multifaceted. While COVID-19 primarily affects the respiratory system, it can also significantly affect CV health. as compared to classical cardiovascular diseases, there are new clinical, cellular and molecular biological factors in CVDs related to COVID-19, that need specific diagnostic assays, prognostic stratification and treatment modules. Therefore, specail care is must taken to treat cardiovascular diseases associated with COVID-19.

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.

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.

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.

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.

(1) Background: There is a need to assess the availability of essential antimicrobials as the availability of an antimicrobial is a critical element of its rational use. We aimed to assess the availability of antimicrobials listed in National List of Essential Medicines 2015, India (primary list) and a selected (secondary) list comprising of agents indicated for commonly encountered infectious illnesses in various healthcare settings and to identify the reasons for their non-availability. (2) Methods: A cross-sectional survey of 25 public, private, and other sector pharmacies was carried out in Rohtak, a district of North Indian state of Haryana, from April to June 2022. (3) Results: Most of the antimicrobials surveyed were optimally available in various sector pharmacies with the exception of benzathine benzyl penicillin, benzyl penicillin, cloxacillin, cefazolin, cefuroxime, cefadroxil, amphotericin B and antimalarials. Most frequent reasons for limited availability were low demand, no prescriptions and non-listing of drugs in state essential medicine list. (4) Conclusions: Enough evidence needs to be generated with respect to status of availability of essential antimicrobials from different regions of India as well as other lower-middle income countries to devise measures for ascertaining better availability of these agents especially antibiotics at regional, national and global scales.

Dietary supplements are widely embraced by cancer patients seeking complementary and integrative approaches to their care. Unfortunately, many patients do not discuss supplement use with physicians, often due to perceptions of physician indifference or negativity toward supplements. This communication gap exposes patients to unreliable information sources and, potentially, unnecessary risk. As the healthcare landscape evolves, patients increasingly value physicians who recognize their pivotal role in shaping healthcare decisions. This patient-centered perspective emphasizes the provision of evidence-based information tailored to individual needs, open discussions on potential risks, and shared decision-making. It underscores the importance of respecting patient autonomy, offering alternative options, documenting preferences, and ensuring ongoing support while coordinating with the healthcare team. To address these needs, healthcare providers should transform their perspectives and become expert guides who embrace patients as informed, empowered participants. This approach prioritizes open dialogue that considers both facts and uncertainties regarding dietary supplement use, allowing for mutually informed decision-making. Here, we review the literature and present a practical approach emphasizing open discussions, transparency, and respect for patient autonomy. Following this approach, healthcare providers can empower patients to navigate the complexities of dietary supplement use in the context of cancer care, ultimately safeguarding patient safety and well-being.

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.

Benign Paroxysmal Positional Vertigo (BPPV) represents the most frequent cause of peripheral vertigo. In most cases it is successfully treated by canalith repositioning procedure (CRP), but it is often followed by a continuous lightheadedness in absence of vertigo or nystagmus (residual dizziness, RD). Our aim is to describe the clinical effectiveness and the urine metabolomics profile treating these patients by a polyphenol compound supplementation. We enrolled 30 patients reporting RD after BPPV successfully treated using CRP. A supplementation with a Polyphenol compound was administered for 60 days, and patients were evaluated after 30 and 60 days of treatment by a self-administered questionnaires (Visual Analog Scales for Dizziness and Nausea, Dizziness Handicap Inventory, DHI) and by urine metabolomics analysis performed by 1H-NMR spectroscopy and multivariate followed by univariate analysis. Most patients reported an excellent or good efficacy of RD with a significant decrease for VAS and DHI values. The metabolomics analysis identified six significant metabolites related to the treatment: 1-methylnicotinamide, anserine, Hippurate, lysine, methyl succinate, and urea indicating an inflammatory activities and antioxidant properties of the polyphenol compound. These preliminary data suggest that supplementation with a polyphenol compound cold induces some metabolic changes that can help recover RD. However, the future steps will require confirmation with a more significant cohort of patients and an extension of the metabolomic evaluation to other problems concerning the different clinical aspects of BPPV, such as the high relapse found in a high percentage of patients.

Pregnancy at advanced maternal age is considered a risk factor for adverse maternal, fetal, and neonatal outcomes. Here we investigated whether maternal age could be associated with differences in the blood levels of newborn screening (NBS) markers for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP). Population-level NBS data from screen-negative singleton infants were examined, which included blood metabolic markers and covariates such as gestational age, birth weight, age at blood collection, infant sex, parent-reported ethnicity, and maternal age at delivery. Marker levels were compared between maternal age groups (age range: 15-44 years) using effect size analyses, which controlled for group size differences and potential confounding from other covariates. Our results showed that 13% of the markers had maternal age-related differences including newborn metabolites with either increased (C14, C16, C18, C18:1, C3DC) or decreased (C5OH) levels at advanced maternal age group (≥35 years, absolute Cohen’s d ≥ 0.2). The increased C3DC levels in this group correlated with a higher false-positive rate in newborn screening for malonic acidemia (p-value < 0.001), while no significant difference in screening performance was seen for other markers. Maternal age at delivery is associated with inborn metabolic differences and should be considered together with other clinical variables in genetic disease screening.

Background. The SARS-CoV-2pandemic has become the greatest public health challenge worldwide. Intensive research started to develop vaccines and by the late 2020 vaccination campaign started. Objective. Collecting information from European countries, how and in what extent were family physicians/general practitioners/FPs/GPs involved in the vaccinations-campaign in 2021 and how was it organized at national level. Method. A short questionnaire was distributed through the secretariats of WONCA-Europe and the European Forum for Primary Care. Results. In most of the countries participation of FPs/GPs was compulsory. The vaccination was usually centrally organized by governmental authorities. At the beginning (web-based) registration of patients was required, mainly at national level. By the mid of 2021, vaccination on walk in basis became available in almost every country for the first and for the booster injections. The remunerations of GPs/FPs were differed, in some countries without extra payment. The Pfizer’s vaccine was used in all countries; while in 9 countries not EMA approved vaccines were also used in primary care settings and at vaccination centres. In some countries, professional homepages helped the GPs. The involvement of PHC providers did not correlate to the vaccination coverage of the entire population of the respective countries. It was the highest in the more developed countries with higher living standard, where participation of GPs was voluntary and appropriate financial incentives were offered for them. Conclusion. The vaccination campaign was a professional and logistic challenge and an excellent performance of PC providers. Experiences gained could be used in the future to manage similar pandemic challenges.

Prostate cancer (PCa) is characterised by androgen-dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate cancer (CRPC) emerges, characterised by heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through the investigation of gene and protein annotations and the integration of several published transcriptomic data, we identified two consensus lists to stratify PCa patients' risk and discriminate CRPC phenotypes based on androgen receptor activity. ROC and Kaplan-Meier survival analyses were used for gene set validation in independent datasets. We further evaluated these genes for their association with cancer dependency. The deregulated expression of the PCa-related genes was associated with overall and disease-specific survival, metastasis and/or high recurrence risk, while the CRPC-related genes clearly discriminated between adeno and neuroendocrine phenotypes. Some of the genes showed context-specific essentiality. We further identified candidate drugs through a computational repositioning approach for targeting these genes and treating lethal variants of PCa. This work provides a proof-of-concept for the use of an integrative approach to identify candidate biomarkers involved in PCa progression and CRPC pathogenesis within the goal of precision medicine.

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.

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.

Using nanoparticles (NPs) in drug delivery has exhibited promising therapeutic potential 13 in various cancer types. Nevertheless, several challenges must be addressed, including the 14 formation of the protein corona, reduced targeting efficiency and specificity, potential immune 15 responses, and issues related to NP penetration and distribution within 3-dimensional tissues. 16 To tackle these challenges, we have successfully integrated iron oxide nanoparticles into 17 neuroblastoma-derived extracellular vesicles (EVs) using the parental labeling method. We first de- 18 veloped a tissue-engineered (TE) neuroblastoma model, confirming the viability and proliferation 19 of neuroblastoma cells for at least 12 days, supporting its utility for EV isolation. Importantly, EVs 20 from long-term cultures exhibited no differences compared to short-term cultures. Concurrently, 21 we designed Rhodamine (Rh), Polyacrylic acid (PAA)-functionalized magnetite nanoparticles 22 (Fe3O4@PAA-Rh) with high crystallinity, purity, and superparamagnetic properties (average size: 23 9.2 ± 2.5 nm). We then investigated the internalization of Fe3O4@PAA-Rh nanoparticles within 24 neuroblastoma cells within the TE model. Maximum accumulation was observed overnight while 25 ensuring robust cell viability. However, nanoparticle internalization was low. Taking advantage of 26 the enhanced glucose metabolism exhibited by cancer cells, glucose (Glc)-functionalized nanoparti- 27 cles (Fe3O4@PAA-Rh-Glc) were synthesized, showing superior cell uptake within the 3D model 28 without inducing toxicity. These glucose-modified nanoparticles were selected for parental labeling 29 of the TE models, showing effective NPs encapsulation into EVs. 30 Our research introduces innovative approaches to advance NPs delivery. By partially addressing 31 the challenges associated with 3D systems, optimizing internalization, and enhancing NPs stability 32 and specificity through EV-based carriers. Also, our findings hold the promise of more precise and 33 effective cancer therapies while minimizing potential side effects.

Background: Citicoline, a medical food, lacks proven efficacy for ischemic stroke and has uncertainties around its harms. The continued prescription should be reevaluated given the more robust, high-quality Evidence against that medical food. This essay is based on a recent Cochrane review and uses only one all-cause mortality as the primary outcome. Therefore, the essay should be considered as something other than an updated Cochrane review but like a reflection based on Evidence-based Medicine and Philosophy of Science analysis. Question Research: Why citicoline (a medical food) should not be prescribed to treat people with acute ischemic stroke: The certainty of the Evidence.? Objective: Demonstrate from evidence-based medicine and philosophy of science perspective that citicoline should not be prescribed for acute ischemic stroke due to lack of efficacy and harm uncertainties. Search publications: We searched in PubMed and Cochrane Library from 2020 until 30 October 2023. We, furthermore, used engineering machines Bing and Google Scholar to detect additional papers. Additionally, we also reviewed reference lists of the retrieved publications and review articles and searched the websites of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Selection criteria: We included systematic reviews, meta-analyses, randomized clinical trials, clinical guidelines focused on acute ischemic stroke and comparing citicoline versus placebo or no intervention. We excluded narrative reviews, observational studies and ongoing trials. Data collection and analysis: We identified only new randomized clinical trials and assessed the risk of bias in seven domains. The other eight trials were already included in the mentioned Cochrane review. The systematic reviews with or without meta-analyses were assessed using McMaster University guidelines. We estimated risk ratios (RRs) for that outcome. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed effect model. We did not use the GRADE approach due to what is shown in a Cochrane review published in 2020 by Martí-Carvajal et al. We used the RevMan 5.4 software from Cochrane Collaboration to conduct the forest plot. We used a Trial Sequential Analysis with Copenhagen Trial Unit Software. We estimated a Bayes factor from the relative risk and 95% confidence interval. Results: We identified only one new RCT (N = 99) reported mortality data and three clinical guidelines. We conducted a new meta-analysis with nine trials (N = 4461) having a high risk of bias and showing little to no difference in mortality between citicoline and placebo (17.1% vs 18.4%; RR 0.94, 95% CI 0.82 to 1.06; I2 = 0%). The Bayes factor was 0.7, indicating weak Evidence for the null over the alternative hypothesis. Trial sequential analysis suggested sufficiency of Evidence for mortality. No guidelines recommend citicoline. Conclusions: This essay reassessed citicoline for acute ischemic stroke after the 2020 Cochrane review. Adding a new RCT further supported the lack of mortality benefit with citicoline. The overall evidence quality could be better. Analyses using evidence-based medicine and philosophy of science approaches do not support prescribing citicoline due to a lack of efficacy substantiation and potential harms.

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.

The COVID-19 pandemic stimulated attention to the medicinal applications of messenger RNA (mRNA). mRNA is expected to be applied not only to vaccines but also to regenerative medicines. The purity of mRNA is important for its medicinal application. However, the current mRNA synthesis techniques have problems, e.g., contamination of undesired 5’-uncapped mRNA and double-stranded RNAs. Recently, our group developed a completely capped mRNA synthesis technology that contributed to the progress of mRNA research. The introduction of chemically modified nucleosides, e.g., N1-methylpseudouridine and 5-methylcytidine, have been demonstrated by Dr. Karikó and Dr. Weissman which opened the practical application of mRNA for vaccines and regenerative medicines. Dr. Yamanaka reported the production of Induced Pluripotent Stem Cells (iPSCs) by the introduction of 4 types of genes using a retrovirus vector. iPSCs are widely used for research about regenerative medicines and the preparation of disease models to screen new drug candidates. Of the Yamanaka factors, Klf4 and c-Myc are oncogenes, and there is a tumor development risk if these are integrated into genomic DNA. Therefore, regenerative medicines using mRNA, which has no risk of genome insertion, have attracted attention. In this review, we summarized the synthesis of mRNA and its application for regenerative medicine.

Regenerative Medicine and Tissue Engineering are interdisciplinary fields that combine cell biology, material science, and bioengineering to develop therapies for tissue repair and regeneration. This field has made significant advances in recent years, particularly in the use of stem cells and biomaterials. Advancements in cell-based therapies have involved the use of cells to repair or replace damaged tissues and organs. Tissue engineering involves using scaffolds and growth factors to promote tissue regeneration. However, a major challenge in this field is the formation of adhesions, which can cause complications, such as intestinal obstruction and chronic pain. Adhesion barriers are used to prevent adhesion of tissues and organs during recovery, thereby reducing the risk of complications. Anti-adhesion materials, such as polysaccharides, proteins, and synthetic polymers, are used to create a physical barrier between tissues and prevent adhesion. These materials can be used alone or in combination, but their effectiveness varies.

Central Nervous System (CNS) cancers pose a formidable challenge in the medical world, characterized by aggressive behaviors and limited therapeutic options. The emergence of nanomedicine has offered new hope in CNS cancer treatment. The COVID-19 pandemic has further accelerated the need for innovative therapeutic strategies, emphasizing the significance of nanomedicine in this era. This mini review explores the current status of nanomedicine in CNS cancer therapy, with a particular focus on the post-COVID-19 landscape. We discuss the unique challenges presented by CNS cancers, the potential of nanomedicine in overcoming these challenges, and the recent developments in the field. Additionally, we highlight the lessons learned from the pandemic and how they can be applied to improve CNS cancer therapeutics. We also shed light on the evolving regulatory landscape and the prospects of personalized nanomedicine in CNS cancer treatment. The integration of nanomedicine in CNS cancer therapy is becoming increasingly promising, and its role in the post-COVID-19 era is poised to shape the future of neuro-oncology.

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.

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.

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.

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.

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.

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.

Cancer is the second major cause of disease-related dead worldwide, and its accurate early diagnosis and therapeutic intervention are fundamental for saving the patient’s life. Cancer, as a complex and heterogeneous disorder, results from disruption and alteration of a wide variety of biological entities, including genes, proteins, mRNAs, miRNAs, and metabolites that eventually emerge as clinical symptoms. Traditionally, diagnosis is based on clinical examination, blood tests for biomarkers, histopathology of biopsy, and imaging (MRI, CT, PET, US). Additionally, omics biotechnologies help to further characterize the genome, metabolome, microbiome traits of the patient that could have an impact on the prognosis and patient’s response to the therapy. The integration of all these data relies on gathering of several experts and may require considerable time, and, unfortunately, it is not without the risk of error in the interpretation and therefore in the decision. Systems biology algorithms exploit Artificial Intelligence (AI) combined with omics technologies to perform a rapid and accurate analysis and integration of patient’s big data and support the physician in making diagnosis and tailoring the most appropriate therapeutic intervention. However, AI is not free from possible diagnostic and prognostic errors in the interpretation of images or biochemical-clinical data. Here, we first describe the methods used by systems biology for combining AI with omics and then discuss the potential, challenges, limitations, and critical issues in using AI in cancer research.

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.