Lung cancer is the leading cause of global cancer-related mortality resulting in ~1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or biobanked sections/biopsy of lung tumors, PDXs, and pleural affusion. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and immune therapy agents. PDOs mainly recapitulated the genomic alterations, transcriptomic landscape and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remained, PDOs showed promise to screen novel therapy drugs. With the technical advance of high throughput, tumor-on-chip, combined microenvironment, and air-liquid interface (ALI), the drug screening using PDOs would serve better for precision care of lung cancer patients.

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

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.

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

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

One of the rapidly developing research areas is the creation of systems. which are commonly referred to as cyberphysical complexes. In such systems, devices and complexes interact with a completely different physical nature. The role of a person in such systems usually consists in the formation of final tasks for “artificial intelligence” and executive mechanisms. The functioning of actuators is controlled by accurate information systems.

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.

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

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder, is increasingly diagnosed and significantly affects communication, behavior, and social interaction. The current diagnostic framework, guided by the DSM-5, has limitations that may lead to clinical gaps due to overlapping symptoms of ASD and other disorders. This study proposes a comprehensive approach to enhance ASD diagnosis through clinical stratification based on comorbidities. We applied precision medicine techniques to identify and categorize ASD into ten clinical profiles. Our findings contribute to a more profound understanding of ASD, including its varied clinical manifestations and comorbidities, and facilitate the development of personalized therapeutic strategies.

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.

Almost one fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumor and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

This paper explores the critical role of biomathematics in cancer research, focusing on how mathematical models enhance our understanding of tumor growth and optimize treatment strategies. It begins with an overview of cancer biology, highlighting the complexities of tumor dynamics and the molecular mechanisms driving growth. The paper then delves into various mathematical modeling approaches, including deterministic, stochastic, and agent-based models, illustrating their applications in predicting tumor behavior and treatment responses. Case studies demonstrate the real-world impact of these models on optimizing chemotherapy, radiation therapy, and immunotherapy. Challenges such as data availability, model complexity, and clinical translation are discussed, alongside future directions in the field, including advances in computational power and personalized medicine. Ultimately, this research emphasizes the transformative potential of biomathematics in improving cancer treatment outcomes and underscores the importance of interdisciplinary collaboration in advancing the field.

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.

This paper discusses the application of artificial intelligence in imaging omics, especially in cancer research. Imaging omics enables detailed analysis of spatial and temporal heterogeneity of tumours through high-throughput extraction of quantitative features from medical images such as MRI, PET, and CT. This paper focuses on applying PARKS systems to automate the recognition, segmentation, and extraction of image features, significantly enhancing the capabilities of clinical decision support systems (CDSS). The future direction is to establish a robust network infrastructure for radiology Medication-led Health care (RLHC) to facilitate the development and application of personalised treatment protocols, and to improve diagnostic accuracy, prognosis assessment, and treatment recommendations by uploading quantitative image features to a shared database and comparing them with historical images.

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.”

Oxidative stress (OS), defined as a disruption in redox balance favoring oxidants, has emerged as a major contributor to numerous diseases in human and veterinary medicine. While several reviews have explored the implication of OS in human pathology, an exhaustive review for the canine species is lacking. This comprehensive review aims to summarize the existing literature on the role of OS in canine diseases, highlighting its potentially detrimental effect on various organs and systems. Some inconsistencies among studies exist, likely due to varying biomarkers and sample types. However, there is substantial evidence supporting the involvement of OS in the development or progression of numerous canine disorders, such as cardiovascular, oncologic, endocrine, gastrointestinal, hematologic, renal, neurologic, infectious and parasitic diseases, among others. Additionally, this review discusses the efficacy of antioxidant and pro-oxidant therapeutic agents for these conditions. Dietary interventions to counteract OS in dogs have gained significant attention in recent years, although further research on the topic is needed. This review aims to serve a foundational resource for future investigations in this promising field.

Background/Objectives: This study aimed to compare croup management patterns between pediatricians and emergency medicine (EM) physicians to enhance pediatric emergency care and inform the training of future specialists. Methods: A retrospective review of medical records was conducted for 1,676 children diagnosed with croup who visited a single pediatric emergency department (PED) from March 2019 to February 2023. Patient characteristics, management patterns, and the impact of physician specialty on emergency care were analyzed. Results: EM physicians used injected dexamethasone monotherapy more frequently, whereas pediatricians favored combined use of nebulized epinephrine and dexamethasone. Pediatricians also prescribed oral antibiotics and corticosteroids at discharge more often. The appropriate use of nebulized epinephrine based on the Westley Croup Score was significantly higher in the EM physician group. Despite these differences, there were no significant disparities in PED length of stay or revisit rates within 48 hours. Conclusions: EM physicians adhered more closely to clinical guidelines for croup management. These findings underscore the need for standardized, evidence-based pediatric emergency care and provide valuable insights for training programs in this field.

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.

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.

Chat generative pre-trained transformer (ChatGPT) is a developed language model and a subgroup of artificial intelligence (AI) which has demonstrated noticeable innovation in interactions between computer models and human studies. The release of ChatGPT in November 2022 attracted over 100 million users in a short time. It has unlimited applications in different fields of studies such as technology and science. ChatGPT utilizes deep learning and internet text to produce responses that resemble human language, although their accuracy is not always guaranteed. ChatGPT and GPT-4 can make a huge revolution in biology, medical, dental research, and health care. However, it's important to acknowledge the limitations of ChatGPT such as limitation in accessing the latest data. ChatGPT has generated both excitement and concern regarding its potential misuse. Its utilization in scientific publications has sparked debates and prompted the development of policies to govern the use of it. Although ChatGPT has certain limitations, it could impact on many different fields of study. There are challenges associated with using ChatGPT in the field of laboratory medicine and biology, particularly in the interpretation of test results. In this article, we review some of the applications of ChatGPT and GPT-4 in biology, dental and medical studies, and concerns about ChatGPT. Despite ChatGPT's conversational abilities are impressive, there are important considerations regarding its use in different fields of research and academic public.

Recent advances in mathematical modelling and artificial intelligence have challenged the use of traditional regression analysis in biomedical research. This study examined artificial and cancer research data using binomial and multinomial logistic regression and compared its performance with other machine learning models such as random forests, support vector machines, Bayesian classifiers, k-nearest neighbours and repeated incremental clipping (RIPPER). The alternative models often outperformed regression in accurately classifying new cases. Logistic regression had a structural problem similar to early single-layer neural networks, which limited its ability to identify variables with high statistical significance for reliable class assignment. Therefore, regression is not always the best model for class prediction in biomedical datasets. The study emphasises the importance of validating selected models and suggests that a mixture of experts approach may be a more advanced and effective strategy for analysing biomedical datasets.

Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and regenerative medicine owing to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs which are currently being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have different secretion potentials and production which may influence their therapeutic effects. To confirm it, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from three different sources: Wharton’s jelly (WJ), dental pulp (DP) and bone marrow (BM). Our analysis focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 differentially expressed human proteins. WJ-MSCs showed the greatest variation compared with the other sources. WJ produced more extracellular matrix (ECM) proteins and ECM-affiliated proteins and appeared more able to modulate the inflammatory and immune response. BM-MSCs displayed enhanced differentiation and paracrine communication capabilities. DP-MSC appeared to promote exosome production. The results obtained confirm the existence of differences between WJ, DP and BM-MSC and the need to select the MSC origin according to the therapeutic objective sought.

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

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

In recent years, the FDA has approved numerous antitumor drugs that are mutation-based for clinical use. These drugs have improved the precision of treatment and reduced adverse effects and side effects. Personalized therapy is a prominent and hot topic of current medicine and also represents the future direction of development. With the continuous advancements in gene sequencing and high-throughput screening, research and development strategies for personalized clinical drugs have developed rapidly. This review elaborated the recent personalized treatment strategies, which include artificial intelligence, multi-omics analysis, chemical proteomics, and computation aided drug design. These technologies rely on the molecular classification of diseases, the global signaling network within organisms, and new models for all targets, which significantly support the development of personalized medicine. Meanwhile, we summarized chemical drugs such as lorlatinib, osimertinib, and other natural products that deliver personalized therapeutic effects based on genetic mutations. This review also highlights potential challenges in interpreting genetic mutations and combining drugs, while providing new ideas for the development of personalized medicine and pharmacogenomics in cancer study.

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

Abstract Introduction There is a clear link between self-medication practice and ongoing pandemic diseases like COVID-19, According to studies conducted globally and the general Ethiopian population turned to self-medication and symptomatic treatment as a result of inadequate COVID-19 treatment and also about 80% of the population amassed drugs for pandemic use. Objective: The objective of this study was to assess self-medication practice for treatment of Covid-19 and reason to use self- medication among residents in Bedelle city and its surrounding, Southwest Oromia, Ethiopia. Methodology: A cross sectional study design was employed and the standardized questionnaire was developed by reviewing relevant literatures then the data was collected using face to face interview. Final data was analyzed by using SPSS version 23. Result: The final study contained 415 respondents in total, with a response rate of 98.5%. The majority of responses were females and between the ages of 18 - 25 Category. In this study population, the use of self-medication since the onset of the Covid-19 epidemic was reported by participants were around 50.6%. Analgesics (42.4%) and cold medicines (29.5%) were the most frequently used medications for treatment of COVID-19. Also the reported uses of these drugs included treatment of Covid-19 symptoms like the Headache (22.2%), Fever (13.2%), respiratory infective (14.3%), and cold (21.4%) were the most frequently reported symptoms for self-medication. Self-medication methods were used more frequently by women than Men. Conclusion: According to this study, analgesics and cold medications are commonly self- medicated drugs used for Covid-19 therapy. It is a serious health concern, particularly when COVID-19 symptoms are present, and high consumption of self-medication has been linked to COVID-19 prevention or treatment. Key words: Covid-19, Medicine, Practice, Bedelle city, Self-Medication

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.

Colorectal cancer prognosis get worse with advancement of disease into metastatic stage. There is a pertinent need to develop prognostic biomarkers that can be used for personalized and precision medicine. Alternative splicing provides an insight into understanding of changes at isoform expression level which may not be evident at gene level. In this direction, we utilized our prior knowledge about significant alternatively spliced genes and chose ADAM12 and MUC4 for further characterization in a metastatic cell line model. These genes were found to be good prognostic indicators in The Cancer Genome Atlas database. We studied the gene organization and designed primers to specifically amplify a group of isoforms. Differential expression of these group of isoforms was observed in normal, primary and metastatic colorectal cancer cell lines. We further validated the results using sanger sequencing. Isoform expression was found to respond to the 5-fluorouracil treatment. RNAseq analysis of the cell lines further validated the differential expression of gene isoforms. Successful detection of ADAM12 and MUC4 in cell lysates varied according to the antibody used which may reflect differential expression of isoforms. This comprehensive study underscores the importance of studying alternatively spliced isoforms and their probable used as prognostic or predictive biomarkers.

Medical and translational scientific research requires the use of animal models as an initial approach to the study of new therapies and treatments, but when the objective is an exploration of translational potentialities, classical models fail to adequately mimic problems in humans. Among the larger animal models that have been explored more intensely in recent decades, small ruminants, namely sheep and goats, have emerged as excellent options. The main advantages associated to the use of these animals in research works are related to their anatomy and dimensions very similar to those of humans in most physiological systems, in addition to their low maintenance and feeding costs, tendency to be docile, long life expectancies and few ethical complications raised in society. The most obvious disadvantages are the significant differences in some systems such as the gastrointestinal, and the reduced amount of data that limits the comparison between works and the validation of the characterization essays. Despite everything, recently these species have been increasingly used as animal models for diseases in different systems, and the results obtained open doors for their more frequent and advantageous use in the future. The purpose of this review is to summarize the general principles related to the use of small ruminants as animal models, with focus on regenerative medicine, to group the most relevant works and results published recently and to highlight the potentials for the near future in medical research.

Introduction: Travel-based continuing medical education (CME) has become a popular format for physicians looking to combine education with travel. Emergency Medicine Update Europe is a biennial accredited CME program combining high quality Emergency Medicine education with structured group activities including cycling, hiking and social activities. This unique design incorporates innovative educational practices but as a whole has not yet been evaluated. Methods: This was a participant observation-based, ethnographic-style case study of the Emergency Medicine Update Europe conference in Provence, France in 2015. Participant interviews and embedded observation methods were used to collect data. Data was then analyzed using thematic content analysis techniques. Results: We describe three phenomena from the data that we feel are highly influential in the success of the program and impact on learning. These include “social engagement and a sense of community”; “the value of a stimulating escape” and “the ‘flat’ faculty-learner relationships”. Discussion: These unique features, prioritized by participants, seem to be key to the apparent success of this model over more traditional CME approaches. To our knowledge this is the first empirical research in this area and improves our understanding of how to leverage these more sociologic components for more effective continuing medical education.

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

Published transcriptomic data from surgically removed metastatic clear cell renal cell carcinoma (ccRCC) samples were re-analyzed from the Genomic Fabric Perspective that considers the transcriptome a multi-dimensional mathematical object, constrained by a dynamic set of expression correlations among genes. Every gene in the chest wall metastasis (MET), two primary tumors (PTA, PTB) and the surrounding normal tissue (NOR) of the right kidney was characterized by three independent measures: average expression level (AVE), relative expression variation (REV) and expression correlation (COR) with each other gene. AVE was used to determine the regulation of the genomic fabrics of ccRCC, apoptosis, chemokine and VEGF signaling pathways. REV quantified the alteration of the transcripts’ abundances control, while COR determined the remodeling of the transcriptomic networks of chemokine signaling and oxidative phosphorylation genes. The gene hierarchy was established in based on Gene Commanding Height and the Gene Master Regulators (GMR) TASOR (PTA), FAM27C (PTB) and ALG13 (MET) and DAPK3 (NOR) were identified in each profiled region. We predict that TASOR overexpression would block transcription in PTA but not in PTB, while slightly stimulating it in NOR. Silencing of ALG3 would slow-down the cell-cycle in all three cancer regions with practically no effect in NOR.

Background: Schizophrenia is a severe psychiatric disorder that has a large impact on patients’ lives. In addition to Western medicine, the use of additional treatments, such as acupuncture, in treating the positive, negative, and cognitive symptoms is increasing. Methods: We conducted a systematic review on the use of acupuncture as an add-on treatment for patients with schizophrenia that are in regular care, with a special focus on the treatment of the often accompanying co-morbid sleep disorders. In this study, we searched the Medline, ScienceDirect, Cochrane Library, Scopus, and ERIC databases with a cut-off date of December 31, 2017, thereby following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our search resulted in 26 eligible studies. Most studies showed limited evidence for the use of acupuncture as add-on therapy in the treatment of clinical symptoms, but beneficial effects have been reported in the treatment of co-morbid sleep disorders. Conclusions: Limited evidence was found for the use of acupuncture as add-on therapy in the treatment of patients with schizophrenia; however, positive results were found in the treatment of sleep disorders, but this result needs to be confirmed in large, randomized, controlled trials.

Despite the strong links between sleep, circadian rhythms, and mental health, sleep education has been neglected in mental healthcare provider training programs. The current pilot study examined the potential efficacy and acceptability of a sleep education workshop for trainee psychologists, called the Sleep Psychology Workshop. Eleven students completing their Master of Psychology degrees (90% female, 24.4 ± 1.6 years old) attended the Sleep Psychology Workshop as part of their Health Psychology course, delivered as three, two-hour lectures (total six hours). Trainees’ sleep psychology knowledge quiz scores (% correct) demonstrated significant improvement from pre- (M = 60%, SD = .09) to post-workshop (M = 79%, SD = .08), t (6) = -5.18, p = .002. Trainees also reported increased self-efficacy to use common sleep-related assessment instruments and empirically supported interventions to manage sleep and circadian rhythm disturbances, along with increased confidence to manage insomnia disorder in clinical practice (all p<.02). Trainees also endorsed the workshop as an acceptable sleep education program for trainee psychologists via a post-workshop feedback survey, focus group, and six-month follow-up survey. This pilot study provides preliminary evidence for the Sleep Psychology Workshop as an effective and acceptable sleep education program for trainee psychologists.

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.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

Endometrial cancer (EC), a prevalent gynecological malignancy, presents significant challenges due to its genetic complexity and heterogeneity. The genomic landscape of EC is underpinned by genetic alterations, such as mutations in PTEN, PIK3CA, and ARID1A, and chromosomal abnormalities. The identification of molecular subtypes—POLE-ultramutated, microsatellite instability (MSI), copy-number low, and copy-number high—illustrates the diverse genetic profiles within EC and underscores the need for subtype-specific therapeutic strategies. The integration of multi-omics technologies such as CRISPR gene editing, single-cell genomics, and spatial transcriptomics, have revolutionized our understanding and approach to studying EC, and offers a holistic perspective that enhances the ability to identify novel biomarkers and therapeutic targets. The translation of these multi-omics findings into personalized medicine and precision oncology is increasingly feasible in clinical practice. Targeted therapies such as PI3K/AKT/mTOR inhibitors have demonstrated the potential for improved treatment efficacy tailored to specific genetic alterations. Despite these advancements, challenges persist in terms of variability in patient responses, the integration of genomic data into clinical workflows, and ethical considerations. This review explores the genomic underpinnings of EC, from genes to clinical practice. It highlights the ongoing need for multidisciplinary research and collaboration to address the complexities of EC and improve diagnosis, treatment, and patient outcomes.

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.

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

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

The field of neurology has undergone a profound transformation over the past two decades, shifting from traditional clinical and pathological approaches to a more genetically informed perspective. This essay explores the drastic turn in neurology from classical disciplines to neurogenetics, examining the factors that have contributed to this shift and the implications for clinical practice and research. The traditional approach to neurology, grounded in clinical examination, neuroanatomy, and neuropathology, has been effective in diagnosing and treating many conditions but has had limitations in understanding the etiology of complex and rare neurological disorders. The emergence of neurogenetics has been driven by advancements in genetic technologies, such as next-generation sequencing (NGS) and genome-wide association studies (GWAS), as well as the recognition of the genetic basis of many neurological disorders. This shift has led to more accurate diagnoses, targeted treatments, and a deeper understanding of the molecular mechanisms underlying neurological disorders. However, challenges remain, including the complexity of genetic architecture and the ethical implications of genetic testing. The future of neurogenetics holds great promise for improving the diagnosis, treatment, and prevention of neurological conditions, with new technologies and interdisciplinary approaches poised to further advance the field.

How many different writers authored the huge number of texts attributed to Galen of Pergamum (129~216 AD), medical doctor and philosopher, a giant in the history of medicine? To find out which texts were his and which ones were written by others is known as the “Galenic Question”. We propose a “solution” to it through a multidisciplinary approach based: (a) on historical research and (b) on a mathematical analysis of the Greek texts. The historical approach has considered historical independent sources and anachronisms. The mathematical approach has been based on a mathematical theory concerning deep–language variables, rarely consciously controlled by any author, therefore capable of giving indications on similarity of texts, with little or no bias. The multidisciplinary approach has convinced us that at least three authors wrote the texts attributed to Galen. The first two very likely were real historical persons: (a) a certain Galen living between the end of the I century BC and the second half of the I century AD; (b) the historical Galen of Pergamum (II–III centuries AD) and (c) several unknown authors hiding under the name Galen, but surely living after Galen of Pergamum’s death.

Adaptive hyperactivity, characterized by increased activity levels and novelty-seeking traits without mood disorders, is prevalent among older adults in Sardinia's "blue zone," an area with high longevity. This study aims to evaluate the adaptive nature of hyperac-tivity concerning quality of life, social rhythms, and mood symptoms in individuals from this region, particularly among older adults over 80. Methods: This observational cross-sectional study included adults and older adults over 80 years from Sardinia's blue zone, recruited from the dermatology clinic at the University Hospital of Cagliari. Partici-pants underwent psychiatric interviews and completed the Mood Disorder Questionnaire (MDQ), Patient Health Questionnaire (PHQ-9), SF-12, and Brief Social Rhythm Scale (BSRS). Data were compared with national and regional normative data. Results: Older adults in the blue zone demonstrated higher MDQ positivity (22.58%) compared to na-tional averages (0.87%), without corresponding increases in dysregulated rhythms, de-pressive symptoms, or reduced quality of life. Younger elders (65-79 years) showed in-creased rhythm dysregulation (BSRS score: 20.64±7.02) compared to adults (17.40±6.09, p=0.040), but this trend was not observed in older elders (80+ years). No significant differ-ences were found in CH3SH and (CH3)2S levels between groups. Conclusions: Hyperactiv-ity observed in older adults from Sardinia's blue zone appears adaptive, not linked to so-cial rhythm dysregulation, depressive symptoms, or diminished quality of life, suggesting resilience factors that may contribute to longevity. These findings support the potential classification of such hyperactivity as beneficial rather than pathological, warranting fur-ther research into biomarkers and psychoeducational interventions to prevent the onset of bipolar disorders in predisposed individuals.

Antimicrobial resistance (AMR) is a growing threat that undermines the effectiveness of global healthcare. The Centers for Disease Control and Prevention and the World Health Organization have identified numerous microbial organisms, particularly members of the ESKAPEE pathogens, as critical threats to global health and economic security. Many clinical isolates of these pathogens have become completely resistant to current antibiotics, making treatment nearly impossible. Herbal remedies, such as those found in Traditional Chinese Medicine (TCM), have been practiced for thousands of years and successfully used to treat a wide range of ailments, including infectious diseases. Surprisingly, despite this extensive knowledge of folk medicine, no plant-derived antibacterial drugs are currently approved for clinical use. This study explores a comprehensive library comprising 664 extracts from 132 distinct TCM plant species for antimicrobial properties against gram-negative (Escherichia coli) and gram-positive (Micrococcus luteus) bacteria using liquid and solid in vitro assays. Intriguingly, our results reveal 17 plant species with potent antimicrobial properties effective primarily against gram-positive organisms, including Streptococcus aureus and epidermidis. Our results indicate that phytobiotics from the identified plants may be potential candidates for novel antimicrobials.

Late-life diseases result from the poorly understood process of senescence (aging), that is largely genetically determined. According to a recently proposed evolutionary physiology-based account, the multifactorial model, senescence is largely caused by evolved but non-adaptive programmatic mechanisms specified by the wild-type (i.e. normal) genome. These act together with disruptions to wild-type function (due e.g. to infectious pathogens, mechanical injury and malnutrition) in a variety of combinations to generate diverse late-life diseases. Here the utility of this model is explored by testing its capacity to provide an account of one complex, late-life disease, osteoarthritis (OA), and a framework for understanding OA etiology suggested. In this framework, the core OA disease mechanism is a futile endochondral ossification quasi-program (non-adaptive developmental program), in which hypertrophic articular chondrocytes alter joint architecture. Programmatic changes prime chondrocytes for quasi-program activation, which can be triggered by secondary causes of OA (e.g. joint mechanical injury). A suggested evolutionary cause of this priming, involving antagonistic pleiotropy, is selection to maximize early life tissue repair benefits at the expense of late-life programmatic costs.

Laboratories generate various forms of wastes which contribute to a complex network of profound and multifaceted environmental challenges and associated public health issues if not properly managed.Traditional laboratory practices particularly in developing countries, often lead to excessive waste generation, chemical contamination and resource depletion, coupled with inefficient waste management which poses risks to both ecosystem and public health. As the environmental impact of laboratory waste escalates, the need for effective waste management becomes increasingly important and urgent for safeguarding environmental health. This review examines the impact of laboratory waste management practices on environmental health and explores sustainable laboratory medicine as a mitigating response. Sustainable laboratory medicine adopts practices such as green laboratory principles involving waste minimization, resource conservation, the use of eco-friendly materials as well as energy-efficient protocols and innovative waste segregation and treatment technologies. This approach complies with regulatory standards as well as emphasizes proactive orientation towards environmental stewardship, operational efficiency and innovation while maintaining scientific integrity. Sustainable laboratory medicine appears to be a crucial framework that mitigates the environmental health impacts associated with laboratory-derived waste. This review advocates for a paradigm shift towards sustainable laboratory operations and emphasizes the need for comprehensive training, institutional commitment, and regulatory support.

Vitronectin is a glycoprotein, present in plasma and extracellular matrix, implicated in cell migration. The high amount of vitronectin found in neuroblastoma biopsies was associated with poor prognosis. However, there are almost no studies of vitronectin levels in neuroblastoma cell culture media nor in plasma of neuroblastoma patients. Vitronectin concentration in culture media of four neuroblastoma cell lines grown in monolayer and in 3D-models, and in plasma of 114 neuroblastoma patients, was quantified using ELISA. Three of the neuroblastoma cell lines secreted vitronectin to culture media when cultured in monolayer and 3D-models. Vitronectin release was higher by neuroblastoma cells cultured in 3D-models than in monolayer, and was still great when cells grown in 3D-scaffolds with cross-linked vitronectin. Vitronectin secretion occurred independently of cell numbers in cultures. Its concentration in plasma of neuroblastoma patients ranged between 52.4 and 870µg/mL (median, 218µg/mL). A ROC curve was used to establish a cutoff of 361µg/mL, above which patients over 18-months-old had worse prognosis (p=0.0018). Vitronectin could be considered a new plasma prognostic biomarker in neuroblastoma, and warrants confirmation in collaborative studies. Drugs inhibiting vitronectin interaction with cells and/or extracellular matrix could represent a significant improvement in survival for neuroblastoma patients.

This study uses machine learning to identify key factors influencing the cost-effectiveness of over-the-counter (OTC) medications. By developing a novel cost-effectiveness rating (CER) from user ratings and prices, we analyzed data from Amazon. The findings indicate that FSA/HSA eligibility, symptom treatment range, safety warnings, special effects, active ingredients, and packaging size significantly impact cost-effectiveness across cold, allergy, digestion, and pain relief medications. Medications eligible for FSA or HSA funds, treating a broader range of symptoms, and having smaller packaging are perceived as more cost-effective. Cold medicines with safety warnings were found to be cost-effective due to their lower average price and effective ingredients like phenylephrine and acetaminophen. Allergy medications with kid-friendly features showed higher cost-effectiveness, and ingredients like calcium, famotidine, and magnesium boosted the cost-effectiveness of digestion medicines. These insights help consumers make informed purchasing decisions and assist manufacturers and retailers in enhancing product competitiveness. Overall, this research supports better decision-making in the pharmaceutical industry by highlighting factors that drive cost-effective medication purchases.

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.

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.

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.

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.

Biocompatibility of ceramic materials in CaO-P2O5 system was investigated using different methods, including in vitro and in vivo tests. Ceramics based on calcium pyrophosphate Ca2P2O7 were obtained by annealing cement-salt stone from highly concentrated hardening suspensions (HCHS). Cement-salt stone was prepared using powder mixtures of calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate (MCPM) Ca(H2PO4)2·H2O. These salts were mixed with each other in such a way that calcium pyrophosphate and calcium polyphosphate were present in the final ceramic product in the following weight ratios: Ca(PO3)2/Ca2P2O7 = 0/100; 5/95; 10/90 and 20/80. Distilled water was added to a homogenized powder mixtures of Ca3(C6H5O7)2·4H2O and Ca(H2PO4)2·H2O by a water/solid ratio of 0,5 by weight. The obtained suspensions were shaped using silicon molds and left to dry in air for a week. The phase composition of the obtained samples of cement-salt stone was represented by brushite CaHPO4·2H2O, monetite CaHPO4, calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate Ca(H2PO4)2·H2O. According to the XRD data, the phase composition of ceramic materials after annealing in the temperature range of 800-1000 0C was mainly represented by the β-Ca2P2O7 phase. In vivo tests shown that obtained ceramic materials can be recommended for regenerative treatments for bone defects.

With rapid advances in gene editing and gene therapy technologies, the development of genetic, cell, or protein-based cures to disease are no longer the realm of science fiction but that of today’s practice. The impact of these technologies are rapidly bringing them to the veterinary market as both enhanced therapeutics and towards modeling their outcomes for translational application. Simply put, gene editing enables scientists to modify an organism’s DNA a priori through the use of site-specific DNA targeting tools like clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Gene therapy is a broader definition that encompasses the addition of exogenous genetic materials into specific cells to correct a genetic defect. More precisely, the U.S Food and Drug Administration (FDA) defines gene therapy as “a technique that modifies a person’s genes to treat or cure disease” by either (i) replacing a disease-causing gene with a healthy copy of the gene; (ii) inactivating a disease-causing gene that was not functioning properly; or (iii) introducing a new or modified gene into the body to help treat a disease. In some instances, this can be accomplished through direct transfer of DNA or RNA into target cells of interest or more broadly through gene editing. While gene therapy is possible through the simple addition of genetic information into cells of interest, gene editing allows the genome to be reprogrammed intentionally through the deletion of diseased alleles, reconstitution of wild type sequence, or targeted integration of exogenous DNA to impart new function. Cells can be removed from the body, altered, and reinfused, or edited in vivo. Indeed, manufacturing and production efficiencies in gene editing and gene therapy in the 21^st century has brought the therapeutic potential of in vitro and in vivo reprogrammed cells, to the front lines of therapeutic intervention (Brooks et al., 2016). For example, CAR-T cell therapy is revolutionizing hematologic cancer care in humans and is being translated to canines by us and others, and gene therapy trials are ongoing for mitral valve disease in dogs.

Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

Background: Studies have tried to identify predictors of functional markers of keratoconus progression, whereas structural outcomes of collagen cross-linking have not been properly investigated. Objective: find and set up a combination of diagnostic modalities and measurements to reliably reflect CXL efficiency. Material and methods: We retrospectively reviewed the medical histories of 107 KC patients (131 eyes) who underwent CXL in a medical center from January 2018 to December 2022. The dataset included preoperative examinations and follow-up results, which provided a total of 796 observations. The cases of other corneal diseases, repeated CXL, pregnancy, and observations without follow-up examinations were excluded. Results: The study findings revealed a significant drop in the central and corneal thickness during 14.01±9.98 months of observations. Linear and polynomial equations suggested different trends in pachymetry change after CXL. The linear model showed corneal thinning, and according to the polynomials, pachymetry findings return to baseline values two years after CXL. Conclusion: The most reliable prognosis of postoperative corneal thickness is achieved with the models trained on keratometry readings and topography indices. BAD indices are also reliable predictors of the corneal thickness after CXL. A combination of the aforementioned structural parameters and their derivatives can reliably predict CXL efficiency.

In recent years, there has been a growing interest in the use of medicinal plants and phytochemicals as potential treatments for acne vulgaris. This condition, characterized by chronic inflammation, predominantly affects adolescents and young adults. Conventional treatment typically targets the key factors contributing to its development: the proliferation of Cutibacterium acnes and the associated inflammation. However, these treatments often involve the use of potent drugs. As a result, the exploration of herbal medicine as a complementary approach has emerged as a promising strategy. By harnessing the therapeutic properties of medicinal plants and phytochemicals, it may be possible to address acne vulgaris while minimizing the reliance on strong drugs. This approach not only offers potential benefits for individuals seeking alternative treatments but also underscores the importance of natural remedies in dermatological care. The primary aim of this study was to assess the antimicrobial, antioxidant, and anti-inflammatory properties of plants and their phytochemical constituents in the management of mild acne vulgaris. A comprehensive search of scientific databases was conducted from 2018 to September 2023. The findings of this review suggest that medicinal plants and their phytochemical components hold promise as treatments for mild acne vulgaris. However, it is crucial to note that further research employing high-quality evidence and standardized methodologies is essential to substantiate their efficacy and safety profiles.

Background/Objectives: Meconopsis has long been used in traditional Tibetan medicine to treat various diseases. However, blue-flowered Meconopsis (M. betonicifolia) is becoming increasingly scarce due to overharvesting. As a potential alternative, yellow-flowered Meconopsis (M. integrifolia) shows promise but requires comprehensive characterization. This study aimed to evaluate and compare the anti-inflammatory potential of yellow- and blue-flowered Meconopsis species. Methods: LC-MS was used to analyze the chemical profiles of yellow- and blue-flowered Meconopsis. Putative targets of shared constituents were subjected to GO and disease enrichment analysis. The LPS-induced RAW264.7 macrophage model was employed to assess anti-inflammatory effects. Metabolomics was applied to gain mechanistic insights. Results: LC-MS revealed over 70% chemical similarity between species. Enrichment analysis associated targets with inflammation-related pathways. In macrophage assays, both species demonstrated dose-dependent anti-oxidative and anti-inflammatory activities, with yellow Meconopsis exhibiting superior efficacy. Metabolomics showed modulation of key inflammatory metabolic pathways. Conclusions: This integrative study validated yellow-flowered Meconopsis as a credible alternative to its blue-flowered counterpart for anti-inflammatory applications. Metabolic profiling provided initial clues regarding their multi-targeted modes of action, highlighting clinical relevance and potential for sustainable utilization and biodiversity conservation.

Modern medicine adopted four presumptions when it evolved from ancient experienced-based mind-body medicine. To understand its failure in finding cures for chronic diseases, we examined four presumptions, and found that statistical population of health properties does not exist for most research purposes, mathematical models are misused to model intensive properties, synthetic drugs are inherently more dangerous than nature-made medicines under their respective application conditions, and reductionist treatments are inferior and inherently dangerous. We found that clinical trials are valid only for research where treatment effect is much stronger than the total effects of all interfering or co-causal factors or errors introduced by misused mathematical models can be tolerated. In all other situations, clinical trials introduce excessive errors and fail to detect treatment effects, or produce biased, incorrect or wrong results. We further found that chronic diseases are manifestation of small departures in multiple process attributes in distinctive personal biological pathways networks, that modern medicine lacks required accuracy for accurately characterizing chronic diseases, and that reductionist treatments are good at controlling symptoms and safe for short term uses. For all stated reasons, as long as modern medicine continues relying on the flawed presumptions, it can never find predictable cures for chronic diseases. By implication, predictable cures to chronic diseases are adjustments to lifestyle, dietary, emotional, and environmental factors to slowly correct departures in process attributes responsible for chronic diseases.

Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.

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

We are all similar, but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly and yeast panels with insightful applications for translational research.

Background: Complementary and alternative medicines (CAM) are widely used, with pharmacies accounting for a significant share of the distribution market. Despite their popularity, many CAMs lack scientific evidence for effectiveness, and some can cause adverse health effects. Limited research exists on CAM-related adverse events and the effectiveness of CAM labels in conveying crucial information. Methods: This cross-sectional study aimed to investigate CAM utilization, consumer perspectives, and the influence of labels on CAM usage in Melbourne, Australia. Data were collected through an online questionnaire and analysed using descriptive statistics, Pearson's correlation, MANOVA, and regression analyses. Results: The study enrolled 125 current CAM users, primarily recruited from pharmacy and supermarket customers (age: predominantly 31-50; gender: 20.8% male, 79.2% female). Participants' perceptions of effectiveness and safety were positively correlated. Label warnings prompted information-seeking, but consultation with healthcare professionals (HCPs), particularly pharmacists, was infrequent (24%). Adverse reactions were reported by 18.5% of participants, with 8.3% experiencing severe reactions. The analysis revealed relationships between CAM usage and demographics. Ordinal logistic regression showed a significant association between calcium consumption and higher age groups (coefficient = 1.658, p = 0.006), while binary logistic regression identified higher iron consumption among females (coefficient = 2.177, p = 0.007). Conclusions: Label warnings significantly prompted consumers to seek more information about CAMs. However, a limited engagement of HCPs, especially pharmacists, suggests an opportunity for improved consumer education and pharmacist involvement in CAMs-related discussions. The findings highlight demographic influences on CAM usage being essential for developing targeted health interventions and policies. Addressing these aspects may lead to safer CAM practices and informed consumer decision-making.

Sleep deprivation is an increasing problem in the modern age. While molecular theories on the mechanism of sleep are still developing, sleep’s importance for cognitive function and physical health has been well reported. In the past 2 decades, major advances in the genetics of sleep have been made. Among families of natural short sleepers averaging around 4-6 hours nightly, mutations on 4 genes (DEC2, ADRB1, NPSR1, and GRM1) have been associated with significantly shorter sleep without observed cognitive or health detriments. Studies in mice have further established causality of these mutations as well as finding increased resistance to neurodegeneration. Yet, despite these promising results, there is a current lack of studies investigating potential chronic risks of sleep deprivation, particularly physical and physiological effects that may not be apparent. For circadian repressor element DEC2, circadian dysregulation risks should be evaluated further. For adrenergic receptor ADRB1, cardiovascular and heart failure risks would be of interest. For NPSR1, asthma and other immune responses, as well as mood disorders are relevant. For the currently least studied G-protein receptor GRM1, its altered regulation of the extracellular signal-regulated kinase (ERK) pathway could result in developmental and proliferation effects. While these familial natural short sleep genes hold potential for our understanding of sleep and therapeutic development, it is critical not to overdraw conclusions. By investigating the possible downstream effects, one can be aware of the potential risks of natural short-sleep genetics, better understand the mechanisms of sleep, and advance research in reducing the harms of sleep deprivation.

The history of health records (later also called medical records), including ones regarding individual patients, is thousands of years old. It finds it roots in the first ancient civilisations. Up until the 19^th century the records’ purpose was mainly an educational one. In the 19^th and 20^th century they started becoming significant in other roles as well, including those not strictly limited to medicine. In particular, to account for medical procedures, insurance proceeds or legal action. Currently we are living in a revolutionary era when it comes to health records, in which their character has changed from a “paper-based” to an electronic one. This paper presents the development of health records from the ancient to modern times, mainly in Europe and North America. Other cultures and civilisations, including China and India, are not discussed. An analysis of available sources was conducted, inter alia digital versions of manuscripts up to hundreds of years old. The analysis was based on PubMed and Google Scholar (several key words, all the available sources). Sources published in non-international languages (e.g. Dutch) were also investigated. Overall, approximately 600 articles were analysed, 158 of which were used and cited in this paper. The conclusions drawn from the analysis are as follows: (1) Health records, priorly used mostly for educational purposes, for about 100 years now have acquired a fully formal status. (2) We are currently facing the most revolutionary changes regarding the transformation of paper-based records into electronic ones. (3) The consequences of this process include systematic applications of solutions within the area of e-health, which allow us to make medical services more flexible, improve the health of individual patients and entire populations and potentially limit expenditure. (4) In the light of the ongoing COVID-19 pandemic, introducing electronic health records could be beneficial in terms of limiting the potential sources of contamination (physical copies of health records), saving time and resources, and improving the network of communication between medical centres.

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.

Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present on the emergency department (ED) admission with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. This case report aims to bring awareness among healthcare professionals regarding the atypical presentation and introduce a potential differential diagnosis when evaluating patients with fever and back pain. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced acute liver failure in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. She had a fever, pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever and vomiting, jaundiced skin, and sclera at the examination in ED. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, hepatocytolysis syndrome, and hyperbilirubinemia with the predominance of indirect bilirubin. We performed then abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess-like collection fused to the interfibrillar level of the left iliopsoas muscle; a diagnosis we most likely would have been missed. After that, the patient was hospitalized in the General Surgery Department, and surgery drainage of the abscess was performed. The patient's evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we aspire that more cases of iliopsoas abscess will be accurately diagnosed.

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6, TNF-α, and TGF-β1) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

Introduction. The management of anemia in chronic kidney disease (CKD-An) presents significant challenges for nephrologists due to variable responsiveness to erythropoietin-stimulating agents (ESA), hemoglobin (Hb) cycling, and multiple clinical factors affecting erythropoiesis. The Anemia Control Model (ACM) is a decision support system designed to personalize anemia treatment, which has shown improvements in achieving Hb targets, reducing ESA doses, and maintaining Hb stability. This study aimed at evaluating the association between ACM-guided anemia management with hospitalizations and survival in a large cohort of hemodialysis patients. Methods. This mul-ti-center, retrospective cohort study evaluated adult hemodialysis patients within the European Fresenius Medical Care NephroCare network from 2014 to 2019. Patients treated according to ACM recommendations were compared to those from centers without ACM. Data on demographics, comorbidities, and dialysis treatment were used to compute a propensity score estimating the like-lihood of receiving ACM-guided care. The primary endpoint was hospitalizations during follow-up; the secondary endpoint was survival. A 1:1 propensity score-matched design was used to minimize confounding bias. Results. A total of 20,209 eligible patients were considered (reference group: 17,101; ACM adherent group: 3,108). Before matching, the mean age was 65.3±14.5 years, with 59.2% men. Propensity score matching resulted in two groups of 1,950 patients each. Matched ACM adherent and non-ACM patients showed negligible differences in baseline characteristics. Hospi-talization rates were lower in the ACM group both before matching (71.3 vs. 82.6 per 100 per-son-years, p<0.001) and after matching (74.3 vs. 86.7 per 100 person-years, p<0.001). During fol-low-up, 385 patients died, showing no significant survival benefit for ACM-guided care (hazard ratio = 0.93; p=0.51). Conclusions: ACM-guided anemia management was associated with a sig-nificant reduction in hospitalization risk among hemodialysis patients. These results further support the utility of ACM as a decision support tool enhancing anemia management in clinical practice.

Background: Tumor mutational burden (TMB) is increasingly recognized as a vital biomarker for predicting the efficacy of immune checkpoint inhibitors (ICIs) in cancer treatment. Despite its growing importance, the effectiveness of TMB as a predictive marker are well established in lung cancer and melanoma but remain ambiguous for breast and prostate cancers. Objective: This study aims to evaluate the role of TMB in predicting response to ICIs across four major cancer types—lung, melanoma, breast, and prostate—and to address the variability in TMB's predictive value in different cancers. Methods: A comprehensive review of the current literature was performed, analysing studies that investigated TMB and its association with ICI therapy outcomes in the specified cancer types. Results: The analysis reveals a strong consensus on the predictive value of TMB in lung cancer and melanoma, where high TMB levels are associated with improved clinical outcomes and better responses to ICIs. In contrast, the evidence for breast and prostate cancers is less conclusive, with variability in results highlighting the need for further research. Specifically, high TMB in these cancers does not consistently predict better responses to ICIs, suggesting that additional biomarkers or refined criteria might be necessary. Conclusion: TMB is a promising biomarker for predicting responses to ICI therapy, particularly in lung cancer and melanoma. However, its predictive value in breast and prostate cancers remains uncertain, underscoring the need for more extensive studies. Future research should focus on standardizing TMB evaluation methods and exploring additional biomarkers to improve treatment personalization and outcomes in these cancer types.

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.

Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2•-) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administrated during reperfusion can suppress the exacerbated mitochondrial O2•- formation after I/R. We used Wistar rats submitted to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received EVs (I/R+EVs group) or saline, I/R group) in the kidney subcapsular space. The 3rd group was of the false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and immediately used. Amplex Red™ was used to measure mitochondrial O2•- formation and MitoTracker® Orange to evaluate Δψ. In vitro studies were carried out by using human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxia conditions. Administration of EVs restored O2•- formation to SHAM levels in all mitochondrial functional conditions. The expression of catalase and superoxide dismutase remained unmodified; transcription of heme oxygenase-1 (HO-1) was upregulated. The co-cultures of HK-2 cells with EVs revealed an intense decrease in apoptosis. We conclude that the mechanisms by which EVs recover the renal structure and function after I/R are related to the normalization of the mitochondrial redox environment. The intravesicular catalase is central in the preservation mechanisms that, with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, depress early processes of cell death after I/R and open new vistas for the treatment of AKI.

This article reviews all the major stages in the origins of life. From the emergence of matter in the initial Big Bang to the modern, civilized human being. On an immaterial level, it is proposed and explained how consciousness necessarily takes precedence over matter. Next, we explain how consciousness, with its ability to process information, selected the water molecule to breathe life into the periodic table of elements. We also explain why the notion of entropy allows us to evolve: "Die Entropie der Welt strebt einem Maximum zu" (second principle) and, therefore, takes precedence over the notion of energy, which, on the contrary, encourages us to preserve what we have: "Die Energie der Welt bleibt konstant" (first principle). This is followed by a discussion of the importance of quantum coherence and the need to rely on a second quantization formalism for a proper understanding of the physical-biochemical properties of water. Moreover, throughout the argument developed on the best and most fundamental things science has to offer, care is taken to link this knowledge to the great philosophies of the West (Greece), the East (China, India) or even to practices of a shamanic nature (Africa, America). Hence, finally, the proposal to reconsider all musical practice within the framework of the diapason of water at a frequency of 429.62 Hz, as well as all therapeutic practice on the basis of seven clearly identified and established frameworks of thought.

Antisense oligonucleotide (ASO)-mediated exon skipping has become a valuable tool for investigating gene function and developing gene therapy. Machine learning-based computational methods such as eSkip-Finder have been developed to predict the efficacy of ASOs via exon skipping. However, these methods are computationally demanding, and the accuracy of predictions remains suboptimal. In this study, we propose a new approach to reduce computational burden and improve prediction performance by using feature selection within machine learning algorithms and ensemble learning techniques. We evaluated our approach using a dataset of experimentally validated exon skipping events, dividing it into training and testing sets. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. Our findings suggest that our approach has the potential to enhance the accuracy and efficiency of predicting ASO efficacy via exon skipping. It could also facilitate the development of novel therapeutic strategies. This study could contribute to the ongoing efforts to improve ASO design and optimize gene therapy approaches.

Plants of the genus Monochoria have long been utilized in food, cosmetics, and traditional herbal treatment. Thailand has the highest species diversity of this genus and a new member, Monochoria angustifolia (G. X. Wang) Boonkerd & Tungmunnithum has been recently described. This plant is called “Siam Violet Pearl” as a common name or “ไข่มุกสีม่วงแห่งสยาม” as its vernacular name in the same meaning in Thai language. Despite their importance, few researches on Monochoria species have been conducted. This study, thus, provided the results to fill in this gap by: i) determining flavonoids phytochemical profiles of 25 natural populations of M. angustifolia covering the whole floristic regions in Thailand, and ii) determining antioxidant activity using various antioxidant assays to investigate the probable mechanism. The results revealed that M. angustifolia presented a higher flavonoid content than the outgroup, M. hastata. Our results also revealed that flavonoids might be used to investigate Monochoria evolutionary connections and for botanical authentication. The various antioxidant assays revealed that M. angustifolia extracts preferentially act through a hydrogen atom transfer antioxidant mechanism. Pearson correlation analysis indicated significant correlations emphasizing that the antioxidant capacity is most probably the result of a complex phytochemical combinations rather than of a single molecule. Altogether, these results showed that this new species provide an attractive alternative starting material with phytochemical variety and antioxidant potential for the phytopharmaceutical industry.

Metabolic diseases are major diseases affecting animal welfare, health and production of small ruminants´ flocks for dairy and meat purposes. In breeding females, they mainly occur from six to eight weeks before and after parturition, respectively. The pregnancy toxemia and lactational ketosis are manifestations of hyperketonemia, primarily due to energetic deficit. Hypocalcemia and hypomagnesemia are related to the metabolic availably of calcium and magnesium, respectively. This review aimed to identify and discuss the current and most relevant aspects related to individual and herd heath management of these interrelated metabolic diseases with impact in the sheep and goats´ farm sustainability. These diseases are primarily due to nutritional deficit, but homeostatic and homeorhetic disruptions are responsible for clinical signs and forms. Currently, their clinical diagnosis and monitoring are mainly supported by biochemistry from animal fluids, and bromatological evaluation of the feed. Epidemiological studies, measuring risks factors, also contributes for their prevention. Nevertheless, research on specific biomarkers and composite indexes related to these diseases, in a context of herd health management and precision medicine, are new pathways driven to a suitable and efficient animal production.

Mass spectrometry (MS) has revolutionized clinical chemistry, offering unparalleled capabilities for biomolecule analysis. This review explores the growing significance of MS, particularly when coupled with liquid chromatography (LC-MS), in identifying disease biomarkers and quantifying biomolecules for diagnostic and prognostic purposes. The unique advantages of MS in accurately identifying and quantifying diverse molecules have positioned it as a cornerstone in personalized medicine advancement. MS-based technologies have transformed precision medicine, enabling comprehensive understanding of disease mechanisms and patient-specific treatment responses. LC-MS has shown exceptional utility in analyzing complex biological matrices, while high-resolution MS has expanded analytical capabilities, allowing detection of low-abundance molecules and elucidation of complex biological pathways. The integration of MS with other techniques, such as ion mobility spectrometry, has opened new avenues for biomarker discovery and validation. As we progress towards precision medicine, MS-based technologies will be crucial in addressing the challenges of individualized patient care, driving innovations in disease diagnosis, prognosis, and treatment strategies.

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein involved in mitochondrial morphology and homeostasis. LETM1 is highly expressed in many human solid cancers and correlates with poor prognosis possibly due to mitochondrial dysfunction. However, the functional role of LETM1 in the progression of hematological malignancies remains to be elucidated. In this study, we found that higher LETM1 expression was associated with a short overall survival in Diffuse Large B-Cell Lymphoma (DLBCL) and in Acute Myeloid Leukemias (AML) patients. The transcriptomic analysis showed that LETM1 expression is positively correlated with oncogenic pathways (e.g., glucose transport, stem cell maintenance, mTOR and Wnt signaling pathways, mitotic G2/M phase transition, and cell proliferation) and negatively correlated with autophagy-related processes and apoptosis. In contrast, low expression of LETM1 associated with upregulation of BECLIN-1-dependent mitophagy, which in turn improves the prognosis in both DLBCL and AML patients. Our data suggest that LETM1 is a valuable prognostic marker and a possible therapeutic target for improving the clinical outcome in hematological malignancies.

The prevalence of patients on buprenorphine therapy presenting for elective surgery has increased. Buprenorphine is a widely used medication for management of patients with chronic pain. It is also used for maintenance therapy for patients with a history of opioid use disorder (OUD). Due to lack of standardized protocol for managing patients on buprenorphine peri-operatively, we performed a retrospective analysis to compare pain score outcomes and post-operative opiate requirements between patients who continued versus discontinued buprenorphine. We identified 35 patients, 11 continued buprenorphine and 24 discontinued buprenorphine. The average Post-Anesthesia Care Unit (PACU) pain score was 7.54 for those who discontinued pre-operative buprenorphine and 5.59 for those who continued (P value 0.0339). The average post-operative Morphine Milligram Equivalent (MME) use was 86.13 for those who continued pre-operative buprenorphine and was 107.70 for those who discontinued buprenorphine (P value 0.6439). The results from our study correlate with several previous studies which showed lower PACU pain scores in patients who continued buprenorphine. There is a benefit of decreased pain post-operatively when pre-operative buprenorphine is continued and having a decrease in relapse in those with a history of OUD.

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.

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.

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.

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

There is some evidence that aspects of nurse-doctor communication are associated with the quality of care and treatment patients receive whilst they are in hospital. To date, no studies have examined stakeholder perceptions of how patient care is influenced by clinical communication between nurses and doctors. We conducted a concept mapping study to generate a deep understanding of how clinical communication impacts patient care. Concept mapping has six phases: preparation, idea generation, structuring, representation, interpretation, and utilization. Twenty patients, 21 nurses, and 21 doctors participated in the study. Brainstorming generated 69 discreet statements about how nurse-doctor communication impacts patient care. The structuring (rating and clustering) phase was completed by 48 participants. The data interpretation workshop selected a five-cluster solution: effective communication, trust, patient safety, impediments to patient care, and interpersonal skills. On the final concept map, the five clusters were arranged in a circle around the center of the map. Clusters were relatively equal in size suggesting, each concept makes a broadly equal contribution to how nurse-doctor communication influences patient care. Our study suggests that there are multiple aspects of clinical communication that impact patient care. Candidate interventions to enhance nurse-doctor communication may need to consider the complex nature of interprofessional working. Registration: This study was prospectively registered with the Open Science Framework (OSF) (https://osf.io/9np8v/) prior to recruiting the first participant.

Background: This study aims to investigate the patient safety culture at a sports medicine hospital and explore quality of healthcare and associated factors. Methods: In a cross-sectional study design, the tool Hospital Survey on Patient Safety Culture (HSOPC) was administered online among staff at a sports medicine hospital in Doha, Qatar. About 319 staff participated from 898 staff who received emails (35.5%). Results: The results showed that 49.2% of the staff rated the patient safety grade as excellent and 36.1% as very good, which sums up to 85.3%. Factors associated with better patient safety grade were work climate (OR 10.3 95% CI (3.2 to 33.6); teamwork OR 7.6 95% CI (2.8 to 20.9) and team communication (OR 2.9 95% CI (1.1 to 7.6). Conclusions: Addressing the work climate, enhancing communication, and cohesive work within teams facilitates a culture of trust that improves patient safety grade. Ensuring quick return to play is a team effort involving multiple disciplines, hence a high performance and safety culture can enhance teamwork. Reducing punitive response to error and encouraging staff and supervisors are key areas that can improve safety culture in sports medicine organizations, and efforts should be placed in this area.

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

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

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

The inter-individual variability of CYP450s enzyme activity may be reduced by comparing the effects of bariatric surgery on CYP-mediated drug elimination in comparable patients before and after surgery. The current research will use a low-dose phenotyping cocktail to simultaneously evaluate the activities of six CYP isoforms and P-gp.The results showed that following weight reduction after surgery, the activity of all enzymes increased compared to the obese period, which was statistically significant in the case of CYP3A, CYP2B6, CYP2C9, and CYP1A2. Furthermore, the activity of P-gp after surgery decreased without reaching a statistical significance (p-value>0.05). Obese individuals had decreased CYP3A and CYP2D6 activity than the control group, albeit only CYP3A was statistically important. In addition, there was a trend to increase activity for CYP1A2, CYP2B6, CYP2C9, and CYP2C19 in obese patients compared to the control group, without reaching statistical insignificance (p-value≥0.05). After six months (at least), all enzymes and the P-gp pump activity were significantly higher than the control group except for CYP2D6.Ultimately, a greater comprehension of phenoconversion can aid in altering the patient's treatment. Further studies are required to confirm the changes in the metabolic ratios of probes after bariatric surgery to demonstrate the findings' clinical application. As a result, the effects of inflammation-induced phenoconversion on medication metabolism may differ greatly across persons and drug CYP pathways. It is essential to apply these results to the clinic to recommend dose adjustments.

Acute appendicitis is the most common surgical emergency worldwide with peak incidence in the age range of 10 – 19 years, and the standard treatment procedure is the surgical removal of the appendix to avoid complications such as its rupture, peritonitis, and sepsis. The COVID-19 pandemic required the global population to stay indoors to stop the spread of virus, which led to a decline in the number of patients visiting the hospital for non- COVID -19 related emergencies. This is a case of a 9-year-old girl who tested positive for COVID -19 and developed acute appendicitis and benefited from individualised classical homeopathy. Further scientific investigation is necessary to establish the relevance of individualised classical homeopathy in treating serious acute conditions such as acute appendicitis.

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

As a conceptual model of disease mechanisms, a disease map integrates available knowledge and is applied for data interpretation, predictions and hypothesis generation. It is possible to model disease mechanisms on different levels of granularity and adjust the approach to the goals of a particular project. This rich environment together with requirements for high-quality network reconstruction makes it challenging for new curators and groups to be quickly introduced to the development methods. In this review, we offer a step-by-step guide for developing a disease map within its mainstream pipeline that involves using the CellDesigner tool for creating and editing diagrams and the MINERVA Platform for online visualisation and exploration. We also describe how the Neo4j graph database environment can be used for managing and querying efficiently such a resource. For assessing the interoperability and reproducibility we apply FAIR principles.

Disabled children on the one hand have a wide range of impairments that translate into functional limitations but at the same time they possess various talents and capacities. These are manifested into the dynamics of society and the environment that they interact with. This article discusses disaster management with disabled children as a focus group. Disaster, disability and its management is discussed in the context of international practices in general and suited to India in particular. The research follows a review of the recommendations of the United States National Commission on Children and Disaster. In addition to this Disaster Medicine as one approach to Disaster Management concerning disabled children has been explored. The research concludes that the understanding of particular issues of Children with disabilities as one stakeholder, their capacity to engage and a shift in mindset and power relations in which they can contribute to disability inclusive disaster management are fundamental to disability-inclusive DRR.

Rheumatoid arthritis (RA) is a chronic, systemic, abnormal inflammatory immune response. It is characterized by the involvement of the synovium and multiple organs and the destruction of joints and articular cartilage. Over the past 30 years, several promising novel compounds and antibodies have been developed for the treatment of RA. The introduction of new drugs and precision medicine for all forms of RA raises several issues related to access to novel treatments by patients, optimal regimen selection, cost-effectiveness, prognosis monitoring and outcome surveillance, particularly with regarding to the development of low drug response rates, drug resistance and adverse side effects. Tremendous attention has been given to the identification of optimized drug combinations for the treatment of RA, particularly in early high-risk vulnerable and early individuals. Addressing these issues requires novel therapeutic approaches with new mechanisms and the establishment of accurate guidelines for drug selection, drug recombination, and non-chemical therapeutic efforts. In this study, we reviewed the most exciting recently established or ongoing novel drugs and methods according to the clinical trial database maintained by the United States National Library of Medicine and discussed the trends in RA drug development and challenges in the treatment, providing a reference significant for the accurate treatment of RA and the research direction in the future.

Medicinal plants are generally defined as rare herbals with potent medicinal activities that can be used as an alternative treatment for diseases. Recent studies exploring novel medicine developments, originating from folk-medicinal practices challenges this notion and suggests that both the circumference of the term medicinal plant and their potential application covers a substantially extensive verse than previously suggested. While medicinal plants are not limited to the borders of any country, Bangladesh and its south-east Asian neighbors do boast a huge collection of potent medicinal plants with considerable folk-medicine history compared to most other countries of the world. MPDB 2.0 is the continuation of MPDB 1.0, it serves as both a data repertoire for medicinal of Bangladesh and a user-friendly interface for researchers, health practitioners, drug developers, and students who wish to study the various medicinal & nutritive plants scattered around Bangladesh and the underlying phytochemicals contributing to their efficacy in folk medicine. While in developing MPDB 2.0 human diseases have been highly focused upon, the information in this database is not limited in its application for human diseases or diseases only, as many of the plants indexed here can serve in developing biofuel or bioremediation technologies or nutritive diets or cosmetics, etc. MPDB 2.0 comprises a collection of more than five hundred medicinal plants from Bangladesh along with a record of their corresponding scientific, family, and local names together with their utilized parts, information regarding ailments, active compounds, and PubMed ID of related publications.

Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or Gemcitabine-Nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/- chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.

Migraine is a common condition that affects children as they develop into adults. Transition of care from pediatric to adult care has becoming an increasingly popular topic in the medical literature. It has been suggested that discussions between patients, their families and providers should be initiated as early as age 13. Patients who are un or underprepared have poorer outcomes due to increased morbidity and worsening of their medical condition. Many children continue to have migraine into adulthood and if efforts are taken to ensure patients receive appropriate transfer of care, the results can significantly decrease the economic burden of this disease.

This paper address the development of a new technic in the sleep analysis domain. Sleep is defined as a periodic physiological state during which vigilance is suspended and reactivity to external stimulations diminished. We sleep on average between six and nine hours per night and our sleep is composed of four to six cycles of about 90-minutes each. Each of these cycles is composed of a succession of several stages of sleep, more or less deep. The analysis of sleep is usually done using a polysomnography. This examination consists of recording, among other things, electrical cerebral activity by electroencephalography (EEG), ocular movements by electrooculography (EOG) and chin muscle tone by electromyography (EMG). The recording is done mostly in a hospital, more specifically in a service for monitoring the pathologies related to sleep. The readings are then interpreted manually by an expert to generate a hypnogram, a curve showing the succession of sleep stages during the night in 30-second epochs. The proposed method is based on the follow-up of the thermal signature that makes it possible to classify the activity into three classes: "awakening", "calm sleep" and "agitated sleep". The contribution of this non-invasive method is part of the screening of sleep disorders, to be validated by a more complete analysis of the sleep. The measure provided by this new system, based on temperature monitoring (patient and ambient), aims to be integrated into the tele-medicine platform developed within the framework of the Smart-EEG project by the SYEL - SYstèmes ELectroniques team. Analysis of the data collected during the first surveys carried out with this method showed a correlation between thermal signature and activity during sleep. The advantage of this method lies in its simplicity and the possibility of carrying out measurements of activity during sleep and without direct contact with the patient at home or hospitals.

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