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

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

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

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

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

Complex diseases are prevalent medical conditions which are characterized by strong inter-patient differences in symptom profiles, disease trajectory and treatment response. The challenges in understanding and managing these diseases are due to their complex pathophysiology, comprising of a combination of genetic and environmental factors. The traditional model of disease assumes a clear distinction between health and disease, as well as between different diagnoses, but recent findings with regards to diseasomes and network pleiotrophy suggest that this dogma is not useful in understanding complex diseases. This paper presents a novel model, in which the individual disease burden is determined as a function of molecular, physiological and pathological factors simultaneously: disease(symptoms(traits(genes AND environment))). From this a high-dimensional space is defined which includes all individual disease burdens, ranging from healthy (i.e. low disease burden) to multi-morbidity (i.e. high disease burden), termed the disease landscape. This model provides a novel way to conceptualize human physiology and pathophysiology in the context of complex diseases and may present a useful concept to simultaneously address the strong interindividual heterogeneity of diagnose cohorts as well as the lack of clear distinction between diagnoses and health and disease, thus facilitating the progression towards personalized medicine.

Objective: Health/wellness applications on mobile devices (Apps) may positively affect the health of seniors (persons age 65+). But for an App to promote health in its target audience, it must achieve meaningful use. Method: For one and a half years, residents at a Life Plan Community (mean age 86) used a wellness App running on iPad. In a digital survey, residents rated their overall satisfaction with the App on a scale from 1 (strongly dislike) to 10 (strongly enjoy). Results: User satisfaction (96 respondents of 252; 38% response rate) was distributed with maximum 8, median 7, mean 6.6, and standard deviation 2.3. Discussion: The results suggest that it is feasible to inspire seniors to pursue whole-person wellness using an App: technology may promote “active aging.”

Patient-derived xenograft (PDX) models are created by engraftment of patients’ tumor tissues into immunocompetent mice. Since PDX model keep the characteristics of primary patient’s tumor such as gene expression profiles and drug sensitivity, it now becomes most reliable in vivo human cancer model. The engraftment rate are increased with the introduction of NOD/Scid based immunocompromised mice, especially, NK cell defective NOD strains such as NOD/Scid/IL2Rγnu (NOG/ NSG) mice and NOD/Scid/Jak3null (NOJ) mice. Success ratio differs from the origin of tumor: Gastrointestinal tumors tend to higher success rate and breast cancer is lower. Subcutaneous transplantation is most popular method to establish PDX, but some tumor needs orthotropic or renal capsule transplantation, and human hormone treatment is needed to establish hormone dependent cancers such as prostate and breast cancer. PDX library with patient’s clinical data, gene-expression patterns, mutational status, drug responsiveness and tumor architecture will be the powerful tool for developing specific biomarker and novel individualized therapy and establishing precision cancer medicine.

Background: Developing patient-centric baseline standards that enable the detection of clinically significant outlier gene products on a genome-scale remains an unaddressed challenge required for advancing personalized medicine beyond the small pools of subjects implied by “precision medicine”. This manuscript proposes a novel approach for reference standard development to evaluate the accuracy of single-subject analyses of metabolomes, proteomes, or transcriptomes. Since distributional assumptions of statistical testing may inadequately model genome dynamics of gene products, the so-called significant results of previous studies may artefactually conflate with real signals. Model confirmation biases escalate when studies use the same analytical methods in the discovery sets and reference standards, as corroboration of results leads to an evaluation of reproducibility confounded with replicated biases rather than a measure of accuracy. We hypothesized that developing method-agnostic reference standards using effect-size and expression-level filtering of results, obtained from multiple discovery methods that are distinct from the one evaluated, would maximize the evaluation of clinical-transcriptomic signals and minimize statistical artefactual biases. We developed and released an R package “referenceNof1” to facilitate the construction of robust reference standards. Results: Since RNA-Seq data analysis methods often rely on binomial and negative binomial assumptions to non-parametric analyses, the differences create statistical noise and make the reference standards method dependent. In our experimental design, the accuracy of 30 distinct combinations of fold changes (FC) and expression levels (EL) were determined for five types of RNA analyses in two different datasets. This design was applied to two distinct datasets: breast cancer cell lines and a yeast study with isogenic biological replicates in two experimental conditions. In addition, the reference standard (RS) comprised all RNA analytical methods with the exception of the method testing accuracy. To mitigate for biased optimization of the RS parameters towards a specific analytical method, similarity between observed results of distinct analytical methods were calculated across all methods (Jaccard Concordance Index). The greatest differences were observed across diametric extremes. For example, filtering out differentially expressed genes (DEGs) using a fold change < 1.2 leads to a 50% increase in concordance between techniques when compared to results with FC > 1.2. Combining this FC cutoff with genes with mean expressions > 30 counts leads to a 65% increase in concordance in comparison to genes with expression levels < 30 counts and with FC < 1.2. Conclusions: We have demonstrated that comparing accuracies of different single-subject analysis methods for clinical optimization requires a new evaluation framework. Reliable and robust reference standards, independent of the evaluated method, can be obtained under a limited number of parameter combinations: fold change (FC) ranges thresholds, expression level cutoffs, and exclusion of the tested method from the RS development process. When applying anticonservative reference standard frameworks (e.g., using the same method for RS development and for prediction), a majority of the concordant signal between prediction and Gold Standard (GS) cannot be confirmed by other methods, which we conclude as biased results. Statistical tests to determine DEGs from a single-subject study generate many biased results that require subsequent filtering for increasing their reliability. Conventional single-subject studies pertain to one or a few measures in one patient over time [1]and need a substantial conceptual framework extension in order to address the tens of thousands of measures in genome-wide analyses of gene products. The proposed referenceNof1 framework addresses some of the inherent challenges in improving transcriptome scale single-subject analyses by providing a robust approach to constructing reference standards. Github: https://github.com/SamirRachidZaim/referenceNof1

Background and objectives: The inadequate knowledge of complementary and alternative medicine (CAM) among health professionals may put their clients in risky situation because they then would find information about CAM from unreliable sources. Clinical psychologists (CPs), as health professionals, have also the opportunity to provide psychoeducation on the latest CAM scientific research to their clients. The current study aimed to explore knowledge and educational needs of CAM among CPs in Indonesia because previous studies on exploring CAM knowledge and educational needs of CAM were primarily conducted in Western countries. Materials and Methods: Data were collected through semi-structured face-to-face interviews with 43 CPs in public health centers (PHCs) in Indonesia. Most interviews were held at the PHCs where participants worked and interviews lasted for 55 minutes, on average. The interview recordings were transcribed and were analyzed using deductive thematic analysis. Results: Five main themes emerged within participants’ responses regarding CAM knowledge and educational needs. First (CAM understanding), participants’ responses ranged from those with little or no prior knowledge of CAM treatments and uses, to those with much greater familiarity. Second (source of knowledge), participants’ access ranged widely in terms of references, from popular to scientific literature. Third (why is it important?), participants identified CAM essentially as part of Indonesian culture and it was therefore crucial to have this cultural knowledge. Fourth (the challenges and what is needed?), the challenges for improving participants’ knowledge came from personal and institutional levels. Fifth (what and how to learn?), participants advised that only CAM treatments that fit in brief psychotherapy sessions should be introduced in professional training. Conclusions: This qualitative study discovered that CAM was neither well-known nor understood widely. Participants advised that professional associations and health institutions should work together in enhancing knowledge of CAM and incorporating CAM education into psychology education.

Health-related data originating from diverse sources are commonly stored in manifold databases and formats, making it difficult to find, access and gather data for research purposes. In addition, so-called secondary use scenarios for health data are usually hindered by local data codes, missing dictionaries and the lack of metadata and context descriptions. Following the FAIR principles (Findable, Accessible, Interoperable and Reusable), we developed a decentralized infrastructure to overcome these hurdles and enable collaborative research by making the meaning of health-related data understandable to both, humans and machines. This infrastructure is currently being implemented in the realm of the Swiss Personalized Health Network (SPHN), a research infrastructure initiative for enabling the use and exchange of health-related data for research in Switzerland. The SPHN ecosystem for FAIR data consists of the SPHN Dataset (semantic definitions), the SPHN RDF Schema (linkage and transport of the semantics in a machine-readable format), a project RDF template, extensive guidelines and conventions on how to generate SPHN RDF schema, a Terminology Service (converter of clinical terminologies in RDF), and a Quality Assurance Framework (automated data validation with SHACLs and SPARQLs). The SPHN ecosystem has been built in a way that it can easily be adapted and extended by any SPHN project to fit individual needs. By providing such a national ecosystem, SPHN supports researchers in generating, processing and sharing FAIR data.

Abstract: Imaging of low (LGG) to high (HGG) grade gliomas is conventionally performed with MRI, which is the non-invasive gold-standard imaging modality to derive data. Gliomas (Grade 1,2,3,4) are lethal and demonstate poor outcomes despite novel therapies. Integrins compose of heterodimeric parasympathetic nervous system; the aVb3 (RGD i.e. Galacto-Arginine-Glycine-Aspartic acid) have been displayed as a potential biomarker that can be imaged via PET in order to trace the angiogenetic pathway. Gliomas are common primary central nervous system (CNS) tumours which are often pose a diagnostic challenge, even to stage and manage because of their heterogeneity in molecular aberrations. Several core mutational core hallmarks of gliomas are inducing/accessing vasculature, tumour promoting inflamation, polymorphic microbes and avoiding/resisting cell death; these ultimately lead to poor prognosis. In 2007, the classification of diffuse gliomas was based on the histopathology and subtype e.g. Pilocytic astrocytoma and low cell proliferation, in 2016, the classification of diffuse gliomas was based on the IDH status, 1p/19q codeletion, subtype and grade; then in 2021, the IDH status (wild-type or mutant), molecular profile, subtype and grade were added in order to improve the classification of diffuse gliomas. Imaging (MRI) techniques progress stalled despite the imperfections in MRI e.g distinguishing RN (radionecrosis) and PsP (Pseudoprogression) hence the exploration of PET probes that detect important hallmarks of gliomas e.g. techniques such as [68Ga]68Ga-RGD positron emission tomography (PET) to be utilised to assess vasculature. This case report aimed to determine the potential clinical utility of molecular imaging with 68Ga-RGD PET used in complementary to traditional MRI techniques.

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

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

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

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

Snakebite envenomation, cognized as a neglected tropical disease, is a dread public health concern with the most susceptible groups being herdsmen, the elderly, active farmers, hunters, fishers, firewood collectors, 10 to 14-year old working children and individuals with limited access to education and health care. Snakebites are fragmentarily documented in Uganda primarily because most occur in rural settings where traditional therapists end up being the first line defence for treatment. Ethnobotanical surveys in Uganda have unveiled that some plants are used to antagonize the activity of various snake venoms. This review was sought to compile the sporadic information on the vegetal species reported as antivenins in Uganda. Electronic data indicate that no study entirely reported on antivenin plants in Uganda. A total of 77 plant species belonging to 65 genera, distributed among 42 botanical families claimed as antiophidic in Uganda are used for treatment of snakebites. Majority of these species belong to family Fabaceae (30.9%), Euphorbiaceae (14.3%), Asteraceae (11.9%), Amaryllidaceae (9.5%) and Solanaceae (9.5%). The antiophidic species listed are shrubs (40.5%), trees (32.9%) and herbs (17.7%), usually found in the wild and uncultivated. Antivenin extracts are primarily prepared from roots and leaves, through decoctions, infusions, powders and juices and administered orally or topically. The most frequently encountered therapeutically important species are Allium cepa L., Carica papaya L., Securidaca longipedunculata Fres., Harrisonia abyssinica Oliv. and Nicotiana tabacum L. Baseline epidemiological data on snake envenomation and antivenin plants in Uganda remain incomplete due to inadequate research and diverse ethnic groups in the country. There is a dire need to isolate and characterize the bioactive compounds in the claimed plants to enable their adroit utilization in handling the plague of snake envenomation. More baseline data should be collected on snake ecology and human behaviour as well as antivenin plants in Uganda. Indigenous knowledge on the use of plant preparations in traditional medicine in Uganda is humongous, but if this is not quickly researched and appropriately documented, indications as to the usefulness of this vegetal treasure house will be lost in the not so distant future.

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating collection of relevant information from health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and make these publicly available to enhance dissemination and assist in making precision public health a reality.

Worldwide, over 2.2 million people are suffered from multiple sclerosis (MS), a multifactorial demyelinating disease of the central nervous system. MS is characterized by a wide range of motor, autonomic, and psychobehavioral symptoms including depression, anxiety, and dementia. The blood, cerebrospinal fluid, and postmortem brain samples of MS patients evidenced the disturbance of reduction-oxidation (redox) homeostasis such as the alterations of oxidative and antioxidative enzyme activities and the presence of degradation products. This review article discussed the components of redox homeostasis including reactive chemical species, oxidative enzymes, antioxidative enzymes, and degradation products. The reactive chemical species covered frequently discussed reactive oxygen/nitrogen species, infrequently featured reactive chemicals such as sulfur, carbonyl, halogen, selenium, and nucleophilic species that potentially act as reductive as well as pro-oxidative stressors. The antioxidative enzyme systems covered the nuclear factor erythroid-2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway. The NRF2 and other transcriptional factors potentially become a biomarker sensitive to the initial phase of oxidative stress. Altered components of the redox homeostasis in MS were discussed in search of a diagnostic, prognostic, predictive, and/or therapeutic biomarker. Finally, monitoring a battery of reactive chemical species, oxidative enzymes, antioxidative enzymes and degradation products helps evaluate the redox status of MS patients to expedite building personalized treatment plans for the sake of better quality of life.

Gliomas are common primary central nervous system (CNS) tumours which are often very difficult to diagnose, stage and manage because of their heterogeneity and molecular aberrations. The notable hallmark of gliomas is integrated genome mutations and methylome that correlates with distinctive patterns of transcription that potentiates glioma heterogeneity, angiogenesis and ultimately poor prognosis. The World Health Organization (WHO) has decided to reclassify gliomas based on molecular markers rather than the traditional anatomical basis; use of Nuclear Medicine techniques e.g. SPECT/PET and Magnetic Resonance Imaging (MRI) techniques based on molecular markers is set to become the future gold standards. This has led to the investigations on potential for the use of non-invasive imaging techniques such as [68Ga]68Ga-RGD positron emission tomography (PET) to be utilised routinely in clinical practice based on angiogenic markers and also the potential to add information that may assist in drug-design and therapeutic decision making. This review aims to provide an overview of the basis of recent advances in glioma imaging using molecular targeting with positron emission tomography and SPECT imaging, as well as the role in patient management i.e. diagnosis, staging, recurrence detection etc.

Providing healthcare workers with cost information about the medications they prescribe can influence their decisions, particularly when that information is provided at the very moment they are faced with a prescribing decision. The current study aimed to analyse the impact of nudges that presented cost information to prescribers through their organisation's electronic prescribing system. The nudges were co-created by the research team (composed of behavioural scientists) and the lead hospital pharmacist. One nudge provided simple cost information (percentage difference between two brands of Mesalazine – Asacol and Octasa). The second nudge provided the potential annual cost-saving that could result if the cheaper medication was selected across the organisation. While the statistical analyses revealed that these nudges were not effective, several administrative barriers were overcome, which may inform future research. For example, presenting aggregated cost information to the prescribers is possible even when the actual cost of medicine is confidential and can not be displaced. In addition, future research could reveal more behavioural factors that facilitate medication optimisation.

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

Objective The healthcare industry has witnessed a paradigm shift with the adoption of Electronic Patient Records (EPRs), transitioning from traditional Paper and Pencil (P&P) methods to sophisticated, technology-driven documentation systems. However, the integration of EPRs into clinical settings has introduced new challenges. This study investigates workflow consequences of switching from P&P to EPR systems. Methods In this study, two independent observers audited surgical ward rounds to assess the effects of transitioning from P&P to EPR. These audits captured number of medical personnel and five key aspects before and after EPR implementation. Additionally, the EPR system's usability was gathered through the System Usability Scale (SUS) and the Post Study System Usability Questionnaire (PSSUQ). Results A total of 192 observations using P&P and 160 with the EPR system were analyzed. Results indicated that physicians spent a lower proportion of time in patient rooms using the P&P modality (median = 0.14, IQR = [0.06, 0.24]) compared to the EPR system (median = 0.19, IQR = [0.12, 0.29]). Conversely, nurses spent more time with the P&P modality (median = 0.13, IQR = [0.08, 0.18]) than with the EPR system (median = 0.10, IQR = [0.06, 0.13]). The typical team in the P&P modality comprised two physicians and four nurses, while teams in the EPR system generally included two or three physicians and three nurses. Usability assessments yielded scores rated as "Not Acceptable." Conclusion The EPR is already known to contribute to an increased administrative burden. Our findings generally align with this view in the physician sample, whereas nurses did not encounter difficulties switching systems. However, usability scores indicated that the EPR system falls short of meeting user acceptance expectations. Given the continuous increase in administrative workload, our results suggest that ururcing administrative tasks could enhance the efficiency of medical duties performed at patient's bedside.

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is 18F-fluorodeoxyglucose (18F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors, metastatic sites, and assessment of tumor response to therapy. In addition to 18F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care.

Maxillomandibular advancement (MMA) is a surgical intervention that reduces the symptoms of obstructive sleep apnea via anterior repositioning of the upper and lower jaws. Pre-operative orthodontic alignment is often a critical component in aiding MMA. Orthodontia are important in intraoperative anchorage for intermaxillary fixation, healthy post-operative occlusion, and post-operative skeletal stability. Sequential clear aligners (SCA) refer to removable orthodontic appliances that are replaced at regular intervals to stimulate dental migration without the use of bonded hardware. These aligners have demonstrated efficacy in aiding orthognathic surgery for dentofacial deformities, which share some technical similarities with MMA for OSA. Here, we explore the treatment protocol for MMA followed by post-operative SCA treatment. Our experiences show that post-operative orthodontic treatment with SCAs results in similarly successful post-operative surgical outcomes given that the patient’s pre-operative occlusion is stable.

Duke University was founded in 1930 primarily due to funds generated from James B. Duke’s tobacco business. Duke achieved great financial wealth primarily due to the early application of machine rolled cigarettes, as opposed to hand rolled. This early adoption of technology allowed Duke Tobacco to out-produce other companies still selling hand rolled cigarettes. By making smoking more inexpensive and easier than pipe smoking, the cigarette formed the foundation for nicotine addiction in the 1900s, generating huge profits for the tobacco industry. At the time Duke University was founded, little was known about the connection between nicotine, cigarettes, and respiratory diseases such as emphysema and lung cancer. Through James Duke’s philanthropy, the devastating harm from cigarettes has been mitigated in part through the founding of one of the world’s most prominent medical centers and research universities.

Unlike plants which have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm known effects of microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 hours of exposure to microgravity via a NASA-developed rotary cell culture system. Fluorescence-guided morphometry revealed microgravity-induced loss of the significant reduction (p &lt; 0.0l) to the nuclear to cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on impact of microgravity on cellular drug-response, in view of the growing need for space medicine, as space exploration grows.

Artificial intelligence (AI) is transforming many healthcare fields including pediatric urology. This in-depth review explores recent advances in AI tools for pediatric urology, emphasizing how state-of-the-art technologies can be used to enhance patient treatment. An initial overview of pediatric urology is given to provide context for this interdisciplinary field and the wide spectrum of problems this entails, before discussing potential uses of AI to improve diagnostic accuracy, treatment planning, and surgical results. AI-powered predictive models are already changing pediatric clinical practice by guiding interpretation of medical images and supporting decision making. In addition to outlining the aims, methods, and conclusions of previous studies on AI applications in pediatric urology, this review also highlights knowledge gaps and priority areas for future study. Particular focus is given to specialized surgeries such pyeloplasty, where AI-guided treatment may help overcome specific technical challenges of this complex procedure. Also highlighted are practical, ethical, and legal aspects of integrating AI into pediatric urology, which will be crucial for responsible innovation in patient-centered treatment. Overall, this article aims to enlighten and inspire clinicians, researchers, and other healthcare stakeholders by offering insight into the future of AI in pediatric urology.

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

The practice of the veterinary profession is regulated by public law and corporate regulations. The most fundamental corporate regulations of veterinary associations, to which membership is a condition of practising the profession, are the codes of veterinary ethics. The codes of ethics contain five basic rules for practising veterinary responsibilities to animals, clients, the public, the veterinary team, and the veterinarians themselves. Veterinarians are often faced with dilemmas about whose interests to protect; this is due to the tasks the profession carries out while protecting the animals of their owners and the public. Ethical principles are a guideline for veterinarians in difficult situations. Depending on the hierarchy of values imposed by codes of ethics, different decisions can be made. In this article, we present the importance that the Polish code of veterinary ethics gives to animal welfare as an obligation of veterinarians towards animals and compare how animal welfare is positioned in the European, American, British and New Zealand codes of veterinary ethics. In contrast to other codes, the Polish code of veterinary ethics does not sufficiently recognise animal welfare as a value to be protected in the practice of the profession.

Breast implant surgery has evolved significantly, yet challenges such as capsular contracture remain a persistent concern. This review presents an in-depth analysis of recent advancements in understanding the immune mechanisms and clinical implications associated with breast implants. The article systematically examines the complex interplay between immune responses and capsular fibrosis, emphasizing the pathophysiological mechanisms of inflammation in the etiology of this fibrotic response. It discusses innovations in biomaterial science, including the development of novel anti-biofilm coatings and immunomodulatory surfaces designed to enhance implant integration and minimize complications. Emphasis is placed on personalized risk assessment strategies, leveraging molecular insights to tailor interventions and improve patient outcomes. Emerging therapeutic targets, advancements in surgical techniques, and the refinement of post-operative care are also explored. Despite notable progress, challenges such as variability in immune responses, long-term efficacy of new interventions, and ethical considerations remain. Future research directions are identified, focusing on personalized medicine, advanced biomaterials, and bridging preclinical findings with clinical applications. As we advance from bench to bedside, this review illuminates the path forward, where interdisciplinary collaboration and continued inquiry weave together to enhance the art and science of breast implant surgery, transforming patient care into a realm of precision and excellence.

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

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

Kawasaki disease is a febrile illness characterised by systemic inflammation of small- and medium-sized blood vessels which commonly occurs in young children. Although self-limiting, there is a risk of developing coronary artery lesions as disease progresses with delay in diagnosis and treatment. Unfortunately, the diagnosis of KD continues to remain a clinical dilemma. Thus, this article not only summarises the key research gaps associated to KD, but also evaluates the possibility of using circulating endothelial injury biomarkers such as, circulating endothelial cells, endothelial microparticles and vascular endothelial cell-free DNA, as diagnostic and prognostic tool of KD: a “liquid biopsy” approach. The challenges of translating liquid biopsies to use in KD, and the opportunities for improvement in its diagnosis and management that such translation may provide are discussed. The use of endothelial damage markers, which are easily obtained via blood collection, as diagnostics is promising and we hope this will be translated to clinical applications in the near future.

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

Adult patients with Autism Spectrum Disorder (ASD) exhibit a range of behaviours that can be disruptive to the medical care of themselves and other patients and as a result, are at higher risk of being sedated. The aim of the present study was to determine whether patients with ASD presenting to hospital for acute psychiatric crises re-ceive more sedative medications compared to similar patients without ASD. 43 adult patients with a previous di-agnosis of ASD who were referred to the mental health team at a single, large emergency department in metro-politan Victoria over the year of 2021 were identified and matched with an equal number of controls within the same cohort. Sedative medications were converted to diazepam and chlorpromazine equivalent doses and com-pared using repeated measures T-tests. Patients with ASD received 5.1mg more diazepam-equivalent benzodiaz-epines on average compared to matched controls (95%CI: 0.41-9.71). This difference was statistically significant (T=2.20, df=42, p=0.034). There was no significance difference in chlorpromazine-equivalent antipsychotic doses. Clinicians should be aware of the higher dose of sedatives, and consider other means of behavioural management in these patients.

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

Background: The aim of the present investigation was to evaluate the clinical success of horizontal ridge augmentation in the severely atrophic maxilla (Cawood and Howell class IV) using freeze-dried custom made bone harvested from cadaver donors tibial hemiplateau and to analyze the marginal bone level gain prior dental implants placement at 9 months after bone grafting and before prosthetic rehabilitation. Methods: A 52-year-old woman received custom made bone grafts. Patient underwent CT scans 2 weeks prior and 9 months after surgery for graft volume and density analysis. Results: The clinical and radiographic bone observations showed a very low rate of resorption after bone graft and implant placement. Conclusions: The custom-made allograft material was a highly effective modality for restoring the alveolar horizontal ridge, resulting in this way to reduce the need to obtain autogenous bone from a secondary site with predictable procedure. Further studies are needed to investigate its behavior at longer time points.

Blood glucose (BG) monitoring is an important issue for critically ill patients. Previous studies reported that poor sugar control was associated with increased mortality in admitted patients. However, repeated blood glucose monitoring can be resource-consuming and cause a healthcare burden in clinical practice. In this study, we aimed to develop a personalized machine-learning model to predict dysglycemia based on electrocardiogram (ECG) findings. The study included patients with more than 20 ECG records during single hospital admission in the Medical Information Mart for Intensive Care III database, focusing on the lead II recordings, along with the corresponding blood sugar data. We processed the data and used ECG features from each heartbeat as inputs to develop a one-class support vector machine (SVM) algorithm to predict dysglycemia. The model prediction for dysglycemia using a single heartbeat had an AUC level of 0.92 ± 0.09, with a sensitivity of 0.92 ± 0.10 and specificity of 0.84 ± 0.04. Based on 10 s majority voting, the model prediction for dysglycemia improved to an AUC of 0.97 ± 0.06. In this study, we found that a personalized machine-learning algorithm could accurately detect dysglycemia using a single-lead ECG.

Antisense oligonucleotides (ASO), short single-stranded polymers based on DNA or RNA chemistries and synthesized in vitro, regulate gene expression by binding in a sequence-specific manner to an RNA target. The functional activity and selectivity in the action of ASOs largely depends on the combination of nitrogenous bases in a target sequence. This simple and natural property of nucleic acids provides an attractive route by which scientists can create different ASO-based techniques. Over the last 50 years, planned and realized applications in the field of antisense and nucleic acid nanotechnologies have produced astonishing results and posed new challenges for further developments, exemplifying the essence of the post-genomic era. Today the majority of ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake. This review critically analyzes some successful cases using the antisense approach in medicine to address severe diseases, such as Duchenne muscular dystrophy and spinal muscular atrophy, and suggests some prospective directions for future research. We also examine in detail the elaboration of unmodified insect-specific DNA insecticides and RNA preparations in the areas of agriculture and forestry, a relatively new branch of ASO that allows circumvention of the use of non-selective chemical insecticides. When considering the variety of successful ASO modifications with an efficient signal-to-noise ratio of action, coupled with the affordability of in vitro oligonucleotide synthesis and post-synthesis procedures, we predict that the next half-century will produce a fruitful yield of tools created from effective ASO-based end products.

The combination of immunoPET—where an antibody (Ab) is labeled with an isotope for PET imaging—and radioimmunotherapy (RIT), using the same antibody with a therapeutic isotope, offers significant advantages in cancer management. ImmunoPET allows non-invasive imaging of antigen expression, which aids in patient selection for a subsequent radioimmunotherapy. It also facilitates the assessment of tumor response to therapy, allowing for treatment adjustments if necessary. In addition, immunoPET provides critical pharmacokinetic data, including antibody biodistribution and clearance rates, which are essential for dosimetry calculations and treatment protocol optimization. There are still challenges to overcome. Identifying appropriate target antigens that are selectively expressed on cancer cells while minimally expressed on normal tissues remains a major hurdle to reduce off-target toxicity. In addition, it is critical to optimize the pharmacokinetics of radio-labeled antibodies to maximize tumor uptake and minimize normal tissue uptake, particularly in vital organs such as the liver and kidney. This approach offers the potential for targeted and personalized cancer therapy with reduced systemic toxicity by exploiting the specificity of monoclonal antibodies and the cytotoxic effects of radiation. However, further research is needed to address remaining challenges and to optimize these technologies for clinical use.

The aim of this study was to investigate the knowledge, attitudes, and behaviors of family physicians regarding testicular cancer and testicular self-examination. This study was conducted with 307 physicians, including family physician specialists, family physician residents, contracted family physician specialist assistants (SAHU), and general practitioners, who agreed to participate in the study. All participants were administered a 33-item questionnaire consisting of sociodemographic questions and questions about testicular cancer and testicular self-examination, developed through literature review. Data analysis was performed using SPSS 22.0 software. 307 family physician specialists, family physician residents, SAHU residents and general practitioners participated in the study. 10.4% of the participants were working as family medicine specialists, 67.4% as family physician assistants, 13.7% as SAHU residents and 8.5% as general practitioners. The mean time spent in the profession was found to be 5.93±5.89. 65.8% of the participants thought that they had partially sufficient knowledge about testicular cancers. 57.7% of the participants stated that they did not know how testicular self-examination was performed. 49.7% of male participants stated that they had never done testicular self-exam before. While 95.8% of the participants thought that regular testicular self-examination was beneficial, 71.0% stated that they did not recommend testicular self-examination to their male patients. 53.4% of the participants thought that testicular self-examination was important; It was determined that 79.2% of them thought it was as important as breast self-examination. The rate of stating that all of the risk factors presented for testicular cancer are risks was found to be statistically significantly higher in specialist family physicians than in general practitioners and resident family physicians. The study revealed that family physicians lacked sufficient knowledge about testicular cancer and testicular self-examination, leading them not to recommend self-testicular examination to patients due to inadequate knowledge. In light of these findings, although self-testicular examination may not be recommended as a screening method, increasing awareness and knowledge among both family physicians and the public is crucial.

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

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

Pharmacogenomic (PGx) testing to inform antidepressant medication selection and dosing is gaining attention from healthcare professionals, patients, and payors in Australia. However, there is often uncertainty regarding which test is most suitable for a particular patient. Here, we identified and evaluated the coverage of CYP2D6 and CYP2C19 variants in commercial antide-pressant PGx testing panels in Victoria, a large and ethnically diverse state of Australia. Test characteristics and star alleles tested for both genes were obtained directly from pathology la-boratories offering PGx testing and compared against the Association of Molecular Pathology’s recommended minimum (Tier 1) and extended (Tier 2) allele sets. Although all tests covered the minimum recommended alleles for CYP2C19, this was not the case for CYP2D6. This study em-phasizes that PGx tests might not be suitable for all individuals in Australia due to the limited range of star alleles assessed. Inadequate haplotype coverage may risk misclassification of an individual’s predicted metabolizer phenotype which has ramifications for depression medica-tion selection and dosage. The study underscores the urgent need for greater standardization in PGx testing and emphasizes the importance of considering genetic ancestry when choosing a PGx testing panel to ensure optimal clinical applicability.

Artificial Intelligence (AI) has emerged as a disruptive technology in various areas, and medicine is no exception. In the last decade, there has been rapid progress in the application of AI in healthcare, from diagnosing and prognosticating diseases to improving operational efficiency in hospitals. This literature review explores the advances of artificial intelligence in the field of medicine, discusses its benefits, and discusses the ethical and regulatory challenges that need to be addressed to maximize its potential.

Background: Immunologic and neuro-inflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. Methods: We performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Results: Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways in-volved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Conclusions: Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

The huge advancement of Internet web facilities as well as the progress in computing and algorithm development, along with current innovations regarding high-throughput techniques enables the scientific community to gain access to biological datasets, clinical data, and several databases containing billions of information concerning scientific knowledge. Consequently, during the last decade the system for managing, analyzing, processing and extrapolating information from scientific data has been considerably modified in several fields including the medical one. As a consequence of the mentioned scenario, scientific vocabulary was enriched by novel lexicons such as Machine Learning (ML)/Deep Learning (DL) and overall Artificial Intelligence (AI). Beyond the terminology, these computational techniques are revolutionizing the scientific research in drug discovery pitch, from the preclinical studies to clinical investigation. Interestingly, between preclinical and clinical research, the translational research is benefitting from computer-based approaches, transforming the design and execution of the translational research, resulting in breakthroughs for advancing human health. Accordingly, in this review article, we analyze the most advanced applications of AI in translational medicine, providing an up-to-date outlook regarding this emerging field.

Discovery of novel variants from data derived from local population provides confident targets for developing biomarkers for personalized medicine. Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. We identified the need to generate high quality sequencing data from local population and understand the pattern of occurrence of variants in colorectal cancer patients. In this report, we used archived samples from Saudi Arabia and used Ampliseq Comprehensive Cancer panel to identify novel somatic variants. We report a comprehensive analysis of next generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in large intestine. APC, RET and EGFR genes were most frequently mutated. Higher number of variants were identified in left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.

Monitoring and measuring magnesium (Mg) values are essential to prevent the development of numerous complications in perioperative medicine and critically ill patients. Although previous studies suggest that measuring free ionized magnesium (iMg) is more useful for estimating Mg status, clinicians currently rely on measurement of total serum magnesium to determine if supplemental magnesium is needed. In this review, we analyzed the recent literature to decide whether it is better to measure ionized serum Mg or total serum Mg when assessing magnesium status, whether iMg predicts clinical outcome, and what are the difficulties in measuring serum iMg levels in intensive care patients and perioperative medicine.

The soccer injury rate is distinctly higher during matches than the training sessions. Rules determine how to play, generating specific kinds of fatigue which is associated with the injury incidence. No research has evaluated the impact of potential rule-induced physical demands in soccer or comparing sports. Understanding the differences might be useful for enhancing rules (e.g., safer sport). Therefore, the aims of this study were: a) to described the differences in the rule-induced physical demands of soccer, futsal, basketball, and handball; and b) to evaluate whether soccer rule-induced physical demands are different than the other invasion intermittent team sports, focusing the impact of the substitutions rules. Data were collected from different sports rules (i.e., soccer, futsal, basketball, and handball), and performed hypothetical corrections to equate the other team sports to the soccer (i.e., court dimensions/number of players). The data showed that soccer has higher rule-induced physical demands: lower substitutions, higher dimensions in absolute (eight to 15 times), and relative (four to eight times) values. Hypothetical corrections showed that soccer has remarkably large differences. Therefore, we conclude that soccer has remarkably higher rule-induced physical demands than other team sports, and allowing unlimited substitutions in soccer is a must.

Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.

Introduction: The management performance of hospitals in emergency departments in coping with clinical hazards is necessary for their success in providing quality services. The purpose of this study is to provide an optimization procedure and applying management performance in health and medical emergency on the rate of emergency preparedness of the suburb city hospitals. Research method: A semi-experimental and interventional descriptive study in the emergency department of Shahid Motahari Hospital in 2015-2016. Data was collected through the standard checklist of hospital emergency responsiveness test to WHO disasters with 90 questions in 9 domains which is codified by the World Health Organization, in the form of interviews and observing evidences , and if necessary a numerical analysis. Initially, the situation was measured according to this checklist. In the next stage, a set of solutions was developed and then the solutions were implemented according to the obtained information. Data analysis before and after proposing the procedure and its application in order to improve the quality of health management performance and emergency preparedness was performed using central indices, and for describing and presenting the survey results, tables and graphs were used. Results: The highest and lowest emergency preparedness rates for disasters and emergencies before the proposed procedure were the Communication Factor (%77/8) and Human resource factor (%2/8) respectively. The degree of preparedness of the medical center was measured in the management performance according to the model (WHO) before proposing the procedure (%77.98). The researcher's procedure provided and applied based on the information obtained from survey environment, location and type of hospital structure. After providing the procedure, the maximum and minimum rates were the continuity of service factor (%58.3) and post-accident rebuilding factor (%100), respectively. Generally, the rate of emergency preparedness of studied medical center in management performance for coping with disasters and medical emergencies was measured (%97.2) according to hospital emergency responsiveness test for accidents and (WHO). The significance level is less than 0.05, so we can say that the effectiveness with confidence (95%) was effective. Conclusion: According to the statistics of accidents and disasters in the suburb cities, the results of the research and the importance of the role of emergency departments in interurban hospitals in controlling accidents, the need for planning and implementation of practical measures such as conducting training courses on health management in disasters and emergencies, having an estimate of critical and essential resources, changing the structure, providing manpower (emergency management) in order to more precise control and ease of service, maintenance and repair of equipment, timely triage and retrofitting of hospitals were effective in improving their preparedness.

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

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

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

Enzymatic hydrolysis of bovine and human hemoglobin yields a diversity of bioactive peptides, some of which are recognized for their antimicrobial properties. Certain small antimicrobial and anticancer peptides target protein synthesis inhibition. This study aims to produce bioactive peptides through enzymatic hemoglobin hydrolysis and evaluate their effects on cell growth inhibition, potentially serving as candidates for biological anticancer drugs. Rapid screening of candidate anticancer peptides derived from enzymatic hydrolysis of bovine and human hemoglobin was conducted using the Lepidium sativum radicle growth technique. The results demonstrate that: 1) the degree of hydrolysis (DH) significantly influences the production of bioactive peptides. DH levels of 3-10% yield considerably stronger radicle growth inhibition compared to DH 0 (native hemoglobin form), exhibiting three to four times greater intensity. 2) Certain peptide fractions from bovine hemoglobin exhibit higher activity than those from human hemoglobin. 3) The structural characteristics of peptides play a crucial role in the observed biological effects. 4) The α137-141 peptide is the most active among the fractions obtained from bovine (IC₅₀ = 29 ± 1 µg/mL) and human hemoglobin (IC₅₀ = 48 ± 2 µg/mL), standing out 10 to 15 times more potent than other hemoglobin fractions. In conclusion, these findings affirm the bioactivity of peptide fractions obtained from bovine and human hemoglobin. The study highlights how enzymatic hydrolysis of bovine and human hemoglobin can yield peptides that inhibit protein synthesis. Ultimately, these results suggest the feasibility of obtaining candidate peptides for biological anticancer drugs from both human and bovine hemoglobin sources. These scientific advances show new hope in the fight against cancer which affects a large number of people around the world.

One of the most promising advancements in healthcare is the application of digital twin technology. Digital twins are virtual replicas of real-world human patients and can be used for monitoring, and diagnosis, and as a tool to design treatment strategies tailored to individual patients. Furthermore, digital twins could also be helpful in finding novel treatment targets and predicting the effects of drugs and other chemical substances in development. This review article delves into the various data sources and methodologies that contribute to the construction of digital twins. Each data source, including blood glucose levels, heart MRI and CT scans, cardiac electrophysiology, written reports, and multi-omics data, comes with different challenges regarding standardization, integration, and interpretation. We showcase how various datasets and methods are used to overcome these obstacles and generate a digital twin. While digital twin technology has seen significant progress, there are still hurdles in the way to achieving a fully comprehensive patient digital twin. Developments in non-invasive and high-throughput data collection, as well as advancements in modeling and computational power will be crucial to improve digital twin systems. We discuss a few critical developments in light of the current state of digital twin technology. Despite challenges, digital twin research holds great promise for personalized patient care and has the potential to shape the future of healthcare innovation.

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

Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs naturally develop a cognitive decline in many aspects including learning and memory, but also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex, including the gyrus proreus, the hippocampus, and in the cerebral vasculature. A growing body of epidemiological data shows that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades that evolve before neurodegenerative changes. Gut microbiome alterations also have been observed in many neurodegenerative diseases including Alzheimer’s and Parkinson’s diseases, and inflammatory CNS diseases. Interestingly, only recently has the dog gut microbiome been recognized to more closely resemble in composition and in functional overlap with the human gut microbiome as compared to rodent models. This article aims to review the physiology of the gut-brain axis (GBA), and its involvement with neurodegenerative diseases in dogs and humans. Additionally, we outline the advantages and disadvantages of traditional in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases using dogs.

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

This work addresses the problem of the application of artificial intelligence to the creation and maintenance of medical documentation and the use of big data in medicine to support efficient patient diagnosis and treatment. This study covers the latest advances in AI and big data, based on literature reviews and interviews with leading experts in these fields. The following conclusions were obtained: (1) Based on the needs of patients and providers of medical services, and given the latest technological advances, all medical documentation should be digital and the processes of its creation, access, sharing, and consistency checking should by supported by suitably designed AI systems. (2) The knowledge contained in medical documentation constitutes a resource of strategic importance for humanity, with almost unlimited potential. (3) All medical documentation should be anonymised and should be made widely available, just like data and research results in the field of experimental physics. (4) This will accelerate development of new treatments, best practice and help to identify new medical emergencies, such as Covid-19. In practice today, unfortunately, the design of medical record systems is fragmented between institutions and countries, often focusing discussions on narrow technical details, and forcing clinicians to waste time on filling up multiple pages of illness history. This leads to many inefficiencies and lost opportunities and necessitates a fundamentally new approach.

In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-August. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. We state six testable alternative hypotheses, analyse their testable predictions using public domain data and evaluate their relative contributions to the downward trend. We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including altered testing efficiency, time lag, improved treatment protocols and herd immunity are not consistently supported, or do not appear to make a major contribution to this trend although they may influence some other patterns of the epidemic.

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

Emphasis on primary health care (PHC) is the most efficient and economical approach to achieving universal health coverage. The aim of the study is to examine PHC publications from 2011 to 2023 in the Asian Pacific region (APR) using the Web of Science (WoS) database. Academic papers in the WoS PHC subject category published in the APR from 2011 to 2023 were retrieved and analyzed. A total of 4,283 papers were published in the WoS PHC category from APR onwards. The annual number of published papers and their citations increased from 2011 to 2023. Australia led PHC publications in APR with 3,049 publications (71.19% of APR regional output). New Zealand had the highest number of citations per paper (13.76) and the highest mean impact factor (3.23±1.80). Publications in the WoS PHC category also covered a wide range of topics, including Medicine General Internal (64.77%), Health Care Sciences Services (21.88%), Health Policy Services and Public Environmental Occupational Health (21.36%), demonstrating the breadth of PHC research. Australia dominates the output of PHC publications in the APR. Australian Family Physician and Australian Journal of Primary Health are the leading journals publishing PHC papers in the APR.

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

Purpose of the study: to reveal how the transfusion and the refraining from it affects the neuro-vascular unit in the congenital heart defects correction with cardiopulmonary bypass. Materials and methods: in vitro research, we formed a model of a neurovascular unit, which contains neu-rons, astrocytes and endothelial cells. This cellular model was cultivated in hypoxia conditions with the oxygen saturation levels of 1, 2, 3, 4%. In addition, this unit was cultivated with the pa-tient's serum adding in two different groups - with minimal and maximal levels of system in-flammatory response that we estimated by IL-6 level. Results: We found that during incubation in hypoxic conditions, the level of transendothelial resistance changed in groups with oxygen levels of 1% and 2% only after 4 hours. When we cultivated neurovascular unit cells with patients' sera, we found a minimal level of transendothelial resistance at 4 hours that increased after 24 hours. Permeability analysis showed that its level significantly decreased in the 1% and 2% oxygen group at 60- and 90-minutes relative to the control group. Conclusion: the system inflammatory response has more expressed but less long effect on the neurovascular unit model than hypoxia.

Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.

The ageing of workers is one of the most important issues for occupational health and safety in Europe. A number of intervention studies on health promotion for older workers were conducted in European workplaces between 2000 and 2015. This review gives an overview of these studies and considers perspectives for workplace health promotion.

Genome sequencing is enabling precision medicine—tailoring treatment to the unique constellation of variants in an individual’s genome. The impact of recurrent pathogenic variants is often understood, leaving a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequent frequent variants and associated mechanisms. Variants of unknown significance (VUS) in these genes are discovered at a rate that outpaces current ability to classify them using databases of previous cases, experimental evaluation, and computational predictors. Clinicians are thus left without guidance about the significance of variants that may have actionable consequences. Computational prediction of the impact of rare genetic variation is increasingly becoming an important capability. In this paper, we review the technical and ethical challenges of interpreting the function of rare variants in two settings: inborn errors of metabolism in newborns, and pharmacogenomics. We propose a framework for a genomic learning healthcare system with an initial focus on early-onset treatable disease in newborns and actionable pharmacogenomics. We argue that (1) a genomic learning healthcare system must allow for continuous collection and assessment of rare variants, (2) emerging machine learning methods will enable algorithms to predict the clinical impact of rare variants on protein function, and (3) ethical considerations must inform the construction and deployment of all rare-variation triage strategies, particularly with respect to health disparities arising from unbalanced ancestry representation.

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

Real-time image processing is crucial in applications such as video surveillance, diagnostic medicine, and autonomous vehicle systems. Parallel computing is essential to address the demands of real-time processing, but challenges persist in its practical implementation. This review analyzes parallel computing techniques applied to real-time image processing, examining parallel architectures and algorithms, identifying effective applications, and evaluating challenges and limitations. The results of this study will contribute to the development of more efficient solutions for real-time image processing. Keywords: Parallel computing, real-time image processing, video surveillance, diagnostic medicine, autonomous vehicle systems.

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

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are reported to have features intermediate between fetal and adult mesenchymal cells. Hence, UC-MSCs were cocultured with chondrocytes and Schwann cells to induce differentiation because of their flexible differentiation potential. US-MSCs were obtained from umbilical cords and cells at second passage were used in the experiments. Atelocollagen sponge was used as the scaffold for coculture; a horizontal, interactive coculture plate with a 0.6-μm pore size filter was placed between the connected vessels. US-MSCs were cocultured separately with chondrocytes and Schwann cells and culture alone served as a control. Five weeks after induction of differentiation, each specimen was evaluated histologically. In specimens cocultured with chondrocytes and the controls, cartilage tissues were detected using hematoxylin-eosin and toluidine blue staining. Cells positive for S100 protein were detected in the specimens cocultured with Schwann cells, but not in the controls. UC-MSCs were easily induced to differentiate into chondrocytes and neural cells by coculture. This indicates that continuously-shared humoral factors were effective in inducing differentiation of UC-MSCs. Coculture appears to be a potential technique for tissue regeneration using MSCs.

Abstract: The promise of regenerative medicine and tissue engineering is founded on the ability to regenerate diseased or damaged tissues and organs into functional tissues and organs or the creation of new tissues and organs altogether. In theory, all damaged and diseased tissues and organs can be regenerated or created using different configurations and combinations of extracellular matrix, cells and inductive biomolecules. Currently, regenerative medicine and tissue engineering can allow the improvement of patients’ quality of life through availing novel treatment options. Tissues and organs have a specific ECM, with specific proteins and factors released by cells residing within the local microenvironment. The coupling of regenerative medicine and tissue engineering field with 3D printing is revolutionizing the treatment of patients in a huge way. 3D bioprinting allows the proper placement of cells and ECMs, allowing the recapitulation of native microenvironments of tissues and organs. 3D bioprinting utilizes different bioinks made up of different formulations of ECM/biomaterials, biomolecules and even cells. The choice of the bioink used during 3D bioprinting is very important as properties such as printability, compatibility and physical strength influence the final construct printed. The extracellular matrix (ECM) provides both physical and mechanical microenvironment needed by cells to survive and proliferate. Decellularized ECM bioink contains biochemical cues from the original native ECM and also the right proportions of ECM proteins. Different techniques and characterization methods are used to derive bioinks from several tissues and organs and to evaluate their quality. This review discusses the uses of decellularized ECM bioinks and argues that they represent the most biomimetic bioinks available. In addition, we briefly discuss some polymer-based bioinks utilized in 3D bioprinting.

Manned missions to Mars and other deep space exploration targets are expected to take place in the next 20 years. These missions will involve prolonged crew exposure to the unique space environment, increasing the risk that astronauts will experience additional physical and psychological health conditions beyond those that would be expected through normal aging on Earth. Thus, there is an acute need to develop therapeutic solutions that can withstand the harsh space environment, while maintaining astronaut health and maximizing crew capabilities to foster successful exploration-class missions. This review covers the nuanced and interdisciplinary challenge that is providing safe and effective pharmaceuticals for future deep space missions. First, the limitations of current pharmaceutical solutions are discussed; the impacts of the space environment on human health and chemical compound stability are covered, along with an evaluation of astronaut medication use on similar missions. Second, potential pharmaceutical solutions and concepts are presented for consideration. Future research should prioritize these and other potential innovations to ensure that our space programs are well equipped to maximize crew safety as astronauts explore deep space objectives.

A significant part of the literature on innovative practice in medicine relates to seizing opportunities and curbing harms for patients in desperate situations. Unfortunately, the term innovation has multiple meanings and a rich rhetorical flourish that adds confusion and misunderstanding to an already difficult debate. This paper aims to enhance the current definition of innovative practice for medicine. First, we replace the term innovation with the more literal of new non-validated practice. To identify this meaning, we analyse the traditional research ethics’ distinction between research, validated practice, and innovation in the Belmont Report. Second, we propose the following explicit definition of new non-validated practice: the first or recent use of diagnostic, therapeutic or preventive interventions that introduce a significant change, with an insufficient level of evidence of safety or efficacy for regular healthcare, and with the main aim to benefit individual patients. This definition is a promising conceptual tool to inform empirical research, ethicists, and the harmonization of its regulation and legislation (e.g. right-to-try laws).

Accumulated data show the utility of diagnostic multi-organ point-of-care ultrasound (PoCUS) in the assessment of patients admitted to an internal medicine ward. Assess whether multi-organ PoCUS (lung, cardiac, and abdomen) provides relevant diagnostic and/or therapeutic information in patients admitted for any reason to an internal medicine ward. Prospective, observational, and single-center study, at a secondary hospital. Multi-organ PoCUS was performed during the first 24 hours of admission. The sonographer had access to the patients’ medical history, physical examination, and basic complementary tests performed in the ED (laboratory, X-ray, electrocardiogram). We considered a relevant ultrasound finding if it implied a significant diagnostic and/or therapeutic change. In the second semester of 2019, 310 patients were enrolled (48.7% men, mean age 70.5 years). Relevant ultrasound findings were detected in 86 patients (27.7%) and in 60 (19.3%) triggered a therapeutic change. These findings were associated with older age (Mantel-Haenszel 2 = 25.6; p&lt; .001) and higher degree of dependency (Mantel Haenszel 2 = 5.7; p = .017). Multi-organ PoCUS provides relevant diagnostic information, complementing traditional physical exam, and facilitates therapy adjustment, regardless of the cause of admission. Multi-organ PoCUS to be useful need to be systematically integrated into the decision-making process in internal medicine.

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

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

Frailty syndrome is a complex and multifaceted condition that significantly impacts the health and well-being of older adults. This article provides a comprehensive overview of frailty syndrome, including its definitions, evolution, and the rising role of biomarkers and electroencephalography (EEG) in its diagnosis. The discussion explores the reasons behind the rise of frailty syndrome, the difficulties in managing it, and the global research efforts aimed at understanding and addressing this condition. The economic costs associated with frailty syndrome are highlighted, along with the countries that are currently and will be more affected in the near future. Strategies to postpone or avoid frailty syndrome are discussed, with an emphasis on the importance of muscle strength exercises over aerobic exercises to combat sarcopenia. The article concludes by emphasizing the need for a multidisciplinary approach to frailty management and the importance of social support and engagement in preventing and managing frailty.

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

Distributed digital manufacturing offers a solution to medical supply and technology shortages during pandemics. To prepare for the next pandemic, this study reviews the state-of-the-art for open hardware designs needed in a COVID-19-like pandemic. It evaluates the readiness of the top twenty technologies requested by the Government of India. The results show that the majority of the actual medical products have had some open source development, however, only 15% of the supporting technologies that make the open source device possible are freely available. The results show there is still considerable work needed to provide open source paths for the development of all the medical hardware needed during pandemics. Five core areas of future work are discussed that include: i) technical development of a wide-range of open source solutions for all medical supplies and devices, ii) policies that protect the productivity of laboratories, makerspaces and fabrication facilities during a pandemic, as well as iii) streamlining the regulatory process, iv) developing Good-Samaritan laws to protect makers and designers of open medical hardware, as well as to compel those with knowledge that will save lives to share it, and v) requiring all citizen-funded research to be released with free and open source licenses.

The field of personalized medicine is undergoing a transformative shift through the integration of multi-omics data, which encompasses genomics, transcriptomics, proteomics, and metabolomics. This synergy allows for a comprehensive understanding of individual health by analyzing genetic, molecular, and biochemical profiles. The generation and integration of multi-omics data enable more precise and tailored therapeutic strategies, improving the efficacy of treatments and reducing adverse effects. However, several challenges hinder the full realization of personalized medicine. Key hurdles include the complexity of data integration across different omics layers, the need for advanced computational tools, and the high cost of comprehensive data generation. Additionally, issues related to data privacy, standardization, and the need for robust validation in diverse populations remain significant obstacles. Looking ahead, the future of personalized medicine promises advancements in technology and methodologies that will address these challenges. Emerging innovations in data analytics, machine learning, and high-throughput sequencing are expected to enhance the integration of multi-omics data, making personalized medicine more accessible and effective. Collaborative efforts among researchers, clinicians, and industry stakeholders are crucial to overcoming these hurdles and fully harnessing the potential of multi-omics for individualized healthcare.

Stem cells can be used in cellular therapy. This happended in order to replace damaged cells or having aim to regenerate organs. The definition of stem cells can be extended. From this point of view, we can mention taking in consideration the idea in which it is known that these cells form the base of the building body. More than, we can mention that stem cells are characterized by two knowing properties namely differentiation and self renewal. Based on the observation that differentiation of adult stem cells into specific derivative scan be controlled by laboratory techniques, it is anticipated that adult stem cells may become the basis of therapies for many, and various types of medical conditions. Taking on stem cells, regenerative medicine (RM) it is known as being one of the hottest topics in biotechnology nowadays. From this purpose, stem cells can be used in regenerative medicine (RM). The principles of regeneration are found in different types of cultures, from long time ago. As an interdisciplinary field of research, regenerative medicine, play a great role in tissues and organs damaged reparation with a higher potential in transplantation if necessary.

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

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

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

Primary Biliary Cholangitis (PBC) is a chronic, cholestatic liver disease with a heterogeneous presentation, symptomatology, disease progression, and response to therapy. The current risk stratification assessment, aimed at identifying patients with a higher risk of disease progression, encompasses an in-depth analysis of demographic data, clinical and laboratory findings, antibody profiles, and the evaluation of liver fibrosis using both invasive and non-invasive techniques. Treatment response scores after one year of therapy remain to date a major factor influencing the prognosis of PBC patients. While the initial therapeutic approach with ursodeoxycholic acid (UDCA) is universally applied, new second-line treatment options have recently emerged, with many others under investigation. Consequently, the prevailing one-size-fits-all approach is poised to be supplanted by tailored strategies, ensuring high-risk patients receive the most appropriate treatment regimen from diagnosis. This will require the development of a risk prediction model to assess, at the time of diagnosis, the course, outcome, and response to first and additional treatments of PBC patients. This manuscript provides a comprehensive overview of the current and emerging tools used for risk stratification in PBC and speculates on how these developments might shape the disease landscape in the near future.

The microbiota is now recognized as one of the major players in human health and disease, in-cluding cancer. As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, it may impact on the onset, progression, and treatment of hormonal dependent cancers, which account for more than 70% of all BCs. The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on one side disruptors can alter the composition and functions of the estrobolome, on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new “oncobiotic” perspective.

The cannabis plant has been known for millennia for its properties such as textile fiber, food, recreational and medicinal use. Since the origin of its domestication in Asia, cannabis has been transported to the rest of the continents by merchants, nomads, settlers, and slaves, who have also carried with them valuable knowledge about its uses. Its medical use was one of the major contributions of this plant in the various civilizations through which it passed. This article aims to understand its origins, dissemination, and medical use over the years to the present day.

In recent years, lung ultrasound (LUS) has been increasingly used for the diagnosis of respiratory diseases in both adult and pediatric patients. However, asthma is a field in which the use of LUS is not yet well defined or is in development. In the following case series, we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of 6 children with asthma: some of them with acute asthma attack and with inadequately controlled allergic asthma or childhood asthma; others with acute asthma and allergic or infantile asthma adequately controlled by preventive therapy. Finally we describe the clinical, laboratory and imaging parameters of a child with severe allergic asthma in the absence of exacerbation. In these cases, albeit at different times, LUS played an important role in both the initial diagnostic process and follow-up. It also showed different ultrasound features depending on the severity of the individual asthma based on the type of asthmatic phenotype and control of it.

Background: Convectional methods for drug delivery often faces setbacks due to systemic distribution, short half-life and degradation of therapeutics and therefore reduce concentrations of drug available to target tissue. Nanotheranostic provide a novel method for treating and diagnosing diseases Methodology: collection and review of relevant literatureResult: while nanotheranostic offer advantage of personalized medicine and often combines diagnosis and therapy using single molecular approach, nuclear medicine relies on radioactive isotopes to diagnosed and destroys cancer cells. In both cases, nanocarriers such as lipid-based, polymer-based, drug-conjugate, inorganic nanoparticles are used to deliver drugs/probes/isotopes to target site, generating images and thereafter chemotherapy/radiotherapy begins.Conclusion: Nanotheranostic plays important role in diseases diagnostic, therapy, imaging, monitoring of disease progression / response through the use of nanocarriers. This is made possible through nanoparticles/nanocarriers that delivers drug to the target tissues/cells.

Background and Objectives: The techniques directed to the cranial field in osteopathy are the most questioned due to the lack of scientific evidence. In osteopathic practice, manual palpation is essential and, therefore, measuring reliability is fundamental. The objective of study is to assess the reliability and validity of osteopathic treatment depending on experience. Materials and Methods: A cross-sectional study of reliability and validity was conducted. For measurements, a strain gauge was placed on the sphenobasilar synchondrosis of the skull base, and three maneuvers (lateral compression, anteroposterior compression and compression maneuver of the mastoids) were repeated 25 times each by osteopaths with different time of experience (5-10 years, 1-5 years, <1 year). Measurement averages were computed for each of the three maneuvers to verify the average effect of each group in comparison to that of the Gold Standard (GS) (>10 years of experience). Data were analyzed to check for inter- and intra-observer reliability using intra-class correlation coefficients (ICC). Results: Reliability and validity in 5-10 experience of observer 1 and observer 2 in the tree maneuvers was excellent (p<0.001) against GS. Poor or enough reproducibility and concordance were observed in osteopaths with less experience. Conclusion: Experience of osteopaths determines the efficacy of cranial maneuvers in osteopathic treatment for patients’ rehabilitation.

Reducing carbohydrates digestion by having low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107, an eight-herb formula that is modified from the RCM-104, has indicated significant weight-loss action in clinical trials. However, no research has been conducted to study its effect on the activity of porcine pancreatic alpha-amylase (PPA), which is involved in carbohydrate absorption. In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were also detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact.

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, with an increasing global incidence. While most cases are successfully treated with surgical excision, a subset can metastasize, leading to significant morbidity and mortality. Current staging systems based on clinical and histopathological features have shown limitations in accurately predicting metastatic risk. This review examines the role of gene expression profiling (GEP), particularly the 40-gene expression profile (40-GEP) test, in improving risk stratification and management of cSCC. We assess the prognostic value of the 40-GEP test, its integration with current staging systems, and its impact on clinical decision-making. Recent studies suggest that incorporating GEP results with traditional staging methods can enhance the identification of high-risk patients, potentially leading to more personalized treatment strategies. The review also explores the challenges of implementing GEP in routine clinical practice, including cost-effectiveness considerations and the need for standardization. Finally, we discuss the implications for future cSCC management and highlight areas for further research. As molecular profiling techniques continue to evolve, GEP represents a promising approach to optimizing care for cSCC patients, aligning with the growing emphasis on personalized medicine in oncology.

Background: Acute injuries of the hamstring muscle complex (HMC) Type 3b (interfascicle / bundle-tear) are frequently observed in various sports disciplines both in elite and recreational sport. The treatment of choice of acute HMC injuries Type 3b is a progressive physiotherapeutic exercise program. Besides this, there is currently only insufficient scientific evidence to support other treatment methods, including local infiltrations and injections of platelet-rich-plasma. Very recently it was demonstrated that extracorporeal shock wave therapy (ESWT) may accelerate regeneration after acute skeletal muscle injury. The aim of the present study is to test the hypothesis that the combination of radial ESWT (rESWT) and a specific rehabilitation program (RP) is effective and safe in treatment of acute HMC injury Type 3b in athletes, and is statistically significantly more effective than the combination of sham-rESWT and RP. Methods/Design: We will perform a double blind, randomized, sham-controlled clinical trial at the clinic KinEf Kinesiología Deportiva, Ciudad Autónoma de Buenos Aires, Argentina. Fourty patients with acute HMC injury Type 3b will be randomly allocated to receive either rESWT (nine rESWT sessions; three sessions per week; 2500 radial extracorporeal shock waves (rESWs) per session; energy density depending on what the patient tolerates) or sham-rESWT. In addition, all patients will receive a specific rehabilitation program that will last for eight weeks. The primary outcome measure will be the individual time (days) necessary to return to play. Secondary outcomes will include the presence or absence of reinjury during a time period of six months after inclusion into the study. Discussion: Because of the lack of adequate treatment options for acute HMC injury Type 3b in athletes and particularly the high reinjury rate, we hypothesize that the results of this trial will be of importance and have impact on clinical practice. Trial registration: ClinicalTrials.gov ID NCT03473899. Registered March 22, 2018.

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

Aging is a complex and inevitable biological process characterized by a gradual decline in physiological function, including increased oxidative stress, chronic inflammation, and mitochondrial dysfunction. While aging is a natural part of life, it is often accompanied by various disorders collectively known as age-related diseases (ARDs) or aging disorders. These include neurodegenerative diseases like Parkinson’s (PD), cardiovascular diseases, diabetes, osteoporosis, and frailty, among others. As the global population ages, the prevalence of ARDs such as PD and frailty is rising, necessitating innovative approaches to enhance healthy aging. Nutraceuticals are natural bioactive compounds in foods that offer health benefits beyond essential nutrition, which is pivotal in preventing and managing aging-related disorders. Nutraceuticals, with their antioxidant, anti-inflammatory, and neuroprotective properties, offer promising strategies to counteract these processes and promote healthy aging. This review highlights the potential of nutraceuticals as valuable adjuncts in managing PD and frailty, two conditions intricately linked to ARD. By examining the differential impacts of these bioactive compounds on the underlying mechanisms of each condition, this study underscores the promise of nutraceuticals in promoting healthy aging. The review aims to inform future research and clinical strategies by advocating for developing novel bioactive compounds, using advanced delivery technologies, and integrating personalized approaches based on genetic and epigenetic profiles. These efforts will pave the way for more precise, effective, and individualized interventions, ultimately extending health span and preventing ARD.

Because of ambiguous and widely debated observations concerning incidence trend and management of TC, we performed this analysis. We drew attention to some events, such as “cancer screening activity,” introduction of noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) to TC types, possibility of papillary thyroid microcarcinoma (PTMC) active surveillance (AS), occurrence of personalized medicine in TC management and finally COVID-19 pandemic time. Because of the opinion that all changes have been made mostly by PTC, we compared it to the rest of types of TC in terms of incidence, clinical and pathological characteristics and treatment. The prevalence of TC significantly increased from 5.15% in 2008 to 13.84% in 2015 and then significantly decreased to 1.33% in 2022 when the pandemic lasted (p<0.0001). A similar trend was observed for PTC, when the incidence significantly increased to 13.99% in 2015 and then decreased to 1.38% in 2022 (p<0.0001). At that time, the NIFTP category was introduced, and observation of PTMC began. The prevalence of FTC and MTC also increased until 2015 and then decreased. Significant differences in age, types of surgery, necessity of reoperation, pTNM, between PTCs and other types of TCs were observed. The average age was significantly lower in PTC patients than in patients with the remaining types of TC (p<0.0001). Four milestones, including NIFTP introduction, the possibility of PTMC AS, personalized cancer medicine and the COVID-19 pandemic, may have influenced the general statistics of TC.