2nd Intl. Symp. on Technological Innovations in Medicine for Sustainable Development

Despite the discovery of new drugs and therapeutics for the treatment of diseases, confirmation of their effectiveness and safety of use requires additional long-term studies. A safe and fast method for this that does not require research on living organisms is computer molecular modeling. The application of artificial intelligence (AI) methods is also an important step today [1,2]. The most well-known and used molecular modeling methods are molecular dynamics and docking methods, and so on [3,4]. However, despite having several advantages, these methods also have disadvantages that can be of critical importance when conducting experiments.

We propose an effective approach to the modeling and study of biological systems and biochemical processes, particularly processes in cells under various scenarios of interaction: an algebraic approach that has been proven effective in many other scientific areas. In the modeling process, we combine an algebraic approach with AI methods.

The algebraic approach is based on the theory of agents and environments initiated by Letychevskyi and Gilbert [5]. This approach is implemented in our software tools for the modeling of biological models.

We have developed a formal model of the cell apoptosis process, which various scenarios of interactions between cell elements and different agents (enzymes, viruses, nanoparticles, etc.) can cause. When running a given model, we can analyze the changes in the environment under certain conditions and explore the properties or states of the environment that can be achieved in the modeling process.

In the developed models, we consider the following properties: (1) reachability of the cell degradation phase or apoptosis process inhibition under given influencing factors and their parameters (quantitative ratio between metalloproteinases/glutaminases and their inhibitors, the influence of nanoparticles and/or irradiation, etc.); and (2) determination of the initial state of the environment (indicators of the temperatures, concentrations, and structures of substances; acidity, characteristics of the studied cell, etc.) needed to reach the desired behavior scenario.

A feature of algebraic modeling, in contrast to simulation modeling and probabilistic methods, is its ability to abstract from specific values and consider multiple scenarios of system behavior rather than one specific scenario. This makes it possible to conduct an effective search for the environment or substances that have the necessary effect on cellular processes and that can be used to destroy diseased cells in the corresponding treatment process, particularly in oncological diseases.

We can consider modeling at different levels of abstraction depending on the chosen experiment: at the level of the atomic structure of substances and quantum–mechanical interaction, at the level of the molecular structure of substances, and at the level of interaction of biological objects. 

To effectively search models and narrow the search space for them due to the high complexity of models, neural networks are used, which are trained on known scenarios of cellular processes.

At this research stage, a method of applying algebraic modeling was developed to study the effect of enzymes such as multidomain zinc metalloproteinase, glutamine, and transglutaminase 2 on the activation and inhibition of the cell apoptosis process.

Augmented reality (AR) involves the overlay of computer-generated images onto the user’s real-world visual field to modify or enhance the user’s visual experience. With respect to neurosurgery, AR integrates preoperative and intraoperative imaging data to create an enriched surgical experience that has been shown to improve surgical planning, refine neuronavigation, and reduce operation time. In addition, AR has the potential to serve as a valuable training tool for neurosurgeons in a way that minimizes patient risk while facilitating comprehensive training opportunities. The increased use of AR in neurosurgery over the past decade has led to innovative research endeavors aiming to develop novel, more efficient AR systems while also improving and refining present ones. In this review, we provide a concise overview of AR, detail current and emerging uses of AR in neurosurgery and neurosurgical training, discuss the limitations of AR, and provide future research directions. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 386 articles were initially identified. Two independent reviewers (GH and AC) assessed article eligibility for inclusion, and 31 articles are included in this review. The literature search included original (retrospective and prospective) articles and case reports published in English between 2013 and 2023. AR assistance has shown promise within neuro-oncology, spinal neurosurgery, neurovascular surgery, skull-base surgery, and pediatric neurosurgery. Intraoperative use of AR was found to primarily assist with surgical planning and neuronavigation. Similarly, AR assistance for neurosurgical training focused primarily on surgical planning and neuronavigation. However, studies included in this review utilize small sample sizes and remain largely in the preliminary phase. Thus, future research must be conducted to further refine AR systems before widespread intraoperative and educational use.

A ¹⁹⁷Au solution with bi-distilled water was prepared using a single gold electrode, connected to a special oscillator with a sinewave voltage of 50 Hz at 160 V. It was known that it was not possible to detect gold in such a solution by chemical analysis at room temperature. Thus, neutron activation analysis (NAA) by creating ¹⁹⁸Au seemed to be the method of choice for detecting the missing gold. ¹⁹⁸Au is a b emitter that decays to an exited state of ¹⁹⁸Hg nucleus, subsequently emitting a g photon of 411.8 keV, that can easily be detected. For this purpose, three solutions were prepared: Sample 0: 100 ml of water as zero-reference in case of impurities. For samples I and II, 200 ml of the same water were treated by a single electrode for 16 hours. Immediately after the treatment, the 200 ml were split into two samples perfectly mixed: sample II, i. e. 100 ml of the treated water was heated above 60°C, sample 0, had been heated before, and sample I, i. e. 100 ml of the treated but not heated water. All 3 samples together were exposed to a flux of thermal neutrons. Result: only the treated and warmed sample II showed the typical peak of g photons with the energy 411.8 keV. Samples 0 and I did not show any trace of gold. Sample I, as well as the other samples, were kept at room temperature for 11 days. The other samples behaved as expected. After a delay of 11 days, sample I was heated above 60°C. Interestingly, no g - photon was detected at 411.8 keV and after a second NAA (on the same, i. e. 11^th day) no trace of Au was present anymore. A tentative theoretical explanation of this phenomenon is given by assuming that water can be considered as a semiconductor. Thus, also a photonic band gap can be expected. In other words, and in this context, the 411.8 keV g - rays were localized, if the temperature of the solution is kept below 60°C. This hypothesis is validated by the experimental results, since after heating up sample I above 60°C a mirrorless lasing happened. The fact that no trace of gold was visible is the proof of concept, that the remaining ¹⁹⁷Au nuclei show a photonuclear reaction ¹⁹⁷Au (g, n) ¹⁹⁶Au decaying rapidly into ¹⁹⁶Hg. However, in a first step the ¹⁹⁸Au (g, n) ¹⁹⁷Au reaction occurred leading to a reversal of the ¹⁹⁷Au (n, g) ¹⁹⁸Au reaction. In other words, the photonuclear reaction excited the collective movements of the neutrons and protons of the ¹⁹⁷Au nucleus leading to giant g resonances, and to the ejection of a neutron. In a second experiment the gold electrode was activated by exposure to thermal neutrons. Very similar results were obtained with the exception that between 15% to 20% of the unheated sample showed the 411.8 keV transition.

Cancer remains a complex and devastating disease, posing significant challenges to global healthcare. To address this pressing issue, pioneering research and innovative therapeutic approaches are essential. A novel frontier in cancer research lies in the investigation of microgravity (µg) conditions, such as those experienced during space travel, as a potential catalyst for advancing cancer research and personalized medicine. We will explore the promising intersection of cancer, microgravity (µg) conditions experienced during space travel, and personalized medicine as a novel frontier in cancer research highlighting the collective potential to revolutionize cancer treatment and therapy development.

Importantly, the limitations of the standard one-size-fits-all cancer treatment have led to a growing emphasis on personalized medicine. Tailoring treatments to individual patients based on their unique genetic makeup, environment, and lifestyle has been shown to enhance treatment efficacy while minimizing adverse effects. In this context, microgravity emerges as an intriguing avenue for exploration, offering new insights into cancer biology and therapeutic interventions.

We will focus on the profound impact of microgravity on cellular behaviour and molecular processes in cancer cells. Investigating real (r-) and simulated (s-) µg environments provides a research platform to identify novel pathways and potential targets for cancer treatment. 

Additionally, µg environments facilitate the formation of three-dimensional (3D) tumour models, such as multicellular spheroids and organoids, which accurately mimic the in vivo tumour microenvironment. These 3D models offer invaluable tools for preclinical drug screening and personalized cancer therapy development.

The confluence of cancer, microgravity, and personalized medicine presents a transformative opportunity to accelerate cancer research and therapeutic development. By harnessing the unique conditions of µg to deepen our understanding of cancer biology and tailoring treatments to individual patients, this novel approach has the potential to pave the way for a new era in cancer care. The integration of personalized medicine with µg-based cancer research holds promise for optimized treatment outcomes and advancing cancer therapy, ultimately bringing us closer to overcoming this formidable disease.

The term “Therapeutic Orphans” was first used by Dr. Harry Shirkey in 1962 to describe pediatric populations. Over fifty years later, pediatric drug development is still largely an unmet area of therapeutic need based on the various physiological, clinical, and formulation challenges associated with age-based population dosing. Moreover, access to pediatric dosage forms is limited throughout the world as highlighted by the World Health Organization’s Global Accelerator for Paediatric Formulations business plan. Access to pediatric formulations is most limited in remote areas where resources are limited, and there is a greater utility of off label use of compounded adult formulations where the dose control is not ensured. Here we will highlight our efforts to address the global need for sustainable, verified strategies to develop reproducible, extemporaneous formulations that can easily be transferred to remote areas where resources are limited. Towards this aim, easily generated pediatric formulation strategies developed at Purdue with the intent to transfer the approaches to collaborators in Africa will be discussed. One of the primary causes for this lack of pediatric drug development is the inability to accurately predict clinical safety and efficacy at different pediatric developmental stages early in translation. This lecture will also highlight some of the challenges that currently face preclinical development of pediatric medicines and the potential utility of the juvenile porcine model as a preclinical model for pharmacokinetic testing during formulation development. Our aim is to develop reproducible pediatric formulation approaches that require minimal technological advances, which can be produced at different doses in remote clinics. We will also highlight our efforts to verify performance by ensuring reproducible exposure in preclinical testing utilizing the juvenile swine model to ensure that safety and efficacy can be met. An illustration of a simple formulation strategy that has been transferred from Purdue to Tanzania

The contact angle (CA: deg) method [1] has been used for the determination of the wettability of solids and semisolid substrates such as cosmetics and formulations for cutaneous applications [2]. As regards biomaterials, this method can evaluate the hydration state of skin [2] and demonstrate its usefulness in the beauty sector field [3].  

On this basis, our work aimed to evaluate the basal moisturizing level of in-vivo skins of a workers group (subjects test) employed in a commercial holding company sited in Treviso (Italy). The skin wettability of each subject test (ST) was evaluated using a portable MobilDrop DSA2 mobile tensiometer (tenskinmeter®)[2] and a single drop of microfiltered water (Ares Solida srls, Treviso, Italia). The water CAs measurements were performed before and after the skin application of a liposome dispersion (Skindecoder®) and a commercial hydration cream (shc). The test was repeated after seven days during which each subject test kept its systemic hydration level administrating two liters of water per day. Our work demonstrated a decrease of water CAs measured after the application of Skindecoder® (ST RU=-58%, ST ROS=-51%, ST GIU=-51.98, ST MATT=-56.80%, ST ROB=-65.54%, ST GRE=-55.16%, ST ILA=-81.28%) and chc (ST RU=-68.77%, ST ROS=-26.30%, ST GIU=-32.23, ST MATT=-45.48%, ST ROB=-41.30%, ST GRE=-48.98%, ST ILA=-45.65%) at t0. That demonstrated the increase of hydration state due to the two formulations' application. The basal water CAs measured after seven days decreased for ST RU (-13.22%), ST ROS (-51.15%), ST GIU (-3.09%), ST MATT (-10.63%), ST ROB (-21.73%), ST GRE (-12.00%), and ILA (-8.02%). 

These data show that the regular administration of 2Lt of water per day causes a decrease in the water CAs of STs with a measurable increase in skin hydration that depends on the biological properties of each worker tested. 

Our pilot study opened with the perspective of considering the moisturizing of the human epidermis as a possible biological parameter to control in a rapid and non-invasive way the employee's health about their water intake during job activities in public and private institutions. 

Chemotherapy as an adjuvant therapy that has largely failed to significantly improve outcomes for aggressive brain tumors; some reasons include a weak blood brain barrier penetration and tumor heterogeneity. Recently, there has been interest in designing effective ways to deliver chemotherapy to the tumor. In this review, we discuss the mechanisms of focused chemotherapies that are currently under investigation. Nanoparticle delivery demonstrates both a superior permeability and retention. However, thus far, it has not demonstrated a therapeutic efficacy for brain tumors. Convection-enhanced delivery is an invasive, yet versatile method, which appears to have the greatest potential. Other vehicles, such as angiopep-2 decorated gold nanoparticles, polyamidoamine dendrimers, and lipid nanostructures have demonstrated efficacy through sustained release of focused chemotherapy and have either improved cell death or survival in humans or animal models. Finally, focused ultrasound is a safe and effective way to disrupt the blood brain barrier and augment other delivery methods. Clinical trials are currently underway to study the safety and efficacy of these methods in combination with standard of care.

When the state of Israel was established in 1948, a severe conflict raised immediately concerning the consumption of wild plants. On the one hand, the decision makers of the new state, mostly Ashkenazi Jews, or with Western-European mentality. This society made very little use of wild plants, both as food and for medicinal purposes. This society demanded total halt of the use of wild plants, and legislations were made to assure that this prohibition was enforced. On the contrary, the local Arab (Palestinian) society made extensive use of many wild plants, mainly for nutrition purposes, but very extensive use for medicinal treatments.

This situation resulted in great tension between the two societies. The Arab society risked the collection of these plants, and when got caught by the Israeli authorities, Arabs had to suffer different punishments and fines.

But the situation can not be summarized as we described above. The prohibition of wild plants use gave its positive results in the next few decades. In some areas, the overuse of wild plants resulted almost extinction, for example, Gundelia tournifortii (عكّوب, עכובית הגלגל), a very nutritious and tasty plant (when cooked), was completely extinct in the Wadi Ara area. The plant survived complete extinction in the entire country since the Arab society in the Northern Negev region, did not eat it, because it is thorny, so “its camel food, not for humans”. But when people of the North realized that the started mass collection, mainly for export purposes, to Jordan, and from Jordan to the Gulf region.

So, the conflict reached a critical point, then the nature preservation authorities realized that some compromise must be made. With great efforts and almost endless discussions, we managed to find this compromise.

Use of wild plants is not only pure science. It is before and after all, human societies and traditions, and these must be respected to an extent of nature preservation and meeting traditional societies needs.

Magnetic gold nanoparticles (mGNP) have become a great interest of research for nanomaterial scientists because of their significant magnetic and plasmonic properties applicable in biomedical applications. Various synthetic approaches and surface modification techniques have been used for mGNP including the most common being the coprecipitation, thermal decomposition, and microemulsion methods in addition to the Brust Schiffrin technique, which involves the reduction of metal precursors in a two-phase system (water and toluene) in the presence of alkanethiol. The hybrid magnetic–plasmonic nanoparticles based on iron core and gold shell are being considered as potential theragnostic agents. Herein, in addition to future works, we will discuss recent developments for synthesis and surface modification of mGNP with their applications in modern biomedical science such as drug and gene delivery, bioimaging, biosensing, and neuro-regenerative disorders. I shall also discuss the techniques based on my research related to the biological applications of mGNP.

Hepatitis B (HBV) and C (HCV) are two among other forms of infections for which co-infection in HIV has been associated with alteration of the immune response, increased risk of progression to liver diseases and increased risk of hepatotoxicity associated to antiretroviral therapy. This study was aim to establish the prevalence of hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCVAb) among HIV patients, treatment outcomes and possible risk factors in Kumba Health, in the South West Region of Cameroon.      

We performed a systematic screening using Rapid Diagnostic Test, for HBsAg and HCVAb among 299 HIV patients enrolled at the treatment centers in Kumba Health District with all positives for HBV or HCV confirmed by the ELISA and results analyzed using SPSS version 20.  Out of the 299 participants, 36 (12.0%) were positive for HBV and 12 (4%) for HCV by both RDT and ELISA, out of which 52 HIV patients, 36 HIV/HBV and 12 HIV/HCV patients were involved in the prospective cohort study for 24 months which permitted monitored the immune response (CD4 counts and viral load test), as well as variation of biochemical parameters (ALAT/ASAT, albumin, bilirubine, creatinine) and weights of the studied participants. There were positive variations in all the biomarkers and immune response measurement which differed among the different groups and so this result could be used for health decisions regarding co-infecteds.

a) Introduction:In 2015, the Hospital Complex of Navarre adhered to the “Best Practices Spotlight Organizations” (BPSO®) project by implementing the guide of good practices "Care and maintenance of vascular accesses to reduce complications".[1] The goal was to implement and improve nursing care strategies for Peripherally Inserted Central Catheters (PICC) based on the latest available evidence. The implantation of a PICC is part of the treatment of choice in oncological processes, being this a long-lasting device that ensures useful venous access, both for the administration of treatment and for obtaining blood samples [2]. However, it is not without potential complications. In the case of the PICC, the main risks are thrombosis and infection [3]), the prevalence of the latter varying between 1.3% and 13.9%, according to various studies [4-6]. To do so, specific nurse training was necessary. However, due to the high mobility of patients and professionals, traditional training was not enough. Currently, there is widespread use of mobile devices and a growing interest by health professionals in leveraging smartphone applications as a means of conducting health behavioral interventions [7-9].HYPOTHESIS The use of the SPAD-CARE app as a training method and resource for validating the status of the venous access and device, both for professionals and patients and/or relatives of PICC carriers, will reduce the main complications derived from them: phlebitis and thrombosis. , as well as accidental removal.b) MethodThere was a need to design and develop an application (APP) for smartphones and tablets, referred to as SPAD-CARE (from Semi-Permanent Access Device CARE), which facilitates untrained professionals, patients and family members to carry out the necessary care of the patients’ PICC safely. technology. The patients were informed and accepted an informed consent to perform the tests. The applicability of the APP will be assessed through a quasi-experimental study with a control group (CG) with the management, monitoring and traditional care of these devices; comparing with an intervention group (IG) composed of a sample of adult patients (>18 years) with PICC whose care has been provided and recorded using the APP. The variables to be compared will be measured with the same definition and exhaustiveness for both groups. As inclusion criteria, all patients with a long-term PICC will be included; inserted by the nurses of the intravenous therapy unit (UTI) of the Hospital Universitario de Navarra and whose use is expected for at least one month; in patients of legal age (>18 years), who have given their written consent to be included in the study, agree to the use of the APP and wish to complete the study. As exclusion criteria, all those patients with limitations in the management of digital resources, APPs or the absence of a smartphone-type mobile device were ignored to form part of the study. In addition, informed consent will be requested from both groups to access their clinical history. for the collection of sociodemographic information and on aspects related to their disease process. Each patient who accepts the use of the APP will be registered in the SPAD-CARE web manager, assigning a user number and a password, which will be provided after inserting the PICC.c) ResultsSPAD-CARE leverages the user's smartphone to identify the access device and validate it in the information system. All actions performed on the specific access device are documented, accredited, and conveniently stored in the information system. Once authenticated, the APP guides the user in the care of the catheter in sterile conditions following the procedure of the health care center. By the date of the congress, it is expected to have a proof of concept of the APP and to have performed X tests with real patients.d) Discussion & ConclusionThe application of new technologies in the field of PICC could be a great advance for both professionals and patients, since it would help untrained professionals and empower patients, family members or caregivers in the proper management of them.

MAPKs signaling proteins that regulate essentially all stimulated cellular processes. Dysregulation of these kinases is involved in many diseases such as cancer and inflammation. A hallmark of the MAPKs’ activity is their nuclear translocation, where they activate many targets including transcription factors and chromatin modifiers. The MAPKs do not use the canonical nuclear shuttling machinery, importin (Imp-α∙β/NLS). Rather, we elucidated the mechanism of stimulated nuclear translocation of ERK1/2 (ERK) that upon stimulation is phosphorylated on its nuclear translocation signal (NTS) that allow interaction with Imp7, that transfers ERK to the nucleus [1]. P38/JNK interact mainly with Imp9 (and to a lesser extent Imp7) that further binds Imp3 to escort these MAPKs to the nucleus  [2]. These mechanisms are very specific to the distinct MAPKs and serve as an unexplored level of transcriptional regulation, crucial for proliferation and differentiation. We identified the Imp7/kinase interaction and prepared peptides based on these sequences. These peptides (EPE for ERK and PERY for p38/JNK) competes out the binding, preventes nuclear translocation, as well as their nuclear and pathological effects [3,4]. The prevention of nuclear translocation in cancer and inflammation models, was more effective with less side effects than the MAPK inhibitors that are currently in clinical use or trials. We are now developing the aforementioned drugs into clinical use for melanoma, as well as pancreatic, colon and breast cancers. 

In 1869 Friedrich Miescher, Basel, first identified "nuclein" inside the nuclei of human white blood cells. This term was later changed to “deoxyribonucleic acid” (DNA) [1]. Erwin Schrödinger published in 1944 “What is Life?” by predicting the role of DNA [1] as genetic code [2]. Based on the work of Nobel Laureate Ilya Prigogine, Hans Leuenberger wrote “What is Life? A new Human Model of Life, Disease and Death – A Challenge for Artificial Intelligence and Bioelectric Medicine Specialists” [3] for the 40th anniversary of SWISS PHARMA. Later he presented “Virtual Patient & in-silico Design of Solid Dosage Forms”[4]. The current model of a Virtual Patient is described by 4 pillars of the Center of Pharmacometrics & Systems Pharmacology, CPSP, at the University of Florida [5] consisting of Population Pharmacokinetic and Pharmacodynamic Modeling, Real World Outcomes, Artificial Intelligence and Mechanistic Modeling. The goal of CPSP is to create a rigorous and integrative academic translational science program in quantitative clinical pharmacology with a focus on bio-simulation. The common denominator is modeling. The first two pillars are linked to many patients. Artificial Intelligence tries to mimic a human being in 4 steps, Machine Learning, Deep Learning, Theory of Mind, and Self Awareness. Mechanistic Modeling is inspired by Physiologically‐Based Pharmacokinetic Modeling and Simulations that need to be complemented by cardio-vascular and nervous wiring system etc. In other words, the holistic VIRTUAL PATIENT can be described as an organic supercomputer able to replicate, consisting of approximately 40 1012 cells as microprocessors [3, 4]. This healthy being corresponds to stage 4 of Artificial Intelligence. The computer operating system of the VIRTUAL PATIENT is, as we know, sensitive to single drugs, to a combination of drugs (HIV treatment), to the combination of Syrosigopine, and Metformin as an anti-cancer agent [6]. Thus, the combination of low dose generic drugs opens a new research avenue in drug discovery [7] avoiding preclinical trials. Since Paracelsus, University of Basel, we know that the toxicity of a substance depends on the dose. Unfortunately, the early dose of a discovered drug is usually high for showing a significant effect. Our system is sensivitive to food, such as grapefruit, which is interacting with drugs, to parasites such as worms, to bugs and to viruses, etc. If our body (computer hardware) is severely damaged by a car accident can it be rebooted as a supercomputer, respectively reanimated as human being in an emergency room? As conclusions, it is proposed 1) to systematically evaluate combinations of n drugs, with n = 2, 3...m low dose generic drugs. In an optimal case new safe therapies of n drugs showing less side effects can be registered. 2) The pharmaceutical industry should adopt the workflow of the automotive industry by first evaluating in-silico the tablet formulations before manufacturing the drug delivery systems [8]. Thus, time to market can be reduced. 3) The sensitivity of the VIRTUAL PATIENT = DIGITAL TWIN can be explored on the basis of Clinical Phase I – III studies using a combination of n low dose generic drugs [7].