New Frontiers In Medicine Research Articles

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks.

Aging is a complex and time-dependent decline in physiological function that affects most organisms, leading to increased risk of age-related diseases. Investigating the molecular underpinnings of aging is crucial to identify geroprotectors, precisely quantify biological age, and propose healthy longevity approaches. This review explores pathways that are currently being investigated as intervention targets and aging biomarkers spanning molecular, cellular, and systemic dimensions. Interventions that target these hallmarks may ameliorate the aging process, with some progressing to clinical trials. Biomarkers of these hallmarks are used to estimate biological aging and risk of aging-associated disease. Utilizing aging biomarkers, biological aging clocks can be constructed that predict a state of abnormal aging, age-related diseases, and increased mortality. Biological age estimation can therefore provide the basis for a fine-grained risk stratification by predicting all-cause mortality well ahead of the onset of specific diseases, thus offering a window for intervention. Yet, despite technological advancements, challenges persist due to individual variability and the dynamic nature of these biomarkers. Addressing this requires longitudinal studies for robust biomarker identification. Overall, utilizing the hallmarks of aging to discover new drug targets and develop new biomarkers opens new frontiers in medicine. Prospects involve multi-omics integration, machine learning, and personalized approaches for targeted interventions, promising a healthier aging population.

Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.

Integrating Artificial Intelligence in the Diagnosis of COPD Globally: A Way Forward.

The advancement of artificial intelligence (AI) capabilities has paved the way for a new frontier in medicine, which has the capability to reduce the burden of COPD globally. AI may reduce health care-associated expenses while potentially increasing diagnostic specificity, improving access to early COPD diagnosis, and monitoring COPD progression and subsequent disease management. We evaluated how AI can be integrated into COPD diagnosing globally and leveraged in resource-constrained settings.AI has been explored in diagnosing and phenotyping COPD through auscultation, pulmonary function testing, and imaging. Clinician collaboration with AI has increased the performance of COPD diagnosing and highlights the important role of clinical decision-making in AI integration. Likewise, AI analysis of computer tomography (CT) imaging in large population-based cohorts has increased diagnostic ability, severity classification, and prediction of outcomes related to COPD. Moreover, a multimodality approach with CT imaging, demographic data, and spirometry has been shown to improve machine learning predictions of the progression to COPD compared to each modality alone. Prior research has primarily been conducted in high-income country settings, which may lack generalization to a global population. AI is a World Health Organization priority with the potential to reduce health care barriers in low- and middle-income countries. We recommend a collaboration between clinicians and an AI-supported multimodal approach to COPD diagnosis as a step towards achieving this goal. We believe the interplay of CT imaging, spirometry, biomarkers, and sputum analysis may provide unique insights across settings that could provide a basis for clinical decision-making that includes early intervention for those diagnosed with COPD.

Interfacial-engineered living drugs with "ON/OFF" switching for oral delivery.

Living drugs offer a new frontier in medicine, paving the way for personalized and potentially curative treatments. A customized living drug generally requires specialized technologies for highly effective and selective delivery to lesion locations. In this study, we explored an interfacial engineering method for living drugs by wrapping them with a "stealth coating", achieving "ON/OFF" switching of the communications between probiotics and the gastrointesinal (GI) tract. This maximized the bioactivity of living drugs following oral administration to exempt acidic insults and then significantly improved the retention through the gastrointestinal tract. With the notable ability to improve oral availability, the interfacial-engineered living drugs represent remarkable effects for enhanced oral delivery and treatment efficacy in the dextran sulfate sodium (DSS)-induced acute colitis model. We believe that this work has the potential to revolutionize medicine by precisely targeting and increasing curative activity in the future of disease treatment.

Exploring the Enigma of VEXAS Syndrome: A New Frontier in Medicine

In the realm of modern medicine, the discovery of novel diseases often presents both challenges and opportunities. VEXAS syndrome, an acronym for Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome, is a striking example of a unique monogenic disorder that has recently come to light. This syndrome represents a bridge between the worlds of rheumatology and hematology, and its clinical manifestations have left clinicians and researchers perplexed. In this editorial, I will delve into the complexity of VEXAS syndrome, exploring its clinical features, genetic underpinnings, and the quest for effective treatments. Furthermore, I will discuss how VEXAS syndrome may serve as a prototype for a new class of diseases that blur the boundaries between hematopoiesis and inflammation.

Genetically engineered Lactobacillus paracasei rescues colonic angiotensin converting enzyme 2 (ACE2) and attenuates hypertension in female Ace2 knock out rats

Engineered gut microbiota represents a new frontier in medicine, in part serving as a vehicle for the delivery of therapeutic biologics to treat a range of host conditions. The gut microbiota plays a significant role in blood pressure regulation; thus, manipulation of gut microbiota is a promising avenue for hypertension treatment. In this study, we tested the potential of Lactobacillus paracasei, genetically engineered to produce and deliver human angiotensin converting enzyme 2 (Lacto-hACE2), to regulate blood pressure in a rat model of hypertension with genetic ablation of endogenous Ace2 (Ace2-/- and Ace2-/y). Our findings reveal a sex-specific reduction in blood pressure in female (Ace2-/-) but not male (Ace2-/y) rats following colonization with the Lacto-hACE2. This beneficial effect of lowering blood pressure was aligned with a specific reduction in colonic angiotensin II, but not renal angiotensin II, suggesting the importance of colonic Ace2 in the regulation of blood pressure. We conclude that this approach of targeting the colon with engineered bacteria for delivery of ACE2 represents a promising new paradigm in the development of antihypertensive therapeutics.

Abstract 087: Genetically Engineered Gut Microbiota For Delivery Of Angiotensin Converting Enzyme 2 Attenuates Hypertension

Engineered gut microbiota represents a new frontier in medicine, in part, serving as a vehicle for the delivery of therapeutic biologics to treat a range of host conditions. Since gut microbiota plays a significant role in blood pressure (BP) regulation, using engineered gut microbiota for treatment of hypertension is a promising novel prospect. In this study, we hypothesized that genetically engineered Lactobacilli that biosynthesize human ACE2 (Lacto-hACE2) target AngII in the gut to lower BP. To test this hypothesis, a novel Ace2 knockout (KO) rat (r Ace2 -/- for female rats, r Ace2 -/y for male rats) was generated using the CRISPR/Cas9 technology. Age and sex-matched Ace2 KO rats were surgically implanted with radiotelemetry transmitters to monitor BP and administered either Lacto-hACE2 (n=8 male; n=8 female) or wild-type Lactobacillus (Lacto-Control, n=7 male, n=8 female) for 3 weeks. BP was monitored by radiotelemetry. ACE2 activity and AngII levels were compared in both sexes. As expected, compared to non-founder control rats, Ace2 KO rats of both sexes had a significantly higher mean arterial pressure (MAP) (females: control vs. r Ace2 -/- , 132±2 mmHg vs 167±10 mmHg, p<0.0001; males: control vs. r Ace2 -/y , 116±2 mmHg vs 132±6 mmHg, p<0.0001). Moreover, both renal and colonic Ang II levels were elevated in the Ace2 KO rats (Renal: females-control vs. rAce 2 -/- , p<0.05; males-control vs. r Ace2 -/y , p<0.0001; Colon: females-control vs. r Ace2 -/- , p<0.001; males-control vs r Ace2 -/y , p<0.05). However, treatment with Lacto-hACE2 showed a sex-specific lowering of BP in females (MAP, control vs. treated, 158±7 mmHg vs 150±7 mmHg, p<0.01), which was not observed in males. The treatment effect was largely due to a significant decrease in diastolic BP (control vs . treated, 145±8 mmHg vs 133±9 mmHg, p<0.001). Interestingly, only colonic AngII, but not renal AngII, was lowered in the treated rats. In conclusion, this study is the first to demonstrate the therapeutic benefit of a commensal microbe engineered to deliver human ACE2 to the colon to lower BP in Ace2 KO rats. Our study is the first to highlight the potential of targeting the colon with engineered bacteria to develop microbiome medicine as the treatment of hypertension.

Medical Aid in Dying: New Frontiers in Medicine, Law, and Culture

Medical aid in dying (MAID) has been a productive target for social scientific inquiry at the intersections of law and medicine over the past two decades. Insofar as MAID crystallizes and reflects personal and cultural understandings of key concepts such as individualism, dependency, dignity, and care, it is a rich site for social scientific theorizing. This article reviews and assesses the contributions of social scientific perspectives to research on MAID. We propose that social scientific research on MAID offers four distinctive contributions: its descriptive (rather than normative) orientation, its focus on cultural meanings, its insights into processes of knowledge production, and its comparative lens. The article's major sections describe ( a) attitudes toward MAID, ( b) MAID-related social movements, ( c) legalization approaches, and ( d) lived experiences of MAID in permissive jurisdictions. We conclude by reflecting on how MAID scholarship can inform social inquiry into other areas in which law and medicine converge.

Assisted Reproductive Technologies, Other New Frontiers in Medicine, and the Income Tax's Role as a Backup Health Insurance System

Assisted Reproductive Technologies, Other New Frontiers in Medicine, and the Income Tax's Role as a Backup Health Insurance System

3D Bioprinting at the Frontier of Regenerative Medicine, Pharmaceutical, and Food Industries.

3D printing technology has emerged as a key driver behind an ongoing paradigm shift in the production process of various industrial domains. The integration of 3D printing into tissue engineering, by utilizing life cells which are encapsulated in specific natural or synthetic biomaterials (e.g., hydrogels) as bioinks, is paving the way toward devising many innovating solutions for key biomedical and healthcare challenges and heralds' new frontiers in medicine, pharmaceutical, and food industries. Here, we present a synthesis of the available 3D bioprinting technology from what is found and what has been achieved in various applications and discussed the capabilities and limitations encountered in this technology.

Insights into Futuristic Renal Medicine.

The revolutionary innovations in biology and information technology influenced many medical and health disciplines. Although it is lagging behind others, renal medicine entered this chain of events. Nephrology and renal transplantation have many inherent challenges that needed to be addressed innovatively to receive these new frontiers in medicine. In a connected high biotech future, the applications of regenerative medicine, nanotechnology, genomics, artificial intelligence, 3D organ bioprinting, and smartphone applications will reshape the practice and research of renal medicine. Certainly, this will have a positive impact on patients' outcomes and the health-care system. These changes are coming, but with new challenges such as excess costs, and many moral challenges. Providing precise equitable care with maintaining patient's privacy and values will be difficult. In this review, we provide insights into future approaches to renal care.

Surgery Versus ATMPs: An Example From Ophthalmology.

Advanced therapy medicinal products (ATMPs) are the new frontier of medicine. Advanced therapy medicinal products are set out to satisfy unmet medical needs and provide new innovative, cutting-edge therapies for serious or life-threatening diseases, thus providing new therapeutic options for people with few or no possibility of treatment. They are divided into four groups including gene therapy medicinal products, cell-based therapy medicinal products, tissue-engineered products, and combined ATMPs, which in Europe refer to products that incorporate one or more medical devices with any of the previously mentioned ATMPs as part of the advanced medicine product (AIFA, 2017; Ten Ham et al., 2018). Advanced therapy medicinal products can potentially have long-term benefits, thus bringing a long-lasting positive impact on patient health. Advanced therapy medicinal product therapies are often administered just once or twice, which gives patients the possibility to heal quickly compared to traditional therapies. They also provide a long-term saving opportunity, both in terms of costs of treatments and procedures that are no longer necessary and in terms of quality of life and productivity. The resolution of the patient’s illness has a monetary impact on the patient, the patient’s caretakers, and especially on the society (Alliance for Regenerative Medicine, 2019). The aim of this paper was to provide an overview on the use of ATMPs approved in Europe, with a focus on blindness and visual impairment and the related economic burden. In this case study, the effective cost of a blind patient in different European countries was compared after treatment with ATMPs or traditional therapies, focusing on visual impairment caused by corneal opacity. Our evaluation includes an overview of the global economic impact of the two types of therapies on the society. We estimated direct healthcare costs, direct non-healthcare costs, and labor productivity losses, to include costs on healthcare, services, patients, their families and for the society in general. We could conclude that the costs of the two therapeutic approaches are comparable.

Radiomics and artificial intelligence: new frontiers in medicine.

Radiomics is a new frontier of medicine based on the extraction of quantitative data from radiological images which can not be seen by radiologist's naked eye and on the use of these data for the creation of clinical decision support systems. The long-term goal of radiomics is to improve the non-invasive diagnosis of focal and diffuse diseases of different organs by understanding links between extracted quantitative imaging data and the underlying molecular and pathological characteristics of lesions. In the last decade, several studies have highlighted the enormous potential of radiomics in both tumoral and non-tumoral diseases of many organs and systems including brain, lung, breast, gastrointestinal and genitourinary tracts. The enormous potential of radiomics needs to be pursued with the methodological rigor of scientific research and by integrating radiological data with other medical disciplines, in order to improve personalized patient management.

Mass-customization of oral tablets via the combination of 3D printing and injection molding

The new frontier of medicine is the personalization of treatment to match a patient's individual needs. Fused-filament fabrication (FFF) offers a platform for the personalization of drug dosage forms, but one of its chief shortcomings compared to other tablet production methods such as dry compression and wet granulation is relatively low throughput. Conversely, injection molding (IM) is a manufacturing technique for the high-volume production of parts, but in which individual part customization is both expensive and slow requiring the modification of expensive mold tooling. Mass-customization is the manufacture of custom products that match the needs of individual consumers but which are produced at the low unit cost associated with high-volume production. We successfully integrated for the first time FFF with IM in a multi-step manufacturing process for the production of custom bilayer tablets loaded with two active pharmaceutical ingredients used in the treatment of cardiovascular disease. The FFF layer was loaded with the diuretic hydrochlorothiazide, while the IM layer was loaded with lovastatin. Infill percentage was varied for the FFF layer as a means to modify drug release. The IM injection pressure was evaluated for its effect on drug release and layer-layer adhesion. The bilayer tablets obtained offered different combinations of drug release profiles, which were governed by a combination of factors, including surface area to volume ratio; IM injection volume penetration into the FFF layer; FFF infill percentage; layer tortuosity and porosity. These different parameters could be utilized to modify the individual release of both drugs from the bilayer tablet. Thus for the first time, we have demonstrated a viable method for the mass-customization of oral tablets which could hasten the rollout of personalized medicine.

Stem Cells: Basics and its Prospective uses in Medical field

Stem cells abilities to self-renew and differentiate have captured the attention of both developmental biologist and medical practitioners. Stem cells are potentially immortal cells capable of self-renewal and give rise to differentiated cells. No area of research except gene therapy has evolved so much enthusiasm and hope as stem cells. Most medical expert view stem cells research as the new frontiers in medicine, a huge breakthrough that could save millions of life. Medicine today’s are based on drug therapy dominated by antibiotics, chemotherapy, and other pharmaceuticals. Medicine of future would be based on cell therapies, focused on repair of tissues/organs by cell transplant i.e. instead of drugs to prevent malfunction or death, diseased cell would be replaced by healthy differentiated stem cell. This article presents a comprehensive review on basics of stem cells and its potential uses in coming future.

In vitro differentiation of primordial germ cells and oocyte-like cells from stem cells.

Infertility is the result of failure due to an organic disorder of the reproductive organs, especially their gametes. Recently, much progress has been made on generating germ cells, including oocytes, from various types of stem cells. This review focuses on advances in female germ cell differentiation from different kinds of stem cells, with emphasis on embryonic stem cells, adult stem cells, and induced pluripotent stem cells. The advantages and disadvantages of the derivation of female germ cells from several types of stem cells are also highlighted, as well as the ability of stem cells to generate mature and functional female gametes. This review shows that stem cell therapies have opened new frontiers in medicine, especially in the reproductive area, with the possibility of regenerating fertility.

Organization and implementation of a cardio-oncology program

Considerable advances in cancer therapies in recent decades have reshaped the prognosis of cancer patients. There are now estimated to be over 20 million cancer survivors in the USA and Europe, numbers unimaginable a few years ago. However, this increase in survival, along with the aging of the patient population, has been accompanied by a rise in adverse cardiovascular effects, particularly when there is a previous history of heart disease. The incidence of cardiotoxicity continues to grow, which can compromise the effectiveness of cancer therapy. Cardiotoxicity associated with conventional therapies, especially anthracyclines and radiation, is well known, and usually leads to left ventricular dysfunction. However, heart failure represents only a fraction of the cardiotoxicity associated with newer therapies, which have diverse cardiovascular effects. There are few guidelines for early detection, prevention and treatment of cardiotoxicity of cancer treatments, and no well-established tools for screening these patients. Echocardiography is the method of choice for assessment of patients before, during and after cancer treatment.It therefore makes sense to adopt a multidisciplinary approach to these patients, involving cardiologists, oncologists and radiotherapists, collaborating in the development of new training modules, and performing clinical and translational research in a cardio-oncology program. Cardio-oncology is a new frontier in medicine and has emerged as a new medical subspecialty that concentrates knowledge, understanding, training and treatment of cardiovascular comorbidities, risks and complications in patients with cancer in a comprehensive approach to the patient rather than to the disease.

Organização e implementação de uma consulta de cardio‐oncologia

Considerable advances in cancer therapies in recent decades have reshaped the prognosis of cancer patients. There are now estimated to be over 20 million cancer survivors in the USA and Europe, numbers unimaginable a few years ago. However, this increase in survival, along with the aging of the patient population, has been accompanied by a rise in adverse cardiovascular effects, particularly when there is a previous history of heart disease. The incidence of cardiotoxicity continues to grow, which can compromise the effectiveness of cancer therapy. Cardiotoxicity associated with conventional therapies, especially anthracyclines and radiation, is well known, and usually leads to left ventricular dysfunction. However, heart failure represents only a fraction of the cardiotoxicity associated with newer therapies, which have diverse cardiovascular effects. There are few guidelines for early detection, prevention and treatment of cardiotoxicity of cancer treatments, and no well‐established tools for screening these patients. Echocardiography is the method of choice for assessment of patients before, during and after cancer treatment.It therefore makes sense to adopt a multidisciplinary approach to these patients, involving cardiologists, oncologists and radiotherapists, collaborating in the development of new training modules, and performing clinical and translational research in a cardio‐oncology program. Cardio‐oncology is a new frontier in medicine and has emerged as a new medical subspecialty that concentrates knowledge, understanding, training and treatment of cardiovascular comorbidities, risks and complications in patients with cancer in a comprehensive approach to the patient rather than to the disease.

Social media use by physicians: a qualitative study of the new frontier of medicine.

BackgroundA growing number of physicians are using social media as a professional platform for health communication. The purpose of this study was to understand perspectives and experiences of these “early adopter” physician bloggers and social media users.MethodsThis was an exploratory qualitative study involving in-depth semi-structured telephone interviews of physicians who were early adopters, defined as physicians who used social media to distribute health information. Participants were recruited through snowball sampling. Interview transcripts were manually analyzed for common themes by three separate investigators who came to common conclusions via the constant comparative method.ResultsSeventeen physicians participated in this study, including 35 % females, 76 % pediatricians and 76 % bloggers. Participants identified multiple perceived benefits and barriers to social media use by physicians; further, four major themes were identified. First, participants often saw themselves as rugged individualists who set their own rules for social media health communications. Second, participants expressed uncertainty about boundaries or strategies for social media use. Third, participants described using social media much like traditional media, as a one-way communication platform, rather than as an interactive forum. Finally, participants expressed disparate views regarding the time involved in participating in social media; some felt that time spent on social media was unproblematic to fit into their day while others felt that it was an impediment to patient care.ConclusionsUncertainty remains regarding roles and responsibilities of physicians providing medical content within social media forums and few providers appeared to be using the platform to its full potential. Future studies may inform best practices to optimize social media health communication to benefit patients.

Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation

The microbiome is recognized as a new frontier in medicine with connections to a variety of diseases. We aimed to evaluate the association of lipopolysaccharide (LPS), a key pro-inflammatory product of the microbiome, with severity of inflammation, symptoms and radiographic abnormalities of knee osteoarthritis (OA). LPS was measured using a recombinant Factor C (rFC) assay, carefully optimized for systemic and synovial fluid (SF) analyses. LPS binding protein (LBP) was tested in both serum and SF of 25 patients (31 knees) from the Etarfolatide cohort for association with OA phenotypic outcomes. Models were adjusted for age, gender and body mass index. Based on LPS spike-and-recovery, both serum and SF dilutions of 0.1% were required to achieve recovery rates of at least 75% in all test specimens. Low coefficients of variation (CVs) (<10%) were achieved with both serum and SF dilutions <0.2%. Serum LPS and LBP were associated with the abundance of activated macrophages in the knee joint capsule and synovium. SF LPS and LBP were associated with the abundance of activated macrophages in the synovium. Serum LPS, LBP and SF LPS were associated with knee osteophyte severity. SF LPS was positively associated with knee joint space narrowing (JSN) severity and total WOMAC score. SF LBP was positively associated with self-reported knee pain score. These data strongly support a role for LPS in the pathogenesis and severity of structural abnormalities and symptoms of knee OA.