Advancing Evidence-based Palliative Care Research: Navigating Challenges and Proposing Solutions.

Amid the increasing demand for palliative care, driven by demographic shifts and medical progress, evidence-based practices face obstacles due to limited research. Complex patient conditions and ethical considerations challenge traditional methodologies, while the absence of comprehensive clinical trials hinders innovative interventions. Empowering practitioners with research skills and establishing a palliative care research network are efforts aimed at bridging these gaps. It is important to emphasise that these initiatives collectively aspire to enhance evidence-based practices, ensuring quality care for individuals facing severe illnesses.

From field to table: Ensuring food safety by reducing pesticide residues in food.

The present review addresses the significance of lowering pesticide residue levels in food items because of their harmful impacts on human health, wildlife populations, and the environment. It draws attention to the possible health risks-acute and chronic poisoning, cancer, unfavorable effects on reproduction, and harm to the brain or immunological systems-that come with pesticide exposure. Numerous traditional and cutting-edge methods, such as washing, blanching, peeling, thermal treatments, alkaline electrolyzed water washing, cold plasma, ultrasonic cleaning, ozone treatment, and enzymatic treatment, have been proposed to reduce pesticide residues in food products. It highlights the necessity of a paradigm change in crop protection and agri-food production on a global scale. It offers opportunities to guarantee food safety through the mitigation of pesticide residues in food. The review concludes that the first step in reducing worries about the negative effects of pesticides is to implement regulatory measures to regulate their use. In order to lower the exposure to dietary pesticides, the present review also emphasizes the significance of precision agricultural practices and integrated pest management techniques. The advanced approaches covered in this review present viable options along with traditional methods and possess the potential to lower pesticide residues in food items without sacrificing quality. It can be concluded from the present review that a paradigm shift towards sustainable agriculture and food production is essential to minimize pesticide residues in food, safeguarding human health, wildlife populations, and the environment. Furthermore, there is a need to refine the conventional methods of pesticide removal from food items along with the development of modern techniques.

Genitourinary Fistula: epidemiology, changing trends in etiology and management: A tertiary care institute's perspective.

INTRODUCTION: Urogenital fistula is a physically, socially and psychologically devastating condition for the patient. In developed countries, these fistulae are typically related to gynecological surgery, pelvic pathology like malignancy or post radiation therapy. In contrast, classical teaching is that urogenital fistulae in the developing countries like India are usually associated with prolonged labor and obstetric complications. This retrospective study conducted at a tertiary care health Institute shows a paradigm shift in epidemiology, etiology and management of genitourinary fistulae in India in recent times. METHODS: This retrospective study included patients undergoing surgical repair for various genitourinary fistulae at our institute from 2016 to 2022. Epidemiology, etiology, site, size and number of fistulae, clinical presentation, and management records of these patients were recorded and reviewed retrospectively. RESULTS: In our study, the mean age of the patients was 38.4 ± 10.2 years. Vesicovaginal Fistula (VVF) was found to be most common fistula in the study population (87.5%) followed by vesicouterine (7.1%) and urethrovaginal fistula (5.4%). The causes of genitourinary fistula were iatrogenic (73.2%), carcinoma of cervix (16.1%), obstructed prolonged labor (7.1%), and genitourinary tuberculosis (3.57%). Among the 48 vesicovaginal fistulas that underwent surgery, 45.8% were treated using a transvaginal approach, 29.2% were managed through a laparoscopic transabdominal repair, and 25% were addressed using a robotic approach. Recurrence occurred in 7.1% of the operated patients. CONCLUSION: Enhanced healthcare services in the country have contributed to a decrease in the incidence of obstructed labor, subsequently reducing related injuries. Iatrogenic injuries resulting from gynecological surgeries and carcinoma cervix have given rise to more complex fistulas, necessitating the implementation of advanced treatment strategies.

Living Synthelectronics: A New Era for Bioelectronics Powered by Synthetic Biology.

Bioelectronics, which converges biology and electronics, has attracted great attention due to their vital applications in human-machine interfaces. While traditional bioelectronic devices utilize nonliving organic and/or inorganic materials to achieve flexibility and stretchability, a biological mismatch is often encountered because human tissues are characterized not only by softness and stretchability but also by biodynamic and adaptive properties. Recently, a notable paradigm shift has emerged in bioelectronics, where living cells, and even viruses, modified via gene editing within synthetic biology, are used as core components in a new hybrid electronics paradigm. These devices are defined as "living synthelectronics," and they offer enhanced potential for interfacing with human tissues at informational and substance exchange levels. In this Perspective, the recent advances in living synthelectronics are summarized. First, opportunities brought to electronics by synthetic biology are briefly introduced. Then, strategic approaches to designing and making electronic devices using living cells/viruses as the building blocks, sensing components, or power sources are reviewed. Finally, the challenges faced by living synthelectronics are raised. It is believed that this paradigm shift will significantly contribute to the real integration of bioelectronics with human tissues.

Stakeholder analysis for effective implementation of water management system: Case of groundwater charge in South Korea.

Groundwater Charge was introduced in 2005 as one of the sustainable resource management measures in South Korea. The implementation rate, however, stagnated around 37 %, indicating that most local governments chose not to adopt this 'optional' regulation. While previous Stakeholder Analysis studies mainly blamed exclusion - or limited involvement - of stakeholders in the designing and structuring stage of policy-making process for policy failures, this study focused on the interest conflicts and dynamics hindered implementation process. This is because the issue with the subject policy, i.e., Groundwater Charge in South Korea, is low 'implementation rate' not the 'collection rate' or 'tax deficit.' If it was simply design or structural issue, the Charge should suffer from tax deficit problem due to lower tax income than operational costs. Thus, in order to investigate the reasons of low Charge adoption rate at the local government level, the Stakeholder Analysis Theory was applied to examine each stakeholder of the Charge to distinguish the interaction among supportive and opposing groups. The analysis revealed that there are only strong opponents of the policy without clearly identifiable supporters. Having agricultural & fishery industry and small independent businesses in spas, hotels, and swimming pool as strong Players, the Context setters (local governments) are not motivated to enforce Groundwater charge. Furthermore, today's social norm governed by economic efficiency is preventing the environmentalists and other Subjects to counteract Players. Under these circumstances, this study recommends the Subject to transform the Crowds (general public) into policy supporters through education. Environmental education is the only viable means to encourage necessary paradigm shift to enable effective implementation of environmental policies like Groundwater charge.

Evidentiary Significance of Routine EEG in Refractory Cases: A Paradigm Shift in Psychiatry.

Over the past decade, the Diagnostic and Statistical Manual's method of prescribing medications based on presenting symptoms has been challenged. The shift toward precision medicine began with the National Institute of Mental Health and culminated with the World Psychiatric Association's posit that a paradigm shift is needed. This study supports that shift by providing evidence explaining the high rate of psychiatric medication failure and suggests a possible first step toward precision medicine. A large psychiatric practice began collecting electroencephalograms (EEGs) for this study in 2012. The EEGs were analyzed by the same neurophysiologist (board certified in electroencephalography) on 1,233 patients. This study identified 4 EEG biomarkers accounting for medication failure in refractory patients: focal slowing, spindling excessive beta, encephalopathy, and isolated epileptiform discharges. Each EEG biomarker suggests underlying brain dysregulation, which may explain why prior medication attempts have failed. The EEG biomarkers cannot be identified based on current psychiatric assessment methods, and depending upon the localization, intensity, and duration, can all present as complex behavioral or psychiatric issues. The study highlights that the EEG biomarker identification approach can be a positive step toward personalized medicine in psychiatry, furthering the clinical thinking of "testing the organ we are trying to treat."

Invited review: Ketone biology-The shifting paradigm of ketones and ketosis in the dairy cow.

Ketosis is currently regarded as a major metabolic disorder of dairy cows, reflective of the animal's efforts to adapt to energy deficit while transitioning into lactation. Currently viewed as a pathology by some, ketosis is associatively implicated in milk production losses and peripartal health complications that increase the risk of early removal of cows from the herd, thus carrying economic losses for dairy farmers and jeopardizing the sustainability of the dairy industry. Despite decades of intense research in the mitigation of ketosis and its sequelae, our ability to lessen its purported effects remains limited. Moreover, the association of ketosis to reduced milk production and peripartal disease is often erratic and likely mired by concurrent potential confounders. In this review, we discuss the potential reasons for these apparent paradoxes in the light of currently available evidence, with a focus on the limitations of observational research and the necessary steps to unambiguously identify the effects of ketosis on cow health and performance via controlled randomized experimentation. A nuanced perspective is proposed that considers the dissociation of ketosis-as a disease-from healthy hyperketonemia. Furthermore, in consideration of a growing body of evidence that highlights positive roles of ketones in the mitigation of metabolic dysfunction and chronic diseases, we consider the hypothetical functions of ketones as health-promoting metabolites and ponder on their potential usefulness to enhance dairy cow health and productivity.

Adaptive Care Planning: A paradigm shift.

A key challenge of implementing advance care planning lies in the fact that decisions made in advance require patients and their family members to imagine what their clinical picture will look like rather than knowing or experiencing the clinical circumstances as they unfold. Even more important is the acknowledgment of the unpredictability of a given clinical course. This type of situation requires adaptiveness and flexibility in decision-making that frequently occurs in the moment(s) triggered by changes in health state(s). We describe an alternative frameshifting approach called "Adaptive Care Planning (AdaptCP)," which features an evolving communication between physicians and patients/families with ongoing incorporation of the patient's/family's perspective. This process continues iteratively until each decision can be reached in a way that is both harmonious with the patient's/family's perspective and is consistent with medical treatment options that are actionable for the healthcare team. We include a table of tools drawn from the literature that can help clinicians when implementing AdaptCP.

Time for a paradigm shift? Small carnivores' sensitivity highlights the importance of monitoring mid-rank predators in future global change studies.

Research Highlight: Jachowski, D. S., Marneweck, C. J., Olfenbuttel, C., & Harris, S. N. (2024). Support for the size-mediated sensitivity hypothesis within a diverse carnivore community. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.13916. A current paradigm in ecological research suggests that top predators are suitable sentinel species to identify ecosystem dysfunctions and monitor the effects of climate change. However, the adequacy of top predators to systematically take this function may be mistakenly inferred or unintentionally conflated from the fact that these species are regarded as biodiversity indicators or keystone, umbrella and flagship species in most ecosystems. Regarding terrestrial mammalian carnivores (order Carnivora), some researchers recently suggested that the smaller species likely possess a higher sensitivity to environmental changes than large carnivores because of their biological attributes and their intermediate position in food webs. To test this hypothesis, Jachowski et al. (2024) used camera trapping followed by occupancy and structural equation modelling to explore the dynamics of a diverse carnivore community and the factors that influence them. Their results confirmed that small carnivores are more sensitive to habitat changes and are interconnected by a greater number of significant pathways compared with larger carnivores. This support for the size-mediated sensitivity hypothesis strengthens the proposition that small carnivores (and other mid-rank predators) are ideal sentinel species for monitoring the effects of the wide range of contemporary and future environmental changes. Time will tell whether this new 'middle-out ecology' paradigm will be considered in future global change studies.

First-line Management of Metastatic Urothelial Cancer: Current and Future Perspectives After the EV-302 and CheckMate-901 Studies.

The standard of care for the first-line management of metastatic urothelial carcinoma has been recently challenged, with the combination of pembrolizumab and enfortumab vedotin (P-EV) strongly arising as a practice-changing option from classical platinum-based chemotherapies. With this paradigm shift on the horizon new questions, including the most suitable second line of treatment for these patients, and the role that the molecular characterization of these tumours will have when selecting these therapies will inevitably arise. Furthermore, after the negative results of the Keynote 361 and IMvigor 130 trials, the combination of nivolumab with platinum-based chemotherapy followed by nivolumab maintenance (Nivo GC-Nivo) has also shown positive results when compared with chemotherapy alone. Translational studies at a molecular, cellular, and functional level will be key to better explain these discordant results. In this Current Perspective, we discuss the potential impact of these results in clinical practice and propose specific guidance for prospective translational research.

A new paradigm for regulatory sciences.

Regulatory science, rooted in legal requirements, provides a mechanism for identifying, assessing, and managing harm to humans and the environment from exposure to hazardous substances. A challenge for regulatory authorities is that many governing laws reflect the scientific paradigm of the mid-20th century. By the nature of legislative processes, most laws are not able to readily adapt to incorporate scientific advances that are inherent in an ever-evolving paradigm. Consequently, the issue of rigid legal frameworks has become prominent in global discussions related to the incorporation of reliable and relevant modern technology to fulfill regulatory needs. To explore this issue, we apply Thomas Kuhn's The Structure of Scientific Revolutions as a conceptual framework to help understand the natural progression of scientific paradigms (from normal science, to anomaly, to crisis, to revolution, and finally to a new normal), identify where we are now in the paradigm cycle, and to explore a path towards a revolution that enables timely implementation of the best available science to fulfil legal requirements.

The scientific reinvention of forensic science.

Forensic science is undergoing an evolution in which a long-standing "trust the examiner" focus is being replaced by a "trust the scientific method" focus. This shift, which is in progress and still partial, is critical to ensure that the legal system uses forensic information in an accurate and valid way. In this Perspective, we discuss the ways in which the move to a more empirically grounded scientific culture for the forensic sciences impacts testing, error rate analyses, procedural safeguards, and the reporting of forensic results. However, we caution that the ultimate success of this scientific reinvention likely depends on whether the courts begin to engage with forensic science claims in a more rigorous way.

Anthropological perspectives on CKDnt in Mexico: time for a paradigm shift on the social determinants of health.

In Mexico, the kidneys of individuals in poor and marginalized communities are failing with little warning and no explanation. Commonly referred to as chronic kidney disease of non-traditional origin (CKDnt), this new variant of kidney disease cannot be accounted for by conventional or discrete etiological explanations, but is instead understood to be a consequence of economic development, environmental degradation and precarious working and living conditions. Drawing on two interconnected ethnographic studies, and the intertwining problems of causation and care, this paper will (1) document the social conditions of disease emergence around Lake Chapala, Central Mexico, and (2) follow the haphazard routes kidney patients take to access resource-intensive biotechnical treatments. Its aim is to both challenge and reconceptualize social determinants as social relations in order to fully account for the profoundly contextual, temporal, and dynamic character of this condition, and to rethink opportunities for care and intervention.

Four key problems that will need to be addressed during the next pandemic.

In June 2023, the UK began official hearings for its independent investigation into pandemic preparedness. Thus far, the inquiry has been told that planning has been wholly inadequate and that a future outbreak is inevitable. We present here four key problems that contributed to significant morbidity and mortality during the Coronavirus 2019 (COVID-19) pandemic over the past 3 years in the UK - and which will contribute to excess morbidity and mortality in the next outbreak. First, there was misunderstanding about what procedures were deemed as aerosol generating. Aerosol transmission has always been a component of respiratory viruses; however, no specific aerosol-generating procedures are required to transmit any respiratory pathogens over long distances. Second, policy-makers were too binary in their answers to the public in terms of questions about severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). This meant that, as evidence evolved and different conclusions were drawn, the public lost faith in both the UK Government and science. Third, public health guidance did not take into account that certain groups would be impacted differentially by public health guidelines and instead used a one-size-fits-all approach to non-pharmaceutical interventions. Finally, there was worsening of existing inequalities, especially in ethnic minority groups, that resulted in excessive numbers within certain cohorts becoming infected.

A Biocratic Paradigm: Exploring the Complexity of Trauma-Informed Leadership and Creating Presence™.

A paradigm shift is under way in the human services because of breakthrough knowledge and research in understanding the underlying etiology of physical, emotional, and social problems at the micro-level of the individual, at the meso-level of the family and institutions, and at the macro-level of the entire society. The three levels of human existence-micro, mezzo, and macro-constitute interactive, interdependent, complex adaptive living systems. The complexity of these problems requires us to use our imaginations to envision health in individuals, organizations, and societies because it does not presently exist. After thousands of years of unrelenting exposure to trauma and adversity, we have all normalized what is a traumatogenic civilization. As a result, we live in a trauma-organized society in ways we are just beginning to understand in this century. This biopsychosocial knowledge base that is drawn upon here has come to be known as "trauma-informed" knowledge because it began with a deepening understanding of the impact of trauma on survivors of combat, disasters, and genocide, but now extends far beyond those specific boundaries. To lead any organization in a time of significant change means leading a revolution in understanding human nature and the fundamental causes of human pathology that are endangering all life on this planet and then helping organizational members develop skills to positively influence the changes necessary. In the 1930s, Dr. Walter B. Cannon, a Harvard physiologist who had named the "fight-flight" response and defined homeostasis, used the word "biocracy" to describe the relationship between the physical body and the social body, emphasizing the vital importance of democracy. This paper is a beginning attempt at integrating the concept of a biocratic organization with that of the trauma-informed knowledge necessary for leadership. Hope lies in properly diagnosing the problem, remembering ancient peace-making strategies, embracing universal life-preserving values, inspiring a new vision for the future, and radically and consciously changing our present self and other-destructive behavior. The paper concludes with a brief description of a new online educational program called Creating Presence™ that is being used in organizations as a method for creating and supporting the development of biocratic, trauma-informed organizations.

Implications of the paradigm shift in management of Helicobacter pylori infections.

The recent availability of susceptibility testing for Helicobacter pylori infections in the United Sates has resulted in paradigm shifts in the diagnosis, therapy, and follow-up of H. pylori infections. Here, we reviewed the English literature concerning changes in H. pylori diagnosis and therapy with an emphasis on the last 3 years. We focus on the new methods that offer rapid and convenient susceptibility testing using either invasive (endoscopic) or noninvasive (stool) methods of obtaining test material. We also discuss the implications of this availability on therapy and follow-up after therapy. The approach to therapy was categorized into four groups: (1) therapies that can be used empirically, (2) therapies that should be restricted to those that are susceptibility-based, (3) potentially effective therapies that have yet to be optimized for local use, and (4), therapies that contain unneeded antibiotics that should not be prescribed. The most convenient and efficient method of susceptibility testing is by using reflexive stool testing in which if the sample is positive, it is automatically also used for determination of susceptibility. Reflexive testing can also be done via reflexive ordering (e.g., for all positive urea breath tests). The post therapy test-of-cure has emerged as a critical component of therapy as it not only provides feedback regarding treatment success but when combined with susceptibility testing also provide evidence regarding the cause of failure (e.g., poor adherence versus emergence of resistance during therapy. Susceptibility testing has made even the most current H. pylori guidelines for diagnosis and therapy generally obsolete. Clarithromycin, metronidazole, and levofloxacin triple therapies should only be administered as susceptibility-based therapy. Regimens containing unneeded antibiotics should not be given. We provide recommendations regarding the details and indications for all current therapies.

The necessity revealed by COVID-19 pandemic: Paradigm shift of Iran's healthcare system.

Background: COVID-19 pandemic has resulted in drastic changes around the world, revealing vulnerable aspects of healthcare systems. This study aimed to explore how Iranian healthcare system experienced the paradigm shift during the pandemic and determine the aspects that need improvement during the pandemic era. Method: This qualitative study was conducted in 2021. A framework analysis approach was used to analyze the content of the 19 semi-structured interviews with the healthcare system experts from Shiraz University of Medical Sciences (SUMS). The interviews' audio files changed into transcript after each session and data was saturated at the 19 interview. To increase the trustworthiness of the study, Guba and Lincoln's criteria including credibility, transferability, dependability, and confirmability were used. Goldsmith's five-step framework analysis was used applying MAX QDA version 10 software. Result: Eight main themes and 20 subthemes were explored. The main themes included "strengthening the electronic health infrastructure," "research for evidence-based decision making," "dedicated financing to the pandemic," "prevention of disruption in the effective provision of services and medicines," "enriching the authority of the Ministry of Health by focusing on interactions," "recruiting, managing and empowering health human resources with attention to financial and non-financial incentives," "reforming educational approaches in training students in medical universities," as well as "lessons learned from neglected aspects." Conclusion: To be ready to respond to a possible future pandemic and for a paradigm shift, bold steps must be taken to make fundamental changes in various aspects of the healthcare system including e-health development, evidence-based decision making, dedicated budgets for pandemics, reinforcement of interactions at the national and international level, as well as sufficient attention to healthcare workers from all financial, non-financial and educational aspects.

A call for a Human Exposome Project.

Four decades of the Human Genome Project and its consequences have shown how the entrepreneurial state, through significant investment into science, can drive scientific progress and advance biomedicine. A certain fraction of diseases can now be explained as caused by genetics, and a more significant fraction as impacted by genetics. Besides another fraction caused by pathogens, the third and probably largest impactor is exposure, i.e., the many physicochemical and lifestyle factors. This article makes the case that it is time to start a Human Exposome Project, which systematically explores and catalogs the exposure side of human health and disease. The envisioned Human Exposome Project needs to be more than a scaled exposomics approach, aiming to assess the totality of relevant exposures through ~omics of human body fluids and forming exposure hypotheses. Exposomics is increasingly complemented by exposure science and biomonitoring to measure exposure, mechanistic understanding, human-relevant microphysiological systems, big data, and artificial intelligence (AI) to mine these data and integrate pieces of evidence. The potential impact of AI on a possible Human Exposome Project is so substantial that we should speak of exposome intelligence (EI) because this allows us to expand our limited current knowledge to the big unknown unknowns of threats to human health.