Controversies regarding transplantation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have tantalized regenerative medicine with their therapeutic potential, yet a cloud of controversies looms over their clinical transplantation. This comprehensive review navigates the intricate landscape of MSC controversies, drawing upon 15 years of clinical experience and research. We delve into the fundamental properties of MSCs, exploring their unique immunomodulatory capabilities and surface markers. The heart of our inquiry lies in the controversial applications of MSC transplantation, including the perennial debate between autologous and allogeneic sources, concerns about efficacy, and lingering safety apprehensions. Moreover, we unravel the enigmatic mechanisms surrounding MSC transplantation, such as homing, integration, and the delicate balance between differentiation and paracrine effects. We also assess the current status of clinical trials and the ever-evolving regulatory landscape. As we peer into the future, we examine emerging trends, envisioning personalized medicine and innovative delivery methods. Our review provides a balanced and informed perspective on the controversies, offering readers a clear understanding of the complexities, challenges, and potential solutions in MSC transplantation.

Non-operative management of rectal cancer: Highlighting the controversies.

There remains much ambiguity on what non-operative management (NOM) of rectal cancer truly entails in terms of the methods to be adopted and the best algorithm to follow. This is clearly shown by the discordance between various national and international guidelines on NOM of rectal cancer. The main aim of the NOM strategy is organ preservation and avoiding unnecessary surgical intervention, which carries its own risk of morbidity. A highly specific and sensitive surveillance program must be devised to avoid patients undergoing unnecessary surgical interventions. In many studies, NOM, often interchangeably called the Watch and Wait strategy, has been shown as a promising treatment option when undertaken in the appropriate patient population, where a clinical complete response is achieved. However, there are no clear guidelines on patient selection for NOM along with the optimal method of surveillance.

Bone marrow necrosis: Facts, controversies, and perspective.

Bone marrow necrosis (BMN) is a clinically and pathologically poorly-defined and readily-overlooked entity. The current facts and guidelines pertaining to this entity are scarce, and there exist controversies. Upon reviewing the literature, we present the facts, analyze these controversies, and discourse on future prospects.

A comprehensive review on ziconotide.

Managing severe chronic pain is a challenging task, given the limited effectiveness of available pharmacological and non-pharmacological treatments. This issue continues to be a significant public health concern, requiring a substantial therapeutic response. Ziconotide, a synthetic peptide initially isolated from Conus magus in 1982 and approved by the US Food and Drug Administration and the European Medicines Agency in 2004, is the first-line intrathecal method for individuals experiencing severe chronic pain refractory to other therapeutic measures. Ziconotide produces powerful analgesia by blocking N-type calcium channels in the spinal cord, which inhibits the release of pain-relevant neurotransmitters from the central terminals of primary afferent neurons. However, despite possessing many favorable qualities, including the absence of tolerance development, respiratory depression, and withdrawal symptoms (largely due to the absence of a G-protein mediation mechanism), ziconotide's application is limited due to factors such as intrathecal administration and a narrow therapeutic window resulting from significant dose-related undesired effects of the central nervous system. This review aims to provide a comprehensive and clinically relevant summary of the literatures concerning the pharmacokinetics and metabolism of intrathecal ziconotide. It will also describe strategies intended to enhance clinical efficacy while reducing the incidence of side effects. Additionally, the review will explore the current efforts to refine the structure of ziconotide for better clinical outcomes. Lastly, it will prospect potential developments in the new class of selective N-type voltage-sensitive calcium-channel blockers.

Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.

PURPOSE: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials. METHODS: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT. RESULTS: We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry. DISCUSSION: There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects. CONCLUSIONS: The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Terminological discrepancies and novelties in the histological description of the female genital system: proposed amendments for clinical-translational anatomy.

Histological terminology of the female genital organs is currently a part of the internationally accepted nomenclature Terminologia Histologica (TH), the latest edition of which dates back to 2008. Many new discoveries have been documented within 16 years since then, and many discrepancies have been found. This paper aims to revise the terminology from clinical and educational perspectives comprehensively. The authors thoroughly searched the current edition of "Terminologia Histologica: International Terms for Human Cytology and Histology," focusing on missing and controversial terms in the chapter Female genital system. The authors identified six controversial and ambiguous terms and four missing important histological terms. The authors also discussed the addition of less used eponymic terms in the histological description of female genital organs like Hamperl cells, Popescu cells, Kroemer lacunae, Balbiani bodies, Call-Exner bodies, membrane of Slavianski, nabothian cysts, or anogenital sweat glands of van der Putte. We expect the second and revised edition of the TH to be published soon and hope that the Federative International Program on Anatomical Terminology will approve and incorporate all these propositions and suggestions. We also strongly recommend using the official internationally accepted Latin and English histological nomenclature-the TH, either in oral or written form, both in theoretical and clinical medicine.

Who are the "Heroes of CRISPR"? Public science communication on Wikipedia and the challenge of micro-notability.

Wikipedia's influence in shaping public perceptions of science underscores the significance of scientists being recognized on the platform, as it can impact their careers. Although Wikipedia offers guidelines for determining when a scientist qualifies for their own article, it currently lacks guidance regarding whether a scientist should be acknowledged in articles related to the innovation processes to which they have contributed. To explore how Wikipedia addresses this issue of scientific "micro-notability," we introduce a digital method called Name Edit Analysis, enabling us to quantitatively and qualitatively trace mentions of scientists within Wikipedia's articles. We study two CRISPR-related Wikipedia articles and find dynamic negotiations of micro-notability as well as a surprising tension between Wikipedia's principle of safeguarding against self-promotion and the scholarly norm of "due credit." To reconcile this tension, we propose that Wikipedians and scientists collaborate to establish specific micro-notability guidelines that acknowledge scientific contributions while preventing excessive self-promotion.

Controversies in in rheumatology and autoimmunity: Is CORA meeting a good educational tool to increase the scientific knowledge?

Rheumatology and Autoimmunity are closely related fields and are among the most exciting areas in Medicine. Many conditions once regarded as mysterious and incurable are better understood and managed nowadays. Part of the great interest in these subjects derives from the fact that many controversial issues have arisen due to the rapid progression of knowledge, which means they are debatable. Over the years, the Controversies in Rheumatology and Autoimmunity (CORA) meetings promoted critical discussions not as an end but as a tool to increase the scientific knowledge of Rheumatologists and Clinical Immunologists. Beyond pursuing knowledge, being critical means questioning our inveterate beliefs and evaluating new conjectures and hypotheses. Thus, the approach to the debates in Medicine should be done with an open mind and free from all prejudices. Freedom of thought and speech are the fundamental values of our University, as exemplified by the motto "Universa Universis Patavine Libertas" which means "Padua freedom is universal for everyone". Patavine libertas initially referred to freedom from political and religious power but also freedom in research and teaching. For these reasons, Galileo Galilei moved to Padua in 1592, where he spent the most prosperous years of his life before being accused of heresy by the catholic church. We aim for the CORA congress to be an open-minded forum where active participation and exchange of ideas are promoted without prejudice. This special Issue of Autoimmunity Reviews is devoted to some controversies debated during the 7th CORA conference held in Turin, Italy, on March 16-18, 2023. Here we will discuss controversial entities, the use of old and new drugs, and insights into the classification, assessment of disease activity, and management of rheumatic diseases.

Controversies around hip fracture treatment: clinical evidence versus trends from national registries.

PURPOSE: Several controversies in the optimal treatment of femoral neck fractures persist, together with large variations in clinical practice. METHODS: A narrative literature review covering 4 current controversies in the surgical management of femoral neck fractures (total hip arthroplasty (THA) versus hemiarthroplasty (HA), cemented versus uncemented HA, internal fixation versus arthroplasty, operative versus non-operative) was performed. Available literature was balanced against annual trends in the management of femoral neck fractures from the public domain of several national registries (Sweden, Norway, The Netherlands, Australia and New Zealand). RESULTS: For most controversies, the literature provides stronger evidence than is reflected by variations encountered in daily practice. Implementation of clinical evidence tends to lag behind and important differences exist between countries. CONCLUSIONS: Trends of clinical practice from national registries indicate that implementation of available clinical evidence needs to be improved.

Is the Current Cut Point for Glycated Haemoglobin (HbA1c) Correct for Diagnosing Diabetes Mellitus in Premenopausal Women? Evidence to Inform Discussion.

INTRODUCTION: Women are on average diagnosed with diabetes mellitus at later age than men but have higher mortality. As the diagnosis of diabetes mellitus is primarily based on HbA1c, the use of a non-specific reference range and cut point for diabetes mellitus that does not account for gender differences in diabetes could potentially lead to underdiagnosis of diabetes mellitus in women and missed opportunities for intervention. We investigated whether a contributing factor to the later diagnosis in women may be a difference in distribution of HbA1c in premenopausal women versus men of the same age by comparing HbA1c values in men and women across multiple sites in the UK. METHODS: We analysed the HbA1c levels of 146,907 individuals who underwent single testing only and had HbA1c ≤ 50 mmol/mol between 2012 and 2019 in one laboratory (cohort 1). This was replicated in six laboratories with 938,678 individuals tested between 2019 and 2021 (cohort 2). RESULTS: In cohort 1, women < 50 years old had an HbA1c distribution markedly lower than that in men by a mean of 1.6 mmol/mol (p < 0.0001), while the difference in the distribution of HbA1c for individuals aged ≥ 50 years was less pronounced (mean difference 0.9 mmol/mol, p < 0.0001). For individuals under the age of 50, HbA1c in women lagged by up to 10 years compared to men. Similar findings were found in cohort 2. We estimated an additional 17% (n = 34,953) of undiagnosed women aged < 50 years in England and Wales could be reclassified to have diabetes mellitus, which may contribute to up to 64% of the difference in mortality rates between men/women with diabetes mellitus aged 16-50 years. CONCLUSION: The HbA1c cut point for diagnosis of diabetes mellitus may need to be re-evaluated in women under the age of 50 years. Early identification of diabetes mellitus in women has the potential to improve women's health outcomes in the longer term.

Constructing the public in public perceptions research: A case study of forest genomics.

Contemporary scientific and technological endeavours face public and political pressure to adopt open, transparent and democratically accountable practices of public engagement. Prior research has identified different ways that experts 'imagine publics' - as uninformed, as disengaged, as a risk to science, and as co-producers of knowledge - but there has yet to be a systematic exploration of how these views emerge, interact and evolve. This article introduces a typology of imagined publics to analyse how publics are constructed in the field of forest genomics. We find that deficit views of publics have not been replaced by co-production. Instead, deficit and co-productive approaches to publics co-exist and overlap, informing both how publics are characterized and how public perceptions are studied. We outline an agenda for deepening and expanding research on public perceptions of novel technologies. Specifically, we call for more diverse and complex methodological approaches that account for relational dynamics over time.

Controversias Diagnósticas en la Clasificación Internacional de las Cefaleas, III Edición / Diagnostic controversies on the International Classifica tion of Headaches Disorders, III Edition

Resumen La revisión consideró los puntos de conflicto que pue dan llevar a confusión en el uso diario de la clasificación internacional de las cefaleas (ICHD-III). Se evaluaron tanto las controversias al momento de confeccionar los criterios como las superposiciones producidas tras su utilización en la práctica diaria, argumentado a través de bibliografía científica. Como puntos relevantes, la anamnesis de un paciente con cefalea debe indicar la intensidad del dolor como así también la duración del episodio doloroso y si su localización es estrictamente unilateral. Estos puntos podrán ser de ayuda en los casos de dolor moderado que no cumplan en forma absoluta los criterios para ninguna de las cefaleas primarias, dilema frecuente en la práctica diaria.

Abstract The review considered points of conflict that may lead to confusion in the daily use of the International Classification of Headache Disorders (ICHD-III). Both the controversies at the time of preparing the criteria and the overlaps produced after their use in daily practice were evaluated, argued through scientific bib liography. As relevant points, the anamnesis of a patient with headache should indicate the intensity of the pain as well as the duration of the painful episode and if its location is strictly unilateral. These points may be help ful in cases of moderate pain that do not fully meet the criteria for any of the primary headaches, a frequent dilemma in daily practice.

Dealing with dissent from the medical ranks: Public health authorities and COVID-19 communication.

During a public health crisis like the COVID-19 pandemic, the public health authorities will typically be criticized for their efforts. When such criticism comes from the ranks of medical personnel, the challenge becomes more pronounced for the authorities, as it suggests a public negotiation of who has sufficient expertise to handle the pandemic. Hence, the authorities are faced with the challenge of defending their competence and advice, while at the same time adhering to a bureaucratic/scientific ethos that imposes communicative boundaries. This explorative study analyzes the response strategies used by the Norwegian public health authorities in this regard. A main finding is that the authorities shunned aggressive language and mostly relied on a strategy pointing to well-established values such as proportionality (between the measures and the gravitas of the epidemiological situation) and relevance (the measures should meet the challenge in question).

The Sociotechnical Construction of Distrust during the Covid-19 Pandemic.

What were the impacts of the Covid-19 pandemic on trust in public health information, and what can be done to rebuild trust in public health authorities? This essay synthesizes insights from science and technology studies, information studies, and bioethics to explore sociotechnical factors that may have contributed to the breakdown of trust in public health information during the Covid-19 pandemic. The field of science and technology studies lays out the dynamic nature of facts, helping to explain rapid shifts in public health messaging during Covid-19 and reasons they produced a lack of trust in public health authorities. The information field looks at how facts are sociotechnically constructed through systems of classification, illustrating how extrascientific factors influence public health authorities. Putting these perspectives alongside bioethics principles raises additional factors to consider. The goal of this essay is to learn from past failures to point toward a brighter future where trust in public health authorities can be rebuilt, not on faith, but rather through striving for calibrated trust within which, through a virtuous circle, trust is validated.

[Diagnostic controversies on the International Classification of Headaches Disorders, III Edition]. / Controversias diagnósticas en la Clasificación Internacional de las Cefaleas, III Edición.

The review considered points of conflict that may lead to confusion in the daily use of the International Classification of Headache Disorders (ICHD-III). Both the controversies at the time of preparing the criteria and the overlaps produced after their use in daily practice were evaluated, argued through scientific bibliography. As relevant points, the anamnesis of a patient with headache should indicate the intensity of the pain as well as the duration of the painful episode and if its location is strictly unilateral. These points may be helpful in cases of moderate pain that do not fully meet the criteria for any of the primary headaches, a frequent dilemma in daily practice.

La revisión consideró los puntos de conflicto que puedan llevar a confusión en el uso diario de la clasificación internacional de las cefaleas (ICHD-III). Se evaluaron tanto las controversias al momento de confeccionar los criterios como las superposiciones producidas tras su utilización en la práctica diaria, argumentado a través de bibliografía científica. Como puntos relevantes, la anamnesis de un paciente con cefalea debe indicar la intensidad del dolor como así también la duración del episodio doloroso y si su localización es estrictamente unilateral. Estos puntos podrán ser de ayuda en los casos de dolor moderado que no cumplan en forma absoluta los criterios para ninguna de las cefaleas primarias, dilema frecuente en la práctica diaria.

Ventilatory Strategies in Traumatic Cervical Spinal Cord Injury: Controversies and Current Updates.

Ventilatory management of patients with traumatic cervical spinal cord injury (CSCI) is a complex and controversial area of critical care medicine. Despite significant advances in our understanding of the pathophysiology of CSCI and the development of novel interventions, there remains a lack of consensus about the optimal approach to ventilatory management in these patients. Some of the key controversies in CSCI ventilatory management include timing of tracheal intubation, non-invasive ventilation versus invasive ventilation, high versus low tidal volume, and early versus late tracheostomy. The objective of this review is to discuss the existing controversies and provide an insight on the current evidence.

Teaching controversial socio-scientific issues in online exhibits of science museums: Covid-19 on the scene.

The Covid-19 pandemic has sparked an unprecedented public debate over socio-scientific controversies, particularly regarding vaccination and social distancing measures. Despite the potential of such subjects for developing critical thinking and a sense of citizenship, the theme of controversies is still incipient in science museums. This documentary study investigates the way three science institutions have proposed online exhibits on Covid-19 on Google Arts & Culture platform and checks their potential for favoring teaching on controversial science topics. Google Arts & Culture platform was searched for Covid-19-related keywords and the filtering of the results was based on focus and organizing institutions. Three exhibits were detected, whose analysis was submitted to an inter-rater agreement (Cohen's kappa). The results revealed the predominance of social and economic aspects that can strongly favor more scientifically progressive views of both science literacy and a socially undistorted science. On the other hand, the superficiality of political discussions on science topics, a lack of naturalization of the controversial discussions, and an excessive use of textual content were identified, thus revealing some initiatives have not explored the interactivity, multimediality, and the way dilemmas that mark the trajectory of science museums extend to online exhibits. From this perspective, we point out paths for teaching and learning socio-scientific controversies in museums.

Melatonin: Facts, Extrapolations and Clinical Trials.

Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from investigating its natural role as a transducer of biological time for physiological systems to hypothesized roles in virtually all clinical conditions. This goes along with the appearance of extensive literature claiming the (generally) positive benefits of high doses of melatonin in animal models and various clinical situations that would not be receptor-mediated. Based on the assumption that melatonin is safe, high doses have been administered to patients, including the elderly and children, in clinical trials. In this review, we critically review the corresponding literature, including the hypotheses that melatonin acts as a scavenger molecule, in particular in mitochondria, by trying not only to contextualize these interests but also by attempting to separate the wheat from the chaff (or the wishful thinking from the facts). We conclude that most claims remain hypotheses and that the experimental evidence used to promote them is limited and sometimes flawed. Our review will hopefully encourage clinical researchers to reflect on what melatonin can and cannot do and help move the field forward on a solid basis.

Controversies in the dental implant treatment planning for anterior maxillary aesthetic zone - A review.

The anterior maxillary region being an aesthetic zone remains critical in decision-making when it comes to replacing a tooth. Treatment planning to place dental implants in aesthetic zone like anterior maxilla needs paramount attention in order to provide best of the treatment outcomes from aesthetic point of view. As the field of dental implants tend to evolve continuously, newer concepts with inadequate research come into practise on regular basis. In this article, some of the controversies regarding dental implant placement and treatment process related to anterior maxillary aesthetic zone are discussed with literature to support evidence.