Morphometrical analysis of myelinated nerve fibers: is there a room for improvement?

Despite advancements in automatic approaches for histomorphometry analysis of peripheral nerves, manual and semi-automated methods are widely utilized. Standard software functions are often unsuitable for analysis due to their irregular shapes, especially in pathological conditions. This study aims to assess the reproducibility of nerves morphometric analysis and compare results obtained using both default and new alternative algorithms. Sciatic nerves from Wistar rats (untreated and after administration of intraperitoneal hydrargyrum chloride), previously embedded in resin, were used. Morphometric analysis (diameters, myelin thickness, g-ratio, and circularity) was conducted using ImageJ on semithin sections, with axon and myelin boundaries manually outlined. Default diameters were calculated as the mean of Feret diameters, with subsequent calculations for myelin thickness and g-ratio. The alternative approach estimated diameters based on the geometric center of axons, iterating through selected coordinates; myelin thickness was obtained using line equations. In the control group, inter-rater agreement was higher or within expected reliability (0.8 ± 0.05). However, in the experimental group, myelin thickness, g-ratio, and axon circularity showed lower agreement (0.66, 0.58, and 0.68, respectively) without visible patterns on Bland-Altman plots. The alternative approach did not reveal significant differences between approaches, except for g-ratio in the control group and fiber diameter in the experimental group (p < 0.05), with effect sizes of 0.29-0.30 and 0.19-0.20, respectively. This study highlights reduced agreement among investigators analyzing nerve fibers under pathological conditions, raising concerns about the current standard measurement methods. The proposed approach, based on a single geometric center, provides more natural estimations for irregular fibers, and can be implemented in automated nerve fibers acquisition systems.

Increased Surveillance or Increased Scrutiny: Curbing Inappropriate Screening of Endometrial Cancer in Transgender Men.

Objective: The transgender male body is often considered a "black box" by even the most senior of attending physicians. Because of the stigma and fear associated with the utilization of Hormone Replacement Therapy (HRT) and the lack of clinical knowledge surrounding the subject, many transgender men will experience unnecessary testing for endometrial cancers. Materials and methods: This narrative review looked through publicly available PubMed and GoogleScholar articles on the topic of the use of pelvic ultrasounds in gynecological screening in transgendered males. 18,000 articles were filtered by relevance, date, clarity of the topic, and clinical recommendations. Of these articles 37 were included for discussion. Results: Of these 18,000 articles, only 37 were included for discussion. The resulting table, diagnostic tree, and discussion section are included within. Conclusion: Herein, the authors discuss the current understanding of the role of imaging in the diagnosis and treatment of gynecological cancers in transgendered men and how unnecessary imaging studies can be curbed for the benefit of the patient and the medical system at large.

Intravenous fluid therapy: a multi-national, cross-sectional survey of common medical student resources.

BACKGROUND: Inappropriate prescription of intravenous fluid therapy is highly prevalent in hospitals, with up to 1 in 5 patients suffering from preventable, additional morbidity. Since trainee physicians are frequently responsible for prescribing intravenous fluids, it is possible that common medical student resources do not sufficiently cover the topic. There is a paucity of recent literature on this issue, which this study was designed to address. METHODS: Two original evaluation tools were created by the authors to evaluate reference books, official guidelines, and online reference sources commonly used by medical students in the United States of America, Australia, and the United Kingdom on their coverage of foundational and clinically relevant principles of intravenous fluid prescription. The choice of student resources was guided by a literature search and personal experience. A total of 10 resources was assessed. RESULTS: Resources were generally deficit in their coverage of basic intravenous fluid topics. The total points each topic accumulated ranged from 0.5 (5%) to 7.5 (75%), with the median score being 4.5 (45%), on a scale from 0 to 10 points. CONCLUSIONS: Popular medical student resources poorly cover intravenous fluid therapy topics. This may be contributing to inadequate fluid prescribing practices.

Correction: Fever of Unknown Origin: The Workup and Diagnosis of Pel-Ebstein Fever.

[This corrects the article DOI: 10.7759/cureus.21959.].

Fever of Unknown Origin: The Workup and Diagnosis of Pel-Ebstein Fever.

The clinical and diagnostic workup of fever of unknown origin (FUO) is key in the treatment of patients on the internal medicine service. In this article, the authors present a case of fever of unknown origin, walk through the differential diagnosis, explain the laboratory testing ordered in the workup of the patient as well as the resulting values of said testing, and discuss the pathophysiology and diagnostic criteria for the diagnosis of Pel-Ebstein fever. The authors also discuss a clinical pearl when working with electronic health records to ensure that the needs of the patient in question are met.

Application of an evidence-based, out-patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease.

The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of our human physiology's most important and vulnerable life-preserving body tissues, our broncho-alveolar gas exchange apparatus. Notwithstanding the fear and the fury of this microbe's potential to raise existential questions across the entire spectrum of human endeavor, the application of an early treatment intervention initiative may represent a crucial tool in our defensive strategy. This strategy is driven by evidence-based medical practice principles, those not likely to become antiquated, given the molecular diversity and mutational evolution of this very clever "world traveler".

Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced 'PANIC' attack.

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health.

Part I. SARS-CoV-2 triggered 'PANIC' attack in severe COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body's tissues. In most symptomatic individuals, the disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized by a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, leading to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate for the first time as a 'Prolific Activation of a Network-Immune-Inflammatory Crisis', or 'PANIC' Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing 'PANIC'; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it.