An Unusual Case of Serologically Confirmed Post-Partum Lyme Disease Following an Asymptomatic Borrelia burgdorferi Infection Acquired during Pregnancy and Lacking Vertical Transmission in Utero.

In this report, we describe a 23-year-old female who, while pregnant, was exposed to Borrelia burgdorferi but did not develop significant signs or symptoms (joint pain, arthritis) of Lyme disease until shortly after delivering a healthy child at term. Serologic testing confirmed infection with B. burgdorferi. A 3-week course of treatment with doxycycline was completely curative. There was no evidence for congenital or perinatal transmission of this pathogen at any point pre-term or postnatally. The key reasons that could account for this unique clinical scenario are discussed in the context of previously published related reports.

Implementing PathElective as an organized means of supplementing pathology education in an osteopathic medical school-the New York Institute of Technology College of Osteopathic Medicine experience.

Pathology is not traditionally chosen by medical students applying to residency. In osteopathic medical schools, limited access to dedicated pathology faculty further complicates this issue. Because of a lack of pathology experiences, osteopathic medical students may not be as familiar with a pathology career. The purpose of this brief report is to describe the pilot experience of implementing a pre-existing web-based, free virtual platform for pathology education as alternative, supplemental exposure to pathology for osteopathic medical students at our institution. We began to offer the online pathology elective for Academic Year 2022-2023. Using the online free service of PathElective, this course provided a valuable exposure to pathology with multiple modules in anatomic, clinical, and digital/molecular pathology, before and after assessments, recorded videos by pathology experts, handouts, and reading assignments. During the first week, three introductory modules were required followed by weeks 2-4, in which the students would complete a total of 10 modules of their own choice. In total, 14 students participated in this virtual rotation from August 2022-May 2023. All chose cardiac pathology as the most popular module. Three of the 14 students matched into pathology residencies. This small cohort of 4th year medical students at our osteopathic medical school successfully completed a virtual elective rotation with the resources of PathElective. We report the success of this experience and hope to continue monitoring progress.

A case of malignant transformation of a serous borderline ovarian tumor effectively treated with BRAF/MEK inhibitor combination.

We describe a patient diagnosed with a metastatic adenocarcinoma of Müllerian origin, harboring a BRAF V600E mutation, ten years after being treated for a serous borderline tumor (SBOT). While BRAF mutations in the setting of SBOTs are common, they have been typically associated with a low chance of transformation or recurrence. The therapeutic approach, which combined hormone inhibition with receptor tyrosine kinase inhibitors (dabrafenib and trametinib), has demonstrated notable and enduring efficacy. This is clinically evidenced through serial PET-CT scans with sustained responses and extended progression-free survival, and serologically confirmed by monitoring CA-125 levels. This case demonstrates the critical role of early next-generation sequencing in detecting actionable molecular changes in rare cancers and possible metastases. It provides valuable insights into treating uncommon Müllerian adenocarcinomas and underscores the importance of targeted therapies in achieving long-lasting treatment outcomes.

Lessons learned from the successful polio vaccine experience not learned or applied with the development and implementation of the COVID-19 vaccines.

The eradication of polio during the latter half of the 20th century can be considered one of the greatest medical triumphs in history. This achievement can be attributed to the development of vaccines that received the public's almost unwavering acceptance of them, especially by parents who had been waiting/hoping for a medical breakthrough that would ensure that their children would not succumb to the devastating effects of infantile paralysis. Sixty years later, the worldwide population was now confronted with an equally devastating disease - Covid-19 - which by the 2020-2021 time period had reached pandemic levels not seen since the flu outbreak of 1918. Unlike polio, however, several vaccines against Covid-19 were rapidly developed and deployed due to advances in microbiologic and immunologic technology. But also, unlike the polio vaccine experience, there was not universal acceptance of the Covid-19 vaccines and this has led to continuation of the pandemic into 2023 (albeit at a reduced level). In addition, acceptance of the Covid-19 vaccines has been confronted with the uncertainty that they do not apparently prevent transmission in asymptomatic people, and the mutation rate of the virus requires periodic re-evaluation and possible upgrading of the vaccines. This review will focus on the various factors that have led to these contrasting attitudes toward these two different vaccines and how resistance and hesitancy to vaccine use can be overcome by implementing various measures, after introducing the key roles that the sciences of microbiology and immunology have played in vaccine development over the past 250+ years.

The major epidemiologic, microbiologic, immunologic, and clinical aspects of Lyme disease that form the basis for a newly developed vaccine that may become available soon for human use.

Working together, two major pharmaceutical companies have developed a Lyme disease vaccine consisting of recombinant-derived outer surface protein A (OspA) of the etiologic agent Borrelia burgdorferi. Multiple clinical trials have shown the vaccine to have good safety and efficacy results, and it is hoped that it would become available for human use at least by the year 2025 after receiving approval from the U.S. Food and Drug Administration. There are still challenges left to ensure that the vaccine has, at most, minimal side effects. Also, because the previously developed Lyme disease vaccine was discontinued in 2002 after four years of distribution, due in part, for frivolous reasons having little or no scientific basis, that even led to legal entanglements involving the vaccine manufacturer and some of the medical personnel overseeing the clinical trials, there will be concerns that this newly developed one could be subject again to some of the same unnecessary scrutiny rendering its implementation suboptimal. Initially this review will focus on the key epidemiological, microbiologic, immunologic and clinical aspects of Lyme disease that provide the foundation for developing this type of vaccine that could have a serious impact on the prevalence of this and even certain other tick-transmitted infections.

Paradoxical reduction of plasma lipids and atherosclerosis in mice with adenine-induced chronic kidney disease and hypercholesterolemia.

Background: Atherosclerotic cardiovascular disease is prevalent among patients with chronic kidney disease (CKD). In this study, we initially aimed to test whether vascular calcification associated with CKD can worsen atherosclerosis. However, a paradoxical finding emerged from attempting to test this hypothesis in a mouse model of adenine-induced CKD. Methods: We combined adenine-induced CKD and diet-induced atherosclerosis in mice with a mutation in the low-density lipoprotein receptor gene. In the first study, mice were co-treated with 0.2% adenine in a western diet for 8 weeks to induce CKD and atherosclerosis simultaneously. In the second study, mice were pre-treated with adenine in a regular diet for 8 weeks, followed by a western diet for another 8 weeks. Results: Co-treatment with adenine and a western diet resulted in a reduction of plasma triglycerides and cholesterol, liver lipid contents, and atherosclerosis in co-treated mice when compared with the western-only group, despite a fully penetrant CKD phenotype developed in response to adenine. In the two-step model, renal tubulointerstitial damage and polyuria persisted after the discontinuation of adenine in the adenine-pre-treated mice. The mice, however, had similar plasma triglycerides, cholesterol, liver lipid contents, and aortic root atherosclerosis after being fed a western diet, irrespective of adenine pre-treatment. Unexpectedly, adenine pre-treated mice consumed twice the calories from the diet as those not pre-treated without showing an increase in body weight. Conclusion: The adenine-induced CKD model does not recapitulate accelerated atherosclerosis, limiting its use in pre-clinical studies. The results indicate that excessive adenine intake impacts lipid metabolism.

COVID-19 vaccines for high risk and immunocompromised patients.

The availability of multiple versions of vaccines designed to help prevent COVID-19 has offered an opportunity to at least control the current pandemic, and possibly to quickly eradicate this disease fully, along with the implementation of other preventive measures. In order to accomplish this feat more effectively, as many people as possible need to be vaccinated, especially for high-risk groups having co-morbid conditions such as diabetes, obesity and old age, and possibly those with various forms of immunodeficiencies, such as HIV/AIDS. This chapter focuses primarily on some of the basic biomedical aspects on vaccine design and use, and any possible concerns that need to be considered in getting people in the high-risk category vaccinated and monitored thereafter for their continuous health and well-being.

COVID-19 Vaccines for HIV-Infected Patients.

Nearly 40 years have passed since the initial cases of infection with the human mmunodeficiency virus (HIV) were identified as a new disease entity and the cause of acquired immunodeficiency disease (AIDS). This virus, unlike any other, is capable of causing severe suppression of our adaptive immune defense mechanisms by directly infecting and destroying helper T cells leading to increased susceptibility to a wide variety of microbial pathogens, especially those considered to be intracellular or opportunistic. After T cells are infected, HIV reproduces itself via a somewhat unique mechanism involving various metabolic steps, which includes the use of a reverse transcriptase enzyme that enables the viral RNA to produce copies of its complementary DNA. Subsequent physiologic steps lead to the production of new virus progeny and the eventual death of the invaded T cell. Fortunately, both serologic and molecular tests (such as PCR) can be used to confirm the diagnosis of an HIV infection. In the wake of the current COVID-19 pandemic, it appears that people living with HIV/AIDS are equally or slightly more susceptible to the etiologic agent, SARS-CoV-2, than the general population having intact immune systems, but they may have more serious outcomes. Limited clinical trials have also shown that the currently available COVID-19 vaccines are both safe and effective in affording protection to HIV/AIDS patients. In this review, we further explore the unique dynamic of HIV/AIDS in the context of the worldwide COVID-19 pandemic and the implementation of vaccines as a protective measure against COVID-19, as well as what immune parameters and safeguards should be monitored in this immunocompromised group following vaccination.

The evolution of rapid antigen detection systems and their application for COVID-19 and other serious respiratory infectious diseases.

Making the correct diagnosis of a patient seeking medical attention is the ultimate goal of a practicing physician, irrespective of whether the cause of the patient's condition is infectious or non-infectious. Antigen detection tests can be used to aid in the diagnosis of various infectious-related disorders including COVID-19 where it has become especially important due to the serious nature of this disease and its worldwide prevalence. These tests closely mimic one of the earliest prototypes - the urine pregnancy test - and as a result they have gained wide acceptance based on their overall simplicity, low cost and relative accuracy. In some situations, especially as a screening test, they can be used instead of the more technically demanding and complex molecular and serologic assays that are still useful and helpful under many different circumstances. Antigen detection systems are based on finding a particular immunogenic component, typically a protein or polysaccharide molecule, that is both unique and an integral part of the pathogen or other biological entity. Because these tests generally provide only qualitative results, they often need to be supplemented with other and sometimes more sophisticated laboratory-based diagnostic procedures to corroborate the initial test result. In this review, we first describe general background information on antigen-detection methods, including any unique aspects of their overall design, and then follow with an extensive description on the merits and limitations of these tests for detecting COVID-19 and, to a lesser extent, for other serious respiratory diseases caused by three common bacterial pathogens - Streptococcus pyogenes, Streptococcus pneumoniae and Legionella pneumophila.

ALT Positivity in Human Cancers: Prevalence and Clinical Insights.

Many exciting advances in cancer-related telomere biology have been made in the past decade. Of these recent advances, great progress has also been made with respect to the Alternative Lengthening of Telomeres (ALT) pathway. Along with a better understanding of the molecular mechanism of this unique telomere maintenance pathway, many studies have also evaluated ALT activity in various cancer subtypes. We first briefly review and assess a variety of commonly used ALT biomarkers. Then, we provide both an update on ALT-positive (ALT+) tumor prevalence as well as a systematic clinical assessment of the presently studied ALT+ malignancies. Additionally, we discuss the pathogenetic alterations in ALT+ cancers, for example, the mutation status of ATRX and DAXX, and their correlations with the activation of the ALT pathway. Finally, we highlight important ALT+ clinical associations within each cancer subtype and subdivisions within, as well as their prognoses. We hope this alternative perspective will allow scientists, clinicians, and drug developers to have greater insight into the ALT cancers so that together, we may develop more efficacious treatments and improved management strategies to meet the urgent needs of cancer patients.

Clinical implications of nicotine as an antimicrobial agent and immune modulator.

Nicotine is perhaps the most important and potent, pharmacologically active substance in tobacco products. This commentary examines the possible effects that nicotine has on microbial viability and also on the host's immune system as it responds to the indigenous microflora (the microbiome) due to nicotine-induced changes to the indigenous microbial environment and any associated antigenic stimulation / immunization that may occur. To our knowledge, the analysis of such profound microbiologic changes attributable to a tobacco-related product, such as nicotine, has not been fully explored in the context of its consequences on the viability of the microbiome/microbiota and on some of the host's basic physiologic processes, such as the immune response, and its possible association on the induction and persistence of certain immunologically related diseases. Future studies should be aimed at uncovering the molecular mechanisms involved in such interactions, especially in the context of manipulating them for therapeutic purposes.

Transfusion-Associated Lyme Disease - Although Unlikely, It Is Still a Concern Worth Considering.

Even though hematogenous spread of the Lyme disease spirochete, Borrelia burgdorferi, has been well documented, and there are more than 300,000 cases per year of Lyme disease in the United States, no evidence (anecdotal or published) of transfusion-associated Lyme disease has been reported. Such a possibility would seem to exist but various factors, as discussed in this perspective, make this less likely to occur. Nonetheless, if not done already, safeguards need to be put in place at blood collection and dispensing facilities, possibly with the assistance of diagnostic microbiology and immunology laboratories, to ensure that the potential for the transfer of the Lyme disease spirochete through a blood transfusion remains a theoretical consideration rather than a real possibility.

Association of Mindfulness With Residency Preference and Curriculum Selection in Preclinical Osteopathic Medical Students.

CONTEXT: Recent studies suggest the shortage of US primary care physicians will be more than 50,000 by the year 2025. Mindful osteopathic medical students may be more inclined to pursue a career in primary care practice than those demonstrating lower levels of mindfulness. If so, assessing mindfulness before and after admission to medical school may reduce this shortage. OBJECTIVE: In this cross-sectional survey-based study, the authors assessed whether mindfulness among preclinical osteopathic medical students was associated with (a) their current preference for primary care practice as a residency, and (b) their choice between 2 alternative curricula. METHOD: Participants were first- and second-year osteopathic medical students enrolled at the New York Institute of Technology College of Osteopathic Medicine (NYITCOM). They completed a 7-factor questionnaire of demographic variables and the online Five Facet Mindfulness Questionnaire (FFMQ) to determine their mindfulness score. They also identified their current preference for a residency. Data were then presented using various descriptive statistics and analyzed using independent t tests, χ2 tests, and multiple logistic regression. RESULTS: Among the 208 respondents, authors found that osteopathic medical students who expressed a preference for primary care practice showed no significant differences in mindfulness compared with those interested in specialist fields, as indicated by mean (SD) mindfulness scores of 3.34 (0.44) vs 3.33 (0.41), respectively (P=.88). However, among demographic variables, female students expressed a preference for primary care practice fields at significantly higher rates than male students (OR, 4.4; 95% CI, 2.2-8.5; P<.001). Also, students who matriculated less than 6 months after completing their undergraduate education were drawn to primary care practice at higher rates than those who delayed enrollment (OR, 2.3; 95% CI, 1.2-4.5; P=.016). None of the remaining demographic variables were associated with students' residency preference. CONCLUSION: Being female and matriculating immediately after undergraduate education was associated with a preference for primary care residency. However, no significant association was found between mindfulness and either residency preference or choice of alternative curricula.

Quadrivalvular marantic endocarditis (ME) mimicking acute bacterial endocarditis (ABE).

Marantic endocarditis (ME) is defined by noninfectious valvular vegetations. The most common disorders associated with ME are malignancy with or without hypercoagulable state, intercardiac instrumentation, residual vegetations from previously treated infective endocarditis (IE), renal insufficiency, and burns. Another important cause of ME is systemic lupus erythematosus when accompanied by vegetations, that is, Libman-Sacks endocarditis. ME should be differentiated from IE because they may present with similar clinical features. Both ME and IE may present with fever and a heart murmur with or without embolic phenomenon. Leukocytosis and elevated erythrocyte sedimentation rate suggest the diagnosis of IE. The hallmark of IE is a cardiac vegetation and continuous high-grade bacteremia. After exclusion of the causes of culture negative endocarditis, the absence of bacteremia clearly differentiates ME from IE. We present a case of ME mimicking acute bacterial endocarditis (ABE). The differential diagnostic features of ME versus IE are discussed. To the best of our knowledge, this is the first reported case of quadrivalvular ME with massive vegetations on all cardiac valves, as well as the aorta, atria, and pulmonary artery.

Was it authentic Lyme disease or some other disorder?

We compared the evidence presented recently that challenges the long-standing belief that, in 1922, two French physicians reported the first case of neurological Lyme disease with a further analysis of the original findings that were translated and re-published in 1993. Alternative possibilities are offered that could explain these discrepant interpretations on what was considered to be a landmark clinical case of historical significance.

Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia.

OBJECTIVE: Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelium leads to arterial calcification in mice. The purpose of this study was to examine the effect of elevated endothelial TNAP on coronary atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in human myocardium. APPROACH AND RESULTS: A vascular pattern of TNAP activity was observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per group); no differences were noted between groups in this study. Endothelial overexpression of TNAP was achieved in mice harboring a homozygous recessive mutation in the low density lipoprotein receptor (whc allele) utilizing a Tie2-cre recombinase (WHC-eTNAP mice). WHC-eTNAP developed significant coronary artery calcification at baseline compared WHC controls (4312 vs 0µm2 alizarin red area, p<0.001). Eight weeks after induction of atherosclerosis, lipid deposition in the coronary arteries of WHC-eTNAP was increased compared to WHC controls (121633 vs 9330µm2 oil red O area, p<0.05). Coronary lesions in WHC-eTNAP mice exhibited intimal thickening, calcifications, foam cells, and necrotic cores. This was accompanied by the reduction in body weight and left ventricular ejection fraction (19.5 vs. 23.6g, p<0.01; 35% vs. 47%, p<0.05). In a placebo-controlled experiment under atherogenic conditions, pharmacological inhibition of TNAP in WHC-eTNAP mice by a specific inhibitor SBI-425 (30mg*kg-1*d-1, for 5 weeks) reduced coronary calcium (78838 vs.144622µm2) and lipids (30754 vs. 77317µm2); improved body weight (22.4 vs.18.8g) and ejection fraction (59 vs. 47%). The effects of SBI-425 were significant in the direct comparisons with placebo but disappeared after TNAP-negative placebo-treated group was included in the models as healthy controls. CONCLUSIONS: Endogenous TNAP activity is present in human cardiac tissues. TNAP overexpression in vascular endothelium in mice leads to an unusual course of coronary atherosclerosis, in which calcification precedes lipid deposition. The prevalence and significance of this mechanism in human atherosclerosis requires further investigations.