VP1 is the primary determinant of neuropathogenesis in a mouse model of enterovirus D68 acute flaccid myelitis.

Enterovirus D68 (EV-D68) is an emerging pathogen that can cause severe respiratory and neurologic disease [acute flaccid myelitis (AFM)]. Intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with US/IL/14-18952 (IL52), a clinical isolate from the 2014 EV-D68 epidemic, results in many of the pathogenic features of human AFM, including viral infection of the spinal cord, death of motor neurons, and resultant progressive paralysis. In distinction, CA/14-4231 (CA4231), another clinical isolate from the 2014 EV-D68 outbreak, does not cause paralysis in mice, does not grow in the spinal cord, and does not cause motor neuron loss following IM injection. A panel of chimeric viruses containing sequences from IL52 and CA4231 was used to demonstrate that VP1 is the main determinant of EV-D68 neurovirulence following IM injection of neonatal SW mice. VP1 contains four amino acid differences between IL52 and CA4231. Mutations resulting in substituting these four amino acids (CA4231 residues into the IL52 polyprotein) completely abolished neurovirulence. Conversely, mutations resulting in substituting VP1 IL52 amino acid residues into the CA4231 polyprotein created a virus that induced paralysis to the same degree as IL52. Neurovirulence following infection of neonatal SW mice with parental and chimeric viruses was associated with viral growth in the spinal cord. IMPORTANCE: Emerging viruses allow us to investigate mutations leading to increased disease severity. Enterovirus D68 (EV-D68), once the cause of rare cases of respiratory illness, recently acquired the ability to cause severe respiratory and neurologic disease. Chimeric viruses were used to demonstrate that viral structural protein VP1 determines growth in the spinal cord, motor neuron loss, and paralysis following intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with EV-D68. These results have relevance for predicting the clinical outcome of future EV-D68 epidemics as well as targeting retrograde transport as a potential strategy for treating virus-induced neurologic disease.

Telaprevir Treatment Reduces Paralysis in a Mouse Model of Enterovirus D68 Acute Flaccid Myelitis.

In 2014, 2016, and 2018, the United States experienced unprecedented spikes in pediatric cases of acute flaccid myelitis (AFM), which is a poliomyelitis-like paralytic illness. Accumulating clinical, immunological, and epidemiological evidence has identified enterovirus D68 (EV-D68) as a major causative agent of these biennial AFM outbreaks. There are currently no available FDA-approved antivirals that are effective against EV-D68, and the treatment for EV-D68-associated AFM is primarily supportive. Telaprevir is an food and drug administration (FDA)-approved protease inhibitor that irreversibly binds the EV-D68 2A protease and inhibits EV-D68 replication in vitro. Here, we utilize a murine model of EV-D68 associated AFM to show that early telaprevir treatment improves paralysis outcomes in Swiss Webster (SW) mice. Telaprevir reduces both viral titer and apoptotic activity in both muscles and spinal cords at early disease time points, which results in improved AFM outcomes in infected mice. Following intramuscular inoculation in mice, EV-D68 infection results in a stereotypic pattern of weakness that is reflected by the loss of the innervating motor neuron population, in sequential order, of the ipsilateral (injected) hindlimb, the contralateral hindlimb, and then the forelimbs. Telaprevir treatment preserved motor neuron populations and reduced weakness in limbs beyond the injected hindlimb. The effects of telaprevir were not seen when the treatment was delayed, and toxicity limited doses beyond 35 mg/kg. These studies are a proof of principle, provide the first evidence of benefit of an FDA-approved antiviral drug with which to treat AFM, and emphasize both the need to develop better tolerated therapies that remain efficacious when administered after viral infections and the development of clinical symptoms. IMPORTANCE Recent outbreaks of EV-D68 in 2014, 2016, and 2018 have resulted in over 600 cases of a paralytic illness that is known as AFM. AFM is a predominantly pediatric disease with no FDA-approved treatment, and many patients show minimal recovery from limb weakness. Telaprevir is an FDA-approved antiviral that has been shown to inhibit EV-D68 in vitro. Here, we demonstrate that a telaprevir treatment that is given concurrently with an EV-D68 infection improves AFM outcomes in mice by reducing apoptosis and viral titers at early time points. Telaprevir also protected motor neurons and improved paralysis outcomes in limbs beyond the site of viral inoculation. This study improves understanding of EV-D68 pathogenesis in the mouse model of AFM. This study serves as a proof of principle for the first FDA-approved drug that has been shown to improve AFM outcomes and have in vivo efficacy against EV-D68 as well as underlines the importance of the continued development of EV-D68 antivirals.

Neutralizing Antibody Given after Paralysis Onset Reduces the Severity of Paralysis Compared to Nonspecific Antibody-Treated Controls in a Mouse Model of EV-D68-Associated Acute Flaccid Myelitis.

Enterovirus D68 (EV-D68) can cause mild to severe respiratory illness and is associated with a poliomyelitis-like paralytic syndrome called acute flaccid myelitis (AFM). Most cases of EV-D68-associated AFM occur in young children who are brought to the clinic after the onset of neurologic symptoms. There are currently no known antiviral therapies for AFM, and it is unknown whether antiviral treatments will be effective if initiated after the onset of neurologic symptoms (when patients are likely to present for medical care). We developed a "clinical treatment model" for AFM, in which individual EV-D68-infected mice are tracked and treated with an EV-D68-specific human-mouse chimeric monoclonal antibody after the onset of moderate paralysis. Mice treated with antibody had significantly better paralysis outcomes compared to nonspecific antibody-treated controls. Treatment did not reverse paralysis that was present at the time of treatment initiation but did slow the further loss of function, including progression of weakness to other limbs, as well as reducing viral titer in the muscle and spinal cords of treated animals. We observed the greatest therapeutic effect in EV-D68 isolates which were neutralized by low concentrations of antibody, and diminishing therapeutic effect in EV-D68 isolates which required higher doses of antibody for neutralization. This work supports the use of virus-specific immunotherapy for the treatment of AFM. It also suggests that patients who present with AFM should be treated as soon as possible if recent infection with EV-D68 is suspected.

Stereoselective Desymmetrizations of Dinitriles to Synthesize Lactones.

Nitriles are important organic functional groups, allowing for installation of nitrogen in organic synthesis. The Pinner reaction transforms nitriles into esters via the imidate group, but in general has previously necessitated harsh acid conditions. This work builds on the utility of the Pinner reaction through a stereoselective desymmetrization of dinitriles to form γ- and δ-lactones in good yields and diastereoselectivites.

Surgical Correction of Torticollis Due to Agenesis of the Sternocleidomastoid: Case Study and Review.

Unilateral agenesis of the sternocleidomastoid (SCM) muscle is a rare phenomenon known to cause torticollis. There have been around 12 reported instances of SCM agenesis in the literature; in almost every case, torticollis was easily resolved nonsurgically with stretching and physical therapy. We report the case of a 6-year-old boy with severe torticollis due to unilateral SCM absence who underwent the surgical release of the contralateral SCM. To our knowledge, this is the first time a surgical release of the SCM was performed to correct torticollis associated with agenesis of the SCM.

Chiral Brønsted Acid Catalyzed Cascade Alcohol Deprotection and Enantioselective Cyclization.

The protection-deprotection sequence is vital to organic synthesis. Here, we describe a novel catalytic cascade where a chiral Brønsted acid selectively removes ether protecting groups and catalyzes intramolecular cyclization in one pot. We tested three model substrates from our previous work and investigated the rate of deprotection through gas chromatography (GC) studies. This work builds on our stereoselective synthesis of lactones by streamlining our synthesis. It also opens the door for additional investigations into other catalytic cascade reactions using chiral Brønsted acid catalysts.

The Mental Health of Elite-Level Coaches: A Systematic Scoping Review.

BACKGROUND: Elite-level coaches are exposed to multiple performance, organisational and personal stressors which may contribute to reduced mental health and wellbeing. This systematic scoping review examined the current body of evidence to explore what is known about the mental health of elite-level coaches (i.e. wellbeing and mental ill-health), the risk and protective factors that influence coach mental health, and the relationship between mental health and coaching effectiveness. METHODS: The review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A systematic search was undertaken and updated in September 2022 using six electronic databases. RESULTS: 12,376 studies were identified and screened, with 42 studies satisfying the inclusion criteria. Despite the paucity of high-quality research, findings indicated that 40% of the included studies examined themes connected to wellbeing, with 76% assessing the nature or prevalence of mental ill-health in elite-level coaches. Among studies exploring mental ill-health, coach burnout was the primary focus, while scant research examined symptoms associated with clinical disorders (e.g. anxiety and depression). Overall, psychological outcomes for elite-level coaches were shaped by risk and protective factors operating at the individual, interpersonal, organisational and societal level. Preliminary evidence was also found to suggest that poor mental health may contribute to reduced coaching effectiveness. It is proposed that coaching effectiveness could therefore be employed as a 'hook' to engage elite-level coaches in greater consideration of their mental health needs. CONCLUSION: Alongside the development of methodologically robust research, there is a need to examine dynamic individual (e.g. psychological skills), interpersonal (e.g. strong social supports) and organisational (e.g. workload) factors that aim to preserve the mental health and optimise the efficacy of elite-level coaches.

Mental Health Among Elite Youth Athletes: A Narrative Overview to Advance Research and Practice.

CONTEXT: Participation in sports during youth is typically beneficial for mental health. However, it is unclear whether elite sport contexts contribute to greater risk of psychological distress or disorder. The aims of this paper are to highlight conceptual issues that require resolution in future research and practice, and to examine the key factors that may contribute to the mental health of elite youth athletes (EYAs). EVIDENCE ACQUISITION: A narrative overview of the literature combined with the clinical and research expertise of the authors. STUDY DESIGN: Narrative overview. LEVEL OF EVIDENCE: Level 5. RESULTS: EYAs experience a range of biopsychosocial developmental changes that interact with mental health in a multitude of ways. In addition, there are various sport-specific factors that contribute to the mental health of EYAs that may become more prominent in elite contexts. These include - but are not limited to - patterns relating to athlete coping and self-relating styles, the nature of peer, parental, and coach relationships, organizational culture and performance pressures, and mental health service provision and accessibility. CONCLUSION: A range of critical factors across individual, interpersonal, organizational, and societal domains have been shown to contribute to mental health among EYAs. However, this evidence is limited by heterogeneous samples and varied or imprecise terminology regarding what constitutes "youth" and "elite" in sport. Nevertheless, it is clear that EYAs face a range of risks that warrant careful consideration to progress to best practice principles and recommendations for mental health promotion and intervention in elite youth sport. SORT: Level C.

Exploring Why Cancer Patients Engage Into Medical Education.

Background and Objectives Patients are recruited to act as educators, sharing experiences of their illness to facilitate active student learning. At our institution, cancer patient educators have been recruited to participate in a weekly teaching session for students. Our study was designed to assess the benefits that partaking in medical education confers on patients who were treated for cancer, as well as explore their motivations for becoming educators and how we can improve their experiences in the future. Methodology Our study used a qualitative exploratory research design, with four current patient educators being selected to participate. The interviews were conducted virtually and were designed to allow patients the opportunity to provide a rich narrative of their experiences. Their accounts were transcribed using built-in transcription software and analysed using interpretative phenomenological analysis (IPA). IPA is an in-depth analytical method used to identify common themes between patients' experiences and explore why these themes exist. Results Four superordinate themes, each with its subthemes were identified following analysis of patient transcripts: the perceived success of the session (relationship between patient educator and facilitator, willingness of students to participate, organisation and planning of the session), motivations for becoming a patient educator (wanting to give something back, personal attributes making them suitable for the role and improving experiences of future patients), perceived benefits of engaging in medical education (improvement in mental health and engaging with medical students) and suggested improvements for the session (logistics and recruitment).  Conclusions Being a cancer patient educator offers significant benefits for patients' well-being, particularly in mental health. Cancer patient educators are motivated by the need to give something back to the staff and institution where they were treated. The educators also referred to improving care for future patients by educating students about negative experiences they encountered and how these could have been avoided. Finally, educators suggested improvements for future sessions by addressing the length of the sessions and having a formal recruitment process.

Supporting The Mental Health Of Elite-Level Coaches Through Early Intervention.

Current evidence indicates that elite-level coaches encounter a range of performance, organizational, and personal stressors that may influence or compromise mental health. With exposure to these stressors, supports need to be established to protect and preserve the mental health of elite-level coaches. Given the paucity of evidence available, this article proposes a number of considerations that should be taken into account when developing a mental health and rehabilitation framework for high-performance coaches. We argue that early intervention should be positioned at the core of this framework, to address the onset of symptoms prior to the emergence of a mental disorder or mental health crisis. Mental health screening and monitoring of coaches, the psychological safety of high-performance environments, the mental health literacy of coaches, and the tailored pathways to support are discussed. Beyond these strategies, it is proposed that rehabilitation and reintegration should be addressed to assist coaches who are currently experiencing mental ill health or have left their role due to mental health reasons. Although further research is needed to implement evidence-based strategies, it is recommended that a future mental health framework should incorporate the perspectives of coaches to ensure it is consistent with their needs and experiences.

Efficacy of an isoxazole-3-carboxamide analog of pleconaril in mouse models of Enterovirus-D68 and Coxsackie B5.

Enteroviruses (EV) cause a number of life-threatening infectious diseases. EV-D68 is known to cause respiratory illness in children that can lead to acute flaccid myelitis. Coxsackievirus B5 (CVB5) is commonly associated with hand-foot-mouth disease. There is no antiviral treatment available for either. We have developed an isoxazole-3-carboxamide analog of pleconaril (11526092) which displayed potent inhibition of EV-D68 (IC50 58 nM) as well as other enteroviruses including the pleconaril-resistant Coxsackievirus B3-Woodruff (IC50 6-20 nM) and CVB5 (EC50 1 nM). Cryo-electron microscopy structures of EV-D68 in complex with 11526092 and pleconaril demonstrate destabilization of the EV-D68 MO strain VP1 loop, and a strain-dependent effect. A mouse respiratory model of EV-D68 infection, showed 3-log decreased viremia, favorable cytokine response, as well as statistically significant 1-log reduction in lung titer reduction at day 5 after treatment with 11526092. An acute flaccid myelitis neurological infection model did not show efficacy. 11526092 was tested in a mouse model of CVB5 infection and showed a 4-log TCID50 reduction in the pancreas. In summary, 11526092 represents a potent in vitro inhibitor of EV with in vivo efficacy in EV-D68 and CVB5 animal models suggesting it is worthy of further evaluation as a potential broad-spectrum antiviral therapeutic against EV.

Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment.

BACKGROUND: In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. METHODS: We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2-4 years, n=207), school-age children (5-7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. RESULTS: Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. CONCLUSIONS: Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.

Ambulatory Same-Day Map-and-Treat Angiography for Selective Internal Radiation Therapy Using a Transradial Approach.

Historically, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) requires a two-week interval between workup and treatment (map and treat). The intervening gap between workup and treatment is used to plan for the dose required and obtain delivery of the radioactive Y-90. During the coronavirus disease 2019 pandemic, the delivery of a robust SIRT service was challenging due to unprecedented demands on all hospital services. Emergent practice changes were required to ensure this service could still be delivered to patients while retaining sufficient inpatient hospital beds and services for acutely unwell patients. In response to this, the interventional radiology team proposed the retention of a full SIRT service by removing the historical two-week interval between map and treat, delivering both components of the SIRT procedure on the same day. A traditional approach using femoral access would require a prolonged period of immobility and potentially an overnight stay. By adopting a transradial approach without sedo-analgesia, an ambulatory day-case map and treat SIRT with no post-procedure immobilisation was performed. This case report demonstrates the technical feasibility of same-day 'map-and-treat' SIRT, highlighting a paradigm shift from the conventional femoral access method and immobilisation to an 'ambulatory' approach with immediate mobilisation post-procedure.

The Ideal Donor Site Dressing: A Comparison of a Chitosan-Based Gelling Dressing to Traditional Dressings.

Donor site wound management is critical in split-thickness skin graft surgeries. These sites typically recover in 7 to 14 days due to the dermal-imbedded keratinocytes that promote skin regeneration. An ideal donor site dressing can help to mitigate pain, reduce infection risk, promote hemostasis, and accelerate healing times. Additionally, this dressing would be easy to apply in the operating room, easily managed, and cost-effective. Chitosan-based gelling dressings (CBGD) possess many of these qualities that make an ideal donor site dressing. We conducted a retrospective chart review of patients who received CBGD as part of their postoperative wound care plan. We collected data on infections, hemostasis, dressing failure, and hospital course over a 14-month period where CBGD was used as the donor site dressing. One hundred and fourteen patients were evaluated. We found an infection rate of 7%, a bleed-through rate of 1.8%, and a re-application rate of 9.6%. The average CBGD cost per patient was $75.15. CBGD has acceptable infection rates, and pain scores as traditional donor site dressings. However, it possesses several qualities of a suitable donor site dressing notably swift healing rates, impressive hemostatic property, and low cost. Our study supports the idea that CBGD is a suitable donor site dressing for split-thickness skin graft surgeries.

Exposure to air pollution in critical prenatal time windows and IgE levels in newborns.

The objective of this study was to analyze the mechanisms by which exposure to ambient air pollutants influences respiratory health may include altered prenatal immune development. To analyze associations between elevated cord serum Immunoglobulin E (IgE) levels and maternal air pollution exposure during each month of gestation. Total cord serum IgE was determined by the CAP system and mothers' total IgE levels by nephelometry for 459 births in the Czech Republic from May 1994 to mid-January 1997. Concentrations of polycyclic aromatic hydrocarbons (PAHs) and particulate matter <2.5 microns in diameter (PM(2.5) ) were measured in ambient air, and arithmetic means were calculated for each gestational month. Log binomial regression models were used to estimate prevalence ratios (PR) for elevated cord serum IgE (≥0.9 IU/ml) adjusting for district of residence, year of birth, and in further models, for maternal IgE (a surrogate for atopy) and gestational season. Heterogeneity by maternal atopy status was evaluated for associations of air pollution and of cigarette smoke. In adjusted models, PAH and PM(2.5) exposures in the second month of gestation were each associated with a lower prevalence of elevated cord serum IgE. For an average increase of 100 ng/m(3) of PAHs, the PR was 0.69 (95% confidence interval (CI): 0.50, 0.95); for 25 µg/m(3) increase in PM(2.5) , the PR was 0.77 (95% CI: 0.55, 1.07). Conversely, exposures later in gestation were associated with a higher prevalence of elevated cord IgE: in the fifth month, the PR for PAH exposure was 1.64 (95% CI: 1.29, 2.08), while for PM(2.5) in the sixth month, it was 1.66 (95% CI: 1.30, 2.13). In analyses stratified by maternal atopy, air pollutants were associated with altered cord serum IgE only among neonates with non-atopic mothers. Similarly, an association of cigarette smoke with elevated cord serum IgE was found only in non-atopic mothers. PAHs and PM(2.5) , constituents of both ambient air pollution and cigarette smoke, appear to influence fetal immune development, particularly among infants whose mothers are not atopic.

Anatomical Changes of the Peripheral Zone Depending on Benign Prostatic Hyperplasia Size and Their Potential Clinical Implications:A Review for Clinicians.

INTRODUCTION: The inverse relationship between benign prostate hypertrophy and incidence/severity of prostate cancer is well documented in the clinical literature. However, this phenomenon is not well understood. The purpose of this review is to offer an update in the evolving hypothesis of how benign prostate hypertrophy may be protective in prostate cancer. METHODS: A literature search was conducted on PubMed limited to articles published within the past 10 years with the search criteria of "interaction" AND "benign prostate hypertrophy" AND "prostate cancer" as well as the key words of this paper. RESULTS: Nine articles from the literature search met inclusion criteria. The articles analyze the prostate on parameters of peripheral zone volume, glandular tissue density and prostate capsule thickness. All 9 articles described peripheral zone atrophy and transition zone hypertrophy in benign prostate hypertrophy patients. CONCLUSIONS: As the transition zone grows in benign prostate hypertrophy, volume and glandular density of the peripheral zone as well as the prostate capsule undergo significant changes. The disease processes outlined in this review support the hypothesis that the growing transition zone compresses the peripheral zone against the prostatic capsule causing secondary atrophy, apoptosis, and necrosis of the peripheral zone's glandular tissue. If this hypertrophy-induced disease process of glandular tissue atrophy within the peripheral zone is confirmed in future studies, it will have relevant clinical implications on the diagnosis and treatment of benign prostate hypertrophy and prostate cancer.

Radial Artery Access for Hepatic Chemosaturation: The First Description of Technical Feasibility.

Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System, Delcath Systems Inc, Wilmington, Delaware) is an interventional radiology procedure that delivers high doses of melphalan, a chemotherapeutic agent, directly to the liver in patients with unresectable primary and secondary liver tumours. Traditionally, CS-PHP is delivered by arterial access via the femoral artery. However, there can be many risks and adverse effects associated with femoral artery punctures, such as retroperitoneal haemorrhage and haematoma formation. The monitoring and bed rest required following the removal of a femoral arterial catheter may also cause significant distress to patients as they remain immobile, potentially prolonging their stay in hospital. The radial artery is an alternative access point, with fewer reported adverse events and increased patient tolerance when compared with femoral access. This case report details the first reported use of Hepatic CHEMOSAT® therapy being delivered via the radial artery. Two patients received hepatic chemosaturation with no reported complications. This report demonstrates that access via the radial artery is a feasible alternative for the delivery of chemotherapy, which may reduce morbidity and the risks usually associated with femoral access.

Possible clinical implications of peripheral zone changes depending on prostate size.

PURPOSE: Although numerous studies have observed an inverse relationship between the size of benign prostate hypertrophy (BPH) and the incidence of prostate cancer (PCa), few studies have explored specific mechanisms by which BPH and PCa may influence one another. In a recent study, one possibility has been brought up that growth in the transition zone due to BPH may cause pressure-induced fibrotic changes in the peripheral zone, an area where 80% of cancer occurs, leading to gland atrophy and the thickening of the prostatic capsule. To shed more light on this phenomenon, we conducted a pilot study examining the quantitative and qualitative histo-anatomical changes that occur in the peripheral zone associated with BPH. METHODS: Thirty-nine prostate specimens of various sizes were selected from patients who had undergone radical prostatectomies. Each prostate was evaluated in six different locations along the dorsal aspect of the peripheral zone by measuring the thickness of the peripheral fibrotic zone (prostate capsule) and its association with gland atrophy. Multiple regression analysis was performed to determine the relationship between prostate size and the average thickness of the prostate capsule. RESULTS: Multiple regression analysis revealed a strong, positive relationship between prostate size and average capsule thickness with a Pearson coefficient of 0.707 (p < 0.05). Fibrotic histo-anatomical changes were spatially associated with gland atrophy: glands found within the peripheral fibrotic zone appeared elongated and atrophic. CONCLUSION: The results suggest that BPH may be associated with the development of fibrotic material and atrophy of glands within the peripheral zone. Because this atrophy involves glands where 80% of prostate cancer originates, this potentially explains the inverse relationship between PCa and BPH.

Understanding Enterovirus D68-Induced Neurologic Disease: A Basic Science Review.

In 2014, the United States (US) experienced an unprecedented epidemic of enterovirus D68 (EV-D68)-induced respiratory disease that was temporally associated with the emergence of acute flaccid myelitis (AFM), a paralytic disease occurring predominantly in children, that has a striking resemblance to poliomyelitis. Although a definitive causal link between EV-D68 infection and AFM has not been unequivocally established, rapidly accumulating clinical, immunological, and epidemiological evidence points to EV-D68 as the major causative agent of recent seasonal childhood AFM outbreaks in the US. This review summarizes evidence, gained from in vivo and in vitro models of EV-D68-induced disease, which demonstrates that contemporary EV-D68 strains isolated during and since the 2014 outbreak differ from historical EV-D68 in several factors influencing neurovirulence, including their genomic sequence, their receptor utilization, their ability to infect neurons, and their neuropathogenicity in mice. These findings provide biological plausibility that EV-D68 is a causal agent of AFM and provide important experimental models for studies of pathogenesis and treatment that are likely to be difficult or impossible in humans.