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Intracerebral inoculation of twelve monkeys with large doses of a virulent strain of Japanese encephalitis virus produced a subclinical encephalomyelitis. When an immunosuppressive dosage schedule of cyclophosphamide was given to a group of four monkeys concurrently with virus, all animals developed prostrating paralysis 12-14 days after infection. Virus was isolated more regularly from the blood and throat swabs of animals treated with cyclophosphamide than from controls. Monkeys inoculated with virus only developed serum antibody, but no antibody was detected in suppressed animals. At time of killing, all spinal cords from suppressed monkeys yielded virus and presented a histological picture resembling that of fatal poliomyelitis, but with a markedly reduced inflammatory response. Virus was isolated from only one of three cords from animals inoculated with virus alone, and histological examination indicated less severe neuronal destruction. [ABSTRACT FROM AUTHOR]

Introduction: Early detection may lead to reduced morbidity and mortality from melanoma. This study aims to establish guidelines for selecting patients suitable for digital monitoring of skin lesions., Methods: A literature review was conducted, followed by consensus among experts appointed by the Israeli Dermatology Association., Results: Two effective methods for early melanoma diagnosis were identified: Total-body photography (TBP) and digital dermoscopy. TBP involves capturing clinical images of the entire skin area for long-term monitoring (6-12 months). Digital dermoscopy focuses on close-up images of distinct lesions for short-term monitoring (3-4 months). Various risk factors for melanoma were identified, including genetic and familial factors, as well as demographic and phenotypic characteristics. Based on these risk factors and feasibility of clinical follow-up, a comprehensive list of indications for TBP was developed, categorized into three groups based on the expected level of benefit. Digital dermoscopy surveillance is recommended for patients with flat or slightly raised skin lesions showing dermoscopic features that do not definitively indicate melanoma., Discussion: TBP significantly improves early melanoma detection, enhancing sensitivity and specificity while reducing unnecessary biopsies. However, due to its high cost and limited coverage by the Israeli public health care system, prioritizing patients who would benefit most from TBP is crucial. The compiled list of indications aligns with international recommendations and provides further details within the article.

In this brief Commentary, Neal Nathanson recounts his memories of the metamorphosis of the American Journal of Hygiene into the American Journal of Epidemiology, and his subsequent service as the Editor-in-Chief from 1964 to 1979., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 7 to 10 9 50% tissue culture infective doses (TCID 50 ) consistently infected all the animals, and many monkeys receiving 10 8 or 10 9 TCID 50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with single high doses ranging from 10 7 to 10 9 TCID 50 Mahoney type 1 virus were infected, and many of the monkeys developed paralysis. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia; tonsil, mesentery lymph nodes, and intestinal mucosa served as major target sites of viral replication. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), thereby supplementing historical reconstructions of poliovirus pathogenesis. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis, candidate antiviral drugs, and the efficacy of new vaccines., (Copyright © 2017 American Society for Microbiology.)

Background: Effective leadership is a cornerstone of successful healthcare delivery in resource limited settings throughout the world. However, few programs in Africa prepare healthcare professionals with the leadership skills vital to the success of the healthcare systems in which they work. One such program, the Afya Bora Consortium Fellowship in Global Health Leadership, has been training health professionals since 2011. The purpose of this study was to assess what career changes, if any, the Afya Bora Fellowship's alumni have experienced since completing the fellowship, and to describe those changes., Methods: The Afya Bora Fellowship is a multidisciplinary, one-year training program that teaches health professionals leadership skills through didactic and experiential learning in four African countries. Between January 2011 and June 2013 the consortium trained 42 nurses and doctors. In November 2013, an electronic survey was sent to all alumni to assess their performance in the workplace post-fellowship., Results: Thirty-one (74 %) of 42 alumni completed surveys. Twenty-one (68 %) reported changes to their position at work; of those, sixteen (76 %) believed the change was due to participation in the fellowship. All alumni reported improved performance at work, and cited the application of a wide range of fellowship skills, including leadership, research, communication, and mentoring. Twenty-six (84 %) alumni spearheaded improvements in their workplaces and almost all (97 %) remained in contact with colleagues from the fellowship. Among the respondents there were five publications, nine manuscripts in preparation, and three international conference presentations., Conclusions: Afya Bora alumni overwhelmingly reported that the one year fellowship positively influenced both their work and career trajectory. Training health professionals in leadership skills through didactic modules with the opportunity to apply learned skills at attachment sites in the Afya Bora Fellowship has an impact on performance in the workplace and the potential to improve long-term institutional capacity.

Training health professionals in leadership and management skills is a key component of health systems strengthening in low-resource settings. The importance of evaluating the effectiveness of these programs has received increased attention over the past several years, although such evaluations continue to pose significant challenges. This article presents evaluation data from the pilot year of the Afya Bora Fellowship, an African-based training program to increase the leadership capacity of health professionals. Firstly, we describe the goals of the Afya Bora Fellowship. Then, we present an adaptation of the transtheoretical model for behavior change called the Health Leadership Development Model, as an analytical lens to identify and describe evidence of individual leadership behavior change among training participants during and shortly after the pilot year of the program. The Health Leadership Development Model includes the following: pre-contemplation (status quo), contemplation (testing and internalizing leadership), preparation - (moving toward leadership), action (leadership in action), and maintenance (effecting organizational change). We used data from surveys, in-depth interviews, journal entries and course evaluations as data points to populate the Health Leadership Development Model. In the short term, fellows demonstrated increased leadership development during and shortly after the intervention and reflected the contemplation, preparation and action stages of the Health Leadership Development Model. However, expanded interventions and/or additional time may be needed to support behavior change toward the maintenance stages. We conclude that the Health Leadership Development Model is useful for informing health leadership training design and evaluation to contribute to sustainable health organizational change., (© The Author(s) 2014.)

Interest in global health (GH) among medical students worldwide is measurably increasing. There is a concomitant emphasis on emphasizing globally-relevant health professions education. Through a structured literature review, expert consensus recommendations, and contact with relevant professional organizations, we review the existing state of GH education in US medical schools for which data were available. Several recommendations from professional societies have been developed, along with a renewed emphasis on competencies in global health. The implementation of these recommendations was not observed as being uniform across medical schools, with variation noted in the presence of global health curricula. Recommendations for including GH in medical education are suggested, as well as ways to formalize GH curricula, while providing flexibility for innovation and adaptation.

The Afya Bora Consortium is a partnership of 8 academic health institutions, 4 in Africa and 4 in the United States. The Consortium is developing a Global Health Leadership Fellowship for medical, nursing, and public health professionals, largely drawn from the 4 African partner countries. The fellowship provides trainees with practical skills to prepare them for future positions leading the design, implementation, and evaluation of large, high-impact programs in governmental agencies, nongovernmental organizations, and academic health institutions in their own countries. This article describes a Pilot of the proposed program., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and been reduced to near-elimination, all within the span of documented medical history. Epidemics of the disease appeared in the late 19th century in many European countries and North America, following which polio became a global disease with annual epidemics. During the period of its epidemicity, 1900-1950, the age distribution of poliomyelitis cases increased gradually. Beginning in 1955, the creation of poliovirus vaccines led to a stepwise reduction in poliomyelitis, culminating in the unpredicted elimination of wild polioviruses in the United States by 1972. Global expansion of polio immunization resulted in a reduction of paralytic disease from an estimated annual prevaccine level of at least 600,000 cases to fewer than 1,000 cases in 2000. Indigenous wild type 2 poliovirus was eradicated in 1999, but unbroken localized circulation of poliovirus types 1 and 3 continues in 4 countries in Asia and Africa. Current challenges to the final eradication of paralytic poliomyelitis include the continued transmission of wild polioviruses in endemic reservoirs, reinfection of polio-free areas, outbreaks due to circulating vaccine-derived polioviruses, and persistent excretion of vaccine-derived poliovirus by a few vaccinees with B-cell immunodeficiencies. Beyond the current efforts to eradicate the last remaining wild polioviruses, global eradication efforts must safely navigate through an unprecedented series of endgame challenges to assure the permanent cessation of all human poliovirus infections.

Poliomyelitis has long served as a model for studies of viral pathogenesis, but there remain many important gaps in our understanding of this disease. It is the intent of this review to highlight these residual but important questions, in light of a possible future moratorium on research with polioviruses. Salient questions include: (1) What cells in the gastrointestinal tract are initially infected and act as the source of excreted virus? (2) What is the receptor used by mouse-adapted strains of poliovirus and how can some polioviruses use both mouse and primate receptors? (3) What determines species differences in susceptibility of the gastrointestinal tract to polioviruses? Why cannot PVR transgenic mice be infected by the natural enteric route? (4) Why are neuroadapted polioviruses unable to infect nonneural cells? (5) What is the role of postentry blocks in replication as determinants of neurovirulence? (6) What route(s) does poliovirus take to enter the central nervous system and how does it cross the blood-brain barrier? (7) Why does poliovirus preferentially attack lower motor neurons in contrast to many other neuronal types within the central nervous system? (8) Does cellular immunity play any role in recovery from acute infection or in vaccine-induced protection? (9) In which cells does poliovirus persist in patients with gamma-globulin deficiencies? (10) Is there any evidence that poliovirus genomes can persist in immunocompetent hosts? (11) Why has type 2 poliovirus been eradicated while types 1 and 3 have not? (12) Can transmission of vaccine-derived polioviruses be prevented with inactivated poliovirus vaccine? (13) What is the best strategy to control and eliminate vaccine-derived polioviruses?

Perforation is an exceptionally rare complication of duodenal diverticula and often presents with nonspecific symptoms and signs. We present a case of a perforated duodenal diverticulum diagnosed on computed tomography and successfully repaired with a diverticulectomy.

In this review, I use the term "perpetuation" for persistence of a virus in a population, since this is a different phenomenon from persistence of a virus in an infected host. Important variables that influence perpetuation differ in small (<1000 individuals) and large (>10,000) populations: in small populations, two important variables are persistence in individuals, and turnover of the population, while in large populations important variables are transmissibility, generation time, and seasonality. In small populations, viruses such as poliovirus that cause acute infections cannot readily be perpetuated, in contrast to viruses such as hepatitis B virus, that cause persistent infections. However, small animal populations can turnover significantly each year, permitting the perpetuation of some viruses that cause acute infections. Large populations of humans are necessary for the perpetuation of acute viruses; for instance, measles required a population of 500,000 for perpetuation in the pre-measles vaccine era. Furthermore, if an acute virus, such as poliovirus, exhibits marked seasonality in large populations, then it may disappear during the seasonal trough, even in the presence of a large number of susceptible persons. Eradication is the converse of perpetuation and can be used as a definitive approach to the control of a viral disease, as in the instance of smallpox. Therefore, the requirements for perpetuation have significant implications for practical public health goals.

Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence.

Study Objectives: A decision instrument based on 5 clinical criteria has been shown to be highly sensitive in selecting patients who require cervical spine imaging after blunt trauma, while simultaneously reducing overall imaging. We examine the performance of this instrument in the elderly and explore some of the common features of geriatric cervical spine injury (CSI)., Methods: The National Emergency X-radiography Utilization Study (NEXUS) was a prospective, observational, multicenter study conducted at 21 geographically diverse centers. We analyzed the performance of the NEXUS decision instrument among patients at least 65 years of age., Results: The study group consisted of 2,943 (8.6%) geriatric patients, representing 8.6% of the entire NEXUS sample. The rate of CSI was twice as great in these patients as it was in nongeriatric patients (4.59% versus 2.19%). Odontoid fractures were particularly common in geriatric patients, accounting for 20% of geriatric fractures compared with 5% of nongeriatric fractures. The frequency of patients meeting NEXUS criteria was similar in the 2 groups, with 14% of geriatric patients and 12.5% of nongeriatric patient classified as low risk. CSI occurred in only 2 low-risk geriatric patients, and these patients' injuries met our preset definition of a clinically insignificant injury. The sensitivity of the NEXUS decision instrument for clinically significant injury in the geriatric group was therefore 100% (95% confidence interval 97.1% to 100%)., Conclusion: The prevalence of CSI, and especially odontoid fracture, is relatively increased among geriatric patients with blunt trauma. The NEXUS decision instrument can be applied safely to these patients, with an expected reduction in cervical imaging comparable with that achieved in nongeriatric patients.