Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation.

A highly conserved threonine near the C terminus of gp120 of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) was investigated for its contributions to envelope protein function and virion infectivity. When this highly conserved Thr residue was substituted with anything other than serine (the other amino acid that can accept O-glycosylation), the resulting virus was noninfectious. We found that this Thr was critical for the association of gp120 with the virion and that amino acid substitution increased the amount of dissociated gp120 in the cell culture supernatant. When HIV virions were generated in cells overexpressing polypeptide N-acetylgalactosaminyltransferase 1 (GalNAcT1), viral infectivity was increased 2.5-fold compared to that of virus produced in wild-type HEK293T cells; infectivity was increased 8-fold when the Thr499Ser mutant was used. These infectivity enhancements were not observed when GalNAcT3 was used. Using HEK293T knockout cell lines totally devoid of the ability to perform O-linked glycosylation, we demonstrated production of normal levels of virions and normal levels of infectivity in the complete absence of O-linked carbohydrate. Our data indicate that O-glycosylation is not necessary for the natural replication cycle of HIV and SIV. Nonetheless, it remains theoretically possible that the repertoire of GalNAc transferase isoforms in natural target cells for HIV and SIV in vivo could result in O-glycosylation of the threonine residue in question and that this could boost the infectivity of virions beyond the levels seen in the absence of such O-glycosylation.IMPORTANCE Approximately 50% of the mass of the gp120 envelope glycoprotein of both HIV and SIV is N-linked carbohydrate. One of the contributions of this N-linked carbohydrate is to shield conserved peptide sequences from recognition by humoral immunity. This N-linked glycosylation is one of the reasons that primary isolates of HIV and SIV are so heavily resistant to antibody-mediated neutralization. Much less studied is any potential contribution from O-linked glycosylation. The literature on this topic to date is somewhat confusing and ambiguous. Our studies described in this report demonstrate unambiguously that O-linked glycosylation is not necessary for the natural replication cycle of HIV and SIV. However, the door is not totally closed because of the diversity of numerous GalNAc transferase enzymes that initiate O-linked carbohydrate attachment and the theoretical possibility that natural target cells for HIV and SIV in vivo could potentially complete such O-linked carbohydrate attachment to further increase infectivity.

Interprofessional mental health training in rural primary care: findings from a mixed methods study.

The benefits of interprofessional care in providing mental health services have been widely recognized, particularly in rural communities where access to health services is limited. There continues to be a need for more continuing interprofessional education in mental health intervention in rural areas. There have been few reports of rural programs in which mental health content has been combined with training in collaborative practice. The current study used a sequential mixed-method and quasi-experimental design to evaluate the impact of an interprofessional, intersectoral education program designed to enhance collaborative mental health capacity in six rural sites. Quantitative results reveal a significant increase in positive attitudes toward interprofessional mental health care teams and self-reported increases in knowledge and understanding about collaborative mental health care delivery. The analysis of qualitative data collected following completion of the program, reinforced the value of teaching mental health content within the context of collaborative practice and revealed practice changes, including more interprofessional and intersectoral collaboration. This study suggests that imbedding explicit training in collaborative care in content focused continuing professional education for more complex and chronic health issues may increase the likelihood that professionals will work together to effectively meet client needs.

Accelerated death rate in population-based cohort of persons with traumatic brain injury.

OBJECTIVES: To determine the influence of preexisting heart, liver, kidney, cancer, stroke, and mental health problems and examine the influence of low socioeconomic status on mortality after discharge from acute care facilities for individuals with traumatic brain injury. PARTICIPANTS: Population-based retrospective cohort study of 33695 persons discharged from acute care hospital with traumatic brain injury in South Carolina, 1999-2010. MAIN MEASURES: Days elapsing from the dates of injury to death established the survival time (T). Data were censored at the 145th month. Multivariable Cox regression was used to examine the independent effect of the variables on death. Age-adjusted cumulative probability of death for each chronic disease of interest was plotted. RESULTS: By the 70th month of follow-up, rate of death was accelerated from 10-fold for heart diseases to 2.5-fold for mental health problems. Adjusted hazard ratios for diseases of the heart (2.13), liver-renal (3.25), cancer (2.64), neurological diseases and stroke (2.07), diabetes (1.89), hypertension (1.43), and mental health problems (1.59) were highly significant (each with P < .001). Compared with persons with private insurance, the hazard ratio was significantly elevated with Medicaid (1.67), Medicare (1.54), and uninsured (1.27) (each with P < .001). CONCLUSION: Specific chronic diseases strongly influenced postdischarge mortality after traumatic brain injury. Low socioeconomic status as measured by the type of insurance elevated the risk of death.

A Disfiguring Rash.

Patients with rheumatologic conditions can have complex dermatologic manifestations. In addition, immunosuppressing treatment for autoimmune disorders can also increase incidence of infectious complications. Skin conditions in rheumatologic patients present particular challenges and this case highlights a rare infectious complication.

Progressive and disseminated histoplasma infection and hemophagocytic lymphohistiocytosis in an immunocompetent adult.

Hemophagocytic lymphohistiocytosis (HLH) in adults is a life-threatening underdiagnosed disorder that complicates different infectious syndromes and overlaps with sepsis. No guidelines are available for the management of HLH in adults. A high index of suspicion is required in patients with disseminated histoplasmosis.

Integrating self-help materials into mental health practice.

PROBLEM ADDRESSED: Patients' mental health issues have become an increasing focus of Canadian family physicians' practices. A self-help approach can help meet this demand, but there are few guidelines for professionals about how to use mental health self-help resources effectively. OBJECTIVE OF PROGRAM: To aid health professionals in integrating self-help materials into their mental health practices. PROGRAM DESCRIPTION: A resource library of print, audiotape, and videotape self-help materials about common mental health issues was developed for a rural community. The materials were prescreened in order to ensure high quality, and health professionals were given training on how to integrate self-help into their practices. The library was actively used by both health professionals and community members, and most resources were borrowed, particularly the nonprint materials. Health professionals viewed the resources as a way to supplement their mental health practice and reduce demands on their time, as patients generally worked through the resources independently. Some improvements are planned for future implementations of the program, such as providing health professionals with a "prescription pad" of resources and implementing Stages of Change and stepped-care models to maximize the program's effectiveness. CONCLUSION: Although more evidence is needed regarding the effectiveness of self-help within a family practice context, this program offers a promising way for family physicians to address mild to moderate mental health problems.

Legal trends in imaging: an update.

In 2004, a similarly titled article,"Legal Trends in Imaging," was published in this Journal; it described medical malpractice cases involving imaging, the role of imaging in criminal trials and evolving legal concerns raised by newer imaging technologies. This article provides an update on the ever-expanding relationship between the law and imaging. Readers are cautioned that nothing contained in this article is intended as legal advice and should not be taken as such.

Diagnosis and treatment of back pain.

Back pain is one of the most prevalent medical problems seen by primary care physicians, and it costs the American public billions of dollars each year. Yet, accurate diagnosis and successful treatment remain elusive. Medical imaging plays an increasing role in helping to diagnose back pain causes, pinpoint treatments and study how back pain might be addressed more adequately.

Highlights from the Third Biennial Strategies for an HIV Cure Meeting: 14-16 November 2016, Bethesda, MD, USA.

Since the first Strategies for an HIV Cure Meeting organised by the National Institute of Allergy and Infectious Diseases (NIAID) in 2012, one of the primary purposes of the meeting has been to facilitate communication and foster collaboration across the NIAID-funded Martin Delaney Collaboratories for HIV cure research (MDC), the broader HIV cure-related research field, and industry and community stakeholders. This year's meeting agenda reflected NIAID's increasing investment over the last 5 years in research to identify strategies for eradicating or achieving long-term remission of HIV infection. Overviews and research highlights were presented from each of the Martin Delaney Collaboratories, as well as projects funded through the Beyond HAART programme, the Consortia for Innovative AIDS Research in Nonhuman Primates (CIAR) programme, the ACTG and IMPAACT clinical trial networks, and the NIAID Vaccine Research Center in hopes of stimulating cross-talk and synergy among these and other programmes focused on HIV cure research. Aside from the oral presentations described here, the meeting also included 75 poster presentations. Finally, community engagement activities and community participation in the MDC was highlighted throughout the first day and in a special session on Day 2. This reflects NIAID's commitment to engage community partners in the earliest stages of research towards curative interventions through the MDC programme. The entire meeting is available for viewing via the NIH VideoCast website at: https://videocast.nih.gov/PastEvents.asp.

Understanding the Intersection of Young Age, Mucosal Injury, and HIV Susceptibility.

Adolescent boys and girls are disproportionately affected in the current HIV epidemic. Numerous sociobehavioral studies have addressed the indirect drivers surrounding this vulnerability-for example, socioeconomic, geographical locale, and all forms of violence. However, the direct factors that may influence infection, such as the anatomical and physiological maturation of the anogenital tracts of adolescents or the trauma and wound-healing processes of injured mucosal tissue, are understudied and represent a gap within the HIV prevention field. This article reviews the epidemiology of HIV infection and violence in adolescents and the available basic science knowledge attending this research area. More importantly, this review highlights the most critical gaps that need to be addressed to design preventive interventions that are safe and effective for this population, which is key to ending the HIV pandemic.

Examining suicide: imaging's contributions.

For many people, the death of hope leads inexorably to the conclusion that the only viable solution, the only way to put an end to unendurable pain, is suicide. What leads a person to commit this final, desperate act, and how might we predict, intervene, and prevent suicide? Health care workers, including radiologic technologists, can play an important role in detecting warning signs in patients and in better understanding what factors may lead to suicide. Although certain forms of suicide such as suicide bombings and assisted suicide are beyond its scope, this article explores medical imaging's contributions to the study of this phenomenon.

The NIH Extracellular RNA Communication Consortium.

The Extracellular RNA (exRNA) Communication Consortium, funded as an initiative of the NIH Common Fund, represents a consortium of investigators assembled to address the critical issues in the exRNA research arena. The overarching goal is to generate a multi-component community resource for sharing fundamental scientific discoveries, protocols, and innovative tools and technologies. The key initiatives include (a) generating a reference catalogue of exRNAs present in body fluids of normal healthy individuals that would facilitate disease diagnosis and therapies, (b) defining the fundamental principles of exRNA biogenesis, distribution, uptake, and function, as well as development of molecular tools, technologies, and imaging modalities to enable these studies,

Legal trends in imaging.

As long ago as 400 BC, Hippocrates and his followers recognized that someone must oversee the practice of medicine and impose effective consequences when practice proves substandard. This article focuses primarily upon negligence law, trends toward using imaging in criminal cases and the intersection between the law and controversial, cutting-edge uses of imaging. The ways in which the law and medicine interact as opponents and as partners are described. After completing this article, readers will: Describe the prevalent civil damage cases involving radiological practices. Know what can be done to help avoid malpractice lawsuits. Be able to identify issues with respect to the current insurance crisis. Understand the key roles imaging plays in criminal cases. Be aware of legal concerns raised by new technologies. This article is a Directed Reading. See the quiz following the conclusion.

Patient advocacy: the technologist's role.

This article provides an overview of the various ways in which imaging professionals can demonstrate patient advocacy on a day-to-day basis and throughout their careers. Advocacy encompasses a wide range of attitudes and activities, and implementing its principles can bring new enthusiasm to the workplace and increase job satisfaction. After completing this article, readers will: Describe the fundamental aspects of advocacy. Know how to handle conflict and explain why conflict is necessary. Understand the challenges to advocacy. Apply patient advocacy in the context of diagnostic imaging. Recognize the radiologic technologist's important role in ensuring patient safety. Identify how professional codes and standards, as well as federal and state laws, encourage advocacy efforts.

Organ donation and transplantation.

Medical imaging plays a key role in many aspects of organ donation, procurement and transplantation. Imaging techniques are used to confirm a diagnosis of brain death, measure organs, assess potential donors and recipients, and evaluate the success of surgery. This article offers an overview of organ donation and transplantation. After completing this article, readers will: Understand what U.S. laws apply to organ donation and which organizations play a part in the transplant process. Describe methods for determining death. Explain how organs are procured and allocated. Describe the role medical imaging plays in organ donation and transplantation. Discuss the controversies surrounding organ donation.

Diagnosis and treatment of migraines.

This article offers an overview of migraines, including their causes, symptoms, differential diagnosis and treatment. After completing it readers will: Understand the different classifications of headaches and their attributes. Know how headaches differ in children and adults. Describe causes, triggers and precipitating factors for migraines. Summarize the economic impact of migraines and how migraine headaches affect patients' lives. Describe the role medical imaging plays in diagnosing and researching migraines. Understand how migraines are treated and managed. Discuss the future of migraine diagnosis and treatment.

Imaging's insights into human violence.

Following every well-publicized act of incomprehensible violence, the news media rush to interview neighbors, family members, and experts in an attempt to discover what could have led an individual to commit such a barbarous act. Certain stock answers are reiterated: video games, bullying, violent films, mental illness, the availability of guns, and a society that is increasingly both anonymous and callous. Might imaging be one of the more valuable keys to unlocking the mysteries of violent, aggressive people? This article explores these questions and their complex answers in the context of violent individuals.

What imaging teaches us about pain.

Pain diminishes the quality of life for many people, although it also may be a vital teacher or a warning message to be heeded. How humans process pain is a complicated, individualized process affected by genetics, personality, life experiences, and straightforward physiological processes. Imaging provides investigators with insight into this complicated phenomenon, and it promises to continue to help experts understand not only how pain is processed, but also why chronic pain develops in some people but not others, how we might better manage pain, and how pain may have played a key role in human evolution.

Imaging sleep and sleep disorders.

Sleep, a natural alteration in consciousness, is increasingly difficult to achieve for more than a third of the U.S. population. Despite breathtaking advances in our understanding of sleep, there remains a considerable need for increased awareness and education concerning this growing public health problem. In November 2011, the National Institutes of Health published a sleep disorders research plan geared toward advancing understanding of sleep disorders and their societal impact, improving treatment of sleep disorders, and recruiting and expanding research in this area. Imaging, with its fast-paced innovations and applications, plays an expanding role in exploring sleep, how it affects the brain, and how lack of sleep can be diagnosed and treated more effectively.

Medical imaging of explosion injuries.

Diagnosing and caring for injuries caused by explosives were once almost exclusively the province of combat medical personnel, but with the increase in foreign and domestic terrorism, civilians have become targets. Blasts create complicated medical pictures and paint a wide swath of injuries. Medical responders and hospitals must focus on planning for mass casualty incidents. Medical imaging personnel can learn from worldwide efforts to diagnose and treat blast-related injuries and apply these lessons to the potential for domestic terrorism and to caring for victims of accidental explosions. They also can better understand long-term effects on military and civilian personnel who have been exposed to blast injuries on foreign soil.