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\"The real story of AIDS--how it originated with a virus in a chimpanzee, jumped to one human, and then infected more than 60 million people--is very different from what most of us think we know. Recent research has revealed dark surprises and yielded a radically new scenario of how AIDS began and spread. Excerpted and adapted from the book Spillover, with a new introduction by the author, Quammen's ... investigation tracks the virus from chimp populations in the jungles of southeastern Cameroon to laboratories across the globe, as he unravels the mysteries of when, where, and under what circumstances such a consequential 'spillover' can happen\"--Page 4 of cover.

Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI. Systemic chronic inflammation increases with age and is linked to the development of several diseases, as presented in this Perspective.

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an ‘overarching’ treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.

\"The reasons behind the increase in autism diagnoses have become hotly contested in the media as well as within the medical, scholarly, and autistic communities. Jordynn Jack suggests the proliferating number of discussions point to autism as a rhetorical phenomenon that engenders attempts to persuade through arguments, appeals to emotions, and representational strategies. In Autism and Gender: From Refrigerator Mothers to Computer Geeks, Jack focuses on the ways gender influences popular discussion and understanding of autism's causes and effects. She identifies gendered theories like the \"refrigerator mother\" theory, for example, which blames emotionally distant mothers for autism, and the \"extreme male brain\" theory, which links autism to the modes of systematic thinking found in male computer geeks. Jack's analysis reveals how people employ such highly gendered theories to craft rhetorical narratives around stock characters--fix-it dads, heroic mother warriors rescuing children from autism--that advocate for ends beyond the story itself while also allowing the storyteller to gain authority, understand the disorder, and take part in debates. Autism and Gender reveals the ways we build narratives around controversial topics while offering new insights into the ways rhetorical inquiry can and does contribute to conversations about gender and disability\"-- Provided by publisher.

In a study involving more than 5.9 million persons in a Danish registry, the presence of a mental disorder (in 11.8% of the population) was associated with subsequent medical conditions encompassing 31 specific diagnoses, with hazard ratios that ranged from 0.82 to 3.62 and varied greatly over time.

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.

Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight ( n  = 321,223) and offspring birth weight ( n  = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight–blood pressure association is attributable to genetic effects, and not to intrauterine programming. An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.

Key Points Biologic agents used for the treatment of rheumatic and immunological disorders can cause allergic adverse events (AEs), including standard infusion reactions and hypersensitivity reactions Biologic agents are associated with an increased risk of severe infection, including reactivation of tuberculosis (high risk: infliximab, adalimumab; intermediate risk: etanercept, abatacept, tocilizumab; low risk: rituximab, anakinra) Combination therapy using biologic agents and immunosuppressive drugs has a higher risk of serious infections than monotherapy, especially in the first 12 months of treatment Organ-specific AEs are commonly hepatic, cutaneous or haematological AEs, whereas immunological syndromes and cardiovascular, noninfectious pulmonary, gastrointestinal and neurological AEs are rare Whether patients receiving biologic therapy have an increased incidence of lymphomas and skin cancers, especially after combination therapy, is unknown Biologic therapy decreases the immune response to primary (but not booster) vaccination; therefore, live vaccines (nasal flu; Bacillus Calmette–Guérin; measles, mumps and rubella; and yellow fever vaccines) during active biologic therapy are prohibited Despite being associated with a high rate of adverse events, biologic agents are now commonly used to treat patients with rheumatic diseases. In this comprehensive Review, the authors describe these adverse events and how rheumatologists should manage patients to treat and avoid such complications. Biologic agents have substantially advanced the treatment of immunological disorders, including chronic inflammatory and autoimmune diseases. However, these drugs are often associated with adverse events (AEs), including allergic, immunological and other unwanted reactions. AEs can affect almost any organ or system in the body and can occur immediately, within minutes to hours, or with a delay of several days or more after initiation of biologic therapy. Although some AEs are a direct consequence of the functional inhibition of biologic-agent-targeted antigens, the pathogenesis of other AEs results from a drug-induced imbalance of the immune system, intermediary factors and cofactors, a complexity that complicates their prediction. Herein, we review the AEs associated with biologic therapy most relevant to rheumatic and immunological diseases, and discuss their underlying pathogenesis. We also include our recommendations for the medical management of such AEs. Increased understanding and improved risk management of AEs induced by biologic agents will enable better use of these versatile immune-response modifiers.