Immune Cell–Derived C3 Is Required for Autoimmune Diabetes Induced by Multiple Low Doses of Streptozotocin

OBJECTIVE: The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. RESEARCH DESIGN AND METHODS: Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. RESULTS: Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model. CONCLUSIONS: The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependen

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

The Genome of Anopheles darlingi, the main neotropical malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vectorhuman and vectorparasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles- darlingi. © 2013 The Author(s)

Operator Assignment and Routing Problems in Home Health Care Services

Human resource planning in Home Health Care (HHC) services is a critical activity on which the quality of the delivered care depends. From the admission of the patient, the service organization has to decide the home operators who will follow the patients during their stay as well as the detailed care delivery plan. The robust resource planning is crucial for operations in the HHC structure, to avoid process inefficiencies, treatment delays and low quality of service. Many of HHC providers pursue the objective of continuity of care which is maintaining the same (principal) operator throughout the time the patient stays in the system. This paper proposes a two–stage approach for assignment and routing decisions in HHC organizations. The main goal is to analyze the interaction between the assignment and routing processes in a single district. All the proposed cases are applied on a instance generated from real data obtained by an Italian HHC provider

Operator assignment and routing problems in home health care services

Human resource planning in Home Health Care (HHC) services is a critical activity on which the quality of the delivered care depends. From the admission of the patient, the service organization has to decide the home operators who will follow the patients during their stay as well as the detailed care delivery plan. The robust resource planning is crucial for operations in the HHC structure, to avoid process inefficiencies, treatment delays and low quality of service. Many of HHC providers pursue the objective of continuity of care which is maintaining the same (principal) operator throughout the time the patient stays in the system. This paper proposes a two–stage approach for assignment and routing decisions in HHC organizations. The main goal is to analyze the interaction between the assignment and routing processes in a single district. All the proposed cases are applied on a instance generated from real data obtained by an Italian HHC provider

Human Resource Scheduling and Routing Problem in Home HealthCare Context: A Literature Review

Home Health Care (HHC) service is an alternative to the conventional hospitalization. The goal is to deliver medical, paramedical and social services to patients at their homes, which help them to improve and keep their best clinical, psychological and social conditions. As a large number of resources (i.e., material and human) contribute to delivering the HHC service, there are many issues that should be considered. Among these, the resource scheduling and routing problem (i.e., deciding in which sequence each operator will visit patients assigned to him/her) is one of the most important issues to be addressed while planning HHC resources. In this paper, we review studies in the literature that address the scheduling and routing problem as a Traveling Salesman Problem (TSP) or Vehicle Routing Problem (VRP) in the HHC context. We analyze each study according to four main categories: i) study characteristics, ii) modeling characteristics, iii) network characteristics, and iv) data characteristics. The objective of this review is to highlight the unexplored issues in researches dealing with the resource scheduling and routing problem, formulated as either TSP or VRP in the HHC context