The benefits of combination antiretroviral therapy (ART) for HIV cognitive disorders vary substantially between individuals. This study evaluated whether cerebrospinal fluid (CSF) drug penetration ...and CSF virological suppression influence the extent of neuropsychological (NP) improvement during ART. Overall performance on a battery of NP tests administered at baseline and follow‐up (median 15 weeks) was computed by using the global deficit score (GDS) methods in 31 cognitively impaired, HIV‐infected individuals who began new ART regimens. Virological suppression (attaining undetectable viral load by RT‐PCR at follow‐up) was assessed separately for plasma and CSF. Subjects on regimens containing greater numbers of CSF‐penetrating drugs showed significantly greater reduction in CSF viral load. Subjects attaining CSF virological suppression demonstrated greater GDS improvement than those who did not (median GDS change, 0.62 vs 0.23; p = 0.01). A similar trend for plasma did not reach statistical significance (p = 0.053). NP improvement was greater in ART‐naive versus treatment‐experienced subjects. In a multivariate model (overall p = 0.0008), significant, independent predictors of GDS reduction were CSF HIV RNA suppression, baseline antiretroviral history, and their interaction. Including CSF‐penetrating drugs in the ART regimen and monitoring CSF viral load may be indicated for individuals with HIV‐associated cognitive impairment Ann Neurol 2004.
For over 15 years, human subcutaneous adipose tissue has been recognized as a rich source of tissue resident mesenchymal stem/stromal cells (MSC). The isolation of perivascular progenitor cells from ...human adipose tissue by a cell sorting strategy was first published in 2008. Since this time, the interest in using pericytes and related perivascular stem/stromal cell (PSC) populations for tissue engineering has significantly increased. Here, we describe a set of experiments identifying, isolating and characterizing PSC from canine tissue (N = 12 canine adipose tissue samples). Results showed that the same antibodies used for human PSC identification and isolation are cross-reactive with canine tissue (CD45, CD146, CD34). Like their human correlate, canine PSC demonstrate characteristics of MSC including cell surface marker expression, colony forming unit-fibroblast (CFU-F) inclusion, and osteogenic differentiation potential. As well, canine PSC respond to osteoinductive signals in a similar fashion as do human PSC, such as the secreted differentiation factor NEL-Like Molecule-1 (NELL-1). Nevertheless, important differences exist between human and canine PSC, including differences in baseline osteogenic potential. In summary, canine PSC represent a multipotent mesenchymogenic cell source for future translational efforts in tissue engineering.
The protein-only infectious agents known as prions exist within cellular matrices as populations of assembled polypeptide phases ranging from particles to amyloid fibres. These phases appear to ...undergo Darwinian-like selection and propagation, yet remarkably little is known about their accessible chemical and biological functions. Here we construct simple peptides that assemble into well-defined amyloid phases and define paracrystalline surfaces able to catalyse specific enantioselective chemical reactions. Structural adjustments of individual amino acid residues predictably control both the assembled crystalline order and their accessible catalytic repertoire. Notably, the density and proximity of the extended arrays of enantioselective catalytic sites achieve template-directed polymerization of new polymers. These diverse amyloid templates can now be extended as dynamic self-propagating templates for the construction of even more complex functional materials.
Early identification and intervention for developmental disorders are critical to the well-being of children and are the responsibility of pediatric professionals as an integral function of the ...medical home. This report models a universal system of developmental surveillance and screening for the early identification of conditions that affect children's early and long-term development and achievement, followed by ongoing care. These conditions include autism, deafness/hard-of-hearing, intellectual and motor disabilities, behavioral conditions, and those seen in other medical conditions. Developmental surveillance is supported at every health supervision visit, as is as the administration of standardized screening tests at the 9-, 18-, and 30-month visits. Developmental concerns elicited on surveillance at any visit should be followed by standardized developmental screening testing or direct referral to intervention and specialty medical care. Special attention to surveillance is recommended at the 4- to 5-year well-child visit, prior to entry into elementary education, with screening completed if there are any concerns. Developmental surveillance includes bidirectional communication with early childhood professionals in child care, preschools, Head Start, and other programs, including home visitation and parenting, particularly around developmental screening. The identification of problems should lead to developmental and medical evaluations, diagnosis, counseling, and treatment, in addition to early developmental intervention. Children with diagnosed developmental disorders are identified as having special health care needs, with initiation of chronic condition management in the pediatric medical home.
The global reach of human activities affects all natural ecosystems, so that the environment is best viewed as a social-–ecological system. Consequently, a more integrative approach to environmental ...science, one that bridges the biophysical and social domains, is sorely needed. Although models and frameworks for social-–ecological systems exist, few are explicitly designed to guide a long-term interdisciplinary research program. Here, we present an iterative framework, "“Press-–Pulse Dynamics"” (PPD), that integrates the biophysical and social sciences through an understanding of how human behaviors affect "“press"” and "“pulse"” dynamics and ecosystem processes. Such dynamics and processes, in turn, influence ecosystem services -–thereby altering human behaviors and initiating feedbacks that impact the original dynamics and processes. We believe that research guided by the PPD framework will lead to a more thorough understanding of social-–ecological systems and generate the knowledge needed to address pervasive environmental problems.
This review was prompted by continued public and professional interest of necrotizing fasciitis as well as worldwide increases in the incidence of streptococcal invasive infections. Our objective was ...to outline the clinical course of necrotizing fasciitis and delineate factors relating to mortality among 163 diagnosed patients. Over 14 years patients diagnosed with necrotizing fasciitis were reviewed for patient history, comorbid conditions, and progression of clinical course. A logistic regression model was used to identify factors increasing mortality risk among necrotizing fasciitis patients. Nearly 17 per cent of the patients showed no identifiable antecedent trauma. Seventy-one per cent of tissue culture-positive patients (145) had multibacterial infections. Although no streptococcal species were recovered from one-third of these culture-positive patients there was an increase in mortality noted with β-Streptococcus infections. Ninety-six per cent of the patient deaths were correlated with variables organized into the following categories: 1) patient history (intravenous drug use and age <1 or >60 years), 2) comorbid conditions (cancer, renal disease, and congestive heart failure), 3) characteristics of clinical course (trunk involvement, positive blood cultures, peripheral vascular disease, and positive cultures for β-streptococcus or anaerobic bacteria), and 4) quantitative timeline of clinical course (time: injury to diagnosis, diagnosis to treatment). Mortality is correlated to patient history, comorbid conditions, and progression of clinical course. Necrotizing fasciitis can occur idiopathically and is generally a polymicrobial infection that sometimes occurs in the absence of streptococci. Clearly the mortality and morbidity associated with necrotizing fasciitis can be decreased with clinical awareness, early diagnosis, adequate surgical debridement, and intensive supportive care.
Relatively little is known about the genomic basis and evolution of wood-feeding in beetles. We undertook genome sequencing and annotation, gene expression assays, studies of plant cell wall ...degrading enzymes, and other functional and comparative studies of the Asian longhorned beetle, Anoplophora glabripennis, a globally significant invasive species capable of inflicting severe feeding damage on many important tree species. Complementary studies of genes encoding enzymes involved in digestion of woody plant tissues or detoxification of plant allelochemicals were undertaken with the genomes of 14 additional insects, including the newly sequenced emerald ash borer and bull-headed dung beetle.
The Asian longhorned beetle genome encodes a uniquely diverse arsenal of enzymes that can degrade the main polysaccharide networks in plant cell walls, detoxify plant allelochemicals, and otherwise facilitate feeding on woody plants. It has the metabolic plasticity needed to feed on diverse plant species, contributing to its highly invasive nature. Large expansions of chemosensory genes involved in the reception of pheromones and plant kairomones are consistent with the complexity of chemical cues it uses to find host plants and mates.
Amplification and functional divergence of genes associated with specialized feeding on plants, including genes originally obtained via horizontal gene transfer from fungi and bacteria, contributed to the addition, expansion, and enhancement of the metabolic repertoire of the Asian longhorned beetle, certain other phytophagous beetles, and to a lesser degree, other phytophagous insects. Our results thus begin to establish a genomic basis for the evolutionary success of beetles on plants.
Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against an invading pathogen. We reveal a dynamic aspect of nutritional immunity during ...infection that involves copper assimilation. Using a combination of laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, and gene expression profiling from infected tissues, we show that readjustments in hepatic, splenic and renal copper homeostasis accompany disseminated Candida albicans infections in the mouse model. Localized host-imposed copper poisoning manifests itself as a transient increase in copper early in the kidney infection. Changes in renal copper are detected by the fungus, as revealed by gene expression profiling and fungal virulence studies. The fungus responds by differentially regulating the Crp1 copper efflux pump (higher expression during early infection and down-regulation late in infection) and the Ctr1 copper importer (lower expression during early infection, and subsequent up-regulation late in infection) to maintain copper homeostasis during disease progression. Both Crp1 and Ctr1 are required for full fungal virulence. Importantly, copper homeostasis influences other virulence traits-metabolic flexibility and oxidative stress resistance. Our study highlights the importance of copper homeostasis for host defence and fungal virulence during systemic disease.
Nearshore estuarine and marine ecosystems-e.g., seagrass meadows, marshes, and mangrove forests-serve many important functions in coastal waters. A better understanding of these habitats, that serve ...as nurseries for marine species, and the factors that create site-specific variability in nursery quality will improve conservation and management of these areas.
The high power consumption of modern processors becomes a major concern because it leads to decreased mission duration (for battery-operated systems), increased heat dissipation, and decreased ...reliability. While many techniques have been proposed to reduce power consumption for uniprocessor systems, there has been considerably less work on multiprocessor systems. In this paper, based on the concept of slack sharing among processors, we propose two novel power-aware scheduling algorithms for task sets with and without precedence constraints executing on multiprocessor systems. These scheduling techniques reclaim the time unused by a task to reduce the execution speed of future tasks and, thus, reduce the total energy consumption of the system. We also study the effect of discrete voltage/speed levels on the energy savings for multiprocessor systems and propose a new scheme of slack reservation to incorporate voltage/speed adjustment overhead in the scheduling algorithms. Simulation and trace-based results indicate that our algorithms achieve substantial energy savings on systems with variable voltage processors. Moreover, processors with a few discrete voltage/speed levels obtain nearly the same energy savings as processors with continuous voltage/speed, and the effect of voltage/speed adjustment overhead on the energy savings is relatively small.
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