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Biological monitoring of polyfluoroalkyl substances: A review.

Polyfluoroalkyl substances (PFSs) are used in industrial and commercial products and can degrade to persistent perfluorocarboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs). Temporal trend studies using human, fish, bird, and marine mammal samples indicate that exposure to PFSs has increased significantly over the past 15-25 years. This review summarizes the biological monitoring of PFCAs, PFSAs, and related PFSs in wildlife and humans, compares concentrations and contamination profiles among species and locations, evaluatesthe bioaccumulation/biomagnification in the environment, discusses possible sources, and identifies knowledge gaps. PFSs can reach elevated concentrations in humans and wildlife inhabiting industrialized areas of North America, Europe, and Asia (2-30,000 ng/ mL or ng/g of wet weight (ww)). PFSs have also been detected in organisms from the Arctic and mid-ocean islands (< or = 3000 ng/g ww). In humans, PFSAs and PFCAs have been shown to vary among ethnic groups and PFCA/PFSA profiles differ from those in wildlife with high proportions of perfluorooctanoic acid and perfluorooctane sulfonate. The pattern of contamination in wildlife varied among species and locations suggesting multiple emission sources. Food web analyses have shown that PFCAs and PFSAs can bioaccumulate and biomagnify in marine and freshwater ecosystems. Knowledge gaps with respect to the transport, accumulation, biodegradation, temporal/spatial trends and PFS precursors have been identified. Continuous monitoring with key sentinel species and standardization of analytical methods are recommended.

Alkanesulfonic Acids↗

Therapeutic use of low molecular weight heparins: knowledge to date and their application to therapy.

Indeed, the accumulating evidence indicates that certain LMW heparins administered subcutaneously may replace classic intravenous heparin therapy. Certain of these subcutaneously administered LMW heparins do not require monitoring. The simplified care offered by LMW heparin therapy offers the possibility of transferring care from in to out of hospital in uncomplicated patients with deep vein thrombosis. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMW heparin therapy will likely prove to be highly cost effective. It is uncertain at present whether the findings associated with an individual LMW heparin preparation can be extrapolated to a different LMW heparins. For this reason, the findings of clinical trials apply only to the particular LMW heparin evaluated and cannot be generalized to the LMW heparins at large.

Animals↗

Docosahexaenoic acid enhances the antioxidant response of human fibroblasts by upregulating gamma-glutamyl-cysteinyl ligase and glutathione reductase.

The chemopreventive effects of dietary n-3 PUFA in various pathologies has so far remained controversial, and we were interested in studying their potential influence on cell redox status. DHA (22 : 6n-3), a typical highly unsaturated n-3 PUFA, was used at 30 micromol/l in a model of human fibroblast cell culture. A dose-response effect, roughly linear, was checked for DHA between 0 and 60 micromol/l, and was accompanied by a large increase in intracellular GSH content. A time course study of this effect shows that, after a short fall, as soon as 4 h after the beginning of the experiment, the large increase in the GSH content was associated with elevated catalytic activities of gamma-glutamyl-cysteinyl ligase, glutathione reductase and glutathione S-transferase. This coordinated response is characteristic of an antioxidant response and was confirmed by the induction of expression of mRNA for gamma-glutamyl-cysteinyl ligase, glutathione reductase and haem-oxygenase. This large increase in the GSH content contributes to decreasing the reactive oxygen species level, as assessed by the decreased accumulation of dichlorofluorescein inside cells. To our knowledge, this is the first report on a specific and potent effect of DHA for decreasing the oxidative stress of human fibroblasts.

Antioxidants↗

Altruism and compassion in the health professions: a search for clarity and precision.

This article presents a conceptual model of altruism grounded in compassion in the health professions. The intent is to bring order out of the current conceptual chaos about the meaning and practical operation of these constructs. The theory-based model proposes that altruism is expressed as overt behavior in specific situations that vary in levels of intensity. It assumes that altruism is not a broad-based, cross-situational personal trait; that altruism can be measured objectively; and that altruism can be increased via education, practice and reinforcement. The article concludes by demonstrating the progression from formation of a theory-based conceptual model, development of objective measures, performing systematic research and accumulating an orderly and consensual body of knowledge about altruism grounded in compassion in the health professions.

Altruism↗

Phloem sap proteins: their identities and potential roles in the interaction between plants and phloem-feeding insects.

The phloem is a well-known target of sucking and piercing insects that utilize the transported fluid as their major nutrient source. In addition to small molecules like sugars and amino acids, phloem sap of higher land plants contains proteins that can accumulate up to high concentrations. Although the knowledge about the identities of these phloem sap proteins is increasing, the functions of most of them are still poorly understood. Since many phloem sap proteins have predicted roles in wound and defence responses, they constitute a class of compounds that can potentially influence plant-insect interactions. However, there are as yet no studies published that have examined direct effects of phloem sap proteins on insect feeding or vice versa. This review summarizes the current knowledge about the identities of phloem sap proteins, focused on polypeptides with probable functions in wound and defence reactions, and their potential impact on plant-insect interactions is discussed.

Animals↗

The short- and long-term impact of multi-disciplinary clinics in addition to standard nephrology care on patient outcomes.

BACKGROUND: This two country case control study of incident dialysis patients evaluates the outcomes of patients exposed to formalized multi-disciplinary clinic (MDC) programmes vs standard nephrologist care. METHODS: Patients commencing dialysis in two centres (Vancouver, Canada and Cremona, Italy) were evaluated at and after dialysis start, as a function of MDC exposure vs nephrologist care alone. Only chronic kidney disease patients, with longer than 3 months of exposure to nephrology care, who had not previously received kidney replacement therapy were included. Study outcomes included laboratory parameters and survival. The MDC was similar in both countries and average exposure was 6-8 h per patient-year, as compared to 2-4 h for standard care. All patients had equal access to resources prior to dialysis and with respect to dialysis start, as all had been referred to the same local nephrology practices. RESULTS: During the evaluation period 288 patients commenced dialysis after receiving more than 3 months nephrology care prior to dialysis. There were no major demographic differences between the cohorts. Mean duration of nephrology care prior to dialysis was 42 months, and dialysis was initiated at similar low glomerular filtration rate (GFR), though statistically significantly different (7.0 and 8.4 ml/min/m2, P = 0.001). The MDC patients had higher haemoglobin (102 vs 90 g/l, P<0.0001), albumin (37.0 vs 34.8 g/l, P = 0.002) and calcium levels (2.29 vs 2.16 mmol/l, P<0.0001) at dialysis start. Survival was significantly better in the MDC group demonstrated by Kaplan-Meier analysis (P = 0.01). Cox proportional hazards analysis demonstrated standard nephrology clinic vs MDC attendance was a statistically significant independent predictor of death (hazards ratio = 2.17, 95% confidence interval 1.11-4.28) after adjusting for other variables known to impact outcomes. CONCLUSIONS: This analysis of outcomes in two different countries suggests that despite equal and long exposure to nephrology care prior to dialysis, there appears to be an association of survival advantage for those patients exposed to formalized clinic care in addition to standard nephrologist follow-up. While other known predictors of survival such as adequacy of dialysis and severity of illness measures were not included in the model, those parameters require time on dialysis to be accumulated. Thus, the data do suggest that knowledge of patient status at the time of dialysis start is important. Further research is needed to determine which specific components of care both prior to dialysis and after its commencement are most important with respect to outcomes.

Adult↗

The process of ageing.

An increasing elderly population involves nurses with older people in a wide sphere of activities. It is essential that an understanding of ageing and its effects is included as part of the knowledge which to common to all nurses. The study of gerontology has intensified in recent years but an interest in the phenomenon of ageing can be traced back through the centuries. A number of theories about the causes of ageing have been put forward but the evidence in support of these is still inconclusive. Control of hte ageing process remains beyond mankind, but it is known that environmental and hereditary factors contribute to the rate of ageing. Knowledge about the effects of ageing is accumulating. The influence of ageing on the functions of the body can be measured. Most functions are reduced in efficiency and the lowered levels of performance have to be considered in their relation to the medical and nursing care of older people. Ageing also has psychological and social implications. Changes in behaviour patterns can occur as a result of the influence of ageing on personality, intellect and memory. There are also changes in the social circumstances of older people resulting from such factors as retirement and bereavement. The growing problem of an elderly population is stimulating increasing research into the causes and effects of ageing.

Aged↗

Antibiotic uptake and the cytoplasmic membrane.

Aminoglycoside antibiotics are accumulated through a unique bacterial transport process. Knowledge of the process and how it can alter susceptibility to aminoglycoside antibiotics may be used to investigate mechanisms that might increase the activity of these compounds. It is possible that aminoglycoside activity could be increased by presenting more drug to the cytoplasmic membrane through alteration of the outer membrane of gram-negative bacteria by increasing transporter concentration or driving force in the form of the electrical potential, by decreasing the rate of enzymatic modification so that active drug can be transported, or by changing aminoglycosides to utilize alternative forms of transport and finally to increase ribosomal affinity for these drugs.

Aminoglycosides↗

Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus.

Current knowledge of the phenotype of mononuclear cells accumulating in pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining their homing into the pancreas is limited. Therefore, a pancreas obtained at the onset of IDDM was studied in detail. Cryostat sections were stained for mononuclear cell types, T cell receptor subtypes, and adhesion molecules of vascular endothelium and studied by immunofluorescence microscopy, and peripheral blood mononuclear cells were phenotyped using flow cytometry. Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V beta 6, V beta 12) were also found. The vascular endothelium of the islets and many small vessels nearby islets strongly expressed intercellular adhesion molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally absent. We conclude: (a) that increased expression of intercellular adhesion molecule-1 on vascular endothelium may increase endothelial adhesion of mononuclear cells and enhance their accumulation in the pancreas during diabetic insulitis; (b) that T cells with certain T cell receptors can be enriched in infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8-positive T cells are involved in pancreatic beta cell destruction at the onset of IDDM.

Antigens, CD↗

Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation.

The last 2 years have seen much excitement in the field of genetics with the identification of a formerly unappreciated level of "structural variation" within the normal human genome. Genetic structural variants include deletions, duplications, and inversions in addition to the recently discovered, copy number variants. Single nucleotide polymorphisms are the most extensively evaluated variant within the genome to date. Combining our knowledge from these studies with our rapidly accumulating understanding of structural variants, it is apparent that the extent of genetic dissimilarity between any 2 individuals is considerable and much greater than that which was previously recognized. Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. With advances in DNA sequencing technology we now have the capacity to perform genome-wide analysis in a high throughput fashion, permitting a detailed genetic analysis of patient and donor prior to transplantation. Understanding the significance of this additional genetic information and applying it in a clinically meaningful way will be one of the challenges faced by transplant clinicians in the future.

Genetic Predisposition to Disease↗

Revision of visual impairment definitions in the International Statistical Classification of Diseases.

BACKGROUND: The existing definitions of visual impairment in the International Statistical Classification of Diseases are based on recommendations made over 30 years ago. New data and knowledge related to visual impairment that have accumulated over this period suggest that these definitions need to be revised. DISCUSSION: Three major issues need to be addressed in the revision of these definitions. First, the existing definitions are based on best-corrected visual acuity, which exclude uncorrected refractive error as a cause of visual impairment, leading to substantial underestimation of the total visual impairment burden by about 38%. Second, the cut-off level of visual impairment to define blindness in the International Statistical Classification of Diseases is visual acuity less than 3/60 in the better eye, but with increasing human development the visual acuity requirements are also increasing, suggesting that a level less than 6/60 be used to define blindness. Third, the International Statistical Classification of Diseases uses the term 'low vision' for visual impairment level less than blindness, which causes confusion with the common use of this term for uncorrectable vision requiring aids or rehabilitation, suggesting that alternative terms such as moderate and mild visual impairment would be more appropriate for visual impairment less severe than blindness. We propose a revision of the definitions of visual impairment in the International Statistical Classification of Diseases that addresses these three issues. According to these revised definitions, the number of blind persons in the world defined as presenting visual acuity less than 6/60 in the better eye would be about 57 million as compared with the World Health Organization estimate of 37 million using the existing International Statistical Classification of Diseases definition of best-corrected visual acuity less than 3/60 in the better eye, and the number of persons in the world with moderate visual impairment defined as presenting visual acuity less than 6/18 to 6/60 in the better eye would be about 202 million as compared with the World Health Organization estimate of 124 million persons with low vision defined as best-corrected visual acuity less than 6/18 to 3/60 in the better eye. CONCLUSION: Our suggested revision of the visual impairment definitions in the International Statistical Classification of Diseases takes into account advances in the understanding of visual impairment. This revised classification seems more appropriate for estimating and tracking visual impairment in the countries and regions of the world than the existing classification in the International Statistical Classification of Diseases.

Biometry↗

Control of the embryonic body plan by activin during amphibian development.

Embryonic induction plays an important role in establishing the fundamental body plan during early amphibian development. The factors mediating this embryonic induction have, however, only recently been discovered. In the mid-1980's, certain peptide growth factors belonging to the FGF and TGF-beta families were found to have a mesoderm-inducing effect on isolated Xenopus blastula ectoderm. The study of embryonic induction subsequently expanded rapidly and knowledge at the molecular level has gradually accumulated. One of these peptide growth factors, activin, a member of the TGF-beta superfamily, is present maternally in the Xenopus early embryo and induces various mesodermal and endodermal tissues in isolated presumptive ectoderm. After exposure of presumptive ectoderm to activin, many genes are expressed in the same manner as in normal embryogenesis. Ectoderm treated with activin can induce a complete secondary embryo, the same as the organizer does in transplantation experiments. These findings suggest that activin is one of the first induction signals responsible for establishing the embryonic body plan in early amphibian development. In this article we shall review to what extent we can control the embryonic body plan in vitro, referring to some significant findings in this field.

Activins↗

The activated sludge biomolecular database.

Tremendous advances have recently been made in the development of molecular tools for analysis of microbial populations in the environment. However, an appropriate scientific basis for quantification of new molecular data must exist to effectively use these tools toward increased understanding of complex waste treatment environments and implementation of corrective actions to maintain or improve system performance. In particular, molecular tools are gaining widespread use in the study of activated-sludge microbial communities and have the potential to improve monitoring and control of wastewater treatment processes. The authors have created a Web-accessible database, the Activated Sludge Biomolecular Database, which provides a scientific basis for interpreting activated-sludge biomolecular information. The database achieves its goal by accumulating and disseminating a large body of knowledge relating the presence and quantity of specific biomolecules to process design, operating conditions, and wastewater characteristics.

Bacteria↗

Experience and lessons learned from sewage sludge pyrolysis in Australia.

Management of sewage sludge via "publicly acceptable" methods is becoming increasingly difficult, primarily due to health and environmental concerns with respect to reuse of the product in agriculture. Consequently thermal processes are gaining popularity with significantly increased interest being shown in pyrolysis and gasification processes, due to their "non-incineration status". One such process is the ENERSLUDGE technology which has been developed and commercialised by Environmental Solutions International Ltd (ESI). The world's first commercial ENERSLUDGE plant is located at the Subiaco Wastewater Treatment Plant (WWTP) that was handed over to the client, the Water Corporation of Western Australia in June 2001. Extensive design knowledge and operational experience has now been accumulated from this commercial pyrolysis facility and future applications of the technology will benefit immensely from the lessons learned and experience gained from this facility.

Agriculture↗

Fetal circulatory responses to oxygen lack.

The knowledge on fetal and neonatal circulatory physiology accumulated by basic scientists and clinicians over the years has contributed considerably to the recent decline of perinatal morbidity and mortality. This review will summarize the peculiarities of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during oxygen lack caused by various experimental perturbations. Furthermore, the relation between oxygen delivery and tissue metabolism during oxygen lack as well as evidence to support a new concept will be presented along with the principal cardiovascular mechanisms involved. Finally, blood flow and oxygen delivery to the principal fetal organs will be examined and discussed in relation to organ function. The fetal circulatory response to hypoxemia and asphyxia is a centralization of blood flow in favour of the brain, heart, and adrenals and at the expense of almost all peripheral organs, particularly of the lungs, carcass, skin and scalp. This response is qualitatively similar but quantitatively different under various experimental conditions. However, at the nadir of severe acute asphyxia the circulatory centralization cannot be maintained. Then there is circulatory decentralization, and the fetus will experience severe brain damage if not expire unless immediate resuscitation occurs. Future work in this field will have to concentrate on the important questions, what factors determine this collapse of circulatory compensating mechanisms in the fetus, how does it relate to neuronal damage, and how can the fetal brain be pharmacologically protected against the adverse effects of asphyxia.

Animals↗

The chemotherapy of leprosy from a microbiological standpoint.

The increased knowledge concerning microbiology and chemotherapy of leprosy is exposed. Great stress is put on the knowledge of chemotherapy of tuberculosis that has accumulated during the last two decades and the guidelines that are equally valid for the chemotherapy of leprosy. The problems of the chemotherapy of the different forms of the disease are exposed and future lines of research indicated.

Animals↗

The sex chromosomes in evolution and in medicine.

The recent emergence of human cytogenetics has a firm foundation in studies on other forms of life. Historical highlights are Mendel's studies on the garden pea (published in 1865 but lost in an obscure journal until 1900); formulation of cytogenic postulates by Sutton and Boveri (1902-1903); Bridges' discovery of chromosome abnormalities in Drosophila (1916), followed by numerous similar studies in plants; and demonstration of the chromosomal basis of the syndromes of Down, Klinefelter and Turner in man (1959).The sex chromosomes (XX and XY) evolved from a pair of undifferentiated autosomes of a premammalian ancestor, the X chromosome changing less than the Y as they evolved. Eleven numerical abnormalities of the sex chromosomes are known in man, and knowledge of their effects on development is accumulating. The abnormal complexes range in size from the XO error of Turner's syndrome to the XXXXY error of a variant of Klinefelter's syndrome.

Adult↗

Undiagnosed neuropathies: the impact of ancillary investigations.

Before the advances in knowledge about peripheral nerve disorders that have accumulated over the past two to three decades, a high proportion of chronic neuropathies seen in tertiary referral centres remained undiagnosed. With intensive investigation, it is now possible to reduce this proportion to 13-14%. The category for which an aetiological diagnosis is most elusive is that of chronic axonal polyneuropathies, although some multifocal neuropathies resist explanation. An aetiological diagnosis is achieved for most demyelinating neuropathies. Some examples of chronic idiopathic axonal polyneuropathy (CIAP) may be of genetic origin; others may have an autoimmune basis. Advances in the molecular genetics and immunopathology of peripheral nerve disorders are likely to lead to the elucidation of some of those neuropathies that currently have to be classified as cryptogenic.

Biopsy↗