Identifying dementia in Down syndrome with the Severe Impairment Battery, Brief Praxis Test and Dementia Scale for People with Learning Disabilities.

BACKGROUND: Individuals with Down syndrome (DS) are at high risk for dementia, specifically Alzheimer's disease. However, many measures regularly used for the detection of dementia in the general population are not suitable for individuals with DS due in part to floor effects. Some measures, including the Severe Impairment Battery (SIB), Brief Praxis Test (BPT) and Dementia Scale for People with Learning Disabilities (DLD), have been used in clinical trials and other research with this population. Validity research is limited, particularly regarding the use of such tools for detection of prodromal dementia in the DS population. The current project presents baseline cross-sectional SIB, BPT and DLD performance in order to characterise their predictive utility in discriminating normal cognition, possible dementia and probable dementia in adult DS. METHOD: Baseline SIB, BPT and DLD performances from 100 individuals (no dementia = 68, possible dementia = 16 & probable dementia = 16) were examined from a longitudinal cohort of aging individuals with DS. Receiver operating characteristic curves investigated the accuracy of these measures in relation to consensus dementia diagnoses, diagnoses which demonstrated high percent agreement with the examining neurologist's independent diagnostic impression. RESULTS: The SIB and BPT exhibited fair discrimination ability for differentiating no/possible versus probable dementia [area under the curve (AUC) = 0.61 and 0.66, respectively]. The DLD exhibited good discrimination ability for differentiating no versus possible/probable dementia (AUC = 0.75) and further demonstrated better performance of the DLD Cognitive subscale compared with the DLD Social subscale (AUC = 0.77 and 0.67, respectively). CONCLUSIONS: Results suggest that the SIB, BPT and DLD are able to reasonably discriminate consensus dementia diagnoses in individuals with DS, supporting their continued use in the clinical assessment of dementia in DS. The general performance of these measures suggests that further work in the area of test development is needed to improve on the AUCs for dementia status discrimination in this unique population. At present, however, the current findings suggest that the DLD may be the best option for reliable identification of prodromal dementia in this population, reinforcing the importance of including informant behaviour ratings in assessment of cognition for adults with DS.

A preliminary study of cerebral blood flow, aging and dementia in people with Down syndrome.

BACKGROUND: People with Down syndrome (DS) develop Alzheimer's disease (AD) at an earlier age of onset than those with sporadic AD. AD neuropathology is typically present in DS by 40 years of age with an onset of dementia approximately 10 years later. This early onset is due to the overexpression of amyloid precursor protein from the third copy of chromosome 21. Cerebrovascular neuropathology is thought to contribute in 40-60% of cases sporadic AD. However, the vascular contribution to dementia in people with DS has been relatively unexplored. We hypothesised that vascular perfusion is compromised in older adults with DS relative to younger individuals and is further exacerbated in those with dementia. METHOD: Cerebral blood flow (CBF) was measured using pulsed arterial spin labelling in 35 cognitively characterised adults with DS (26-65 years). DS participants were also compared with 15 control subjects without DS or dementia (26-65 years). Linear regression evaluated the difference in CBF across groups and diagnosis along with assessing the association between CBF and cognitive measures within the DS cohort. RESULTS: Cerebral blood flow was significantly lower among DS participants with probable AD compared with controls (P = 0.02) and DS participants with no dementia (P = 0.01). Within the DS cohort, CBF was significantly associated with the Severe Impairment Battery (SIB) measure and the Dementia Questionnaire for People with Learning Disabilities (DLD) rating (F3,25  = 5.13; P = 0.007). Both the SIB (ß = 0.74; t = 2.71; P = 0.01) and DLD (ß = -0.96; t = -3.87; P < 0.001) indicated greater impairment as global CBF decreased. Age was significantly associated with CBF among participants with DS. There was a non-linear effect of age, whereby CBF declined more rapidly after 45 years of age. CONCLUSIONS: This preliminary study of CBF in DS indicates that cerebrovascular pathology may be a significant contributor to dementia in DS. CBF was associated with diagnosis, cognition and age. Notably, CBF decreases at a greater rate after age 45 and may represent a significant prodromal event in AD progression.

Global transboundry disease politics: the OIE perspective.

Reviewed in this paper are the steps for listing or de-listing of an aquatic animal disease, the current list of OIE listed aquatic animal diseases, and the reporting requirements for listed diseases by member countries. The current OIE listed aquatic animal diseases includes two diseases of amphibians, nine of fish, seven of mollusks, and eight of crustaceans. Of interest is the difference in importance of the listed diseases in each of the four groups of aquatic animals. In mollusks, parasitic diseases dominate the list, while in fish and crustaceans virus diseases are dominant. Whether a listed disease is due to a virus, fungus, bacterium or a parasite, the occurrence of the disease may adversely affect international trade among trading partners that have, or do not have, the listed disease. By its very nature, the international trade in terrestrial animals and aquatic animals, and their products, is influenced by national and international politics. When the occurrence of an OIE listed or emerging disease becomes an issue between trading partners, trade restrictions may be put in place and disputes are often a consequence. The World Trade Organization named the OIE as the reference body for animal health as it relates to international trade. This action recognized the 88 year history of the work by the OIE in disease control, listing of diseases, the development of the terrestrial and aquatic codes and the diagnostic manuals, and the prompt notification of members by the OIE of the occurrence of listed diseases. The intent of the WTO with this action was likely to minimize disease related trade disputes brought before the WTO.

Historic emergence, impact and current status of shrimp pathogens in the Americas.

Shrimp farming in the Americas began to develop in the late 1970s into a significant industry. In its first decade of development, the technology used was simple and postlarvae (PLs) produced from wild adults and wild caught PLs were used for stocking farms. Prior to 1990, there were no World Animal Health Organization (OIE) listed diseases, but that changed rapidly commensurate with the phenomenal growth of the global shrimp farming industry. There was relatively little international trade of live or frozen commodity shrimp between Asia and the Americas in those early years, and with a few exceptions, most of the diseases known before 1980 were due to disease agents that were opportunistic or part of the shrimps' local environment. Tetrahedral baculovirosis, caused by Baculovirus penaei (BP), and necrotizing hepatopancreatitis (NHP) and its bacterial agent Hepatobacterium penaei, were among the "American" diseases that eventually became OIE listed and have not become established outside of the Americas. As the industry grew after 1980, a number of new diseases that soon became OIE listed, emerged in the Americas or were introduced from Asia. Spherical baculovirus, caused by MBV, although discovered in the Americas in imported live Penaeus monodon, was subsequently found to be common in wild and farmed Asian, Australian and African penaeids. Infectious hypodermal and hematopoietic necrosis virus (IHHNV) was introduced from the Philippines in the mid 1970s with live P. monodon and was eventually found throughout the Americas and subsequently in much of the shrimp farming industry in the eastern hemisphere. Taura syndrome emerged in Penaeus vannamei farms in 1991-1992 in Ecuador and was transferred to SE Asia with live shrimp by 1999 where it also caused severe losses. White Spot Disease (WSD) caused by White spot syndrome virus (WSSV) emerged in East Asia in ∼1992, and spread throughout most of the Asian shrimp farming industry by 1994. By 1995, WSSV reached the eastern USA via frozen commodity products and it reached the main shrimp farming countries of the Americas located on the Pacific side of the continents by the same mechanism in 1999. As is the case in Asia, WSD is the dominant disease problem of farmed shrimp in the Americas. The most recent disease to emerge in the Americas was infectious myonecrosis caused by IMN virus. As had happened before, within 3years of its discovery, the disease had been transferred to SE Asia with live P. vannamei, and because of its impact on the industry and potential for further spread in was listed by the OIE in 2005. Despite the huge negative impact of disease on the shrimp farming industry in the Americas, the industry has continued to grow and mature into a more sustainable industry. In marked contrast to 15-20years ago when PLs produced from wild adults and wild PLs were used to stock farms in the Americas, the industry now relies on domesticated lines of broodstock that have undergone selection for desirable characteristics including disease resistance.

Disease will limit future food supply from the global crustacean fishery and aquaculture sectors.

Seafood is a highly traded food commodity. Farmed and captured crustaceans contribute a significant proportion with annual production exceeding 10 M metric tonnes with first sale value of $40bn. The sector is dominated by farmed tropical marine shrimp, the fastest growing sector of the global aquaculture industry. It is significant in supporting rural livelihoods and alleviating poverty in producing nations within Asia and Latin America while forming an increasing contribution to aquatic food supply in more developed countries. Nations with marine borders often also support important marine fisheries for crustaceans that are regionally traded as live animals and commodity products. A general separation of net producing and net consuming nations for crustacean seafood has created a truly globalised food industry. Projections for increasing global demand for seafood in the face of level or declining fisheries requires continued expansion and intensification of aquaculture while ensuring best utilisation of captured stocks. Furthermore, continued pressure from consuming nations to ensure safe products for human consumption are being augmented by additional legislative requirements for animals (and their products) to be of low disease status. As a consequence, increasing emphasis is being placed on enforcement of regulations and better governance of the sector; currently this is a challenge in light of a fragmented industry and less stringent regulations associated with animal disease within producer nations. Current estimates predict that up to 40% of tropical shrimp production (>$3bn) is lost annually, mainly due to viral pathogens for which standard preventative measures (e.g. such as vaccination) are not feasible. In light of this problem, new approaches are urgently required to enhance yield by improving broodstock and larval sourcing, promoting best management practices by farmer outreach and supporting cutting-edge research that aims to harness the natural abilities of invertebrates to mitigate assault from pathogens (e.g. the use of RNA interference therapeutics). In terms of fisheries losses associated with disease, key issues are centred on mortality and quality degradation in the post-capture phase, largely due to poor grading and handling by fishers and the industry chain. Occurrence of disease in wild crustaceans is also widely reported, with some indications that climatic changes may be increasing susceptibility to important pathogens (e.g. the parasite Hematodinium). However, despite improvements in field and laboratory diagnostics, defining population-level effects of disease in these fisheries remains elusive. Coordination of disease specialists with fisheries scientists will be required to understand current and future impacts of existing and emergent diseases on wild stocks. Overall, the increasing demand for crustacean seafood in light of these issues signals a clear warning for the future sustainability of this global industry. The linking together of global experts in the culture, capture and trading of crustaceans with pathologists, epidemiologists, ecologists, therapeutics specialists and policy makers in the field of food security will allow these issues to be better identified and addressed.

Virus diseases of farmed shrimp in the Western Hemisphere (the Americas): a review.

Penaeid shrimp aquaculture is an important industry in the Americas, and the industry is based almost entirely on the culture of the Pacific White Shrimp, Litopenaeus vannamei. Western Hemisphere shrimp farmers in 14 countries in 2004 produced more than 200,000 metric tons of shrimp, generated more than $2 billion in revenue, and employed more than 500,000 people. Disease has had a major impact on shrimp aquaculture in the Americas since it became a significant commercial entity in the 1970s. Diseases due to viruses, rickettsial-like bacteria, true bacteria, protozoa, and fungi have emerged as major diseases of farmed shrimp in the region. Many of the bacterial, fungal and protozoan caused diseases are managed using improved culture practices, routine sanitation, and the use of chemotherapeutics. However, the virus diseases have been far more problematic to manage and they have been responsible for the most costly epizootics. Examples include the Taura syndrome pandemic that began in 1991-1992 when the disease emerged in Ecuador, and the subsequent White Spot Disease pandemic that followed its introduction to Central America from Asia in 1999. Because of their socioeconomic significance to shrimp farming, seven of the nine crustacean diseases listed by the World Animal Organization (OIE) are virus diseases of shrimp. Of the seven virus diseases of penaeid shrimp, five are native to the Americas or have become enzootic following their introduction. The shrimp virus diseases in the Americas are increasingly being managed by exclusion using a combination of biosecurity and the practice of culturing domesticated specific pathogen-free (SPF) stocks or specific pathogen-resistant (SPR) stocks. Despite the significant challenges posed by disease, the shrimp farming industry of the Americas has responded to the challenges posed by disease and it has developed methods to manage its diseases and mature into a sustainable industry.

A real-time PCR for the detection of hepatopancreatic parvovirus (HPV) of penaeid shrimp.

Hepatopancreatic parvovirus (HPV) causes a common shrimp disease that occurs in many shrimp farming regions, especially in the Indo Pacific, and infects most of the cultured penaeid species. There are seven geographic HPV isolates known, so a method to detect different HPV types is needed. We developed a sensitive and generic real-time PCR assay for the detection of HPV. A pair of primers and TaqMan probe based on an HPV sequence obtained from samples of Fenneropenaeus chinensis from Korea were selected, and they were used to amplify a 92 bp DNA fragment. This real-time PCR was found to be specific to HPV and did not react with other shrimp viruses. A plasmid (pHPV-2) containing the target HPV sequence was constructed and used for determination of the sensitivity of this assay. The assay could detect a single copy of plasmid DNA, and it was used successfully in finding HPV in shrimp samples from the China-Yellow Sea region, Taiwan, Korea, Thailand, Madagascar, New Caledonia and Tanzania.

Methylvinylmaleimide from bilirubin photooxidation.

Irradiation of an oxygenated methanolic solution of bilirubin IXalpha in the absence of known singlet oxygen sensitizers gave methylvinylmaleimide among other products.

Blue light and bilirubin excretion.

Blue light converts bilirubin in the skin of jaundiced rats to metastable geometric isomers that are transported in blood and excreted in bile. The same reaction probably occurs in jaundiced babies exposed to light, particularly during treatment with phototherapy. Excretion of unisomerized bilirubin is prevented by intramolecular hydrogen bonding, and the pigment has to be metabolized to more polar derivatives to be excreted efficiently.

Development of a method for the detection of infectious myonecrosis virus by reverse-transcription loop-mediated isothermal amplification and nucleic acid lateral flow hybrid assay.

We report the development of a reverse-transcription loop-mediated isothermal amplification and nucleic acid lateral flow method (RT-LAMP-NALF) for detection of infectious myonecrosis virus (IMNV). The RT-LAMP-NALF method combines simplified nucleic acid extraction, a reverse-transcription loop-mediated isothermal amplification platform, and one-step visual colorimetric confirmation of the IMNV amplified sequences using a generic NALF qualitative detection test strip. The sensitivity of RT-LAMP (using two and three primer pairs) and nested RT-LAMP (using three primer pairs) was compared by real-time reverse-transcription-polymerase chain reaction (RT-PCR) using TaqMan probe. The detection of RT-LAMP (three primer pairs) products was accomplished by using a NALF-test strip. The RT-LAMP-NALF showed equivalent sensitivity to RT-LAMP (using three primer pairs), and it was found to be 100 and 10 times more sensitive than one-step RT-PCR and RT-LAMP (two primer pairs), respectively. On the other hand, the RT-LAMP-NALF was 10 and 100 times less sensitive than nested RT-PCR and real-time RT-PCR, respectively. The simplified RNA extraction method ranged from 4.4 x 10(6) to 2.2 x 10(8) IMNV copy numbers microL(-1) RNA, and it was similar with the standard RNA extraction (from 1.2 x 10(6) to 6.3 x 10(7) IMNV copy numbers microL(-1) RNA). These results clearly demonstrate that the RT-LAMP-NALF method is specific, sensitive, can shorten the time for analysis, and has potential application for IMNV diagnosis in resource-poor diagnostic settings.

Development and characterization of a monoclonal antibody against Taura syndrome virus.

We produced a panel of monoclonal antibodies (MAbs) from the fusion of Taura syndrome virus variants from Belize (TSV-BZ) immunized BALB/cJ mouse spleen cells and non-immunoglobulin secreting SP2/0 mouse myeloma cells. One antibody, 2C4, showed strong specificity and sensitivity for TSV in dot-blot immunoassay and immunohistochemistry (IHC) analysis. The MAb reacted against native TSV-BZ, TSV variants from Sinaloa, Mexico (TSV-SI) and TSV variants from Hawaii (TSV-HI) in dot-blot immunoassay. By IHC, the antibody identified the virus in a pattern similar to the digoxigenin-labelled TSV-cDNA probe for the TSV-BZ, TSV-HI and TSV-SI variants, but not for the TSV variants from Venezuela (TSV-VE) and the TSV variants from Thailand (TSV-TH). MAb 2C4 did not react against other shrimp pathogens or with normal shrimp tissue. Western blot analysis showed a strong reaction against CP2, a region of high antigenic variability amongst TSV variants. This antibody has potential diagnostic application in detection and differentiation of certain TSV biotypes.

Comparison of Taura syndrome virus (TSV) detection methods during chronic-phase infection in Penaeus vannamei.

Methods to detect Taura syndrome virus (TSV) were assessed for their ability to detect the virus during chronic phase infection in the Pacific white shrimp Penaeus vannamei. In situ hybridization (ISH), immunohistochemistry (IHC) using monoclonal antibody 1A1, conventional RT-PCR and real-time quantitative (q)RT-PCR were compared using shrimp sampled over 60 wk following experimental TSV infection. Between Weeks 7 and 60, hematoxylin-eosin histology confirmed the presence of lymphoid organ spheroids (LOS) and an absence of lesions in the cuticular epithelium. ISH detected TSV in LOS over the duration of the study. IHC was generally less sensitive than ISH, and after Week 24, was often unable to confirm TSV infection. Detection of TSV by RT-PCR was highly dependent on sample source after Week 43, where viral RNA was detected in 12 of 14 hemolymph samples but only 5 of 16 pleopod samples. qRT-PCR detected TSV over the 60 wk in both hemolymph and pleopods, although RNA copy numbers in pleopods were consistently lower throughout the study. This study demonstrates that ISH and qRT-PCR are the most reliable methods for detecting TSV during late chronic phase infection. RT-PCR was also reliable if hemolymph was used as the sample source.

Opportunities for training in shrimp diseases.

Opportunities for formal training in shrimp diseases were not available 30 years ago. This was because the shrimp farming industry was in its infancy with few significant disease issues and even fewer shrimp disease specialists investigating the causes of production losses. In 2006, more than two million metric tons of the marine penaeid shrimp were farmed, accounting for more than half of the world's supply. With most of the world's shrimp fisheries at maximum sustainable yields, the ratio of farmed to fished shrimp appears likely to continue to increase. The remarkable growth of sustainable shrimp farming was made possible through the development of methods to diagnose and manage disease in the world's shrimp farms. This occurred as the result of the development of training opportunities in shrimp disease diagnosis and control methods and the application of that knowledge, by an ever increasing number of shrimp diseases specialists, to disease management at shrimp farms. The first type of formal training to become generally available to the industry was in the form of special short courses and workshops. The first of these, which was open to international participants, was given at the University of Arizona in 1989. Since that first course several dozen more special short courses and workshops on shrimp diseases have been given by the University of Arizona. Dozens more special courses and workshops on shrimp diseases have been given by other groups, including other universities, industry cooperatives, governments and international aid agencies, in a wide range of countries (and languages) where shrimp farming constitutes an important industry. In parallel, graduate study programs leading to post graduate degrees, with shrimp disease as the research topic, have developed while formal courses in shrimp diseases have not become widely available in veterinary or fisheries college curricula in the USA and Europe, such courses are appearing in university programs located in some of the shrimp farming countries of SE Asia. The trend towards more formal training programs in shrimp diseases and disease management is likely to continue as the industry continues to mature and become increasingly sustainable.

Application of molecular diagnostic methods to penaeid shrimp diseases: advances of the past 10 years for control of viral diseases in farmed shrimp.

The most important diseases of farmed penaeid shrimp have infectious aetiologies. Among these are diseases with viral, rickettsial, bacterial, fungal and parasitic aetiologies. Diagnostic methods for these pathogens include the traditional methods of gross pathology, histopathology, classical microbiology, animal bioassay, antibody-based methods, and molecular methods using DNA probes and DNA amplification. While methods using clinical chemistry and tissue culture are standard methods in veterinary and human diagnostic laboratories, the former has not been routinely applied to the diagnosis of penaeid shrimp diseases and the latter has yet to be developed, despite considerable research and development efforts that have spanned the past 40 years. No continuous shrimp cell lines, or lines from other crustaceans, have been developed. Hence, when molecular methods began to be routinely applied to the diagnosis of infectious diseases in humans and domestic animals in the mid- to late 1980s, the technology was applied to the diagnosis of certain important diseases of penaeid shrimp for which only classical diagnostic methods were previously available. A DNA hybridization assay for the parvovirus IHHNV was the first molecular test developed for a shrimp disease. This was followed within a year by the first PCR test for MBV, an important baculovirus disease of shrimp. Today, shrimp disease diagnostic laboratories routinely use molecular tests for diagnostic and surveillance purposes for most of the important penaeid shrimp diseases.

Electrochemical reduction of the biliverdin-serum albumin complex as monitored by absorption and circular dichroism spectroscopy.

The cathodic reduction at the mercury electrode of a biliverdin IX alpha-serum albumin complex at physiological pH in an aqueous buffer containing percentages of DMSO ranging from 4% to 20% is studied by cyclic voltametry and controlled potential coulometry. The progression of pigment disappearance and the (stereochemical) nature of the product are monitored by chromatography, UV-visible absorption and circular dichroism spectroscopy. Upon reduction, albumin-bound biliverdin IX alpha, with a slight preference for the P-helicity, affords the corresponding bound bilirubin IX alpha -with an M-chirality conformation. The complex is reduced at -0.64 V (vs. SCE; 8% DMSO), only a little shifted compared to reduction of free biliverdin IX alpha under the same conditions. In contrast, an analogous bilirubin IX alpha-serum albumin complex is essentially inert towards cathodic reduction under conditions where free bilirubin IX alpha is reduced, indicating a better shielding by the protein of the bilirubin IX alpha molecule from the electrode surface. The presence of relative position (as in the biliverdins IX alpha and XIII alpha) or absence (as in mesobiliverdin IX alpha) of vinyl groups in the pigment does not have a significant effect upon its electroreduction behaviour, indicating that the process is not sensitive to the subtle differences imposed by vinyl groups upon the structure of the corresponding biliverdin-albumin complexes.

Biliary excretion of a stretched bilirubin in UGT1A1-deficient (Gunn) and Mrp2-deficient (TR-) rats.

The metabolism and biliary excretion of a stretched bilirubin analog with a p-xylyl group replacing the central CH2 hinge were investigated in normal rats, Gunn rats deficient in bilirubin conjugation, and TR- rats deficient in bilirubin glucuronide hepatobiliary transport. Unlike bilirubin, the analog was excreted rapidly in bile unchanged in all three rat strains after intravenous administration. In TR- rats biliary excretion of the analog was diminished, but still substantial, demonstrating that the ATP-binding cassette transporter Mrp2 is not required for its hepatic efflux. These effects are attributable to differences in the preferred conformations of bilirubin and the analog.

'Like a shrivelled blood orange'--bilirubin, jaundice, and phototherapy.

The biochemistry of bilirubin is reviewed with particular reference to newborn infants. The formation, properties, and metabolism of bilirubin are summarized and the importance of molecular shape, hydrogen-bonding, and polarity on the biologic disposition of bilirubin is emphasized. The chemical basis for the subtle influence of visible (blue) light on bilirubin structure and metabolism is explained, and recent concepts of the mechanism of phototherapy are presented. A glossary of current jargon is appended.

Contemporary urologic management of patients with spinal cord injury.

Urologic management strategies in patients with spinal cord injury are discussed herein, and the underlying pathophysiology and urodynamic principles are emphasized. Contemporary management of the spinal cord-injured bladder has allowed for near-elimination of renal failure as the primary cause of long-term morbidity in these patients; low urine storage, sterile urine, and effective emptying are imperative for good long-term results.

Treatment options for women with stress urinary incontinence.

About one-quarter million surgical procedures are performed each year in the United States for stress urinary incontinence. After outlining the presentation and diagnostic evaluation of stress urinary incontinence, this review concentrates specifically on the numerous conservative management strategies and minimally invasive surgical options for women with this common complaint. In the evaluation of nursing home residents with incontinence, the Minimum Data Set and Resident Assessment Protocol facilitate nonspecialist evaluation and management. In healthy adults, the therapeutic implications of the physical examination of the pelvic floor, assessing for the presence and strength of the voluntary contraction of the pelvic floor muscles, are detailed as the basis for all conservative management strategies. Reports on the effectiveness of pelvic floor muscle reeducation and pelvic floor electrical stimulation vary substantially, as do long-term results of surgical interventions. Surgical management is highly effective in the appropriate candidate. The current theory and practice of surgical treatment of stress urinary incontinence are outlined, with certain caveats regarding the lack of long-term follow-up for newer less invasive techniques.