Expanding Medical Education for Local Health Promoters Among Remote Communities of the Peruvian Amazon: An Exploratory Study of an Innovative Program Model.

PURPOSE: Community health workers (CHWs) play integral roles in primary health care provision in low- and middle-income countries (LMICs). This is particularly true in underdeveloped areas where there are acute shortages of health workers. In this study, we evaluated the development and community utilization of a CHW training program in the Loreto province of Peru. Additionally, a community-oriented training model was designed to augment access to basic health information in underserved and isolated areas of the Amazon. METHODS: Health resource utilization was compared in each community by surveying community members before and after implementation of the CHW training program, which utilized a community participatory program development (CPPD) model. RESULTS: All communities demonstrated significantly increased CHW utilization (p = 0.026) as their initial point of contact for immediate health concerns following CHW training implementation. This increase in CHW utilization was accompanied by trends toward decreased preferences for local shamans or traveling to the closest health post as the initial health resource. CONCLUSION: The community-focused, technology-oriented model utilized in this study proved an effective way to promote the use of CHWs in the Amazon region of Loreto, and could prove valuable to CHW capacitation efforts within other Peruvian provinces and in other LMICs around the world.

Meningioma mimics: five key imaging features to differentiate them from meningiomas.

There are a wide variety of intracranial mass lesions, both benign and malignant, which can closely mimic meningioma on imaging. We present five characteristic imaging features that can alert the radiologist to consider other differential diagnoses. Of the five imaging characteristics that were rarely seen in meningiomas, but common and specific for meningioma mimics, absence of dural tail is the most common (83.7%). Homogeneous T2 hyperintensity or T2 hypointensity are seen in nearly half of meningioma mimics and osseous destruction and leptomeningeal extension are present in 40.5% and 21.6% of meningioma mimics, respectively. The distinction between meningioma and its mimics is important because a large portion of the meningioma mimics requires substantially different clinical and surgical management.

Floral Reversion in Arabidopsis suecica Is Correlated with the Onset of Flowering and Meristem Transitioning.

Angiosperm flowers are usually determinate structures that may produce seeds. In some species, flowers can revert from committed flower development back to an earlier developmental phase in a process called floral reversion. The allopolyploid Arabidopsis suecica displays photoperiod-dependent floral reversion in a subset of its flowers, yet little is known about the environmental conditions enhancing this phenotype, or the morphological processes leading to reversion. We have used light and electron microscopy to further describe this phenomenon. Additionally, we have further studied the phenology of flowering and floral reversion in A. suecica. In this study we confirm and expand upon our previous findings that floral reversion in the allopolyploid A. suecica is photoperiod-dependent, and show that its frequency is correlated with the timing for the onset of flowering. Our results also suggest that floral reversion in A. suecica displays natural variation in its penetrance between geographic populations of A. suecica.

An activated unfolded protein response promotes retinal degeneration and triggers an inflammatory response in the mouse retina.

Recent studies on the endoplasmic reticulum stress have shown that the unfolded protein response (UPR) is involved in the pathogenesis of inherited retinal degeneration caused by mutant rhodopsin. However, the main question of whether UPR activation actually triggers retinal degeneration remains to be addressed. Thus, in this study, we created a mouse model for retinal degeneration caused by a persistently activated UPR to assess the physiological and morphological parameters associated with this disease state and to highlight a potential mechanism by which the UPR can promote retinal degeneration. We performed an intraocular injection in C57BL6 mice with a known unfolded protein response (UPR) inducer, tunicamycin (Tn) and examined animals by electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT) and histological analyses. We detected a significant loss of photoreceptor function (over 60%) and retinal structure (35%) 30 days post treatment. Analysis of retinal protein extracts demonstrated a significant upregulation of inflammatory markers including interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and IBA1. Similarly, we detected a strong inflammatory response in mice expressing either Ter349Glu or T17M rhodopsin (RHO). These mutant rhodopsin species induce severe retinal degeneration and T17M rhodopsin elicits UPR activation when expressed in mice. RNA and protein analysis revealed a significant upregulation of pro- and anti-inflammatory markers such as IL-1ß, IL-6, p65 nuclear factor kappa B (NF-kB) and MCP-1, as well as activation of F4/80 and IBA1 microglial markers in both the retinas expressing mutant rhodopsins. We then assessed if the Tn-induced inflammatory marker IL-1ß was capable of inducing retinal degeneration by injecting C57BL6 mice with a recombinant IL-1ß. We observed ~19% reduction in ERG a-wave amplitudes and a 29% loss of photoreceptor cells compared with control retinas, suggesting a potential link between pro-inflammatory cytokines and retinal pathophysiological effects. Our work demonstrates that in the context of an established animal model for ocular disease, the persistent activation of the UPR could be responsible for promoting retinal degeneration via the UPR-induced pro-inflammatory cytokine IL-1ß.

Allopolyploidization lays the foundation for evolution of distinct populations: evidence from analysis of synthetic Arabidopsis allohexaploids.

Polyploidization is an important mechanism for introducing diversity into a population and promoting evolutionary change. It is believed that most, if not all, angiosperms have undergone whole genome duplication events in their evolutionary history, which has led to changes in genome structure, gene regulation, and chromosome maintenance. Previous studies have shown that polyploidy can coincide with meiotic abnormalities and somatic cytogenetic mosaics in Arabidopsis allotetraploids, but it is unclear whether this phenomenon can contribute to novel diversity or act as a mechanism for speciation. In this study we tested the hypothesis that mosaic aneuploidy contributes to the formation of incipient diversity in neoallopolyploids. We generated a population of synthesized Arabidopsis allohexaploids and monitored karyotypic and phenotypic variation in this population over the first seven generations. We found evidence of sibling line-specific chromosome number variations and rapidly diverging phenotypes between lines, including flowering time, leaf shape, and pollen viability. Karyotypes varied between sibling lines and between cells within the same tissues. Cytotypic variation correlates with phenotypic novelty, and, unlike in allotetraploids, remains a major genomic destabilizing factor for at least the first seven generations. While it is still unclear whether new stable aneuploid lines will arise from these populations, our data are consistent with the notion that somatic aneuploidy, especially in higher level allopolyploids, can act as an evolutionary relevant mechanism to induce rapid variation not only during the initial allopolyploidization process but also for several subsequent generations. This process may lay the genetic foundation for multiple, rather than just a single, new species.

Exploring cultural drivers for wildlife trade via an ethnoprimatological approach: a case study of slender and slow lorises (Loris and Nycticebus) in South and Southeast Asia.

Illegal and unsustainable trade in wildlife is a major conservation challenge. For Asian primates, economic and cultural traditions, and increased forest access mean that trade may have become detrimental for certain species. Slow and slender lorises (Nycticebus and Loris) are primates particularly prevalent in trade, determined until now by focused counts of lorises in regional markets. Here, we use international trade statistics and a participant-observer approach to assess culturally specific drivers for trade in lorises in South and Southeast Asia, to provide a broader context to help mitigate this practice. Analysis of international records for the last 30 years revealed that live animal trade was more prevalent than trade in body parts (slow lorises, 86.4%; slender lorises, 91.4%), with Laos, Cambodia, and Thailand the largest exporters. We then examine drivers of international and domestic trade based on long-term data from 1994-2009 in Sri Lanka, Cambodia, and Indonesia. We show that slender lorises are important in Sri Lankan folklore, but their use as pets and for traditional medicine is rare. Trade in Bengal slow and pygmy lorises in Cambodia for use in traditional medicines, a practice with deeply historical roots, is widespread. Despite its own set of myths about the magical and curative properties of lorises, trade in Javan, Bornean, and greater slow lorises in Indonesia is largely for pets. Conservation practices in Asia are often generalized and linked with the region's major religions and economies. We show here that, in the case of wildlife trade, culturally specific patterns are evident among different ethnic groups, even within a country. Revealing such patterns is the foundation for developing conservation management plans for each species. We suggest some participatory methods for each country that may aid in this process.

Hypothetical fears and quantitative risk analysis.

Hypothetical fears are concepts, not quantities. Their conceptual nature makes impractical conventional quantitative risk analyses (QRA) based on benefit/cost/risk, so they become an unmeasured influence in national decision making. The decision process involves two steps, the Analytic Stage (QRA based) and the Priority Stage (resource allocation competition). This article suggests that a quantitative estimate of the social cost of fear reduction to acceptable levels be used as a surrogate QRA input to the Priority Stage.

Barriers to prostate cancer screening.

The revised prostate cancer screening guidelines of the American Cancer Society recommend that men be informed of the risks associated with prostate cancer screening. However, there are no published studies on men's fear of impotence and its impact on prostate cancer screening. In addition, little is known about barriers to prostate cancer screening when the two main barriers of cost and lack of knowledge are eliminated. This study reports the association between barriers and free prostate cancer screening after a prostate cancer education program. All men were called 1 month after a prostate cancer education program and asked: "What would (or did) make it hard for you to get your prostate checkup done?" A total postbarrier score was created to measure how many barriers each man indicated. The following barriers were significant in predicting participation in prostate cancer screening: "put it off," "doctor hours not convenient," "didn't know kind of doctor," "didn't know where to go," and "refuse to go." Fear of impotence was not a significant barrier. Suggestions for reducing barriers to prostate cancer screening are given.

Chemoenzymatic preparation of dermatan sulfate oligosaccharides as arylsulfatase B and alpha-L-iduronidase substrates.

Dermatan sulfate was partially depolymerized with chondroitin ABC lyase to obtain an oligosaccharide mixture from which an unsaturated disulfated tetrasaccharide was purified and characterized using nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. Chemical removal of the unsaturated uronate residue with mercuric acetate, followed by de-4-O-sulfation with arylsulfatase B (N-acetylgalactosamine 4-sulfatase) and N- acetylhexosaminidase catalyzed removal of the 2-acetamido-2-deoxy-D-galactospyranosyl residue at the non-reducing end afforded a monosulfated disaccharide of the structure alpha-L-idopyranosyluronic acid (1-->3)-alpha,beta-D-2-acetamido-2-deoxy-4-O-sulfo galactopyranose. This monosulfated disaccharide serves as a substrate for mammalian alpha-L-iduronidase as demonstrated using fluorophore assisted carbohydrate electrophoresis.

The ultimate uncertainty--intergenerational planning.

The philosophic and practical aspects of intergenerational planning for a 50-100-year time frame are reviewed, with recognition of its speculative quality. Society's near term choice of future physical pathways based on comparative quantitative benefit/cost/risk analyses of alternatives is usually modified by the intervention of a variety of time-dependent, nontechnical value systems. Further, the continuous competition among society's disparate technical systems, capital investment choices, and planning objectives all contribute to the uncertainty of the intergenerational outcome of any plan. Nevertheless, the quantitative planning process provides an essential base. Benefit/cost/risk projections are discussed for both the case with a historical database and the case without such a historical base. The end-objectives and continuous nature of such benefit/cost/risk analyses are described.

Metabolic and genetic determinants of HDL metabolism and hepatic lipase activity in normolipidemic females.

The metabolic and genetic determinants of HDL cholesterol (HDL-C) levels and HDL turnover were studied in 36 normolipidemic female subjects on a whole-food low-fat metabolic diet. Lipid, lipoprotein, and apolipoprotein levels, lipoprotein size, and apolipoprotein turnover parameters were determined, as were genetic variation at one site in the hepatic lipase promoter and six sites in the apolipoprotein AI/CIII/AIV gene cluster. Menopause had no significant effect on HDL-C or turnover. Stepwise multiple regression analysis revealed that HDL-C was most strongly correlated with HDL size, apolipoprotein A-II (apoA-II), and apolipoprotein A-I (apoA-I) levels, which together could account for 90% of the variation in HDL-C. HDL size was inversely correlated with triglycerides, body mass index, and hepatic lipase activity, which together accounted for 82% of the variation in HDL size. The hepatic lipase promoter genotype had a strong effect on hepatic lipase activity and could account for 38% of the variation in hepatic lipase activity. The apoA-I transport rate (AI-TR) was the major determinant of apoA-I levels, but AI-TR was not associated with six common genetic polymorphism in the apoAI/CIII/AIV gene cluster.A simplified model of HDL metabolism is proposed, in which A-I and apoA-II levels combined with triglycerides, and hepatic lipase activity could account for 80% of the variation in HDL-C.

Effect of methylene blue, indigo carmine, and Renografin on human sperm motility.

OBJECTIVES: To evaluate the effect of commonly used intraoperative vasography and tissue staining agents, indigo carmine, methylene blue, and Renografin, on sperm motility. METHODS: Semen from 20 healthy men was obtained after 2 to 4 days of abstinence. Sperm motility was initially evaluated in each specimen. Standard solutions of indigo carmine, methylene blue, and Renografin-60 were diluted 2x and 4x with lactated Ringer's solution. Equal aliquots of sperm were mixed with undiluted and diluted drugs, and sperm motility was assessed. RESULTS: Initial mean sperm motility was 70.3%+/-3.0%. Undiluted methylene blue and Renografin severely depressed sperm motility to 1.1%+/-0.5% and 2.3%+/-0.7%, respectively (P <0.05). Diluted methylene blue depressed motility to 4.9%+/-1.8% and 11.2%+/-3.0% (P < 0.05). Diluted Renografin depressed motility to 25.1%+/-4.1% and 55.3%+/-3.3% (P < 0.05). Although undiluted and 2x-diluted indigo carmine moderately decreased sperm motility (48.9%+/-3.2% and 61.7%+/-3.0%, P < 0.05), 4x-diluted indigo carmine had minimal effect on sperm motility (67.3%+/-2.8%, P > 0.05). Lactated Ringer's solution had no effect on sperm motility. CONCLUSIONS: We found a severe, immediate reduction in sperm motility after exposure to undiluted standard solutions of methylene blue and Renografin. Dilution of Renografin significantly decreased its negative impact on the sperm motility, whereas the adverse effect of methylene blue remained fairly constant even with increasing dilution. Sperm motility should be assessed prior to application of these agents. Sperm should be aspirated for immediate use and/or cryopreservation prior to the use of these agents. Indigo carmine may be safely used as a tissue stain or vasography agent with a minimal effect on sperm motility in dilutions of 4x and higher.

Direct measurement of unfractionated heparin using a biochemical assay.

A number of investigations have noted that functional biological assays for heparin are not always reliable and may not reflect the actual biochemical level of heparin in patients receiving anticoagulant therapy. This creates the possibility that patients receiving anticoagulant treatment may have an excess or deficiency of circulating levels of heparin. To address this problem, we have developed a direct biochemical measurement of heparin. The heparin assay uses fluorophore-assisted carbohydrate electrophoresis (FACE) to directly measure the predominate disaccharide of unfractionated heparin. In this study, unfractionated heparin was measured in vitro throughout a wide range of heparin concentrations in plasma. Seven in vivo pharmacokinetic studies in five normal subjects given 3,000 USP units of unfractionated heparin intravenously showed a three-phase elimination process with higher peak plasma levels and shorter elimination times than predicted from previous studies. At these doses, heparin is largely eliminated intact through urinary excretion. Body weight has a significant effect on heparin kinetics. When we compared the direct biochemical assay with two biological clotting assays, we found the latter can overestimate biochemical heparin concentrations. The FACE assay, due to its sensitivity, is also able to measure circulating levels of endogenous heparin in plasma and urine. Direct heparin measurement using the FACE technique is practical and useful for studies of the correlation of biochemical and biological activities.

Determining when to refer periodontal patients--clinical guidelines.

As part of the examination and evaluation of the patient, it is the dentist's responsibility to evaluate the periodontal tissues for the presence or absence of periodontal disease. If the practitioner finds that periodontal disease is present and is unwilling or unable to accurately diagnose and/or treat the type or extent of the disease, the dentist must offer the patient the opportunity to be evaluated by a practitioner who can complete the examination and diagnostic process.