Clinical vignette: Zero in 60 in 48 hours

Cirrhosis is a known cause of thrombocytopenia but it is important to consider other etiologies when the degree of thrombocytopenia is severe, especially in light of impending life-threatening bleeding. One must always maintain a low threshold for additional diagnostic entities when patients present acutely and confirmatory testing reveals profound thrombocytopenia. A 34-year-old man with cirrhosis secondary to Hepatitis C and alcohol abuse presented with persistent bleeding from preexisting oral ulcers and hematuria. Patient denied melena, hematemesis or hematochezia. His past medical history was significant for pancytopenia secondary to cirrhosis, active hepatitis C infection and hypersplenism. He denied any recent change in his medications nor taking any herbal medications or supplements. Vital signs were normal on admission. Physical examination was positive for dried blood on the lips and hepatosplenomegaly. Lab work revealed a platelet count of 0 with chronic leukopenia and anemia. His baseline platelet count is approximately 35,000. Urine analysis indicated gross blood. Coagulation workup was not suggestive of Disseminated Intravascular Coagulation (DIC). Peripheral smear was significant for complete lack of platelets without schistocytes. He was started on daily platelet transfusions with minimal change in his platelet count. A diagnosis of secondary Immune Thrombocytopenic Purpura (ITP) was made and therapy was initiated with intravenous immunoglobulin (IVIG) and dexamethasone. His platelet count failed to improve with worsening hematuria. He also received Rituximab, Romiplostim infusions and high dose methylprednisolone. The patient underwent splenic artery embolization three times. In spite of all efforts he continued to have hematuria and bleeding from intravenous lines with only transient rise in counts. He was taken for laparoscopic splenectomy with a platelet count of 35,000; following which the bleeding subsided and his platelet count improved to 100,000. Patient had a complicated hospital course but was eventually discharged home and currently his platelet counts are within normal limits. This patient appeared to have developed secondary ITP from his active Hepatitis C. Though he had chronic thrombocytopenia from cirrhosis and splenomegaly, it would be unusual to see this degree of platelet drop from these causes alone. ITP is a diagnosis of exclusion and bleeding is usually not proportionate to level of thrombocytopenia as in this patient. This case illustrates the fact that a clinician must have a low threshold for expanding the differential diagnosis of thrombocytopenia, especially diagnoses that are likely to harm the patient such as Thrombotic Thrombocytopenic Purpura, Disseminated Intravascular Coagulation and ITP. This case also demonstrates the challenging nature of managing severe refractory ITP. Splenectomy is the preferred therapy for patients with ITP who are refractory to first-line therapy with glucocorticoids or IVIG and is shown to cause sustained remission in two-thirds of patients

Pollution Load Allocation on Water Pollution Control in the Citarum River

The Citarum River is a strategic river in Indonesia, but has poor water quality.  The existing pollution control program has no impact on the river's water quality, because it uses a regulatory approach and prioritizes industrial sources. To improve the quality of the river, every pollutant source needs to reduce the pollution load discharged into the river based on the ability of the river to receive pollution. The purpose of this study was to measure pollution load allocation based on the total maximum daily load (TMDL) of the river. The results show that non-point sources contribute the highest pollution load (85%) compared with point sources (15%). The results of the measurement of pollution load allocation showed that the highest contribution of pollution load was from domestic waste (83.5%), followed by industrial waste (6.6%). The target of pollution load reduction for domestic sources is 81.8%, and for industries is 79.5%. The improvement of river water quality should be started at tributaries and domestic sources. This study can be used by local governments to develop water pollution control programs, for instance as a basis for determining the wastewater discharge permit of pollutant sources and permit trading

Mytilus galloprovincialis Myticin C: A Chemotactic Molecule with Antiviral Activity and Immunoregulatory Properties

Previous research has shown that an antimicrobial peptide (AMP) of the myticin class C (Myt C) is the most abundantly expressed gene in cDNA and suppressive subtractive hybridization (SSH) libraries after immune stimulation of mussel Mytilus galloprovincialis. However, to date, the expression pattern, the antimicrobial activities and the immunomodulatory properties of the Myt C peptide have not been determined. In contrast, it is known that Myt C mRNA presents an unusual and high level of polymorphism of unidentified biological significance. Therefore, to provide a better understanding of the features of this interesting molecule, we have investigated its function using four different cloned and expressed variants of Myt C cDNA and polyclonal anti-Myt C sera. The in vivo results suggest that this AMP, mainly present in hemocytes, could be acting as an immune system modulator molecule because its overexpression was able to alter the expression of mussel immune-related genes (as the antimicrobial peptides Myticin B and Mytilin B, the C1q domain-containing protein MgC1q, and lysozyme). Moreover, the in vitro results indicate that Myt C peptides have antimicrobial and chemotactic properties. Their recombinant expression in a fish cell line conferred protection against two different fish viruses (enveloped and non-enveloped). Cell extracts from Myt C expressing fish cells were also able to attract hemocytes. All together, these results suggest that Myt C should be considered not only as an AMP but also as the first chemokine/cytokine-like molecule identified in bivalves and one of the few examples in all of the invertebrates

Will all scientists working on snails and the diseases they transmit please stand up?

Copyright © 2012 Adema et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.No abstract available

Study of water supply & sanitation practices in India using geographic information systems: some design & other considerations in a village setting

Background & objectives: Availability of clean water and adequate sanitation facilities are of prime importance for limiting diarrhoeal diseases. We examined the water and sanitation facilities of a village in southern India using geographic information system (GIS) tools. Methods: Places of residence, water storage and distribution, sewage and places where people in the village defaecated were mapped and drinking water sources were tested for microbial contamination in Nelvoy village, Vellore district, Tamil Nadu. Results: Water in the village was found to be microbiologically unfit for consumption. Analysis using direct observations supplemented by GIS maps revealed poor planning, poor engineering design and lack of policing of the water distribution system causing possible contamination of drinking water from sewage at multiple sites. Interpretation & conclusions: Until appropriate engineering designs for water supply and sewage disposal to suit individual village needs are made available, point-of-use water disinfection methods could serve as an interim solution

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Controlled Chaos of Polymorphic Mucins in a Metazoan Parasite (Schistosoma mansoni) Interacting with Its Invertebrate Host (Biomphalaria glabrata)

Invertebrates were long thought to possess only a simple, effective and hence non-adaptive defence system against microbial and parasitic attacks. However, recent studies have shown that invertebrate immunity also relies on immune receptors that diversify (e.g. in echinoderms, insects and mollusks (Biomphalaria glabrata)). Apparently, individual or population-based polymorphism-generating mechanisms exists that permit the survival of invertebrate species exposed to parasites. Consequently, the generally accepted arms race hypothesis predicts that molecular diversity and polymorphism also exist in parasites of invertebrates. We investigated the diversity and polymorphism of parasite molecules (Schistosoma mansoni Polymorphic Mucins, SmPoMucs) that are key factors for the compatibility of schistosomes interacting with their host, the mollusc Biomphalaria glabrata. We have elucidated the complex cascade of mechanisms acting both at the genomic level and during expression that confer polymorphism to SmPoMuc. We show that SmPoMuc is coded by a multi-gene family whose members frequently recombine. We show that these genes are transcribed in an individual-specific manner, and that for each gene, multiple splice variants exist. Finally, we reveal the impact of this polymorphism on the SmPoMuc glycosylation status. Our data support the view that S. mansoni has evolved a complex hierarchical system that efficiently generates a high degree of polymorphism—a “controlled chaos”—based on a relatively low number of genes. This contrasts with protozoan parasites that generate antigenic variation from large sets of genes such as Trypanosoma cruzi, Trypanosoma brucei and Plasmodium falciparum. Our data support the view that the interaction between parasites and their invertebrate hosts are far more complex than previously thought. While most studies in this matter have focused on invertebrate host diversification, we clearly show that diversifying mechanisms also exist on the parasite side of the interaction. Our findings shed new light on how and why invertebrate immunity develops

Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections

Copyright: © 2013 Baron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by ANR (ANR-07-BLAN-0214 and ANR-12-EMMA-00O7-01), CNRS and INRA. PvW was financially supported by the BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Thermal Stress Triggers Broad Pocillopora damicornis Transcriptomic Remodeling, while Vibrio coralliilyticus Infection Induces a More Targeted Immuno-Suppression Response

Global change and its associated temperature increase has directly or indirectly changed the distributions of hosts and pathogens, and has affected host immunity, pathogen virulence and growth rates. This has resulted in increased disease in natural plant and animal populations worldwide, including scleractinian corals. While the effects of temperature increase on immunity and pathogen virulence have been clearly identified, their interaction, synergy and relative weight during pathogenesis remain poorly documented. We investigated these phenomena in the interaction between the coral Pocillopora damicornis and the bacterium Vibrio coralliilyticus, for which the infection process is temperature-dependent. We developed an experimental model that enabled unraveling the effects of thermal stress, and virulence vs. non-virulence of the bacterium. The physiological impacts of various treatments were quantified at the transcriptome level using a combination of RNA sequencing and targeted approaches. The results showed that thermal stress triggered a general weakening of the coral, making it more prone to infection, non-virulent bacterium induced an ‘efficient’ immune response, whereas virulent bacterium caused immuno-suppression in its host