General Practice Observed: The Distress of Dying

A simple method of recording the distress of dying patients is described. Significant differences occurred between deaths at home and in hospital for three factors. Patients dying at home were (a) more likely to be fully alert shortly before death (P < 0·05); (b) less likely to be suffering from vomiting, incontinence, or bedsores (P < 0·001); and (c) less likely to have unrelieved physical distress (P < 0·05). No significant differences occurred in the distress of patients dying in general-practitioner compared with other hospitals, though the numbers compared were small and a larger study might prove useful.     

The Predictive Diagnostic Value of Serial Daily Bedside Ultrasonography for Severe Dengue in Indonesian Adults

Background

Identification of dengue patients at risk for progressing to severe disease is difficult. Significant plasma leakage is a hallmark of severe dengue infection which can suddenly lead to hypovolemic shock around the time of defervescence. We hypothesized that the detection of subclinical plasma leakage may identify those at risk for severe dengue. The aim of the study was to determine the predictive diagnostic value of serial ultrasonography for severe dengue.

Methodology/Principal Findings

Daily bedside ultrasounds were performed with a handheld ultrasound device in a prospective cohort of adult Indonesians with dengue. Timing, localization and relation to dengue severity of the ultrasonography findings were determined, as well as the relation with serial hematocrit and albumin values. The severity of dengue was retrospectively determined by WHO 2009 criteria. A total of 66 patients with proven dengue infection were included in the study of whom 11 developed severe dengue. Presence of subclinical plasma leakage at enrollment had a positive predictive value of 35% and a negative predictive value of 90% for severe dengue. At enrollment, 55% of severe dengue cases already had subclinical plasma leakage, which increased to 91% during the subsequent days. Gallbladder wall edema was more pronounced in severe than in non-severe dengue patients and often preceded ascites/pleural effusion. Serial hematocrit and albumin measurements failed to identify plasma leakage and patients at risk for severe dengue.

Conclusions/Significance

Serial ultrasonography, in contrast to existing markers such as hematocrit, may better identify patients at risk for development of severe dengue. Patients with evidence of subclinical plasma leakage and/or an edematous gallbladder wall by ultrasonography merit intensive monitoring for development of complications.     

Impact of Six Rounds of Mass Drug Administration on Brugian Filariasis and Soil-Transmitted Helminth Infections in Eastern Indonesia

Background

The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA).

Methodology/Principal Findings

We evaluated the effect of MDA using DEC and albendazole on B. timori and soil transmitted helminths (STH) in a cross-sectional study of a sentinel village on Alor Island annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was 26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34 months after the 6^th round of MDA, MF and antibody rates were only 0.17% and 6.4%, respectively. The MDA campaign had also a beneficial effect on STH. Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and 11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the 5^th round of MDA. Unfortunately, STH rates rebounded 34 months after cessation of MDA and approached pre-MDA rates. However, the intensity of STH infection in 2009 was still reduced, and no heavy infections were detected.

Conclusions/Significance

MDA with DEC/albendazole has had a major impact on B. timori MF and IgG4 antibody rates, providing a proof of principle that elimination is feasible. We also documented the value of annual DEC/albendazole as a mass de-worming intervention and the importance of continuing some form of STH control after cessation of MDA for filariasis.     

Photoresponse ontogeny and its relation to development of pineal organ and eye in larval bagrid catfish Mystus nemurus (Valenciennes)

The artificially reared bagrid catfish Mystus nemurus was observed for the histological development of the pineal organ and retina and photoresponse in a test tank at hatching to 14?d after hatching. The pineal organ was functional at hatching, and the lens-like tissue was partly ossified forming a pineal window at 6?d. The retina became morphologically functional when the outer segments of single cones were formed, and the eyes were innervated with the optic tectum at 18?h and rods were formed at 36?h. Long and thin single cones were not observed. The larvae exhibited undirected kinetic movement at hatching to 12?h and directed tactic swimming away from a torch after 18?h in response to a torch light. The photoresponse of the larvae was negative at hatching to 30?h and at 6?d to the end of the observation at 14?d, but neutral during a period at 36?h to 5?d. It was evident that the kinetic movement was mediated by light perception with the pineal organ, which was not capable of detecting directed signal information, and that the larvae were capable of directed tactic movement only when vision was involved. The vigorous negative phototaxis at 6–14?d was attributed to the improvement of photosensitivity of the retina and the pineal organ.     

Identification of bioactive metabolites against adenosine A1 receptor using NMR-based metabolomics

Marine sponges are relatively less explored for their chemical features but highly anticipated resource for bioactive compounds. In this paper we report the screening of marine sponges crude extracts for their potential to bind the adenosine A1 receptor. Many samples showed very promising activity and in order to identify the active components, a metabolomics-chemometrics approach is employed. Nuclear magnetic resonance spectroscopy is used for the metabolic profiling of the marine sponges and partial least squares (PLS) and orthogonal PLS (OPLS) algorithms are used to correlate the metabolomics with bioactivity data. Using several two dimensional-NMR techniques, the resonances responsible for the separation of high activity samples from the medium and low activity samples were identified as associated to metabolites like halisulfate 1, halisulfate 3–5, and suvanine (1–5), all belongs to sesterterpenes class. The reference compounds for these metabolites are also tested for the activity, which endorse the findings of the applied methodology.     

N-Acetylfarnesylcysteine is a novel class of peroxisome proliferator-activated receptor γ ligand with partial and full agonist activity in vitro and in vivo

The thiazolidedione (TZD) class of drugs is clinically approved for the treatment of type 2 diabetes. The therapeutic actions of TZDs are mediated via activation of peroxisome proliferator-activated receptor γ (PPARγ). Despite their widespread use, concern exists regarding the safety of currently used TZDs. This has prompted the development of selective PPARγ modulators (SPPARMs), compounds that promote glucose homeostasis but with reduced side effects due to partial PPARγ agonism. However, this also results in partial agonism with respect to PPARγ target genes promoting glucose homeostasis. Using a gene expression-based screening approach we identified N-acetylfarnesylcysteine (AFC) as both a full and partial agonist depending on the PPARγ target gene (differential SPPARM). AFC activated PPARγ as effectively as rosiglitazone with regard to Adrp, Angptl4, and AdipoQ, but was a partial agonist of aP2, a PPARγ target gene associated with increased adiposity. Induction of adipogenesis by AFC was also attenuated compared with rosiglitazone. Reporter, ligand binding assays, and dynamic modeling demonstrate that AFC binds and activates PPARγ in a unique manner compared with other PPARγ ligands. Importantly, treatment of mice with AFC improved glucose tolerance similar to rosiglitazone, but AFC did not promote weight gain to the same extent. Finally, AFC had effects on adipose tissue remodeling similar to those of rosiglitazone and had enhanced antiinflammatory effects. In conclusion, we describe a new approach for the identification of differential SPPARMs and have identified AFC as a novel class of PPARγ ligand with both full and partial agonist activity in vitro and in vivo.     

Chromium accumulation in soil,water and forage samples in automobile emission area

Environmental contamination caused by various pollutants due to automobile emissions is an alarming issue. One important type of the pollutants are heavy metals, including chromium (Cr) added by the exhaust of toxic smoke of vehicles. These pollutants are added to forage crops cultivated near roadsides, soil and irrigation water. However, rare studies have been conducted to infer Cr accumulation near heavy automobile emission areas. This study was conducted to determine Cr concentration in irrigation water, soil and forage. Water, forage and soil samples were collected from area impacted by heavy traffic. Atomic absorption spectrophotometer was used to appraise Cr values in the collected samples. Chromium values ranged from 0.50 to 1.14 mg/kg in water samples and from 0.04 to 2.23 mg/kg in soil samples. It was highest in Zea mays grown soil, whereas minimum in Brassica campestris soil. The Cr values in forages ranged from 0.09 to 1.06 mg/kg. Z. mays observed the highest Cr accumulation, whereas the lowest Cr accrual was noted for B. campestris. The pollution load index (PLI) was the highest for Trifolium alexandrinum, while the lowest for Z. mays. Bio-concentration factor (BCF) ranged from 0.14 to 8.63. The highest BCF was noted for T. alexandrinum, while the lowest for Z. mays. The highest and the lowest daily intake of metal (DIM) was noted for Z. mays at different sites. Health risk index (HRI) was highest for Z. mays and lowest for B. campestris. The results add valuable information on heavy metal accumulation in water, soil and forage samples near to automobile emission area.     

The sticky tasty: the nutritional content of the exudativorous diet of the Javan slow loris in a lowland forest

Primates - Plant exudates are an important food source for many primates. The Critically Endangered Javan slow loris (Nycticebus javanicus) was previously found to prefer Acacia decurrens exudate...