Prevalence and Predictors of Sub-Acute Phase Disability after Injury among Hospitalised and Non-Hospitalised Groups: A Longitudinal Cohort Study

Introduction

To reduce the burden on injury survivors and their supporters, factors associated with poor outcomes need to be identified so that timely post-injury interventions can be implemented. To date, few studies have investigated outcomes for both those who were hospitalised and those who were not.

Aim

To describe the prevalence and to identify pre-injury and injury-related predictors of disability among hospitalised and non-hospitalised people, three months after injury.

Methods

Participants in the Prospective Outcomes of Injury Study were aged 18–64 years and on an injury entitlement claims register with New Zealand''s no-fault injury compensation insurer, following referral by healthcare professionals. A wide range of pre-injury demographic, health and injury-related characteristics were collected at interview. Participants were categorised as ‘hospitalised’ if they were placed on New Zealand''s National Minimum Data Set within seven days of the injury event. Injury severity scores (NISS) and 12 injury categories were derived from ICD-10 codes. WHODAS assessed disability. Multivariable analyses examined relationships between explanatory variables and disability.

Results

Of 2856 participants, 2752 (96%) had WHODAS scores available for multivariable analysis; 673 were hospitalised; 2079 were not. Disability was highly prevalent among hospitalised (53.6%) and non-hospitalised (39.4%) participants, three-months after injury. In both groups, pre-injury disability, obesity and higher injury severity were associated with increased odds of post-injury disability. A range of other factors were associated with disability in only one group: e.g. female, ≥2 chronic conditions and leg fracture among hospitalised; aged 35–54 years, trouble accessing healthcare, spine or lower extremity sprains/dislocations and assault among non-hospitalised.

Significance

Disability was highly prevalent among both groups yet, with a few exceptions, factors associated with disability were not common to both groups. Where possible, including a range of injured people in studies, hospitalised and not, will increase understanding of the burden of disability in the sub-acute phase.     

Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease

To date, no suitable vaccine or specific antiviral drug is available to treat Chikungunya viral (CHIKV) fever. Hence, it is essential to identify drug candidates that could potentially impede CHIKV infection. Here, we present the development of a homology model of nsP2 protein based on the crystal structure of the nsP2 protein of Venezuelan equine encephalitis virus (VEEV). The protein modeled was optimized using molecular dynamics simulation; the junction peptides of a nonstructural protein complex were then docked in order to investigate the possible protein–protein interactions between nsP2 and the proteins cleaved by nsP2. The modeling studies conducted shed light on the binding modes, and the critical interactions with the peptides provide insight into the chemical features needed to inhibit the CHIK virus infection. Energy-optimized pharmacophore mapping was performed using the junction peptides. Based on the results, we propose the pharmacophore features that must be present in an inhibitor of nsP2 protease. The resulting pharmacophore model contained an aromatic ring, a hydrophobic and three hydrogen-bond donor sites. Using these pharmacophore features, we screened a large public library of compounds (Asinex, Maybridge, TOSLab, Binding Database) to find a potential ligand that could inhibit the nsP2 protein. The compounds that yielded a fitness score of more than 1.0 were further subjected to Glide HTVS and Glide XP. Here, we report the best four compounds based on their docking scores; these compounds have IDs of 27943, 21362, ASN 01107557 and ASN 01541696. We propose that these compounds could bind to the active site of nsP2 protease and inhibit this enzyme. Furthermore, the backbone structural scaffolds of these four lead compounds could serve as building blocks when designing drug-like molecules for the treatment of Chikungunya viral fever.     

Purinergic receptors in gastrointestinal inflammation

Purinergic receptors comprise a family of transmembrane receptors that are activated by extracellular nucleosides and nucleotides. The two major classes of purinergic receptors, P1 and P2, are expressed widely in the gastrointestinal tract as well as immune cells. The purinergic receptors serve a variety of functions from acting as neurotransmitters, to autocoid and paracrine signaling, to cell activation and immune response. Nucleosides and nucleotide agonist of purinergic receptors are released by many cell types in response to specific physiological signals, and their levels are increased during inflammation. In the past decade, the advent of genetic knockout mice and the development of highly potent and selective agonists and antagonists for the purinergic receptors have significantly advanced the understanding of purinergic receptor signaling in health and inflammation. In fact, agonist/antagonists of purinergic receptors are emerging as therapeutic modalities to treat intestinal inflammation. In this article, the distribution of the purinergic receptors in the gastrointestinal tract and their physiological and pathophysiological role in intestinal inflammation will be reviewed.     

Induction of allergen-specific IgE and IgG responses by anti-idiotypic antibodies

In order to explore idiotypic, anti-idiotypic, and anti-anti-idiotypic responses to allergens, BALB/c mice were immunized with affinity-purified human idiotypic antibodies directed against a highly purified shrimp allergen. This resulted in the production of anti-idiotypic antibodies which were quantitated by using rabbit idiotypic antibodies raised against the same purified allergen. The mouse anti-idiotypic antibodies recognized shrimp-specific human idiotypic antibodies of the IgE isotype from 18 of 20 individuals, and IgG antibodies from 14 of 20 shrimp-sensitive patients. Immunization of BALB/c mice with affinity-purified, allergen-specific anti-idiotypic antibodies induced anti-allergen IgE and IgG responses in the absence of the allergen. This paper thus presents evidence that anti-idiotypic antibodies raised against allergen-specific idiotypic antibodies may substitute for the original allergen in the induction of allergen-specific idiotypic antibodies. The demonstration of shared idiotopes on IgG and IgE antibodies in the sera of shrimp-sensitive patients supports the use of allergen-specific anti-idiotypic antibodies as surrogate allergens.     

Alteration of DMBA-induced oxidative stress by additive action of a modified indigenous preparation--Kalpaamruthaa

The present study investigated the protective efficacy of the novel preparation named as Kalpaamruthaa (KA, includes Semecarpus anacardium Linn nut milk extract (SA), dried powder of Phyllanthus emblica fruit and honey) on the peroxidative damage and abnormal antioxidant levels in the hepatic mitochondrial fraction of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma rats. Female Sprague-Dawley rats of weight 180+/-10 g were categorized into six groups. Three groups were administered DMBA (25 mg/rat dissolved in olive oil, orally) to induce mammary carcinoma. One of these groups received KA treatment (300 mg/kg b.wt., orally) and other group received SA (200 mg/kg b.wt., orally) for 14 days after 90 days of DMBA induction. Vehicle-treated control and drug control groups were also included. The hepatic mitochondrial fraction of untreated DMBA rats showed 2.96-fold increase in MDA content when compared to control rats and abnormal changes in the activities/levels of mitochondrial enzymic (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzymic (glutathione, vitamin C and vitamin E) antioxidants were observed. DMBA-treated rats also showed decline in the activities of mitochondrial enzymes such as succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase. In contrast, rats treated with SA and KA showed normal lipid peroxidation antioxidant defenses and mitochondrial enzymes, thereby showing the protection rendered by SA and KA. Although, KA treatment exhibited more profound effect in inhibiting DMBA-induced oxidative stress than sole SA treatment. Results of the study indicate that the anticarcinogenic activity of KA during DMBA-initiated mammary carcinogenesis is mediated through alteration of hepatic antioxidant status as well as modulation of TCA cycle enzymes. On the basis of the observed results, KA can be considered as a readily accessible, promising and novel cancer chemopreventive agent.     

Chromium binding Bacillus cereus VITSH1—a promising candidate for heavy metal clean up

Bacteria survive metal stress by several mechanisms and metal binding is one such mechanism which has been screened in the present study to investigate the survival strategies of metal resistant bacteria. The production of siderophores, a metal chelating agent, was detected by chrome azurol S agar assay. The changes in cell wall studied by analysing the peptidoglycan and teichoic acid content indicated an increase in the cell wall content. Evaluation of morphological and physiological alterations like cell size, granularity analysed by SEM and flow cytometry analysis revealed an increase in cell size and granularity respectively. The transformation of phosphates monitored by ³¹P NMR analysis indicated the presence of inorganic phosphate. Based on the cell wall changes and the ³¹P NMR analysis, the surface charge of the organism was studied by zeta potential which displayed a difference at pH7.     

Vibriostatic effects of probiotic Bacillus licheniformis Dahb1 and its molecular phylogeny resolved through RAPD markers

The in vitro vibriostatic effects of probiotic Bacillus licheniformis strains (Dahb1 to Dahb7) from both wild and commercial sources were evaluated against pathogenic Vibrios isolated from shrimp hatcheries and farms. Agar antagonism assay results showed that, out of seven B. licheniformis strains, strain Dahb1 showed the biggest inhibitory zone (6–12 mm) tested against 162 isolates of Vibrio spp. viz., V. harveyi (53 isolates), V. anguillarum (42 isolates), V. vulnificus (31 isolates) and Photobacterium damselae ssp. damselae (36 isolates) obtained from Penaeus monodon culture hatcheries and ponds. The genetic status of these seven strains were analyzed through randomly amplified polymorphic DNA analysis using 18 random primers. Of the 18 primers studied, only 6 generated repeatable polymorphic DNA bands with sizes ranging from 250 to 1,000 bp in seven isolates of B. licheniformis. The dendrogram generated from resolved gel profiles showed two major branches with three clusters. The results of the present study allow us to conclude that B. licheniformis Dahb1 can be used as an effective probiotic to control Vibrios. Field studies are needed to evaluate probiotic efficiency to control diseases in aquatic organisms.