The impact of an oral rehydration clinical pathway in a paediatric emergency department

OBJECTIVE:

To measure the impact of implementing an oral rehydration clinical pathway for children with mild to moderate dehydration from gastroenteritis in the paediatric emergency department (ED) on the indicators of health care utilization.

METHODS:

ED charts of children, six months to 17 years of age, meeting the criteria for the oral rehydration clinical pathway were reviewed. There were three 12-month periods of data collection: pre-implementation, transition and postimplementation. The clinical pathway consisted of a standard nursing assessment form and instructions on oral rehydration to be initiated and maintained by caregivers while waiting to see a physician. The primary outcome measure was ED length of visit (LOV) for children treated using the clinical pathway. This was compared with LOV for all other ED visits during the study periods to highlight the effect of the clinical pathway implementation. Secondary outcome measures included rate of intravenous rehydration, unscheduled return visits to the ED and hospital admission.

RESULTS:

During the three data collection periods, 11,816 children met the eligibility criteria. A decrease in the mean LOV of 24 min (95% CI 17 to 31) was observed, as well as a trivial decrease in the rate of intravenous rehydration therapy (14.6% to 12%) with implementation of the clinical pathway.

CONCLUSION:

The implementation of an oral rehydration clinical pathway in the ED led to a modest reduction in the ED LOV.     

Protective immunity to H7N9 influenza viruses elicited by synthetic DNA vaccine

Despite an intensive vaccine program influenza infections remain a major health problem, due to the viruses’ ability to change its envelope glycoprotein hemagglutinin (HA), through shift and drift, permitting influenza to escape protection induced by current vaccines or natural immunity. Recently a new variant, H7N9, has emerged in China causing global concern. First, there have been more than 130 laboratory-confirmed human infections resulting in an alarmingly high death rate (32.3%). Second, genetic changes found in H7N9 appear to be associated with enabling avian influenza viruses to spread more effectively in mammals, thus transmitting infections on a larger scale. Currently, no vaccines or drugs are effectively able to target H7N9. Here, we report the rapid development of a synthetic consensus DNA vaccine (pH7HA) to elicit potent protective immunity against the H7N9 viruses. We show that pH7HA induces broad antibody responses that bind to divergent HAs from multiple new members of the H7N9 family. These antibody responses result in high-titer HAI against H7N9. Simultaneously, this vaccine induces potent polyfunctional effector CD4 and CD8T cell memory responses. Animals vaccinated with pH7HA are completely protected from H7N9 virus infection and any morbidity associated with lethal challenge. This study establishes that this synthetic consensus DNA vaccine represents a new tool for targeting emerging infection, and more importantly, its design, testing and development into seed stock for vaccine production in a few days in the pandemic setting has significant implications for the rapid deployment of vaccines protecting against emerging infectious diseases.     

Downregulation of MMP-2 and -9 by proteasome inhibition: a possible mechanism to decrease LEC migration and prevent posterior capsular opacification

PURPOSE: The proliferation, epithelial-mesenchymal transition (EMT), and migration of residual lens epithelial cells (LECs) after cataract surgery leads to the development of posterior capsular opacification (PCO). The authors have shown that proteasome inhibition suppresses LEC proliferation and EMT. The present study investigates the prevention of LEC migration by proteasome inhibition through the suppression of matrix metalloproteinase (MMP) expression and activity. METHODS: HLE B-3 and primary human LEC migration assays were performed using polycarbonate membrane inserts and 20% fetal bovine serum (FBS) as chemoattractant. Cultured cells were treated with 1 ng TGF-beta(2), with or without MG132 (proteasome inhibitor) or GM 6001 (MMP inhibitor). Capsular bags with intraocular lenses (IOLs) were prepared from human donor eyes and cultured in serum-free DMEM. The capsular bags were then treated with 1 or 10 ng/mL TGF-beta(2), with or without MG132 (2.5 or 10 muM, respectively). The medium was sampled and replaced every 2 days and analyzed for MMP-2 and -9 activities by SDS-PAGE zymography. Protein and RNA expression were analyzed by Western blotting and RT-PCR, respectively. RESULTS: Proteasome inhibition blocks LEC migration in HLE B-3 and primary human LECs. To further evaluate the mechanism of decrease in LEC migration by proteasome inhibition, the authors measured MMP-2 mRNA and protein expression and MMP-2 and -9 activities. In HLE B-3 cells, TGF-beta(2) increased MMP-2 mRNA and protein levels; these increases were inhibited by MG132 cotreatment. Medium from HLE B-3 cultures showed MMP-2 and -9 activities, which were induced by TGF-beta(2) treatment and inhibited by MG132 co-treatment. TGF-beta(2) treatment also increased MMP-2 and -9 activities in IOL capsular bag cultures; these were progressively decreased by proteasome inhibition. CONCLUSIONS: Proteasome inhibition decreases LEC migration. This inhibition is correlated with decreased MMP-2 and -9 activities, observed both with and without TGF-beta(2) treatment. These findings support proteasome inhibition as a therapeutic strategy to prevent PCO.     

Comparison of vitreoretinal disorders in fellow eyes of lamellar macular holes versus epiretinal membrane foveoschisis

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate and compare the rate and characteristics of vitreoretinal disorders in fellow eyes of lamellar macular holes (LMH)...     

Some nutritional properties of the seeds of three Mucuna species

The seeds of Mucuna nivea, M. pruriens and M. utilis showed ash 4.3-5.1%, oil 4.9-5.5%, protein 25.9-27.5%, L-dopa 3.6-4.2%, trypsin 28.5-39.7 mg/g and chymotrypsin inhibitor activity 19.3-24.6 mg/g. The trypsin and chymotrypsin inhibitor activity increased in pod hull and seeds while the amount of protein increased in seeds and decreased in pod hull with maturity. The essential amino acid profile was comparable to the FAO pattern (lysine 6.0-6.4%). The fatty acid composition had total unsaturated acids 51.9-55.9%, but were poor in oil contents.     

Relationship between mobility, violence and HIV/STI among female sex workers in Andhra Pradesh, India

ABSTRACT: BACKGROUND: Violence and mobility have been identified as critical factors contributing to the spread of HIV worldwide. This study aimed to assess the independent and combined associations of mobility and violence with sexual risk behaviors and HIV, STI prevalence among female sex workers (FSWs) in India. METHODS: Data were drawn from a cross-sectional, bio-behavioral survey conducted among 2042 FSWs across five districts of southern India in 2005--06. Regression models were used to estimate odds ratios and 95% confidence intervals (CIs) for sexual risk behaviors and HIV infection based on experience of violence and mobility after adjusting for socio-demographic and sex work related characteristics. RESULTS: One-fifth of FSWs (19%) reported experiencing violence; 68% reported travelling outside their current place of residence at least once in the past year and practicing sex work during their visit. Mobile FSWs were more likely to report violence compared to their counterparts (23% vs. 10%, p < 0.001). Approximately 1 in 5 tested positive for HIV. In adjusted models, FSWs reporting both mobility and violence as compared to their counterparts were more likely to be infected with HIV (Adjusted odds ratio (adjusted OR): 2.07, 95% CI: 1.42--3.03) and to report unprotected sex with occasional (adjusted OR: 2.86, 95% CI: 1.76--4.65) and regular clients (adjusted OR: 2.07, 95% CI: 1.40--3.06). CONCLUSIONS: The findings indicate that mobility and violence were independently associated with HIV infection. Notably, the combined effect of mobility and violence posed greater HIV risk than their independent effect. These results point to the need for the provision of an enabling environment and safe spaces for FSWs who are mobile, to augment existing efforts to reduce the spread of HIV/AIDS.     

An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge

One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV(mac)251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV(mac)251 challenge. Peak control correlated with the expansion of HLA-DR(+) CD8(+) T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.     

Silver carbene complexes: An emerging class of anticancer agents

Cancer is a major global health problem with large therapeutic challenges. Although substantial progress has been made in cancer therapy, there still remains a need to develop novel and effective treatment strategies to treat several relapsed and refractory cancers. Recently, there has been growing demand for considering organometallics as antineoplastic agents. This review is focused on a group of organometallics, silver N-heterocyclic carbene complexes (SCCs) and their anticancer efficacy in targeting multiple pathways in various in vitro cancer model systems. However, the precise molecular mechanism of SCCs anticancer properties remains unclear. Here, we discuss the SCCs chemistry, potential molecular targets, possible molecular mechanism of action, and their application in cancer therapies.     

Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats

This study investigated whether intrarenal endothelin-1(ET-1) contributes to sodium excretion in aged rats. Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET(A) receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na(+), K(+)-ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P < 0.001) as well as renin activity (P < 0.05), but had no significant effect on gene expression of ENaC or Na(+), K(+)-ATPase subunits. In aged rats, darusentan treatment increased ion excretion (P < 0.05), reduced cortical gene expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase (both P < 0.05), and increased plasma aldosterone levels (P < 0.01). These data demonstrate a decrease of sodium and potassium excretion in aged rats, changes that are partly sensitive to ETA receptor blockade. Treatment with darusentan also reduced cortical expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase and increased plasma aldosterone levels independently of blood pressure, electrolytes, renin activity, or angiotensin converting enzyme activity. These findings may provide new pathogenetic links between aging and sodium sensitivity.