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  • 1
    In: Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 63, No. 8 ( 2011-06-30), p. 1008-1014
    Abstract: A hydrotropic formulation containing a percutaneous enhancer was developed for the transdermal formulation of a water-soluble drug and the solubilizing mechanisms of a percutaneous enhancer in water by a hydrotropic agent were investigated. The enhancement effect was also compared with the hydrotropic formulation and the other formulations using ethanol, propylene glycol or mixed micelles. Methods Sodium salicylate (SA) and sodium benzoate (BA) were selected as hydrotropic agents, and polyol fatty acid ester (POFE) and 5-fluorouracil (5-FU) were selected as a percutaneous enhancer and a water-soluble drug, respectively. Near-infrared (NIR) spectrophotometric and 1H NMR spectroscopic studies were carried out to investigate the solubilizing mechanisms. The mean particle size in the hydrotropic formulation was measured. The in-vitro skin permeation of 5-FU and the accumulation in the skin of propylene glycol monocaprylate (PGMC), one of the monoesters of POFE, from the hydrotropic formulation or the other formulations were investigated by using Franz-type diffusion cell. Key findings The presence of SA and BA had a visible effect on the O–H stretching band of water in the NIR region. The surface tension of SA and BA aqueous solutions was found to decrease with an increase in SA or BA concentration. Although SA interacted with PGMC in the presence of water, it did not interact with PGMC in the absence of water. Mean particle size in a solution consisting of 5% (v/v) PGMC and 30% SA aqueous solution was approximately 14 nm. 1H NMR spectroscopic studies indicated that the hydrotropic salts formed aggregates with which PGMC interacted from the outside. The hydrotropic formulation prepared in this study enhanced skin permeation of 5-FU when compared with the other formulations. Conclusions SA and BA solubilized monoesters of POFE in water, and SA interacted with PGMC in water. The hydrotropic formulation prepared in this study significantly enhanced skin permeation of 5-FU compared with the other formulations. The results suggest that a hydrotropic formulation containing PGMC may be a useful transdermal formulation for water-soluble drugs.
    Type of Medium: Online Resource
    ISSN: 2042-7158 , 0022-3573
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
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    detail.hit.zdb_id: 2050532-2
    SSG: 15,3
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  • 2
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 69, No. 6 ( 2019-08-30), p. 1071-1078
    Abstract: We sought datasets with granular age distributions of rotavirus-positive disease presentations among children 〈 5 years of age, before the introduction of rotavirus vaccines. We identified 117 datasets and fit parametric age distributions to each country dataset and mortality stratum. We calculated the median age and the cumulative proportion of rotavirus gastroenteritis events expected to occur at ages between birth and 5.0 years. The median age of rotavirus-positive hospital admissions was 38 weeks (interquartile range [IQR], 25–58 weeks) in countries with very high child mortality and 65 weeks (IQR, 40–107 weeks) in countries with very low or low child mortality. In countries with very high child mortality, 69% of rotavirus-positive admissions in children 〈 5 years of age were in the first year of life, with 3% by 10 weeks, 8% by 15 weeks, and 27% by 26 weeks. This information is critical for assessing the potential benefits of alternative rotavirus vaccination schedules in different countries and for monitoring program impact.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2002229-3
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  • 3
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 224, No. Supplement_3 ( 2021-09-01), p. S161-S173
    Abstract: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. Methods Sentinel hospitals report cases of children & lt;5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. Results From 2014 through 2019, & gt;137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children & lt;1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%] ), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. Conclusions This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health. The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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  • 4
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 227, No. 10 ( 2023-05-12), p. 1220-1220
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1473843-0
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  • 5
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 224, No. Supplement_3 ( 2021-09-01), p. S174-S183
    Abstract: The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018. Methods Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus. Results A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with & gt;10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks. Conclusions Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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  • 6
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 3 ( 2023-02-08), p. e1047-e1053
    Abstract: Diarrhea is the second leading cause of death in children younger than 5 years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low- and middle-income countries. Methods Data from the World Health Organization (WHO)-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children & lt;5 years of age who were hospitalized with diarrhea between 2008 and 2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. Results This analysis comprises 234 781 cases, including 1219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for & lt;6 months compared with older ages, odds ratio [OR] = 3.54; 95% confidence interval [CI] , 2.81–4.50), female sex (OR = 1.18; 95% CI, 1.06–1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI, 1.01–3.25), no vomiting (OR = 1.13; 95% CI, .98–1.30), severe dehydration (OR = 3.79; 95% CI, 3.01–4.83), and being negative for rotavirus on an enzyme-linked immunosorbent assay test (OR = 2.29; 95% CI, 1.92–2.74). Cases from the African Region had the highest odds of death compared with other WHO regions (OR = 130.62 comparing the African Region with the European Region; 95% CI, 55.72–422.73), whereas cases from the European Region had the lowest odds of death. Conclusions Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2002229-3
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  The Journal of Infectious Diseases Vol. 224, No. Supplement_3 ( 2021-09-01), p. S184-S193
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 224, No. Supplement_3 ( 2021-09-01), p. S184-S193
    Abstract: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction. Methods Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018. Results Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7–7.1) and 4.2 (95% CI, 2.1–8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction. Conclusions Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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  • 8
    In: Human Molecular Genetics, Oxford University Press (OUP), Vol. 30, No. 15 ( 2021-07-09), p. 1384-1397
    Abstract: Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintain the structural integrity of tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly in an autosomal dominant manner. Here, we identified a homozygous stop-gain mutations in DSG2 (c.C355T, p.R119X) that led to complete desmoglein-2 deficiency in a patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition of desmosome proteins, disrupted intercalated disk structures in the myocardium. Induced pluripotent stem cells (iPSCs) were generated from the patient (R119X-iPSC), and the mutated DSG2 gene locus was heterozygously corrected to a normal allele via homology-directed repair (HDR-iPSC). Both isogenic iPSCs were differentiated into cardiomyocytes [induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)]. Multielectrode array analysis detected abnormal excitation in R119X-iPSC-CMs but not in HDR-iPSC-CMs. Micro-force testing of three-dimensional self-organized tissue rings (SOTRs) revealed tissue fragility and a weak maximum force in SOTRs from R119X-iPSC-CMs. Notably, these phenotypes were significantly recovered in HDR-iPSC-CMs. Myocardial fiber structures in R119X-iPSC-CMs were severely aberrant, and electron microscopic analysis confirmed that desmosomes were disrupted in these cells. Unexpectedly, the absence of desmoglein-2 in R119X-iPSC-CMs led to decreased expression of desmocollin-2 but no other desmosome proteins. Adeno-associated virus-mediated replacement of DSG2 significantly recovered the contraction force in SOTRs generated from R119X-iPSC-CMs. Our findings confirm the presence of a desmoglein-2-deficient cardiomyopathy among clinically diagnosed dilated cardiomyopathies. Recapitulation and correction of the disease phenotype using iPSC-CMs provide evidence to support the development of precision medicine and the proof of concept for gene replacement therapy for this cardiomyopathy.
    Type of Medium: Online Resource
    ISSN: 0964-6906 , 1460-2083
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474816-2
    SSG: 12
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