PMID: 

J Virol. 2016 06 1 ;90(11):5270-5279. Epub 2016 May 12. PMID: 26984727

Abstract Title: 

Generation of a More Immunogenic Measles Vaccine by Increasing Its Hemagglutinin Expression.

Abstract: 

UNLABELLED: Imported measles virus (MV) outbreaks are maintained by poor vaccine responders and unvaccinated people. A convenient but more immunogenic vaccination strategy would enhance vaccine performance, contributing to measles eradication efforts. We report here the generation of alternative pediatric vaccines against MV with increased expression of the H protein in the background of the current MV vaccine strain. We generated two recombinants: MVvac2-H2, with increased full-length H expression resulting in a 3-fold increase in H incorporation into virions, and MVvac2-Hsol, vectoring a truncated, soluble form of the H protein that is secreted into the supernatants of infected cells. Replication fitness was conserved despite the duplication of the H cistron for both vectors. The modification to the envelope of MVvac2-H2 conferred upon this virus a measurable level of resistance to in vitro neutralization by MV polyclonal immune sera without altering its thermostability. Most interestingly, both recombinant MVs with enhanced H expression were significantly more immunogenic than their parental strain in outbred mice, while MVvac2-H2 additionally proved more immunogenic after a single, human-range dose in genetically modified MV-susceptible mice.IMPORTANCE: Measles incidence was reduced drastically following the introduction of attenuated vaccines, but progress toward the eradication of this virus has stalled, and MV still threatens unvaccinated populations. Due to the contributions of primary vaccine failures and too-young-to-be-vaccinated infants to this problem, more immunogenic measles vaccines are highly desirable. We generated two experimental MV vaccines based on a current vaccine's genome but with enriched production of the H protein, the main MV antigen in provoking immunity. One vaccine incorporated H at higher rates in the viral envelope, and the other secreted a soluble H protein from infected cells. The increased expression of H by these vectors improved neutralizing responses induced in two small-animal models of MV immunogenicity. The enhanced immunogenicity of these vectors, mainly from the MV that incorporates additional H, suggests their value as potential alternative pediatric MV vaccines.

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PMID: 

Vaccine. 2016 05 23 ;34(24):2750-7. Epub 2016 Apr 22. PMID: 27109563

Abstract Title: 

Measles antibodies in cord blood in Portugal: Possible consequences for the recommended age of vaccination.

Abstract: 

The optimum age to give the first dose of measles vaccine must balance the risks of disease and vaccine failure. Both are influenced by the levels of transplacentally acquired maternal antibodies. This study was conducted in the Obstetric service of Portuguese hospital, in 2012-2013. Mothers were recruited after informed consent. Measles IgG was measured in 206 cord sera, using a commercial immunoassay. Geometric mean concentrations (and 95% CI) were 1849mIU/ml (1196-2857) and 790mIU/ml (618-1008) in cord sera of newborns from unvaccinated and vaccinated mothers respectively. Maternal age and vaccination status were both associated with the concentration in cord sera, but maternal age was the major predictor. The likely explanation is the same already mentioned in other studies: as a vaccination program progresses, vaccination coverage increases as measles incidence decreases. That results newborns from younger vaccinated mothers having less measles antibodies while the older mothers are more likely to have been infected with the wild virus. As the proportion of vaccinated mothers increase, developed countries tend to anticipate the recommended age of the first dose to 12 months of age. Models using hypothetical measles antibody decay rates in infancy were explored. Anticipating the first dose of MMR1 in Portugal to the age of 12 months might have not been the best decision but results were not conclusive, and arguments supporting or not the anticipation were discussed.

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PMID: 

J Neuroinflammation. 2016 05 13 ;13(1):107. Epub 2016 May 13. PMID: 27178303

Abstract Title: 

Interferon gamma protects neonatal neural stem/progenitor cells during measles virus infection of the brain.

Abstract: 

BACKGROUND: In the developing brain, self-renewing neural stem/progenitor cells (NSPC) give rise to neuronal and glial lineages. NSPC survival and differentiation can be altered by neurotropic viruses and by the anti-viral immune response. Several neurotropic viruses specifically target and infect NSPCs, in addition to inducing neuronal loss, which makes it difficult to distinguish between effects on NSPCs that are due to direct viral infection or due to the anti-viral immune response.METHODS: We have investigated the impact of anti-viral immunity on NSPCs in measles virus (MV)-infected neonates. A neuron-restricted viral infection model was used, where NSPCs remain uninfected. Thus, an anti-viral immune response was induced without the confounding issue of NSPC infection. Two-transgenic mouse lines were used: CD46+ mice express the human isoform of CD46, the MV entry receptor, under the control of the neuron-specific enolase promoter; CD46+/IFNγ-KO mice lack the key anti-viral cytokine IFNγ. Multi-color flow cytometry and Western Blot analysis were used to quantify effects on NSPC, neuronal, and glial cell number, and quantify effects on IFNγ-mediated signaling and cell markers, respectively.RESULTS: Flow cytometric analysis revealed that NSPCs were reduced in CD46+/IFNγ-KO mice at 3, 7, and 10 days post-infection (dpi), but were unaffected in CD46+ mice. Early neurons showed the greatest cell loss at 7 dpi in both genotypes, with no effect on mature neurons and glial cells. Thus, IFNγ protected against NSPC loss, but did not protect young neurons. Western Blotanalyses on hippocampal explants showed reduced nestin expression in the absence of IFNγ, and reduced doublecortin and βIII-tubulin in both genotypes. Phosphorylation of STAT1 and STAT2 occurred independently of IFNγ in the hippocampus, albeit with distinct regulation of activation.CONCLUSIONS: This is the first study to demonstrate bystander effects of anti-viral immunity on NSPC function. Our results show IFNγ protects the NSPC population during a neonatal viral CNS infection. Significant loss of NSPCs in CD46+/IFNγ-KO neonates suggests that the adaptive immune response is detrimental to NSPCs in the absence of IFNγ. These results reveal the importance and contribution of the anti-viral immune response to neuropathology and may be relevant to other neuroinflammatory conditions.

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PMID: 

Vaccine. 2016 Apr 19 ;34(18):2092-5. Epub 2016 Mar 14. PMID: 26988260

Abstract Title: 

Monitoring the process of measles elimination by serosurveillance data: The Apulian 2012 study.

Abstract: 

In 2003 Italy adopted the National Plan for Measles and Congenital Rubella Elimination, but some outbreaks of measles are still occurring, as the target coverage rate (≥ 95%) for new-borns has currently not been achieved. In order to support the monitoring of the measles elimination programme, the authors carried out a survey about the seroprevalence of measles among Apulia young adults. The study was carried out from May 2011 to June 2012 among blood donors ofthe Department of Transfusion Medicine of Policlinico General Hospital in Bari. Subjects were enrolled by a convenience sampling. For each enrolled patient we collected a 5 mL serum sample. Collected sera were tested by chemiluminescence (CLIA) for anti-Measles IgG. We enrolled 1764 subjects; 1362 (77.2%) were male with a mean age of 38.4 ± 11.7 years. Anti-Measles IgG titre was>16.5UA/mL in 95.1% (95% CI=94.1-96.1) of enrolled subjects with a Geometric Mean Titre (GMT) of 2.3± 0.4, which did not differ dividing the enrolled subjects into age groups. As our data showed, the universal routine vaccination changed the epidemiological pattern among adults, in particular young adults (18-24 years), who showed lowest seropositivity rates; in these groups of population there is a risk of the onset of outbreaks due to the presence of susceptible population. This is a paradox linked to the vaccination strategy: when coverage rates keep sub-optimal, measles is more likely to affect young adults and a higher percentage of complications is expected. According to our data, health authorities have to plan a mop-up strategy to actively offer measles vaccination to susceptible young adults.

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PMID: 

Trends Mol Med. 2015 Dec ;21(12):789-801. Epub 2015 Nov 18. PMID: 26602762

Abstract Title: 

Variability in Humoral Immunity to Measles Vaccine: New Developments.

Abstract: 

Despite the existence of an effective measles vaccine, resurgence in measles cases in the USA and across Europe has occurred, including in individuals vaccinated with two doses of the vaccine. Host genetic factors result in inter-individual variation in measles vaccine-induced antibodies, and play a role in vaccine failure. Studies have identified HLA (human leukocyte antigen) and non-HLA genetic influences that individually or jointly contribute to the observed variability in the humoral response to vaccination among healthy individuals. In this exciting era, new high-dimensional approaches and techniques including vaccinomics, systems biology, GWAS, epitope prediction and sophisticated bioinformatics/statistical algorithms provide powerful tools to investigate immune response mechanisms to the measles vaccine. These might predict, on an individual basis, outcomes of acquired immunity post measles vaccination.

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PMID: 

J Dent Child (Chic). 2018 Jan 15 ;85(1):40-42. PMID: 29663975

Abstract Title: 

Gingival Enlargement Caused by Vitamin C Deficiency (Scurvy) in a Boy.

Abstract: 

Localized gingival enlargement associated with vitamin C deficiency (scurvy) is rarely encountered in the modern era. The purpose of this paper is to report a case of extensive inflammatory gingival enlargement in the mandibular anterior region associated with vitamin C deficiency in a 10 year-old boy. There was a significant improvement of the gingival enlargement seven days after starting oral vitamin C supplementation. Vitamin C deficiency should be included in the differential diagnosis of any gingival enlargement, especially in children.

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PMID: 

J Alzheimers Dis. 2019 ;72(3):947-956. PMID: 31743998

Abstract Title: 

Effects of a Modified Tai Chi Program on Older People with Mild Dementia: A Randomized Controlled Trial.

Abstract: 

BACKGROUND: Tai Chi exercise is a non-pharmacological therapy that has received increased attention in recent years. A Tai Chi program has been specifically modified for older people with cognitive impairments by the research team.OBJECTIVE: We aim to assess the effects of this Tai Chi program on mild dementia.METHODS: Eighty older people with mild dementia were recruited and randomly assigned to a Tai Chi group or a control group. The Tai Chi group practiced the Tai Chi program three times a week for 10 months, while the control group continued receiving routine treatments. All participants were assessed for cognitive function, behavior/mood, and activities of daily living at baseline, 5 months, and 10 months.RESULTS: The Tai Chi group performed better than the control group. Repeated measures ANOVA revealed a significant group×time interaction in the Montreal Cognitive Assessment (MoCA). Further analysis of sub-items of the MoCA showed a significant time effect in naming and abstraction. It was statistically significant in both main effect of time and group×time interaction in the Neuropsychiatric Inventory (NPI) and Geriatric Depression Scale (GDS). Paired sample t test showed the Tai Chi group scored lower at 5 and 10 months in the NPI and at 10 months in the GDS compared with baseline. The Tai Chi group scored lower than the control group at 10 months in the NPI and GDS.CONCLUSION: The results suggest this Tai Chi program may help improve cognitive function and mental well-being for older adults with mild dementia.

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PMID: 

Biomed Res Int. 2019 ;2019:4853695. Epub 2019 Oct 17. PMID: 31915695

Abstract Title: 

Possible Effects of Proton Pump Inhibitors on Hearing Loss Development.

Abstract: 

Considered safe and often available as over-the-counter (OTC) drugs, proton pump inhibitors (PPI) are one of the most frequently used medicines. Over recent years much research analyzing PPI has been conducted and these studies shed light on PPI side effects and the mechanisms of these processes. In this study we summarize the findings of these studies and through deduction present some hypotheses on the impact of PPI on health. Of particular interest is the impact of PPI on hearing loss development. However, despite this side effect being localized, its mechanisms are complex, systemic and involve changes in whole body. This paper summarizes how through, inter alia, alterations in the circulatory system, respiratory system, central nervous system and metabolism PPI can cause hearing impairment, which can occur in every age group and is connected with long-term use of this group of drugs. This article also discusses the role PPI plays in the acceleration of presbycusis development, in relation to the fact that older people are the group who most frequently use PPI in long term. Hearing loss negatively impacts affects quality of life, especially among older patients who are also the most afflicted group; administration of PPI should therefore be considered carefully, taking into consideration all potential benefits and side effects.

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PMID: 

Sci Rep. 2020 Jan 21 ;10(1):866. Epub 2020 Jan 21. PMID: 31964941

Abstract Title: 

Long-term Proton Pump Inhibitor Administration Caused Physiological and Microbiota Changes in Rats.

Abstract: 

Proton pump inhibitors (PPIs) are used for the long-term treatment of gastroesophageal disorders and the non-prescription medicines for acid reflux. However, there is growing concerns about PPI misuse, overuse and abuse. This study aimed to develop an animal model to examine the effects of long-term use of PPI in vivo. Twenty one Wistar rats were given omeprazole orally or intravenously for 30 days, and caerulein as a positive control. After euthanization, the serum and stool were collected to perform MS-based quantitative analysis of metabolites. We carried out 16S-based profiling of fecal microbiota, assessed the expression of bile acid metabolism regulators and examined the immunopathological characteristics of bile ducts. After long-term PPI exposure, the fecal microbial profile was altered and showed similarity to those observed in high-fat diet studies. The concentrations of several metabolites were also changed in various specimens. Surprisingly, morphological changes were observed in the bile duct, including ductal epithelial proliferation, micropapillary growth of biliary epithelium, focal bile duct stricture formation and bile duct obstruction. These are characteristics of precancerous lesions of bile duct. FXR and RXRα expressions were significantly reduced, which were similar to that observed in cholangiocarcinoma in TCGA and Oncomine databases. We established a novel animal model to examine the effects of long-term use of omeprazole. The gut microbes and metabolic change are consequences of long-term PPI exposure. And the results showed the environment in vivo tends to a high-fat diet. More importantly, we observed biliary epithelial hyperplasia, which is an indicator of a high-fat diet.

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PMID: 

Biomedicines. 2020 Jan 21 ;8(2). Epub 2020 Jan 21. PMID: 31973028

Abstract Title: 

Protective Effects of Astaxanthin Supplementation against Ultraviolet-Induced Photoaging in Hairless Mice.

Abstract: 

Ultraviolet (UV) light induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Astaxanthin (AST), a ketocarotenoid isolated from, has been extensively studied owing to its possible effects on skin health as well as UV protection. In addition, AST attenuates the increased generation of reactive oxygen species (ROS) and capillary regression of the skeletal muscle. In this study, we investigated whether AST could protect against UV-induced photoaging and reduce capillary regression in the skin of HR-1 hairless mice. UV light induces wrinkle formation, epidermal thickening, and capillary regression in the dermis of HR-1 hairless mice. The administration of AST reduced the UV-induced wrinkle formation and skin thickening, and increased collagen fibers in the skin. AST supplementation also inhibited the generation of ROS, decreased wrinkle formation, reduced epidermal thickening, and increased the density of capillaries in the skin. We also found an inverse correlation between wrinkle formation and the density of capillaries. An association between photoaging and capillary regression in the skin was also observed. These results suggest that AST can protect against photoaging caused by UV irradiation and the inhibitory effects of AST on photoaging may be associated with the reduction of capillary regression in the skin.

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