Helen Maureen Massa

Predominant Bacteria Detected from the Middle Ear Fluid of Children Experiencing Otitis Media: A Systematic Review

Background Otitis media (OM) is amongst the most common childhood diseases and is associated with multiple microbial pathogens within the middle ear. Global and temporal monitoring of predominant bacterial pathogens is important to inform new treatment strategies, vaccine development and to monitor the impact of vaccine implementation to improve progress toward global OM prevention. Methods A systematic review of published reports of microbiology of acute otitis media (AOM) and otitis media with effusion (OME) from January, 1970 to August 2014, was performed using PubMed databases. Results This review confirmed that Streptococcus pneumoniae and Haemophilus influenzae, remain the predominant bacterial pathogens, with S. pneumoniae the predominant bacterium in the majority reports from AOM patients. In contrast, H. influenzae was the predominant bacterium for patients experiencing chronic OME, recurrent AOM and AOM with treatment failure. This result was consistent, even where improved detection sensitivity from the use of polymerase chain reaction (PCR) rather than bacterial culture was conducted. On average, PCR analyses increased the frequency of detection of S. pneumoniae and H. influenzae 3.2 fold compared to culture, whilst Moraxella catarrhalis was 4.5 times more frequently identified by PCR. Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation, such as after introduction of the 7-valent pneumococcal conjugate vaccine. Conclusions Globally, S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture; however, molecular methods continue to improve the frequency and accuracy of detection of individual serotypes. Ongoing monitoring with appropriate detection methods for OM pathogens can support development of improved vaccines to provide protection from the complex combination of otopathogens within the middle ear, ultimately aiming to reduce the risk of chronic and recurrent OM in vulnerable populations.

Digital lecture recording: a cautionary tale.

Increasing application of information technology including web-based lectures and live-lecture recording appears to have many advantages for undergraduate nursing education. These include greater flexibility, opportunity for students to review content on demand and the improved academic management of increasing class sizes without significant increase in physical infrastructure. This study performed a quasi-experimental comparison between two groups of nursing students undertaking their first anatomy and physiology course, where one group was also provided access to streaming of recorded copies of the live lectures and the other did not. For the course in which recorded lectures were available student feedback indicated overwhelming support for such provision with 96% of students having accessed recorded lectures. There was only a weak relationship between access of recorded lectures and overall performance in the course. Interestingly, the nursing students who had access to the recorded lectures demonstrated significantly poorer overall academic performance (P < 0.001). Although this study did not specifically control for student demographics or other academic input, the data suggests that provision of recorded lectures requires improved and applied time management practices by students and caution on the part of the academic staff involved.

Vaccination against respiratory Pseudomonas aeruginosa infection

Respiratory infections caused by Pseudomonas aeruginosa are a major clinical problem globally, particularly for patients with chronic pulmonary disorders, such as those with cystic fibrosis (CF), non-CF bronchiectasis (nCFB) and severe chronic obstructive pulmonary disease (COPD). In addition, critically ill and immunocompromised patients are also at significant risk of P. aeruginosa infection. For almost half a century, research efforts have focused toward development of a vaccine against infections caused by P. aeruginosa, but a licensed vaccine is not yet available. Significant advances in identifying potential vaccine antigens have been made. Immunisations via both the mucosal and systemic routes have been trialled in animal models and their effectiveness in clearing acute infections demonstrated. The challenge for translation of this research to human applications remains, since P. aeruginosa infections in the human respiratory tract can present both as an acute or chronic infection. In addition, immunisation prior to infection may not be possible for many patients with CF, nCFB or COPD. Therefore, development of a therapeutic vaccine provides an alternative approach for treatment of chronic infection. Preliminary animal and human studies suggest that mucosal immunisation may be effective as a therapeutic vaccine against P. aeruginosa respiratory infections. Nevertheless, more research is needed to improve our understanding of the basic biology of P. aeruginosa and the mechanisms needed to upregulate the induction of host immune pathways to prevent infection. Recognition of variability in the host immune responses for a range of patient health conditions at risk from P. aeruginosa infection is also required to support development of a successful vaccine delivery strategy and vaccine. Activation of mucosal immune responses may provide improved efficacy of vaccination for P. aeruginosa during both acute exacerbations and chronic infection.

α-Tocopheryloxyacetic acid is superior to α-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability

Breast cancer is the number one neoplastic disease of women, with the HER2‐high carcinomas presenting a considerable challenge for efficient treatment. Therefore, a search for novel agents active against this type of cancer is warranted. We tested two vitamin E (VE) analogs, the esterase‐hydrolyzable α‐tocopheryl succinate (α‐TOS) and the non‐hydrolyzable ether α‐tocopheryloxyacetic acid (α‐TEA) for their effects on HER2‐positive breast carcinomas using a breast tumor mouse model and breast cancer cell lines. Ultrasound imaging documented that α‐TEA suppressed breast carcinomas in the transgenic animals more efficiently than found for its ester counterpart. However, both agents exerted a comparable apoptotic effect on the NeuTL breast cancer cells derived from the FVB/N c‐neu mice as well as in the human MBA‐MD‐453 and MCF7HER2‐18 cells with high level of HER2. The superior anti‐tumor effect of α‐TEA over α‐TOS in vivo can be explained by longer persistence of the former in mice, possibly due to the enhanced plasma and hepatic processing of α‐TOS in comparison to the esterase‐non‐cleavable α‐TEA. Indeed, the stability of α‐TOS in plasma was inferior to that of α‐TEA. We propose that α‐TEA is a promising drug efficient against breast cancer, as documented by its effect on experimental HER2‐positive breast carcinomas that present a considerable problem in cancer management.

Student perception of a new integrated anatomy practical program: does students' prior learning make a difference?

While there is evidence that science and non‐science background students display small differences in performance in basic and clinical sciences, early in a 4‐year, graduate entry medical program, this lessens with time. With respect to anatomy knowledge, there are no comparable data as to the impact previous anatomy experience has on the student perception of the anatomy practical learning environment. A study survey was designed to evaluate student perception of the anatomy practical program and its impact on student learning, for the initial cohort of a new medical school. The survey comprised 19 statements requiring a response using a 5‐point Likert scale, in addition to a free text opportunity to provide opinion of the perceived educational value of the anatomy practical program. The response rate for a total cohort of 82 students was 89%. The anatomy practical program was highly valued by the students in aiding their learning of anatomy, as indicated by the high mean scores for all statements (range: 4.04–4.7). There was a significant difference between the students who had and had not studied a science course prior to entering medicine, with respect to statements that addressed aspects of the course related to its structure, organization, variety of resources, linkage to problem‐based learning cases, and fairness of assessment. Nonscience students were more positive compared to those who had studied science before (P levels ranging from 0.004 to 0.035). Students less experienced in anatomy were more challenged in prioritizing core curricular knowledge. Clin. Anat. 24:664–670, 2011.

Dietary phytoestrogens maintain contractile responses to carbachol with age in the female rat isolated bladder

AIMS Development of urinary incontinence, for many women, occurs following menopause. Dietary phytoestrogens consumed over the long term may affect the contractile function and maintenance of the urinary bladder in post menopausal women. This study examined the muscarinic receptor mediated contractile responses in the rat isolated bladder in response to ovariectomy and long term dietary phytoestrogen consumption. MAIN METHODS Ovariectomised or sham-operated female Wistar rats (8 weeks) were fed either normal rat chow (soy, phytoestrogens) or a non-soy (phytoestrogen free) diet. Bladders were dissected from rats at 12, 24 and 52 weeks of age and placed in 25 ml organ baths filled with McEwans solution. KEY FINDINGS The contractile response to carbachol, in 12 week old female rats did not change as a result of dietary phytoestrogens or ovariectomy (P>0.05). At 24 weeks of age, detrusor muscle strip responses to carbachol from non-soy fed ovariectomised rats were attenuated (P<0.05). At 52 weeks, bladder detrusor strip responses to carbachol were reduced in all treatment groups with the exception of the soy-fed sham operated rats. SIGNIFICANCE These results suggest an age-related reduction in the contractile response of the detrusor to the muscarinic receptor agonist carbachol, which may be prevented by long term dietary phytoestrogen intake.

Effect of GPR84 deletion on obesity and diabetes development in mice fed long chain or medium chain fatty acid rich diets

PurposeAlthough there is good evidence showing that diets rich in medium chain fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than diets rich in long chain fatty acids (LCFAs), the role of the pro-inflammatory, medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose intolerance is not well characterised. We set out to determine whether GPR84 expression influences obesity and glucose intolerance susceptibility in MCFA and LCFA rich diet fed mice.MethodsWild type (WT) and GPR84 knockout (KO) mice were fed a control, MCFA or LCFA diet, and body mass, heart, liver and epididymal fat mass was assessed, as well as glucose tolerance and adipocyte size.ResultsLCFA diets increased body mass and decreased glucose tolerance in both WT and GPR84 KO animals while MCFA diets had no effect on these parameters. There were no differences in body weight when comparing WT and GPR84 KO mice on the respective diets. Glucose tolerance was also similar in WT and GPR84 KO mice irrespective of diet. Liver mass was increased following LCFA feeding in WT but not GPR84 KO mice. Hepatic triglyceride content was increased in GPR84 KO animals fed MCFA, and myocardial triglyceride content was increased in GPR84 KO animals fed LCFA.ConclusionsGPR84 deletion had no effects on body weight or glucose tolerance in mice fed either a high MCFA or LCFA diet. GPR84 may influence lipid metabolism, as GPR84 KO mice had smaller livers and increased myocardial triglyceride accumulation when fed LCFA diets, and increased liver triglyceride accumulation in responses to increased dietary MCFAs.

Epitope-specific immune recognition of the nontypeable Haemophilus influenzae outer membrane protein 26.

Previous studies using rodent respiratory infection models of nontypeable Haemophilus influenzae (NTHi) infection have established the 26-kDa outer membrane protein of the bacterium, OMP26, as a potential vaccine antigen for NTHi. This study undertook a comprehensive immunological identification of OMP26 T- and B-cell epitopes. A series of OMP26 peptides were constructed and regions of the OMP26 antigen involved in recognition by lymphocyte receptors and induction of acquired immune responses were identified. The dominant T-cell epitopes for OMP26 were located toward the C-terminus between amino acid residues 95 and 197 (T3+T4 region) as mapped using antigen-specific lymphocyte proliferation assays. The newly identified T-cell epitopes exhibited strong capacity for efficient T-cell activation, suggesting that, compared with other OMP26 regions; epitopes within the T3+T4 region have the highest affinity for binding to major histocompatibility complex molecules. In contrast, the predominant B-cell epitopes of OMP26 were located more centrally within the molecule between amino acid residues 45 and 145 (T2+T3 region) as determined using enzyme-linked immunosorbent assay and surface plasmon resonance assays. The T2+T3 region was immunodominant in several species including chinchilla, mice and rats when assessed using both mucosal and parenteral immunization regimes. In addition, the antibodies directed against the T2+T3 region bound to intact NTHi cell surface, according to flow cytometry. Collectively, these results specifically locate the amino acid sequences containing the OMP26 T- and B-cell epitopes, which, as newly mapped antigenic epitopes for lymphocyte recognition, will be useful to improve existing NTHi vaccine strategies. Comprehensive definition of the minimum epitope length required for optimal B- and T-cell responses requires further study.

Middle Ear and Eustachian Tube Mucosal Immunology

Abstract Mucosal immune responses within the middle ear and eustachian tube generally provide an effective and efficient response to the presence of microbial pathogens, with approximately 80% of clinically recognizable middle ear infections resolved within 7days. Particularly for young children aged less than 3years of age, the proximity and direct connection of the middle ear, via the eustachian tube, to the nasopharynx provide increased risk of commensal bacteria and upper respiratory tract viruses infecting the middle ear. Mucosal immunological defense in the middle ear and eustachian tube utilizes a number of mechanisms, including physicochemical barriers of mucus and the mucosal epithelial cells and innate immune responses such as inflammation, cellular infiltration, effusion, and antimicrobial protein secretions, in addition to adaptive host immune responses. Recent advances in otopathogen recognition via microbial pattern recognition receptors and elucidation of complex signaling cascades have improved understanding of the coordination and regulation of the middle ear mucosal response. These advances support vaccine development aiming to reduce the risk of otitis media in children.