The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats.

AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system. METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P < 0·05). Strain L. fermentum DR9 demonstrated improved expression of SOD in bone and muscle compared to the aged rats (P < 0·05). In the evaluation of myogenesis-related genes, L. paracasei OFS 0291 and L. fermentum DR9 increased the mRNA expression of IGF-1; L. helveticus OFS 1515 and L. fermentum DR9 reduced the expression of MyoD, in contrast to the aged controls (P < 0·05). Protective effects of L. fermentum DR9 on ageing muscle were believed to be contributed by increased AMPK-α2 expression. Among the osteoclastogenesis genes studied, TNF-α expression was highly elevated in tibia of aged rats, while all three probiotics strains ameliorated the expression. Lactobacillus fermentum DR9 also reduced the expression of IL-6 and TRAP in tibia when compared to the aged rats (P < 0·05). All probiotics treatment resulted in declined proinflammatory cytokines IL-1ß in muscle and bone. CONCLUSIONS: Lactobacillus fermentum DR9 appeared to be the strongest strain in modulation of musculoskeletal health during ageing. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the protective effects of the bacteria on muscle and bone through antioxidative and anti-inflammatory actions. Therefore, L. fermentum DR9 may serve as a promising targeted anti-ageing therapy.

A multi-centre analysis of a decade of endoscopic pharyngeal pouch surgery in Cheshire and Merseyside.

BACKGROUND: There are sparse data on the outcomes of endoscopic stapling of pharyngeal pouches. The Mersey ENT Trainee Collaborative compared regional practice against published benchmarks. METHODS: A 10-year retrospective analysis of endoscopic pharyngeal pouch surgery was conducted and practice was assessed against eight standards. Comparisons were made between results from the tertiary centre and other sites. RESULTS: A total of 225 procedures were performed (range of 1.2-9.2 cases per centre per year). All centres achieved 90 per cent resumption of oral intake within 2 days. All centres achieved less than 2-day hospital stays. Primary success (84 per cent (i.e. abandonment of endoscopic stapling in 16 per cent)), symptom resolution (83 per cent) and recurrence rates (13 per cent) failed to meet the standard across the non-tertiary centres. CONCLUSION: Endoscopic pharyngeal pouch stapling is a procedure with a low mortality and brief in-patient stay. There was significant variance in outcomes across the region. This raises the question of whether this service should become centralised and the preserve of either tertiary centres or sub-specialist practitioners.

Epistaxis and atorvastatin: is there an association and are clinicians aware? A retrospective audit of 100 patients.

OBJECTIVE: Epistaxis is a common ENT presentation. The British National Formulary lists epistaxis as a common side effect of atorvastatin. This study aimed to better understand the relationship between epistaxis and atorvastatin use, and determine whether ENT doctors are aware of its side effect profile. METHODS: A retrospective analysis over 10 months identified 100 individuals who presented to hospital with epistaxis. A questionnaire of 24 ENT registrars was undertaken. RESULTS: Of the 100 patients admitted with epistaxis, 27 were receiving atorvastatin and 21 simvastatin. None of the 24 ENT registrars were aware that epistaxis was a listed common side effect of atorvastatin. CONCLUSION: There was no apparent difference in the proportion of patients admitted with epistaxis taking atorvastatin versus simvastatin. Epistaxis is an unknown side effect of atorvastatin; doctors have an obligation to be aware of the pharmaceutical literature and to consider alternatives, particularly in re-admissions cases.

Therapist Reports of EBP Client Engagement Challenges in Sessions with Diverse Youth and Families in Community Mental Health Settings.

BACKGROUND: The implementation of evidence-based practices (EBPs) in community settings appears to result in reduced benefit relative to controlled trials. This difference in outcomes may be attributable in part to engagement challenges therapists encounter when delivering EBPs to low-income ethnic minority youth and families. OBJECTIVE: The current study sought to identify therapist, client, and session characteristics associated with therapist-reported engagement challenges in therapy sessions, as well the associations between two types of client engagement challenges and therapists' self-reported ability to deliver the EBP in sessions within a system-driven implementation in public children's mental health services. METHOD: One hundred and three therapists reported on two types of engagement challenges-Limited Client Engagement and Expressed Client Concerns-in 702 sessions with 274 clients. RESULTS: Results indicated that therapists reported a higher frequency of Limited Client Engagement in sessions with male clients and in sessions where the youth was present, and by therapists with smaller caseloads. No variables significantly predicted Expressed Client Concerns. Both types of engagement challenges were negatively associated with therapists' report of their ability to carry out intended activities in the same session. CONCLUSIONS: Findings suggest that therapists may benefit from learning strategies to address these two distinct types of engagement challenges encountered in implementation of EBPs with diverse families in community settings.

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats.

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated gut microbiota profiles in Malaysian pre-school children.

This 10-months randomised, double-blind, parallel and placebo-controlled study evaluated the effects of Bifidobacterium longum BB536 on diarrhoea and/or upper respiratory illnesses in 520 healthy Malaysian pre-school children aged 2-6 years old. The subjects randomly received a one-gram sachet containing either BB536 (5×109 cfu) or placebo daily. Data analysis was performed on 219 subjects who fully complied over 10-months (placebo n=110, BB536 n=109). While BB536 did not exert significant effects against diarrhoea in children, Poisson regression with generalised estimating equations model indicated significant intergroup difference in the mean number of times of respiratory illnesses over 10 months. The duration of sore throat was reduced by 46% (P=0.018), with marginal reduction for duration of fever (reduced by 27%, P=0.084), runny nose (reduced by 15%, P=0.087) and cough (reduced by 16%, P=0.087) as compared to the placebo. Principal coordinate analysis at genus level of the gut microbiota revealed significant differences between 0 and 10 months in the BB536 group (P<0.01) but not in placebo group (P>0.05). The abundance of the genus Faecalibacterium which is associated with anti-inflammatory and immuno-modulatory properties was significantly higher in the BB536 group (P<0.05) compared to the placebo group. Altogether, our present study illustrated the potential protective effects of BB536 against upper respiratory illnesses in pre-school Malaysian children, with gut microbiota modulating properties.

The BeSMART (Best Supportive Management for Adults Referred with Tonsillopharyngitis) multicentre observational study.

Introduction Tonsillopharyngitis is the most common ear, nose and throat emergency admission, with 80,000 episodes recorded in England in 2015-2016. Despite this, there is a paucity of evidence addressing the supportive management of tonsillopharyngitis in inpatients. The aim of this retrospective multicentre observational study was to consider the Best Supportive Management for Adults Referred with Tonsillopharyngitis (BeSMART) in the inpatient setting, and to establish any associations between practice and outcomes. Methods Seven hospitals in North West England and North East Scotland participated in the study. Overall, 236 adult patients admitted with tonsillopharyngitis were included. The main outcome measures were interval to return to soft diet, length of stay (LOS), pain scores and readmissions. Results Women were more likely to seek professional help before presenting to secondary care (p=0.04). Patients admitted at the weekend were more likely to have a shorter LOS (p=0.03). There was no relationship between day of admission and seniority or specialty of the doctor initially seen. Prescription of corticosteroid, analgesia and a higher initial intravenous fluid infusion rate were not related to a shorter LOS. Conclusions This study is the first to yield valuable insights into the inpatient management of tonsillopharyngitis. This work represents part of an ongoing project to establish the evidence for common medical interventions for sore throat. Patient and professional surveys as well as a prospective interventional study are planned for the future.

What is the publication rate for presentations given at the British Academic Conference in Otolaryngology (BACO)?

OBJECTIVES: The publication rate of some large academic meetings such as the American Academy of Otolaryngology-Head and Neck Surgery has been reported as 32%. We aimed to compare the rate of publication at the British Academic Conference in Otolaryngology (BACO) to allow surveillance of research activity in the United Kingdom (UK). DESIGN AND SETTING: The abstract records of both BACO 2009 and 2012 were examined. The MEDLINE database was searched using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and an iterative approach. We recorded time to publication as well as the authors' region and journal. MAIN OUTCOME MEASURES: publication rate by conference, region and journal. RESULTS: Twice the number of presentations were made at BACO 2012 (n = 814) compared to BACO 2009 (n = 387). Absolute numbers of publications were 158 in 2012 and 92 in 2009. Overall, the publication rate dropped from 24% overall in 2009 to 19% in 2012. This difference in proportions was not significant (P = 0.08). The number of abstracts accepted for BACO 2012 doubled from BACO 2009 in nearly every subspecialty category, except the general/training category, which trebled. For both conferences, head and neck was the largest subspecialty abstract category, as well as the largest subspecialty publication category. CONCLUSIONS: This study showed that the majority of abstracts presented at BACO 2009 and 2012 did not progress to publication. The rate of publication was similar to that seen in other general ENT meetings but do not compare favourably to the 69% rate seen for presentations made at the Otorhinolaryngological Research Society (ORS). The large increase in accepted abstracts at BACO 2012 may reflect growing competition for entry to specialist training.

A re-appraisal of publication rates of scientific papers presented at the Otorhinolaryngology Research Society meetings.

OBJECTIVES: To review the rate of publication of papers in peer-reviewed journals after oral presentations at the Otorhinolaryngology Research Society meetings between 1996 and 2013 and to compare trends with the previous review (1979-1995). DESIGN: Literature review. SETTING: Merseyside ENT Research Collaborative. PARTICIPANTS: The abstracts of presentations at Otorhinolaryngology Research Society meetings are published in Clinical Otolaryngology. A structured search of PubMed was undertaken to identify published Otorhinolaryngology Research Society presentations. MAIN OUTCOME MEASURES: Publication rates. RESULTS: A total of 460 abstracts were identified. The interobserver reliability among reviewers was 98%. Of the total, 259 (56.3%) abstracts were published in peer-reviewed journals. The average time from Otorhinolaryngology Research Society presentation to publication was 27.7 months (median 23), which was not significantly different from the previous review. Publication by subspeciality was as follows: head and neck (45.6%), otology (30.5%), rhinology (22%) and others (1.9%). Most published Otorhinolaryngology Research Society presentations were published in Clinical Otolaryngology (22.4%), followed by the Journal of Laryngology and Otology (8.1%) and the Laryngoscope (7.3%). Clinical research was the most common category of abstracts being presented at Otorhinolaryngology Research Society meetings, followed by laboratory-based research. Over half (56.5%) of laboratory research presented were head and neck themed, while otology and rhinology predominated clinical research presentations. Over half (52.1%) of Otorhinolaryngology Research Society abstracts originated from units in the North of England. Bristol presented the most abstracts (30.1%), followed by Newcastle (25.1%). CONCLUSIONS: The publication rate of Otorhinolaryngology Research Society presentations remains high and many are subsequently published in high-impact factor otolaryngology journals. More Otorhinolaryngology Research Society presentations are now published in American and European journals.

The rising rate of admissions for tonsillitis and neck space abscesses in England, 1991-2011.

INTRODUCTION: Sore throats and tonsillitis represent a considerable health burden as well as a significant source of expenditure for the National Health Service (NHS). As part of the recent NHS savings drive, the introduction of 'procedures of low clinical effectiveness' (PoLCE) lists has reinforced a large reduction in the number of tonsillectomies performed. We carried out a cross-sectional study of trends in emergency sore throat admissions in the context of the number of tonsillectomies performed. METHODS: Hospital Episode Statistics (HES) data were extracted. Office for National Statistics data were also used. RESULTS: Between 1991 and 2011, the overall tonsillectomy rate fell by 44%. In the same time, the admission rate for tonsillitis rose by 310% (Pearson's r=-0.67, p=0.01). The peritonsillar abscess admission rate rose by 31% (r=-0.79, p<0.01). Between 1996 and 2011, the overall tonsillectomy rate fell by 41% and the retro and parapharyngeal abscess admission rate rose by 39% (r=-0.55, p=0.026). There was a 14% overall increase in tonsillectomy and sore throat associated bed days. This was despite the large fall in tonsillectomy numbers and the reduction in length of hospital stay. CONCLUSIONS: Efforts to reduce the tonsillectomy rate are correlated with a significant rise in emergency admissions. The rise in the retro and parapharyngeal abscess rate is perhaps most alarming given the very high mortality of these conditions. Bed day data suggest that no net saving has been made despite the new measures.

Interferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections.

1. Hyper-induction of cytokines and chemokines was found in human blood macrophages infected with the avian influenza H5N1 and H9N2/G1 viruses, as compared to those infected with human influenza H1N1 virus. 2. IRF3 played a significant role in the hyperinduction of cytokines including IFN-ß, IFN-λ1,IFN-α subtypes, MCP-1, and TNF-α, and also played a part in subsequent cytokine-induced cell signalling cascades. 3. Compared with H1N1 viruses, avian influenza viruses including H5N1/97 and its precursors triggered a caspase-mediated but delayed apoptotic response in human macrophages. 4. Therapies that can minimise immunopathology-associated dysregulation of innate immunity without impairing effective host defence may be valuable adjuncts to antiviral therapy.

A novel mechanism: Erxian Decoction, a Chinese medicine formula, for relieving menopausal syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Many clinical and experimental reports demonstrated that Erxian Decoction (EXD) was effective in relieving menopausal syndrome. AIM OF THE STUDY: The mechanisms of action of EXD were explored on the endocrine and antioxidant regimen. MATERIALS AND METHODS: Menopause causes a decline in both endocrine function and activities of antioxidant enzymes. In this study, 12-month-old female Sprague-Dawley-rats (SD-rats) with a low serum estradiol level were employed. Their endocrine functions after treatment with EXD were assessed by the determination of their serum estradiol level and ovarian mRNA levels of aromatase, which is a key enzyme for biosynthesis of estradiol. Meanwhile, superoxide dismutase-1 (SOD), catalase (CAT) and glutathione peroxidase (GPx-1) in the liver were also determined to assess the effect of EXD on the antioxidant regimen. RESULTS: Results revealed a significant elevation in serum estradiol level and the mRNA level of ovarian aromatase and liver CAT in the EXD-treated menopausal rat model. CONCLUSIONS: The results obtained from mRNA and estradiol level of the present investigation revealed that the EXD relieves the menopausal syndrome involved an increase of endocrine and antioxidant function through, at least, the activation of aromatase and CAT detoxifying pathways.

Induction of matrix metalloproteinases by Epstein-Barr virus latent membrane protein 1 isolated from nasopharyngeal carcinoma.

Epstein--Barr virus latent infection is associated with human malignancies including Burkitt's lymphoma, gastric carcinoma and the highly invasive nasopharyngeal carcinoma (NPC). Increased expression of EBV latent membrane protein 1, LMP1, is correlated with tumor progression and metastasis in NPC. LMP1 induces cellular proteins including cytokines and matrix metalloproteinases (e.g., MMP1, MMP2 and MMP9). MMPs are endopeptidases involved in the degradation of extracellular matrix proteins; and their upregulation in cancer implicates their potential role in tumor metastasis. In light of the role of LMP1 in cytokine dysregulation and the fact that MMPs are regulated by cytokines, we examined whether LMP1 promotes NPC metastasis via the induction of MMPs. To delineate the oncogenic role of LMP1 in NPC, we first investigated the induction of MMP1, MMP2, MMP3 and MMP9 in LMP1-positive NPC tumor samples (n=15) by quantitative RT-PCR. We showed a significant induction of MMP1 and MMP3 transcripts in the EBV LMP1-positive NPC tissues, compared with biopsies obtained from the adjacent non-tumor tissues. To investigate the role of LMP1 in MMP expression in NPC, we cloned the LMP1 gene from NPC samples and transiently expressed it in MRC5 cells (human lung fibroblasts). Following transfection, a time-dependent elevation of endogenous MMP3 expression was found in the LMP1-transfectants by quantitative RT-PCR and Western analysis. Taken together, we observed that MMP3 is upregulated in LMP1-positive NPC tumors and LMP1-expression in fibroblasts is associated with MMP3 and cytokine expression. Our results suggest that LMP1 may contribute to invasiveness of NPC cells via the expression of MMP3 in fibroblasts.

Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?

BACKGROUND: In 1997, the first documented instance of human respiratory disease and death associated with a purely avian H5N1 influenza virus resulted in an overall case-fatality rate of 33%. The biological basis for the severity of human H5N1 disease has remained unclear. We tested the hypothesis that virus-induced cytokine dysregulation has a role. METHODS: We used cDNA arrays and quantitative RT-PCR to compare the profile of cytokine gene expression induced by viruses A/HK/486/97 and A/HK/483/97 (both H5N1/97) with that of human H3N2 and H1N1 viruses in human primary monocyte-derived macrophages in vitro. Secretion of tumour necrosis factor alpha (TNF alpha) from macrophages infected with the viruses was compared by ELISA. By use of naturally occurring viral reassortants and recombinant viruses generated by reverse genetic techniques, we investigated the viral genes associated with the TNF-alpha response. FINDINGS: The H5N1/97 viruses induced much higher gene transcription of proinflammatory cytokines than did H3N2 or H1N1 viruses, particularly TNF alpha and interferon beta. The concentration of TNF-alpha protein in culture supernatants of macrophages infected with these viruses was similar to that induced by stimulation with Escherichia coli lipopolysaccharide. The non-structural (NS) gene-segment of H5N1/97 viruses contributed to the increase in TNF alpha induced by the virus. INTERPRETATION: The H5N1/97 viruses are potent inducers of proinflammatory cytokines in macrophages, the most notable being TNF alpha. This characteristic may contribute to the unusual severity of human H5N1 disease.

Barriers to providing effective mental health services to Asian Americans.

Using the research framework recommended by L. Rogler, R. Malgady, and D. Rodriguez (1989), the current paper examines the barriers to providing effective mental health services to Asian Americans. Beginning with the recognition that Asian Americans consists of numerous heterogeneous subgroups, the issue of the stereotype of Asian Americans as the "model minority" was also discussed. The primary focus of the paper is on Stages 2, 3, and 4 within the Rogler et al. (1989) model and the identification and discussion of cultural factors that hinder the delivery of mental health services to Asian Americans. The paper is therefore organized into these three sections: (a) help-seeking or mental health service utilization, (b) evaluation of mental health problems, and (c) psychotherapeutic services. In each of the sections, not only are the barriers to delivery of effective mental health services discussed but so are the research and methodological problems as well as some directions for future research. This critical review of the literature has been prepared with the goal of serving as a "blueprint" for us to pursue rigorous but relevant research to identify and reduce these cultural barriers to providing effective mental health services to Asian Americans.

Quantitative competitive reverse transcription-PCR as a method to evaluate retrovirus removal during chromatography procedures.

Chinese hamster ovary cells used for pharmaceutical protein production express non-infectious retrovirus-like particles. To assure the safety of pharmaceutical proteins, validation of the ability of manufacturing process to clear retrovirus-like particles is required for product registration. Xenotropic murine leukemia virus (X-MuLV) is often used as a model virus for validation studies. Some chromatography procedures used for pharmaceutical protein purification utilize low pH (< pH 4.0) elution buffers which readily inactivate X-MuLV. Therefore, cell-based infectivity assays are unable to evaluate the physical removal of X-MuLV by these chromatography procedures. To distinguish viral inactivation by low pH treatment from viral removal by chromatography, a quantitative competitive reverse transcription PCR method capable of quantifying both infectious and non-infectious X-MuLV has been developed. This method quantifies X-MuLV particles in chromatography pools by quantifying the X-MuLV particle RNA (pRNA). The difference between the amount of X-MuLV pRNA in the load pool and the product-containing elution pool represents the extent of X-MuLV removal. This method is an extremely powerful complement to cell based-infectivity assays as it allows physical removal of X-MuLV by chromatography and filtration procedures to be distinguished from X-MuLV inactivation when buffers with the ability to inactivate retrovirus are used.

Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells.

Persistent infections by viruses such as HIV-1 and hepatitis B virus can pose long-term health hazards. Because establishment of persistent infections involves close interactions and adjustments in both host and virus, it would be informative to establish a paradigm with which a normally cytolytic viral infection can be easily converted to persistent infection, so that the different stages in developing persistent infection can be examined. Such a model system is described in this paper. Highly cytolytic encephalomyocarditis virus (EMCV) infection was shifted to persistent infection as a result of repressed expression of the double-stranded RNA-dependent protein kinase (PKR) in the promonocytic U937 cells. Because of the apoptogenic potential of PKR, a deficiency of PKR resulted in a delay in virus-induced apoptosis in EMCV-infected U937 cells, allowing the eventual establishment of persistent EMCV infection in these cells (U9K-AV2). That this was a bona fide persistent infection was demonstrated by the ability of infected cells to propagate as long-term virus-shedding cultures; electron microscopy studies showing presence of intracellular EMCV virions and chromatin condensation; detection of virus-induced chromosomal DNA fragmentation and sustained expression of apoptogenic p53 and IL-1beta converting enzyme; and demonstration of active EMCV transcription by reverse transcription-PCR. In addition, a host-virus coevolution was observed in U9K-AV2 cultures over time: U9K-AV2 cells exhibited slower growth rates, resistance to viral super-infection, and cessation of IFN-alpha synthesis, whereas the infectivity of EMCV was drastically attenuated. Finally, data are presented on the suitability of this model to study establishment of persistent infection by other viruses such as Sendai virus and reovirus.