Pediatric tympanostomy tube assessment via deep learning.

PURPOSE: Tympanostomy tube (TT) placement is the most frequently performed ambulatory surgery in children under 15. After the procedure it is recommended that patients follow up regularly for "tube checks" until TT extrusion. Such visits incur direct and indirect costs to families in the form of days off from work, copays, and travel expenses. This pilot study aims to compare the efficacy of tympanic membrane (TM) evaluation by an artificial intelligence algorithm with that of clinical staff for determining presence or absence of a tympanostomy tube within the TM. METHODS: Using a digital otoscope, we performed a prospective study in children (ages 10 months-10 years) with a history of TTs who were being seen for follow up in a pediatric otolaryngology clinic. A smartphone otoscope was used by study personnel who were not physicians to take ear exam images, then through conventional otoscopic exam, ears were assessed by a clinician for tubes being in place or tubes having extruded from the TM. We trained and tested a deep learning (artificial intelligence) algorithm to assess the images and compared that with the clinician's assessment. RESULTS: A total of 123 images were obtained from 28 subjects. The algorithm classified images as TM with or without tube in place. Overall classification accuracy was 97.7 %. Recall and precision were 100 % and 96 %, respectively, for TM without a tube present, and 95 % and 100 %, respectively, for TM with a tube in place. DISCUSSION: This is a promising deep learning algorithm for classifying ear tube presence in the TM utilizing images obtained in awake children using an over-the-counter otoscope available to the lay population. We are continuing enrollment, with the goal of building an algorithm to assess tube patency and extrusion.

Exploring the presence of markers of decidualization in the fallopian tubes: a systematic review.

The fallopian tubes (FTs) are part of the female upper genital tract. The healthy FT provides the biological environment for successful fertilization and facilitates the subsequent movement of the conceptus to the endometrial cavity. However, when the FT is damaged, as with salpingitis, pyosalpinx, and hydrosalpinx, it may increase the risk of an ectopic pregnancy, a life-threatening condition. Decidualization refers to a multifactorial process by which the endometrium changes to permit blastocyst implantation. The decidualization reaction is vital for endometrial receptivity during the window of implantation. To date, no comprehensive review that collates evidence on decidualization in the human FT has been conducted. Therefore, the aim of this review is to compile the current evidence on cellular decidualization occurring in the healthy and pathological FT in women of reproductive age. A literature search was conducted using five databases and identified 746 articles, 24 of which were analyzed based on inclusion and exclusion criteria. The available evidence indicates that the FT are able to undergo decidual changes under specific circumstances; however, the exact mechanism by which this occurs is poorly understood. Further research is needed to elucidate the mechanism by which decidualization can occur in the FT.

Intra-host changes in Kaposi sarcoma-associated herpesvirus genomes in Ugandan adults with Kaposi sarcoma.

Intra-host tumor virus variants may influence the pathogenesis and treatment responses of some virally-associated cancers. However, the intra-host variability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma (KS), has to date been explored with sequencing technologies that possibly introduce more errors than that which occurs in the viral population, and these studies have only studied variable regions. Here, full-length KSHV genomes in tumors and/or oral swabs from 9 Ugandan adults with HIV-associated KS were characterized. Furthermore, we used deep, short-read sequencing using duplex unique molecular identifiers (dUMI)-random double-stranded oligonucleotides that barcode individual DNA molecules before library amplification. This allowed suppression of PCR and sequencing errors to ~10-9/base as well as afforded accurate determination of KSHV genome numbers sequenced in each sample. KSHV genomes were assembled de novo, and rearrangements observed were confirmed by PCR and Sanger sequencing. 131-kb KSHV genome sequences, excluding major repeat regions, were successfully obtained from 23 clinical specimens, averaging 2.3x104 reads/base. Strikingly, KSHV genomes were virtually identical within individuals at the point mutational level. The intra-host heterogeneity that was observed was confined to tumor-associated KSHV mutations and genome rearrangements, all impacting protein-coding sequences. Although it is unclear whether these changes were important to tumorigenesis or occurred as a result of genomic instability in tumors, similar changes were observed across individuals. These included inactivation of the K8.1 gene in tumors of 3 individuals and retention of a region around the first major internal repeat (IR1) in all instances of genomic deletions and rearrangements. Notably, the same breakpoint junctions were found in distinct tumors within single individuals, suggesting metastatic spread of rearranged KSHV genomes. These findings define KSHV intra-host heterogeneity in vivo with greater precision than has been possible in the past and suggest the possibility that aberrant KSHV genomes may contribute to aspects of KS tumorigenesis. Furthermore, study of KSHV with use of dUMI provides a proof of concept for utilizing this technique for detailed study of other virus populations in vivo.

Stability of inflammation markers in human blood collected using volumetric absorptive microsampling (VAMS) under typical laboratory storage temperatures.

Dried blood spots (DBS) collected on filter paper such as Guthrie cards are stored for years at room temperature. The assumption is that once dried, the samples remain stable and quantifiable indefinitely since the metabolites these were initially designed to measure, are known for their extended stability. The concentration of other blood proteins such as cytokines, however, are known to vary with storage even in liquid samples stored at -80 °C for extended periods of time. We sought to determine if cytokines are stable for up to 5 months when stored as a dried blood sample using volumetric absorptive microsampling (VAMS) devices. To test this, blood was collected from 4 healthy participants, spiked with recombinant cytokines, and collected into 30 µL VAMS devices. These prepared VAMS devices were stored at room temperature, 4 °C, or -20 °C for up to 5 months and matching VAMS liquid extracts were stored at -80 °C for the same period of time. At each timepoint, the samples were extracted from the VAMS devices and the extracts were analysed by Luminex® for quantification of up to 31 cytokines. These methods were also tested in a remote clinical study over a period of up to 8 months. Cytokine analysis revealed that room temperature, the current standard for DBS and VAMS storage, performed the poorest out of all storage temperatures with significant losses in 13/21 analytes compared to 4 °C at 5 months. Storage at 4 °C or colder performed well for the majority of analytes tested, however out of those, the optimal storage temperature differed for each analyte. There were a small number of analytes that performed poorly regardless of storage conditions and for fractalkine, this was found to be caused by inefficient recovery during extraction. Cytokine concentrations from finger-prick samples were also found to be much more variable that those in venous blood samples. Our results highlight the need to understand the stability of analytes of interest before committing to longitudinal collection and storage of samples in VAMS devices. These data give confidence that storage at 4 °C or colder was beneficial for cytokine stability. Wherein 25/31 cytokines were quantifiably stable at -20 °C when stored for 3 months and 17/21 were quantifiably stable after 5 months when stored at 4 °C.

Filtering Crosstalk from Bath Non-Markovianity via Spacetime Classical Shadows.

From an open system perspective non-Markovian effects due to a nearby bath or neighboring qubits are dynamically equivalent. However, there is a conceptual distinction to account for: neighboring qubits may be controlled. We combine recent advances in non-Markovian quantum process tomography with the framework of classical shadows to characterize spatiotemporal quantum correlations. Observables here constitute operations applied to the system, where the free operation is the maximally depolarizing channel. Using this as a causal break, we systematically erase causal pathways to narrow down the progenitors of temporal correlations. We show that one application of this is to filter out the effects of crosstalk and probe only non-Markovianity from an inaccessible bath. It also provides a lens on spatiotemporally spreading correlated noise throughout a lattice from common environments. We demonstrate both examples on synthetic data. Owing to the scaling of classical shadows, we can erase arbitrarily many neighboring qubits at no extra cost. Our procedure is thus efficient and amenable to systems even with all-to-all interactions.

Treatment Persistence of Renin-Angiotensin-Aldosterone-System Inhibitors Over Time in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding the frequency, timing or predictors of early treatment discontinuation in clinical practice. METHODS: Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with > 5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation. RESULTS: Over median follow-up of 18 months, frequency of drug discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.7% (444 of 3509 users), 10.4% (140 of 1352 users), and 20.4% (435 of 2129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEis/ARBs, and 447 (12.7%) of ACEi/ARB users were switched to ARNIs during follow-up. Across sites, the median proportion of discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.5% (25th-75th percentiles 6.9%-18.9%), 18.8% (25th-75th percentiles 12.5%-28.6%), and 19.6% (25th-75th percentiles 10.7%-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P < 0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEis/ARBs and ARNIs (both P < 0.001) but not of MRAs. Investigator clinical experience was predictive of lower risks of discontinuation of ACEis/ARBs and MRAs (P < 0.02) but not of ARNIs. All other independent predictors of discontinuation were unique to individual therapeutic classes. CONCLUSIONS: One in 10 patients discontinue ACEis/ARBs or ARNIs, and 1 in 5 discontinue MRAs in routine clinical practice of heart failure with reduced ejection fraction. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

An examination of housing interventions among youth experiencing homelessness: an investigation into racial/ethnic and sexual minority status.

OBJECTIVES: The purpose of this study is to explore main and interaction effects of minority and multiple minority statuses on exits from homelessness and the stability of homelessness exits overtime. METHODS: This study utilized the Homeless Management Information System administrative data of 10 922 youth experiencing homelessness collected from a convenience sample of 16 geographically diverse communities across the USA between 2015-17. Using multinomial logistic regression analyses and logistic regression, main effects and interaction effects of racial/ethnic minority identity and sexual/gender minority identity were examined on various homelessness exits (n = 9957) and housing sustainability (n = 5836). RESULTS: Black youth, relative to White youth, were disproportionately exiting homelessness through incarceration (P < 0.001). Black and Latinx youth were less likely to successfully self-resolve their homelessness (both P < 0.05). Black heterosexual and Black and Latinx non-heterosexual youth were most frequently lost to the homeless system (all P < 0.01). Black youth, relative to White youth, were approximately half as likely to remain stably housed after returning to family (P < 0.01). CONCLUSIONS: With respect to housing exits and exit stability, Black and Latinx heterosexual youth are consistently at a disadvantage. Homelessness/housing systems and programs need to conduct a deeper investigation into how they implement and develop equitable outreach and engagement practices.

High-content phenotypic screening identifies novel chemistries that disrupt mosquito activity and development.

New classes of chemistries are needed to control insecticide resistant populations of mosquitoes and prevent transmission of vector-borne diseases (VBDs). Organismal screens of chemical collections have played an important role in the search for new vector insecticides and the identification of active ingredients (AIs) that cause rapid mortality of mosquitoes. Advances in image-based screening offer an opportunity to identify chemistries that operate via novel biochemical modes and investigate the range of phenotypes exhibited by mosquitoes following exposure to lethal and sub-lethal chemical dose. An automated, high throughput phenotypic screen (HTS) employing high-content imaging of first instar (L1) Aedes aegypti larvae was developed to identify chemistries associated with mortality and atypical morphological phenotypes. A pilot screen of the Library of Pharmacologically Active Compounds (LOPAC1280) identified 92 chemistries that disrupted larval activity and development, including conventional insecticides and chemistries known to modulate G protein-coupled receptors (GPCRs) and other molecular targets in mammalian systems. Secondary assay series were used to evaluate a selection of chemistries for impacts on mosquito activity, survival and development. Ritodrine hydrochloride reduced mobility of larvae but had no observable effect on survival and development of mosquitoes. High doses of metergoline suppressed larval activity and sub-lethal dose resulted in pupal mortality. Assay data support the utility of phenotypic screening and diverse entomological end-points for discovery of novel insecticidal chemical scaffolds. The insecticide discovery process must consider how multi-modal efficacy spectra contribute to vector and VBD control.

Variation in use and dosing escalation of renin angiotensin system, mineralocorticoid receptor antagonist, angiotensin receptor neprilysin inhibitor and beta-blocker therapies in heart failure and reduced ejection fraction: Association of comorbidities.

BACKGROUND: In patients with heart failure and reduced ejection fraction (HFrEF), angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), or angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists (MRA), and beta-blockers (ßB) are underutilized. It is unknown if patients with and without comorbidities have similar ACEi/ARB/ARNI, MRA, and ßB prescription patterns. METHODS: Baseline data from the CHAMP-HF (Change the Management of Patients with Heart Failure) registry were categorized by history of atrial fibrillation, asthma/chronic lung disease, obstructive sleep apnea, and depression. Using multivariate hierarchical logistic models, associations of ACEi/ARB/ARNI, MRA and ßB medication use and dose by comorbidities were assessed after adjusting for patient characteristics. RESULTS: Of 4,815 HFrEF patients from 152 CHAMP-HF sites, ACEi/ARB/ARNI use was lower in patients with more comorbidities, and generally, MRA use was low and ßB use was high. In adjusted analyses, patients with HFrEF and comorbid obstructive sleep apnea, vs. without, were more likely to be prescribed ARNI (OR [95% CI]: 1.25 [1.00, 1.55]); P = .047 and MRA (1.31 [1.11, 1.55]); P = .002 and less likely to be prescribed ACEi (0.74 [0.63, 0.88]); P < .001. Patients with atrial fibrillation, vs. without, were less likely to receive ACEi/ARB (0.82 [0.71, 0.95]); P = .006 and any study medication (0.81 [0.67, 0.97]); P = .020. Comorbid lung disease and history of depression were not associated with HFrEF prescriptions. CONCLUSIONS: Renin-angiotensin-aldosterone blockade therapy prescription and dose varied by comorbidity status, but ßB therapy did not. In quality efforts, leaders need to consider use and dosing of prescriptions in light of prevalent comorbidities.

Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).

BACKGROUND: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. OBJECTIVES: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. METHODS: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40-80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0-100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. RESULTS: 64 adults (54 females, 10 males) aged 48-79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. CONCLUSIONS: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800.

AIMS: Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well-characterized GRAS host. METHODS AND RESULTS: This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. CONCLUSIONS: Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.

Quantitative proteomic profiling of shake flask versus bioreactor growth reveals distinct responses of Agrobacterium tumefaciens for preparation in molecular pharming.

The preparation of Agrobacterium tumefaciens cultures with strains encoding proteins intended for therapeutic or industrial purposes is an important activity prior to treatment of plants for transient expression of valuable protein products. The rising demand for biologic products such as these underscores the expansion of molecular pharming and warrants the need to produce transformed plants at an industrial scale. This requires large quantities of A. tumefaciens culture, which is challenging using traditional growth methods (e.g., shake flask). To overcome this limitation, we investigate the use of bioreactors as an alternative to shake flasks to meet production demands. Here, we observe differences in bacterial growth among the tested parameters and define conditions for consistent bacterial culturing between shake flask and bioreactor. Quantitative proteomic profiling of cultures from each growth condition defines unique growth-specific responses in bacterial protein abundance and highlights the functional roles of these proteins, which may influence bacterial processes important for effective agroinfiltration and transformation. Overall, our study establishes and optimizes comparable growth conditions for shake flask versus bioreactors and provides novel insights into fundamental biological processes of A. tumefaciens influenced by such growth conditions.

Internal Delensing of Cosmic Microwave Background Polarization B-Modes with the POLARBEAR Experiment.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

The intestinal protist Blastocystis is not a common member of the healthy infant gut microbiota in a Westernized country (Ireland).

Research into the gut microbiota of human infants is necessary in order to better understand how inter-species interactions and ecological succession shape the diversity of the gut microbiota, and in turn, how the specific composition of the gut microbiota impacts on host health both during infancy and in later years. Blastocystis is a ubiquitous intestinal protist that has been linked to a number of intestinal and extra-intestinal diseases. However, emerging data show that asymptomatic carriage is common and that Blastocystis is prevalent in the healthy adult gut microbiota. Nonetheless, little is known about the prevalence and diversity of this microorganism in the healthy infant gut, including when and how individuals become colonized by Blastocystis. Here, we surveyed the prevalence and diversity of Blastocystis in an infant population (n = 59) from an industrialized country (Ireland) using Blastocystis-specific primers at three or more time-points up to 24 months old. Only three infants were positive for Blastocystis (prevalence = 5%) and this was only noted for samples collected at month 24. This rate is comparatively low relative to previously reported prevalence rates in the contemporaneous adult population. These data suggest that infants in Westernized countries that are successfully colonized by Blastocystis most likely acquire this microorganism via horizontal transfer.

The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles.

Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), an enzyme involved in cholesterol synthesis in higher organisms and in isoprenoid biosynthesis in some bacteria. We hypothesized that statins may influence the microbial community in the gut through either direct inhibition or indirect mechanisms involving alterations to host responses. We therefore examined the impact of rosuvastatin (RSV) on the community structure of the murine gastrointestinal microbiota. RSV was orally administered to mice and the effects on the gut microbiota, host bile acid profiles, and markers of inflammation were analyzed. RSV significantly influenced the microbial community in both the cecum and feces, causing a significant decrease in α-diversity in the cecum and resulting in a reduction of several physiologically relevant bacterial groups. RSV treatment of mice significantly affected bile acid metabolism and impacted expression of inflammatory markers known to influence microbial community structure (including RegIIIγ and Camp) in the gut. This study suggests that a commonly used statin (RSV) leads to an altered gut microbial composition in normal mice with attendant impacts on local gene expression profiles, a finding that should prompt further studies to investigate the implications of statins for gut microbiota stability and health in humans.NEW & NOTEWORTHY This work demonstrates that rosuvastatin administration in mice affects the gastrointestinal microbiota, influences bile acid metabolism, and alters transcription of genes encoding factors involved in gut homeostasis and immunity in the gastrointestinal tract.

A Multibacteriocin Cheese Starter System, Comprising Nisin and Lacticin 3147 in Lactococcus lactis, in Combination with Plantaricin from Lactobacillus plantarum.

Functional starter cultures demonstrating superior technological and food safety properties are advantageous to the food fermentation industry. We evaluated the efficacies of single- and double-bacteriocin-producing starters of Lactococcus lactis capable of producing the class I bacteriocins nisin A and/or lacticin 3147 in terms of starter performance. Single producers were generated by mobilizing the conjugative bacteriophage resistance plasmid pMRC01, carrying lacticin genetic determinants, or the conjugative transposon Tn5276, carrying nisin genetic determinants, to the commercial starter L. lactis CSK2775. The effect of bacteriocin coproduction was examined by superimposing pMRC01 into the newly constructed nisin transconjugant. Transconjugants were improved with regard to antimicrobial activity and bacteriophage insensitivity compared to the recipient strain, and the double producer was immune to both bacteriocins. Bacteriocin production in the starter was stable, although the recipient strain proved to be a more efficient acidifier than transconjugant derivatives. Overall, combinations of class I bacteriocins (the double producer or a combination of single producers) proved to be as effective as individual bacteriocins for controlling Listeria innocua growth in laboratory-scale cheeses. However, using the double producer in combination with the class II bacteriocin producer Lactobacillus plantarum or using the lacticin producer with the class II producer proved to be most effective for reducing bacterial load. As emergence of bacteriocin tolerance was reduced 10-fold in the presence of nisin and lacticin, we suggest that the double producer in conjunction with the class II producer could serve as a protective culture providing a food-grade, multihurdle approach to control pathogenic growth in a variety of industrial applications.IMPORTANCE We generated a suite of single- and double-bacteriocin-producing starter cultures capable of generating the class I bacteriocin lacticin 3147 or nisin or both bacteriocins simultaneously via conjugation. The transconjugants exhibited improved bacteriophage resistance and antimicrobial activity. The single producers proved to be as effective as the double-bacteriocin producer at reducing Listeria numbers in laboratory-scale cheese. However, combining the double producer or the lacticin-producing starter with a class II bacteriocin producer, Lactobacillus plantarum LMG P-26358, proved to be most effective at reducing Listeria numbers and was significantly better than a combination of the three bacteriocin-producing strains, as the double producer is not inhibited by either of the class I bacteriocins. Since the simultaneous use of lacticin and nisin should reduce the emergence of bacteriocin-tolerant derivatives, this study suggests that a protective starter system produced by bacteriocin stacking is a worthwhile multihurdle approach for food safety applications.

The altered gut microbiota in adults with cystic fibrosis.

BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed. RESULTS: The CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV1 (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV1 ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (-0.383, Simpson's Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity. CONCLUSIONS: This is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to develop CF specific probiotics to minimise microbiota alterations.

Supplementation with omega-3 fish oil has no effect on bone mineral density in adults with knee osteoarthritis: a 2-year randomized controlled trial.

UNLABELLED: This study aimed to determine the effect of fish oil on bone mineral density (BMD). There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD. This randomized controlled trial did not demonstrate any efficacy of omega-3 fatty acids on bone loss in adults. INTRODUCTION: The purpose of this study is to investigate whether supplementation with high dose omega-3 fish oil could have an impact on BMD. METHODS: In a multicentre, double-blind randomized controlled trial (RCT) (ACTRN 12607000415404), 202 Australian participants aged ≥40 with knee osteoarthritis (mean age, 61.0 ± 10.0 years; 49 % female) were randomized to receive either high dose (4.5 g eicosapentaenoic acid and docosahexaenoic acid daily) or low dose (0.45 g/day) omega-3 fish oil for 2 years. BMD was assessed at baseline and 2 years by dual energy X-ray absorptiometry. RESULTS: In subjects with baseline and 2-year assessments, mean standardized BMD at baseline for low or high dose group was 1198 ± 198 and 1157 ± 169 mg/cm(2), respectively, for the lumbar spine and was 1035 ± 165 and 1017 ± 174 mg/cm(2), respectively, for the femoral neck. There were no differences in the 2-year BMD measures between high and low dose groups after adjusting for baseline BMD in the complete case regression analyses (lumbar spine 3.7, 95 % confidence interval (CI) -7.9 to 15.3 mg/cm(2) and femoral neck -5.5, 95 % CI -14.9 to 3.9 mg/cm(2)). The findings did not change with additional adjustments of age, gender, study centre and uses of bone-related drugs during the study period as well as using the intention-to-treat analysis or limiting to older participants (≥55 years at the baseline) (all P ≥ 0.25). Mild adverse events such as headache and gastrointestinal intolerance were common but did not occur more frequently in either group. There were no serious adverse events related to the intervention. CONCLUSION: A 2-year supplementation with high-dose omega-3 fish oil did not alter bone loss among men and women with knee osteoarthritis.

Prevalence and associations of gout and hyperuricaemia: results from an Australian population-based study.

BACKGROUND: Despite gout and hyperuricaemia being major comorbid health issues worldwide, there is a knowledge gap regarding their impact in the Australian community. AIMS: To determine the prevalence and associations of self-reported medically diagnosed gout and hyperuricaemia in an Australian population-based cohort. METHODS: The North West Adelaide Health Study is a longitudinal cohort study consisting of three stages of data collection. Each stage comprised a self-complete questionnaire, clinic assessment and computer-assisted telephone interview. In Stage 3 (2008-2010), participants were asked if a doctor had ever diagnosed them with gout. Additional data included demographics, comorbidities, laboratory data and Short Form 36 (SF-36). Participants were defined as having gout if they had self-reported medically diagnosed gout or were taking any gout-specific medication (allopurinol, colchicine, probenecid). Hyperuricaemia was defined as a serum uric acid (SUA) level >0.42 mmol/L in men and >0.34 mmol/L in women. RESULTS: The overall prevalence of gout was 5.2%. Males were significantly more likely to have gout than females (8.5 vs 2.1%, P < 0.001). The overall prevalence of hyperuricaemia was 16.6%, with being male again identified as a significant risk factor (17.8 vs 15.4%, P < 0.01). Both gout and hyperuricaemia were associated with male sex, body mass index and renal disease after multivariable adjustment. There was no significant difference reported in quality of life (mean SF-36) scores in participants with gout compared to unaffected individuals. CONCLUSION: The prevalence of gout and hyperuricaemia is high in the South Australian population. This study emphasises the need for optimal diagnosis and management of gout in Australia.