The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis.

Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.

Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice.

OBJECTIVE: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model. METHODS: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1ß, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1ß, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR. RESULTS: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1ß, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males. CONCLUSIONS: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.

Impact of COVID-19 on CT-diagnosed acute appendicitis and diverticulitis: was there collateral damage?

AIM: To evaluate the change in diagnosis rates, disease severity at presentation, and treatment of acute appendicitis and diverticulitis during the COVID-19 shutdown. MATERIALS AND METHODS: Following institutional review board approval, 6,002 CT examinations performed at five hospitals for suspected acute appendicitis and/or diverticulitis over the 12 weeks preceding and following the shutdown were reviewed retrospectively. Semi-automated language analysis (SALA) of the report classified 3,676 CT examinations as negative. Images of the remaining 2,326 CT examinations were reviewed manually and classified as positive or negative. Positive cases were graded as non-perforated; perforated, contained; and perforated, free. RESULTS: CT examinations performed for suspected appendicitis and/or diverticulitis decreased from 3,558 to 2,200 following the shutdown. The rates of positive diagnoses before and after shutdown were 4% (144) and 4% (100) for appendicitis and 8% (284) and 7% (159) for diverticulitis (p>0.2 for both). For positive CT examinations, the rates of perforation, hospitalisation, surgery, and catheter drainage changed by -2%, -3%, -2%, and -3% for appendicitis (n=244, p>0.3 for all) and +6% (p=0.2) +9% (p=0.06), +4% (p=0.01) and +1% (p=0.6) for diverticulitis (n=443). CONCLUSION: CT examinations performed for suspected appendicitis or diverticulitis declined after the shutdown, likely reflecting patients leaving urban centres and altered triage of non-COVID-19 patients. The diagnosis rates, disease severity at presentation, and treatment approach otherwise remained mostly unchanged.

COVID-19 vaccine perceptions in the initial phases of US vaccine roll-out: an observational study on reddit.

BACKGROUND: Open online forums like Reddit provide an opportunity to quantitatively examine COVID-19 vaccine perceptions early in the vaccine timeline. We examine COVID-19 misinformation on Reddit following vaccine scientific announcements, in the initial phases of the vaccine timeline. METHODS: We collected all posts on Reddit (reddit.com) from January 1 2020 - December 14 2020 (n=266,840) that contained both COVID-19 and vaccine-related keywords. We used topic modeling to understand changes in word prevalence within topics after the release of vaccine trial data. Social network analysis was also conducted to determine the relationship between Reddit communities (subreddits) that shared COVID-19 vaccine posts, and the movement of posts between subreddits. RESULTS: There was an association between a Pfizer press release reporting 90% efficacy and increased discussion on vaccine misinformation. We observed an association between Johnson and Johnson temporarily halting its vaccine trials and reduced misinformation. We found that information skeptical of vaccination was first posted in a subreddit (r/Coronavirus) which favored accurate information and then reposted in subreddits associated with antivaccine beliefs and conspiracy theories (e.g. conspiracy, NoNewNormal). CONCLUSIONS: Our findings can inform the development of interventions where individuals determine the accuracy of vaccine information, and communications campaigns to improve COVID-19 vaccine perceptions, early in the vaccine timeline. Such efforts can increase individual- and population-level awareness of accurate and scientifically sound information regarding vaccines and thereby improve attitudes about vaccines, especially in the early phases of vaccine roll-out. Further research is needed to understand how social media can contribute to COVID-19 vaccination services.

The Politicization of Health and Science: Role of Political Cues in Shaping the Beliefs of the Vaccine-Autism Link.

One critical lesson learned from public opinion research about climate change is that the cost of politicization is disastrous. Although the literature has shown the dire consequences of politicized science issues, few have examined how such politicization is possibly triggered by political leaders in a seemingly nonpartisan science topic. Using two experiments (total n = 1,249), this article demonstrates how political cues over scientific expertise shape individuals' beliefs in the vaccine and autism debate. The results indicate that Republicans tend to follow President Trump compared to scientists in the subject matter. On the other hand, Democrats follow scientists but are not influenced by Trump. The implications of political encroachment into health and science are discussed.

Red Media, Blue Media, Trump Briefings, and COVID-19: Examining How Information Sources Predict Risk Preventive Behaviors via Threat and Efficacy.

Upon the growing concern over a massive infodemic and politicization of health issues during the COVID-19 pandemic, this study investigated how individuals' use of partisan media and Trump briefings, along with other information sources, predicts risk preventive behaviors. Drawing on the Extended Parallel Process Model (EPPM), our survey analysis (n= 1,106) revealed that those obtaining COVID-19 information from conservative media and Trump briefings were less likely to believe that COVID-19 is a serious threat (perceived threat) and that recommended preventive behaviors are effective and feasible (perceived efficacy). These beliefs, in turn, resulted in their decreased intentions to adopt risk preventative behaviors. In contrast, those who got COVID-19 information from liberal media, health organizations' briefings, and traditional media reported heightened threat and efficacy perception, which, in turn, led to their willingness to take risk preventive actions.

Incidence of subsequent osteoporotic fractures after distal radius fractures and mortality of the subsequent distal radius fractures: a retrospective analysis of claims data of the Korea National Health Insurance Service.

A better understanding of the features of subsequent fractures after distal radius fracture (DRF) is important for the prevention of further osteoporotic fractures. This study found that the cumulative incidence of subsequent osteoporotic fractures in South Korea increased over time and that the mortality rates of subsequent DRFs were lower than those of first-time DRFs. INTRODUCTION: We examined the incidence of osteoporotic fractures following distal radius fractures (DRFs) and the mortality rate after subsequent DRFs using claims data from the Korea National Health Insurance (KNHI) Service. METHODS: We identified records for 41,417 patients with first-time DRFs in 2012. The occurrence of osteoporotic fractures of the spine, hip, wrist, and humerus at least 6 months after the index DRF was tracked through 2016. All fractures were identified by specific diagnosis and procedure codes. One-year mortality rates and standardized mortality ratios (SMRs) for initial and subsequent DRFs were calculated for all patients. RESULTS: The 4-year cumulative incidence of all subsequent osteoporotic fractures was 14.74% (6105/41,417; 9.47% in men, 15.9% in women). The number of associated subsequent fractures was 2850 for the spine (46.68%), 2271 for the wrist (37.2%), 708 for the hip (11.6%), and 276 for the humerus (4.52%). The cumulative mortality rate 1 year after the first-time and subsequent DRF was 1.47% and 0.71%, respectively, and the overall SMR was 1.48 (95% CI: 1.37-1.61) and 0.71 (95% CI: 0.42-1.21), respectively. CONCLUSION: The cumulative incidence of osteoporotic fractures following DRFs increased over the study period and was higher among women. The cumulative mortality rates and SMRs of subsequent DRFs were lower than those of first-time DRFs at the 1-year follow-up. Given the increasing incidence rate of DRFs, the incidence of subsequent osteoporotic fractures may also increase.

Prediction of Hospitalization Length. Quantile Regression Predicts Hospitalization Length and its Related Factors better than Available Methods.

BACKGROUND: Length of hospitalization is one of the most important indices in evaluating the efficiency and effectiveness of hospitals and the optimal use of resources. Identifying these indices' associated factors could be useful. This study aimed to investigate effective factors of the length of hospitalization in Zanjan teaching hospitals in 2018 using the Quantile regression model. METHODS: This cross-sectional study was conducted on 1,031 patients. The study population consisted of patients in orthopaedic, pediatric, internal, surgical and intensive care units. The samples were selected by multistage random sampling. The information was collected by a pre-designed checklist. The Quantile regression model and ordinary regression model were performed on the data. RESULTS: Of the 1,031 patients admitted to different units, 624 (60.52%) were male. Mean and standard deviation of length of hospitalization for men, women and all patients were 7.25±5.48, 8.09±6.35 and 7.58±5.83 respectively. For 90 percent of patients the length of hospitalization was less than 14 days. Twenty-five percent of patients in pediatric and orthopedic units and ten percent of patients in internal and surgery units were hospitalized less than three days. In all quantiles, patients' length of hospitalization in surgery and orthopedic units, compared to the intensive care unit, and patients hospitalized for injuries and poisonings compared to other causes, had a statistically significant difference. (p<0.05). CONCLUSION: Due to the heterogeneity (skewness) of the length of hospital stay in different units of the hospital, the quantile regression model predicts the length of hospital stay more precisely than the ordinary regression models.

Septicaemia is associated with increased disease activity and mortality in systemic lupus erythematosus: a retrospective analysis from Taiwan.

OBJECTIVE: This study aimed to investigate how septicaemia, non-septicaemia infection and the disease itself are associated with disease activity and mortality in inpatients with systemic lupus erythematosus (SLE) in Taiwan. METHODS: We retrospectively reviewed 1115 patients and enrolled 427 with SLE admitted for lupus flare-ups and co-morbidities. Disease activity and infection type/site were recorded and categorized according to the causes of admission and mortality into three categories, of which two were specified as follows: (a) septicaemia admissions, non-septicaemia admissions; and (b) septicaemia mortality, non-septicaemia infection mortality and non-infection mortality. The relationships between lupus flare-ups and mortality in different groups were analysed using an unpaired t-test, Mann-Whitney U-test and logistic regression. RESULTS: Septicaemia was the major cause of mortality in SLE inpatients. There were 98 (22.95%) mortality patients among all 427 SLE patients. The septicaemia admissions had higher disease activity (SLE Disease Activity Index 2000 = 13.00 ± 7.98) than the non-septicaemia admissions (9.77 ± 5.72; p < 0.01). The mean current SLEDAI score of the septicaemia mortality group (14.91 ± 8.01) was higher than that of the non-septicaemia infection mortality group (10.05 ± 5.75; p = 0.02), in spite of the similar mean earlier SLEDAI score. The risk of mortality in the septicaemia mortality group due to previous septicaemia admissions was 13.2 times (odds ratio) higher than in the non-septicaemia infection mortality group and 15.6 times higher than in the non-infection mortality group. CONCLUSION: Septicaemia relates to increased lupus disease activity and is associated with a greater risk of mortality in the SLE patients than other causes of admission. Fewer previous septicaemia admissions decrease the risk of septicaemia mortality.

Cardiometabolic risk prediction algorithms for young people with psychosis: a systematic review and exploratory analysis.

OBJECTIVE: Cardiometabolic risk prediction algorithms are common in clinical practice. Young people with psychosis are at high risk for developing cardiometabolic disorders. We aimed to examine whether existing cardiometabolic risk prediction algorithms are suitable for young people with psychosis. METHODS: We conducted a systematic review and narrative synthesis of studies reporting the development and validation of cardiometabolic risk prediction algorithms for general or psychiatric populations. Furthermore, we used data from 505 participants with or at risk of psychosis at age 18 years in the ALSPAC birth cohort, to explore the performance of three algorithms (QDiabetes, QRISK3 and PRIMROSE) highlighted as potentially suitable. We repeated analyses after artificially increasing participant age to the mean age of the original algorithm studies to examine the impact of age on predictive performance. RESULTS: We screened 7820 results, including 110 studies. All algorithms were developed in relatively older participants, and most were at high risk of bias. Three studies (QDiabetes, QRISK3 and PRIMROSE) featured psychiatric predictors. Age was more strongly weighted than other risk factors in each algorithm. In our exploratory analysis, calibration plots for all three algorithms implied a consistent systematic underprediction of cardiometabolic risk in the younger sample. After increasing participant age, calibration plots were markedly improved. CONCLUSION: Existing cardiometabolic risk prediction algorithms cannot be recommended for young people with or at risk of psychosis. Existing algorithms may underpredict risk in young people, even in the face of other high-risk features. Recalibration of existing algorithms or a new tailored algorithm for the population is required.

Association of exposure to secondhand smoke at home with early age at menarche in South Korea.

OBJECTIVES: The secular trend in age at menarche (AAM) has declined both worldwide and in Korea. Early AAM is associated with the risk of several diseases, reproductive capacity, and psychological problems. We aimed to investigate the relationship between secondhand smoke (SHS) exposure at home and early puberty onset using AAM in Korean adolescents. STUDY DESIGN: This is a retrospective cross-sectional study. METHODS: This study used data from the Korea Youth Risk Behavior Web-based Survey 2014-2015. We used the mean AAM (12.2 years) as a determinant of early AAM. After the exclusion of girls without menarche or who did not respond, the total population comprised 63,618 participants. We categorized AAM as 'early' and 'average or late.' Adolescents with SHS exposure were assigned to the 'never exposed,' 'light exposure,' and 'heavy exposure' groups. Multiple logistic regression analyses were performed. RESULTS: We observed a positive association, approximately 1.12 times, between early AAM and high SHS exposure (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.05-1.19). Girls who started smoking before the age of 12 years (OR, 1.68; 95% CI, 1.41-1.99) showed a stronger association with early AAM than non-smokers. Active smoking showed a stronger association with early AAM. Never smokers with high SHS exposure at home were 1.13 times likelier to have an early AAM (OR, 1.13; 95% CI, 1.05-1.22) than those without SHS exposure. CONCLUSIONS: In addition to active smoking, SHS may also be a risk factor for early AAM. Education aimed at active and secondhand smoking prevention is needed to protect children against early AAM.

Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents.

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled "Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens" to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government. This and the accompanying minireview on nonclinical PK/PD summarize the workshop discussions and recommendations. It is important to consider how information like PK/PD can support the clinical effectiveness of new antibacterial drugs, as PK/PD data have become central to antibacterial drug development programs. Key clinical considerations for antibacterial dose selection and clinical PK/PD characterization discussed in this minireview include a robust assessment of PK in the patient population of interest, critical considerations for assessing drug penetration in the lung for the treatment of pneumonia, and an emphasis on special populations, including patients with renal impairment and augmented renal function, as well as on dosing in obese and pediatric patients. Successful application of such approaches is now used to provide a more informative drug development package to support the approval of new antibiotics.

From Social Media to Mainstream News: The Information Flow of the Vaccine-Autism Controversy in the US, Canada, and the UK.

Despite increasing warnings about inaccurate information online, little is known about how social media contribute to the widespread diffusion of unverified health information. This study addresses this issue by examining the vaccine-autism controversy. By looking into a large dataset of Twitter, Reddit posts, and online news over 20 months in the US, Canada, and the UK, our time-series analysis shows that Twitter drives news agendas, and Reddit follows news agendas regarding the vaccine-autism debate. Additionally, the results show that both Twitter and Reddit are more likely to discuss the vaccine-autism link compared to online news content.

Inactivation of chikungunya virus in blood components treated with amotosalen/ultraviolet A light or amustaline/glutathione.

BACKGROUND: Chikungunya virus, a mosquito-borne arbovirus, often co-circulates with the Zika, dengue, and yellow fever viruses in Aedes mosquito-infested areas where cases of arbovirus transfusion-transmitted infections have been reported. Building on past experience to help maintain the availability of safe components during major outbreaks of chikungunya virus in La Reunion, Italy, and Thailand and of Zika virus in the Pacific, the Caribbean, and the Americas, pathogen inactivation is a mitigation strategy to reduce the risk of transfusion-transmitted infection. Inactivation of chikungunya virus was investigated for platelets in 100% plasma using amotosalen/ultraviolet A light, and in red blood cells using amustaline/glutathione. STUDY DESIGN AND METHODS: Platelets in 100% plasma and red blood cells (RBCs) were spiked with chikungunya virus. Infectious chikungunya virus titers were measured in contaminated blood products before and after treatment with amotosalen/ultraviolet A light for platelets in 100% plasma and after treatment with amustaline/glutathione for RBCs. Viral infectivity was quantified by plaque assay. RESULTS: The mean chikungunya virus infectivity titers before inactivation were 6.50 log10 plaque-forming units/mL for platelets in 100% plasma and 7.60 log10 plaque-forming units/mL for RBCs. No infectivity was detected after amotosalen/ultraviolet A light or amustaline/glutathione treatment, corresponding to greater than 6.5 log10 plaque-forming units/mL and greater than 7.1 log10 plaque-forming units/mL of inactivation, respectively. CONCLUSION: Robust levels of chikungunya virus inactivation were achieved for platelets in 100% plasma and for RBC components. The licensed amotosalen/ultraviolet A light technology and the amustaline/glutathione pathogen-reduction system under development may provide an opportunity for comprehensive mitigation of the risk of chikungunya virus transfusion-transmitted infection by plasma, platelets, and RBCs.

miRNA expression profile of mucoepidermoid carcinoma.

OBJECTIVES: MicroRNAs (miRNAs) are single-stranded RNAs that have been implicated in cancer initiation and progression and act as tumour suppressors or oncogenes. In this study, miRNA profiling was conducted on the most frequent malignancy of salivary glands, mucoepidermoid carcinoma (MEC), in comparison with normal tissues. MATERIALS AND METHODS: The TaqMan Human miRNA Cards Array was used for the miRNA profiling of MEC and normal tissues. To validate the differentially expressed miRNAs in MEC, we used real-time PCR (qRT-PCR). RESULTS: miR-302a was the most significantly increased miRNA in cancer tissues (p < .05). Here, we demonstrate that the upregulation of miR-302a expression in SGT cell lines induced cancer cell invasion in vitro. CONCLUSIONS: These promising results suggest the need for further studies to establish mir-302a as a marker of invasion and aggressiveness in MEC.

A method of evaluating facial pores using optical 2D images and analysis of age-dependent changes in facial pores in Koreans.

BACKGROUND: Enlarged facial pores and changes in pore area are of concern for cosmetic reasons. To evaluate pores, measuring tools based on 3D methodology are used. Yet, these methods are limited by their measuring ranges. In this study, we performed pore analysis by measuring the whole face using 2D optical images. We further sought to understand how the pores of Korean women change with age. MATERIALS AND METHODS: One hundred sixteen Korean female subjects aged 20-60 years were recruited for this study. Facial images were taken using the VISIA-CR® adjusted light source. Images were processed using Image-Pro Plus 9.2. Statistical significance was assumed when P < .05. RESULTS: The pore area, as indicated by pixel count, gradually increased in patients through their 40s, but decreased through their 50s and 60s. Facial pores generally exhibited directionality through the patients' 30s, but this isotropic feature was more prominent in their 50s. Pore elongation increased stepwise. The first increase occurred during the transition from patients' 30s to their 40s and the second increase occurred during the transition from patients' 50s to their 60s. This indicated that the pores deformed from a circular shape to a long elliptic shape over time. CONCLUSION: A new evaluation method using 2D optical images facilitates the analysis of pore distribution and elongation throughout the entire cheek. This is an improvement over an analysis of pores over a narrow region of interest.

A new technique for evaluating heel xerosis grade and the effects of moisturizer on heel skin dryness.

BACKGROUND: Dryness-related heel skin problems are common; however, there are very few studies about heel skin dryness. The objective of this study was to develop new assessment methods for evaluating heel skin dryness, to clarify the characteristics associated with heal skin dryness, and assess the effectiveness of moisturizer use according to dryness severity. MATERIALS AND METHODS: We investigated the heel skin of 150 Korean women (aged 20-78 years). Heel skin images were taken using a DSLR camera and the distribution or severity of flakes, scaling, cracking, and fissures were visually assessed. Skin properties such as hydration, transepidermal water loss (TEWL), amount of dead skin cells, and efficacy of moisturizer were evaluated according to heel xerosis grade. Furthermore, as conventional evaluation methods for desquamation are not appropriate for heel skin, we developed new techniques using binarization of magnified images. RESULTS: Skin hydration tended to decrease and TEWL tended to increase as heel dryness grade increased. The amount of dead skin cells increased with increasing dryness grade using the new technique. Subjects in the severe dryness group achieved similar hydration levels as normal subjects at baseline after 3 hours of moisturizer application. CONCLUSION: Our new methods of visually classifying heel dryness and quantifying dead skin cells using magnified images effectively evaluated heel skin properties. As heel skin is prone to dryness, daily repetitive application of moisturizer might be helpful for hydrating dry heel skin, and ultimately preventing complications.

Inpatient burden of esophageal cancer and analysis of factors affecting in-hospital mortality and length of stay.

Esophageal cancer (EC) continues to be a major source of morbidity and mortality in the United States. However, there has been a relative dearth of research into hospital utilization in patients with EC. This study examines temporal trends in hospital admissions, length of stay (LOS), mortality, and costs associated with EC. In addition, we also analyzed factors associated with inpatient mortality and LOS. We interrogated National Inpatient Sample (NIS), a large registry of inpatient data, to retrieve information about various demographic and factors associated with hospital stay in patients who were admitted for EC between the years 1998 and 2013 in the United States. After examining trends over time, multivariate analysis was performed to identify factors associated with LOS and mortality. During 1998-2013, 538,776 hospital stays with principal diagnosis of EC were reviewed. Number of hospital stays and inpatient charges increased by 397 per year (±67.8; P < 0.0001) and $3,033 per patient per year (±135; <0.0001) respectively. Mortality and LOS decreased by 0.23% per year (±0.03; P < 0.0001) and 0.07 days per year (±0.006; P < 0.0001) respectively. Multiple factors associated with LOS and mortality were outlined. Despite overall increase in hospital utilization with respect to number of admissions and inpatient charges, inpatient mortality and LOS associated with EC declined. Factors associated with inpatient mortality and LOS may help drive clinical decision-making and influence healthcare or hospital policy.

Adherence to Canada's Food Guide recommendations among Alberta's multi-ethnic youths is a major concern: findings from the WHY ACT NOW project.

BACKGROUND: Dietary habits formed during youth may result in the development of obesity and chronic diseases in adulthood. We aimed to determine the frequency of the consumption of foods and beverages and the degree of adherence to Canada's Food Guide recommendations among multi-ethnic youths. METHODS: Participants were recruited from 12 schools in the Edmonton, Alberta area by use of posters, school newsletters and advertisements. A 30-item food frequency questionnaire was administered by a trained interviewer to assess dietary intake in a convenience sample of 557 (328 females and 229 males) youths aged 11-23 years; for the purpose of the present study, only the 14-18 years age group was considered in the analysis. Participants were divided by sex and self-identified ethnicity into four groups [Indigenous, African & Middle Eastern (AME), Asian, and European]. Statistical analysis of the data was undertaken using t-tests, Welch's analysis of variance and Games-Howell tests. P < 0.05 was considered statistically significant. RESULTS: Vegetables and Fruit recommendations were the least likely to be followed, with 90.7-96.8% of participants in all groups not consuming the recommended number of servings day-1 . The mean frequency of fruit consumption was lower among Indigenous youths compared to Asian youths (0.90 versus 1.37 times day-1 ). A greater proportion of males than females (55.9% versus 44.3%) did not meet the minimum recommendations for Meat and Alternatives (P = 0.016). The percentage of youths not adhering to recommendations for Milk and Alternatives was 81.7% for Indigenous, 73.3% for AME, 78.6% for Asian and 63.5% for European youths. Indigenous youths more frequently consumed potato chips and soft drinks compared to other ethnic youths. The most frequently consumed beverage was milk (1.25 times day-1 ). CONCLUSIONS: The majority of youths did not consume minimum daily recommended servings of Vegetables and Fruit, Milk and Alternatives, and/or Meat and Alternatives food groups. Evidence-based dietary interventions and public health strategies are needed.

Differential protein stability and clinical responses of EML4-ALK fusion variants to various ALK inhibitors in advanced ALK-rearranged non-small cell lung cancer.

Background: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro. However, there are only limited data on the specific EML4-ALK variants and clinical responses of patients to various ALK inhibitors. Patients and methods: By multiplex reverse-transcriptase PCR, which detects 12 variants of known EML4-ALK rearrangements, we retrospectively determined ALK fusion variants in 54 advanced ALK rearrangement-positive NSCLCs. We subdivided the patients into two groups (variants 1/2/others and variants 3a/b) by protein stability and evaluated correlations of the variant status with clinical responses to crizotinib, alectinib, or ceritinib. Moreover, we established the EML4-ALK variant-expressing system and analyzed patterns of sensitivity of the variants to ALK inhibitors. Results: Of the 54 tumors analyzed, EML4-ALK variants 3a/b (44.4%) was the most common type, followed by variants 1 (33.3%) and 2 (11.1%). The 2-year progression-free survival (PFS) rate was 76.0% [95% confidence interval (CI) 56.8-100] in group EML4-ALK variants 1/2/others versus 26.4% (95% CI 10.5-66.6) in group variants 3a/b (P = 0.034) among crizotinib-treated patients. Meanwhile, the 2-year PFS rate was 69.0% (95% CI 49.9-95.4) in group variants 1/2/others versus 32.7% (95% CI 15.6-68.4) in group variants 3a/b (P = 0.108) among all crizotinib-, alectinib-, and ceritinib-treated patients. Variant 3a- or 5a-harboring cells were resistant to ALK inhibitors with >10-fold higher half maximal inhibitory concentration in vitro. Conclusion: Our findings show that group EML4-ALK variants 3a/b may be a major source of ALK inhibitor resistance in the clinic. The variant-specific genotype of the EML4-ALK fusion allows for more precise stratification of patients with advanced NSCLC.