Neural correlates of appetite in adolescents.

Appetitive characteristics are associated with child adiposity, but their biological underpinnings are unclear. We sought to investigate the neural correlates of psychometric and behavioral measures of appetitive characteristics in youth. Adolescents (14-18y; 39F, 37M) varying in familial obesity risk and body weight (20% with overweight, 24% with obesity) viewed pictures of high energy-density (ED) foods, low-ED foods and non-foods during fMRI scanning on two separate days. On one day participants consumed a 474 ml preload of water (0 kcal, fasted) and on another (counter-balanced) 474 ml milkshake (480 kcal, fed), before scanning. A multi-item ad libitum meal (ALM) followed scanning. Parents completed Child Eating Behavior Questionnaire (CEBQ) sub-scales assessing food approach and food self-regulation. Caloric compensation was calculated as the percentage of preload intake compensated for by down-regulation of ALM intake in the fed vs. fasted condition. Analyses correcting for multiple comparisons demonstrated that, for the fasted condition, higher CEBQ Food Responsiveness scores were associated with greater activation to high-ED (vs. low-ED) foods in regions implicated in food reward (insula, rolandic operculum, putamen). In addition, higher caloric compensation was associated with greater fed vs. fasted activations in response to foods (vs. non-foods) in thalamus and supramarginal gyrus. Uncorrected analyses provided further support for associations of different measures of appetitive characteristics with brain responses to food cues in each condition. Measures of appetitive characteristics demonstrated overlapping and distinct associations with patterns of brain activation elicited by food cues in fasted and fed states. Understanding the neural basis of appetitive characteristics could aid development of biobehaviorally-informed obesity interventions.

Incidence Rate and Risk Factors Associated with Travelers' Diarrhea in International Travelers Departing from Utah, USA.

Despite knowledge on the causes and prevention strategies for travelers' diarrhea (TD), it continues to be one of the most common illnesses experienced by U.S. international travelers. However, studies of risk factors associated with TD among U.S. travelers are limited. In this study, we aimed to determine the incidence rate of TD, the proportion of travelers who experience TD, and to identify risk factors associated with TD. In this cross-sectional study, we collected and analyzed data from anonymous posttravel questionnaires submitted by international travelers recruited during their pretravel visit at two travel clinics in Salt Lake City, Utah, from October 2016 to March 2020. Of 571 travelers who completed posttravel surveys, 484 (85%) answered the TD question, of which 111 (23%) reported TD, for an incidence rate of 1.1 episodes per 100 travel-days (95% confidence interval [CI]: 0.9-1.4). In a multivariable model, visiting Southeast Asian (odds ratio [OR]: 2.60; 95% CI: 1.45-4.72) and African (OR: 2.06; 95% CI: 1.09-3.93]) WHO regions, having 10 or more individuals in the group (OR: 3.91; 95% CI: 1.50-11.32]), longer trip duration (OR: 1.01; 95% CI: 1.00-1.02), visiting both urban and rural destinations (OR: 1.94; 95% CI: 1.01-3.90), and taking medications/supplements to prevent TD (OR: 2.74; 95% CI: 1.69-4.47) were statistically significantly associated with increased odds of reporting TD. TD continues to be common in international travelers from the United States. Our findings provide insights regarding travelers' behaviors regarding TD in international travelers from high-income countries and shows the need for additional research into prevention strategies for travelers' diarrhea.

EPIC: an evaluation of the psychological impact of early-phase clinical trials in cancer patients.

BACKGROUND: Anxiety and depression in patients with cancer is associated with decreased quality of life and increased morbidity and mortality. However, these are often overlooked and untreated. Early-phase clinical trials (EPCTs) recruit patients with advanced cancers who frequently lack future treatment options, which may lead to increased anxiety and depression. Despite this, EPCTs do not routinely consider psychological screening for patients. PATIENTS AND METHODS: This prospective observational study explored levels of anxiety and depression alongside impact of trial participation in the context of EPCTs. The Hospital Anxiety and Depression Scale and the Brief Illness Perceptions Questionnaire were completed at the point of EPCT consent, the end of screening and at pre-specified time points thereafter. RESULTS: Sixty-four patients (median age 56 years; median Eastern Cooperative Oncology Group performance status 1) were recruited. At consent, 57 patients returned questionnaires; 39% reported clinically relevant levels of anxiety whilst 18% reported clinically relevant levels of depression. Sixty-three percent of patients experiencing psychological distress had never previously reported this. Males were more likely to be depressed (P = 0.037) and females were more likely to be anxious (P = 0.011). Changes in anxiety or depression were observed after trial enrolment on an individual level, but not significant on a population level. CONCLUSIONS: Patients on EPCTs are at an increased risk of anxiety and depression but may not seek relevant support. Sites offering EPCTs should consider including psychological screening to encourage a more holistic approach to cancer care and consider the sex of individuals when tailoring psychological support to meet specific needs.

Strategies to increase rural maternal utilization of skilled health personnel for childbirth delivery in low- and middle-income countries: a narrative review.

BACKGROUND: Skilled attendance at birth is considered key to accomplishing Sustainable Development Goal (SDG) 3.1 aimed at reducing maternal mortality. Many maternal deaths can be prevented if a woman receives care by skilled health personnel. Maternal utilization of skilled health delivery services in rural areas in low- and middle-income countries is 70% compared to 90% in urban areas. Previous studies have found community-based interventions may increase rural maternal uptake of skilled health delivery services, but evidence is lacking on which strategies are most effective. OBJECTIVE: To review the effectiveness of community-based strategies to increase rural maternal utilization of skilled health personnel for childbirth delivery in low-and middle-income countries. METHODS: We conducted a narrative review. PubMed, CINAHL, Cochrane Library, and PsycINFO databases were searched for articles from database inception through 13 November 2019. Key search terms were pre-determined. Information was extracted on studies meeting our inclusion criteria: cluster and randomized trials, rural setting, reproductive aged women, community engagement, low- and middle-income countries. Studies were considered effective if statistically significant (p < 0.05). A narrative synthesis was conducted. RESULTS: Ten cluster randomized trials out of 5,895 candidate citations met the inclusion criteria. Strategies included home-based visits, women's groups, and combined approaches. Out of the ten articles, only three studies were found to significantly increase maternal uptake of skilled health personnel for delivery, and each used a different strategy. The results are inconclusive as to which strategies are most effective. Limitations of this review include heterogeneity and generalizability of studies. CONCLUSIONS: This research suggests that different strategies may be effective at improving maternal utilization of skilled health personnel for delivery in certain rural settings while ineffective in others. More research is warranted to better understand the context in which strategies may be effective and under what conditions.

Impact of COVID-19 Social Distancing Mandates on Gastrointestinal Pathogen Positivity: Secondary Data Analysis.

BACKGROUND: Acute gastrointestinal (GI) illnesses are of the most common problems evaluated by physicians and some of the most preventable. There is evidence of GI pathogen transmission when people are in close contact. The COVID-19 pandemic led to the sudden implementation of widespread social distancing measures in the United States. There is strong evidence that social distancing measures impact the spread of SARS-CoV-2, and a growing body of research indicates that these measures also decrease the transmission of other respiratory pathogens. OBJECTIVE: This study aims to investigate the impact of COVID-19 social distancing mandates on the GI pathogen positivity rates. METHODS: Deidentified GI Panel polymerase chain reaction test results from a routinely collected diagnostic database from January 1, 2019, through August 31, 2020, were analyzed for the GI pathogen positivity percentage. An interrupted time series analysis was performed, using social distancing mandate issue dates as the intervention date. The following 3 target organisms were chosen for the final analysis to represent different primary transmission routes: adenovirus F40 and 41, norovirus GI and GII, and Escherichia coli O157. RESULTS: In total, 84,223 test results from 9 states were included in the final data set. With the exception of E coli O157 in Kansas, Michigan, and Nebraska, we observed an immediate decrease in positivity percentage during the week of social distancing mandates for all other targets and states. Norovirus GI and GII showed the most notable drop in positivity, whereas E coli O157 appeared to be least impacted by social distancing mandates. Although we acknowledge the analysis has a multiple testing problem, the majority of our significant results showed significance even below the .01 level. CONCLUSIONS: This study aimed to investigate the impact of social distancing mandates for COVID-19 on GI pathogen positivity, and we discovered that social distancing measures in fact decreased GI pathogen positivity initially. The use of similar measures may prove useful in GI pathogen outbreaks. The use of a unique diagnostic database in this study exhibits the potential for its use as a public health surveillance tool.

Travel-Related Behaviors and Health Outcomes of Adolescents Compared with Adults on Short-Term International Service Missions.

With an increasing number of adolescents participating in international travel, little is known about travel-related behaviors and health risks in this age group. In the years 2015-2016, we conducted an anonymous, posttravel, questionnaire-based survey with the aim to compare self-reported practices and travel-related symptoms between adolescents (< 18 years old, N = 87) and adults (≥ 18 years old, N = 149) who came to our travel clinic before their humanitarian missions. They had the same pretravel health education, and traveled together to perform similar activities. In univariate analysis, compared with adults, we found that adolescents reported less prior international travel (P < 0.001), more often wore long-sleeved clothing for malaria prevention (P < 0.001) but less often for sun protection (P = 0.009), more often used insect repellents (P = 0.011), and less often had diarrhea (P = 0.024). All other practices and health outcomes were similar between the groups. Multivariate analyses using Bayesian network show strong associations between adults and prior travel experience, and not wearing long-sleeve clothing for malaria prevention. We also found strong associations between prior international travel and sustaining an injury, and having jet lag, as well as between taking malaria prophylaxis and not having diarrhea. Overall, most practices and health outcomes were similar between age groups. Adolescent age and lack of prior international travel experience did not have significant impacts on practices and health outcomes. Our findings highlight the need for more effective strategies to improve the behaviors and health outcomes in both adolescents and adults.

Relationship between distance of referring facilities and haemoglobin change in children in Malawi.

BACKGROUND: Anaemia is a significant cause of mortality in children in sub-Saharan Africa where blood transfusion is often available only at referral hospitals. Understanding the pattern of referrals by health facilities is essential to identify the delays that affect child survival. AIM: To determine if there was a correlation between change in haemoglobin (Hb) level and distance from referring facilities to Kamuzu Central Hospital (KCH) in Malawi, and whether distance affected mortality rates. METHODS: This was a retrospective cohort study of 2259 children referred to KCH whose Hb was measured at the referring facility or at KCH. Maps were created using ArcGIS® software. The relationship between distance from KCH and change in Hb was assessed by χ2 analysis and multiple linear regression with SAS© software. RESULTS: The majority of children were referred by health facilities in the Lilongwe District. When categorised as Hb <4, 4-6 or >6 g/dL, 87.0% of children remained in the same category during transfer. There was no significant relationship between Hb drop and distance from KCH. Distance from KCH was not a significant predictor of Hb level at KCH or Hb change. However, mortality rates were significantly higher in facilities that were 10-50 km from KCH than in those which were <10 km away. CONCLUSIONS: Using distance as a proxy for time, this suggests that referring facilities are transferring children sufficiently quickly to avert significant reductions in Hb. Despite this, there is a need to identify the factors that influence the decision to transfer anaemic children.

Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry.

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection. OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)]. METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF ≤ 57% (i.e. median). We defined reduced EF/PARADIGM-HF as EF < 40%, mildly reduced EF/PARAGON-HF ≤ median as EF 40-49%, and normal EF/PARAGON-HF > median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario). RESULTS: Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes. CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered.

Naive Forecast for COVID-19 in Utah Based on the South Korea and Italy Models-the Fluctuation between Two Extremes.

Differences in jurisdictional public health actions have played a significant role in the relative success of local communities in combating and containing the COVID-19 pandemic. We forecast the possible COVID-19 outbreak in one US state (Utah) by applying empirical data from South Korea and Italy, two countries that implemented disparate public health actions. Forecasts were created by aligning the start of the pandemic in Utah with that in South Korea and Italy, getting a short-run forecast based on actual daily rates of spread, and long-run forecast by employing a log-logistic model with four parameters. Applying the South Korea model, the epidemic peak in Utah is 169 cases/day, with epidemic resolution by the end of May. Applying the Italy model, new cases are forecast to exceed 200/day by mid-April, with the potential for 250 new cases a day at the epidemic peak, with the epidemic continuing through the end of August. We identify a 3-month variation in the likely length of the pandemic, a 1.5-fold difference in the number of daily infections at outbreak peak, and a 3-fold difference in the expected cumulative cases when applying the experience of two developed countries in handling this virus to the Utah context.

"Real World" Eligibility for Sacubitril/Valsartan in Unselected Heart Failure Patients: Data from the Swedish Heart Failure Registry.

PURPOSE: PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril in patients with heart failure and reduced ejection fraction (HF-REF). How widely applicable sacubitril/valsartan treatment is in unselected patients with HF-REF is not known. We examined eligibility of patients with HF-REF for treatment with sacubitril/valsartan, according to the criteria used in PARADIGM-HF, in the Swedish Heart Failure Registry (SwedeHF). METHODS: Patients were considered potentially eligible if they were not hospitalized, had symptoms (NYHA class II-IV) and a reduced LVEF (≤ 40%), and were prescribed an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at a dose equivalent to enalapril ≥ 10 mg daily. In these patients, we evaluated further eligibility according to the main additional PARADIGM-HF inclusion criteria. RESULTS: Of 12,866 outpatients in NYHA functional class II-IV with an LVEF ≤ 40%, 9577 were prescribed at least 10 mg of enalapril (or equivalent) daily. Complete additional data were available for 3099 of these patients (32.4%) and of them 75.5% were potentially eligible for treatment with sacubitril/valsartan. The most common reason for ineligibility was a low natriuretic peptide level (n = 462, 14.9%). Only a small proportion of patients were ineligible due to low eGFR or serum potassium level. Because only 78% of patients were taking ≥ 10 mg enalapril or equivalent daily, only 58.9% of all patients (75.5% of 78%) were eligible for sacubitril/valsartan. CONCLUSIONS: Between 34 and 76% of symptomatic patients with HF-REF in a 'real world' population are eligible for treatment with sacubitril/valsartan, depending on background ACEI/ARB dose. The most common reason for ineligibility is a low natriuretic peptide level.

Determining Physical and Mental Health Conditions Present in Older Adult Refugees: A Mini-Review.

In 2017, there were over 65 million displaced persons at the global level, with approximately 23 million of these people living as refugees around the world. In this same year, the US resettled 53,716 refugees, with the State of Utah receiving 954 of those refugees. Refugees, in general, often face health-related challenges upon resettlement. Since the health of aging refugee men and women is of growing concern, host communities face significant challenges in accommodating the health needs of a diverse refugee population. This study, a review of physical and mental health data from the Utah Department of Health, was undertaken in an effort to ascertain the prevalence of health conditions among refugee men and women 60 years and older arriving in Utah. Findings include information on diseases correlated with increasing age, such as hypertension, decreases in vision, arthritis, and low back pain, which are common among this population of refugees aged 60 years and older. Overall, most of the health conditions assessed affect women and men with a similar prevalence. Some notable exceptions are a history of torture and violence, and a propensity for tobacco use. When dealing with refugee men older than 60 years, providers should consider the psychological ramifications of having endured such atrocities, as well as introduction to evidence-based tobacco cessation programs. When working with refugee women of the same age, an increase in the prevalence of musculoskeletal pain and urinary tract infections should be considered.

Clinical genetic testing in pediatric cardiomyopathy: Is bigger better?

BACKGROUND: For clinical genetic testing of cardiomyopathy (CMP), current guidelines do not address which gene panels to use: targeted panels specific to a CMP phenotype or expanded (panCMP) panels that include genes associated with multiple phenotypic subtypes. AIM: Our objective was to assess the clinical utility of targeted versus panCMP panel testing in pediatric CMPs. METHODS: 151 pediatric patients with primary hypertrophic (n = 66), dilated (n = 64), restrictive (n = 8), or left-ventricular non-compaction (n = 13) CMP who underwent clinical genetic panel testing at a single centre were included. PanCMP (n = 47) and targeted panel testing (n = 104) were compared for yield of pathogenic variants and variants of unknown significance (VUS). RESULTS: Pathogenic variants were identified in 26% of patients, 42% had indeterminate results (only VUS detected), and 32% had negative results. Yield was lower (15%) in panCMP vs. targeted panel testing (32%) (P = .03) in all CMP subtypes. VUS detection was higher with panCMP (87%) than targeted panel testing (30%) (P <.0001). PanCMP panel testing only identified pathogenic variants in genes that overlapped targeted panels. CONCLUSION: PanCMP testing did not increase diagnostic yield compared to targeted panel testing. Until accuracy of variant interpretation with panCMP panels improves, targeted panels may be suitable for clinical testing in pediatric CMP.

Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy.

Children with hypertrophic cardiomyopathy (HCM) experience sudden cardiac death (SCD) and other life-threatening events. We assessed if affected gene and variant burden predict outcomes. Patients <18 years old with primary HCM with a pathogenic variant or variant of uncertain significance in cardiomyopathy genes were included. Association of gene and variant number and type with freedom from major adverse cardiac events (MACE), that is, ICD insertion, myectomy, aborted SCD, transplantation or death, was assessed by Cox regression. A total of 98 of 155 gene-tested patients carried a non-benign variant. The primary affected gene was MYH7 in 35% (MYH7+) and MYBPC3 in 49% (MYBPC3+). MYH7+ patients had earlier disease onset and higher risk of MACE (hazard ratio 2.7, 95% CI 1.3-5.7). Risk of MACE was also higher in patients with multiple variants (n = 16) (HR 2.5, CI: 1.1-5.9) compared to a propensity score-matched single variant subset, after adjustment for primary gene, and in patients with de novo (n = 18) vs inherited variants (HR 5.7, CI: 2.6-12.7). Affected gene (eg, MYH7), higher variant burden and de novo variant status are independently associated with earlier onset and higher frequency of adverse outcomes in pediatric HCM, highlighting the importance of genetic risk stratification in HCM.

Caloric compensation in preschool children: Relationships with body mass and differences by food category.

Maintaining a healthy weight may involve compensating for previously consumed calories at subsequent meals. To test whether heavier children demonstrated poorer caloric compensation across a range of conditions, and to explore whether compensation failure was the result of inadequate adjustment of overall intake or specific over-consumption of highly palatable, high energy-density 'junk' foods, we administered two compensation tests to a sample of 4-5 y olds. For Test A, preloads varied only in carbohydrate content and were organoleptically indistinguishable (200 ml orange-flavored beverage [0 kcal vs. 200 kcal]). For Test B, the preloads varied substantially in both macronutrient composition and learned gustatory cues to caloric content (200 ml water [0 kcal] vs. 200 ml strawberry milkshake [200 kcal]). Each preload was followed 30 min later by a multi-item ad-libitum meal containing junk foods (chocolate cookies, cheese-flavored crackers) and core foods (fruits and vegetables, bread rolls, protein foods). Testing took place at the children's own school under normal lunch-time conditions. Children were weighed and measured. Caloric compensation occurred in both tests, in terms of total, junk and core food intake (RMANOVA, all p < 0.01). Higher BMI z scores were associated with greater average caloric compensation (r = -0.26; p < 0.05), such that overweight/obese children showed least compensation (41%), children over the 50th centile the next least (59%), and children under the 50th centile (80%) the most. For Test A only, obese/overweight children compensated less well than normal-weight children in terms of junk food intake (RMANOVA preload-by-weight group interaction p < 0.05), with no significant effect for core foods. Our results suggest that caloric compensation is consistently poorer in heavier children, and that overweight/obese children's preferences for junk foods may overwhelm intake regulation mechanisms within meals containing those foods.

Rural Community Disaster Preparedness and Risk Perception in Trujillo, Peru.

Introduction Disasters will continue to occur throughout the world and it is the responsibility of the government, health care systems, and communities to adequately prepare for potential catastrophic scenarios. Unfortunately, low-and-middle-income countries (LMICs) are especially vulnerable following a disaster. By understanding disaster preparedness and risk perception, interventions can be developed to improve community preparedness and avoid unnecessary mortality and morbidity following a natural disaster. Problem The purpose of this study was to assess disaster preparedness and risk perception in communities surrounding Trujillo, Peru. METHODS: After designing a novel disaster preparedness and risk perception survey based on guidelines from the International Federation of Red Cross and Red Crescent Societies (IFRC; Geneva, Switzerland), investigators performed a cross-sectional survey of potentially vulnerable communities surrounding Trujillo, Peru. Data were entered and analyzed utilizing the Research Electronic Data Capture (REDCap; Harvard Catalyst; Boston, Massachusetts USA) database. RESULTS: A total of 230 study participants were surveyed, composed of 37% males, 63% females, with ages ranging from 18-85 years old. Those surveyed who had previously experienced a disaster (41%) had a higher perception of future disaster occurrence and potential disaster impact on their community. Overall, the study participants consistently perceived that earthquakes and infection had the highest potential impact of all disasters. Twenty-six percent of participants had an emergency supply of food, 24% had an emergency water plan, 24% had a first aid kit at home, and only 20% of the study participants had an established family evacuation plan. CONCLUSION: Natural and man-made disasters will remain a threat to the safety and health of communities in all parts of the world, especially within vulnerable communities in LMICs; however, little research has been done to identify disaster perception, vulnerability, and preparedness in LMIC communities. The current study established that selected communities near Trujillo, Peru recognize a high disaster impact from earthquakes and infection, but are not adequately prepared for potential future disasters. By identifying high-risk demographics, targeted public health interventions are needed to prepare vulnerable communities in the following areas: emergency food supplies, emergency water plan, medical supplies at home, and establishing evacuation plans. Stewart M , Grahmann B , Fillmore A , Benson LS . Rural community disaster preparedness and risk perception in Trujillo, Peru. Prehosp Disaster Med. 2017;32(4):387-392.

Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.

BACKGROUND: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. OBJECTIVE: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. METHODS: The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). RESULTS: We included 271 cases (mean age at disease onset of 15.7years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p=0.01). CONCLUSIONS: While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies.

Clostridium difficile infection in returning travellers.

Background: There is increasing recognition of the contribution of community-acquired cases to the global burden of Clostridium difficile infection (CDI). The epidemiology of CDI among international travellers is poorly understood, and factors associated with international travel, such as antibiotic use and changes in gut microbiota, could potentially put travellers at higher risk. Methods: We summarized demographic, travel-associated and geographic characteristics of travellers with CDI in the GeoSentinel database from 1997 to 2015. We also surveyed GeoSentinel sites to compare various testing indications, approaches, and diagnostic modalities. Results: We identified 260 GeoSentinel records, including 187 that satisfied criteria for analysis (confirmed cases in non-immigrant travellers aged >2 years, seen <12 weeks post-travel). CDI was reported in all age groups and in travellers to all world regions; the largest proportions of cases having destinations in Asia (31%), Central/South America or the Caribbean (30%) and Africa (24%). Our site survey revealed substantial heterogeneity of testing approaches between sites; the most commonly used test was the C. difficile toxin gene PCR. Conclusions: CDI is encountered in returning international travellers, although there is considerable variability in testing practices. These data underscore the importance of awareness of C. difficile as a potential cause of travel-associated diarrhoea.

Bioreductively activatable prodrug conjugates of phenstatin designed to target tumor hypoxia.

A variety of solid tumor cancers contain significant regions of hypoxia, which provide unique challenges for targeting by potent anticancer agents. Bioreductively activatable prodrug conjugates (BAPCs) represent a promising strategy for therapeutic intervention. BAPCs are designed to be biologically inert until they come into contact with low oxygen tension, at which point reductase enzyme mediated cleavage releases the parent anticancer agent in a tumor-specific manner. Phenstatin is a potent inhibitor of tubulin polymerization, mimicking the chemical structure and biological activity of the natural product combretastatin A-4. Synthetic approaches have been established for nitrobenzyl, nitroimidazole, nitrofuranyl, and nitrothienyl prodrugs of phenstatin incorporating nor-methyl, mono-methyl, and gem-dimethyl variants of the attached nitro compounds. A series of BAPCs based on phenstatin have been prepared by chemical synthesis and evaluated against the tubulin-microtubule protein system. In a preliminary study using anaerobic conditions, the gem-dimethyl nitrothiophene and gem-dimethyl nitrofuran analogues were shown to undergo efficient enzymatic cleavage in the presence of NADPH cytochrome P450 oxidoreductase. Each of the eleven BAPCs evaluated in this study demonstrated significantly reduced inhibitory activity against tubulin in comparison to the parent anti-cancer agent phenstatin (IC50=1.0µM). In fact, the majority of the BAPCs (seven of the eleven analogues) were not inhibitors of tubulin polymerization (IC50>20µM), which represents an anticipated (and desirable) attribute for these prodrugs, since they are intended to be biologically inactive prior to enzyme-mediated cleavage to release phenstatin.