Health problems after travel to developing countries

Travelers to developing countries participated in a follow-up study of the health risks associated with short (less than three months) visits to these nations. Travelers to the Greek or Canary Islands served as a control cohort. Participants completed a questionnaire to elicit information regarding pretravel vaccinations, malaria prophylaxis, and health problems during and after their journey. Relevant infections were confirmed by the respondent's personal physician. The questionnaire was completed by 10,524 travelers; the answer rate was 73.8%. After a visit to developing countries, 15% of the travelers reported health problems, 8% consulted a doctor, and 3% were unable to work for an average of 15 days. The incidence of infection per month abroad was as follows: giardiasis, 7/1,000; amebiasis, 4/1,000; hepatitis, 4/1,000; gonorrhea, 3/1,000; and malaria, helminthiases, or syphilis, less than 1/1,000. There were no cases of typhoid fever or cholera.     

In Vitro Drug Combination Studies of Letermovir (AIC246, MK-8228) with Approved Anti-Human Cytomegalovirus (HCMV) and Anti-HIV Compounds in Inhibition of HCMV and HIV Replication

Despite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti-HCMV agent in clinical development that acts via a novel mode of action and has demonstrated anti-HCMV activity in vitro and in vivo. For the future, drug combination therapies, including letermovir, might be indicated under special medical conditions, such as the emergence of multidrug-resistant virus strains in transplant recipients or in HCMV-HIV-coinfected patients. Accordingly, knowledge of the compatibility of letermovir with other HCMV or HIV antivirals is of medical importance. Here, we evaluated the inhibition of HCMV replication by letermovir in combination with all currently approved HCMV antivirals using cell culture checkerboard assays. In addition, the effects of letermovir on the antiviral activities of selected HIV drugs, and vice versa, were analyzed. Using two different mathematical techniques to analyze the experimental data, (i) additive effects were observed for the combination of letermovir with anti-HCMV drugs and (ii) no interaction was found between letermovir and anti-HIV drugs. Since none of the tested drug combinations significantly antagonized letermovir efficacy (or vice versa), our findings suggest that letermovir may offer the potential for combination therapy with the tested HCMV and HIV drugs.     

n-3 Fatty Acids Attenuate the Risk of Diabetes Associated With Elevated Serum Nonesterified Fatty Acids: The Multi-Ethnic Study of Atherosclerosis

OBJECTIVE

Chronically high nonesterified fatty acids (NEFAs) are a marker of metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison, n-3 fatty acids (FAs) have been shown to have various health benefits and may protect against disease development. In 5,697 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate to risk of incident type 2 diabetes and further tested whether plasma n-3 FA levels may interact with this relation.

RESEARCH DESIGN AND METHODS

NEFAs were measured in fasting serum using an enzymatic colorimetric assay and phospholipid n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma through gas chromatography-flame ionization detection in 5,697 MESA participants. Cox proportional hazards regression evaluated the association between NEFA levels and incident type 2 diabetes and whether plasma n-3 FAs modified this association adjusting for age, sex, race, education, field center, smoking, and alcohol use.

RESULTS

Over a mean 11.4 years of the study period, higher diabetes incidence was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0; Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (P_trend < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and type 2 diabetes was also observed (P_interaction = 0.03). For individuals with lower n-3 levels (<75th percentile), a higher risk of type 2 diabetes was observed across quartiles of NEFAs: Q1, 1.0; Q2, 1.41 (1.07, 1.84); Q3, 1.77 (1.35, 2.31); and Q4, 2.18 (1.65, 2.88) (P_trend < 0.001). No significant associations were observed in those with n-3 FAs ≥75th percentile (P_trend = 0.54).

CONCLUSIONS

NEFAs are a marker of type 2 diabetes and may have clinical utility for detecting risk of its development. The modifying influence of n-3 FAs suggests a protective effect against disease and/or metabolic dysfunction related to NEFAs and requires further study.     

Characterisation of ecto- and endoparasites in domestic cats from Tirana,Albania

During 2008 to 2011, faecal samples, ear swabs, and ectoparasites obtained by full body search and total body comb were collected from 252 cats originating from the greater Tirana area. Faecal samples were examined using the McMaster and Baermann techniques, and a subset of 58 samples was tested for Giardia-specific antigen using a coproantigen enzyme-linked immunosorbent assay (ELISA). The ear swabs were examined for the presence of parasitic mites. Overall, almost 93 % of the cats were identified harbouring one or more parasites: 59.1 % (95 % confidence interval (CI), 53.0–65.0) and 86.9 % (95 % CI, 82.7–91.1) of the cats tested positive for ecto- or endoparasites, respectively; 53.2 % of the cats had evidence for concomitant ectoparasite infestation and endoparasite infection. For ectoparasite infestation, prevalence was 52.0 % for total fleas (Ctenocephalides felis, 51.2 %; Ctenocephalides canis, 2.0 %; and Leptopsylla segnis, 0.4 %), 8.3 % each for Felicola subrostratus and Otodectes cynotis and 4.0 % for Rhipicephalus sanguineus sensu lato. The most prevalent endoparasites were Toxocara ascarids (48.0 %), followed by Aelurostrongylus lungworms (39.7 %), Capillaria spp. (31.7 %), hookworms (32.9 %), dipylidiid cestodes (27.8 %), Cystoisospora spp. (23.4 %) and taeniid cestodes (2.0 %). One animal was found shedding Pseudamphistomum truncatum eggs. Giardia-specific antigen was detected in 29.3 % of the 58 cats tested. Mixed infections with up to six endoparasites concurrently (excluding Giardia) and mixed infestations with two or three species of ectoparasites were recorded in 73.1 and 22.8 % of the parasite-positive cats, respectively. Cats ≤9 months of age were more frequently tested (p?Toxocara and Cystoisospora infections than cats >9 months while these cats tested more often (p?Aelurostrongylus-positive compared with the younger cats. The prevalence of infestation with ectoparasites did not differ between the cats of these two age groups. Given the impact that some of the parasites may have upon animal health as well as the zoonotic potential of some of them, measures should be taken to minimise the transmission of these parasites.     

Skin and Adhesive Issues With Continuous Glucose Monitors: A Sticky Situation

Background:The purpose of this article is to describe challenges associated with successful use of continuous glucose monitoring (CGM) by young children with type 1 diabetes (T1D) and to detail the techniques and products used to improve the duration of sensor wear.Methods:The DirecNet Study Group conducted 2 studies in 169 children with T1D between the ages of 1 and 9 years who were instructed to wear a CGM device daily. Problems related to skin irritation and sensor adhesiveness in these young children presented challenges to daily use of the CGM. Study coordinators instituted a variety of techniques using commercially available products to attempt to overcome these problems.Results:Three primary factors that contributed to reduced CGM use were identified: the limited body surface area in smaller children, ambient temperature and humidity, as well as the type and duration of physical activity. Using supplemental products to minimize the impact of these factors resulted in improved adherence and reduced skin irritation.Conclusion:Achieving satisfactory adhesion of the CGM sensor and transmitter may involve finding the right supplemental product or combination of products through trial and error. Optimizing adhesion and minimizing skin irritation can significantly improve duration of use and tolerability of CGM devices by young children.     

Synthesis and biological evaluation of heteroalicyclic cyanoguanidines at histamine receptors

Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR‐PI376, as highly potent agonists at the human histamine H₄ receptor (hH₄R). While imidazole‐containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six‐membered heterocycles (piperidine, morpholine, thiomorpholine, and N‐methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C₃–C₅) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand‐binding assays exhibited only very weak activity at the hH₁R and hH₃R, while nearly all compounds were inactive at the hH₂R and hH₄R. In the case of piperidine‐containing compounds, moderate affinities at the hH₃R over the single‐digit micromolar range were detected.