Type,Number or Both? A Population-Based Matched Case-Control Study on the Risk of Fall Injuries among Older People and Number of Medications beyond Fall-Inducing Drugs

Objectives

Drug use is a modifiable risk factor for fall-related injuries in older people. Whereas the injurious effect of polypharmacy is established, that of low numbers of medications has not been fully ascertained. Neither do we know whether it is the number per se or the type of medications that actually matters. We assessed this question for fall injuries leading to hospitalization.

Design

National register-based, population-based, matched case-control study.

Setting

Community dwellers aged 65+ years living in Sweden between March 2006 and December 2009.

Methods

Cases (n = 64,399) were identified in the national inpatient register and four controls per case were randomly matched by gender, date of birth and residential area. The association between number of prescribed medications, assessed through linkage with the Swedish prescribed drug register, and the risk of injurious falls was estimated with odds ratios with 95% confidence intervals using conditional logistic regression, adjusted for demographic and health status.

Results

The number of medications was associated with an increased risk of fall injury in a dose-response fashion, even after adjustment for marital status, comorbidity and number of fall-risk-inducing drugs (FRIDs). Using ten or more medications was associated with an almost two-fold higher risk (adjusted OR: 1.76, 95% CI: 1.66 to 1.88). When stratified by use (or not) of at least one FRID, the association weakened slightly among both non-users (adjusted OR: 1.50, 95% CI: 1.34 to 1.67) and users (adjusted OR: 1.67, 95% CI: 1.58 to 1.77).

Conclusion

In older people, not only large but also small numbers of medications may affect the risk for them to sustain injurious falls. Although the mechanisms lying behind this are complex, the finding challenges the prevention strategies targeting either specific types of medications (FRIDs) or high numbers of them.     

Genome-wide association mapping of QTLs implied in potato virus Y population sizes in pepper: evidence for widespread resistance QTL pyramiding

In this study, we looked for genetic factors in the pepper (Capsicum annuum) germplasm that control the number of potato virus Y (PVY) particles entering the plant (i.e. effective population size at inoculation) and the PVY accumulation at the systemic level (i.e. census population size). Using genotyping-by-sequencing (GBS) in a core collection of 256 pepper accessions, we obtained 10 307 single nucleotide polymorphisms (SNPs) covering the whole genome. Genome-wide association studies (GWAS) detected seven SNPs significantly associated with the virus population size at inoculation and/or systemic level on chromosomes 4, 6, 9 and 12. Two SNPs on chromosome 4 associated with both PVY population sizes map closely to the major resistance gene pvr2 encoding the eukaryotic initiation factor 4E. No obvious candidates for resistance were identified in the confidence intervals for the other chromosomes. SNPs detected on chromosomes 6 and 12 colocalized with resistance quantitative trait loci (QTLs) previously identified with a biparental population. These results show the efficiency of GBS and GWAS in C. annuum, indicate highly consistent results between GWAS and classical QTL mapping, and suggest that resistance QTLs identified with a biparental population are representative of a much larger collection of pepper accessions. Moreover, the resistance alleles at these different loci were more frequently combined than expected by chance in the core collection, indicating widespread pyramiding of resistance QTLs and widespread combination of resistance QTLs and major effect genes. Such pyramiding may increase resistance efficiency and/or durability.     

Maternal presence influences vocal development in the Japanese quail (Coturnix c. japonica)

Social influences on vocal development of young birds have been widely studied in oscine songbirds who learn to sing by vocal imitation of conspecifics, mainly male adults. In contrast, vocal development of non-vocal learners such as Galliformes is considered as being under strong genetic influence and independent of the social environment. In this study, we investigated the role of the mother on the vocal development of young Japanese quail (Coturnix coturnix japonica). We compared the vocal development of mothered and non-mothered chicks during the first 21 days of life. We analysed the structural changes of two vocalisations: a) the rally call, emitted during long-distance communication and in stressful situations, b) the contact call, emitted during short-distance communication when chicks are in visual and/or auditory contact with congeners. We showed that temporal and spectral structures of the two types of calls changed during development and differed between mothered and non-mothered chicks. These results demonstrate that maternal presence influences the vocal development of the young in the Japanese quail. Even if the adaptive value of such changes was not assessed, these results highlight that plasticity of vocalisations in species considered as non-vocal learners has been underestimated.     

Latent Dirichlet Allocation reveals spatial and taxonomic structure in a DNA‐based census of soil biodiversity from a tropical forest

High‐throughput sequencing of amplicons from environmental DNA samples permits rapid, standardized and comprehensive biodiversity assessments. However, retrieving and interpreting the structure of such data sets requires efficient methods for dimensionality reduction. Latent Dirichlet Allocation (LDA) can be used to decompose environmental DNA samples into overlapping assemblages of co‐occurring taxa. It is a flexible model‐based method adapted to uneven sample sizes and to large and sparse data sets. Here, we compare LDA performance on abundance and occurrence data, and we quantify the robustness of the LDA decomposition by measuring its stability with respect to the algorithm's initialization. We then apply LDA to a survey of 1,131 soil DNA samples that were collected in a 12‐ha plot of primary tropical forest and amplified using standard primers for bacteria, protists, fungi and metazoans. The analysis reveals that bacteria, protists and fungi exhibit a strong spatial structure, which matches the topographical features of the plot, while metazoans do not, confirming that microbial diversity is primarily controlled by environmental variation at the studied scale. We conclude that LDA is a sensitive, robust and computationally efficient method to detect and interpret the structure of large DNA‐based biodiversity data sets. We finally discuss the possible future applications of this approach for the study of biodiversity.     

Antifungal 3,5-disubstituted furanones: From 5-acyloxymethyl to 5-alkylidene derivatives

5-Acetoxymethyl-3-(4-bromophenyl)-2,5-dihydrofuran-2-one previously described as highly antifungally active was found to provide the corresponding 5-methylene derivative via an unusual DMSO-promoted elimination of the ester group at C5 under antifungal assay conditions. Since the latter possessed nearly the same antifungal effect as that originally reported for the former, the 5-acetoxymethyl furanone just served as a precursor of the actual antifungally active species. A few series of compounds with alkyloxy, aryloxy and alkylidene substituents at C5 of the parent furanone structure were therefore prepared and evaluated. In line with the ease of elimination of the substituent from C5, low activities of the 5-alkoxy compounds were observed. On the other hand, their 5-aryloxymethyl congeners were found to be capable of liberating the antifungally active 5-methylene furanone into the testing medium. The antifungal effect of the 5-alkylidene derivatives was highly sensitive to substitution of the alkylidene moiety; a substituent in the allylic position was necessary for a compound to retain high activity. Parallel evaluation of cytostatic activity showed moderate activities of the antifungally active derivatives against HeLa S3 and CCRF-CEM lines. Cell cycle analysis of CCRF-CEM cells following the treatment with 5-methylene-3-(4-bromophenyl)-2,5-dihydrofuran-2-one revealed that this compound is a necrotic agent.