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Integrating and conjugative elements (ICEs) are one of the three principal types of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids, transfer via conjugation; but unlike plasmids and similar to many phages, these elements integrate into and replicate along with the host chromosome. Members of the SXT/R391 family of ICEs have been isolated from several species of gram-negative bacteria, including Vibrio cholerae, the cause of cholera, where they have been important vectors for disseminating genes conferring resistance to antibiotics. Here we developed a plasmid-based system to capture and isolate SXT/R391 ICEs for sequencing. Comparative analyses of the genomes of 13 SXT/R391 ICEs derived from diverse hosts and locations revealed that they contain 52 perfectly syntenic and nearly identical core genes that serve as a scaffold capable of mobilizing an array of variable DNA. Furthermore, selection pressure to maintain ICE mobility appears to have restricted insertions of variable DNA into intergenic sites that do not interrupt core functions. The variable genes confer diverse element-specific phenotypes, such as resistance to antibiotics. Functional analysis of a set of deletion mutants revealed that less than half of the conserved core genes are required for ICE mobility; the functions of most of the dispensable core genes are unknown. Several lines of evidence suggest that there has been extensive recombination between SXT/R391 ICEs, resulting in re-assortment of their respective variable gene content. Furthermore, our analyses suggest that there may be a network of phylogenetic relationships among sequences found in all types of mobile genetic elements.

Mauro Colombo Golgi Cenci Foundation, Milan, Italy Correspondence: Mauro Colombo, Email [email protected] View the original paper by Dr Azhar and colleagues

Background Loneliness and social isolation can occur at any stage of life, but some predictors may be more common among older adults. Due to growing population ageing, loneliness and social isolation are relevant social issues. Many studies apply the main definitions of loneliness and social isolation offered by the literature without considering how individual representations, socio-cultural context and the culture of care may influence their perception. This study wishes to fill in these literature gaps by analysing empirical definitions of loneliness and social isolation arising from a mixed-gender randomized sample of Italian oldest old people. Methods Between January and March 2019, 132 older people, most aged 80+, living in a northern Italian town, were asked to answer a questionnaire and a semi-structured interview. According to a mixed-method analysis the definitions of loneliness and social isolation were analysed by respondents’ gender, living arrangement (e.g., living alone or with partners or other people), and years of education to find possible associations to the meanings attributed to the two concepts. Results The sample was gender-balanced and mid-low educated; more than one fourth of respondents lived alone. The results underline how the empirical definitions of loneliness and social isolation are closer to each other than the academic ones. The two concepts are often perceived by participants as distinct, but they are strongly interconnected so that they can be used interchangeably by older Italian people. The two main themes identified by the analysis are loneliness as “death” and social isolation as “guilt”. In the respondents’ opinion, the main loneliness driver is the loss of loved, close persons, while social isolation is driven by disability. Age, educational level, and living arrangements did not influence the meanings attributed to social isolation. On the contrary, living arrangement ( P  = 0.002) and educational level ( p  = 0.023) seem to influence the empirical definitions of loneliness. Conclusion The knowledge of the meanings that oldest old give to the two concepts may inspire advanced intervention aimed at buffering the psychological and social consequences of loneliness and social isolation in the older population.

Identifying older adults at increased dementia risk is a public health priority. Existing scores often emphasize midlife factors or variables of limited utility in late life. We developed a late-life dementia risk score using data from the InveCe.Ab cohort, including 1100 dementia-free individuals aged 70–74 and followed for 12 years. Candidate risk and protective factors were selected based on systematic reviews and expert consensus. Stepwise Cox models were used to construct a weighted score with and without adjustment for non-modifiable factors. External validation was performed in the TRELONG cohort. The selected modifiable factors were diabetes, alcohol consumption, hypercholesterolemia, social participation, and cognitive activity, with strong predictive accuracy for dementia incidence (HR = 1.23; 95% CI 1.14–1.33; p < 0.026), also after adjustment for non-modifiable factors. In the TRELONG cohort, the score remained significant (HR = 1.19; 95% CI 1.05–1.10; p = 0.008), though its predictive value decreased when adjusting for non-modifiable factors. The LateDem-Risk score offers a practical tool for risk stratification in adults aged ≥ 70 years. Further studies are needed to evaluate its predictive performance in different settings and populations.

The relationship between aging, mitochondrial dysfunction, neurodegeneration, and the onset of Alzheimer’s disease (AD) is a complex area of study. Aging is the primary risk factor for AD, and it is associated with a decline in mitochondrial function. This mitochondrial dysfunction is believed to contribute to the neurodegenerative processes observed in AD. Neurodegeneration in AD is characterized by the progressive loss of synapses and neurons, particularly in regions of the brain involved in memory and cognition. It is hypothesized that mitochondrial dysfunction plays a pivotal role by disrupting cellular energy metabolism and increasing the production of reactive oxygen species (ROS), which can damage cellular components and exacerbate neuronal loss. Despite extensive research, the precise molecular pathways linking mitochondrial dysfunction to AD pathology are not fully understood. Various hypotheses have been proposed, including the mitochondrial cascade hypothesis, which suggests that mitochondrial dysfunction is an early event in AD pathogenesis that triggers a cascade of cellular events leading to neurodegeneration. With this narrative review, we aim to summarize some specific issues in the literature on mitochondria and their involvement in AD onset, with a focus on the development of therapeutical strategies targeting the mitochondria environment and their potential application for the treatment of AD itself.

SXT-R391 Integrative conjugative elements (ICEs) are self-transmissible mobile genetic elements able to confer multidrug resistance and other adaptive features to bacterial hosts, including Vibrio cholerae , the causative agent of cholera. ICEs are arranged in a mosaic genetic structure composed of a conserved backbone interspersed with variable DNA clusters located in conserved hot spots. In this study, we investigated ICE acquisition and subsequent microevolution in pandemic V. cholerae . Ninety-six ICEs were retrieved from publicly available sequence databases from V. cholerae clinical strains and were compared to a set of reference ICEs. Comparative genomics highlighted the existence of five main ICE groups with a distinct genetic makeup, exemplified by ICE Vch Ind5, ICE Vch Moz10, SXT, ICE Vch Ind6, and ICE Vch Ban11. ICE Vch Ind5 (the most frequent element, represented by 70 of 96 elements analyzed) displayed no sequence rearrangements and was characterized by 46 single nucleotide polymorphisms (SNPs). SNP analysis revealed that recent inter-ICE homologous recombination between ICE Vch Ind5 and other ICEs circulating in gammaproteobacteria generated ICE Vch Moz10, ICE Vch Ind6, and ICE Vch Ban11. Bayesian phylogenetic analyses indicated that ICE Vch Ind5 and SXT were independently acquired by the current pandemic V. cholerae O1 and O139 lineages, respectively, within a period of only a few years. IMPORTANCE SXT-R391 ICEs have been recognized as key vectors of antibiotic resistance in the seventh-pandemic lineage of V. cholerae , which remains a major cause of mortality and morbidity on a global scale. ICEs were acquired only recently in this clade and are acknowledged to be major contributors to horizontal gene transfer and the acquisition of new traits in bacterial species. We have reconstructed the temporal dynamics of SXT-R391 ICE acquisition and spread and have identified subsequent recombination events generating significant diversity in ICEs currently circulating among V. cholerae clinical strains. Our results showed that acquisition of SXT-R391 ICEs provided the V. cholerae seventh-pandemic lineage not only with a multidrug resistance phenotype but also with a powerful molecular tool for rapidly accessing the pan-genome of a large number of gammaproteobacteria. SXT-R391 ICEs have been recognized as key vectors of antibiotic resistance in the seventh-pandemic lineage of V. cholerae , which remains a major cause of mortality and morbidity on a global scale. ICEs were acquired only recently in this clade and are acknowledged to be major contributors to horizontal gene transfer and the acquisition of new traits in bacterial species. We have reconstructed the temporal dynamics of SXT-R391 ICE acquisition and spread and have identified subsequent recombination events generating significant diversity in ICEs currently circulating among V. cholerae clinical strains. Our results showed that acquisition of SXT-R391 ICEs provided the V. cholerae seventh-pandemic lineage not only with a multidrug resistance phenotype but also with a powerful molecular tool for rapidly accessing the pan-genome of a large number of gammaproteobacteria.

Background The progressive aging of the population and the increasing complexity of health issues contribute to a growing number of older individuals seeking emergency care. This study aims to assess the state of the art of care provided to older people in the Emergency Departments of Lombardy, the most populous region in Italy, counting over 2 million people aged 65 years and older. Methods An online cross-sectional survey was developed and disseminated among emergency medicine physicians and physicians affiliated to the Lombardy section of the Italian Society of Geriatrics and Gerontology (SIGG), during June and July 2023. The questionnaire covered hospital profiles, geriatric consultation practices, risk assessment tools, discharge processes and perspectives on geriatric emergency care. Results In this mixed method research, 219 structured interviews were collected. The majority of physicians were employed in hospitals, with 54.7% being geriatricians. Critical gaps in older patient’s care were identified, including the absence of dedicated care pathways, insufficient awareness of screening tools, and a need for enhanced professional training. Conclusions Tailored protocols and geriatric educational programs are crucial for improving the quality of emergency care provided to older individuals. These measures might also help relieve the burden on the Emergency Departments, thereby potentially enhancing overall efficiency and ensuring better outcomes.

V. cholerae is the etiological agent of cholera, a major public health concern in most developing countries. Virulence of V. cholerae relies on the powerful cholera toxin, encoded by the CTX prophage. The emergence of new pathogenic variants in the recent years has been mostly associated with new CTX prophage rearrangements. In this retrospective study, we show that the epidemic V. cholerae O1 El Tor strain responsible for the 2006 outbreak in Angola is clonally and genetically different from El Tor strains circulating in the 1990s in the same area. Strains from 2006 carry ICEVchAng3 of the SXT/R391 family. This ICE is associated with a narrower multidrug resistance profile compared to the one conferred by plasmid p3iANG to strains of the 1990s. The CTX prophage carried by 2006 El Tor strains is characterized by rstR(ET) and ctxB(Cla) alleles organized in a RS1-RS2-Core array on chromosome I. Interestingly, the newly emerging atypical strain belongs to a clade previously known to comprise only clinical isolates from the Indian subcontinent that also contain the same ICE of the SXT/R391 family. Our findings remark the appearance of a novel V. cholerae epidemic variant in Africa with a new CTXΦ arrangement previously described only in the Indian Subcontinent.

The present study aimed to explore the effects of foliar application of a leonardite-based product on sugar beet ( Beta vulgaris L.) plants grown in the field. The approach concerned the evaluation of the community compositional structure of plant endophytic bacteria through a metabarcoding approach, the expression level of a gene panel related to hormonal metabolism and signaling, and the main sugar beet productivity traits. Results indicated that plants treated with leonardite (dosage of 2,000 ml ha –1 , dilution 1:125, 4 mg C l –1 ) compared with untreated ones had a significant increase ( p < 0.05) in (i) the abundance of Oxalicibacterium spp., recognized to be an endophyte bacterial genus with plant growth-promoting activity; (ii) the expression level of LAX2 gene, coding for auxin transport proteins; and (iii) sugar yield. This study represents a step forward to advance our understanding of the changes induced by leonardite-based biostimulant in sugar beet.