Search

Background: Trazodone, an antidepressant drug is also largely used in several medical contexts. Insomnia, behavioral disorders, and anxiety may be underlying symptoms for prescribing trazodone. This cross‐sectional study aims to identify reasons for trazodone prescription, assess the efficacy, as well as identify any related side effects in older persons living in long term care facilities (LTCFs). Methods: Older adults aged ≥ 60 years, at risk of or affected with Covid‐19 and enrolled in the GeroCovid Observational study from LTCFs, and using trazodone were included. A structured questionnaire was administered to treating physicians regarding reasons for trazodone prescription, discontinuation, possible adverse events and benefits. Results: Thirty‐seven out 74 LTCFs participating in both the GeroCovid and GeroCovid Vax studies completed the questionnaire regarding trazodone use. Of the 427 participants included in this study analysis, we found that 43% had diagnoses of dementia and depression, 33% had dementia, no behavioral and psychological symptoms of dementia (BPSD) and no depression, 14% had dementia with BPSD and no depression, and < 11% had only depression. The main reasons for trazodone prescription included agitation, insomnia, depression and anxiety. Trazodone use was reported as partially or totally effective in more than 90% of participants using the drug. Falls were the most frequent adverse event (30% of participants). Conclusions: Our data suggest that trazodone behaves as an eclectic antidepressant that, in the clinical practice, may also be used for BPSD and insomnia, especially in older people with dementia. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Malnutrition and sarcopenia significantly increase the risk of intra-hospital delirium, particularly among older adults. Given the potential correlation between calf circumference (CC) and these conditions, CC emerges as a promising predisposing factor for delirium. This study aims to investigate the independent association between delirium and anthropometric parameters, focusing on evaluating CC's predictive capacity for intra-hospital delirium risk. Additionally, it aims to compare CC's predictive performance with the widely used Mini Nutritional Assessment (MNA), while also considering potential gender disparities. Methods: This is a retrospective study which enrolled patients aged ≥ 65 years from September 2021 to March 2022 at the Padova Hospital (Italy). Physical characteristics, intra-hospital delirium incidence, and body composition were assessed. Sarcopenia was diagnosed using the 2019 European Consensus criteria. Results: Among 207 subjects, delirium affected 19% of patients. CC showed a significant association with intra-hospital delirium among the analyzed anthropometric parameters. ROC curves indicated that CC's predictive capacity for delirium onset was comparable to MNA (p = 0.98), particularly in women. In a multivariable logistic regression model, female gender and higher cognitive and CC scores emerged as protective factors against delirium onset, with each unit increase in CC associated with a 24% reduction in the odds of delirium. Conversely, sarcopenia did not significantly influence delirium onset. Conclusions: CC shows promise as a predisposing factor for intra-hospital delirium, similar to MNA, albeit with significant gender differences. CC could serve as a valuable tool for assessing delirium risk among female patients. Further validation of these findings is necessary through larger-scale studies. [ABSTRACT FROM AUTHOR]

This study aims to unveil correlations between wastewater microbiota and the catchment-specific population health risk, specifically alcohol abuse, with smoking and obesity as confounding factors. Our study highlights the importance of extracting human-associated microbial communities from wastewater metagenomes by excluding environmental microorganisms, due to their irrelevance to human health. After excluding environmental microbes, we observed strong associations of all three health risk factors, including alcohol abuse, smoking and obesity, with the human gut microbiome in wastewater. The linear discriminant analysis effect size (LEfSe) analysis showed Lactococcus_A, Leuconostoc, Aeromicrobium, Akkermansia, Weissella, Limosilactobacillus, Klebsiella_A, Desulfovibrio and Cloacibacillus as potential microbial biomarkers for alcoholism, after accounting for the confounding effects of smoking and obesity. Functional annotations of microorganisms linked with lower alcoholism rates are primarily related to energy metabolism and intercellular communication. Microorganisms associated with higher alcoholism rates are predominantly involved in immune regulation and cellular DNA architecture. This study highlights the need for a comprehensive exploration of different health risk factors together to identify potential associations between the wastewater microbiome and population lifestyle. [ABSTRACT FROM AUTHOR]

Background: Grewia flava infusions are consumed to assist with kidney problems and stomach ailments. However, there are no scientific data on the phytochemical profile or biological properties to validate its folklore use. Thus, the study aimed to assess the phytochemical profile, antioxidant, and antimicrobial activities of Grewia flava twig extracts. Methodology: The antioxidant activities of the extracts were assayed using 1,1-diphenyl-2-picrylhydrazyl radical scavenging, reducing power, metal chelation, and total phenolic and flavonoid content assays. The agar well diffusion and microdilution methods were used for crude extracts and fractions (from 80% methanol extract) for antimicrobial screening against P. aeruginosa, S. aureus, E. coli, B. subtilis, A. niger, and R. oryzae. Results: The 80% methanol twig extract (250.00 ± 2 GAE/g) exhibited a high concentration of phenolic content, followed by the distilled water extract (192.00 ± 2 mg GAE/g) and the hexane extract (43.10 ± 0.2 mg GAE/g). Fraction 14 of the methanol twig extract exhibited MIC values of 0.21–0.31 mg/mL against all test microorganisms. The root and twig extracts exhibited significant antioxidant and antimicrobial activities, which were attributed to the extracts of bioactive phytochemical compounds such as alkaloids, flavonoids, saponins, steroids, glycosides, anthraquinones, and tannins that were detected in the extracts. Also, the root and twig non-polar extracts were subjected to gas chromatography–mass spectrometry analysis, which identified several bioactive compounds like betulin, β-amyrin, palmitic acid, lupenone, and phytol, highlighting the potential of the plant species as a botanical drug. Conclusions: The study supports the traditional use of plant roots and twigs for treating various ailments, indicating their medicinal value. The twigs can be used in place of the roots to guarantee Grewia flava harvesting that is sustainable. However, a comparison of the quantities of the active compound in the twigs and roots using LC–MS is crucial. [ABSTRACT FROM AUTHOR]

This study evaluates whether social interaction level modifies the association between frailty and cognitive decline in older adults. A total of 2701 adults aged ≥65 years enrolled in the Progetto Veneto Anziani (Pro.V.A.), participated in the study. At baseline, participants were classified as having low, moderate, or high social interactions based on: cohabiting status, frequency of contacts with relatives/friends or involvement in childcare activities, and frequency of participation in social or community activities. Baseline frailty was defined as the presence of ≥3 criteria among: weight loss, weakness, slowness, low physical activity, and exhaustion. Cognitive function was assessed through the Mini-Mental State Examination (MMSE) at baseline and after 4.4 and 7 years. The association between frailty and MMSE changes over time was evaluated through linear mixed models. Interaction and subgroup analyses explored the modifying effect of social interaction level on the above association. The mean age of participants was 76.1 years, and 59.1% were women. Frail individuals had a steeper annual MMSE decline than their non-frail counterparts (ß=-0.40, 95%CI: −0.59, −0.20). When stratifying participants by social interaction level, we found that the association between frailty and MMSE changes over time was stronger in those with low social interactions (ß=-0.74, 95%CI: −1.33, −0.15) while attenuated in those with moderate (ß=-0.42, 95%CI: −0.74, −0.11) or high social interaction level (ß=-0.29, 95%CI: −0.58, 0.01). Maintaining frequent social interactions might mitigate the negative impact of frailty on older people's cognitive functions. [ABSTRACT FROM AUTHOR]

Objectives How to detect the clinical impact of anticholinergic (AC) burden in people with HIV (PWH) remains poorly investigated. We cross-sectionally described the prevalence and type of AC signs/symptoms and the screening accuracy of three AC scales in detecting their presence in a modern cohort of PWH. Methods We calculated AC Burden Scale (ABS), AC Risk Score (ARS) and AC Drug Score (ADS) in 721 adult PWH and recorded the presence of AC signs/symptoms over the previous 3 months. High AC risk was defined by ABS score ≥2, and ARS or ADS score ≥3. Comparisons among the scale were based on Cohen's inter-rater agreement, and their screening accuracy was assessed by receiver operating characteristics (ROC) curves and performance measures. Results We enrolled 721 PWH, of whom 72.0% of participants were male; the median age was 53 years, and 164 participants (22.7%) were on at least one AC drug. Among these, 28.6% experienced at least one AC sign/symptom. Agreement in AC risk classification was substantial only between ARS and ADS (k = 0.6). Lower and higher risk of AC signs/symptoms was associated with dual regimens [adjusted OR (aOR) = 0.12 versus three-drug regimens, P = 0.002] and increasing number of AC drugs (aOR = 12.91, P < 0.001). Depression and COPD were also associated with higher risk of AC signs/symptoms in analysis unadjusted for number of AC drugs. ABS and ADS showed the best area under the ROC curve (AUROC) of 0.85 (0.78–0.92) and 0.84 (0.75–0.92; P < 0.001 for both). However, at the cut-off used for the general population, the sensitivity of all three scales was very low (34.0%, 46.8% and 46.8%). Conclusions Up to one-fourth of participants in our cohort were exposed to at least one AC drug, and among them AC signs/symptoms affected more than one-fourth. Both polypharmacy (as number of antiretrovirals and of co-medications with AC properties) and to a lesser extent specific comorbidities shaped the risk of developing AC signs/symptoms. Sensitive screenings for AC risk in PWH should prefer ABS or ADS based on lower cut-offs than those suggested for the general population. [ABSTRACT FROM AUTHOR]

Background: This study analyzes the effect of frailty and Post-Operative Delirium (POD) on the functional status at hospital discharge and at 4-month follow-up in patients with hip fracture (HF). Methods: Multicenter prospective observational study of older patients with HF admitted to 12 Italian Orthogeriatric centers (July 2019-August 2022). POD was assessed using the 4AT. A 26-item Frailty Index (FI) was created using data collected on admission. The outcome measures were Cumulated Ambulation Score (CAS) ≤ 2 at discharge and a telephone-administered CAS ≤ 2 after 4 months. Poisson regression models were used to assess the effect of frailty and POD on outcomes. Results: 984 patients (median age 84 years, IQR = 79–89) were recruited: 480 (48.7%) were frail at admission, 311 (31.6%) developed POD, and 158 (15.6%) had both frailty and POD. In a robust Poisson regression, frailty alone (Relative Risk, RR = 1.56, 95% Confidence Intervals, CI 1.19–2.04, p = 0.001) and its combination with POD (RR = 2.57, 95% CI 2.02–3.26, p < 0.001) were associated with poor functional status at discharge. At 4-month follow-up, the combination of frailty with POD (RR 3.65, 95% CI 1.85–7.2, p < 0.001) increased the risk of poor outcome more than frailty alone (RR 2.38, 95% CI 1.21–4.66, p < 0.001). Conclusions: POD development exacerbates the negative effect that frailty exerts on functional outcomes in HF patients. [ABSTRACT FROM AUTHOR]

Proteases contribute to a broad spectrum of cellular functions. Given a relatively limited amount of experimental data, developing accurate sequence-based predictors of substrate cleavage sites facilitates a better understanding of protease functions and substrate specificity. While many protease-specific predictors of substrate cleavage sites were developed, these efforts are outpaced by the growth of the protease substrate cleavage data. In particular, since data for 100+ protease types are available and this number continues to grow, it becomes impractical to publish predictors for new protease types, and instead it might be better to provide a computational platform that helps users to quickly and efficiently build predictors that address their specific needs. To this end, we conceptualized, developed, tested and released a versatile bioinformatics platform, ProsperousPlus , that empowers users, even those with no programming or little bioinformatics background, to build fast and accurate predictors of substrate cleavage sites. ProsperousPlus facilitates the use of the rapidly accumulating substrate cleavage data to train, empirically assess and deploy predictive models for user-selected substrate types. Benchmarking tests on test datasets show that our platform produces predictors that on average exceed the predictive performance of current state-of-the-art approaches. ProsperousPlus is available as a webserver and a stand-alone software package at http://prosperousplus.unimelb-biotools.cloud.edu.au/. [ABSTRACT FROM AUTHOR]

Background and Objectives: One of the pathogenetic hypotheses of delirium is the "neuroinflammatory theory" with consequent neurotoxicity of brain connectivity networks. Micronutrients may play a significant role in the prevention of neuroinflammation. This systematic review addresses the role of micronutrients in the development of delirium in older populations. Methods: The EBSCO, Cochrane, PubMed, and Web of Science databases were searched for articles on delirium and micronutrients. The methodological quality of the studies included in the review was evaluated with the Newcastle-Ottawa Scales for observational studies and for case-control studies. Results: 1326 papers were identified from the searches, 7 of which met the inclusion criteria (see section 2.3). All the papers included were written in English. Delirium was predominantly secondary to post-operative dysfunction or acute medical conditions. By altering the production of neurotransmitters resulting in an imbalance, and by reducing their immunomodulatory role with a consequent increase in inflammatory oxidative stress, micronutrient deficiency seems to be associated with an increased incidence of delirium. Conclusions: This review supports the existence of an association between micronutrient deficiency (i.e. cobalamin, thiamine, and vitamin D) and an increased incidence of delirium, with a greater prevalence in hospitalized patients. [ABSTRACT FROM AUTHOR]

The diversity of COVID-19 disease in otherwise healthy people, from seemingly asymptomatic infection to severe life-threatening disease, is not clearly understood. We passaged a naturally occurring near-ancestral SARS-CoV-2 variant, capable of infecting wild-type mice, and identified viral genomic mutations coinciding with the acquisition of severe disease in young adult mice and lethality in aged animals. Transcriptomic analysis of lung tissues from mice with severe disease elucidated a host antiviral response dominated mainly by interferon and IL-6 pathway activation in young mice, while in aged animals, a fatal outcome was dominated by TNF and TGF-β signaling. Congruent with our pathway analysis, we showed that young TNF-deficient mice had mild disease compared to controls and aged TNF-deficient animals were more likely to survive infection. Emerging clinical correlates of disease are consistent with our preclinical studies, and our model may provide value in defining aberrant host responses that are causative of severe COVID-19. [ABSTRACT FROM AUTHOR]

Background Promoters are DNA regions that initiate the transcription of specific genes near the transcription start sites. In bacteria, promoters are recognized by RNA polymerases and associated sigma factors. Effective promoter recognition is essential for synthesizing the gene-encoded products by bacteria to grow and adapt to different environmental conditions. A variety of machine learning-based predictors for bacterial promoters have been developed; however, most of them were designed specifically for a particular species. To date, only a few predictors are available for identifying general bacterial promoters with limited predictive performance. Results In this study, we developed TIMER, a Siamese neural network-based approach for identifying both general and species-specific bacterial promoters. Specifically, TIMER uses DNA sequences as the input and employs three Siamese neural networks with the attention layers to train and optimize the models for a total of 13 species-specific and general bacterial promoters. Extensive 10-fold cross-validation and independent tests demonstrated that TIMER achieves a competitive performance and outperforms several existing methods on both general and species-specific promoter prediction. As an implementation of the proposed method, the web server of TIMER is publicly accessible at http://web.unimelb-bioinfortools.cloud.edu.au/TIMER/. [ABSTRACT FROM AUTHOR]

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle. Bovine herpesvirus-1 (BHV-1) is one of the main culprits of BRD; however, research on BHV-1 is hampered by the lack of suitable models for infection and drug testing. In this study, we established a novel bovine tracheal organoid culture grown in a basement membrane extract type 2 (BME2) matrix and compared it with the air–liquid interface (ALI) culture system. After differentiation, the matrix-embedded organoids developed beating cilia and demonstrated a transcriptomic profile similar to the ALI culture system. The matrix-embedded organoids were also highly susceptible to BHV-1 infection and immune stimulation by Pam2Cys, an immunomodulator, which resulted in robust cytokine production and tracheal antimicrobial peptide mRNA upregulation. However, treatment of bovine tracheal organoid cultures with Pam2Cys was not sufficient to inhibit viral infection or replication, suggesting a role of the non-epithelial cellular microenvironment in vivo. [ABSTRACT FROM AUTHOR]

A single experimental method alone often fails to provide the resolution, accuracy, and coverage needed to model integral membrane proteins (IMPs). Integrating computation with experimental data is a powerful approach to supplement missing structural information with atomic detail. We combine RosettaNMR with experimentally-derived paramagnetic NMR restraints to guide membrane protein structure prediction. We demonstrate this approach using the disulfide bond formation protein B (DsbB), an α-helical IMP. Here, we attached a cyclen-based paramagnetic lanthanide tag to an engineered non-canonical amino acid (ncAA) using a copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry reaction. Using this tagging strategy, we collected 203 backbone HN pseudocontact shifts (PCSs) for three different labeling sites and used these as input to guide de novo membrane protein structure prediction protocols in Rosetta. We find that this sparse PCS dataset combined with 44 long-range NOEs as restraints in our calculations improves structure prediction of DsbB by enhancements in model accuracy, sampling, and scoring. The inclusion of this PCS dataset improved the Cα-RMSD transmembrane segment values of the best-scoring and best-RMSD models from 9.57 Å and 3.06 Å (no NMR data) to 5.73 Å and 2.18 Å, respectively. [ABSTRACT FROM AUTHOR]

Background: Proximal femur fractures have a negative impact on loss of functional autonomy and mortality. Objective: The aim of this retrospective study was to evaluate functional autonomy and mortality in a group of older adults with hip fractures managed in an orthogeriatric setting 12 months after discharge and to determine if gender affected outcome. Methods: In all participants, we assessed clinical history, functional pre-fracture status using activities of daily living (ADL) and in-hospital details. At 12 months after discharge, we evaluated functional status, place of residence, hospital readmissions and mortality. Results: We studied 361 women and 124 men and we observed a significant reduction in the ADL score at 6 months (1.15 ± 1.58/p < 0.001 in women and 1.45 ± 1.66/p < 0.001 in men). One-year mortality (33.1% in men and 14.7% in women) was associated with pre-fracture ADL score and reduction in ADL at 6 months (HR 0.68/95%, CI 0.48–0.97/p < 0.05 and HR 1.70/95%, CI 1.17–2.48/p < 0.01, respectively) in women, and new hospitalisations at 6 months and polypharmacy in men (HR 1.65/95%, CI 1.07–2.56/p < 0.05 and HR 1.40/95%, CI 1.00–1.96/p = 0.05, respectively) in Cox's regression model. Discussion and Conclusions: Our study suggests that functional loss in older adults hospitalised for proximal femur fractures is greatest in the first 6 months after discharge, and this increases the risk of death at 1 year. Cumulative mortality at 12 months is higher in men and appears to be related to polypharmacy and new hospital admissions 6 months after discharge. [ABSTRACT FROM AUTHOR]

A-to-I editing is the most prevalent RNA editing event, which refers to the change of adenosine (A) bases to inosine (I) bases in double-stranded RNAs. Several studies have revealed that A-to-I editing can regulate cellular processes and is associated with various human diseases. Therefore, accurate identification of A-to-I editing sites is crucial for understanding RNA-level (i.e. transcriptional) modifications and their potential roles in molecular functions. To date, various computational approaches for A-to-I editing site identification have been developed; however, their performance is still unsatisfactory and needs further improvement. In this study, we developed a novel stacked-ensemble learning model, ATTIC (A-To-I ediTing predICtor), to accurately identify A-to-I editing sites across three species, including Homo sapiens , Mus musculus and Drosophila melanogaster. We first comprehensively evaluated 37 RNA sequence-derived features combined with 14 popular machine learning algorithms. Then, we selected the optimal base models to build a series of stacked ensemble models. The final ATTIC framework was developed based on the optimal models improved by the feature selection strategy for specific species. Extensive cross-validation and independent tests illustrate that ATTIC outperforms state-of-the-art tools for predicting A-to-I editing sites. We also developed a web server for ATTIC, which is publicly available at http://web.unimelb-bioinfortools.cloud.edu.au/ATTIC/. We anticipate that ATTIC can be utilized as a useful tool to accelerate the identification of A-to-I RNA editing events and help characterize their roles in post-transcriptional regulation. [ABSTRACT FROM AUTHOR]

Noncanonical amino acids (ncAAs) for photo‐ and chemical crosslinking are powerful biochemical tools for studying and manipulating interactions between proteins both in vitro and in intact cells. Since the first crosslinking ncAAs were genetically encoded about 20 years ago, the technology has now ripened beyond the proof‐of‐principle demonstrations and is contributing to the study of relevant biological questions in the frame of modern integrative approaches. Here, we provide an overview of available photo‐activatable ncAAs for photo‐crosslinking and electrophilic ncAAs for genetically encoded chemical crosslinking (GECX), with a major focus on the most recent entries such as ncAAs for SuFEx click chemistry and photo‐activatable ncAAs for chemical crosslinking. We present recent examples of the application of genetically encoded crosslinkers to capture protein–protein interactions and identify interaction partners in live cells, to investigate molecular mechanisms of protein function, to stabilize protein complexes for structural studies, to derive structural information about protein complexes from the physiological cell environment, up to perspective applications of GECX‐ncAAs for the development of covalent drugs. [ABSTRACT FROM AUTHOR]

Climate change and water are inseparably connected. Extreme weather events cause water to become more scarce, polluted, and erratic than ever. Therefore, we urgently need to develop solutions to reduce water contamination. This review intends to demonstrate that pectin-based materials are an excellent route to detect and mitigate pollutants from water, with several benefits. Pectin is a biodegradable polymer, extractable from vegetables, and contains several hydroxyl and carboxyl groups that can easily interact with the contaminant ions. In addition, pectin-based materials can be prepared in different forms (films, hydrogels, or beads) and cross-linked with several agents to change their molecular structure. Consequently, the pectin-based adsorbents can be tuned to remove diverse pollutants. Here, we will summarize the existing water remediation technologies highlighting adsorption as the ideal method. Then, the focus will be on the chemical structure of pectin and, from a historical perspective, on its structure after applying different cross-linking methods. Finally, we will review the application of pectin as an adsorbent of water pollutants considering the pectin of low degree methoxylation. [ABSTRACT FROM AUTHOR]

Cognitive Reserve (CR) plays a protective role in neurological and acute/chronic diseases. Its effect on mood, however, is still unclear, although it may be relevant in a hospital setting. We aimed to explore the relationship between CR and depressive mood in older inpatients, evaluating possible gender- and age-related differences. This study involved 86 inpatients aged ≥65 years with an MMSE ≥15. Participants underwent a multidimensional evaluation that included the assessment of CR with the Cognitive Reserve Index questionnaire, divided into three sections (Education, Working Activity, and Leisure Time). Depressive mood was assessed with the 15-item Geriatric Depression Scale (GDS). The relationship between CR and GDS was evaluated by multivariable linear regressions. Significant inverse associations between CR and GDS scores emerged in the total sample (β = −0.03 [SD = 0.02], p =.047), especially in men (β = −0.05 [SD = 0.02], p =.005) and in individuals aged <85 years (β = −0.07 [SD = 0.03], p =.01). Among the single CRI sections, CRI-Leisure Time was significantly associated with GDS in the total sample, in men, and participants <85 years. CR seems to be inversely associated with depressive mood in older inpatients. This relationship is particularly marked for CR related to Leisure Time, which may be modifiable even in older age through social support and interaction. [ABSTRACT FROM AUTHOR]

A new variant of Streptococcus pyogenes serotype M1 (designated 'M1UK') has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor S. pyogenes 'M1global' and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 S. pyogenes. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing S. pyogenes in Asia. A single SNP in the 5' transcriptional leader sequence of the transfer-messenger RNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator read-through in the M1UK lineage. This represents a previously unappreciated mechanism of toxin expression and urges enhanced international surveillance. A variant of group A Streptococcus serotype M1 (UK) has been increasingly reported and can be differentiated from the global variant by its overexpression of the superantigen SpeA. Here, Davies et al probe the mechanism behind enhanced SpeA expression and demonstrate that a SNP in the 5' leader sequence of ssrA is responsible for this virulence phenotype. [ABSTRACT FROM AUTHOR]

Vascular wilt caused by the ascomycete fungal pathogen Fusarium oxysporum f. sp. cubense (Foc) is a major constraint of banana production around the world. The virulent race, namely Tropical Race 4, can infect all Cavendish-type banana plants and is now widespread across the globe, causing devastating losses to global banana production. In this study, we characterized Foc Subtropical Race 4 (STR4) resistance in a wild banana relative which, through estimated genome size and ancestry analysis, was confirmed to be Musa acuminata ssp. malaccensis. Using a self-derived F2 population segregating for STR4 resistance, quantitative trait loci sequencing (QTL-seq) was performed on bulks consisting of resistant and susceptible individuals. Changes in SNP index between the bulks revealed a major QTL located on the distal end of the long arm of chromosome 3. Multiple resistance genes are present in this region. Identification of chromosome regions conferring resistance to Foc can facilitate marker assisted selection in breeding programs and paves the way towards identifying genes underpinning resistance. [ABSTRACT FROM AUTHOR]

Group A streptococcal (GAS) disease shows increasing incidence worldwide. We characterised children admitted with GAS infection to European hospitals and studied risk factors for severity and disability. This is a prospective, multicentre, cohort study (embedded in EUCLIDS and the Swiss Pediatric Sepsis Study) including 320 children, aged 1 month to 18 years, admitted with GAS infection to 41 hospitals in 6 European countries from 2012 to 2016. Demographic, clinical, microbiological and outcome data were collected. A total of 195 (61%) patients had sepsis. Two hundred thirty-six (74%) patients had GAS detected from a normally sterile site. The most common infection sites were the lower respiratory tract (LRTI) (22%), skin and soft tissue (SSTI) (23%) and bone and joint (19%). Compared to patients not admitted to PICU, patients admitted to PICU more commonly had LRTI (39 vs 8%), infection without a focus (22 vs 8%) and intracranial infection (9 vs 3%); less commonly had SSTI and bone and joint infections (p < 0.001); and were younger (median 40 (IQR 21–83) vs 56 (IQR 36–85) months, p = 0.01). Six PICU patients (2%) died. Sequelae at discharge from hospital were largely limited to patients admitted to PICU (29 vs 3%, p < 0.001; 12% overall) and included neurodisability, amputation, skin grafts, hearing loss and need for surgery. More patients were recruited in winter and spring (p < 0.001). Conclusion: In an era of observed marked reduction in vaccine-preventable infections, GAS infection requiring hospital admission is still associated with significant severe disease in younger children, and short- and long-term morbidity. Further advances are required in the prevention and early recognition of GAS disease. What is Known: • Despite temporal and geographical variability, there is an increase of incidence of infection with group A streptococci. However, data on the epidemiology of group A streptococcal infections in European children is limited. What is New: • In a large, prospective cohort of children with community-acquired bacterial infection requiring hospitalisation in Europe, GAS was the most frequent pathogen, with 12% disability at discharge, and 2% mortality in patients with GAS infection. • In children with GAS sepsis, IVIG was used in only 4.6% of patients and clindamycin in 29% of patients. [ABSTRACT FROM AUTHOR]

The transcriptional response to genotoxic stress involves gene expression arrest, followed by recovery of mRNA synthesis (RRS) after DNA repair. We find that the lack of the EXD2 nuclease impairs RRS and decreases cell survival after UV irradiation, without affecting DNA repair. Overexpression of wild-type, but not nuclease-dead EXD2, restores RRS and cell survival. We observe that UV irradiation triggers the relocation of EXD2 from mitochondria to the nucleus. There, EXD2 is recruited to chromatin where it transiently interacts with RNA Polymerase II (RNAPII) to promote the degradation of nascent mRNAs synthesized at the time of genotoxic attack. Reconstitution of the EXD2-RNAPII partnership on a transcribed DNA template in vitro shows that EXD2 primarily interacts with an elongation-blocked RNAPII and efficiently digests mRNA. Overall, our data highlight a crucial step in the transcriptional response to genotoxic attack in which EXD2 interacts with elongation-stalled RNAPII on chromatin to potentially degrade the associated nascent mRNA, allowing transcription restart after DNA repair. Here the authors show that the exonuclease EXD2 is involved in the recovery of class II gene transcription after UV irradiation. EXD2 travels from the mitochondria to the nucleus to interact with RNA Pol II and degrade new synthetized mRNA to allow transcription following DNA repair. [ABSTRACT FROM AUTHOR]

Background: Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG.Methods: We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017-2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012-2015).Results: Sampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000-2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p < 0.001), with high percentage of most genomic clusters (12/14) identified in NCD, reflecting its role as a potential national amplifier.Conclusions: The acquisition and evolution of drug resistance among the major clades of Beijing strain threaten the success of DR-TB treatment in PNG. With continued transmission of this strain in PNG, genotypic drug resistance surveillance using whole genome sequencing is essential for improved public health response to outbreaks. With occurrence of resistance to newer drugs such as bedaquiline, knowledge of full drug resistance profiles will be important for optimal treatment selection. [ABSTRACT FROM AUTHOR]

Depression is one of the most common mood disorders in the late-life population and is associated with poor quality of life and increased morbidity, disability and mortality. Nevertheless, in older adults, it often remains undetected and untreated. This narrative review aims at giving an overview on the main definitions, clinical manifestations, risk and protective factors for depression in the elderly, and at discussing the main reasons for its under/misdiagnosis, such as cognitive decline and their overlapping symptomatology. A practical approach for the global and multidisciplinary care of the older adult with depression, derived from cross-checking evidence emerging from the literature with everyday clinical experience, is thus provided, as a short and flexible "pocket" guide to orient clinicians in recognizing, diagnosing and treating depression in the elderly. [ABSTRACT FROM AUTHOR]

Background and aims: The most recent guidelines suggest treating patients whose FRAX 10-year fracture risk scores are ≥ 20%. However, this method of evaluation does not take into account parameters that are nonetheless relevant to the therapeutic choice. Our aim was to compare the therapeutic choices for treatment based on a wider assessment (real-world practice) with those based on FRAX scores, taking 20% as the cut-off score. Methods: We obtained the medical history, bone mineral density (BMD) values, and the presence of major fragility fractures in a sample of 856 postmenopausal women. The 10-year FRAX risk of major osteoporotic fracture was calculated, and patients were grouped into risk classes ("FRAX < 20%" = low, "FRAX ≥ 20%" = high); we then compared the treated and untreated patients in each class. After an average interval of 2.5 years, changes in lumbar and femoral BMD and appearances of new fragility fractures were recorded. Results: 83% of high-risk patients and 57% of low-risk patients were treated. The therapeutic decision was based mainly on densitometric values and the presence of vertebral fractures. At the 2.5 year follow-up, lumbar spine and femur BMD had decreased in the untreated group; 9.9% of the treated patients developed new vertebral fragility fractures, compared with 5.3% of the untreated patients. Discussion and conclusions: Our wider assessment designated as at high fracture risk a group of patients who had not been identified by the FRAX assessment. FRAX could underestimate the risk of fracture in older people, for which the therapeutic choice should consider a broader approach, also based on individual patient's needs. [ABSTRACT FROM AUTHOR]

Copyright of Ricerca Psicoanalitica is the property of PAGEPress and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Motivation Accurate annotation of different genomic signals and regions (GSRs) from DNA sequences is fundamentally important for understanding gene structure, regulation and function. Numerous efforts have been made to develop machine learning-based predictors for in silico identification of GSRs. However, it remains a great challenge to identify GSRs as the performance of most existing approaches is unsatisfactory. As such, it is highly desirable to develop more accurate computational methods for GSRs prediction. Results In this study, we propose a general deep learning framework termed DeepGenGrep, a general predictor for the systematic identification of multiple different GSRs from genomic DNA sequences. DeepGenGrep leverages the power of hybrid neural networks comprising a three-layer convolutional neural network and a two-layer long short-term memory to effectively learn useful feature representations from sequences. Benchmarking experiments demonstrate that DeepGenGrep outperforms several state-of-the-art approaches on identifying polyadenylation signals, translation initiation sites and splice sites across four eukaryotic species including Homo sapiens , Mus musculus , Bos taurus and Drosophila melanogaster. Overall, DeepGenGrep represents a useful tool for the high-throughput and cost-effective identification of potential GSRs in eukaryotic genomes. Availability and implementation The webserver and source code are freely available at http://bigdata.biocie.cn/deepgengrep/home and Github (https://github.com/wx-cie/DeepGenGrep/). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background: Long-term care facility (LTCF) residents often present asymptomatic or paucisymptomatic features of SARS-CoV-2 infection. We aimed at investigating signs/symptoms, including their clustering on SARS-CoV-2 infection and mortality rates associated with SARS-CoV-2 infection in LTCF residents. Methods: This is a cohort study of 586 aged ≥ 60 year-old residents at risk of or affected with COVID-19 enrolled in the GeroCovid LTCF network. COVID-19 signs/symptom clusters were identified using cluster analysis. Cluster analyses associated with SARS-CoV-2 infection and mortality were evaluated using logistic regression and Cox proportional hazard models. Results: Cluster 1 symptoms (delirium, fever, low-grade fever, diarrhea, anorexia, cough, increased respiratory rate, sudden deterioration in health conditions, dyspnea, oxygen saturation, and weakness) affected 39.6% of residents and were associated with PCR swab positivity (OR = 7.21, 95%CI 4.78–10.80; p < 0.001). Cluster 1 symptoms were present in deceased COVID-19 residents. Cluster 2 (increased blood pressure, sphincter incontinence) and cluster 3 (new-onset cognitive impairment) affected 20% and 19.8% of residents, respectively. Cluster 3 symptoms were associated with increased mortality (HR = 5.41, 95%CI 1.56–18.8; p = 0.008), while those of Cluster 2 were not associated with mortality (HR = 0.82, 95%CI 0.26–2.56; p = 730). Conclusions: Our study highlights that delirium, fever, and low-grade fever, alone or in clusters should be considered in identifying and predicting the prognosis of SARS-CoV-2 infection in older LTCF patients. [ABSTRACT FROM AUTHOR]

Objectives: The GeroCovid Study is a multi-setting, multinational, and multi-scope registry that includes the GeroCovid home and outpatients' care cohort. The present study aims to evaluate whether outpatient and home care services with remote monitoring and consultation could mitigate the impact of the COVID-19 pandemic on mental and affective status, perceived well-being, and personal capabilities of outpatients and home care patients with cognitive disorders. Methods: Prospectively recorded patients in an electronic web registry provided by BlueCompanion Ltd. Up to October 31, 2020, the sample included 90 patients receiving regular care from the Center for Cognitive Disorders and Dementia in Catanzaro Lido, Italy. It was made of 52 ambulatory outpatients and 38 home care patients, mean age 83.3 ± 7.54 years. Participants underwent a multidimensional assessment at baseline (T0) and after 90 days (T1). For each patient, we administered the Mini-Mental State Examination (MMSE) for cognitive functions, the Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales for functional capabilities, the Cumulative Illness Rating Scale (CIRS) for comorbidities and their impact on patients' health, the 5-items Geriatric Depression Scale (GDS) for mood, and the Euro Quality of Life (EuroQoL) for perceived quality of life. Contacts with both ambulatory and home care patients were managed in person or via telephone, preferably through video calls (WhatsApp or FaceTime). Results: Contacts with patients were kept at T0 through telephone. At T1, visits were made in person for over 95% out of the cases. The ADL, IADL, CIRS, GDS, MMSE, and EuroQoL changed slightly between T0 and T1. Most of the patients were clinically stable over time on the majority of the scales explored, but behavioral changes were found in 24.4% of patients and anxiety and insomnia in 17.7% of patients. Conclusion: Our study suggests that contacts through telephone and video consultations are likely associated with a health status preservation of the patients. [ABSTRACT FROM AUTHOR]

Copyright of Summa, Animali da Reddito is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Summa, Animali da Reddito is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Summa, Animali da Reddito is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG. Methods: We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017–2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012–2015). Results: Sampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000–2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p < 0.001), with high percentage of most genomic clusters (12/14) identified in NCD, reflecting its role as a potential national amplifier. Conclusions: The acquisition and evolution of drug resistance among the major clades of Beijing strain threaten the success of DR-TB treatment in PNG. With continued transmission of this strain in PNG, genotypic drug resistance surveillance using whole genome sequencing is essential for improved public health response to outbreaks. With occurrence of resistance to newer drugs such as bedaquiline, knowledge of full drug resistance profiles will be important for optimal treatment selection. [ABSTRACT FROM AUTHOR]

Copyright of Summa, Animali da Reddito is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Summa, Animali da Reddito is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)