What is the impact of multimorbidity on the risk of hospitalisation in older adults? A systematic review study protocol

INTRODUCTION: The development of multiple coexisting chronic diseases (multimorbidity) is increasing globally, along with the percentage of older adults affected by it. Multimorbidity is associated with the concomitant use of multiple medications, a greater possibility of adverse effects, and increased risk of hospitalisation. Therefore, this systematic review study protocol aims to analyse the impact of multimorbidity on the occurrence of hospitalisation in older adults and assess whether this impact changes according to factors such as sex, age, institutionalisation and socioeconomic status. This study will also review the average length of hospital stay and the occurrence of hospital readmission. METHODS AND ANALYSIS: A systematic review of the literature will be carried out using the PubMed, Embase and Scopus databases. The inclusion criteria will incorporate cross-sectional, cohort and case-control studies that analysed the association between multimorbidity (defined as the presence of ≥2 and/or ≥3 chronic conditions and complex multimorbidity) and hospitalisation (yes/no, days of hospitalisation and number of readmissions) in older adults (aged ≥60 years or >65 years). Effect measures will be quantified, including ORs, prevalence ratios, HRs and relative risk, along with their associated 95% CI. The overall aim of this study is to widen knowledge and to raise reflections about the association between multimorbidity and hospitalisation in older adults. Ultimately, its findings may contribute to improvements in public health policies resulting in cost reductions across healthcare systems. ETHICS AND DISSEMINATION: Ethical approval is not required. The results will be disseminated via submission for publication to a peer-reviewed journal when complete. PROSPERO REGISTRATION NUMBER: CRD42021229328

Mapping the root systems of individual trees in a natural community using genotyping-by-sequencing

•The architecture of root systems is an important driver of plant fitness, competition and ecosystem processes. However, the methodological difficulty of mapping roots hampers the study of these processes. Existing approaches to match individual plants to belowground samples are low throughput and species specific. Here, we developed a scalable sequencing-based method to map the root systems of individual trees across multiple species. We successfully applied it to a tropical dry forest community in the Brazilian Caatinga containing 14 species. • We sequenced all 42 individual shrubs and trees in a 14 × 14 m plot using double-digest restriction site-associated sequencing (ddRADseq). We identified species-specific markers and individual-specific haplotypes from the data. We matched these markers to the ddRADseq data from 100 mixed root samples from across the centre (10 × 10 m) of the plot at four different depths using a newly developed R package. • We identified individual root samples for all species and all but one individual. There was a strong significant correlation between belowground and aboveground size measurements, and we also detected significant species-level root-depth preference for two species. • The method is more scalable and less labour intensive than the current techniques and is broadly applicable to ecology, forestry and agricultural biology

Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8⁺ T cells in human cutaneous leishmaniasis

Cytotoxic activity mediated by CD8+ T cells is the main signature of the immunopathogenesis of cutaneous leishmaniasis (CL). Here, we performed a broad evaluation of natural killer (NK) cell phenotypic and functional features during cutaneous leishmaniasis. We demonstrate for the first time that CL patients present the accumulation of circulating NK cells with multiple features of replicative senescence including low proliferative capacity and shorter telomeres, elevated expression of CD57, KLRG1 but diminished CD27 stimulatory receptor expression. Moreover, they exhibited higher cytotoxic and inflammatory potential than age‐matched controls. The accumulation of circulating senescent NK cells (CD56dim CD57bright) correlated positively with skin lesion size in the same patients, suggesting that they, like circulating senescent CD8+ T cells, may contribute to the immunopathology of CL. However, this senescent population had lower cutaneous lymphocyte antigen expression and so had diminished skin‐homing potential compared with total or senescent CD8+ T cells. This was confirmed in CL skin lesions where we found a predominance of CD8+ T cells (both senescent and non‐senescent) that correlated with the severity of the disease. Although there was also a correlation between the proportions of senescent NK cells (CD56+ CD57+) in the skin and lesion size, this was less evident. Collectively our results demonstrate first‐hand that senescent cytotoxic cells may mediate skin pathology during human cutaneous leishmaniasis. However, as senescent cytotoxic CD8+ T cells predominate in the skin lesions, they may have a greater role than NK cells in mediating the non‐specific skin damage in CL

Leishmania Parasites Drive PD-L1 Expression in Mice and Human Neutrophils With Suppressor Capacity

Neutrophils play an important role in the outcome of leishmaniasis, contributing either to exacerbating or controlling the progression of infection, a dual effect whose underlying mechanisms are not clear. We recently reported that CD4+ and CD8+ T cells, and dendritic cells of Leishmania amazonensis-infected mice present high expression of PD-1 and PD-L1, respectively. Given that the PD-1/PD-L1 interaction may promote cellular dysfunction, and that neutrophils could interact with T cells during infection, we investigated here the levels of PD-L1 in neutrophils exposed to Leishmania parasites. We found that both, promastigotes and amastigotes of L. amazonensis induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites in vitro. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of L. amazonensis-infected mice, assessed through cell cytometry and intravital microscopy. Moreover, expression of PD-L1 progressively increased in neutrophils from ear lesions as the disease evolved to the chronic phase. Co-culture of infected neutrophils with in vitro activated CD8+ T cells inhibits IFN-γ production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that in vitro infection of human neutrophils by L braziliensis induced PD-L1+ expression and also PD-L1+ neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the Leishmania parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response

Mapping the root systems of individual trees in a natural community using genotyping-by-sequencing.

This is the final version. Available from Wiley via the DOI in this record.The architecture of root systems is an important driver of plant fitness, competition and ecosystem processes. However, the methodological difficulty of mapping roots hampers the study of these processes. Existing approaches to match individual plants to belowground samples are low throughput and species specific. Here, we developed a scalable sequencing-based method to map the root systems of individual trees across multiple species. We successfully applied it to a tropical dry forest community in the Brazilian Caatinga containing 14 species. We sequenced all 42 individual shrubs and trees in a 14 × 14 m plot using double-digest restriction site-associated sequencing (ddRADseq). We identified species-specific markers and individual-specific haplotypes from the data. We matched these markers to the ddRADseq data from 100 mixed root samples from across the centre (10 × 10 m) of the plot at four different depths using a newly developed R package. We identified individual root samples for all species and all but one individual. There was a strong significant correlation between belowground and aboveground size measurements, and we also detected significant species-level root-depth preference for two species. The method is more scalable and less labour intensive than the current techniques and is broadly applicable to ecology, forestry and agricultural biology.Natural Environment Research Council (NERC)Natural Environment Research Council (NERC)Fundação de Amparo à Pesquisa do Estado de São Paul

PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis

Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL-1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4^{+} and CD8^{+} T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1^{+}, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-γ production, but not TNF-α secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8^{+}CD45RA^{+}CD27^{-} T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis

The Dilemma of Influenza Vaccine Recommendations when Applied to the Tropics: The Brazilian Case Examined Under Alternative Scenarios

Since 1999 the World Health Organization issues annually an additional influenza vaccine composition recommendation. This initiative aimed to extend to the Southern Hemisphere (SH) the benefits—previously enjoyed only by the Northern Hemisphere (NH)—of a vaccine recommendation issued as close as possible to the moment just before the onset of the influenza epidemic season. A short time between the issue of the recommendation and vaccine delivery is needed to maximize the chances of correct matching between putative circulating strains and one of the three strains present in the vaccine composition. Here we compare the effectiveness of the SH influenza vaccination adopted in Brazil with hypothetical alternative scenarios defined by different timings of vaccine delivery and/or composition. Scores were based on the temporal overlap between vaccine-induced protection and circulating strains. Viral data were obtained between 1999 and 2007 from constant surveillance and strain characterization in two Brazilian cities: Belém, located at the Equatorial region, and São Paulo, at the limit between the tropical and subtropical regions. Our results show that, among currently feasible options, the best strategy for Brazil would be to adopt the NH composition and timing, as in such case protection would increase from 30% to 65% (p<.01) if past data can be used as a prediction of the future. The influenza season starts in Brazil (and in the equator virtually ends) well before the SH winter, making the current delivery of the SH vaccination in April too late to be effective. Since Brazil encompasses a large area of the Southern Hemisphere, our results point to the possibility of these conclusions being similarly valid for other tropical regions

Poor prospects for avian biodiversity in amazonian oil palm

Expansion of oil palm plantations across the humid tropics has precipitated massive loss of tropical forest habitats and their associated speciose biotas. Oil palm plantation monocultures have been identified as an emerging threat to Amazonian biodiversity, but there are no quantitative studies exploring the impact of these plantations on the biome’s biota. Understanding these impacts is extremely important given the rapid projected expansion of oil palm cultivation in the basin. Here we investigate the biodiversity value of oil palm plantations in comparison with other dominant regional land-uses in Eastern Amazonia. We carried out bird surveys in oil palm plantations of varying ages, primary and secondary forests, and cattle pastures. We found that oil palm plantations retained impoverished avian communities with a similar species composition to pastures and agrarian land-uses and did not offer habitat for most forest-associated species, including restricted range species and species of conservation concern. On the other hand, the forests that the oil palm companies are legally obliged to protect hosted a relatively species-rich community including several globally-threatened bird species. We consider oil palm to be no less detrimental to regional biodiversity than other agricultural land-uses and that political pressure exerted by large landowners to allow oil palm to count as a substitute for native forest vegetation in private landholdings with forest restoration deficits would have dire consequences for regional biodiversity

Brazilian Bidens pilosa Linné yields fraction containing quercetin-derived flavonoid with free radical scavenger activity and hepatoprotective effects

Bidens pilosa is a plant used by Amazonian and Asian folks for some hepatopathies. The hydroethanol crude extract and three fractions were assessed for antioxidant and hepatoprotective effects. Higher levels of scavenger activity on the 1,1-diphenyl-2-picrylhydrazyl radical, inhibition of deoxyribose oxidation and lipid peroxidation in vitro were detected for the ethyl acetate fraction (IC50~4.3–32.3 µg/ml) followed by the crude extract (IC50~14.2–98.0 µg/ml). The ethyl acetate fraction, again followed by the crude extract, showed high contents of total soluble polyphenols (3.6±0.2 and 2.1±0.2 GAE/mg, respectively) and presence of a quercetin-derived flavonoid identified as quercetin 3,3′-dimethyl ether 7-O-β-D-glycopyranoside. Both products were assayed for hepatoprotector effects against CCl4-induced liver injury in mice. Markers of oxidative stress and hepatic injury were evaluated. The results showed that the 10-day pretreatments (15 mg/kg, p.o.) protected the livers against injury by blocking CCl4-induced lipid peroxidation and protein carbonylation and the DNA fragmentation was decreased (~60%). The pretreatments avoided the loss of the plasma ferric reducing/antioxidant power and the elevation of serum transaminases and lactate dehydrogenase activities. The results suggest that the main constituents responsible for the hepatoprotective effects with free radical scavenger power associated are well extracted by performing fractionation with ethyl acetate. The findings support the Brazilian traditional use of this plant and justify further evaluations for the therapeutic efficacy and safety of the constituents of the ethyl acetate fraction to treat some liver diseases