Violence Against the Elderly: Social Representations of Portuguese and Brazilian Caregivers

The increase in life expectancy and elderly people in society, coupled with changes in family structure, have highlighted the importance of formal and informal caregivers of elderly people. Objective: To analyse the social representations of violence against the elderly, of two groups of formal and informal caregivers. Methods: Exploratory, quantitative and qualitative research, supported by the theoretical-methodological reference of the Social Representations Theory and in the context of this, the Central Core Theory. The sample was participated in by 81 formal caregivers from the project “Aging in Safety in the Alentejo - Understanding to Act, of the University of Évora” and 20 informal caregivers from the project “Qualification of caregivers and aspects related to the quality of life of the elderly people dependent on primary and tertiary care: Implementation and protocol evaluation, of the State University of Southwest of Bahia”. We used the Free Word Association Technique. The data was analysed by prototypical analysis based on two matrices by the software IRAMUTEQ (Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires) 0.7 alpha 2. Results: In Portugal, the elements “bad, mistreatment, I will be, sad, anger, patience, physical, injustice, irritation and meanness” stood out in the central core. In Brazil the mention of “hitting” was emphasized. Conclusions: In both Portugal and Brazil, physical violence takes on particular significance in the social representations of caregivers, rather than verbal and psychological violence, which is not present in the central core of social representations of violence against the elderly in either of the countries

Linking compact dwarf starburst galaxies in the resolve survey to downsized blue nuggets

Abstract We identify and characterize compact dwarf starburst (CDS) galaxies in the RESOLVE survey, a volume-limited census of galaxies in the local universe, to probe whether this population contains any residual “blue nuggets,” a class of intensely star-forming compact galaxies first identified at high redshift z. Our 50 low-z CDS galaxies are defined by dwarf masses (stellar mass M* < 109.5 M⊙), compact bulged-disk or spheroid-dominated morphologies (using a quantitative criterion, \mu _\Delta > 8.6), and specific star formation rates above the defining threshold for high-z blue nuggets (log SSFR [Gyr−1] > −0.5). Across redshifts, blue nuggets exhibit three defining properties: compactness relative to contemporaneous galaxies, abundant cold gas, and formation via compaction in mergers or colliding streams. Those with halo mass below Mhalo ∼ 1011.5 M⊙ may in theory evade permanent quenching and cyclically refuel until the present day. Selected only for compactness and starburst activity, our CDS galaxies generally have Mhalo ≲ 1011.5 M⊙ and gas-to-stellar mass ratio ≳1. Moreover, analysis of archival DECaLS photometry and new 3D spectroscopic observations for CDS galaxies reveals a high rate of photometric and kinematic disturbances suggestive of dwarf mergers. The SSFRs, surface mass densities, and number counts of CDS galaxies are compatible with theoretical and observational expectations for redshift evolution in blue nuggets. We argue that CDS galaxies represent a maximally-starbursting subset of traditional compact dwarf classes such as blue compact dwarfs and blue E/S0s. We conclude that CDS galaxies represent a low-z tail of the blue nugget phenomenon formed via a moderated compaction channel that leaves open the possibility of disk regrowth and evolution into normal disk galaxies

In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic? F127-based polymeric micelle system against Leishmania amazonensis infection.

New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome? were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome? , Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-?, IL-12, TNF-?, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease