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Late-life depression (LLD) arises from a complex interplay among biological, psychological, and social factors. Biologically, three main hypotheses have been proposed to explain the distinct clinical features of LLD. The vascular hypothesis supports vascular-related white matter changes in the development of LLD, while the neurodegenerative hypothesis suggests that LLD might be a prodrome of neurodegenerative diseases. The inflammatory hypothesis, which is the main focus of this review, posits that heightened inflammation underlies LLD directly or indirectly through neurodegenerative and microvascular alterations.
Methods:
This is a non-systematic review on the role played by inflammation in the pathophysiology of LLD and the related opportunities to define biomarkers and therapeutic targets. We searched PubMed from January 2010 through March 2025 for relevant English-language studies.
Results:
Patients with LLD have elevated circulating levels of inflammatory biomarkers (e.g., C-reactive protein and interleukin-6) as well as evidence of neuroinflammation. Although the exact origin of this inflammatory profile remains unclear, it is thought to be exacerbated by immune cell senescence and the presence of physical comorbidities, including cardiovascular and metabolic diseases. Pharmacological (e.g., selective serotonin receptor inhibitors) and non-pharmacological (e.g., diet, physical interventions) approaches for LLD seem to exert their therapeutic effect, at least in part, through inflammation-related mechanisms.
Conclusion:
Recognizing the unique features of LLD compared to depression in other periods of life is an important step toward its proper management. More specifically, understanding the role of inflammation in LLD holds both theoretical and practical implications, including anti-inflammatory or immune-based strategies as potential therapeutic interventions.
The number of published systematic reviews has increased over the last years, with a non-negligible proportion displaying methodological concerns. We aimed to develop and evaluate a tool to assess the reported methodological quality of medical systematic reviews. The developed tool (ReMarQ) consists of 26 dichotomous items. We applied an item response theory model to assess the difficulty and discrimination of the items and decision tree models to identify those items more capable of identifying systematic reviews with higher reported methodological quality. ReMarQ was applied to a representative sample of medical systematic reviews (excluding those published in the Cochrane Database of Systematic Reviews) to describe their methodological quality and identify associated factors. We assessed 400 systematic reviews published between 2010 and 2020, of which 196 (49.0%) included meta-analysis. The most discriminative items were (i) conducting a risk of bias assessment, (ii) having a published protocol and (iii) reporting methods for solving disagreements. More recent systematic reviews (adjusted yearly RR=1.03; 95%CI=1.02 −1.04, p<0.001) and those with meta-analysis (adjusted RR=1.34; 95%CI=1.25 −1.43, p<0.001) were associated with higher reported methodological quality. Such an association was not observed with the journal impact factor. The items most frequently fulfilled were (i) reporting search dates, (ii) reporting bibliographic sources and (iii) searching multiple electronic bibliographic databases. ReMarQ, consisting of dichotomous items and whose application does not require subject content expertise, may be important (i) in supporting an efficient quality assessment of systematic reviews and (ii) as the basis of automated processes to support that assessment.
This study aimed to evaluate the effect of marine-based rumen buffer (Lithothamnium calcareum) supplementation on rumen health as well as milk yield and composition and also behavioural and metabolic parameters of dairy cows. Thirty-six lactating multiparous Holstein cows were used with a milk yield average of 39 kg/d and 64 d in milk. The experiment was conducted over 60 d using two groups: control (CON; n = 18) was supplemented with sodium bicarbonate at 1.1% dry matter and a treatment group that received Lithothamnium calcareum at 0.5% of dry matter (LITHO; n = 18). Each group was fed daily with the buffers mixed to the total mixed ration containing 29.28% starch. Ruminal fluid collections were performed weekly to evaluate pH and volatile fatty acids. Feeding behaviour data were obtained through automatic feeders, while overall behavioural data were obtained using monitoring collars. Milk yield was recorded daily and adjusted for fat and energy. Milk samples were retrieved once weekly for analysis of fat, protein, lactose and total solids. Blood samples were collected weekly for metabolic analysis and faecal samples were collected weekly to evaluate pH and starch concentrations. LITHO produced more fat- and energy-corrected milk (P ≤ 0.01) as well as the highest percentage of fat and solids (P < 0.05) when compared to the CON group. Data on feeding behaviour showed an increased eating time (P ≤ 0.01) in the LITHO group but a higher eating rate (P < 0.01) in the CON group. Animals from the LITHO group had lower faecal pH (P < 0.05). The treatment did not affect dry matter intake, animal behaviour, ruminal acid–base balance, or faecal starch. In summary, Lithothamnium calcareum supplementation at 0.5% of dry matter improved milk yield, milk composition and, presumably, feed conversion efficiency.
Exploring the phylogenetic signal of morphological traits using geometric morphometry represents a powerful approach to assess the relative weights of convergence and shared evolutionary history in shaping species' forms. We evaluated the phylogenetic signal in shape and size of ventral and dorsal haptoral anchors of 10 species of monogenoids (Hamatopeduncularia, Chauhanellus and Susanlimocotyle) occurring in marine catfish (Siluriformes: Ariidae) from the Atlantic coast of South America. The phylogenetic relationships among these species were mapped onto the morphospaces of shape and size of dorsal and ventral anchors. Two different tests (squared change-parsimony and Kmult) were applied to establish whether the spatial positions in the phylomorphospace were influenced by phylogenetic relationships. A significant phylogenetic signal was found between anchor form and parasite phylogeny. Allometric effects on anchor shape were non-significant. Phylogenetically distant species on the same host differed markedly in anchor morphology, suggesting little influence of host species on anchor form. A significantly higher level of shape variation among ventral anchors was also found, suggesting that the evolutionary forces shaping ventral anchor morphology may operate with differing intensities or exhibit distinct mechanisms compared to their dorsal counterparts. Our results suggest that phylogenetic relationships were a key driver of changes in shape (but not size) of anchors of monogenoids of South American ariids. However, it seems that the emergence of the digitiform haptor in Hamatopenducularia and in some species of Chauhanellus played an important role in the reduction in anchor size and may cause secondary losses of anchors in other groups of monogenoids.
Burnout is highly prevalent among medical students. This study aimed to assess burnout levels over the course of a semester and identify variables that might explain burnout’s variance over time.
Method
This longitudinal study involved medical students from a Portuguese school. Participants completed the Maslach Burnout Inventory and Mental Health Inventory-5, along with questions related to social support, help-seeking behaviours, academic performance, mental health and lifestyle assessment at the beginning (first phase), middle (second phase) and end (third phase) of the first semester of 2018–2019 academic year.
Results
A total of 108 participants provided responses in all phases (paired sample). The prevalence of burnout in the first phase was 28.2%, which increased to 34% in the second and 39.5% in the third. To explore factors contributing to burnout levels, we used the 332 responses obtained in the third phase (non-paired sample). Higher burnout levels were associated with poor academic performance, mental health stigma, consumption of tranquillisers and living away from home. Conversely, they were negatively associated with social support and a healthy lifestyle.
Conclusions
The study reveals a high prevalence of burnout among medical students, with burnout levels increasing throughout the semester. These levels are influenced by modifiable variables.
This work aimed to study the role of different SARS-CoV-2 lineages in the epidemiology of multiple waves of the COVID-19 pandemic in Ribeirão Preto (São Paulo state), with comparison within Brazil and globally. Viral genomic sequencing was combined with clinical and sociodemographic information of 2,379 subjects at a large Brazilian hospital. On the whole 2,395 complete SARS-CoV-2 genomes were obtained from April 2020 to January 2022. We report variants of concern (VOC) and interest (VOI) dynamics and the role of Brazilian lineages. We identified three World Health Organization VOCs (Gamma, Delta, Omicron) and one VOI (Zeta), which caused distinct waves in this cohort. We also identified 47 distinct Pango lineages. Consistent with the high prevalence of Gamma in Brazil, Pango lineage P.1 dominated infections in this cohort for half of 2021. Each wave of infection largely consisted of a single variant group, with each new group quickly and completely rising to dominance. Despite increasing vaccination in Brazil starting in 2021, this pattern was observed throughout the study and is consistent with the hypothesis that herd immunity tends to be SARS-CoV-2 variant-specific and does not broadly protect against COVID-19.
Oxidative stress is an undesirable effect of in vitro culture, which requires antioxidant supplementation. This study investigated the analogue of resveratrol (RA33) as an alternative to resveratrol, an antioxidant molecule, for the in vitro culture of in vitro-fertilized bovine embryos. The effect of different concentrations of RA33 on embryo development was evaluated and a comparison between RA33 and resveratrol was performed. The cleavage rate was higher (P < 0.05) with 2.5 μM (69.0 ± 4.4%) than at 0, 0.1 or 0.5 μM RA33 (62.1 ± 2.0%, 60.7 ± 5.9% and 56.7 ± 5.8%, respectively). The blastocyst rates on days 7 and 8 post-fertilization with 2.5 μM RA33 (19.4 ± 3.3% and 24.6 ± 3.3%, respectively) were higher (P < 0.05) than for 0 μM (12.4 ± 2.5% and 15.2±2.5%, respectively). When 2.5 μM RA33 was compared with 0.5 μM resveratrol, similar (P > 0.05) cleavage and blastocyst rates were found between them, but the cleavage rate was higher (P < 0.05) in the control (80.8 ± 3.4%) than for the resveratrol treatment (76.4 ± 3.6%). The numbers of apoptotic cells and the apoptotic index were lower (P < 0.05) with RA33 (6.5 ± 0.6 cells and 6.4 ± 0.7%, respectively) and resveratrol (5 ± 0.8 cells and 5.5 ± 1.0%, respectively) than in the control group (9.8 ± 1.2 cells and 8.9 ± 1.1%, respectively). In conclusion, RA33 can enhance the preimplantation development of in vitro-fertilized bovine embryos and be an alternative to resveratrol in embryo culture medium.
The objective of this study was to investigate the prevalence and carry out epidemiology using sociodemographic data from patients with symptoms suggestive of coronavirus disease (COVID-19) (SARS-CoV-2) in 3 bordering Brazilian municipalities.
Methods:
An epidemiological survey of positive cases of COVID-19 through reverse transcriptase polymerase chain reaction (RT-PCR) was carried out in 1874 patients, seen in the Unified Health System (SUS), ages between 0 and 99 years, who had symptoms suggestive of COVID-19, from the cities of Assis Chateaubriand, Tupãssi, and Formosa do Oeste.
Results:
It was possible to observe that of the 1874 patients seen in the public health network of the 3 municipalities, 354 were diagnosed as positive. The predominance of cases was in female patients (51.97%) and in patients who lived in urban areas (93.50%), and the predominant age group was 20–29 years (19.78%).
Conclusion:
The result of this study demonstrated the epidemiological profile of patients with respiratory and flu-like symptoms, positive for COVID-19, in 3 municipalities bordering Paraguay and Argentina. It was evident that the age group has its specificities regarding the susceptibility of the infection. Although the borders are closed, there was probably a spread of the virus in this region, due to the diversion, which showed an increase during the pandemic period.
This article presents a methodology to reduce the energy consumption of an industrial robot. We propose a design for a 3R serial manipulator of general geometry. We show an analytical model aiming to analyze the search space of architectures based on the torsion angles of the robot to determine the optimal architecture that allows the efficient use of energy. The analytical model provides a theoretical estimation of the energy consumption and is validated by monitoring the experimental robot. The numerical calculations obtained with a particular case reduced the energy consumption by approximately 7.5%.
Lipopolysaccharide (LPS) endotoxemia has been negatively associated with fertility. This study aimed to investigate the effect of LPS-induced inflammation on gene expression associated with bovine fertility in the uterus and oviduct. Sixteen healthy heifers were divided into two groups. The LPS group (n = 8) received two intravenous (i.v.) injections of 0.5 µg/kg of body weight of LPS with a 24-h interval, and the control group (n = 8) received two i.v. injections of saline solution with the same interval of time. All the animals had the follicular wave synchronized. Three days after the second injection of LPS, all animals were slaughtered and uterine and oviduct samples were collected. Gene expression associated with inflammatory response, thermal and oxidative stresses, oviduct environment quality, and uterine environment quality was evaluated. Body temperature and leucogram demonstrated that LPS induced an acute systemic inflammatory response. In the uterus, the expression of PTGS2 and NANOG genes was downregulated by the LPS challenge. However, no change in expression was observed in the other evaluated genes in the uterus, nor those evaluated in the oviduct. In conclusion, the inflammatory process triggered by LPS did not persist in the uterus and oviduct 3 days after challenge with LPS. Nonetheless, reduction in PTGS2 and NANOG expression in the uterus suggested that, indirectly, LPS may have a prolonged effect, which may affect corpus luteum and endometrial functions.
In order to better understand the different grieving trajectories of the family caregivers (FCs), this study aims to examine the evolution of prolonged grief disorder (PGD) symptoms and the predictive role of the caregiving-related factors in the FCs' grieving trajectory from pre- to post-death.
Method
A prospective cohort study was carried out with advanced cancer FCs evaluated before death (T1) and 6–12 months post-loss (T2).
Results
Participants in T1 (n = 156) were mostly female, adult child, or spouse of the care recipient, with a mean age of 51.78 (SD = 13.29). At T2, 87 FCs participated in the survey. PGD prevalence was higher pre-death (38.6%) than in bereavement (33.7%). Of those who met the PGD criteria before death, most also met these criteria after death (n = 26, 61.9%). Psychological distress and caregiver burden were highly correlated with pre-death grief, which in turn played a critical role in mediating the link between psychological distress and bereavement outcome. Great emotional closeness in the relationship was predictive of PGD symptoms persistence. In contrast, the long-term consequences of caregiver burden were not confirmed.
Significance of results
This study provides evidence for the diversity of individual FC responses and the complex pattern of interactions between caregiving-related factors, relationship quality, and PGD symptoms evolution from pre- to post-death.
Pancreatic eurytrematosis (PE) is an under diagnosed and neglected parasitosis in goats and sheep in the Americas. Clinical and pathological features of PE are not well defined in small ruminants worldwide. Natural cases of PE in small ruminants were detected in the Federal District, Brazil. A survey of necropsy records, including epidemiological and clinicopathological data, in goats and sheep was conducted. Most cases of PE occurred during the rainy season in adult females, with an incidence of 12.9% in goats and 0.8% in sheep. Clinical signs varied from asymptomatic infections to anorexia, lethargy, weakness, marked weight loss and death in some goats. Overall, most cases of PE in goats and sheep were incidental necropsy findings with minor pancreatic lesions. Three goats, however, showed severe chronic pancreatitis, dilation of major pancreatic ducts with numerous trematodes present and marked abdominal fat necrosis. Morphological and molecular characterization of flukes detected Eurytrema coelomaticum. Our findings shed light on the prevalence of E. coelomaticum infections in small ruminants in the region and highlight the possibility of severe and lethal cases in goats. PE must be further investigated in small ruminant populations in relevant livestock production regions of the Americas.
To evaluate associations between selected dietary concerns and eating practices and determine the association of these concerns/practices with demographic and socio-economic characteristics in a population from a large Brazilian city.
Design:
Population-based cross-sectional study. We investigated concerns regarding salt intake, the use of highly processed seasoning and the custom of reading the Na content on food labels. We also analysed concerns regarding the use of pesticides on food products and the practice of consuming organic foods. These variables were analysed according to sex, age group, schooling and income. Multivariate Poisson regression analysis was performed for the estimation of prevalence ratios.
Setting:
Campinas, state of São Paulo, Brazil.
Participants:
The representative sample consisted of 1710 adults and seniors.
Results:
A total 62·3 % of the population were concerned with salt intake, 34·7 % did not use highly processed seasoning and 10·6 % checked the Na content on food labels; 27·5 % were concerned with pesticides and 26·5 % consumed organic foods. The practices analysed were associated with the respective concerns. Women and seniors had a better profile, except for reading Na content in both groups and the consumption of organic foods among seniors. The frequency of checking the Na content and consuming organic foods increased with the level of schooling. The higher income group had a better profile, except for concern with salt intake.
Conclusions:
Considerable social differences were found regarding the dietary practices, and the practices were associated with concerns. The present findings underscore the need for different dietary counseling strategies targeting specific groups.
Background: Kidney transplant recipients are a group of patients at risk for healthcare-related infections. The results of this study make an important clinical contribution and contribute to findings options to decrease the infection-related morbidity and mortality that affects this patient population. Objectives: We evaluated the prevalence of colonization by multidrug-resistant bacteria, Klebsiella pneumoniae carbapenemase (KPC)–producing bacteria, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA) in renal transplant patients; we identified the infection rate, morbidity, and mortality in this population. Methods: Prospective cohort study was conducted at the Kidney and Hypertension Hospital from 2012 to 2015. This project was approved by the Unifesp Research Ethics Committee (no. 1630/11) and an informed consent form was obtained from patients included in the study. Study protocol: Data collection was performed in 2 phases: within the first 24 hours after transplantation and 7 days after transplantation. For all included patients, the following data were collected: identification data, clinical data, and laboratory tests of the first day in the study. All included patients (colonized or not) were followed prospectively for 6 months or until treatment change or death. Results: The study included 200 renal transplant patients in accordance with the inclusion and exclusion criteria. We observed that 76 (38%) patients included in our sample were colonized; 8% S. aureus, 11% Enterococcus, and 19% K. pneumoniae. We verified the presence of concomitant colonization of 1 or more of these pathogens. The most prevalent concomitance identified in our population was E. coli and K. pneumoniae. We identified the presence of diabetes and diabetes associated with hypertension as risk factor for colonization. Thus, patients with more systemic complications may be at risk for colonization by multidrug-resistant bacteria. Another risk factor for colonization was antibiotic use in the 6 months prior to transplantation. Transplant-related outcomes were length of stay after transplantation, delayed graft function (ie, dialysis after the transplantation) and postoperative care in an intensive care unit. At the 6-month follow-up, we identified urinary infection and surgical site infection as risk factors. One death occurred due to stroke in the group of colonized patients, unrelated to infectious causes. Conclusions: These results show fundamental aspects for health professionals for bacterial characterization, transmission, and resistance mechanisms and, mainly, tools for prevention and control of multidrug-resistant bacteria from patients colonized under conservative treatment before the complexity of high-risk procedures begins, such as dialysis and transplantation to reduce morbidity and mortality.
Funding: FAPESP São Paulo Research Support Foundation
The timing of the Neanderthal-associated Middle Palaeolithic demise and a possible overlap with anatomically modern humans (AMH) in some regions of Eurasia continues to be debated. The Iberian Peninsula is considered a possible refuge zone for the last Neanderthals, but the chronology of the later Middle Palaeolithic record has undergone revision and has increased the debate on the timing of Neanderthal extinction. Here we report on a study of the 5-m-thick archaeological stratigraphy of the Cardina-Salto do Boi, an open-air site located in inland Iberia, from which optically stimulated luminescence (OSL) ages were obtained for Middle and Upper Palaeolithic occupations preserved in overbank alluvial deposits. Geomorphology, archaeostratigraphy, stone-tool evolution, and OSL dating support the persistence of Neanderthals after 41 ka in central Iberia; the transition between the Middle Palaeolithic material culture and the AMH-associated Aurignacian blade and bladelet production is estimated to lie between 34.0 ± 2.0 ka and 38.4 ± 1.9 ka. Our results demonstrate that investigations focusing on different geomorphological situations are necessary to overcome the current limitations of the evidence and to establish more consistent models for Neanderthal disappearance and AMH expansion in the Iberian Peninsula.
The Colombian industrial sector is moving toward alternative forms of treatment of industrial waste, considering that the waste can be a source of raw material in the production chain. Thus, aiming at the decrease in mineral fertilizer use, and maintaining or even raising the crop yield, the sugarcane industry has recently advanced in the composting of the industrial waste and application in the field, both of them being potentially sustainable practices. This manuscript reports the economic benefits and the greenhouse gas (GHG) emissions related to the sugarcane production system in Colombia that has been simulated in this study to evaluate the beneficial effects of reusing industrial waste from ethanol production. This study was performed using the Virtual Sugarcane Biorefinery (VSB) modeling software for the simulation of agricultural and industrial parameters on integrated alternatives for the sugarcane industry. Colombian sugarcane sector was modeled using three scenarios representing agricultural systems that do not use composted industrial waste vs a paired scenario for each condition where composted waste is utilized. Regarding compost and vinasse use as fertilizer and soil conditioner, GHG emissions from the biogenic origin are not included as a reported item in the matrix of GHG emissions of the sugarcane sector. Inputs for the economic and environmental assessment models are based on actual operational data from two mill sites, one located in the traditional sugarcane production region of Cauca River Valley and the other one, on the agricultural expansion region of Llanos Orientales. Here, we have found that the reuse of composted industrial waste is beneficial and provides an economic cost savings of 2–6% per year. However, it also results in an annual increase of 10–20% in the GHG emissions.
Although accumulating evidence supports the hypothesis that immune/inflammatory mechanisms are associated with the pathophysiology of bipolar disorder (BD), data about the profile of chemokines (chemotactic cytokines) and chemokine receptors are still scarce. The current study was designed to evaluate the expression of chemokine receptors on lymphocytes of patients with BD in comparison with controls.
Methods:
Thirty-three patients with type I BD (N = 21 in euthymia; N = 6 in mania/hypomania; N = 6 in depression) and 22 age- and sex-matched controls were subjected to clinical evaluation and peripheral blood draw. The expression of chemokine receptors CCR3, CCR5, CXCR4, and CXCR3 on CD4+ and CD8+ lymphocytes was assessed by flow cytometry.
Results:
Patients with BD had decreased percentage of CD4+CXCR3+ (p = 0.024), CD4+CCR3+ (p = 0.042), and CD4+CCR5+ (0.013) lymphocytes in comparison with controls. The percentage of both CD4+ and CD8+ lymphocytes expressing the chemokine receptor CXCR4 was similar in patients with BD and controls. Likewise, the percentages of CD8+CXCR3+, CD8+CCR3+, and CD8+CCR5+ lymphocytes were similar in patients with BD and controls.
Conclusion:
Our findings reinforce the hypothesis that immune pathways, especially involving CD4+ lymphocytes, are involved in the physiopathology of BD.