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Pancreatic cancer is a deadly and highly metastatic disease, although how metastatic lesions establish is not fully understood. A key feature of pancreatic tumours is extensive fibrosis and deposition of extracellular matrix (ECM). While pancreatic cancer cells are programmed by stimuli derived from a stiff ECM, metastasis requires loss of attachment and adaptation to a softer microenvironment at distant sites. Growing evidence suggests that stiff ECM influences pancreatic cancer cell behaviour. Here, we argue that this influence is reversible and that pancreatic cancer cells can be reprogrammed upon sensing soft substrates. Using engineered polyacrylamide hydrogels with tuneable mechanical properties, we show that collagen VI is specifically upregulated in pancreatic cancer cells on soft substrates, due to a lack of integrin engagement. Furthermore, the expression of collagen VI is inversely correlated with mechanosensing and activity of YAP (also known as YAP1), which might be due to a direct or indirect effect on transcription of genes encoding collagen VI. Collagen VI supports migration in vitro and metastasis formation in vivo. Metastatic nodules formed by pancreatic cancer cells lacking Col6a1 display stromal cell-derived collagen VI deposition, suggesting that collagen VI derived from either cancer cells or the stroma is an essential component of the metastatic niche. This article has an associated First Person interview with Vasileios Papalazarou, joint first author of the paper.
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Colágeno , Neoplasias Pancreáticas , Humanos , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Integrinas/metabolismo , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
Studies on the impact of the COVID-19 pandemic in sub-Saharan Africa have yielded varying results, although authors universally agree the real burden surpasses reported cases. The primary objective of this study was to determine SARS-CoV-2 seroprevalence among patients attending Monkole Hospital in Kinshasa (D.R. Congo). The secondary objective was to evaluate the analytic performance of two chemiluminescence platforms: Elecsys® (Roche) and VirClia® (Vircell) on dried blood spot samples (DBS). The study population (N = 373) was recruited in two stages: a mid-2021 blood donor cohort (15.5% women) and a mid-2022 women cohort. Crude global seroprevalence was 61% (53.9%-67.8%) pre-Delta in 2021 and 90.2% (84.7%-94.2%) post-Omicron in 2022. Anti-spike (S) antibody levels significantly increased from 53.1 (31.8-131.3) U/mL in 2021 to 436.5 (219.3-950.5) U/mL in 2022 and were significantly higher above 45 years old in the 2022 population. Both platforms showed good analytic performance on DBS samples: sensitivity was 96.8% for IgG (antiN/S) (93.9%-98.5%) and 96.0% (93.0%-98.0%) for anti-S quantification. These results provide additional support for the notion that exposure to SARS-CoV-2 is more widespread than indicated by case-based surveillance and will be able to guide the pandemic response and strategy moving forward. Likewise, this study contributes evidence to the reliability of DBS as a tool for serological testing and diagnosis in resource-limited settings.
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COVID-19 , SARS-CoV-2 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , COVID-19/diagnóstico , COVID-19/epidemiologia , República Democrática do Congo/epidemiologia , Pandemias , Reprodutibilidade dos Testes , Estudos Soroepidemiológicos , Anticorpos AntiviraisRESUMO
Environmental microbes routinely colonize wildlife body surface microbiota. However, animals experience dynamic environmental shifts throughout their daily routine. Yet, the effect of ecological shifts in wildlife body surface microbiota has been poorly explored. Here, we sequenced the hypervariable region V3-V4 of the 16S rRNA gene to characterize the body surface microbiota of wild Magellanic penguins (Spheniscus magellanicus) under two ecological contexts: (1) Penguins walking along the coast and (2) Penguins sheltered underground in their nest, across three subantarctic breeding colonies in the Magellan Strait, Chile. Despite ecological contexts, our results revealed that Moraxellaceae bacteria were the most predominant and abundant taxa associated with penguin body surfaces. Nevertheless, we detected colony-specific core bacteria associated with penguin bodies. The most abundant were: Deinococcus in the Contramaestre colony, Fusobacterium in the Tuckers 1 colony, and Clostridium sensu stricto 1 in the Tuckers 2 colony. Our results give a new perspective on the niche environmental hypothesis for wild seabirds. First, the ecological characteristics of each colony were associated with the microbial communities from the nest soil and the body surface of penguins inside the nests. For example, in the colonies with heterogenous vegetation cover (i.e. the Tuckers Islets), there was a similar microbial composition between the nest soil and the body surface of penguins. In contrast, on the more arid colony (Contramaestre), we detected differences in the microbial communities between the nest soil and the body surface of penguins.
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PREMISE: Evolution of cross-pollination efficiency depends on the genetic variation of flower traits, the pollen vector, and flower trait matching between pollen donors and recipients. Trait matching has been almost unexplored among nonheterostylous species, and we examined whether the match of anther length in pollen donors and stigma length in pollen recipients influences the efficiency of cross-pollination. To explore potential constraints for evolutionary response, we also quantified genetic variation and covariation among sepal length, petal length and width, stamen length, style length, and herkogamy. METHODS: We created 58 experimental arrays of Turnera velutina that varied in the extent of mismatch in the position of anthers and stigmas between single-flowered plants. Genetic variation and correlations among flower traits were estimated under greenhouse conditions. RESULTS: Style length, but not herkogamy, influenced the efficiency of cross-pollination. Plants with stamen length that matched the style length of other plants were more efficient pollen donors, whereas those with the style protruding above the stamens of other plants were more efficient pollen recipients. Significant broad-sense heritability (0.22 > hB 2 < 0.42) and moderate genetic correlations (0.33 > r < 0.85) among floral traits were detected. CONCLUSIONS: Our results demonstrated that anther-stigma mismatch between flowers contributed to variation in the efficiency of cross-pollination. The genetic correlations between stamen length and other floral traits suggests that any change in cross-pollination efficiency would be driven by changes in style rather than in stamen length.
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Flores , Pólen , Polinização , Flores/fisiologia , Flores/anatomia & histologia , Flores/genética , Pólen/fisiologia , Pólen/genética , Variação Genética , FenótipoRESUMO
OBJECTIVES: To summarise the available evidence and assess the effectiveness of medium and long-term physiotherapy treatment in adults with fibromyalgia (FM). METHODS: This systematic review was registered in PROSPERO: CRD42023388356. The databases searched were MEDLINE, PEDro, Scopus, Cinhal, LatinIndex, and Cochrane, using the following keywords: "fibromyalgia", "physiotherapy", "treatment", "therapeutic exercise", "TENS", "laser therapy" and "manual therapy." The included articles analysed treatments with active or passive physiotherapy approaches in patients with FM. The variables included structural characteristics, such as: author, publication year, research question, and main outcome variables. The data on the findings of the articles comprised the following aspects: number of participants, intervention, follow-up, results, and principal conclusions. RESULTS: Thirty-three articles were analysed, with an overall PRISMA score of 18.63±3.36. The active treatment methods analysed were: movement and body awareness therapies (stretching, tai chi, yoga and Pilates); hydrotherapy; physical or aerobic exercise; and multidisciplinary therapy. The passive therapies analysed were: manual therapy; repetitive transcranial magnetic stimulation (rTMS); and other therapies (hyperbaric oxygen therapy, vibration therapy, virtual reality, transcutaneous electric nervous stimulation (TENS), pain neuroscience education, and acupuncture). Evidence was found on the positive effect of physiotherapy treatment on the signs and symptoms of fibromyalgia, such as pain, impairment of physical capacity and worse quality of life. CONCLUSIONS: The effectiveness of the active and passive therapies analysed in the management of the symptoms and signs of the disease was positive in most of the studies. However, more specific descriptions of the treatment protocol, frequency, intensity and treatment dose are required to reach a consensus, as well as primary studies for a more extended follow-up period to better evaluate long-term effects.
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Fibromialgia , Modalidades de Fisioterapia , Humanos , Fibromialgia/terapia , Fibromialgia/fisiopatologia , Fibromialgia/reabilitação , Fibromialgia/diagnóstico , Resultado do Tratamento , Fatores de Tempo , Adulto , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: During the first COVID-19 pandemic wave (1st CoPW), nursing homes (NHs) experienced a high rate of COVID-19 infection and death. Residents who survived the COVID-19 infection may have become frailer. This study aimed to determine the predictive value of having a COVID-19 infection during the 1st CoPW for 2-year mortality in NH residents. METHODS: This was a retrospective study conducted in three NHs. Residents who had survived the 1st CoPW (March to May 2020) were included. The diagnosis of COVID-19 was based on the results of a positive reverse transcriptase-polymerase chain reaction test. The collected data also included age, sex, length of residence in the NH, disability status, legal guardianship status, nutritional status, need for texture-modified food, hospitalization or Emergency Department visits during lockdown and SARS-COV2 vaccination status during the follow-up. Non-adjusted and adjusted Cox models were used to analyse factors associated with 2-year post-1st CoPW mortality. RESULTS: Among the 315 CoPW1 survivors (72% female, mean age 88 years, 48% with severe disability), 35% presented with COVID-19. Having a history of COVID-19 was not associated with 2-year mortality: hazard ratio (HR) [95% confidence interval] = 0.96 [0.81-1.13], p = 0.62. The factors independently associated with 2-year mortality were older age (for each additional year, HR = 1.05 [1.03-1.08], p < 0.01), severe disability vs. moderate or no disability (HR = 1.35 [1.12-1.63], p < 0.01) and severe malnutrition vs. no malnutrition (HR = 1.29 [1.04-1.60], p = 0.02). Considering that vaccination campaign started during the follow-up, mortality was associated with severe malnutrition before and severe disability after the start of the campaign. Vaccination was independently associated with better survival (HR 0.71 [0.55-0.93], p = 0.02). CONCLUSIONS: Having survived a COVID-19 infection during the 1st CoPW did not affect subsequent 2-year survival in older adults living in NHs. Severe malnutrition and disability remained strong predictor of mortality in this population, whereas vaccination was associated to better survival.
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COVID-19 , Casas de Saúde , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Casas de Saúde/tendências , Feminino , Masculino , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Idoso , Instituição de Longa Permanência para Idosos/tendências , SARS-CoV-2 , PandemiasRESUMO
OBJECTIVE: To compare the effects of electrical dry needling with a non-invasive multi-component intervention in patients with chronic low back pain. DESIGN: A randomised single-blind clinical trial. SETTING: Outpatient Physiotherapy Clinic; home. PARTICIPANTS: Sixty-four patients with chronic low back pain aged 30-65 years. INTERVENTIONS: Six-week electrical dry needling on myofascial trigger points, and a non-invasive multicomponent intervention (home exercise programme, stretching and ischemic compression). MAIN MEASURES: Pain (Visual Analogue Scale), disability (Roland-Morris Disability Questionnaire and Oswestry Disability Index), kinesiophobia (Tampa Scale of Kinesiophobia), quality of life and sleep (Short Form 36-item Health Survey and Pittsburgh Sleep Quality Index), isometric endurance of trunk flexor muscles (McQuade test), lumbar mobility in flexion (finger-to-floor distance), and pressure pain threshold (algometer) were assessed at baseline, after 6 weeks, and after 2 months. RESULTS: ANOVA showed statistically significant differences in group-by-time interaction for most pain pressure thresholds of myofascial trigger points (P < 0.05), for disability (Roland-Morris Disability Questionnaire: F = 6.14, P = 0.016; and Oswestry Disability Index: F = 7.36, P = 0.009), for trunk anteflexion (F = 10.03, P = 0.002) and for habitual sleep efficacy (F = 6.65, P = 0.012), use of hypnotics (F = 4.77, P = 0.033) and total score of quality of sleep (F = 8.23, P = 0.006). CONCLUSIONS: In comparison to a non-invasive multicomponent intervention, electrical dry needling has more positive effects on disability, pain intensity, kinesiophobia, and reducing patients' sensitivity to myofascial trigger points pressure, at post-treatment and at 2 months. CLINICAL TRIAL REGISTRATION NUMBER: NCT04804228. Registered on May 28th, 2021. Available at https://clinicaltrials.gov/ct2/show/NCT04804228.
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Dor Lombar , Pontos-Gatilho , Humanos , Dor Lombar/diagnóstico , Dor Lombar/terapia , Indução Percutânea de Colágeno , Qualidade de Vida , Método Simples-Cego , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Glioma cells overexpress different peptide receptors that are useful for research, diagnosis, management, and treatment of the disease. Oncogenic peptides favor the proliferation, migration, and invasion of glioma cells, as well as angiogenesis, whereas anticancer peptides exert antiproliferative, antimigration, and anti-angiogenic effects against gliomas. Other peptides exert a dual effect on gliomas, that is, both proliferative and antiproliferative actions. Peptidergic systems are therapeutic targets, as peptide receptor antagonists/peptides or peptide receptor agonists can be administered to treat gliomas. Other anticancer strategies exerting beneficial effects against gliomas are discussed herein, and future research lines to be developed for gliomas are also suggested. Despite the large amount of data supporting the involvement of peptides in glioma progression, no anticancer drugs targeting peptidergic systems are currently available in clinical practice to treat gliomas.
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Antineoplásicos , Glioma , Peptídeos , Humanos , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Animais , Receptores de Peptídeos/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismoRESUMO
Capacitation involves tyrosine phosphorylation (TP) as a key marker. Lifestyle-related factors, such as obesity and smoking, are recognized for their adverse effects on semen quality and male fertility, yet the underlying mechanisms, including their potential impact on TP, remain unclear. Moreover, the effect of sperm cryopreservation on TP at the human sperm population level is unexplored. Flow cytometry analysis of global TP was performed on pre-capacitated, post-capacitated and 1- and 3-hours' incubated fresh and frozen-thawed samples from sperm donors (n = 40). Neither being overweight nor smoking (or both) significantly affected the percentage of sperm showing TP. However, elevated BMI and smoking intensity correlated with heightened basal TP levels (r = 0.226, p = 0.003) and heightened increase in TP after 3 h of incubation (r = 0.185, p = 0.017), respectively. Cryopreservation resulted in increased global TP levels after capacitation but not immediately after thawing. Nonetheless, most donors' thawed samples showed increased TP levels before and after capacitation as well as after incubation. Additionally, phosphorylation patterns in fresh and frozen-thawed samples were similar, indicating consistent sample response to capacitation stimuli despite differences in TP levels. Overall, this study sheds light on the potential impacts of lifestyle factors and cryopreservation on the dynamics of global TP levels during capacitation.
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Índice de Massa Corporal , Criopreservação , Capacitação Espermática , Espermatozoides , Tirosina , Humanos , Criopreservação/métodos , Masculino , Fosforilação , Tirosina/metabolismo , Espermatozoides/metabolismo , Adulto , Fumar Cigarros/efeitos adversos , Preservação do Sêmen/métodos , Análise do SêmenRESUMO
The Arp2/3 complex is essential for the assembly of branched filamentous actin, but its role in physiology and development is surprisingly little understood. Melanoblasts deriving from the neural crest migrate along the developing embryo and traverse the dermis to reach the epidermis, colonising the skin and eventually homing within the hair follicles. We have previously established that Rac1 and Cdc42 direct melanoblast migration in vivo We hypothesised that the Arp2/3 complex might be the main downstream effector of these small GTPases. Arp3 depletion in the melanocyte lineage results in severe pigmentation defects in dorsal and ventral regions of the mouse skin. Arp3 null melanoblasts demonstrate proliferation and migration defects and fail to elongate as their wild-type counterparts. Conditional deletion of Arp3 in primary melanocytes causes improper proliferation, spreading, migration and adhesion to extracellular matrix. Collectively, our results suggest that the Arp2/3 complex is absolutely indispensable in the melanocyte lineage in mouse development, and indicate a significant role in developmental processes that require tight regulation of actin-mediated motility.
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Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Adesão Celular , Proliferação de Células , Melanócitos/metabolismo , Pigmentação da Pele , Pele/metabolismo , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Animais , Linhagem Celular , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Melanócitos/citologia , Camundongos , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Pele/citologia , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Heart failure (HF) admission in chronic coronary syndrome (CCS) patients has a prognostic impact. Stratification schemes have been described for predicting this endpoint, but none of them has been externally validated. OBJECTIVES: Our aim was to develop point scores for predicting incident HF admission with data from previous studies, to perform an external validation in an independent prospective cohort and to compare their discriminative ability for this event. METHODS: Independent predictive variables of HF admission in CCS patients without baseline HF were selected from four previous prospective studies (CARE, PEACE, CORONOR and CLARIFY), generating scores based on the relative magnitude of the coefficients of Cox of each variable. Finally, the scores were validated and compared in a monocentric prospective cohort. RESULTS: The validation cohort included 1212 patients followed for up to 17 years, with 171 patients suffering at least one HF admission in the follow-up. Discriminative ability for predicting HF admission was statistically significant for all, and paired comparisons among them were all nonsignificant except for CORONOR score was superior to CLARIFY score (C-statistic 0.73, 95%CI 0.69-0.76 vs. 0.69, 95% CI 0.65-0.73; p = 0.03). CONCLUSION: All tested scores showed significant discriminative ability for predicting incident HF admission in this independent validation study. Their discriminative ability was similar, with significant differences only between the two scores with higher and lower performance.
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Insuficiência Cardíaca , Humanos , Estudos Prospectivos , Estudos de Coortes , Síndrome , Fatores de Risco , Insuficiência Cardíaca/epidemiologia , Prognóstico , Medição de RiscoRESUMO
PURPOSE: To explore the efficacy and safety of individualized follitropin delta dosing, based on serum anti-Müllerian hormone (AMH) concentration and bodyweight, in a long gonadotropin-releasing hormone (GnRH) agonist protocol. METHODS: Clinical outcomes after one treatment cycle are reported in women with AMH: 5-35 pmol/L. Oocytes were inseminated by intracytoplasmic sperm injection, blastocyst transfer was on Day 5 and remaining blastocysts were cryopreserved. Data collection included live births and neonatal health follow-up for all fresh/frozen transfers performed within one year after treatment allocation. RESULTS: In total, 104 women started stimulation, of whom 101 had oocyte recovery and 92 had blastocyst transfer. The average daily dose of follitropin delta was 11.0 ± 1.6 µg and the duration of stimulation was 10.3 ± 1.6 days. The mean number of oocytes was 12.5 ± 6.4, the mean number of blastocysts was 5.1 ± 3.4, and 85% had at least one good-quality blastocyst. Following mostly single blastocyst transfer (95%), the ongoing pregnancy rate was 43%, the live-birth rate was 43%, and the cumulative live-birth rate was 58% per started stimulation. There were 6 cases of early OHSS (5.8%) graded as mild (n = 3) and moderate (n = 3) and 6 cases of late OHSS (5.8%) graded as moderate (n = 3) and severe (n = 3). CONCLUSION: In this first evaluation of the individualized follitropin delta dosing in a long GnRH agonist protocol, the cumulative live-birth rate was high. A randomized trial comparing follitropin delta in a long GnRH agonist protocol versus in a GnRH antagonist protocol should provide further insight into the efficacy and safety of this treatment option. TRIAL REGISTRATION NUMBER: NCT03564509; June 21, 2018.
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Coeficiente de Natalidade , Síndrome de Hiperestimulação Ovariana , Feminino , Humanos , Masculino , Gravidez , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/agonistas , Nascido Vivo , Indução da Ovulação/métodos , Taxa de Gravidez , SêmenRESUMO
Dietary polyamines have been associated with slowing ageing processes and various pathologies, raising the importance of establishing reference values at different ages throughout life. This study aimed to analyse age-dependent variations in polyamine content using peripheral blood cells and plasma in a healthy and homogeneous population. Peripheral blood of 193 volunteers of both sexes (20-70 years), selected by convenience, was processed to separate cells and plasma. A pre-column derivatization method was used to determine the amines by HPLC (nmol or pmol/mg protein or nmol/ml) to analyse their association with the age (continuous or ordinal in decades) of the subjects. Putrescine and spermine weakly declined significantly in mononuclear cells with age. In erythrocytes and plasma, putrescine showed an evident decrease in the 60-70-year-old group compared to the rest. The ratios between polyamines, mainly in erythrocytes, decreased in the 60-70 years age group and increased the ratio of putrescine in mononuclear cells/erythrocytes. The ratio of putrescine in mononuclear cells/erythrocytes was higher in the 60-70-year-old age group than in the rest. In a sample of subjects (20-29 vs. 60-70 years), whole blood polyamines were not significantly different when differences existed in erythrocytes. Polyamine homeostasis in blood cells and plasma changed with age. Putrescine declined in mononuclear cells and decreased in erythrocytes and plasma in the decade of the 60 s. Further studies should establish an age-dependent phenotype and whether polyamines' supplementation could restore the decreased values and be associated with long-term overall biological benefits.
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Poliaminas , Putrescina , Masculino , Feminino , Animais , Espermidina , Espermina , Células SanguíneasRESUMO
The ultimate goal of a preimplantation genetic testing and human leukocyte antigen (PGT-HLA) matching programme is the birth of a healthy, HLA-compatible child for the treatment or cure of a sick sibling. Several authors have published successful cases of the births of children HLA-matched to siblings affected by different conditions and diseases. However, there are many reports of failed attempts. Couples seeking an HLA-matched sibling for their affected child look for positive outcomes in the shortest possible time. Nevertheless, there is no published consensus or guidelines with recommendations for these cases. Here, the authors aimed to analyse different approaches for these programmes, highlighting the most promising strategies for the families and fertility units. Furthermore, the authors mention a successful case of a PGT-HLA matching programme after a previous failed attempt following the strategies proposed. Which is the most cost-effective and time-efficient approach in a PGT-HLA matching programme?
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Diagnóstico Pré-Implantação , Irmãos , Gravidez , Feminino , Criança , Humanos , Fertilização in vitro , Testes Genéticos , Antígenos HLA/genética , Aneuploidia , BlastocistoRESUMO
Our objective was to investigate whether short-chain fatty acids (SCFAs), specifically acetate and butyrate, could prevent vascular dysfunction and elevated blood pressure (BP) in mice with systemic lupus erythematosus (SLE) induced by TLR7 activation using imiquimod (IMQ). Treatment with both SCFAs and dietary fibers rich in resistant starch (RS) or inulin-type fructans (ITF) effectively prevented the development of hypertension and cardiac hypertrophy. Additionally, these treatments improved aortic relaxation induced by acetylcholine and mitigated vascular oxidative stress. Acetate and butyrate treatments also contributed to the maintenance of colonic integrity, reduced endotoxemia, and decreased the proportion of helper T (Th)17 cells in mesenteric lymph nodes (MLNs), blood, and aorta in TLR7-induced SLE mice. The observed changes in MLNs were correlated with increased levels of GPR43 mRNA in mice treated with acetate and increased GPR41 levels along with decreased histone deacetylase (HDAC)- 3 levels in mice treated with butyrate. Notably, the effects attributed to acetate, but not butyrate, were nullified when co-administered with the GPR43 antagonist GLPG-0974. T cell priming and differentiation into Th17 cells in MLNs, as well as increased Th17 cell infiltration, were linked to aortic endothelial dysfunction and hypertension subsequent to the transfer of faecal microbiota from IMQ-treated mice to germ-free (GF) mice. These effects were counteracted in GF mice through treatment with either acetate or butyrate. To conclude, these findings underscore the potential of SCFA consumption in averting hypertension by restoring balance to the interplay between the gut, immune system, and vascular wall in SLE induced by TLR7 activation.
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Microbioma Gastrointestinal , Hipertensão , Lúpus Eritematoso Sistêmico , Microbiota , Animais , Camundongos , Acetatos , Butiratos , Ácidos Graxos Voláteis , Microbioma Gastrointestinal/fisiologia , Hipertensão/prevenção & controle , Receptor 7 Toll-LikeRESUMO
We report herein the synthesis and characterization of two unprecedented isomorphous spin-crossover two-dimensional coordination polymers of the Hofmann-type formulated {FeII(Hdpyan)2(µ2-[MII(CN)4])2}, with MII = Pd, Pt and Hdpyan is the in situ partially protonated form of 2,5-(dipyridin-4-yl)aniline (dpyan). The FeII is axially coordinated by the pyridine ring attached to the 2-position of the aniline ring, while it is equatorially surrounded by four [MII(CN)4]2- planar groups acting as trans µ2-bidentate ligands defining layers, which stack parallel to each other. The other pyridine group of Hdpyan, being protonated, remains peripheral but involved in a strong [MII-C≡N···Hpy+] hydrogen bond between alternate layers. This provokes a nearly 90° rotation of the plane defined by the [MII(CN)4]2- groups, with respect to the average plane defined by the layers, forcing the observed uncommon bridging mode and the accumulation of negative charge around each FeII, which is compensated by the axial [Hdpyan]+ ligands. According to the magnetic and calorimetric data, both compounds undergo a strong cooperative spin transition featuring a 10-12 K wide hysteresis loop centered at 220 (Pt) and 211 K (Pd) accompanied by large entropy variations, 97.4 (Pt) and 102.9 (Pd) J/K mol. The breaking symmetry involving almost 90° rotation of one of the two coordinated pyridines together with the large unit-cell volume change per FeII (ca. 50 Å3), and subsequent release of significantly short interlayer contacts upon the low-spin â high-spin event, accounts for the strong cooperativity.
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A model system of identical particles interacting via a hard-sphere potential is essential in condensed matter physics; it helps to understand in and out of equilibrium phenomena in complex fluids, such as colloidal dispersions. Yet, most of the fixed time-step algorithms to study the transport properties of those systems have drawbacks due to the mathematical nature of the interparticle potential. Because of this, mapping a hard-sphere potential onto a soft potential has been recently proposed [Báez et al., J. Chem. Phys. 149, 164907 (2018)]. More specifically, using the second virial coefficient criterion, one can set a route to estimate the parameters of the soft potential that accurately reproduces the thermodynamic properties of a monocomponent hard-sphere system. However, real colloidal dispersions are multicomponent or polydisperse, making it important to find an efficient way to extend the potential model for dealing with such kind of many-body systems. In this paper, we report on the extension and applicability of the second virial coefficient criterion to build a description that correctly captures the phenomenology of both multicomponent and polydisperse hard-sphere dispersions. To assess the accuracy of the continuous potentials, we compare the structure of soft polydisperse systems with their hard-core counterpart. We also contrast the structural and thermodynamic properties of soft binary mixtures with those obtained through mean-field approximations and the Ornstein-Zernike equation for the two-component hard-sphere dispersion.
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INTRODUCTION: In nursing homes, where residents are at elevated risk for malnutrition, the specific additive effect of the coronavirus disease 2019 (COVID-19) on weight loss has not yet been adequately evaluated. This study aimed to determine the factors independently associated with weight loss in nursing home residents who survived the first wave of the COVID-19 pandemic, whether they have contracted COVID-19 or not. METHODS: This research was a retrospective study conducted in three nursing homes. Residents who survived the first French COVID-19 lockdown (March to May 2020) were included, provided their weight records were available. Baseline data included the body mass index (BMI), capacity to self-feed, need for texture-modified food, disability, and legal guardianship status. The diagnosis of COVID-19 was based on the results of a positive reverse transcriptase-polymerase chain reaction test. Univariate and multivariate logistic regression analyses were used to investigate associations between resident characteristics, COVID-19 status, and at least 5% weight loss. RESULTS: Of the 316 included residents (72% female, mean age of 88 years, 48% severely disabled, and 38% under legal guardianship), 111 (35%) contracted COVID-19 and 102 (32%) lost at least 5% of their body weight. No difference was observed between the baseline characteristics of residents subsequently affected or unaffected by COVID-19. In the univariate analysis, old age, severe disability, texture-modified food, the need for close mealtime supervision, and COVID-19 were significantly associated with at least 5% weight loss. In the multivariate logistic regression analysis, COVID-19 (p = 0.02) and the need for close mealtime supervision (p = 0.02) were associated with weight loss in a model that also included age, BMI, texture-modified food, disability, and nursing home. CONCLUSION: For nursing home residents, COVID-19 was an independent risk factor for weight loss. Weight loss was most common in residents needing close mealtime supervision, suggesting that organizational issues may have affected the quality of the nutritional care provided during the lockdown.
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COVID-19 , Pandemias , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Casas de Saúde , Redução de Peso , Fatores de RiscoRESUMO
Background: Glycated hemoglobin measurements are a valuable tool for long-term blood glucose monitoring and the diagnosis of diabetes. Its widespread use has been made possible due to the development of new analytical methods with improved performances and standardization with reference materials. The aim of the present study was to evaluate the Trinity Biotech Premier Hb9210 analyzer for the measurement of HbA1c.Methods: The precision was assessed using the CLSI EP-15A3 and EP-10A3 protocols. The latter was also used to investigate linearity, carryover, and linear drift. The comparison study was performed between Premier Hb910 and Tosoh HLC-723 G8 through Passing-Bablok regression and the Bland-Altman plot. The Fleiss Kappa index was used to assess the degree of agreement. The interference of Hb variants was investigated using samples with Hb variants S, C, D, E, J, and Seville.Results: Within-run and between-run imprecision fell between 0.37% and 1.16%. No statistically significant nonlinearity, carry-over, and/or drift were observed. The resulting regression line of the Passing-Bablok analysis was y = 0.00 + 1.00x. The Pearson correlation coefficient was 0.997. In the Bland-Altman plot, the relative bias was 0.01%. The overall Fleiss Kappa index was 0.9. No interference from hemoglobin variants was observed.Conclusion: The Premier Hb9210 demonstrated a high degree of automation, reproducibility, good agreement, minimal carry-over effect, and excellent linearity across the wide range of HbA1c levels commonly found in diabetic patients and was not influenced by Hb variants.
Premier Hb9210 can be used as an alternative to monitor glycemic status.Premier Hb9210 is not affected by common hemoglobin variants.Premier Hb9210 can correctly classify diabetic patients.
Assuntos
Automonitorização da Glicemia , Diabetes Mellitus , Humanos , Hemoglobinas Glicadas , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão/métodos , GlicemiaRESUMO
BACKGROUND: In older adults, physical activity (PA) is important in maintaining physical performance. Data on the effectiveness of public open-access community-based programs on physical performance and fall prevention are scarce. METHODS: Prospective observational controlled study in community centers providing an open-access public prevention program. Retirees aged ≥60 years who chose to participate in weekly PA workshops for 3 months were compared to those who chose the cognitive stimulation (CS) workshops. Collected data: handgrip strength, five times sit-to-stand, single-leg stance, Timed Up and Go tests, gait speed, short physical performance battery (SPPB) and frailty status at baseline (M0) and at 3 months (M3). The proportion of participants reporting a history of falls was assessed at baseline and using follow-up telephone interviews (F-Up). RESULTS: Two hundred eighty-eight participants (age 73.8 years, 87% women) were included. The sit-to-stand test, single-leg stance and SPPB scores improved significantly between M0 and M3 in both groups. A greater SPPB increase was observed in the PA than in the CS group (+0.39 vs. +0.32 points, P = 0.02) after adjustment for age, sex, number of sessions attended, fall history and SPPB at baseline. During F-Up (median 22 months), the proportion of participants reporting at least one fall decreased from 55% to 31% (P = 0.01) in the PA group and from 27% to 19% (P = 0.12) in the CS group. CONCLUSION: In a public open-access community-based program participants improved physical performance and reduced fall incidence when participating in the PA or the CS workshops. Older adults may benefit most from multifaceted prevention programs.