Cellular senescence in brain aging and neurodegeneration.

Cellular senescence is a state of terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory phenotype. In the brain, senescent cells naturally accumulate during aging and at sites of age-related pathologies. Here, we discuss the recent advances in understanding the accumulation of senescent cells in brain aging and disorders. Here we highlight the phenotypical heterogeneity of different senescent brain cell types, highlighting the potential importance of subtype-specific features for physiology and pathology. We provide a comprehensive overview of various senescent cell types in naturally occurring aging and the most common neurodegenerative disorders. Finally, we critically discuss the potential of adapting senotherapeutics to improve brain health and reduce pathological progression, addressing limitations and future directions for application and development.

Drosophila nasuta (Diptera, Drosophilidae) in Brazil: a decade of invasion and occupation of more than half of the country.

As a result of human activities and natural dispersal, exotic species can be brought to new areas, where they become established and spread, becoming invaders. These species are responsible for the loss of biodiversity and cause ecosystemic harm throughout the world. In this paper, we report the rapid, broad geographic expansion of the invasive fly Drosophila nasuta in Brazil. An 84% increase was found in its area of occupation in the country compared to previous studies. The present data reveal its arrival to the Pantanal wetlands in a location more than one thousand kilometers from the closest previous record in the Cerrado biome. We present the first record of D. nasuta in the Atlantic Forest in the states of Paraíba and Bahia. We report its introduction in the Amazon Forest in the state of Amazonas approximately 700 kilometers from previous records. The relative abundance of D. nasuta in this biome increased fivefold in comparison to a previous study. In the first decade of invasion in Brazil, D. nasuta has already colonized more than half of the country. The present data reveal its invasive potential and underscore the importance of following up the possible negative effects of this biological invasion.

Circulating monocytes expressing senescence-associated features are enriched in COVID-19 patients with severe disease.

Accurate biomarkers for predicting COVID-19 severity have remained an unmet need due to an incomplete understanding of virus pathogenesis and heterogeneity among patients. Cellular senescence and its pro-inflammatory phenotype are suggested to be a consequence of SARS-CoV-2 infection and potentially drive infection-dependent pathological sequelae. Senescence-associated markers in infected individuals have been identified primarily in the lower respiratory tract, while little is known about their presence in more easily accessible bio-specimens. Here, we measured the abundance of senescence-associated signatures in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and patients without an infection. Bulk transcriptomic and targeted proteomic assays revealed that the level of senescence-associated markers, including the senescence-associated secretory phenotype (SASP), is predictive of SARS-CoV-2 infection. Single-cell RNA-sequencing data demonstrated that a senescence signature is particularly enriched in monocytes of COVID-19 patients, partially correlating with disease severity. Our findings suggest that monocytes are prematurely induced to senescence by SARS-CoV-2 infection, might contribute to exacerbating a SASP-like inflammatory response and can serve as markers and predictors for COVID-19 and its sequelae.

Contextual and individual determinants of tooth loss in the Afro-descendant older adult populations of different countries: a scoping review.

BACKGROUND: The Black population has poorer oral health than other racial groups; however, little is known about the mechanisms that explain this difference. OBJECTIVE: To study the association between race and tooth loss and map the evidence on factors associated with tooth loss in Black older populations. METHODS: Scoping review following the PRISMA Extension for Scoping Reviews conducted according to the recommendations of the Joanna Briggs Institute. A three-step search strategy was applied, and data were collected between April and July 2021. Searches were performed in the PubMed, Lilacs, and SciELO databases. The grey literature was searched using Google Scholar (https://www.scholar.google.com/). The reference lists of included studies were used as additional sources. Studies published in English and Portuguese of the association between tooth loss and different racial groups and the factors associated with tooth loss and tooth retention in Black older adult populations were included. RESULTS: Twenty-one of 913 original articles published between 1995 and 2020 were included. Of these, 75% were research articles, 15% were reports, and 10% dissertations. Eighty per cent reported cross-sectional and 20% longitudinal data. African ancestry was associated with increased odds of tooth loss in older adult populations. Periodontal disease, female sex, and advanced age were the exposures most frequently associated with tooth loss. CONCLUSION: Race, educational level, advanced age, and oral diseases such as periodontitis are associated with increased tooth loss in Afro-descendant older populations.

[First- and second-line hospital management of ophthalmologic emergencies: Clinical pathway study of 1360 patients]. / Prise en charge des urgences ophtalmologiques en premier et second recours hospitaliers : analyse du parcours de 1360 patients.

The general practitioner (GP) might offer a good alternative for the management of certain ophthalmologic emergencies in his or her practice, given the increasing demand for ophthalmological care and difficulties with access to ophthalmologists. The main objective of the study was to describe ophthalmological complaints and their management in general emergency departments compared to ophthalmological emergency departments in order to assess which pathologies can be treated by the GP. This was a single-center retrospective study at the University Hospital of Reims, based on consultation data from the general and ophthalmological emergency departments for all adult patients presenting for an ophthalmological problem in September 2019 and September 2020. Consultations where patients were brought back following a first emergency consultation and consultations for another non-ophthalmological reason were excluded. Out of 1360 consultations recorded, 16% of patients had initially consulted their GP. The 4 most frequent diagnoses were: "ocular trauma," "conjunctivitis," "eye pain" and "visual impairment." A prescription for medication was issued in 77% of cases, 37% of which were for antibiotics. Only 29% of consultations carried out in general emergency departments led to a request for a complementary ophthalmology consultation. The GP might therefore be able to manage certain ophthalmological emergencies in his or her practice as a first line and refer certain ophthalmologic emergencies. However, the training of GPs in this specialty must be reinforced in collaboration with ophthalmologists.

Lactobacillus delbrueckii UFV-H2b20 increases IFN-γ production and CD39+CD73+ Treg cell numbers in lungs, and protects mice against experimental allergic asthma.

Asthma is a disorder characterized by airflow obstruction, inflammation, declining airway function, bronchial hyperresponsiveness and tissue remodelling. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host". The use of probiotics is becoming increasingly studied and recent evidence has suggested that it may provide therapeutic benefits in asthma and other diseases. Lactobacillus delbrueckii UFV-H2b20 fulfils all the requirements to be classified as probiotic. Previous studies have already shown the ability of L. delbrueckii UFV-H2b20 to stimulate the immune system. Our objective was to evaluate the protective effects of L. delbrueckii UFV-H2b20 in experimental allergic asthma. We used a murine model of ovalbumin-induced allergic airway inflammation to mimic allergic asthma. Oral treatment with L. delbrueckii UFV-H2b20 improves respiratory parameters and inhibits the inflammatory response in the lungs by decreasing the numbers of inflammatory monocytes, eosinophils and alveolar macrophages, as well as IgE levels. Treatment increased the IFN-γ/IL-4 cytokine ratio. Levels of IL-10 in the lungs were also increased in treated animals. Our results also showed that the probiotic administration increases the number of CD39+CD73+ T regulatory lymphocytes in the lung, suggesting a role for purinergic signals in the regulation of inflammation promoted by the treatment. Understanding the mechanisms of modulation of the immune system by probiotics could allow the development of probiotic preparations that are safe and have a direct action. Our results suggest that oral administration of L. delbrueckii UFV-H2b20 could be helpful to treat chronic inflammatory airway diseases, such as asthma.

Third-degree atrioventricular block secondary to infiltrative cardiac hemangiosarcoma in a dog.

A nine-year-old male, castrated Pembroke Welsh Corgi presented with a two-month history of lethargy, hyporexia, and occasional vomiting. There was also a two-week history of exercise intolerance; no syncopal episodes were reported. Auscultation revealed bradycardia with an irregular rhythm and otherwise normal heart and lung sounds. Third-degree atrioventricular block was diagnosed. Two-dimensional transthoracic echocardiography revealed a soft tissue structure arising from the atrioventricular junction and interatrial septum. There was scant abdominal effusion. Pacemaker implantation was offered, but the owner elected humane euthanasia due to the unknown prognosis. Necropsy was consistent with cardiac hemangiosarcoma infiltrating the interatrial and interventricular septum.

Arrhythmogenic right ventricular cardiomyopathy in dogs.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease seen in dogs, cats, and humans. A common entity in Boxers and the related English bulldog, the disease is characterized by fatty or fibrofatty replacement of the myocardium, ventricular arrhythmias, and the potential for syncope or sudden death. In some individuals, concomitant left ventricular involvement results in systolic dysfunction and a progression to congestive heart failure. The clinical and pathological characteristics of ARVC share many similarities in dogs and humans, and Boxers serve as an important spontaneous model of the disease. Although multiple mechanisms have been implicated in the pathogenesis of ARVC, the disease is ultimately considered to be a disorder of the desmosome. Multiple causal genetic mutations have been identified in people, and over 50% of affected humans have an identifiable mutation in desmosomal proteins. To date, only a single genetic mutation has been associated with ARVC in Boxer dogs. Other as-yet-undiscovered genetic mutations and epigenetic modifiers of the disease are likely. Treatment of ARVC in dogs is focused on controlling ventricular arrhythmias and associated clinical signs. This article will review the pathophysiology, clinical diagnosis, treatment, and prognosis of ARVC in the dog.

Genotoxic and mutagenic effects of methyl ether dillapiole on the development of Aedes aegypti (Diptera: Culicidae).

Dillapiole, extracted from Piper aduncum essential oil and its derivatives, has been shown to be a potential alternative to the control of Aedes aegypti, which has become resistant to synthetic insecticides. Methyl ether dillapiole (MED) and temephos (TM) were compared to complement the data on the genotoxicity and developmental changes of Ae. aegypti. Over four generations (G1 -G4 ), third stage larvae were treated with MED at 60, 80 and 100 µg/mL and TM at 0.002, 0.005 and 0.007 µg/mL for 4 h. Adult females were separated to estimate oviposition and hatching rates, and total egg length. Over the four generations, a significant reduction was recorded in oviposition and hatching rates, and in mean egg length (Tukey, P < 0.05), compared with the negative control (NC). Cytological slide preparations were done from adult oocytes and larval neuroblasts. The cumulative effects of genotoxic (bridges, budding and nuclear fragmentation) and mutagenic (micronucleus and chromosomal breakage) damage was observed in the neuroblasts and oocytes of exposed mosquitoes. Developmental changes and damage to the genome of MED-treated Ae. aegypti were greater than those caused by TM. Further studies should focus on understanding the effects of the MED molecule on Ae. aegypti.

Occurrence of multidrug-resistant Enterococcus faecium isolated from environmental samples.

Enterococcus species are present in the microbiota of humans and animals and have also been described in the environment. Among the species, Enterococcus faecium is one of the main pathogens associated with nosocomial infections worldwide. Enterococcus faecium isolates resistant to different classes of antimicrobials have been increasingly reported, including multidrug-resistant (MDR) isolates in environmental sources, which is worrying. Therefore, this study aimed to characterize E. faecium isolates obtained from soil and water samples regarding antimicrobial resistance and virulence determinants. A total 40 E. faecium isolates were recovered from 171 environmental samples. All isolates were classified as MDR, highlighting the resistance to the fluoroquinolones class, linezolid and vancomycin. Furthermore, high-level aminoglycoside resistance and high-level ciprofloxacin resistance were detected in some isolates. Several clinically relevant antimicrobial resistance genes were found, including vanC1, ermB, ermC, mefAE, tetM, tetL, ant(6')-Ia, ant(4')-Ia, aph(3')-IIIa and aac(6')-Ie-aph(2″)-Ia. Three virulence genes were detected among the MDR E. faecium isolates, such as esp, gelE and ace. The results of this study contribute to a better understanding of MDR E. faecium isolates carrying antimicrobial resistance and virulence genes in environmental sources and report for the first time in the world the presence of vanC1-producing E. faecium isolated from soil.

Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest.

The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2 min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC = 1·33, 1·4 and 5·2 µg ml-1 , respectively) and Cryptococcus gattii strains (MIC = 5·3, 2·8 and 9·2 µg ml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.

Chemical and physical properties of nanocrystalline chitosan by the method: Modified nanochitosan complex and process of obtaining modified nanochitosan.

Nanocrystalline chitosan (NCC) is a modified form of chitosan, prepared from the method for obtaining chitosan acetate (CA). Due to the greater crystallinity of chitosan nanoparticles in relation to CA, NCC is more thermally stable and thus has great potential in the development of a new generation of biomaterials potentially useful in regenerative medicine and tissue engineering. NCC is also characterized by having similar properties to its precursor chitosan, such as its biocompatibility, bioactivity, ability to be bioabsorbed and lack of toxicity. One of the major problems associated with obtaining NCC is the low productivity of the methods. While known methods of obtaining nanostructures produce small amounts (milligrams), the method of synthesis for creating NCC from its salt is often more productive and less costly, and is patented by the authors of this work (registration number: BR10201702272). Thus, the objective of this study was to characterize NCC obtained through this innovative method, and analyze its chemical and physical properties using Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC) and mechanical property analysis with the mean values for the elasticity module, the resistance to tensile strength and the tensile strength. The results indicate that this new process of obtaining the NCC did not modify the chemical structure of the chitosan. The structure of the film surface created was homogeneous and the mechanical properties emphasized the plastifying effect of glycerol under NCC. The thermogravimetric analysis of NCC indicated greater stability in the polysaccharide structure of the nanocrystalline, due to an increased crystalline region compared to the CA which was confirmed by DSC.

Chronic aerobic exercise associated to low-dose L-NAME improves contractility without changing calcium handling in rat cardiomyocytes.

Nitric oxide (NO) inhibition by high-dose NG-nitro-L-arginine methyl ester (L-NAME) is associated with several detrimental effects on the cardiovascular system. However, low-dose L-NAME increases NO synthesis, which in turn induces physiological cardiovascular benefits, probably by activating a protective negative feedback mechanism. Aerobic exercise, likewise, improves several cardiovascular functions in healthy hearts, but its effects are not known when chronically associated with low-dose L-NAME. Thus, we tested whether the association between low-dose L-NAME administration and chronic aerobic exercise promotes beneficial effects to the cardiovascular system, evaluating the cardiac remodeling process. Male Wistar rats were randomly assigned to control (C), L-NAME (L), chronic aerobic exercise (Ex), and chronic aerobic exercise associated to L-NAME (ExL). Aerobic training was performed with progressive intensity for 12 weeks; L-NAME (1.5 mg·kg-1·day-1) was administered by orogastric gavage. Low-dose L-NAME alone did not change systolic blood pressure (SBP), but ExL significantly increased SBP at week 8 with normalization after 12 weeks. Furthermore, ExL promoted the elevation of left ventricle (LV) end-diastolic pressure without the presence of cardiac hypertrophy and fibrosis. Time to 50% shortening and relaxation were reduced in ExL, suggesting a cardiomyocyte contractile improvement. In addition, the time to 50% Ca2+ peak was increased without alterations in Ca2+ amplitude and time to 50% Ca2+ decay. In conclusion, the association of chronic aerobic exercise and low-dose L-NAME prevented cardiac pathological remodeling and induced cardiomyocyte contractile function improvement; however, it did not alter myocyte affinity and sensitivity to intracellular Ca2+ handling.

Chronic aerobic exercise associated to low-dose L-NAME improves contractility without changing calcium handling in rat cardiomyocytes

Nitric oxide (NO) inhibition by high-dose NG-nitro-L-arginine methyl ester (L-NAME) is associated with several detrimental effects on the cardiovascular system. However, low-dose L-NAME increases NO synthesis, which in turn induces physiological cardiovascular benefits, probably by activating a protective negative feedback mechanism. Aerobic exercise, likewise, improves several cardiovascular functions in healthy hearts, but its effects are not known when chronically associated with low-dose L-NAME. Thus, we tested whether the association between low-dose L-NAME administration and chronic aerobic exercise promotes beneficial effects to the cardiovascular system, evaluating the cardiac remodeling process. Male Wistar rats were randomly assigned to control (C), L-NAME (L), chronic aerobic exercise (Ex), and chronic aerobic exercise associated to L-NAME (ExL). Aerobic training was performed with progressive intensity for 12 weeks; L-NAME (1.5 mg·kg-1·day-1) was administered by orogastric gavage. Low-dose L-NAME alone did not change systolic blood pressure (SBP), but ExL significantly increased SBP at week 8 with normalization after 12 weeks. Furthermore, ExL promoted the elevation of left ventricle (LV) end-diastolic pressure without the presence of cardiac hypertrophy and fibrosis. Time to 50% shortening and relaxation were reduced in ExL, suggesting a cardiomyocyte contractile improvement. In addition, the time to 50% Ca2+ peak was increased without alterations in Ca2+ amplitude and time to 50% Ca2+ decay. In conclusion, the association of chronic aerobic exercise and low-dose L-NAME prevented cardiac pathological remodeling and induced cardiomyocyte contractile function improvement; however, it did not alter myocyte affinity and sensitivity to intracellular Ca2+ handling.

Diarrhoeagenic Escherichia coli and Escherichia albertii in Brazil: pathotypes and serotypes over a 6-year period of surveillance.

Diarrhoeagenic Escherichia coli (DEC) is a leading cause of infectious diarrhoea worldwide. In recent years, Escherichia albertii has also been implicated as a cause of human enteric diseases. This study describes the occurrence of E. coli pathotypes and serotypes associated with enteric illness and haemolytic uremic syndrome (HUS) isolated in Brazil from 2011 to 2016. Pathotypes isolated included enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and Shiga toxin-producing E. coli (STEC). PCR of stool enrichments for DEC pathotypes was employed, and E. albertii was also sought. O:H serotyping was performed on all DEC isolates. A total of 683 DEC and 10 E. albertii strains were isolated from 5047 clinical samples. The frequencies of DEC pathotypes were 52.6% (359/683) for EPEC, 32.5% for EAEC, 6.3% for ETEC, 4.4% for EIEC and 4.2% for STEC. DEC strains occurred in patients from 3 months to 96 years old, but EPEC, EAEC and STEC were most prevalent among children. Both typical and atypical isolates of EPEC and EAEC were recovered and presented great serotype heterogeneity. HUS cases were only associated with STEC serotype O157:H7. Two E. albertii isolates belonged to serogroup O113 and one had the stx2f gene. The higher prevalence of atypical EPEC in relation to EAEC in community-acquired diarrhoea in Brazil suggests a shift in the trend of DEC pathotypes circulation as previously EAEC predominated. This is the first report of E. albertii isolation from active surveillance. These results highlight the need of continuing DEC and E. albertii surveillance, as a mean to detect changes in the pattern of pathotypes and serotypes circulation and provide useful information for intervention and control strategies.

Correlations between resistance training-induced changes on phase angle and biochemical markers in older women.

The main purpose of this study was to investigate the effects of 12 weeks of resistance training (RT) on phase angle (PhA), inflammatory and oxidative stress biomarkers, and to evaluate whether these RT-induced adaptations are related to PhA changes. Fifty-one older women (70.6 ± 5.1 years; 26.9 ± 4.2 kg/m2 ) were randomly allocated into a training group (TG) that performed 12-week RT or a nonexercising control group (CG). The PhA (Xitron), body composition (DXA), and blood sample measurements (after a 12 hours fast) were performed before and after the intervention. The TG showed a significant (P < .05) increase in PhA (TG: +7.4±5.9% vs CG: -3.6 ± 8.8%), and interleukin-10 (IL-10; TG: +51.8 ± 71.1% vs CG: -46.6 ± 38.0%), and a decrease in tumor necrosis factor alpha (TNF-α; TG: -15.2 ± 11.1% vs CG: +6.9±17.7%), interleukin-6 (IL-6; TG: -17.9 ± 17.8% vs CG: +6.1 ± 24.8%), and C-reactive protein (CRP; TG: -24.1 ± 19.9% vs CG: +43.8 ± 31.1%). Moreover, TG upregulated catalase (TG: +11.4 ± 15.0% vs CG: -6.7 ± 10.2%). Changes in TNF-α (r = -.71), CRP (r = -.65), lower advanced oxidation protein products (r = -.55), and catalase (r = +.73) after RT were correlated with changes in PhA (P < .05). These results suggest that RT improves PhA, inflammatory and oxidative stress biomarkers, and the changes in inflammatory and oxidative damage markers are correlated with changes in PhA.

Prevalence of Rhodococcus equi from the nasal cavity of 1010 apparently healthy horses.

BACKGROUND: Rhodococcus equi is an important cause of foal pneumonia. While its isolation from different sources has been widely evaluated, there is a need to better understand the R. equi epidemiology from samples of the nasal cavity of healthy horses. OBJECTIVES: To determine the prevalence of R. equi from the nasal cavity of healthy horses, along with its virulence profile, antimicrobial susceptibility and environmental variables associated. STUDY DESIGN: Cross-sectional study. METHODS: Swabs from the nasal cavity of 1010 apparently healthy horses from 341 farms were submitted for bacteriological analyses. The identity and virulence profile of the R. equi isolates were assessed by multiplex PCR; antimicrobial susceptibility was determined by the disk-diffusion method. The occurrence of R. equi was calculated at the level of both animal and farm. The association of seven specific environmental factors with R. equi isolation was assessed using logistic regression and by a spatial scan statistical method to determine the presence of local clusters. RESULTS: Antimicrobial-sensitive R. equi was isolated from 10 (1%) of 1010 horses ranging between 3 and 29 years old. Ten farms (3%) had at least one positive horse. Only one R. equi isolate (10%) was classified as virulent. Red-Yellow Argisol (PVA/PV) soils were significantly associated with R. equi isolation (odds ratio (OR) 8.02; CI95% , 1.98-32.50, P = 0.01), and areas with well-drained soil were less likely to be test positive (OR 0.85; CI95% , 0.76-0.96, P = 0.03). MAIN LIMITATIONS: The use of culture-based method instead of PCR-based assay and the lack of soil sampling. CONCLUSIONS: Antimicrobial-sensitive R. equi may be considered a minor part of the normal bacterial flora in the nasal cavity of healthy and immunologically functional horses breeding on pasture. Further studies are warranted to determine if soils rich in iron and well-drained are, in fact, associated with the occurrence of R. equi.