Vascular units as advanced living materials for bottom-up engineering of perfusable 3D microvascular networks.

The timely establishment of functional neo-vasculature is pivotal for successful tissue development and regeneration, remaining a central challenge in tissue engineering. In this study, we present a novel (micro)vascularization strategy that explores the use of specialized "vascular units" (VUs) as building blocks to initiate blood vessel formation and create perfusable, stroma-embedded 3D microvascular networks from the bottom-up. We demonstrate that VUs composed of endothelial progenitor cells and organ-specific fibroblasts exhibit high angiogenic potential when embedded in fibrin hydrogels. This leads to the formation of VUs-derived capillaries, which fuse with adjacent capillaries to form stable microvascular beds within a supportive, extracellular matrix-rich fibroblastic microenvironment. Using a custom-designed biomimetic fibrin-based vessel-on-chip (VoC), we show that VUs-derived capillaries can inosculate with endothelialized microfluidic channels in the VoC and become perfused. Moreover, VUs can establish capillary bridges between channels, extending the microvascular network throughout the entire device. When VUs and intestinal organoids (IOs) are combined within the VoC, the VUs-derived capillaries and the intestinal fibroblasts progressively reach and envelop the IOs. This promotes the formation of a supportive vascularized stroma around multiple IOs in a single device. These findings underscore the remarkable potential of VUs as building blocks for engineering microvascular networks, with versatile applications spanning from regenerative medicine to advanced in vitro models.

Copaiba oil and Neem extract can be a potential alternative for the behavioral control of Sitophilus zeamais

Abstract Insects' ethology is an important factor when it is desired to carry out pest management. This knowledge makes it possible to manipulate behavioral activities, repel, or attract insects according to needs and interests. The maize weevil Sitophilus zeamais (Mots., 1855) (Coleoptera: Curculionidae), one of the main stored grain pests, has been the target of studies of behavioral changes studies through natural substances due to its resistance to different insecticidal classes. Thus, this study aimed to evaluate the effect of sublethal concentrations of neem extract and copaiba oil on the locomotor behavior of S. zeamais. The behavioral characteristic considered were walking activity, the frequency of contact of insects with the treated grain mass, and the time spent for this behavior. The walking activity of the S. zeamais increased with exposure to Neem extract and Copaiba oil. In general, the Neem extract and Copaiba oil-induced more contact with grain mass than the control, suggesting an attractive effect on the insect, however more significant for the Neem oil. The insect's behavior was altered, presenting a specific path due to Copaiba oil and Neem extract stimuli. These results indicate that Copaiba oil and Neem extract can be a potential alternative for controlling S. zeamais on stored products since changes in this pests' behavior can reduce qualitative and quantitative grain damage. Thus, the development of products based on Copaiba oil and Neem extract may be helpful for storage pest management.

Resumo A etologia dos insetos é um fator importante quando se deseja relizar manejo de pragas. Através deste conhecimento, é possível manipular atividades comportamentais, repelir, ou atrair os insetos de acordo com as necessidades e interesses. O gorgulho do milho Sitophilus zeamais (Mots., 1855) (Coleoptera: Curculionidae), uma das principais pragas de grãos armazenados tem sido alvo de estudos de alterações comportamentais através de substâncias naturais devido à sua resistência a diferentes classes de insecticidas. Assim, este estudo teve como objetivo avaliar o efeito de concentrações subletais de extrato de neem e do óleo de copaíba sobre o comportamento de movimentação de S. zeamais. As características comportamentais consideradas foram: a atividade de caminhamento, a frequência do contato dos insetos com a massa de grãos tratada, e o tempo gasto para realização destes comportamentos. A atividade de caminhamento do S. zeamais aumentou quando os insetos foram expostos ao extrato de Neem e ao óleo de copaíba. Em geral, o extrato de Neem e o óleo de Copaíba induziram mais contato com a massa de grãos do que o controle, sugerindo um efeito atrativo sobre o inseto, contudo este efeito foi mais significativo para o óleo de Neem. O comportamento do inseto foi alterado, apresentando um caminhamento específico devido aos estímulos do óleo de copaíba e do extrato de Neem. Estes resultados indicam que o óleo de copaíba e o extrato de Neem podem ser alternativas potenciais para o controle do S. zeamais em produtos armazenados, uma vez que alterações no comportamento desta praga podem reduzir os danos qualitativos e quantitativos nos grãos. Assim, o desenvolvimento de produtos baseados no óleo de copaíba e no extrato de Neem pode ser útil para o manejo de pragas de armazenamento.

Association study between ceftriaxone and a synthetic amide against strains of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a non-lactose fermenting Gram-negative bacteria responsible for causing numerous nosocomial infections. The present research aimed to analyze the anti-Pseudomonas aeruginosa potential of 2-Chloro-N-(4-fluoro-3-nitrophenyl)acetamide (A8). The antibacterial potential of A8 was evaluated from the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Association using the checkerboard method. MIC and MBC values were 512 µg/mL for all P. aeruginosa strains evaluated, demonstrating predominantly bactericidal activity. Furthermore, when A8 was associated with the drug ceftriaxone, pharmacological additivity and indifference were evidenced. In this sense, the synthetic amide was interesting, since it demonstrates the potential to become a possible candidate for an antimicrobial drug.

The effects of resistance exercise on cognitive function, amyloidogenesis, and neuroinflammation in Alzheimer's disease.

With the increasing prevalence of Alzheimer's disease (AD) and difficulties in finding effective treatments, it is essential to discover alternative therapies through new approaches. In this regard, non-pharmacological therapies, such as physical exercise, have been proposed and explored for the treatment of AD. Recent studies have suggested that resistance exercise (RE) is an effective strategy for promoting benefits in memory and cognitive function, producing neuroprotective and anti-inflammatory effects, and reducing amyloid load and plaques, thereby reducing the risk, and alleviating the neurodegeneration process of AD and other types of dementia in the elderly. In addition, RE is the exercise recommended by the World Health Organization for the elderly due to its benefits in improving muscle strength and balance, and increasing autonomy and functional capacity, favoring improvements in the quality of life of the elderly population, who is more likely to develop AD and other types of dementia. In this mini-review, we discuss the impact of RE on humans affected by MCI and AD, and animal models of AD, and summarize the main findings regarding the effects of RE program on memory and cognitive functions, neurotrophic factors, Aß deposition and plaque formation, as well as on neuroinflammation. Overall, the present review provides clinical and preclinical evidence that RE plays a role in alleviating AD symptoms and may help to understand the therapeutic potential of RE, thereby continuing the advances in AD therapies.

Mouse organoids as an in vitro tool to study the in vivo intestinal response to cytotoxicants.

Cross-species comparison of drug responses at the organoid level could help to determine the human relevance of findings from animal studies. To this end, we first need to evaluate the in vitro to in vivo translatability of preclinical organoids. Here, we used 5-fluorouracil (5-FU) as an exemplar drug to test whether the in vivo gut response to this cytotoxicant was preserved in murine intestinal organoids. Mice treated with 5-FU at 20 or 50 mg/kg IV (low and high dose, respectively) displayed diarrhea at clinically relevant exposures. 5-FU also induced intestinal lesions, increased epithelial apoptosis, and decreased proliferation in a dose-dependent manner. To enable comparison between the in vitro and in vivo response, top nominal in vitro drug concentrations that caused significant cytotoxicity were chosen (dose range 1-1000 µM). The inferred intracellular concentration in organoids at 1000 µM was within the tissue exposure range related to intestinal toxicity in vivo. 5-FU at ≥ 100 µM decreased ATP levels and increased Caspase-3 activity in intestinal organoids. In keeping with the in vivo findings, 5-FU increased the percentage of Caspase-3-positive cells and reduced Ki67 staining. At the transcriptome level, there was an overlap in the activity of pathways related to 5-FU's mode of action, lipid and cholesterol metabolism and integrin signaling across in vivo gut and organoids. The predicted activity state of upstream regulators was generally well preserved between setups. Collectively, our results suggest that despite their inherent limitations, organoids represent an adequate tool to explore the intestinal response to cytotoxicants.

Complex patterns on HEp-2 indirect immunofluorescence assay in a large sample referred for anti-cell autoantibodies detection.

Introduction: The combination of patterns is a frequent and challenging situation in the daily laboratory routine of autoantibodies testing using HEp-2 cells indirect immunofluorescence assay (HEp-2-IFA). Recently, the Brazilian Consensus on Autoantibodies (BCA) named these combinations as complex patterns (CPs) and organized them into 3 subtypes: multiple, mixed, and composite. This study aimed to describe the most frequent combinations of HEp-2-IIF patterns according to this new nomenclature. Methods: Routine HEp-2-IFA results reported in January and June 2017 were reviewed using the new BCA classification. Visual pattern recognition was performed by experts on HEp-2-IFA readings, using the International Consensus on Antinuclear Antibodies (ANA) Patterns (ICAP) and BCA recommendations. Results: 54,990 serum samples from different patients were tested for ANA-HEp-2, and 11,478 (20.9%) were positive at a titer ≥ 1/80. Among these positive samples, 1,111 (9.7%) displayed CPs, divided into 95 different combinations. A higher proportion of CPs was observed in the pediatric age group. Multiple, mixed, and composite patterns were present in 85.3, 5.4, and 9.5% of the samples, respectively. In the multiple/mixed pattern group (n=1,005), double, triple, and quadruple combinations (ICAP/BCA codes) were observed in 97.7%, 2.2%, and 0.1%, respectively. The double nuclear pattern was the most prevalent combination observed (67.6%). The most common CPs registered were AC-4 (nuclear fine speckled) + AC-6,7 (nuclear discrete dots) (n=264); AC-2 (nuclear dense fine speckled) + AC-6,7 (n=201); AC-4+AC-8,9,10 (nucleolar) (n=129); and AC-3 (centromere)+AC-4 (n=124). All of these combinations were in the multiple subgroup. Conclusion: Almost 10% of positive results in the HEp-2 procedure displayed CPs. Among the 3 subtypes of CPs proposed, the multiple pattern was the most prevalent, especially in the pediatric population. The AC-4, AC-2, and AC-6,7 were the most prevalent single patterns observed in the combinations described in this study. There was a significant association between age and the prevalence of most combined patterns. The AC-4+AC-6,7 combination was the most prevalent complex pattern detected regardless of the age group. The AC-2+AC-6,7 was more prevalent in younger individuals. The concepts involved in the CPs definition should add value to the reading and interpretation of the HEp-2-IIF assay.

Antibacterial activity improvement of dental glass-ceramic by incorporation of AgVO3 nanoparticles.

OBJECTIVE: This study aimed to investigate the role of the incorporation of an antibacterial nanoceramic (AgVO3) on the properties of a restorative dental glass-ceramic. METHOD: A commercially available restorative glass-ceramic, commonly designated as porcelain (IPS d.SIGN) was functionalized with an antibacterial agent (nanostructured ß-AgVO3), synthesized by a hydrothermal route. Both functionalized and pristine samples were processed according to the manufacturer's instructions. All samples were characterized by X-ray diffraction, Rietveld refinement, particle size distribution, Scanning Electron Microscopy, chemical solubility, and Inductively Coupled Plasma Spectroscopy. Their antibacterial potential (Mueller-Hinton test) was analyzed against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli). RESULTS: The commercial glass-ceramic showed leucite (KAlSi2O6) as the only detectable crystalline phase, and, for both strains, no antibacterial activity could be detected in the Mueller-Hinton agar plates test. A monophasic, needle-shaped, and nanometric ß-AgVO3 powder was successfully synthesized by a simple hydrothermal route. After thermal treatment, glass-ceramic samples containing different percentages of ß-AgVO3 showed a second crystalline phase of microline [K0.95(AlSi3O8)]. For modified samples, inhibition halos were easily visible on the Mueller-Hinton test, which ranged from 11.1 ± 0.5 mm to 16.6 ± 0.5 mm and 12.7 ± 0.3 mm to 15.5 ± 0.3 mm in the S. aureus and E.coli cultures, respectively, showing that the halos formed were dose-dependent. Also, increasing the percentage of ß-AgVO3 promoted a significant increase in chemical solubility, from 72 µg/cm2 (samples with 1 wt% of ß-AgVO3) to 136 µg/cm2 (samples with 2 wt% of ß-AgVO3), which was associated with the silver and vanadium ions released from the glass matrix. SIGNIFICANCE: Our in vitro results indicate that IPS d.SIGN, as most of the dental glass-ceramics, do not exhibit antibacterial activity per se. Nonetheless, in this concept test, we demonstrated that it is possible to modify dental veneering materials giving them antibacterial properties by adding at least 2 wt% of ß-AgVO3, a nanomaterial easily synthesized by a simple route.

Gestational weight gain and visceral adiposity in adult offspring: Is there a link with the fecal abundance of Acidaminococcus genus?

Intrauterine environment can influence the offspring's body adiposity whose distribution affect the cardiometabolic risk. Underlying mechanisms may involve the gut microbiome. We investigated associations of gestational weight gain with the adult offspring's gut microbiota, body adiposity and related parameters in participants of the Nutritionists' Health Study. METHODS: This cross-sectional analysis included 114 women who had early life and clinical data, body composition, and biological samples collected. The structure of fecal microbiota was analyzed targeting the V4 region of the 16 S rRNA gene. Beta diversity was calculated by PCoA and PERMANOVA used to test the impact of categorical variables into the diversity. Bacterial clusters were identified based on the Jensen-Shannon divergence matrix and Calinski-Harabasz index. Correlations were tested by Spearman coefficient. RESULTS: Median age was 28 (IQR 24-31) years and BMI 24.5 (IQR 21.4-28.0) kg/m2. Fifty-eight participants were assigned to a profile driven by Prevotella and 56 to another driven by Blautia. Visceral adipose tissue was correlated to abundance of Acidaminococcus genus considering the entire sample (r = 0.37; p < 0.001) and the profiles (Blautia: r = 0.35, p = 0.009, and Prevotella: r = 0.38, p = 0.006). In Blautia-driven profile, the same genus was also correlated to maternal gestational weight gain (r = 0.38, p = 0.006). CONCLUSIONS: Association of Acidaminococcus with gestational weight gain could reinforce the relevance with mothers' nutritional status for gut colonization at the beginning of life. Whether Acidaminococcus abundance could be a marker for central distribution of adiposity in young women requires further investigation.

Estudios mamográficos en un centro metropolitano de referencia en imágenes mamarias: Chile 2008-2018 ¿Vamos por el camino correcto? / Analysis of mammograms performed in a public imaging center in Santiago, Metropolitan Region Chile 2008-2018

BACKGROUND: Mammograms are one of the most effective preventive means for the early detection of breast cancer. OBJECTIVE: To describe the features of patients and results of mammograms performed at a public breast imaging service of the Santiago Metropolitan Area. MATERIAL AND METHODS: We reviewed the reports of mammograms performed on 174,017 women and 18 men, between 2008 and 2018 in an Imaging Center. The BI-RADS classification was used in the reports. RESULTS: Forty-six percent of mammograms (75,781) were reported as BI-RADS 2. The high proportion of BI-RADS 4 reports (674 reports) was seen in patients aged 40 to 49 years, corresponding to 30% of reports in this age range. Among patients aged 50 to 59 years, there were 779 BI-RADS 4 reports (35%). BI-RADS 5 reports were more common among patients aged 50 to 59 years (50 reports, 30%) and among patients aged 70 years or older (83 reports, 28%). CONCLUSIONS: The presence of a significant number of women between 40 and 49 years of age with a BI-RADS 4 mammography result stands out; being an opportunity to develop new clinical research and public health strategies within the framework of the Universal Health Care policy for breast cancer in Chile.

Racial disparity and prognosis in patients with mouth and oropharynx cancer in Brazil.

BACKGROUND: Oral and oropharyngeal cancer (OPC) is an important cause of morbidity and mortality worldwide. Populations in situations of social vulnerability tend to have higher incidences of cancer, a higher proportion of late diagnosis, greater difficulties in accessing health services, and, consequently, worse prognosis. The aim of this study was to evaluate the relationship between race/skin color and OPC prognosis in Brazil. MATERIAL AND METHODS: This is a cross-sectional epidemiological study using OPC data from the National Cancer Institute between the years 2000 and 2019. The selected variables were: gender, race/skin color, age, education, smoking and alcohol consumption, stage of the disease and disease status at the end of the 1st treatment. RESULTS: 154,214 cases were recorded. Black men, in the 6th decade of life, were the most affected population. Blacks had a lower level of education when compared to non-blacks (p<0.001). Blacks were more exposed to smoking and alcohol consumption (p<0.001). At the time of diagnosis, the black population was at the most advanced stage when compared to non-blacks (p<0.001). At the end of the 1st treatment, more black patients had disease in progression, as well as more black patients died (p<0.001). CONCLUSIONS: Blacks had a worse prognosis for OPC in Brazil. Despite the limitations, these results are important to elucidate the scenario of health disparities in relation to the race/skin color of the Brazilian population.

Copaiba oil and Neem extract can be a potential alternative for the behavioral control of Sitophilus zeamais.

Insects' ethology is an important factor when it is desired to carry out pest management. This knowledge makes it possible to manipulate behavioral activities, repel, or attract insects according to needs and interests. The maize weevil Sitophilus zeamais (Mots., 1855) (Coleoptera: Curculionidae), one of the main stored grain pests, has been the target of studies of behavioral changes studies through natural substances due to its resistance to different insecticidal classes. Thus, this study aimed to evaluate the effect of sublethal concentrations of neem extract and copaiba oil on the locomotor behavior of S. zeamais. The behavioral characteristic considered were walking activity, the frequency of contact of insects with the treated grain mass, and the time spent for this behavior. The walking activity of the S. zeamais increased with exposure to Neem extract and Copaiba oil. In general, the Neem extract and Copaiba oil-induced more contact with grain mass than the control, suggesting an attractive effect on the insect, however more significant for the Neem oil. The insect's behavior was altered, presenting a specific path due to Copaiba oil and Neem extract stimuli. These results indicate that Copaiba oil and Neem extract can be a potential alternative for controlling S. zeamais on stored products since changes in this pests' behavior can reduce qualitative and quantitative grain damage. Thus, the development of products based on Copaiba oil and Neem extract may be helpful for storage pest management.

[Analysis of mammograms performed in a public imaging center in Santiago, Metropolitan Region Chile 2008-2018]. / Estudios mamográficos en un centro metropolitano de referencia en imágenes mamarias: Chile 2008-2018 ¿Vamos por el camino correcto?

BACKGROUND: Mammograms are one of the most effective preventive means for the early detection of breast cancer. OBJECTIVE: To describe the features of patients and results of mammograms performed at a public breast imaging service of the Santiago Metropolitan Area. MATERIAL AND METHODS: We reviewed the reports of mammograms performed on 174,017 women and 18 men, between 2008 and 2018 in an Imaging Center. The BI-RADS classification was used in the reports. RESULTS: Forty-six percent of mammograms (75,781) were reported as BI-RADS 2. The high proportion of BI-RADS 4 reports (674 reports) was seen in patients aged 40 to 49 years, corresponding to 30% of reports in this age range. Among patients aged 50 to 59 years, there were 779 BI-RADS 4 reports (35%). BI-RADS 5 reports were more common among patients aged 50 to 59 years (50 reports, 30%) and among patients aged 70 years or older (83 reports, 28%). CONCLUSIONS: The presence of a significant number of women between 40 and 49 years of age with a BI-RADS 4 mammography result stands out; being an opportunity to develop new clinical research and public health strategies within the framework of the Universal Health Care policy for breast cancer in Chile.

Factors predicting non-ventilated hospital-acquired pneumonia: systematic review and meta-analysis.

BACKGROUND: Hospital-acquired pneumonia (HAP) results in approximately 15-20% of all infections in hospitals, with more than two-thirds being in patients not using mechanical ventilation. The incidence of non-ventilated hospital-acquired pneumonia (NVHAP) is increasing, and it is associated with a longer length of stay, the need for intensive care unit hospitalization and mechanical ventilation use, and higher mortality. AIM: To identify, quantify, and summarize predictive factors for NVHAP in adult patients admitted to non-intensive care units as determined by previous observational studies. METHODS: PubMed, Embase, Scopus, and LILACS were systematically searched. Case-control and cohort studies were included, and a meta-analysis was performed for all factors studied more than once. National Institute of Health assessment tools were applied to assess the quality of the studies. FINDINGS: Thirty-eight articles showing 204 predictive factors were included. A meta-analysis was performed for 58 factors, 32 of which were significantly associated with NVHAP. When the sensitivity analysis was performed without poor-quality studies, 24 factors remained associated with NVHAP. CONCLUSION: Although there is a lack of good-quality studies to establish predictive factors for NVHAP, the results of this study showed 24 factors associated with the development of this infectious complication. Knowledge of the significant predictive factors for NVHAP will enable the identification of patients most likely to develop it.

Pain and physical activity levels among Rheumatoid Arthritis patients between the ages of 18 to 50 years in South Africa.

Background: Little epidemiological research on rheumatoid arthritis (RA) has been done in Africa, suggesting that it is an uncommon illness. In rural South Africa, RA has an overall prevalence of 0.07% and a prevalence of 2.5% in urban areas; therefore, it is not as uncommon as perceived by the lack of research. Patient-centred programmes to improve physical function have been lacking and, as a result, the prior assumption was that physical activity should be avoided. Objectives: To determine pain and physical activity levels among RA patients between the ages of 18 to 50 years in South Africa. Methods: A combination of two questionnaires were used, namely, the Global Physical Activity Questionnaire (2002) and the Pain Outcomes Questionnaire (2003). The collated questionnaires were distributed by rheumatologists and on social media platforms to RA patients between the ages of 18 to 50 years old living in South Africa. This study had a sample size of 105 participants, with participation occurring through the online Google forms platform. Results: One hundred and five participants with RA were recruited with an average age of 38±9 years. Most of the participants were females (93.3%). Seventy-two percent of the sample was classified as physically active, where work, leisure and travel activities were considered. No significant correlation between pain and physical activity was evident (r=0.10; p=0.311). Results showed significant correlations between pain and personal grooming (r=0.30; p=0.002), pain and ambulation (r=0.60; p=0.000), and pain and stair climbing (r=0.60; p=0.000). Conclusion: Physical activity has proven to have multiple benefits for those suffering with RA. In this South African sample of RA patients, the majority were classified as physically active, and pain did not affect the activity levels of the involved participants. This study opens further research questions regarding RA prevalence in South Africa, and the type and intensity of physical activity that would be beneficial for RA.