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PURPOSE: This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, and cyclophosphamide in doses of > 1500 mg/m2 and the combination of cyclophosphamide and an anthracycline (AC) in women with breast cancer. METHODS: A systematic review report following the PRISMA guidelines of the literature from January 1, 2015, until February 1, 2023, was performed. PubMed (Ovid), Scopus (Google), and the Cochrane Database of Systematic Reviews were searched. The literature search was limited to randomized controlled trials, systematic reviews, and meta-analyses. RESULTS: Forty-six new references were determined to be relevant. The main topics identified were (1) steroid-sparing regimens, (2) olanzapine-containing regimens, and (3) other issues such as comparisons of antiemetics of the same drug class, intravenous NK1 receptor antagonists, and potentially new antiemetics. Five updated recommendations are presented. CONCLUSION: There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC. Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC. No major differences between 5-HT3 receptor antagonists or between NK1 receptor antagonists were identified. No new antiemetic agents qualified for inclusion in the updated recommendations.

In this paper, we review some recent findings related to the Casimir effect. Initially, the thermal corrections to the vacuum Casimir energy density are calculated, for a quantum scalar field, whose modes propagate in the (3+1)-dimensional Euclidean spacetime, subject to a nontrivial compact boundary condition. Next, we analyze the Casimir effect induced by two parallel plates placed in a weak gravitational field background. Finally, we review the three-dimensional wormhole solutions sourced by the Casimir density and pressures associated with the quantum vacuum fluctuations of the Yang-Mills field.

The correct diagnosis is fundamental for the appropriate treatment to be employed in a particular pathology. The best treatment is not the one that solves only local problems, fragmenting the patient, and therefore, it is necessary to integrate the entire systemic condition of the individual before initiating any local treatment. This context inevitably requires dentistry to participate in a multidisciplinary approach, where the role of the dentist is expanded in concepts that encompass ethics, human dignity, and professional valorization. This article describes a clinical case of a patient with mucopolysaccharidosis type I, whose treatment of cystic lesions present in the mandible was exclusively performed through marsupialisation. The objective of this study is to demonstrate, within the complexity of this rare syndrome, the difficulties of diagnosis and the need for evaluation of the patient beyond the limits of the oral cavity, as well as to report two cases of large dentigerous cysts, surgically treated conservatively through marsupialisation, without the need for re-approach for enucleation and without recurrences over a 20-year period.

Aedes aegypti and Aedes albopictus are vectors of arboviruses and have different levels of resistance to synthetic insecticides, such as the organophosphate temephos, according to their area of occurrence. As an alternative, there are semisynthetic substances with potential insecticidal effect; however, they need to be fully tested by an effective method for the mosquito control. The semi-synthetic dillapiole n-butyl ether exhibits toxic ovicidal and larvicidal activity in both mosquito species. However, has no proven the mutagenicity and cytotoxicity risks of this larvicide in drinking water effect for consumption by non-target organisms, such as in humans neither in other vertebrates, which access pools of water contain this sprayed substance. In this sense, both of the biomarkers of the genotoxicity, the micronucleus (MN) and comet, using this substance were tested in Balb/C mice to assess the genetic damage and risks of its application as a mitigating measure against Ae. aegypti. Male specimens (n = 60) were exposed to dillapiole n-butyl ether at concentrations of 10, 20 and 40 mg/kg via a comet assay in peripheral blood (n = 30) and a micronucleus test in bone marrow cells (n = 30). The induction of mutagenicity and cytotoxicity of dillapiole n-butyl ether in these animals occurred only at a concentration of 40 mg/kg, in multiple treatments. However, dillapiole n-butyl ether at concentrations of 20 and 10 mg/kg has potential for use against Ae. aegypti in the form of a larvicide in water for consumption by humans and other vertebrates a new vector control measure.

The activities developed by Community Health Agents are strategic for child growth and development due to the uniqueness and proximity with which these actors perform their interventions in the community. Such actions favor children's health, resulting in a reduction in child mortality, improvement in growth deficit and malnutrition, and an increase in vaccination coverage and breastfeeding. The objective of the study was to know the perception of community health agents about child growth and development. This is an exploratory descriptive, qualitative study, carried out with 30 Community Health Agents who worked in Primary Care and Family Health Strategy Teams in a municipality in the central region of Rio Grande do Sul, Brazil. Data were collected from April to July 2021, through an online questionnaire and analyzed according to Discursive Textual Analysis. Data analysis allowed the construction of four categories, namely: Growth as a process of physical evolution of children; Child development as a broad process of evolution; Elements that facilitate the work of Community Health Agents; and Elements that hinder the work of Community Health Agents. For the study participants, children growth is associated with the physical evolution of children, while child development is understood as a broader process that is influenced by the environment and the external conditions in which children live. The Community Health Agents have a strategic and unique professional role in the monitoring of these processes, as they are capable of identifying diseases that need specific attention and providing care in a timely manner.

A participação política é indissociável da democracia e partimos da premissa de que não existe uma sem a outra. Entretanto, nos estudos sobre juventudes, não existe um consenso em relação ao conceito de participação política, podendo variar de acordo com o entendimento de democracia dos(as) autores(as). Os(as) adeptos(as) da democracia representativa possuem a crença de que o Estado é o garantidor da participação política dos sujeitos, enquanto os(as) autores(as) de tendências mais libertárias, que entendem a democracia como um projeto de autonomia, têm como base a disjunção entre Estado e democracia. Nesse sentido, o presente artigo tem como intuito fazer uma breve discussão sobre a participação política a partir dessas duas perspectivas e trazer a teoria libertária “estadocrítica” como proposta teórico-metodológica para a compreensão da participação política das juventudes, utilizando a tríade com/contra/apesar do Estado como eixo norteador.

IntroductionFoot-and-mouth disease (FMD) affects multiple food-animal species and spreads rapidly among ungulate populations, posing significant challenges for disease control. Understanding the dynamics of FMD transmission and evaluating the effectiveness of control measures are critical for mitigating its impact. This study introduces a multiscale compartmental stochastic model to simulate FMD spread and assess countermeasures.MethodsWe developed a model that integrates population dynamics, including births, deaths, and species-specific transmission dynamics, at both the between-farm and within-farm levels. Four scenarios were created to evaluate different control strategies: the base scenario included vaccinating 20 farms and depopulating four infected farms, while alternative scenarios increased vaccination and depopulation capacities or omitted vaccination altogether.ResultsOur simulations showed that bovines were the most frequently infected species, followed by swine and small ruminants. After 10 days of initial spread, the number of infected farms ranged from 1 to 123, with 90.12% of simulations resulting in fewer than 50 infected farms. Most secondary spread occurred within a 25 km radius. An early response to control actions significantly reduced the time spent managing outbreaks, and increasing daily depopulation and vaccination capacities further enhanced control efforts.DiscussionEmergency vaccination effectively reduced the magnitude and duration of outbreaks, while increasing depopulation without vaccination also eliminated outbreaks. These findings highlight the importance of rapid response and capacity scaling in controlling FMD outbreaks, providing valuable insights for future decision-making processes in disease management.

Cytotoxic activity is a hallmark of the immunopathogenesis in human cutaneous leishmaniasis (CL). In this study, we identified accumulation of CD4+ granzyme B producing T cells with increased cytotoxic capacity in CL lesions. These cells showed enhanced expression of activating NK receptors (NKG2D and NKG2C), diminished expression of inhibitory NKG2A, along with the upregulation of the senescence marker CD57. Notably, CD4+ T cells freshly isolated from CL lesions demonstrated remarkable capacity to mediate NL-like bystander cytolysis. Phenotypic analyses revealed that lesional CD4+ T cells are mainly composed of late-differentiated effector (CD27-CD45RA-) and terminally differentiated (senescent) TEMRA (CD27-CD45RA+) subsets. Interestingly, the TEMRA CD4+ T cells exhibited higher expression of granzyme B and CD107a. Collectively, our results provide the first evidence that senescent cytotoxic CD4+ T cells may support the skin pathology of human cutaneous leishmaniasis and, together with our previous findings, support the notion that multiple subsets of cytotoxic senescent cells may be involved in inducing the skin lesions in these patients.

Experimental Myocardial infarction (MI) using ligation procedure induces cardiac dysfunction, high level of ROS, inflammation, apoptosis, fibrosis and cardiomyocyte (CM) loss. AAV overexpressing human Trx-2, specifically in CM mitochondria improves mouse cardiac function, reduces the size of cardiac infarct, increases the expression of cardiac anti-inflammatory markers, reduces apoptosis and oxidative stress. However, it does not increase CM proliferation.

Diabetes is a complex metabolic disease which most commonly has a polygenic origin; however, in rare cases, diabetes may be monogenic. This is indeed the case in both Maturity Onset Diabetes of the Young (MODY) and neonatal diabetes. These disease subtypes are believed to be simpler than Type 1 (T1D) and Type 2 Diabetes (T2D), which allows for more precise modelling. During the three last decades, many studies have focused on rodent models. These investigations provided a wealth of knowledge on both pancreas development and beta cell function. In particular, they allowed the establishment of a hierarchy of the transcription factors and highlighted the role of microenvironmental factors in the control of progenitor cell proliferation and differentiation. Transgenic mice also offered the possibility to decipher the mechanisms that define the functional identity of the pancreatic beta cells. Despite such interest in transgenic mice, recent data have also indicated that important differences exist between mice and human. To overcome these limitations, new human models are necessary. In the present review, we describe these ex vivo models, which are created using stem cells and organoids, and represent an important step toward islet cell therapy and drug discovery.

Resumo O artigo visa a realizar um balanço crítico das relações econômicas entre Brasil e China nos últimos 20 anos. O texto busca sintetizar os temas e eixos destacados na literatura que tem analisado as relações econômicas bilaterais com ênfase nos temas de comércio e investimento, enfatizando a necessidade de avanços qualitativos para além do que se consolidou nas duas décadas iniciais do século XXI. Essa necessidade é decorrente do longo processo de desindustrialização pelo qual a economia brasileira vem passando, e reforçado pelo cenário complexo de transformações que vem ocorrendo na economia global depois da grande crise financeira (GCF) de 2008 e pelas mudanças nas estratégias de desenvolvimento que a própria China vem adotando desde então.

Abstract Invasive species are a leading threat to biodiversity worldwide. Nypa palm (Nypa fruticans) has emerged as the predominant invasive species in the Niger Delta region of Nigeria. While endemic mangroves have high rates of carbon sequestration, stabilize coastlines and protect biodiversity, Nypa does not provide these services outside its native region of Southeast Asia. Oil exploration and urbanization in this region also exacerbate mangrove loss and Nypa spread. As Nypa is difficult to distinguish from endemic mangrove species in remotely sensed data, estimates of mangrove and ecosystem services losses in Nigeria are highly uncertain. Here, we analyse multisensor satellite data with machine learning to quantify the rapid expansion of Nypa from 2015 to 2020 in Nigeria. Using Landsat imagery and random forest classification, we quantify total potential Nypa extent in Nigeria in 2019. We then produced a Nypa extent map using iterative combinations of Sentinel‐1 SAR, Sentinel‐2 MSI and ALOS PALSAR. Random forest classifications using SAR data from ALOS and Sentinel‐1 were best suited for mapping Nypa extent with similar accuracies (78% and 75%, respectively). Based on data availability and accuracy, we focussed our change analysis on Sentinel‐1 SAR. Our results show ~28 000 ha of mangroves were converted to Nypa in Nigeria by 2020 and covered a larger extent than endemic mangroves, compounding the effect of the existing degradation and deforestation in the region. We also compared forest height and complexity estimates from Global Ecosystem Dynamics Investigation LiDAR to further distinguish between endemic mangroves and Nypa in three dimensions. Nypa structural variability, measured by top‐of‐canopy height, vegetation cover, plant area index, and foliage height diversity, was lower than that of mangroves. At current rates of Nypa expansion, the entire area of study would be invaded by Nypa by 2028, with potentially detrimental consequences to the ecosystem services provided by mangroves.

Contexto: Hace 136 años se produjo un hecho científico de especial relevancia para la ciencia y la tecnología en Camagüey y Cuba. Objetivo: Presentar una reproducción comentada del folleto Memoria sobre unos fósiles vegetales encontrados en El Chorrillo (Puerto Príncipe), publicado en 1887 por el Padre Pío Galtés, Escolapio. Métodos: Se trabajó básicamente con la revisión documental y la consulta a personal especializado. Se comparó la información localizada, sobre las ediciones de 1887. Se recopiló información básica sobre el autor, las instituciones en que laboró en Cuba, así como de las personas, especies botánicas y localidades que se mencionan en el texto, con precisiones referidas a la toponimia actual. Resultados: Durante la primera estancia del Padre Pío Galtés en Cuba (1870-1887), dirigió el internado de las escuelas Pías de Guanabacoa (1873-1885) y fue rector de la de Puerto Príncipe (1885-1987). En este último año realizó una expedición a El Chorrillo, allí colectó fósiles vegetales que estudió en detalle y publicó una memoria de 19 páginas, publicada en la propia ciudad por la Imprenta El Fanal, que se pone a disposición de los lectores contemporáneos. Conclusiones: Se rinde homenaje al Padre Pío Galtés, pionero de la ciencia, que desarrolló su labor en condiciones muy difíciles, pero con un importante legado, que debe ser estudiado por las actuales y futuras generaciones.

This study delves into the comprehensive characterization of the Ti–25Ta-xNb alloy system, whith a focus on its potential biomedical applications. Int intriguing insights into these alloys properties were unveiled through a systematic investigation encompassing EDS analysis, density measurements, chemical mapping, X-ray diffraction, microstructural examination, and microhardness assessments. The chemical composition results confirm that these alloys exhibit the appropriate stoichiometries, with the melting process yielding homogeneous compositions. Notably, the Ti–25Ta–10Nb and Ti–25Ta–20Nb alloys showcase the coexistence of α and β phases, while those with 30 % and 40 % Nb consist solely of the β phase, highlighting the β-stabilizing role of Nb and Ta. These results align seamlessly with X-ray diffractograms, Rietveld refinement data, and microstructural observations. The analysis further reveals a decrease in edges B and C of the α'' structure, consistent with previous literature, indicating the alloys sensitivity to Nb additions. In terms of hardness, a discernible trend emerges with the stabilizing of the β phase, leading to reduced hardness values, as anticipated. Excitingly, not all alloys in the Ti–25Ta-xNb system exhibited cytotoxic effects, while they facilitated the crucial process of cell adhesion. This presents a promising prospect for their application in biomaterials. Among the developed alloys, the Ti–25Ta–30Nb alloy stands out due to its proximity to pure titanium in terms of hardness and its potential to promote cell proliferation.These findings underscore the potential of the Ti–25Ta-xNb alloy system for biomedical applications, provided that further studies optimize their suitability for such purposes.

ZnO nanoparticles functionalized with APTES were obtained to evaluate their CH4 and CO2 adsorption at 298 K in a range between 0 and 10 bar. First, ZnO nanoparticles were obtained by a precipitation method and subsequently coated with (3-aminopropyl)triethoxysilane (APTES). As a preliminary study, the results were compared with previously reported naked nanoparticles in order to evaluate the influence of APTES coating on CO2 selectivity. UV-Vis, FT-IR spectroscopy, TGA, XRD, TEM/EDX, XPS and N2 adsorption at 77 K were used to characterize the evaluated material. It was observed that the amount of gas adsorbed on the surface of the nanostructure was very small in comparison with other materials traditionally used for this purpose but slightly higher than those obtained in naked nanoparticles evaluated in previous studies. The affinity of CO2 for the amines groups of the APTES ligand was also discussed.

ABSTRACT Synthetic chemical insecticides are widely used in population control of pests. Aedes aegypti is the primary vector of dengue, Zika, chikungunya and yellow fever to humans, and has proven resistance to chemical insecticides. As an alternative vector control method, the ethanolic extract of the leaves of Piper peltatum L. (Piperaceae) showed larvicidal activity against Ae. aegypti. Despite the wide medicinal use of this plant, the biological activity of its isolated constituents remains unexplored. In this sense, we isolated, identified and evaluated the larvicidal activity of 4-nerolidylcatechol (4-NC) from P. peltatum against Ae. aegypti, Culex quinquefasciatus and Anopheles darlingi, focusing on the larvicidal, adulticidal and genotoxic potential of 4-NC on Ae. aegypti. Larvae were captured in the city of Manaus, Amazonas state, Brazil. 4-NC was isolated from the extract of the leaves of P. peltatum via silica gel chromatography. This was identified using nuclear magnetic resonance spectroscopy and tested in Artemia franciscana (6.25, 12.5, 25, 50, 100 and 200 µg/mL). In the toxicity bioassay, Ae. aegypti larvae were exposed to 30, 50, 70, 90, and 110 µg/mL of 4-NC, while Cx. quinquefasciatus and An. darlingi were exposed to 6.25, 12.5, 25, 50 and 100 µg/mL. Ae. aegypti larvae were also subjected to 40 and 60 µg/mL of 4-NC (genotoxicity bioassay), and adult females to 62.5 to 1,000 µg/mL (adulticidal bioassay). The results of the 4-NC toxicity assays showed that there was 100% mortality in larvae of Ar. franciscana at the concentration of 200 µg/mL, with an LC50 of 8.0 μg/mL. In the larvae of Ae. aegypti, mortality was 100%, with an LC50 of 62 μg/mL. In larvae of Cx. quinquefasciatus, 97% mortality occurred, with an LC50 of 52.3 μg/mL, and in An. darlingi larvae there was an 83% mortality rate, with an LC50 of 55.8 μg/mL. In adults of Ae. aegypti, however, there was no adulticidal activity. In the larvae of Ae. aegypti, the genotoxic effect of 4-NC (40 and 60 µg/mL) showed significant frequency (p < 0.05) of cellular abnormalities (micronuclei, budding and nuclear bridges) of interphasic nuclei of neuroblasts and oocytes in relation to the negative control. This result may be associated with a decrease in oviposition of females, which was observed in two generations. We can confirm that 4-NC has larvicidal activity against Ae. aegypti, Cx. quinquefasciatus and An. darlingi. Although it does not present adulticidal activity in Ae. aegypti, it reduced the oviposition of females. Therefore, 4-NC seems to be a strong candidate for the development of an alternative method for the control of these mosquitoes in the immature phase.

Introduction Venous thromboembolism (VTE) is a serious, frequent, and preventable medical complication in hospitalized patients. Although the efficacy of prophylaxis (pharmacological and/or mechanical) has been demonstrated, compliance with prophylaxis is poor at international and national levels. Aim To determine the indication and use of pharmacological thromboprophylaxis in hospitalized patients in Uruguay. Methods An observational, descriptive, cross-sectional, multicentre study involving 31 nationwide healthcare facilities was conducted. Baseline characteristics associated with hospital admission, the percentage of the population with an indication for thromboprophylaxis, and the percentage of patients receiving pharmacological thromboprophylaxis were assessed. The VTE risk was determined using the Padua score for medical patients; the Caprini score for surgical patients; the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines for pregnant-postpartum patients. Results 1925 patients were included, representing 26% of hospitalized patients in Uruguay. 71.9% of all patients were at risk of VTE. Of all patients at risk of VTE, 58.6% received pharmacological thromboprophylaxis. The reasons for not receiving thromboprophylaxis were prescribing omissions in 16.1% of cases, contraindication in 15.9% and 9.4% of patients were already anticoagulated for other reasons. Overall, just 68% of patients were “protected” against VTE. Recommendations of major thromboprophylaxis guidelines were followed in 70.1% of patients at risk. Conclusions Despite the progress made in adherence to thromboprophylaxis indications, nonadherence remains a problem, affecting one in six patients at risk of VTE in Uruguay

Contexto: Interés por profundizar en el conocimiento de la vida y obra de Roig y Mesa, relevante botánico cubano de los siglos XIX y XX. Objetivo: Valorar la obra del autor, con énfasis en sus aportes al conocimiento de la flora de Cuba, con vistas a facilitar su localización por parte de investigadores contemporáneos y futuros. Métodos: Revisión documental, histórico-lógico, analítico-sintético e inductivo-deductivo. Se localizó información científica referida al autor páginas web de diferentes universidades del mundo. Se ordenaron cronológica, alfabética y taxonómicamente, en dependencia de la temática abordada. Se siguió la norma APA VII, para los asentamientos. Resultados: Roig y Mesa se distinguió como científico y educador. Dejó una fecunda obra escrita. Se compendia y actualiza su bibliografía activa y pasiva. Se confirma la publicación de 132 publicaciones con su autoría, de ellas 119 como primer autor (90 %). Se relaciona 99 citas de otros autores, con 38 reportes de prensa, 8 entrevistas, 41 homenajes o comentarios sobre su obra y 13 sellos de correo dedicados. Se compendia, por primera vez, información referida a los nombres de plantas que él aportó a la ciencia y los que le fueron dedicados. Conclusiones: Roig y Mesa trasciende como el primero en defender la necesidad del uso sostenible y conservación de los bosques cubanos y se le presenta como abanderado en la divulgación de la utilidad económica de las plantas cubanas, en especial las medicinales.

Abstract Mitochondrial function is vital for energy metabolism in thermogenic adipocytes. Impaired mitochondrial bioenergetics in brown adipocytes are linked to disrupted thermogenesis and energy balance in obesity and aging. Phospholipid cardiolipin (CL) and phosphatidic acid (PA) jointly regulate mitochondrial membrane architecture and dynamics, with mitochondria-associated endoplasmic reticulum membranes (MAMs) serving as the platform for phospholipid biosynthesis and metabolism. However, little is known about the regulators of MAM phospholipid metabolism and their connection to mitochondrial function. We discover that LCN2 is a PA binding protein recruited to the MAM during inflammation and metabolic stimulation. Lcn2 deficiency disrupts mitochondrial fusion-fission balance and alters the acyl-chain composition of mitochondrial phospholipids in brown adipose tissue (BAT) of male mice. Lcn2 KO male mice exhibit an increase in the levels of CLs containing long-chain polyunsaturated fatty acids (LC-PUFA), a decrease in CLs containing monounsaturated fatty acids, resulting in mitochondrial dysfunction. This dysfunction triggers compensatory activation of peroxisomal function and the biosynthesis of LC-PUFA-containing plasmalogens in BAT. Additionally, Lcn2 deficiency alters PA production, correlating with changes in PA-regulated phospholipid-metabolizing enzymes and the mTOR signaling pathway. In conclusion, LCN2 plays a critical role in the acyl-chain remodeling of phospholipids and mitochondrial bioenergetics by regulating PA production and its function in activating signaling pathways.

Abstract Background Caregiver self-efficacy is thought to be a key component for successful family-based treatment (FBT) for individuals with eating disorders. As such, interventions aimed at enhancing caregiver self-efficacy, often measured via the Parents Versus Anorexia scale, have been a focal point of FBT literature. However, studies looking at the relationship between caregiver self-efficacy and treatment outcomes have been mixed. We aimed to better understand the influence of caregiver self-efficacy on eating disorder treatment outcomes during FBT. Methods Caregiver self-efficacy was measured using the Parents Versus Eating Disorders (PVED) scale, an adapted version of the Parents Versus Anorexia scale, in a sample of 1051 patients with an eating disorder and 1528 caregivers (patients can have more than one caregiver) receiving virtual FBT. Across two multilevel models, we tested how caregiver self-efficacy changed over time and its association with changes in eating disorder symptoms and weight over the first 16 weeks of treatment. Results Over treatment, PVED scores increased (b = 0.79, SE = 0.04, CI [0.72, 0.86]) and starting PVED scores were predictive of improved eating disorder symptoms (b = − 0.73, SE = 0.22, CI [− 1.15, − 0.30]), but not weight (b = − 0.96, SE = 0.59, CI [− 2.10, 0.19]). We also found that PVED change-from-baseline scores were predictive of weight (b = − 0.48, SE = 0.03, CI [− 0.53, − 0.43]) such that patient weight was lower when caregiver reports of PVED were higher. Likewise, the association between caregiver change in PVED scores and weight varied as a function of treatment time (b = 0.27, SE = 0.01, CI [0.24, 0.29]). Results were consistent when isolating patients with anorexia nervosa. Conclusions Caregiver self-efficacy during FBT improved over time but was not robustly associated with treatment outcomes. This may, in part, be due to psychometric properties of the PVED scale. We describe these issues and illustrate the need for development of a new measure of self-efficacy for caregivers supporting their loved ones through eating disorder treatment.

Abstract The microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of 13C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.

This study analyzes whether the low rate of universalizing water supply and sanitation services in Brazil is related to the low participation of private companies in the concession of these services in municipalities in the country. To this end, it discusses basic sanitation in Brazil and its current scenario, its problems from the point of view of environmental injustice, and the existing public/private conflicts. The empirical analysis conducted a data survey of eight municipalities defined in four population groups, comparing data from 13 operational, efficiency, quality, and cost indicators of the services provided. Each population group compared two municipalities providing water and sewerage services, one provided by a public company and the other by a private company. The compared data were from 2021, obtained through the Brazilian National Sanitation Information System (SNIS). As a result of the comparative analyses, it was shown that the performance of public companies was more positive for most indicators, compared to private companies. It is concluded that the main challenge to overcome the social and environmental injustice resulting from the deficit in basic sanitation coverage lies in the promotion of public management instruments that enable the articulation of public and private investments in the expansion of basic sanitation services, in the improvement of the quality of services with the inclusion of social control through popular participation.

Foxb1 -expressing neurons occur in the dorsal premammillary nucleus (PMd) and further rostrally in the parvafox nucleus, a longitudinal cluster of neurons in the lateral hypothalamus of rodents. The descending projection of these Foxb1+ neurons end in the dorsolateral part of the periaqueductal gray (dlPAG). The functional role of the Foxb1+ neuronal subpopulation in the PMd and the parvafox nucleus remains elusive. In this study, the activity of the Foxb1+ neurons and of their terminal endings in the dlPAG in mice was selectively altered by employing chemo- and optogenetic tools. Our results show that in whole-body barometric plethysmography, hM3Dq-mediated, global Foxb1+ neuron excitation activates respiration. Time-resolved optogenetic gain-of-function manipulation of the terminal endings of Foxb1+ neurons in the rostral third of the dlPAG leads to abrupt immobility and bradycardia. Chemogenetic activation of Foxb1+ cell bodies and ChR2-mediated excitation of their axonal endings in the dlPAG led to a phenotypical presentation congruent with a ‘freezing-like’ situation during innate defensive behavior.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention.Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases.Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons.Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated.Clinical Trial Registration:Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.