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.

Liver X receptor alpha ensures blood-brain barrier function by suppressing SNAI2.

In Alzheimer's disease (AD) more than 50% of the patients are affected by capillary cerebral amyloid-angiopathy (capCAA), which is characterized by localized hypoxia, neuro-inflammation and loss of blood-brain barrier (BBB) function. Moreover, AD patients with or without capCAA display increased vessel number, indicating a reactivation of the angiogenic program. The molecular mechanism(s) responsible for BBB dysfunction and angiogenesis in capCAA is still unclear, preventing a full understanding of disease pathophysiology. The Liver X receptor (LXR) family, consisting of LXRα and LXRß, was reported to inhibit angiogenesis and particularly LXRα was shown to secure BBB stability, suggesting a major role in vascular function. In this study, we unravel the regulatory mechanism exerted by LXRα to preserve BBB integrity in human brain endothelial cells (BECs) and investigate its role during pathological conditions. We report that LXRα ensures BECs identity via constitutive inhibition of the transcription factor SNAI2. Accordingly, deletion of brain endothelial LXRα is associated with impaired DLL4-NOTCH signalling, a critical signalling pathway involved in vessel sprouting. A similar response was observed when BECs were exposed to hypoxia, with concomitant LXRα decrease and SNAI2 increase. In support of our cell-based observations, we report a general increase in vascular SNAI2 in the occipital cortex of AD patients with and without capCAA. Importantly, SNAI2 strongly associated with vascular amyloid-beta deposition and angiopoietin-like 4, a marker for hypoxia. In hypoxic capCAA vessels, the expression of LXRα may decrease leading to an increased expression of SNAI2, and consequently BECs de-differentiation and sprouting. Our findings indicate that LXRα is essential for BECs identity, thereby securing BBB stability and preventing aberrant angiogenesis. These results uncover a novel molecular pathway essential for BBB identity and vascular homeostasis providing new insights on the vascular pathology affecting AD patients.

Metacercariae of Heterodiplostomum lanceolatum (Trematoda: Proterodiplostomidae) found in Leptodactylus podicipinus (Anura: Leptodactylidae) from Brazil: a morphological, molecular and ecological study.

The trematodes from South American reptiles are poorly known, with only one life cycle completely characterized. We used molecular and morphological methods to characterize diplostomoid metacercariae found in 29 of 86 pointedbelly frogs, Leptodactylus podicipinus (Cope, 1862) collected in a marsh pond in Selvíria, in the central-west region of Brazil. The metacercariae were identified as Heterodiplostomum lanceolatum Dubois, 1936 (Proterodiplostomidae), a rarely reported species that matures in snakes. In phylogenetic analysis of partial sequences from 28S rDNA, H. lanceolatum fell within a polytomy with the proterodiplostomid Crocodilicola pseudostoma (molecular divergence of 4.1%) and other members of the superfamily Diplostomoidea. Our collections provide insights into the ecology of this parasite, in that infected frogs were smaller than uninfected frogs, and metacercariae were more numerous in the abdominal cavity and hindlimb muscles than in abdominal muscles, which suggests directions for future research on the transmission and pathology of this proterodiplostomid.

Bilateral synovial cyst of the thoracic spine causing paraparesis.

Spinal synovial cysts are degenerative extradural lesions mostly found in the lumbar region, and more rarely at cervical or thoracic levels and in a bilateral presentation. We report a patient with a history of progressive paraparesis associated with bilateral cervicothoracic synovial cysts, causing spinal canal narrowing and cord compression, ultimately resulting in myelopathy. A review of the literature summarizes previous reports on this topic. Surgical excision of the extradural mass, decompression of the spinal canal and instrumented fusion were performed, improving lower limb deficit and gait. Post-surgical MRI showed evidence of complete cyst resection, and good arthrodesis consolidation with adequate sagittal balance. Surgical excision is indicated in case of medical treatment failure or increasing symptom severity. Given the strong pathophysiological link between synovial cysts and spinal instability, concomitant instrumented fusion may help improve outcome.

Molecular cloning of TaMATE2 homoeologues potentially related to aluminium tolerance in bread wheat (Triticum aestivum L.).

Recently, members of the MATE family have been implicated in aluminium (Al) tolerance by facilitating citrate efflux in plants. The aim of the present work was to perform a molecular characterisation of the MATE2 gene in bread wheat. Here, we cloned a member of the MATE gene family in bread wheat and named it TaMATE2, which showed the typical secondary structure of MATE-type transporters maintaining all the 12 transmembrane domains. Amplification in Chinese Spring nulli-tetrasomic and ditelosomic lines revealed that TaMATE2 is located on the long arm of homoeologous group 1 chromosomes. The transcript expression of TaMATE2 homoeologues in two diverse bread wheat genotypes, Barbela 7/72/92 (Al-tolerant) and Anahuac (Al-sensitive), suggested that TaMATE2 is expressed in both root and shoot tissues of bread wheat, but mainly confined to root rather than shoot tissues. A time-course analysis of TaMATE2 homoeologue transcript expression revealed the Al responsive expression of TaMATE2 in root apices of the Al-tolerant genotype, Barbela 7/72/92. Considering the high similarity of TaMATE2 together with similar Al responsive expression pattern as of ScFRDL2 from rye and OsFRDL2 from rice, it is likely that TaMATE2 also encodes a citrate transporter. Furthermore, the TaMATE2-D homoeologue appears to be near the previously reported locus (wPt0077) on chromosome 1D for Al tolerance. In conclusion, molecular cloning of TaMATE2 homoeologues, particularly TaMATE2-D, provides a plausible candidate for Al tolerance in bread wheat that can be used for the development of more Al-tolerant cultivars in this staple crop.

Hepatitis C: The beginning of the end-key elements for successful European and national strategies to eliminate HCV in Europe.

Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely "silent pandemic," its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high-level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.

Link Between the Adult and the Metacercaria of Clinostomum heluans Braun, 1899 (Trematoda: Clinostomidae) Through DNA Sequences, and its Phylogenetic Position Within the Genus Clinostomum Leidy, 1856.

The phylogenetic position of Clinostomum heluans Braun, 1899 within the genus Clinostomum Leidy, 1856 is reported in this study based on sequences of the barcoding region of the mitochondrial cytochrome c oxidase subunit 1 gene ( COX1). Additionally, molecular data are used to link the adult and the metacercariae of the species. The metacercariae of C. heluans were found encysted infecting the cichlid fish Australoheros sp. in Minas Gerais, Brazil, whereas the adults were obtained from the mouth cavity of the Great White Egret, Ardea alba, in Campeche, Mexico. The COX1 sequences obtained for the Mexican clinostomes and the Brazilian metacercaria were almost identical (0.2% molecular divergence), indicating conspecificity. Similar molecular divergence (0.2-0.4%) was found between sequences of C. heluans reported here and Clinostomum sp. 6 previously obtained from a metacercaria recovered from the cichlid Cichlasoma boliviense in Santa Cruz, Bolivia. Both maximum likelihood and Bayesian inference analyses unequivocally showed the conspecificity between C. heluans and Clinostomum sp. 6, which form a monophyletic clade with high nodal support and very low genetic divergence. Moreover, tree topology reveals that C. heluans occupies a basal position with respect to New World species of Clinostomum, although a denser taxon sampling of species within the genus is further required. The metacercaria of C. heluans seems to be specific to cichlid fish because both samples from South America were recovered from species of this fish family, although not closely related.

Psittacara leucophthalmus (Aves: Psittacidae) como um novo hospedeiro de Paratanaisia bragai (Trematoda: Eucotylidae) no Brasil: achados clínicos e patológicos: relato de caso / Psittacara leucophthalmus as a new host of Paratanaisia bragai (Trematoda: Eucotylidae) in Brazil: clinical and pathological findings: case report

Paratanaisia bragai é um trematódeo que parasita rins e ureteres de aves domésticas e selvagens. Apesar de considerado pouco patogênico pode levar a complicações clínicas e morte em infecções severas. No presente estudo, um caso de parasitismo fatal em maritaca (Psittacara leucophthalmus) por P. bragai é relatado. A ave, oriunda da área urbana do município de Lavras, Minas Gerais, Brasil, teve manifestações clínicas de apatia, desidratação, dispneia e veio a óbito. Na necropsia foram observados rins aumentados de volume, pálidos, com superfície irregular e nodulações esbranquiçadas. Ao corte verificaram-se parasitos nos rins, que foram processados para montagem de lâminas permanentes e identificados segundo técnica de rotina como P. bragai. No exame histopatológico dos rins foram constatados infiltrado inflamatório linfoplasmocítico multifocal moderado, dilatação de túbulos e focos de regeneração tubular, associados a fibrose intersticial moderada no córtex renal. Na medula renal havia infiltrado de macrófagos, heterófilos, eosinófilos e células gigantes multinucleadas associado a parasitos em ductos coletores dilatados. O parasitismo de P. leucophthalmus por P. bragai é relatado pela primeira vez. A importância de se considerar este parasito entre as possibilidades diagnósticas em aves com insuficiência renal é brevemente discutida.(AU)

Paratanaisia bragai is a trematode parasite of the kidneys and ureters of poultry and wild birds. Despite its low pathogenicity, this parasite can lead to several clinical complications and death in heavy infections. In the present study, a fatal case of parasitism by P. bragai in a specimen of the White-eyed Parakeet, Psittacara leucophthalmus, is reported. The bird, coming from the urban area of the county of Lavras, Minas Gerais, Brazil, was clinically evaluated and revealed apathy, dehydration, dyspnea, and death. The gross findings were pale and enlarged kidneys, which also had irregular surface with whitish nodulations. Parasites were observed on cutting surface of the renal parenchyma. They were processed for assembly of permanent slides and identified as P. bragai according to routine technique. The histologic findings were mild multifocal lymphoplasmacytic infiltrate, tubular dilatation and foci of tubular regeneration related to mild interstitial fibrosis in the renal cortex, and infiltration of macrophages, heterophils, eosinophils and multinucleated giant cells associated with metazoan parasites in the collecting ducts in renal medulla. The parasitism of P. leucophthalmus by P. bragai is reported for the first time. The importance of considering this parasite among the diagnostic possibilities in birds with renal insufficiency is briefly discussed.(AU)

Centrocestus formosanus (Trematoda: Heterophyidae) in Melanoides tuberculata (Gastropoda: Thiaridae) from Vila do Abraão, Ilha Grande, Rio de Janeiro, Brazil / Centrocestus formosanus (Trematoda: Heterophyidae) em Melanoides tuberculata (Gastropoda, Thiaridae) da Vila do Abraão, Ilha Grande, Rio de Janeiro, Brasil

Abstract Pleurolophocercous cercariae found in the invasive gastropod Melanoides tuberculata (Müller, 1774) collected in a stream of the Vila do Abraão, Ilha Grande, Angra dos Reis, Rio de Janeiro, Brazil were used for experimental infection that enabled the identification of the heterophyid trematode Centrocestus formosanus (Nishigori, 1924). The parasite has been found in the locality since 2007, after two years of the introduction of M. tuberculata. Recently, from a sample of 483 specimens collected in June 2013, 101 (21%) were found infected with parasite. The potential environmental impacts caused by the parasite occurrence could be underestimated in the country, and actions to monitor and control both the parasite and the mollusk are necessary.

Resumo Cercárias do tipo pleurolofocerca encontradas no gastrópode invasor Melanoides tuberculata (Müller, 1774) coletados em um riacho da Vila do Abraão em Ilha Grande, Angra dos Reis, Rio de Janeiro, Brasil foram utilizadas em estudos de infecção experimental que possibilitaram a identificação do trematódeo heterofiídeo Centrocestus formosanus (Nishigori, 1924). O parasito vem sendo encontrado na localidade desde 2007, dois anos após a introdução do molusco. Recentemente, de uma amostra de 483 espécimes coletados em junho de 2013, 101 (21%) apresentavam-se infectados pelo parasito. Os potenciais impactos ambientais ocasionados pela ocorrência deste parasito podem estar sendo subestimados no país, sendo necessárias ações visando o monitoramento e controle tanto do parasito quanto do molusco.

Early Rehospitalization Post-Kidney Transplant Due to Infectious Complications: Can We Predict the Patients at Risk?

INTRODUCTION: Rehospitalization early post-kidney transplant is common and has a negative impact in morbidity, graft survival, and health costs. Infection is one the most common causes, and identifying the risk factors for early readmission due to infectious complications may guide a preventive program and improve outcome. The aim of this study was to evaluate the incidence, characterize the population, and identify the risk factors associated with early readmission for infectious complications post-kidney transplantation. METHODS: We performed a retrospective cohort study of all the kidney transplants performed during 2015. The primary outcome was readmission in the first 3 months post-transplant due to infectious causes defined by clinical and laboratory parameters. RESULTS: We evaluated 141 kidney transplants; 71% of subjects were men, with an overall mean age of 50.8 ± 15.4 years. Prior to transplant, 98% of the patients were dialysis dependent and 2% underwent pre-emptive living donor kidney transplant. The global readmission rate was 49%, of which 65% were for infectious complications. The most frequent infection was urinary tract infection (n = 28, 62%) and the most common agent detected by blood and urine cultures was Klebsiella pneumonia (n = 18, 40%). The risk factors significantly associated with readmission were higher body mass index (P = .03), diabetes mellitus (P = .02), older donor (P = .007), and longer cold ischemia time (P = .04). There were 3 graft losses, but none due to infectious complications. CONCLUSION: There was a high incidence of early rehospitalization due to infectious complications, especially urinary tract infections to nosocomial agents. The risk factors identified were similar to other series.

Nephrotic Range Proteinuria in Renal Transplantation: Clinical and Histologic Correlates in a 10-year Retrospective Study.

INTRODUCTION: There is a high incidence of nephrotic proteinuria in renal transplant recipients, which is an accurate predictor of graft loss. Despite this, its histologic correlates and prognostic implications are still not well characterized. We assessed the clinical and histological correlates of kidney transplantation patients with nephrotic range proteinuria. METHODS: We have retrospectively analyzed clinical and histological data from 50 kidney transplantation biopsy specimens from 44 renal transplant recipients with nephrotic range proteinuria between 2006 and 2015. The median follow-up time was 93 months (range, 14 months to 190 months). RESULTS: The mean age of the patients was 45.2 ± 13.7 years and our cohort included 86% recipients of deceased-donor grafts. The maintenance immunosuppressive regimen included calcineurin inhibitors in 68% and mammalian target of rapamycin inhibitors in 32% of patients. The average proteinuria was 6.9 ± 3.8 g/d and 52% of patients presented with nephrotic syndrome. The main histological findings were transplant glomerulopathy (22%), de novo glomerular disease (22%), and recurrence of primary disease (22%). Tubular atrophy and interstitial fibrosis was present in 78% of the biopsy specimens. Thirty-one patients (62%) lost the graft at follow-up. There was no statistically significant difference between the histologic diagnosis nor the proteinuria levels and the outcome of the graft. CONCLUSIONS: The main causes of nephrotic range proteinuria in patients undergoing biopsy were transplant glomerulopathy, recurrence of the underlying disease, and de novo glomerulonephritis. Nephrotic range proteinuria was related to a high rate of graft loss.

Surgical Complications in Early Post-transplant Kidney Recipients.

BACKGROUND: The purpose of this study was to determine the incidence of early surgical complications of kidney transplantation in our institution and its association with donor and recipient factors, as well as patient and transplant outcome. METHODS: A retrospective cohort study of all kidney transplants performed during 2015 was made. We evaluated the incidence of surgical complications and the outcome of patients and grafts at a 3-month follow-up interval. RESULTS: During the study period, 141 kidney transplants occurred. Seventeen patients had surgical complications (6 urologic, 6 vascular, and 5 other complications). Five patients lost the graft during the follow-up. Older age was associated with other surgical complications (P = .023), and graft loss was associated with the existence of surgical complications, namely, vascular complications (P <.001). For both surgical complications in general and urologic complications, a statistically significant relationship was found with patient weight (P = .003 and P = .034, respectively). The correlation between body mass index (BMI) and surgical complications was not statistically significant. CONCLUSIONS: Our study reveals that older and heavier patients have a higher risk of surgical complications and that vascular complications are associated with graft loss. A statistically significant relationship was not found between BMI and surgical complications, which could indicate that BMI is not the ideal obesity marker. The incidence of surgical complications found in our study is similar to the literature. The selection of transplant recipients is a difficult task, and the possibility of additional surgical complications in older and overweight patients should be taken into account.

What Can We Do When All Collapses? Fatal Outcome of Collapsing Glomerulopathy and Systemic Lupus Erythematosus With Diffuse Alveolar Hemorrhage: Case Report.

INTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury. Although commonly associated with human immunodeficiency virus (HIV) infection, it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT: We present the case of a 50-year-old man, with chronic kidney disease secondary to focal and segmental glomerulosclerosis, who received a cadaveric kidney transplant in 2007. There were no relevant intercurrences until May 2015, when he presented with nephrotic range proteinuria (± 4 g/d). A graft biopsy was performed and it did not show any significant pathological changes. In September, he developed a full nephrotic syndrome (proteinuria 19 g/d) and a graft biopsy was repeated. CG features were evident with a rich immunofluorescence. Antinuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies were positive; the remaining immunologic study was normal. Viral markers for HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) were negative. The patient was treated with corticosteroid pulses and plasmapheresis (seven treatments). A rapid deterioration of kidney function was seen and he became dialysis dependent. He was discharged with a low-dose immunosuppressive treatment. In October, he was hospitalized with diffuse alveolar hemorrhage (DAH). The auto-immune study was repeated, revealing complement consumption and positive titers of ANA and Anti-dsDNA antibodies. Anti-neutrophil cytoplasmic antibodies (ANCAs) and antiglomerular basement membrane antibody (anti-GBM) were negative. Treatment with intravenous corticosteroids, plasmapheresis, and human immunoglobulin was ineffective and the outcome was fatal. CONCLUSION: This case report highlights the possible association of CG and SLE. To our knowledge, it is the first case of SLE presenting with CG and DAH, with the singularity of occurring in a kidney transplant recipient receiving immunosuppression.

Adsorption and migration of single metal atoms on the calcite (10.4) surface.

Transition metal atoms are one of the key ingredients in the formation of functional 2D metal organic coordination networks. Additionally, the co-deposition of metal atoms can play an important role in anchoring the molecular structures to the surface at room temperature. To gain control of such processes requires the understanding of adsorption and diffusion properties of the different transition metals on the target surface. Here, we used density functional theory to investigate the adsorption of 3d (Ti, Cr, Fe, Ni, Cu), 4d (Zr, Nb, Mo, Pd, Ag) and 5d (Hf, W, Ir, Pt, Au) transition metal adatoms on the insulating calcite (10.4) surface. We identified the most stable adsorption sites and calculated binding energies and corresponding ground state structures. We find that the preferential adsorption sites are the Ca-Ca bridge sites. Apart from the Cr, Mo, Cu, Ag and Au all the studied metals bind strongly to the calcite surface. The calculated migration barriers for the representative Ag and Fe atoms indicates that the metal adatoms are mobile on the calcite surface at room temperature. Bader analysis suggests that there is no significant charge transfer between the metal adatoms and the calcite surface.

Waist-to-height ratio is independently related to whole and central body fat, regardless of the waist circumference measurement protocol, in non-alcoholic fatty liver disease patients.

BACKGROUND: Waist-to-height ratio (WHtR) has been reported as a preferable risk related body fat (BF) marker, although no standardised waist circumference measurement protocol (WCmp) has been proposed. The present study aimed to investigate whether the use of a different WCmp affects the strength of relationship between WHtR and both whole and central BF in non-alcoholic fatty liver disease (NAFLD) patients. METHODS: BF was assessed with dual energy X-ray absorptiometry (DXA) in 28 NAFLD patients [19 males, mean (SD) 51 (13) years and nine females, 47 (13) years]. All subjects also underwent anthropometric evaluation including height and waist circumference (WC) measurement using four different WCmp (WC1, minimal waist; WC2, iliac crest; WC3, mid-distance between iliac crest and lowest rib; WC4, at the umbilicus) and WHtR was calculated using each WC measurements (WHtR1, WHtR2, WHtR3 and WHtR4, respectively). Partial correlations were conducted to assess the relation of WHtR and DXA assessed BF. RESULTS: All WHtR were particularly correlated with central BF, including abdominal BF (r = 0.80, r = 0.84, r = 0.84 and r = 0.78, respectively, for WHtR1, WHtR2, WHtR3 and WHtR4) and central abdominal BF (r = 0.72, r = 0.77, r = 0.76 and r = 0.71, respectively, for WHtR1, WHtR2, WHtR3 and WHtR4), after controlling for age, sex and body mass index. There were no differences between the correlation coefficients obtained between all studied WHtR and each whole and central BF variable. CONCLUSIONS: Waist-to-height ratio was found a suitable BF marker in the present sample of NAFLD patients and the strength of the relationship between WHtR and both whole and central BF was not altered by using different WCmp in the present sample of NAFLD patients.

Centrocestus formosanus (Trematoda: Heterophyidae) in Melanoides tuberculata (Gastropoda: Thiaridae) from Vila do Abraão, Ilha Grande, Rio de Janeiro, Brazil.

Pleurolophocercous cercariae found in the invasive gastropod Melanoides tuberculata (Müller, 1774) collected in a stream of the Vila do Abraão, Ilha Grande, Angra dos Reis, Rio de Janeiro, Brazil were used for experimental infection that enabled the identification of the heterophyid trematode Centrocestus formosanus (Nishigori, 1924). The parasite has been found in the locality since 2007, after two years of the introduction of M. tuberculata. Recently, from a sample of 483 specimens collected in June 2013, 101 (21%) were found infected with parasite. The potential environmental impacts caused by the parasite occurrence could be underestimated in the country, and actions to monitor and control both the parasite and the mollusk are necessary.