Prophylactic Anticoagulation Reduces the Risk of Kidney Graft Venous Thrombosis in Recipients From Uncontrolled Donation After Circulatory Death Donors With High Renal Resistive Index.

Background: Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplantation (KT) at the expense of a higher risk of primary graft nonfunction (PNF). At least half of the cases of PNF are secondary to graft venous thrombosis. The potential benefit from prophylactic anticoagulation in this scenario remains unclear. Methods: In this single-center retrospective study we compared 2 consecutive cohorts of KT from uDCD with increased (≥0.8) renal resistive index (RRI) in the Doppler ultrasound examination performed within the first 24-72 h after transplantation: 36 patients did not receive anticoagulation ("nonanticoagulation group") and 71 patients underwent prophylactic anticoagulation until normalization of RRI in follow-up Doppler examinations ("anticoagulation group"). Results: Anticoagulation was initiated at a median of 2 d (interquartile range, 2-3) after transplantation and maintained for a median of 12 d (interquartile range, 7-18). In 4 patients (5.6%), anticoagulation had to be prematurely stopped because of the development of a hemorrhagic complication. In comparison with the nonanticoagulation group, recipients in the anticoagulation group had a lower 2-wk cumulative incidence of graft venous thrombosis (19.4% versus 0.0%; P < 0.001) and PNF (19.4% versus 2.8%; P = 0.006). The competing risk analysis with nonthrombotic causes of PNF as the competitive event confirmed the higher risk of graft thrombosis in the nonanticoagulation group (P = 0.0001). The anticoagulation group had a higher incidence of macroscopic hematuria (21.1% versus 5.6%; P = 0.049) and blood transfusion requirements (39.4% versus 19.4%; P = 0.050) compared with the nonanticoagulation group. No graft losses or deaths were attributable to complications potentially associated with anticoagulation. Conclusions: Early initiation of prophylactic anticoagulation in selected KT recipients from uDCD with an early Doppler ultrasound RRI of ≥0.8 within the first 24-72 h may reduce the incidence of graft venous thrombosis as a cause of PNF.

Association between urinary fluoride concentrations and the prevalence of metabolic syndrome in adult individuals from the Central Region of Mexico.

Emerging scientific studies have supported the hypothesis that exposure to environmental chemicals increases the incidence of diverse human metabolic disorders. Therefore, this study aimed to evaluate the association between fluoride exposure and metabolic syndrome (MetS) prevalence in people from the Central Region of Mexico. This research included 575 adult individuals. Urinary fluoride concentrations were determined using a potentiometric method. Anthropometric measurements and blood pressure were also acquired. Serum fasting glucose and lipid levels were quantified. For the MetS screening, we used the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The mean urinary fluoride levels were 3.50 ± 2.50 mg/L. The prevalence of MetS was approximately 27 and 25% according to NCEP ATP III and IDF criteria, respectively. A multivariate logistic regression analysis showed significant associations (p < 0.05) between urinary fluoride concentrations and MetS occurrence using NCEP ATP III criteria (OR = 1.60; 95% CI 1.05-2.10) and IDF criteria (OR = 1.35; 95% CI 0.95-1.45). These findings emphasize the need to discover the underlying mechanisms that fluoride exposure has on MetS pathogenesis.

The aryl hydrocarbon receptor (AhR) activation mediates benzo(a)pyrene-induced overexpression of AQP3 and Notch1 in HaCaT cells.

The aim of this study was twofold: (1) evaluate the effect of benzo[a]pyrene (BaP) on expression levels of AQP3 and Notch1 genes in HaCaT cells exposed "in vitro" and (2) investigate the possible biological role of assessed genes by bioinformatics methods. Cells were exposed to increasing concentrations of BaP (0.0-4.0 µM) for 1-4 days. After treatments, cell viability and expression levels of AhR, CYP1A1, AQP3, and Notch1 genes were evaluated. The possible biological role of assessed genes was evaluated using bioinformatics tools. Low cytotoxicity in HaCaT cells dosed with BaP was detected. A significant overexpression (p < .05) of CYP1A1, AQP3, and Notch1 was found in exposed HaCaT cells. The gene expression upregulation was dependent on AhR activation. The bioinformatics analysis showed that these genes were enriched in related cancer signaling pathways. The findings suggest that AQP3 and Notch1 are upregulated by AhR activation in HaCaT cells exposed to BaP.

Obesity related pathophysiological aspects favouring Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a complex entity and one of the most frequents in general population. Association of GERD with obesity is clearly defined from an epidemiological point of view, where up to 40% of patients with overweight and obesity present reflux. Most of the risk factors associated to GERD are shared and especially frequent in patients with obesity. The pathophysiology that explain this correlation is complex and multifactorial, and includes both aspects related to physiology of motility, and anatomic changes. The malfunction of the lower esophageal sphincter, the greater transdiaphragmatic pressure gradient, pathological accumulation of fat and the high rate of hiatal hernia that comes with overweight will be the main factors that explain this correlation. Other factor like pathological eating habits or obesity related diseases have also an important role. In summary, it is the sum of the factors more than just one of them what would explain the pathophysiology of GERD in obese population.

Influence of donor capnometry on renal graft evolution in uncontrolled donation after circulatory death.

AIM: To analyse the association between donor capnometry data and the short-term evolution of kidney grafts in cases of uncontrolled donation after circulatory death (uDCD). METHOD: We used an ambispective observational study design, conducted in the Community of Madrid between January and December 2019, inclusive. Patients who suffered out-of-hospital cardiac arrest (CA) with no response to advanced cardiopulmonary resuscitation (CPR) were selected as potential donors. Donor capnometry levels were measured at the start, midpoint and transfer to hospital then compared with indicators of renal graft evolution. RESULTS: The initial selection included 34 possible donors, of which 12 (35.2%) were viable donors from whom 22 (32.3%) kidneys were recovered. There was a correlation between the highest capnometry values and less need for post-transplant dialysis (≥24 mmHg, p < 0.017), fewer dialysis sessions and fewer days to recover correct renal function (Rho -0.47, p < 0.044). There was a significant inverse correlation between the capnometry values at transfer and 1-month post-transplant creatinine levels (Rho -0.62, p < 0.033). There were no significant differences between the capnometry values at transfer and primary nonfunction (PNF) or warm ischaemia time. One-year patient survival was 100% for patient receiving organ donation, while graft survival was 95%. CONCLUSIONS: Capnometry levels at transfer are a useful predictor of the short-term function and viability of kidney transplants from uncontrolled donations after circulatory death.

Effect of Glutamic Acid and 6-benzylaminopurine on Flower Bud Biostimulation, Fruit Quality and Antioxidant Activity in Blueberry.

Blueberry is a highly demanded and consumed fruit due to its beneficial effects on human health, because of its bioactive compounds with a high antioxidant capacity. The interest in increasing the yield and quality of blueberries has led to the application of some innovative techniques such as biostimulation. The objective of this research was to assess the effect of the exogenous application of glutamic acid (GLU) and 6-benzylaminopurine (6-BAP) as biostimulants on flower bud sprouting, fruit quality, and antioxidant compounds in blueberry cv. Biloxi. The application of GLU and 6-BAP positively affected bud sprouting, fruit quality, and antioxidant content. The application of 500 and 10 mg L-1 GLU and 6-BAP, respectively, increased the number of flower buds, while 500 and 20 mg L-1 generated fruits with higher content of flavonoids, vitamin C, and anthocyanins and higher enzymatic activity of catalase and ascorbate peroxidase enzymes. Hence, the application of these biostimulants is an effective way to enhance the yield and fruit quality of blueberries.

Multipixel x ray detection integrated at the end of a narrow multicore fiber.

We introduce and demonstrate the concept of a multipixel detector integrated at the tip of an individual multicore fiber. A pixel consists here of an aluminum-coated polymer microtip incorporating a scintillating powder. Upon irradiation, the luminescence released by the scintillators is efficiently transferred into the fiber cores owing to the specifically elongated metal-coated tips that ensure efficient luminescence matching to the fiber modes. With each pixel being selectively coupled to one of the cores of the multicore optical fiber, the resulting fiber-integrated x ray detection process is totally free from inter-pixel cross talk. Our approach holds promise for fiber-integrated probes and cameras for remote x and gamma ray analysis and imaging in hard-to-reach environments.

Correction: Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

[This corrects the article DOI: 10.1371/journal.pntd.0009145.].

Expression levels and network analysis of inflammamiRs in peripheral blood mononuclear cells exposed to DDE "in vitro".

Recent studies have demonstrated that dichlorodiphenyldichloroethylene (DDE) induced a pro-inflammatory condition in peripheral blood mononuclear cells (PBMC). However, the molecular mechanisms implicated in this condition are poorly understood. Therefore, this study aimed to evaluate miR-155, miR-126, and miR-21 expression levels in PBMC exposed "in vitro" to DDE. PBMC were dosed with increasing concentrations of DDE (10-80 µg mL-1) at different treatment times (0-24 h). The results showed an up-regulation in the expression levels of assessed miRNAs (miR-155, miR-146, and miR-21) after PBMCs were exposed to DDE. Besides, bioinformatic analysis was performed to understand the biological roles of assessed miRNAs. The bioinformatic analysis shows that assessed miRNAs are associated with regulating signaling pathways involved in cancer, apoptosis, cell cycle, inflammation, metabolism, etc. These findings offer new insights into the molecular mechanisms related to the inflammatory processes and their regulation induced by DDE in PBMC exposed "in vitro".

Transcriptomic Analysis of the Aged Nulliparous Mouse Ovary Suggests a Stress State That Promotes Pro-Inflammatory Lipid Signaling and Epithelial Cell Enrichment.

Ovarian cancer (OC) incidence and mortality peaks at post-menopause while OC risk is either reduced by parity or increased by nulliparity during fertile life. The long-term effect of nulliparity on ovarian gene expression is largely unknown. In this study, we describe a bioinformatic/data-mining analysis of 112 coding genes upregulated in the aged nulliparous (NP) mouse ovary compared to the aged multiparous one as reference. Canonical gene ontology and pathway analyses indicated a pro-oxidant, xenobiotic-like state accompanied by increased metabolism of inflammatory lipid mediators. Up-regulation of typical epithelial cell markers in the aged NP ovary was consistent with synchronized overexpression of Cldn3, Ezr, Krt7, Krt8 and Krt18 during the pre-neoplastic phase of mOSE cell cultures in a former transcriptome study. In addition, 61/112 genes were upregulated in knockout mice for Fshr and for three other tumor suppressor genes (Pten, Cdh1 and Smad3) known to regulate follicular homeostasis in the mammalian ovary. We conclude that the aged NP ovary displays a multifaceted stress state resulting from oxidative imbalance and pro-inflammatory lipid signaling. The enriched epithelial cell content might be linked to follicle depletion and is consistent with abundant clefts and cysts observed in aged human and mouse ovaries. It also suggests a mesenchymal-to-epithelial transition in the mOSE of the aged NP ovary. Our analysis suggests that in the long term, nulliparity worsens a variety of deleterious effects of aging and senescence thereby increasing susceptibility to cancer initiation in the ovary.

Schizophrenia-derived hiPSC brain microvascular endothelial-like cells show impairments in angiogenesis and blood-brain barrier function.

Schizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed to a possible vascular deficiency that could be acting synergistically with neuronal dysfunction in SZ. As SZ is a neurodevelopmental disease, the use of human-induced pluripotent stem cells (hiPSC) allows disease biology modeling while retaining the patient's unique genetic signature. Previously, we reported a VEGFA signaling impairment in SZ-hiPSC-derived neural lineages leading to decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective blood-brain barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BEC's conditioned media reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis tracing schizophrenia origins to brain development and BBB dysfunction.

Plastia mitral en endocarditis infecciosa: reporte de un caso / Mitral valve repair in infective endocarditis: a case report / Plastia mitral em endocardite infecciosa: relato de um caso

La endocarditis infecciosa es una patología heterogénea con una alta mortalidad y requiere tratamiento quirúrgico en al menos la mitad de los casos. Cuando asienta en posición mitral, la reparación valvular en lugar de su sustitución, si bien representa un desafío técnico, ha ido ganando terreno en los últimos años. Describimos el caso de un paciente que se presentó con una endocarditis sobre válvula nativa mitral en quien se realizó una plastia valvular exitosa. Revisaremos la evidencia acerca de su beneficio.

Infective endocarditis is a heterogeneous disease with a high mortality and that requires surgical treatment in at least half of cases. When seated in mitral position, valve repair rather than replacement, while technically challenging, has been gaining popularity in recent years. We describe the case of a patient who presented with a mitral valve endocarditis in whom a successful valve repair was performed. Evidence supporting its use will be reviewed.

A endocardite infecciosa é uma doença heterogênea com alta mortalidade que requer tratamento cirúrgico em pelo menos metade dos casos. Quando sentado na posição mitral, o reparo da válvula, em vez da substituição da válvula, embora seja um desafio técnico, tem ganhado espaço nos últimos anos. Descrevemos o caso de um paciente que apresentou endocardite valvar mitral nativa, no qual foi realizada plastia valvar com sucesso. Vamos revisar as evidências sobre o seu benefício.

Hipertensión pulmonar en cardiopatías congénitas del adulto / Pulmonary hypertension in adult congenital heart disease / Hipertensão pulmonar na cardiopatia congênita do adulto

Introducción: la hipertensión pulmonar asociada a cardiopatías congénitas del adulto implica un amplio espectro de situaciones clínicas complejas de difícil manejo para el cardiólogo clínico. Revisión: se repasarán los principales aspectos fisiopatológicos relacionados con el desarrollo de hipertensión pulmonar en los diferentes grupos de cardiopatías congénitas, así como los criterios para establecer el diagnóstico. Se discutirá el tratamiento guiado por perfil de riesgo y los grupos farmacológicos disponibles en nuestro medio. Por último, se discutirán grupos especiales, como el síndrome de Eisenmenger y la embarazada con cardiopatía e hipertensión pulmonar. Conclusión: es importante tener presente de todas formas que la hipertensión pulmonar en este escenario puede tener un mal pronóstico (como en el síndrome de Eisenmenger), por lo cual se deben realizar los mayores esfuerzos para hacer un diagnóstico precoz y tratamiento oportuno de estos pacientes.

Introduction: pulmonary hypertension associated with congenital heart disease in adults involves a wide spectrum of complex clinical situations that are difficult to manage for the clinical cardiologist. Review: the main pathophysiological aspects related to the development of pulmonary hypertension in the different groups of congenital heart disease will be reviewed, as well as the criteria to establish the diagnosis. Treatment guided by risk profile and the pharmacological groups available in our setting will be discussed. Finally, special groups such as Eisenmenger syndrome and pregnant women with heart disease and pulmonary hypertension will be discussed. Conclusion: it is important to keep in mind, however, that pulmonary hypertension in this scenario could have a poor prognosis (for example in Eisenmenger syndrome), which is why every effort should be made to make an early diagnosis and timely treatment of these patients.

Introdução: a hipertensão pulmonar associada à cardiopatia congênita em adultos envolve um amplo espectro de situações clínicas complexas e de difícil manejo para o cardiologista clínico. Revisão: serão revistos os principais aspectos fisiopatológicos relacionados ao desenvolvimento da hipertensão pulmonar nos diferentes grupos de cardiopatias congênitas, bem como os critérios para estabelecer o diagnóstico. Serão discutidos o tratamento guiado pelo perfil de risco e os grupos farmacológicos disponíveis em nosso meio. Por fim, serão discutidos grupos especiais como síndrome de Eisenmenger e gestantes com cardiopatia e hipertensão pulmonar. Conclusão: de qualquer forma, é importante ter em mente que a hipertensão pulmonar nesse cenário pode ter um prognóstico ruim (como na síndrome de Eisenmenger), razão pela qual todo esforço deve ser feito para o diagnóstico precoce e tratamento oportuno desses pacientes.

Intra-host genetic population diversity: Role in emergence and persistence of drug resistance among Mycobacterium tuberculosis complex minor variants.

Drug resistant tuberculosis (DR-TB) is an important public health issue in different parts of the world. Mycobacterium tuberculosis complex variants (MTBC vars) preferentially infect certain hosts, limiting their distribution to different ecosystems. However, MTBC vars can infect other hosts beyond their preferred target potentially contributing to persistence of drug resistance (DR) in other niches. Here, we performed a comprehensive intra-host genetic analysis for the identification of DR-related mutations among all MTBC minor vars whole genome sequences (8,095 strains) publicly available worldwide. High confidence drug-resistance mutations in katG (isoniazid), rpsL (streptomycin), pncA (pyrazinamide), rpoB (rifampicin) and gyrA (fluoroquinolones) genes were identified among intrahost minor sub-populations in 197 different strains (2.43%) belonging to vars africanum, bovis, caprae, microti, orygis and pinnipedii. In addition, a three-dimensional structure modeling analysis to assess the role of novel mutations was also performed. Our findings highlight the importance of detecting discrete intra-host populations carrying DR mutations.

Analysis of the Management of Cholelithiasis in Bariatric Surgery Patients: a Single-Center Experience.

PURPOSE: Cholelithiasis is an issue in bariatric surgery patients. The incidence of cholelithiasis is increased in morbidly obese patients. After bariatric surgery, the management maybe sometimes challenging. There is no consensus about how to deal with cholelithiasis prior to bariatric surgery. MATERIALS AND METHODS: A retrospective review from our prospectively collected bariatric surgery database. Primary bariatric procedures from 2009 to 2020 were included. Prevalence of cholelithiasis and its management prior to bariatric surgery and the incidence and management of postoperative biliary events were analyzed. RESULTS: Over 1445 patients analyzed, preoperatively cholelithiasis was found in 153 (10.58%), and 68 out of them (44.44%) were symptomatic. Seventy-six patients had a concomitant cholecystectomy. In those cases, the bariatric procedure did not show increased operative time, length of stay, morbidity, or mortality compared to the rest of primary bariatric procedures. Twelve patients (15.58%) with previous cholelithiasis and no concomitant cholecystectomy presented any kind of biliary event and required cholecystectomy. De novo cholelithiasis rate requiring cholecystectomy was 3.86%. Postoperative biliary events both in de novo and persistent cholelithiasis population did not show any difference between the type of surgery, weight loss, and other characteristics. CONCLUSIONS: Cholelithiasis was present in 10.58% of our primary bariatric surgery population. Concomitant cholecystectomy was safe in our series. Non-surgical management of asymptomatic cholelithiasis did not lead to a higher risk of postoperative biliary events. The global postoperative cholecystectomy rate was equivalent to the general population.

A first assessment of the distribution and abundance of large pelagic species at Cocos Ridge seamounts (Eastern Tropical Pacific) using drifting pelagic baited remote cameras.

Understanding the link between seamounts and large pelagic species (LPS) may provide important insights for the conservation of these species in open water ecosystems. The seamounts along the Cocos Ridge in the Eastern Tropical Pacific (ETP) ocean are thought to be ecologically important aggregation sites for LPS when moving between Cocos Island (Costa Rica) and Galapagos Islands (Ecuador). However, to date, research efforts to quantify the abundance and distribution patterns of LPS beyond the borders of these two oceanic Marine Protected Areas (MPAs) have been limited. This study used drifting-pelagic baited remote underwater video stations (BRUVS) to investigate the distribution and relative abundance of LPS at Cocos Ridge seamounts. Our drifting-pelagic BRUVS recorded a total of 21 species including elasmobranchs, small and large teleosts, dolphins and one sea turtle; of which four species are currently threatened. Depth of seamount summit was the most significant driver for LPS richness and abundance which were significantly higher at shallow seamounts (< 400 m) compared to deeper ones (> 400m). Distance to nearest MPA was also a significant predictor for LPS abundance, which increased at increasing distances from the nearest MPA. Our results suggest that the Cocos Ridge seamounts, specifically Paramount and West Cocos which had the highest LPS richness and abundance, are important aggregation sites for LPS in the ETP. However, further research is still needed to demonstrate a positive association between LPS and Cocos Ridge seamounts. Our findings showed that drifting pelagic BRUVS are an effective tool to survey LPS in fully pelagic ecosystems of the ETP. This study represents the first step towards the standardization of this technique throughout the region.

Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

Identifying the Mycobacterium tuberculosis resistance mutation patterns is of the utmost importance to assure proper patient's management and devising of control programs aimed to limit spread of disease. Zoonotic Mycobacterium bovis infection still represents a threat to human health, particularly in dairy production regions. Routinary, molecular characterization of M. bovis is performed primarily by spoligotyping and mycobacterial interspersed repetitive units (MIRU) while next generation sequencing (NGS) approaches are often performed by reference laboratories. However, spoligotyping and MIRU methodologies lack the resolution required for the fine characterization of tuberculosis isolates, particularly in outbreak settings. In conjunction with sophisticated bioinformatic algorithms, whole genome sequencing (WGS) analysis is becoming the method of choice for advanced genetic characterization of tuberculosis isolates. WGS provides valuable information on drug resistance and compensatory mutations that other technologies cannot assess. Here, we performed an analysis of the most frequently identified mutations associated with tuberculosis drug resistance and their genetic relationship among 2,074 Mycobacterium bovis WGS recovered primarily from non-human hosts. Full-length gene sequences harboring drug resistant associated mutations and their phylogenetic relationships were analyzed. The results showed that M. bovis isolates harbor mutations conferring resistance to both first- and second-line antibiotics. Mutations conferring resistance for isoniazid, fluoroquinolones, streptomycin, and aminoglycosides were identified among animal strains. Our findings highlight the importance of molecular surveillance to monitor the emergence of mutations associated with multi and extensive drug resistance in livestock and other non-human mammals.