Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

BACKGROUND: Kidney transplantation is the optimal treatment for kidney failure. Donation, transport and transplant of kidney grafts leads to significant ischaemia reperfusion injury. Static cold storage (SCS), whereby the kidney is stored on ice after removal from the donor until the time of implantation, represents the simplest preservation method. However, technology is now available to perfuse or "pump" the kidney during the transport phase ("continuous") or at the recipient centre ("end-ischaemic"). This can be done at a variety of temperatures and using different perfusates. The effectiveness of these treatments manifests as improved kidney function post-transplant. OBJECTIVES: To compare machine perfusion (MP) technologies (hypothermic machine perfusion (HMP) and (sub) normothermic machine perfusion (NMP)) with each other and with standard SCS. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies until 15 June 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs comparing machine perfusion techniques with each other or versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory death (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The results of the literature search were screened, and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Survival analyses (time-to-event) were performed with the generic inverse variance meta-analysis of hazard ratios (HR). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was the incidence of delayed graft function (DGF). Secondary outcomes included graft survival, incidence of primary non-function (PNF), DGF duration, economic implications, graft function, patient survival and incidence of acute rejection. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Twenty-two studies (4007 participants) were included. The risk of bias was generally low across all studies and bias domains. The majority of the evidence compared non-oxygenated HMP with standard SCS (19 studies). The use of non-oxygenated HMP reduces the rate of DGF compared to SCS (16 studies, 3078 participants: RR 0.78, 95% CI 0.69 to 0.88; P < 0.0001; I2 = 31%; high certainty evidence). Subgroup analysis revealed that continuous (from donor hospital to implanting centre) HMP reduces DGF (high certainty evidence). In contrast, this benefit over SCS was not seen when non-oxygenated HMP was not performed continuously (low certainty evidence). Non-oxygenated HMP reduces DGF in both DCD and DBD settings in studies performed in the 'modern era' and when cold ischaemia times (CIT) were short. The number of perfusions required to prevent one episode of DGF was 7.69 and 12.5 in DCD and DBD grafts, respectively. Continuous non-oxygenated HMP versus SCS also improves one-year graft survival (3 studies, 1056 participants: HR 0.46, 0.29 to 0.75; P = 0.002; I2 = 0%; high certainty evidence). Assessing graft survival at maximal follow-up confirmed a benefit of continuous non-oxygenated HMP over SCS (4 studies, 1124 participants (follow-up 1 to 10 years): HR 0.55, 95% CI 0.40 to 0.77; P = 0.0005; I2 = 0%; high certainty evidence). This effect was not seen in studies where HMP was not continuous. The effect of non-oxygenated HMP on our other outcomes (PNF, incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. Studies performing economic analyses suggest that HMP is either cost-saving (USA and European settings) or cost-effective (Brazil). One study investigated continuous oxygenated HMP versus non-oxygenated HMP (low risk of bias in all domains); the simple addition of oxygen during continuous HMP leads to additional benefits over non-oxygenated HMP in DCD donors (> 50 years), including further improvements in graft survival, improved one-year kidney function, and reduced acute rejection. One large, high-quality study investigated end-ischaemic oxygenated HMP versus SCS and found end-ischaemic oxygenated HMP (median machine perfusion time 4.6 hours) demonstrated no benefit compared to SCS. The impact of longer periods of end-ischaemic HMP is unknown. One study investigated NMP versus SCS (low risk of bias in all domains). One hour of end ischaemic NMP did not improve DGF compared with SCS alone. An indirect comparison revealed that continuous non-oxygenated HMP (the most studied intervention) was associated with improved graft survival compared with end-ischaemic NMP (indirect HR 0.31, 95% CI 0.11 to 0.92; P = 0.03). No studies investigated normothermic regional perfusion (NRP) or included any donors undergoing NRP. AUTHORS' CONCLUSIONS: Continuous non-oxygenated HMP is superior to SCS in deceased donor kidney transplantation, reducing DGF, improving graft survival and proving cost-effective. This is true for both DBD and DCD kidneys, both short and long CITs, and remains true in the modern era (studies performed after 2008). In DCD donors (> 50 years), the simple addition of oxygen to continuous HMP further improves graft survival, kidney function and acute rejection rate compared to non-oxygenated HMP. Timing of HMP is important, and benefits have not been demonstrated with short periods (median 4.6 hours) of end-ischaemic HMP. End-ischaemic NMP (one hour) does not confer meaningful benefits over SCS alone and is inferior to continuous HMP in an indirect comparison of graft survival. Further studies assessing NMP for viability assessment and therapeutic delivery are warranted and in progress.

Morphological comparison of the larynx and trachea of Chelonia mydas (Linnaeus, 1758), Caiman yacare (Daudin, 1802) and Caiman latirostris (Daudin, 1802).

The larynx is in the lower respiratory tract and has the function of protecting the airways, controlling, and modulating breathing, assisting the circulatory system, and vocalizing. This study aims to describe the anatomy and histology of the skeleton of the larynx and trachea of the species Chelonia mydas, Caiman yacare and Caiman latirostris. The study was conducted at the Federal University of Espírito Santo (UFES), using nine specimens of Ch. mydas, 20 of Ca. yacare and four of Ca. latirostris. Samples of the larynx and trachea were collected, fixed, and sent for dissection of the structures and subsequent macroscopic analysis. For histology, samples were processed by the routine paraffin embedding method and stained with hematoxylin-eosin and Verhoeff. For the three species, two arytenoid cartilages, a cricoid cartilage, a hyoid apparatus composed of a base and two horns were found. In Ch. mydas, two structures called thyroid wings were observed, not found in crocodilians. The trachea of crocodilians presented incomplete tracheal rings and musculature, while the trachea of Ch. mydas presented complete tracheal rings. Histologically, the entire cartilaginous skeleton of the larynx of the three species, as well as the tracheal rings, are constituted by hyaline cartilage.

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Assessment of inter-centre agreement across multidisciplinary team meetings for patients with retroperitoneal sarcoma.

BACKGROUND: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings. METHODS: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected. The main outcome was inter-centre reliability, which was quantified using overall agreement, as well as the chance-corrected Krippendorff's alpha statistic. Based on the latter, the level of agreement was classified as: 'slight' (0.00-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80), or 'near-perfect' (>0.80). RESULTS: Twenty-one patients were reviewed at 12 retroperitoneal sarcoma multidisciplinary team meetings, giving a total of 252 assessments for analysis. Consistency between centres was only 'slight' to 'fair', with rates of overall agreement and Krippendorff's alpha statistics of 85.4 per cent (211 of 247) and 0.37 (95 per cent c.i. 0.11 to 0.57) for resectability; 80.4 per cent (201 of 250) and 0.39 (95 per cent c.i. 0.33 to 0.45) for treatment allocation; and 53.0 per cent (131 of 247) and 0.20 (95 per cent c.i. 0.17 to 0.23) for the organs proposed to be resected. Depending on the centre that they had attended, 12 of 21 patients could either have been deemed resectable or unresectable, and 10 of 21 could have received either potentially curative or palliative treatment. CONCLUSIONS: Inter-centre agreement between retroperitoneal sarcoma multidisciplinary team meetings was low. Multidisciplinary team meetings may not provide the same standard of care for patients with retroperitoneal sarcoma across Great Britain.

Machine perfusion in liver transplantation.

BACKGROUND: Liver transplantation is the only chance of cure for people with end-stage liver disease and some people with advanced liver cancers or acute liver failure. The increasing prevalence of these conditions drives demand and necessitates the increasing use of donated livers which have traditionally been considered suboptimal. Several novel machine perfusion preservation technologies have been developed, which attempt to ameliorate some of the deleterious effects of ischaemia reperfusion injury. Machine perfusion technology aims to improve organ quality, thereby improving outcomes in recipients of suboptimal livers when compared to traditional static cold storage (SCS; ice box). OBJECTIVES: To evaluate the effects of different methods of machine perfusion (including hypothermic oxygenated machine perfusion (HOPE), normothermic machine perfusion (NMP), controlled oxygenated rewarming, and normothermic regional perfusion) versus each other or versus static cold storage (SCS) in people undergoing liver transplantation. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 10 January 2023. SELECTION CRITERIA: We included randomised clinical trials which compared different methods of machine perfusion, either with each other or with SCS. Studies comparing HOPE via both hepatic artery and portal vein, or via portal vein only, were grouped. The protocol detailed that we also planned to include quasi-randomised studies to assess treatment harms. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall participant survival, 2. quality of life, and 3. serious adverse events. Secondary outcomes were 4. graft survival, 5. ischaemic biliary complications, 6. primary non-function of the graft, 7. early allograft function, 8. non-serious adverse events, 9. transplant utilisation, and 10. transaminase release during the first week post-transplant. We assessed bias using Cochrane's RoB 2 tool and used GRADE to assess certainty of evidence. MAIN RESULTS: We included seven randomised trials (1024 transplant recipients from 1301 randomised/included livers). All trials were parallel two-group trials; four compared HOPE versus SCS, and three compared NMP versus SCS. No trials used normothermic regional perfusion. When compared with SCS, it was uncertain whether overall participant survival was improved with either HOPE (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.42 to 1.98; P = 0.81, I2 = 0%; 4 trials, 482 recipients; low-certainty evidence due to imprecision because of low number of events) or NMP (HR 1.08, 95% CI 0.31 to 3.80; P = 0.90; 1 trial, 222 recipients; very low-certainty evidence due to imprecision and risk of bias). No trials reported quality of life. When compared with SCS alone, HOPE was associated with improvement in the following clinically relevant outcomes: graft survival (HR 0.45, 95% CI 0.23 to 0.87; P = 0.02, I2 = 0%; 4 trials, 482 recipients; high-certainty evidence), serious adverse events in extended criteria DBD liver transplants (OR 0.45, 95% CI 0.22 to 0.91; P = 0.03, I2 = 0%; 2 trials, 156 participants; moderate-certainty evidence) and clinically significant ischaemic cholangiopathy in recipients of DCD livers (OR 0.31, 95% CI 0.11 to 0.92; P = 0.03; 1 trial, 156 recipients; high-certainty evidence). In contrast, NMP was not associated with improvement in any of these clinically relevant outcomes. NMP was associated with improved utilisation compared with SCS (one trial found a 50% lower rate of organ discard; P = 0.008), but the reasons underlying this effect are unknown. We identified 11 ongoing studies investigating machine perfusion technologies. AUTHORS' CONCLUSIONS: In situations where the decision has been made to transplant a liver donated after circulatory death or donated following brain death, end-ischaemic HOPE will provide superior clinically relevant outcomes compared with SCS alone. Specifically, graft survival is improved (high-certainty evidence), serious adverse events are reduced (moderate-certainty evidence), and in donors after circulatory death, clinically relevant ischaemic biliary complications are reduced (high-certainty evidence). There is no good evidence that NMP has the same benefits over SCS in terms of these clinically relevant outcomes. NMP does appear to improve utilisation of grafts that would otherwise be discarded with SCS; however, the reasons for this, and whether this effect is specific to NMP, is not clear. Further studies into NMP viability criteria and utilisation, as well as head-to-head trials with other perfusion technologies are needed. In the setting of donation following circulatory death transplantation, further trials are needed to assess the effect of these ex situ machine perfusion methods against, or in combination with, normothermic regional perfusion.

Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).

A new species of Comahuesuchus Bonaparte, 1991 (Crocodyliformes: Notosuchia) from the Upper Cretaceous of Neuquén, Lake Barreales, Patagonia, Argentina.

Notosuchian crocodyliforms were major components of the South American Cretaceous biota and, for over 125 years, paleontological fieldwork in this continent recovered several well-preserved fossils of these animals. They are largely recognized for terrestrial life and specialized feeding habits, frequently presenting bizarre taxa such as Comahuesuchus. A new species, Comahuesuchus bonapartei n. sp. (MUCPv 597; cast MN), is described from geological strata of Sierra Barrosa Formation (Upper Turonian) and Portezuelo Formation (Lower Coniacian) of Lake Barreales, Patagonia, Argentina. The new fossil comprises a right dentary bone that shares important and unique anatomical features with specimens of Comahuesuchus brachybuccalis, such as the presence of a well-marked shelf on the lateral surface of the bone; a flat, low, and wide mandibular symphysis; an enlarged, labiolingually compressed caniniform tooth at caudal position in the dentary; the presence of serrated mesial and distal carinae in the caniniform with a faceted labial surface, and the absence or extremely reduction in number of the postcaniniform dentition. C. bonapartei differs from C. brachybuccalis in having individual dentary alveoli, rather a dentition set in groove. Phylogenetic analyses support a sister-relationship between both species, which are well nested within notosuchians.

First record of insect-plant interaction in Late Cretaceous fossils from Nelson Island (South Shetland Islands Archipelago), Antarctica.

Despite the enormous paleobotanical record on different islands of the Antarctic Peninsula, the evidence of insect activity associated with fossilized plants is scarce. Here we report the first evidence of insect-plant interaction from Cretaceous deposits, more precisely from a new locality at the Rip Point area, Nelson Island (Antarctic Peninsula). The macrofossil assemblage includes isolated Nothofagus sp. leaf impressions, a common component of the Antarctic paleoflora. Two hundred leaves were examined, of which 15 showed evidence of insect activity, displaying variations in size, shape, and preservation. Two types of interaction damage, galls and mines, were identified. A single specimen retained a circular scar recognized as galling scar, while meandering tracks were considered mines. These traces of herbivore insect activity, correspond to the oldest known record of this type of interaction of West Antarctica and the oldest record of insect-plant interaction in Nothofagus sp. reported so far.

Study of the phytoremediation potential of native plant species identified in an area contaminated by volatile organic compounds: a systematic review.

Phytoremediation is a process that uses plants in situ to promote remediation of environments contaminated by organic or inorganic compounds. Phytoremediating species develop methods such as phytoextraction, rhizofiltration, phytodegradation, and phytovolatilization, which can manifest themselves individually or together in a single plant. This study aims to evaluate, through a systematic review, the potential phytoremediation techniques of the genera Syagrus (Mart.), Nephrolepis, Cyperus (L.), Mimosa (L.), Schinus (L.), Brachiaria, and Eryngium (L.) found in a humid area of Rio Grande do Sul, Brazil. The genera that presented significant numbers in the databases consulted were Cyperus and Brachiaria, followed by Nephrolepis. The first two are considered the most promising for phytoremediation processes. The other genera mentioned obtained favorable results for organic contaminants. The studies around these genera are still recent. It is necessary, in research, to highlight which phytoremediation processes the plants exert in relation to the contaminant of the place. In addition, priority should be given to native species that can establish themselves in the environment and that would not unbalance and harm the surrounding biota and ecosystem.

The research presents a survey of two decades in four multidisciplinary and international databases, identifying the limitation of research related to volatile and semi-volatile organic compounds, as well as contributing to the identification of native plant species that perform phytoremediation mechanisms.

Use of Deep Neural Networks in the Detection and Automated Classification of Lesions Using Clinical Images in Ophthalmology, Dermatology, and Oral Medicine-A Systematic Review.

Artificial neural networks (ANN) are artificial intelligence (AI) techniques used in the automated recognition and classification of pathological changes from clinical images in areas such as ophthalmology, dermatology, and oral medicine. The combination of enterprise imaging and AI is gaining notoriety for its potential benefits in healthcare areas such as cardiology, dermatology, ophthalmology, pathology, physiatry, radiation oncology, radiology, and endoscopic. The present study aimed to analyze, through a systematic literature review, the application of performance of ANN and deep learning in the recognition and automated classification of lesions from clinical images, when comparing to the human performance. The PRISMA 2020 approach (Preferred Reporting Items for Systematic Reviews and Meta-analyses) was used by searching four databases of studies that reference the use of IA to define the diagnosis of lesions in ophthalmology, dermatology, and oral medicine areas. A quantitative and qualitative analyses of the articles that met the inclusion criteria were performed. The search yielded the inclusion of 60 studies. It was found that the interest in the topic has increased, especially in the last 3 years. We observed that the performance of IA models is promising, with high accuracy, sensitivity, and specificity, most of them had outcomes equivalent to human comparators. The reproducibility of the performance of models in real-life practice has been reported as a critical point. Study designs and results have been progressively improved. IA resources have the potential to contribute to several areas of health. In the coming years, it is likely to be incorporated into everyday life, contributing to the precision and reducing the time required by the diagnostic process.

Pharmacological testing of therapeutics using normothermic machine perfusion: A pilot study of 2,4-dinitrophenol delivery to steatotic human livers.

INTRODUCTION: Normothermic machine perfusion (NMP) provides a platform for drug-delivery. However, pharmacological considerations for therapeutics delivered during NMP are scarcely reported. We aimed to demonstrate the ability of NMP as a platform for pharmacological testing, using a drug which increases metabolism (2,4-dinitrophenol; DNP) as an example therapeutic. METHODS: We performed 25 h of NMP on human livers which had been declined for transplant due to steatosis (n = 7). Three livers received a DNP bolus, three were controls, and one received a DNP infusion. RESULTS: Toxicity studies revealed DNP delivery was safe, without hepatotoxic effects. The liver surface temperature was increased in the DNP group (p = 0.046), but no livers suffered hyperthermia-the mechanism of DNP toxicity in vivo. Pharmacokinetic studies revealed DNP elimination with first-order kinetics and 7.7 h half-life (95% CI = 5.1-15.9 hrs). The clearance of DNP in bile was negligible. As expected, DNP significantly increased oxygen consumption (p = 0.023); this increase was closely correlated with perfusate DNP concentration (r2  = 0.975; p = 0.002) and the effect was lost as DNP was eliminated by the liver. A DNP infusion rate, calculated using our pharmacokinetic data, successfully maintained perfusate DNP concentration. DISCUSSION: Detailed pharmacological testing can be performed during NMP. Our therapeutic (DNP) is rapidly eliminated by the ex vivo liver, meaning the drug effect of increased metabolism is only transient. This demonstrates the importance of assessing pharmacokinetics when delivering therapeutics during NMP, especially for prolonged perfusion of organs with established roles in drug elimination. Rigorous pharmacological testing is needed to unlock the potential of NMP as a clinical drug-delivery platform.

Paleoenvironment of the Cerro Negro Formation (Aptian, Early Cretaceous) of Snow Island, Antarctic Peninsula.

A study of macro and microfacies, palynoflora and palynofacies of the non-marine Cerro Negro Formation at President Head Peninsula, Snow Island, northwest of the Antarctic Peninsula, was developed. Two assemblages were recognized: Palynofacies assemblage 1 (P1) at the base of the section with a dominance of fern spores and conifer pollen grains, and facies association consisting of a clastic layer, with the predominance of mudstones; and Palynofacies assemblage 2 (P2) at the top of the section, with remarkable abundance of AOM/Pseudoamorphous particles, associated with facies that includes tuffs. The complete section shows in some levels the presence of freshwater algae and translucent phytoclasts. The integrated data characterizes a fluvial-lacustrine environment, what is reinforced by the occurrence of freshwater algae (Botryococcus) in some levels of P1 and P2. We could verify an increase in volcanic activity towards the top of the section that apparently has played an important role in the collapse of the palynoflora. The occurrence of the spore species Muricingulisporis annulatus, Sotasporites elegans, S. triangularis, Foraminisporis wonthaggiensis, and F. asymmetricus in the Cerro Negro Formation allows the correlation with sections in South America and Australia, suggesting an Aptian age for these deposits.

Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P = .009), decreased expression of injury biomarker NGAL (P = .012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P = .019, medulla P = .001), downregulation of interleukin (IL)-1ß (P = .050), and upregulation of IL-10 (P < .047) and Indolamine-2, 3-dioxygenase (P = .050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P < .001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

Histoplasma capsulatum-induced extracellular DNA trap release in human neutrophils.

Neutrophils are leukocytes that are capable of eliminating both intra- and extracellular pathogens by mechanisms such as phagocytosis, degranulation, and release of neutrophil extracellular traps (NETs). Histoplasma capsulatum var. capsulatum (H. capsulatum) is a dimorphic fungus with a global distribution that causes histoplasmosis, a disease that is endemic in different geographic areas and is spreading worldwide. The release of NETs has been described as an important host defense mechanism against different fungi; however, there are no reports demonstrating that this process is implicated in neutrophil response to H. capsulatum infection. Therefore, the aim of this work is to investigate whether isolated human neutrophils release NETs in response to H. capsulatum and the potential mechanisms involved, as well as delineate the NETs antifungal activity. Using both confocal fluorescence and scanning electron microscopy techniques, we determined that NETs are released in vitro in response to H. capsulatum via an oxidative mechanism that is downstream of activation of the Syk and Src kinase pathways and is also dependent on CD18. NETs released in response to H. capsulatum yeasts involve the loss of neutrophil viability and are associated with elastase and citrullinated histones, however also can occur in a PAD4 histone citrullination independent pathway. This NETs also presented fungicidal activity against H. capsulatum yeasts. Our findings may contribute to the understanding of how neutrophils recognize and respond as immune effector cells to H. capsulatum, which may lead to better knowledge of histoplasmosis pathophysiology and treatment.

Morphological variation in the dentition of Uruguaysuchidae (Crocodyliformes: Notosuchia).

Uruguaysuchidae was a diverse group of crocodyliforms with widespread Gondwanan distribution. Recent phylogenies recover a clade comprising six species of Araripesuchus and one Uruguaysuchus. We reviewed the morphological variation in the dentition of uruguaysuchid specimens, including unpublished fossils from the Crato (SMNK PAL 6404) and Romualdo (MN 7061-V) formations of the Araripe Basin. Dental patterns are clearly distinct between species, with important taxonomic and possible ecological implications. Neither Araripesuchus nor Uruguaysuchus have characters suggesting exclusive herbivory, even for species in which tooth-tooth occlusion is observed. New data on A. gomesii shows differences in teeth number between the new specimen MN 7061-V and the holotype, probably due to preservation. The specimen SMNK PAL 6404 has a unique combination of dental characters, which reinforces the hypothesis that it might belong to a new Araripesuchus species. The alveoli pattern of A. rattoides is very distinctive in comparison to other araripesuchids, what also suggests different taxonomic affinities. One interpretation for the morphological variation in the dentition of Uruguaysuchidae is foraging specializations for different life habits. Niche partitioning and ecological specialization could have been an important process in explaining the high taxonomic diversity and widespread spatial distribution of these animals in the Cretaceous of Gondwana.

IndoorPlant: A Model for Intelligent Services in Indoor Agriculture Based on Context Histories.

The application of ubiquitous computing has increased in recent years, especially due to the development of technologies such as mobile computing, more accurate sensors, and specific protocols for the Internet of Things (IoT). One of the trends in this area of research is the use of context awareness. In agriculture, the context involves the environment, for example, the conditions found inside a greenhouse. Recently, a series of studies have proposed the use of sensors to monitor production and/or the use of cameras to obtain information about cultivation, providing data, reminders, and alerts to farmers. This article proposes a computational model for indoor agriculture called IndoorPlant. The model uses the analysis of context histories to provide intelligent generic services, such as predicting productivity, indicating problems that cultivation may suffer, and giving suggestions for improvements in greenhouse parameters. IndoorPlant was tested in three scenarios of the daily life of farmers with hydroponic production data that were obtained during seven months of cultivation of radicchio, lettuce, and arugula. Finally, the article presents the results obtained through intelligent services that use context histories. The scenarios used services to recommend improvements in cultivation, profiles and, finally, prediction of the cultivation time of radicchio, lettuce, and arugula using the partial least squares (PLS) regression technique. The prediction results were relevant since the following values were obtained: 0.96 (R2, coefficient of determination), 1.06 (RMSEC, square root of the mean square error of calibration), and 1.94 (RMSECV, square root of the mean square error of cross validation) for radicchio; 0.95 (R2), 1.37 (RMSEC), and 3.31 (RMSECV) for lettuce; 0.93 (R2), 1.10 (RMSEC), and 1.89 (RMSECV) for arugula. Eight farmers with different functions on the farm filled out a survey based on the technology acceptance model (TAM). The results showed 92% acceptance regarding utility and 98% acceptance for ease of use.

Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

Importance: Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective: To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants: Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11 052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions: Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures: The primary end point was 90-day survival. Results: Of all randomized patients, 10 520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11; P = .46). There was no significant interaction between fluid type and infusion rate (P = .98). Conclusions and Relevance: Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02875873.

Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial.

IMPORTANCE: Intravenous fluids are used for almost all intensive care unit (ICU) patients. Clinical and laboratory studies have questioned whether specific fluid types result in improved outcomes, including mortality and acute kidney injury. OBJECTIVE: To determine the effect of a balanced solution vs saline solution (0.9% sodium chloride) on 90-day survival in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, factorial, randomized clinical trial conducted at 75 ICUs in Brazil. Patients who were admitted to the ICU with at least 1 risk factor for worse outcomes, who required at least 1 fluid expansion, and who were expected to remain in the ICU for more than 24 hours were randomized between May 29, 2017, and March 2, 2020; follow-up concluded on October 29, 2020. Patients were randomized to 2 different fluid types (a balanced solution vs saline solution reported in this article) and 2 different infusion rates (reported separately). INTERVENTIONS: Patients were randomly assigned 1:1 to receive either a balanced solution (n = 5522) or 0.9% saline solution (n = 5530) for all intravenous fluids. MAIN OUTCOMES AND MEASURES: The primary outcome was 90-day survival. RESULTS: Among 11 052 patients who were randomized, 10 520 (95.2%) were available for the analysis (mean age, 61.1 [SD, 17] years; 44.2% were women). There was no significant interaction between the 2 interventions (fluid type and infusion speed; P = .98). Planned surgical admissions represented 48.4% of all patients. Of all the patients, 60.6% had hypotension or vasopressor use and 44.3% required mechanical ventilation at enrollment. Patients in both groups received a median of 1.5 L of fluid during the first day after enrollment. By day 90, 1381 of 5230 patients (26.4%) assigned to a balanced solution died vs 1439 of 5290 patients (27.2%) assigned to saline solution (adjusted hazard ratio, 0.97 [95% CI, 0.90-1.05]; P = .47). There were no unexpected treatment-related severe adverse events in either group. CONCLUSION AND RELEVANCE: Among critically ill patients requiring fluid challenges, use of a balanced solution compared with 0.9% saline solution did not significantly reduce 90-day mortality. The findings do not support the use of this balanced solution. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02875873.

Hypothermic machine perfusion is superior to static cold storage in deceased donor kidney transplantation: A meta-analysis.

BACKGROUND: There remains a lack of consensus on the optimal storage method for deceased donor kidneys. This meta-analysis compares storage with hypothermic machine perfusion (HMP) vs traditional static cold storage (SCS). METHODS: The Cochrane Kidney and Transplant Specialised Register was searched to identify (quasi-) randomized controlled trials (RCTs) to include in our meta-analysis. PRISMA guidelines were used to perform and write this review. RESULTS: There is high-certainty evidence that HMP reduces the risk of delayed graft function (DGF) when compared to SCS (2138 participants from 14 studies, RR = 0.77; 0.67-0.90, P = .0006). This benefit is significant in both donation following circulatory death (DCD; 772 patients from seven studies, RR = 0.75; 0.64-0.87, P = .0002) and donation following brainstem death (DBD) grafts (971 patients from four studies, RR = 0.78; 0.65-0.93, P = .006). The number of perfusions required to prevent one episode of DGF was 7.26 and 13.60 in DCD and DBD grafts, respectively. There is strong evidence that HMP also improves graft survival in both DBD and DCD grafts, at both 1 and 3 years. Economic analyses suggest HMP is cost-saving at 1 year compared with SCS. CONCLUSION: Hypothermic machine perfusion is superior to SCS in deceased donor renal transplantation. Direct comparisons with normothermic machine perfusion in RCTs are essential to identify optimal preservation methods in kidney transplantation.