Toll like receptor 4 mediates the inhibitory effect of SARS-CoV-2 spike protein on proximal tubule albumin endocytosis.

Tubular proteinuria is a common feature in COVID-19 patients, even in the absence of established acute kidney injury. SARS-CoV-2 spike protein (S protein) was shown to inhibit megalin-mediated albumin endocytosis in proximal tubule epithelial cells (PTECs). Angiotensin-converting enzyme type 2 (ACE2) was not directly involved. Since Toll-like receptor 4 (TLR4) mediates S protein effects in various cell types, we hypothesized that TLR4 could be participating in the inhibition of PTECs albumin endocytosis elicited by S protein. Two different models of PTECs were used: porcine proximal tubule cells (LLC-PK1) and human embryonic kidney cells (HEK-293). S protein reduced Akt activity by specifically inhibiting of threonine 308 (Thr308) phosphorylation, a process mediated by phosphoinositide-dependent kinase 1 (PDK1). GSK2334470, a PDK1 inhibitor, decreased albumin endocytosis and megalin expression mimicking S protein effect. S protein did not change total TLR4 expression but decreased its surface expression. LPS-RS, a TLR4 antagonist, also counteracted the effects of the S protein on Akt phosphorylation at Thr308, albumin endocytosis, and megalin expression. Conversely, these effects of the S protein were replicated by LPS, an agonist of TLR4. Incubation of PTECs with a pseudovirus containing S protein inhibited albumin endocytosis. Null or VSV-G pseudovirus, used as control, had no effect. LPS-RS prevented the inhibitory impact of pseudovirus containing the S protein on albumin endocytosis but had no influence on virus internalization. Our findings demonstrate that the inhibitory effect of the S protein on albumin endocytosis in PTECs is mediated through TLR4, resulting from a reduction in megalin expression.

Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n = 124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/ß0, 7 S/ß+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P = 0.03) with stroke was found in HbS/ß-thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r = -0.316; P < 0.001), age at first job (r = 0.221; P = 0.018), personal (r = 0.23; P = 0.012) and per capita familiar incomes (r = 0.303; P = 0.001), personal (r = 0.61; P = 0), maternal (r = 0.536; P = 0), and paternal educational status (r = 0.441; P = 0). We further sought independent predictors of performance using multivariable regressions and increased education was an independent predictor of better scores in MoCA (0.8099, 95% confidence interval [CI]: 0.509-1.111). Brain imaging analysis showed significant and progressive atrophy in important cerebral areas related to memory, learning, and executive function. These data point to the high prevalence and impact of cognitive decline in adult SCD patients, mirrored in brain atrophic areas. It is also possible to observe the influence of sociodemographic conditions on patients' cognitive performances and the need for creating focused therapeutic plans that address these deficiencies. Moreover, the absence of a significant correlation of MoCA values with stroke in the SS and SC groups may be related to the worst sociocultural and economic conditions of the Brazilian African descent population, in which the impact of low educational stimulation on cognitive function can outweigh even the anatomical damage caused by the disease.

Binding evolution of the Dengue Virus Envelope against DC-SIGN: A combined approach of phylogenetics and molecular dynamics analyses over 30 years of Dengue Virus in Brazil.

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.

Animal models to study cognitive impairment of chronic kidney disease.

Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD) and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives and society. However, the underlying pathomechanisms are poorly understood and current therapies mostly aim at supporting patients in their daily life. This illustrates the urgent need to elucidate the pathogenesis, and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modelling of cognitive disorders in CKD. We discuss the use of mice, rats and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving therapy of people with CKD and MCI.

Individualized positive end-expiratory pressure reduces driving pressure in obese patients during laparoscopic surgery under pneumoperitoneum: a randomized clinical trial.

Introduction: During pneumoperitoneum (PNP), airway driving pressure (ΔPRS) increases due to the stiffness of the chest wall and cephalic shift of the diaphragm, which favors atelectasis. In addition, depending on the mechanical power (MP) formulas, they may lead to different interpretations. Methods: Patients >18 years of age with body mass index >35 kg/m2 were included in a single-center randomized controlled trial during their admission for bariatric surgery by abdominal laparoscopy. Intra-abdominal pressure was set at 15 mmHg at the pneumoperitoneum time point (PNP). After the recruitment maneuver, the lowest respiratory system elastance (ERS) was detected during the positive end-expiratory pressure (PEEP) step-wise decrement. Patients were randomized to the 1) CTRL group: ventilated with PEEP of 5 cmH2O and 2) PEEPIND group: ventilated with PEEP value associated with ERS that is 5% higher than its lowest level. Respiratory system mechanics and mean arterial pressure (MAP) were assessed at the PNP, 5 min after randomization (T1), and at the end of the ventilation protocol (T2); arterial blood gas was assessed at PNP and T2. ΔPRS was the primary outcome. Three MP formulas were used: MPA, which computes static PEEP × volume, elastic, and resistive components; MPB, which computes only the elastic component; and MPC, which computes static PEEP × volume, elastic, and resistive components without inspiratory holds. Results: Twenty-eight patients were assessed for eligibility: eight were not included and 20 patients were randomized and allocated to CTRL and PEEPIND groups (n = 10/group). The PEEPIND ventilator strategy reduced ΔPRS when compared with the CTRL group (PEEPIND, 13 ± 2 cmH2O; CTRL, 22 ± 4 cmH2O; p < 0.001). Oxygenation improved in the PEEPIND group when compared with the CTRL group (p = 0.029), whereas MAP was comparable between the PEEPIND and CTRL groups. At the end of surgery, MPA and MPB were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). At the end of the surgery, MPA and MPC were correlated in both the CTRL (rho = 0.71, p = 0.019) and PEEPIND (rho = 0.84, p = 0.020) groups but showed different bias (CTRL, -1.9 J/min; PEEPIND, +10.0 J/min). Conclusion: Individualized PEEP was associated with a reduction in ΔPRS and an improvement in oxygenation with comparable MAP. The MP, which solely computes the elastic component, better reflected the improvement in ΔPRS observed in the individualized PEEP group. Clinical Trial Registration: The protocol was registered at the Brazilian Registry of Clinical Trials (U1111-1220-7296).

An adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in familial hypercholesterolemia: A pilot study protocol

BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Cellular energy regulates mRNA degradation in a codon-specific manner.

Codon optimality is a major determinant of mRNA translation and degradation rates. However, whether and through which mechanisms its effects are regulated remains poorly understood. Here we show that codon optimality associates with up to 2-fold change in mRNA stability variations between human tissues, and that its effect is attenuated in tissues with high energy metabolism and amplifies with age. Mathematical modeling and perturbation data through oxygen deprivation and ATP synthesis inhibition reveal that cellular energy variations non-uniformly alter the effect of codon usage. This new mode of codon effect regulation, independent of tRNA regulation, provides a fundamental mechanistic link between cellular energy metabolism and eukaryotic gene expression.

Designing, development and validation of an app to reduce the response time of the emergency medical services.

INTRODUCTION: Delays in prehospital care attributable to the call-taking process can often be traced back to miscommunication, including uncertainty around the call location. Geolocation applications have the potential to streamline the call-taking process by accurately identifying the caller's location. OBJECTIVE: To develop and validate an application to geolocate emergency calls and compare the response time of calls made via the application with those of conventional calls made to the Brazilian Medical Emergency System (Serviço de Atendimento Médico de Urgência-SAMU). METHODS: This study was conducted in two stages. First, a geolocating application for SAMU emergency calls (CHAMU192) was developed using a mixed methods approach based on design thinking and subsequently validated using the System Usability Scale (SUS). In the second stage, sending time of the geolocation information of the app was compared with the time taken to process information through conventional calls. For this, a hypothetical case control study was conducted with SAMU in the Maringá, Paraná, Brazil. A control group of 350 audio recordings of emergency calls from 2019 was compared to a set of test calls made through the CHAMU192 app. The CHAMU192 group consisted of 201 test calls in Maringá. In test calls, the location was obtained by GPS and sent to the SAMU communication system. Comparative analysis between groups was performed using the Mann-Whitney test. RESULTS: CHAMU192 had a SUS score of 90, corresponding to a "best imaginable" usability rating. The control group had a median response time of 35.67 seconds (26.00-48.12). The response time of the CHAMU192 group was 0.20 (0.15-0.24). CONCLUSION: The use of the CHAMU192 app by emergency medical services could significantly reduce response time. The results demonstrate the potential of app improving the quality and patient outcomes related to the prehospital emergency care services.

Neurocognition and brain functional connectivity in a non-clinical population-based sample with psychotic experiences.

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia.

Identification of Peptides in Spider Venom Using Mass Spectrometry.

Spider venoms are composed of hundreds of proteins and peptides. Several of these venom toxins are cysteine-rich peptides in the mass range of 3-9 kDa. Small peptides (<3 kDa) can be fully characterized by mass spectrometry analysis, while proteins are generally identified by the bottom-up approach in which proteins are first digested with trypsin to generate shorter peptides for MS/MS characterization. In general, it is sufficient for protein identification to sequence two or more peptides, but for venom peptidomics it is desirable to completely elucidate peptide sequences and the number of disulfide bonds in the molecules. In this chapter, we describe a methodology to completely sequence and determine the number of disulfide bonds of spider venom peptides in the mass range of 3-9 kDa by multiple enzyme digestion, mass spectrometry of native and digested peptides, de novo analysis, and sequence overlap alignment.

Physiological evaluation of yeast strains under anaerobic conditions using glucose, fructose, or sucrose as the carbon source.

The aim of this study was to evaluate the physiology of 13 yeast strains by assessing their kinetic parameters under anaerobic conditions. They included Saccharomyces cerevisiae CAT-1 and 12 isolated yeasts from different regions in Brazil. The study aimed to enhance understanding of the metabolism of these strains for more effective applications. Measurements included quantification of sugars, ethanol, glycerol, and organic acids. Various kinetic parameters were analyzed, such as specific substrate utilization rate (qS), maximum specific growth rate (µmax), doubling time, biomass yield, product yield, maximum cell concentration, ethanol productivity (PEth), biomass productivity, and CO2 concentration. S. cerevisiae CAT-1 exhibited the highest values in glucose for µmax (0.35 h-1), qS (3.06 h-1), and PEth (0.69 gEth L-1 h-1). Candida parapsilosis Recol 37 did not fully consume the substrate. In fructose, S. cerevisiae CAT-1 stood out with higher values for µmax (0.25 h-1), qS (2.24 h-1), and PEth (0.60 gEth L-1 h-1). Meyerozyma guilliermondii Recol 09 and C. parapsilosis Recol 37 had prolonged fermentation times and residual substrate. In sucrose, only S. cerevisiae CAT-1, S. cerevisiae BB9, and Pichia kudriavzevii Recol 39 consumed all the substrate, displaying higher PEth (0.72, 0.51, and 0.44 gEth L-1 h-1, respectively) compared to other carbon sources.

Effects of the use of a cocoon on the autonomic, motor, and regulatory systems in preterm newborns: Randomized clinical trial.

INTRODUCTION: The wrapping of the newborn in an orthopedic tubular mesh, simulating a cocoon, can allow the infant to regain the feeling of security and stability experienced in the uterus given that the movement of one of the parts of the body exerts tactile and pressure variation in others. OBJECTIVE: We aimed to evaluate the influence of an orthopedic tubular mesh, simulating a cocoon, in therapeutic positioning, on the variables of the autonomous, motor, and regulatory systems of preterm newborns. METHODS: A controlled and randomized clinical trial was conducted with preterm newborns positioned in dorsal decubitus and divided into two groups: (a) cocoon - newborns covered with an orthopedic tubular mesh, and (b) control - newborns positioned according to the sector's routine and without the use of an orthopedic mesh. During the follow-up, each newborn was placed in the position for 30 min and was recorded for a total of 2 min, once at the beginning and again at the end of the observation period. Variables related to the autonomous system (heart rate, respiratory rate, and peripheral oxygen saturation), motor system (general movements), and regulatory system (Neonatal Infant Pain Scale) were evaluated before and after the intervention. The videos were evaluated by a researcher blind to the purpose of the study, and the resulting data were analyzed using SPSS. RESULTS: Of the 40 preterm newborns evaluated (32.5 ± 1.83 weeks), 21 were female, and 20 were allocated to the cocoon group. The variables related to the autonomous, motor, and regulatory systems remained unchanged following the positioning in the cocoon, as compared to the typical positioning employed in the neonatal unit. CONCLUSION: The simulation of a cocoon, utilizing an orthopedic tubular mesh, when applied to preterm newborns admitted to a neonatal intensive care unit can contribute to maintaining low levels of stress, without altering variables of the autonomous, motor, and regulatory systems.

Agency in urgency and uncertainty. Vaccines and vaccination in European media discourses.

Although Covid-19 was not the first pandemic, it was unique in the scale and intensity with which societies responded. Countries reacted differently to the threat posed by the new virus. The public health crisis affected European societies in many ways. It also influenced the way the media portrayed vaccines and discussed factors related to vaccine hesitancy. Europeans differed in their risk perceptions, attitudes towards vaccines and vaccine uptake. In European countries, Covid-19-related discourses were at the centre of media attention for many months. This paper reports on a media analysis which revealed significant differences as well as some similarities in the media debates in different countries. The study focused on seven European countries and considered two dimensions of comparison: between the pre-Covid period and the beginning of the Covid pandemic period, and between countries. The rich methodological approach, including linguistics, semantic field analysis and discourse analysis of mainstream news media, allowed the authors to explore the set of meanings related to vaccination that might influence actors' agency. This approach led the authors to redefine vaccine hesitancy in terms of characteristics of the "society in the situation" rather than the psychological profile of individuals. We argue that vaccine hesitancy can be understood in terms of agency and temporality. This dilemma of choice that transforms the present into an irreversible past and must be taken in relation to an uncertain future, is particularly acute under the pressure of urgency and when someone's health is at stake. As such, it is linked to how vaccine meaning is co-produced within public discourses.

Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients.

BACKGROUND: Several risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight. RESULTS: Hospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56+CD16-) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56+CD16+), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4+CD38+ cells than controls. Contrasting changes were reported in CD25+CD127low/neg regulatory T cells, with increased and decreased proportions found in CD4+ and CD8+ T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated - TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4+ and CD8+) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8+CD57+NKG2A+ cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19. CONCLUSIONS: These findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.

Structural Characterization and Rat Aortic Vascular Reactivity of Bradykinin-Potentiating Peptides (BPPs) from the Snake Venom of Bothrops moojeni from Delta do Parnaíba Region, Brazil.

Snake venoms contain various bradykinin-potentiating peptides (BPPs). First studied for their vasorelaxant properties due to angiotensin converting enzyme (ACE) inhibition, these molecules present a range of binding partners, among them the argininosuccinate synthase (AsS) enzyme. This has renewed interest in their characterization from biological sources and the evaluation of their pharmacological activities. In the present work, the low molecular weight fraction of Bothrops moojeni venom was obtained and BPPs were characterized by mass spectrometry. Eleven BPPs or related peptides were sequenced, and one of them, BPP-Bm01, was new. Interestingly, some oxidized BPPs were detected. The three most abundant peptides were BPP-Bm01, BPP-Bax12, and BPP-13a, and their putative interactions with the AsS enzyme were investigated in silico. A binding cavity for these molecules was predicted, and docking studies allowed their ranking. Three peptides were synthesized and submitted to vasorelaxation assays using rat aortic rings. While all BPPs were active, BPP-Bm01 showed the highest potency in this assay. This work adds further diversity to BPPs from snake venoms and suggests, for the first time, a putative binding pocket for these molecules in the AsS enzyme. This can guide the design of new and more potent AsS activators.

Ruptured Intracranial Aneurysm in a 60-Day-Old Infant: An Extreme Case.

The prevalence of aneurysms in children is low when compared to adults, being even rarer in the first year of life. They can be secondary to infections, traumatic brain injury, autoimmune diseases, or connective tissue diseases. Dissecting etiology is rare. A 60-day-old female infant, previously healthy, presented to the emergency department (ED) with irritability and loss of appetite since the preceding day, a fever of one-hour duration, and vomiting. Laboratory analysis revealed a hemoglobin level of 6.5 g/dL, without elevation of inflammatory markers. In the ED, she experienced two episodes, with a one-hour interval, of clonic movements of the upper eyelid and right upper limb, along with conjugate gaze deviation to the same side, which resolved after intravenous diazepam. Levetiracetam was initiated after the second episode. The anterior fontanelle became progressively tense. Brain computed tomography (CT) showed a voluminous intraparenchymal and subarachnoid hemorrhage with an aneurysm at the bifurcation of the left middle cerebral artery (MCA). Initially, an endovascular approach was tried but was not successful due to technical problems. Consequently, a Vaso-CT scan was performed that confirmed a dissecting aneurysm/pseudoaneurysm (8 mm × 10 mm × 10 mm) of the left MCA, originating from the upper wall of the M1 segment. Next, she underwent microsurgical exclusion of the aneurysm using microclips. Post-surgery brain CT showed acute ischemia in the entire MCA region. Follow-up angiography showed complete exclusion of the aneurysm. She evolved to grade 3 monoparesis of the upper limb at the six-month interval follow-up, which has been gradually improving with physical rehabilitation. The next-generation sequencing (NGS) panel for aneurysms and arterial dissections did not detect any pathogenic variants. Clinical presentation of cerebral aneurysms in infants can be subtle, and a high index of suspicion is required in cases of irritability, altered consciousness, seizures, bulging fontanelle, and motor deficits. Early detection is of utmost importance as it is associated with moderate mortality. Surgical treatment with the use of clips proved to be effective in this case.

Novel Aphid-Repellent Fiber Mats Based on Poly(lactic acid)-Containing Ionic Liquids.

To protect crops as well as human and animal health, the development of novel repellents based on biopolymers is critical for a growing world population. Here, novel aphid-repellent electrospun mats containing epoxidized ionic liquids (ILs) covalently bonded to the carboxyl or hydroxyl groups of poly(lactic acid) (PLA) were designed to produce nonwoven mats. First, di-, tri-, and tetra-epoxidized imidazolium ILs were synthesized and incorporated in different weight fractions (3, 5, and 10 wt %) into the PLA solution. Then, the effect of ILs' microstructure, thermal properties, mechanical performance, and hydrophobic behavior were investigated. It was found that the incorporation of ILs resulted in a reduction of the fiber diameters while the mechanical properties of the mats, i.e., the three-dimensional fibrous porous structure, were maintained. Finally, the effect of these three ILs against the pea aphid Acyrthosiphon pisum (Harris) was evaluated for the first time, showing an attractive effect for the diepoxidized IL and a repellent effect for the tri- and tetra-epoxidized ILs. By exploiting the chemical nature of ILs, an environmentally friendly strategy can be developed to limit the need for chemical pesticides and petroleum-based polymers.

The Role of Ultrasonography in the Process of Weaning from Mechanical Ventilation in Critically Ill Patients.

Weaning patients from mechanical ventilation (MV) is a complex process that may result in either success or failure. The use of ultrasound at the bedside to assess organs may help to identify the underlying mechanisms that could lead to weaning failure and enable proactive measures to minimize extubation failure. Moreover, ultrasound could be used to accurately identify pulmonary diseases, which may be responsive to respiratory physiotherapy, as well as monitor the effectiveness of physiotherapists' interventions. This article provides a comprehensive review of the role of ultrasonography during the weaning process in critically ill patients.

Enhanced bacterial cellulose production in Komagataeibacter sucrofermentans: impact of different PQQ-dependent dehydrogenase knockouts and ethanol supplementation.

BACKGROUND: Bacterial cellulose (BC) is a biocompatible material with unique mechanical properties, thus holding a significant industrial potential. Despite many acetic acid bacteria (AAB) being BC overproducers, cost-effective production remains a challenge. The role of pyrroloquinoline quinone (PQQ)-dependent membrane dehydrogenases (mDH) is crucial in the metabolism of AAB since it links substrate incomplete oxidation in the periplasm to energy generation. Specifically, glucose oxidation to gluconic acid substantially lowers environmental pH and hinders BC production. Conversely, ethanol supplementation is known to enhance BC yields in Komagataeibacter spp. by promoting efficient glucose utilization. RESULTS: K. sucrofermentans ATCC 700178 was engineered, knocking out the four PQQ-mDHs, to assess their impact on BC production. The strain KS003, lacking PQQ-dependent glucose dehydrogenase (PQQ-GDH), did not produce gluconic acid and exhibited a 5.77-fold increase in BC production with glucose as the sole carbon source, and a 2.26-fold increase under optimal ethanol supplementation conditions. In contrast, the strain KS004, deficient in the PQQ-dependent alcohol dehydrogenase (PQQ-ADH), showed no significant change in BC yield in the single carbon source experiment but showed a restrained benefit from ethanol supplementation. CONCLUSIONS: The results underscore the critical influence of PQQ-GDH and PQQ-ADH and clarify the effect of ethanol supplementation on BC production in K. sucrofermentans ATCC 700178. This study provides a foundation for further metabolic pathway optimization, emphasizing the importance of diauxic ethanol metabolism for high BC production.