Search

Plastics are a cornerstone of the modern world, yet the durable material properties that we have come to depend upon have made them recalcitrant environmental pollutants. Biological solutions in the form of engineered enzymes offer low energy and sustainable approaches to recycle and upcycle plastic waste, uncoupling their production and end of life from fossil fuels and greenhouse gases. These enzymes however, encounter immense challenges acting on plastics: facing hydrophobic surfaces, molecular crowding, and high levels of substrate heterogeneity. There have been mixed reports about the benefits of fusing partner domains to polyethylene terephthalate (PET) degrading enzymes, with moderate improvements identified under specific conditions, but no clarity into the factors that underlie the mechanisms. Here, we use the SpyCatcher003:SpyTag003 technology, which demonstrates a profound 47 °C shift in Tm upon irreversible complex formation, to investigate the influence of the thermal stability of the fusion partner on a range of PETases selected for their optimal reaction temperatures. We find that the thermal stability of the fusion partner does not have a positive correlation on the activity of the enzymes or their evident kinetic and thermal stabilities. Instead, it appears that the fusion to less stable SpyCatcher003 tends to increase the measured activation energy of unfolding compared to the more stable complex and wildtype enzymes. Despite this, the fusions to SpyCatcher003 do not show significantly better catalytic activity on PET films, with or without SpyTag003, and were found to be sometimes disruptive. The approach we highlight here, in using a fusion partner with controllable melting temperature, allowed us to dissect the impact of the stability of a fusion partner on enzyme properties. Although fusion stability did not appear to be coupled with identifiable trends in enzymatic activities, careful analysis of the unfolding pathways, and solid and solution activities of a wider range of enzymes may yield a more detailed understanding. [ABSTRACT FROM AUTHOR]

Background Accurate tools to distinguish Crohn's disease [CD] from cryptoglandular disease in patients with perianal fistulas without detectable luminal inflammation on ileocolonoscopy and abdominal enterography (isolated perianal fistulas [IPF]) are lacking. We assessed the ability of video capsule endoscopy [VCE] to detect luminal inflammation in patients with IPF. Methods We studied consecutive adults [>17 years] with IPF who were evaluated by VCE after a negative ileocolonoscopy and abdominal enterography between 2013 and 2022. We defined luminal CD by VCE as diffuse erythema, three or more aphthous ulcers, or a Lewis score greater than 135. We compared rates of intestinal inflammation in this cohort with age- and sex-matched controls without perianal fistulas, who underwent VCE for other indications. We excluded persons with pre-existing inflammatory bowel disease [IBD] and exposure to non-steroidal anti-inflammatory drugs or immunosuppressive treatments. Results A total of 45 patients with IPF underwent VCE without complications. Twelve patients [26%] met our definition of luminal CD. Luminal CD was more common in patients with IPF than in controls [26% vs 3%; p  <0.01]. Among patients with IPF, male sex (OR [odds ratio], 9.2; 95% confidence interval [CI] [1.1-79.4]), smoking (OR, 4.5; 95% CI [0.9-21.2]), abscess (OR, 6.3; 95% CI [1.5-26.8]), rectal enhancement on magnetic resonance imaging [MRI] (OR, 9.0; 95% CI [0.8-99.3]), and positive antimicrobial serology (OR, 7.1; 95% CI, [0.7-70.0]) were more common in those with a positive VCE study. Conclusions VCE detected small intestinal inflammation suggestive of luminal CD in approximately one-quarter of patients with IPF. Larger studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical response of parasacral transcutaneous electrical neural stimulation (parasacral TENS) associated with urotherapy in children with primary monosymptomatic nocturnal enuresis (PMNE) compared to urotherapy alone. Material and Methods: This prospective controlled clinical trial enrolled 72 children over 5 years of age with PMNE. Children were randomly divided into two groups, control group (CG), treated with urotherapy and scapular stimulation, and experimental group (EG), treated with urotherapy and parasacral TENS. In both groups, 20 sessions were performed, 3 times weekly, for 20 min each, with 10 Hz frequency, 700 μS pulse width and intesity determinated by the patient threshold. The percentages of dry nights were analyzed for 14 days before treatment (T0), after the 20th session (T1), 15 (T2), 30 (T3), 60 (T4), and 90 (T5) days after the end of the sessions. Patients of both groups were followed with intervals of 2 weeks in the first month and monthly for three consecutive months. Results: Twenty‐eight enuretic children, 14 girls (50%) with a mean age of 9.09 ± 2.23 years completed the study. There was no difference in mean age between groups. Mean percentage of dry nights in EG at T0 was 36%, at T1 49%, at T2 54%, at T3 54%, at T4 54%, and 57% at T5; while in CG, these percentages were 28%, 39%, 37%, 35%, 36%, and 36%, respectively. Conclusions: Parasacral TENS associated with urotherapy improves the percentage of dry nights in children with PMNE, although no patient had complete resolution of symptoms in this study. [ABSTRACT FROM AUTHOR]

Enzyme‐based depolymerization is a viable approach for recycling of poly(ethylene terephthalate) (PET). PETase from Ideonella sakaiensis (IsPETase) is capable of PET hydrolysis under mild conditions but suffers from concentration‐dependent inhibition. In this study, this inhibition is found to be dependent on incubation time, the solution conditions, and PET surface area. Furthermore, this inhibition is evident in other mesophilic PET‐degrading enzymes to varying degrees, independent of the level of PET depolymerization activity. The inhibition has no clear structural basis, but moderately thermostable IsPETase variants exhibit reduced inhibition, and the property is completely absent in the highly thermostable HotPETase, previously engineered by directed evolution, which simulations suggest results from reduced flexibility around the active site. This work highlights a limitation in applying natural mesophilic hydrolases for PET hydrolysis and reveals an unexpected positive outcome of engineering these enzymes for enhanced thermostability. [ABSTRACT FROM AUTHOR]

Since the pioneering discoveries, by the Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll and Toll-like receptors can sense pathogenic microorganisms and initiate, in vertebrates and invertebrates, innate immune responses against microbial infections, many other families of pattern recognition receptors (PRRs) have been described. One of such receptor clusters is composed by, if not all, at least several members of the scavenger receptor cysteine-rich (SRCR) superfamily. Many SRCR proteins are plasma membrane receptors of immune cells; however, a small subset consists of secreted receptors that are therefore in circulation. We here describe the first characterization of biological and functional roles of the circulating human protein SSC4D, one of the least scrutinized members of the family. Within leukocyte populations, SSC4D was found to be expressed by monocytes/macrophages, neutrophils, and B cells, but its production was particularly evident in epithelial cells of several organs and tissues, namely, in the kidney, thyroid, lung, placenta, intestinal tract, and liver. Similar to other SRCR proteins, SSC4D shows the capacity of physically binding to different species of bacteria, and this opsonization can increase the phagocytic capacity of monocytes. Importantly, we have uncovered the capacity of SSC4D of binding to several protozoan parasites, a singular feature seldom described for PRRs in general and here demonstrated for the first time for an SRCR family member. Overall, our study is pioneer in assigning a PRR role to SSC4D. [ABSTRACT FROM AUTHOR]

Crown policies and private enterprise combined to increase efficiency levels in Portuguese overseas expansion. Within this framework, this paper will emphasize three themes. Firstly, the dependence of the Portuguese empire on shipping efficiency; while the debate largely focuses on shipbuilding and seafarers, we show how crown policies and individual enterprises adapted to the evolving requirements of an empire based on sea power. Secondly, we demonstrate how informal and self-organized mechanisms at times contributed to, and sometimes blocked, state-oriented policies. Thirdly, we gauge the extent to which local inputs, such as raw materials, labour and techniques, contributed to efficiency levels within a universe that became multi-continental. [ABSTRACT FROM AUTHOR]

Summary: The characterization of the architecture, structure and extracellular interactions of the CD6 glycoprotein, a transmembrane receptor expressed in medullary thymocytes and all mature T‐cell populations, has been enhanced by the existence of monoclonal antibodies (mAbs) that specifically recognize the various scavenger receptor cysteine‐rich (SRCR) domains of the ectodomain. Using engineered isoforms of CD6 including or excluding each of the three SRCR domains, either expressed at the membranes of cells or in soluble forms, we provide conclusive and definitive evidence that domain 2 of CD6, previously not identifiable, can be recognized by the CD6 mAbs OX125 and OX126, and that OX124 targets domain 3 and can block the interaction at the cell surface of CD6 with its major ligand CD166. Alternative splicing‐dependent CD6 isoforms can now be confidently identified. We confirm that following T‐cell activation there is a partial replacement of full‐length CD6 by the CD6Δd3 isoform, which lacks the CD166‐binding domain, and we find no evidence for the expression of other CD6 isoforms at the mRNA or protein levels. [ABSTRACT FROM AUTHOR]

Shipbuilding was an essential element in the creation of overseas empires during the early modern period. It generated demand for raw materials, technology and manpower, and in many cases received direct support from the state. The Portuguese shipbuilding industry enjoyed various incentives from the Crown, but was always a mix between state and private enterprise. With Portugal expanding overseas, building and repairing ships in the various Portuguese possessions became an option. Initially, it was viewed critically by the metropolitan authorities, as they feared losing control. Soon, however, the logistical needs of empire meant that public and private agencies began providing shipbuilding facilities in Portugal's overseas territories. In Brazil, the abundance of high-quality wood militated in favour of the establishment of shipyards. Wood cut there or on the Atlantic coast of Africa was also transported to metropolitan Portugal. Shipbuilding specialists were sent out to Brazil to supervise the selection of suitable wood, and soon started to operate shipyards there. Little is known about shipbuilding in the Portuguese possessions in western Africa, while more can be said about the industry on the shores of the Indian Ocean. Shipyards in India, particularly in Goa and Cochin, were developed to meet the challenges and needs of formal and informal 'empire', particularly regarding ship repairs. The Ribeira de Goa replicated first the Ribeira das Naus of Lisbon, but soon individual shipyards took over specific functions. Crown control, initially tight and systematic, proved difficult to maintain. Indian woods were known for their hardness and durability and were shipped to Europe to build ships for the Indian Route. Expert labourers migrated from Portugal to overseas possessions, with specialists in metallurgy joining the shipbuilders. The scope of the operation also required the recruitment of local shipbuilders. In general, and for its financial resources, Portuguese colonial shipbuilding soon relied on a cooperation of state and private initiative, much as at home. [ABSTRACT FROM AUTHOR]

Introduction and aims: Splenic marginal zone lymphoma, an uncommon subtype of non-Hodgkin lymphoma (NHL), is usually present with symptomatic splenomegaly. Although splenectomy has long been considered the first-line therapy in symptomatic or cytopenic patients, it can lead to significant morbidity and mortality. Splenic irradiation is an option for patients who have a poor response to systemic therapy and/or are not surgical candidates. In this paper, we present a case report of a patient who received splenic radiotherapy for symptomatic splenomegaly. Methods: An 85-year-old Caucasian man with a 4 year history of low-grade NHL presented with progressive pancytopenia, significant weight loss and symptomatic splenomegaly (abdominal discomfort, sense of fullness and limitation of mobility due to spleen size). The patient refused splenectomy and, in December 2017, was referred to palliative splenic radiotherapy. He was initially treated with five fractions of one Grey (Gy) in order to evaluate clinical and haematology response. After that, 1.5 Gy daily, 5 days a week for 3 weeks. 3D conformal radiotherapy, multiple fields and mixed energy (6 and 15 Mv) were used. Results: Radiotherapy allowed significant splenic reduction to almost half the size, resolving abdominal discomfort and improving quality of life. There was no decline of haemoglobin, leukocytes and platelet counts; in fact, there was a marginal increase. Conclusion: Palliative splenic irradiation was well tolerated confirming that it is a safe treatment option for palliation of symptomatic splenomegaly. Thereby, splenic irradiation should be strongly considered in the management of symptomatic splenomegaly, for selected patients who are refractory to or unsuitable for other options or when the patient refuses other treatments. [ABSTRACT FROM AUTHOR]

Lisbon has been affected by several moderate to strong earthquakes that caused considerable damage and produced significant economic and social impacts (e.g., the November 1st, 1755, earthquake). Studies on the potential damage due to a seismic event have been done considering Lisbon's moderate to high seismic hazard, but the seismic site effects have not yet been investigated at the city scale. The local ground conditions can locally modify the characteristics of surface seismic motion. Based on a multidisciplinary dataset composed of surface geology, a geotechnical database, and a geophysical database that compiles all the available geophysical tests carried out in Lisbon, an integrated approach to seismic ground characterisation was performed. A regression analysis of the shear-wave velocity values compiled in the geophysical database was done for each geological unit. The peak frequency distribution in the city, assessed from the ambient vibration measurements, showed a pattern in peak frequency variation. It decreases from the oldest to the most recent geological formations that outcrop in the SW-NE direction. Three zones based on peak frequency value distribution were proposed. An estimation of the impedance contrast depths was computed through two processes, considering the previous results: (i) the shallower contrast depth was assessed through a sharp variation of NSPT values available in the geotechnical database, and (ii) the deeper contrast depth was estimated based on geology data and deep borehole information. The results showed that for the upper ∼100 m of depth, a consistent relationship between the contrasts identified through different data was obtained, even if uncertainty increased with depth. • A multidisciplinary dataset-based contribution to seismic microzonation. • V S -depth equations defined for each geological formation. • Peak frequency distribution at the city scale. • Impedance contrast depth map based on an integrated approach. • Consistent relationship between the contrasts identified through different data. [ABSTRACT FROM AUTHOR]

Biocatalysis, hydrolases, mesophilic enzymes, PETase, plastics Keywords: biocatalysis; hydrolases; mesophilic enzymes; PETase; plastics EN biocatalysis hydrolases mesophilic enzymes PETase plastics 1 1 1 04/25/23 20230421 NES 230421 B The Cover Feature b shows the effect of concentration dependent inhibition of natural enzymes that break down poly(ethylene terephthalate) (PET), a polymer widely used in consumer packaging and which contributes to plastic pollution. Cover Feature: Concentration-Dependent Inhibition of Mesophilic PETases on Poly(ethylene terephthalate) Can Be Eliminated by Enzyme Engineering (ChemSusChem 8/2023). [Extracted from the article]

The scavenger receptor cysteine-rich (SRCR) family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP) of bacteria, fungi, or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion, which contains five SRCR modules, and a large C-terminal mucin-like domain. Toward establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR) properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSc5D (N-SSc5D), thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein-bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to Escherichia coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively), and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time, and label-free surface plasmon resonance (SPR)-based assay and examined the capacity of N-SSc5D, Spα, sCD5, and sCD6 to bind to different bacteria. We demonstrated that N-SSc5D compares with Spα in the capacity to bind to E. coli and Listeria monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3). Our work thus advocates the utility of SPR-based assays as sensitive tools for the rapid screening of interactions between immune-related receptors and PAMP-bearing microbes. The analysis of our results suggests that SRCR domains of different members of the family have a differential capacity to interact with bacteria, and further that the same receptor can discriminate between different bacteria strains and species. [ABSTRACT FROM AUTHOR]

In palliative care, drugs are considered futile if they do not have a short-term benefit in symptom control or quality of life. The authors examined pharmacotherapy prescribed for patients referred to palliative care to identify futile drugs. This was a retrospective analysis of patients referred over 6 months, focusing on the prescription of gastric protectants, antidiabetic agents, bisphosphonates, anticoagulants, antidementia drugs, statins, and antihypertensive agents. The sample consisted of 448 patients. Gastric protectants were prescribed futilely in 50% of cases (125/248), statins in 97% (69/71), antihypertensive agents in 27% (42/155), antidiabetic drugs in 1% (1/70), bisphosphonates in 27% (4/15), and antidementia drugs in 100% (9/9). This study reveals that many patients with advanced cancer continue to be treated with inappropriate drugs and points to the need for medical training in palliative care, drawing attention to the need for therapeutic review at each medical visit. [ABSTRACT FROM AUTHOR]

T lymphocytes stimulated through their antigen receptor (TCR) preferentially express mRNA isoforms with shorter 3´ untranslated regions (3´-UTRs) derived from alternative pre-mRNA cleavage and polyadenylation (APA). However, the physiological relevance of APA programs remains poorly understood. CD5 is a T-cell surface glycoprotein that negatively regulates TCR signaling from the onset of T-cell activation. CD5 plays a pivotal role in mediating outcomes of cell survival or apoptosis, and may prevent both autoimmunity and cancer. In human primary T lymphocytes and Jurkat cells we found three distinct mRNA isoforms encoding CD5, each derived from distinct poly(A) signals (PASs). Upon T-cell activation, there is an overall increase in CD5 mRNAs with a specific increase in the relative expression of the shorter isoforms. 3´-UTRs derived from these shorter isoforms confer higher reporter expression in activated T cells relative to the longer isoform. We further show that polypyrimidine tract binding protein (PTB/PTBP1) directly binds to the proximal PAS and PTB siRNA depletion causes a decrease in mRNA derived from this PAS, suggesting an effect on stability or poly(A) site selection to circumvent targeting of the longer CD5 mRNA isoform by miR-204. These mechanisms fine-tune CD5 expression levels and thus ultimately T-cell responses. [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (or Group B Streptococcus, GBS) is a commensal bacterium present in the intestinal and urinary tracts of approximately 30% of humans. We and others previously showed that the PI-2a pilus polymers, made of the backbone pilin PilB, the tip adhesin PilA and the cell wall anchor protein PilC, promote adhesion to host epithelia and biofilm formation. Affinity-purified PI-2a pili from GBS strain NEM316 were recognized by N-acetylneuraminic acid (NeuNAc, also known as sialic acid) specific lectins such as Elderberry Bark Lectin (EBL) suggesting that pili are sialylated. Glycan profiling with twenty different lectins combined with monosaccharide composition by HPLC suggested that affinity-purified PI-2a pili are modified by N-glycosylation and decorated with sialic acid attached to terminal galactose. Analysis of various relevant mutants in the PI-2a pilus operon by flow-cytometry and electron microscopy analyses pointed to PilA as the pilus subunit modified by glycosylation. Double labeling using PilB antibody and EBL lectin, which specifically recognizes N-acetylneuraminic acid attached to galactose in α-2, 6, revealed a characteristic binding of EBL at the tip of the pilus structures, highly reminiscent of PilA localization. Expression of a secreted form of PilA using an inducible promoter showed that this recombinant PilA binds specifically to EBL lectin when produced in the native GBS context. In silico search for potentially glycosylated asparagine residues in PilA sequence pointed to N427 and N597, which appear conserved and exposed in the close homolog RrgA from S. pneumoniae, as likely candidates. Conversion of these two asparagyl residues to glutamyl resulted in a higher instability of PilA. Our results provide the first evidence that the tip PilA adhesin can be glycosylated, and suggest that this modification is critical for PilA stability and may potentially influence interactions with the host. [ABSTRACT FROM AUTHOR]

Promoting a more transparent, clearer and more effective communication between citizens, scientists and policy-makers has been a priority goal of the European Commission and other institutions in recent years. Science communication matters for the extent to which citizens may be more or less available to participate and to get involved in the debate and in the regulatory process related to scientifictechnological developments thus helping guarantee the quality of scientific results and the democratization of decisions. In the last two decades, the concept of Public Engagement with Science and Technology (PEST) has become central to analyses of the relation between citizens and technoscience. However, its meaning is not always clear as there are ambiguities and divergences between different sources. This article aims to map the views of different scholars, and to contribute to a clearer understanding of the concept of PEST and its implications. Further to discussing different understandings of PEST's objectives, the article evaluates the way in which the concept has been used in Portugal through an analysis of legal texts and of the mission and goals of research and higher education institutions. We conclude that instrumental arguments still prevail in the normative discourses that frame the Portuguese scientific activity. [ABSTRACT FROM AUTHOR]

In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a), alanine racemase (Alr), D-alanyl-D-alanine synthetase (Ddl), isoleucyl-tRNA sinthetase (IARS), DNA gyrase subunit B, topoisomerase IV (TopoIV), dihydropteroate synthetase (DHPS) and dihydrofolate reductase (DHFR) using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins) the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets. [ABSTRACT FROM AUTHOR]

Copyright of Onco.news is the property of Portuguese Association of Oncology Nursing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Glyceraldehyde 3-phosphate dehydrogenases (GAPDH) are cytoplasmic glycolytic enzymes that, despite lacking identifiable secretion signals, have been detected at the surface of several prokaryotic and eukaryotic organisms where they exhibit non-glycolytic functions including adhesion to host components. Group B Streptococcus (GBS) is a human commensal bacterium that has the capacity to cause life-threatening meningitis and septicemia in newborns. Electron microscopy and fluorescence-activated cell sorter (FACS) analysis demonstrated the surface localization of GAPDH in GBS. By addressing the question of GAPDH export to the cell surface of GBS strain NEM316 and isogenic mutant derivatives of our collection, we found that impaired GAPDH presence in the surface and supernatant of GBS was associated with a lower level of bacterial lysis. We also found that following GBS lysis, GAPDH can associate to the surface of many living bacteria. Finally, we provide evidence for a novel function of the secreted GAPDH as an inducer of apoptosis of murine macrophages. [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS) is the leading cause of neonatal pneumonia, septicemia, and meningitis. We have previously shown that in adult mice GBS glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an extracellular virulence factor that induces production of the immunosuppressive cytokine interleukin-10 (IL-10) by the host early upon bacterial infection. Here, we investigate whether immunity to neonatal GBS infection could be achieved through maternal vaccination against bacterial GAPDH. Female BALB/c mice were immunized with rGAPDH and the progeny was infected with a lethal inoculum of GBS strains. Neonatal mice born from mothers immunized with rGAPDH were protected against infection with GBS strains, including the ST-17 highly virulent clone. A similar protective effect was observed in newborns passively immunized with anti-rGAPDH IgG antibodies, or F(ab')2 fragments, indicating that protection achieved with rGAPDH vaccination is independent of opsonophagocytic killing of bacteria. Protection against lethal GBS infection through rGAPDH maternal vaccination was due to neutralization of IL-10 production soon after infection. Consequently, IL-10 deficient (IL-10-/- ) mice pups were as resistant to GBS infection as pups born from vaccinated mothers. We observed that protection was correlated with increased neutrophil trafficking to infected organs. Thus, anti-rGAPDH or anti-IL-10R treatment of mice pups before GBS infection resulted in increased neutrophil numbers and lower bacterial load in infected organs, as compared to newborn mice treated with the respective control antibodies. We showed that mothers immunized with rGAPDH produce neutralizing antibodies that are sufficient to decrease IL-10 production and induce neutrophil recruitment into infected tissues in newborn mice. These results uncover a novel mechanism for GBS virulence in a neonatal host that could be neutralized by vaccination or immunotherapy. As GBS GAPDH is a structurally conserved enzyme that is metabolically essential for bacterial growth in media containing glucose as the sole carbon source (i.e., the blood), this protein constitutes a powerful candidate for the development of a human vaccine against this pathogen. [ABSTRACT FROM AUTHOR]

Background Chronic heart failure is a complex syndrome manifested by hemodynamic disturbances, exercise intolerance, increased mortality and reduced quality of life (Heidenreich et al., 2006). Besides impaired cardiac function, a variety of changes in peripheral skeletal muscles may contribute to the major and debilitating symptoms of chronic heart failure, dyspnea and fatigue (Coats et al., 1994). The aim of this study was to evaluate the perception of quality of life and physical performance in patients with heart failure. Methods A total of 47 patients, of both genders, with chronic heart failure, were recruited (55,5±12,3 years), and divided into two groups. One group (n=28) clinical and another group (n=19) surgical. Fifty five percent of the patients had NYHA class III and forty five percent NYHA class III. Quality of life was assessed, in both groups, with the Minnesota Living with Heart Failure Questionnaire (Rector et al; 1992). The physical activity level was measured by an accelerometer (number of steps) during seven consecutive days. Results For the quality of life, were found significant differences (p≤0.05), in the physical dimensions of chronic heart failure patients. The surgical group showed a better quality of life. Considering the physical activity, the clinical group appear with better performance (p≤0,01). In the daily activities, there weren't observed vigorous or very vigorous intensity activities. Conclusions These results indicate that chronic heart failure patients differ in their daily physical activity, especially in high-impact activities, due to age, gender, and disease progression (Rector, 2005). Further investigation should be directed towards the impact of the different components of the rehabilitation process upon quality of live improvement in patients with chronic heart failure. [ABSTRACT FROM AUTHOR]

Body temperature changes in laboratory mice are often assessed by invasive and stressful methods, which may confound the measurement. Infrared thermography is a possible non-invasive alternative, but the cost of standard thermal cameras, lack of dedicated software for biomedical purposes, and labour-intensiveness of thermal image analysis have limited their use. An additional limitation lies on the scarcity of research on the causing factors of differences between body surface and core body temperature. We propose a method for automatic assessment of mean body surface temperature in freely-moving mice, using dedicated software for thermal image analysis. While skin surface temperature may not necessarily be linearly correlated with core body temperature (in itself an imprecise concept), under standardized environmental conditions, such as those in which laboratory animals are kept, mean body surface temperature can provide useful information on their thermal status (i.e. deviations from normothermia, namely hypo- and hyperthermia). We developed a publicly available software that includes an imaging analysis workflow/algorithm for automatic segmentation of the pixels associated with the animal from the pixels associated with the background, removing the need for manually defining the area of analysis. A batch analysis mode is also available, for automatic and high-throughput analysis of all image files located in a folder. The software is compatible with the most widespread thermal camera manufacturer, 'FLIR Systems', as well as with the low-cost 'Thermal Expert TE-Q1' miniaturized high-resolution thermal camera used for this study. Furthermore, the software has been validated in a mouse model expressing non-transient hypothermia, where the thermal analysis results were compared with readings from implanted thermo-sensitive passive integrated transponders tags. Thermography allows for thermal assessment of laboratory animals without the effect of handling stress on their physiology or behaviour. Our automatic image analysis software also removes observer errors and bias, while speeding up the data processing. • Body temperature variation gives valuable information on animal health and welfare • Thermal assessment of laboratory animals raises technical and welfare challenges • IR thermography is an option, but analysis is laborious and prone to variability • We propose a novel user-friendly software for analysis of thermal images of mice • The new analysis methodology was validated in LPS-injected mice showing hypothermia [ABSTRACT FROM AUTHOR]

Background Drowning is the third leading cause of death worldwide (WHO, 2010). According to Brenner et al (2009) participating in swimming lessons (SL) can reduce by 88% the risk of drowning in children 1-4 years old, despite some controversy regarding the most appropriate swimming programs (Ward, 2009). On the other hand no studies tested the skills acquired in SL in drowning prevention. So we proposed a test to evaluate the survivability of a child that accidentally falls into the water. Methods Twenty two children (4.68±0.82yrs) who practice SL (2.01±0.91yrs/practice) were subjected to two tests: aquatic readiness (AR) (Stallman et al, 2008); and survival test (ST), which consisted of an inflatable boat ride (unknown pool; presence of the usual swim teacher; wearing t-shirt) which 'accidentally' turns. Recorded images were later observed by 6 field experts whose observations obtained an overall index of concordance (IC) of 89%. Results In ST 15 children had positive responses (n=10, 100% IC; n=1, 66% IC; n=1, 83% IC; n=3, 50% IC) and 7 (n=6, 100% IC; n=1, 66% IC) would be in danger. Conclusions Through this test, we found that not all children whose result was positive in AR had a positive performance in the ST. This brings us to observe according to Langendörfer (2011) that the positive or negative response of the subject depends on the interaction of various constraints such as individual characteristics, the environment conditions, and the state in which the swimmer is. The application of ST suggests that the inclusion of safety and prevention activities in swimming lessons, aiming to develop attitudes and motor skills as a defense to drowning, must be taken into account. More studies are necessary to provide valid information to assist pediatricians in advising parents regarding what type of SL are more appropriate to reduce drowning. [ABSTRACT FROM AUTHOR]

Objective Orolingual angioedema (OA) is a well known early complication of treatment with alteplase in ischemic stroke patients. Our aim was to study risk factors for OA in these patients, namely insular cortex ischemia. Methods Retrospective case-cohort study using the prospective registry of all consecutive ischemic stroke patients submitted to intravenous thrombolysis with alteplase. Clinical data was retrieved from the registry and medical records. Two independent observers evaluated early signs of insular cortex ischemia on pre-thrombolysis computed tomography (CT) and of insular cortex infarct on early follow-up imaging. Univariate and multivariate analysis were performed to identify predictors of OA. Results Of the 659 patients with acute ischemic stroke treated with alteplase, 32 developed OA (4.9%, 95%CI = 3.3–6.6). Frequency of early signs of insular cortex ischemia on pre-thrombolysis CT and of insular cortex infarct on follow-up imaging was similar in patients with and without OA ( p = 0.241 and p = 0.145, respectively). The only independent predictors of OA occurrence were female sex (OR = 5.47, 95%CI = 1.98–15.10) and angiotensin-converting enzyme inhibitor (ACE-I) use (OR = 3.87, 95%CI = 1.71–8.75). Conclusions Female sex and ACE-I use are independent risk factors for OA occurrence in ischemic stroke patients treated with alteplase. Early signs of insular cortex ischemia on pre-thrombolysis CT were not significantly associated with OA. [ABSTRACT FROM AUTHOR]

Sepsis is the third most common cause of neonatal death, with Group B Streptococcus (GBS) being the leading bacterial agent. The pathogenesis of neonatal septicemia is still unsolved. We described previously that host susceptibility to GBS infection is due to early IL-10 production. In this study, we investigated whether triggering TLR2 to produce IL-10 is a risk factor for neonatal bacterial sepsis. We observed that, in contrast to wild-type (WT) pups, neonatal TLR2-deficient mice were resistant to GBSinduced sepsis. Moreover, if IL-10 signaling were blocked in WT mice, they also were resistant to sepsis. This increased survival rate was due to an efficient recruitment of neutrophils to infected tissues that leads to bacterial clearance, thus preventing the development of sepsis. To confirm that IL-10 produced through TLR2 activation prevents neutrophil recruitment, WT pups were treated with the TLR2 agonist Pam3CSK4 prior to nebulization with the neutrophil chemotactic agent LTB4. Neutrophil recruitment into the neonatal lungs was inhibited in pups treated with Pam3CSK4. However, the migration was restored in Pam3CSK4- treated pups when IL-10 signaling was blocked (either by anti-IL-10R mAb treatment or by using IL-10-deficient mice). Our findings highlight that TLR2-induced IL-10 production is a key event in neonatal susceptibility to bacterial sepsis. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) alone caused over a billion deaths in the last 200 years, making it one of the deadliest diseases to humankind. Understanding the immune mechanisms underlying protection or pathology in TB is key to uncover the much needed innovative approaches to tackle TB. The scavenger receptor cysteine-rich molecule CD5 antigen-like (CD5L) has been associated with TB, but whether and how CD5L shapes the immune response during the course of disease remains poorly understood. Here, we show an upregulation of CD5L in circulation and at the site of infection in C57BL/6 Mycobacterium tuberculosis-infected mice. To investigate the role of CD5L in TB, we studied the progression of M. tuberculosis aerosol infection in a recently described genetically engineered mouse model lacking CD5L. Despite the increase of CD5L during infection of wild-type mice, absence of CD5L did not impact bacterial burden, histopathology or survival of infected mice. Absence of CD5L associated with a modest increase in the numbers of CD4+ T cells and the expression of IFN-γ in the lungs of infected mice, with no major effect in overall immune cell dynamics. Collectively, this study confirms CD5L as a potential diagnostic biomarker to TB, showing no discernible impact on the outcome of the infection., (© 2024 John Wiley & Sons Ltd.)

Background: The success of haemodialysis (HD) critically depends on the effective use of arteriovenous fistulas (AVFs). The precise needling technique is vital to minimise complications and ensure functional vascular access., Objective: This study assesses the effectiveness of a nursing consultation protocol, which integrates physical examination (PE) with Doppler Ultrasound (DUS), in preparing patients for the first AVF needling., Design/participants: A cross-sectional analysis at a Portuguese National Health Service Hospital engaged thirty new HD patients, four HD needling experienced nurses and one HD vascular access nurse. This study examines the accuracy of PE in assessing the matured AVF by the four nurses compared to a trained vascular access nurse encompassing systematic PE and DUS., Measurements: The primary data incorporated AVF characteristics derived from PE (inspection, palpation, and auscultation) and DUS findings (vein depth, diameter, and blood flow). A secondary focus was evaluating the change in nurses' perceived needling complexity following the nursing consultation., Results: The nursing consultation significantly enhanced the identification of crucial AVF features, such as accessory veins (p = 0.002), and improved the accuracy of AVF morphology assessments. This led to identifying longer needling tracks (p = 0.031) and a higher number of safe needling points (p = 0.016). Nurses reported a notable reduction in perceived complexity and potential adverse events following this method (p = 0.027)., Conclusions: Integrating structured PE with DUS in a nursing consultation framework significantly improves the preparation for AVF needling. This approach enhances the efficiency and safety of AVF needling and boosts nurse confidence and patient care in HD settings., (© 2024 European Dialysis & Transplant Nurses Association/European Renal Care Association.)