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Supplementary Tables from Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen

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Aromatase inhibitors (AI) are being evaluated as long-term adjuvant therapies and chemopreventives in breast cancer. However, there are concerns about bone mineral density loss in an estrogen-free environment. Unlike nonsteroidal AIs, the steroidal AI exemestane may exert beneficial effects on bone through its primary metabolite 17-hydroexemestane. We investigated 17-hydroexemestane and observed it bound estrogen receptor α (ERα) very weakly and androgen receptor (AR) strongly. Next, we evaluated 17-hydroexemestane in MCF-7 and T47D breast cancer cells and attributed dependency of its effects on ER or AR using the antiestrogen fulvestrant or the antiandrogen bicalutamide. 17-Hydroexemestane induced proliferation, stimulated cell cycle progression and regulated transcription at high sub-micromolar and micromolar concentrations through ER in both cell lines, but through AR at low nanomolar concentrations selectively in T47D cells. Responses of each cell type to high and low concentrations of the non-aromatizable synthetic androgen R1881 paralleled those of 17-hydroexemestane. 17-Hydroexemestane down-regulated ERα protein levels at high concentrations in a cell type–specific manner similarly as 17β-estradiol, and increased AR protein accumulation at low concentrations in both cell types similarly as R1881. Computer docking indicated that the 17β-OH group of 17-hydroexemestane relative to the 17-keto group of exemestane contributed significantly more intermolecular interaction energy toward binding AR than ERα. Molecular modeling also indicated that 17-hydroexemestane interacted with ERα and AR through selective recognition motifs employed by 17β-estradiol and R1881, respectively. We conclude that 17-hydroexemestane exerts biological effects as an androgen. These results may have important implications for long-term maintenance of patients with AIs. [Mol Cancer Ther 2007;6(11):2817–27]

Supplementary Fig. S1 from Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen

Supplementary Figure Legends from Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen

Supplementary Figure 1 from The G Protein–Coupled Receptor GPR30 Inhibits Proliferation of Estrogen Receptor–Positive Breast Cancer Cells

Supplementary Methods from The G Protein–Coupled Receptor GPR30 Inhibits Proliferation of Estrogen Receptor–Positive Breast Cancer Cells

The rapid industrial growth and the necessity of recovering and recycling raw materials increased the interest in the production of highly selective and efficient separation tools. In this perspective, a relevant input was given by the membrane-based technology and the production of imprinted membranes, which possess specific recognition properties at molecular and ionic level, offers the possibility of developing sustainable and green processes. Furthermore, the integration of imprinted membranes with traditional or membrane-based approaches is a promising strategy in the logic of process intensification, which means the combination of different operations in a single apparatus. This work discusses the concept and separation mechanisms of imprinted membranes. Furthermore, it presents an overview of their application in organic solvent nanofiltration, for the removal of toxic agents and recovery solvent, as well as valuable compounds. The recent advances in water treatment, such as pesticide removal and recovery of metal ions, are also discussed. Finally, potential applications of imprinted membranes in hybrid processes are highlighted, and a look into the future of membrane separations for water treatment and recovery of critical raw materials is offered.

Some distributed optimization applications require privacy, meaning that the values of certain parameters local to a node should not be revealed to other nodes in the network during the joint optimization process. A special case is the problem of private distributed averaging, in which a network of nodes computes the global average of individual node reference values in a distributed manner while preserving the privacy of each reference. We present simple iterative methods that guarantee accuracy (i.e., the exact asymptotic computation of the global average) and privacy (i.e., no node can estimate another node’s reference value). To achieve this, we require that the digraph modeling the communication between nodes satisfy certain topological conditions. Our method is hot-pluggable (meaning no reinitialization of the averaging process is required when the network changes or a node enters or leaves, when there is a communication or computation fault, or when a node’s reference value changes); it does not require an initial scrambling phase; it does not inject noise or other masking signals into the distributed computation; it does not require random switching of edge weights; and it does not rely on homomorphic encryption.

In this work controlled release devices for transdermal administration of metoprolol were developed. Poly(vinyl alcohol) and poly(vinyl pyrrolidone) were used for producing membranes by solvent- casting technique. The release kinetic of the drug from the membranes was evaluated by ex-vivo experimental studies. All the prepared membranes exhibited a linear release profile in the investigated time. The enhancer Tween 80 was added into the polymeric matrices for improving their performance. Different mathematical models were used for fitting the experimental release data. The model that well described the release mechanism was the zero order, indicating a constant drug release in the time

Bovine tuberculosis is an infectious, zoonotic disease, caused by Mycobacterium bovis. The bovine is the primary host. Other species can be infected (pigs, goats, horses, etc). Man can be infected by air (lung disease), clinically indistinguishable from that produced by Mycobacterium tuberculosis or by oral or cutaneous route (extrapulmonary forms: digestive, lymph node, skin). Contagion has been mainly related to contact with livestock and the consumption of unpasteurized dairy products. It was also reported the possible contagion between people. It is described the case of an adolescent patient, from the province of Buenos Aires, with prolonged febrile syndrome and abdominal lymph node conglomerate, with a history of ingestion of unpasteurized milk. We consider the importance of warning about the correct processing of food, especially at this time when new food trends (homemade dairy intake or bought at informal fairs) could put the health of the population at risk.

Resume La fibroscopie bronchique est un geste de pratique courante en pneumopediatrie, qui selon les cas peut etre realise en ambulatoire ou en hospitalisation conventionnelle. Sa manipulation, similaire a celle des instruments utilises chez l’adulte, gagne a etre employee par des pediatres qui connaissent les pathologies et indications specifiques a l’enfant. L’endoscopie a un interet diagnostique mais aussi therapeutique. Elle concerne certaines maladies respiratoires de l’enfant dont elle depasse neanmoins le spectre, interessant d’autres surspecialites: ORL, infectiologie, medecine interne, cardiologie, anesthesie et reanimation, chirurgie infantile. Sa securite de realisation repose sur l’organisation d’un plateau technique dedie.

The on demand delivery of novel peptide actives, traditional pharmaceuticals, nutrients and/or vitamins is a ever present challenge due to the digestive and metabolic degradation of the active and the delivery vehicle. Biodegradable biopolymer hydrogels have long held promise as candidates for creating tailored release profiles due to the ability to control gel porosity. The present study describes the creation of novel hierarchical biopolymer hydrogels for the controlled release of lipids/lipophilic actives pharmaceutical ingredients (APIs), and mathematically describes the mechanisms that affect the timing of release. The creation of phase separated protein/polysaccharide core (6.6 wt% gelatin, 40 wt% Oil in water emulsion) shell structures (7 g/L xanthan with 70–140 g/L β-lactoglobulin) altered enzyme mass transport processes. This core shell structure enabled the creation of a tailorable burst release of API during gastrointestinal digestion where there is a delay in the onset of release, without affecting the kinetics of release. The timing of the delay could be readily programmed (with release of between 60 and 240 min) by controlling either the thickness or protein concentration (between 70 g/L and 140 g/L β-lactoglobulin) of the outer mixed biopolymer hydrogel shell (7 g/L xanthan with 70–140 g/L β-lactoglobulin). Enzyme diffusion measurements demonstrated that surface erosion was the main degradation mechanism. A kinetic model was created to describe the delayed burst release behaviour of APIs encapsulated within the core, and successfully predicted the influence of shell thickness and shell protein density on the timing of gastro-intestinal release (in vitro). Our work highlights the creation of a novel family of core-shell hydrogel oral dosage forms capable of programmable delivery of lipids/lipophilic APIs. These findings could have considerable implications for the delivery of peptides, poorly soluble drugs, or the programmed delivery of lipids within the gastrointestinal tract.

A regimen of escalating doses of thalidomide, in combination with bortezomib and high-dose melphalan (mel/vel/thal), was evaluated as a conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients with a prior transplant who had relapsed or achieved less than a complete remission following a prior ASCT. Thalidomide was dose escalated starting from 600 mg to 1000 mg on days −5 to −1 in a 3 × 3 design, bortezomib was administered at 1.6 mg/m2 intravenously on days −4 and −1 and melphalan 200 mg/m2 was administered on day −2. No dose-limiting toxicity was seen in the phase I portion of the trial. An additional 20 patients were enrolled at the maximum tolerated dose of thalidomide of 1000 mg daily. The overall response rate was 69% with 38% complete remission. Median PFS and OS were 9.3 and 65.4 months, respectively, with a median follow-up of 17.8 months. The most common grade 3–4 adverse events (AEs) were neutropenic fever (58.6%), mucositis (6.9%), and diarrhea (6.9%). Serious AEs included somnolence (13.8%) and tumor lysis syndrome (3.4%). The addition of high-dose thalidomide to bortezomib and melphalan as conditioning for salvage ASCT was well tolerated and was an effective conditioning regimen.

Further to a previous publication by the European Council of Legal Medicine (ECLM) concerning on-site forensic and medico-legal scene and corpse investigation, this publication provides guidance for forensic medical specialists, pathologists and, where present, coroners' activity at a scene of death inspection and to harmonize the procedures for a correct search, detection, collection, sampling and storage of all elements which may be useful as evidence, and ensure documentation of all these steps. This ECLM's inspection form provides a checklist to be used on-site for the investigation of a corpse present at a crime or suspicious death scene. It permits the collection of all relevant data not only for the pathologist, but also for forensic anthropologists, odontologists, geneticists, entomologists and toxicologists, thus supporting a collaborative work approach. Detailed instructions for the completion of forms are provided.

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes., Author summary COVID-19, the disease caused by the SARS-CoV-2 virus, has a varied clinical course with limited treatment options. While some patients mount a productive immune response leading to recovery, others progress to rapid respiratory deterioration that may require hospitalization and mechanical ventilation. Our institution conducted a clinical trial to evaluate the efficacy of convalescent plasma therapy (CPT) to treat patients hospitalized with COVID-19 pneumonia. In this arm of the study, we sought to examine immune analytes in donor plasma as well as evaluate the recipients’ plasma before CPT infusion, and at Day 3 and Day 10 post-CPT infusion. We found some analytes to be elevated in plasma donors, compared to healthy controls, even after recovery. Plasma composition in CPT recipients prior to infusion showed elevations in several analytes associated with immune activation. Some significant differences were seen in plasma composition in patients in our Track 2 cohort (hospitalized without mechanical ventilation) compared to the Track 3 cohort (hospitalized with mechanical ventilation). In addition, we obtained plasma samples for hospitalized COVID-19 patients that did not receive CPT and noted several differences in the course of immune analyte production over time compared to the CPT-treated patients.

Circulating nucleic acids, encapsulated within small extracellular vesicles (EVs), provide a remote cellular snapshot of biomarkers derived from diseased tissues, however selective isolation is critical. Current laboratory‐based purification techniques rely on the physical properties of small‐EVs rather than their inherited cellular fingerprints. We established a highly‐selective purification assay, termed EV‐CATCHER, initially designed for high‐throughput analysis of low‐abundance small‐RNA cargos by next‐generation sequencing. We demonstrated its selectivity by specifically isolating and sequencing small‐RNAs from mouse small‐EVs spiked into human plasma. Western blotting, nanoparticle tracking, and transmission electron microscopy were used to validate and quantify the capture and release of intact small‐EVs. As proof‐of‐principle for sensitive detection of circulating miRNAs, we compared small‐RNA sequencing data from a subset of small‐EVs serum‐purified with EV‐CATCHER to data from whole serum, using samples from a small cohort of recently hospitalized Covid‐19 patients. We identified and validated, only in small‐EVs, hsa‐miR‐146a and hsa‐miR‐126‐3p to be significantly downregulated with disease severity. Separately, using convalescent sera from recovered Covid‐19 patients with high anti‐spike IgG titers, we confirmed the neutralizing properties, against SARS‐CoV‐2 in vitro, of a subset of small‐EVs serum‐purified by EV‐CATCHER, as initially observed with ultracentrifuged small‐EVs. Altogether our data highlight the sensitivity and versatility of EV‐CATCHER., ‘A customizable, low background, high‐affinity assay for specific immuno‐capture and release of circulating small extracellular vesicles prior to small‐RNA sequencing for identification of miRNA biomarkers or in‐vitro evaluation: The EV‐CATCHER assay (Extracellular Vesicle Capture by AnTibody of CHoice and Enzymatic Release)’.

The chestnut processing industry is characterized by the production of a considerable amount of byproducts including leaves, burs and shells. Different studies have been performed to valorise these wastes, particularly shells, for their exploitation in different fields. Indeed, these wastes are an excellent source of tannins (condensed and hydrolysable), phenolic acids (ellagic and gallic acids) and flavonoids (catechin, epicatechin, apigenin, quercetin and rutin) well recognized for their biological activities, including antioxidant, anti-inflammatory and anticancer activities. The richess in bioactive compounds reinforced the potential of shell valorisation as natural antioxidants and prebiotics and emphasized the possible benefits of designing high-added value products with attractive applications in food and nutraceutical fields. Furthermore, the valorisation of these wastes, through the implementation of efficient and eco-friendly extraction processes, represents a great challenge for the chestnut processing industries. This work has been focused, for the first time, on the development of a sustainable integrated membrane process for separating and purifying different classes of bioactive compounds from dried chestnut shell extracts. The experimental process, investigated on lab scale, is based on a preliminary extraction of dried chestnut shells followed by clarification, fractionation and concentration of the extract with ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) membranes in a sequential design. The operating parameters of the extraction process (as temperature and type of extracting solvent) have been optimized for maximizing the polyphenols yield. The obtained results showed a maximum polyphenol yield of about 6.6 g/L at an operating temperature of 50 °C and a water-to-solid ratio of 9 mL/g. The aqueous extract has been previously clarified with hollow fiber UF membranes of 500 kDa in order to remove macromolecules and suspended solids. Then, the UF permeate was treated by a spiral-wound NF membrane (MWCO, 300-500 Da): an average permeate flux of about 50 L/m2h was measured in selected operating conditions. Ellagic and gallic acids have been totally recovered in the NF retentate stream (Figure 1). In addition, most of gallic acid has been recovered in the NF permeate and concentrated through a final RO step with the production of fresh water (RO permeate). Results of the investigated process indicate the effective valorization of the chestnut shells and the reduction of the environmental impact by supporting the transition towards a circular economy for meeting the "zero waste" goals proposed by the 2030 agenda.

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness. © 2021 The Author(s)

Chestnut shell (Castanea sativa Mill.), an abundant agro-industrial by-product generated during chestnut peeling process, is usually discarded or used as fuel. However, this by-product has been recognized as a remarkable source of biophenols, such as gallic and ellagic acids, well recognized for their protective activities as antioxidants and the prevention of several types of human diseases [1]. The growing interest of both consumers and producers towards these substances has intensified research efforts to develop novel and sustainable procedures for their extraction, separation, and purification in an efficient and environmentally friendly manner without affecting their stability [2]. In this contest, this work was aimed at investigating, for the first time, an integrated biorefinery strategy for the extraction, separation and concentration of bioactive compounds (mainly gallic and ellagic acids) from dried chestnut shell. The process is based on a preliminary extraction of dried chestnut shell followed by clarification, fractionation and concentration of the extract with ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) membranes in a sequential design. The extraction process has been optimized for obtaining the maximum yield of polyphenols by following an eco-friendly route. At this purpose, different parameters such as extraction temperature and type of solvent (water and alcohol/water mixture) have been optimized. The obtained results showed a maximum polyphenol yield of about 6.6 g/L at an operating temperature of 50 °C and a water-to-solid ratio of 9 mL/g. The aqueous extract was previously clarified with hollow fiber UF membranes of 500 kDa in order to remove macromolecules and suspended solids. Then, the UF permeate has been treated by a spiral-wound NF membrane (MWCO, 300-500 Da): an average permeate flux of about 50 L/m2h was measured in selected operating conditions. Ellagic acid was totally recovered in the retentate stream, while most of gallic acid was recovered in the permeate and concentrated through a final RO step with the production of clean water (RO permeate). The proposed process, based on circular economy approach, allows (i) the recovery of valuable compounds for the formulation of functional ingredients and (ii) minimise the highly expensive and environmentally risky disposal of chestnut shell.

Bacteria deploy rearrangement hotspot (Rhs) proteins as toxic effectors against both prokaryotic and eukaryotic target cells. Rhs proteins are characterized by YD-peptide repeats, which fold into a large β-cage structure that encapsulates the C-terminal toxin domain. Here, we show that Rhs effectors are essential for type VI secretion system (T6SS) activity in Enterobacter cloacae (ECL). ECL rhs(−) mutants do not kill Escherichia coli target bacteria and are defective for T6SS-dependent export of hemolysin-coregulated protein (Hcp). The RhsA and RhsB effectors of ECL both contain Pro−Ala−Ala−Arg (PAAR) repeat domains, which bind the β-spike of trimeric valine−glycine repeat protein G (VgrG) and are important for T6SS activity in other bacteria. Truncated RhsA that retains the PAAR domain is capable of forming higher-order, thermostable complexes with VgrG, yet these assemblies fail to restore secretion activity to ∆rhsA ∆rhsB mutants. Full T6SS-1 activity requires Rhs that contains N-terminal transmembrane helices, the PAAR domain, and an intact β-cage. Although ∆rhsA ∆rhsB mutants do not kill target bacteria, time-lapse microscopy reveals that they assemble and fire T6SS contractile sheaths at ∼6% of the frequency of rhs(+) cells. Therefore, Rhs proteins are not strictly required for T6SS assembly, although they greatly increase secretion efficiency. We propose that PAAR and the β-cage provide distinct structures that promote secretion. PAAR is clearly sufficient to stabilize trimeric VgrG, but efficient assembly of T6SS-1 also depends on an intact β-cage. Together, these domains enforce a quality control checkpoint to ensure that VgrG is loaded with toxic cargo before assembling the secretion apparatus.

Autologous hematopoietic stem cell transplantation (ASCT) is a standard-of-care treatment for many hematologic malignancies. Progression of disease after ASCT is the primary cause of treatment failure. In this Phase Ib trial, we studied the safety and clinical effect of combined checkpoint inhibition therapy (CPIT) with ipilimumab and nivolumab as a consolidation strategy after ASCT for patients with high-risk diffuse large B cell lymphoma (DLBCL), mature T cell lymphoma (TCL), and multiple myeloma (MM). Starting at 14 to 28 days after ASCT, patients received ipilimumab (1 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 16, and 22) and nivolumab (3 mg/kg i.v. on day 1 of weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, and 26). Patients received a median of 5 doses of ipilimumab and 8 doses of nivolumab. Thirty-five patients were included in the intent-to-treat population. Ninety-four percent of the patients experienced immune-related adverse events (irAEs) of any grade. Ninety-seven percent of irAEs resolved spontaneously or after holding study drugs and instituting high-dose corticosteroid therapy. Progression-free and overall survival at 18 months post-ASCT for each disease cohort were 85.7% and 100% for primary refractory DLBCL, 28.6% and 57.1% for relapsed DLBCL, not evaluable and 80% for frontline TCL, 25% and 75% for relapsed TCL, 57.1% and 87% for high-risk transplant-naive MM, and 40% and 100% for MM relapsed within 3 years of first ASCT. We conclude that combined CPIT appears to be tolerable as a consolidation strategy after ASCT and in addition to the potential clinical efficacy observed in some subsets of disease, T cell receptor repertoire, T regulatory cell phenotype, and gut microbiota profiles provide a biologic rationale warranting further study of this approach.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti–SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response., Patients with COVID-19 pneumonia receiving high-titer convalescent plasma showed antibody transfer with preservation of endogenous production, and database survival comparison is promising for the early group.

OBJECTIVESTo determine the rate of intubation, overall survival, viral clearance, and the development of endogenous antibodies in patients with COVID-19 pneumonia treated with convalescent plasma containing high levels of neutralizing anti-SARS-CoV-2 antibodies. We also aimed to describe the laboratory parameters of the plasma products.DESIGNThis was a phase IIa, single institution, prospective study in adults hospitalized with SARS-CoV-2 pneumonia.SETTINGHackensack University Medical Center, a 770-bed research and teaching hospital located in Bergen County NJ, 11 km from New York City. The study was conducted between April 15 and June 18, 2020.PARTICIPANTS47 hospitalized adult patients were treated: 32 in the non-mechanically ventilated group and 15 in the mechanically ventilated group. All patients had confirmed SARS-CoV-2 pneumonia by radiographic and laboratory evaluation.INTERVENTIONFresh or frozen convalescent plasma from donors with high titers of viral neutralizing antibodies was administered.MAIN OUTCOME MEASURESIncidence of intubation, overall survival, and discharge rate of patients divided in cohorts based on severity of disease. Description of infused plasma characteristics. Evaluation of recipients’ pre-treatment viral immunity, immunity transfer from convalescent plasma administration, and late immunity 30 and 60 days after treatment. Rates of viral clearance by nasopharyngeal PCR at 10 and 30 days. Outcomes of patients with no pre-treatment immunity. Survival comparison with institutional data for each cohort.RESULTSAnalysis for the non-mechanically ventilated patients showed an intubation rate of 15.6% (95% CI: 5.3%-32.8%) and a day-30 survival rate of 87.5% (28/32; 95% CI:70.2%-96.4%). The overall survival for a comparative group based on institutional data was 66% (675/1023; p=0.012). The rates of negative nasopharyngeal swab by PR-PCR on day+10 and +30 post treatment were 42.9% (95% CI: 24%-63%) and 78% (95% CI: 56%-93%) respectively. Patients mechanically ventilated had a day-30 mortality of 46.7% (95% CI:21.3%-73.4%); the mortality for a comparative group based on institutional data was 68.5% (217/317; p=0.093). The rates of negative nasopharyngeal swab by PR-PCR at day+10 and +30 was 85.7% (95% CI: 42-100%; n=7) and 100% (95% CI: 63-100%; n=8). Seven patients (15%) had no pre-infusion immunity, and all were found to have anti-SARS-CoV-2 neutralizing titers three days post infusion. All evaluable patients were found to have neutralizing antibodies on day+30 (n=30) and on day+60 (n=12) post treatment. There was no difference in outcomes within the ranges of high antiviral neutralizing titers used, mostly greater than 1:1000. There was also no difference between fresh or frozen plasma. The only adverse event was a mild rash in one patient.CONCLUSIONIn this study of adult patients hospitalized with SARS-CoV-2 pneumonia, convalescent plasma was safe and conferred effective transfer of immunity while preserving endogenous immune response. Intubation rates, survival rates compared with institutional data, and viral clearance rates, support the continued evaluation of this antiviral modality.STUDY REGISTRATIONClinicalTrials.gov NTC04343755

Resume L’endoscopie des voies respiratoires n’apporte rien dans le bilan d’un asthme standard. Chez le jeune enfant elle est cependant parfois utile au titre du diagnostic differentiel, particulierement lorsqu’existent des symptomes atypiques. Son apport est incontestable dans le cadre de l’asthme difficile a traiter, mettant en evidence une gamme variee de comorbidites dont la prise en charge specifique permet d’ameliorer la reponse au traitement de fond: hypertrophie des vegetations adenoides, anomalies fonctionnelles du larynx et des cordes vocales, colonisation bacterienne des voies respiratoires inferieures.

Os corantes sintéticos utilizados no segmento têxtil, além de gerarem grande impacto ambiental, podem causar problemas à saúde humana, como dermatites de contato. Os corantes naturais podem ser uma alternativa a eles, alguns possuindo, até mesmo, propriedades que ofereçam proteção UPF. Considerando a biodiversidade brasileira e o interesse mundial, este artigo pretende contribuir para o desenvolvimento de um corante oriundo de substratos da espécie Dipteryx alata Vogel, que além de seus variados benefícios à saúde também poderá ser utilizado como corante natural e agente de fotoproteção. Os resultados obtidos do desenvolvimento do método de tingimento de substratos têxteis apresentam informações interessantes, mas que exigem continuidade nos estudos para melhora com o propósito de alcançar novos mercados.

La inhalacion de un cuerpo extrano es un accidente domestico que afecta a todos los tramos de edad, con un pico de frecuencia bien conocido en pediatria en los ninos pequenos, asi como otro, menos importante, en los adolescentes. El sindrome de penetracion, que es el modo de revelacion habitual, puede estar ausente y tanto la clinica como la radiografia son enganosas en ocasiones. El diagnostico y el tratamiento se basan en la endoscopia, flexible o rigida, cuyas modalidades varian segun la presentacion. Las complicaciones agudas, vitales o cronicas, relacionadas con la ignorancia del accidente, justificarian unos esfuerzos de prevencion, que actualmente son muy insuficientes. En Francia, no se dispone de ningun dato epidemiologico respecto a este accidente, que todos los anos motiva que cientos de ninos consulten en urgencias.

SUMMARY T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ) production in a nutrient-poor environment. Unlike naive (TN) or central memory T (TCM) cells, effector memory T (TEM) cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments., In Brief Ecker et al. distinguish unique metabolic and functional properties of naive and memory T cell subsets during glucose limitation. During glucose starvation, T cells begin to differentially rely on fatty acid synthesis and glutamine utilization to survive. Unexpectedly, reliance on fatty acid synthesis alters the ability to produce IFN-γ.