Transition from Hashimoto thyroiditis to Graves's Disease: an unpredictable change?

PURPOSE: Hashimoto thyroiditis and Graves's disease are two related autoimmune disorders, representing the leading causes of hypothyroidism and hyperthyroidism. Autoimmune hypothyroidism is generally irreversible but very rarely, some patients would shift to hyperthyroidism. The aim of the study was to seek for possible clinical predictors of the transition from hypo to hyperthyroidism in patients with Hashimoto thyroiditis and to outline their clinical phenotype. METHODS: Twelve patients with overt autoimmune hypothyroidism who had at least one transition from hypothyroidism to autoimmune hyperthyroidism were compared with 294 consecutive patients with autoimmune hypothyroidism and 69 consecutive patients with autoimmune hyperthyroidism that accessed the outpatient clinic over six months. Demographic, hormonal data and autoantibodies titers were compared. RESULTS: Prevalence of smoking habit was significantly higher in switchers compared to controls. Switchers showed a significantly higher prevalence of personal and familial history of non-thyroidal autoimmune disorders. TSH levels were significantly lower in the switcher group during the hypothyroid phase and levothyroxine dose required was lower. TSH concentrations were significantly lower while free fT4 and free fT3 values were higher in GD patients compared to switchers during the hyperthyroid phase despite comparable TRAb levels. Prevalence and type of hyperthyroid symptoms and orbitopathy were similar between switchers and GD group. Mean dose of anti-thyroid drugs was significantly higher in GD patients compared to switchers. No differences were observed in the remission rate from hyperthyroidism between the two groups, despite switchers showed a significantly lower time-to-remission. CONCLUSIONS: Conversion of Hashimoto Thyroiditis towards Graves' disease is a rare phenomenon which can occur almost at any time after the development of autoimmune hypothyroidism. Our findings suggest active surveillance of hypothyroid patients who require frequent reduction of levothyroxine during follow up and testing for TSHR antibodies in these patients.

Molecular Determinants of EphA2 and EphB2 Antagonism Enable the Design of Ligands with Improved Selectivity.

With the aim of identifying novel antagonists selective for the EphA receptor family, a combined experimental and computational approach was taken to investigate the molecular basis of the recognition between a prototypical Eph-ephrin antagonist (UniPR1447) and two representative receptors of the EphA and EphB subfamilies, namely, EphA2 and EphB2 receptors. The conformational free-energy surface (FES) of the binding state of UniPR1447 within the ligand binding domain of EphA2 and EphB2, reconstructed from molecular dynamics (MD) simulations performed on the microsecond time scale, was exploited to drive the design and synthesis of a novel antagonist selective for EphA2 over the EphB2 receptor. The availability of compounds with this pharmacological profile will help discriminate the importance of these two receptors in the insurgence and progression of cancer.

"Somewhere Between an Actual Disease and a Disease": A Grounded Theory Study on Diagnosing Functional Neurological Disorders From a Multi-Informant Perspective.

Functional Neurological Disorders are characterized by sensory-motor or cognitive symptoms. Recent research has revealed their complex nature involving biological, psychological, and social factors. Care requires a multidisciplinary approach, which, to date, has yet to be considered. A Constructivist Grounded Theory study was conducted to understand the reasons behind this, exploring Functional Neurological Disorders diagnosis, communication, and understanding from multiple perspectives (patients and healthcare professionals). The core category was "negotiating Functional Neurological Disorders meanings and care amid a dissatisfying dichotomy," with sub-categories: i) seeking to "word" the disease, ii) exposing reductionism, and iii) a pluralist vision emerging. Diagnosing and communicating Functional Neurological Disorders is a process of negotiating meanings and care that hinges on participants' diverse ontological perspectives regarding the condition. Results highlight the difficulty in finding common ground and achieving mutual understanding among the various viewpoints, creating a challenge in establishing a unified approach to Functional Neurological Disorders care. In this context, only a few healthcare professionals emphasized the potential benefits of increased integration. A shift is required from a reductionist to an integrated biopsychosocial perspective to develop a more cohesive approach. Defining a medical paradigm through dialogue with teams and patients is essential in addressing Functional Neurological Disorders effectively. Furthermore, the required interdisciplinary approach holds the potential to mitigate the dissatisfaction arising from fragmented and compartmentalized care (the "dissatisfying dichotomy") experienced by our participants. It signifies a comprehensive strategy that could address the concerns of all involved parties and enhance the overall quality of care provided.

Poly-Lactic Acid-Bagasse Based Bio-Composite for Additive Manufacturing.

Beer bagasse is a residue waste produced in great amounts; nevertheless, it is still underestimated in the industry. The aim of this paper is to develop an innovative and efficient methodology to recycle the beer bagasse by producing Poly-lactic acid(PLA)-based bio-composites, in the forms of pellets and filaments, to be used in additive manufacturing processes. To assess the suitability of beer bagasse for extrusion-based 3D printing techniques, it was, firstly, physically and chemically characterized. Then, it was added in combination with different kinds of plasticizers to PLA to make bio-composites, analyzing their thermal and physical properties. The results prove the great potential of bagasse, evidencing its printability. Both composites' pellets and filaments were used in two different 3D printing machines and the mechanical properties of the 3D-printed models were evaluated as a function of the composition and the kind of technology used. All the used plasticizers improved processability and the polymer-bagasse interface. Compared to neat PLA, no changes in thermal properties were detected, but a lowering of the mechanical properties of the 3D-printed composites compared to the neat polymers was observed. Finally, a comparison between the efficiency of the two 3D printing techniques to be used with the bio-based composites was performed.

Osmolarity modulates the de-differentiation of horse articular chondrocytes during cell expansion in vitro: implications for tissue engineering in cartilage repair.

Due to the importance of joint disease and ostearthritis (OA) in equine athletes, new regenerative treatments to improve articular cartilage repair after damage are gaining relevance. Chondrocyte de-differentiation, an important pathogenetic mechanism in OA, is a limiting factor when differentiated articular chondrocytes are used for cell-based therapies. Current research focuses on the prevention of this de-differentiation and/or on the re-differentiation of chondrocytes by employing different strategies in vitro and in vivo. Articular chondrocytes normally live in a condition of higher osmolarity (350-450 mOsm/L) compared to normal physiological fluids (~ 300 mOsm/L) and some studies have demonstrated that osmolarity has a chondroprotective effect in vitro and in vivo. Therefore, the response of horse articular chondrocytes to osmolarity changes (280, 380, and 480 mOsm/L) was studied both in proliferating, de-differentiated chondrocytes grown in adhesion, and in differentiated chondrocytes grown in a 3D culture system. To this aim, cell proliferation (cell counting), morphology (optical microscopy), and differentiation (gene expression of specific markers) were monitored along with the expression of osmolyte transporters involved in volume regulation [betaine-GABA transporter (BGT-1), taurine transporter (SLC6A6), and neutral amino acid transporter (SNAT)] real-time qPCR. Proliferating chondrocytes cultured under hyperosmolar conditions showed low proliferation, spheroidal morphology, a significant reduction of de-differentiation markers [collagen type I (Col1) and RUNX2] and an increase of differentiation markers [collagen type II (Col2) and aggrecan]. Notably, a persistently high level of BGT-1 gene expression was maintained in chondrocyte cultures at 380 mOsm/L, and particularly at 480 mOsm/L both in proliferating and differentiated chondrocytes. These preliminary data encourage the study of osmolarity as a microenvironmental co-factor to promote/maintain chondrocyte differentiation in both 2D and 3D in vitro culture systems.

Long-term follow-up of a case of feline leishmaniosis treated with a combination of allopurinol and meglumine antimoniate.

A 9-year-old domestic cat, positive for antibodies to feline immunodeficiency virus (FIV), was brought to a veterinary clinic with alopecia, ulcerative skin lesions, and upper respiratory tract (URT) signs. This was after being treated for suspected allergic dermatitis, without clinical improvement, for 2 y. Biopsy of the skin and fine-needle aspirates of the spleen and of the lymph nodes were taken which detected the presence of Leishmania amastigotes. Leishmania infection was further confirmed by detection of a high titer of anti-Leishmania antibodies (≥ 3200) with an indirect fluorescent antibody technique (IFAT) serology. After the diagnosis of feline leishmaniosis (FeL) was made, allopurinol and meglumine antimoniate were started and led to quick and complete clinical improvement. After 7 mo, allopurinol administration was briefly interrupted but was resumed following relapse of the skin lesions. One month later, the cat was treated for suspected acute kidney injury, which prompted reduction of the total daily dose of allopurinol by 50%. The cat remained clinically well, with complete resolution of the cutaneous and URT signs, for nearly 24 mo after the diagnosis of FeL; at which point it was euthanized for worsening cardiac disease. To our knowledge, this represents a rare case of successful treatment of FeL with a suspected nephrotoxic effect associated with long-term use of allopurinol. Further studies are required to clarify the relationship, if any, between leishmaniosis and congestive heart failure in cats.

Suivi à long terme d'un cas de leishmaniose féline traité par une association d'allopurinol et d'antimoniate de méglumine. Un chat domestique de 9 ans, positif pour les anticorps contre le virus de l'immunodéficience féline (FIV), a été présenté dans une clinique vétérinaire avec une alopécie, des lésions cutanées ulcéreuses et des signes des voies respiratoires supérieures (URT). Ceci après avoir été traité pour une suspicion de dermatite allergique sans amélioration clinique, pendant 2 ans. Une biopsie de la peau et des ponctions à l'aiguille fine de la rate et des ganglions lymphatiques ont été réalisées et ont détecté la présence d'amastigotes de Leishmania. L'infection à Leishmania a été confirmée par la détection d'un titre élevé d'anticorps sériques anti-Leishmania (≥ 3200) par une technique d'immunofluorescence indirecte (IFAT). Après le diagnostic de leishmaniose féline (FeL), un traitement à l'allopurinol et l'antimoniate de méglumine a été instauré et a entraîné une amélioration clinique rapide et complète. Après 7 mois, l'administration d'allopurinol a été brièvement interrompue mais a été reprise après la rechute des lésions cutanées. Un mois plus tard, le chat a été traité pour une lésion rénale aiguë suspectée, ce qui a entraîné une réduction de 50 % de la dose quotidienne totale d'allopurinol. Le chat est resté cliniquement en bonne santé, avec une résolution complète des signes cutanés et urinaires, pendant près de 24 mois après le diagnostic de FeL; à quel point il a été euthanasié pour aggravation de la maladie cardiaque.À notre connaissance, ceci représente un cas rare de traitement réussi de FeL avec un effet néphrotoxique suspecté associé à une utilisation à long terme d'allopurinol. D'autres études sont nécessaires pour clarifier la relation, le cas échéant, entre la leishmaniose et l'insuffisance cardiaque congestive chez les chats.(Traduit par Dr Serge Messier).

Pharmacological characterization of second generation FXR agonists as effective EphA2 antagonists: A successful application of target hopping approach.

It is well demonstrated the key role of Eph-ephrin system, specifically of EphA2 receptor, in supporting tumor growth, invasion, metastasis and neovascularization. We previously identified FXR agonists as eligible antagonists of Eph-ephrin system. Herein we characterize new commercially available FXR (Farnesoid X Receptor) agonists as potential Eph ligands including Cilofexor, Nidufexor, Tropifexor, Turofexorate isopropyl and Vonafexor. Our exploration based on molecular modelling investigations and binding assays shows that Cilofexor binds specifically and reversibly to EphA2 receptor with a Ki value in the low micromolar range. Furthermore, Cilofexor interferes with the phosphorylation of EphA2 and the cell retraction and rounding in PC3 prostate cancer cells, both events depending on EphA2 activation. In conclusion, we can confirm that target hopping can be a successful approach to discover new moiety of protein-protein inhibitors.

Progestogens for maintenance tocolysis in symptomatic women. A systematic review and meta-analysis.

OBJECTIVE: Prevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct molecular structures and biological effects, we conducted a systematic review and pairwise meta-analysis to investigate the individual role played by 17-alpha-hydroxyprogesterone caproate (17-HP), vaginal progesterone (Vaginal P) and oral progesterone (Oral P). METHODS: The search was performed in MEDLINE, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 October 2021. Published RCTs comparing progestogens to placebo or no treatment for maintenance tocolysis were considered. We included women with singleton gestations, excluding quasi-randomized trials, studies on women with preterm premature rupture of membrane, or receiving maintenance tocolysis with other drugs. Primary outcomes were preterm birth (PTB) < 37 weeks' and < 34 weeks'. We assessed risk of bias and evaluated certainty of evidence with the GRADE approach. RESULTS: Seventeen RCTs including 2152 women with singleton gestations were included. Twelve studies tested vaginal P, five 17-HP, and only 1 oral P. PTB < 34 weeks' did not differ among women receiving vaginal P (RR 1.21, 95%CI 0.91 to 1.61, 1077 participants, moderate certainty of evidence), or oral P (RR 0.89, 95%CI 0.38 to 2.10, 90 participants, low certainty of evidence) as opposed to placebo. Instead, 17-HP significantly reduced the outcome (RR 0.72, 95% CI 0.54 to 0.95, 450 participants, moderate certainty of evidence). PTB < 37 weeks' did not differ among women receiving vaginal P (RR 0.95, 95%CI 0.72 to 1.26, 8 studies, 1231 participants, moderate certainty of evidence) or 17-HP (RR 0.86, 95%CI 0.60 to 1.21, 450 participants, low certainty of evidence) when compared to placebo/no treatment. Instead, oral P significantly reduced the outcome (RR 0.58, 95% CI 0.36 to 0.93, 90 participants, low certainty of evidence). CONCLUSIONS: With a moderate certainty of evidence, 17-HP prevents PTB < 34 weeks' gestation among women that remained undelivered after an episode of threatened preterm labour. However, data are insufficient to generate recommendations in clinical practice. In the same women, both 17-HP and vaginal P are ineffective in the prevention of PTB < 37 weeks'.

Being a technician during COVID-19: a qualitative cross-sectional survey on the experiences of clinical neurophysiology technicians.

BACKGROUND: During the Sars-CoV-2 virus pandemic, Italy faced an unrivaled health emergency. Its impact has been significant on the hospital system and personnel. Clinical neurophysiology technicians played a central role (but less visibly so compared to other healthcare workers) in managing the COVID-19 pandemic. This research aims to explore the experiences of clinical neurophysiology technicians during the pandemic and contribute to the debate on the well-being of healthcare workers on the front line. METHODS: We implemented a cross-sectional survey across Italy. It contained questions that were open-ended for participants to develop their answers and acquire a fuller perspective. The responses were analyzed according to the framework method. RESULTS: One hundred and thirty-one responses were valid, and the following themes were generated: technicians' experiences in their relationship with patients, technicians' relationship with their workgroup and directors, and technicians' relationship with the context outside of their work. The first theme included sub-themes: fear of infection, empathy, difficulty, a sense of obligation and responsibility, anger, and sadness. The second theme contained selfishness/solidarity in the workgroup, lack of protection/collaboration from superiors, stress, and distrust. The last theme included fear, stress/tiredness, serenity, sadness, and anger. CONCLUSION: This study contributes to building a humanized perspective for personnel management, bringing attention to the technical work of healthcare professionals in an emergency and the emotional and relational dimensions. These are the starting points to define proper, contextually adequate support.

An Overview on Wood Waste Valorization as Biopolymers and Biocomposites: Definition, Classification, Production, Properties and Applications.

Bio-based polymers, obtained from natural biomass, are nowadays considered good candidates for the replacement of traditional fossil-derived plastics. The need for substituting traditional synthetic plastics is mainly driven by many concerns about their detrimental effects on the environment and human health. The most innovative way to produce bioplastics involves the use of raw materials derived from wastes. Raw materials are of vital importance for human and animal health and due to their economic and environmental benefits. Among these, wood waste is gaining popularity as an innovative raw material for biopolymer manufacturing. On the other hand, the use of wastes as a source to produce biopolymers and biocomposites is still under development and the processing methods are currently being studied in order to reach a high reproducibility and thus increase the yield of production. This study therefore aimed to cover the current developments in the classification, manufacturing, performances and fields of application of bio-based polymers, especially focusing on wood waste sources. The work was carried out using both a descriptive and an analytical methodology: first, a description of the state of art as it exists at present was reported, then the available information was analyzed to make a critical evaluation of the results. A second way to employ wood scraps involves their use as bio-reinforcements for composites; therefore, the increase in the mechanical response obtained by the addition of wood waste in different bio-based matrices was explored in this work. Results showed an increase in Young's modulus up to 9 GPa for wood-reinforced PLA and up to 6 GPa for wood-reinforced PHA.

Growth Arrest of Alveolar Cells in Response to Cytokines from Spike S1-Activated Macrophages: Role of IFN-γ.

Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and high-permeability pulmonary edema. A hallmark of the disease is the presence of lung inflammation with features of diffuse alveolar damage. The molecular pathogenetic mechanisms of COVID-19-associated ARDS (CARDS), secondary to SARS-CoV-2 infection, are still not fully understood. Here, we investigate the effects of a cytokine-enriched conditioned medium from Spike S1-activated macrophage on alveolar epithelial A549 cells in terms of cell proliferation, induction of autophagy, and expression of genes related to protein degradation. The protective effect of baricitinib, employed as an inhibitor of JAK-STAT, has been also tested. The results obtained indicate that A549 exhibits profound changes in cell morphology associated to a proliferative arrest in the G0/G1 phase. Other alterations occur, such as a blockade of protein synthesis and the activation of autophagy, along with an increase of the intracellular amino acids content, which is likely ascribable to the activation of protein degradation. These changes correlate to the induction of IFN-regulatory factor 1 (IRF-1) due to an increased secretion of IFN-γ in the conditioned medium from S1-activated macrophages. The addition of baricitinib prevents the observed effects. In conclusion, our findings suggest that the IFN-γ-IRF-1 signaling pathway may play a role in the alveolar epithelial damage observed in COVID-19-related ARDS.

Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters.

BACKGROUND: Cervical blood and cerebrospinal fluid (CSF) flow rates can be quantified with Phase-contrast (PC) MRI, which is routinely used for clinical studies. Previous MRI studies showed that venous and CSF flow alterations are linked to various pathological conditions. Since it is well known that, besides the heart beating, the thoracic pump influences the blood and CSF dynamics, we studied the effect of different respiration modes on blood and CSF flow rates using a real-time (RT)-PC prototype. METHODS: Thirty healthy volunteers were examined with a 3 T scanner. A RT-PC sequence was acquired at the first cervical level to quantify the flow rates of internal carotid arteries, internal jugular veins (IJVs) and CSF. Each RT-PC acquisition was repeated three times, while the subjects were asked to breathe in three different ways for 60 s each: freely (F), with a constant rate (PN) and with deep and constant respiration rate (PD). The average flow rates were computed, they were removed from the respective signals and integrated in the inspiratory and expiratory phases (differential volumes). Finally, the power spectral density was computed for each detrended flow rate. High- and very-high frequency peaks were identified on the spectra while their frequencies were compared to the respiratory and cardiac frequencies estimated using a thoracic belt and a pulse oximeter. The area under the spectra was computed in four 0.5 Hz-wide ranges, centered on the high-frequency peak, on very-high frequency peak and its 2nd and 3rd harmonics, and then they were normalized by the flow rate variance. The effect of breathing patterns on average flow rates, on systolic and diastolic peaks, and on the normalized power was tested. Finally, the differential volumes of inspiration were compared to those of expiration. RESULTS: The frequencies of the high- and very-high spectral peaks corresponded to the respiratory and cardiac frequencies. The average flow rate progressively decreased from F to PN to PD breathing, and the cardiac modulations were less predominant especially for the IJVs. The respiratory modulation increased with PD breathing. The average volumes displaced in the inspiratory phases were not significantly different from those of the expiratory one. CONCLUSIONS: The spectral analyses demonstrated higher respiratory modulations in PD compared to free breathing, even prevailing the cardiac modulation in the IJVs, showing an increment of the thoracic pump affecting the flow rate shape.

Expression and Function of ABC Transporters in Human Alveolar Epithelial Cells.

ATP-binding cassette (ABC) transporters are a large superfamily of membrane transporters that facilitate the translocation of different substrates. While ABC transporters are clearly expressed in various tumor cells where they can play a role in drug extrusion, the presence of these transporters in normal lung tissues is still controversial. Here, we performed an analysis of ABC transporters in EpiAlveolarTM, a recently developed model of human alveoli, by defining the expression and activity of MDR1, BCRP, and MRPs. Immortalized primary epithelial cells hAELVi (human alveolar epithelial lentivirus-immortalized cells) were employed for comparison. Our data underline a close homology between these two models, where none of the ABC transporters here studied are expressed on the apical membrane and only MRP1 is clearly detectable and functional at the basolateral side. According to these findings, we can conclude that other thus-far-unidentified transporter/s involved in drug efflux from alveolar epithelium deserve investigations.

The JAK1/2 Inhibitor Baricitinib Mitigates the Spike-Induced Inflammatory Response of Immune and Endothelial Cells In Vitro.

The purpose of this study was to examine the effect of the JAK-STAT inhibitor baricitinib on the inflammatory response of human monocyte-derived macrophages (MDM) and endothelial cells upon exposure to the spike S1 protein from SARS-CoV-2. The effect of the drug has been evaluated on the release of cytokines and chemokines from spike-treated MDM, as well as on the activation of endothelial cells (HUVECs) after exposure to conditioned medium collected from spike-activated MDM. Results obtained indicate that, in MDM, baricitinib prevents the S1-dependent phosphorylation of STAT1 and STAT3, along with the induction of IP-10- and MCP-1 secretion; the release of IL-6 and TNFα is also reduced, while all other mediators tested (IL-1ß, IL-8, RANTES, MIP-1α and MIP-1ß) are not modified. Baricitinib is, instead, poorly effective on endothelial activation when HUVECs are exposed to supernatants from S1-activated macrophages; the induction of VCAM-1, indeed, is not affected by the drug, while that of ICAM-1 is only poorly inhibited. The drug, however, also exerts protective effects on the endothelium by limiting the expression of pro-inflammatory mediators, specifically IL-6, RANTES and IP-10. No effect of baricitinib has been observed on IL-8 synthesis and, consistently, on neutrophils chemiotaxis. Our in vitro findings reveal that the efficacy of baricitinib is limited, with effects mainly focused on the inhibition of the IL-6-mediated inflammatory loop.

Effectiveness of mobile health interventions targeting parents to prevent and treat childhood Obesity: Systematic review.

Childhood obesity is a high prevalence condition that causes a high burden of disease in adulthood. Mobile phone app are increasingly used to prevent it. We summarized the evidence on the effectiveness of mobile apps for devices used by parents to prevent and treat childhood and adolescent obesity. An update of a systematic review of the literature (De Lepeleere et al., 2017) was carried out. PubMed, Embase, Cochrane, CINAHL, PsycINFO, Scopus, and ERIC were searched up to 2020. The included studies should target children 1-18 years, compare an app aimed at preventing or treating overweight and obesity, as stand-alone intervention or as part of a complex program, installed on parents' mobile devices, to no intervention or an intervention without the app. Outcomes related to weight status, diet, and physical activity (PA) behaviors were considered. Nineteen studies (14 RCTs and 5 non-randomized trials) were included. The app was mainly used to record food consumption and PA, to set goals, to view progress, and send health promotion messages. One study reported a significant decrease and one a suggestive decrease in anthropometric measures in obese and overweight children, while other studies observed no effect. One study reported a significant increase in PA. Six interventions proved to be effective in changing dietary behaviors. Interventions targeting overweight and/or obese children had the most positive results. All studies reported high acceptability and feasibility of interventions. The differences between interventions and the small sample size of the studies did not allow this review to reach conclusion on effectiveness.

Innovative Closed-Loop Recyclable Bio-Based Composites from Epoxidized Waste Flour and Recycled Carbon Fibers.

Epoxy-based composites are designed for long-lasting applications, though their wide use is in contrast with their poor recyclability, which poses serious end-of-life issues. In order to reduce their environmental impact, precursors derived from fossil fuel based raw materials should be replaced with eco-friendly sources. This can be attained by using naturally derived epoxy matrices, or by finding a suitable solution for recycling at the end of life. In this paper, both strategies were analyzed, by replacing traditional monomers with epoxidized waste flour (EWF), an innovative bio-precursor derived from the organic waste stream, and a cleavable hardener, which allowed the recyclability of the matrix. The recyclable matrix was reinforced with recycled carbon fibers, derived from pyrolysis. DSC measurements were carried out in order to optimize the curing steps of the matrix, then flexural tests were performed in order to evaluate the mechanical response of the composite. A green recycling procedure was then investigated, which involved the use of non-toxic solvents and mild working conditions, and allowed recovery of the matrix while still preserving the properties of the carbon fibers. The components obtained after recycling were analyzed by FTIR analysis, which revealed the presence of the epoxy ring on the recycled waste flour. Hence, recycled waste flour was again used as a precursor and mixed with the cleavable hardener, thus, obtaining a closed-loop recycling.

Cardiac and Respiratory Influences on Intracranial and Neck Venous Flow, Estimated Using Real-Time Phase-Contrast MRI.

The study of brain venous drainage has gained attention due to its hypothesized link with various neurological conditions. Intracranial and neck venous flow rate may be estimated using cardiac-gated cine phase-contrast (PC)-MRI. Although previous studies showed that breathing influences the neck's venous flow, this aspect could not be studied using the conventional segmented PC-MRI since it reconstructs a single cardiac cycle. The advent of real-time PC-MRI has overcome these limitations. Using this technique, we measured the internal jugular veins and superior sagittal sinus flow rates in a group of 16 healthy subjects (12 females, median age of 23 years). Comparing forced-breathing and free-breathing, the average flow rate decreased and the respiratory modulation increased. The flow rate decrement may be due to a vasoreactive response to deep breathing. The respiratory modulation increment is due to the thoracic pump's greater effect during forced breathing compared to free breathing. These results showed that the breathing mode influences the average blood flow and its pulsations. Since effective drainage is fundamental for brain health, rehabilitative studies might use the current setup to investigate if respiratory exercises positively affect clinical variables and venous drainage.

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus.

OBJECTIVE: HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. DESIGN: We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. METHODS: Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. RESULTS: Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. CONCLUSION: In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection.

Immune-Mediated Inflammatory Responses of Alveolar Epithelial Cells: Implications for COVID-19 Lung Pathology.

BACKGROUND: Clinical and experimental evidence point to a dysregulated immune response caused by SARS-CoV-2 as the primary mechanism of lung disease in COVID-19. However, the pathogenic mechanisms underlying COVID-19-associated ARDS (Acute Respiratory Distress Syndrome) remain incompletely understood. This study aims to explore the inflammatory responses of alveolar epithelial cells to either the spike S1 protein or to a mixture of cytokines secreted by S1-activated macrophages. METHODS AND RESULTS: The exposure of alveolar A549 cells to supernatants from spike-activated macrophages caused a further release of inflammatory mediators, with IL-8 reaching massive concentrations. The investigation of the molecular pathways indicated that NF-kB is involved in the transcription of IP-10 and RANTES, while STATs drive the expression of all the cytokines/chemokines tested, with the exception of IL-8 which is regulated by AP-1. Cytokines/chemokines produced by spike-activated macrophages are also likely responsible for the observed dysfunction of barrier integrity in Human Alveolar Epithelial Lentivirus-immortalized cells (hAELVi), as demonstrated by an increased permeability of the monolayers to mannitol, a marked decrease of TEER and a disorganization of claudin-7 distribution. CONCLUSION: Upon exposure to supernatants from S1-activated macrophages, A549 cells act both as targets and sources of cytokines/chemokines, suggesting that alveolar epithelium along with activated macrophages may orchestrate lung inflammation and contribute to alveolar injury, a hallmark of ARDS.

Desmopressin Stimulates Nitric Oxide Production in Human Lung Microvascular Endothelial Cells.

Desmopressin (dDAVP) is the best characterized analogue of vasopressin, the endocrine regulator of water balance endowed with potent vasoconstrictive effects. Despite the use of dDAVP in clinical practice, ranging from the treatment of nephrogenic diabetes insipidus to bleeding disorders, much remains to be understood about the impact of the drug on endothelial phenotype. The aim of this study was, thus, to evaluate the effects of desmopressin on the viability and function of human pulmonary microvascular endothelial cells (HLMVECs). The results obtained demonstrate that the vasopressor had no cytotoxic effect on the endothelium; similarly, no sign of endothelial activation was induced by dDAVP, indicated by the lack of effect on the expression of inflammatory cytokines and adhesion molecules. Conversely, the drug significantly stimulated the production of nitric oxide (NO) and the expression of the inducible isoform of nitric oxide synthase, NOS2/iNOS. Since the intracellular level of cAMP also increased, we can hypothesize that NO release is consequent to the activation of the vasopressin receptor 2 (V2R)/guanylate cyclase (Gs)/cAMP axis. Given the multifaceted role of NOS2-deriving NO for many physio-pathological conditions, the meanings of these findings in HLMVECs appears intriguing and deserves to be further addressed.