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Introduction: Acute thrombosis of an infrarenal abdominal aortic aneurysm (ATAAA) represents an uncommon but catastrophic pathology, which can lead to life threatening complications. This is a report of the infrequent use of an endovascular solution to successfully treat ATAAA in a patient with COVID-19 viral pneumonia and ischaemia induced lower extremity neurological deficits. Report: An 89 year old white male, with a history of cardiovascular comorbidities was admitted to the emergency room with dyspnoea associated with the sudden onset of abdominal and back pain followed by partial motor and sensory deficits in both legs. The CT scan showed both an 8 cm infrarenal AAA with middle (inferior mesenteric artery patent) and distal thrombotic occlusion of the sac and non-aneurysmal but thrombosed common iliac arteries. An additional finding was imaging features typical of interstitial pneumonia. After the molecular test detected active COVID-19 infection, the patient was treated as an emergency with an aorto-uni-iliac stent graft and femorofemoral crossover graft. The post-operative course was uneventful with AAA exclusion and disappearance of ischaemic symptoms. There were no vascular complications. At three month follow up the patient remained asymptomatic and was looking after himself. Discussion: This case supports the feasibility and safety of a minimally invasive endovascular procedure to treat ATAAA in selected patients with favourable anatomy and high risk of respiratory complications in the context of the COVID-19 pandemic.

Gut microbiota has implications in Central Nervous System (CNS) disorders. Our study systematically identified preclinical studies aimed to investigate the possible gut microbiota contribution in neuropathy and neuropathic pain. The systematic review is reported in accordance with PRISMA checklist and guidelines outlined updated to 2020. We included research articles reporting neuropathy-related behavioral evaluations and/or neurological scores coupled to gut microbiota analysis performed by high-throughput technologies in the last ten years. Two investigators performed a search through 3 electronic bibliographic databases for full-text articles (PubMed, Scopus, and EMBASE) and three registries (Prospero, SyRF, and bioRxiv), cross-references, and linear searches. We assessed the methodological quality via the CAMARADES checklist and appraised the heterogeneous body of evidence by narrative synthesis. In total, there were 19 eligible studies. The most of these reports showed significant changes in gut microbiota setting in neuropathy conditions. The major gut microbiome remodeling was through fecal microbiome transplantation. Mechanistic proof of the gut-CNS communication was achieved by measuring inflammatory mediators, metabolic products, or neurotransmitters. As a limitation, we found considerable heterogeneity across eligible studies.We conclude that the current understanding of preclinical findings suggested an association between neuropathy and/or neuropathic pain and gut microbiota modifications. Our analysis provides the basis for further studies targeting microbiota for managing symptoms of neuropathy or other neuroinflammation-based CNS disorders. The systematic review protocol was registered on the international database Prospero under the registration number (257628).

Abstract Background Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. Methods We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. Results Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. Conclusion The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

Abstract Background Dermatochalasis of the upper eyelids (blepharochalasis) is a typical age-related change in the upper third of the face and a major concern for facial aesthetics. Nowadays both surgical and nonsurgical interventions are available for patients complaining of upper eyelid dermatochalasis. Although nonsurgical treatments are often easier to perform, if they are not performed correctly, complications may ensue and worsen the condition. Case presentation We describe the case of a Caucasian patient presenting with bilateral upper eyelid dermatochalasis, previously treated with multiple injections of hyaluronic acid filler. Following these procedures, the patient reported nonspecific eye symptoms (such as a sense of heaviness and asthenopia) and cosmetic concerns. We decided to perform an upper eyelid blepharoplasty. During the procedure we found a ribbon of hard, fibrous material, which was carefully removed. The patient reported resolution of functional eye symptoms owing to the reduction of upper lid heaviness, which also resulted in subjective improvement of the visual field. Patient satisfaction was assessed preoperatively and 3 months postoperatively using the Blepharoplasty Outcomes Evaluation (BOE), which showed an overall satisfaction rate of 95.8 %. Conclusions Blepharoplasty not only treated the patient’s blepharochalasis but also allowed us to correct the previous nonsurgical intervention by removing the excessive amount of injected hyaluronic acid. Both aesthetic and functional results were successfully achieved.

This study employs a survey to investigate the societal response to COVID-19 in Italy. Data were collected via snowball sampling during the period April 2020 to April 2021 using the ArcGIS Survey 123 survey instrument. The study collected and analyzed 64 responses to investigate various aspects related to COVID-19. The areas covered in the analysis include socioeconomics, changing symptoms, relocation, physical distancing, health, social behaviors (past and future), personal attitudes, perceptions of government/public response and efficacy, beliefs, travel habits, well-being, current event worries, pandemic challenges, depression, vaccine, public opinion, personality, public health measures, social media preference, and contact with others. The study’s results provide a snapshot of how people across Italy experienced the crisis caused by the COVID-19 pandemic, and can help public health organizations, decision-makers, and the general public address policies related to symptoms, social distance, policy measures/regulations, and social behaviors during the different policy phases and wave measures related to COVID-19 effects.

Inflammation of the adipose tissue contributes to the onset and progression of several chronic obesity-related diseases. The two most important lipophilic diterpenoid compounds found in the root of Salvia milthorrhiza Bunge (also called Danshen), tanshinone IIA (TIIA) and cryptotanshinone (CRY), have many favorable pharmacological effects. However, their roles in obesity-associated adipocyte inflammation and related sub-networks have not been fully elucidated. In the present study, we investigated the gene, miRNAs and protein expression profile of prototypical obesity-associated dysfunction markers in inflamed human adipocytes treated with TIIA and CRY. The results showed that TIIA and CRY prevented tumor necrosis factor (TNF)-α induced inflammatory response in adipocytes, by counter-regulating the pattern of secreted cytokines/chemokines associated with adipocyte inflammation (CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, IL-6, IL-8, MIF and PAI-1/Serpin E1) via the modulation of gene expression (as demonstrated for CCL2/MCP-1, CXCL10/IP-10, CCL5/RANTES, CXCL1/GRO-α, and IL-8), as well as related miRNA expression (miR-126-3p, miR-223-3p, miR-124-3p, miR-155-5p, and miR-132-3p), and by attenuating monocyte recruitment. This is the first demonstration of a beneficial effect by TIIA and CRY on adipocyte dysfunction associated with obesity development and complications, offering a new outlook for the prevention and/or treatment of metabolic diseases.

Microplastics (MPs) pollution has increasingly exposed the pelagic biota to physical harm. The small size of micro-particles makes them more suitable for passive ingestion by a wide variety of organisms with serious effects on growth rates, respiration and vital functions, bioaccumulation of pollutants, and, ultimately, species survival. Nevertheless, our knowledge of plastic intake in nursery habitats is still very limited. When encounters with MPs occur at the larval stage, it is suggested that fish can develop altered feeding behaviors with cascading effects on the entire food web. This study provides a step-by-step protocol to identify and enumerate polymer particles found in fish diets. The procedure is intended for the analysis of larval and juvenile fish populations with a developed digestive tract. It includes guiding questions for research design, a list of supplies and reagents to extract and mount the fish diets on microscope slides for semi-permanent conservation, the protocol for microscopic and statistical analysis, and the interpretation of the results. We suggest that the gut content could be used to assess (i) the bioavailability of polymers in water systems, (ii) the incidence of an encounter between larval fish and MPs, and (iii) the possible alternations in fish’ feeding behaviors as soon as they leave their parental stage.

Background: Multicomponent interventions based on a comprehensive geriatric assessment (CGA) could promote active aging and improve health status in older people with Noncommunicable Chronic Diseases (NCDs), but conflicting evidences are available. Aim: To evaluate the efficacy of a CGA-based multicomponent personalized preventive program (PPP) in reducing unplanned hospitalization rates during 12-month follow-up in community-dwelling older people with NCDs. Materials and methods: In this randomized clinical trial (RCT), 1216 older adults recruited by 33 general practitioners (GPs) will be randomly allocated to intervention group (IG) or usual care control group (CG). The IG will receive a multicomponent PPP developed on the findings of the CGA-based Multidimensional Prognostic Index short-form (Brief-MPI), including structured interventions to improve functional, physical, cognitive, and nutritional status, to monitor NCDs and vaccinations, and to prevent social isolation. Participants in the CG will receive usual care. Brief-MPI, resilience, and health-related quality of life will be assessed after 6 and 12 months. Moreover, saliva samples will be collected at baseline in IG to measure biomarkers of oxidative stress, inflammatory cytokines, and oral microbiome. Expected results: The CGA-based PPP might reduce unplanned hospitalization rates and potentially institutionalization rates, emergency department (ED) and unplanned GP visits, and mortality. Further outcomes explored in the IG will be the adherence to PPP, resilience, health-related quality of life, and multidimensional frailty as assessed by the Brief-MPI. Conclusions: Results will suggest whether the CGA-based multicomponent PPP is able to improve specific outcomes in a primary care setting. Trial registration: ClinicalTrials.gov; identifier: NCT06224556; Registered January 25, 2024. [ABSTRACT FROM AUTHOR]

Introduction: Transboundary pollution is a major global challenge and monitoring beach litter along international borders can reveal some of the pathways by which litter enters water bodies, and hence advance the implementation of measures to prevent pollution emissions into international waters. Methods: In this paper, participatory mapping was used to detect beach litter in Imperial Beach, California, along the U.S.-Mexico international border. This study implemented a 3-step protocol including an introductory awareness workshop, a macro-debris survey to categorize and remove beach litter, and a qualitative assessment of pollution drivers. Results: Results show that plastic litter is the most dominant across all transects (304 debris, 52.6% of all litter observations), with an average density of 76 pieces/transect, with plastic being the most common material. Participants identified some of the major causes of pollution with paucity of waste management facilities, tourism activities near/on the beach, and inflow of pollution across the border. Discussion: The paper highlights the role of citizen science in monitoring pollution along large and border regions. Implications of this study include methodological and practical contributions to the study of marine pollution to supplement the current paucity of information on pollution movement and distribution. [ABSTRACT FROM AUTHOR]

This article presents the findings of a 24-week retrospective study that aimed to evaluate the efficacy and safety of bimekizumab (BKZ) in elderly patients with moderate-to-severe plaque psoriasis. The study involved 15 elderly patients who were treated with BKZ, and the results showed a significant decrease in Psoriasis Area and Severity Index (PASI) scores over the course of the study. The treatment was well tolerated, with only two patients discontinuing due to minor adverse events. The study suggests that BKZ is an effective treatment option for elderly patients with plaque psoriasis. However, further research with larger cohorts and longer follow-up periods is needed to validate these findings. [Extracted from the article]

Objective Testosterone concentrations, albeit rarely, may be in the normal range (>3.0 ng/mL) in men with a prolactin-secreting pituitary adenoma (PSPA-nt). The evolution of total, bioavailable testosterone, gonadotropin levels, and that of graded symptoms of testosterone deficiency (TD) are uncertain in these patients. Design Retrospective case-control longitudinal study at a tertiary referral center. Methods From 287 men, we selected 25 PSPA-nt men undergoing prolactin normalization (<20.0 ng/mL) during the follow-up. Graded symptoms of TD were investigated by structured interviews. Biochemical changes and TD symptoms were compared to those of a matched cohort of 61 men with pituitary neoplasms and normal testosterone levels (PA-nt). Results Baseline testosterone levels were similar between PSPA-nt and PA-nt subjects. The prevalence of specific and suggestive symptoms of TD was higher in PSPA-nt (20% and 68%) than in PAnt (3.3 and 29.5%; P =.02 and P =.0015, respectively). At the follow-up, total and bioavailable testosterone levels increased in PSPA-nt but not in PA-nt patients (Δ change: 1.28 ± 2.1 vs0.03 ± 1.5 ng/mL, + 0.33 ± 0.55 vs-0.26 ± 0.60 ng/mL; P =.0028 and P =.0088, respectively). LH and FSH levels also increased in PSPA-nt men (P <.05). Specific and suggestive, but not nonspecific symptoms of TD, improved only in PSPA-nt men (P <.05 for both). Baseline testosterone and LH were the strongest predictors of testosterone improvement in PSPA-nt patients. Conclusion Despite having normal testosterone levels at baseline, patients with PSPA-nt experience a relief of TD symptoms and an improvement of their pituitary-gonadal axis function following prolactin normalization, especially when baseline TT and LH levels are in the low-normal range. [ABSTRACT FROM AUTHOR]

Purpose: The paper aims to carry out a comprehensive literature mapping to synthesise and descriptively analyse the research trends of biodiversity accounting, providing implications for managers and policymakers, whilst also outlining a future agenda for scholars. Design/methodology/approach: A bibliometric analysis is carried out by adopting the Preferred Reporting Items for Systematic Review and Meta-Analyses protocol for searching and selecting the scientific contributions to be analysed. Citation analysis is used to map a current research front and a bibliographic coupling is conducted to detect the connection networks in current literature. Findings: Biodiversity accounting is articulated in five thematic clusters (sub-areas), such as "Natural resource management", "Biodiversity economic evaluation", "Natural capital accounting", "Biodiversity accountability" and "Biodiversity disclosure and reporting". Critical insights emerge from the content analysis of these sub-areas. Practical implications: The analysis of the thematic evolution of the biodiversity accounting literature provides useful insights to inform both practice and research and infer implications for managers, policymakers and scholars by outlining three main areas of intervention, i.e. adjusting evaluation tools, integrating ecological knowledge and establishing corporate social legitimacy. Social implications: Currently, the level of biodiversity reporting is pitifully low. Therefore, organisations should properly manage biodiversity by integrating diverse and sometimes competing forms of knowledge for the stable and resilient flow of ecosystem services for future generations. Originality/value: This paper not only updates and enriches the current state of the art but also identifies five thematic areas of the biodiversity accounting literature for theoretical and practical considerations. [ABSTRACT FROM AUTHOR]

Background: In carefully selected patients with an arthritic valgus knee, distal femoral osteotomy (DFO) can improve symptoms at medium- to long-term follow-up, reducing osteoarthritis progression. To date, there is no clear evidence in the current literature regarding the role of postoperative joint line obliquity (JLO) in valgus deformity correction. Purpose: To assess the clinical and radiological outcomes of medial closing-wedge DFO (MCW-DFO) for the treatment of valgus knees, considering both tibial- and femoral-based deformities, as well as to verify the efficacy and safety of MCW-DFO according to JLO boundaries (≤4°). Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective analysis was conducted on a cohort of patients with valgus knees. Patients were divided into 2 groups: femoral-based valgus (FB-V) and tibial-based valgus (TB-V). Knee radiographs were collected before surgery and at the last follow-up. The clinical outcome was evaluated through several validated scores (International Knee Documentation Committee, Knee Society Score, Knee injury and Osteoarthritis Outcome Score, Tegner, Numeric Rating Scale, Crosby-Insall). Results: A total of 30 patients (34 knees) with a mean age of 49.3 ± 9.1 years were included in the study. The overall mean follow-up was 9.4 ± 5.9 years. The mean preoperative hip-knee-ankle angle was 187.6°± 3.3° (range, 181.5°-191°) and the postoperative angle was 180°± 3.1° (range, 176°-185°). Most postoperative JLOs were within the safe zone of ≤4° in both groups (the postoperative JLO was >4° in 4 patients in the TB-V group and 1 patient in the FB-V group), although FB-V knees exhibited significant superior JLO correction (postoperative JLO in the TB-V group: mean, 4.0°± 2.5° [ P =.1]; postoperative JLO in the FB-V group: mean, 2.4°± 1.4° [ P =.5]). Significant improvements in all clinical scores were observed in both groups (P <.01). Additionally, the severity of the osteoarthritis did not worsen at the last follow-up. Conclusion: MCW-DFO is an effective procedure for treating pathological valgus knees, regardless of the site of the deformity. Both FB-V and TB-V groups showed comparable improvements in the clinical scores, development of osteoarthritis, and the restoration of a neutral mechanical axis. Notably, FB-V knees achieved more JLO correction compared with the TB-V ones. [ABSTRACT FROM AUTHOR]

Thousands of disease cases and hundreds of deaths occur globally each year due to invasive meningococcal disease. Neisseria meningitidis serogroup B (MenB) is the leading cause of such disease in developed countries. Two vaccines, 4CMenB and MenB‐fHbp, that protect against MenB are available and include one or two forms respectively of factor H binding protein (fHbp), a key protective antigen. Studies of circulating meningococci have identified over 1380 different fHbp amino acid sequences, which form three immunologically distinct clusters, termed variants 1, 2, and 3. Neither of the current vaccines contains a variant 2 antigen, which is less well characterized than fHbp variants 1 and 3. We characterized the interaction of fHbp variant 2 with humAb 1B1 using biochemical methods and live meningococcal assays. Further, we determined the crystal structure of the complex at 2.4 Å resolution, clearly revealing the epitope and providing the first detailed report of an antibody with distinct specificity for fHbp variant 2. Extensive mutagenesis and binding studies elucidated key hotspots in the interface. This combination of structural and functional studies provides a molecular explanation for the bactericidal potency and specificity of humAb 1B1 for fHbp variant 2. Our studies, focused on fHbp variant 2, expand the understanding of this previously under characterized group of the vast family of variants of fHbp, a virulence factor present on all meningococci. Moreover, the definition of a protective conformational epitope on fHbp variant 2 may support the design and development of novel variant 2‐containing MenB vaccines affording greater breadth of protection. [ABSTRACT FROM AUTHOR]

Background: Despite extensive studies on the neurobiological correlates of traumatic brain injury (TBI), little is known about its molecular determinants on long-term consequences, such as dementia and Alzheimer's disease (AD). Methods: Here, we carried out behavioural studies and an extensive biomolecular analysis, including inflammatory cytokines, gene expression and the combination of LC-HRMS and MALDI-MS Imaging to elucidate the targeted metabolomics and lipidomics spatiotemporal alterations of brains from wild-type and APP-SWE mice, a genetic model of AD, at the presymptomatic stage, subjected to mild TBI. Results: We found that brain injury does not affect cognitive performance in APP-SWE mice. However, we detected an increase of key hallmarks of AD, including Aβ1-42 levels and BACE1 expression, in the cortices of traumatized transgenic mice. Moreover, significant changes in the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), occurred, including increased levels of the endocannabinoid 2-AG in APP-SWE mice in both the cortex and hippocampus, and N-acylserotonins, detected for the first time in the brain. The gene expression of enzymes for the biosynthesis and inactivation of eCBs and eCB-like mediators, and some of their main molecular targets, also underwent significant changes. We also identified the formation of heteromers between cannabinoid 1 (CB1) and serotonergic 2A (5HT2A) receptors, whose levels increased in the cortex of APP-SWE mTBI mice, possibly contributing to the exacerbated pathophysiology of AD induced by the trauma. Conclusions: Mild TBI induces biochemical changes in AD genetically predisposed mice and the eCBome may play a role in the pathogenetic link between brain injury and neurodegenerative disorders also by interacting with the serotonergic system. [ABSTRACT FROM AUTHOR]

Abstract The cause of hepatic portal vein gas (HPVG) is variable. Good knowledge of the possible causes, combined with the clinical assessment of the patient and a good quality imaging, is required to correctly identify the underlying cause of HPVG and to best predict the prognosis.

Maria Grazia Ferraro,1 Marialuisa Piccolo,1 Alessandro Pezzella,2 Fabrizia Guerra,1 Francesco Maione,1 Gian Carlo Tenore,1 Rita Santamaria,1 Carlo Irace,1 Ettore Novellino1 1Department of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, Naples, 80131, Italy; 2Department of Chemical Sciences, University of Naples “Federico II”, Naples, 80126, ItalyCorrespondence: Carlo Irace;Rita SantamariaDepartment of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, Via D. Montesano 49, Naples, 80131, ItalyTel +39 081 678416; +39 081 678421Fax +39 081 678403Email carlo.irace@unina.it; rita.santamaria@unina.itIntroduction: Melanocytes are engaged in synthesis, transport, and release of pigments at the epidermal-melanin units in response to the finely regulated melanogenic pathway. A multifaceted combination of both intrinsic and extrinsic factors – from endocrine and paracrine dynamics to exogenous stimuli such as sunlight and xenobiotics – modulates expression and activity of proteins involved in pigmentation, including the rate-limiting enzyme tyrosinase. As well as playing critical physiological functions comprising skin photoprotection, melanins define hair and skin pigmentation which in turn have impacted considerably to human social communication since time immemorial. Additionally, numerous skin diseases based on pigmentation alterations can have serious public influence. While several melanogenesis inhibitors are already available, the number of melanin activators and tyrosinase stimulators as drug-like agents is still limited.Methods: To explore the biological effects of an Annurca Apple-based nutraceutical preparation (AMS) on melanin production, experiments in cellular models of human skin were performed. Both primary cultures and co-cultures of epidermal melanocytes (HEMa) and follicular keratinocytes (HHFK) were used.Results: We show that AMS, by now branded for its cutaneous beneficial effects, induces in total biocompatibility a significant promelanogenic effect in human primary melanocytes. In line, we found melanin cytosolic accumulation consistent with tyrosinase up-regulation.Conclusion: Disposal of skin pigmenting agents would be attractive for the treatment of hypopigmentation disorders, to postpone skin photoaging or simply for fashion, so that discovery and development of melanogenesis stimulators, especially from natural sources, is nowadays a dynamic area of research.Keywords: melanins, skin pigmentation, tyrosinase, skin pigmenting agents, natural bioactive molecules

Abstract Background The display of recombinant proteins on cell surfaces has a plethora of applications including vaccine development, screening of peptide libraries, whole-cell biocatalysts and biosensor development for diagnostic, industrial or environmental purposes. In the last decades, a wide variety of surface display systems have been developed for the exposure of recombinant proteins on the surface of Escherichia coli, such as autotransporters and outer membrane proteins. Results In this study, we assess three approaches for the surface display of a panel of heterologous and homologous mature lipoproteins in E. coli: four from Neisseria meningitidis and four from the host strain that are known to be localised in the inner leaflet of the outer membrane. Constructs were made carrying the sequences coding for eight mature lipoproteins, each fused to the delivery portion of three different systems: the autotransporter adhesin involved in diffuse adherence-I (AIDA-I) from enteropathogenic E. coli, the Lpp’OmpA chimaera and a truncated form of the ice nucleation protein (INP), InaK-NC (N-terminal domain fused with C-terminal one) from Pseudomonas syringae. In contrast to what was observed for the INP constructs, when fused to the AIDA-I or Lpp’OmpA, most of the mature lipoproteins were displayed on the bacterial surface both at 37 and 25 °C as demonstrated by FACS analysis, confocal and transmission electron microscopy. Conclusions To our knowledge this is the first study that compares surface display systems using a number of passenger proteins. We have shown that the experimental conditions, including the choice of the carrier protein and the growth temperature, play an important role in the translocation of mature lipoproteins onto the bacterial surface. Despite all the optimization steps performed with the InaK-NC anchor motif, surface exposure of the passenger proteins used in this study was not achieved. For our experimental conditions, Lpp’OmpA chimaera has proved to be an efficient surface display system for the homologous passenger proteins although cell lysis and phenotype heterogeneity were observed. Finally, AIDA-I was found to be the best surface display system for mature lipoproteins (especially heterologous ones) in the E. coli host strain with no inhibition of growth and only limited phenotype heterogeneity.

Perfluorocarbons (PFCs) are amongst the most potent greenhouse gases listed under the United Nations Framework Convention on Climate Change (UNFCCC). With atmospheric lifetimes on the order of thousands to tens of thousands of years, PFC emissions represent a permanent alteration to the global atmosphere on human timescales. While the industries responsible for the vast majority of these emissions – aluminium smelting and semi-conductor manufacturing – have made efficiency improvements and introduced abatement measures, the global mean mole fractions of three PFCs, namely tetrafluoromethane (CF4, PFC-14), hexafluoroethane (C2F6, PFC-116) and octafluoropropane (C3F8, PFC-218), continue to grow. In this study, we update baseline growth rates using in situ high-frequency measurements from the Advanced Global Atmospheric Gases Experiment (AGAGE) and, using data from four European stations, estimate PFC emissions for northwest Europe. The global growth rate of CF4 decreased from 1.3 ppt yr−1 in 1979 to 0.6 ppt yr−1 around 2010 followed by a renewed steady increase to 0.9 ppt yr−1 in 2019. For C2F6, the growth rate grew to a maximum of 0.125 ppt yr−1 around 1999, followed by a decline to a minimum of 0.075 ppt yr−1 in 2009, followed by weak growth thereafter. The C3F8 growth rate was around 0.007 ppt yr−1 until the early 1990s and then quickly grew to a maximum of 0.03 ppt yr−1 in 2003–2004. Following a period of decline until 2012 to 0.015 ppt yr−1, the growth rate slowly increased again to ∼ 0.017 ppt yr−1 in 2019. We used an inverse modelling framework to infer PFC emissions for northwest Europe. No statistically significant trend in regional emissions was observed for any of the PFCs assessed. For CF4, European emissions in early years were linked predominantly to the aluminium industry. However, we link large emissions in recent years to a chemical manufacturer in northwest Italy. Emissions of C2F6 are linked to a range of sources, including a semi-conductor manufacturer in Ireland and a cluster of smelters in Germany's Ruhr valley. In contrast, northwest European emissions of C3F8 are dominated by a single source in northwest England, raising the possibility of using emissions from this site for a tracer release experiment.

Abstract Neuropathic pain (NP) remains an untreatable disease due to the complex pathophysiology that involves the whole pain neuraxis including the forebrain. Sensory dysfunctions such as allodynia and hyperalgesia are only part of the symptoms associated with neuropathic pain that extend to memory and affectivity deficits. The development of multi-target molecules might be a promising therapeutic strategy against the symptoms associated with NP. 2-pentadecyl-2-oxazoline (PEA-OXA) is a plant-derived agent, which has shown effectiveness against chronic pain and associated neuropsychiatric disorders. The molecular mechanisms by which PEA-OXA exerts its effects are, however, only partially known. In the current study, we show that PEA-OXA, besides being an alpha2 adrenergic receptor antagonist, also acts as a modulator at histamine H3 receptors, and report data on its effects on sensory, affective and cognitive symptoms associated with the spared nerve injury (SNI) model of neuropathic pain in mice. Treatment for 14 days with PEA-OXA after the onset of the symptoms associated with neuropathic pain resulted in the following effects: (i) allodynia was decreased; (ii) affective/cognitive impairment associated with SNI (depression, spatial, and working memories) was counteracted; (iii) long-term potentiation in vivo in the lateral entorhinal cortex-dentate gyrus (perforant pathway, LPP) was ameliorated, (iv) hippocampal glutamate, GABA, histamine, norepinephrine and dopamine level alterations after peripheral nerve injury were reversed, (v) expression level of the TH positive neurons in the Locus Coeruleus were normalized. Thus, a 16-day treatment with PEA-OXA alleviates the sensory, emotional, cognitive, electrophysiological and neurochemical alterations associated with SNI-induced neuropathic pain.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by impaired left ventricular (LV) diastolic function, with normal LV ejection fraction. Aortic valve stenosis can cause an HFpEF-like syndrome by inducing sustained pressure overload (PO) and cardiac remodeling, as cardiomyocyte (CM) hypertrophy and fibrotic matrix deposition. Recently, in vivo studies linked PO maladaptive myocardial changes and DNA damage response (DDR) activation: DDR-persistent activation contributes to mouse CM hypertrophy and inflammation, promoting tissue remodeling, and HF. Despite the wide acknowledgment of the pivotal role of the stromal compartment in the fibrotic response to PO, the possible effects of DDR-persistent activation in cardiac stromal cell (C-MSC) are still unknown. Finally, this novel mechanism was not verified in human samples. This study aims to unravel the effects of PO-induced DDR on human C-MSC phenotypes. Human LV septum samples collected from severe aortic stenosis with HFpEF-like syndrome patients undergoing aortic valve surgery and healthy controls (HCs) were used both for histological tissue analyses and C-MSC isolation. PO-induced mechanical stimuli were simulated in vitro by cyclic unidirectional stretch. Interestingly, HFpEF tissue samples revealed DNA damage both in CM and C-MSC. DDR-activation markers γH2AX, pCHK1, and pCHK2 were expressed at higher levels in HFpEF total tissue than in HC. Primary C-MSC isolated from HFpEF and HC subjects and expanded in vitro confirmed the increased γH2AX and phosphorylated checkpoint protein expression, suggesting a persistent DDR response, in parallel with a higher expression of pro-fibrotic and pro-inflammatory factors respect to HC cells, hinting to a DDR-driven remodeling of HFpEF C-MSC. Pressure overload was simulated in vitro, and persistent activation of the CHK1 axis was induced in response to in vitro mechanical stretching, which also increased C-MSC secreted pro-inflammatory and pro-fibrotic molecules. Finally, fibrosis markers were reverted by the treatment with a CHK1/ATR pathway inhibitor, confirming a cause-effect relationship. In conclusion we demonstrated that, in severe aortic stenosis with HFpEF-like syndrome patients, PO induces DDR-persistent activation not only in CM but also in C-MSC. In C-MSC, DDR activation leads to inflammation and fibrosis, which can be prevented by specific DDR targeting.