Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.

On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection1. This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Palladium-modified TiO2 films in a photocatalytic microreactor: evaluation of radiation absorption properties and pollutant degradation efficiency.

Pure (TiO2) and 0.1 nominal atomic percent of palladium-modified TiO2 (Pd-TiO2) films were synthesized via a sol-gel method and compared through their physicochemical properties and photocatalytic activity in the degradation of an emerging contaminant, 17-α-ethinylestradiol (EE2). The activity of the films was studied using a continuous flow, planar microreactor under simulated sunlight. Catalysts characterization included X-ray diffraction, UV-Visible diffuse reflectance and transmittance spectroscopy, atomic force microscopy, transmission electron microscopy, Raman spectroscopy, N2 physisorption analysis, and X-ray photoelectron spectroscopy. The modification of TiO2 with palladium confined the size of anatase phase crystallites, increased the specific surface area and improved radiation absorption. PdO domains on TiO2 were observed. In all the tested conditions, higher conversion of EE2 was achieved with the Pd-TiO2 film compared with the TiO2 film, presenting an 80% increase in the reaction rate. The performance of the catalytic films was also assessed by the calculation of two efficiency parameters: radiation absorption efficiency and quantum efficiency of reaction. The Pd-TiO2 film showed a notable enhancement of the absorption of the incident radiation and a more efficient utilization of the absorbed photons to degrade the target pollutant.

Sleep and emotionality in adolescents with anorexia nervosa during the Covid-19 pandemic.

PURPOSE: The recent Covid-19 pandemic and its lockdown measures raised concerns about people's mental health, leading to an increased interest in identifying vulnerable groups especially at risk for mental distress. This cross-sectional study investigated the impact of this unprecedented situation on sleeping patterns and emotionality in adolescents with anorexia nervosa (AN). METHODS: Variations in sleeping patterns and emotionality of two groups of adolescents with AN, assessed before (N = 50) and during (N = 51) the Covid-19 lockdown were analysed. We further investigated these variations over time, considering the two lockdown periods in France. RESULTS: Adolescents self-reported significantly more sleep difficulties and lower rates of positive emotions during lockdown, compared to those evaluated before it. Furthermore, present findings overall suggest that as the lockdown progresses, adolescents with AN show an increased deterioration of sleep quality, as indicated by greater insomnia severity levels. They also show a significant decrease in the subjective experience of positive emotionality, in particular in feelings of tenderness. CONCLUSIONS: These sleep and emotionality alterations may have amplified the severity and the incidence of AN in adolescents during the Covid-19 pandemic. These features may therefore represent therapeutic targets to optimise care of adolescents with AN. This is particularly urgent, considering kinetics of the deterioration. Tools such as those provided by cognitive behavioural therapy for insomnia and by the positive psychology framework seem appropriate to guide clinicians in this context. LEVEL OF EVIDENCE: Level V, descriptive study (evaluation data retrospectively studied).

Carriage meningococcal isolates with capsule null locus dominate among high school students in a non-endemic period, Italy, 2012-2013.

Meningococcal disease incidence in Italy remains quite low in the overall population except for infants. Within a study on carriage isolates among high school students we aimed to define: i) the prevalence of carriage isolates, ii) the phenotypic and iii) the molecular features of meningococci by Whole Genome Sequencing (WGS). A total of 1697 pharyngeal samples from undergraduate students (age range 14-19 years) were collected from 2012 to 2013 from six larger cities in Italy. One hundred and twenty culture positive meningococci (7%) were analyzed. Carriage isolates were sent to the National Reference Laboratory for invasive meningococcal disease (IMD) for PCR-based serogroup identification, Multilocus Sequence Typing, PorA and FetA typing. Moreover, factor H binding protein (fHbp), Neisseria Heparin Binding Antigen (NHBA) and Neisserial adhesin A (NadA) were typed. Core genome MLST (cgMLST) was performed on a subsample of 75 carriage isolates. Capsule null locus (cnl) predominated (47%), followed by serogroup B (27%). The antimicrobial susceptibility profile revealed an high prevalence of reduced susceptibility to penicillin G (54%) and a full susceptibility to ceftriaxone, ciprofloxacin and rifampicin. Carriage isolates presented a high genetic diversity: the clonal complexes (ccs) cc1136, cc198 and cc41/44, were the predominant. An high heterogeneity was also observed for PorA and FetA types. The fhbp and nhba genes were identified in all the carriage isolates; only 5% of the carriage isolates presented the nadA gene. The core genome MLST analysis revealed that the majority of the cnl isolates clustered in a distinct group. The evidence gathered during this study provides the estimate of carriage isolates in high school students in a non-epidemic period in Italy that was lower than expected. Moreover, the highest proportion of carriage isolates were cnl and, overall, they were molecular heterogeneous.

Vibrio cholerae non-O1, non-O139 bacteraemia associated with pneumonia, Italy 2016.

This paper describes an elderly male patient, living in the Veneto Region, Italy, who developed Vibrio cholerae bacteraemia and pneumonia. Some days previously, while on holiday in the Lagoon of Venice, he had been collecting clams in seawater, during which he suffered small abrasions of the skin. On admission to hospital, he was confused, had fever and a cough, but neither diarrhoea nor signs of gastroenteritis were found. Both blood and stool cultures grew V. cholerae of non-O1 non-O-139 type, and the patient recovered after prompt administration of intravenous ceftriaxone for 2 weeks. This clinical case emphasises the role of global warming and climate changes in causing increasing numbers of water-borne infections.

Persistent occurrence of serogroup Y/sequence type (ST)-23 complex invasive meningococcal disease among patients aged five to 14 years, Italy, 2007 to 2013.

In Italy, the incidence of invasive meningococcal disease (IMD) has remained stable since 2007 (around 0.3 cases/100,000 inhabitants). However, as reported for other European countries, an increase of serogroup Y Neisseria meningitidis has been observed. In this study we report IMD cases from 2007 to 2013 in Italy and investigate the clinical and epidemiological features of cases affected by serogroup Y. Molecular characteristics of serogroup Y strains are also described. During the study period, the proportion of IMD cases due to serogroup Y increased, ranging from 2% in 2007 to 17% in 2013 (odds ratio (OR): 8.8), whereby the five to 14 years age group was mostly affected (p < 0.001). Overall 81 serogroup Y IMD cases were identified, with a median age of 18 years, ranging from three months to 84 years. Of the 81 respective patient samples, 56 were further subject to molecular typing. The sequence type (ST)-23 complex (clonal complex (cc)23) was predominant among serogroup Y meningococci (54/56 samples), and included nine different STs. Presumably, ST-23 was the founding genotype, with all the other STs presenting as single-locus variants. All cc23 isolates analysed harboured mutations in the lpxL1 gene; however, no associations among lpxL1 mutations, ST and age group were identified. Overall, these findings generate scientific evidence for the use of the quadrivalent meningococcal conjugate vaccine in the five to 14 years age group.

Research note: Virtual historical archive of the Faculty of Psychology, University of Buenos Aires, Argentina.

This article describes the organization, operation, and contents of the Virtual Historical Archive of the Faculty of Psychology, University of Buenos Aires, Argentina. The organization of this archive started in 2008, as part of the activities planned by the Chair II of History of Psychology, and gained the support of the Faculty of Psychology. From its beginnings to the present, several documentary sources and materials related to the history of psychology in Argentina have been incorporated. It currently contains six thematic sections and three special collections, and it is expected that in the future it will be extended to other thematic areas. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Degradation of carbamazepine in surface water: performance of Pd-modified TiO2 and Ce-modified ZnO as photocatalysts.

Carbamazepine is a widely used antiepileptic drug to control and treat a variety of disorders that is frequently detected in surface water, and in municipal and urban wastewater. This recalcitrant pollutant could be removed by alternative advanced oxidation technology such as heterogeneous photocatalysis. Ce-modified ZnO and Pd-modified TiO2 were synthesized by a microwave-assisted sol-gel method. According to the characterizations (Raman spectroscopy, UV-Vis diffuse reflectance spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy), a mixture of oxides was determined in both materials: CeO2/ZnO and PdO/TiO2. Photocatalytic degradation of carbamazepine in pure water under visible light (3 h) was assayed. The degradation percentage obtained with each catalyst was 80%, 53%, 20%, and 9% for ZnO, Ce-modified ZnO, TiO2, and Pd-modified TiO2, respectively. The leaching of Zn as a possible source of water contamination was tested, finding the lowest value for Ce-modified ZnO by adjusting the initial pH up to neutrality. Later, an environmentally relevant concentration of carbamazepine (228 µg L-1) was assayed, using local surface water (pH = 8.3). Despite the presence of other compounds in the real water matrix, after 5 h of photocatalysis, a 56% of degradation of the pharmaceutical and low leaching of Zn were achieved. The use of Ce-modified ZnO activated by visible light is a promising strategy for the abatement of pharmaceutical active compounds.

Sustainable Particleboards Based on Brewer's Spent Grains.

Brewer's spent grain (BSG) is the main solid waste generated in beer production and primarily consists of barley malt husks. Based on the active promotion of circular economy practices aimed at recycling food industry by-products, this study assessed for the first time the production of particleboards based on BSG as the sole source of lignocellulosic material and natural adhesive without the use of additives or other substrates. In order to achieve particleboards from entirely sustainable sources, BSG particles have to self-bind by thermo-compression with water. In this context, the aim of this study is to assess the effects of pressing temperatures and particle size on properties such as modulus of elasticity, modulus of rupture, internal bond, thickness swelling, and water absorption. The performance of binderless boards was compared with that of a control panel (control) using BSG combined with phenolic resin. Processing conditions were selected to produce boards with a target density of 1000 kg/m³ and a thickness of 5 mm. To confirm the efficiency of the self-adhesion process, scanning electron microscopy was used to examine the boards. The processes of self-adhesion and particle-to-particle contact were facilitated at a pressing temperature of 170 °C and a particle size range of 200-2380 µm (ground BSG), resulting in improved flexural properties and enhanced water resistance. The properties of BSG-based binderless boards were comparable to those reported for other biomass residues, suggesting that they might be used in non-structural applications, such as interior decoration.

3D in vitro Models of Pathological Skeletal Muscle: Which Cells and Scaffolds to Elect?

Skeletal muscle is a fundamental tissue of the human body with great plasticity and adaptation to diseases and injuries. Recreating this tissue in vitro helps not only to deepen its functionality, but also to simulate pathophysiological processes. In this review we discuss the generation of human skeletal muscle three-dimensional (3D) models obtained through tissue engineering approaches. First, we present an overview of the most severe myopathies and the two key players involved: the variety of cells composing skeletal muscle tissue and the different components of its extracellular matrix. Then, we discuss the peculiar characteristics among diverse in vitro models with a specific focus on cell sources, scaffold composition and formulations, and fabrication techniques. To conclude, we highlight the efficacy of 3D models in mimicking patient-specific myopathies, deepening muscle disease mechanisms or investigating possible therapeutic effects.

Rapid Antigen Test LumiraDxTM vs. Real Time Polymerase Chain Reaction for the Diagnosis of SARS-CoV-2 Infection: A Retrospective Cohort Study.

Background: Real time reverse transcription polymerase chain reaction (real time RT-PCR) testing is the gold standard for the diagnosis of SARS-CoV-2 infections. However, to expand the testing capacity, new SARS-CoV-2 rapid antigen tests (Ag-RDTs) have been implemented. Ag-RDTs are more rapid, but less reliable in terms of sensitivity, and real-life data on their performance in comparison with the real time RT-PCR test are lacking. Methods: We aimed at assessing the diagnostic performance of the third-generation antigenic swab LumiraDx™ compared with real time RT-PCR in a retrospective cohort study at the Infectious Diseases Unit of Padua. All of the patients who were consecutively tested for SARS-CoV-2 in our centre (by both real time RT-PCR and Ag-RTD LumiraDxTM) from 19 January to 30 May 2021, were included. Cycle-threshold (Ct) values of positive real time RT-PCR were recorded as well as the number of days from symptoms' onset to testing. Results: Among the 282 patients included, 80.9% (N = 228) tested positive to real time RT-PCR, and among these, 174 tested positive also to LumiraDx™. Compared with real time RT-PCR, which is considered as the gold standard for the assessment of the presence/absence of SARS-CoV-2 infection, LumiraDx™ showed an overall sensitivity of 76.3% and specificity of 94.4%. Sensitivity increased to 91% when testing was performed <10 days from symptoms' onset, and to 95% when considering Ct < 25. Multivariable binomial logistic regression showed that false negative LumiraDx™ results were significantly associated with high Ct values, and with further testing from symptoms' onset. Conclusions: The results of our study suggested that the LumiraDx™ SARS-CoV-2 antigen assay may be appropriate for the detection of SARS-CoV-2 infection, especially in its early phase when the test largely meets the performance requirements of the European Centre for Disease Prevention and Control (ECDC).

[Cardiac compromise in patients recovered from COVID-19 without troponin elevation assessed by cardiac magnetic resonance imaging]. / Hallazgos en resonancia cardiaca post COVID-19 en pacientes sin elevación de troponinas.

Background: The disease caused by coronavirus (COVID-19) affects the cardiovascular system, whether by direct viral aggression or indirectly through systemic inflammation and multiple organ compromise. A widely used method to determine cardiac injury is troponin measurement. The aim of this study is to evaluate the prevalence of cardiac involvement (CINV) in a population recovered from COVID-19, referred to cardiac MRI (CMR), who did not present troponin elevation. Methods: There were 156 patients that recovered from COVID-19 and who did not present troponin elevation referred to CMR. CINV was considered to be the presence of: late gadolinium enhancement (LGE), edema, myocarditis, pericarditis, left ventricular systolic dysfunction (LVSD) and/or depressed right ventricular systolic dysfunction (RVSD). Results: Prevalence of CINV was 28.8%, being more frequent in men (p=0.002), in patients who required hospitalization (p=0.04) and in those who experienced non-mild cases of infection (p=0.007). RVSD (17.9%) and LVSD (13.4%) were the most frequent findings. The rate of myocarditis was 0.6%. LGE manifested in 7.1% of patients and its presence was related to less left ventricular ejection fraction (LVEF) (p=0.0001) and right ventricular ejection fraction (RVEF) (p=0.04). Conclusion: In patients who recovered from COVID-19, 28.8% of CINV was found. It was more frequent in men, in patients who required admission and in patients with cases of non-mild infection. The patients that presented LGE had less LVEF and RVSF.

Antecedentes: La enfermedad por coronavirus 2019 (COVID-19) afecta al sistema cardiovascular, ya sea mediante la agresión directa viral o indirectamente por medio de la inflamación sistémica y afectación multiorgánica. Las troponinas son ampliamente utilizadas para determinar lesión cardiaca. La finalidad de este estudio es evaluar la prevalencia de afectación cardiaca (ACARD) en una población recuperada de COVID-19, derivada a resonancia magnética cardiaca (RMC), sin elevación de troponinas al momento del estudio. Métodos: Ciento cincuenta y seis pacientes que se recuperaron de COVID-19 y que no presentaron elevación de troponinas fueron derivados a RMC. Se consideró ACARD a la presencia de: realce tardío de gadolinio (RTG), edema, miocarditis, pericarditis, deterioro de la función sistólica del ventrículo izquierdo (DFSVI) y/o depresión de la función sistólica del ventrículo derecho (DFSVD). Resultados: La prevalencia de ACARD fue del 28.8%, siendo más frecuente en hombres (p = 0.002), en pacientes que requirieron hospitalización (p = 0.04) y en aquellos que cursaron cuadro no leve de infección (p = 0.007). La DFSVD (17.9%) y la DFSVI (13.4%) fueron las hallazgos más frecuentes. La frecuencia de miocarditis fue del 0.6%. El RTG se manifestó en el 7.1% de los pacientes y se relacionó con menor fracción de eyección del ventrículo izquierdo (FEVI) (p = 0.0001) y derecho (FEVD) (p = 0.04). Conclusión: La prevalencia de ACARD fue del 28.8%. Esta es más frecuente en hombres, en pacientes que requirieron internación y que cursaron cuadros de infección no leve. La miocarditis presentó una prevalencia muy baja. Los pacientes que presentaron RTG tuvieron menor FEVI y FSVD.

V-doped TiO2 photocatalysts and their application to pollutant degradation.

V-doped TiO2 materials (0.01, 0.05, 0.10, and 1.00 nominal atomic %) were synthesized by the sol-gel method and characterized by X-ray diffraction, Raman spectroscopy, UV-visible diffuse reflectance spectroscopy, N2 adsorption-desorption isotherms, X-ray photoelectron spectroscopy, and H2-temperature programmed reduction. Two vanadium precursors (vanadyl acetylacetonate and ammonium metavanadate) and three calcination temperatures (400, 500, and 600 °C, with and without air circulation) were assayed. The efficiency of the materials as photocatalysts was studied by the degradation of phenol with UV and visible lamps. The photocatalyst prepared from vanadium acetylacetonate, with a vanadium content of 0.01 nominal atomic %, calcination at 400 °C without air circulation (0.01VTi-400), showed the best performance, reaching 100% and 30% degradation of phenol (50 µM) by irradiation with UV lamps (3 h) and visible lamps (5 h), respectively. To evaluate the efficiency of this catalyst in the degradation of other structurally related compounds, two substituted phenols were selected: 4-chlorophenol and 4-nitrophenol. The 0.01VTi-400 photocatalyst showed to be applicable to the degradation of phenolic compounds when the substituent was an activating group or a weakly deactivating group (for electrophilic reactions). Additionally, the selectivity of 0.01VTi-400 for phenol degradation in the presence of Aldrich humic acid was tested: phenol degradation reached 68% (3 h, UV lamps). The performance of 0.01VTi-400 indicated that it is a promising material for further applications.

Prolonged SARS-CoV-2-RNA Detection from Nasopharyngeal Swabs in an Oncologic Patient: What Impact on Cancer Treatment?

The pandemic of SARS-CoV-2 is a serious global challenge affecting millions of people worldwide. Cancer patients are at risk for infection exposure and serious complications. A prompt diagnosis of SARS-CoV-2 infection is crucial for the timely adoption of isolation measures and the appropriate management of cancer treatments. In lung cancer patients the symptoms of infection 19 may resemble those exhibited by the underlying oncologic condition, possibly leading to diagnostic overlap and delays. Moreover, cancer patients might display a prolonged positivity of nasopharyngeal RT-PCR assays for SARS-CoV-2, causing long interruptions or delay of cancer treatments. However, the association between the positivity of RT-PCR assays and the patient's infectivity remains uncertain. We describe the case of a patient with non-small cell lung cancer, and a severe ab extrinseco compression of the trachea, whose palliative radiotherapy was delayed because of the prolonged positivity of nasopharyngeal swabs for SARS-CoV-2. The patient did not show clinical symptoms suggestive of active infection, but the persistent positivity of RT-PCR assays imposed the continuation of isolation measures and the delay of radiotherapy for over two months. Finally, the negative result of SARS-CoV-2 viral culture allowed us to verify the absence of viral activity and to rule out the infectivity of the patient, who could finally continue her cancer treatment.

SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo'.

In February and March 2020, two mass swab testing campaigns were conducted in Vo', Italy. In May 2020, we tested 86% of the Vo' population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8-4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7-100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0-28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2-36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression.

Caveolin1 and YAP drive mechanically induced mesothelial to mesenchymal transition and fibrosis.

Despite their emerging relevance to fully understand disease pathogenesis, we have as yet a poor understanding as to how biomechanical signals are integrated with specific biochemical pathways to determine cell behaviour. Mesothelial-to-mesenchymal transition (MMT) markers colocalized with TGF-ß1-dependent signaling and yes-associated protein (YAP) activation across biopsies from different pathologies exhibiting peritoneal fibrosis, supporting mechanotransduction as a central driving component of these class of fibrotic lesions and its crosstalk with specific signaling pathways. Transcriptome and proteome profiling of the response of mesothelial cells (MCs) to linear cyclic stretch revealed molecular changes compatible with bona fide MMT, which (i) overlapped with established YAP target gene subsets, and were largely dependent on endogenous TGF-ß1 signaling. Importantly, TGF-ß1 blockade blunts the transcriptional upregulation of these gene signatures, but not the mechanical activation and nuclear translocation of YAP per se. We studied the role therein of caveolin-1 (CAV1), a plasma membrane mechanotransducer. Exposure of CAV1-deficient MCs to cyclic stretch led to a robust upregulation of MMT-related gene programs, which was blunted upon TGF-ß1 inhibition. Conversely, CAV1 depletion enhanced both TGF-ß1 and TGFBRI expression, whereas its re-expression blunted mechanical stretching-induced MMT. CAV1 genetic deficiency exacerbated MMT and adhesion formation in an experimental murine model of peritoneal ischaemic buttons. Taken together, these results support that CAV1-YAP/TAZ fine-tune the fibrotic response through the modulation of MMT, onto which TGF-ß1-dependent signaling coordinately converges. Our findings reveal a cooperation between biomechanical and biochemical signals in the triggering of MMT, representing a novel potential opportunity to intervene mechanically induced disorders coursing with peritoneal fibrosis, such as post-surgical adhesions.

Blockage of interleukin-1ß with canakinumab in patients with Covid-19.

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0-30, IQR 4-11). Median PaO2/FiO2 increased from 160 (range 53-409, IQR 122-210) at baseline to 237 (range 72-533, IQR 158-331) at day 7 after treatment with canakinumab (p < 0.0001). Improvement of oxygen support category was observed in 61.4% of cases. Median duration of hospitalization following administration of canakinumab was 6 days (range 0-30, IQR 4-11). At 7 days, 58% of patients had been discharged and 12 (13.6%) had died. Significant differences between baseline and 7 days were observed for absolute lymphocyte counts (mean 0.60 vs 1.11 × 109/L, respectively, p < 0.0001) and C-reactive protein (mean 31.5 vs 5.8 mg/L, respectively, p < 0.0001).Overall survival at 1 month was 79.5% (95% CI 68.7-90.3). Oxygen-support requirements improved and overall mortality was 13.6%. Confirmation of the efficacy of canakinumab for Covid-19 warrants further study in randomized controlled trials.

HDAC1 inhibition by MS-275 in mesothelial cells limits cellular invasion and promotes MMT reversal.

Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in a variety of conditions including peritoneal dialysis (PD), post-surgery adhesions and peritoneal metastases. The acquisition of invasive and pro-fibrotic abilities by mesothelial cells (MCs) through induction of MMT, a cell-specific form of EMT, plays a main role in this process. Aim of this study was to evaluate possible effects of histone deacetylase (HDAC) inhibitors, key components of the epigenetic machinery, in counteracting MMT observed in MCs isolated from effluent of PD patients. HDAC inhibitors with different class/isoform selectivity have been used for pharmacological inhibition. While the effect of other inhibitors was limited to a partial E-cadherin re-expression, MS-275, a HDAC1-3 inhibitor, promoted: (i) downregulation of mesenchymal markers (MMP2, Col1A1, PAI-1, TGFß1, TGFßRI) (ii) upregulation of epithelial markers (E-cadherin, Occludin), (iii) reacquisition of an epithelial-like morphology and (iv) marked reduction of cellular invasiveness. Results were confirmed by HDAC1 genetic silencing. Mechanistically, MS-275 causes: (i) increase of nuclear histone H3 acetylation (ii) rescue of the acetylation profile on E-cadherin promoter, (iii) Snail functional impairment. Overall, our study, pinpointing a role for HDAC1, revealed a new player in the regulation of peritoneal fibrosis, providing the rationale for future therapeutic opportunities.