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Background Allogeneic hematopoietic stem-cell transplantation is the standard of care for Hurler syndrome (mucopolysaccharidosis type I, Hurler variant [MPSIH]). However, this treatment is only partially curative and is associated with complications. Methods We are conducting an ongoing study involving eight children with MPSIH. At enrollment, the children lacked a suitable allogeneic donor and had a Developmental Quotient or Intelligence Quotient score above 70 (i.e., none had moderate or severe cognitive impairment). The children received autologous hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with an alpha-L-iduronidase (IDUA)-encoding lentiviral vector after myeloablative conditioning. Safety and correction of blood IDUA activity up to supraphysiologic levels were the primary end points. Clearance of lysosomal storage material as well as skeletal and neurophysiological development were assessed as secondary and exploratory end points. The planned duration of the study is 5 years. Results We now report interim results. The children's mean (+/- SD) age at the time of HSPC gene therapy was 1.9 +/- 0.5 years. At a median follow-up of 2.10 years, the procedure had a safety profile similar to that known for autologous hematopoietic stem-cell transplantation. All the patients showed prompt and sustained engraftment of gene-corrected cells and had supraphysiologic blood IDUA activity within a month, which was maintained up to the latest follow-up. Urinary glycosaminoglycan (GAG) excretion decreased steeply, reaching normal levels at 12 months in four of five patients who could be evaluated. Previously undetectable levels of IDUA activity in the cerebrospinal fluid became detectable after gene therapy and were associated with local clearance of GAGs. Patients showed stable cognitive performance, stable motor skills corresponding to continued motor development, improved or stable findings on magnetic resonance imaging of the brain and spine, reduced joint stiffness, and normal growth in line with World Health Organization growth charts. Conclusions The delivery of HSPC gene therapy in patients with MPSIH resulted in extensive metabolic correction in peripheral tissues and the central nervous system. (Funded by Fondazione Telethon and others; ClinicalTrials.gov number, ; EudraCT number, .)Hematopoietic Gene Therapy for Hurler Syndrome Eight patients with Hurler syndrome who lacked suitable allogeneic donors received autologous hematopoietic stem and progenitor cells transduced ex vivo with an alpha-L-iduronidase-encoding lentiviral vector. This therapy resulted in extensive metabolic correction in peripheral tissues and the central nervous system.

Patients with beta-thalassemia show 5-fold increase in agestandardized lethality due to SARS-CoV-2 infection, representing a high-risk population compared with age- and sex-matched healthy subjects.(1) Vaccination against SARS-CoV-2 is crucial to reduce mortality and morbidity of frail patients.(2) Up to now, limited data have been available on the responses of patients with beta-thalassemia immunized with anti-SARS-CoV-2 mRNA vaccines.(3)

O objeto deste artigo é o de desenhar outros modelos de cura em sistemas complexos, nos quais os métodos são de uma visão das resiliências de modo atualizado, em que metáforas das áreas do meio ambiente que atualmente enfrenta danos muito próximos, porém que em algumas ações regenerativas que respeitam um fluxo natural via inserção também de novas técnicas, têm trazido melhores resultados. A justificativa é a neces-sidade de se usar as metodologias dos chamados Objetivos de Desenvolvimento Sustentável, que pregam há alguns anos a unificação entre Problemas Sociais e Ambientais, bem como agregam parcerias tecnológicas, públicas, organizacionais e educativas, visando qualidade de vida e humanização da cidade como um todo. Autores como Alier, Castells, Brown, fazem parte de pesquisa pós-doutoral via CCA/USP.

Item does not contain fulltext Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research. 01 juni 2023

Endurance exercise is known to cause a rise in serum creatinine. It is not known to what extent this rise reflects renal stress and a potential acute kidney injury (AKI). Increases in Insulin Like Growth Factor Binding Protein 7 (IGFBP7) and Tissue Inhibitor of Metalloprotinases-2 (TIMP-2), urinary biomarkers of cell cycle arrest and renal stress, are associated with the development of AKI in clinical populations.Repeated measures study.Runners were recruited at the 2019 Brighton Marathon (UK) and provided urine and blood samples at baseline, immediately post-race and 24 h post-race. Serum creatinine, urinary creatinine and urinary IGFBP7 and TIMP-2 were analysed from the samples.Seventy nine participants (23 females, 56 males), aged 43 ± 10 yrs. (mean ± SD), finish time 243 ± 40mins were included for analysis. Serum creatinine increased over the race by 40 ± 26% (p 0.001), TIMP-2 increased by 555 ± 697% (p 0.001) and IGFBP7 increased by 1094 ± 1491% (p 0.001) over the race. A subset of twenty-two participants supplied samples 24 h post-race, reporting values similar to baseline for all variables.This study is the first to report large rises in IGFBP7 and TIMP-2 following marathon running. This suggests that rises in creatinine are not fully explained by changes in production and clearance and marathon running induces a state of kidney stress and potential injury.

We report data on survival and complications for a longitudinal cohort of 709 transfusion-dependent β-thalassemia major patients (51.1% males) born between 1970 and 1997 and followed through 2020 at seven major centers in Italy. Overall survival probability at 30 years was 83.6% (95%CI: 78.5-89.1) in the oldest birth cohort (1970-1974) compared with 93.3% (95%CI: 88.6-98.3) in the youngest birth cohort (1985-1997) (p = 0.073). Females showed better survival than males (p = 0.022). There were a total of 93 deaths at a median age of 23.2 years with the most frequent disease-related causes being heart disease (n = 53), bone marrow transplant (BMT) complication (n = 10), infection (n = 8), liver disease (n = 4), cancer (n = 3), thromboembolism (n = 2) and severe anemia (n = 1). There was a steady decline in the number of deaths due to heart disease from the year 2000 onwards and no death from BMT was observed after the year 2010. A progressive decrease in the median age of BMT was observed in younger birth cohorts (p 0.001). A total of 480 (67.7%) patients developed ≥1 complication. Patients in younger birth cohorts demonstrated better complication-free survival (p 0.001) which was comparable between sexes (p = 0.230). Independent risk factors for death in multivariate analysis included heart disease (HR: 4.63, 95%CI: 1.78-12.1, p = 0.002), serum ferritin1000 ng/mL (HR: 15.5, 95%CI: 3.52-68.2, p 0.001), male sex (HR: 2.75, 95%CI: 0.89-8.45, p = 0.078), and splenectomy (HR: 6.97, 95%CI: 0.90-54.0, p 0.063). Survival in patients with β-thalassemia major continues to improve with adequate access to care, best practice sharing, continued research, and collaboration between centers.

Since ancient times, Artemisia annua (A. annua) has been used as a medicinal plant in Traditional Chinese Medicine. In addition, recent studies have investigated the cytotoxic effects of A. annua extracts towards cancer cells. The leading aim of the present research is to evaluate the cytotoxic effects of an hydroalcoholic extract of A. annua on two canine osteosarcoma (OSA) cell lines, OSCA-8 and OSCA-40, focusing on the possible involvement of ferroptosis. The quantitative determination of artemisinin concentration in the extract, culture medium and OSA cells was carried out through the use of an instrumental analytical method based on liquid chromatography coupled with spectrophotometric detection and tandem mass spectrometry (LC-DAD-MS/MS). OSCA-8 and OSCA-40 were exposed to different dilutions of the extract for the EC

Postoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes.

To expand our understanding of the role of angiotensin II (ANGII) in coronavirus infectious disease 2019 (COVID-19), we conducted an international, multicenter registry study to assess the use of ANGII in patients with COVID-19 compared to patients not receiving ANGII. Critically ill adult patients who were diagnosed with COVID-19 and received ANGII were matched with COVID-19 patients not receiving ANGII according to age, respiratory support, history of hypertension, use of angiotensin-converting enzyme inhibitors and/or ANGII receptor blocker, and date of admission. All outcomes were exploratory in nature and included improvement in oxygenation, duration of organ support, and mortality. In one year, 132 patients were included (65 in the ANGII group and 67 in the control group), and patients were comparable in baseline characteristics. During the first 12 h of infusion, patients in the ANGII had a faster decrease in FiO2and maintained similar mean arterial pressure levels. Hospital mortality was not statistically significantly different between the groups (53.8% vs. 40.3%; p = 0.226). Within the limitations of such a study design, our findings confirm previous observations of a potentially positive effect of ANGII on blood pressure and FiO2 but no effect on patient-centered outcomes.

In endemic regions (West Africa and the Congo Basin), the genetic diversity of monkeypox virus (MPXV) is geographically structured into two major clades (clade I and II) that differ in virulence and host associations. Clade IIb is closely related to the B.1 lineage, which is dominating a worldwide outbreak initiated in 2022. Lineage B.1 has however accumulated mutations of unknown significance that most likely result from APOBEC3 (apolipoprotein B mRNA editing catalytic polypeptide-like 3) editing. We applied a population genetics-phylogenetics approach to investigate the evolution of MPXV during historical viral spread in Africa and to infer the distribution of fitness effects. We observed a high preponderance of codons evolving under strong purifying selection, particularly in viral genes involved in morphogenesis and replication or transcription. However, signals of positive selection were also detected and were enriched in genes involved in immunomodulation and/or virulence. In particular, several genes showing evidence of positive selection were found to hijack different steps of the cellular pathway that senses cytosolic DNA. Also, a few selected sites in genes that are not directly involved in immunomodulation are suggestive of antibody escape or other immuno-mediated pressures. Because orthopoxvirus host range is primarily determined by the interaction with the host immune system, we suggest that the positive selection signals represent signatures of host adaptation and contribute to the different virulence of clade I and II MPXV. We also used the calculated selection coefficients to infer the effects of mutations that define the predominant hMPXV1 lineage B.1, as well as the changes that have been accumulating during the worldwide outbreak. Results indicated that a proportion of deleterious mutations were purged from the predominant outbreak lineage, whose spread was not driven by the presence of beneficial changes. Polymorphic mutations with a predicted beneficial effect on fitness are few and have a low frequency. It remains to be determined whether they have any significance for ongoing virus evolution.

Ray Bradbury’s book is a narrative, in a dystopian context, of how the language of power manages to be pervasive, to infiltrate reality, in people’s experiences, in the consciousness of an entire society, so as to powerfully transform the meanings of commonly used words, as well as the normative qualifications of acts and professions. A reflection will be proposed on some “semantic spies” present in Fahrenheit 451, to highlight the centrality of some uses of language, aimed at influencing not only the behaviour of the members but also at modifying some institutions, manipulating rules and procedures, for the benefit of those who social control operates by administering power. The proposed intervention will deal with the specific function of propaganda language. Finally, a reflection on the power of the word will be proposed, as a tool capable of fully understanding the present and allowing all individuals to lay the foundations for new social, legal and political realities for the future.

Termites (Insecta, Blattodea, Termitoidae) are a widespread and diverse group of eusocial insects known for their ability to digest wood matter. Herein, we report the draft genome of the subterranean termite Reticulitermes lucifugus, an economically important species and among the most studied taxa with respect to eusocial organization and mating system. The final assembly (~813 Mb) covered up to 88% of the estimated genome size and, in agreement with the Asexual Queen Succession Mating System, it was found completely homozygous. We predicted 16,349 highly supported gene models and 42% of repetitive DNA content. Transposable elements of R. lucifugus show similar evolutionary dynamics compared to that of other termites, with two main peaks of activity localized at 25% and 8% of Kimura divergence driven by DNA, LINE and SINE elements. Gene family turnover analyses identified multiple instances of gene duplication associated with R. lucifugus diversification, with significant lineage-specific gene family expansions related to development, perception and nutrient metabolism pathways. Finally, we analysed P450 and odourant receptor gene repertoires in detail, highlighting the large diversity and dynamical evolutionary history of these proteins in the R. lucifugus genome. This newly assembled genome will provide a valuable resource for further understanding the molecular basis of termites biology as well as for pest control.

Background: Iron-chelation therapy is life-saving in patients on a chronic transfusion regimen as it reduces organ damage related to iron deposition in the tissues. Deferasirox, an iron-chelator, is characterized by pharmacokinetics variability, and some patients may discontinue the treatment due to toxicities. Objective: Understanding whether deferasirox plasma levels are related to patients' specific characteristics could help optimize DFX dosage. Methods: We analyzed deferasirox plasma concentration in 57 transfusion-dependent anemic patients using the HPLC method in this prospective-retrospective cohort study. All outpatients (3 to 98 years) were treated with deferasirox (film-coated tablet) for at least one year (median dose, 16.5 mg/Kg once a day). Deferasirox plasma concentration was normalized for dose/Kg (C/dose) and corrected with a linear regression model that relates C/dose and the time of blood sampling (Cref/dose). Results: No significant differences in Cref/dose were found between males and females, either between different types of hemoglobinopathies or depending on the presence of the UGT1A1*28 polymorphism. Cref/dose has a positive and significant correlation with age, creatinine, and direct bilirubin. Cref/dose, instead, has a negative and significant correlation with Liver Iron Concentration (LIC), ferritin, and eGFR. Cref/dose was significantly different between three age categories 50yrs, with Cref/dose median values of 1.0, 1.2, and 1.5, respectively. Conclusion: The study evidenced that to ensure the efficacy of deferasirox in terms of control over LIC and, at the same time, a lesser influence on renal function, the dose of the drug to be administered to an elderly patient could be reduced.

The Phasmida genus Candovia comprises nine traditionally recognized species, all endemic to Australia. In this study, Candovia diversity is explored through molecular species-delimitation analyses using the COIFol gene fragment and phylogenetic inferences leveraging seven additional mitochondrial and nuclear loci. Molecular results were integrated with morphological observations, leading us to confirm the already described species and to the delineation of several new taxa and of the new genus Paracandovia. New Candovia species from various parts of Queensland and New South Wales are described and illustrated (C. alata sp. nov., C. byfieldensis sp. nov., C. dalgleishae sp. nov., C. eungellensis sp. nov., C. karasi sp. nov., C. koensi sp. nov. andC. wollumbinensis sp. nov.). New combinations are proposed and species removed from synonymy with the erection of the new genus Paracandovia (P. cercata stat. rev., comb. nov., P. longipes stat. rev., comb. nov., P. pallida comb. nov., P. peridromes comb. nov., P. tenera stat. rev., comb. nov.). Phylogenetic analyses suggest that the egg capitulum may have independently evolved multiple times throughout the evolutionary history of these insects. Furthermore, two newly described species represent the first taxa with fully developed wings in this previously considered apterous clade.

A intoxicação exógena compreende um conjunto de efeitos nocivos ao organismo produzidos pela interação de um ou mais agentes tóxicos com o sistema biológico, causando um desequilíbrio orgânico. Os casos de intoxicação exógena, em sua grande maioria, são provocados por saneantes domissanitários, principalmente relacionados à ingestão acidental ou proposital. Os produtos usados para a higienização, desinfecção ou desinfestação de áreas domiciliares ou públicas são chamados de domissanitários, e são caracterizados como a terceira maior causa de intoxicação exógena, uma vez que estão voltados para atender as necessidades da população em relação a higienização dos ambientes, utensílios, móveis e outros artigos. As exposições a estes produtos nocivos são mais comuns principalmente em crianças e adolescentes, porém também são frequentes em mulheres adultas. Isto ocorre, em especial, devido a sua apresentação, com embalagens coloridas e características organolépticas como cor, odor e aspecto atrativos, o que desperta a curiosidade das crianças. Outro fator que influencia na ocorrência de casos de intoxicação é o armazenamento e manuseio inadequado do produto, o que pode estar relacionado a não leitura de rótulos e o não uso ou uso inadequado ou insuficiente de Equipamentos de Proteção Individuais (EPI). Vale destacar ainda que o manuseio destes produtos está crescendo frente ao cenário recente de pandemia, com isso o surgimento de acidentes e quadros de intoxicações e de variada expressão toxicológica, têm assumido um destaque no cenário das intoxicações.

The proposed paper will discuss the meaning of the "opposite of peace", assumed by the experience of the Red Brigades in Italy. Some Kelsen concepts will be used to interpret the war of the Red Brigades against the state and their failed attempt to found a new political, juridical and social order.

The compromised viability and function of cardiovascular cells are rescued by small molecules of triazole derivatives (Tzs), identified as 3a and 3b, by preventing mitochondrial dysfunction. The oxidative phosphorylation improves the respiratory control rate in the presence of Tzs independently of the substrates that energize the mitochondria. The F1FO-ATPase, the main candidate in mitochondrial permeability transition pore (mPTP) formation, is the biological target of Tzs and hydrophilic F1 domain of the enzyme is depicted as the binding region of Tzs. The protective effect of Tz molecules on isolated mitochondria was corroborated by immortalized cardiomyocytes results. Indeed, mPTP opening was attenuated in response to ionomycin. Consequently, increased mitochondrial roundness and reduction of both length and interconnections between mitochondria. In in-vitro and ex-vivo models of cardiovascular pathologies (i.e., hypoxia-reoxygenation and hypertension) were used to evaluate the Tzs cardioprotective action. Key parameters of porcine aortic endothelial cells (pAECs) oxidative metabolism and cell viability were not affected by Tzs. However, in the presence of either 1μM 3a or 0.5μM 3b the impaired cell metabolism of pAECs injured by hypoxia-reoxygenation was restored to control respiratory profile. Moreover, endothelial cells isolated from SHRSP exposed to high-salt treatment rescued the Complex I activity and the endothelial capability to form vessel-like tubes and vascular function in presence of Tzs. As a result, the specific biochemical mechanism of Tzs to block Ca2+-activated F1FO-ATPase protected cell viability and preserved the pAECs bioenergetic metabolism upon hypoxia-reoxygenation injury. Moreover, SHRSP improved vascular dysfunction in response to a high-salt treatment.

Luigi Ferrajoli’s book is an opportunity to discuss some profiles of theoretical and philosophical-legal interest. Among these, two reflections on the fundamental right to peace will be proposed. We will discuss the commitment of the right to peace led by specific actors and its guarantee through the control of the use of force; finally, we will discuss peace in relation to the current war situation between the Russian Federation and Ukraine.

Patients with hypoxemic respiratory failure due to community acquired pneumonia are actually treated with a wide range of oxygen devices from nasal cannula to mechanical ventilation. In this monocentric, open label, randomized controlled trial we aimed to compare the efficacy of combined High Flow Nasal Cannula (HFNC) and Non-Invasive Ventilation (NIV) versus HFNC alone in acute Hypoxemic Respiratory Failure (hARF) in patients affected by Community Acquired Pneumonia (CAP). We enrolled 49 patients affected by CAP with hypoxemic respiratory failure (PO2/FiO2 < 300). The patients were randomized into two groups: one has been treated with HFNC alone (group A) while the other received NIV alternated to HFNC every 3 hours (group B). The primary outcome was PO2/FiO2 change from baseline to 21 hours. Secondary outcomes included variation of pH and pCO2, need to continue HFNC or NIV/HFNC after 45 hours, orotracheal intuba-tion, mortality rate, and device comfort. No statistically significant differences between the two arms were shown in PO2/FiO2 change at 21 hours since baseline, in pCO2 and pH variation, mortality at hospital and at follow-up. Further research is needed to better understand the role of combined HFNC and NIV in hypoxemic respiratory failure in patients with CAP. r.

Coronaviruses are a family of viruses that cause disease in mammals and birds. In humans, coronaviruses cause infections on the respiratory tract that can be fatal. These viruses can cause both mild illnesses such as the common cold and lethal illnesses such as SARS, MERS, and COVID-19. Air transmission represents the principal mode by which people become infected by SARS-CoV-2. To reduce the risks of air transmission of this powerful pathogen, we devised a method of inactivation based on the propagation of electromagnetic waves in the area to be sanitized. We optimized the conditions in a controlled laboratory environment mimicking a natural airborne virus transmission and consistently achieved a 90% (tenfold) reduction of infectivity after a short treatment using a Radio Frequency (RF) wave emission with a power level that is safe for people according to most regulatory agencies, including those in Europe, USA, and Japan. To the best of our knowledge, this is the first time that SARS-CoV-2 has been shown to be inactivated through RF wave emission under conditions compatible with the presence of human beings and animals. Additional in-depth studies are warranted to extend the results to other viruses and to explore the potential implementation of this technology in different environmental conditions.

Gain-of-function (GoF) mutations in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis, an autosomal dominant hemolytic anemia characterized by high reticulocyte count, a tendency to macrocytosis, and mild jaundice, as well as by other variably penetrant clinical features, such as perinatal edema, severe thromboembolic complications after splenectomy, and hepatic iron overload. PIEZO1 mutations in DHS lead to slowing inactivation kinetics of the ion channel and/or facilitating channel opening in response to physiological stimuli. To characterize the alterations of red blood cell proteome in PIEZO1 mutated patients, we used a differential approach to compare the proteome of DHS patients (16 patients from 13 unrelated pedigrees) versus healthy subjects. We identified new actors in the regulation of the complex landscape of ion and volume balance of erythrocytes mediated by PIEZO1. Particularly, the main impaired processes in DHS patients were: ion homeostasis, transmembrane transport, regulation of vesicle-mediated transport, and the proteasomal catabolic process. Functional assays demonstrated a co-expression of PIEZO1 and Band3 when PIEZO1 was activated. Moreover, the alteration of the vesicle-mediated transport was functionally demonstrated by the increased vesiculation rate in DHS patients compared to healthy controls. This finding provides also an explanation of the pathogenetic mechanism underlying the increased thrombotic rate observed in these patients. Finally, the newly identified proteins, involved in the intracellular signaling pathways altered by PIEZO1 mutations, could be used in the future as potential druggable targets in DHS.

Automated tools for antimicrobial resistance surveillance are critical for improving detection of drug-resistant organisms and informing prevention and control interventions. In this study, the WHONET-SaTScan software was used at a multihospital level in Tuscany, Italy, to identify case clusters consistent with hospital outbreaks caused by drug-resistant pathogens.Antimicrobial resistance surveillance data from all Tuscany hospitals between January 2018 and December 2020 were analyzed using WHONET. The SaTScan package was used to detect case clusters applying a simulated prospective approach and the space-time permutation algorithm. Clusters were identified using resistance profiles and two distinct spatial variables: single medical services ('service') or groups of related services ('metaservice').Data from eight bacterial pathogens were provided from 49 hospitals for 312,779 isolates from 158,809 patients. Single service-based analysis detected 693 hospital clusters, while metaservice-based analysis identified 635. There was no evidence for a difference between the two methods in terms of cluster length, cluster size, recurrence intervals, number of alerts, distribution across years or hospitals. Among clusters involving multiple services identified by both analyses, metaservice-detected clusters were usually larger and more statistically significant.WHONET-SaTScan proved to be a valuable multi-facility cluster detection tool that can be implemented for real-time surveillance.

In this interview, Marie-José Mondzain, prominent French philosopher, historian, and cultural critic, discusses some of the key concepts in critical visual studies central to her work. In her typical keen, learned fashion, Mondzain demonstrates the unbreakable relationships among image, desire, subjectivity, collective identity, and the broader sociocultural milieu, in which image making and unmaking work in situ to constitute our political realities and the conflicts therein. Never a mere visual object, an image, as Mondzain shows, is as dynamic an element in the display of power as all the acts of negotiations and struggles that make up what is called politics. In plain but lively language and peppered with ticking examples, Mondzain’s replies to the interviewer provide a helpful introduction to her work on culture, theory, criticism, and politics over more than forty years.

Purpose To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%-50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality. Correction in: Intensive Care Medicine, vol. 48, issue 8, pages 1130-1131.DOI: 10.1007/s00134-022-06801-2

BioVRSea was recently introduced as an unique multi-biometric system that combine Virtual Reality with a moving platform to induce Motion Sickness (MS). Electromyography (EMG) and balance features measuring the center of pressure (CoP) are among the bio-signals measured during a six segments protocol on BioVRSea. A total of 262 participants has been measured and all of them underwent an MS questionnaire to self-assess the MS relative symptoms and personal information like smoking, physical activity and Body Mass Index. From the last three data a binary lifestyle index is created and Machine Learning models are used to classify it starting from EMG and CoP groups of features taken individually and together. After an appropriate feature's selection, multiple algorithms are applied and the best results for the lifestyle index classification are reached with the K Nearest Neighbors algorithm (0.83 of maximum accuracy and 0.60 of recall) while Random Forest perform the best AUCROC (0.64). The most relevant features for the best models are the CoP ones during the second segment of the experiment, before the platform movements, and during its first light movements. These results show that an unhealthy lifestyle influences in a negative way the performance of a person in term of balance in a induced MS task. They can also be used as a preliminary input to study the influence of lifestyle in the behavior of people who suffers of serious MS problems or neurodegenerative patients using the novel BioVRSea platform.

BackgroundThe pandemic may undermine the equity of access to and utilisation of health services for conditions other than COVID-19. The objective of the study is to evaluate the indirect impact of COVID-19 and lockdown measures on sociodemographic inequalities in healthcare utilisation in seven Italian areas.MethodsIn this multicentre retrospective study, we evaluated whether COVID-19 modified the association between educational level or deprivation and indicators of hospital utilisation and quality of care. We also assessed variations in gradients by sex and age class. We estimated age-standardised rates and prevalence and their relative per cent changes comparing pandemic (2020) and pre-pandemic (2018–2019) periods, and the Relative Index of Inequalities (RIIs) fitting multivariable Poisson models with an interaction between socioeconomic position and period.ResultsCompared with 2018–2019, hospital utilisation and, to a lesser extent, timeliness of procedures indicators fell during the first months of 2020. Larger declines were registered among women, the elderly and the low educated resulting in a shrinkage (or widening if RII ConclusionsThe socially patterned reduction of hospital utilisation may lead to a potential exacerbation of health inequalities among groups who were already vulnerable before the pandemic. The healthcare service can contribute to contrast health disparities worsened by COVID-19 through more efficient communication and locally appropriate interventions.

Carbapenemase-producing Enterobacterales (CPE), particularly those producing metallo-β-lactamases, are among the most challenging antibiotic-resistant pathogens, causing outbreaks of difficult-to-treat nosocomial infections worldwide. Since November 2018, an outbreak of New Delhi metallo-β-lactamases-positive CPE (NDM-CPE) has emerged in Tuscany, Italy. In this study, we aimed to investigate the NDM-CPE associated with the outbreak and characterise the responsible Klebsiella pneumoniae clone.We used whole-genome sequencing and bioinformatic analysis to characterise NDM-CPE isolates that caused bloodstream infections in 53 patients at 11 hospitals in Tuscany and that were collected between Jan 1, 2018, and July 5, 2019 (ie, the early phase of the outbreak and preceding months). The CPE isolates characterised in this study were isolated and identified at the species level and as NDM producers by six diagnostic microbiology laboratories that serve the 11 hospitals. We used comparative genomic analysis, antimicrobial susceptibility testing, plasmid conjugal transfer assays, evaluation of virulence potential in the Galleria mellonella infection model, and serum bactericidal assays to further characterise the clone causing the outbreak.The outbreak was sustained by an ST147 K pneumoniae producing NDM-1, which had a complex resistome that mediated resistance to most antimicrobials (except cefiderocol, the aztreonam-avibactam combination, colistin, and fosfomycin). The clone belonged to a sublineage of probably recent evolution, occurred by the sequential acquisition of an integrative and conjugative element encoding the yersiniabactin siderophore, an FIB(pQil)-type multiresistance plasmid carrying blaThis description of a sublineage of ST147 K pneumoniae with a complex resistome and virulome that is capable of sustaining a large regional outbreak adds to existing research on the evolutionary trajectories within high-risk clones of K pneumoniae. Global surveillance programmes are warranted to track the dissemination of these lineages, and to prevent and control their spread.Italian Ministry of Health and Department of Experimental and Clinical Medicine, University of Florence.

Human decisions on water can have a wide effect, impacting rivers, ecosystems, economies, livelihoods, cultures and spiritual values. To make decisions more equitable, researchers and practitioners need to engage directly with the people affected and understand the norms, values and forms of knowledge surrounding water which underlie these decisions. The participation of people affected by the decisions, known as “stakeholders”, is deeply connected to power relations, and effective models are needed to understand these relations and enable meaningful participation for diverse stakeholders.

Aim Long-term-care facility residents are a vulnerable population who experienced reduced healthcare access during the pandemic. This study aimed to assess the indirect impact of the COVID-19 pandemic, in terms of hospitalisation and mortality rates, among this population in two Italian Regions, Tuscany and Apulia, during 2020 in comparison with the pre-pandemic period. Subject and methods We conducted a retrospective cohort study on people residing in long-term-care facilities from 1 January 2018 to 31 December 2020 (baseline period: 1 January 2018–8 March 2020; pandemic period: and 9 March–31 December 2020). Hospitalisation rates were stratified by sex and major disease groups. Standardised weekly rates were estimated with a Poisson regression model. Only for Tuscany, mortality risk at 30 days after hospitalisation was calculated with the Kaplan–Meier estimator. Mortality risk ratios were calculated using Cox proportional regression models. Results Nineteen thousand two hundred and fifty individuals spent at least 7 days in a long-term-care facility during the study period. The overall mean non-Covid hospital admission rate per 100 000 residents/week was 144.1 and 116.2 during the baseline and pandemic periods, with a decrease to 99.7 and 77.3 during the first (March–May) and second lockdown (November–December). Hospitalisation rates decreased for all major disease groups. Thirty-day mortality risk ratios for non-Covid conditions increased during the pandemic period (1.2, 1.1 to 1.4) compared with baseline. Conclusion The pandemic resulted in worse non-COVID-related health outcomes for long-term-care facilities’ residents. There is a need to prioritise these facilities in national pandemic preparedness plans and to ensure their full integration in national surveillance systems.

International audience; The Perseverance rover landed on the floor of Jezero crater in February 2021. The initial set of images taken from the landing site of the residual butte Kodiak showed a deltaic architecture consistent with a paleolake, but at a level ~100 m lower than expected, suggestive of a closed lake system. After spending ~1 year studying the crater floor, the rover reached the front of the deltaic fan in April 2022. Here, we report observations of the facies, structure and composition of these sedimentary deposits using the SuperCam instrument. SuperCam can take images for texture analysis with the Remote Micro-Imager (RMI), visible and infrared reflectance (VISIR) spectra as well as Raman spectra for mineralogical analysis, and data from laser induced breakdown spectroscopy (LIBS) for chemical analysis. The rover investigated the basal strata of the delta along two traverses at the SE of the delta front. The transition between the crater floor and the delta is not well determined due to regolith and strongly degraded outcrops, and is currently under assessment. The ~20 m thick basal layers that are well-visible on orbital data consist of fine-grained sandstones and siltstones deposited in sub-horizontal planar beds with millimeter thick laminations. These deposits display a substantial alteration highlighted by the detection of both sulfates and phyllosilicates, with exception of local boulders of igneous texture lacking alteration. Texture and composition are both consistent with a quiet regime of deposition such as in lake deposits or distal delta slopes. These beds are considered of topmost importance for sample return and were cored in two locations. Pebbly sandstones and conglomerates with pebbles limited to a few centimeters are observed immediately above these strata. The texture is matrix-supported suggesting an emplacement through gravity sliding or turbidity flows below water rather than fluvial deposition. The composition is more variable than in underlying finer-grained beds and includes local carbonate detections. Uppermost deposits have not been reached by the rover yet, but have been analyzed remotely by RMI images, and VISIR for some of them. They consist of cross-bedded sandstones and conglomerates in all locations of the delta front. The diversity in texture of these deposits suggests a variability in depositional regimes including high-energy floods, either during the lacustrine phase, or subsequently. Boulders present within these layers are rounded suggesting a substantial abrasion by fluvial transport. These boulders are also interesting targets for sampling distant crustal rocks. The top of the delta will be analyzed and sampled along the traverse of the rover in 2023.