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Introduction: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.Aims: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy.Methods: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for >= 6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included prospective and retrospective data (12 months prior to switching to rIX-FP).Results: Data were collected from 59 male patients (median age 30.1 years) enrolled by 23 Italian centres. Of them, 50 were on prophylaxis during the entire observation period and completed the study. The infusion frequency changed from 2-3 times/week in 86.0% of patients with previous treatment, to less than once a week in 84.0% of patients treated with rIX-FP at the 2nd-year fol low-up. The annual number of infusions decreased by about 70%, whereas the mean FIX activity trough level increased from 3.8% to 14.4% (mean > 10% in all the infusion regimens). Median Annualised Bleeding Rate of .0 was achieved across all prophylaxis regimens. Subjects with zero bleedings increased from 66.0% to 78.0% with rIX-FP.Conclusion: Treatment with rIX-FP reduced infusion frequency, while providing higher FIX trough levels with substantial benefit in terms of annualised bleeding rate and a good safety profile.

To evaluate the neurovascular bundle preservation grades during robotic-assisted radical prostatectomy and compared to the trifecta combined outcome (oncologic control, continence, and sexual function) twelve months after the surgery.Cohort of patients who underwent nerve-sparing robotic-assisted radical prostatectomy had the neurovascular bundle preservation retrospectively graded from 0 to 8 according to the Hopkins subjective visual classification. Patients then were divided into two groups, according to the median of nerve-sparing grading: those with score six or high and those with score less than six. Main outcome was the trifecta combined outcome and secondary outcomes was the individual trifecta criteria (prospective analysis). A secondary analysis with groups divided according to pre-operatory SHIM score was made.One hundred robotic-assisted nerve-sparing radical prostatectomy were performed, of which 83 were included. There were 53 patients with grading greater than or equal to six (group 1) and 30 patients less than six (group 2). 66.6% patients (35/53) in group 1 had a trifecta combined outcome of compared to 33.3% (10/30) in group 2 (p = 0.017). Individually, the erectile function was higher in group 1 (73.6%) compared to group 2 (46.7%) (p = 0.014). Both the results of the combined endpoint trifecta and erection were also maintained in the group with preoperative SHIM ≥ 17.The grading of preservation of the neurovascular bundle in radical prostatectomy is related to a better combined trifecta outcome one year after surgery.

Background and Aims Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. Methods This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. Results Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p Conclusions Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

Adelaide Ristori was among the first actresses to build an iconic image of herself, which spread internationally since her Parisian debut in 1855. Aware of the importance of photography, she did not hesitate to be portrayed by the most important photographers. Ristori thus entered the pantheon of illustrious people, known throughout Europe and beyond its borders. Her portraits in carte de visite format quickly integrated into the circuit of the press, establishing a complex relationship with pre-existing graphic techniques, such as engraving. The article analyses the progressive diffusion of Adelaide Ristori’s photographs, focusing in particular on the carte de visite format and on newspapers. The corpus includes three photographs of the actress kept at the Bibliothèque Nationale de France (BNF): a portrait by August Bertsch and two cartes de visite by André Adolphe Eugène Disdéri and Étienne Carjat. What image of the actress do these pictures convey? How do press, graphic arts and photography interact in creating the iconic image of the actress?

Esplorando dal punto di vista storico, antropologico e artistico l'incredibile successo e diffusione del motivo della Madonna Lactans, il presente scritto si propone di indagare le dinamiche politiche associate al motivo stesso e alla devozione ad esso correlata. Il motivo è un utile punto di accesso per indagare quali orizzonti simbolici, soprattutto legati alla corporeità, vengano attivati nel difficile rapporto tra élite di potere e cultura popolare nello stabilire la legittimità politica. Questa indagine si prefigge di esplorare questo rapporto in diversi contesti socio-culturali del Mediterraneo arricchendo l'analisi tramite una comparazione tra la censura post-tridentina sul motivo e la ripresa del tema nell’impero mughal tra il secolo XVI ed il XVII.

The gut microbiota regulates chronic inflammation and has been implicated in the pathogenesis of a broad spectrum of disease including autoimmunity and cancer. Microbial short-chain fatty acids (SCFAs) e.g., butyrate have demonstrated immunomodulatory effects and are thought to be key mediators of the host-microbiome interaction. Here, we investigated the effect of butyrate on effector functions of blood derived human NK cells stimulated for 18 h with a combination of IL-12/IL-15, a potent mix of cytokines that drive NK cell activation. We show that butyrate has a strong anti-inflammatory effect on NK cells. NK cells cultured in the presence of butyrate expressed lower levels of activating receptors (TRAIL, NKp30, NKp44) and produced lower levels of cytokines (IFNγ, TNF-α, IL-22, granzyme B, granzyme A, perforin) in response to IL-12/IL-15. Butyrate restricted NK cell function by downregulation of mTORC1 activity, c-Myc mRNA expression and metabolism. Using a shotgun proteomic approach, we confirmed the effect of butyrate on NK cell cytokine signaling and metabolism and identified BRD2, MAT2A and EHD1 as downstream mediators of these effects. This insight into the immunomodulatory activity of butyrate on human NK cell function might help to develop new ways to limit NK cell function during chronic inflammation.

Background Robotic laparoscopically assisted radical prostatectomy (RARP) is an option for the treatment of localized prostate cancer. The objective of the present study was to evaluate the pentafecta outcomes (biochemical recurrence, continence, potency, surgical complications and surgical margins) in patients undergoing RARP during the initial experience in a university hospital. Methods This is a retrospective study of patients who had RARP for localized prostate adenocarcinoma at a university hospital from August 2013 to October 2019 to evaluate pentafecta outcomes (biochemical recurrence, continence, potency, surgical complications and surgical margins). Data were collected and stored via Microsoft Office Excel program and analyzed using SPSS Software, version 20.0. Results One hundred and sixty-three RARP were performed, the mean age is 64.16 ± 6.54 years, PSA 6.20 (IQR = 4.91–8.95) ng/dl, BMI 27.14 (IQR = 24.22–29.26) kg/m2, D’Amico risk classification was 35 (22.3%) low risk, 81 (51.6%) intermediate risk and 41 (26.1%) high risk. One hundred and fifty-four patients entered the analysis of pentafecta with a rate of 38.3% reaching this outcome. Complications: Twenty-three (14.1%) patients had minor complications (Clavien I and II) and eight patients had major complications (Clavien IIIa, IIIb and IVa). Surgical margins were negative in 69.9% of patients. The biochemical recurrence-free rate was 89.5%. The overall continence rate was 93.5%, and the potency rate was 63.5%. Multivariate analysis showed that T2 patients are 2.7 times more likely to achieve pentafecta outcome than patients ≥ T3 (p Conclusions Preliminary pentafecta outcome of RARP in this university hospital is promising.

The so-called nefs were an important ‘presence’ in the European courts starting from the Late Middle Ages. They were precious miniature ships, shown during banquets held in the halls of the nobility. In addition to delighting the sight of diners thanks to their ornamental richness, they were used as containers of spices, drinks, or luxury silverware. The preciousness of the vessel and of its content were just some of the elements that determined the function of ostentation of power through the nefs. Taking into consideration sources and examples ranging from the fourteenth century to the early sixteenth century, the purpose of this contribution is to investigate both the spatial relationships in the practices of use of the object and those intrinsic to the object itself. The main trajectories of analysis refer to three spatial relationships: that of container and content, that of long-distance travel embedded in the object, and the geography of power in noble banqueting rituals. These spatial relationships reflect power relationships that will be investigated on a case-by-case basis in the course of our study.

Direct oral anticoagulants (DOAC) measurement is recommended in specific conditions. A point-of-care testing should be used in emergency to qualitatively rule out relevant DOAC concentrations. The DOAC-CHECK Study aims to evaluate whether the use of CoaguChek® Pro II (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) coagulation testing device can provide reliable information in patients treated with DOAC. The study was carried out in two FCSA (Italian Federation of Thrombosis Centers) centers. We choose 3 different concentration thresholds for our analysis (30, 50 and 100 ng/mL) and by ROC curves the ideal cut-off point was selected to be the one that yielded a sensitivity of at least 95% associated with the highest possible specificity. 512 patients were enrolled. For Edoxaban and Rivaroxaban, both CoaguChek® Pro II prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests showed a sensitivity >95% corresponding to satisfying specificity values; negative predictive values resulted in the range 90-100%. At variance, CoaguChek® Pro II PT and aPTT tests did not seem to be useful for identifying Apixaban and Dabigatran concentrations higher than the pre-defined thresholds. Our results suggest that CoaguChek® Pro II coagulation testing device can be used to qualitatively identify relevant concentrations of Edoxaban or Rivaroxaban, but not of Apixaban or Dabigatran.

Not available.

BACKGROUND Infection is an important complication of epidermolysis bullosa (EB), and Staphylococcus aureus has been pointed out as the most common pathogen among this population. The objective of this study was to investigate the prevalence and antimicrobial resistance profile of S. aureus colonizing EB patients in Brazil. METHODS This cross-sectional multicenter study was conducted between December 2015 and December 2017. We included a total of 89 individuals with EB from medical centers across Brazil. Data were obtained through clinical and bacteriological investigation. S. aureus were identified by biochemical tests. The nuc and mecA genes were confirmed by PCR assay. Antimicrobial susceptibility was investigated by disk diffusion method. RESULTS The overall prevalence of S. aureus was 51.7% (46/89). Methicillin-resistant S. aureus (MRSA) was detected in 24.7% (19/77) of all S. aureus isolates, colonizing 15.7% (14/89) of all patients. Community-associated (CA)-MRSA strains were resistant against sulfamethoxazole/trimethoprim and levofloxacin (P

A Tuberculose (TB) é a principal causa de morte em razão de um único agente infeccioso em adultos em todo o mundo. Deste total, a doença osteoarticular constitui de 10 a 20% dos casos e de 1 a 3% de todos os casos de tuberculose. Dessa forma, o objetivo deste estudo é analisar as internações por tuberculose óssea (TBO), em pessoas entre 40 e 80 anos ou mais, no Brasil e suas regiões, nos últimos 5 anos. Trata-se de um estudo epidemiológico, acerca das internações decorrentes de TBO, elaborado através de dados secundários, em pessoas entre 40 e 80 anos ou mais, no período de 2018 a 2022, no Brasil e suas macrorregiões. No período analisado, foram registradas 242 internações por tuberculose óssea, em pessoas entre 40 e 80 anos ou mais, no Brasil. No que tange às regiões geográficas, o maior número de internações concentra-se na região Sudeste. Em relação à faixa etária, os pacientes de 50 a 59 anos foram as mais acometidas. Em relação ao sexo biológico, o sexo masculino foi o que predominou, totalizando 183 das internações. Esta pesquisa demonstra que a tuberculose óssea é um problema de saúde pública, sendo passível de diagnóstico precoce e cuidados preventivos, devendo haver ações como educação em saúde, visando minimizar gastos desnecessários e melhorar a qualidade de vida das pessoas.

O uso descontrolado de agrotóxicos em lavouras nos sistemas de produção agrícola nos impulsionou a buscar por medidas alternativas no controle de doença fúngica de potencial relevante como é o caso da antracnose em lavouras de banana e de maracujá, tornando estas medidas de controle menos agressivas ao meio ambiente e ao ser humano. Neste contexto, o trabalho teve como objetivo reunir publicações com potencial antifúngico de óleos essenciais no controle alternativo de Colletotrichum sp.

Bluelined goatfish (Upeneichthys lineatus) exhibit dynamic body colour changes and transform rapidly from a pale, buff/white, horizontally banded pattern to a conspicuous, vertically striped, red pattern when foraging. This red pattern is potentially an important foraging signal for communication with conspecifics, provided that U. lineatus can detect and discriminate the pattern. Using both physiological and behavioural experiments, we first examined whether U. lineatus possess visual pigments with sensitivity to long (“red”) wavelengths of light, and whether they can discriminate the colour red. Microspectrophotometric measurements of retinal photoreceptors showed that while U. lineatuslack visual pigments dedicated to the red part of the spectrum, their pigments likely confer some sensitivity in this spectral band. Behavioural colour discrimination experiments suggested that U. lineatuscan distinguish a red reward stimulus from a grey distractor stimulus of variable brightness. Furthermore, when presented with red stimuli of varying brightness they could mostly discriminate the darker and lighter reds from the grey distractor. We also obtained anatomical estimates of visual acuity, which suggest that U. lineatus can resolve the contrasting bands of conspecifics approximately 7 m away in clear waters. Finally, we measured the spectral reflectance of the red and white colouration on the goatfish body. Visual models suggest that U. lineatus can discriminate both chromatic and achromatic differences in body colouration where longer wavelength light is available. This study demonstrates that U. lineatus have the capacity for colour vision and can likely discriminate colours in the long-wavelength region of the spectrum where the red body pattern reflects light strongly. The ability to see red may therefore provide an advantage in recognising visual signals from conspecifics. This research furthers our understanding of how visual signals have co-evolved with visual abilities, and the role of visual communication in the marine environment.

Inherited epidermolysis bullosa is a group of genetic diseases characterized by skin fragility and blistering on the skin and mucous membranes in response to minimal trauma. Epidermolysis bullosa is clinically and genetically very heterogeneous, being classified into four main types according to the layer of skin in which blistering occurs: epidermolysis bullosa simplex (intraepidermal), junctional epidermolysis bullosa (within the lamina lucida of the basement membrane), dystrophic epidermolysis bullosa (below the basement membrane), and Kindler epidermolysis bullosa (mixed skin cleavage pattern). Furthermore, epidermolysis bullosa is stratified into several subtypes, which consider the clinical characteristics, the distribution of the blisters, and the severity of cutaneous and extracutaneous signs. Pathogenic variants in at least 16 genes that encode proteins essential for the integrity and adhesion of skin layers have already been associated with different subtypes of epidermolysis bullosa. The marked heterogeneity of the disease, which includes phenotypes with a broad spectrum of severity and many causal genes, hinders its classification and diagnosis. For this reason, dermatologists and geneticists regularly review and update the classification criteria. This review aimed to update the state of the art on inherited epidermolysis bullosa, with a special focus on the associated clinical and genetic aspects, presenting data from the most recent reclassification consensus, published in 2020.

Essential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2–dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. The recent spreadout of the COVID-19 pandemic requires a re-organization of Anticoagulation Clinics to prevent person-to-person viral diffusion and continue to offer the highest possible quality of assistance to patients. In this paper, based on the Italian Federation of Anticoagulation Clinics statements, we offer some advice aimed at improving patient care during COVID-19 pandemic, with particular regard to the lockdown and reopening periods. We give practical guidance regarding the following points: (1) re-thinking the AC organization, (2) managing patients on anticoagulants when they become infected by the virus, (3) managing anticoagulation surveillance in non-infected patients during the lockdown period, and (4) organizing the activities during the reopening phases.

Knowledge of the distribution of risk factors for superficial thrombosis (SVT) in low-risk population is fundamental to improve the prevention of the disease in each individual and high-risk settings of patients. Exact frequency data for the low-risk population are scarce, but could be useful for optimal use of prophylactic strategies against venous thrombosis. Blood donors represent a low-risk population, because are healthier than the general population. The objective of this study was to assess the prevalence of vein thrombosis, particularly SVT, and associated risk factors in a low-risk population such as blood donors. In this multicentre cross-sectional study, donors from six Italian blood banks responded to a self-administered questionnaire. The enrolment lasted from 1st June 2017 to 30th July 2018. History of vein thrombosis was referred by 89 (0.76%) individuals, (49 men) with an age-dependent effect. The prevalence reached 2.9% in women and 0.8% in men aged ≥ 49 years, with a significant difference only for women. After controlling for potential confounders, a significant and independent association was found between a history of vein thrombosis and age (OR: 1.03, 95%CI 1.01–1.05), varicose veins (OR: 15.8, 95%CI 7.7–32.6), plaster cast/bed rest (OR: 2.3, 95% CI 1.0–5.3) and transfusion (OR: 5.1, 95% CI 1.3–19.5). This study shows that low-risk individuals share the same risk factors for SVT as patients in secondary care. It also suggests that transfusion confers an increased risk of SVT in healthy population.

Introduction Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half‐life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A. Aim Evaluate the efficacy and safety of turoctocog alfa pegol treatment for major and minor surgeries in the pathfinder 3 and 5 phase III trials. Methods Adults/adolescents aged ≥12 years with severe haemophilia A (FVIII 80% during major surgery (pathfinder 3). The primary end point was haemostatic efficacy during surgery; secondary end points were blood loss, haemostatic effect postsurgery, consumption, transfusions, safety and health economics. Children (0‐11 years) undergoing minor surgeries received 20‐75 IU/kg turoctocog alfa pegol at Investigator's discretion (pathfinder 5). Results pathfinder 3 included 35 patients undergoing 49 major surgeries. Haemostasis was successful in 47/49 (95.9%) surgeries; two had moderate haemostatic responses. Median (mean) blood loss during major surgery was 75 (322.6) mL. Four bleeds were reported postsurgery; three were successfully treated with turoctocog alfa pegol (one was not evaluated). On the day of surgery, overall mean (median) dose was 75.5 (74.5) IU/kg and mean (median) number of doses was 1.7 (2.0). Five procedures required 11 transfusions on the day of surgery or days 1‐6. No safety concerns or inhibitors were identified. Forty‐five minor surgeries in 23 children were performed without complications. Conclusion Turoctocog alfa pegol was effective for perioperative haemostatic management of major and minor surgeries in patients across age groups with severe haemophilia A.

ClC-5, the electrogenic chloride/proton exchanger strongly expressed in renal proximal tubules, belongs to the endocytic macromolecular complex responsible for albumin and low-molecular-weight protein uptake. ClC-5 was found to be overexpressed in glomeruli of glomerulonephritis and in cultured human podocytes under albumin overload. The transcriptional regulation of human ClC-5 is not fully understood. Three functional promoters of various strengths and 11 different 5’ untranslated region (5'UTR) isoforms of CLCN5 messenger RNA (mRNA) were detected in the human kidney (variants 1-11). The aim of this study was to investigate the expression pattern of CLCN5 5'UTR variants and the CLCN5 common translated region in glomerulonephritis. The 5'UTR ends and the translated region of CLCN5 mRNA were analyzed using quantitative relative real-time PCR or quantitative comparative endpoint PCR with GAPDH as housekeeping gene in 8 normal kidneys and 12 renal biopsies from patients with glomerulonephritis. The expression profile for all variants in normal and glomerulonephritis biopsies was similar, and variant 3 and alternative variant 4 were the most abundantly expressed in both sets. In glomerulonephritis biopsies, isoforms under the control of a weak promoter (variants 4, 6 and 7) showed an increased expression leading to an increase in the CLCN5 translated region, underscoring their importance in kidney pathophysiology. Since weak promoters can be turned on by different stimuli, these data support the hypothesis that proteinuria could be one of the stimuli capable of starting a signaling pathway that induces an increase in CLCN5 transcription.

Optimal duration of anticoagulation in patients with a first venous thromboembolism (VTE) is still uncertain. Extended anticoagulant treatment beyond the first 3 to 6 months is recommended in patients with unprovoked VTE for their high risk of recurrence, provided the risk of bleeding during anticoagulation is not high. Recent meta-analyses indicated that only one-third of these patients have a recurrence 10 years after anticoagulation is stopped, whereas the risk of major bleeding is consistent and persistent during anticoagulation. We designed the prospective, multicenter Apidulcis study to test whether serial D-dimer measurements, using commercial assays with predefined sex-specific cutoffs (350 ng/mL and 500 ng/mL for men and women, respectively, for assays expressing results as fibrinogen equivalent units), may be useful to stratify patients for the risk of recurrence. Those presenting positive D-dimer results, considered at higher risk, will receive low dose Apixaban, 2.5 mg tablets BID for 18 months, whereas those with persistently negative D-dimer results, considered at lower risk, will remain without anticoagulant treatment. Outpatients with a first VTE (unprovoked or associated with weak risk factors), aged 18 to 74 years, who have already received anticoagulation for at least 12 months are eligible for the study.

Microplastics are ubiquitous in the marine environment worldwide, and pose a physical and chemical risk to marine organisms. Their small size makes them bioavailable to a range of organisms with evidence of ingestion across the food chain. Despite an increasing body of research into microplastics, few studies have explored how consumption changes complex behaviours such as predator awareness and sociality. Furthermore, our understanding surrounding the trophic transfer of associated microplastic contaminants and the resultant effects on the food web remain largely unknown. My research assessed the impacts of microplastics on the ecology of marine biota and the potential for trophic transfer using coastal ecosystems as a model. Beachhoppers (Platorchestia, smithi) readily ingested microplastics with subsequent alterations in behaviour. Contaminated beachhoppers were fed to Krefft’s frillgobies (Bathygobius, krefftii), and changes in personality were assessed. There was no effect on fish personality due to an increased plastic diet suggesting trophic transfer of microplastic is not an additional exposure pathway for contaminants. This study suggests consumption of microplastics may compromise some behaviours necessary for survival. While in the short term there is no behavioural evidence of trophic transfer, further studies should seek to understand the longer term effects of microplastics and their effect on the food web.

Background and Aims Evidence suggests patients with inflammatory bowel disease [IBD] receiving TNF antagonists have attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and of various medications for treatment of IBD on antibody responses to vaccination against COVID-19. Methods Patients with IBD [n = 270] and healthy controls [HC, n = 116] were recruited prospectively, and quantitative antibody responses were assessed following COVID-19 vaccination. The impact of IBD and of medications for treatment of IBD on vaccine response rates was investigated. Results Of HC, 100% seroconverted following complete vaccination with two vaccine doses; 2% of patients with IBD failed to seroconvert. Median anti-spike protein [SP] immunoglobulin [Ig]G levels following complete vaccination in our IBD cohort was significantly lower than among HC [2613 AU/mL versus 6871 AU/mL, p ≤0.001]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [β coefficient -0.2, p = 0.001]. Use of mRNA vaccines was independently associated with higher anti-SP IgG levels [β coefficient 0.25, p ≤0.001]. Patients with IBD receiving TNF inhibitors had significantly lower anti-SP IgG levels [2445 AU/mL] than IBD patients not receiving TNF inhibitors [3868 AU/mL, p ≤0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared with HC [3868 AU/mL versus 8747 AU/mL, p = 0.001]. Conclusions Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively affects anti-SP IgG levels further. Patients who do not seroconvert following vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.

Exploring the incredible success and diffusion of the Nursing Madonna motif from an historical, anthropological and artistic point of view, this paper aims to investigate the political dynamics associated with the motif itself and the devotion related to it. The Nursing Madonna motif is a useful point of access to see which symbolic horizons, especially those linked to corporeity, are activated in the difficult relationship between the power élites and popular culture in establishing political legitimacy. This investigation aims at exploring this relationship in different socio-cultural contexts of the Mediterranean by enriching the analysis through a comparison between the post-Tridentine censorship on the motif and the revival of the theme in the mughal empire between the 16th and 17th centuries. Esplorando dal punto di vista storico, antropologico e artistico l'incredibile successo e diffusione del motivo della Madonna Lactans, il presente scritto si propone di indagare le dinamiche politiche associate al motivo stesso e alla devozione ad esso correlata. Il motivo è un utile punto di accesso per indagare quali orizzonti simbolici, soprattutto legati alla corporeità, vengano attivati nel difficile rapporto tra élite di potere e cultura popolare nello stabilire la legittimità politica. Questa indagine si prefigge di esplorare questo rapporto in diversi contesti socio-culturali del Mediterraneo arricchendo l'analisi tramite una comparazione tra la censura post-tridentina sul motivo e la ripresa del tema nell’impero mughal tra il secolo XVI ed il XVII.

Background: The ISTH Bleeding Assessment Tool (ISTH-BAT) has been validated for clinical screening of suspected von Willebrand disease (VWD) and for bleeding prediction. Recently it has been validated for subjects with inherited platelet disorders (IPD) (BAT-VAL study). Objectives: To determine whether the ISTH-BAT bleeding score (BS) predicts subsequent bleeding events requiring treatment in IPD patients. Methods: Patients with IPD, type 1 VWD (VWD-1) and age- and sex-matched healthy controls enrolled in the BAT-VAL study were prospectively followed-up for 2years and bleeding episodes requiring treatment were recorded. Results: Of the 1098 subjects initially enrolled, 955 were followed-up and 124 suffered hemorrhages during follow-up, 60% of whom had inherited platelet function disorders (IPFD). Total number of events was significantly higher in IPFD (n=235) than VWD-1 (n=52) or inherited thrombocytopenia (IT; n=20). Events requiring transfusions were 66% in IPFD, 5.7% in VWD-1, and 3% in IT. Baseline BS was significantly higher in IPFD patients with a bleeding event at follow-up than in those without (p&nbsp

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. About a quarter of the anticoagulated patients require temporary cessation of direct oral anticoagulants (DOACs) or vitamin K antagonists for a planned intervention within 2 years from anticoagulation inception. Several clinical issues about DOAC interruption remain unanswered: many questions are tentatively addressed daily by thousands of physicians worldwide through an experience-based balancing of thrombotic and bleeding risks. Among possible valuable answers, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) proposes some experience-based suggestions and expert opinions. In particular, FCSA provides practical guidance on the following issues: (1) multiparametric assessment of thrombotic and bleeding risks based on patients' individual and surgical risk factor, (2) testing of prothrombin time, activated partial thromboplastin time, and DOAC plasma levels before surgery or invasive procedure, (3) use of heparin, (4) restarting of full-dose DOAC after high risk bleeding surgery, (5) practical nonpharmacological suggestions to manage patients perioperatively. Finally, FCSA suggests creating a multidisciplinary “anticoagulation team” with the aim to define the optimal perioperative management of anticoagulation.

Tosetto, Everton Giachini, Bertrand, Arnaud, Neumann-Leitão, Sigrid (2021): First record of Cnidocodon leopoldi Bouillon, 1978 (Cnidaria: Anthoathecata) in the Atlantic Ocean. Papéis Avulsos de Zoologia 61: 1-4, DOI: 10.11606/1807-0205/2021.61.97, URL: http://dx.doi.org/10.11606/1807-0205/2021.61.97

Shark bites on humans are rare but are sufficiently frequent to generate substantial public concern, which typically leads to measures to reduce their frequency. Unfortunately, we understand little about why sharks bite humans. One theory for bites occurring at the surface, e.g. on surfers, is that of mistaken identity, whereby sharks mistake humans for their typical prey (pinnipeds in the case of white sharks). This study tests the mistaken identity theory by comparing video footage of pinnipeds, humans swimming and humans paddling surfboards, from the perspective of a white shark viewing these objects from below. Videos were processed to reflect how a shark's retina would detect the visual motion and shape cues. Motion cues of humans swimming, humans paddling surfboards and pinnipeds swimming did not differ significantly. The shape of paddled surfboards and human swimmers was also similar to that of pinnipeds with their flippers abducted. The difference in shape between pinnipeds with abducted versus adducted flippers was bigger than between pinnipeds with flippers abducted and surfboards or human swimmers. From the perspective of a white shark, therefore, neither visual motion nor shape cues allow an unequivocal visual distinction between pinnipeds and humans, supporting the mistaken identity theory behind some bites.

O objetivodesteestudoéanalisar o perfil dos diagnósticos por displasia do desenvolvimento do quadril (DDQ), em nascidos vivos, no Brasil, no período de 2016 a 2020. Trata-se de um estudo descritivo, retrospectivo e analítico, acerca das internações decorrentes de DDQ, Código Internacional de Doenças (CID) Q650 a Q659, elaborado através de dados secundários obtidos do Sistema de Informações sobre Nascidos Vivos do Sistema Único de Saúde (SISNAC/SUS), disponibilizados pelo Departamento de Informática do SUS (DATASUS), em recém nascidos, no período de 2016 e 2020, no Brasil. No período analisado, foram registradas 1.150 diagnósticos por deformidades congênitas do quadril, em nascidos vivos, no Brasil. No que tange ao CID das deformidades congênitas do quadril, o maior número de casos concentra-se no CID Q650, luxação congênita unilateral do quadril, com 410 casos (35,65%), seguida do CID Q652, luxação congênita específica do quadril, responsável por 202 casos (21,29%). Quanto à etnia informada dos nascidos vivos, o maior número de casos prevaleceu nas crianças de etnia parda, com um total de 553 casos (448,08%). Em seguida, a etnia branca foi responsável por 475 casos (41,30%). Conclusão: Portanto, esse levantamento evidencia que os casos por displasia do desenvolvimento do quadril por ano, em nascidos vivos, apresentam um valor aproximado, sem grandes variações. Isso ressalta a necessidade de delimitação epidemiológica, para que as políticas públicas, voltadas tanto para o tratamento quanto para a prevenção, sejam direcionadas.

Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3 months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged ≤ 65 years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5–4.5%) and 0.4% (95% CI 0–2.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (

Orientador: Silvio Roberto Andrietta Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica Resumo: O objetivo geral deste trabalho foi avaliar os efeitos de algumas substancias organicas presentes no melaco de cana-de-acucar sobre cepas de leveduras de uso industrial. O Capitulo I refere-se a uma breve introducao e historico da fermentacao alcoolica. No Capitulo II, foi analisado amostras de melacos industriais, provenientes de 10 unidades produtoras de acucar e alcool, localizadas nos estados de Sao Paulo, Minas Gerais, Goias e Parana, com a finalidade de determinar e quantificar alguns compostos organicos presentes no mesmo. Para tanto foi utilizada a tecnica de Cromatografia Liquida de Alta Eficiencia (CLAE). No Capitulo III foram realizados ensaios para escolher as cepas de melhor desempenho em condicoes de estresse, utilizando-se o planejamento fatorial 23 tipo estrela com triplicata no ponto central. Os fatores estudados foram: a pressao osmotica (utilizando KCl), temperatura e concentracao inicial de Alcool. As cepas Y904 e SA1 foram as que mais se destacaram. No Capitulo IV foram avaliados os efeitos dos compostos organicos (acidos cafeico, galico, latico, piruvico, siringico, vanilico, acetico, formico, butirico e Hidroximetilfurfural) sobre as cepas SA1 e Y904, atraves de fermentacoes em triplicata, utilizando meio sintetico controle e variando as concentracoes de cada composto. Dentro das concentracoes estudadas, apenas os acidos galico, latico, acetico, formico, butirico e Hidroximetilfurfural demonstraram influencia sobre as cepas. A avaliacao do efeito acumulativo das substancias quando se trabalha com reciclo de celulas esta descrita no Capitulo V. Todos os experimentos foram realizados em triplicata e repetidos por oito vezes consecutivas (8 ciclos). O acido latico foi a substancia que mais interferiu no rendimento em etanol (YP/S) e na produtividade, parametros estes de maior importancia nos processos industriais para producao de alcool. Por outro lado, o acido formico apresentou a menor interferencia e efeito negativo para praticamente todos os parametros estudados. Finalmente no Capitulo VI, foram analisados os efeitos dos acidos latico e formico sobre o comportamento cinetico das cepas SA1 e Y904. Os testes foram realizados em biorreator de bancada, por dez horas de fermentacao. O acido latico aumentou tanto a inibicao pelo substrato como pelo produto, mostrando-se ser uma substancia com alto grau de toxicidade para as celulas de leveduras das linhagens estudadas. " RANAXTAU/EJAXGU" / fermentacao alcoolica, cinetica, substratos industriais, compostos organicos, inibicao, levedura Abstract: The general objective of this project was the evaluation of the effects of some organic substances present in molasses, sugar cane on strains of yeast for industrial use. Chapter I refer to a brief introduction and history of alcoholic fermentation. In Chapter II, samples of industrial molasses were examined, from 10 units producing sugar, located in the states of Sao Paulo, Minas Gerais, Goias, and Parana, in order to determine and quantify some organic compounds present in them. In order to this, the technique for High Performance Liquid Chromatography (HPLC) was used. In Chapter III trials were conducted to choose the strains of better performance in terms of stress, using a 23 factorial planning star type with triplicate in central point. The studied factors were: the osmotic pressure (using KCl), temperature and initial concentration of alcohol. The strains Y904 and SA1 were those which stressed most. In Chapter IV were assessed the effects of organic compounds (caffeic, gallic, lactic, pyruvic, syringic, vanillic, acetic, formic, butyric and Hidroximetilfurfural acids) on the strains SA1 and Y904 by the fermentation in triplicate, using synthetic medium and control varying concentrations of each compound. Within the concentrations studied, only the gallic acid, lactic acid, acetic acid, formic, butyric and Hidroximetilfurfural demonstrated influence on the strains. The assessment of the cumulative effect of the substances when working with recycle cell is described in Chapter V. All experiments were performed in triplicate and repeated by eight consecutive times (8 cycles). The lactic acid is the substance that interfere most in income in ethanol (YP/S) and productivity, these parameters of most importance in industrial processes to produce alcohol. Moreover, the formic acid showed the smallest negative interference for almost all parameters studied. Finally in Chapter VI, were analyzed the effects of lactic acid and formic on the behavior of kinetic strains SA1 and Y904. The tests were performed in bench bioreactor for ten hours of fermentation. The lactic acid increased by inhibiting both the substrate and the product, showing to be a substance with a high degree of toxicity to the strains of yeast cells studied. YQTFU" /" alcoholic fermentation, kinetics, industrial substract, organic compounds, inhibition, yeast Doutorado Desenvolvimento de Processos Biotecnológicos Doutor em Engenharia Química

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by enhanced platelet production and thrombotic complications. The inhibition of platelet cyclooxygenase (COX) activity by the standard once-daily aspirin is mostly incomplete due to accelerated thrombopoiesis. The phase II Aspirin Regimens in EsSential thrombocythemia (ARES) trial has recently compared the efficacy of once- vs. twice- or three-times daily low-dose aspirin in inhibiting platelet thromboxane (TX) A2 production, as reflected by serum (s) TXB2 measurements. The present substudy characterized the determinants of the highly variable response to the standard aspirin 100 mg once-daily regimen in fully compliant patients with ET and the effects of the experimental dosing regimens on response variability. By multivariable analysis, the platelet count (directly) and cytoreductive treatment (inversely) were significantly associated with sTXB2 values in 218 patients with ET. However, the platelet count positively correlated with sTXB2 in patients not being treated with cytoreductive drugs (ρ = 0.51, P

Bluelined goatfish (Upeneichthys lineatus) exhibit dynamic body colour changes and transform rapidly from a pale, buff/white, horizontally banded pattern to a conspicuous, vertically striped, red pattern when foraging. This red pattern is potentially an important foraging signal for communication with conspecifics, provided that U. lineatus can detect and discriminate the pattern. Using both physiological and behavioural experiments, we first examined whether U. lineatus possess visual pigments with sensitivity to long ("red") wavelengths of light, and whether they can discriminate the colour red. Microspectrophotometric measurements of retinal photoreceptors showed that while U. lineatuslack visual pigments dedicated to the red part of the spectrum, their pigments likely confer some sensitivity in this spectral band. Behavioural colour discrimination experiments suggested that U. lineatuscan distinguish a red reward stimulus from a grey distractor stimulus of variable brightness. Furthermore, when presented with red stimuli of varying brightness they could mostly discriminate the darker and lighter reds from the grey distractor. We also obtained anatomical estimates of visual acuity, which suggest that U. lineatus can resolve the contrasting bands of conspecifics approximately 7 m away in clear waters. Finally, we measured the spectral reflectance of the red and white colouration on the goatfish body. Visual models suggest that U. lineatus can discriminate both chromatic and achromatic differences in body colouration where longer wavelength light is available. This study demonstrates that U. lineatus have the capacity for colour vision and can likely discriminate colours in the long-wavelength region of the spectrum where the red body pattern reflects light strongly. The ability to see red may therefore provide an advantage in recognising visual signals from conspecifics. This research furthers our understanding of how visual signals have co-evolved with visual abilities, and the role of visual communication in the marine environment.