Applying a Digital Twin and wastewater analysis for robust validation of COVID-19 pandemic forecasts: insights from Catalonia.

Monitoring SARS-CoV-2 spread is challenging due to asymptomatic infections, numerous variants, and population behavior changes from non-pharmaceutical interventions. We developed a Digital Twin model to simulate SARS-CoV-2 evolution in Catalonia. Continuous validation ensures our model's accuracy. Our system uses Catalonia Health Service data to quantify cases, hospitalizations, and healthcare impact. These data may be under-reported due to screening policy changes. To improve our model's reliability, we incorporate data from the Catalan Surveillance Network of SARS-CoV-2 in Sewage (SARSAIGUA). This paper shows how we use sewage data in the Digital Twin validation process to identify discrepancies between model predictions and real-time data. This continuous validation approach enables us to generate long-term forecasts, gain insights into SARS-CoV-2 spread, reassess assumptions, and enhance our understanding of the pandemic's behavior in Catalonia.

Recovery of rare earth elements (Nd3+ and Dy3+) by using carbon-based adsorbents from spent tire rubber.

Two samples of spent tire rubber (rubber A and rubber B) were submitted to thermochemical conversion by pyrolysis process. A450, B450 and A900, B900 chars were obtained from rubber A and rubber B at 450 °C and 900 °C, respectively. The chars were then applied as recovery agents of Nd3+ and Dy3+ from aqueous solutions in mono and bicomponent solutions, and their performance was benchmarked with a commercial activated carbon. The chars obtained at 900 °C were the most efficient adsorbents for both elements with uptake capacities around 30 mg g-1. The chars obtained at 450 °C presented uptake capacities similar to the commercial carbon (≈ 11 mg g-1). A900 and B900 chars presented a higher availability of Zn ions that favored the ion exchange mechanism. It was found that Nd3+ and Dy3+ were adsorbed as oxides after Zn was released from silicate structures (Zn2SiO4). A900 char was further selected to be tested with Nd/Dy binary mixtures and it was found a trend to adsorb a slightly higher amount of Dy3+ due to its smaller ionic radius. The uptake capacity in bicomponent solutions was generally higher than for single component solutions due to the higher driving force triggered by the higher concentration gradient.

In-person school reopening and the spread of SARS-CoV-2 during the second wave in Spain.

We investigate the effects of school reopening on the evolution of COVID-19 infections during the second wave in Spain studying both regional and age-group variation within an interrupted time-series design. Spain's 17 Autonomous Communities reopened schools at different moments in time during September 2020. We find that in-person school reopening correlates with a burst in infections in almost all those regions. Data from Spanish regions gives a further leverage: in some cases, pre-secondary and secondary education started at different dates. The analysis of those cases does not allow to conclude whether reopening one educational stage had an overall stronger impact than the other. To provide a plausible mechanism connecting school reopening with the burst in contagion, we study the Catalan case in more detail, scrutinizing the interrupted time-series patterns of infections among age-groups and the possible connections between them. The stark and sudden increase in contagion among older children (10-19) just after in-person school reopening appears to drag the evolution of other age-groups according to Granger causality. This might be taken as an indirect indication of household transmission from offspring to parents with important societal implications for the aggregate dynamics of infections.

Culicoides spp. found near Lusitano stud farms in mainland Portugal which may contribute for IBH studies.

Insect Bite Hypersensitivity (IBH) is a common cutaneous disease, affecting a large number of horses worldwide. Several studies have identified Culicoides spp. saliva as a clinically relevant allergen source. The prevalence of IBH in Portugal, particularly in Lusitano horses, is still not known. However, the environmental characteristics of the national territory are favorable to the activity of Culicoides, and several species of this genus can be found, namely C. imicola and C. obsoletus/C. scoticus. In this study we characterized the Culicoides population present in Lusitano stud farms with a history of IBH. Thirteen stud farms with Lusitano horses were selected in several regions of mainland Portugal for having a previous history of IBH-affected horses, with a minimum of 5 affected horses. Culicoides were collected in May and June 2016 using OVI traps, placed in these stud farms, and we were able to identify several Culicoides species. We could also verify that C. obsoletus/C. scoticus, and C. imicola were the ones most frequently found, but other species like C. pulicaris were also found.

Anaphylaxis in an emergency department: a retrospective 10-year study in a tertiary hospital.

Summary: Background. Anaphylaxis is a potentially fatal medical emergency. The frequency of hospital admissions for anaphylaxis seems to be increasing in the recent decades. Objective. Characterize the patients admitted for anaphylaxis to the adult emergency department (ED) of a tertiary care hospital over a 10-year period, discriminating aetiologies, clinical features and therapy administered. Methods. Retrospective, descriptive and inferential study, evaluating age, sex, Manchester triage system, suspected allergen, site of allergen exposure, comorbidities, cofactors, clinical findings and symptoms, treatment and management. Patients admitted between January 2007 and December 2016 were included. Results. Forty-three patients were enrolled: 23 males, mean age 54.3 ± 16.2 years, n = 22 had history of allergic disease. Two patients were triaged as non-urgent. The most frequently suspected causes of anaphylaxis were: drugs (33%, n = 14), Hymenoptera venoms (23%, n = 10), foods (21%, n = 9) and iodinated contrast products (12%, n = 5). Adrenaline was used in 88% of the episodes (n = 38), 55% of which (n = 21) intramuscularly. Mortality was registered in one case. At discharge, adrenaline auto-injector was prescribed in 7% (n = 3) of the patients, and Allergy and Clinical Immunology consultation (ACIC) was requested in 65% of the episodes (n = 28). Statistically significant associations (p minor 0.05) were established: a, anaphylaxis to drugs associated with a low intramuscular adrenaline use and with frequent oxygen therapy; b, anaphylaxis to food associated with intramuscular adrenaline administration; c, anaphylaxis to Hymenoptera venom associated with male sex; and d, anaphylaxis to iodinated contrasts associated with referral to ACIC and with shock. All obese patients developed shock. Conclusions. Anaphylaxis is a life-threatening condition that requires early recognition. Although most patients received adrenaline, administration was not always performed by the recommended route and only a few patients were prescribed adrenaline auto-injector.

Dog hepatocytes are key effector cells in the liver innate immune response to Leishmania infantum.

Hepatocytes constitute the majority of hepatic cells, and play a key role in controlling systemic innate immunity, via pattern-recognition receptors (PRRs) and by synthesizing complement and acute phase proteins. Leishmania infantum, a protozoan parasite that causes human and canine leishmaniasis, infects liver by establishing inside the Kupffer cells. The current study proposes the elucidation of the immune response generated by dog hepatocytes when exposed to L. infantum. Additionally, the impact of adding leishmanicidal compound, meglumine antimoniate (MgA), to parasite-exposed hepatocytes was also addressed. L. infantum presents a high tropism to hepatocytes, establishing strong membrane interactions. The possibility of L. infantum internalization by hepatocytes was raised, but not confirmed. Hepatocytes were able to recognize parasite presence, inducing PRRs [nucleotide oligomerization domain (NOD)1, NOD2 and Toll-like receptor (TLR)2] gene expression and generating a mix pro- and anti-inflammatory cytokine response. Reduction of cytochrome P 450s enzyme activity was also observed concomitant with the inflammatory response. Addition of MgA increased NOD2, TLR4 and interleukin 10 gene expression, indicating an immunomodulatory role for MgA. Hepatocytes seem to have a major role in coordinating liver's innate immune response against L. infantum infection, activating inflammatory mechanisms, but always balancing the inflammatory response in order to avoid cell damage.

RNA sequencing differential gene expression analysis of isolated perfused bovine udders experimentally inoculated with Streptococcus agalactiae.

The aim of this study was to elucidate the differential gene expression in the RNA sequencing transcriptome of isolated perfused udders collected from 4 slaughtered Holstein × Zebu crossbred dairy cows experimentally inoculated with Streptococcus agalactiae. We studied 3 different statistical tools (edgeR, baySeq, and Cuffdiff 2). In summary, 2 quarters of each udder were experimentally inoculated with Strep. agalactiae and the other 2 were used as a control. Mammary tissue biopsies were collected at times 0 and 3 h after infection. The total RNA was extracted and sequenced on an Illumina HiSeq 2000 (Illumina Inc., San Diego, CA). Transcripts were assembled from the reads aligned to the bovine UMD 3.1 reference genome, and the statistical analyses were performed using the previously mentioned tools (edgeR, baySeq, and Cuffdiff 2). Finally, the identified genes were submitted to pathway enrichment analysis. A total of 1,756, 1,161, and 3,389 genes with differential gene expression were identified when using edgeR, baySeq, and Cuffdiff 2, respectively. A total of 122 genes were identified by the overlapping of the 3 methods; however, only the platelet activation presented a significantly enriched pathway. From the results, we suggest the FCER1G, GNAI2, ORAI1, and VASP genes shared among the 3 methods in this pathway for posterior biological validation.

Cr(III) removal from synthetic and industrial wastewaters by using co-gasification chars of rice waste streams.

Blends of rice waste streams were submitted to co-gasification assays. The resulting chars (G1C and G2C) were characterized and used in Cr(III) removal assays from a synthetic solution. A Commercial Activated Carbon (CAC) was used for comparison purposes. The chars were non-porous materials mainly composed by ashes (68.3-92.6% w/w). The influences of adsorbent loading (solid/liquid ratio - S/L) and initial pH in Cr(III) removal were tested. G2C at a S/L of 5 mg L-1 and an initial pH of 4.50 presented an uptake capacity significantly higher than CAC (7.29 and 2.59 mg g-1, respectively). G2C was used in Cr(III) removal assays from an industrial wastewater with Cr(III) concentrations of 50, 100 and 200 mg L-1. Cr(III) removal by precipitation (uptake capacity ranging from 11.1 to 14.9 mg g-1) was more effective in G2C, while adsorption (uptake capacity of 16.1 mg g-1) was the main removal mechanism in CAC.

Analyzing similarities in genome sequences.

This article investigates aspects of similarity between complete sequences of mitochondrial DNA by determining the distribution of the relative frequencies of words with different lengths and the characteristics of their relevance throughout the sequences. The degree of similarity is obtained by comparing the distances between words contained within these sequences. Our results indicate that the best groupings among different species depend on the lengths of words and their respective relative frequencies. We also observed that the longer the word the more consistent the grouping between the sequences becomes. The application of our results, together with the perspective of analyzing DNA sequences belonging to a single biological species, may be important for the construction of phylogenetic trees, which are appropriate structures for understanding the evolutionary history of the species.

Leishmania infantum exerts immunomodulation in canine Kupffer cells reverted by meglumine antimoniate.

Kupffer cells (KC) are the liver macrophage population that resides in the hepatic sinusoids and efficiently phagocyte pathogens by establishing an intimate contact with circulating blood. KC constitute the liver host cells in Leishmania infection, nevertheless little is described about their role, apart from their notable contribution in granulomatous inflammation. The present study aims to investigate how canine KC sense and react to the presence of Leishmania infantum promastigotes and amastigotes by evaluating the gene expression of specific innate immune cell receptors and cytokines, as well as the induction of nitric oxide and urea production. Complementarily, the impact of a leishmanicidal drug - meglumine antimoniate (MgA) - in infected KC was also explored. KC revealed to be susceptible to both parasite forms and no major differences were found in the immune response generated. L. infantum parasites seem to interact with KC innate immune receptors and induce an anergic state, promoting immune tolerance and parasite survival. The addition of MgA to infected KC breaks the parasite imposed silence and increased gene expression of Toll-like receptors (TLR) 2 and TLR4, possibly activating downstream pathways. Understanding how KC sense and react to parasite presence could bring new insights into the control or even elimination of canine leishmaniasis.

Role of de novo donor-specific anti-HLA antibodies in kidney graft failure: A case-control study.

The role of de novo donor-specific anti-human leukocyte antigen (anti-HLA) antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002 and 2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy. All patients had at least one serum collected 1 year before failure (in cases) or end of follow-up (in controls). Cases and controls were very well-matched in several baseline characteristics. Post-transplant anti-HLA antibodies were found in 84% of cases and only 36% of controls (P < .001), with 54% of cases and 16% of controls (P < .001) having dnDSA at time of detection. Chronic active antibody-mediated rejection was significantly more common (P < .001) in patients with dnDSA (61% vs 12%), in 53 (47%) patients that had at least one graft biopsy performed during follow-up. dnDSA was a significant risk factor (odds ratio [OR] = 6.06; P = .003) for graft failure in a multivariable conditional logistic regression model. dnDSA as a time-dependent variable, was also an independent predictor [hazard ratio (HR) = 2.46; P = .002] of graft failure in a multivariable Cox regression analysis. In both statistical approaches, only dnDSA-II (OR = 11.90; P = .006) (HR = 2.30; P = .014) was significantly associated with graft failure. Post-transplant dnDSA was clearly associated with graft loss, particularly if against HLA class II antigens. dnDSA detection should be a tool for post-transplant monitoring of kidney graft recipients, allowing for the identification of those with a higher risk of graft failure.

Properties of chars from the gasification and pyrolysis of rice waste streams towards their valorisation as adsorbent materials.

Rice straw (RS), rice husk (RH) and polyethylene (PE) were blended and submitted to gasification and pyrolysis processes. The chars obtained were submitted to textural, chemical, and ecotoxic characterisations, towards their possible valorisation. Gasification chars were mainly composed of ashes (73.4-89.8wt%), while pyrolysis chars were mainly composed of carbon (53.0-57.6wt%). Silicon (Si) was the major mineral element in all chars followed by alkaline and alkaline-earth metal species (AAEMs). In the pyrolysis chars, titanium (Ti) was also a major element, as the feedstock blends contained high fractions of PE which was the main source of Ti. Gasification chars showed higher surface areas (26.9-62.9m2g-1) and some microporosity, attributed to porous silica. On the contrary, pyrolysis chars did not present a porous matrix, mainly due to their high volatile matter content. The gasification bed char produced with 100% RH, at 850°C, with O2 as gasification agent, was selected for further characterization. This char presented the higher potential to be valorised as adsorbent material (higher surface area, higher content of metal cations with exchangeable capacity, and lowest concentrations of toxic heavy metals). The char was submitted to an aqueous leaching test to assess the mobility of chemical species and the ecotoxic level for V. fischeri. It was observed that metallic elements were significantly retained in the char, which was attributed mainly to its alkaline character. This alkaline condition promoted some ecotoxicity level on the char eluate that was eliminated after the pH correction.

SHORT-COMMUNICATION Evaluation of perfused bovine udder for gene expression studies in dairy cows.

Intramammary infections are one of the main causes of productivity loss in dairy cows. To better understand the immune system response and to avoid the use of live animals, we validated the use of isolated bovine udder as an ex situ model. Six mammary glands were collected from cows ready for culling. Three udders were perfused with Tyrode's solution and three were not-perfused. During six hours, we collected perfusate samples for biochemical analysis. We also collected alveolar and teat canal tissue to evaluate gene expression. The biochemical parameters indicated that the perfused udders remained viable for the entire period of the experiment. A real-time polymerase chain reaction showed an increase in 18S rRNA gene expression in the alveolar tissue at 3 and 4 h after perfusion. There was also an increase in the Ubiquitin gene in the teat canal from not-perfused udders at 1, 3, and 4 h after slaughter. In general, gene expression was stable during the experiment. Our results indicated that the isolated perfused bovine udder model is appropriate for genetic studies, opening a new perspective in animal experimentation methods.

Evaluation of the global DNA methylation in canine mast cell tumour samples by immunostaining of 5-methyl cytosine.

Cutaneous mast cell tumours (MCT) are the most common skin tumour in dogs, and to our knowledge, there are no previous studies regarding the global methylation of these tumours. DNA hypomethylation and hypermethylation have been described in several tumours and both mechanisms can lead to carcinogenesis. The purpose of this study was to evaluate the global DNA methylation in canine MCT. A total of 48 MCT samples were classified in grades 1, 2 and 3 or high-grade or low-grade. Monoclonal antibodies were used for the immunohistochemical detection of the 5-methylcytosine. The immunostained nuclei were classified in strong, weak or negative pattern, and these were quantified in five distinct microscopic fields (40× objective) in each slide. The results showed that global DNA hypomethylation was predominant in grade 3, high-grade, less differentiated MCT. These epigenetic changes in neoplastic mast cells warrant further detailed investigation aiming the establishment of tumour epigenetic therapies.

Leishmania infantum antigens modulate memory cell subsets of liver resident T lymphocyte.

In the recent years, the liver has been recognized as an important immune organ with major regulatory functions and immune memory, adding to the well-described vital metabolic functions. There are evidences from experimental infections performed with visceral Leishmania species that immune responses to parasite infection can be organ-specific. The liver is the compartment of acute resolving infection, with minimal tissue damage and resistance to reinfection, whereas the spleen is the compartment of parasite persistence. Control of hepatic infection in mice requires a coordinated immune response that involves the development of inflammatory granulomas. It is also described that the liver harbors populations of resident lymphocytes, which may exhibit memory characteristics. Therefore, the present study aims to address the role of the liver as an immune memory organ in the context of Leishmania infantum infection, by characterizing phenotypically resident liver T lymphocytes. The dynamics of memory T cells in L. infantum infected BALB/c mice and the effect of anti-leishmanial treatment in the differentiation of memory cell subsets were analyzed. The potential of recognition, differentiation and selection of memory lymphocytes by three L. infantum recombinant proteins were also explored. L. infantum infection generates effector and central memory T cells, but the cells did not expand when recalled, demonstrating a possible parasite silencing effect. The treatment with a leishmanicidal drug (antimoniate meglumine) increases the levels of memory and effector T cells, eliciting a more robust hepatic immune response. L. infantum parasites with a decreased sensitivity to the leishmanicidal drug favor the expansion of memory CD8+ T cell subset, but inhibit the proliferation of CD8+ T effector cells, possibly assuring their own survival. The recombinant proteins LirCyp1 and LirSOD are strongly recognized by memory cells of treated mice, indicating that these proteins might be used in a prophylactic or therapeutic vaccine formulation. Thus, L. infantum released antigens induce the development of immune memory subsets in the liver resident T cell population that specifically recognized parasite antigens, including recombinant proteins.

Adding value to gasification and co-pyrolysis chars as removal agents of Cr3.

The present work aims to assess the efficiency of chars, obtained from the gasification and co-pyrolysis of rice wastes, as adsorbents of Cr3+ from aqueous solution. GC and PC chars, produced in the gasification and co-pyrolysis, respectively, of rice husk and polyethylene were studied. Cr3+ removal assays were optimised for the initial pH value, adsorbent mass, contact time and Cr3+ initial concentration. GC showed a better performance than PC with about 100% Cr3+ removal, due to the pH increase that caused Cr precipitation. Under pH conditions in which the adsorption prevailed (pH<5.5), GC presented the highest uptake capacity (21.1mg Cr3+ g-1 char) for the following initial conditions: 50mg Cr3+ L-1; pH 5; contact time: 24h;L/S ratio: 1000mLg-1. The pseudo-second order kinetic model showed the best adjustment to GC experimental data. Both the first and second order kinetic models fitted well to PC experimental data. The ion exchange was the dominant phenomenon on the Cr3+ adsorption by GC sample. Also, this char significantly reduced the ecotoxicity of Cr3+ solutions for the bacterium Vibrio fischeri. GC char proved to be an efficient material to remove Cr3+ from aqueous solution, without the need for further activation.

Financial impact of sarcopenia on hospitalization costs.

BACKGROUND/OBJECTIVES: This study aims to increase knowledge regarding the association of sarcopenia with hospitalization costs among a wide-ranging sample of adult hospitalized patients. SUBJECTS/METHODS: A prospective study was conducted among hospitalized adult patients. Sarcopenia was identified according to the European Working Group on Sarcopenia in Older People, as low muscle mass, assessed by bioelectrical impedance analysis and low muscle function evaluated by handgrip strength. Hospitalization cost was calculated for each patient based on discharge diagnosis-related group codes and determined on the basis of a relative weight value. Costs were defined as the percentage of deviation from the cost of a patient with a relative weight equal to one. Multivariable linear regression models were performed to identify the factors independently associated with hospitalization costs. RESULTS: A total of 656 hospitalized patients aged ⩾18 years (24.2% sarcopenic) composed the study sample. Sarcopenia increased hospitalization costs by [euro ]1240 (95% confidence interval (CI): [euro ]596-1887) for patients aged <65 years and [euro ]721 (95% CI: [euro ]13-1429) for patients aged ⩾65 years. Sarcopenic overweight was related to an increase in hospitalization costs of [euro ]884 (95% CI: [euro ]295-1476). CONCLUSIONS: Sarcopenia is independently related to hospitalization costs. This condition is estimated to increase hospitalization costs by 58.5% for patients aged <65 years and 34% for patients aged ⩾65 years.

Rotating effects on the Landau quantization for an atom with a magnetic quadrupole moment.

Based on the single particle approximation [Dmitriev et al., Phys. Rev. C 50, 2358 (1994) and C.-C. Chen, Phys. Rev. A 51, 2611 (1995)], the Landau quantization associated with an atom with a magnetic quadrupole moment is introduced, and then, rotating effects on this analogue of the Landau quantization is investigated. It is shown that rotating effects can modify the cyclotron frequency and breaks the degeneracy of the analogue of the Landau levels.

Sarcopenia and length of hospital stay.

BACKGROUND/OBJECTIVES: We aimed to quantify the association of sarcopenia with length of hospital stay (LOS) and to identify factors associated with sarcopenia among hospitalized patients. SUBJECTS/METHODS: A total of 655 patients composed the study sample. A longitudinal study was conducted in a University Hospital. Sarcopenia was defined, according to European Consensus criteria, as low muscle mass (bioelectrical impedance analysis) and low muscle function (handgrip strength). Logistic regression, Kaplan-Meier and Cox adjusted proportional hazards methods were used. LOS was determined from the date of hospital admission and discharge home (event of interest). RESULTS: Participants were aged 18 to 90 years (24.3% sarcopenic). Factors associated with sarcopenia were male gender, age ⩾65 years, moderate or severe dependence, undernutrition and being admitted to a medical ward. Sarcopenic patients presented a lower probability of being discharged home (hazard ratio (HR), 95% confidence interval (CI)=0.71, 0.58-0.86). However, after stratifying for age groups, this effect was visible only in patients aged <65 years (HR, 95% CI= 0.66, 0.51-0.86). Moreover, sarcopenic overweight or obese patients presented a higher probability of being discharged home (HR, 95% CI=0.78, 0.61-0.99) than nonoverweight sarcopenic patients (HR, 95% CI=0.63, 0.48-0.83). CONCLUSIONS: Being male, age ⩾65 years, presenting dependence, being undernourished and admitted to a medical ward were factors associated with sarcopenia among hospitalized adult patients. Sarcopenia is independently associated with longer LOS, although this association is stronger for patients aged <65 years. Moreover, sarcopenic overweight was associated with a higher probability of discharge home than nonoverweight sarcopenia.