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.

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.

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.

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.

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.

Comparative analysis of undernutrition screening and diagnostic tools as predictors of hospitalisation costs.

BACKGROUND: Undernutrition is associated with higher hospitalisation costs. The present study aims (i) to explore whether undernutrition status at hospital admission, as evaluated by different screening and diagnostic tools, can predict patient's hospitalisation costs and (ii) to provide an updated economic analysis of undernutrition burden. METHODS: A prospective study was conducted in a university hospital. Participants' (n = 637) nutritional risk was evaluated within 72 h of admission using the Nutritional Risk Screening (NRS-2002) and the Malnutrition Universal Screening Tool ('MUST'). Undernutrition status was determined by Academy of Nutrition and Dietetics (AND) and American Society for Parenteral and Enteral Nutrition (ASPEN) recommended clinical characteristics and by the Patient Generated Subjective Global Assessment (PG-SGA). The hospitalisation cost was calculated for each inpatient using the diagnosis-related group system. Multivariable linear regression analysis was conducted to identify predictors of hospitalisation costs via percentage deviation from the mean cost, after adjustment for patients' characteristics and comorbidities. RESULTS: Undernutrition risk according to NRS-2002 and high undernutrition risk according to 'MUST' increased patient's costs, respectively, by 21.1% [95% confidence interval (CI) = 9.0-33.2%] and 28.8% (95% CI = 13.7-39.9%). Severe undernutrition by AND-ASPEN recommended clinical characteristics and by PG-SGA was also associated with higher hospitalisation costs, respectively 19.4% (95% CI = 7.3-31.5%) and 27.5% (95% CI = 14.0-41.1%). The cost of a nutritionally-at-risk or undernourished patient is between €416 (95% CI = €156-675) and €617 (95% CI = €293-855) higher than the average of the respective diagnosis-related group. CONCLUSIONS: Undernutrition is a predictor of hospitalisation costs, increasing costs by between 19% and 29%. Undernutrition screening tools have an ability for predicting hospitalisation costs similar to that of diagnostic tools. An updated analysis of undernutrition associated costs was provided, highlighting the economic burden of undernutrition.

Colonization of the Mediterranean basin by the vector biting midge species Culicoides imicola: an old story.

Understanding the demographic history and genetic make-up of colonizing species is critical for inferring population sources and colonization routes. This is of main interest for designing accurate control measures in areas newly colonized by vector species of economically important pathogens. The biting midge Culicoides imicola is a major vector of orbiviruses to livestock. Historically, the distribution of this species was limited to the Afrotropical region. Entomological surveys first revealed the presence of C. imicola in the south of the Mediterranean basin by the 1970s. Following recurrent reports of massive bluetongue outbreaks since the 1990s, the presence of the species was confirmed in northern areas. In this study, we addressed the chronology and processes of C. imicola colonization in the Mediterranean basin. We characterized the genetic structure of its populations across Mediterranean and African regions using both mitochondrial and nuclear markers, and combined phylogeographical analyses with population genetics and approximate Bayesian computation. We found a west/east genetic differentiation between populations, occurring both within Africa and within the Mediterranean basin. We demonstrated that three of these groups had experienced demographic expansions in the Pleistocene, probably because of climate changes during this period. Finally, we showed that C. imicola could have colonized the Mediterranean basin in the Late Pleistocene or Early Holocene through a single event of introduction; however, we cannot exclude the hypothesis involving two routes of colonization. Thus, the recent bluetongue outbreaks are not linked to C. imicola colonization event, but rather to biological changes in the vector or the virus.

The corrosion resistance of Wiron(®)88 in the presence of S. mutans and S. sobrinus bacteria.

The corrosion resistance of Wiron(®)88, a Ni-Cr-Mo alloy, was evaluated in liquid growth media in the absence and presence of the Streptococcus sobrinus and Streptococcus mutans strains. Open circuit potential measurements, cyclic voltammetry, linear sweep voltammetry, as well as electronic microscopy coupled to electron diffraction spectroscopy (SEM/EDS), were the main techniques used in this study. It was concluded that the presence of S. sobrinus and S. mutans have only a slight effect on the corrosion resistance of the Wiron(®)88 alloy, with the S. mutans being slightly more aggressive. For both strains the corrosion resistance R p is of the same order (kΩ cm(2)). After 24 h immersion the S. sobrinus lead to and R p of 11.02, while the S. mutans lead to of 5.59 kΩ cm(2). SEM/EDS studies on the Wiron(®)88 samples, with 24 days of immersion, at 37 °C, have confirmed bio-corrosion of the alloy occurring through the dissolution of Ni as Ni(2+) and formation of chromium and molybdenum oxides. The bacterial adhesion to the surface is not uniform.

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.

Incidence of bovine leukocyte adhesion deficiency, complex vertebral malformation, and deficiency of uridine-5-monophosphate synthase carriers in Brazilian Girolando cattle.

Among the various hereditary diseases that have been widely studied in dairy cattle, bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine-5-monophosphate synthase (DUMPS), and complex vertebral malformation (CVM) are noteworthy because of their high impact on overall herd productivity as a consequence of increased calf mortality. The aim of this study was to verify the frequency of carriers of BLAD, CVM, and DUMPS mutant alleles in cows and bulls from the National Girolando Progeny Test carried out in Brazil by using polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR assays. A total of 777 animals were genotyped for BLAD, 783 for CVM, and 122 for DUMPS. The frequencies of carriers for BLAD and CVM were 0.77 and 1.53%, respectively, whereas no carriers of DUMPS were observed.

Effect of ionizing radiation on antioxidant compounds present in cork wastewater.

A preliminary study of the gamma radiation effects on the antioxidant compounds present in cork cooking water was carried out. Radiation studies were performed using radiation between 20 and 50 kGy at 0.4 and 2.4 kGy h(-1). The radiation effects on organic matter content were evaluated by chemical oxygen demand. The antioxidant activity was measured by ferric reducing power assay. The total phenolic content was studied using the Folin-Ciocalteau method. Results show that gamma radiation increases both the amount of phenolic compounds and antioxidant capacity of cork cooking water. These results highlight the potential of this technology for increasing the added value of cork waters.

Expression of IL-1ß, IL-6, TNF-α, and iNOS in pregnant women with periodontal disease.

Periodontal disease is one of the most prevalent oral diseases. An association between this disease and pregnancy has been suggested, but available findings are controversial. We evaluated the expression levels of interleukins (IL-1ß and IL-6), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in pregnant women with and without periodontal disease in comparison with non-pregnant women with and without periodontal disease since studies have suggested a relationship between periodontitis and the expression levels of these genes. The women in the sample were distributed into four groups: pregnant and non-pregnant women, with or without periodontal disease, a total of 32 women. The periodontal condition was evaluated according to the probing depth, clinical attachment level and bleeding on probing. Analysis of gene expression was performed by real-time PCR. Comparisons were made of the level of gene expression among the four groups. Expression of IL-1ß in the non-pregnant women with periodontal disease was 12.6 times higher than in the non-pregnant women without periodontal disease (P < 0.01), while expression of TNF-α in the non-pregnant women without periodontal disease was 3.5 times higher than in the pregnant women with periodontal disease (P < 0.05). Despite these differences, our overall findings indicate no differences in the expression levels of the cytokines IL-1ß, IL-6, TNF-α, and iNOS in pregnant women with and without periodontal disease in comparison with expression of the same genes in non-pregnant women with and without periodontal disease, suggesting that periodontal disease is not influenced by pregnancy.

Spittle protein profile of Mahanarva spectabilis (Hemiptera: Cercopidae) fed various elephant grass genotypes.

An understanding of the interaction between spittlebugs and forage grasses is essential for establishing factors that favor productive pastures. In the present study, we evaluated the protein profiles of the spittle of Mahanarva spectabilis (Distant, 1909) (Hemiptera: Cercopidae) fed various elephant grass genotypes. Each plant was infested with a single fifth-instar M. spectabilis. After 24 h, samples of the spittle produced by each nymph were collected and stored at -20°C, after which their protein profiles were analyzed. The exclusivity or interactions of the proteins present in the spittle produced by the insects revealed the susceptibility of the tested genotypes. The results indicate that groups of genotypes show identical spittle protein profiles when subjected to attack by spittlebugs. Resistant and susceptible elephant grass genotypes exhibited high similarity indices within each group. The similarity index was low for the resistance control species (Brachiaria brizantha) compared with that of the tested elephant grass genotypes. Qualitative and quantitative studies of the proteins expressed in the most promising materials will be performed in an ongoing genetic improvement program seeking to develop genotypes resistant to spittlebugs, which are the main biotic pests of elephant grasses.

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.

Differential expression of genes during mastitis in Holstein-Zebu crossbreed dairy cows.

Among the potential public health problems of animal production, infectious-contagious diseases stand out. Mastitis is among the main diseases affecting dairy cattle. One of the most promising options to reduce the problems caused by this disease, besides proper sanitary and management practices, is selective breeding of resistant animals. To shed light on the immune response mechanisms involved in the resistance/susceptibility phenotype to this disease, we quantified the relative expression of the genes IL-2, IL-6, IL-8, IL-12, IFN-γ, TNF-α, TLR-2, SEMA5A, and FEZL in cells of crossbreed dairy cows, divided into two groups, one healthy and the other suffering from clinical mastitis. Total RNA was extracted from the cells in the milk from the animals in each group (with and without clinical mastitis). Gene expression was determined using the real-time PCR method. The levels of gene expression were compared, and the cows with mastitis were found to express 2.5 times more TLR-2 than those free of mastitis (P < 0.05). There were no significant differences in the expression of the other genes.

Erythropoietin production by distal nephron in normal and familial amyloidotic adult human kidneys.

BACKGROUND/AIM: the kidney is the major site of erythropoietin production. Many efforts have been made to identify renal erythropoietin-producing cells. Previous studies showed conflicting results, but the predominant localization reported was the peritubular interstitial and tubular epithelial cells. This study was conducted to identify the erythropoietin-producing cells in renal biopsies from 10 cadaveric donors and 45 patients with familial amyloidosis ATTR V30M, thirteen of them with anemia. Familial amyloidosis Type I (FAP-I) is a genetic disorder caused by a transthyretin (TTR) protein variant presenting a single amino acid substitution of methionine for valine at position 30 of the polypeptide chain (TTR V30M). Anemia in FAP-I is associated with inappropriately low serum erythropoietin levels. METHODS: erythropoietin expression was detected by in situ hybridization (ISH) and confirmed by laser capture microdissection followed by PCR. Renal segments were identified by immunohistochemistry. RESULTS: erythropoietin was mainly expressed by epithelial distal tubular cells and collecting tubules and additionally, in a few biopsies, by glomerular cells. A similar expression pattern was observed in donors and FAP-I patients. No increased mRNA erythropoietin expression was found in anemic patients, all of them presenting only a slight expression in medulla and cortex. CONCLUSIONS: these results suggest the distal nephron as the major site of erythropoietin production, and support the notion that an inappropriate erythropoietin production is the cause of anemia in familial amyloidosis ATTR V30M.

Molecular mobility of nematic E7 confined to molecular sieves with a low filling degree.

The nematic liquid crystalline mixture E7 was confined with similar filling degrees to molecular sieves with constant composition but different pore diameters (from 2.8 to 6.8 nm). Fourier transform infrared analysis proved that the E7 molecules interact via the cyanogroup with the pore walls of the molecular sieves. The molecular dynamics of the system was investigated by broadband dielectric spectroscopy (10(-2)-10(9) Hz) covering a wide temperature range of approximately 200 K from temperatures well above the isotropic-nematic transition down to the glass transition of bulk E7. A variety of relaxation processes is observed including two modes that are located close to the bulk behavior in its temperature dependence. For all confined samples, two relaxation processes, at frequencies lower than the processes observed for the bulk, were detected. At lower temperatures, their relaxation rates have different temperature dependencies whereas at higher temperatures, they seem to collapse into one chart. The temperature dependence of the slowest process (S-process) obeys the Vogel-Fulcher-Tammann law indicating a glassy dynamics of the E7 molecules anchored to the pore surface. The pore size dependence of both the Vogel temperature and fragility revealed a steplike transition around 4 nm pore size, which indicates a transition from a strong to a fragile behavior. The process with a relaxation rate in between the bulklike and the S-process (I-process) shows no dependence on the pore size. The agreement of the I-process with the behavior of a 5CB surface layer adsorbed on nonporous silica leads to the assignment of E7 molecules anchored at the outer surface of the microcrystals of the molecular sieves.

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.