MYLK*FLNB and DOCK1*LAMA2 gene-gene interactions associated with rheumatoid arthritis in the focal adhesion pathway.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease caused by a combination of genetic and environmental factors. Rare variants with low predicted effects in genes participating in the same biological function might be involved in developing complex diseases such as RA. From whole-exome sequencing (WES) data, we identified genes containing rare non-neutral variants with complete penetrance and no phenocopy in at least one of nine French multiplex families. Further enrichment analysis highlighted focal adhesion as the most significant pathway. We then tested if interactions between the genes participating in this function would increase or decrease the risk of developing RA disease. The model-based multifactor dimensionality reduction (MB-MDR) approach was used to detect epistasis in a discovery sample (19 RA cases and 11 healthy individuals from 9 families and 98 unrelated CEU controls from the International Genome Sample Resource). We identified 9 significant interactions involving 11 genes (MYLK, FLNB, DOCK1, LAMA2, RELN, PIP5K1C, TNC, PRKCA, VEGFB, ITGB5, and FLT1). One interaction (MYLK*FLNB) increasing RA risk and one interaction decreasing RA risk (DOCK1*LAMA2) were confirmed in a replication sample (200 unrelated RA cases and 91 GBR unrelated controls). Functional and genomic data in RA samples or relevant cell types argue the key role of these genes in RA.

Lsr2, a pleiotropic regulator at the core of the infectious strategy of Mycobacterium abscessus.

Mycobacterium abscessus is a non-tuberculous mycobacterium, causing lung infections in cystic fibrosis patients. During pulmonary infection, M. abscessus switches from smooth (Mabs-S) to rough (Mabs-R) morphotypes, the latter being hyper-virulent. Previously, we isolated the lsr2 gene as differentially expressed during S-to-R transition. lsr2 encodes a pleiotropic transcription factor that falls under the superfamily of nucleoid-associated proteins. Here, we used two functional genomic methods, RNA-seq and chromatin immunoprecipitation-sequencing (ChIP-seq), to elucidate the molecular role of Lsr2 in the pathobiology of M. abscessus. Transcriptomic analysis shows that Lsr2 differentially regulates gene expression across both morphotypes, most of which are involved in several key cellular processes of M. abscessus, including host adaptation and antibiotic resistance. These results were confirmed through quantitative real-time PCR, as well as by minimum inhibitory concentration tests and infection tests on macrophages in the presence of antibiotics. ChIP-seq analysis revealed that Lsr2 extensively binds the M. abscessus genome at AT-rich sequences and appears to form long domains that participate in the repression of its target genes. Unexpectedly, the genomic distribution of Lsr2 revealed no distinctions between Mabs-S and Mabs-R, implying more intricate mechanisms at play for achieving target selectivity.IMPORTANCELsr2 is a crucial transcription factor and chromosome organizer involved in intracellular growth and virulence in the smooth and rough morphotypes of Mycobacterium abscessus. Using RNA-seq and chromatin immunoprecipitation-sequencing (ChIP-seq), we investigated the molecular role of Lsr2 in gene expression regulation along with its distribution on M. abscessus genome. Our study demonstrates the pleiotropic regulatory role of Lsr2, regulating the expression of many genes coordinating essential cellular and molecular processes in both morphotypes. In addition, we have elucidated the role of Lsr2 in antibiotic resistance both in vitro and in vivo, where lsr2 mutant strains display heightened sensitivity to antibiotics. Through ChIP-seq, we reported the widespread distribution of Lsr2 on M. abscessus genome, revealing a direct repressive effect due to its extensive binding on promoters or coding sequences of its targets. This study unveils the significant regulatory role of Lsr2, intricately intertwined with its function in shaping the organization of the M. abscessus genome.

Gram-Negative ESKAPE Bacteria Surveillance in COVID-19 Pandemic Exposes High-Risk Sequence Types of Acinetobacter baumannii MDR in a Tertiary Care Hospital.

The interruption of bacteriological surveillance due to the COVID-19 pandemic brought serious consequences, such as the collapse of health systems and the possible increase in antimicrobial resistance. Therefore, it is necessary to know the rate of resistance and its associated mechanisms in bacteria causing hospital infections during the pandemic. The aim of this work was to show the phenotypic and molecular characteristics of antimicrobial resistance in ESKAPE bacteria in a Mexican tertiary care hospital in the second and third years of the pandemic. For this purpose, during 2021 and 2022, two hundred unduplicated strains of the ESKAPE group (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were collected from various clinical sources and categorized by resistance according to the CLSI. An analysis of variance (ANOVA) complemented by the Tukey test was performed to search for changes in antimicrobial susceptibility profiles during the study period. Finally, the mechanisms of resistance involved in carbapenem resistance were analyzed, and the search for efflux pumps and high-risk sequence types in A. baumannii was performed by multilocus analysis (MLST). The results showed no changes in K. pneumoniae resistance during the period analyzed. Decreases in quinolone resistance were identified in E. coli (p = 0.039) and P. aeruginosa (p = 0.03). Interestingly, A. baumannii showed increases in resistance to penicillins (p = 0.004), aminoglycosides (p < 0.001, p = 0.027), carbapenems (p = 0.027), and folate inhibitors (p = 0.001). Several genes involved in carbapenem resistance were identified (blaNDM, blaVIM, blaOXA, blaKPC, blaOXA-40, and blaOXA-48) with a predominance of blaOXA-40 and the adeABCRS efflux pump in A. baumannii. Finally, MLST analysis revealed the presence of globally distributed sequence types (ST369 and ST758) related to hospital outbreaks in other parts of the world. The results presented demonstrate that the ESKAPE group has played an important role during the COVID-19 pandemic as nosocomial antibiotic-resistant pathogens and in particular A. baumannii MDR as a potential reservoir of resistance genes. The implications of the increases in antimicrobial resistance in pathogens of the ESKAPE group and mainly in A. baumannii during the COVID-19 pandemic are analyzed and discussed.

Diverse Xylaria in the Ecuadorian Amazon and their mode of wood degradation.

BACKGROUND: Xylaria is a diverse and ecologically important genus in the Ascomycota. This paper describes the xylariaceous fungi present in an Ecuadorian Amazon Rainforest and investigates the decay potential of selected Xylaria species. Fungi were collected at Yasuní National Park, Ecuador during two collection trips to a single hectare plot divided into a 10-m by 10-m grid, providing 121 collection points. All Xylaria fruiting bodies found within a 1.2-m radius of each grid point were collected. Dried fruiting bodies were used for culturing and the internal transcribed spacer region was sequenced to identify Xylaria samples to species level. Agar microcosms were used to assess the decay potential of three selected species, two unknown species referred to as Xylaria 1 and Xylaria 2 and Xylaria curta, on four different types of wood from trees growing in Ecuador including balsa (Ochroma pyramidale), melina (Gmelina arborea), saman (Samanea saman), and moral (Chlorophora tinctoria). ANOVA and post-hoc comparisons were used to test for differences in biomass lost between wood blocks inoculated with Xylaria and uninoculated control blocks. Scanning electron micrographs of transverse sections of each wood and assay fungus were used to assess the type of degradation present. RESULTS: 210 Xylaria collections were sequenced, with 106 collections belonging to 60 taxa that were unknown species, all with less than 97% match to NCBI reference sequences. Xylaria with sequence matches of 97% or greater included X. aff. comosa (28 isolates), X. cuneata (9 isolates) X. curta and X. oligotoma (7 isolates), and X. apiculta (6 isolates)., All Xylaria species tested were able to cause type 1 or type 2 soft rot degradation in the four wood types and significant biomass loss was observed compared to the uninoculated controls. Balsa and melina woods had the greatest amount of biomass loss, with as much as 60% and 25% lost, respectively, compared to the controls. CONCLUSIONS: Xylaria species were found in extraordinary abundance in the Ecuadorian rainforest studied. Our study demonstrated that the Xylaria species tested can cause a soft rot type of wood decay and with the significant amount of biomass loss that occurred within a short incubation time, it indicates these fungi likely play a significant role in nutrient cycling in the Amazonian rainforest.

Regulation Transcriptional of Antibiotic Resistance Genes (ARGs) in Bacteria Isolated from WWTP.

The incidence of antibiotics and transcriptional regulation of ARGs in isolated bacteria from wastewater needs to be explored. By HPLC, in samples of untreated wastewater, ampicillin (49.74 ± 5.70 µg/mL), chloramphenicol (0.60 ± 0.03 µg/mL), tylosin (72.95 ± 2.03 µg/mL), and oxytetracycline (0.22 ± 0.01 µg/mL) was determined. Through metagenomic analysis identified 58 bacterial species belonging to 9 phyla and at least 14 species have shown resistance to a variety of antibiotics. Twenty-two bacterial isolates were proved to be resistant to fifteen antibiotics of new generation and used in medical research to combat infectious diseases. Fourteen strains were shown to harbor plasmids in size ranges of 2-5 Kb, 6-10 Kb and plasmids with size greater than 10 Kb. By quantitative PCR it was possible to identify genes sul, qnr, cat1, aadA1, and sat-1 gene were shown to be present in gDNA samples from treated and untreated samples of wastewater and by relative expression analysis, differential expression of cat1, ermB, act, and tetA genes was demonstrated in strains that showed identity with Escherichia coli, Bacteroides fragilis, and Salmonella thyphi, and that were stressed with different concentrations of antibiotics. The presence of ARGs in untreated water samples, as well as in bacterial isolates, was indicative that in these habitats there are microorganisms that can resist ß-lactams, aminoglycosides, tetracyclines, sulfonamides, and quinolones.

Non-Structural Proteins (Nsp): A Marker for Detection of Human Coronavirus Families.

SARS-CoV-2 was the cause of the global pandemic that caused a total of 14.9 million deaths during the years 2020 and 2021, according to the WHO. The virus presents a mutation rate between 10-5 and 10-3 substitutions per nucleotide site per cell infection (s/n/c). Due to this, studies aimed at knowing the evolution of this virus could help us to foresee (through the future development of new detection strategies and vaccines that prevent the infection of this virus in human hosts) that a pandemic caused by this virus will be generated again. In this research, we performed a functional annotation and identification of changes in Nsp (non-structural proteins) domains in the coronavirus genome. The comparison of the 13 selected coronavirus pangenomes demonstrated a total of 69 protein families and 57 functions associated with the structural domain's differentials between genomes. A marked evolutionary conservation of non-structural proteins was observed. This allowed us to identify and classify highly pathogenic human coronaviruses into alpha, beta, gamma, and delta groups. The designed Nsp cluster provides insight into the trajectory of SARS-CoV-2, demonstrating that it continues to evolve rapidly. An evolutionary marker allows us to discriminate between phylogenetically divergent groups, viral genotypes, and variants between the alpha and betacoronavirus genera. These types of evolutionary studies provide a window of opportunity to use these Nsp as targets of viral therapies.

Impact of the COVID-19 Pandemic on the Profile of Patients in SAMU-Asturias EMS (Spain): A Two-Year Retrospective Analysis of Advanced Life Support Unit Data.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic had important consequences on the health system. Emergency Medical Services (EMS) were a key element in the response and were forced to modify their daily procedures. The main objective of this study was to find out if there were differences in response times and in the profile of patients treated by the Advanced Life Support (ALS) units of Servicio de Asistencia Médica Urgente (SAMU)-Asturias, the EMS of the Principality of Asturias, between the pre-pandemic period and the pandemic period. METHODOLOGY: This was a descriptive, cross-sectional, observational, and retrospective study that included all patients treated by SAMU-Asturias ALS from January 1, 2019 through December 31, 2020. RESULTS: The pandemic has had an impact on daily activity of SAMU-Asturias, with a 9.2% decrease in daily ALS services during the pandemic, longer prehospital times during the pandemic period (mean = 54'35"; SD = 0'48"; P = 0.00) mainly due to an increase in scene time (mean = 28'01"; SD = 12'57"; P = 0.00), and a slight increase in the average age of patients during the pandemic in relation to the pre-pandemic period. No differences were found between the types of incidents for ALS or between the resolution of the patients. CONCLUSIONS: The COVID-19 pandemic mainly affects prehospital times in an emergency service, with no differences being observed in types of incidents; in EMS future pandemic planning, this should be taken into consideration.

Complicaciones en la extracción de terceros molares mandibulares incluídos, retenidos e impactados. Revisión de la literatura / Complications in the extraction of impacted, and retained third molars. Literature Review

La literatura científica sostiene que los terceros molares muy a menudo son lo que contemplan varías complicaciones al momento del procedimiento quirúrgico, debido no solo a su erupción sino también a sus diferentes características que suceden como anatomía, forma, posición de su erupción, etc. Para ello el estudio complementario Integral antes de pasar al acto quirúrgico es la primera opción que se hace. Para que un correcto tratamiento post-quirúrgico sea efectivo tanto antibiótico farmacológico, biomateriales integrales, etc. Objetivo: Establecer por medio de una revisión de la literatura cuáles son las acciones o procedimientos quirúrgicos ejecutándose que pueden evitar las complicaciones más prevalentes en la extracción de terceros molares mandibulares incluídos, retenidos e impactados. Materiales y métodos: Se plantea un estudio de tipo descriptivo y de análisis respectivamente con 2 tipos de bases electrónicas: PubMed y SciELO tomando como sustentación artículos que contemplen meta-análisis, revisiones sistemáticas, revisiones literarias, etc. Resultados: Se confirmó que el mejor procedimiento ante quizás una posible: hemorragia, fracturas, laceraciones, etc. es el buen manejo quirúrgico farmacológico durante la cirugía y posterior a esta. Conclusión: Con esta revisión de la literatura se llega a la idea de que un correcto diagnóstico, manejo estricto farmacológico y el conocimiento de las complicaciones que pueden suscitarse durante y posterior en las extracciones dentales son acciones correctas que se utilizan muy comúnmente durante el procedimiento quirúrgico, lo que evita sus respectivas dificultades.

After the various articles compiled by different authors, is becomes clear that the third molars are very often what contemplate various complications at the time of the surgical procedure, due not only to their eruption but also to their different characteristics that occur such as anatomy, shape, position of its eruption, etc. For this reason, the comprehensive complementary study before proceeding to the surgical act is the first option that is made. For a correct post-surgical treatment to be effective both antibiotic-pharmacological, integral biomaterials, etc. Purpose: To establish through a review of the literatura which are the actions or surgical procedures being performed that can avoid the most prevalent complications in the extraction of included, retained and impacted mandibular third molars. Materials and methods: A descriptive and analytical study is proposed, respectively, with 2 types of electronic databases: PubMed and SciELO, taking as support articles that include meta-analyses, systematic reviews, literary reviews, etc. Results: It was confirmed that the best procedure for perhaps a possible one: hemorrhage, fractures, lacerations, etc. It is good pharmacological surgical management during and after surgery. Conclusion: With this review of the literature, the idea is reached that a correct diagnosis, strict pharmacological management and knowledge of the complications that can arise during and after dental extractions are correct actions that are very commonly used during the surgical procedure. , which avoids their respective difficulties.

The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes.

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

Manejo del Síndrome de Klippel-Trenaunay: reporte de caso / Management of Klippel-Trenaunay Syndrome: case report / Manejo da Síndrome de Klippel-Trenaunay: relato de caso

El Síndrome de Klippel-Trenaunay se constituye en una malformación vascular compleja con una incidencia de 2 a 3 casos por cada 100.000 nacidos vivos, clínicamente presenta una triada clásica: manchas cutáneas en vino de Oporto, venas varicosas de localización atípica e hipertrofia ósea y de tejidos blandos. Se presenta el caso de una paciente femenina de 33 años, sin antecedentes patológicos o quirúrgicos de importancia quien acude a consulta por aumento de volumen de la extremidad derecha, mancha violácea ipsilateral, además de dolor y parestesias. Al examen físico se evidencia aumento longitudinal de miembro inferior derecho, nevus hiperpigmentario en cara lateral de pierna derecha y muslo que se extiende al glúteo ipsilateral además de venas varicosas atípicas. Se practica ecografía Doppler venosa con transductor lineal que reporta incompetencia de vena Safena Mayor y perforantes suprageniculares. Se realizó manejo quirúrgico mediante safenectomía, corrección de deformidad y referencia a dermatología para terapia láser por el nevus hiperpigmentario. La paciente mostró evolución clínico - quirúrgica favorable con remisión de la sintomatología que motivó su consulta.

Klippel-Trenaunay syndrome is a complex vascular malformation with an incidence of 2 to 3 cases per 100,000 live births. Clinically, it presents a classic triad: port-wine stains, varicose veins of atypical location and bone and soft tissue hypertrophy. We present the case of a 33-year-old female patient, with no pathologic or surgical history of importance, who comes to the clinic for an increase in volume of the right extremity, ipsilateral violaceous spot, in addition to pain and paresthesia. Physical examination revealed longitudinal enlargement of the right lower limb, hyperpigmented nevus on the lateral aspect of the right leg and thigh extending to the ipsilateral buttock and atypical varicose veins. Venous Doppler ultrasound with linear transducer reported incompetence of the greater saphenous vein and supragenicular perforators. Surgical management was performed by saphenectomy, deformity correction and referral to dermatology for laser therapy for hyperpigmented nevus. The patient showed favorable clinical-surgical evolution with remission of the symptomatology that motivated her consultation.

A síndrome de Klippel-Trenaunay é uma malformação vascular complexa com uma incidência de 2 a 3 casos por 100.000 nascidos vivos. Clinicamente, apresenta uma tríade clássica: manchas vinho do porto, veias varicosas de localização atípica e hipertrofia óssea e de tecidos moles. Apresentamos o caso de uma paciente do sexo feminino, 33 anos, sem histórico patológico ou cirúrgico de importância, que consultou por aumento de volume do membro direito, mancha violácea ipsilateral, além de dor e parestesia. O exame físico revelou aumento longitudinal do membro inferior direito, nevo hiperpigmentado na face lateral da perna e coxa direitas, estendendo-se até a nádega ipsilateral e veias varicosas atípicas. Foi realizado ultrassom Doppler venoso com transdutor linear, que relatou incompetência da veia safena magna e das perfurantes suprageniculares. O tratamento cirúrgico foi realizado por meio de safenectomia, correção da deformidade e encaminhamento à dermatologia para terapia a laser para nevo hiperpigmentado. A paciente apresentou uma evolução clínico-cirúrgica favorável com remissão dos sintomas que a levaram à consulta.

Assessment of post-infarct ventricular septal defects through 3D printing and statistical shape analysis.

Background: Post-infarct ventricular septal defect (PIVSD) is a serious complication of myocardial infarction. We evaluated 3D-printing models in PIVSD clinical assessment and the feasibility of statistical shape modeling for morphological analysis of the defects. Methods: Models (n = 15) reconstructed from computed tomography data were evaluated by clinicians (n = 8). Statistical shape modeling was performed on 3D meshes to calculate the mean morphological configuration of the defects. Results: Clinicians' evaluation highlighted the models' utility in displaying defects for interventional/surgical planning, education/training and device development. However, models lack dynamic representation. Morphological analysis was feasible and revealed oval-shaped (n = 12) and complex channel-like (n = 3) defects. Conclusion: 3D-PIVSD models can complement imaging data for teaching and procedural planning. Statistical shape modeling is feasible in this scenario.

Following heart attacks, the heart muscle becomes scarred and weaker, making it prone to tearing under high pressures. These tears are known as 'post-infarct ventricular septal defects'. Their shape varies greatly as the heart beats. The approach to fixing these can range from plugging them with a device or patching them by open heart surgery. We created 15 3D-printed models of hearts with these kinds of defects and made digital reconstructions of the tears to see the different sizes/shapes that they can have. Doctors agreed that 3D-printed models could help in planning repairs and training other doctors. The digital reconstructions of the tears showed that many were round, but some had irregular shapes which would mean devices used to fix them may not fit.

[Economic cost estimation of a sample of occupational disease cases accepted by the National Institute of Social Security and evaluated at Parc de Salut Mar, 2014-2021]. / Estimación económica de una muestra de casos de enfermedad profesional confirmados por el Instituto Nacional de la Seguridad Social atendidos en el Parc de Salut Mar, 2014-2021.

Underreporting of occupational diseases (OD) is a social and economic problem, because it has negative consequences for both the welfare of the affected workers and its impact on budgetary planning for the management of health services. We evaluated the healthcare costs of a sample of 13 cases of OD treated at a public hospital in Barcelona between 2014 and 2021, and officially accepted by the National Institute of Social Security (INSS). The total cost of care was €474,859, with an average cost of €36,528 per patient. By diagnostic group, the highest costs were associated with cancer cases, accounting for 79% of the total (€375,068). The findings of this study reflect the economic impact of health care provided by a public hospital to patients with an OD recognized by the INSS.

La infranotificación de enfermedades profesionales (EEPP) es un problema social y económico, pues repercute en el bienestar del trabajador afectado, y en las estimaciones presupuestarias que se planifican anualmente para la gestión de los servicios sanitarios. Los costes asistenciales fueron evaluados en una muestra de 13 casos de EEPP con resolución positiva por el Instituto Nacional de la Seguridad Social atendidos en el Parc de Salut Mar (Barcelona) entre 2014 y 2021. El coste de la asistencia generada del total de casos fue de 474.859 €, con un coste medio de 36.528 € por paciente. Por grupo diagnóstico, el coste más alto lo originaron los casos de cánceres que supusieron el 79% del gasto total (375.068 €). Los hallazgos del estudio reflejan el impacto económico que supone la asistencia sanitaria prestada por un hospital público a pacientes con una EEPP reconocida en el INSS.

Vertical tubular flocculator: Alternative technology for the improvement of drinking water treatment processes in rural areas.

The guarantee of access to safe drinking water for rural communities is a great challenge due to the increase in contamination and deterioration of water sources. Rural areas face technological, financial, and operational limitations, having poor water quality, generally. The purpose of this study was to evaluate the efficiency of a vertical tubular flocculator (VTF) to be used as part of the purification process in rural areas where small flows are used. An experimental treatment system (ETS) implemented in the field was used. The VTF was implemented using PVC pipes and fittings. Tests were carried out with the same raw water used from a conventional treatment plant with aluminum sulfate as a coagulant. The optimal coagulant dose applied in the ETS was determined by the jar test. In the VTF, the length, turbidity, and flow of the raw water were varied. The hydraulic behaviour of the VTF was evaluated with the analysis of the time distribution curve of concentration of a tracer applying the Wolf-Resnick model. A low residence time VTF was obtained, representing a new efficient flocculation model for the reduction of turbidity and colour. The results showed that the turbidity of the raw water, the residence time, and the degree of agitation are important parameters in the operation and efficiency of a VTF. There was a predominance of plug flow in the reactor. The obtained results were compared with the efficiency of a conventional water treatment plant used in the study site. The results obtained indicated that this ETS that integrates a VTF with settling and filtration can be a useful tool for rural areas. It was recommended to replicate this study with wastewater, other dimensions of the VTF, to establish a specific methodology for the design of the VTF, to evaluate the dosage with dose bombs for improving the results of VTF, and to elaborate a hydraulic model for VTF.

Estimación económica de una muestra de casos de enfermedad profesional confirmados por el Instituto Nacional de la Seguridad Social atendidos en el Parc de Salut Mar, 2014-2021 / Economic cost estimation of a sample of occupational disease cases accepted by the National Institute of Social Security and evaluated at Parc de Salut Mar, 2014-2021

La infranotificación de enfermedades profesionales (EEPP) es un problema social y económico, pues repercute en el bienestar del trabajador afectado, y en las estimaciones presupuestarias que se planifican anualmente para la gestión de los servicios sanitarios. Los costes asistenciales fueron evaluados en una muestra de 13 casos de EEPP con resolución positiva por el Instituto Nacional de la Seguridad Social atendidos en el Parc de Salut Mar (Barcelona) entre 2014 y 2021. El coste de la asistencia generada del total de casos fue de 474.859 €, con un coste medio de 36.528 € por paciente. Por grupo diagnóstico, el coste más alto lo originaron los casos de cánceres que supusieron el 79% del gasto total (375.068 €). Los hallazgos del estudio reflejan el impacto económico que supone la asistencia sanitaria prestada por un hospital público a pacientes con una EEPP reconocida en el INSS (AU)

Underreporting of occupational diseases (OD) is a social and economic problem, because it has negative consequences for both the welfare of the affected workers and its impact on budgetary planning for the management of health services. We evaluated the healthcare costs of a sample of 13 cases of OD treated at a public hospital in Barcelona between 2014 and 2021, and officially accepted by the National Institute of Social Security (INSS). The total cost of care was €474,859, with an average cost of €36,528 per patient. By diagnostic group, the highest costs were associated with cancer cases, accounting for 79% of the total (€375,068). The findings of this study reflect the economic impact of health care provided by a public hospital to patients with an OD recognized by the INSS (AU)

Correlative tomography and authentication features of a shrunken head (tsantsa).

Museum personnel and the general public have become quite familiar with the presence of shrunken heads in museum collections, but the procedures to authenticate the history and origin of these unique cultural items are not yet reliable. These shrunken heads, called tsantsas, are meant to be the cultural material remains of ceremonies conducted by the Shuar and Achuar Peoples of South America. This project seeks to integrate the use of micro-computed tomography (micro-CT) scanning with methods used in previous studies (clinical computed tomography (CT) and visual inspections) to examine authentication procedures of shrunken heads (tsantsas) held in contemporary museum collections. We use a correlative tomographic approach using several scans at successively higher resolutions to determine whether a tsantsa was created from human remains, and if so, what key features can best contribute to its authentication. Conclusively, our correlative tomographic approaches provide new insights into the determination process of whether a tsantsa was created from real human remains or not. Also, this study questions whether the previously conceptualized dichotomy of ceremonial or commercial might be better thought of as a continuum of practice. Investigating and redefining the examination and authentication procedures of tsantsas is crucial for future ethical curation, management, and repatriation efforts of this unique cultural material of the Shuar and Achuar Peoples.

Constraints on the evolution of toxin-resistant Na,K-ATPases have limited dependence on sequence divergence.

A growing body of theoretical and experimental evidence suggests that intramolecular epistasis is a major determinant of rates and patterns of protein evolution and imposes a substantial constraint on the evolution of novel protein functions. Here, we examine the role of intramolecular epistasis in the recurrent evolution of resistance to cardiotonic steroids (CTS) across tetrapods, which occurs via specific amino acid substitutions to the α-subunit family of Na,K-ATPases (ATP1A). After identifying a series of recurrent substitutions at two key sites of ATP1A that are predicted to confer CTS resistance in diverse tetrapods, we then performed protein engineering experiments to test the functional consequences of introducing these substitutions onto divergent species backgrounds. In line with previous results, we find that substitutions at these sites can have substantial background-dependent effects on CTS resistance. Globally, however, these substitutions also have pleiotropic effects that are consistent with additive rather than background-dependent effects. Moreover, the magnitude of a substitution's effect on activity does not depend on the overall extent of ATP1A sequence divergence between species. Our results suggest that epistatic constraints on the evolution of CTS-resistant forms of Na,K-ATPase likely depend on a small number of sites, with little dependence on overall levels of protein divergence. We propose that dependence on a limited number sites may account for the observation of convergent CTS resistance substitutions observed among taxa with highly divergent Na,K-ATPases (See S1 Text for Spanish translation).