Evaluating the QileX-RhE skin corrosion test for chemical subcategorization in accordance with OECD TG 431.

Skin corrosion testing is integral to evaluating the potential harm posed by chemicals, impacting regulatory decisions on safety, transportation, and labeling. Traditional animal testing methods are giving way to in vitro alternatives, such as reconstructed human epidermis (RhE) models, aligning with evolving ethical standards. This study evaluates the QileX-RhE test system's performance for chemical subcategorization within the OECD TG 431 framework. Results demonstrate its ability to differentiate subcategories, accurately predicting 83% of UN GHS Category 1A and 73% of UN GHS Category 1B/1C chemicals with 100% sensitivity in corrosive prediction. Additionally, this study provides a comprehensive assessment of the test method's performance by employing nuanced parameters such as positive predictive value (PPV), negative predictive value (NPV), post-test odds and likelihood rations, offering valuable insights into the applicability and effectiveness of the QileX-RhE test method.

An effective method for culturing functional human corneal endothelial cells using a xenogeneic free culture medium.

Endothelial dysfunction is a leading cause of corneal blindness in developed countries and the only available treatment is the endothelial transplantation. However, the limited availability of suitable donors remains a significant challenge, driving the exploration of alternative regenerative therapies. Advanced Therapy Medicinal Products show promise but must adhere to strict regulations that prohibit the use of animal-derived substances. This study investigates a novel culture methodology using Plasma Rich in Growth Factors (PRGF) as the only source of growth factors for primary cultures of human corneal endothelial cells (CECs). CECs were obtained from discarded corneas or endothelial rings and cultured in two different media: one supplemented with xenogeneic factors and other xenogeneic-free, using PRGF. Comprehensive characterization through immunofluorescence, morphological analyses, trans-endothelial electrical resistance measurements, RNA-seq, and qPCR was conducted on the two groups. Results demonstrate that CECs cultured in the xenogeneic-free medium exhibit comparable gene expression, morphology, and functionality to those cultured in the xenogeneic medium. Notably, PRGF-expanded CECs share 46.9% of the gene expression profile with native endothelium and express all studied endothelial markers. In conclusion, PRGF provides an effective source of xenogeneic-free growth factors for the culture of CECs from discarded corneal tissue. Further studies will be necessary to demonstrate the applicability of these cultures to cell therapies that make clinical translation possible.

Functional outcomes of patients with NORSE and FIRES treated with immunotherapy: A systematic review.

OBJECTIVE: To determine the frequency of good functional outcomes in patients with NORSE and FIRES treated with immunotherapy. METHODS: We performed a systematic search of the MedLine and EMBASE databases to gather studies including at least 5 patients with NORSE or FIRES and at least one patient treated with immunotherapy, and reporting functional outcomes. Good functional outcome was defined as a modified Rankin Scale (mRS) score ≤ 2 (or an equivalent measure) at the last available follow-up assessment. Only patients with known functional outcomes were included in the analysis. RESULTS: We analyzed 16 studies including a total of 161 patients with NORSE. Six studies were carried out only with FIRES patients (n = 64). Of the 161 patients with NORSE, 141 (87.5%) received immunotherapy. Outcome data were available for 135, 56 of whom (41.4%) achieved good functional outcomes. Twenty-four of the 58 patients with FIRES treated with immunotherapy and for whom outcome data were available achieved good functional outcomes (41.3%). Mortality rates in patients with NORSE and FIRES treated with immunotherapy were 20/121 (16.5%) and 6/58 (10.3%), respectively. By type of immunotherapy, good functional outcomes were achieved in 36/89 patients receiving glucocorticoids (40.4%), 27/71 patients receiving IV immunoglobulins (38%), 11/37 patients treated with plasma exchange (29.7%), 5/17 patients receiving rituximab (29.4%), and 2/13 patients receiving cyclophosphamide (15.3%). CONCLUSION: Despite the lack of randomised clinical trials, immunotherapy is frequently prescribed to patients with NORSE and FIRES. However, rates of functional dependence and mortality remain high in these patients. Second-line therapies achieved lower rates of good outcomes, probably because they were administered to patients with more severe, refractory disease.

[Adverse events and essential actions for patient safety]. / Eventos adversos y acciones esenciales para la seguridad del paciente.

INTRODUCTION: The adverse events (AE) in hospitalized patients occur with increasing frequency due to the increase in complexity of medical care, which implies a greater risk of committing a human error inherent to the care, constituting a serious threat to the safety of the patient. MATERIAL AND METHODS: Cross-sectional study, including patients older than 16years, with hospital stay longer than 24h and discharge from the general surgery service, patients treated in emergency observation units or other hospital services were not considered. AE were identified, classified by cause according to the essential actions for patient safety (EAPS), and compliance with the EAPS was verified. RESULTS: 352 clinical records were reviewed, 61 (17%) were positive on screening. Of the positives, 66% resulted in AE (47 cases). The prevalence of AE was 13%. The AE were: 40% related to procedures; 39% with infections; 17% with medication; 4% with patient identification. The EAPS with the best rating was EAPS5 and the lowest rating was EAPS4. The night shifts with the greatest opportunity area, only with 40% and 44% correct procedures. CONCLUSIONS: The study shows that the two methodologies used, one to identify AE and the other to establish its causes and classification according to the EAPS, demonstrated usefulness and synergy for patient safety, when detecting AE, as well as determining their causes and evaluate compliance with the EAPS.

Xeno-free approach for the expansion of human adipose derived mesenchymal stem cells for ocular therapies.

To restore corneal transparency and vision loss after an injury on the ocular surface, the use of human stem cells from different origins has been recently proposed. Mesenchymal stem cells (MSCs) seem to be an appropriate adult source of autologous stem cells due to their accessibility, high proliferation rate, and multipotent capacity. In this work, we developed a simple culture system to prepare a graft based on a fibrin membrane seeded with human MSCs. A commercial kit, PRGF Endoret®, was used to prepare both, the growth factors used as culture media supplement and the fibrin membrane grafts. Adipose-derived MSCs (Ad-MSCs) were expanded, characterised by flow cytometry and their multilineage differentiation potential confirmed by inducing adipogenesis, osteogenesis and chondrogenesis. Ad-MSCs seeded on the fibrin membranes were grafted onto athymic mice showing good biocompatibility with no adverse reactions observed during the follow up period. These findings support the assumption that a system in which all the biological components (cells, grow factors and carrier) are autologous, could potentially be used for future ex vivo expansion of Ad-MSCs to treat ocular conditions such as an inflammatory milieu, traumatic scars and loss of the regenerative capacity of the corneal epithelium that compromise the quality of vision.

Case fatality of COVID-19 in patients with neurodegenerative dementia. / Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa.

INTRODUCTION: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. METHODS: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. RESULTS: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. DISCUSSION: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities.

Identificación por catálogo y detección molecular de bovinos Holstein portadores de braquiespina en Uruguay / Identification through sire catalogues analysis and molecular detection of brachyspina carriers in Uruguayan Holstein

Resumen El síndrome de braquiespina es una condición genética de la raza Holstein, detectada en el año 2006. Es causado por una deleción de 3.3 Kb en el gen FANCI localizado en el cromosoma bovino 21. La mutación fue identificada en poblaciones de Holstein de Europa, América del Norte y Asia. Dada la importancia económica del defecto y su amplia distribución mundial, el objetivo de este trabajo ha sido la identificación de animales portadores en el núcleo de selección genética de la raza en Uruguay y el diagnóstico molecular del alelo deletéreo en animales del rodeo nacional. En el presente estudio se analizaron 2598 registros de toros Holstein del catálogo de padres del sistema de evaluación genética lechera, los registros de toros pertenecientes a los catálogos de semen Holstein disponible para Uruguay de los años 2014 al 2018; y 71 vacas pertenecientes al rodeo general. Se encontraron 28 toros portadores de braquiespina de un total de 377 toros con información genética del catálogo de padres y cuatro vacas portadoras de un total de 71 genotipificadas en nuestro laboratorio. Se demostró una disminución en el ingreso de semen de animales portadores al país entre los años 2014 y 2018. La frecuencia significativa de animales portadores en Uruguay evidencia la necesidad de implementar estrategias que permitan eliminar gradualmente el defecto de la población.

Abstract Brachyspina syndrome is a hereditary recessive disease of recent identification in the Holstein breed. It is caused by a deletion of 3.3Kb in the FANCI gene located in the bovine chromosome 21. The mutation was identified in Holstein populations of Europe, North America and Asia. Given the economic importance of the defect and its wide distribution, the objective of this work was the identification of carrier animals in the genetic selection nucleus of the breed in Uruguay and the molecular verification of the deleterious allele in animals of the national herd. In the present study, 2598 records of Holstein bulls were analyzed from the list of parents of the dairy genetic evaluation system, records of bulls belonging to the Holstein semen catalogs available for Uruguay from 2014 to 2018; and 71 cows belonging to the general herd. Twenty-eight brachyspina carrier bulls were found of a total of 377 bulls with genetic information from the list of parents and four carrier cows of a total of 71 genotyped in our laboratory. A decrease in the income of semen from carrier animals to the country between 2014 and 2018 was demonstrated. The significant frequency of carrier animals in Uruguay evidences the need to implement strategies to gradually eliminate the population defect.

Diseases and parasites of wild and cultivated mussels along the Patagonian coast of Argentina, southwest Atlantic Ocean.

A histological survey of the commercially edible mussels Mytilus platensis and M. chilensis from wild and cultivated populations along the coast of Patagonia, Argentina (42°00' to 54°47'S), was carried out to determine their health status. Diagnostic results included 3 types of inflammatory responses (infiltrative, nodular, and encapsulation), disseminated neoplasia disease, 2 abnormal reproductive conditions (gonadal atresia and intersex), prokaryotic inclusions, protozoans, and metazoans. Pathogen prevalence and infection intensity among mussels of different sampling sites and between those of wild and cultivated populations were compared. Inflammatory responses were recorded in all mussels from all sites, while disseminated neoplasia only occurred in the most southern cultivated M. chilensis. Intracellular prokaryotic inclusions were broadly distributed in the mussels from both northern and southern Patagonian coasts. Ciliates showed the highest prevalence among wild mussels from the colder waters of Bahía Brown. Turbellaria were recorded at higher prevalence in cultured mussels (41.7%), and trematode metacercariae occurred exclusively in intertidal wild mussels. None of the parasites found appears to be a problem to the fishery or farming, although disseminated neoplasia should be monitored. In addition, we found that mytilid species coexisting with M. platensis (Aulacomya atra and Perumytilus purpuratus) at one location shared the same pathological conditions and parasites, which differed from those of M. platensis at a distant locality. These results suggest that pathological conditions and parasites were influenced more by ecological habitat factors than by the species of mussels present, based on similar parasite assemblages found among closely related mytilid hosts in the same geographical area.

Management of abdominal distension in the preterm infant with noninvasive ventilation: Comparison of cenit versus 2x1 technique for the utilization of feeding tube.

BACKGROUND: Preterm infants are fed by orogastric / nasogastric tube until they reach maturation and coordination of sucking, swallowing and respiration at approximately 32-34 weeks of corrected age. While being on non-invasive ventilation (NIV), they frequently present abdominal distension. Currently at our institution two techniques are used for the management of abdominal distension in preterm infants fed by bolus via orogastric tube: cenit and 2 x 1.The aim of this study was to compare the proportion of preterm infants presenting NIV-associated abdominal distension with each of these techniques. STUDY DESIGN: We conducted a randomized clinical trial including infants of <  36.6 weeks of gestation and <  1500 g of birth weight who were admitted to our NICU during the period of April 1, 2016 to April 1, 2018 and received NIV. The presence of abdominal distension >  2 cm was the primary outcome. Secondary outcomes were presence of reflux, regurgitation, oxygen saturation during feeding and days to reach full feedings. Feeding tube drainage, stool characteristics and the use of prokinetics were confounding variables. RESULTS: A total of 97 patients were included. Forty-six in the cenit group and 51 in the 2 x 1 group. There was no difference in the proportion of infants with abdominal distension >  2 cm between groups. Oxygen saturation during feeding at volume of 150 ml/kg/day was higher in the cenit group with statistical significance. CONCLUSION: The use of cenit or 2 x 1 technique in preterm infants with NIV did not improve abdominal distension or other indicators of feeding tolerance.

[Case fatality of COVID-19 in patients with neurodegenerative dementia]. / Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa.

Introduction: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. Methods: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. Results: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. Discussion: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

Delays in making initial treatment contact after the first onset of mental health disorders in the Argentinean Study of Mental Health Epidemiology.

AIMS: While there are effective treatments for psychiatric disorders, many individuals with such disorders do not receive treatment and those that do often take years to get into treatment. Information regarding treatment contact failure and delay in Argentina is needed to guide public health policy and planning. Therefore, this study aimed to provide data on prompt treatment contact, lifetime treatment contact, median duration of treatment delays and socio-demographic predictors of treatment contact after the first onset of a mental disorder. METHODS: The Argentinean Study of Mental Health Epidemiology (EAESM) is a multistage probability sample representative of adults (aged 18+) living in large urban areas of Argentina. A total of 2116 participants were evaluated with the World Mental Health Composite International Diagnostic Interview to assess psychiatric diagnosis, treatment contact and delay. RESULTS: Projections of cases that will make treatment contact by 50 years taken from a survival curve suggest that the majority of individuals with a mood (100%) or anxiety disorder (72.5%) in Argentina whose disorder persist for a sufficient period of time eventually make treatment contact while fewer with a substance disorder do so (41.6%). Timely treatment in the year of onset is rare (2.6% for a substance disorder, 14.6% for an anxiety disorder and 31.3% of those with a mood disorder) with mean delays between 8 years for mood disorders and 21 years for anxiety disorders. Younger cohorts are more likely to make treatment contact than older cohorts, whereas those with earlier ages of disorder onset are least likely to make treatment contact. Those with anxiety disorders and major depressive disorder are more likely to make treatment contact when they have comorbid disorders, whereas those with substance use disorders are less likely. CONCLUSIONS: Argentina needs to implement strategies to get individuals with substance use disorders into treatment, and to reduce treatment delays for all, but particularly to target early detection and treatment among children and adolescents.

Morphology and molecular systematic of marine gregarines (Apicomplexa) from Southwestern Atlantic spionid polychaetes.

Gregarines are a common group of parasites that infect the intestines of marine invertebrates, and particularly polychaetes. Here, we describe for the first time four gregarine species that inhabit the intestines of three spionid species: Dipolydora cf. flava, Spio quadrisetosa and Boccardia proboscidea from the Patagonian coast, Argentina, using light and scanning electron microscopy and molecular phylogenetic analyses of small subunit (SSU) rDNA sequences. Even though the spionid species thrive in the same environments, our results showed a high host specificity of the gregarine species. Selenidium cf. axiferens and Polyrhabdina aff. polydorae were both identified from the intestine of D. cf. flava. The new species, Polyrhabdina madrynense sp. n. and Selenidium patagonica sp. n., were described from the intestines of S. quadrisetosa and the invasive species B. proboscidea, respectively. All specimens of D. cf. flava and S. quadrisetosa were infected by gregarines (P = 100%), recording the highest mean intensity values of infection (MI = 80; 60 respectively), in contrast to B. proboscidea (P = 60%; MI = 38). We associated this finding with the recent invasion of this host. It is expected that in the future, an increase of its population density might favour a rising intensity of this gregarine infection.

The Geographic Structure of Viruses in the Cuatro Ciénegas Basin, a Unique Oasis in Northern Mexico, Reveals a Highly Diverse Population on a Small Geographic Scale.

The Cuatro Ciénegas Basin (CCB) is located in the Chihuahuan desert in the Mexican state of Coahuila; it has been characterized as a site with high biological diversity despite its extreme oligotrophic conditions. It has the greatest number of endemic species in North America, containing abundant living microbialites (including stromatolites and microbial mats) and diverse microbial communities. With the hypothesis that this high biodiversity and the geographic structure should be reflected in the virome, the viral communities in 11 different locations of three drainage systems, Churince, La Becerra, and Pozas Rojas, and in the intestinal contents of 3 different fish species, were analyzed for both eukaryotic and prokaryotic RNA and DNA viruses using next-generation sequencing methods. Double-stranded DNA (dsDNA) virus families were the most abundant (72.5% of reads), followed by single-stranded DNA (ssDNA) viruses (2.9%) and ssRNA and dsRNA virus families (0.5%). Thirteen families had dsDNA genomes, five had ssDNA, three had dsRNA, and 16 had ssRNA. A highly diverse viral community was found, with an ample range of hosts and a strong geographical structure, with very even distributions and signals of endemicity in the phylogenetic trees from several different virus families. The majority of viruses found were bacteriophages but eukaryotic viruses were also frequent, and the large diversity of viruses related to algae were a surprise, since algae are not evident in the previously analyzed aquatic systems of this ecosystem. Animal viruses were also frequently found, showing the large diversity of aquatic animals in this oasis, where plants, protozoa, and archaea are rare.IMPORTANCE In this study, we tested whether the high biodiversity and geographic structure of CCB is reflected in its virome. CCB is an extraordinarily biodiverse oasis in the Chihuahuan desert, where a previous virome study suggested that viruses had followed the marine ancestry of the marine bacteria and, as a result of their long isolation, became endemic to the site. In this study, which includes a larger sequencing coverage and water samples from other sites within the valley, we confirmed the high virus biodiversity and uniqueness as well as the strong biogeographical diversification of the CCB. In addition, we also analyzed fish intestinal contents, finding that each fish species eats different prey and, as a result, presents different viral compositions even if they coexist in the same pond. These facts highlight the high and novel virus diversity of CCB and its "lost world" status.

Gross anatomy of the heart of the alpaca (Vicugna pacos, Linnaeus 1758).

The available information about anatomical characteristics of the cardiovascular system of the alpaca (Vicugna pacos, Linnaeus 1758) is scarce. The general objective of this work was to describe its heart anatomy. We dissected six adult animals and five neonates. The heart of the alpaca was located in the middle mediastinum, with a craniocaudal extension from the third to the sixth rib. No ligament that connected the fibrous pericardium to the sternum or to the diaphragm was detected. In the right atrium, there was a developed crista terminalis and small pectinate muscles. In the right ventricle, the septomarginal trabecula was very large. From the proximities of the interventricular septum arose small septomarginal trabeculae that ended in carnous trabeculae of the septal wall. The left atrium included little developed pectinate muscles. On the left ventricle, both papillary muscles were bilobed. Two left septomarginal trabeculas were detected in this ventricle. The left subclavian artery was originated from the aortic arch separately from the brachiocephalic trunk, and bicarotid trunk was present. The other branches of the subclavian artery were similar to the domestic ruminants. The arterial supply of the heart was of the right type. In conclusion, the heart anatomy of alpaca and the irrigation of thoracic cavity were more similar to those of old world camels and different from domestic ruminants.

Arterial distribution to the pelvic cavity and pelvic limb in the pampas deer (Ozotoceros bezoarticus, Linnaeus 1758).

This research is a study about the arterial vascularization of pelvic cavity and pelvic limb in pampas deer. For this study, 25 dead animals were used. The vascularization of the organs was investigated using a latex injection technique. Two animals were injected in the common carotid artery with contrast to cardiac angiography, and then, radiographs were taken. The aorta showed the two external iliac arteries, and after a short course, the aorta ended in two internal iliac arteries. The median sacral artery was originated from the dorsal surface cranially to the emergence of the internal iliac arteries. The last one gave off parietal (iliolumbar, cranial and caudal gluteal arteries) and visceral (umbilical and internal pudendal arteries) branches. The external iliac artery gave as first branch the deep circumflex iliac artery which was divided into a cranial and a caudal branch. After a short distance from the external iliac artery, the femoral and deep femoral arteries were originated. The deep femoral artery gave origin to the pudendoepigastric trunk and to the medial femoral circumflex artery. Based on the arterial distribution of the pelvic cavity and pelvic limb in the pampas deer, it is concluded that the internal iliac artery has a pattern of intermediate development. In reference to the distribution of the external iliac artery and its branches, the pattern of development is the cranial tibial type.

Asymmetrical size and functionality of the pampas deer (Ozotoceros bezoarticus) testes: Right testis is bigger but left testis is more efficient in spermatogenesis.

Information about gonadal asymmetries in ruminants is very scarce. In this work, we performed three complementary studies to compare characteristics of both testes: (i) weight and size of offspring and adult dead males; (ii) the tissue:fluid relationship determined by ultrasound scanning; and (iii) the spermatogenic status using fine needle aspiration cytology. The right testis was heavier than the left one in both offspring and adult animals and had greater width and volume in adult males than the left one. The ultrasound pixel intensity was similar in both testes. The right testis tended to have more spermatogonia (p = .06) and had a greater percentage of early spermatids (p = .004) than the left testis. On the other hand, the left testis had a greater percentage of spermatozoa (p = .05). The left testis had a greater spermatozoa/spermatogonia ratio (p = .02) and tended to have more spermatozoa/Sertoli cells ratio (p = .07). The spermatogenic index tended to be greater in the left than in the right testis (p = .06). Overall, we concluded that the right testis of pampas deer males is bigger but according to the cytology, it seems to be less spermatogenically effective than the left one, but these differences are not explained by different tissue:fluid ratio in each testis. Although differences were greater in adults than in offspring, asymmetry was observed even in just born offspring.

Recent advances in controlling the internal and external properties of self-assembling cyclic peptide nanotubes and dimers.

One of the most powerful strategies for the preparation of nanotubes is based on the stacking of flat-shaped cyclic peptide components. This strategy allows precise control of the nanotube internal diameter, the external properties and, more recently, the structural characterisitics of the internal cavity. The recent advances in these technologies and the applications of the resulting materials are described.