Numerical simulations of granular dam break: Comparison between discrete element, Navier-Stokes, and thin-layer models.

Granular flows occur in various contexts, including laboratory experiments, industrial processes, and natural geophysical flows. To investigate their dynamics, different kinds of physically based models have been developed. These models can be characterized by the length scale at which dynamic processes are described. Discrete models use a microscopic scale to individually model each grain, Navier-Stokes models use a mesoscopic scale to consider elementary volumes of grains, and thin-layer models use a macroscopic scale to model the dynamics of elementary columns of fluids. In each case, the derivation of the associated equations is well-known. However, few studies focus on the extent to which these modeling solutions yield mutually coherent results. In this article, we compare the simulations of a granular dam break on a horizontal or inclined planes for the discrete model convex optimization contact dynamics (COCD), the Navier-Stokes model Basilisk, and the thin-layer depth-averaged model SHALTOP. We show that, although all three models allow reproducing the temporal evolution of the free surface in the horizontal case (except for SHALTOP at the initiation), the modeled flow dynamics are significantly different, and, in particular, during the stopping phase. The stresses measured at the flow's bottom, reflecting the flow dynamics, are in relatively good agreement, but significant variations are obtained with the COCD model due to complex and fast-varying granular lattices. Similar conclusions are drawn using the same rheological parameters to model a granular dam break on an inclined plane. This comparison exercise is essential for assessing the limits and uncertainties of granular flow modeling.

[Architecture as experience, living differently with the philosophy of John Dewey]. / L'architecture comme expérience, habiter autrement avec la philosophie de John Dewey.

If architecture can be considered an art form, it is at the cost of reconfiguring what we consider to be an aesthetic experience. Thus conceived as processes, not finished objects, refuting the separation between the active creator and the passive spectator and between ideas, actions and affects, the architectural projects accompanied and documented by the urban and architectural experiments laboratory la Preuve par 7 engage a collective, experimental, sensitive and political understanding of their discipline.

Serotonergic neurons are involved in the counter-regulatory response to hypoglycemia.

OBJECTIVES: Intensive insulin therapy provides optimal glycemic control in patients with diabetes. However, intensive insulin therapy causes so-called iatrogenic hypoglycemia as a major adverse effect. The ventromedial hypothalamus (VMH) has been described as the primary brain area initiating the counter-regulatory response (CRR). Nevertheless, the VMH receives projections from other brain areas which could participate in the regulation of the CRR. In particular, studies suggest a potential role of the serotonin (5-HT) network. Thus, the objective of this study was to determine the contribution of 5-HT neurons in CRR control. METHODS: Complementary approaches have been used to test this hypothesis in quantifying the level of 5-HT in several brain areas by HPLC in response to insulin-induced hypoglycemia, measuring the electrical activity of dorsal raphe (DR) 5-HT neurons in response to insulin or decreased glucose level by patch-clamp electrophysiology; and measuring the CRR hormone glucagon as an index of the CRR to the modulation of the activity of 5-HT neurons using pharmacological or pharmacogenetic approaches. RESULTS: HPLC measurements show that the 5HIAA/5HT ratio is increased in several brain regions including the VMH in response to insulin-induced hypoglycemia. Patch-clamp electrophysiological recordings show that insulin, but not decreased glucose level, increases the firing frequency of DR 5-HT neurons in the DR. In vivo, both the pharmacological inhibition of 5-HT neurons by intraperitoneal injection of the 5-HT1A receptor agonist 8-OH-DPAT or the chemogenetic inhibition of these neurons reduce glucagon secretion, suggesting an impaired CRR. CONCLUSION: Taken together, these data highlight a new neuronal network involved in the regulation of the CRR. In particular, this study shows that DR 5-HT neurons detect iatrogenic hypoglycemia in response to the increased insulin level and may play an important role in the regulation of CRR.

Leishmaniasis visceral. Presentación de un caso y revisión de la entidade

La leishmania la describieron Leishman y Donovan en 1903, al aislar el parásito del bazo de las personas afectadas. La leishmaniasis es una enfermedad tropical y subtropical, causada por un protozoo intracelular del género Leishmania y transmitida a los humanos por la picadura de vectores Lutzomyias infectadas. Tiene como reservorios a los perros, roedores, lobos, zorros y el humano como huésped incidental. Clínicamente la leishmaniasis puede clasificarse en tres formas principales: leishmaniasis cutánea (LC), localizada (LCL) o difusa (LCD), leishmaniasis destructiva mucocutánea (LMC) y leishmaniasis visceral (LV o Kala-Azar). La enfermedad se manifiesta clínicamente con la invasión del parásito y daño en funcionamiento de órganos vitales como son la médula ósea, el hígado y el bazo. Se presenta el caso de un paciente masculino adolescente de 11 anos de edad de zona rural que presenta un cuadro clínico de aumento de volumen de abdomen superior, palidez marcada, decaimento, con hepato y esplenomegalia atendido en Bahía, Brasil en 2018 con diagnóstico de leishmaniasis. Se describe la clínica, médios diagnósticos y tratamiento.

Leishmania was described by Leishman and Donovan in 1903, when the parasite was isolated from the spleen of affected people. Leishmaniasis is a tropical and subtropical disease, caused by an intracellular protozoan of the genus Leishmania and transmitted to humans by the bite of infected Lutzomyia vectors. It has as reservoirs dogs, rodents, wolves, foxes and humans as incidental hosts. Clinically, leishmaniasis can be classified into three main forms: cutaneous (LC), localized (LCL) or diffuse (LCD) leishmaniasis, mucocutaneous destructive leishmaniasis (CML), and visceral leishmaniasis (VL or Kala-Azar). The disease manifests clinically with the invasion of the parasite and damage to the functioning of vital organs such as the bone marrow, liver and spleen.We present the case of an 11-year-old adolescent male patient from rural areas who presented a clinical picture of increased volume of the upper abdomen, marked pallor, decay, with hepato and splenomegaly treated in Bahia, Brazil in 2018 with a diagnosis of leishmaniasis. The clinic, diagnostic methods and treatment are described.

A leishmania foi descrita por Leishman e Donovan em 1903, quando o parasita foi isolado do baço das pessoas afetadas. A leishmaniose é uma doença tropical e subtropical, causada por um protozoário intracelular do gênero Leishmania e transmitida aos seres humanos pela picada de vetores de Lutzomyia infectados. Tem como reservatórios cães, roedores, lobos, raposas e humanos como hospedeiros incidentais. Clinicamente, a leishmaniose pode ser classificada em três formas principais: leishmaniose cutânea (LCL), localizada (LCL) ou difusa (LCD), leishmaniose mucocutânea destrutiva (LMC) e leishmaniose visceral (LV ou Kala-Azar). A doença se manifesta clinicamente com a invasão do parasita e danos ao funcionamento de órgãos vitais, como a medula óssea, fígado e baço.Apresentamos o caso de um adolescente de 11 anos, do sexo masculino, de áreas rurais, que apresentou quadro clínico de aumento do volume do abdome superior, palidez acentuada, cárie, com hepato e esplenomegalia tratado na Bahia, Brasil, em 2018, com diagnóstico de leishmaniose. A clínica, os métodos de diagnóstico e o tratamento são descritos.

Insulin modulates emotional behavior through a serotonin-dependent mechanism.

Type-2 Diabetes (T2D) is characterized by insulin resistance and accompanied by psychiatric comorbidities including major depressive disorders (MDD). Patients with T2D are twice more likely to suffer from MDD and clinical studies have shown that insulin resistance is positively correlated with the severity of depressive symptoms. However, the potential contribution of central insulin signaling in MDD in patients with T2D remains elusive. Here we hypothesized that insulin modulates the serotonergic (5-HT) system to control emotional behavior and that insulin resistance in 5-HT neurons contributes to the development of mood disorders in T2D. Our results show that insulin directly modulates the activity of dorsal raphe (DR) 5-HT neurons to dampen 5-HT neurotransmission through a 5-HT1A receptor-mediated inhibitory feedback. In addition, insulin-induced 5-HT neuromodulation is necessary to promote anxiolytic-like effect in response to intranasal insulin delivery. Interestingly, such an anxiolytic effect of intranasal insulin as well as the response of DR 5-HT neurons to insulin are both blunted in high-fat diet-fed T2D animals. Altogether, these findings point to a novel mechanism by which insulin directly modulates the activity of DR 5-HT neurons to dampen 5-HT neurotransmission and control emotional behaviors, and emphasize the idea that impaired insulin-sensitivity in these neurons is critical for the development of T2D-associated mood disorders.

Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain.

Descending control from the brain to the spinal cord shapes our pain experience, ranging from powerful analgesia to extreme sensitivity. Increasing evidence from both preclinical and clinical studies points to an imbalance toward descending facilitation as a substrate of pathological pain, but the underlying mechanisms remain unknown. We used an optogenetic approach to manipulate serotonin (5-HT) neurons of the nucleus raphe magnus that project to the dorsal horn of the spinal cord. We found that 5-HT neurons exert an analgesic action in naïve mice that becomes proalgesic in an experimental model of neuropathic pain. We show that spinal KCC2 hypofunction turns this descending inhibitory control into paradoxical facilitation; KCC2 enhancers restored 5-HT-mediated descending inhibition and analgesia. Last, combining selective serotonin reuptake inhibitors (SSRIs) with a KCC2 enhancer yields effective analgesia against nerve injury-induced pain hypersensitivity. This uncovers a previously unidentified therapeutic path for SSRIs against neuropathic pain.

Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis.

BACKGROUND: Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. A pronounced reduction in absolute lymphocyte counts (ALCs) early after treatment initiation has been suggested to be associated with the occurrence of lymphopenia thereafter. OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and evaluate whether the degree of decrease in the ALCs three months after initiation of DMF treatment is a predictor of the subsequent development of lymphopenia. METHODS: In this real-world Spanish prospective multicenter study conducted in MS patients who started DMF between 2014 and 2019, we analyzed the association between DMF-related lymphopenia and the percentage of early ALCs decline using regression models, considering both, significant lymphopenia (grades 2 + 3) and severe lymphopenia (grade 3). The cutoff values of early ALCs declines were obtained using the ROC curve. RESULTS: Among 532 MS patients treated with DMF, 193 (36.3%) developed any grade of lymphopenia. Older age and lower ALCs at treatment onset predicted the risk for lymphopenia but the best predictive risk factor was the reduction of ALCs within the three first months of treatment. Specifically, a reduction in ALCs≥21.2% was associated with a 6.5-fold higher risk of developing significant lymphopenia, and a decrease in ALCs≥40.2% with a 12.7-fold higher risk of developing severe lymphopenia. CONCLUSIONS: A pronounced reduction in ALCs early after initiation of DMF in MS patients is the best predictive risk factor for the subsequent development of significant lymphopenia.

Exploratory Study on Application of MALDI-TOF-MS to Detect SARS-CoV-2 Infection in Human Saliva.

SARS-CoV-2 has caused a large outbreak since its emergence in December 2019. COVID-19 diagnosis became a priority so as to isolate and treat infected individuals in order to break the contamination chain. Currently, the reference test for COVID-19 diagnosis is the molecular detection (RT-qPCR) of the virus from nasopharyngeal swab (NPS) samples. Although this sensitive and specific test remains the gold standard, it has several limitations, such as the invasive collection method, the relative high cost and the duration of the test. Moreover, the material shortage to perform tests due to the discrepancy between the high demand for tests and the production capacities puts additional constraints on RT-qPCR. Here, we propose a PCR-free method for diagnosing SARS-CoV-2 based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling and machine learning (ML) models from salivary samples. Kinetic saliva samples were collected at enrollment and ten and thirty days later (D0, D10 and D30), to assess the classification performance of the ML models compared to the molecular tests performed on NPS specimens. Spectra were generated using an optimized protocol of saliva collection and successive quality control steps were developed to ensure the reliability of spectra. A total of 360 averaged spectra were included in the study. At D0, the comparison of MS spectra from SARS-CoV-2 positive patients (n = 105) with healthy healthcare controls (n = 51) revealed nine peaks that significantly distinguished the two groups. Among the five ML models tested, support vector machine with linear kernel (SVM-LK) provided the best performance on the training dataset (accuracy = 85.2%, sensitivity = 85.1%, specificity = 85.3%, F1-Score = 85.1%). The application of the SVM-LK model on independent datasets confirmed its performances with 88.9% and 80.8% of correct classification for samples collected at D0 and D30, respectively. Conversely, at D10, the proportion of correct classification had fallen to 64.3%. The analysis of saliva samples by MALDI-TOF MS and ML appears as an interesting supplementary tool for COVID-19 diagnosis, despite the mitigated results obtained for convalescent patients (D10).

Telomere shortening causes distinct cell division regimes during replicative senescence in Saccharomyces cerevisiae.

BACKGROUND: Telomerase-negative cells have limited proliferation potential. In these cells, telomeres shorten until they reach a critical length and induce a permanently arrested state. This process called replicative senescence is associated with genomic instability and participates in tissue and organismal ageing. Experimental data using single-cell approaches in the budding yeast model organism show that telomerase-negative cells often experience abnormally long cell cycles, which can be followed by cell cycles of normal duration, before reaching the terminal senescent state. These series of non-terminal cell cycle arrests contribute to the heterogeneity of senescence and likely magnify its genomic instability. Due to their apparent stochastic nature, investigating the dynamics and the molecular origins of these arrests has been difficult. In particular, whether the non-terminal arrests series stem from a mechanism similar to the one that triggers terminal senescence is not known. RESULTS: Here, we provide a mathematical description of sequences of non-terminal arrests to understand how they appear. We take advantage of an experimental data set of cell cycle duration measurements performed in individual telomerase-negative yeast cells that keep track of the number of generations since telomerase inactivation. Using numerical simulations, we show that the occurrence of non-terminal arrests is a generation-dependent process that can be explained by the shortest telomere reaching a probabilistic threshold length. While the onset of senescence is also triggered by telomere shortening, we highlight differences in the laws that describe the number of consecutive arrests in non-terminal arrests compared to senescence arrests, suggesting distinct underlying mechanisms and cellular states. CONCLUSIONS: Replicative senescence is a complex process that affects cell divisions earlier than anticipated, as exemplified by the frequent occurrence of non-terminal arrests early after telomerase inactivation. The present work unravels two kinetically and mechanistically distinct generation-dependent processes underlying non-terminal and terminal senescence arrests. We suggest that these two processes are responsible for two consequences of senescence at the population level, the increase of genome instability on the one hand, and the limitation of proliferation capacity on the other hand.

Uso de plasma convaleciente en pacientes con COVID 19. Revisión bibliográfica / Use of convalescent plasma in patients with COVID 19. Literature review / Uso de plasma convalescente em pacientes com COVID 19. Revisão da literatura

RESUMEN Se realizó una revisión bibliográfica, con el objetivo de actualizar a los profesionales de diferentes disciplinas vinculados directa o indirectamente al tratamiento con plasma convaleciente a los pacientes con COVID 19. Se realizó una revisión de las bases de datos PubMed, Cumed, Lilacs, Clinicalkey y OPS desde 2020 hasta el 2021, así como sitios Web de instituciones y asociaciones de las Ciencias Biomédicas relacionadas con la temática. Se incluyeron artículos de revisión y artículos originales. La investigación abordó los principales aspectos a tener en cuenta, desde el origen de la enfermedad, forma de transmisión, los principales síntomas de la enfermedad, complicaciones de la enfermedad, el diagnóstico, y el tratamiento complementario con plasma convaleciente en pacientes afectados con COVID 19, así como su metodología para su aplicación. Se logró una actualización en los conocimientos sobre el uso del plasma convaleciente en pacientes con COVID 19, de gran utilidad para los profesionales de la salud.

ABSTRACT A bibliographic review was carried out, with the aim of updating professionals from different disciplines directly or indirectly linked to convalescent plasma treatment for patients with COVID 19. A review of the PubMed, Cumed, Lilacs, Clinicalkey and PAHO from 2020 to 2021, as well as websites of institutions and associations of Biomedical Sciences related to the subject. Review articles and original articles were included. The research addressed the main aspects to take into account, from the origin of the disease, mode of transmission, the main symptoms of the disease, complications of the disease, diagnosis, and complementary treatment with convalescent plasma in patients affected with COVID 19, as well as its methodology for its application. An update was achieved in the knowledge on the use of convalescent plasma in patients with COVID 19, of great utility for health professionals.

RESUMO Foi realizada uma revisão bibliográfica, com o objetivo de atualizar profissionais de diferentes disciplinas direta ou indiretamente ligadas ao tratamento de plasma convalescente para pacientes com COVID 19. Uma revisão do PubMed, Cumed, Lilacs, Clinicalkey e OPAS de 2020 a 2021, também como sites de instituições e associações de Ciências Biomédicas relacionadas ao assunto. Artigos de revisão e artigos originais foram incluídos. A pesquisa abordou os principais aspectos para levar em consideração, desde a origem da doença, o modo de transmissão, os principais sintomas da doença, as complicações da doença, o diagnóstico e o tratamento complementar com plasma convalescente em pacientes portadores de COVID 19, como bem como sua metodologia de aplicação. Realizou-se uma atualização do conhecimento sobre o uso do plasma convalescente em pacientes com COVID 19, de grande utilidade para os profissionais de saúde.

Schwannoma del nervio vago / Vagus-nerve schwannoma

Introducción:los schwannomas, también llamados neurilemomas o neurinomas, son tumores de origen neuroectodérmico, encapsulados y benignos, que generalmente aparecen como una masa laterocervical asintomática de crecimiento lento. Son pocos frecuentes en el área de cabeza y cuello.Caso clínico:mujer de 39 años con una historia de un año de evolución de una masa cervical derecha de crecimiento lento, pulsátil, dolorosa y móvil en el lado derecho del cuello. La imagen de la angiotomografía computarizada preoperatoria demostró que la masa involucraba la bifurcación carotídea, compatible con un paraganglioma carotídeo. La disección cuidadosa a través de una cervicotomía longitudinal mostró que la masa surgía de un único fascículo del nervio vago. La masa se envió a anatomía patológica con el resultado de schwannoma. En el posoperatorio la paciente presentó una función sensorial y motora del vago normal, con un leve síndrome de Horner.Discusión:los tumores nerviosos del cuello surgen a partir de grandes troncos nerviosos, los IX, X, XI y XII pares craneales, el simpático cervical, el plexo cervical y el plexo braquial. El nervio vago es un lugar infrecuente de aparición, con muy pocos casos reportados. Son lesiones de diagnóstico preoperatorio difícil, cuyo tratamiento de elección es la exéresis quirúrgica; en ocasiones, es difícil conservar el nervio de origen.(AU)

Introduction:schwannomas, neurilemomas or neurinomas, are benign, encapsulated, neuroectodermal tumors that generally appear as a slow-growing, asymptomatic laterocervical mass. They are rare in the head and neck area.Clinical case:a 39-year-old woman with a one-year history of a slowly enlarging, pulsatile, painful and movable right cervical mass on the right side of the neck. Preoperative computed angiotomography image demonstrated that the mass involved the carotid bifurcation compatible with a carotid paraganglioma. Careful dissection through a longitudinal cervicotomy, showed that the mass arose from a single fascicle of the vagus nerve. The mass was sent to the pathologists and found to be a schwannoma. The patient had normal vagus sensory and motor function postoperatively, with a slight Horner syndrome.Discussion:nerve tumors of the neck arise from large nerve trunks, the IX, X, XI, and XII cranial nerves, the cervical sympathetic, the cervical plexus, and the brachial plexus. The vagus nerve is an infrequent place of appearance with very few reported cases. They are difficult preoperative diagnosis lesions; whose treatment of choice is surgical excision; sometimes it is difficult to preserve the nerve of origin.(AU)

Efficacy of non-invasive intelligent volume assured pressure support (iVAPS) and pressure support ventilation (PSV) in clinical practice.

AIMS OF THE STUDY: Noninvasive ventilation (NIV) is a well-established treatment option for hypercapnic respiratory failure; however, the best mode of ventilation remains unknown. The aim of this retrospective study was to compare patients’ adherence to NIV using either pressure support ventilation (PSV) or intelligent volume-assured pressure support (iVAPS). PATIENTS AND METHODS: In this retrospective cohort study, we assessed in- and outpatients suffering from hypercapnic respiratory failure of various aetiologies (chronic obstructive pulmonary disease [COPD], obese COPD [body mass index >30 kg/m2], obesity hypoventilation syndrome and other diseases such as amyotrophic lateral sclerosis or interstitial lung disease) after NIV initiation with PSV or iVAPS. Adherence to treatment was compared between these modes using the Wilcoxon test. Within-group differences were tested using linear regression models. Mortality and emergency hospital readmission rates were modelled using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: Adherence to treatment was similar in both groups throughout the observation period – after 6 weeks: PSV 363 min/night (interquartile range [IQR] 200–448), iVAPS 369 min/night (IQR 310–468) (p = 0.619); after 1 year: PSV 423 (323–500), iVAPS 429 (298–475) (p = 0.901); at the last follow up: PSV 481 (395–586), iVAPS 426 (391–565) (p = 0.284). NIV reduced PaCO2 significantly compared with baseline at all follow-ups: PSV −1.29/−1.49/−1.49 kPa, iVAPS −1.47/−1.23/−1.24 kPa, p <0.001 each, PSV vs iVAPS: p = 0.250, 0.756 and 0.352, respectively. Median survival time (PSV 5.06 years, iVAPS median not reached; p = 0.800) and time to first readmission (PSV 3.6 years, iVAPS 7.33 years, p = 0.200) did not differ between groups. Obese COPD patients had a longer time to hospital readmission than lean COPD patients (3.8 vs 1.5 years, hazard ratio (HR) 0.39, 95% confidence interval [CI] 0.16–0. 74; p = 0.007). Good adherence (>4 h/night and >80% nightly usage) was associated with a lower mortality rate (HR 0.34, 95% CI 0.15–0.77; p = 0.010). CONCLUSION: In a real-world setting of a mixed population with hypercapnic respiratory failure, iVAPS and PSV seem to be similarly effective in improving gas exchange and demonstrate excellent adherence to treatment. A longer survival was noted in NIV-adherent patients. Randomised controlled studies are necessary to identify patients who might benefit more from hybrid ventilation modes.

Animal Welfare Issues in Capture-Based Aquaculture.

Capture-based aquaculture (CBA) represents a type of intensive aquaculture production system for some economically valuable fish species, such as bluefin tuna (Thunnus thynnus), eel (Anguilla spp.) and Atlantic cod (Gadus morhua). In CBA, fish are captured from the wild in certain periods of the year, and following a recovery phase, they are kept in rearing facilities for a period of time, until they reach the market size. In this case, the fish are wild and have not gone through domestication like other fish species that are reproduced and farmed under the established farming systems. Therefore, these fish are not genetically adapted to live under the intensive farming conditions, and thus their welfare may be compromised in different manners compared to their domesticated counterparts. This review presents an overview of the current situation of CBA, while focusing on the assessment of fish welfare in CBA. The most commonly used fish welfare indicators will be discussed in relation to the different stages of CBA.

Tratamiento híbrido de aneurisma micótico de la aorta visceral / Hybrid treatment of a mycotic aneurysm of the visceral aorta

Introducción: los aneurismas micóticos son una entidad grave y poco frecuente, cuyo tratamiento quirúrgico se ha basado históricamente en la resección del tejido infectado y en la reconstrucción arterial. En los últimos años, la importancia del uso de técnicas de reparación endovascular ha ido en aumento. Caso clínico: se presenta el caso de una mujer de 84 años con un aneurisma micótico de la aorta visceral tratado mediante un abordaje híbrido. Se revascularizan las arterias mesentérica superior y hepática y, posteriormente, se coloca una endoprótesis de aorta. Discusión: el empleo de dispositivos endovasculares para la reparación de los aneurismas micóticos genera controversia debido a que no se elimina el tejido infectado. Sin embargo, existen publicaciones que avalan su uso, ya que permiten el tratamiento, principalmente, de pacientes de alto riesgo quirúrgico sin aumentar el número de complicaciones.(AU)

Introduction: mycotic aneurysms are a serious and rare entity, whose surgical treatment has historically been based on resection of infected tissue and arterial reconstruction. In recent years, the importance of using endovascular repair techniques has increased. Case report: an 84-year-old woman with a mycotic aneurysm of the visceral aorta is presented, treated by a hybrid approach, revascularizing the superior mesenteric and hepatic arteries, and the placement of an aortic stent. Discussion: the use of endovascular devices for the repair of mycotic aneurysms generates controversy due to the maintenance of the infected tissue. However, there are publications that support its use since they allow the treatment mainly of patients at high surgical risk not increasing the rate of complications.(AU)

Diagnostic precision and identification of rare diseases is dependent on distance of residence relative to tertiary medical facilities.

BACKGROUND: Diagnostic precision and the identification of rare diseases is a daily challenge, which needs specialized expertise. We hypothesized, that there is a correlation between the distance of residence to the next tertiary medical facility with highly specialized care and the diagnostic precision, especially for rare diseases. RESULTS: Using a nation-wide hospitalization database, we found a negative association between diagnostic diversity and travel time to the next tertiary referral hospital when including all cases throughout the overall International Classification of Diseases version 10 German Modification (ICD-10-GM) diagnosis codes. This was paralleled with a negative association of standardized incidence rates in all groups of rare diseases defined by the Orphanet rare disease nomenclature, except for rare teratologic and rare allergic diseases. CONCLUSION: Our findings indicate a higher risk of being mis-, under- or late diagnosed especially in rare diseases when living more distant to a tertiary medical facility. Greater distance to the next tertiary medical facility basically increases the chance for hospitalization in a non-comprehensive regional hospital with less diagnostic capacity, and, thus, impacts on adapted health care access. Therefore, solutions for overcoming the distance to specialized care as an indicator of health care access are a major goal in the future.

The impact of insulin on the serotonergic system and consequences on diabetes-associated mood disorders.

The idea that insulin could influence emotional behaviours has long been suggested. However, the underlying mechanisms have yet to be solved and there is no direct and clear-cut evidence demonstrating that such action involves brain serotonergic neurones. Indeed, initial arguments in favour of the association between insulin, serotonin and mood arise from clinical or animal studies showing that impaired insulin action in type 1 or type 2 diabetes causes anxiety- and depressive symptoms along with blunted plasma and brain serotonin levels. The present review synthesises the main mechanistic hypotheses that might explain the comorbidity between diabetes and depression. It also provides a state of knowledge of the direct and indirect experimental evidence that insulin modulates brain serotonergic neurones. Finally, it highlights the literature suggesting that antidiabetic drugs present antidepressant-like effects and, conversely, that serotonergic antidepressants impact glucose homeostasis. Overall, this review provides mechanistic insights into how insulin signalling alters serotonergic neurotransmission and related behaviours bringing new targets for therapeutic options.

Uso de plasma convaleciente en pacientes con COVID 19. Revisión bibliográfica / Use of convalescent plasma in patients with COVID 19. Literature review

Se realizó una revisión bibliográfica, con el objetivo de actualizar a los profesionales de diferentes disciplinas vinculados directa o indirectamente al tratamiento con plasma convaleciente a los pacientes con COVID 19. Se realizó una revisión de las bases de datos PubMed, Cumed, Lilacs, Clinicalkey y OPS desde 2020 hasta el 2021, así como sitios Web de instituciones y asociaciones de las Ciencias Biomédicas relacionadas con la temática. Se incluyeron artículos de revisión y artículos originales. La investigación abordó los principales aspectos a tener en cuenta, desde el origen de la enfermedad, forma de transmisión, los principales síntomas de la enfermedad, complicaciones de la enfermedad, el diagnóstico, y el tratamiento complementario con plasma convaleciente en pacientes afectados con COVID 19, así como su metodología para su aplicación. Se logró una actualización en los conocimientos sobre el uso del plasma convaleciente en pacientes con COVID 19, de gran utilidad para los profesionales de la salud(AU)

A bibliographic review was carried out, with the aim of updating professionals from different disciplines directly or indirectly linked to convalescent plasma treatment for patients with COVID 19. Areview of the PubMed, Cumed, Lilacs, Clinicalkey and PAHO from 2020 to 2021, as well as websites of institutions and associations of Biomedical Sciences related to the subject. Review articles and original articles were included. The research addressed the main aspects to take into account, from the origin of the disease, mode of transmission, the main symptoms of the disease, complications of the disease, diagnosis, and complementary treatment with convalescent plasma in patients affected with COVID 19, as well as its methodology for its application. An update was achieved in the knowledge on the use of convalescent plasma in patients with COVID 19, of great utility for health professionals(EU)

Characteristics of Asthma-related Nocturnal Cough: A Potential New Digital Biomarker.

INTRODUCTION: The nature of nocturnal cough is largely unknown. It might be a valid marker for asthma control but very few studies characterized it as a basis for better defining its role and its use as clinical marker. This study investigated prevalence and characteristics of nocturnal cough in asthmatics over the course of four weeks. METHODS: In two centers, 94 adult patients with physician-diagnosed asthma were recruited. Patient-reported outcomes and nocturnal sensor data were collected by a smartphone with a chat-based study app. RESULTS: Patients coughed in 53% of 2212 nights (range: 0-345 coughs/night). Median coughs per hour were 0 (IQR 0-1). Nocturnal cough rates showed considerable inter-individual variance. The highest counts were measured in the first 30 min in bed (4.5-fold higher than rest of night). Eighty-six percent of coughs were part of a cough cluster. Clusters consisted of a median of two coughs (IQR 2-4). Nocturnal cough was persistent within patient. CONCLUSION: To the best of the authors' knowledge, this study is the first to describe prevalence and characteristics of nocturnal cough in asthma over a period of one month, demonstrating that it was a prevalent symptom with large variance between patients and high persistence within patients. Cough events in asthmatics were 4.5 times more frequent within the first 30 min in bed indicating a potential role of positional change, and not more frequent during the early morning hours. An important next step will investigate the association between nocturnal cough and asthma control.