Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight

Strontium ranelate effect on bone mineral density is modified by previous bisphosphonate treatment

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on bone mineral density (BMD) and boneturnover markers after 1 year of treatment. Additionally, theeffect of SrR in bisphosphonate-naïve patients (BP-naïve)compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included482 postmenopausal women treated with SrR (2 g/day) for 1year in ten Argentine centers; 41 patients were excludeddue to insufficient data, while 441 were included. Participants were divided according to previous bisphosphonatetreatment in two groups: BP-naïve (n = 87) and BP-prior (n = 350). Data are expressed as mean ± SEM. After 1 year oftreatment with SrR the bone formation markers total alkaline phosphatase and osteocalcin were increased (p < 0.0001),while the bone resorption marker s-CTX was decreased (p =0.0579). Also increases in BMD at the lumbar spine (LS,3.73%), femoral neck (FN, 2.00%) and total hip (TH, 1.54%) [p < 0.0001] were observed. These increments were significant(p < 0.0001) both among BP-naïve and BP-prior patients. Interestingly, the change in BMD after 1 year of SrR treatmentwas higher in BP-naïve patients: LS: BP-naïve = 4.58 ± 0.62%; BP-prior = 3.45 ± 0.28% (p = 0.078). FN: BP-naïve = 2.79 ±0.56%; BP-prior = 2.13 ± 0.29% (p = 0.161). TH: BP-naïve = 3.01± 0.55%; BP-prior = 1.22 ± 0.27% (p = 0.0006). SrR treatmentincreased BMD and bone formation markers and decreaseda bone resorption marker in the whole group, with betterresponse in BP-naïve patients.Fil: Brun, Lucas Ricardo Martín. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galich, Ana M.. Hospital Italiano; ArgentinaFil: Vega, Eduardo. Instituto de la Mujer. Buenos Aires; ArgentinaFil: Salerni, Helena. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo ; ArgentinaFil: Maffei, Laura. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Premrou, Valeria. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Costanzo, Paulo R. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo ; ArgentinaFil: Sarli, Marcelo A. Instituto de Investigaciones Metabólicas Dr. Zanchetta; ArgentinaFil: Rey, Paula. Instituto de Investigaciones Metabólicas Dr. Zanchetta; ArgentinaFil: Larroudé, Maria S.. Hospital César Milstein; ArgentinaFil: Moggia, Maria S.. Centro Tiempo; ArgentinaFil: Brance, María Lorena. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; ArgentinaFil: Sánchez, Ariel. Centro de Endocrinología; ArgentinaFil: Grupo Argentino de Estudio del Ranelato de Estroncio. No especifica

Reference Values of Three-Dimensional Proximal Femur Parameters from Bone Densitometry Images in Healthy Subjects from Argentina

Objective: New methodologies for the assessment of bone mass from by DXA have been developed in the last years. The threedimensional analysis of the proximal femur by (3D-DXA) allows the evaluation of cortical and trabecular bone separately and has shown a good correlation with computed tomography. We aimed to obtain reference values in a healthy population of both sexesin Argentina.Methods: Adults female and male subjects (n=992) from four cities from Argentina were included. BMD (g/cm2) was measured by DXA on the femoral neck and total hip. The 3D analysis was performed with 3D-Shaper software (v2.9, Galgo Medical, Spain).The cortical BMD (sDens - mg/cm2) and trabecular volumetric BMD (trab vBMD - mg/cm3) were consider. The distribution of the data was evaluated with the Shapiro-Wilk test and parametricor non-parametric tests were used as appropriate. Data were expressed as mean±SD and p<0.05 was considered significant.Results: 75.5% women (n=749) and 24.5% men (n=243) were included. The mean age was 54.8±16.8 y and BMI was 27.3±5.4 kg/m2. The data according to each decade and a comparison with a references group (decade 20-30) are shown in the following table (*indicates significant differences compared to decade 20-30).Conclusion: A significant decrease in trabecular vBMD from D40 was observed in women, while in men this decrease was observed later (D60). The cortical parameter sDens was observed decreasefrom D50 in women and in men, an increase in D40 and cortical bone maintenance according to age was found.Fil: Brance, M. L.. Reumatología y Enfermedades Óseas; ArgentinaFil: Saravi, Fernando Daniel. Escuela de Medicina Nuclear; ArgentinaFil: Henríquez, M. M.. Escuela de Medicina Nuclear; ArgentinaFil: Longobardi, V.. Instituto de Investigaciones Metabólicas; ArgentinaFil: Zanchetta, M. B.. Instituto de Investigaciones Metabólicas; ArgentinaFil: Larroudé, M. S.. Centro de Diagnostico Rossi; ArgentinaFil: Ulla, M. R.. Instituto Latinoamericano de Investigaciones Médicas; ArgentinaFil: Matos, F.. Instituto Latinoamericano de Investigaciones Médicas; ArgentinaFil: Salerni, H.. No especifíca;Fil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Bonanno, Marina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Meneses, N. L.. No especifíca;Fil: Di Gregorio, S.. Fundacion Cetir.; EspañaFil: Brum, L. R.. Universidad Nacional de Rosario; ArgentinaWorld Congress on Osteoporosis, Osteoarthritis and Musculoskeletal DiseasesVirtualBélgicaInternational Osteoporosis FoundationEuropean Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease

Foreign bodies in the ears causing complications and requiring hospitalization in children 0-14 age: results from the ESFBI study

The occurrence of foreign bodies (FBs) in otorhinolaryngological practice is a common and serious problem among patients in paediatric age. The aim of this work is to characterize the risk of complications and prolonged hospitalization due to foreign bodies in ears in terms of the characteristics of the injured patients (age, gender), typology and features of the foreign bodies, the circumstances of the accident and the hospitalization's details

Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BPprior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMDand decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.Facultad de Ciencias Médica

Densitometric Response in Postmenopausal Osteoporosis Treated with Strontium Ranelate or Denosumab

Tanto el ranelato de estroncio (RSr) como el denosumab (Dmab) son eficaces en el tratamiento de la osteoporosis (OP) posmenopáusica (PM). El efecto de cada fármaco por separado sobre la densidad mineral ósea (DMO) ha sido estudiado recientemente. Con ambas drogas se observó, al año de tratamiento, un aumento significativo de la DMO en columna lumbar (CL), cuello femoral (CF) y cadera total (CT). En este trabajo comparamos la respuesta densitométrica al año de tratamiento con una y otra droga. Utilizamos los registros de 425 pacientes PMOP tratadas con Dmab y 441 tratadas con RSr. En cada paciente analizamos el porcentaje de cambio; se clasificaron como respondedoras aquellas que mostraron un cambio ≥3%. Adicionalmente se comparó la respuesta en pacientes no previamente tratadas con bifosfonatos (BF-naïve) en comparación con pacientes que habían recibido previamente un BF. Al analizar el grupo completo para Dmab, el porcentaje de pacientes respondedoras fue de 68,4% en CL, 63,3% en CF y 49,3% en CT. Por otro lado, en el grupo de pacientes tratadas con RSr, el porcentaje de respondedoras (53,8% en CL, 40,0% en CF y 35,6% en CT) fue estadísticamente menor. Cuando comparamos la respuesta entre las pacientes BF-naïve que recibieron RSr o Dmab, el Dmab indujo mayor respuesta en CL y CF que el grupo RSr, sin diferencias en CT. Cuando se analizaron los subgrupos BF-previo, las tratadas con Dmab mostraron mayor respuesta en todas las regiones. Conclusión: en pacientes con OP-PM, el tratamiento con Dmab produjo mayores incrementos densitométricos que el RSr, siendo el porcentaje de pacientes respondedoras mayor con Dmab que con RSr.Both strontium ranelate (SrR) and denosumab (Dmab) are effective in the treatment of postmenopausal osteoporosis (PMOP). The effect of each drug on bone mineral density (BMD) has been studied separately by us. With both treatments, there was a significant increase after one year of treatment at the lumbar spine (LS) and hip. In this paper we compared the densitometric response after one year of treatment with both drugs used separately. We used the clinical records of 425 PM patients treated with Dmab and 441 treated with SrR. For each patient we analyzed the percentage of change; those who showed a change ≥3% were classified as responders. Additionally, the response was compared in patients not previously treated with bisphosphonates (BP-naïve) compared to patients who had previously received a BP. When analyzing the complete group for Dmab, the percentage of “responders” was 65.2% at the LS, 62.9% at the femoral neck (FN) and 47.4% at the total hip (TH). On the other hand, in the group of patients treated with SrR the percentage of responders (53.8% at the LS, 40.0% at the FN and 35.6% at the TH) was statistically lower. When comparing the response between in BF-naïve patients receiving RSr or Dmab, Dmab induced a greater response at the LS and FN than the RSr group, with no statistical differences at the TH. When the subgroups with prior BP treatment were analyzed, those treated with Dmab showed greater response in all regions. Conclusion: in patients with PMOP treatment with Dmab produced greater densitometric increments than SrR, and the percentage of responders was higher with Dmab than with SrR.Facultad de Ciencias Médica

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores ((Formula presented.) and (Formula presented.)). By applying a logistic regression with both IPGS, ((Formula presented.) (or indifferently (Formula presented.)) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%

Ultra-rare RTEL1 gene variants associate with acute severity of COVID-19 and evolution to pulmonary fibrosis as a specific long COVID disorder

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused an ongoing pandemic of a pathology termed Coronavirus Disease 19 (COVID-19). Several studies reported that both COVID-19 and RTEL1 variants are associated with shorter telomere length, but a direct association between the two is not generally acknowledged. Here we demonstrate that up to 8.6% of severe COVID-19 patients bear RTEL1 ultra-rare variants, and show how this subgroup can be recognized. Methods: A cohort of 2246 SARS-CoV-2-positive subjects, collected within the GEN-COVID Multicenter study, was used in this work. Whole exome sequencing analysis was performed using the NovaSeq6000 System, and machine learning methods were used for candidate gene selection of severity. A nested study, comparing severely affected patients bearing or not variants in the selected gene, was used for the characterisation of specific clinical features connected to variants in both acute and post-acute phases. Results: Our GEN-COVID cohort revealed a total of 151 patients carrying at least one RTEL1 ultra-rare variant, which was selected as a specific acute severity feature. From a clinical point of view, these patients showed higher liver function indices, as well as increased CRP and inflammatory markers, such as IL-6. Moreover, compared to control subjects, they present autoimmune disorders more frequently. Finally, their decreased diffusion lung capacity for carbon monoxide after six months of COVID-19 suggests that RTEL1 variants can contribute to the development of SARS-CoV-2-elicited lung fibrosis. Conclusion: RTEL1 ultra-rare variants can be considered as a predictive marker of COVID-19 severity, as well as a marker of pathological evolution in pulmonary fibrosis in the post-COVID phase. This notion can be used for a rapid screening in hospitalized infected people, for vaccine prioritization, and appropriate follow-up assessment for subjects at risk. Trial Registration NCT04549831 (www.clinicaltrial.org