Mood symptoms and suicidality across the autism spectrum

Abstract Background Autism spectrum is a psychopathological dimension which encompasses a wide range of clinical presentations: from subthreshold forms and autistic traits (AT), that can be found in the general population, to full-blown autism spectrum disorder (ASD). Many studies reported high rates of comorbidity between both ASD and AT and mood disorders, as well as a high prevalence of suicidal ideation among patients with ASD/AT. The aim of this study was to investigate the presence of mood symptoms and suicidal ideation and behaviors in patients with full-blown ASD and in subjects with AT, as well in a healthy control (HC) group, with a specific focus on which of the autistic features may be predictive of suicidal ideation and behaviors. Methods We recruited 262 adult subjects: 34 with ASD without intellectual impairment or language disability (ASD group), 68 fulfilling only one symptom criterion for ASD according to DSM-5 but who do not meet criteria for a full-blown diagnosis of ASD (AT group), and 160 HC. All subjects were assessed with the Structured Clinical Interview for DSM-5 (SCID-5); in addition, they were asked to fill two questionnaires: The Mood Spectrum, Self-report (MOODS-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). Results ASD subjects reported significantly higher AdAS Spectrum and MOODS-SR total scores, as well as higher MOODS-SR depressive component total scores, when compared with AT and HC subjects. AT subjects scored significantly higher than the HC group. No significant differences were reported between ASD and AT subjects for the suicidality score according to MOODS-SR, despite both groups scored significantly higher than the HC group. The strongest predictor of suicidality score were MOODS-SR depressive component score and AdAS Spectrum Restricted interests and rumination domain score. Conclusions Our results highlight a correlation between autism and mood spectrum, as well as between suicidality and both ASD and AT. Subthreshold forms of ASD should be accurately investigated due to their relationship with suicidal thoughts and behaviors

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

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care(1) or hospitalization(2-4) after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease. © 2022, The Author(s)

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

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 asresponders. 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 responnders was higher with Dmab than with SrR.Fil: Sánchez, Ariel. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología SRL; ArgentinaFil: Brun, Lucas Ricardo Martín. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario; ArgentinaFil: Salerni, Helena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Costanzo Caso, Pablo Alejandro. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios de Investigación Clínica Endocrinológica y del Metabolismo Óseo; ArgentinaFil: Maffei, Ana Laura. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Pemrou, Valeria. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Consultorios Asociados de Endocrinología Dra. Laura Maffei; ArgentinaFil: Sarli, Marcelo A.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Rey, Paula. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Larraoudé, María Silvia. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Hospital Milstein; ArgentinaFil: Brance, María Lorena. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Laboratorio de Biología Ósea; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galich, Ana María. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Servicio de Endocrinología del Hospital Italiano de Buenos Aires; ArgentinaFil: Gonzalez, Diana. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: Bagur, Alicia Cristina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Mautalen Salud e Investigación; ArgentinaFil: 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. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Vega, Eduardo. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Cesan; Argentina. Instituto de la Mujer; ArgentinaFil: Zanchetta, María B.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Farias, Vanina. Grupo Argentino de Estudio de la Osteoporosis; Argentina. IInstituto de Investigaciones Metabólicas; ArgentinaFil: Manzur, José L.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteoporosis; ArgentinaFil: Moggia, María S.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro Tiempo; ArgentinaFil: Ulla, María R.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Centro de Endocrinología y Osteopatías Médicas; ArgentinaFil: Pavlove, María M.. Grupo Argentino de Estudio de la Osteoporosis; Argentina. Gobierno de la Ciudad Autonoma de Buenos Aires. Hospital General de Agudos Carlos Durand.; ArgentinaFil: Karlsbrum, Silvia. Hospital Durand; Argentina. Grupo Argentino de Estudio de la Osteoporosis; ArgentinaFil: Grupo Argentino de Estudio de la Osteoporosis. No especifíca

Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study

Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients.Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (&lt;60y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.Results: Overall, we found TLR7 deleterious variants in 2.1% of severely affected males and in none of the asymptomatic participants. The functional gene expression profile analysis demonstrated a reduction in TLR7-related gene expression in patients compared with controls demonstrating an impairment in type I and II IFN responses.Conclusion: Young males with TLR7 loss-of-function variants and severe COVID-19 represent a subset of male patients contributing to disease susceptibility in up to 2% of severe COVID-19