Bone symptoms can be an early manifestation of Gaucher disease implications for diagnosis

Gaucher disease (GD) is caused by mutations in the gene GBA1, which encodes for the synthesis of the enzyme lysosomal glucocerebrosidase (GCase). Lack or deficiency of GCase activity causes accumulation of glucosylceramide in the lysosomes of the monocyte-macrophage system in the bone marrow, spleen, and liver, and less frequently in the lungs and the central nervous system; this accumulation results in cell damage and organ dysfunction.Currently available diagnostic algorithms are based on the well-recognized hematological manifestations (cytopenia and splenomegaly), which are the manifestations most commonly associated with GD. However, 25 to 32% of patients have been found to present with bone signs and/or symptoms as the only or main presenting sign of the disease.A number of physicians may be unaware of this clinical presentation of GD, and may therefore delay in establishing diagnosis and initiating treatment, when necessary.We developed an educational program for early detection and diagnosis of GD, which includes a diagnostic algorithm based on GD-related bone manifestations.We herein report the case of a girl with bone symptoms as the only first manifestation of GD that were mistaken for stress fracture and osteomyelitis, and who was seen by 5 different specialists over a 4-year period before she was accurately diagnosed with GD.The case presented here shows the usefulness of the educational program for early detection and diagnosis of GD based on bone symptoms.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; ArgentinaFil: Delgado González, Diana Catherine. Mautalen Salud e Investigación; ArgentinaFil: Ferrari, Emma. Hospital SAMCO Villa Ocampo; Argentin

Short-Term Exposure to Nanoplastics Does Not Affect Bisphenol A Embryotoxicity to Marine Ascidian Ciona robusta

Plastic pollution is recognized as a global environmental threat and concern is increasing regarding the potential interactions of the smallest fragments, nanoplastics (1 m), with either physical and chemical entities encountered in the natural environment, including toxic pollutants. The smallest size of nanoplastics (<100 nm) rebounds to their safety associated with remarkable biological, chemical and physical reactivity that allow them to interact with cellular machinery by crossing biological barriers and causing damage to living beings. Recent findings on nanoplastic occurrence inmarine coastal waters, including the Mediterranean Sea, leave open the question on their ability to act as a vector of other contaminants of emerging concerns (CECs) concomitantly released by wastewater treatment plants and reaching marine coastal waters. Here, we assess for the first time the role of non-functionalized polystyrene nanoparticles (PS NPs, 20 nm) as a proxy for nanoplastics (1 and 10 g/mL) alone and in combinationwith bisphenolA(BPA) (4.5 and 10 m) on Ciona robusta embryos (22 h post fertilization, hpf) by looking at embryotoxicity through phenotypic alterations. We confirmed the ability of BPA to impact ascidian C. robusta embryo development, by affecting sensory organs pigmentation, either alone and in combination with PS NPs. Our findings suggest that no interactions are taking place between PS NPs and BPA in filtered sea water (FSW) probably due to the high ionic strength of seawater able to trigger the sorption surface properties of PS NPs. Further studies are needed to elucidate such peculiarities and define the risk posed by combined exposure to BPA and PS NPs in marine coastal waters

Prenatal diagnosis and follow-up of a case of branchio-oto-renal syndrome displays renal growth impairment after the second trimester

Branchio-oto-renal syndrome combines branchial arch defects, hearing impairment and renal malformations or hypoplasia. Due to the high phenotypic variability, prenatal diagnosis has a limited prognostic value in mutation-positive cases. We report the first branchio-oto-renal syndrome molecular prenatal diagnosis and ultrasonographic follow-up, showing a normal renal growth until the 24th week of pregnancy, a growth deceleration during the third trimester and a renal volume recovery during the first months of life

Single-photon detection and cryogenic reconfigurability in Lithium Niobate nanophotonic circuits

Lithium-Niobate-On-Insulator (LNOI) is emerging as a promising platform for integrated quantum photonic technologies because of its high second-order nonlinearity and compact waveguide footprint. Importantly, LNOI allows for creating electro-optically reconfigurable circuits, which can be efficiently operated at cryogenic temperature. Their integration with superconducting nanowire single-photon detectors (SNSPDs) paves the way for realizing scalable photonic devices for active manipulation and detection of quantum states of light. Here we report the first demonstration of these two key components integrated in a low loss (0.2 dB/cm) LNOI waveguide network. As an experimental showcase of our technology, we demonstrate the combined operation of an electrically tunable Mach-Zehnder interferometer and two waveguide-integrated SNSPDs at its outputs. We show static reconfigurability of our system with a bias-drift-free operation over a time of 12 hours, as well as high-speed modulation at a frequency up to 1 GHz. Our results provide blueprints for implementing complex quantum photonic devices on the LNOI platform

Domestic violence and mental health: a cross-sectional survey of women seeking help from domestic violence support services.

BACKGROUND: Domestic violence and abuse (DVA) are associated with an increased risk of mental illness, but we know little about the mental health of female DVA survivors seeking support from domestic violence services. OBJECTIVE: Domestic violence and abuse (DVA) are associated with an increased risk of mental illness, but we know little about the mental health of female DVA survivors seeking support from domestic violence services. DESIGN: Baseline data on 260 women enrolled in a randomized controlled trial of a psychological intervention for DVA survivors was analyzed. We report prevalence of and associations between mental health status and severity of abuse at the time of recruitment. We used logistic and normal regression models for binary and continuous outcomes, respectively. Mental health measures used were: Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), Patient Health Questionnaire, Generalized Anxiety Disorder Assessment, and the Posttraumatic Diagnostic Scale (PDS) to measure posttraumatic stress disorder. The Composite Abuse Scale (CAS) measured abuse. RESULTS: Exposure to DVA was high, with a mean CAS score of 56 (SD 34). The mean CORE-OM score was 18 (SD 8) with 76% above the clinical threshold (95% confidence interval: 70-81%). Depression and anxiety levels were high, with means close to clinical thresholds, and all respondents recorded PTSD scores above the clinical threshold. Symptoms of mental illness increased stepwise with increasing severity of DVA. CONCLUSIONS: Exposure to DVA was high, with a mean CAS score of 56 (SD 34). The mean CORE-OM score was 18 (SD 8) with 76% above the clinical threshold (95% confidence interval: 70-81%). Depression and anxiety levels were high, with means close to clinical thresholds, and all respondents recorded PTSD scores above the clinical threshold. Symptoms of mental illness increased stepwise with increasing severity of DVA

First-trimester prediction model for placental vascular disorders: an observational prospective study

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0–12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications

Domestic violence and mental health:a cross-sectional survey of women seeking help from domestic violence support services

BACKGROUND: Domestic violence and abuse (DVA) are associated with increased risk of mental illness, but we know little about the mental health of female DVA survivors seeking support from domestic violence services. OBJECTIVE: Our goal was to characterise the demography and mental health of women who access specialist DVA services in the United Kingdom and to investigate associations between severity of abuse and measures of mental health and health state utility, accounting for important confounders and moderators. DESIGN: Baseline data on 260 women enrolled in a randomized controlled trial of a psychological intervention for DVA survivors were analysed. We report the prevalence of and associations between mental health status and severity of abuse at the time of recruitment. We used logistic and normal regression models for binary and continuous outcomes, respectively. The following mental health measures were used: Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM), Patient Health Questionnaire, Generalised Anxiety Disorder Assessment, and the Posttraumatic Diagnostic Scale to measure posttraumatic stress disorder (PTSD). The Composite Abuse Scale (CAS) measured abuse. RESULTS: Exposure to DVA was high, with a mean CAS score of 56 (SD 34). The mean CORE-OM score was 18 (SD 8) with 76% above the clinical threshold (95% confidence interval: 70-81%). Depression and anxiety levels were high, with means close to clinical thresholds, and more than three-quarters of respondents recorded PTSD scores above the clinical threshold. Symptoms of mental illness increased stepwise with increasing severity of DVA. CONCLUSIONS: Women DVA survivors who seek support from DVA services have recently experienced high levels of abuse, depression, anxiety, and especially PTSD. Clinicians need to be aware that patients presenting with mental health conditions or symptoms of depression or anxiety may be experiencing or have experienced DVA. The high psychological morbidity in this population means that trauma-informed psychological support is needed for survivors who seek support from DVA services

Early diagnosis of Gaucher disease based on bone symptoms

La enfermedad de Gaucher (EG) es causada por una deficiencia genética de la glucocerebrosidasa (GCasa) que provoca acumulación de glucocerebrósido en hígado, bazo y médula ósea. La terapia temprana de reemplazo enzimático revierte citopenias, visceromegalias y previene lesiones óseas irreversibles, por lo cual el diagnóstico precoz es fundamental. Los algoritmos diagnósticos en uso apuntan a manifestaciones hematológicas clásicas. Los síntomas óseos están presentes en 25-32% de los pacientes pero no suelen despertar sospecha de EG. Diseñamos un programa educativo sobre la afectación ósea de la EG y un algoritmo focalizado en la presentación con manifestaciones óseas para facilitar su diagnóstico precoz (proyecto BIG: Bone Involvement in Gaucher Disease). El objetivo del trabajo es describir el proyecto BIG y los resultados de su aplicación en nuestra consulta. Entre marzo de 2017 y diciembre de 2018 se recibieron 38 muestras de sangre seca de pacientes con alguna manifestación ósea sospechosa de EG para cuantificar la actividad de GCasa. Una muestra no cumplía los criterios de inclusión y en 3 de las 37 restantes se observó actividad deficiente de GCasa. El diagnóstico de EG se confirmó por medición de GCasa en leucocitos en dos niñas con manifestaciones óseas de 4 y 2 años de evolución, respectivamente, sin citopenia ni visceromegalia clínicamente evidentes. En el otro paciente con baja actividad la medición en leucocitos fue normal. Los casos detectados muestran la efectividad de un programa educacional de difusión y la utilidad de un algoritmo de detección precoz basado en síntomas óseos que facilitaría el diagnóstico de EG.Gaucher disease (GD) is caused by a genetic deficiency of the lysosomal enzyme glucocerebrosidase (GCase) leading to the accumulation of glucocerebroside in the liver, spleen, and bone marrow. The early diagnosis allows a prompt enzyme replacement therapy reversing cytopenias and visceromegaly and preventing irreversible bone lesions. Current diagnostic algorithms are based on well-recognized hematological manifestations. Although bone symptoms are present in 25-32% of the patients, they are not usually suspected as associated with Gaucher disease at clinical presentation. We designed an educational program aimed to give advice on the skeletal involvement in GD and a new diagnostic algorithm that considers bone symptoms to facilitate its early diagnosis (BIG project: Bone Involvement in Gaucher Disease). The study aims at describing the BIG project and the results of its application in our clinic in various cities in Argentina. Within the frame of this project, between March 2017 and December 2018, 38 dry blood spot samples from patients with bone manifestations suspected of having GD were submitted to quantification of GCase activity. One sample did not meet the inclusion criteria. Deficient GCase activity was detected in three of the remaining 37 samples. The diagnosis of GD was confirmed in two girls who presented bone manifestations of 4 and 2 years of evolution, respectively, without hematological alterations. The third patient with low enzyme activity had normal leukocyte GCase. The two newly diagnosed cases of GD show the efficacy of our dual strategy aimed to facilitate the early diagnosis of this rare disease.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; ArgentinaFil: González, Diana. Mautalén, Salud e Investigación; ArgentinaFil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ferrari, Emma. Hospital Samco; ArgentinaFil: Gutierrez, Gladys. Hospital Juan Pablo II. Servicio de Hemato-oncología; Argentin