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A novel methodology is introduced to dynamically analyze the complex scaling behavior of financial data across various investment horizons. This approach comprises two steps: (a) the application of a distribution-based method for the estimation of time-varying self-similarity matrices. These matrices consist of entries that represent the scaling parameters relating pairs of distributions of price changes constructed for different temporal scales (or investment horizons); (b) the utilization of information theory, specifically the Normalized Compression Distance, to quantify the relative complexity and ascertain the similarities between pairs of self-similarity matrices. Through this methodology, distinct patterns can be identified and they may delineate the levels and the composition of market liquidity. An application to the U.S. stock index S&P500 shows the effectiveness of the proposed methodology.
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The present study proposes a fiducial marker for location systems that uses computer vision. The marker employs a set of tape-shaped markers that facilitate their positioning in the environment, allowing continuous reading to cover the entire perimeter of the environment and making it possible to minimize interruptions in the location service. Because the marker is present throughout the perimeter of the environment, it presents hierarchical coding patterns that allow it to be robust against multiple detection scales. We implemented an application to help the user generate the markers with a floor plan image. We conducted two types of tests, one in a 3D simulation environment and one in a real-life environment with a smartphone. The tests made it possible to measure the performance of the tape-shaped marker with readings at multiple distances compared to ArUco, QRCode, and STag with detections at distances of 10 to 0.5 m. The localization tests in the 3D environment analyzed the time of marker detection during the journey from one room to another in positioning conditions (A) with the markers positioned at the baseboard of the wall, (B) with the markers positioned at camera height, and (C) with the marker positioned on the floor. The localization tests in real conditions allowed us to measure the time of detections in favorable conditions of detections, demonstrating that the tape-shaped-marker-detection algorithm is not yet robust against blurring but is robust against lighting variations, difficult angle displays, and partial occlusions. In both test environments, the marker allowed for detection at multiple scales, confirming its functionality.
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Optical diffraction tomography (ODT) is a label-free technique for three dimensional imaging of micron-sized objects. Coherence and limited sampling of 3D Fourier space are often responsible for the appearance of artifacts. Here we present an ODT microscope that uses low temporal coherence light and spatial light modulators to retrieve reliable 3D maps of the refractive index. A common-path interferometer, based on a spatial light modulator, measures the complex fields transmitted by a sample. Measured fields, acquired while scanning the illumination direction using a digital micro-mirror device, are fed into a Rytov reconstruction algorithm to obtain refractive index maps whose accuracy is directly evaluated on microfabricated 3D test objects. Even for challenging shapes such as pyramids, bridges, and dumbbells, we obtain volumetric reconstructions that compare very well with electron microscopy images.
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BACKGROUND: Delirium is frequent though undetected in older patients admitted to the Emergency Department (ED). AIMS: To develop and validate a delirium risk assessment tool for older persons admitted to the ED Observation Unit (OU). METHODS: We used data from two samples of 65 + year-old patients, one admitted to the ED of Brescia Hospital (n = 257) and one to the ED of Desio Hospital (n = 107), Italy. Data from Brescia were used as training sample, those collected in Desio as testing one. Delirium was assessed using the 4AT and patients' characteristic were retrieved from medical charts. Variables found to be associated with delirium in the training sample were tested for the creation of a delirium risk assessment tool. The resulting tool's performances were assessed in the testing subsample. RESULTS: Of all possible scores tested, the combination with the highest discriminative ability in the training sample included: age ≥ 75 years, dementia diagnosis, chronic use of neuroleptics, and hearing impairment. The delirium score exhibited an AUC of 0.874 and 0.893 in the training and testing samples, respectively. For a 1-point increase in the score, the odds of delirium increased more than twice in both samples. DISCUSSION: We propose a delirium risk assessing tool that includes variables that can be easily collected at ED admission and that can be calculated rapidly. CONCLUSION: A risk assessment tool could help improving delirium detection in older persons referring to ED.
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Unidades de Observación Clínica , Delirio , Anciano , Anciano de 80 o más Años , Delirio/diagnóstico , Delirio/epidemiología , Servicio de Urgencia en Hospital , Evaluación Geriátrica , Humanos , Estudios Prospectivos , Medición de RiesgoRESUMEN
Results: The results highlighted that 40 laboratories fall into the "low risk" and the remaining 2 into the "moderate risk" category. Conclusions: Labs with risk factors are a minority. These were properly identified using the proposed methodology. Background and aim: Biomedical research in academic settings is an important issue for Public Health and Environment protection. As workplaces, the facilities for research expose their personnel to different hazards and health risks. The University of L'Aquila (Italy) carried out a field study aimed at creating and applying a checklist intended for laboratory staff. Methods: The proposed checklist was derived from the procedure illustrated in the Appendix (procedure followed for the identification of a numerical index of biological risk for university facilities) and consists of 9 items. The study was conducted in 42 laboratories.
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Lista de Verificación , Laboratorios , Humanos , Medición de Riesgo , Universidades , Lugar de TrabajoRESUMEN
OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.
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Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/transmisión , Parto Obstétrico/efectos adversos , Transmisión Vertical de Enfermedad Infecciosa , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , Complicaciones Infecciosas del Embarazo/diagnóstico , Adulto , COVID-19 , Femenino , Humanos , Recién Nacido , Italia , Masculino , Pandemias , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Retrospectivos , SARS-CoV-2 , Vagina/virologíaRESUMEN
In 2017, Italy experienced a large measles epidemic with 5408 cases and four deaths. As Subnational Reference Laboratory of the Measles and Rubella surveillance NETwork (MoRoNET), the EpiSoMI (Epidemiology and Molecular Surveillance of Infections) Laboratory (University of Milan) set up rapid and active surveillance for the complete characterisation of the Measles virus (Mv) responsible for the large measles outbreak in Milan and surrounding areas (Lombardy, Northern Italy). The aims of this study were to describe the genetic profile of circulating viruses and to track the pathway of measles transmission. Molecular analysis was performed by sequencing the highly variable 450 nucleotides region of the N gene (N-450) of Mv genome. Two-hundred and ninety-nine strains of Mv were analysed. The phylogenetic analysis showed five different variants, two not previously described in the studied area, belonging to D8 and B3 genotypes. Three events of continuous transmission of autochthonous variants (D8-Osaka, D8-London and B3-Milan variants) and two events of continuous transmission of imported variants (B3-Dublin and D8-Hulu Langat) tracked five different transmission pathways. These pathways outlined two epidemic peaks: the first in April and the second in July 2017. The correlation between Mv variant and the epidemiological data may enable us to identify the sources of virus importation and recognise long-lasting virus transmission pathways.
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Epidemias , Genotipo , Virus del Sarampión/genética , Sarampión/epidemiología , Humanos , Italia/epidemiología , Sarampión/virología , Virus del Sarampión/clasificación , FilogeniaRESUMEN
When a rough surface is illuminated by a laser beam, it scatters the light, producing a random interference pattern also known as speckle pattern. By imaging the speckle pattern with a line-scan CCD, we are able to measure the acoustic vibrations of a scattering surface, which can be up to 300 m distant. We also show that our instrument can be used as a laser microphone capable of detecting ambient sound such as a human voice.
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A safe and effective use of nanoparticles in biology and medicine requires a thorough understanding, down to the molecular level, of how nanoparticles interact with cells in the physiological environment. This study evaluated the two-way interaction between inorganic nanomaterials (INMs) and cells from A549 human lung carcinoma cell line. The interaction between silica and zinc oxide INMs and cells was investigated using both standard methods and advanced characterization techniques. The effect of INMs on cell properties was evaluated in terms of cell viability, chemical modifications, and volume changes. The effect of cells and culture medium on INMs was evaluated using dynamic light scattering (DLS), scanning electron microscopy and energy-dispersive X-ray spectroscopy (SEM-EDS), high performance liquid chromatography (HPLC), gas chromatography-mass spectroscopy (GC-MS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). No cytotoxic effect was detected in the case of silicon oxide INMs, while for high doses of zinc oxide INMs a reduction of cell survival was observed. Also, increased cell volume was recorded after 24 h incubation of cells with zinc oxide INMs. A better dimensional homogeneity and colloidal stability was observed by DLS for silicon oxide INMs than for zinc oxide INMs. SEM-EDS analysis showed the effectiveness of the adopted dispersion procedure and confirmed in the case of zinc oxide INMs the presence of residual substances derived from organosilane coating. HPLC and GC-MS performed on INMs aqueous dispersions after 24 h incubation showed an additional peak related to the presence of an organic contaminant only in the case of zinc oxide INMs. FTIR Chemical Imaging carried out directly on the cells showed, in case of incubation with zinc oxide INMs, a modification of the spectra in correspondence of phospholipids, nucleic acids and proteins characteristic absorption bands when compared with untreated cells. Overall, our results confirm the importance of developing new experimental methods and techniques for improving the knowledge about the biosafety of nanomaterials.
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Supervivencia Celular/efectos de los fármacos , Nanopartículas/toxicidad , Células A549 , Tamaño de la Célula/efectos de los fármacos , Humanos , Espectroscopía Infrarroja por Transformada de FourierAsunto(s)
Enfermedad de Gaucher , Mieloma Múltiple , Humanos , Enfermedad de Gaucher/complicaciones , Enfermedad de Gaucher/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Terapia de Reemplazo Enzimático , Glucosilceramidasa/uso terapéuticoRESUMEN
INTRODUCTION: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), previously known as hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) or pigmentary orthochromatic leukodystrophy (POLD), is the most frequent non-vascular adult-onset leukoencephalopathy. It is caused by autosomal dominant mutations in CSF1R gene. Recently, also autosomal recessive mutations in AARS2 gene were found to be the cause of an adult-onset leukodystrophy with axonal spheroids. Our aim was to achieve a genetic diagnosis in a cohort of CSF1R-negative patients, performing a sequence analysis of AARS2 gene. MATERIAL AND METHODS: AARS2 sequencing was performed in 38 CSF1R-negative patients with clinical and magnetic resonance imaging (MRI) findings of adult-onset leukoencephalopathy. RESULTS: Three patients carrying AARS2 compound heterozygous mutations have been found. All patients were female with ovarian failure and leukoencephalopathy. In 2 patients, MRI findings were consistent with previous reports while the third patient showed focal white matter (WM) lesions in the centrum semiovale and the corpus callosum in the absence of extensive involvement and rarefaction of the WM. MRI spectroscopy showed the presence of increased lactate in 2 patients, thus linking AARS2-related leukoencephalopathy with other mitochondrial leukoencephalopathies with high levels of cerebral lactate. CONCLUSION: We recommend screening for mutations in AARS2 gene in CSF1R-negative patients, also in the absence of a clear family history and peculiar MRI findings. Our results also suggest that findings of conventional MRI and MR spectroscopy may be useful in prompting the genetic screening.
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Alanina-ARNt Ligasa/genética , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/genética , Imagen por Resonancia Magnética/métodos , Mutación/genética , Enfermedades del Ovario/diagnóstico por imagen , Enfermedades del Ovario/genética , Adulto , Anciano , Anciano de 80 o más Años , Cuerpo Calloso/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen/métodosRESUMEN
Implantology research framed the implant surface as a key element for a good and sustainable osseointegration of an implant fixture. The aim of this study was to analyze the antibacterial properties of anatase-coated titanium healing screws through microbiological and scanning electron microscopy. The comparison of the bacterial colonies growth between the anatase-coated titanium healing screws and non-coated titanium healing screws showed comparable antibacterial properties, without significant statistical differences. The scanning electron microscopy observations confirmed the microbiological study. These data, also considering previous reports on the positive effects on osteoblasts genetic expressions, might suggest a use of the anatase-coated titanium healing screws to preserve the tissues surrounding implants from microbial attacks.
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Biopelículas/efectos de los fármacos , Materiales Biocompatibles Revestidos/farmacología , Implantes Dentales/microbiología , Saliva/microbiología , Titanio/farmacología , Adulto , Antiinfecciosos Locales , Diseño de Prótesis Dental , Femenino , Voluntarios Sanos , Humanos , Microscopía Electrónica de Rastreo , Oseointegración , Propiedades de SuperficieRESUMEN
OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease caused by NOTCH3 gene mutations. CADASIL women are frequently considered at high risk of systemic vascular events during pregnancy and often prescribed with antithrombotic drugs. This decision is not evidence-based considering the lack of data about pregnancy outcome in CADASIL. We describe our experience on pregnancy in CADASIL patients. MATERIALS AND METHODS: We reviewed records of 50 CADASIL females followed in our center, and we collected prospective information in six patients for a total of 93 pregnancies. RESULTS: No woman had the disease onset or suffered from cerebral vascular ischemic events during pregnancy. Sixteen miscarriages (17.2%) were recorded. There were 72 vaginal births, and five cesarean sections. Considering the six patients followed prospectively (for a total of eight pregnancies), data on fetal growth and newborns weight were in line with those from the general population. Considering gestational complications, we recorded mild proteinuria without hypertension in one patient and hyperinsulinemia and pre-eclampsia in another affected by a known nephropathy. Antithrombotic drugs were used in three patients, in one for an unrelated coexisting prothrombotic condition. CONCLUSIONS: CADASIL does not seem to be associated with an unfavorable outcome of pregnancy either for women and fetuses. Patients and treating physicians should be reassured that pregnancy can be safely initiated in CADASIL, as there is no evidence to support a specific preventive antithrombotic treatment during pregnancy in CADASIL. Larger studies are needed to definitively confirm these conclusions.
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CADASIL/epidemiología , Complicaciones del Embarazo/epidemiología , Adulto , Peso al Nacer , CADASIL/diagnóstico , CADASIL/terapia , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapia , Resultado del EmbarazoRESUMEN
Oral surgery procedures involve traumatization of mucosal and bony tissues, and lengthy interventions can lead to inflammatory post-operative sequelae. In the bony tissues in particular, the inflammatory processes can affect healing. Modern drug therapies provide valid support for lowering the risk of occurrence of post-operative inflammatory signs. The two main types of agents used are nonsteroidal anti-inflammatory drugs and/or corticosteroids, which act on two different molecular pathways in the inflammatiory process. The aim of this systematic review is to examine the different corticosteroids used in oral surgery procedures, their indications for use, and their route of administration, to provide the clinician with a useful scheme for correct pharmacological management of post-operative inflammation. To identify studies eligible for inclusion in this systematic review, we performed a literature search up to April 2017 of the electronic databases, considering published papers from 2007 to 2017. The search terms included steroids, third molar, oral surgery, RCT [randomized controlled trial], human, and clinical trial. Only articles in English language were considered.
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Corticoesteroides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Extracción Dental , Ensayos Clínicos como Asunto , Dexametasona/uso terapéutico , Humanos , Metilprednisolona/uso terapéutico , Tercer Molar/efectos de los fármacos , Tercer Molar/microbiología , Tercer Molar/cirugía , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/fisiopatologíaRESUMEN
INTRODUCTION: Primary-prevention by prophylactic vaccination against HPV-related cancers and HPV-based screening programs are based on HPV-type distribution in immunocompetent individuals. HIV-infected women are at high risk of invasive HPV-disease sustained by a broader range of HPV-types and have higher multi-type infection rates than immunocompetent hosts. METHODS: This is a cross-sectional analysis of High Risk HPV (HR HPV) type distribution in 805 HIV+ women (HIW) compared with a control group of 1402 immunocompetent HIV- women (SPW) enrolled in the VALHIDATE study in order to define HPV type-specific distribution according to cytology. RESULTS: HIW had a 3.8, 3.6, and 2.7 times higher risk of atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL) than SPW respectively. HPV-DNA prevalence was 28.4% in HIW and 11.81% in SPW (p<0.0001). The prevalence of infection increased from normal cytology to HSIL both in HIW (from 21.45% to 90.91%) and SPW (from 9.54% to 75%). The OR for women with normal cytology of having a positive HPV-DNA test result of was 2.6 times higher in HIW than in SPW. The cumulative prevalence of HPV-16/18 in HSIL is much lower in HIW (36.4±28.4) than SPW (62.5±33.5). CONCLUSIONS: A higher prevalence of infection and broader HPV type distribution were observed in HIV+ women compared to the general population. More than 60% of HSIL lesions of HIW patients are caused by single or multi-type infections from non-HPV16/18 HPVs. The potential 9v-HPV vaccine coverage could be even higher than that expected for the general population given the wide panel of HPV-types observed in the HSIL of HIV+ women.
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Células Escamosas Atípicas del Cuello del Útero/virología , Cuello del Útero/virología , Infecciones por VIH/epidemiología , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/virología , Adulto , Células Escamosas Atípicas del Cuello del Útero/patología , Estudios de Casos y Controles , Cuello del Útero/patología , Coinfección/epidemiología , Estudios Transversales , ADN Viral/genética , Femenino , Genotipo , Humanos , Inmunocompetencia , Huésped Inmunocomprometido , Italia/epidemiología , Persona de Mediana Edad , Epidemiología Molecular , Oportunidad Relativa , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/epidemiología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patologíaRESUMEN
We demonstrate that Digital Holographic Microscopy can be used for accurate 3D tracking and sizing of a colloidal probe trapped in a diamond anvil cell (DAC). Polystyrene beads were optically trapped in water up to Gigapascal pressures while simultaneously recording in-line holograms at 1 KHz frame rate. Using Lorenz-Mie scattering theory to fit interference patterns, we detected a 10% shrinking in the bead's radius due to the high applied pressure. Accurate bead sizing is crucial for obtaining reliable viscosity measurements and provides a convenient optical tool for the determination of the bulk modulus of probe material. Our technique may provide a new method for pressure measurements inside a DAC.
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The aim of this study was to investigate the epidemiological profile of HPV oropharyngeal infections in HIV-infected men who have sex with men. A total of 135 subjects were enrolled at the L. Sacco University Hospital (Milan, Italy) to evaluate their HPV oropharyngeal infection status at baseline and at a follow-up visit at least 12 months later. HPV DNA was detected from oropharyngeal swabs using an in-house nested PCR that amplifies a segment of the L1 gene. The PCR products were then sequenced and genotyped. A greater percentage of high-risk genotypes was identified compared to low-risk genotypes (13·7% vs. 6·9%, P < 0·05), and two uncommon alpha-HPV genotypes were detected, i.e. HPV-102 and HPV-114. HPV infection prevalence was 24·4% and the cumulative incidence was 24·1%. During the follow-up period, one case of HPV infection (HPV-33) persisted, while the overall rate of infection clearance was 58·3%. HPV oropharyngeal infection was widespread in the cohort examined, and most of the infections were transient and cleared within 12 months. These results may help to clarify the role of HPV in the oropharynx and may also improve our understanding of the need to implement preventive strategies in at-risk populations.
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Infecciones por VIH/epidemiología , Homosexualidad Masculina , Orofaringe/virología , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Mucosa Respiratoria/virología , Adulto , Anciano , Genotipo , Infecciones por VIH/virología , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Prevalencia , Adulto JovenRESUMEN
INTRODUCTION: Chlamydia trachomatis (Ct) is the most common bacterial cause of sexually transmitted infections (STI) and is associated with severe long-term sequelae in female populations. In Italy Ct infections are not submitted to a screening programme, and its epidemiological profile is understudied. Even scarcer information is available about the genetic diversity on ompA gene, whose sequence defines 18 different genovars. This study aims at evaluating the prevalence of Ct infection in young sexually active asymptomatic women aged 18-25, and characterizing the molecular epidemiology of the different circulating genovars in this population. METHODS: Cervical samples collected from 909 sexually-activeyoung women (mean age 21.5 years) were analyzed through molecular assay for the detection of Ct infection. Phylogenetic analysis on the ompA gene was performed on Ct positive samples to identify the circulating genovars. RESULTS: The overall prevalence of Ct-infection was 4.4% (95%CI: 3.2-5.9%): 5.3% among women aged 18-21 years and 3.5% among those aged 22-25 years. Phylogenetic analysis has identified 5 different genovars: D, E, F, G, and H. The most common genovar was the E (46%), followed by genovar F and G (18.9% each), D (13.5%), and H (2.7%). CONCLUSIONS: This study underlines the high prevalence of asymptomatic Ct-infections among young women. Overall, about half of the asymptomatic infections is sustained by genovar E. The introduction in Italy of a systematic screening program should be considered to allow a better understanding of Ct spreading and providing women with an opportunity for early treatment to protect their sexual and reproductive health.
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Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis/genética , Adulto , Chlamydia trachomatis/aislamiento & purificación , Femenino , Genotipo , Humanos , Italia/epidemiología , Epidemiología Molecular , Filogenia , Prevalencia , Adulto JovenRESUMEN
OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by NOTCH3 mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of NOTCH3-negative patients with a phenotype closely resembling that of CADASIL. MATERIALS AND METHODS: We performed NOTCH3 analysis (exons 2-23) in 117 probands because of a clinician's suspicion of CADASIL. The CADASIL scale, a recently developed tool that allows to better select patients for NOTCH3 analysis, was retrospectively applied to NOTCH3-negative patients; the patient subgroup that scored higher than the screening cutoff for CADASIL was defined as CADASIL-like. RESULTS: Thirty-four CADASIL-like patients (mean age at onset 57.8 years [52.1-63.4], 50% males) were identified. Compared with 25 patients with CADASIL for clinical, familial, and neuroimaging features, only the following variables were significantly (α level <0.05) different in frequency between patients with CADASIL and CADASIL-like patients: a positive family history for stroke at age ≤ 60 years, more frequent in patients with CADASIL, and hypertension, more frequent in CADASIL-like patients. CONCLUSIONS: Our experience highlights the growing number of patients presenting with a high suspicion of a cerebral small vessel disease with an autosomal dominant pattern of inheritance and a phenotype closely similar to that of CADASIL but without NOTCH3 mutations. This group remains to be characterized from the genetic point of view. The role of other genes or NOTCH3 alterations on exons other than 2-23 or introns has to be further assessed.
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CADASIL/complicaciones , CADASIL/genética , CADASIL/patología , Edad de Inicio , Encéfalo/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Fenotipo , Receptor Notch3 , Receptores Notch/genética , Estudios RetrospectivosRESUMEN
PURPOSE: Childbearing delay contributes to the increase of subfertile couples that require assisted reproductive technology (ART). Subfertility relates with reproductive aging (RA). In vitro aging (IvA) (due to extended culture) may also impair oocyte competence. Aims of this study were to evaluate and compare the oocyte ultrastructure after RA and IvA. METHODS: Cumulus-oocyte complexes (COCs) (n = 68), with metaphase II oocyte and expanded cumulus, from consenting patients (<35 years old and ≥35 years old, n = 36), were selected by phase contrast microscopy and fixed at pick up, or after 24 h culture. COCs (n = 44) were studied by light and qualitative/morphometric transmission electron microscopy. Two-way ANOVA, with age and culture as grouping factors, was applied for statistical analysis (p < 0.05). Metaphase II cumulus-free oocytes (n = 24) were selected for confocal microscopy observations. RESULTS: Significant decrease of mitochondria-smooth endoplasmic reticulum aggregates, increase of mitochondria-vesicle complexes size and amount, decrease of cortical granules and microvilli, and alterations of the spindle structure characterized both RA and IvA oocytes. These changes were significantly more evident in the RA oocytes submitted to IvA. RA oocytes also showed changes of the zona pellucida and occurrence of vacuoles after culture. Cumuli appeared re-compacted after culture, irrespective of the age of the patients. CONCLUSIONS: These data demonstrated that aging is related to decay of oocyte ultrastructural quality, and that oocytes from elder women are more sensitive to prolonged culture (IvA) than the oocytes from younger women. These morphological results should be considered when applying ART in aged patients, rescue ICSI, or artificial oocyte activation.