Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The ...vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3′ terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3′-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3′ end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.
Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects a large proportion of women. Due to its heterogeneity, the best diagnostic strategy has been a matter of contention. ...Since 1990 scientific societies in the field of human reproduction have tried to define the pivotal criteria for the diagnosis of PCOS. The consensus Rotterdam diagnostic criteria included the presence of hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology (PCOM), and have now been updated to evidence based diagnostic criteria in the 2018 and 2023 International Guideline diagnostic criteria endorsed by 39 societies internationally. Within the Rotterdam Criteria, at least two out of three of the above-mentioned features are required to be present to diagnose PCOS, resulting in four phenotypes being identified: phenotype A, characterized by the presence of all the features, phenotype B, exhibiting hyperandrogenism and oligo-anovulation, phenotype C, presenting as hyperandrogenism and PCOM and finally the phenotype D that is characterized by oligo-anovulation and PCOM, lacking the hyperandrogenic component. However, it is the hypothesis of the EGOI group that the Rotterdam phenotypes A, B, and C have a different underlying causality to phenotype D. Recent studies have highlighted the strong correlation between insulin resistance and hyperandrogenism, and the pivotal role of these factors in driving ovarian alterations, such as oligo-anovulation and follicular functional cyst formation. This new understanding of PCOS pathogenesis has led the authors to hypothesis that phenotypes A, B, and C are endocrine-metabolic syndromes with a metabolic clinical onset. Conversely, the absence of hyperandrogenism and metabolic disturbances in phenotype D suggests a different origin of this condition, and point towards novel pathophysiological mechanisms; however, these are still not fully understood. Further questions have been raised regarding the suitability of the “phenotypes” described by the Rotterdam Criteria by the publication by recent GWAS studies, which demonstrated that these phenotypes should be considered clinical subtypes as they are not reflected in the genetic picture. Hence, by capturing the heterogeneity of this complex disorder, current diagnostic criteria may benefit from a reassessment and the evaluation of additional parameters such as insulin resistance and endometrial thickness, with the purpose of not only improving their diagnostic accuracy but also of assigning an appropriate and personalized treatment. In this framework, the present overview aims to analyze the diagnostic criteria currently recognized by the scientific community and assess the suitability of their application in clinical practice in light of the newly emerging evidence.
•The Rotterdam clinical subtypes represent different manifestations of PCOS, however; they remain mostly ignored in study design and clinical practice. These exhibit differences that should be considered for diagnosis and tailored therapy.•The diagnostic tools adopted by physicians rely on parameters and techniques which require further revision, as also noted by the ESHRE commission. The diagnosis of PCOS should be updated and renewed according to the most recent literature.•A correlation between insulin resistance and hyperandrogenism has indicated how these factors may contribute to ovarian alterations. Consequently, PCOS subtypes A, B, and C may be endocrine-metabolic syndromes with a metabolic clinical onset.•Clinical subtype D lacks hyperandrogenic features and exhibits a lower incidence of metabolic and endocrine issues. Therefore, it could be described as the only subtype with a solely ovarian pathogenesis.
Depression is a common disorder in patients with chronic kidney disease (CKD), and some data support its relationship with functional capacity and quality of life. However, to date, this has not been ...evaluated systematically or through meta-analysis. We sought to investigate the relationship of quality of life and functional capacity with depressive disorder in patients with CKD on hemodialysis. This systematic review considered studies published up to 2021 and included cross-sectional and cohort studies. PubMed, Embase, SPORTDiscus, Web of Science, and Cochrane (CENTRAL) databases were used to search for studies. The New Castle-Ottawa Quality Assessment scale was used to measure the quality of the studies. A total of 4,626 studies were found and, after applying the selection criteria, 16 studies (2,175 patients) remained for qualitative analysis and 10 for meta-analysis (1,484 patients). The physical component summary (MD=-6.563; 95%CI: -9.702 to -3.424) and mental component summary (MD=-18.760; 95%CI: -28.641 to -8.879) were lower in depressive patients, as in all Short Form Health Survey 36 (SF-36) domains. Only one study provided data regarding functional capacity, but it was not evaluated by the defined outcome measure. Twelve studies were classified as "moderate quality" (5 to 6 stars) and four were classified as "low-quality" (0 to 4 stars). This meta-analysis with CKD patients on hemodialysis showed a negative relationship between depression and quality of life, with worsening in all physical and mental domains of the SF-36 in depressed patients.
Abstract Purpose To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA ...genetic testing. Patients and methods The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008. Results 179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%). Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers. Conclusion Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment.
Objectif
: L’échographie clinique en médecine d’urgence (ECMU) est un outil essentiel de notre pratique. L’objectif principal de notre étude était d’évaluer les caractéristiques des médecins ...pratiquant l’ECMU au sein de notre territoire. L’objectif secondaire était d’analyser les facteurs influençant une pratique régulière.
Matériel et méthodes
: Étude descriptive multicentrique et déclarative, réalisée auprès de médecins urgentistes travaillant au sein d’un réseau territorial de médecine d’urgence à l’aide d’un questionnaire en ligne.
Résultats
: Cent onze questionnaires sur 120 envoyés ont été renseignés (92 %). Onze services (92 %) étaient dotés en échographe dont neuf (82 %) en dotation propre. Soixantesix médecins (59 %) déclaraient pratiquer l’échographie régulièrement. La FAST (
focused assessment with sonography for traumas
) était la plus pratiquée (80 médecins, 72 %), suivie de l’exploration hémodynamique (50 médecins, 45 %) et pleurale (44 médecins, 40 %). Dans le groupe des médecins ne pratiquant pas l’ECMU, 17 médecins sur 22 (77 %) l’expliquaient par un manque de formation. Dans le même temps, l’intérêt porté à l’ECMU par les urgentistes était coté à 7 ± 2 sur une échelle de 0 à 9. Les facteurs associés à la fréquence de la pratique de l’ECMU étaient le sexe (
p
< 0,001), le type d’activité (
p
= 0,005), le type de formation à l’échographie (
p
< 0,001) et l’ancienneté d’équipement de son service en échographe (
p
< 0,001).
Conclusion
: Cette enquête a montré que la pratique régulière était majoritaire avec un intérêt porté par les praticiens à l’ECMU élevé. Cependant, le frein principal à son développement était un niveau de formation jugé insuffisant par certains praticiens.
Aim
: Emergency point-of-care ultrasound (EPOCUS) is an essential tool of our practice. The main objective of our study was to evaluate characteristics of physicians practicing EPOCUS within the emergency medicine structures of our territory. The secondary objective was to analyze factors influencing regular EPOCUS practice.
Procedure
: Multicenter, declarative and descriptive study focusing on practice of EPOCUS by emergency physicians working in a French emergency network by an online survey.
Results
: 111 out of 120 surveys were filled in (92%). Eleven emergency departments (92%) had sonographs, nine of which were own-staffing (82%). Sixty-six physicians (59%) were reported performing EPOCUS regularly. FAST (focused assessment with sonography for traumas) appeared to be the most widely practiced (80 physicians, 72%), followed by hemodynamic (50 physicians, 45%) and pleural (44 physicians, 40%) exploration. In the group of physicians not practicing EPOCUS, 17 out of 22 (77%) explained it by a lack of training. At the same time, interest of EPOCUS by emergency physicians was rated at 7 ± 2 on a scale from zero to nine. Factors significantly associated with practice of EPOCUS were sex-ratio (
P
< 0.001), type of emergency activity (
P
= 0.005), type of ultrasound training (
P
< 0.001) and seniority of ultrasound equipment (
P
< 0.001).
Conclusion
: This practice survey showed that the regular practice was predominant with a high interest of emergency physicians in EPOCUS practice. However, the principal obstacle to this development was a level of training deemed insufficient by some physicians.
Characterizations of urban and regional sources of particulate matter (PM) were performed in the Milan area (North of Italy) during Föhn and stagnant (non-Föhn) conditions. The measurements were ...performed at two different places: in an urban area North of Milan (Bresso) and in a regional area at the EMEP-GAW station in Ispra (about 65 km NW from Milan) during the winter periods of the years 2002–2007. Particle size distributions and chemical bulk analysis of aerosols are combined with single particle mass spectrometry to obtain information about the chemical content of the particles and their mixing state. Föhn conditions are characterized by extremely clean background air from which background aerosol is scavenged, and consequently local sources (here defined as sources between the sampling sites and the mountain range top about 100–150 km away depending on the wind direction) determine the aerosol properties.
It was observed that during Föhn events the accumulation mode in the size range 50 nm
<
d
<
300 nm practically disappears and that the size fraction below 50 nm dominates the total number distribution. The significant change in the number size distribution and the large decrease in PM10 mass during Föhn events are accompanied by a significant change in the chemical composition of the particles. Results from bulk chemical analysis showed high amounts of carbonaceous compounds and very low concentrations of ammonium nitrate (as indicator for secondary chemistry) during Föhn episodes, in contrast to stagnant conditions, when secondary components are dominating the aerosol composition. Single particle measurements confirm the high contribution of carbonaceous compounds in locally emitted particles.
It was concluded that particles that originated in the urban area come mainly from combustion processes, especially direct traffic emissions, domestic heating and industrial activities, whereas the regionally emitted particles are different with much less traffic contribution.
We estimate that under prevailing (non-Föhn) winter conditions, about 50–65% of the aerosol mass load in the city of Milan are caused by local emissions, and about 35–50% come from regional background. This finding suggests that in order to improve air quality in a big city like Milan, it is important to combine local traffic restriction interventions with other long-term regional scale air-quality-measures.
Stable weather conditions together with extensive use of coal combustion often lead to severe smog episodes in certain urban environments, especially in Eastern Europe. In order to identify the ...specific sources that cause the smog episodes in such environments, and to better understand the mixing state and atmospheric processing of aerosols, both single particle and bulk chemical characterization analysis of aerosols were performed in Krakow, Poland, during winter 2005.
Real-time measurements of the bulk PM10 aerosol during a severe smog episode (PM10 mass
>
400 µg m
−
3
) showed a stable concentration of black carbon in the aerosol, and an increase in the sulphate and chlorine mass contributions towards the end of the episode. Chemical characterization of single particles further helped to identify residential coal burning as the main source that caused this severe smog episode, consisting of single particles with major signals for carbon with simultaneous absence of sulphate, chlorine and calcium. Particles from industrial coal combustion gained importance towards the end of that episode, after residential coal combustion was switched off, indicated by an increase of the percentage of sulphate and chlorine containing particles. Traffic was not a significant source during the severe smog episode. During a lighter smog episode, residential and industrial coal combustion was still predominant, with an increased contribution of traffic and processed/aged aerosols. On a clean day, particle classes containing nitrate were the most abundant. In addition, the aerosol was more internally mixed showing that there were more sources contributing to the total aerosol population.
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