IVF embryos have historically been evaluated by morphological characteristics. The time-lapse system (TLS) has become a promising tool, providing an uninterrupted evaluation of morphological and ...dynamic parameters of embryo development. Furthermore, TLS sheds light on unknown phenomena such as direct cleavage and incomplete morula compaction. We retrospectively analyzed the morphology (Gardner Score) and morphokinetics (KIDScore) of 835 blastocysts grown in a TLS incubator (Embryoscope+), which were biopsied for preimplantation genetic testing for aneuploidy (PGT-A). Only the embryos that reached the blastocyst stage were included in this study and time-lapse videos were retrospectively reanalysed. According to the pattern of initial cleavages and morula compaction, the embryos were classified as: normal (NC) or abnormal (AC) cleavage, and fully (FCM) or partially compacted (PCM) morulae. No difference was found in early cleavage types or morula compaction patterns between female age groups (< 38, 38-40 and > 40 yo). Most of NC embryos resulted in FCM (≅ 60%), while no embryos with AC resulted in FCM. Aneuploidy rate of AC-PCM group did not differ from that of NC-FCM group in women < 38 yo, but aneuploidy was significantly higher in AC-PCM compared to NC-FCM of women > 40 yo. However, the quality of embryos was lower in AC-PCM blastocysts in women of all age ranges. Morphological and morphokinetic scores declined with increasing age, in the NC-PCM and AC-PCM groups, compared to the NC-FCM. Similar aneuploidy rates among NC-FCM and AC-PCM groups support the hypothesis that PCM in anomalous-cleaved embryos can represent a potential correction mechanism, even though lower morphological/morphokinetic scores are seen on AC-PCM. Therefore, both morphological and morphokinetic assessment should consider these embryonic development phenomena.
Introduction
Alexithymia, that is the inability to recognize and describe one’s own emotions, is a transdiagnostic feature across eating disorders (EDs) and it has been associated to a prolonged ...stress exposure.
Objectives
Therefore, we evaluated whether alexithymia affects the hypothalamus-pituitary-adrenal (HPA) axis functioning in patients with anorexia nervosa (AN) or bulimia nervosa (BN).
Methods
Twenty-six women with AN and 26 with BN participated in the study. Alexithymia was evaluated by the Toronto Alexithymia Scale–20 and eating-related psychopathology was measured by the Eating Disorder Inventory-2. The activity of the HPA axis was assessed by the salivary cortisol awakening response (CAR). Group differences in saliva CAR were tested by repeated measures 3-way ANOVA with diagnosis and alexithymia as between-subject factors.
Results
The prevalence of alexithymia did not differ significantly between the two diagnostic groups (c
2
=1.24, p=0.26). Alexithymia was associated with more severe eating-related psychopathology in AN women but not in BN women. A significant reduction in the magnitude of CAR occurred in alexithymic patients with BN compared to non-alexithymic patients with BN (t = 3.39, p = 0.008), but not in alexithymic women with AN (t = 0.67, p = 0.54).
Conclusions
These results confirm the presence of a more severe eating-related psychopathology in alexithymic individuals with AN and show, for the first time, an association between alexithymia and a dampened basal activity of the HPA axis in BN.
Disclosure
No significant relationships.
Sensitivity to punishment (SP) and sensitivity to reward (SR) are personality characteristics that may have relevance for the pathophysiology of eating disorders (EDs). Moreover, personality ...characteristics are known to modulate the activity of the hypothalamus-pituitary-adrenal (HPA) axis, which is the main component of the endogenous stress response system. As stress has been implicated in the aetiology and the maintenance of EDs, we aimed to study the HPA axis activity in relation to SP and SR, as conceptualized by Gray's reinforcement sensitivity theory (RST), in patients with anorexia nervosa (AN) or bulimia nervosa (BN).
Twenty-five women with AN, 23 women with BN and 19 healthy women volunteered for the study. HPA axis activity was assessed by measurement of the salivary cortisol awakening response (CAR). The subjects' SP and SR were measured by the behavioural inhibition system (BIS)/behavioural approach system (BAS) scales.
The CAR was significantly enhanced in AN patients, but not in BN patients, compared to healthy women. The CAR correlated significantly with BAS measures, negatively in healthy controls and positively in binge-purging AN patients and BN women. SP, measured by the BIS scale, was higher in patients than in controls.
These findings confirm the occurrence of an enhanced activity of the HPA axis in symptomatic AN, but not in symptomatic BN, and show for the first time that the CAR is associated with SR, as conceptualized by the RST, negatively in healthy subjects but positively in binge-purging ED patients.
Introduction
Bipolar Disorder (BD) has been suggested to be a risk factor for development of Parkinson Disease. Psychiatric drugs used as standard treatment of BD includes many drugs that are known ...to induce drug-induced parkinsonism (DIP).
Objectives
Clinical differentiation between PD and DIP is a clinical and scientific crucial result. It might be aided by functional neuroimaging of the dopaminergic nigrostriatal pathway.
Methods
Twenty consecutive BD patients with parkinsonism were clinically assessed and underwent
123
I-ioflupane dopamine transporter SPECT. Imaging data of BD patients with pathological nigrostriatal pathway were further compared to a population of
de-novo
PD patients.
Results
Four BD patients had abnormal scans; they had higher putaminal binding ratio and putamen-to-caudate ratios than PD patients, despite similar motor symptom burden.
Conclusions
in our initial results, up to 20% of BD patients with parkinsonism might have an underlying dopaminergic deficit, which is higher than excepted in the general population. This evidences supports that BD represents a risk factor for subsequent development of neurodegenerative parkinsonism.
Disclosure of Interest
None Declared
Childhood trauma is a non specific risk factor for adult eating disorders (ED), and the hypothalamic-pituitary-adrenal (HPA) axis seems to mediate such a risk. Here we explored the impact of ...different types of childhood trauma and of traumatic load on the cortisol awakening response (CAR) of women with anorexia nervosa (AN) or bulimia nervosa (BN).
Saliva samples were collected at awakening and after 15, 30, 60 min to measure cortisol levels by 121 women (44 AN patients, 36 BN patients and 41 healthy women). Participants filled in the Childhood Trauma Questionnaire.
AN and BN patients with childhood maltreatment exhibited an attenuated CAR compared with non-maltreated ones. In the whole ED patient group, the CAR showed a progressive impairment with the increasing number of reported trauma types. Although significant negative correlations emerged between the type or the number of traumas and the CAR, only the number of traumas remained significantly associated with the CAR in a stepwise multiple regression analysis.
Present findings confirm that childhood trauma is associated with an impaired CAR in adult AN and BN patients and demonstrate for the first time a negative dose-dependent effect of the traumatic load on HPA axis activity.
Introduction
The intestinal microbiota has been indicated to have a role in the pathophysiology of AN.
Objectives
Aim of this study was to analyze fecal microbiome profiles of AN women before and ...after weight restoration and to combine them with fecal metabolomic profiles according to a multi-omics approach.
Methods
The gut microbiome and fecal metabolites were characterized in 21 underweight AN women and after weight restoration and compared with those of 20 healthy women. Microbiome data were correlated with the relevant fecal metabolites.
Results
AN subjects showed a decreased intra-individual bacterial richness, an increased Bacteroidetes-to-Firmicutes abundance ratio and significant changes in the relative abundances of several bacteria at different order levels in both the underweight and weight-restored condition compared to healthy women. The untargeted metabolomic procedure allowed the characterization of 224 metabolites involved in energy, lipid and amino acid metabolism. A genetic algorithm identified 49 relevant metabolites. The relationships among these fecal metabolites and bacteria genera showed structures of different complexity in the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acute phase of AN than in the weight-restored phase or normal controls. Finally, in acute AN 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome.
Conclusions
Our results provide a picture of the connections between gut bacteria and fecal metabolites in both the acute phase of AN and after short-term weight restoration. Further studies should aim to investigate the significance of gut microbiome perturbations in development and treatment of AN.
Purpose
Worldwide publications follow the gold standard method—the polymerase chain reaction (PCR)—for detecting Y-chromosome microdeletions; however, markers are frequently variable between the ...studies. Can we detect the deletions by another molecular method with more genomic coverage? The Y chromosome harbors several different genes responsible for testicular development and spermatogenesis, and its repetitive conformation predisposes it to complex rearrangements that have clinical impact. Our aim was to evaluate a molecular diagnostic method, the Multiplex Ligand Probe-dependent Amplification (MLPA), which is also a valuable ancillary method for the identification of deletions, duplications, and rearrangements in a single and faster reaction, leading to a better comprehension of patients’ phenotypes, and should be considered a useful tool for detection of Y chromosome deletions.
Methods
This is a study of diagnostic accuracy (transversal prospective study) conducted to investigate Y-chromosome deletions in 84 individuals through PCR and MLPA methods. Forty-three infertile men (azoospermic and oligozoospermic) and 41 controls (40 fertile men and 1 normal karyotyped woman) were analyzed by PCR and MLPA techniques.
Results
We diagnosed seven (7) deletions (16.2%) by PCR and 9 with MLPA (21%). In addition, we found five (5) duplications and a suggestive mosaic.
Conclusion
Our results demonstrate that MLPA technique is valuable in the investigation of microdeletions and microduplications. Besides deletions, duplications can cause instability of chromosome genes, possibly leading to infertility. Both studied techniques provide an advantageous diagnostic strategy, thus enabling a better genetic counseling.
Introduction
The coronavirus disease 2019 (COVID-19) pandemic and the resulting containment measures, such as “lockdown” and “social distancing”, have had important consequences on people’s mental ...and physical health.
Objectives
We aimed to study the effect of social isolation and subsequent re- exposure and eventual changes in general and ED-specific psychopathology in people with Eating Disorders (EDs).
Methods
Three-hundred twelve Italian people with EDs (179 Anorexia Nervosa, 83 Bulimia Nervosa, 48 Binge Eating Disorder and 22 Other Specific Feeding Eating Disorder) were asked to fill-in an online survey to explore several dimensions such as: anxiety, depression, panic, insomnia, suicide ideation, stress, post-traumatic stress and obsessive-compulsive symptoms. Differences in ED specific and general symptoms among the 3 investigated time periods (before, during and after the end of lockdown) were assessed with a one-way ANOVA with repeated measures. Subsequently, ED diagnosis was introduced as covariate in the analysis in order to investigate the possible contribution on psychopathological changes.
Results
ED core symptoms increased during the lockdown but most of them returned to pre-COVID19 levels at re-opening. The severity of general psychopathology also increased during the lockdown and persisted high in the following phase, except for depression and suicide ideation. None of this symptoms was affected by ED diagnosis, participants’age and illness duration.
Conclusions
People with EDs showed worsening of both general and specific psychopathology; moreover, changes in general psychopathology persisted in the re-opening period suggesting a higher stress vulnerability in this kind of patients.
Disclosure
No significant relationships.
Keyword
COVID19 and Eating Disorders
Objectives: Brain‐derived neurotrophic factor (BDNF) has been proposed as a candidate molecule in the pathophysiology of major depressive disorder (MDD) and bipolar disorders (BD). Reduced levels of ...peripheral BDNF have been found in drug‐free MDD patients, in drug‐treated depressed or manic patients with BD type I (BD‐I), but not in drug‐treated euthymic BD‐I individuals. No study has been done in patients with BD type II (BD‐II). Moreover, the influence of Axis I psychiatric comorbidity on circulating BDNF in affective patients has never been evaluated. Therefore, in the present study, we aimed: (i) to confirm previous findings on peripheral BDNF in MDD and BD‐I patients; (ii) to assess whether changes in circulating BDNF occur also in patients with BD‐II; and (iii) to exclude the possibility that comorbid psychiatric disorders exerted an effect on BDNF levels in affective patients.
Methods: We measured serum BDNF concentrations by an enzyme‐linked immunosorbent assay method in 85 subjects, including 24 euthymic patients with unipolar depression (UD), 17 euthymic patients with BD‐I, 11 euthymic patients with BD‐II, 11 UD patients with a current major depressive episode and 22 drug‐free healthy controls. At the time of the study, 15 patients were drug‐treated; the remaining ones were drug‐free for at least four weeks.
Results: Compared to healthy controls, serum BDNF concentrations were significantly reduced in all the patient groups (F4,80 = 3.840, p = 0.006) with no significant difference among them. Drug treatments and comorbid psychiatric disorders had no effect on lowered circulating BDNF levels in affective patients.
Conclusions: Present results confirm previous independent findings of reduced circulating BDNF in patients with MDD and report, for the first time, decreased serum BDNF levels in euthymic patients with UD, BD‐I and BD‐II, independently from drug treatment status and concomitant Axis I psychiatric disorders.
To investigate the pharmacokinetics, pharmacodynamics, and exposure-response of the approved 900/1,200 mg dosing regimen for the terminal complement component 5 (C5) inhibitor eculizumab in patients ...with generalized myasthenia gravis (gMG).
The analysis used data from 62 patients aged ≥ 18 years with anti-acetylcholine receptor (AChR) antibody-positive refractory gMG who received eculizumab during the REGAIN study (ClinicalTrials.gov: NCT01997229). One- and two-compartment population-pharmacokinetic models were evaluated, and the impact of covariates on pharmacokinetic parameters was assessed. Relationships between eculizumab exposure and free C5 concentration,
hemolytic activity, clinical response, and tolerability were characterized.
Steady-state serum eculizumab concentrations were achieved by Week 4 and were sustained throughout the 26-week treatment period. The eculizumab pharmacokinetic data were well-described by a two-compartment model with first-order elimination, including effects of body weight on pharmacokinetic parameters and plasma-exchange events on clearance. Complete inhibition of terminal complement was achieved in nearly all patients at the time of trough and peak eculizumab concentrations at all post-dose timepoints assessed (free C5 < 0.5 μg/ml in 92% of patients;
hemolysis < 20% in 87% of patients). Serum eculizumab concentrations of ≥116 μg/ml achieved free C5 concentrations of < 0.5 μg/ml. Clinical efficacy and tolerability were consistent across the eculizumab exposure range.
Rigorous, quantitative, model-based exposure-response analysis of serum eculizumab concentration and response data demonstrated that the approved eculizumab dosing (900/1,200 mg) for adults with anti-AChR antibody-positive refractory gMG rapidly achieved complete inhibition of terminal complement activation and provided sustained clinical efficacy across the eculizumab exposure range.
PDF
