Follicular flushing leads to higher oocyte yield in monofollicular IVF: a randomized controlled trial.

STUDY QUESTION: Does follicular flushing increase the number of mature oocytes in monofollicular IVF? SUMMARY ANSWER: Follicular flushing increases the number of mature oocytes in monofollicular IVF. WHAT IS KNOWN ALREADY: Flushing increases neither the oocyte yield nor the pregnancy rate in polyfollicular IVF or in poor responder patients. In monofollicular IVF, the effect of flushing has so far been addressed by two studies: (i) a prospective study with minimal stimulation IVF demonstrated an increased oocyte yield, and (ii) a retrospective study with natural cycle (NC)-IVF showed an increased oocyte yield and an increased transfer rate. STUDY DESIGN, SIZE, DURATION: Randomized controlled trial including 164 women who were randomized for either aspiration with or without flushing from 2016 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women 18-42 years of age with an indication for IVF treatment at a university-based infertility unit. Women undergoing monofollicular IVF were randomized to either follicular aspiration only or follicular aspiration directly followed by five follicular flushes at a 1:1 ratio. The intervention was done without anaesthesia, using a gauge 19 single-lumen needle. Flushing volume was calculated (sphere formula) based on the size of the follicle. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 164 women were included; 81 were allocated to 'aspiration only' and 83 to additional 'flushing'. Primary analysis was based on the intention-to-treat: oocyte yield, defined as the collected mature oocyte rate, was higher (n = 64/83, 77.1%) in the flushing group compared to the aspiration only group (n = 48/81, 59.3%, adjusted risk difference (RD): 18.2% (95% CI 3.9-31.7%), P-value = 0.02). In the flushing group, most oocytes were retrieved within the first three flushes (63/83, 75.8%). Fertilization rate was higher in the flushing group (n = 53/83, 63.9% vs n = 38/81, 46.9%; adjusted RD: 16.8% (96% CI 1.5-31.4%), P = 0.045). Transfer rate was also higher in the flushing group (n = 52/83, 62.7% vs n = 38/81, 46.9%; RD: 15.71 (95% CI 0.3-30.3%)), but the difference was not significant (P = 0.06). The clinical pregnancy rate n = 9/83 versus n = 9/81 (RD: -0.3% (95% CI -9.9% to 9.5%)) and live birth rate n = 7/83 versus n = 8/81 (RD: -1.5% (95% CI -10.4% to 7.1%)) were not significantly different between the flushing and the aspiration group. The median duration of the intervention was significantly longer with flushing (2.38 min; quartiles 2.0, 2.7) versus aspiration only (0.43 min; quartiles 0.3, 0.5) (P < 0.01). There was no significant difference in the mean (±SD) visual analogue scales pain score between the follicular flushing (3.4 ± 1.8) and the aspiration group (3.1 ± 1.89). LIMITATIONS, REASONS FOR CAUTION: Blinding of the procedure was not possible. WIDER IMPLICATIONS OF THE FINDINGS: Our study proved that flushing of single follicles in NC-IVF increases the oocyte yield. In contrast to polyfollicular IVF flushing seems to be beneficial in a monofollicular setting if the technique used in our study (single-lumen needle, 5 flushings with flushing volume adaptation) is applied. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the financial sources of the division and in part by a research grant provided by NMS Biomedical SA, Switzerland. The company did not have any roles in design or conduct of the study or in the preparation of the manuscript. The authors have no other conflicts of interest. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02641808. TRIAL REGISTRATION DATE: 29 December 2015. DATE OF FIRST PATIENT'S ENROLMENT: 22 August 2016.

The temporal association between incident late-life depression and incident dementia.

OBJECTIVE: There is an established association between depression and subsequent dementia. The present study examined temporal associations between incident late-life depression and subsequent dementia, also considering age and sex. METHODS: We used longitudinal health claims data from the largest German health insurance provider ('Allgemeine Ortskrankenkasse') considering up to 9 follow-up years in piecewise exponential models. ICD-10 codes were used to define incident depression and dementia in individuals ≥65 years (n = 97 110). RESULTS: Incident depression was associated with a higher risk of subsequent dementia (incidence rate ratios (IRR) adjusted for age and sex: IRR = 1.58, 95% CI = 1.51-1.64). The strongest association was found for the shortest interval of 1 quarter (IRR = 2.04, 95% CI = 1.88-2.21), with significant associations up to an interval of roughly 3 years. The association was more pronounced and lasted for more quarters in the younger portion of this study group (ages from 65-74: IRR = 2.00, 95% CI = 1.83-2.18; 75-84: IRR = 1.64, 95% CI = 1.55-1.73; ≥85: IRR = 1.19, 95% CI = 1.08-1.31). It was stronger among men than women (men: IRR = 1.98, 95% CI = 1.84-2.14; women: IRR = 1.44, 95% CI = 1.37-1.51) with no sex-specific temporal association. CONCLUSION: This large claims data study confirmed that incident late-life depression is associated with a higher risk of dementia within the 3 years following diagnosis. Hence, incident late-life depression should prompt further cognitive examinations and referrals to specialists. This might apply especially to younger seniors and men.

Septopreoptic holoprosencephaly in intracranial abnormalities: an under-diagnosed midline finding.

BACKGROUND: Septopreoptic holoprosencephaly is a mild form of holoprosencephaly in which the midline non-separation is restricted to the septal or preoptic regions. This entity has only been described in a small case series in which associated intracranial abnormalities were limited to the midline structures. OBJECTIVE: To describe the radiologic findings of septopreoptic holoprosencephaly and highlight that it can be associated with a variety of intracranial abnormalities, not merely with abnormalities restricted to midline structures as previously reported. MATERIALS AND METHODS: We retrospectively identified 22 children whose MRIs were confirmed to have non-separation restricted to the septal and preoptic region, fulfilling the criteria for septopreoptic holoprosencephaly. We then categorized MRIs as having, in addition, either intracranial abnormalities limited to the midline structures or major abnormalities not limited to the midline structures. RESULTS: Five children had intracranial abnormalities limited to the midline structures. Seventeen children had major intracranial abnormalities not limited to the midline structures. The major abnormalities included: patterning defects of the midbrain-hindbrain (elongated midbrain, shortened pons, shortened/elongated medulla, partial rhombencephalosynapsis), bilateral perisylvian polymicrogyria, microcephaly, megalencephaly and a spheno-ethmoidal encephalocele. Recognized syndromes/chromosomal abnormalities were also observed in this patient group. CONCLUSION: Our results suggest that septopreoptic holoprosencephaly has been under-recognized and under-reported to date. We propose that searching for this anomaly should be part of the complete assessment of the midline in all children undergoing brain MRI for intracranial malformations.

Activation of a novel p70 S6 kinase 1-dependent intracellular cascade in the basolateral nucleus of the amygdala is required for the acquisition of extinction memory.

Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning. We found that rapamycin attenuated the consolidation of extinction memory. In contrast, genetic deletion and pharmacological inhibition of S6K1, a downstream effector of mTORC1, blocked within-session extinction, indicating a role for S6K1 independent of protein synthesis. Indeed, the activation of S6K1 during extinction required extracellular signal-regulated kinase (ERK) activation in the basolateral nucleus of the amygdala (BLA) and was necessary for increased phosphorylation of the GluA1 (Thr840) subunit of the AMPA receptor following extinction training. Mice exposed to brief uncontrollable stress showed impaired within-session extinction as well as a downregulation of ERK and S6K1 signaling in the amygdala. Finally, using fiber photometry we were able to record calcium signals in vivo, and we found that inhibition of S6K1 reduces extinction-induced changes in neuronal activity of the BLA. These results implicate a novel ERK-S6K1-GluA1 signaling cascade critically involved in extinction.

Parkinson's disease in Germany: prevalence and incidence based on health claims data.

BACKGROUND: In Germany, epidemiological information on Parkinson's disease (PD) is rare and outdated. Considering aging populations, current prevalences and incidence rates about this age-related disease would be important for adequate public health planning. METHODS: We used newly available health claims data sets from the largest German health insurer dating 2004-2007 and 2007-2010 with an analysis population in the base years of 491 038 persons aged 50 and older. Quarter-specific information about ICD-10 diagnoses and PD drug prescriptions from the inpatient and outpatient sectors was used to validate PD cases. Estimations were presented for two validation strategies relying on repeated PD diagnoses (SIa) and on one PD diagnosis followed by at least one PD drug prescription (SIb). RESULTS: The standardized prevalence was 797 (SIb) to 961/100 000 persons (SIa), showing an age-specific increase up to category 85-89 and a decline thereafter. The standardized incidence rate was 192 to 229/100 000 person-years with a similar age-specific shape. Prevalences and incidences rates were higher for men compared to women in regard to age. CONCLUSIONS: Health claims data are found to be suitable for PD assessment using the repeated diagnoses or PD drug prescriptions as necessary criteria.

Distribution of Silica-Coated Silver/Gold Nanostars in Soft- and Hardwood Applying SERS-Based Imaging.

Nanoparticles (NPs) in aqueous suspension have just begun to be exploited for the preservative treatment of wood. However, at present, there is very little information available on the distribution of NPs in wood after impregnation, due to associated analytical challenges. In this study, we present the detection of model NPs in softwood and hardwood by surface-enhanced Raman spectroscopy (SERS). SERS is a highly sensitive analytical method requiring no fluorescent labeling. The NP distribution after impregnation is evaluated with one representative species of the two wood types. To show the feasibility of the method, we prepared SERS-active Au/Ag nanostars coated with silica to act as a model NP system. We show herein that NPs can be imaged in very low quantities in both wood types without any matrix interactions. The presence of the NPs in the wood was confirmed by scanning electron microscopy (SEM) imaging and energy dispersive X-ray analysis (EDX). The fast detection of NPs in a complex matrix, without complicated sample preparation, marks a huge step forward in the development and application of nanotechnology for wood preservation and the quest to optimize the properties of one of the world's most important raw materials.

A critical review of the current knowledge regarding the biological impact of nanocellulose.

Several forms of nanocellulose, notably cellulose nanocrystals and nanofibrillated cellulose, exhibit attractive property matrices and are potentially useful for a large number of industrial applications. These include the paper and cardboard industry, use as reinforcing filler in polymer composites, basis for low-density foams, additive in adhesives and paints, as well as a wide variety of food, hygiene, cosmetic, and medical products. Although the commercial exploitation of nanocellulose has already commenced, little is known as to the potential biological impact of nanocellulose, particularly in its raw form. This review provides a comprehensive and critical review of the current state of knowledge of nanocellulose in this format. Overall, the data seems to suggest that when investigated under realistic doses and exposure scenarios, nanocellulose has a limited associated toxic potential, albeit certain forms of nanocellulose can be associated with more hazardous biological behavior due to their specific physical characteristics.

Reliability of the German version of the Children's Assessment of Participation and Enjoyment (CAPE) and Preferences for Activities of Children (PAC).

BACKGROUND: The introduction of the International Classification of Functioning, Disabilities and Health of the World Health Organization in 2001 made social participation a major rehabilitation outcome and the ultimate goal of rehabilitation services. There is no available instrument to measure the youth participation in leisure activities apart from asking the youth themselves. The goal of this study was to present a German version of the Children's Assessment of Participation and Enjoyment and Preferences for Activities of Children (CAPE/PAC). METHODS: The CAPE/PAC questionnaire was translated into German, a cultural adaptation process was designed and a reliability study was conducted. One hundred and fifty-two youths with and without disabilities, with a mean age of 15.2 years (standard deviation 1.7), participated in the study. The participants completed CAPE and PAC twice within 4 weeks. Reliability was examined by intraclass correlation coefficients, standard error of measurement, smallest detectable change and Cronbach's alpha. RESULTS: The absolute values of participation differ between the typically developed youth group and those with impairments; the reliability of the CAPE/PAC is comparable in both groups. Intraclass correlation coefficients ranged from 0.43 to 0.74 for the CAPE and from 0.71 to 0.83 for the PAC in all participants. The alpha values for internal consistency ranged from 0.42 to 0.82 for the CAPE and from 0.65 to 0.92 for the PAC. CONCLUSIONS: The German version of the PAC showed satisfactory reliability; however, reliability was not satisfactory for all scores of the CAPE, but comparable with versions in other languages. The need for newly developed participation measurements requires further discussion.

Managing fetuses at high risk of retinoblastoma: lesion detection on screening MRI.

OBJECTIVE: This study aimed to describe tumour identification on magnetic resonance imaging (MRI) in a 35-week fetus with familial retinoblastoma (RB) and report the use of prenatal ultrasound (US) and MRI screening in the management of fetuses at high risk of RB. METHOD: This is a retrospective review of the prenatal course and immediate postnatal findings in all children considered at high risk of RB who had prenatal imaging with both US and MRI at our institution over a 5-year period. RESULTS: Five patients met the inclusion criteria. No lesions were identified on US in any patients. Fetal MRI identified bilateral posterior pole lesions in one patient at 35 weeks' gestation. Of the four remaining patients, three developed lesions by 5 weeks of age. Only one fetus was delivered early following detection of RB. CONCLUSION: We present the first reported case of RB detected in a high-risk fetus on screening MRI at 35 weeks' gestation. A protocol for screening this population using both imaging modalities is presented.

Apert syndrome: temporal lobe abnormalities on fetal brain imaging.

OBJECTIVES: Apert syndrome is characterized by craniosynostosis and complex hand and foot syndactyly, and an increased risk of brain, palate, heart, and visceral malformations, and intellectual disability. This study aims to describe the structural brain abnormalities detected by dedicated neuroimaging of fetuses with Apert syndrome. METHODS: Retrospective review of ultrasound and magnetic resonance imaging brain imaging obtained in six fetuses with a diagnosis of Apert syndrome. RESULTS: Five fetuses had attenuation of the septal leaflets, and two had corpus callosum dysgenesis. All six had temporal lobe expansion and overconvolution and temporal lobe clefts. The temporal lobe abnormalities preceded the development of cranial deformity in two fetuses. CONCLUSION: Overexpansion and overconvolution of the temporal lobe is evident antenatally and is particularly conspicuous in the fetus when the normal brain is still relatively smooth (approximately 24 to 28 weeks of gestation).

[Measuring Participation - Discussion of the Theoretical Foundations of Current Assessment Instruments]. / Partizipation - theoretische Grundlagen und aktuelle Messinstrumente im Kindes- und Jugendalter.

BACKGROUND: For children and adolescents social participation is a central goal of rehabilitation processes. Available measurements and evaluation tools are exposed to the problem that the theoretical foundation of the construct of participation is still unclear as well as differentiation from activity in the International Classification of Functioning, Disabilities and Health (ICF/ICF-CY) of the WHO is not made sufficiently. OBJECTIVES: The objectives of this article were (1) to illustrate the scientific discussions on the term and understanding of participation from rehabilitation science perspectives and (2) to conclude implications for practice and science. MATERIALS AND METHODS: A systematic search for participation instruments was performed in MEDLINE, CINAHL, PsycINFO, ERIC und EMBASE in August 2014. RESULTS: The available instruments are based on very different definitions of participation. The discussion about the term seems to be not yet complete. A major demand is a better operationalization of activity and participation according to the ICF/ICF-CY in the instruments. CONCLUSIONS: Before using an existing instrument, the transferability should be tested for the own context. The theoretical assumptions of participation in conjunction to ICF/ICF-CY as well as the objectives of the instrument should all be clearly understood before using an existing instrument but also before the development of new instruments.

Antenatal imaging of anomalies of the corpus callosum: a decade of experience.

PURPOSE: To assess the diagnostic accuracy of antenatal ultrasound and foetal magnetic resonance imaging (FMRI) over the past decade in the diagnosis of anomalies of the corpus callosum in a tertiary referral centre. METHODS: A single tertiary referral centre ultrasound database was searched for cases of suspected callosal anomalies between 2003 and 2012. All subsequent ultrasound scans, MRIs, neonatal imaging, postmortem investigations and birth records were reviewed. Callosal anomalies were classified into isolated or complex based on the presence or absence of accompanying congenital anomalies. RESULTS: Forty-three cases of callosal anomaly were detected; 60 % were investigated by FMRI revealing additional diagnoses in 23 %; half of which were anomalies of cortical development. Of those considered isolated who underwent FMRI, 21 % were diagnosed with additional anomalies, changing the classification to a complex callosal anomaly. CONCLUSION: In cases of callosal anomaly suspected on ultrasound, FMRI provides greater certainty and the potential to identify significant additional anomalies. The additional information may alter or clarify prognosis and help parents to better understand the pathology, allowing for informed decisions about the pregnancy to be made. However, some cases may still be diagnosed with additional anomalies after delivery and parents should be aware of such limitations of antenatal imaging.

The Contribution of MRI after Fetal Anomalies Have Been Diagnosed by Ultrasound: Correlation with Postnatal Outcomes.

OBJECTIVE: The aim of this study was to investigate the additional value of fetal magnetic resonance imaging (MRI) in the assessment and management of fetuses with abnormal findings on ultrasound. METHODS: A total of 257 patients who had fetal MRI following the ultrasound diagnosis of a fetal anomaly, or were at high risk, were included. The patients were grouped by referral category for fetal MRI. Fetal MRI was compared to ultrasound in the detection of anomalies, i.e. whether additional findings were identified and if this changed diagnosis, prognosis and management during pregnancy. RESULTS: Ultrasound findings were confirmed on fetal MRI in 89% of the cases. Additional findings were seen with MRI in 28% of all patients. The diagnosis changed in 21% and the prognosis in 19% of the cases. Perinatal management changed in 8%. The antenatal findings were confirmed in all cases that had a postmortem examination following termination of pregnancy. In all the pregnancies that continued to delivery and for which the postnatal outcome is known, the findings correlated in 97% of the cases. CONCLUSION: Fetal MRI provided additional detection of fetal anomalies, leading to a change in diagnosis and prognosis in 19% of the cases. Neonatal and postmortem findings mostly confirmed the fetal MRI diagnosis, suggesting it to be a useful tool for clinical decision making in perinatal management.

[Spirituality in schizophrenic diseases]. / Spiritualität bei schizophrenen Erkrankungen.

OBJECTIVE: The aim of this study was to investigate different dimensions of religiosity and spirituality among schizophrenic inpatients (F 2x) compared to addiction patients (F 10.2, F 19.2) and to healthy controls. In addition the dimensions of religious and spiritual well-being were examined and related to different parameters of mental illness. METHOD: The group of schizophrenic patients (n = 39) was compared to a group of addiction patients (n = 33) and a healthy control group (n = 38) by means of the multidimensional inventory for religious/spiritual well-being (MI-RSWB). Additionally, dimensions of RSWB were related to the Beck depression inventory (BDI) and the brief symptom inventory (BSI) in the group of schizophrenic patients. RESULTS: The group of schizophrenic patients did not differ from the addiction patients or from the healthy controls in the RSWB dimensions, except for the hope transcendent sub-dimension. Furthermore, dimensions of RSWB turned out to be negatively correlated with the severity of psychiatric symptoms (BDI and BSI). CONCLUSION: As assumed a positive relationship between RSWB and subjective well-being can be confirmed also for the group of schizophrenic patients. Existentially oriented dimensions such as hope and forgiveness might be specifically relevant for the group of schizophrenics.

Serial position effects in patients with mild cognitive impairment and early and moderate Alzheimer's disease compared with healthy comparison subjects.

BACKGROUND/AIMS: This study aimed to investigate whether the serial position effects in memory can differentiate patients with different subtypes of mild cognitive impairment (MCI) from healthy controls and patients with different stages of Alzheimer's disease (AD). METHODS: The serial position effects was tested with the CERAD word list task in 184 persons (39 healthy control subjects, 15 amnestic MCI single domain subjects, 23 amnestic MCI multiple domain subjects, 31 nonamnestic MCI subjects, 45 early or mild AD patients, and 31 moderate AD patients). RESULTS: With progression of dementia, memory deficits increased and the impairment in the primacy effect during the learning trials advanced, whereas the recall of recent items was less impaired. The serial position profile of nonamnestic MCI patients resembled that of healthy control subjects, whereas amnestic MCI patients showed poorer performance in all 3 positions but no significant difference as a function of serial word position. CONCLUSION: Analyses of the serial position effect may be a useful complement to clinical neuropsychological measures for distinguishing amnestic MCI patients from normal aging and patients with different stages of dementia.

Perinatal and short-term neonatal outcomes of posterior fossa anomalies.

OBJECTIVE: To describe the perinatal and neonatal outcomes for fetuses with posterior fossa (PF) anomalies - mega-cisterna magna (MCM), persistent Blake's pouch (PBP) or the Dandy-Walker continuum (DWC) - using a new classification. METHODS: 46 cases with PF anomaly diagnosed on ultrasound (US) between 16 and 28 weeks' gestation were included. The images were reviewed and classified as one of the following: MCM, PBP or DWC. Outcomes were obtained from patient records. RESULTS: 30 cases with DWC, 6 with MCM, and 10 with PBP were identified. Associated anomalies were present in all groups, but more frequent in DWC. Agenesis of the corpus callosum and ventriculomegaly were more common in DWC than in MCM or PBP. Only fetuses with DWC were found to have chromosomal abnormalities. Perinatal outcomes differed significantly, with terminations of pregnancy more frequent in DWC. In the immediate postnatal period, infants with DWC had worse outcomes than those with MCM and PBP. Across all groups, those with associated anomalies had worse outcomes than those with an isolated PF anomaly. CONCLUSION: Infants antenatally diagnosed with DWC had worse perinatal and short-term neonatal outcomes than those with MCM or PBP. Those with associated anomalies had uniformly poorer outcomes than those with isolated anomalies.

Religious/Spiritual Well-being, personality and mental health: a review of results and conceptual issues.

The current paper provides background to the development of the Multidimensional Inventory for Religious/Spiritual Well-being and then summarises findings derived from its use with other measures of health and personality. There is substantial evidence for religiosity/spirituality being positively related to a variety of indicators of mental health, including subjective well-being and personality dimensions. Furthermore, religiosity/spirituality can play an important role in the process of recovering from mental illness as well as providing a protective function against addictive or suicidal behaviours. However, further research is needed to examine the mechanisms through which religiosity/spirituality have an impact on health-related conditions.

The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.