Long-Term Changes of Central Ocular Motor Signs in Patients with Vestibular Migraine

Background: A high percentage of patients with vestibular migraine (VM)were reported to have central ocular motor dysfunctions (COMD) in thesymptom-free interval. Since VM is a chronic disorder, it is of interestif COMD worsen over time. Methods: Thirty VM patients and 11 controlpatients participated in an 8-year-long observational study withfollow-up. All patients underwent standardized neuro-ophthalmologicaland neuro-otological examinations at the initial presentation and atfollow-up. The primary outcome measure was change in COMD at follow-up.Results: In general, COMD in the symptom-free interval were subtle,consisting of a saccadic horizontal and/or vertical pursuit

Vestibular Function and Quality of Life in Vestibular Schwannoma: Does Size Matter?

Objectives: Patients with vestibular schwannoma (VS) frequently suffer from disabling vestibular symptoms. This prospective follow-up study evaluates vestibular and auditory function and impairment of quality of life due to vertigo, dizziness, and imbalance in patients with unilateral VS of different sizes before/after microsurgical or radiosurgical treatment. Methods: Thirty-eight patients with unilateral VS were included. Twenty-two received microsurgery, 16 CyberKnife radiosurgery. Two follow-ups took place after a median of 50 and 186.5 days. Patients received a standardized neuro-ophthalmological examination, electronystagmography with bithermal caloric testing, and pure-tone audiometry. Quality of life was evaluated with the Dizziness Handicap Inventory (DHI). Patient data was grouped and analyzed according to the size of the VS (group 1: <20 mm vs group 2: ≥20 mm). Results: In group 1, the median loss of vestibular function was +10.5% as calculated by Jongkees Formula (range −43 to +52; group 2: median +36%, range −56 to +90). The median change of DHI scores was −9 in group 1 (range −68 to 30) and +2 in group 2 (−54;+20). Median loss of hearing was 4 dB (−42; 93) in group 1 and 12 dB in group 2 (5; 42). Conclusion: Loss of vestibular function in VS clearly correlates with tumor size. However, loss of vestibular function was not strictly associated with a long-term deterioration of quality of life. This may be due to central compensation of vestibular deficits in long-standing large tumors. Loss of hearing before treatment was significantly influenced by the age of the patient but not by tumor size. At follow-up 1 and 2, hearing was significantly influenced by the size of the VS and the manner of treatment

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10−3) and candidate genes from knockout mice (P = 5.2 × 10−3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000–185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts

The role of sucrose and sensory systems in fruit selection and consumption of Ateles geoffroyi in Yucatan, Mexico

Our aim was to evaluate the role of sucrose and the role of smell, taste and touch in the selection and consumption of fruit in wild spider monkeys. We recorded the feeding bouts of 14 adults for 9 mo in the Otoch Ma’ax Yetel Kooh Reserve, Punta Laguna, Yucatan, Mexico. For each of 2346 inspections on fruits of six species the consumption or rejection and the use of touch, smell and taste was recorded. Ten fruit samples (five ripe and five unripe) from each species were collected and the sucrose concentration was determined with a refractometer. As expected, sucrose concentrations were higher in ripe than unripe fruits. The difference in sucrose concentration between ripe and unripe fruits was positively associated with the proportion of inspections on ripe fruits and the proportion of consumed ripe fruits. Furthermore, the senses of touch and taste were used more often when fruits were ripe, whereas the sense of smell was used more often when fruits were unripe. The results suggest that sensory cues and sucrose concentration play important roles in fruit selection in spider monkeys

Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve split-hand/foot malformation type 3

Split-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. Yet, the disease patho-mechanism remains unsolved. Here we investigate the functional consequences of SHFM3-associated rearrangements on chromatin conformation and gene expression in vivo in transgenic mice. We show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. Re-engineering of a SHFM3-associated duplication and a newly reported inversion in mice results in restructuring of the chromatin architecture. This leads to ectopic activation of the Lbx1 and Btrc genes in the apical ectodermal ridge (AER) in an Fgf8-like pattern induced by AER-specific enhancers of Fgf8. We provide evidence that the SHFM3 phenotype is the result of a combinatorial effect on gene misexpression in the developing limb. Our results reveal insights into the molecular mechanism underlying SHFM3 and provide conceptual framework for how genomic rearrangements can cause gene misexpression and disease.This study was supported by grants from the Deutsche Forschungsgemeinschaft (MU 880/16-1, MU 880/20-1) to S.M. We thank the transgenic unit, sequencing core and animal facility of Max Planck Institute for Molecular Genetics for technical assistance, Ute Fischer for technical support and Norbert Brieske for help with whole mount in situ hybridizations and image processing

The Day-to-Day Impact of Urogenital Aging: Perspectives from Racially/Ethnically Diverse Women

Urogenital symptoms affect up to half of women after menopause, but their impact on women’s day-to-day functioning and wellbeing is poorly understood. Postmenopausal women aged 45 to 80 years reporting urogenital dryness, soreness, itching, or pain during sex were recruited to participate in in-depth focus groups to discuss the impact of their symptoms. Focus groups were homogenous with respect to race/ethnicity and stratified by age (for White or Black women) or language (for Latina women). Transcripts of sessions were analyzed according to grounded theory. Six focus groups were conducted, involving 44 women (16 White, 14 Black, 14 Latina). Five domains of functioning and wellbeing affected by symptoms were identified: sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations. For some participants, symptoms primarily affected their ability to have and enjoy sex, as well as be responsive to their partners. For others, symptoms interfered with everyday activities, such as exercising, toileting, or sleeping. Participants regarded their symptoms as a sign that they were getting old or their body was deteriorating; women also associated symptoms with a loss of womanhood or sexuality. Additionally, participants reported feeling depressed, embarrassed, and frustrated about their symptoms, and expressed reluctance to discuss them with friends, family, or health care providers. Urogenital symptoms can have a marked impact on sexual functioning, everyday activities, emotional wellbeing, body image, and interpersonal relations after menopause. Clinicians may need to question women actively about these symptoms, as many are reluctant to seek help for this problem

Drosophila evolution over space and time (DEST):A new population genomics resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last years. A major challenge is the integration of disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 previously published and unpublished population samples from over 100 locations in > 20 countries on four continents. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. We further provide guidelines on how to use Pool-Seq data for model-based demographic inference. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.DrosEU is funded by a Special Topic Networks (STN) grant from the European Society for Evolutionary Biology (ESEB). MK (M. Kapun) was supported by the Austrian Science Foundation (grant no. FWF P32275); JG by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900) and by the Spanish Ministry of Science and Innovation (BFU-2011-24397); TF by the Swiss National Science Foundation (SNSF grants PP00P3_133641, PP00P3_165836, and 31003A_182262) and a Mercator Fellowship from the German Research Foundation (DFG), held as a EvoPAD Visiting Professor at the Institute for Evolution and Biodiversity, University of Münster; AOB by the National Institutes of Health (R35 GM119686); MK (M. Kankare) by Academy of Finland grant 322980; VL by Danish Natural Science Research Council (FNU) grant 4002-00113B; FS Deutsche Forschungsgemeinschaft (DFG) grant STA1154/4-1, Project 408908608; JP by the Deutsche Forschungsgemeinschaft Projects 274388701 and 347368302; AU by FPI fellowship (BES-2012-052999); ET Israel Science Foundation (ISF) grant 1737/17; MSV, MSR and MJ by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200178); AP, KE and MT by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia (451-03-68/2020-14/200007); and TM NSERC grant RGPIN-2018-05551.Peer reviewe

L'attaccamento va in tribunale: protezione e affidamento dei minori

In molti contesti professionali, compreso quello del Tribunale per i minorenni, si fa riferimento alla teoria dell’attaccamento e alla relativa ricerca, con fraintendimenti ampiamente diffusi che spesso si traducono in applicazioni scorrette. La finalità di questa dichiarazione di consenso è, pertanto, quella di migliorarne la comprensione, contrastare la disinformazione a riguardo e guidarne l’uso nel contesto del tribunale per i minorenni secondo una modalità basata sulle evidenze, considerando in particolare i processi decisionali circa la protezione e l’affidamento dei minori. L’articolo è diviso in due parti. Nella prima ci occupiamo dei problemi relativi all’utilizzo di teoria e ricerca sull’attaccamento nel contesto del Tribunale per i minorenni e ne discutiamo le ragioni. A questo proposito, esaminiamo le applicazioni della teoria che si ispirano al principio elettivo del superiore interesse del minore, discutiamo i fraintendimenti a riguardo e identifichiamo i fattori che ne hanno ostacolato un’accurata implementazione. Nella seconda parte, forniamo indicazioni per una sua adeguata e corretta applicazione. A tal fine, siamo partiti da tre principi di riferimento: il bisogno del bambino di caregiver familiari e non abusanti, il valore della continuità di cure sufficientemente buone e i benefici delle reti di relazioni di attaccamento. Discutiamo, inoltre, di quanto le valutazioni sulla qualità dell’attaccamento e sul comportamento di cura siano adeguate a ispirare i processi decisionali forensi rivolti ai minori. Concludiamo che la valutazione dei comportamenti di cura dovrebbe ricoprire un ruolo centrale. Nonostante non ci sia fra noi completo consenso riguardo all’utilizzo delle valutazioni sulla qualità dell’attaccamento nelle decisioni attinenti all’affidamento e alla protezione del minore, tali valutazioni si rivelano, al momento, le più adatte a individuare obiettivi e modalità degli interventi di sostegno. Infine, offriamo indicazioni per organizzare le future collaborazioni di ricerca interdisciplinare