Instrumental Assessment and Pharmacological Treatment of Migraine-Related Vertigo in Pediatric Age.

BACKGROUND: The most frequent form of vertigo in pediatric age is represented by vertigo linked to migraine, with a prevalence of 32.7%. This group of pathologies has received a redefinition of the diagnostic criteria to adapt them to the pediatric age with a new classification of the clinical pictures. We have several kinds of problems with these conditions that often have a significant impact on patients' and parents' quality of life: the diagnostic approach involves different tools for the different age groups contained in the pediatric range; the treatment of this type of vertigo is not consolidated due to the limited availability of trials carried out on pediatric patients. Focusing on this topic, the aim of this review was to provide an update on the more recent clinical advances in the diagnosis and treatment of Vestibular Migraine (VM) in children. METHODS: We searched the PubMed, Embase, and Cochrane library databases for articles published in English from January 2015 to April 2023. The secondary search included articles from reference lists, identified by the primary search. Records were first screened by title/abstract, and then full-text articles were retrieved for eligibility evaluation. The searches combined a range of key terms ("Pediatric" AND "Childhood" AND "dizziness" OR "vertigo" AND "vestibular"). RESULTS: Migraine-related vertigo, in its most recent definitions and classifications, is the most frequent group of balance pathologies in pediatric age. The results from the various experiences present in the literature suggest a clinical approach to be integrated with the use of instrumental tests selected according to the age of the patient and the reliability of the results. CONCLUSION: Knowing the timeline of the applicability of vestibular tests and the information that can be obtained from them is fundamental for diagnostic accuracy. Therapy is strongly conditioned by the limited availability of pediatric trials and by the wide range it includes, from very young children to adolescents.

Hagfish genome elucidates vertebrate whole-genome duplication events and their evolutionary consequences.

Polyploidy or whole-genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and 2R occurred in the gnathostome stem-lineage, maximally in the late Cambrian-earliest Ordovician, after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced an additional independent genome triplication. Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only in the gnathostome but not in the cyclostome lineage, calling into question the general expectation that WGDs lead to leaps of bodyplan complexity.

The Evolution of Temperature and Desiccation-Related Protein Families in Tardigrada Reveals a Complex Acquisition of Extremotolerance.

Tardigrada is an ecdysozoan lineage famed for its resilience. Tardigrades can tolerate high doses of radiation, low-oxygen environments, desiccation, and both high and low temperatures under a dormant state called "anhydrobiosis", which is a reversible halt of metabolism upon almost complete desiccation. A large amount of research has focused on the genetic pathways related to these capabilities, and a number of genes have been identified and linked to the extremotolerant response of tardigrades. However, the history of these genes is unclear, and the origins and history of extremotolerant genes within Tardigrada remain a mystery. Here, we generate the first phylogenies of six separate protein families linked with desiccation and radiation tolerance in Tardigrada: cytosolic abundant heat-soluble protein, mitochondrial abundant heat-soluble protein, secretory abundant heat-soluble protein, meiotic recombination 11 homolog, and the newly discovered Echiniscus testudo abundant heat-soluble proteins (alpha and beta). The high number of independent gene duplications found amongst the six gene families studied suggests that tardigrades have a complex history with numerous independent adaptations to cope with aridity within the limnoterrestrial environment. Our results suggest that tardigrades likely transitioned from a marine environment to a limnoterrestrial environment only twice, once in stem Eutardigrada and once in Heterotardigrada, which explains the unique adaptations to anhydrobiosis present in both classes.

ATP synthase evolution on a cross-braced dated tree of life.

The timing of early cellular evolution, from the divergence of Archaea and Bacteria to the origin of eukaryotes, is poorly constrained. The ATP synthase complex is thought to have originated prior to the Last Universal Common Ancestor (LUCA) and analyses of ATP synthase genes, together with ribosomes, have played a key role in inferring and rooting the tree of life. We reconstruct the evolutionary history of ATP synthases using an expanded taxon sampling set and develop a phylogenetic cross-bracing approach, constraining equivalent speciation nodes to be contemporaneous, based on the phylogenetic imprint of endosymbioses and ancient gene duplications. This approach results in a highly resolved, dated species tree and establishes an absolute timeline for ATP synthase evolution. Our analyses show that the divergence of ATP synthase into F- and A/V-type lineages was a very early event in cellular evolution dating back to more than 4 Ga, potentially predating the diversification of Archaea and Bacteria. Our cross-braced, dated tree of life also provides insight into more recent evolutionary transitions including eukaryogenesis, showing that the eukaryotic nuclear and mitochondrial lineages diverged from their closest archaeal (2.67-2.19 Ga) and bacterial (2.58-2.12 Ga) relatives at approximately the same time, with a slightly longer nuclear stem-lineage.

Defining eukaryotes to dissect eukaryogenesis.

The origin of eukaryotes is among the most contentious debates in evolutionary biology, attracting multiple seemingly incompatible theories seeking to explain the sequence in which eukaryotic characteristics were acquired. Much of the controversy arises from differing views on the defining characteristics of eukaryotes. We argue that eukaryotes should be defined phylogenetically, and that doing so clarifies where competing hypotheses of eukaryogenesis agree and how we may test among aspects of disagreement. Some hypotheses make predictions about the phylogenetic origins of eukaryotic genes and are distinguishable on that basis. However, other hypotheses differ only in the order of key evolutionary steps, like mitochondrial endosymbiosis and nuclear assembly, which cannot currently be distinguished phylogenetically. Stages within eukaryogenesis may be made identifiable through the absolute dating of gene duplicates that map to eukaryotic traits, such as in genes of host or mitochondrial origin that duplicated and diverged functionally prior to emergence of the last eukaryotic common ancestor. In this way, it may finally be possible to distinguish heat from light in the debate over eukaryogenesis.

Fossilization can mislead analyses of phenotypic disparity.

Analyses of morphological disparity can incorporate living and fossil taxa to facilitate the exploration of how phenotypic variation changes through time. However, taphonomic processes introduce non-random patterns of data loss in fossil data and their impact on perceptions of disparity is unclear. To address this, we characterize how measures of disparity change when simulated and empirical data are degraded through random and structured data loss. We demonstrate that both types of data loss can distort the disparity of clades, and that the magnitude and direction of these changes varies between the most commonly employed distance metrics and disparity indices. The inclusion of extant taxa and exceptionally preserved fossils mitigates these distortions and clarifies the full extent of the data lost, most of which would otherwise go uncharacterized. This facilitates the use of ancestral state estimation and evolutionary simulations to further control for the effects of data loss. Where the addition of such reference taxa is not possible, we urge caution in the extrapolation of general patterns in disparity from datasets that characterize subsets of phenotype, which may represent no more than the traits that they sample.

Surgical Management of Endolymphatic Sac Tumor: A Systematic Review and Meta-Analysis.

The aim of our study was to report rates of facial nerve palsy and residual tumor following surgical intervention and subsequent tumor recurrence in patients with endolymphatic sac tumors. A systematic literature review of preoperative assessment and surgical management is also included. Studies including patient/s affected by sporadic or von Hippel-Lindau disease related endolymphatic sac tumors, reporting levels of facial nerve function, residual and recurrence pathology following a surgical procedure, were considered. Data were combined for proportional meta-analysis, and the selected studies' methodological quality was also evaluated. Overall 34 papers, including 202 subjects (209 cases of endolymphatic sac tumors) were analyzed. Pooled proportion rate (95% CI) of overall facial nerve palsy was 39.7% (28.2-51.9) and residual tumor was 16.5% (10.3-23.7) after surgical procedure. Pooled proportion rate (95% CI) of tumor recurrence was 14.0% (9.7-19.3) during a mean follow-up period of 49.7 months (8-136). Our results showed that preoperative facial nerve function is impaired in almost 30% of patients with endolymphatic sac tumors. Surgical management of endolymphatic sac tumor may cause a worsening of facial nerve function in a low percentage of treated subjects. Residual and/or recurrence of endolymphatic sac tumors are not rare events, and follow-up strategies should be designed accordingly.

A timescale for placental mammal diversification based on Bayesian modeling of the fossil record.

The timing of the placental mammal radiation has been the focus of debate over the efficacy of competing methods for establishing evolutionary timescales. Molecular clock analyses estimate that placental mammals originated before the Cretaceous-Paleogene (K-Pg) mass extinction, anywhere from the Late Cretaceous to the Jurassic. However, the absence of definitive fossils of placentals before the K-Pg boundary is compatible with a post-Cretaceous origin. Nevertheless, lineage divergence must occur before it can be manifest phenotypically in descendent lineages. This, combined with the non-uniformity of the rock and fossil records, requires the fossil record to be interpreted rather than read literally. To achieve this, we introduce an extended Bayesian Brownian bridge model that estimates the age of origination and, where applicable, extinction through a probabilistic interpretation of the fossil record. The model estimates the origination of placentals in the Late Cretaceous, with ordinal crown groups originating at or after the K-Pg boundary. The results reduce the plausible interval for placental mammal origination to the younger range of molecular clock estimates. Our findings support both the Long Fuse and Soft Explosive models of placental mammal diversification, indicating that the placentals originated shortly prior to the K-Pg mass extinction. The origination of many modern mammal lineages overlapped with and followed the K-Pg mass extinction.

Vestibular Impairment in Patients with Vestibular Schwannoma: A Journey through the Pitfalls of Current Literature.

Vestibular Schwannoma is the most common tumour of Ponto Cerebellar Angle and is capable of strongly impacting the patient's quality of life. In recent decades, the proposals for the management of the disease have multiplied, just as the diagnostic capacity has improved. While in the past, the primary objective was the preservation of the facial function, and subsequently also of the auditory function, the attention to the vestibular symptomatology, which appears to be one of the main indicators of deterioration of quality of life, is still unsatisfactory. Many authors have tried to provide guidance on the best possible management strategy, but a universally recognized guideline is still lacking. This article offers an overview of the disease and the proposals which have advanced in the last twenty years, evaluating their qualities and defects in a critical reading.

Exploring genome gene content and morphological analysis to test recalcitrant nodes in the animal phylogeny.

An accurate phylogeny of animals is needed to clarify their evolution, ecology, and impact on shaping the biosphere. Although datasets of several hundred thousand amino acids are nowadays routinely used to test phylogenetic hypotheses, key deep nodes in the metazoan tree remain unresolved: the root of animals, the root of Bilateria, and the monophyly of Deuterostomia. Instead of using the standard approach of amino acid datasets, we performed analyses of newly assembled genome gene content and morphological datasets to investigate these recalcitrant nodes in the phylogeny of animals. We explored extensively the choices for assembling the genome gene content dataset and model choices of morphological analyses. Our results are robust to these choices and provide additional insights into the early evolution of animals, they are consistent with sponges as the sister group of all the other animals, the worm-like bilaterian lineage Xenacoelomorpha as the sister group of the other Bilateria, and tentatively support monophyletic Deuterostomia.

Diabetes Mellitus and Hearing Loss: A Complex Relationship.

Background and Objectives: Discussion is open about the relationship between diabetes (DM) and hearing loss (HL). There is a lot of evidence in the literature suggesting a causal link between these conditions, beyond being considered simple comorbidities. The difficulty in identifying populations free from confounding factors makes it difficult to reach definitive conclusions on the pathophysiological mechanisms at play. Nonetheless, there is numerous evidence that demonstrates how the population affected by DM is more affected by sensorineural HL (SNHL) and exhibit a higher prevalence of idiopathic sudden sensorineural HL (ISSNHL). Materials and Methods: Articles reporting potentially relevant information were reviewed, and the most significant results are discussed in this article. Starting from the possible mechanisms relating to auditory impairment in the diabetic condition, this article summarizes the studies on auditory evaluation in subjects with DM1 and DM2 and addresses the relationship between DM and ISSNHL. Results: DM is considered a risk factor for SNHL, although some studies have reported no relationship when the associations were adjusted for age, gender, and hypertension. Macro and microvascular insults that cause decreased blood flow, oxygen exchange, and ion transport are major complications of hypertension and DM and can have a direct effect on the sensory and support cells of the cochlea. Conclusions: Given the difficulty of carrying out studies on populations without confounding factors, new laboratory studies are strongly required to clarify which specific physiopathological mechanisms underlie the diabetic damage caused to the hearing organs and how pharmacological management may contribute to counteracting the pathophysiological effects of the diabetic condition on the auditory system.

The unbearable uncertainty of panarthropod relationships.

Panarthropoda, the clade comprising the phyla Onychophora, Tardigrada and Euarthropoda, encompasses the largest majority of animal biodiversity. The relationships among the phyla are contested and resolution is key to understanding the evolutionary assembly of panarthropod bodyplans. Molecular phylogenetic analyses generally support monophyly of Onychophora and Euarthropoda to the exclusion of Tardigrada (Lobopodia hypothesis), which is also supported by some analyses of morphological data. However, analyses of morphological data have also been interpreted to support monophyly of Tardigrada and Euarthropoda to the exclusion of Onychophora (Tactopoda hypothesis). Support has also been found for a clade of Onychophora and Tardigrada that excludes Euarthropoda (Protarthropoda hypothesis). Here we show, using a diversity of phylogenetic inference methods, that morphological datasets cannot discriminate statistically between the Lobopodia, Tactopoda and Protarthropoda hypotheses. Since the relationships among the living clades of panarthropod phyla cannot be discriminated based on morphological data, we call into question the accuracy of morphology-based phylogenies of Panarthropoda that include fossil species and the evolutionary hypotheses based upon them.

The Role of Quantic Molecular Resonance (QMR) in the Treatment of Inferior Turbinate Hypertrophy (ITH): Our Experience With Long-Term Follow-Up in Allergic and Nonallergic Rhinitis Refractory to Medical Therapy. Preliminary Results.

OBJECTIVE: The aim of this study was to assess the long-term effectiveness of quantic molecular resonance (QMR) in the treatment of inferior turbinate hypertrophy (ITH) in allergic and nonallergic rhinitis refractory to medical therapy. METHODS: This study enrolled 281 patients, 160 males (56.9%) and 121 females (43.1%), mean age 37.8 ± 4.1 years, range 18 to 71. Fifty-four patients have been lost to follow up and have been therefore excluded from the final analysis. Based on skin prick test results, 69 patients were considered allergic (group A) and 158 nonallergic (group B). All subjects underwent before surgery (T0) and 3 (T1), 12 (T2), 24 (T3), and 36 months (T4) after QMR treatment to: 4-phase rhinomanometric examination, nasal endoscopy evaluation, and visual analogue scale to quantify the subjective feelings about nasal obstruction. RESULTS: Subjective and objective parameters showed statistically significant improvement in both groups. Group B parameters not changed during follow-up, while group A showed significant worsening between T1 and subsequent assessments. T4 outcome indicates a better result in nonallergic patients. CONCLUSIONS: In accordance with the literature, our preliminary data validate QMR treatment as a successful therapeutic option for nasal obstruction due to ITH. Nonallergic patients had a very good T4 outcome. Allergic patients showed a worsening trend after 1 year probably due to other causes.

Resolving tricky nodes in the tree of life through amino acid recoding.

Genomic data allowed a detailed resolution of the Tree of Life, but "tricky nodes" such as the root of the animals remain unresolved. Genome-scale datasets are heterogeneous as genes and species are exposed to different pressures, and this can negatively impacts phylogenetic accuracy. We use simulated genomic-scale datasets and show that recoding amino acid data improves accuracy when the model does not account for the compositional heterogeneity of the amino acid alignment. We apply our findings to three datasets addressing the root of the animal tree, where the debate centers on whether sponges (Porifera) or comb jellies (Ctenophora) represent the sister of all other animals. We show that results from empirical data follow predictions from simulations and suggest that, at the least in phylogenies inferred from amino acid sequences, a placement of the ctenophores as sister to all the other animals is best explained as a tree reconstruction artifact.

Phylogenomics: Is less more when using large-scale datasets?

Phylogenetic studies have traditionally placed the simple Xenoacoelomorph worms as the sister group of all other animals with bilateral body symmetry. A new study shows that misidentification of orthologous genes might have been the source of at least some support for this placement.

The pharmacological treatment of acute vestibular syndrome.

Acute vestibular syndrome (AVS) represents a clinical picture that involves urgent management due to the important procession of symptoms accompanying the event, which can be positively or negatively influenced by therapeutic choices and intervention timing. This forces a differential diagnosis and therapeutic choices to be made in conditions that are not always favorable and often not in the specialist field. In this work, we will examine in detail the pharmacological therapeutic possibilities, correlating them to the differential and, as far as possible, to the etiological diagnosis. In particular, the pharmacological possibilities for the two main conditions we can face will be investigated, namely, vestibular neuritis and posterior circulation stroke.

Comparison between overlay and underlay primary myringoplasty: retrospective analysis on anatomical and functional results in 497 adult patients

PURPOSE: Retro-auricular approach using an autologous graft is the main surgical method for myringoplasty (MPL). Endaural and transcanal or endoscopic approaches are also used. There is no definitive consensus on the best MPL surgical technique. The aim of this study is to compare the two most used technique, over and underlay MPL, to evaluate the difference in anatomical and functional outcomes. MATERIALS AND METHODS: We made a retrospective analysis of 497 adult patients who underwent underlay or overlay primary MPL, between 2010 and 2018, and evaluated the difference in anatomical and functional outcomes. RESULTS: Successful functional results, evaluated 18 months after surgery, were obtained in 380 patients (76,4%); the underlay MPL obtained a successful result in 85% of patients, while the overlay technique in the 68%. We observed anatomical failure in 13.4% patients, in detail 9,8% of underlay MPL and 17,2% of overlay MPL had an anatomical failure. CONCLUSION: Our results show less complications related to the underlay technique. We believe that this remains the technique to prefer, except in subtotal or wide anterior perforations that could be better managed using the overlay technique.

Audiovestibular Disorders after COVID-19 Vaccine: Is There an Association?

The SARS-CoV-2 vaccination campaign is probably one of the most historic public hygiene measures in modern medicine. The drama of the pandemic has forced the scientific community to accelerate the development and commercialization of vaccines, thereby enhancing the phases of active surveillance. Among the adverse events following immunization (AEFI) reported, those of an audiovestibular interest, such as sudden sensorineural hearing loss (SSNHL), tinnitus, dizziness, and vertigo, constitute a very small percentage. There are many plausible etiological hypotheses, and scientific research needs to pay more attention to the correct collection of data, which up until now have often been inadequate and fragmented, on which to base future studies. SSNHL, new onset tinnitus, vertigo, and dizziness require a prompt evaluation, while the proposed treatment is the same as it is for events unrelated to vaccination. These are uncommon adverse events, and the risk rates for these diseases have not increased in conjunction with the COVID-19 vaccinations, therefore there is no justification of any hesitation towards the vaccination campaign.

Symptoms and clinical features in patients affected by endolymphatic sac tumor: a systematic review and meta-analysis.

PURPOSE: Most ELST data in the literature are case studies or limited to small cohorts (< 16 patients). We evaluated the main clinical signs observed at endolymphatic sac tumor (ELST) diagnosis in patients with or without Von Hippel-Lindau disease. METHODS: We conducted a comprehensive literature search in PubMed, Scopus, and Web of Science. We included studies with at least 1 patient, of any age, affected by sporadic or VHL-related ELSTs reporting levels of hearing loss and facial nerve function and a comprehensive description of presenting symptoms at ELST diagnosis. We combined data for proportional meta-analysis. p values of 0.05 were considered statistically significant. Methodological quality was evaluated. Analyses were performed with MedCalc 14.8.1 software. RESULTS: A total of 26 studies, including 113 patients and 118 cases of ELSTs were included. Pooled proportion rates (95% CI) of overall hearing loss was 88.7%, (82.4-93.4), severe hearing loss was 21.6% (12.8-32.1) profound hearing loss was 39.8% (28.7-51.5), vertigo/imbalance was 42.0% (33.8-50.5), tinnitus was 61.8% (53.4-69.8) and facial nerve palsy was 30.6% (23.2-38.9). Generally, symptoms were homogeneous or moderately heterogeneous among included studies. CONCLUSION: This is the first systematic review of clinical presentations at ELST diagnosis. The most serious clinical events include profound hearing loss and facial impairment. Fluctuating hearing loss, tinnitus and vertigo are frequently reported and may confound correct and prompt ELST diagnosis.

The Pharmacological Treatment of Pediatric Vertigo.

Vertigo in children is a challenging topic. The lack of dedicated trials, guidelines and papers causes inhomogeneity in the treatment of vertigo in children. Meniere's disease, migraine equivalents, vestibular neuritis, paroxysmal positional benign vertigo (BPPV), persistent postural-perceptual dizziness (PPPD) and motion sickness may affect children with various degrees of incidence and clinical severity compared to adults. Several drugs are proposed for the management of these conditions, even if their use is subordinated to the child's age. In this review, we summarize the existing evidence related to the use of drugs for this clinical condition in children as a start point for new trials, stating the urgent need for international guidelines.