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Suicide, one of the top causes of life lost in developed countries, is a major health problem, especially today, with the dramatic increase in mental health difficulties that was triggered during the Coronavirus pandemic (COVID-19). Opportunely, the recent emergence of internet-based crowdsourcing platforms (e.g., Amazon’s Mechanical Turk) may accelerate research on suicide prevention, however, this type of suicide research online involves a difficult ethical challenge: how to keep participants’ safe without compromising their privacy. To address this ethical challenge, a consortium of experts from multiple research institutions was assembled. The consortium discussed the advantages and disadvantages for participants involved in crowdsourcing-based studies that address suicide risk. This discussion resulted in a consensual step-by-step protocol for researchers who wish to conduct suicide research online, using the crowdsourcing platforms. This article provides a detailed description of the protocol and outlines key ethical arguments that led to its formulation. Unresolved issues are discussed as well and other researchers are encouraged to implement the proposed protocol and suggest further improvements. It is our hope that the current protocol will facilitate the research on large and diverse populations online and thus contribute to the global efforts to reduce suicide rates around the world.

Human craniofacial shape is highly variable yet highly heritable with numerous genetic variants interacting through multiple layers of development. Here, we hypothesize that Mendelian phenotypes represent the extremes of a phenotypic spectrum and, using achondroplasia as an example, we introduce a syndrome-informed phenotyping approach to identify genomic loci associated with achondroplasia-like facial variation in the general population. We compare three-dimensional facial scans from 43 individuals with achondroplasia and 8246 controls to calculate achondroplasia-like facial scores. Multivariate GWAS of the control scores reveals a polygenic basis for facial variation along an achondroplasia-specific shape axis, identifying genes primarily involved in skeletal development. Jointly modeling these genes in two independent control samples, both human and mouse, shows craniofacial effects approximating the characteristic achondroplasia phenotype. These findings suggest that both complex and Mendelian genetic variation act on the same developmentally determined axes of facial variation, providing insights into the genetic intersection of complex traits and Mendelian disorders. Vanneste et al. introduce a syndrome-informed approach to GWAS, identifying a polygenic basis for achondroplasia-like facial shape variation in the general population, and showing that complex traits and Mendelian disorders share genetic pathways. [ABSTRACT FROM AUTHOR]

Objective: To provide pooled analyses on the association between COVID-19 vaccine and the incidence of idiopathic sudden sensorineural hearing loss (ISSNHL). Data sources: "Medline" via "PubMed", "EMBASE", and "Google scholar". Review methods: Data sources were inspected from January 2020 to January 2024 using search terms relevant to vaccines for COVID-19. Included were papers with reported numbers of vaccinated populations and incidence if ISSNHL in those populations. Quality assessment was performed with the Newcastle–Ottawa Quality Assessment Scale Criteria. Results: Three publications encompassing more than 191.8 million patients and at least 283 million vaccine doses were included in the quantitative data synthesis. The pooled reported incidence (95%confidence interval) of ISSNHL among COVID-19 vaccine recipients was 1.2588 per 100,000 (0.1385–3.4836). This incidence is significantly lower than the incidence of 5–27 and 60 per 100,000/year reported in the United States and in the European Union, respectively (P < 0.0001). Conclusion: There is no evidence to indicate that the COVID-19 vaccine is associated with the incidence of ISSNHL. [ABSTRACT FROM AUTHOR]

Objective: Steroids given systemically, locally, or both are the mainstay of treatment for acute acoustic trauma (AAT). The overall recovery rate (full, partial, and none) is undetermined. Study design: Original case series and systematic literature review. Setting: Case series of a tertiary referral center and a systematic literature review. Methods: Cases of AAT between 2012 and 2022 were retrospectively analyzed for demographics, acoustic trauma characteristics, treatment modality and delay and prognosis. This case series was added to the series identified by a systematic literature review. This review included "Medline" via "PubMed", "EMBASE", and "Google scholar". All series were pooled for meta-analysis defining prognosis following steroidal treatment for AAT patients. Results: The pooled analyses included 662 ears, out of which 250 underwent complete recovery of hearing (overall proportion = 0.2809, 95%confidence interval [CI] = 0.1611–0.4178). Any recovery was recorded for 477 ears (overall proportion = 0.7185, 95% CI = 0.5671–0.8493) and no recovery was documented for 185 ears (overall proportion = 0.2815, 95% CI = 0.1507–0.4329). Conclusion: The rate of overall recovery for AAT is around 70%, and around 30% for full recovery when steroids are initiated within the first 2 weeks following the insult. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause for emergency department (ED) visits. Still, large scale studies that assess the management of AECOPD in the ED are limited. Our aim was to evaluate treatment characteristics of AE-COPD in the ED on a national scale. A prospective study as part of the COPD Israeli survey, conducted between 2017 and 2019, in 13 medical centers. Patients hospitalized with AECOPD were included and interviewed. Clinical data related to their ED and hospital stay were collected. 344 patients were included, 38% females, mean age of 70 ± 11 years. Median (IQR) time to first ED treatment was 59 (23–125) minutes and to admission 293 (173–490) minutes. Delayed ED treatment (> 1 h) was associated with older age (p = 0.01) and lack of a coded diagnosis of COPD in hospital records (p = 0.01). Long ED length-of-stay (> 5 h) was linked with longer hospitalizations (p = 0.01). Routine ED care included inhalations of short-acting bronchodilators (246 patients, 72%) and systemic steroids (188 patients, 55%). Receiving routine ED care was associated with its continuation during hospitalization (p < 0.001). In multivariate analysis, predictors for patients not receiving routine care were obesity (adjusted odds ratio 0.5, 95% CI 0.3–0.8, p = 0.01) and fever (AOR 0.3, 95% CI 0.1–0.6, p < 0.01), while oxygen saturation < 91% was an independent predictor for ED routine treatment (AOR 3.6, 95% CI 2.1–6.3, p < 0.01). Our findings highlight gaps in the treatment of AECOPD in the ED on a national scale, with specific predictors for their occurrence. [ABSTRACT FROM AUTHOR]

Background: Adults with bipolar disorder (BD) commonly present with cognitive deficits. Many also report subjective or perceived cognitive failures. For this study, we identified four distinct clusters of adults with BD on the basis of both BD symptoms (depression and hypo/mania) and perceived cognitive errors (i.e., forgetfulness, distractibility, false triggering). We hypothesized that participants reporting more BD symptoms and cognitive errors would report lower psychological well-being (i.e., self-efficacy, life scheme, life satisfaction). A second objective was to determine if and how clusters differed in terms of BD related factors (e.g., subtypes, sleep, medications) and sociodemographic differences such as age of participants. From the BADAS (Bipolar Affective Disorder and older Adults) Study, we identified 281adults with BD (M = 44.27 years of age, range 19–81), recruited via social media. Results: All clusters significantly differed across all grouping variables except symptoms of hypo/mania due to low frequency. Across clusters, perceived cognitive failures and BD symptoms increased in lockstep; that is, those reporting more cognitive errors also reported significantly higher symptoms of both depression and hypo/mania. As hypothesized, they also reported significantly lower psychological well-being. Conclusions: Age did not significantly differ across clusters in contrast to existing research in which cognitive loss is objectively measured. That is, perceived cognitive errors are significantly associated with lower psychological well-being for both young and older adults with BD. [ABSTRACT FROM AUTHOR]

Purpose: Temporal bone paraganglioma (TBP) are the most common tumors of the middle ear. They pose a challenge in otologic surgery due to their extensive vascularity and intricate location within the middle ear. This meta-analysis aimed to compare the safety and efficacy of two surgical approaches, microscopic middle ear surgery (MMES) and endoscopic middle ear surgery (EMES), in the resection of TBP. Methods: Eligible studies published after 1988 were identified through systematic searches of "PubMed", "Scopus" and "Google Scholar". Retrospective studies and randomized/non-randomized control trials reporting on surgical approaches for TBP with a minimum of five adult patients were included. Results: A total of 595 records were initially identified. After removing 229 duplicates, 349 articles were excluded based upon article subject, title and abstract. Following the review of full texts, 13 articles were assessed for eligibility. The pooled analysis included a total of 529 ears, with a complication rate of 7.8% for EMES and 14.2% for MMES. Subgroup differences indicated no significant variation between the two methods (p = 0.2945). Conclusion: Both EMES and MMES demonstrated favorable surgical outcomes with low complication rates for TBP resection. These findings suggest that EMES is a safe and effective method for TBP resection and one that is comparable to MMES. Since the risk of bleeding is significant in these tumors, a third-hand technique, endoscopic bipolar cautery or laser-assisted hemostasis should be considered. Conversion to MMES is another option when visibility is critically affected by bleeding. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

The brain is an intricate system that controls a variety of functions. It consists of a vast number of cells that exhibit diverse characteristics. To understand brain function in health and disease, it is crucial to classify neurons accurately. Recent advancements in machine learning have provided a way to classify neurons based on their electrophysiological activity. This paper presents a deep-learning framework that classifies neurons solely on this basis. The framework uses data from the Allen Cell Types database, which contains a survey of biological features derived from single-cell recordings from mice and humans. The shared information from both sources is used to classify neurons into their broad types with the help of a joint model. An accurate domain-adaptive model, integrating electrophysiological data from both mice and humans, is implemented. Furthermore, data from mouse neurons, which also includes labels of transgenic mouse lines, is further classified into subtypes using an interpretable neural network model. The framework provides state-of-the-art results in terms of accuracy and precision while also providing explanations for the predictions. [ABSTRACT FROM AUTHOR]

Determining the thermal profile of ignition is important because the desired ignition behavior varies with the objective. For example, extended ignition prolongs the time that the engine runs; however, fast ignition offers a higher power gain. The pollution caused by undesirable chemical reactions, as determined by the ignition profile, is another important aspect. Based on a previously developed method, we examined the impact of different theoretical particle size distributions (PSDs) on the thermal ignition profile. We compared different PSDs of polydispersed fuel spray with normal distributions with various means, each corresponding to the same fuel volume. Our results revealed a significant dependence of thermal ignition on the PSD. Systems that comprised only low-radius droplets did not reach ignition, whereas systems with only high-radius droplets required a long time to establish ignition. Moreover, the change in the mean droplet radius unexpectedly resulted in a double hump in the maximum temperature of the combustion process. [ABSTRACT FROM AUTHOR]

Mutational patterns caused by APOBEC3 cytidine deaminase activity are evident throughout human cancer genomes. In particular, the APOBEC3A family member is a potent genotoxin that causes substantial DNA damage in experimental systems and human tumors. However, the mechanisms that ensure genome stability in cells with active APOBEC3A are unknown. Through an unbiased genome-wide screen, we define the Structural Maintenance of Chromosomes 5/6 (SMC5/6) complex as essential for cell viability when APOBEC3A is active. We observe an absence of APOBEC3A mutagenesis in human tumors with SMC5/6 dysfunction, consistent with synthetic lethality. Cancer cells depleted of SMC5/6 incur substantial genome damage from APOBEC3A activity during DNA replication. Further, APOBEC3A activity results in replication tract lengthening which is dependent on PrimPol, consistent with re-initiation of DNA synthesis downstream of APOBEC3A-induced lesions. Loss of SMC5/6 abrogates elongated replication tracts and increases DNA breaks upon APOBEC3A activity. Our findings indicate that replication fork lengthening reflects a DNA damage response to APOBEC3A activity that promotes genome stability in an SMC5/6-dependent manner. Therefore, SMC5/6 presents a potential therapeutic vulnerability in tumors with active APOBEC3A. Synopsis: APOBEC3A is a prominent source of mutagenesis across many cancer types. This study defines a novel role of the SMC5/6 complex in maintaining genomic stability and viability of cancer cells in which APOBEC3A is active, revealing a potential therapeutic vulnerability. In the absence of functional SMC5/6, APOBEC3A activity results in genotoxic cell death SMC5/6 dysfunction augments APOBEC3A-mediated DNA damage during replication PrimPol generates single-strand DNA gaps upon APOBEC3A activity at replication forks SMC5/6 may play a critical role in maintaining genome stability during APOBEC3A activity by stabilization of replication forks containing single-strand DNA gaps Maintaining genome stability in the presence of active APOBEC3A involves SMC5/6-dependent stabilization of forks with single-strand gaps, suggesting a potential vulnerability of cancer cells. [ABSTRACT FROM AUTHOR]

The quality of romantic relationships can predict health consequences related to aging. DNA methylation-based biomarkers of aging accurately estimate chronological age. We developed several highly accurate epigenetic aging clocks, based on highly conserved mammalian CpGs, for the socially monogamous prairie vole (Microtus ochrogaster). In addition, our dual-species human-vole clock accurately measured relative age and illustrates high species conservation of epigenetic aging effects. Next, we assessed how pair bonding impacts epigenetic aging. We did not find evidence that pair-bonded voles exhibit accelerated or decelerated epigenetic aging effects in blood, ear, liver, or brain tissue. Our epigenome wide association study identified CpGs in five genes strongly associated with pair bonding: Foxp4, Phf2, Mms22l, Foxb1, and Eif1ad. Overall, we present accurate DNA methylation-based estimators of age for a species of great interest to researchers studying monogamy in animals. We did not find any evidence that sex-naive animals age differently from pair-bonded animals. [ABSTRACT FROM AUTHOR]

Purpose: Although considered contributors to idiopathic bronchiectasis (IB), neither dysphagia nor silent aspiration have been systematically evaluated in IB patients. We aimed to explore the prevalence of asymptomatic dysphagia and silent aspiration in IB patients and to identify parameters predictive of their presence. Methods: This prospective cohort study included IB patients from our Pulmonary Institute without prior history of dysphagia and without prior dysphagia workup. Swallowing function was assessed by the Eating Assessment Tool (EAT-10) questionnaire and by the Fiberoptic Endoscopic Evaluation of Swallowing (FEES) test. Results: Forty-seven patients (31 females, mean age 67 ± 16 years) were recruited. An EAT-10 score ≥ 3 (risk for swallowing problems) was present in 21 patients (44.6%). Forty-two patients (89.3%) had at least one abnormal swallowing parameter in the FEES test. Six patients (12.7%) had a penetration aspiration score (PAS) in the FEES of at least 6, indicating aspiration. An EAT-10 score of 3 was found to be the ideal cutoff to predict aspiration in the FEES, with a good level of accuracy (area under the curve = 0.78, 95% CI 0.629–0.932, p = 0.03) and sensitivity of 83%. This cutoff also showed a trend towards a more severe disease using the FACED (forced expiratory volume, age, colonization with pseudomonas, extension of lung involvement, dyspnea) score (p = 0.05). Conclusion: Dysphagia is prevalent in IB and may be undiagnosed if not specifically sought. We recommend screening all patients with IB for dysphagia by the EAT-10 questionnaire and referring all those with a score of ≥ 3 to formal swallowing assessment. [ABSTRACT FROM AUTHOR]

Background: Severe COVID-19, with the need in supplemental oxygen and hospitalization, leads to major burden on patients and healthcare systems. As a result, safe and effective ambulatory treatment strategies for severe COVID-19 are of urgent need. In this systematic review, we aimed to evaluate interventions to transition care to the ambulatory setting for patients with active severe COVID-19 that required supplemental oxygen. Methods: We searched Medline, Scopus, Web of Science, and DOAJ databases to identify articles with original data published until the 1st of April 2023. Characteristics and outcomes of interventions to transition care to home management were reviewed. Given the heterogeneous settings and outcomes studied, a meta-analysis was not performed. Results: Of the 235 studies identified, 11 observational studies, with 2645 patients, were included. The interventions were initiated from the emergency department, observation units or inpatient units, and included continuous home telemonitoring (n = 8), mobile applications (n = 2), and patient-initiated medical contact (n = 3). Included patients had an overall short length of hospital stay, high readmission rates, and positive patients' feedback. There was a lack of prospective controlled data and cost-effectiveness analyses. Conclusion: Our findings highlight the potential in treating severe COVID-19 at the ambulatory setting and the lack of high-quality data in this field. Dedicated medical teams, adjusted monitoring methods, improving clinical trajectory, and correct inclusion settings are needed for safe and effective transition of care. [ABSTRACT FROM AUTHOR]

Purpose: Blood culture obtainment prior to antibiotic administration, in patients with suspected infection, is considered the best practice in international guidelines. However, there is little data regarding the effect of a single dose of antibiotics on blood culture sterilization. Methods: We conducted a prospective study, enrolling consecutive patients with suspected infection, hospitalized in an internal medicine ward between December 2019 and January 2023. Included patients had a positive blood culture prior to antibiotic administration and a set of blood cultures taken within 24 h after a single dose of antibiotics. The rate of patients with pathogen isolation after antibiotic administration was assessed. Logistic regression was performed to examine factors associated with blood culture positivity. Results: A total of 155 patients were recruited for the study of which 131 (50.8% female 77.5 ± 13.4 years) met the inclusion criteria. The overall rate of patients with a positive blood culture after a single dose of antibiotics was 42.0% (55/131 patients). Increasing time between antibiotic administration and post-antibiotic culture was an independent predictor for blood culture sterilization (odds ratio 0.89 [95% confidence interval, 0.83–0.97; p = 0.006] for every 60 min). Blood culture volume was an independent predictor for blood culture positivity in a sensitivity analysis which included 82 patients (OR = 1.26 [95% CI 1.03–1.57] for every 1 ml increase; p = 0.024). Conclusion: Blood culture positivity is reduced by antimicrobial therapy but remains high after a single dose of antibiotics. If cultures are not obtained prior to antibiotic administration, they should be obtained as soon as possible afterwards. [ABSTRACT FROM AUTHOR]

Let ρ : G → GL 2 (K) be a continuous representation of a compact group G over a complete discretely valued field K with ring of integers O and uniformiser π . We prove that tr ρ is reducible modulo π n if and only if ρ is reducible modulo π n . More precisely, there exist characters χ 1 , χ 2 : G → (O / π n O) × such that det (t - ρ (g)) ≡ (t - χ 1 (g)) (t - χ 2 (g)) (mod π n) for all g ∈ G , if and only if there exists a G-stable lattice Λ ⊆ K 2 such that Λ / π n Λ contains a G-invariant, free, rank one O / π n O -submodule. Our result applies in the case that ρ is not residually multiplicity-free, in which case it answers a question of Bellaïche and Chenevier (J Algebra 410:501–525, 2014, pp. 524). As an application, we prove an optimal version of Ribet's lemma, which gives a condition for the existence of a G-stable lattice Λ that realises a non-split extension of χ 2 by χ 1 . [ABSTRACT FROM AUTHOR]

In this study, we examined a mathematical model of breast cancer (BC) treatment that combines an oral oestrogen receptor inhibitor, AZD9496 with Palbociclib, a selective inhibitor of cyclin- dependent kinases CDK4 and CDK6. Treatment is described by analytical functions that enable us to control the dosage and time interval of the treatment, thus personalising the treatment for each patient. Initially, we investigated the effect of each treatment separately, and finally, we investigated the combination of both treatments. By applying numerical simulations, we confirmed that the combination of AZD9496 with palbociclib was the optimal treatment for BC. The dosage of AZD9496 increased and decreased throughout the treatment period, while the intervals were constant between treatments. Palbociclib changed almost cyclically, whereas the time intervals remained constant. To investigate the mathematical model, we applied the singularly perturbed homotopy analysis method, which is a numerical algorithm. The significant advantage of this method is that the mathematical model does not have to contain a small parameter (as is standard in perturbation theory). However, it is possible to artificially introduce a small parameter into the system of equations, making it possible to study the model using asymptotic methods. [ABSTRACT FROM AUTHOR]

Suicide, one of the top causes of life lost in developed countries, is a major health problem, especially today, with the dramatic increase in mental health difficulties that was triggered during the Coronavirus pandemic (COVID-19). Opportunely, the recent emergence of internet-based crowdsourcing platforms (e.g., Amazon's Mechanical Turk) may accelerate research on suicide prevention, however, this type of suicide research online involves a difficult ethical challenge: how to keep participants' safe without compromising their privacy. To address this ethical challenge, a consortium of experts from multiple research institutions was assembled. The consortium discussed the advantages and disadvantages for participants involved in crowdsourcing-based studies that address suicide risk. This discussion resulted in a consensual step-by-step protocol for researchers who wish to conduct suicide research online, using the crowdsourcing platforms. This article provides a detailed description of the protocol and outlines key ethical arguments that led to its formulation. Unresolved issues are discussed as well and other researchers are encouraged to implement the proposed protocol and suggest further improvements. It is our hope that the current protocol will facilitate the research on large and diverse populations online and thus contribute to the global efforts to reduce suicide rates around the world. [ABSTRACT FROM AUTHOR]

Objectives: To question the value of drilling the site of the stalk ("insertion site" or "stalk" drilling) of a pedunculated external auditory canal osteoma (EACO) in reducing recurrence. Data sources: A retrospective medical chart review of all patients treated for EACO in one tertiary medical center, a systematic literature review using Medline via "PubMed", "Embase", and "Google scholar" search, and a meta-analysis of the proportion for recurrence of EACO with and without drilling. Results: The local cohort included 19 patients and the EACO origin was the anterior EAC wall in 42% and the superior EAC wall in 26%. The most common presenting symptoms were aural fullness and impacted cerumen (53% each), followed by conductive hearing loss (42%). All patients underwent post-excision canaloplasty, and one sustained EACO recurrence. Six studies suitable for analysis were identified (63 EACOs). Hearing loss, aural fullness, otalgia, and cerumen impaction were the most common clinical presentations. The most common EACO insertion site was the anterior EAC wall (37.5%), followed by the superior EAC and posterior walls (25% each). The inferior EAC wall was least affected (12.5%). There was no significant difference in recurrence between EACOs whose stalk insertions were drilled (proportion 0.09, 95% confidence interval [CI] 0.01–0.22) to the ones whose insertion was not drilled (proportion 0.05, 95% CI 0.00–0.17). The overall recurrence proportion was 0.07 (95% confidence interval 0.02–0.15). Conclusion: EACO insertion site drilling does not reduce recurrence and should be avoided in the absence of a definite pedicle projecting to the EAC lumen. [ABSTRACT FROM AUTHOR]

Gtf2i encodes the general transcription factor II-I (TFII-I), with peak expression during pre-natal and early post-natal brain development stages. Because these stages are critical for proper brain development, we studied at the single-cell level the consequences of Gtf2i's deletion from excitatory neurons, specifically on mitochondria. Here we show that Gtf2i's deletion resulted in abnormal morphology, disrupted mRNA related to mitochondrial fission and fusion, and altered autophagy/mitophagy protein expression. These changes align with elevated reactive oxygen species levels, illuminating Gtf2i's importance in neurons mitochondrial function. Similar mitochondrial issues were demonstrated by Gtf2i heterozygous model, mirroring the human condition in Williams syndrome (WS), and by hemizygous neuronal Gtf2i deletion model, indicating Gtf2i's dosage-sensitive role in mitochondrial regulation. Clinically relevant, we observed altered transcript levels related to mitochondria, hypoxia, and autophagy in frontal cortex tissue from WS individuals. Our study reveals mitochondrial and autophagy-related deficits shedding light on WS and other Gtf2i-related disorders. A neurobiological study reveals Gtf2i's pivotal roles in brain development and mediating neuronal mitochondrial function, validated by human brain samples derived from individuals with Williams syndrome. [ABSTRACT FROM AUTHOR]

Acceptance and commitment therapy (ACT) was found to be effective with a diverse range of clinical conditions. The aim of this study is to evaluate the efficacy of ACT-based treatment for individuals with tinnitus. Meta-analysis of the scientific literature of Medline via PubMed, EMBASE, Web of Science and Google Scholar. The meta-analysis included 3 studies. The pooled mean difference in the Tinnitus Handicap Inventory (THI) score was 17.67 points lower [95% CI (− 23.50) to (− 11.84)] for the intervention arm compared to the non-treated control arm. The significant clinical reduction in the THI score indicates that ACT is an effective treatment for tinnitus. [ABSTRACT FROM AUTHOR]

Medical follow-up of symptomatic patients after acute Coronavirus Disease 2019 (COVID-19) results in major burdens on patients and healthcare systems. The value of serological markers as part of this follow-up remains undetermined. We aimed to evaluate the clinical implications of serological markers for follow-up of acute COVID-19. For this purpose, we conducted an observational cohort study of patients 3 months after acute COVID-19. Participants visited a respiratory-clinic between October 2020 and March 2021, and completed pulmonary function tests (PFTs), serological tests, symptom-related questionnaires, and chest CT scans. Overall, 275 patients were included at a median of 82 days (IQR 64–111) post infection. 162 (59%) patients had diffusing capacity for carbon monoxide corrected for hemoglobin (DLCOc) below 80%, and 69 (25%) had bilateral chest abnormalities on CT scan. In multivariate analysis, anti-S levels were an independent predictor for DLCOc (β = − 0.14, p = 0.036). Anti-S levels were also associated with severe COVID-19 and older age, and correlated with anti-nucleocapsid (r = 0.30, p < 0.001) and antibodies to receptor binding domain (RBD, r = 0.37, p < 0.001). Other serological variables were not associated with clinical outcomes. In conclusion, symptomatic patients 3-months after COVID-19 had high respiratory symptomatic burden, in which anti-S levels were significantly associated with previous severe COVID-19 and DLCOc. [ABSTRACT FROM AUTHOR]

Holter electrocardiography (ECG) assists in the diagnosis of arrhythmias. Its use in the inpatient setting has been described solely for the evaluation of stroke and syncope. Our aim was to assess its diagnostic value for other conditions in the internal medicine department. We included all hospitalized patients between 2018 and 2021 in a tertiary referral center. The primary outcome was a diagnostic Holter recording a new arrhythmia that led to a change in treatment. Overall, 289 patients completed a 24-h inpatient Holter ECG for conditions other than syncope or stroke, with 39 (13%) diagnostic findings. The highest diagnostic value was found in patients admitted for pre-syncope (19%), palpitations (18%), and unexplained heart failure exacerbation/dyspnea (17%). A low diagnostic yield was found for the evaluation of chest pain (5%). Heart failure with preserved ejection fraction (adjusted OR 2.3, 95% CI 1.1–5.4, p = 0.04), and baseline ECG with either a bundle branch block (AOR 4.2, 95% CI 1.9–9.2, p < 0.01) or atrioventricular block (first or second degree, AOR 5, 95% CI 2.04–12.3, p < 0.01) were among the independent predictors for a diagnostic test. Inpatient Holter ECG monitoring may have value as a diagnostic tool for selected patients with conditions other than syncope or stroke. [ABSTRACT FROM AUTHOR]

Objective: To study the association between neurovascular conflict (NVC) of the 8th cranial nerve (CN8) and unilateral sudden sensorineural hearing loss SSNHL (SSNHL). Methods: A systematic literature search of "MEDLINE" via "PubMed," "Embase," and "Google-Scholar" was conducted. Meta-analysis of pooled data was performed for NVC prevalence of SSNHL affected ears versus controls. Results: The literature search identified 941 publications, of which, 9 included in qualitative synthesis (1030 ears) and 5 in quantitative synthesis (484 ears). NVC was as prevalent as 0.8–69% for affected ears and as 19–57% for controlled ears. No association between MRI protocol and NVC prevalence was proved. An odds ratio of 1.05 (95% confidence interval = 0.79–1.39) was calculated for association of NVC in unilateral SSNHL ears versus controls. Conclusion: The prevalence of NVC of CN8 in unilateral SSNHL affected ears is not significantly bigger than controls. Hence, NVC of CN8 is probably NOT associated with unilateral SSNHL. Level of evidence: 1 [ABSTRACT FROM AUTHOR]

Aim: Implementing genetic analyses have unraveled rare alterations causing early-onset obesity and complications, in whom treatment is challenging. We aimed to report on the effects of adjuvant off-label therapy with liraglutide, glucagon-like peptide-1 analogue (GLP-1a), in rare genetic diagnoses. Methods: Case scenarios and review of the literature. Results: Case 1: Nine-year-old boy with early-onset severe obesity and nonalcoholic fatty liver disease (NAFLD) due to a homozygous mutation in the MC4R gene deteriorated under lifestyle change and metformin therapy [at 10.5 years: body mass index (BMI) 51.2kg/m2, 226% of the 95th percentile, fat percentage (FP) 65% and muscle-to-fat ratio (MFR) z-score of −2.41]. One year of liraglutide treatment halted progressive weight gain [BMI 50.3kg/m2, 212% of the 95th percentile, 63.7% FP and MFR z-score of −2.34], with biochemical improvement. Case 2: Twelve-year-old boy with obesity presented with diabetes and progressive NAFLD. Exome analysis revealed two heterozygous mutations compatible with monogenic diabetes (HNF1A) and familial hypercholesterolemia (LDLR). Lifestyle modifications resulted in clinical and laboratory improvement (BMI 87th percentile, 32.8% FP, MFR z-score of −1.63, HbA1c 5.5%) without the expected recovery in liver transaminases. Liraglutide treatment augmented the improvement in weight status (BMI 68th percentile, 22.6% FP, MFR z-score of −1.13) with normalization of liver transaminases. Case 3: Nineteen-year-old male with spinal muscular atrophy type 3 presented with sarcopenic obesity and comorbidities. Treatment strategy included dietary counseling and multiple drug therapies (metformin, anti-hypertensive and statins). Liraglutide therapy led to a gradual recovery of metabolic complications allowing tapering-down other medications. Conclusions: Considering the pleiotropic effects of GLP1-a beyond BMI reduction, this treatment modality may serve as a game changer in challenging cases. [ABSTRACT FROM AUTHOR]

Intracellular pH dynamics is increasingly recognized to regulate myriad cell behaviors. We report a finding that intracellular pH dynamics also regulates adult stem cell lineage specification. We identify an intracellular pH gradient in mouse small intestinal crypts, lowest in crypt stem cells and increasing along the crypt column. Disrupting this gradient by inhibiting H+ efflux by Na+/H+ exchanger 1 abolishes crypt budding and blocks differentiation of Paneth cells, which are rescued with exogenous WNT. Using single-cell RNA sequencing and lineage tracing we demonstrate that intracellular pH dynamics acts downstream of ATOH1, with increased pH promoting differentiation toward the secretory lineage. Our findings indicate that an increase in pH is required for the lineage specification that contributes to crypt maintenance, establishing a role for intracellular pH dynamics in cell fate decisions within an adult stem cell lineage. Myriad extracellular and intracellular cues regulate stem cell fate choice. Here, Liu et al. report intracellular pH dynamics as a previously unrecognized regulator to selectively mediate the secretory cell fate decision of the intestinal stem cell. [ABSTRACT FROM AUTHOR]

Objectives: To identify the earliest sites and spread patterns of bony erosions on high-resolution temporal bone computerized tomographic (HRTBCT) scans and conjugate the radiological findings with clinical/laboratory data for guiding the interpretation of CT images of skull base osteomyelitis (SBOM) from malignant otitis externa (MOE). Study design: Retrospective and prospective medical records analysis. Methods: The medical records of all patients who presented to a referral medical center during 2015–2022 and initially diagnosed with SBOM. Radiological assessment of each sub-site was performed by 2 qualified neuro-radiologist, who were blind to the clinical data. Results: 33 patients were enrolled. All patients suffered edema and exudates of the external auditory canal (EAC). The most common osseous markers for SBOM were dehiscence or irregularity of the anterior EAC wall and temporomandibular joint (TMJ) medial wall (21/33, 64% patients, each), followed by a fistula from the TMJ to the EAC (20/33, 61% patients). Eustachian tube bony walls and condylar irregularity and/or dehiscence were as prevalent as 16/33, 48% of patients, each. EAC inferior and posterior walls of the EACs were irregular or dehiscent in patients with more advanced disease. Conclusions: The high symptomatologic overlap between SBOM and other aural pathologies might cause diagnostic (and subsequent treatment) delay and result in dire complications. EAC edema and irregularity or dehiscence of the anterior EAC wall are the most common early CT findings associated with SBOM caused by MOE. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Abstract The state of the transcriptome reflects a balance between mRNA production and degradation. Yet how these two regulatory arms interact in shaping the kinetics of the transcriptome in response to environmental changes is not known. We subjected yeast to two stresses, one that induces a fast and transient response, and another that triggers a slow enduring response. We then used microarrays following transcriptional arrest to measure genome‐wide decay profiles under each condition. We found condition‐specific changes in mRNA decay rates and coordination between mRNA production and degradation. In the transient response, most induced genes were surprisingly destabilized, whereas repressed genes were somewhat stabilized, exhibiting counteraction between production and degradation. This strategy can reconcile high steady‐state level with short response time among induced genes. In contrast, the stress that induces the slow response displays the more expected behavior, whereby most induced genes are stabilized, and repressed genes are destabilized. Our results show genome‐wide interplay between mRNA production and degradation, and that alternative modes of such interplay determine the kinetics of the transcriptome in response to stress.

Purpose: The safety of drainless lateral neck dissection (ND) remains to be proven. Hereby, we describe outcomes of drainless ND using fibrin sealant (FS). Methods: A retrospective, single academic institute, matched cased control. The study group included patients who underwent drainless ND (drainless group), matched to control patients by age, sex, body mass index, laterality and median number of levels dissected. Additional comparison of patients who underwent at least II–IV lateral ND for a thyroid cancer indication was also conducted. Outcomes were post-operative seroma\infections. Results: A total of 118 patients (42 cases and 76 controls) were included in the study. Groups did not differ in pre-operative characteristics, percentage of bilateral ND, and extension of ND. No significant difference was found in terms of post-operative infections, seroma, aspirations, and post-operative antibiotic use. The additional analysis included 23 drainless lateral ND and matched controls, of which 91% underwent concomitant level V dissection. No significant difference was found in terms of post-operative seroma or infection. These findings were confirmed with a multivariate analysis. Conclusions: Drainless ND using FS in non-violating mucosa surgeries appears to be feasible and safe, without significantly increasing post-operative seroma and its associated complications. [ABSTRACT FROM AUTHOR]

Purpose: Women carriers of FMR1 premutation are at increased risk of early ovarian dysfunction and even premature ovarian insufficiency. The aim of this study was to examine a possible association between FMR1 permutation and numeric sex chromosome variations. Methods: A retrospective case-control study conducted in the reproductive center of a university-affiliated medical center. The primary outcome measure was the rate of sex chromosomal numerical aberrations, as demonstrated by haplotype analyses, in FMR1 premutation carriers compared to X-linked preimplantation genetic testing for monogenic/single gene defect (PGT-M) cycles for other indications that do not affect the ovarian follicles and oocytes. Results: A total of 2790 embryos with a final genetic analysis from 577 IVF PGT-M cycles were included in the final analysis. Mean age was similar between the groups, however, FMR1 carriers required more gonadotropins, and more women were poor responders with three or less oocytes collected. The ratio of embryos carrying a numeric sex chromosome variation was similar: 8.3% (138/1668) of embryos in the FMR1 group compared to 7.1% (80/1122) in the controls. A subgroup analysis based on age and response to stimulation has not demonstrated a significant difference either. Conclusions: Although carriers of FMR1 premutation exhibit signs of reduced ovarian response, it does not seem to affect the rate of numeric sex chromosomal variation compared to women undergoing PGT-M for other indications. This suggests that the mechanism for chromosomal number aberrations in women at advanced maternal age are different to those FMR1 premutation carriers with poor ovarian reserve. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of with tympanostomy tubes (TT) on infrared tympanic membrane thermometer (ITMT) results and to provide a systematic review of ITMT results in non-naïve tympanic membranes. Study design: Original prospective blinded case series and systematic literature review. Settings: A single tertiary university-affiliated medical center. Methods: ITMT measurements of patients with unilateral TT and contralateral naïve control ear were randomly conducted by a single investigator blinded to the TT side before and after cerumen was removed from the external auditory canals. A systematic literature search of "MEDLINE" via "PubMed," "Embase," and "Google Scholar" on comparable published cases was performed. Results: The mean paired differences (95% confidence interval [CI]) between ventilated and non-ventilated ears before and after cerumen removal were 0.08 ºC/0.14 ºF (−0.04 to 0.19 ºC/− 0.07º–0.34º) and 0.62 ºC/1.12 ºF (0.04–0.25 ºC/0.07–0.45 ºF), respectively (P < 0.001 and P = 0.01, respectively). Conclusion: These findings support the validity and accuracy of ITMT in the setting of ventilated ears. [ABSTRACT FROM AUTHOR]

The contemporary parenting challenge of regulating children's screen time became even more difficult during the coronavirus pandemic (COVID-19). The current research addresses the characteristics of this challenge and explores mothers' perceptions regarding their children's screen use, through two consecutive studies. Study 1 included 299 mothers of elementary school children, who were asked to complete questionnaires regarding their children's screen habits. Mothers were also asked about their own attitudes towards screens, as parents, and about their personal feelings of frustration and guilt. Study 2 replicated this procedure among a new sample of 283 mothers who also completed validated scales assessing their sense of parental competence and authority style. Retrospective reports of mothers indicated that, during the lockdown, entertainment use of screens increased by 73% among 4th–6th graders and by 108% among 1st–3rd graders. Educational use increased by 86% in both age groups. Mothers' guilt increased as well and was predicted by children's entertainment use (but not educational use), after accounting for demographic variables and mothers' attitudes. Other factors, such as parenting style and having at-least one child with a diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD), were associated with entertainment use (regardless of the COVID-19 lockdown). Factors that were found to moderate the lockdown effect were mothers' attitudes towards screens and parental confidence. The findings are discussed in the context of parents' efforts to regulate their children's screen use. Highlights: Children's screen time is a major parenting challenge today. Children's screen use for entertainment and educational purposes increased during the COVID-19 pandemic. Mothers' guilt also increased but was associated only with entertainment use of screens. The increase in entertainment use was moderated by mothers' attitudes and parental confidence. Parents may derive insights from this study regarding their own parental approach. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the impact of eustachian tube (ET) function (ETF) on therapeutic success on candidates for intra-tympanic administration of steroids (ITAoS), due to idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: Medical chart review in two university-affiliated medical centers was performed. Included were consecutive adult patients diagnosed with unilateral ISSNHL between 2012 and 2019 who were treated with ITAoS due to incomplete or no recovery following systemic steroidal therapy. ETF was assessed by means tympanometry, before the initiation of ITAoS. The cohort was divided into an ET dysfunction group (ETD(+)) and a functioning ET group (control: ETD(−)). The audiologic response to treatment was recorded at the last follow-up. Results: A total of 64 suitable patients [median (interquartile, IQR) age 49 (38–63) years] were enrolled. The ETD(+) group included 20 patients and the remaining 44 patients served as controls. Demographic and clinical parameters were not significantly different between the two groups at presentation. Hearing thresholds were improved significantly better, at frequencies 250, 500, 1, 2, 4, and 8 kHz (p = 0.001–0.040) in the ETD(+) group. Conclusion: ETD(+) is associated with better efficacy of ITAoS. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Although much has been written on the topic of social behavior, many terms referring to different aspects of social behavior have become inappropriately conflated and the specific mechanisms governing them remains unclear. It is therefore critical that we disentangle the prosocial and antisocial elements associated with different forms of social behavior to fully understand the social brain. The lateral septum (LS) mediates social behaviors, emotional processes, and stress responses necessary for individuals to navigate day-to-day social interactions. The LS is particularly important in general and selective prosocial behavior (monogamy) but its role in how these two behavioral domains intersect is unclear. Here, we investigate the effects of chemogenetic-mediated LS activation on social responses in male prairie voles when they are 1) sex-naïve and generally affiliative and 2) after they become pair-bonded and display selective aggression. Amplifying neural activity in the LS augments same-sex social approach behaviors. Despite partner preference formation remaining unaltered, LS activation in pair-bonded males leads to reduced selective aggression while increasing social affiliative behaviors. These results suggest that LS activation alters behavior within certain social contexts, by increasing sex-naïve affiliative behaviors and reducing pair bonding-induced selective aggression with same-sex conspecifics, but not altering bonding with opposite-sex individuals. Selective DREADD-mediated activation of the lateral septum reveals its importance in enabling male prairie voles to adjust selective and nonselective social behavior to account for important life-history shifts linked with reproductive success. [ABSTRACT FROM AUTHOR]

The Wolffian ducts (WD) are paired epithelial tubules central to the development of the mammalian genitourinary tract. Outgrowths from the WD known as the ureteric buds (UB) generate the collecting ducts of the kidney. Later during development, the caudal portion of the WD will form the vas deferens, epididymis and seminal vesicle in males, and will degenerate in females. While the genetic pathways controlling the development of the UB are firmly established, less is known about those governing development of WD portions caudal to the UB. Sprouty proteins are inhibitors of receptor tyrosine kinase (RTK) signaling in vivo. We have recently shown that homozygous mutation of a conserved tyrosine (Tyr53) of Spry1 results in UB defects indistinguishable from that of Spry1 null mice. Here, we show that heterozygosity for the Spry1 Y53A allele causes caudal WD developmental defects consisting of ectopically branched seminal vesicles in males and persistent WD in females, without affecting kidney development. Detailed analysis reveals that this phenotype also occurs in Spry1+/– mice but with a much lower penetrance, indicating that removal of tyrosine 53 generates a dominant negative mutation in vivo. Supporting this notion, concomitant deletion of one allele of Spry1 and Spry2 also recapitulates the genital phenotype of Spry1Y53A/+ mice with high penetrance. Mechanistically, we show that unlike the effects of Spry1 in kidney development, these caudal WD defects are independent of Ret signaling, but can be completely rescued by lowering the genetic dosage of Fgf10. In conclusion, mutation of tyrosine 53 of Spry1 generates a dominant negative allele that uncovers fine-tuning of caudal WD development by Sprouty genes. [ABSTRACT FROM AUTHOR]

Objectives: To report adverse events (AEs) associated with systemic steroid treatment in idiopathic sudden sensorineural hearing loss (ISSNHL). Material and methods: A retrospective chart review of consecutive patients newly diagnosed with ISSNHL necessitating systemic steroidal treatment was conducted from 1/2017 to 2/2021. Blood pressure (BP) was monitored three times daily and morning fasting glucose was monitored once daily during treatment. An AE was defined as a fasting blood glucose level > 160 mg/dl, systolic BP > 80 mmHg, and diastolic BP > 100 mmHg. Results: In total, 143 patients were enrolled [69 (48%) males and 74 (52%) females] of whom 29 (20%) had diabetes mellitus (DM) and 46 (32%) had hypertension (HTN). The cohort's median age (interquartile range) was 58 (37–69) years. Fifty-three patients (37%) did not complete the oral steroidal treatment due to any AE (glycemic or hypertensive). Background DM highly correlated with increased risk of a glycemic event (0.59 vs. 0.13 for diabetic and non-diabetic patients, respectively, P < 0.001). HTN correlated significantly with increased risk of an overall AE (0.54 vs. 0.29 for hypertensive and non-hypertensive patients, respectively, P = 0.001). Neither pre-treatment BP nor glucose level predicted the risk of an AE (P = 0.310 and 0.521, respectively). Conclusions: AEs due to systemic steroidal treatment are common among ISSNHL patients. Demographic and baseline values cannot predict the risk of AEs which can occur throughout the entire duration of treatment. Patients with DM and HTN are at the greatest risk of AEs. Tight blood glucose and BP monitoring are recommended during treatment. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Objective: To date, there is no consensus about the benefits of paper patching over spontaneous healing in the management of isolated acute traumatic tympanic membrane perforations (IATTMP). In this systematic literature review and case series, we compared paper patching of IATTMP to spontaneous healing in terms of healing rate and time to heal. Databases reviewed: A systematic literature search of English-language studies published from 1/1975 to 9/2020 was conducted using PubMed via MEDLINE, and 201 studies were identified. Another 346 studies were derived from the references of those articles. Twenty-four studies remained after omitting duplications and articles that did not meet the inclusion criteria. Methods: Demographics, medical history, physical examination, and audiometric results in the selected publications and in a new series of patients treated for IATTMP between 1/2018 and 1/2021 in a single tertiary referral center were retrieved and analyzed. Results: The literature review yielded 2796 ears of which 466 underwent paper patching (intervention arm). Complete perforation healing was documented in 67–97% of control arm and 92–93% of intervention arm. Our new series included 29 ears of which six underwent paper patching. Complete healing was observed in 83% and 78% in the interventional and control arms, respectively. Conclusions: Although paper patching and watchful waiting had similar success rates in patients with IATTMP, healing after paper patching was slightly quicker among our patients. Patching is a readily applicable and technically simple office-based intervention that should be preferentially considered for IATTMP. [ABSTRACT FROM AUTHOR]

This correction notice addresses an error in the original publication of an article in the International Journal of Bipolar Disorders. The correction involves updating the affiliations of the authors Ophir Haglili and Ariel Pollock Star. The correct affiliations are now listed in this correction article, ensuring accuracy in the authorship details. [Extracted from the article]

In this study, we retrospectively evaluated the deviation from the planned axis of 3 Toric intraocular lenses (TIOL). Included in the study 190 eyes, operated by two surgeons using two different manual marking techniques. The patients were implanted with either AcrySof IQ Toric SN6AT (Alcon) (n = 90), POD FT (PhysIOL) (n = 50), or TECNIS Symfony Toric (J&J) (n = 50). At least 1 month postoperatively, the IOL was photographed, and the axis was measured using a designed software. The difference between the planned and actual axis was defined as axis deviation. The effect of IOL type, astigmatism direction, and marking techniques on the average degree and direction of the IOL deviation were evaluated and compared. There was no significant difference in the average deviation between the IOLs (TECNIS Symfony: 4.03° ± 4.34, POD FT: 3.52° ± 3.38, and SN6AT: 4.24° ± 4.10), and its direction (55.8%, 39.0%, and 56.6% clockwise (CW) deviation, respectively). With the rule, astigmatism had significantly more CW deviation compared with against the rule and oblique astigmatism (64.3%, 43.8%, and 41.7%, respectively, P = 0.027), but the average deviation was similar. The marking techniques did not influence the degree or direction of the deviation. [ABSTRACT FROM AUTHOR]

We propose exploiting symmetries (exact or approximate) of the Standard Model (SM) to search for physics Beyond the Standard Model (BSM) using the data-directed paradigm (DDP). Symmetries are very powerful because they provide two samples that can be compared without requiring simulation. Focusing on the data, exclusive selections which exhibit significant asymmetry can be identified efficiently and marked for further study. Using a simple and generic test statistic which compares two matrices already provides good sensitivity, only slightly worse than that of the profile likelihood ratio test statistic which relies on the exact knowledge of the signal shape. This can be exploited for rapidly scanning large portions of the measured data, in an attempt to identify regions of interest. We also demonstrate that weakly supervised Neural Networks could be used for this purpose as well. [ABSTRACT FROM AUTHOR]

The Hedgehog (HH) pathway is critical for development and adult tissue homeostasis. Aberrant HH signaling can lead to congenital malformations and diseases including cancer. Although cholesterol and several oxysterol lipids have been shown to play crucial roles in HH activation, the molecular mechanisms governing their regulation remain unresolved. Here, we identify Canopy4 (CNPY4), a Saposin-like protein, as a regulator of the HH pathway that modulates levels of membrane sterol lipids. Cnpy4–/– embryos exhibit multiple defects consistent with HH signaling perturbations, most notably changes in digit number. Knockdown of Cnpy4 hyperactivates the HH pathway in vitro and elevates membrane levels of accessible sterol lipids, such as cholesterol, an endogenous ligand involved in HH activation. Our data demonstrate that CNPY4 is a negative regulator that fine-tunes HH signal transduction, revealing a previously undescribed facet of HH pathway regulation that operates through control of membrane composition. Although lipids are known to affect Hedgehog (Hh) signalling, the underlying mechanisms remain unclear. Here, the authors show that Canopy4 regulates membrane sterol lipid levels, with knockout mouse embryos exhibiting digit number changes and other Hh signalling-related developmental defects. [ABSTRACT FROM AUTHOR]

Adult COVID-19 patients can present with acute muscle and/or cardiac involvement. Our study aims to describe the incidence and characteristics of patients with the co-occurrence of COVID-19 myopathy and inflammatory cardiac disease. We retrospectively reviewed all COVID-19 patients admitted to a large tertiary center to assess the co-occurrence of myopathy and inflammatory cardiac disease. We conducted a literature review of prior relevant case reports. There were three COVID-19 patients with concurrent involvement from our center and five cases in the published literature. Overall, mean age was 57.7 ± 16, four were females (50%) and only two patients (25%) had major relevant comorbidities. Muscle involvement included rhabdomyolysis or myositis and cardiac involvement included myocarditis or pericarditis. Most patients (75%) had no respiratory COVID-19 symptoms. Troponin and creatine phosphokinase levels were higher than twofold of the upper limit of normal for all patients. Steroids were used in the treatment of most patients (75%). All patients had a resolution or improvement of their extra-pulmonary involvement while two (25%) deteriorated due to COVID-19 pneumonia. The incidence for this co-occurrence is 0.07% among hospitalized COVID-19 patients. Patients with these rare COVID-19 simultaneous manifestations have distinct features. They are generally younger, present with extra-pulmonary symptoms and do not have severe respiratory compromise. An underdiagnosis causing treatment delay is possible. Further study is needed. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is a β-herpesvirus that increases morbidity and mortality in immunocompromised individuals including transplant recipients and newborns. New anti-HCMV therapies are an urgent medical need for diverse patient populations. HCMV infection of a broad range of host tissues is dependent on the gH/gL/gO trimer and gH/gL/UL28/UL130/UL131A pentamer complexes on the viral envelope. We sought to develop safe and effective therapeutics against HCMV by generating broadly-neutralizing, human monoclonal antibodies (mAbs) from VelocImmune® mice immunized with gH/gL cDNA. Following high-throughput binding and neutralization screening assays, 11 neutralizing antibodies were identified with unique CDR3 regions and a high-affinity (KD 1.4-65 nM) to the pentamer complex. The antibodies bound to distinct regions within Domains 1 and 2 of gH and effectively neutralized diverse clinical strains in physiologically relevant cell types including epithelial cells, trophoblasts, and monocytes. Importantly, combined adminstration of mAbs with ganciclovir, an FDA approved antiviral, greatly limited virus dissemination. Our work identifies several anti-gH/gL mAbs and sheds light on gH neutralizing epitopes that can guide future vaccine strategies. A panel of neutralizing human monoclonal antibodies targeting human cytomegalovirus offers a combination approach geared toward virus entry and replication to prevent viral dissemination. [ABSTRACT FROM AUTHOR]

Purpose: To characterize postoperative pain after tympanoplasty and tympanomastoidectomy and correlate between pain severity and various technical aspects of the surgery. Methods: We carried out a prospective cohort study of patients undergoing ear surgery in a tertiary referral center between 7/2018 and 7/2019. Patients filled in a pain questionnaire and scored pain intensity on a visual analog scale preoperatively and on postoperative days (POD) 1–4, 21, and 49. The responses were correlated with clinical and operative data, including surgical technique-related details. Results: Sixty-two patients participated in the study (27 males and 35 females, average age 41.1 ± 20.02 years [range 18–68]). The median preoperative VAS was 5, followed by 6 on POD1, 5 on POD3, and 1 at 3 and 9 weeks. The preoperative questionnaire score normalized to 10 was 4.5 (32/70), 5.1 on POD1, 4.7 on POD3, 0.85 at 3 weeks and 0.85 at 9 weeks. The predictive factors for increased postoperative pain were younger age, the presence of a comorbidity, revision surgery, preoperative dizziness or tinnitus and postoperative tinnitus. The predictive factors for decreased pain were smoking and the addition of a mastoidectomy. None of the factors related to the surgical technique (e.g., surgical approaches, type of reconstruction, specific surgeon) significantly affected the questionnaire responses or the pain VAS intensity scores. Conclusions: We demonstrated that younger age, the presence of a comorbidity, revision surgery, preoperative dizziness or tinnitus and postoperative tinnitus were predictors of increased pain after tympanoplasty and tympanomastoidectomy, while the inclusion of a mastoidectomy was a predictor of decreased pain. [ABSTRACT FROM AUTHOR]

Amid growing concern regarding the potential added burden of care due to population aging, we have very little understanding of what is the burden of care in aging populations. To answer this question, we introduce a novel metric that encompasses demographic complexity and social context to summarize unpaid family care work provided to children, elderly, and other family members across the life cycle at a population level. The measure (Care Life Expectancy), an application of the Sullivan method, estimates the number of years and proportion of adult life that people spend in an unpaid caregiving role. We demonstrate the value of the metric by using it to describe gender differences in unpaid care work in 23 European aging countries. We find that at age 15, women and men are expected to be in an unpaid caregiving role for over half of their remaining life. For women in most of the countries, over half of those years will involve high-level caregiving for a family member. We also find that men lag in caregiving across most countries, even when using the lowest threshold of caregiving. As we show here, demographic techniques can be used to enhance our understanding of the gendered implications of population aging, particularly as they relate to policy research and public debate. [ABSTRACT FROM AUTHOR]

Objective: To validate a smartphone-based Rinne test employing the vibration application of mobile telephones. Study design: Prospective controlled clinical study. Setting: Tertiary referral medical center. Methods: Twenty consecutive patients hospitalized in the otolaryngology department of a tertiary medical center due to unilateral hearing loss (HL study group), and 30 consecutive inpatients on the same ward who had no otological history (controls) were enrolled. Each participant underwent the traditional 512 Hz tuning fork-based Rinne test, as well as a smartphone-based Rinne test by means of a single uncovered smartphone with a vibration application. The test results were compared to those of formal audiometry. Results: The overall agreement between the traditional Rinne test and the smartphone-based test was 98%. The Sensitivity was 85% for both tests, specificity was 90% and 93% for smartphone and tuning fork tests, respectively. The smartphone-based Rinne test could correctly discriminate between patients with an air–bone gap ≥ 25 dB at 512 Hz from patients with a lower or no air–bone gap at 512 Hz. The smartphone-based Rinne could not evaluate two patients with a moderately severe/severe sensorineural hearing loss due to their inability to detect the vibrations. Conclusion: A smartphone-based Rinne test was validated for the detection of an air–bone gap ≥ 25 dB at 512 Hz in the clinical setting. The validity of patient-operated smartphone-based Rinne test awaits further study. Level of evidence: 2B. [ABSTRACT FROM AUTHOR]