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Objectives: This study investigated the effectiveness of a specialized manual physical therapy (PT) program at improving voice among patients diagnosed with concomitant muscle tension dysphonia (MTD) and cervicalgia at a tertiary care voice center., Materials and Methods: Cervicalgia was determined by palpation of the anterior neck. Both voice therapy (VT) and PT was recommended for all patients diagnosed with MTD and cervicalgia. PT included full-body manual physical therapy with myofascial release. Patients underwent: 1) VT alone, 2) concurrent PT and VT (PT with VT), 3) PT alone, 4) VT, but did not have PT ordered by treating clinician (VT without PT order) or 5) VT followed by PT (VT then PT). The pairwise difference in post-Voice Handicap Index-10 (VHI-10) controlling for baseline variables was calculated with a linear regression model., Results: 178 patients met criteria. All groups showed improvement with treatment. The covariate-adjusted differences in mean post-VHI-10 improvement comparing the VT alone group as a reference were as follows: PT with VT 9.95 (95% confidence interval 7.70, 12.20); PT alone 8.31 (6.16, 10.45); VT without PT order 8.51 (5.55, 11.47); VT then PT 5.47 (2.51, 8.42)., Conclusion: Among patients diagnosed with MTD with cervicalgia, treatment with a specialized PT program was associated with improvement in VHI-10 scores regardless of whether they had VT. While VT is the standard of care for MTD, PT may also offer benefit for MTD patients with cervicalgia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The Physical Therapy intervention in this study is a copyrighted program. Vanderbilt University Medical Center, 2013 with revisions 2019: All Rights Reserved. Created by co-author Carey A. Tomlinson, Physical Therapist for the Vanderbilt Dayani Center. All necessary permission was obtained for use of this program in this study.

The prognosis of uveal melanoma is significantly influenced by the risk of metastasis, which varies according to clinical and genetic features. Driver mutations can predict the likelihood of disease progression and survival, although the data in the literature are inconsistent. This meta-analysis aimed to evaluate the prognostic significance of driver mutations, including GNAQ , GNA11 , BAP1 , and SF3B1 , in the advancement of uveal melanoma. A comprehensive search of databases yielded relevant studies, and data from 13 studies (848 eyes) were synthesized to assess the impact of these mutations on metastasis-free survival. The BAP1 mutation and negative immunohistochemistry were associated with a higher risk of metastasis (logHR = 1.44, 95% CI 1.05-1.83). GNAQ , GNA11 , and SF3B1 mutations did not show a significant increase in risk. In summary, BAP1 has proven to reliably predict the likelihood of disease progression in uveal melanoma, while further studies are needed to establish the significance of other driver mutations.

Suicide is a leading cause of death among Black emerging adults. The concurrent effect of the COVID-19 pandemic and racial discrimination were projected to exacerbate suicide vulnerability for Black Americans. The purpose of the present study was to utilize a risk-resilience model to examine the effects of racial discrimination and COVID-related stress on suicide risk for Black emerging adults, as well as the moderating effect of three central components of radical healing: critical consciousness, resilience, and cultural authenticity. Study participants included 521 Black emerging adults between the ages of 18 and 29 (51.6% male; M age = 24.6, SD = 2.6) who completed measures evaluating symptoms of racial discrimination, COVID-related stress, suicide risk, and psychological well-being. After controlling for age, gender, socioeconomic status, and general stress, structural equation modeling analyses revealed unique and interactive effects of racial discrimination, COVID-related stress, and culturally relevant protective factors on suicide risk for Black emerging adults. These findings provide preliminary insight into novel risk and protective factors that influence suicide risk for Black emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The emergence of plant pathogens is often associated with waves of unique evolutionary and epidemiological events. Xanthomonas hortorum pv. gardneri is one of the major pathogens causing bacterial spot disease of tomatoes. After its first report in the 1950s, there were no formal reports on this pathogen until the 1990s, despite active global research on the pathogens that cause tomato and pepper bacterial spot disease. Given the recently documented global distribution of X. hortorum pv. gardneri , our objective was to examine genomic diversification associated with its emergence. We sequenced the genomes of X. hortorum pv. gardneri strains collected in eight countries to examine global population structure and pathways of emergence using phylodynamic analysis. We found that strains isolated post-1990 group by region of collection and show minimal impact of recombination on genetic variation. A period of rapid geographic expansion in X. hortorum pv. gardneri is associated with acquisition of a large plasmid conferring copper tolerance by horizontal transfer and coincides with the burgeoning hybrid tomato seed industry through the 1980s. The ancestry of X. hortorum pv. gardneri is consistent with introduction to hybrid tomato seed production and dissemination during the rapid increase in trade of hybrid seeds.

The mucosal surfaces of fish, including their intestines, gills, and skin, are constantly exposed to various environmental threats, such as water quality fluctuations, pollutants, and pathogens. However, various cells and microbiota closely associated with these surfaces work in tandem to create a functional protective barrier against these conditions. Recent research has shown that incorporating specific feed ingredients into fish diets can significantly boost their mucosal and general immune response. Among the various ingredients being investigated, insect meal has emerged as one of the most promising options, owing to its high protein content and immunomodulatory properties. By positively influencing the structure and function of mucosal surfaces, insect meal (IM) has the potential to enhance the overall immune status of fish. This review provides a comprehensive overview of the potential benefits of incorporating IM into aquafeed as a feed ingredient for augmenting the mucosal immune response of fish., Competing Interests: Declaration of competing interest The authors have no person relationship or financial interests that could appeared to the influence of work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: A small number of Idiopathic subglottic stenosis (iSGS) patients are treated at institutions across the country. Divergence in operative techniques for endoscopic dilation (ED) of iSGS has been anecdotally recognized but not formally characterized. Additionally, the relationship between procedural variation and clinical outcome has not been studied., Methods: Secondary analysis of the NoAAC iSGS 1000 cohort investigated variation in procedural techniques and treatment outcomes in patients treated with ED across high-enrolling treatment centers (enrolled >10 patients in PR-02 trial)., Results: Thirteen NoAAC centers each enrolled >10 patients treated with ED for a total of 281 subjects. There was significant variation in procedural details and rate of recurrence among institutions. Hierarchal cluster analysis revealed significant heterogeneity among institutions and clusters in all procedural variables. However, analysis demonstrated a transient delay in disease recurrence in cluster 2 which disappeared with longer longitudinal follow-up. Patient-reported outcome and peak expiratory flow data supported the potential benefit of the technical variation in Cluster 2. Distinct to cluster 2, however, was routine use of adjuvant triple medical therapy (proton pump inhibitor (PPI), antibacterial agent, and steroid inhaler)., Conclusions: Both outcome and procedural technique vary among centers employing ED to treat iSGS. A transient delay in recurrence was observed among centers that routinely prescribed adjuvant medical therapy (antibiotic, inhaled corticosteroid, and PPI) to iSGS patients after endoscopic dilation, which was further supported by patient-reported data and peak expiratory flow data. Prospective studies are needed to understand the effects of adjuvant medical therapy on recurrence after endoscopic dilation., Level of Evidence: 4 Laryngoscope, 134:3260-3266, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: Diagnosing pediatric induced laryngeal obstruction (ILO) requires equipment typically available in specialist settings, and patients often see multiple providers before a diagnosis is determined. This study examined the financial burden associated with the diagnosis and treatment of ILO in pediatric patients with reference to socioeconomic disadvantage., Methods: Adolescents and children (<18 years of age) diagnosed with ILO were identified through the University of Madison Voice and Swallow Outcomes Database. Procedures, office visits, and prescribed medications were collected from the electronic medical record. Expenditures were calculated for two time periods (1) pre-diagnosis (first dyspnea-related visit to diagnosis), and (2) the first year following diagnosis. The Area Deprivation Index (ADI) was used to estimate patient socioeconomic status to determine if costs differed with neighborhood-level disadvantage., Results: A total of 113 patients met inclusion criteria (13.9 years, 79% female). Total pre-diagnosis costs of ILO averaged $6486.93 (SD = $6604.14, median = $3845.66) and post-diagnosis costs averaged $2067.69 (SD = $2322.78; median = $1384.12). Patients underwent a mean of 3.01 (SD = 1.9; median = 2) procedures and 5.8 (SD = 4.7; median = 5) office visits prior to diagnosis. Pharmaceutical, procedure/office visit, and indirect costs significantly decreased following diagnosis. Patients living in neighborhoods with greater socioeconomic disadvantage underwent fewer procedures and were prescribed more medication than those from more affluent areas. However, total expenditures did not differ based on ADI., Conclusions: Pediatric ILO is associated with considerable financial costs. The source of these costs, however, differed according to socioeconomic advantage. Future work should determine how ILO diagnosis and management can be more efficient and equitable across all patients. Laryngoscope, 134:3384-3390, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST)., Methods: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications., Results: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m 2 ) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36)., Conclusion: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days., Level of Evidence: III Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Physiological disorders impact the yield and quality of marketable fruit in tomato. Puffy fruit caused by cavities inside the locule can be problematic for processing and fresh market quality. In this paper, we used a recombinant inbred line (RIL) and three derived processing tomato populations to map and validate quantitative trait loci (QTLs) for fruit puffiness across environments. Binary interval mapping was used for mapping the incidence of fruit puffiness, and non-parametric interval mapping and parametric composite interval mapping were used for mapping severity. Marker-trait regressions were carried out to validate putative QTLs in subsequent crosses. QTLs were detected on chromosome (Chr) 1, 2, and 4. Only the QTL on Chr 1 was validated in progeny from subsequent crosses. This QTL explained up to 22.5% of the variance in the percentage of puffy fruit, with a significant interaction between loci on Chr 2 and 4, increasing the percentage of puffy fruit by an additional 15%. The allele responsible for puffy fruit on Chr 1 was inherited from parent FG02-188 and was dominant towards increased incidence and severity. Marker-assisted selection (MAS) for the QTL on Chr 1 was as efficient as genomic selection (GS) in reducing the incidence and severity of puffy fruit, despite the potential contribution of other loci.

Purpose: To report a rare case of keratitis due to monkeypox infection., Methods: A 45-year-old male presented with an epithelial corneal ulcer 20 days following initial diagnosis of monkeypox from genital and perioral lesions. PCR analysis of the epithelium confirmed the presence of human monkeypox virus., Results: The patient was hospitalized, and ganciclovir gel, as well as povidone iodine 0.6% and moxifloxacin eyedrops were prescribed. Oral tecovirimat 600 mg was administered during 14 days. A therapeutic contact lens was used. Twenty days after the initial diagnosis of keratitis, the corneal defect closed leaving a faint subepithelial haze, and visual acuity was 0.8., Conclusions: This is an uncommon case report of epithelial keratitis due to human monkeypox. PCR positivity for monkeypox in the corneal epithelium confirmed the presence of viral material in the cornea.

Determining the macronutrient requirements for commercially valuable aquaculture species remains crucial for maximising production efficiency. Yet, such information is lacking for Australian hybrid abalone ( Haliotis rubra × Haliotis laevigata ), particularly with respect to life stage and water temperatures. The present study aimed to evaluate the effect of dietary protein inclusion level on the growth performance, nutrient utilisation and nutritional quality of juvenile (3·3 g) Australian hybrid abalone reared at three different temperatures representative of winter (12°C), average annual (17°C) and summer (22°C) grow-out periods and fed five diets containing graded dietary protein levels of 35, 38, 41, 44 and 47 %. Abalone growth increased with increasing water temperature with weight gains of approximately 100, 280 and 380 % of their initial weight at 12, 17 and 22°C, respectively. Furthermore, the present study clearly demonstrated that higher dietary protein inclusion levels (41 %) than those currently used commercially (35 %) would significantly improve the growth performance when water temperatures are ≥17°C without any adverse impacts on nutrient utilisation, nutrient deposition or nutritional quality of the abalone soft tissue. For example, at 22°C abalone fed a diet containing 41 % protein obtained a significantly higher weight gain percentage (421 %) compared with those fed a diet containing 35 % protein (356 %). Lastly, it is suggested that maintaining a dietary protein inclusion level of 35 % or implementing a 'least cost' feeding approach during cooler seasons, or where water temperatures are ∼12°C, may be beneficial, considering only marginal growth improvements were observed during these periods of slow growth.

Objectives: Thyroid cancer incidence increased over 200% from 1992 to 2018, whereas mortality rates had not increased proportionately. The increased incidence has been attributed primarily to the detection of subclinical disease, raising important questions related to thyroid cancer control. We developed the Papillary Thyroid Carcinoma Microsimulation model (PATCAM) to answer them, including the impact of overdiagnosis on thyroid cancer incidence., Methods: PATCAM simulates individuals from age 15 until death in birth cohorts starting from 1975 using 4 inter-related components, including natural history, detection, post-diagnosis, and other-cause mortality. PATCAM was built using high-quality data and calibrated against observed age-, sex-, and stage-specific incidence in the United States as reported by the Surveillance, Epidemiology, and End Results database. PATCAM was validated against US thyroid cancer mortality and 3 active surveillance studies, including the largest and longest running thyroid cancer active surveillance cohort in the world (from Japan) and 2 from the United States., Results: PATCAM successfully replicated age- and stage-specific papillary thyroid cancers (PTC) incidence and mean tumor size at diagnosis and PTC mortality in the United States between 1975 and 2015. PATCAM accurately predicted the proportion of tumors that grew more than 3 mm and 5 mm in 5 years and 10 years, aligning with the 95% confidence intervals of the reported rates from active surveillance studies in most cases., Conclusions: PATCAM successfully reproduced observed US thyroid cancer incidence and mortality over time and was externally validated. PATCAM can be used to identify factors that influence the detection of subclinical PTCs., Competing Interests: Author Disclosures Links to the disclosure forms provided by the authors are available here., (Copyright © 2024. Published by Elsevier Inc.)

In the first years of life, infants progressively develop attention selection skills to gather information from visually clustered environments. As young as newborns, infants are sensitive to the distinguished differences in color, orientation, and luminance, which are the components of visual saliency. However, we know little about how saliency-driven attention emerges and develops socially through everyday free-viewing experiences. The present work assessed the saliency change in infants' egocentric scenes and investigated the impacts of manual engagements on infant object looking in the interactive context of object play. Thirty parent-infant dyads, including infants in two age groups (younger: 3- to 6-month-old; older: 9- to 12-month-old), completed a brief session of object play. Infants' looking behaviors were recorded by the head-mounted eye-tracking gear, and both parents' and infants' manual actions on objects were annotated separately for analyses. The present findings revealed distinct attention mechanisms that underlie the hand-eye coordination between parents and infants and within infants during object play: younger infants are predominantly biased toward the characteristics of the visual saliency accompanying the parent's handled actions on the objects; on the other hand, older infants gradually employed more attention to the object, regardless of the saliency in view, as they gained more self-generated manual actions. Taken together, the present work highlights the tight coordination between visual experiences and sensorimotor competence and proposes a novel dyadic pathway to sustained attention that social sensitivity to parents' hands emerges through saliency-driven attention, preparing infants to focus, follow, and steadily track moving targets in free-flow viewing activities., Competing Interests: Declaration of competing interest All the authors have no conflict of interest or relationship, financial or otherwise., (Copyright © 2024. Published by Elsevier B.V.)

Neuromodulation through implantable pulse generators (IPGs) represents an important treatment approach for neurological disorders. While the field has observed the success of state-of-the-art interventions, such as deep brain stimulation (DBS) or responsive neurostimulation (RNS), implantable systems face various technical challenges, including the restriction of recording from a limited number of brain sites, power management, and limited external access to the assessed neural data in a continuous fashion. To the best of our knowledge, for the first time in this study, we investigated the feasibility of recording human intracranial EEG (iEEG) using a benchtop version of the Brain Interchange (BIC) unit of CorTec, which is a portable, wireless, and externally powered implant with sensing and stimulation capabilities. We developed a MATLAB/SIMULINK-based rapid prototyping environment and a graphical user interface (GUI) to acquire and visualize the iEEG captured from all 32 channels of the BIC unit. We recorded prolonged iEEG (~ 24 h) from three human subjects with externalized depth leads using the BIC and commercially available clinical amplifiers simultaneously in the epilepsy monitoring unit (EMU). The iEEG signal quality of both streams was compared, and the results demonstrated a comparable power spectral density (PSD) in all the systems in the low-frequency band (< 80 Hz). However, notable differences were primarily observed above 100 Hz, where the clinical amplifiers were associated with lower noise floor (BIC-17 dB vs. clinical amplifiers <  - 25 dB). We employed an established spike detector to assess and compare the spike rates in each iEEG stream. We observed over 90% conformity between the spikes rates and their spatial distribution captured with BIC and clinical systems. Additionally, we quantified the packet loss characteristic in the iEEG signal during the wireless data transfer and conducted a series of simulations to compare the performance of different interpolation methods for recovering the missing packets in signals at different frequency bands. We noted that simple linear interpolation has the potential to recover the signal and reduce the noise floor with modest packet loss levels reaching up to 10%. Overall, our results indicate that while tethered clinical amplifiers exhibited noticeably better noise floor above 80 Hz, epileptic spikes can still be detected successfully in the iEEG recorded with the externally powered wireless BIC unit opening the road for future closed-loop neuromodulation applications with continuous access to brain activity., (© 2024. The Author(s).)

Objective: To describe the development of a new position statement regarding balancing the risks and benefits of sun exposure for Australian adults., Methods: We conducted a Sun Exposure Summit in March 2021, with presentations from invited experts and a workshop including representation from academic, clinical, policy, and patient stakeholder organisations. The group considered advice about balancing the risks and benefits of sun exposure for Australian adults and developed a revised consensus position statement., Results: The balance of risks and benefits of sun exposure is not the same for everybody. For people at very high risk of skin cancer, the risks of exposure likely outweigh the benefits; sun protection is essential. Conversely, people with deeply pigmented skin are at low risk of skin cancer but at high risk of vitamin D deficiency; routine sun protection is not recommended. For those at intermediate risk of skin cancer, sun protection remains a priority, but individuals may obtain sufficient sun exposure to maintain adequate vitamin D status., Conclusions: The new position statement provides sun exposure advice that explicitly recognises the differing needs of Australia's diverse population., Implications for Public Health: Mass communication campaigns should retain the focus on skin cancer prevention. The new position statement will support the delivery of personalised advice., Competing Interests: Conflicts of interest David Whiteman reports a relationship with Pierre Fabre Australia that includes speaking and lecture fees. Peter Ebeling reports a relationship with Healthy Bones Australia that includes board membership. Peter Ebeling reports a relationship with the American Society for Bone and Mineral Research that includes board membership. Peter Ebeling reports a relationship with International Osteoporosis Foundation that includes: board membership. Peter Ebeling reports a relationship with the Asian Pacific Consortium on Osteoporosis that includes board membership. Craig Sinclair reports a relationship with Cancer Council Victoria that includes employment. Christian Girgis reports a relationship with the Australian and New Zealand Bone and Mineral Society that includes board membership. Christian Girgis reports a relationship with the University of Sydney that includes employment. Stephen Shumack reports a relationship with the Australasian College of Dermatologists that includes non-financial support., (Copyright © 2024. Published by Elsevier B.V.)

Scope: Tomato consumption is associated with many health benefits including lowered risk for developing certain cancers. It is hypothesized that tomato phytochemicals are transported to the liver and other tissues where they alter gene expression in ways that lead to favorable health outcomes. However, the effects of tomato consumption on mammalian liver gene expression and chemical profile are not well defined., Methods and Results: The study hypothesizes that tomato consumption would alter mouse liver transcriptomes and metabolomes compared to a control diet. C57BL/6J mice (n = 11-12/group) are fed a macronutrient matched diet containing either 10% red tomato, 10% tangerine tomato, or no tomato powder for 6 weeks after weaning. RNA-Seq followed by gene set enrichment analyses indicates that tomato type and consumption, in general, altered expression of phase I and II xenobiotic metabolism genes. Untargeted metabolomics experiments reveal distinct clustering between control and tomato fed animals. Nineteen molecular formulas (representing 75 chemical features) are identified or tentatively identified as steroidal alkaloids and isomers of their phase I and II metabolites; many of which are reported for the first time in mammals., Conclusion: These data together suggest tomato consumption may impart benefits partly through enhancing detoxification potential., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Objective: Idiopathic subglottic stenosis is a rare disease, and time to diagnosis is often prolonged. In the United States, some estimate it takes an average of 9 years for patients with similar rare disease to be diagnosed. Patient experience during this period is termed the diagnostic odyssey. The aim of this study is to use qualitative methods grounded in behavioral-ecological conceptual frameworks to identify drivers of diagnostic odyssey length that can help inform efforts to improve health care for iSGS patients., Methods: Qualitative study using semi-structured interviews. Setting consisted of participants who were recruited from those enrolled in a large, prospective multicenter trial. We use directed content analysis to analyze qualitative semi-structured interviews with iSGS patients focusing on their pathways to diagnosis., Results: Overall, 30 patients with iSGS underwent semi-structured interviews. The patient-reported median time to diagnosis was 21 months. On average, the participants visited four different health care providers. Specialists were most likely to make an appropriate referral to otolaryngology that ended in diagnosis. However, when primary care providers referred to otolaryngology, patients experienced a shorter diagnostic odyssey. The most important behavioral-ecological factors in accelerating diagnosis were strong social support for the patient and providers' willingness to refer., Conclusion: Several factors affected time to diagnosis for iSGS patients. Patient social capital was a catalyst in decreasing time to diagnosis. Patient-reported medical paternalism and gatekeeping limited specialty care referrals extended diagnostic odysseys. Additional research is needed to understand the effect of patient-provider and provider-provider relationships on time to diagnosis for patients with iSGS., Level of Evidence: 4 Laryngoscope, 134:815-824, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Critical genes involved in embryonic development are often transcription factors, regulating many downstream genes. LMX1B is a homeobox gene that is involved in formation of the limbs, eyes and kidneys, heterozygous loss-of-function sequence variants and deletions cause Nail-Patella syndrome. Most of the reported variants are localised within the gene's coding sequence, however, approximately 5%-10% of affected individuals do not have a pathogenic variant identified within this region. In this study, we present a family with four affected individuals across two generations with a deletion spanning a conserved upstream LMX1B-binding sequence. This deletion is de novo in the mother of three affected children. Furthermore, in this family, the manifestations appear limited to the nails and limbs, and therefore may reflect an attenuated phenotype of the classic Nail-Patella phenotype that includes ophthalmological and renal manifestations., (© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Objective: Idiopathic subglottic stenosis (iSGS) is a rare, recurrent, fibroinflammatory disease affecting the larynx and proximal trachea. Given it occurs primarily in adult females, estrogen is speculated to play a central pathophysiological role. This study aimed to evaluate relationships between estrogen exposure, disease progression, and recurrence., Methods: North American Airway Collaborative (NoAAC) data of adults with iSGS obstructive airway lesions, who underwent index endoscopic airway dilation, were used to identify associations between estrogen exposure, disease characteristics, and time to recurrence (TTR), and interventions were analyzed using Kruskal-Wallis test and Pearson coefficient. Cox proportional hazards regression models compared hazard ratios by estrogen exposure. Kaplan-Meier curves were plotted for TTR based on menopausal status., Results: In all, 533 females had complete estrogen data (33% premenopausal, 17% perimenopausal, 50% postmenopausal). Median estrogen exposure was 28 years. Overall, there was no dose-response relationship between estrogen exposure and disease recurrence. Premenopausal patients had significantly shorter time from symptom manifestation to diagnosis (1.17 vs. 1.42 years perimenopausal vs. 2.08 years postmenopausal, p < 0.001), shorter time from diagnosis to index endoscopic airway dilation (1.90 vs. 2.50 vs. 3.76 years, p = 0.005), and higher number of procedures (1.73 vs. 1.20 vs. 1.08 procedures, p < 0.001)., Conclusions: We demonstrate premenopausal patients may have a more aggressive disease variant than their peri- and postmenopausal counterparts. However, it is unclear as to whether this is related to reduced estrogen in the peri- and postmenopausal states or the age-related physiology of wound healing and inflammation, regardless of estrogen., Level of Evidence: 3 Laryngoscope, 134:825-830, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To describe the anatomical and functional outcomes following use of the inverted flap technique (IFT) to close idiopathic macular holes (MH) of diameter greater than 400 μm. To compare the changes in the macular microvascularization following surgery in operated and healthy fellow eyes., Methods: Retrospective study of 24 patients who underwent vitrectomy and IFT for large MH closure. The main variables were closure pattern, best corrected visual acuity (BCVA) and recovery of the external limiting membrane (ELM) and ellipsoid zone (EZ). Foveal avascular zones (FAZ) and vessel and perfusion densities, obtained by OCT angiography scans, were compared with those in healthy fellow eyes., Results: Complete MH closure was achieved in 95.8% (23/24) of patients 6 months after surgery. There was a significant improvement in postoperative BCVA, from 1.0 to 0.4 logMAR (p < 0.001). The most frequent closure pattern was 1a (62.5%, 15/24), followed by 2c (12.5%, 3/24). The closure pattern was not correlated with height, minimum or maximum diameters or macular hole index (MHI) (p > 0.05). ELM and EZ recovery occurred in 87.5% and 83.3% of cases, respectively. FAZ were smaller in operated eyes than in the fellow eyes (p = 0.012). There were no differences in the vessel or perfusion densities between the operated and fellow eyes (p > 0.05)., Conclusions: Use of the inverted flap technique for large MH closure provides a high rate of functional and anatomical recovery. We observed a reduction in the FAZ following surgery, with no differences in the macular microvascularization parameters, suggesting that the technique is safe., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

By conducting hierarchical clustering along a sliding window, we generated haplotypes across hundreds of re-sequenced genomes in a few hours. We leveraged our method to define cryptic introgressions underlying disease resistance in tomato (Solanum lycopersicum L.) and to discover resistant germplasm in the tomato seed bank. The genomes of 9 accessions with early blight (Alternaria linariae) disease resistance were newly sequenced and analyzed together with published sequences for 770 tomato and wild species accessions, most of which are available in germplasm collections. Identification of common ancestral haplotypes among resistant germplasm enabled rapid fine mapping of recently discovered quantitative trait loci (QTL) conferring resistance and the identification of possible causal variants. The source of the early blight QTL EB-9 was traced to a vintage tomato named 'Devon Surprise'. Another QTL, EB-5, as well as resistance to bacterial spot disease (Xanthomonas spp.), was traced to Hawaii 7998. A genomic survey of all accessions forecasted EB-9-derived resistance in several heirloom tomatoes, accessions of S. lycopersicum var. cerasiforme, and S. pimpinellifolium PI 37009. Our haplotype-based predictions were validated by screening the accessions against the causal pathogen. There was little evidence of EB-5 prevalence in surveyed contemporary germplasm, presenting an opportunity to bolster tomato disease resistance by adding this rare locus. Our work demonstrates practical insights that can be derived from the efficient processing of large genome-scale datasets, including rapid functional prediction of disease resistance QTL in diverse genetic backgrounds. Finally, our work finds more efficient ways to leverage public genetic resources for crop improvement., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Seaweed, also known as macroalgae, represents a vast resource that can be categorized into three taxonomic groups: Rhodophyta (red), Chlorophyta (green), and Phaeophyceae (brown). They are a good source of essential nutrients such as proteins, minerals, vitamins, and omega-3 fatty acids. Seaweed also contains a wide range of functional metabolites, including polyphenols, polysaccharides, and pigments. This study comprehensively discusses seaweed and seaweed-derived metabolites and their potential as a functional feed ingredient in aquafeed for aquaculture production. Past research has discussed the nutritional role of seaweed in promoting the growth performance of fish, but their effects on immune response and gut health in fish have received considerably less attention in the published literature. Existing research, however, has demonstrated that dietary seaweed and seaweed-based metabolite supplementation positively impact the antioxidant status, disease resistance, and stress response in fish. Additionally, seaweed supplementation can promote the growth of beneficial bacteria and inhibit the proliferation of harmful bacteria, thereby improving gut health and nutrient absorption in fish. Nevertheless, an important balance remains between dietary seaweed inclusion level and the resultant metabolic alteration in fish. This review highlights the current state of knowledge and the associated importance of continued research endeavors regarding seaweed and seaweed-based functional metabolites as potential modulators of growth, immune and antioxidant response, and gut microbiota composition in fish.

Background: The use of thyroid ultrasound increases yearly, adding to costs and overdetection of clinically irrelevant nodules. We investigated which indications most commonly prompt referral for thyroid ultrasound and the diagnostic utility by indication. Methods: We performed a retrospective observational cohort study of adults (≥18 years) undergoing an initial dedicated thyroid ultrasound between 2017 and 2019 at a tertiary academic center. Indicated reasons for referral were categorized into suspected palpable nodule (SPN), compressive symptoms (CS), metabolic symptoms (MS), screening due to high-risk factors, follow-up of incidental finding on other imaging, and combination of factors. Percentage of ultrasounds with an identifiable nodule and with a nodule recommended for biopsy was compared by indication. Separate logistic regression models were used to identify factors associated with finding any nodule and a biopsy-recommended nodule. Results: Among the 1739 patients included, the most common indication for thyroid ultrasound was SPN (40%), followed by incidental imaging (28%), CS (13%), combination (11%), MS (6%), and high-risk factors (2%). Overall, 62% of ultrasounds identified a nodule. Ultrasounds performed for incidental findings had the highest rate of nodule identification (94%), compared with 55%, 39%, and 43%, for SPN, CS, and MS, respectively ( p  < 0.05). Only 27% of ultrasounds identified a biopsy-recommended nodule. Nodules found incidentally had the highest rate of biopsy-recommended nodules at 55%. Rates of biopsy-recommended nodules for SPN, CS, and MS were 21%, 6%, and 10%, respectively. Logistic regression demonstrated that compared with patients referred for an SPN, those with incidental nodules were 10 times more likely to have a nodule found on ultrasound (odds ratio [OR] = 10.6 [CI 7.0-16.0]), while those referred for CS were half as likely to have a nodule (OR = 0.5 [CI 0.4-0.7]). Similar factors were associated with identification of biopsy-recommended nodules. Conclusions: Of all new dedicated thyroid ultrasounds, only a quarter find biopsy-recommended nodules, and nearly 40% do not identify a nodule at all. Notably, only 55% of ultrasounds done for SPN found a nodule. Ultrasound for CS and MS had the lowest rates of detecting nodules. Providing clear guidance on when to order thyroid ultrasounds can help reduce unnecessary health care utilization and potential overtreatment.

Importance: Tracheotomies are frequently performed by nonotolaryngology services. The factors that determine which specialty performs the procedure are not defined in the literature but may be influenced by tracheotomy approach (open vs percutaneous) and other clinicodemographic factors., Objective: To evaluate demographic and clinical characteristics associated with tracheotomies performed by otolaryngologists compared with other specialists and to differentiate those factors from factors associated with use of open vs percutaneous tracheotomy., Design, Setting, and Participants: This multicenter, retrospective cohort study included patients aged 18 years or older who underwent a tracheotomy for cardiopulmonary failure at 1 of 8 US academic institutions between January 1, 2013, and December 31, 2016. Data were analyzed from September 2022 to July 2023., Exposure: Tracheotomy., Main Outcomes and Measures: The primary outcome was factors associated with an otolaryngologist performing tracheotomy. The secondary outcome was factors associated with use of the open tracheotomy technique., Results: A total of 2929 patients (mean [SD] age, 57.2 [17.2] years; 1751 [59.8%] male) who received a tracheotomy for cardiopulmonary failure (652 [22.3%] performed by otolaryngologists and 2277 [77.7%] by another service) were analyzed. Although 1664 of all tracheotomies (56.8%) were performed by an open approach, only 602 open tracheotomies (36.2%) were performed by otolaryngologists. Most tracheotomies performed by otolaryngologists (602 of 652 [92.3%]) used the open technique. Multivariable regression analysis revealed that self-reported Black race (odds ratio [OR], 1.89; 95% CI, 1.52-2.35), history of neck surgery (OR, 2.71; 95% CI, 2.06-3.57), antiplatelet and/or anticoagulation therapy (OR, 1.74; 95% CI, 1.29-2.36), and morbid obesity (OR, 1.54; 95% CI, 1.24-1.92) were associated with greater odds of an otolaryngologist performing tracheotomy. In contrast, history of neck surgery (OR, 1.36; 95% CI, 0.96-1.92), antiplatelet and/or anticoagulation therapy (OR, 0.80; 95% CI, 0.56-1.14), and morbid obesity (OR, 0.94; 95% CI, 0.74-1.19) were not associated with undergoing open tracheotomy when performed by any service, and Black race (OR, 0.56; 95% CI, 0.44-0.71) was associated with lesser odds of an open approach being used. Age-adjusted Charlson Comorbidity Index score greater than 4 was associated with greater odds of both an otolaryngologist performing tracheotomy (OR, 1.26; 95% CI, 1.03-1.53) and use of the open tracheotomy technique (OR, 1.48, 95% CI, 1.21-1.82)., Conclusions and Relevance: In this study, otolaryngologists were significantly more likely than other specialists to perform a tracheotomy for patients with history of neck surgery, morbid obesity, and ongoing anticoagulation therapy. These findings suggest that patients undergoing tracheotomy performed by an otolaryngologist are more likely to present with complex and challenging clinical characteristics.

Background/objectives: As surgical techniques evolve, there remains underutilisation of secondary intention healing as a valid reconstruction option. This is largely due to concerns regarding inferiority of wound cosmesis, increased downtime with wound healing and infection risk (Dermatol Surg. 2020; 46(12): 1492-97)., Methods: We sought to look at the outcome of secondary intention healing in a cohort of patients seen at a private dermatology practice with small to medium sized scalp defects. All patients completed a satisfaction survey that further evaluated its feasibility., Results: Excellent cosmetic outcome was noted with secondary intention healing for small to medium scalp defects, specifically in patients with thinning scalps that allowed healing without patchy alopecia., Conclusions: Secondary intention healing should be considered as a reconstructive option for scalp defects, especially in the right patient cohort., (© 2023 Australasian College of Dermatologists.)

Crop breeding for mechanized harvesting has driven modern agriculture. In tomato, machine harvesting for industrial processing varieties became the norm in the 1970s. However, fresh-market varieties whose fruits are suitable for mechanical harvesting are difficult to breed because of associated reduction in flavour and nutritional qualities. Here we report the cloning and functional characterization of fs8.1, which controls the elongated fruit shape and crush resistance of machine-harvestable processing tomatoes. FS8.1 encodes a non-canonical GT-2 factor that activates the expression of cell-cycle inhibitor genes through the formation of a transcriptional module with the canonical GT-2 factor SlGT-16. The fs8.1 mutation results in a lower inhibitory effect on the cell proliferation of the ovary wall, leading to elongated fruits with enhanced compression resistance. Our study provides a potential route for introducing the beneficial allele into fresh-market tomatoes without reducing quality, thereby facilitating mechanical harvesting., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To report the management and outcome of a case of necrotizing scleritis due to Hormographiella aspergillata ., Methods: Case report., Results: A 79-year-old woman developed scleral inflammation following accidental trauma with a gorse plant in her left eye. An abscess formed at the site of the injury, which was surgically drained. Filamentous fungi were identified from the abscess contents, and oral voriconazole and topical voriconazole and natamycin drops were prescribed. Phenotypic analysis confirmed the presence of Hormographiella aspergillata , with low minimum inhibitory concentrations (MIC) for voriconazole and amphotericin B. Two weeks later the patient presented with an area of necrotizing scleritis which required surgical debridement and scleral grafting. Three months later, the scleral inflammation had resolved leaving an area of scleromalacia., Conclusions: Hormographiella aspergillata is a common environmental fungus that has recently emerged as a human pathogen and a rare cause of scleritis. To the best of our knowledge, this is the first report of scleritis in which a pure culture of H. aspergillata was obtained. Successful management poses a challenge as there are limited reports on antifungal susceptibility and a combination of medical and surgical treatment is often required.

Objectives: Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea., Methods: Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score. Within patients undergoing SILSI, demographics, time from last procedure, and PEF at initiation of SILSI were evaluated to determine the effect on recurrence., Results: Two hundred and ninety patients were included, 238 undergoing endoscopic dilation alone and 52 undergoing dilation and SILSI. No differences in baseline characteristics were observed. There was no difference in time to recurrence (hazard ratio: 0.64; p = 0.183). There were no differences in PEF or CCQ across the 2.5-year study period. Among 52 patients undergoing SILSI, PEF at the time of starting SILSI did not affect recurrence (χ 2  = 0.09, p = 0.77)., Conclusion: Patients undergoing and not undergoing SILSI had similar times to recurrence, PEF, and CCQ. Factors predicting recurrence among patients undergoing SILSI were not identified. These results support a randomized controlled trial with a uniform SILSI protocol to quantify the effects of SILSI on objective and subjective outcomes and help determine which iSGS patients benefit most., Level of Evidence: 3 Laryngoscope, 133:2255-2263, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Genetics researchers increasingly combine data across many sources to increase power and to conduct analyses that cross multiple individual studies. However, there is often a lack of alignment on outcome measures when the same constructs are examined across studies. This inhibits comparison across individual studies and may impact the findings from meta-analysis. Using a well-characterized genotypic (brain-derived neurotrophic factor: BDNF) and phenotypic constructs (working memory and reading comprehension), we employ an approach called Rosetta, which allows for the simultaneous examination of primary studies that employ related but incompletely overlapping data. We examined four studies of BDNF, working memory, and reading comprehension with a combined sample size of 1711 participants. Although the correlation between working memory and reading comprehension over all participants was high, as expected (ρ = 0.45), the correlation between working memory and reading comprehension was attenuated in the BDNF Met/Met genotype group (ρ = 0.18, n.s.) but not in the Val/Val (ρ = 0.44) or Val/Met (ρ = 0.41) groups. These findings indicate that Met/Met carriers may be a unique and robustly defined subgroup in terms of memory and reading comprehension. This study demonstrates the utility of the Rosetta method when examining complex phenotypes across multiple studies, including psychiatric genetic studies, as shown here, and also for the mega-analysis of cohorts generally.

Purpose: This study aimed to examine changes in English and Spanish morphosyntactic standardized scores over time in bilingual children., Method: One hundred bilingual children participated in this longitudinal study. The average age of the children at the beginning of the study was 5;11 (years;months). A subset of the participants was identified as children with developmental language disorder (DLD, n = 43). Children completed behavioral testing in Spanish and English at three time points over a period of 2 years. Growth curve modeling was employed to analyze longitudinal data., Results: Distinct patterns of Spanish and English language growth were observed. While the average standard score in English increased, the average score in Spanish decreased over time for both groups. Children with DLD showed persistent language difficulties in both Spanish and English over time in comparison to their peers., Conclusions: The results of this study provide evidence of a shift in language proficiency from Spanish to English for bilingual children with and without language disorders. This study also shows that bilingual children with DLD show a protracted but parallel growth in morphosyntactic skills in comparison to children without DLD., Supplemental Material: https://doi.org/10.23641/asha.23671464.

Purpose: To report on the outcomes of amniotic membrane transplantation (AMT) for corneal ulceration following infectious keratitis., Method: In this retrospective cohort study of 654 patients with culture-proven infectious keratitis from 8 hospitals in Galicia (Spain), a total of 43 eyes of 43 patients (6.6%) underwent AMT for postinfectious corneal ulceration. The indications for AMT were sterile persistent epithelial defects, severe corneal thinning or perforation., Results: AMT was successful in 62.8% of cases, with 37.2% requiring an additional surgery. Median time to healing was 40.0 days (IQR 24.2-101.7 days) and final BCVA was lower than baseline ( p  = 0.001). Ulcers were large (>3 mm) in 55.8% of cases. Previous herpetic keratitis and topical steroid use were more common in patients who received AMT ( p  < 0.001). 49 microorganisms (43 bacteria and 6 fungi) were isolated., Conclusions: AMT is a therapeutic option for complications following infectious keratitis, which present with a sterile persistent epithelial defect, significant corneal thinning or perforation.

Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner., (© 2023. The Author(s).)

Primary radiation therapy using interstitial brachytherapy (IBT) provides excellent local tumor control for early-stage squamous cell carcinoma of the lip. Technical aspects of treatment are important to optimize outcomes. In this report, we discuss patient selection criteria, procedural details, and dosimetric considerations for performing IBT for cancers of the lip. Catheters are inserted across the length of tumor entering and exiting approximately 5 mm beyond the palpable tumor extent. A custom mouthpiece is fabricated to facilitate normal tissue sparing. Patients undergo computed tomography imaging, the gross tumor volume is contoured based on physical examination and computed tomography findings, and an individualized brachytherapy plan is generated with the goals of achieving gross tumor volume D90% ≥ 90% and minimizing V150%. Ten patients with primary (n = 8) or recurrent (n = 2) cancers of the lip who received high-dose-rate lip IBT using 2.0- to 2.5-week treatment regimens are described (median prescription: 47.6 Gy in 14 fractions of 3.4 Gy). Local tumor control was 100%. There were no cases of acute grade ≥4 or late grade ≥2 toxicity, and cosmesis scores were graded as good to excellent in all patients. IBT represents an excellent treatment option for patients with lip squamous cell carcinoma. With careful attention to technical considerations furthered described in the present report, high rates of tumor control, low rates of toxicity, and favorable esthetic and functional outcomes can be achieved with IBT for lip cancer., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

This study characterizes the DNA methylation patterns specific to fragile X syndrome (FXS) with a full mutation (FM > 200 CGGs), premutation (PM 55-199 CGGs), and X inactivation in blood and brain tissues at the 3' boundary of the FMR1 promoter. Blood was analyzed from 95 controls and 462 individuals (32% males) with FM and PM alleles. Brain tissues (62% males) were analyzed from 12 controls and 4 with FXS. There was a significant increase in intron 1 methylation, extending to a newly defined 3' epigenetic boundary in the FM compared with that in the control and PM groups ( p < 0.0001), and this was consistent between the blood and brain tissues. A distinct intron 2 site showed a significant decrease in methylation for the FXS groups compared with the controls in both sexes ( p < 0.01). In all female groups, most intron 1 (but not intron 2 sites) were sensitive to X inactivation. In all PM groups, methylation at the 3' epigenetic boundary and the proximal sites was significantly decreased compared with that in the control and FM groups ( p < 0.0001). In conclusion, abnormal FMR1 intron 1 and 2 methylation that was sensitive to X inactivation in the blood and brain tissues provided a novel avenue for the detection of PM and FM alleles through DNA methylation analysis.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective: We aimed to discern clinico-demographic predictors of large (≥8) tracheostomy tube size placement, and, secondarily, to assess the effect of large tracheostomy tube size and other parameters on odds of decannulation before hospital discharge., Summary of Background Data: Factors determining choice of tracheostomy tube size are not well-characterized in the current literature, despite evidence linking large tracheostomy tube size with posttracheotomy tracheal stenosis. The effect of tracheostomy tube size on timing of decannulation is also unknown, an important consideration given reported associations between endotracheal tube size and probability of failed extubation., Methods: We collected information pertaining to patients who underwent tracheotomy at 1 of 10 U.S. health care institutions between 2010 and 2019. Tracheostomy tube size was dichotomized (≥8 and <8). Multivariable logistic regression models were fit to identify predictors of (1) large tracheostomy tube size, and (2) decannulation before hospital discharge., Results: The study included 5307 patients, including 2797 (52.7%) in the large tracheostomy cohort. Patient height (odds ratio [OR] = 1.060 per inch; 95% confidence interval [CI] 1.041-1.070) and obesity (1.37; 95% CI 1.1891.579) were associated with greater odds of large tracheostomy tube; otolaryngology performing the tracheotomy was associated with significantly lower odds of large tracheostomy tube (OR = 0.155; 95% CI 0.131-0.184). Large tracheostomy tube size (OR = 1.036; 95% CI 0.885-1.213) did not affect odds of decannulation., Conclusions: Obesity was linked with increased likelihood of large tracheostomy tube size, independent of patient height. Probability of decannulation before hospital discharge is influenced by multiple patient-centric factors, but not by size of tracheostomy tube., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: WWOX is an autosomal recessive cause of early infantile developmental and epileptic encephalopathy (WWOX-DEE), also known as WOREE (WWOX-related epileptic encephalopathy). We analyzed the epileptology and imaging features of WWOX-DEE, and investigated genotype-phenotype correlations, particularly with regard to survival., Methods: We studied 13 patients from 12 families with WWOX-DEE. Information regarding seizure semiology, comorbidities, facial dysmorphisms, and disease outcome were collected. Electroencephalographic (EEG) and brain magnetic resonance imaging (MRI) data were analyzed. Pathogenic WWOX variants from our cohort and the literature were coded as either null or missense, allowing individuals to be classified into one of three genotype classes: (1) null/null, (2) null/missense, (3) missense/missense. Differences in survival outcome were estimated using the Kaplan-Meier method., Results: All patients experienced multiple seizure types (median onset = 5 weeks, range = 1 day-10 months), the most frequent being focal (85%), epileptic spasms (77%), and tonic seizures (69%). Ictal EEG recordings in six of 13 patients showed tonic (n = 5), myoclonic (n = 2), epileptic spasms (n = 2), focal (n = 1), and migrating focal (n = 1) seizures. Interictal EEGs demonstrated slow background activity with multifocal discharges, predominantly over frontal or temporo-occipital regions. Eleven of 13 patients had a movement disorder, most frequently dystonia. Brain MRIs revealed severe frontotemporal, hippocampal, and optic atrophy, thin corpus callosum, and white matter signal abnormalities. Pathogenic variants were located throughout WWOX and comprised both missense and null changes including five copy number variants (four deletions, one duplication). Survival analyses showed that patients with two null variants are at higher mortality risk (p-value = .0085, log-rank test)., Significance: Biallelic WWOX pathogenic variants cause an early infantile developmental and epileptic encephalopathy syndrome. The most common seizure types are focal seizures and epileptic spasms. Mortality risk is associated with mutation type; patients with biallelic null WWOX pathogenic variants have significantly lower survival probability compared to those carrying at least one presumed hypomorphic missense pathogenic variant., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

We aimed to determine whether SNP-microarray genomic testing of saliva had a greater diagnostic yield than blood for pathogenic copy number variants (CNVs). We selected patients who underwent CMA testing of both blood and saliva from 23,289 blood and 21,857 saliva samples. Our cohort comprised 370 individuals who had testing of both, 224 with syndromic intellectual disability (ID) and 146 with isolated ID. Mosaic pathogenic CNVs or aneuploidy were detected in saliva but not in blood in 20/370 (4.4%). All 20 individuals had syndromic ID, accounting for 9.1% of the syndromic ID sub-cohort. Pathogenic CNVs were large in size (median of 46 Mb), and terminal in nature, with median mosaicism of 27.5% (not exceeding 40%). By contrast, non-mosaic pathogenic CNVs were 100% concordant between blood and saliva, considerably smaller in size (median of 0.65 Mb), and predominantly interstitial in location. Given that salivary microarray testing has increased diagnostic utility over blood in individuals with syndromic ID, we recommend it as a first-tier testing in this group., (© 2022. The Author(s).)

Background: Prior studies of post-thyroidectomy vocal cord paralysis (VCP) present static and limited evaluations. We comprehensively assessed the experience of patients with VCP post-thyroidectomy over 1 year., Methods: Voice Handicap Index (VHI), Eating Assessment Tool (EAT-10), 12-Item Short Form Survey (SF-12), and qualitative interviews were assessed preoperatively, and 2-weeks, 6-weeks, 6-months, and 1-year postoperatively., Outcomes: 7 of 44 patients (15.9%) had postoperative VCP. Compared to those without complication, mean VHI scores for VCP patients increased significantly from baseline at 2-weeks (27.9 point increase vs 1.6, p < 0.01) and 6-weeks (26.3 vs. -0.3, p < 0.01) postoperative. There were no significant differences between groups in SF-12 or EAT-10 scores at any point. Qualitative interviews showed that both groups noted bothersome voice symptoms at 2-weeks; however, by 6-weeks, only VCP patients noted voice symptoms negatively affecting their life., Conclusion: While both patients with and without VCP reported subjective voice symptoms immediately postoperatively, those with VCP had worse quantitative measures. Understanding the longitudinal experience of VCP can help providers tailor counseling for these patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose. Dr. Sippel was funded for the original study by the National Institutes of Health (NCT02138214)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Epiretinal membrane (ERM) formation is a known postoperative complication following retinal detachment (RD) repair surgery. Prophylactic peeling of the internal limiting membrane (ILM) during surgery has been shown to reduce the risk of developing postoperative ERM formation. Some baseline characteristics and degrees of surgical complexity may act as risk factors for ERM development. In this review we aimed to investigate the benefit of ILM peeling in patients without significant proliferative vitreoretinopathy (PVR) who underwent pars plana vitrectomy for RD repair. A literature search using PubMed and various keywords retrieved relevant papers from which data were extracted and analyzed. Finally, the results of 12 observational studies (3420 eyes) were summarized. ILM peeling significantly reduced the risk of postoperative ERM formation (RR = 0.12, 95% CI 0.05-0.28). The groups did not differ in final visual acuity (SMD 0.14 logMAR (95% CI - 0.03-0.31)). The risk of RD recurrence (RR = 0.51, 95% CI 0.28-0.94) and the need for secondary ERM surgery (RR = 0.05, 95% CI 0.02-0.17) were also higher in the non-ILM peeling groups. In summary, although prophylactic ILM peeling appears to reduce the rate of postoperative ERM, this benefit does not translate into consistent visual recovery across studies and potential complications must be considered., (© 2023. The Author(s).)

Background: Hazardous drinking and posttraumatic stress disorder (PTSD) are commonly co-occurring conditions among adults. Motivational enhancement interventions, such as personalized feedback interventions (PFI), have demonstrated efficacy for reducing hazardous drinking. Emerging though scant literature has evaluated PFI for co-occurring PTSD and hazardous alcohol use. A transdiagnostic risk factor that may underlie this co-occurrence and inform novel PFI development is anxiety sensitivity (AS)., Objective: To use a randomized controlled trial to evaluate the efficacy of a novel, computer-based PFI for hazardous drinkers with at least subclinical PTSD and elevated AS (AP-PFI), against a time-matched comparison condition (C-PFI)., Methods: Participants ( N  = 100) will be recruited and enrolled from the Houston, TX community. The study includes: an in-person visit (baseline diagnostic assessment, a brief intervention, and a post-intervention assessment) and two follow-up assessments (1-week and 1-month). Participants who meet study inclusion criteria will be randomized to one of two conditions at baseline: AP-PFI or C-PFI. AP-PFI will consist of a brief, single-session, computer-delivered, PFI-based intervention that provides integrative and normative feedback about alcohol use, AS, and PTSD symptoms. C-PFI will be time-matched but will only include alcohol-related feedback., Conclusions: AP-PFI is designed to provide feedback about alcohol use, PTSD symptoms, and AS and their interplay and deliver psychoeducation on harm-reduction techniques, interoceptive exposure exercises, and stress management strategies. The intervention may address extant gaps in treatment for these co-occurring conditions by providing a brief, evidence-based, motivational enhancement intervention that is cost-effective with potential to be disseminated across a variety of healthcare settings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89-43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific-Quantitative Melt Aanalysis (MS-QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS-QMA in blood (n = 68; R 2  = 0.597; p = 1.4 × 10 -10 ) and buccal epithelial cells (BEC) (n = 62; R 2  = 0.24; p = 0.003), with these measures also showing relationships with intellectual functioning scores (p < 0.01). However, these relationships were not as strong for mSB, with ~40% of males with only FM alleles that were 100% methylated and non-mosaic by mSB, showing methylation mosaicism by MS-QMA. This was confirmed through presence of detectable levels of FMR1 mRNA in blood. In summary, FMR1 methylation levels in blood and BEC examined by MS-QMA were significantly associated with FMR1 mRNA levels and intellectual functioning in males with FXS. These relationships were not as strong for mSB, which underestimated prevalence of mosaicism., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Imaging and genetic studies have characterized biological risk factors contributing to specific reading disability (SRD). The current study aimed to apply this literature to a family of twins discordant for SRD and an older sibling with reading difficulty. Intraclass correlations were used to understand the similarity of imaging phenotypes between pairs. Reading-related genes and brain region phenotypes, including asymmetry indices representing the relative size of left compared to right hemispheric structures, were descriptively examined. SNPs that corresponded between the SRD siblings and not the typically developing (TD) siblings were in genes ZNF385D , LPHN3 , CNTNAP2 , FGF18 , NOP9 , CMIP , MYO18B , and RBFOX2 . Imaging phenotypes were similar among all sibling pairs for grey matter volume and surface area, but cortical thickness in reading-related regions of interest (ROIs) was more similar among the siblings with SRD, followed by the twins, and then the TD twin and older siblings, suggesting cortical thickness may differentiate risk for this family. The siblings with SRD had more symmetry of cortical thickness in the transverse temporal and superior temporal gyri, while the TD sibling had greater rightward asymmetry. The TD sibling had a greater leftward asymmetry of grey matter volume and cortical surface area in the fusiform, supramarginal, and transverse temporal gyrus. This exploratory study demonstrated that reading-related risk factors appeared to correspond with SRD within this family, suggesting that early examination of biological factors may benefit early identification. Future studies may benefit from the use of polygenic risk scores or machine learning to better understand SRD risk.

Objective: Evidence indicates a counterintuitive positive relationship between physical activity and alcohol consumption, suggesting that people who engage in more physical activity consume more alcohol. Impulsivity, which has a well-documented role in alcohol use disorders, has been shown to moderate the between-person physical activity-drinking association among emerging adults. However, only a handful of studies have explored within-person associations of physical activity and drinking and potential moderators of this relationship. The current study evaluated the effects of both subjective and behavioral impulsivity on the within- and between-person association between physical activity and alcohol consumption among college students., Method: Undergraduate students ( N = 250) between ages 18 and 25 years were asked to report their daily physical activity and drinking over 21 days. Physical activity was also recorded objectively through Pacer, a smartphone app. Subjective impulsivity was assessed using the UPPS-P Impulsive Behavior Scale, and behavioral impulsivity was evaluated using the Balloon Analogue Risk Task., Results: Within- and between-subject physical activity-drinking associations were differentially moderated by behavioral impulsivity and self-reported impulsivity. For instance, behavioral impulsivity moderated the within-person association between drinking and self-reported vigorous physical activity, whereas negative urgency moderated the between-person association between drinking and objective physical activity., Conclusions: Impulsivity, whether measured subjectively or behaviorally, significantly moderates the physical activity-alcohol consumption association. Importantly, this effect operates differently when predicting variation in behavior within individuals as compared with predicting differences in behavior between individuals.

Diets rich in fruits and vegetables have been shown to exert positive effects on the gut microbiome. However, little is known about the specific effect of individual fruits or vegetables on gut microbe profiles. This study aims to elucidate the effects of tomato consumption on the gut microbiome, as tomatoes account for 22% of vegetable consumption in Western diets, and their consumption has been associated with positive health outcomes. Using piglets as a physiologically relevant model of human metabolism, 20 animals were assigned to either a control or a tomato powder-supplemented diet (both macronutrient matched and isocaloric) for 14 days. The microbiome was sampled rectally at three time points: day 0 (baseline), day 7 (midpoint), and day 14 (end of study). DNA was sequenced using shotgun metagenomics, and reads were annotated using MG-RAST. There were no differences in body weight or feed intake between our two treatment groups. There was a microbial shift which included a higher ratio of Bacteroidota to Bacillota (formerly known as Bacteroidetes and Firmicutes , respectively) and higher alpha-diversity in tomato-fed animals, indicating a shift to a more desirable phenotype. Analyses at both the phylum and genus levels showed global microbiome profile changes (permutational multivariate analysis of variance [PERMANOVA], P  ≤ 0.05) over time but not with tomato consumption. These data suggest that short-term tomato consumption can beneficially influence the gut microbial profile, warranting further investigation in humans. IMPORTANCE The composition of the microorganisms in the gut is a contributor to overall health, prompting the development of strategies to alter the microbiome composition. Studies have investigated the role of the diet on the microbiome, as it is a major modifiable risk factor contributing to health; however, little is known about the causal effects of consumption of specific foods on the gut microbiota. A more complete understanding of how individual foods impact the microbiome will enable more evidence-based dietary recommendations for long-term health. Tomatoes are of interest as the most consumed nonstarchy vegetable and a common source of nutrients and phytochemicals across the world. This study aimed to elucidate the effect of short-term tomato consumption on the microbiome, using piglets as a physiologically relevant model to humans. We found that tomato consumption can positively affect the gut microbial profile, which warrants further investigation in humans.