Central Nervous System Infections in Patients With Ventriculoperitoneal Shunts Admitted for Primary Abdominal Infections: A US Nationwide Cohort Analysis.

BACKGROUND AND OBJECTIVES: Although ventriculoperitoneal (VP) shunts are a common treatment for hydrocephalus, there are complication risks including infections. Late complications such as ventriculitis from ascending abdominal infections can have severe consequences. However, the incidence of central nervous system (CNS) infections in VP shunt patients with abdominal infections is not well understood. We aimed to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections. METHODS: Using the National Inpatient Sample, we studied patients from 2016 to 2019 to determine the incidence of CNS infections in VP shunt patients admitted with abdominal infections. Results were compared with VP shunt patients admitted for primary pneumonia. RESULTS: Among 725 VP shunt patients presenting with abdominal infections, 20 (2.8%) had CNS infections. Chronic obstructive pulmonary disease, hypertension, older age, and a smoking history were more common in patients with CNS infections and primary abdominal infection (P < .05). Patients who developed CNS infection had a significantly higher likelihood of both blood transfusion and coma but a lower likelihood of seizures. VP shunt patients with CNS infections were more likely to undergo shunt removal (odds ratio [OR] = 23.167, P < .001). 4.1% of VP shunt patients with primary abdominal infections died during admission. In a population of primary abdominal infection and pneumonia patients with VP shunts, a multivariate logistic regression analysis controlling for age, sex, and comorbidities identified abdominal infection as an independent risk factor for both CNS infection (OR = 51.208, P < .001) and inpatient death (OR = 3.417, P < .001). Among 6620 VP shunt patients admitted with primary pneumonia, only 5 (0.1%) had CNS infection compared with 20 (2.8%) in those with a primary abdominal infection (OR = 37.532, P < .001), and mortality was 1.6% vs 4.1% for those with a primary abdominal infection (P < .05). CONCLUSION: CNS infections in VP-shunted patients with abdominal infections are relatively rare but may lead to increased risks of death and other serious adverse outcomes.

Association of reductions in rescue medication requirements with vagus nerve stimulation: Results of long-term community collected data from a seizure diary app.

OBJECTIVE: To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications. METHODS: Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model. RESULTS: We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe. SIGNIFICANCE: This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time.

Health Utility Values Among Patients With Diabetic Retinopathy, Wet Age-Related Macular Degeneration, and Cataract in Thailand: A Multicenter Survey Using Time Trade-Off, EQ-5D-5L, and Health Utility Index 3.

OBJECTIVES: This study aimed to establish normative health utility data in Thai patients with diabetic retinopathy, wet age-related macular degeneration, and cataract; evaluate the sensitivity of different utility instruments to visual impairment; explore the relationship among these health utility values with the vision-specific quality of life (QoL); and assess the association of baseline characteristics and visual acuity level with health utility values and vision-specific QoL. METHODS: This multicenter cross-sectional survey included 309 patients from tertiary eye centers. We used health utility instruments (time trade-off [TTO], EuroQol five-dimension [EQ-5D-5L], and Health Utility Index 3 [HUI3]) and vision-specific QoL instrument (National Eye Institute Visual Function Questionnaire) for face-to-face interviews. Demographic data and Early Treatment Diabetic Retinopathy Study visual acuity were recorded during the participants ophthalmic visits. Univariable and multivariable mixed-effect models were used to evaluate factors associated with the utility scores. Health utility scores among each type of eye disease were compared. RESULTS: The overall mean utility values from the TTO, EQ-5D-5L, and HUI3 were 0.84 ± 0.25, 0.70 ± 0.19, and 0.68 ± 0.26, respectively. The health utility scores obtained from TTO and HUI3 showed a significant response to severe visual impairment or worse. Health utility scores from HUI3 (r = 0.54; P < .01) and EQ-5D-5L (r = 0.43; P < .01) displayed a moderate correlation with the National Eye Institute Visual Function Questionnaire score. There were no significant differences in health utility value among the 3 diseases upon adjusting for the visual acuity level and demographics. CONCLUSIONS: Visual acuity level has a greater impact on a patient's QoL than the type of eye disease. HUI3 and EQ-5D-5L and TTO are suitable for measuring health utility in leading causes of blindness.

The Impact of Occupational Exposures on Chronic Rhinosinusitis: A Scoping Review.

Chronic rhinosinusitis (CRS) is a prevalent and burdensome condition worldwide, characterized by inflammation of the paranasal sinuses. Ideally, instead of treating CRS, we would identify ways to prevent the development of this chronic condition. Occupational exposures may be an excellent target for prevention. Occupational exposures have been shown to play a critical role in the pathogenesis of multiple lower airway diseases, such as asthma, silicosis, asbestosis, and hypersensitivity pneumonitis. However, evidence for the association between occupational exposures and the development of upper airway disease, like CRS, is less well-defined. This manuscript examines the association between occupational exposures and CRS. A scoping review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 19 relevant studies. The populations examined and the methods and criteria used for defining CRS diagnosis and occupational variables significantly varied between the studies. Diagnosis of CRS was most often determined by self-reported symptoms or medical record review. Occupational variables ranged from employment status to occupation type to specific exogenous compounds encountered. Overall, substantial evidence demonstrates a general association between occupational exposures and CRS diagnosis; however, limitations in study methodologies, including variations in CRS diagnostic criteria, occupational exposures, assessment methods, and populations, hinder drawing more specific conclusions. Moving forward, rigorous research methodologies and standardized criteria are essential to draw conclusions supported by multiple studies. Critical components of future studies should include large, diverse populations, use of consensus CRS diagnostic criteria, and inclusion of many specific and quantitatively defined exposures. Ultimately, such efforts can help inform preventative measures and interventions for CRS, thus mitigating the burden of CRS on individuals and populations worldwide.

Transoral robotic surgery for pediatric upper airway pathology: An institutional update.

OBJECTIVE: Provide an update on our institution's experience with utilizing transoral robotic surgery (TORS) in pediatric airway surgery and compare these results to surgery by traditional methods. METHODS: Pediatric patients who underwent TORS for treatment of upper airway pathology between 2010 and 2021 at our institution were retrospectively identified and compared to patients with the same or similar pathology who underwent a traditional (open or endoscopic) surgical approach over the same time period. Outcomes of interest included patient demographics, operative times, adverse events, hospital length of stay (LOS), and modified barium swallow (MBSS) results. RESULTS: Forty children (19M, 21F) underwent 46 TORS procedures. Mean age was 6.4 years (range: 6 days-17 years). Most commonly treated pathology included: laryngeal clefts (LC) (n = 18), lymphatic malformations (n = 9), and base of tongue masses (n = 7). Surgical time was decreased in traditional type I LC repairs (mean: 111 vs 149 min, P = 0.04) and lymphatic malformation excisions (59 vs 120 min, p = 0.005). Hospital LOS was increased in TORS type I LC repairs (2.6 vs 1.2 days, P = 0.04). Adverse event rate was similar between TORS and traditional cohorts (17 % vs 16 % cases, P = 0.9). Postoperative MBSS results were improved for TORS type I LC repairs at 6 months (70 % vs 33 %, P = 0.09) and 12 months (82 % vs 43 %, P = 0.05). CONCLUSIONS: Pediatric TORS is practical and safe and has comparable outcomes to traditional surgery. Robotic-assisted LC repair displayed improved postoperative swallow results versus traditional approaches and may be particularly useful in recurrent cases.

Description, life cycle, and development of the myxozoan Myxobolus rasmusseni n. sp. in fathead minnows, Pimephales promelas: A possible emerging pathogen in southern Alberta, Canada.

Morphological, gene sequence, host tissue tropism, and life cycle characteristics were utilized to describe the myxozoan, Myxobolus rasmusseni n. sp. from fathead minnow, Pimephales promelas, collected from reservoirs in southern Alberta. Results from serial histological sections of whole heads showed that myxospores were contained within irregular-shaped and sized coelozoic capsules (=plasmodia). Clusters of membrane-bound, myxospore-filled plasmodia filled the head cavities of juvenile fathead minnows, leading to the development of large, white, disfiguring lesions in mid to late summer. Bilateral exopthalmia (pop-eye disease) was a common outcome of M. rasmusseni n. sp. development. BLASTn search of a 1974 bp sequence of the 18S rDNA gene isolated from myxospores indicated that M. rasmusseni n. sp. was distinct from other coelozoic and histozoic Myxobolus spp. cataloged in GenBank. 18S rDNA gene sequences from triactinomyxon spores released from the oligochaete Tubifex were 100% identical to sequences from myxospores collected from syntopic fathead minnows. Results from a longitudinal survey of the 2020 cohort of fathead minnows showed that young-of-the-year are exposed at 1-5 mo and that 60-90% of these had developed myxospore-filled lesions approximately one year later. Data regarding potential sources and timing of M. rasmusseni n. sp. emergence in fathead minnow populations are needed.

Inhalational exposure history is associated with differential sinonasal gene expression profiles and clinical outcomes in chronic rhinosinusitis patients: A pilot study.

KEY POINTS: Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant factor across differential gene expression analyse IE history was associated with pro-inflammatory transcriptome changes and worse clinical outcomes.

Dengue viremia kinetics and effects on platelet count and clinical outcomes: An analysis of 2340 patients from Vietnam.

Background: Viremia is a critical factor in understanding the pathogenesis of dengue infection, but limited data exist on viremia kinetics. This study aimed to investigate the kinetics of viremia and its effects on subsequent platelet count, severe dengue, and plasma leakage. Methods: We pooled data from three studies conducted in Vietnam between 2000 and 2016, involving 2340 dengue patients with daily viremia measurements and platelet counts after symptom onset. Viremia kinetics were assessed using a random effects model that accounted for left-censored data. The effects of viremia on subsequent platelet count and clinical outcomes were examined using a landmark approach with a random effects model and logistic regression model with generalized estimating equations, respectively. The rate of viremia decline was derived from the model of viremia kinetics. Its effect on the clinical outcomes was assessed by logistic regression models. Results: Viremia levels rapidly decreased following symptom onset, with variations observed depending on the infecting serotype. DENV-1 exhibited the highest mean viremia levels during the first 5-6 days, while DENV-4 demonstrated the shortest clearance time. Higher viremia levels were associated with decreased subsequent platelet counts from day 6 onwards. Elevated viremia levels on each illness day increased the risk of developing severe dengue and plasma leakage. However, the effect size decreased with later illness days. A more rapid decline in viremia is associated with a reduced risk of the clinical outcomes. Conclusions: This study provides comprehensive insights into viremia kinetics and its effect on subsequent platelet count and clinical outcomes in dengue patients. Our findings underscore the importance of measuring viremia levels during the early febrile phase for dengue studies and support the use of viremia kinetics as outcome for phase-2 dengue therapeutic trials. Funding: Wellcome Trust and European Union Seventh Framework Programme.

RNA regulatory mechanisms controlling TGF-ß signaling and EMT in cancer.

Epithelial-mesenchymal transition (EMT) is a major contributor to metastatic progression and is prominently regulated by TGF-ß signalling. Both EMT and TGF-ß pathway components are tightly controlled by non-coding RNAs - including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) - that collectively have major impacts on gene expression and resulting cellular states. While miRNAs are the best characterised regulators of EMT and TGF-ß signaling and the miR-200-ZEB1/2 feedback loop plays a central role, important functions for lncRNAs and circRNAs are also now emerging. This review will summarise our current understanding of the roles of non-coding RNAs in EMT and TGF-ß signaling with a focus on their functions in cancer progression.

Sensitivity of cartilage mechanical behaviour to spatial variations in material properties.

Articular cartilage tissue exhibits a spatial dependence in material properties that govern mechanical behaviour. A mathematical model of cartilage tissue under one dimensional confined compression testing is developed for normal tissue that takes account of these variations in material properties. Modifications to the model representative of a selection of mechanisms driving osteoarthritic cartilage are proposed, allowing application of the model to both physiological and pathophysiological, osteoarthritic tissue. Incorporating spatial variations into the model requires the specification of more parameters than are required in the absence of these variations. A global sensitivity analysis of these parameters is implemented to identify the dominant mechanisms of mechanical response, in normal and osteoarthritic cartilage tissue, to both static and dynamic loading. The most sensitive parameters differ between dynamic and static mechanics of the cartilage, and also differ between physiological and osteoarthritic pathophysiological cartilage. As a consequence changes in cartilage mechanics in response to alterations in cartilage structure are predicted to be contingent on the nature of loading and the health, or otherwise, of the cartilage. In particular the mechanical response of cartilage, especially deformation, is predicted to be much more sensitive to cartilage stiffness in the superficial zone given the onset of osteoarthritic changes to material properties, such as superficial zone increases in permeability and reductions in fixed charge. In turn this indicates that any degenerative changes in the stiffness associated with the superficial cartilage collagen mesh are amplified if other elements of osteoarthritic disease are present, which provides a suggested mechanism-based explanation for observations that the range of mechanical parameters representative of normal and osteoarthritic tissue can overlap substantially.

A serotype-specific and tiled amplicon multiplex PCR method for whole genome sequencing of dengue virus.

Dengue fever, a mosquito-borne viral disease of significant public health concern in tropical and subtropical regions, is caused by any of the four serotypes of the dengue virus (DENV1-4). Cutting-edge technologies like next-generation sequencing (NGS) are revolutionizing virology, enabling in-depth exploration of DENV's genetic diversity. Here, we present an optimized workflow for full-genome sequencing of DENV 1-4 utilizing tiled amplicon multiplex PCR and Illumina sequencing. Our assay, sequenced on the Illumina MiSeq platform, demonstrates its ability to recover the full-length dengue genome across various viral abundances in clinical specimens with high-quality base coverage. This high quality underscores its suitability for precise examination of intra-host diversity, enriching our understanding of viral evolution and holding potential for improved diagnostic and intervention strategies in regions facing dengue outbreaks.

A two-generation study of attachment in mothers and their young adult offspring: Latent classes of attachment and associations with anxiety and depression.

BACKGROUND: Evidence supports the conceptualization of adult attachment as existing along a continuum of attachment security and insecurity; however, ongoing debates persist regarding the use of categorical versus continuous approaches to studying attachment. Attachment data collected from a large community sample of mothers and their offspring in young adulthood were used to examine i) latent classes of adult attachment, ii) associations between mother and offspring attachment, iii) the relationship between adult attachment and mental health symptoms. METHODS: Mothers and offspring were each administered the Attachment Style Questionnaire when offspring were aged 21-years. Latent class analyses (LCA) were performed to examine response patterns across ASQ items. Associations between mothers' and offspring attachment, and correlations between attachment domains and depression/anxiety subscales were examined. RESULTS: LCA identified four latent classes across a continuum of secure and insecure attachment rather than four distinct adult attachment styles. Anxious attachment subscales correlated strongly with depression/anxiety symptoms in both cohorts. Mothers' attachment was significantly but weakly correlated with their young adult offspring attachment. LIMITATIONS: Attachment was measured at one time point and as such, a causal maternal-offspring attachment relationship could not be established. CONCLUSIONS: Findings support a dimensional view of attachment security and insecurity over a four-category model of adult attachment. Attachment correlated with anxiety and depressive symptoms and highlights the importance of considering adult attachment when addressing mental health. There was limited evidence of a relationship between middle aged mothers and their offspring in young adulthood, suggesting other factors influence attachment in adulthood.

An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis.

Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.

Reanalysis of cluster randomised trial data to account for exposure misclassification using a per-protocol and complier-restricted approach.

The intention-to-treat (ITT) analysis of the Applying Wolbachia to Eliminate Dengue (AWED) trial estimated a protective efficacy of 77.1% for participants resident in areas randomised to receive releases of wMel-infected Aedes aegypti mosquitoes, an emerging dengue preventive intervention. The limiting assumptions of ITT analyses in cluster randomised trials and the mobility of mosquitoes and humans across cluster boundaries indicate the primary analysis is likely to underestimate the full public health benefit. Using spatiotemporally-resolved data on the distribution of Wolbachia mosquitoes and on the mobility of AWED participants (n = 6306), we perform complier-restricted and per-protocol re-examinations of the efficacy of the Wolbachia intervention. Increased intervention efficacy was estimated in all analyses by the refined exposure measures. The complier-restricted analysis returned an estimated efficacy of 80.7% (95% CI 65.9, 89.0) and the per-protocol analysis estimated 82.7% (71.7, 88.4) efficacy when comparing participants with an estimated wMel exposure of ≥ 80% compared to those with <20%. These reanalyses demonstrate how human and mosquito movement can lead to underestimation of intervention effects in trials of vector interventions and indicate that the protective efficacy of Wolbachia is even higher than reported in the primary trial results.

Pediatric Robotic Laryngeal Cleft Repair.

OBJECTIVE: Compare surgical and swallow outcomes in robotic versus traditional laryngeal cleft (LC) repairs. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. METHODS: Pediatric patients who underwent robotic or traditional (open or endoscopic) LC repair between 2010 and 2021 were identified. Patient characteristics, operative times, adverse events, hospital length of stay (LOS), and modified barium swallow study (MBSS) results were compared. RESULTS: Eighteen robotic and thirty traditional LC repairs were identified. Mean surgical (149 vs 111 min, P < .05) and OR times (207 vs 139 min, P < .002) were increased for robotic type I LC repairs, but were similar for type II and III LC. Mean hospital LOS was increased for robotic type I LC repairs (2.6 vs 1.2 days, P < .006), but was decreased for type II (4 vs 12.2 days) and type III (4.3 vs 94.5 days) LC. Postoperative MBSS results were improved for robotic type I LC repairs at 12 months (82% vs 43%, P = .05), and trended toward improvement at 6 months for type II (75% vs 22%), and type III (67% vs 50%) LC repairs, although significance was limited for type II and III LC due to the number of subjects. A robotic approach was used successfully to revise all recurrent LC that failed traditional repairs. CONCLUSION: Robotic type 1 LC repairs demonstrated increased operative times and hospital LOS but improved postoperative swallow outcomes compared to traditional approaches may be particularly useful in cases of recurrent clefts.

Large Nasopharyngeal Hairy Polyp Causing Immediate Respiratory Distress at Birth.

This article presents a rare case of a large hairy polyp, a developmental malformation causing a benign tumor, within the nasopharynx. The patient, born with the polyp obstructing the airway, required immediate intubation and a combined transnasal-transoral surgical approach for excision. The case underscores the challenges in diagnosing and managing such polyps, emphasizing the importance of imaging for surgical planning, and the consideration of multiple approaches to ensure complete resection and prevent recurrence. Laryngoscope, 134:4118-4121, 2024.

Successful introgression of wMel Wolbachia into Aedes aegypti populations in Fiji, Vanuatu and Kiribati.

Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of Aedes aegypti mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium Wolbachia pipientis (wMel strain) into Ae. aegypti populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of wMel-infected Ae. aegypti in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of wMel-infected Ae. aegypti mosquitoes for between 2 to 5 months resulted in wMel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of wMel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years.

Feasibility and safety of stereoelectroencephalography in young children.

PURPOSE: Stereoelectroencephalography (SEEG) is a diagnostic surgery that implants electrodes to identify areas of epileptic onset in patients with drug-resistant epilepsy (DRE). SEEG is effective in identifying the epileptic zone; however, placement of electrodes in very young children has been considered contraindicated due to skull thinness. The goal of this study was to evaluate if SEEG is safe and accurate in young children with thin skulls. METHODS: Four children under the age of two years old with DRE underwent SEEG to locate the region of seizure onset. Presurgical planning and placement of electrodes were performed using ROSA One Brain. Preoperative electrode plans were merged with postoperative CT scans to determine accuracy. Euclidean distance between the planned and actual trajectories was calculated using a 3D coordinate system at both the entry and target points for each electrode. RESULTS: Sixty-three electrodes were placed among four patients. Mean skull thickness at electrode entry sites was 2.34 mm. The mean difference between the planned and actual entry points was 1.12 mm, and the mean difference between the planned and actual target points was 1.73 mm. No significant correlation was observed between planned and actual target points and skull thickness (Pearson R = - 0.170). No perioperative or postoperative complications were observed. CONCLUSIONS: This study demonstrates that SEEG can be safe and accurate in children under two years of age despite thin skulls. SEEG should be considered for young children with DRE, and age and skull thickness are not definite contraindications to the surgery.

Comparison of permeable cell culture inserts for use in culture of a human in vitro air-liquid interface model system.

In this study, we compared 12 mm cell culture inserts with permeable polyester membranes (0.4 µm pores) from two different manufacturers: CELLTREAT® and Corning®. Physical dimensions and masses of the inserts were found to be very similar between the two brands, with CELLTREAT® inserts having a slightly smaller diameter and growth area (11.91 mm; 1.11 cm2 ) compared to Corning® Transwells® (12 mm; 1.13 cm2 ). We compared cell differentiation outcomes of human nasal epithelial cells (HNECs) at air-liquid interface grown on inserts from the two different manufacturers, including trans-epithelial electrical resistance, ciliary beat frequency, ciliated area, and gene expression. HNECs from three male donors were used for all endpoints. No statistically significant differences were observed between paired cultures grown on different brands of insert. In conclusion, these inserts are comparable for use with airway epithelial cell model systems and likely do not impact cellular differentiation or cell culture quality.