Automated translation accurately translates recorded pediatric neurosurgery clinic conversations between Spanish and English.

OBJECTIVE: The purpose of this study is to analyze an automated voice to text translation device by reporting the translation accuracy for recorded pediatric neurosurgery clinic conversations, classifying errors in translation according to their impact on overall understanding, and comparing the incidence of these errors in English to Spanish vs. Spanish to English conversations. METHODS: English and Spanish speaking patients at a single academic health system's outpatient pediatric neurosurgery clinic had their conversations recorded. These recordings were played back to a Google Pixel handheld smartphone with Live Translate voice to text translation software. A certified medical interpreter evaluated recordings for incidence of minor errors, errors impacting understanding, and catastrophic errors affecting patient-provider relationship or care. Two proportion t-testing was used to compare these outcomes. RESULTS: 50 patient visits were recorded: 40 English recordings translated to Spanish and 10 Spanish recordings translated to English. The mean transcript length was 4244 ± 992 words. The overall accuracy was 98.2% ± 0.5%. On average, 46 words were missed in translation (1.09% error rate), 31 understanding-altering translation errors (0.73% error rate), and 0 catastrophic errors were made. There was no significant difference in English to Spanish or vice versa. CONCLUSION: Voice to text translation devices using automatic speech recognition accurately translate recorded clinic conversations between Spanish and English with high accuracy and low incidence of errors impacting medical care or understanding. Further study should investigate additional languages, assess patient preferences and potential concerns with respect to device use, and compare these devices directly to medical interpreters in live clinic settings.

Low surgical weight associated with ETV failure in pediatric hydrocephalus patients.

The use of endoscopic third ventriculostomy (ETV) for treatment of pediatric hydrocephalus has higher failure rates in younger patients. Here we investigate the impact of select perioperative variables, specifically gestational age, chronological age, birth weight, and surgical weight, on ETV failure rates. A retrospective review was performed on patients treated with ETV - with or without choroid plexus cauterization (CPC) - from 2010 to 2021 at a large academic center. Analyses included Cox regression for independent predictors and Kaplan-Meier survival curves for time to-event outcomes. In total, 47 patients were treated with ETV; of these, 31 received adjunctive CPC. Overall, 66% of the cohort experienced ETV failure with a median failure of 36 days postoperatively. Patients aged < 6 months at time of surgery experienced 80% failure rate, and those > 6 months at time of surgery experienced a 41% failure rate. Univariate Cox regression analysis showed weight at the time of ETV surgery was significantly inversely associated with ETV failure with a hazard ratio of 0.92 (95% CI 0.82, 0.99). Multivariate analysis redemonstrated the inverse association of weight at time of surgery with ETV failure with hazard ratio of 0.76 (95% CI 0.60, 0.92), and sensitivity analysis showed < 4.9 kg as the optimal cutoff predicting ETV/CPC failure. Neither chronologic age nor gestational age were found to be significantly associated with ETV failure.In this study, younger patients experienced higher ETV failure rates, but multivariate regression found that weight was a more robust predictor of ETV failure than chronologic age or gestational age, with an optimal cutoff of 4.9 kg in our small cohort. Given the limited sample size, further study is needed to elucidate the independent role of weight as a peri-operative variable in determining ETV candidacy in young infants. Previous presentations: Poster Presentation, Congress of Neurological Surgeons.

Nurses' Perceived Effects of Visitor Restrictions in Hospital Maternity Units.

PURPOSE: To explore how perinatal nurses perceive the effects of visitor restrictions on patient care within a hospital setting. STUDY DESIGN AND METHODS: We distributed a cross-sectional survey online to perinatal nurses in May of 2022. Characteristics of respondents were analyzed using descriptive statistics. Responses to an open-ended question were analyzed via conventional content analysis. RESULTS: Among our sample of 101 nurses, we identified seven codes representing positive effects and seven codes representing negative effects. The most frequently reported positive effects were ability to provide person-centered care (n = 36, 35.6%) and less patient stress and more rest (n = 29, 28.7%). The most frequently reported negative effects were limited patient support (n = 22, 21.8%) and emotional distress to the patient (n = 15, 14.9%). Fourteen percent (n = 14) of respondents cited both positive and negative effects. CLINICAL IMPLICATIONS: Nurses perceived that visitor restrictions resulted in both positive and negative patient experiences. Balancing clinical needs and safety considerations with emotional needs of the childbearing individual requires careful consideration by maternity care clinicians and health care systems. Subsequent research is needed to determine optimal visitation policies during intrapartum and postpartum with consideration to hospital context and patient preferences for optimal care.

Postconception age at surgery as a predictor of ventriculoperitoneal shunt failure.

OBJECTIVE: The gold standard of pediatric hydrocephalus management is the ventriculoperitoneal (VP) shunt. However, VP shunts have high failure rates, and both young age and prematurity have been identified as potential risk factors for shunt failure, although neither variable describes total development at the time of surgery. This study aimed to further characterize age and shunt failure through the use of postconception age at surgery (PCAS) as well as investigate the 40-week PCAS threshold initially described in 1999. METHODS: A retrospective analysis was conducted on all first-time shunt placements at the authors' institution from 2010 to 2021. The National Surgical Quality Improvement Program (NSQIP) pediatric hydrocephalus dataset was used as a parallel analysis to ensure representativeness of the national pediatric hydrocephalus population. RESULTS: In the institutional cohort, infants with a PCAS < 40 weeks exhibited 2.4 times greater odds of shunt failure than those with a PCAS ≥ 40 weeks. In the NSQIP dataset, infants with a PCAS < 40 weeks had 1.45 times greater odds of shunt failure compared with those with a PCAS ≥ 40 weeks. CONCLUSIONS: The 40-week PCAS threshold appears to be a significant predictor of shunt failure in pediatric patients with hydrocephalus. This finding underscores the importance of considering the developmental stage at the time of surgery, rather than just prematurity status, when assessing shunt failure risk.

Phosphorylation of Syntaxin 4 by the Insulin Receptor Drives Exocytic SNARE Complex Formation to Deliver GLUT4 to the Cell Surface.

A major consequence of insulin binding its receptor on fat and muscle cells is the stimulation of glucose transport into these tissues. This is achieved through an increase in the exocytic trafficking rate of the facilitative glucose transporter GLUT4 from intracellular stores to the cell surface. Delivery of GLUT4 to the cell surface requires the formation of functional SNARE complexes containing Syntaxin 4, SNAP23, and VAMP2. Insulin stimulates the formation of these complexes and concomitantly causes phosphorylation of Syntaxin 4. Here, we use a combination of biochemistry and cell biological approaches to provide a mechanistic link between these observations. We present data to support the hypothesis that Tyr-115 and Tyr-251 of Syntaxin 4 are direct substrates of activated insulin receptors, and that these residues modulate the protein's conformation and thus regulate the rate at which Syntaxin 4 forms SNARE complexes that deliver GLUT4 to the cell surface. This report provides molecular details on how the cell regulates SNARE-mediated membrane traffic in response to an external stimulus.

EFR3 and phosphatidylinositol 4-kinase IIIα regulate insulin-stimulated glucose transport and GLUT4 dispersal in 3T3-L1 adipocytes.

Insulin stimulates glucose transport in muscle and adipocytes. This is achieved by regulated delivery of intracellular glucose transporter (GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, resulting in increased cell surface GLUT4 levels. Recent work identified a potential further regulatory step, in which insulin increases the dispersal of GLUT4 in the plasma membrane away from the sites of vesicle fusion. EFR3 is a scaffold protein that facilitates localization of phosphatidylinositol 4-kinase type IIIα to the cell surface. Here we show that knockdown of EFR3 or phosphatidylinositol 4-kinase type IIIα impairs insulin-stimulated glucose transport in adipocytes. Using direct stochastic reconstruction microscopy, we also show that EFR3 knockdown impairs insulin stimulated GLUT4 dispersal in the plasma membrane. We propose that EFR3 plays a previously unidentified role in controlling insulin-stimulated glucose transport by facilitating dispersal of GLUT4 within the plasma membrane.

Knockout of syntaxin-4 in 3T3-L1 adipocytes reveals new insight into GLUT4 trafficking and adiponectin secretion.

Adipocytes are key to metabolic regulation, exhibiting insulin-stimulated glucose transport that is underpinned by the insulin-stimulated delivery of glucose transporter type 4 (SLC2A4, also known and hereafter referred to as GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, and increase cell surface GLUT4 levels. Adipocytokines, such as adiponectin, are secreted via a similar mechanism. We used genome editing to knock out syntaxin-4, a protein reported to mediate fusion between GLUT4-containing vesicles and the plasma membrane in 3T3-L1 adipocytes. Syntaxin-4 knockout reduced insulin-stimulated glucose transport and adiponectin secretion by ∼50% and reduced GLUT4 levels. Ectopic expression of haemagglutinin (HA)-tagged GLUT4 conjugated to GFP showed that syntaxin-4-knockout cells retain significant GLUT4 translocation capacity, demonstrating that syntaxin-4 is dispensable for insulin-stimulated GLUT4 translocation. Analysis of recycling kinetics revealed only a modest reduction in the exocytic rate of GLUT4 in knockout cells, and little effect on endocytosis. These analyses demonstrate that syntaxin-4 is not always rate limiting for GLUT4 delivery to the cell surface. In sum, we show that syntaxin-4 knockout results in reduced insulin-stimulated glucose transport, depletion of cellular GLUT4 levels and inhibition of adiponectin secretion but has only modest effects on the translocation capacity of the cells. This article has an associated First Person interview with Hannah L. Black and Rachel Livingstone, joint first authors of the paper.

A scoping review of cross-cultural experiences of siblings of individuals with intellectual and developmental disabilities in the United States.

BACKGROUND: Siblings undergo unique experiences in growing up with brothers and sisters with intellectual and developmental disabilities (IDD). Although sibling relationships or adjustments among individuals with IDD have received greater attention from the disability field, there has been still less attention to how cultural identities (e.g., race, ethnicity) may influence experiences of siblings of individuals with IDD. AIM: This study used scoping review methodology to understand cross-cultural experiences of siblings of individuals with IDD in the United States. METHOD: Eight articles met inclusion criteria, using the PubMed, Web of Knowledge, PsycINFO, and ERIC databases. RESULTS: Studies reported the impact of cultural identities on sibling emotional and behavioral functioning, school functioning, and caregiving responsibilities. CONCLUSIONS: The need for culturally responsive sibling interventions and implications for international contexts is discussed.

Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes.

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)-containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA-GLUT4-GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA-GLUT4-GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells.

Single-Cell Profiling Reveals Sex, Lineage, and Regional Diversity in the Mouse Kidney.

Chronic kidney disease affects 10% of the population with notable differences in ethnic and sex-related susceptibility to kidney injury and disease. Kidney dysfunction leads to significant morbidity and mortality and chronic disease in other organ systems. A mouse-organ-centered understanding underlies rapid progress in human disease modeling and cellular approaches to repair damaged systems. To enhance an understanding of the mammalian kidney, we combined anatomy-guided single-cell RNA sequencing of the adult male and female mouse kidney with in situ expression studies and cell lineage tracing. These studies reveal cell diversity and marked sex differences, distinct organization and cell composition of nephrons dependent on the time of nephron specification, and lineage convergence, in which contiguous functionally related cell types are specified from nephron and collecting system progenitor populations. A searchable database, Kidney Cell Explorer (https://cello.shinyapps.io/kidneycellexplorer/), enables gene-cell relationships to be viewed in the anatomical framework of the kidney.

Multisite tyrosine phosphorylation of the N-terminus of Mint1/X11α by Src kinase regulates the trafficking of amyloid precursor protein.

Mint/X11 is one of the four neuronal trafficking adaptors that interact with amyloid precursor protein (APP) and are linked with its cleavage to generate ß-amyloid peptide, a key player in the pathology of Alzheimer's disease. How APP switches between adaptors at different stages of the secretory pathway is poorly understood. Here, we show that tyrosine phosphorylation of Mint1 regulates the destination of APP. A canonical SH2-binding motif ((202) YEEI) was identified in the N-terminus of Mint1 that is phosphorylated on tyrosine by C-Src and recruits the active kinase for sequential phosphorylation of further tyrosines (Y191 and Y187). A single Y202F mutation in the Mint1 N-terminus inhibits C-Src binding and tyrosine phosphorylation. Previous studies observed that co-expression of wild-type Mint1 and APP causes accumulation of APP in the trans-Golgi. Unphosphorylatable Mint1 (Y202F) or pharmacological inhibition of Src reduced the accumulation of APP in the trans-Golgi of heterologous cells. A similar result was observed in cultured rat hippocampal neurons where Mint1(Y202F) permitted the trafficking of APP to more distal neurites than the wild-type protein. These data underline the importance of the tyrosine phosphorylation of Mint1 as a critical switch for determining the destination of APP. The regulation of amyloid precursor protein (APP) trafficking is poorly understood. We have discovered that the APP adapter, Mint1, is phosphorylated by C-Src kinase. Mint1 causes APP accumulation in the trans-Golgi network, whereas inhibition of Src or mutation of Mint1-Y202 permits APP recycling. The phosphorylation status of Mint1 could impact on the pathological trafficking of APP in Alzheimer's disease.

Studies of the regulated assembly of SNARE complexes in adipocytes.

Insulin plays a fundamental role in whole-body glucose homeostasis. Central to this is the hormone's ability to rapidly stimulate the rate of glucose transport into adipocytes and muscle cells [1]. Upon binding its receptor, insulin stimulates an intracellular signalling cascade that culminates in redistribution of glucose transporter proteins, specifically the GLUT4 isoform, from intracellular stores to the plasma membrane, a process termed 'translocation' [1,2]. This is an example of regulated membrane trafficking [3], a process that also underpins other aspects of physiology in a number of specialized cell types, for example neurotransmission in brain/neurons and release of hormone-containing vesicles from specialized secretory cells such as those found in pancreatic islets. These processes invoke a number of intriguing biological questions as follows. How is the machinery involved in these membrane trafficking events mobilized in response to a stimulus? How do the signalling pathways that detect the external stimulus interface with the trafficking machinery? Recent studies of insulin-stimulated GLUT4 translocation offer insight into such questions. In the present paper, we have reviewed these studies and draw parallels with other regulated trafficking systems.

Weissella confusa septicemia in a foal.

Weissella confusa is a Gram-positive bacterium that has been identified in environmental and food samples from around the world. Rare cases of bacteremia in immunocompromised people have been reported. A 2-day-old foal was presented for weakness and suspected sepsis. Blood culture yielded pure growth of a Gram-positive coccobacillus, which was identified as W. confusa through sequencing of the 16S ribosomal DNA. Although the foal initially responded to antimicrobial therapy with ceftiofur and metronidazole, it later developed septic complications of the right tarsocrural joint and right digital flexor tendon sheath and was euthanized. Postmortem examination and histology revealed subcutaneous icterus, severe diffuse interstitial pneumonia, septic synovitis, necrotizing vasculitis with marked thrombosis and hemorrhage in the medial digital vessels of the right hind limb, and ischemic necrosis of the right hind hoof laminae. Gram-positive, coccobacilli were observed in the vascular lesion.