Endoscopic Repair of Internal Carotid Artery Injury with a Lateral Tongue Muscle Patch Graft: Novel Technique and Literature Review.

Objectives Iatrogenic injury to the internal carotid artery (ICA) is one of the most catastrophic complications of endoscopic sinus and skull base surgery. Previous research has shown that packing with a crushed muscle graft at the injury site can be an effective management technique to control bleeding and prevent the need for ICA sacrifice. Here, we describe a novel and readily available repair donor site-an autologous lateral tongue muscle patch. Design Three representative cases of a successful repair of ICA injuries using a lateral tongue muscle patch are included in this study. The graft measured approximately 2 × 3 cm and was taken from the lateral intrinsic tongue musculature. We describe the harvest of the graft, its advantages, and the details of operative repair. Results The lateral tongue provides a large and readily accessible source of muscle within the surgical field that can be quickly harvested during an endoscopic procedure. For the first case, an expanding parasellar ICA pseudoaneurysm was managed with a tongue muscle patch and nasal packing. In the second case, a cavernous ICA injury was sustained during craniopharyngioma resection. Case three involved an ICA injury during endonasal debridement of invasive fungal rhinosinusitis. None of the patients required embolization or neurovascular stenting. Postoperative angiograms and serial computed tomography angiograms showed complete resolution of the pseudoaneurysm, and the patients continued to do well at least 1 year after repair. Conclusion Lateral tongue muscle graft is an effective and efficient method to manage ICA injuries during endoscopic endonasal surgery. Advantages include the speed of harvest, donor site being readily accessible in the surgical field, and low donor site morbidity. It should be added to the repertoire of possible donor sites for addressing catastrophic sinonasal bleeding.

To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes.

Selection of the correct start codon is critical for high-fidelity protein synthesis. In eukaryotes, this is typically governed by a multitude of initiation factors (eIFs), including eIF2·GTP that directly delivers the initiator tRNA (Met-tRNAi Met ) to the P site of the ribosome. However, numerous reports, some dating back to the early 1970s, have described other initiation factors having high affinity for the initiator tRNA and the ability of delivering it to the ribosome, which has provided a foundation for further work demonstrating non-canonical initiation mechanisms using alternative initiation factors. Here we provide a critical analysis of current understanding of eIF2A, eIF2D, and the MCT-1·DENR dimer, the evidence surrounding their ability to initiate translation, their implications in human disease, and lay out important key questions for the field. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes Translation > Mechanisms Translation > Regulation.

Perceptual decoupling or trigger happiness: the effect of response delays and shorter presentation times on a go-no-go task with a high go prevalence.

In the current investigation, we modified the high Go, low No-Go Sustained Attention to Response Task (SART). Some researchers argue a commission error, an inappropriate response to a No-Go stimulus, in the SART is due to the participant being inattentive, or perceptually decoupled, during stimulus onset. Response delays in the SART reduce commission errors. A response delay may therefore enable a participant who is initially inattentive to recouple their attention in time to appropriately perceive the stimulus and withhold a response to a No-Go stimulus. However, shortening stimulus display duration in the SART should limit the possibility of the participant identifying the stimulus later, if they are initially not attending the stimulus. A response delay should not reduce commission errors if stimulus duration is kept to the minimum duration enabling stimulus recognition. In two experiments, we shortened stimulus onset to offset duration and added response delays of varying lengths. In both experiments, even when stimulus duration was shortened, response delays notably reduced commission errors if the delay was greater than 250 ms. In addition, using the Signal Detection Theory perspective in which errors of commission in the SART are due to a lenient response bias-trigger happiness, we predicted that response delays would result in a shift to a more conservative response bias in both experiments. These predictions were verified. The errors of commission in the SART may not be a measures of conscious awareness per se, but instead indicative of the level of participant trigger happiness-a lenient response bias.

Response uncertainty influences response bias in the sustained attention to response task: a signal detection theory perspective.

In the current investigation, we modified the high Go, low No-Go Sustained Attention to Response Task (SART) by replacing the single response on Go trials with a dual response to increase response uncertainty. In three experiments, a total of 80 participants completed either the original SART with no response uncertainty regarding the Go stimuli, or versions of the dual response SART in which response probabilities for the two possible responses to the Go stimuli varied from 0.9-0.1, 0.7-0.3, to 0.5-0.5. This resulted in a scale of increasing response uncertainty based on information theory to the Go stimuli. The probability of No-Go withhold stimuli was kept.11 in all experiments. Using the Signal Detection Theory perspective proposed by Bedi et al. (Psychological Research: 1-10, 2022), we predicted that increasing response uncertainty would result in a conservative response bias shift, noted by decreased errors of commission and slower response times to both Go and No-Go stimuli. These predictions were verified. The errors of commission in the SART may not be a measures of conscious awareness per se, but instead indicative of the level of participant trigger happiness-the willingness to respond quickly.

Intragraft B cell differentiation during the development of tolerance to kidney allografts is associated with a regulatory B cell signature revealed by single cell transcriptomics.

Mouse kidney allografts are spontaneously accepted in select, fully mismatched donor-recipient strain combinations, like DBA/2J to C57BL/6 (B6), by natural tolerance. We previously showed accepted renal grafts form aggregates containing various immune cells within 2 weeks posttransplant, referred to as regulatory T cell-rich organized lymphoid structures, which are a novel regulatory tertiary lymphoid organ. To characterize the cells within T cell-rich organized lymphoid structures, we performed single-cell RNA sequencing on CD45+ sorted cells from accepted and rejected renal grafts from 1-week to 6-months posttransplant. Analysis of single-cell RNA sequencing data revealed a shifting from a T cell-dominant to a B cell-rich population by 6 months with an increased regulatory B cell signature. Furthermore, B cells were a greater proportion of the early infiltrating cells in accepted vs rejecting grafts. Flow cytometry of B cells at 20 weeks posttransplant revealed T cell, immunoglobulin domain and mucin domain-1+ B cells, potentially implicating a regulatory role in the maintenance of allograft tolerance. Lastly, B cell trajectory analysis revealed intragraft differentiation from precursor B cells to memory B cells in accepted allografts. In summary, we show a shifting T cell- to B cell-rich environment and a differential cellular pattern among accepted vs rejecting kidney allografts, possibly implicating B cells in the maintenance of kidney allograft acceptance.

Caregiver experiences of feeding children with developmental disabilities: a qualitative study using interpretative phenomenological analysis from India.

OBJECTIVE: We aimed to explore caregiver experiences of feeding children with developmental disabilities, in the context of it being influenced by biological, personal and social factors. DESIGN: This study applied a qualitative study design through focus group discussions (FGDs), using interpretative phenomenological analysis. Data were analysed using thematic content analysis. SETTING: This study was conducted at the Child Psychiatry Unit of a tertiary care centre in South India, between March and November 2020. PARTICIPANTS: Seventeen mothers of children with developmental disabilities, who provided written informed consent, participated in four FGDs. RESULTS: Three over-arching themes were identified. Feeding experience: (a) a tedious, confusing task; (b) disproportionate onus on mothers; (c) influenced by sociocultural norms. CONCLUSION: Feeding can be a stressful activity for both caregiver and child, influenced by family structure and sociocultural belief systems. Considering caregivers' emotional status, facilitatory and hindering environmental factors, and actively exploring strategies to promote the generalisation of strategies learnt into real-life outcomes are essential in tailoring deficit-specific feeding interventions.

Experimental investigation of the parameters that affect droplet size and distribution for design calculations of two-phase separators.

The critical design parameter when sizing a separator is the size of oil droplets in the water phase. This study improves the design of a separator by investigating the parameters that control droplet size, frequency, and distribution. Experimental work was performed to investigate the effect of flow rates and oil layer thickness on these parameters. Experiments were performed using a transparent laboratory separator to allow the measurement of droplet properties. The Design of the Experiment (DOE) method with the Taguchi analysis was applied to investigate statistically if droplet properties are solely a function of the independent variables or if they interact. The findings show that the results can be modelled using Gaussian distributions. Droplet size distribution and the number of droplets produced are functions of the interaction between oil flow rate and oil pad thickness. The oil flow rate dominates the droplet size though layer thickness has a minor effect. The number of droplets (Frequency) increases with both oil and water flow rates but decreases with oil pad thickness. There are clear interactions between all variables resulting in different droplet frequencies for combined effects. The distribution of the droplet sizes is controlled by oil layer thickness, where the spread is seen to rise with thickness. However, interactions between the fluid flows and oil pad thickness give rise to different droplet distributions if either variable were changed on its own.

Dual-task effects between tone counting and mathematical calculations.

We examined the impact of performing a tone counting task of varying cognitive loads and mathematical calculations simultaneously, compared to performance on the same tasks done individually. Participants performed continuous mathematical calculations, performed a high and a low cognitive load tone counting task, and also performed the math and counting tasks simultaneously. Performing the two tasks together resulted in significant dual-task interference. We also compared these results to previous studies employing the tone counting tasks with physically demanding tasks (climbing, kayaking and running). The interference between tone counting and mathematical calculations was worse than the interference between tone counting and running and kayaking. For climbing, the difference in interference was more nuanced with evidence indicating climbing uniquely asserts task prioritization. These findings have implications for operations requiring dual or multi-tasking.

Translation reinitiation after uORFs does not fully protect mRNAs from nonsense-mediated decay.

It is estimated that nearly 50% of mammalian transcripts contain at least one upstream open reading frame (uORF), which are typically one to two orders of magnitude smaller than the downstream main ORF. Most uORFs are thought to be inhibitory as they sequester the scanning ribosome, but in some cases allow for translation reinitiation. However, termination in the 5' UTR at the end of uORFs resembles premature termination that is normally sensed by the nonsense-mediated mRNA decay (NMD) pathway. Translation reinitiation has been proposed as a method for mRNAs to prevent NMD. Here, we test how uORF length influences translation reinitiation and mRNA stability in HeLa cells. Using custom 5' UTRs and uORF sequences, we show that reinitiation can occur on heterologous mRNA sequences, favors small uORFs, and is supported when initiation occurs with more initiation factors. After determining reporter mRNA half-lives in HeLa cells and mining available mRNA half-life data sets for cumulative predicted uORF length, we conclude that translation reinitiation after uORFs is not a robust method for mRNAs to prevent NMD. Together, these data suggest that the decision of whether NMD ensues after translating uORFs occurs before reinitiation in mammalian cells.

Balloon Sinuplasty and Stenting in the Management of Complex Frontal Sinus Outflow Tract Fractures.

OBJECTIVE: Classical management of complex fractures involving the frontal sinus outflow tract (FSOT) favors obliteration or cranialization to avoid delayed complications. We aim to exhibit success with a novel application of balloon sinuplasty and frontal stenting in the management of complex injuries disrupting the FSOT, which might have otherwise required more invasive interventions. STUDY DESIGN: Retrospective review. SETTING: Single institution, level 1 trauma center. METHODS: Retrospective review of patients presenting to a level 1 trauma center with fractures involving the FSOT. Outcomes include patency of the FSOT on imaging and endoscopy, rate of complications, degree of residual tabular displacement, and need for revision surgery. RESULTS: Twenty-five patients met inclusion criteria, with complete FSOT obstruction seen in all cases on computed tomography. All patients underwent balloon sinuplasty with frontal sinus stenting; 48% underwent concurrent anterior table repair, and 36% open repair of nasoorbitoethmoid complex fractures. The mean follow-up length was 13.9 months, at which time 91.3% of patients demonstrated radiographic and endoscopic FSOT patency. No residual sinus opacification or pneumocephalus was observed. CONCLUSION: Balloon sinuplasty with frontal sinus stenting is a straightforward and minimally invasive technique that can create a safe sinus in complex fractures disrupting the FSOT while avoiding the need for more invasive procedures.

Feeding Difficulties Among Children With Special Needs: A Cross-Sectional Study From India.

Deficits in feeding can lead to impairments in occupational performance for children with special needs. This correlational study assessed the relationship between oromotor deficits, behavior problems related to feeding, and caregiver perception of the behavior in children with special needs. We included children with neurodevelopmental disorders (n=79), between 2 and 12 years of chronological age, and their caregivers. Those fulfilling the selection criteria were administered the Behavioral Pediatric Feeding Assessment Scale (BPFAS) and Schedule for Oromotor Assessment (SOMA). More than half the sample had skill deficits and behavioral problems related to feeding. There was a statistically significant correlation of oromotor deficits with specific food consistencies and feeding-related behavior problems. Children with special needs have impaired participation in feeding. Deficits at the body system level are associated with parental and cultural factors, which would have to be mitigated to optimize performance.

Go-stimuli probability influences response bias in the sustained attention to response task: a signal detection theory perspective.

The sustained attention to response task (SART) is a popular measure in the psychology and neuroscience of attention. The underlying psychological cause for errors, in particular errors of commission, in the SART is actively disputed. Some researchers have suggested task-disengagement due to mind-wandering or mindlessness, and others have proposed strategic choices. In this study we explored an alternative perspective based on Signal Detection Theory, in which the high rate of commission errors in the SART reflects simply a shift in response bias (criterion) due to the high prevalence of Go-stimuli. We randomly assigned 406 participants to one of ten Go-stimuli prevalence rates (50%, 64%, 74%, 78%, 82%, 86%, 90%, 94%, 98% and 100%). As Go-stimuli prevalence increased reaction times to both Go and No-Go stimuli decreased, omission errors decreased and commission errors increased. These all were predicted from a hypothesized bias shift, but the findings were not compatible with some alternative theories of SART performance. These findings may have implications for similar tasks.

Presymptomatic diagnosis of postoperative infection and sepsis using gene expression signatures.

PURPOSE: Early accurate diagnosis of infection ± organ dysfunction (sepsis) remains a major challenge in clinical practice. Utilizing effective biomarkers to identify infection and impending organ dysfunction before the onset of clinical signs and symptoms would enable earlier investigation and intervention. To our knowledge, no prior study has specifically examined the possibility of pre-symptomatic detection of sepsis. METHODS: Blood samples and clinical/laboratory data were collected daily from 4385 patients undergoing elective surgery. An adjudication panel identified 154 patients with definite postoperative infection, of whom 98 developed sepsis. Transcriptomic profiling and subsequent RT-qPCR were undertaken on sequential blood samples taken postoperatively from these patients in the three days prior to the onset of symptoms. Comparison was made against postoperative day-, age-, sex- and procedure- matched patients who had an uncomplicated recovery (n =151) or postoperative inflammation without infection (n =148). RESULTS: Specific gene signatures optimized to predict infection or sepsis in the three days prior to clinical presentation were identified in initial discovery cohorts. Subsequent classification using machine learning with cross-validation with separate patient cohorts and their matched controls gave high Area Under the Receiver Operator Curve (AUC) values. These allowed discrimination of infection from uncomplicated recovery (AUC 0.871), infectious from non-infectious systemic inflammation (0.897), sepsis from other postoperative presentations (0.843), and sepsis from uncomplicated infection (0.703). CONCLUSION: Host biomarker signatures may be able to identify postoperative infection or sepsis up to three days in advance of clinical recognition. If validated in future studies, these signatures offer potential diagnostic utility for postoperative management of deteriorating or high-risk surgical patients and, potentially, other patient populations.

Prevalence of intellectual disability in India: A meta-analysis.

BACKGROUND: Burden due to intellectual disability (ID) is only third to the depressive disorders and anxiety disorders in India. This national burden significantly contributes to the global burden of ID and hence one has to think globally and act locally to reduce this burden. At its best the collective prevalence of ID is in the form of narrative reviews. There is an urgent need to document the summary prevalence of ID to enhance further policymaking, national programs and resource allocation. AIM: To establish the summary prevalence of ID during the past 60 years in India. METHODS: Two researchers independently and electronically searched PubMed, Scopus, and the Cochrane library from January 1961 to December 2020 using appropriate search terms. Two other investigators extracted the study design, setting, participant characteristics, and measures used to identify ID. Two other researchers appraised the quality of the studies using the Joanna Briggs Institute critical appraisal format for Prevalence Studies. Funnel plot and Egger's regression test were used to ascertain the publication and small study effect on the prevalence. To evaluate the summary prevalence of ID, we used the random effects model with arcsine square-root transformation. Heterogeneity of I 2 ≥ 50% was considered substantial and we determined the heterogeneity with meta-regression. The analyses were performed using STATA (version 16). RESULTS: Nineteen studies were included in the meta-analysis. There was publication bias; the trim-and-fill method was used to further ascertain bias. Concerns with control of confounders and the reliable measure of outcome were noted in the critical appraisal. The summary prevalence of ID was 2% [(95%CI: 2%, 3%); I 2 = 98%] and the adjusted summary prevalence was 1.4%. Meta-regression demonstrated that age of the participants was statistically significantly related to the prevalence; other factors did not influence the prevalence or heterogeneity. CONCLUSION: The summary prevalence of ID in India was established to be 2% taking into consideration the individual prevalence studies over the last six decades. This knowledge should improve the existing disability and mental health policies, national programs and service delivery to reduce the national and global burden associated with ID.

Pediatric Anesthesia Emergence Delirium Scale: A diagnostic meta-analysis.

BACKGROUND: Emergence delirium (EmD) is a troublesome motoric, emotional, and cognitive disturbance associated with morbidity. It is often misdiagnosed despite being present in a substantial proportion of children and adolescents during emergence from anesthesia. AIM: To evaluate the summary diagnostic accuracy of Pediatric Anesthesia Emergence Delirium Scale (PAEDS) for EmD among children and adolescents. METHODS: Two researchers electronically and hand searched the published literature from May 2004 to February 2021 that evaluated the diagnostic accuracy of PAEDS for EmD among children and adolescents, using appropriate terms. Two independent researchers extracted the diagnostic parameters and appraised the study quality with QUADAS-2. Overall, the diagnostic accuracy of the measures was calculated with the summary receiver operating characteristic curve (SROC), the summary sensitivity and specificity, and diagnostic odds ratio (DOR) for EmD. Various diagnostic cut-off points were evaluated for their diagnostic accuracy. Heterogeneity was analyzed by meta-regression. RESULTS: Nine diagnostic accuracy studies of EmD that conformed to our selection criteria and PRISMA guidelines were included in the final analysis. There was no publication bias. The area under the SROC was 0.97 (95% confidence interval [CI]: 95%-98%). Summary sensitivity and specificity were 0.91 (95%CI: 0.81-0.96; I 2 = 92.93%) and 0.94 (95%CI: 0.89-0.97; I 2 = 87.44%), respectively. The summary DOR was 148.33 (95%CI: 48.32-455.32). The effect size for the subgroup analysis of PAEDS cut-off scores of < 10, ≥ 10, and ≥ 12 was 3.73, 2.19, and 2.93, respectively; they were not statistically significantly different. The setting of the study and reference standard were statistically significantly related to the sensitivity of PAEDS but not specificity. CONCLUSION: The PAEDS is an accurate diagnostic measure for the diagnosis of EmD among children and adolescents. Further studies should document its clinical utility.

Indian Academy of Pediatrics Consensus Guidelines on Prevention and Management of Suicidal Behavior in Adolescents.

JUSTIFICATION: Suicide is an important cause of adolescent mortality and morbidity in India. As pediatricians are often the first point of contact for adolescents and their families in the healthcare system, they need guidelines to screen, assess, manage and prevent adolescent suicidal behavior to ensure survival, health and mental well-being of this vulnerable population. OBJECTIVES: To formulate guidelines to aid pediatricians for prevention and management of adolescent suicidal behavior. PROCESS: Indian Academy of Pediatrics, in association with Adolescent Health Academy, formed a multidisciplinary committee of subject experts in June, 2019 to formulate guidelines for adolescent suicide prevention and management. After a review of current scientific literature and preparation of draft guidelines, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by refining of draft guidelines, and discussions over e-mail where suggestions were incorporated and the final document was approved. GUIDELINES: Pediatricians should screen for mental distress, mental disorders and suicidal and para-suicidal (non-suicidal self-injury) behavior during adolescent health visits. Those with suicidal behavior should be referred to a psychiatrist after providing emergency healthcare, risk assessment, immediate counselling and formulation of a safety plan. Pediatricians should partner with the community and policymakers for primary and secondary prevention of adolescent suicide.

The impact of cognitive load on kayaking and kayaking on cognitive performance.

OBJECTIVE: We examined the impact of performing a cognitive task of varying loads and kayaking simultaneously, compared to performance on the same tasks individually. BACKGROUND: When two tasks are performed together, performance often suffers compared to performance on either task alone. Interference not only occurs in competing cognitive tasks, but has also been found with certain physically demanding activities, such as climbing. METHOD: Skilled kayakers performed a kayak course on open water, performed a high and a low cognitive load tone counting task, and also performed the kayak and counting tasks simultaneously. RESULTS: Despite some past research finding dual task facilitation with laboratory aerobic activities, simultaneous kayaking and tone counting led to dual-task interference. CONCLUSION: Concurrent counting and kayaking led to performance impairments in both tasks, relative to single task performance. APPLICATION: The present results are applicable to occupations involving concurrent demanding physical activity and cognitive task performance, such as the work of first responders and military operators. PRéCIS: Kayaking, like climbing, appears to hinder cognitive performance more than the low-risk physical tasks carried out in laboratory conditions.

Evaluation of the binding performance of flavonoids to estrogen receptor alpha by Autodock, Autodock Vina and Surflex-Dock.

Molecular docking is a widely used method to predict the binding modes of small-molecule ligands to the target binding site. However, it remains a challenge to identify the correct binding conformation and the corresponding binding affinity for a series of structurally similar ligands, especially those with weak binding. An understanding of the various relative attributes of popular docking programs is required to ensure a successful docking outcome. In this study, we systematically compared the performance of three popular docking programs, Autodock, Autodock Vina, and Surflex-Dock for a series of structurally similar weekly binding flavonoids (22) binding to the estrogen receptor alpha (ERα). For these flavonoids-ERα interactions, Surflex-Dock showed higher accuracy than Autodock and Autodock Vina. The hydrogen bond overweighting by Autodock and Autodock Vina led to incorrect binding results, while Surflex-Dock effectively balanced both hydrogen bond and hydrophobic interactions. Moreover, the selection of initial receptor structure is critical as it influences the docking conformations of flavonoids-ERα complexes. The flexible docking method failed to further improve the docking accuracy of the semi-flexible docking method for such chemicals. In addition, binding interaction analysis revealed that 8 residues, including Ala350, Glu353, Leu387, Arg394, Phe404, Gly521, His524, and Leu525, are the key residues in ERα-flavonoids complexes. This work provides reference for assessing molecular interactions between ERα and flavonoid-like chemicals and provides instructive information for other environmental chemicals.

Meta-Analysis of RCTs of Technology-Assisted Parent-Mediated Interventions for Children with ASD.

Technology-assisted parent-mediated interventions improve accessibility and are acceptable but not proven to be effective. We conducted a systematic search of 6 databases. We included and analysed results from studies on social and communication outcomes. Sixteen Randomised-Controlled-Trials (RCTs) with 748 participants were included. Most studies were rated as of good quality. Meta-analysis suggested that interventions were probably effective in improving emotion recognition. No significant differences were found in social communication, social functioning or language outcomes. At present, isolated tech interventions do not fulfil criteria for promising or established evidence-based interventions for ASD. Future research needs to focus on improving the effectiveness of technology-assisted parent-mediated interventions for ASD. Prospero Registration Number: CRD42020162825.

Novel intragraft regulatory lymphoid structures in kidney allograft tolerance.

Intragraft events thought to be relevant to the development of tolerance are here subjected to a comprehensive mechanistic study during long-term spontaneous tolerance that occurs in C57BL/6 mice that receive life sustaining DBA/2 kidneys. These allografts rapidly develop periarterial Treg-rich organized lymphoid structures (TOLS) that form in response to class II but not to class I MHC disparity and form independently of lymphotoxin α and lymphotoxin ß receptor pathways. TOLS form in situ in the absence of lymph nodes, spleen, and thymus. Distinctive transcript patterns are maintained over time in TOLS including transcripts associated with Treg differentiation, T cell checkpoint signaling, and Th2 differentiation. Pathway transcripts related to inflammation are expressed in early stages of accepted grafts but diminish with time, while B cell transcripts increase. Intragraft transcript patterns at one week posttransplant distinguish those from kidneys destined to be rejected, that is, C57BL/6 allografts into DBA/2 recipients, from those that will be accepted. In contrast to inflammatory tertiary lymphoid organs (iTLOs) that form in response to chronic viral infection and transgenic Lta expression, TOLS lack high endothelial venules and germinal centers. TOLS represent a novel, pathogenetically important type of TLO that are in situ markers of regulatory tolerance.