A new family of bacterial ribosome hibernation factors.

To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage1,2. In bacteria, two families of hibernation factors have been described, but the low conservation of these proteins and the huge diversity of species, habitats and environmental stressors have confounded their discovery3-6. Here, by combining cryogenic electron microscopy, genetics and biochemistry, we identify Balon, a new hibernation factor in the cold-adapted bacterium Psychrobacter urativorans. We show that Balon is a distant homologue of the archaeo-eukaryotic translation factor aeRF1 and is found in 20% of representative bacteria. During cold shock or stationary phase, Balon occupies the ribosomal A site in both vacant and actively translating ribosomes in complex with EF-Tu, highlighting an unexpected role for EF-Tu in the cellular stress response. Unlike typical A-site substrates, Balon binds to ribosomes in an mRNA-independent manner, initiating a new mode of ribosome hibernation that can commence while ribosomes are still engaged in protein synthesis. Our work suggests that Balon-EF-Tu-regulated ribosome hibernation is a ubiquitous bacterial stress-response mechanism, and we demonstrate that putative Balon homologues in Mycobacteria bind to ribosomes in a similar fashion. This finding calls for a revision of the current model of ribosome hibernation inferred from common model organisms and holds numerous implications for how we understand and study ribosome hibernation.

Glioblastoma and radiotherapy: A multicenter AI study for Survival Predictions from MRI (GRASP study).

BACKGROUND: The aim was to predict survival of glioblastoma at 8 months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. METHODS: Retrospective and prospective data were collected from 206 consecutive glioblastoma, isocitrate dehydrogenase -wildtype patients diagnosed between March 2014 and February 2022 across 11 UK centers. Models were trained on 158 retrospective patients from 3 centers. Holdout test sets were retrospective (n = 19; internal validation), and prospective (n = 29; external validation from 8 distinct centers). Neural network branches for T2-weighted and contrast-enhanced T1-weighted inputs were concatenated to predict survival. A nonimaging branch (demographics/MGMT/treatment data) was also combined with the imaging model. We investigated the influence of individual MR sequences; nonimaging features; and weighted dense blocks pretrained for abnormality detection. RESULTS: The imaging model outperformed the nonimaging model in all test sets (area under the receiver-operating characteristic curve, AUC P = .038) and performed similarly to a combined imaging/nonimaging model (P > .05). Imaging, nonimaging, and combined models applied to amalgamated test sets gave AUCs of 0.93, 0.79, and 0.91. Initializing the imaging model with pretrained weights from 10 000s of brain MRIs improved performance considerably (amalgamated test sets without pretraining 0.64; P = .003). CONCLUSIONS: A deep learning model using MRI images after radiotherapy reliably and accurately determined survival of glioblastoma. The model serves as a prognostic biomarker identifying patients who will not survive beyond a typical course of adjuvant temozolomide, thereby stratifying patients into those who might require early second-line or clinical trial treatment.

Structural and Functional Insights into Viral Programmed Ribosomal Frameshifting.

Protein synthesis by the ribosome is the final stage of biological information transfer and represents an irreversible commitment to gene expression. Accurate translation of messenger RNA is therefore essential to all life, and spontaneous errors by the translational machinery are highly infrequent (∼1/100,000 codons). Programmed -1 ribosomal frameshifting (-1PRF) is a mechanism in which the elongating ribosome is induced at high frequency to slip backward by one nucleotide at a defined position and to continue translation in the new reading frame. This is exploited as a translational regulation strategy by hundreds of RNA viruses, which rely on -1PRF during genome translation to control the stoichiometry of viral proteins. While early investigations of -1PRF focused on virological and biochemical aspects, the application of X-ray crystallography and cryo-electron microscopy (cryo-EM), and the advent of deep sequencing and single-molecule approaches have revealed unexpected structural diversity and mechanistic complexity. Molecular players from several model systems have now been characterized in detail, both in isolation and, more recently, in the context of the elongating ribosome. Here we provide a summary of recent advances and discuss to what extent a general model for -1PRF remains a useful way of thinking.

Otoplasty: The Belfast Experience. A 10-Year Review of 2333 Ear Outcomes.

BACKGROUND: "Prominent ear" remains one of the most common referrals to pediatric plastic surgery. The perceived deformity has been corrected using a multitude of techniques for over a century, and significant variation in practice still exists. Recent studies suggesting that cartilage-scoring techniques are associated with more major complications than suture techniques may have led to an adverse international perception of the technique. Thus, waning use of anterior scoring prominent ear correction appears to be occurring. For appropriate cases, the authors have used anterior scoring for over 20 years, with high patient satisfaction and low complication rates. They present a review of all cases and outcomes from 2005 to 2015. The authors believe this is the largest case series of anterior scoring otoplasty published to date. METHODS: All pediatric cases undergoing prominent ear correction from 2005 to 2015 were included in this retrospective case note analysis and follow-up study. Patient demographics, operative details including early and late complications, and postoperative results were analyzed. METHODS: Over a 10-year period, 1199 otoplasties were performed (1134 bilateral, 65 unilateral), for a total of 2333 ear corrections. A total of 1575 ears were corrected using the anterior scoring technique. The remaining cases underwent correction by means of suture only, cartilage reduction, or combination techniques. There was a significantly lower all-cause reoperation rate for anterior scoring compared to suture-only techniques ( P = 0.0039; significant at P < 0.025). There were no reported cases of cartilage necrosis. CONCLUSIONS: This study demonstrates that in appropriately selected patients, anterior scoring otoplasty is a low-morbidity procedure. In the authors' institution, when compared to suture techniques, it was associated with a lower rate of complications and reoperation rate than suture-only techniques. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Overcoming challenges of translating deep-learning models for glioblastoma: the ZGBM consortium.

OBJECTIVE: To report imaging protocol and scheduling variance in routine care of glioblastoma patients in order to demonstrate challenges of integrating deep-learning models in glioblastoma care pathways. Additionally, to understand the most common imaging studies and image contrasts to inform the development of potentially robust deep-learning models. METHODS: MR imaging data were analysed from a random sample of five patients from the prospective cohort across five participating sites of the ZGBM consortium. Reported clinical and treatment data alongside DICOM header information were analysed to understand treatment pathway imaging schedules. RESULTS: All sites perform all structural imaging at every stage in the pathway except for the presurgical study, where in some sites only contrast-enhanced T1-weighted imaging is performed. Diffusion MRI is the most common non-structural imaging type, performed at every site. CONCLUSION: The imaging protocol and scheduling varies across the UK, making it challenging to develop machine-learning models that could perform robustly at other centres. Structural imaging is performed most consistently across all centres. ADVANCES IN KNOWLEDGE: Successful translation of deep-learning models will likely be based on structural post-treatment imaging unless there is significant effort made to standardise non-structural or peri-operative imaging protocols and schedules.

Attribution of Space-Time Variability in Global-Ocean Dissolved Inorganic Carbon.

The inventory and variability of oceanic dissolved inorganic carbon (DIC) is driven by the interplay of physical, chemical, and biological processes. Quantifying the spatiotemporal variability of these drivers is crucial for a mechanistic understanding of the ocean carbon sink and its future trajectory. Here, we use the Estimating the Circulation and Climate of the Ocean-Darwin ocean biogeochemistry state estimate to generate a global-ocean, data-constrained DIC budget and investigate how spatial and seasonal-to-interannual variability in three-dimensional circulation, air-sea CO2 flux, and biological processes have modulated the ocean sink for 1995-2018. Our results demonstrate substantial compensation between budget terms, resulting in distinct upper-ocean carbon regimes. For example, boundary current regions have strong contributions from vertical diffusion while equatorial regions exhibit compensation between upwelling and biological processes. When integrated across the full ocean depth, the 24-year DIC mass increase of 64 Pg C (2.7 Pg C year-1) primarily tracks the anthropogenic CO2 growth rate, with biological processes providing a small contribution of 2% (1.4 Pg C). In the upper 100 m, which stores roughly 13% (8.1 Pg C) of the global increase, we find that circulation provides the largest DIC gain (6.3 Pg C year-1) and biological processes are the largest loss (8.6 Pg C year-1). Interannual variability is dominated by vertical advection in equatorial regions, with the 1997-1998 El Niño-Southern Oscillation causing the largest year-to-year change in upper-ocean DIC (2.1 Pg C). Our results provide a novel, data-constrained framework for an improved mechanistic understanding of natural and anthropogenic perturbations to the ocean sink.

The use of Liposuction to treat significant contour abnormalities associated with Lipomyeloeningocoele.

INTRODUCTION: Since 1972 when first pioneered, liposuction has developed and is now one of the commonest aesthetic procedures performed worldwide. Evidence of its application in aesthetic lipomodelling is widely known, but there are scant reports in the literature on the use of liposuction in more unusual cases. We report its use as a safe and successful method of contour correction in two cases of lipomyelomeningocoele (LMMC), a form of spina bifida. To our knowledge, this has never been reported before. METHOD: A prospective review was performed and both cases were followed up during the treatment period. Both patients were treated at the Royal Belfast Hospital for Sick Children. Patient charts were reviewed and magnetic resonance imaging was used. RESULTS: Two patients, aged 11 and 17 years, had a large LMMC over the lumbosacral area. Preoperative imaging was obtained in each case to ensure the procedure could safely avoid the underlying spinal cord structures. The use of the Microaire© suction device allowed precise fat extraction. Postoperative images demonstrate reduction of lipomatous bulk and improved contour. CONCLUSION: We have shown that when used with caution liposuction is a safe and effective technique for volume reduction of a LMMC in carefully selected cases.

Insights from structural studies of the cardiovirus 2A protein.

Cardioviruses are single-stranded RNA viruses of the family Picornaviridae. In addition to being the first example of internal ribosome entry site (IRES) utilization, cardioviruses also employ a series of alternative translation strategies, such as Stop-Go translation and programmed ribosome frameshifting. Here, we focus on cardiovirus 2A protein, which is not only a primary virulence factor, but also exerts crucial regulatory functions during translation, including activation of viral ribosome frameshifting and inhibition of host cap-dependent translation. Only recently, biochemical and structural studies have allowed us to close the gaps in our knowledge of how cardiovirus 2A is able to act in diverse translation-related processes as a novel RNA-binding protein. This review will summarize these findings, which ultimately may lead to the discovery of other RNA-mediated gene expression strategies across a broad range of RNA viruses.

Sorting nexin 24 is required for α-granule biogenesis and cargo delivery in megakaryocytes.

Germline defects affecting the DNA-binding domain of the transcription factor FLI1 are associated with a bleeding disorder that is characterized by the presence of large, fused α-granules in platelets. We investigated whether the genes showing abnormal expression in FLI1-deficient platelets could be involved in platelet α-granule biogenesis by undertaking transcriptome analysis of control platelets and platelets harboring a DNA-binding variant of FLI1. Our analysis identified 2,276 transcripts that were differentially expressed in FLI1-deficient platelets. Functional annotation clustering of the coding transcripts revealed significant enrichment for gene annotations relating to protein transport, and identified Sorting nexin 24 (SNX24) as a candidate for further investigation. Using an induced pluripotent stem cell-derived megakaryocyte model, SNX24 expression was found to be increased during the early stages of megakaryocyte differentiation and downregulated during proplatelet formation, indicating tight regulatory control during megakaryopoiesis. CRISPR-Cas9 mediated knockout (KO) of SNX24 led to decreased expression of immature megakaryocyte markers, CD41 and CD61, and increased expression of the mature megakaryocyte marker CD42b (P=0.0001), without affecting megakaryocyte polyploidisation, or proplatelet formation. Electron microscopic analysis revealed an increase in empty membrane-bound organelles in SNX24 KO megakaryocytes, a reduction in α-granules and an absence of immature and mature multivesicular bodies, consistent with a defect in the intermediate stage of α-granule maturation. Co-localization studies showed that SNX24 associates with each compartment of α-granule maturation. Reduced expression of CD62P and VWF was observed in SNX24 KO megakaryocytes. We conclude that SNX24 is required for α-granule biogenesis and intracellular trafficking of α-granule cargo within megakaryocytes.

The impact of COVID-19 on cleft services in Great Britain & Northern Ireland.

INTRODUCTION: Cleft lip and/or palate is the most common craniofacial anomaly and occurs in 1 in 650 to 700 live births in the United Kingdom (UK). The majority of cleft surgery is elective, and as a result, almost all cleft surgery was suspended across the UK in March 2020 during the first national lockdown. The UK has centralised regional Cleft Services which all use the same agreed target-age standards for primary surgery including lip and palate repairs. The coronavirus disease-2019 (COVID-19) response has caused a delay in carrying out procedures. The severity of this delay depends on the impact of COVID-19 on local trusts and R-value within that region. As the country goes through the second and third wave, the impact could be long lasting, and we aimed to quantify it so that the data could be used to guide service prioritisation in the NHS and help future workforce planning. METHODS: An online survey was designed based on the cleft quality dashboard indicators and circulated nationally to all nine cleft regions in the UK. The survey was divided into three main headings: • Duration of suspended cleft services • Quantification of the impact on delayed in surgery/services • Changes needed to restart surgery/services RESULTS: We obtained a 60% response rate with five completed surveys from five out of nine regions. All regions reported that they suspended their cleft services in March 2020 around the time of the first wave and the first national lockdown. There has been an impact on delayed surgical and clinical interventions for cleft patients. Regions were affected differently with some on an exponential waiting list growth projection, whereas other teams are on track to recover from the backlog within 7-22 weeks. There has been an impact on the allied health professionals' services within the cleft multidisciplinary team. The cleft nurses' 24-h reviews, Speech And Language Therapy (SALT), and psychology maintained service delivery in some format. Patient-facing services such as audiology and dentistry were significantly disrupted and continue to experience delays due to reduced capacity. CONCLUSIONS: Various regions have seen a varied impact from COVID-19 on their services, from all cleft regions there seems to be an impact on achieving surgery within the national target age. The adverse effect of the COVID-19 impact is unlikely to be known for a few years to come; however, the data are a useful guide when supporting the allocation of resources within the healthcare setting. A prospective long-term study is required to assess the impact of COVID-19 on cleft surgery, follow-up, assess access to allied health professional MDT clinics, and long-term complications.

Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch.

Programmed -1 ribosomal frameshifting (PRF) in cardioviruses is activated by the 2A protein, a multi-functional virulence factor that also inhibits cap-dependent translational initiation. Here we present the X-ray crystal structure of 2A and show that it selectively binds to a pseudoknot-like conformation of the PRF stimulatory RNA element in the viral genome. Using optical tweezers, we demonstrate that 2A stabilises this RNA element, likely explaining the increase in PRF efficiency in the presence of 2A. Next, we demonstrate a strong interaction between 2A and the small ribosomal subunit and present a cryo-EM structure of 2A bound to initiated 70S ribosomes. Multiple copies of 2A bind to the 16S rRNA where they may compete for binding with initiation and elongation factors. Together, these results define the structural basis for RNA recognition by 2A, show how 2A-mediated stabilisation of an RNA pseudoknot promotes PRF, and reveal how 2A accumulation may shut down translation during virus infection.

Investigating molecular mechanisms of 2A-stimulated ribosomal pausing and frameshifting in Theilovirus.

The 2A protein of Theiler's murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed -1 ribosomal frameshifting (PRF) during infection. Here, we present the X-ray crystal structure of TMEV 2A and define how it recognises the stimulatory RNA element. We demonstrate a critical role for bases upstream of the originally predicted stem-loop, providing evidence for a pseudoknot-like conformation and suggesting that the recognition of this pseudoknot by beta-shell proteins is a conserved feature in cardioviruses. Through examination of PRF in TMEV-infected cells by ribosome profiling, we identify a series of ribosomal pauses around the site of PRF induced by the 2A-pseudoknot complex. Careful normalisation of ribosomal profiling data with a 2A knockout virus facilitated the identification, through disome analysis, of ribosome stacking at the TMEV frameshifting signal. These experiments provide unparalleled detail of the molecular mechanisms underpinning Theilovirus protein-stimulated frameshifting.

Throat Packs in Cleft and Craniofacial Surgery.

ABSTRACT: Throat packs are used in a wide range of surgical and dental procedures. Indications for use include; airway stabilization, reducing the risk of aspiration, and postoperative nausea and vomiting. Despite these perceived benefits, a retained throat pack can be fatal. This has been highlighted since the 1970s but as of yet no effective fail-safe mechanisms exist to prevent the potential tragic consequences of a retained throat pack.A multifaceted questionnaire was distributed at the annual Craniofacial Society of Great Britain and Ireland 2017 to identify current views and practices amongst cleft surgeons. The questionnaire contained seventeen questions related to throat pack use. The responses to the questions were collated and discussed in the context of the current literature.Twenty-four cleft surgeons completed the questionnaire; 67% always use a throat pack, with 84% not securing the throat pack in any way. Almost half (48%) had encountered a serious adverse incident secondary to the use of a throat pack.This survey and review of the literature highlight ongoing discrepancies and a lack of standardization on a national basis. Adverse incidents and fatalities are still occurring. Overwhelming evidence now confirms the lack of benefit regarding postoperative nausea and vomiting and the authors urge both surgeons and anesthetists to strongly consider the need for a throat pack in routine elective procedures.

Designed Antitumor Peptide for Targeted siRNA Delivery into Cancer Spheroids.

Antimicrobial/anticancer peptides (AMPs/ACPs) have shown promising results as new therapeutic agents in cancer thearpy. Among them, the designed amphiphilic α-helical peptide G(IIKK)3I-NH2 (G3) displayed great affinity and specificity in targeting cancer cells. Here, we report new insights on how G3 penetrates cancer cells. G3 showed high specificity to HCT-116 colon cancer cells compared to the HDFs (human neonatal primary dermal fibroblasts) control. With high concentrations of peptide, a clear cancer cell membrane disruption was observed through SEM. Gene knockdown of the endocytic pathways demonstrated that an energy-dependent endocytic pathway is required for the uptake of the peptide. In addition, G3 can protect and selectively deliver siRNAs into cancer cells and successfully modulated their gene expression. Gene delivery was also tested in 3D cancer spheroids and showed deep penetration delivery into the cancer spheroids. Finally, the in vivo toxicity of G3 was evaluated on zebrafish embryos, showing an increasing toxicity effect with concentration. However, the toxicity of the peptide was attenuated when complexed with siRNA. In addition, negligible toxicity was observed at the concentration range for efficient gene delivery. The current results demonstrate that G3 is promising as an excellent agent for cancer therapy.

Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.

Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless.

The product of the interferon-stimulated gene C19orf66, Shiftless (SHFL), restricts human immunodeficiency virus replication through downregulation of the efficiency of the viral gag/pol frameshifting signal. In this study, we demonstrate that bacterially expressed, purified SHFL can decrease the efficiency of programmed ribosomal frameshifting in vitro at a variety of sites, including the RNA pseudoknot-dependent signals of the coronaviruses IBV, SARS-CoV and SARS-CoV-2, and the protein-dependent stimulators of the cardioviruses EMCV and TMEV. SHFL also reduced the efficiency of stop-codon readthrough at the murine leukemia virus gag/pol signal. Using size-exclusion chromatography, we confirm the binding of the purified protein to mammalian ribosomes in vitro. Finally, through electrophoretic mobility shift assays and mutational analysis, we show that expressed SHFL has strong RNA binding activity that is necessary for full activity in the inhibition of frameshifting, but shows no clear specificity for stimulatory RNA structures.

Pharyngoplasty for Speech Disorders Following Brain Injury.

INTRODUCTION: Dysarthria is one of the commonest neurological speech disorders resulting from brain injury. However, hypernasality commonly co-exists in this subgroup of patients and is commonly overlooked. The authors aim to investigate the merit of surgery in improving hypernasality and speech intelligibility in patients with a mixed pattern of dysarthria and hypernasality secondary to brain injury. MATERIALS AND METHODS: Data was collected from the regional plastic surgery unit over a 10-year period. All patients who underwent a pharyngoplasty for speech improvement following total brain injury from either a traumatic injury or a cerebrovascular accident were included. Patients were followed up post-operatively to assess; improvement in speech rehabilitation, complications and the need for surgical revision. RESULTS: Six patients had a pharyngoplasty for speech improvement. Either a Hynes or Jackson pharyngoplasty was performed, with one patient requiring a hemi-pharyngoplasty. Post-operatively, 1 patient experienced self-limiting sleep apnea which resolved within 1 month. One patient developed obstructive symptoms and required revision. Overall, 83% of patients had clear improvement in speech intelligibility and articulation. CONCLUSIONS: The authors have shown that surgical intervention, in the form of a pharyngoplasty, is an effective method of improving speech intelligibility and articulation, by improving hypernasality and restoring communication in this cohort of patients. The aim of this paper is to highlight this option to colleagues and to heighten the awareness that many patients with a total brain injury have a mixed pattern of speech disturbance and not solely the dysarthria that is attributed to this condition.

The Cleft Nurse Specialist: A Key Building Block in the Cleft Multidisciplinary Team.

INTRODUCTION: The cleft nurse specialist (CNS) plays a key role in counselling and supporting parents from the diagnosis onward. The CNS started in 2012 and we aimed to perform a qualitative study to determine the benefits this brought to the cleft community from the parents' perspective. METHODS: The cleft database was used to locate babies born in 2010/2011 and 2013/2014. Parents were contacted by phone by 2 authors and completed a questionnaire on the care and support they received following the diagnosis, in the early days and around the time of surgery. RESULTS: Parents of 38 babies completed the survey. In 2010/2011, only 21% had an antenatal diagnosis compared to 47% in 2013/2014.2011/2012: 3 unilateral cleft lip and palate (UCLP), 3 bilateral cleft lip and palate (BCLP), 4 CLO, 9 cleft palate only (CPO).2013/2014: 5 UCLP, 7 BCLP, 7 CPO.2011/2012: 68% were counselled by a surgeon, 42% were seen >1 week after birth, with some over a month.2013/2014: 84% were counselled by the CNS, 53% were seen within 48 hours, and 100% within 7 days.Parents in 2013/2014 felt more supported by the cleft team throughout pregnancy and the early days, with home visits being particularly advantageous. CONCLUSION: The introduction of the CNS to the cleft multidisciplinary team has significantly improved the pathway for parents and is a key link with the wider cleft team. With the improvement in antenatal diagnosis, counselling occurs at an earlier stage and prepares parents for the difficulties commonly experienced in the early days. Key themes included; home visits and direct contact with the CNS.

Human and Doll's Hair in a Gastric Trichobezoar, Endoscopic Retrieval Hazards.

Trichobezoars are masses of ingested hair, usually the individual's own hair, that accumulate in the gastrointestinal tract, most commonly in the stomach. When extending into the small intestine, this is termed "Rapunzel syndrome." Removal has traditionally been by laparotomy; however, successful endoscopic removal has also been described. We report the case of a 9-year-old-girl with undiagnosed coeliac disease and Rapunzel syndrome who underwent endoscopic removal of a large trichobezoar, which was followed by unexpected multiple perforations of the small bowel and stomach. Argon plasma coagulation (APC) and snare electrocautery were employed during endoscopy to remove the trichobezoar piecemeal, and approximately 70% was removed without any clear signs of damage to the mucosa. It was discovered subsequently that about 20 of her dolls were found without hair. On investigating the composition of a specific doll hair from the manufacturer, it was discovered that it could be hazardous if burned. It was, therefore, hypothesized that a constellation of factors had conspired to lead to perforation, that is, the potentially hazardous gas produced from the electrical energy applied to the synthetic hair and possible mucosal damage by the physical abrasion of this hair. A review of the literature on endoscopic attempts to remove trichobezoars irrespective of the result reveals a success rate of 30.7%.