Whole blood: total blood product ratio impacts survival in injured children.

INTRODUCTION: Some studies in both children and adults have shown a mortality benefit for the use of low titer group O whole blood (LTOWB) compared to component therapy for traumatic resuscitation. Although LTOWB is not widely available at pediatric trauma centers, its use is increasing. We hypothesized that in children who received whole blood after injury, the proportion of whole blood in relation to the total blood product resuscitation volume would impact survival. METHODS: The trauma database from a single academic pediatric level 1 trauma center was queried for pediatric (age < 18 years) recipients of LTOWB after injury (years 2015-2022). Weight-based blood product (LTOWB, red blood cells, plasma and platelet) transfusion volumes during the first 24 hours of admission were recorded. The ratio of LTOWB to total transfusion volume was calculated. The primary outcome was in-hospital mortality. Multivariable logistic regression model adjusted for the following variables: age, sex, mechanism of injury, injury severity score, shock index, and Glasgow Coma Scale (GCS) score. Adjusted odds ratio representing the change in the odds of mortality by a 10% increase in the LTOWB:total transfusion volume ratio was reported. RESULTS: There were 95 pediatric LTOWB recipients included in the analysis, with median (IQR) age of 10 years (5-14), 58% male, median (IQR) injury severity score of 26 (17-35), 25% penetrating mechanism. The median(IQR) volume of LTOWB transfused was 17 (15-35) mL/kg. LTOWB comprised a median (IQR) of 59% (33-100) of the total blood product resuscitation. Among patients who received LTOWB, there was a 38% decrease in in-hospital mortality for each 10% increase in the proportion of WB within total transfusion volume (p < 0.001) after adjusting for age, sex, mechanism of injury, injury severity score, shock index, and GCS score. CONCLUSION: Increased proportions of LTOWB within the total blood product resuscitation was independently associated with survival in injured children. Based on existing data that suggests safety and improved outcomes with whole blood, consideration may be given to increasing the use of LTOWB over CT resuscitation in pediatric trauma resuscitation. ARTICLE TYPE: Level 3 Evidence; Observational Cohort Study.

Impact of hypocalcemia on mortality in pediatric trauma patients who require transfusion.

INTRODUCTION: Admission hypocalcemia has been associated with poor outcomes in injured adults. The impact of hypocalcemia on mortality has not been widely studied in pediatric trauma. METHODS: A pediatric trauma center database was queried retrospectively (2013-2022) for children age < 18 years who received blood transfusion within 24 hours of injury and had ionized calcium (iCal) level on admission. Children who received massive transfusion (>40 mL/kg) prior to hospital arrival or calcium prior to laboratory testing were excluded. Hypocalcemia was defined by the laboratory lower limit (iCal <1.00). Main outcomes were in-hospital mortality and 24-hour blood product requirements. Logistic regression analysis was performed to adjust for injury severity score (ISS), admission shock index, Glasgow Coma Score (GCS) and weight-adjusted total transfusion volume. RESULTS: In total, 331 children with median (IQR) age of 7 years (2-13) and median (IQR) ISS 25 (14-33) were included, 32 (10%) of whom were hypocalcemic on arrival to the hospital. The hypocalcemic cohort had higher ISS (median (IQR) 30(24-36) vs 22(13-30)) and lower admission GCS (median (IQR) 3 (3-12) vs 8 (3-15)). Age, sex, race, and mechanism were not significantly different between groups. On univariate analysis, hypocalcemia was associated with increased in-hospital (56% vs 18%; p < 0.001) and 24-hour (28% vs 5%; p < 0.001) mortality. Children who were hypocalcemic received a median (IQR) of 22 mL/kg (7-38) more in total weight-adjusted 24-hour blood product transfusion following admission compared to the normocalcemic cohort (p = 0.005). After adjusting for ISS, shock index, GCS, and total transfusion volume, hypocalcemia remained independently associated with increased 24-hour (Odds Ratio(OR) 95% Confidence Interval(CI) = 4.93(1.77-13.77); p = 0.002) and in-hospital mortality (OR 95% CI =3.41(1.22-9.51); p = 0.019). CONCLUSION: Hypocalcemia is independently associated with mortality and receipt of greater weight-adjusted volumes of blood product transfusion after injury in children. The benefit of timely calcium administration in pediatric trauma needs further exploration. LEVEL OF EVIDENCE: III; prognostic/epidemiological.

The Efficacy of Low-Titer Group O Whole Blood Compared With Component Therapy in Civilian Trauma Patients: A Meta-Analysis.

OBJECTIVES: To assess if transfusion with low-titer group O whole blood (LTOWB) is associated with improved early and/or late survival compared with component blood product therapy (CT) in bleeding trauma patients. DATA SOURCES: A systematic search of PubMed, CINAHL, and Web of Science was performed from their inception through December 1, 2023. Key terms included injury, hemorrhage, bleeding, blood transfusion, and whole blood. STUDY SELECTION: All studies comparing outcomes in injured civilian adults and children who received LTOWB versus CT were included. DATA EXTRACTION: Data including author, publication year, sample size, total blood volumes, and clinical outcomes were extracted from each article and reported following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Main outcomes were 24-hour (early) and combined 28-day, 30-day, and in-hospital (late) mortality rates between recipients of LTOWB versus CT, which were pooled using random-effects models. DATA SYNTHESIS: Of 1297 studies reviewed, 24 were appropriate for analysis. Total subjects numbered 58,717 of whom 5,164 received LTOWB. Eleven studies included adults-only, seven included both adults and adolescents, and six only included children. The median (interquartile range) age for patients who received LTOWB and CT was 35 years (24-39) and 35.5 years (23-39), respectively. Overall, 14 studies reported early mortality and 22 studies reported late mortality. LTOWB was associated with improved 24-hour survival (risk ratios [RRs] [95% CI] = 1.07 [1.03-1.12]) and late (RR [95% CI] = 1.05 [1.01-1.09]) survival compared with component therapy. There was no evidence of small study bias and all studies were graded as a moderate level of bias. CONCLUSIONS: These data suggest hemostatic resuscitation with LTOWB compared with CT improves early and late survival outcomes in bleeding civilian trauma patients. The majority of subjects were injured adults; multicenter randomized controlled studies in injured adults and children are underway to confirm these findings.

The Use of Extracorporeal Support to Rescue Patients With Acute Respiratory Distress Syndrome Following Thoracic Surgery.

Postoperative acute respiratory distress syndrome (ARDS) following a general thoracic procedure is associated with high morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) offers an alternate means of cardiopulmonary support in the setting of refractory respiratory failure. We report indications and outcomes patients who after complex general thoracic surgery developed ARDS requiring ECMO support. We performed a retrospective analysis of all patients requiring venovenous (VV) ECMO support in the postoperative period following a general thoracic surgical procedure from January 2011 to December 2019. Exclusion criteria include those who underwent a cardiac procedure, venoarterial (VA) ECMO, cardiothoracic transplantation, or required ECMO only for intraoperative support. Forty instances of postoperative VV ECMO were utilized in patients who underwent a surgery with the thoracic surgical service. Lung procedures were the most common index operations performed (45%) followed by esophageal procedures (40%). Mean time to ECMO initiation from the index operation was 5.45 days with a range of 0 days to 1.3 months. Median length of ECMO support was 9.41 days with a range of 12 hours to 33 days. Patients were cannulated in an elective (70%) or emergent (30%) fashion. ECMO-related complications included a major bleeding event in seven patients. Thirty day survival was 62.5% for the entire cohort and 52.5% of patients were discharged from the hospital and 80.95% of these patients were still alive 90 days after discharge. ECMO is a viable means of cardiopulmonary support that can provide a survival advantage for patients who experience severe refractory respiratory failure following a complex general thoracic surgery.

Ocular coherence tomography image data of the retinal laminar structure in a mouse model of oxygen-induced retinopathy.

The data presented in this article are related to the research paper entitled "Norrin treatment improves ganglion cell survival in an oxygen-induced model of retinal ischemia" (Dailey et al., 2017) [1] This article describes treatment with the human Norrin protein, an atypical Wnt-protein, to improve the survival of retinal ganglion cells in a murine model of Oxygen-Induced Retinopathy (OIR). That study utilized Optical coherence tomography (OCT) to visualize retinal layers at high resolution in vivo, and to quantify changes to nerve fiber layer thickness. Organization of the laminar structure of other retinal layers in this model in vivo, were not known because of uncertainties regarding potential artifacts during the processing of tissue for traditional histology. The OCT image data provided here shows researchers the retinal laminar structural features that exist in vivo in this popular mouse OIR model. Traditional H&E stained retinal tissue sections are also provided here for comparison.

Norrin treatment improves ganglion cell survival in an oxygen-induced retinopathy model of retinal ischemia.

Treatment of a mouse model of oxygen-induced retinopathy (OIR) with recombinant human Norrin (Norrie Disease Protein, gene: NDP) accelerates regrowth of the microvasculature into central ischemic regions of the neural retina, which are generated after treatment with 75% oxygen. While this reduces the average duration and severity of ischemia overall, we do not know if this accelerated recovery of the microvasculature results in any significant survival of retinal ganglion cells (RGCs). The purpose of this study was to investigate ganglion cell survival with and without the intravitreal injection of Norrin in the murine model of oxygen induced retinopathy (OIR), using two strains of mice: C57BL/6J and Thy1-YFP mice. Intravitreal injections of Norrin or vehicle were done after five days of exposure to 75% oxygen from ages P7 to P12. The C57BL/J mice were followed by Spectral-Domain Optical Coherence Tomography (SD-OCT), and the average nerve fiber layer (NFL) and inner-plexiform layer (IPL) thicknesses were measured at twenty-four locations per retina at P42. Additionally, some C57BL/J retinas were flat mounted and immunostained for the RGC marker, Brn3a, to compare the population density of surviving retinal ganglion cells. Using homozygous Thy1-YFP mice, single intrinsically fluorescent RGCs were imaged in live animals with a Micron-III imaging system at ages P21, 28 and P42. The relative percentage of YFP-fluorescent RGCs with dendritic arbors were compared. At age P42, the NFL was thicker in Norrin-injected OIR eyes, 14.4 µm, compared to Vehicle-injected OIR eyes, 13.3 µm (p = 0.01). In the superior retina, the average thickness of the IPL was greater in Norrin-injected OIR eyes, 37.7 µm, compared to Vehicle-injected OIR eyes, 34.6 µm (p = 0.04). Retinas from Norrin injected OIR mice had significantly more surviving RGCs (p = 0.03) than vehicle-injected mice. Based upon NFL thickness and counts of RGCs, we conclude that Norrin treatment, early in the ischemic phase, increased the relative population density of surviving RGCs in the central retinas of OIR mice.

Explaining Delusions: Reducing Uncertainty Through Basic and Computational Neuroscience.

Delusions, the fixed false beliefs characteristic of psychotic illness, have long defied understanding despite their response to pharmacological treatments (e.g., D2 receptor antagonists). However, it can be challenging to discern what makes beliefs delusional compared with other unusual or erroneous beliefs. We suggest mapping the putative biology to clinical phenomenology with a cognitive psychology of belief, culminating in a teleological approach to beliefs and brain function supported by animal and computational models. We argue that organisms strive to minimize uncertainty about their future states by forming and maintaining a set of beliefs (about the organism and the world) that are robust, but flexible. If uncertainty is generated endogenously, beliefs begin to depart from consensual reality and can manifest into delusions. Central to this scheme is the notion that formal associative learning theory can provide an explanation for the development and persistence of delusions. Beliefs, in animals and humans, may be associations between representations (e.g., of cause and effect) that are formed by minimizing uncertainty via new learning and attentional allocation. Animal research has equipped us with a deep mechanistic basis of these processes, which is now being applied to delusions. This work offers the exciting possibility of completing revolutions of translation, from the bedside to the bench and back again. The more we learn about animal beliefs, the more we may be able to apply to human beliefs and their aberrations, enabling a deeper mechanistic understanding.

Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study.

BACKGROUND: The neural underpinnings of impaired consciousness and of the variable severity of behavioural deficits from one absence seizure to the next are not well understood. We aimed to measure functional MRI (fMRI) and electroencephalography (EEG) changes in absence seizures with impaired task performance compared with seizures in which performance was spared. METHODS: In this cross-sectional study done at the Yale School of Medicine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA. We did simultaneous EEG, fMRI, and behavioural testing in patients aged 6-19 years with childhood or juvenile absence epilepsy, and with an EEG with typical 3-4 Hz bilateral spike-wave discharges and normal background. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioural responses analysed by t test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioural responses compared with seizures with spared responses. FINDINGS: 93 patients were enrolled between Jan 1, 2005, and Sept 1, 2013; we recorded 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks. In the default mode network, fMRI amplitude was 0·57% (SD 0·26) for seizures with impaired and 0·40% (0·16) for seizures with spared behavioural responses (mean difference 0·17%, 95% CI 0·11-0·23; p<0·0001). In the task-positive network, fMRI amplitude was 0·53% (SD 0·29) for seizures with impaired and 0·39% (0·15) for seizures with spared behavioral responses (mean difference 0·14%, 95% CI 0·08-0·21; p<0·0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41% (0·25) for seizures with impaired and 0·34% (0·14) for seizures with spared behavioural responses (mean difference 0·07%, 95% CI 0·01-0·13; p=0·02). Mean fractional EEG power in the frontal leads was 50·4 (SD 15·2) for seizures with impaired and 24·8 (6·5) for seizures with spared behavioural responses (mean difference 25·6, 95% CI 21·0-30·3); middle leads 35·4 (6·5) for seizures with impaired, 13·3 (3·4) for seizures with spared behavioural responses (mean difference 22·1, 95% CI 20·0-24·1); posterior leads 41·6 (5·3) for seizures with impaired, 24·6 (8·6) for seizures with spared behavioural responses (mean difference 17·0, 95% CI 14·4-19·7); p<0·0001 for all comparisons. Mean seizure duration was longer for seizures with impaired behaviour at 7·9 s (SD 6·6), compared with 3·8 s (3·0) for seizures with spared behaviour (mean difference 4·1 s, 95% CI 3·0-5·3; p<0·0001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with behavioural impairment. INTERPRETATION: Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioural impairment. These finding suggest that a vulnerable state might exist at the initiation of some absence seizures leading them to have more severe physiological changes and altered consciousness than other absence seizures. FUNDING: National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Science, the Loughridge Williams Foundation, and the Betsy and Jonathan Blattmachr Family.

The Effector Domain of MARCKS Is a Nuclear Localization Signal that Regulates Cellular PIP2 Levels and Nuclear PIP2 Localization.

Translocation to the nucleus of diacylglycerol kinase (DGK)- ζ is dependent on a sequence homologous to the effector domain of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS). These data would suggest that MARCKS could also localize to the nucleus. A single report demonstrated immunofluorescence staining of MARCKS in the nucleus; however, further experimental evidence confirming the specific domain responsible for this localization has not been reported. Here, we report that MARCKS is present in the nucleus in GBM cell lines. We then over-expressed wild-type MARCKS (WT) and MARCKS with the effector domain deleted (ΔED), both tagged with V5-epitope in a GBM cell line with low endogenous MARCKS expression (U87). We found that MARCKS-WT localized to the nucleus, while the MARCKS construct without the effector domain remained in the cytoplasm. We also found that over-expression of MARCKS-WT resulted in a significant increase in total cellular phosphatidyl-inositol (4,5) bisphosphate (PIP2) levels, consistent with prior evidence that MARCKS can regulate PIP2 levels. We also found increased staining for PIP2 in the nucleus with MARCKS-WT over-expression compared to MARCKS ΔED by immunofluorescence. Interestingly, we observed MARCKS and PIP2 co-localization in the nucleus. Lastly, we found changes in gene expression when MARCKS was not present in the nucleus (MARCKS ΔED). These data indicate that the MARCKS effector domain can function as a nuclear localization signal and that this sequence is critical for the ability of MARCKS to regulate PIP2 levels, nuclear localization, and gene expression. These data suggests a novel role for MARCKS in regulating nuclear functions such as gene expression.

The value of muscle biopsies in Pompe disease: identifying lipofuscin inclusions in juvenile- and adult-onset patients.

BACKGROUND: Pompe disease, an inherited deficiency of lysosomal acid alpha-glucosidase (GAA), is a metabolic myopathy with heterogeneous clinical presentations. Late-onset Pompe disease (LOPD) is a debilitating progressive muscle disorder that can occur anytime from early childhood to late adulthood. Enzyme replacement therapy (ERT) with recombinant human GAA is currently available for Pompe patients. Although ERT shows some benefits, the reversal of skeletal muscle pathology - lysosomal glycogen accumulation and autophagic buildup - remains a challenge. In this study, we examined the clinical status and muscle pathology of 22 LOPD patients and one atypical infantile patient on ERT to understand the reasons for muscle resistance to ERT. RESULTS: The patients were divided into three groups for analysis, based on the age of onset and diagnosis: adult-onset patients, juvenile-onset patients, and those identified through newborn screening (NBS). The areas of autophagic buildup found in patients' biopsies of all three groups, contained large autofluorescent inclusions which we show are made of lipofuscin, an indigestible intralysosomal material typically associated with ageing. These inclusions, analysed by staining, spectral analysis, time-resolved Fluorescence Lifetime Imaging (FLIM), and Second Harmonic Generation (SHG) imaging, were the major pathology remaining in many fibers after ERT. The best outcome of ERT both clinically and morphologically was observed in the NBS patients. CONCLUSIONS: The muscle biopsy, in spite of its shortcomings, allowed us to recognize an underreported, ERT-resistant pathology in LOPD; numerous lysosomes and autolysosomes loaded with lipofuscin appear to be a hallmark of LOPD skeletal muscle. Lipofuscin accumulation - a result of inefficient lysosomal degradation - may in turn exacerbate both lysosomal and autophagic abnormalities.

Immunohistochemical characterization of axonal sprouting in mice.

PURPOSE: Transgenic manipulation of mouse physiology facilitates the preclinical study of genetic risk factors, neural plasticity, and reactive processes accompanying Alzheimer's disease. Alternatively, entorhinal cortex lesions (ECLs) model pathophysiological denervation and axonal sprouting in rat. Given reports of anatomical differences between the mouse and rat hippocampus, application of the ECL paradigm to transgenic mice first requires comprehensive characterization of axonal sprouting in the wild-type. METHODS: Adult male C57BL/6 mice sustained unilateral transections of the perforant pathway. Subjects were sacrificed at 1, 4, 10, 18, and 28 days postlesion, and hippocampal sections were stained for AChE, the postsynaptic terminal marker drebrin, and the presynaptic terminal proteins SNAP-25, GAP-43, synapsin, and synaptophysin. To examine synaptic turnover and reinnervation, ipsilateral-to-contralateral staining densities were determined within the dentate molecular layer, and shrinkage-corrected ratios were compared to 28 day-yoked sham cases. RESULTS: At 28 days postlesion, ipsilateral terminal marker densities exhibited significant depression. In contrast, qualitative analyses at earlier time points suggested altered AChE staining patterns and increased SNAP-25 and synapsin immunoreactivity in the inner molecular layer (IML) of the dentate gyrus. CONCLUSIONS: C57BL/6 mice exhibit synaptic reorganization following perforant path transections. The IML may provide a key target for evaluation and intervention in ECL mouse models.

Skeletal muscle pathology of infantile Pompe disease during long-term enzyme replacement therapy.

BACKGROUND: Pompe disease is an autosomal recessive metabolic neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). It has long been believed that the underlying pathology leading to tissue damage is caused by the enlargement and rupture of glycogen-filled lysosomes. Recent studies have also implicated autophagy, an intracellular lysosome-dependent degradation system, in the disease pathogenesis. In this study, we characterize the long-term impact of enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) on lysosomal glycogen accumulation and autophagy in some of the oldest survivors with classic infantile Pompe disease (IPD). METHODS: Muscle biopsies from 8 [4 female, 4 male; 6 cross-reactive immunologic material (CRIM)-positive, 2 CRIM-negative] patients with a confirmed diagnosis of classic IPD were examined using standard histopathological approaches. In addition, muscle biopsies were evaluated by immunostaining for lysosomal marker (lysosomal-associated membrane protein-2; LAMP2), autophagosomal marker (microtubule-associated protein 1 light chain 3; LC3), and acid and alkaline ATPases. All patients received rhGAA by infusion at cumulative biweekly doses of 20-40 mg/kg. RESULTS: Median age at diagnosis of classic IPD was 3.4 months (range: 0 to 6.5 months; n = 8). At the time of muscle biopsy, the patients' ages ranged from 1 to 103 months and ERT duration ranged from 0 (i.e., baseline, pre-ERT) to 96 months. The response to therapy varied considerably among the patients: some patients demonstrated motor gains while others experienced deterioration of motor function, either with or without a period of initial clinical benefit. Skeletal muscle pathology included fiber destruction, lysosomal vacuolation, and autophagic abnormalities (i.e., buildup), particularly in fibers with minimal lysosomal enlargement. Overall, the pathology reflected clinical status. CONCLUSIONS: This is the first study to investigate the impact of rhGAA ERT on lysosomal glycogen accumulation and autophagic buildup in patients with classic IPD beyond 18 months of treatment. Our findings indicate that ERT does not fully halt or reverse the underlying skeletal muscle pathology in IPD. The best outcomes were observed in the two patients who began therapy early, namely at 0.5 and 1.1 months of age.

What else is in store for autophagy? Exocytosis of autolysosomes as a mechanism of TFEB-mediated cellular clearance in Pompe disease.

It is hard to find an area of biology in which autophagy is not involved. In fact, the topic extends beyond scientific research to stimulate intellectual exercise and entertainment-autophagy has found its way into a crossword puzzle (Klionsky, 2013). We have found yet another function of autophagy while searching for a better treatment for Pompe disease, a devastating metabolic myopathy resulting from excessive lysosomal glycogen storage. To relieve this glycogen burden, we stimulated lysosomal exocytosis through upregulation of transcription factor EB (TFEB). Overexpression of TFEB in Pompe muscle clears the cells of enlarged lysosomes, reduces glycogen levels, and alleviates autophagic buildup, the major secondary abnormality in Pompe disease. Unexpectedly, the process of exocytosis does not seem to be a purely lysosomal event; vesicles arranged along the plasma membrane are double-labeled with the lysosomal marker LAMP1 and the autophagosomal marker LC3, indicating that TFEB induces the exocytosis of autolysosomes. Furthermore, the effects of TFEB are almost abrogated in autophagy-deficient Pompe mice, suggesting a previously unrecognized role of autophagy in TFEB-mediated cellular clearance.

Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease.

A recently proposed therapeutic approach for lysosomal storage disorders (LSDs) relies upon the ability of transcription factor EB (TFEB) to stimulate autophagy and induce lysosomal exocytosis leading to cellular clearance. This approach is particularly attractive in glycogen storage disease type II [a severe metabolic myopathy, Pompe disease (PD)] as the currently available therapy, replacement of the missing enzyme acid alpha-glucosidase, fails to reverse skeletal muscle pathology. PD, a paradigm for LSDs, is characterized by both lysosomal abnormality and dysfunctional autophagy. Here, we show that TFEB is a viable therapeutic target in PD: overexpression of TFEB in a new muscle cell culture system and in mouse models of the disease reduced glycogen load and lysosomal size, improved autophagosome processing, and alleviated excessive accumulation of autophagic vacuoles. Unexpectedly, the exocytosed vesicles were labelled with lysosomal and autophagosomal membrane markers, suggesting that TFEB induces exocytosis of autophagolysosomes. Furthermore, the effects of TFEB were almost abrogated in the setting of genetically suppressed autophagy, supporting the role of autophagy in TFEB-mediated cellular clearance.

WITHDRAWN: Clearance of lysosomal glycogen accumulation by Transcription factor EB (TFEB) in muscle cells from lysosomal alpha-glucosidase deficient mice.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.