Prevention of Parenteral Nutrition-associated Cholestasis Using Reduced Dose Soybean Lipid Emulsion: A Multicenter Randomized Trial.

INTRODUCTION: Reducing soybean lipid emulsion (SLE) dose may prevent parenteral nutrition-associated cholestasis (PNAC) but effects on growth and neurodevelopment are unknown. The purpose of this study was to evaluate the effect of reduced dose SLE on growth and neurodevelopment. METHODS: Surgical neonates at 4 centers were randomized to standard SLE (3 g/kg/day) or reduced SLE (1 g/kg/day) over a 12-week period. Bilirubin levels and growth parameters were measured baseline and weekly while on study. The effects of time and group on direct bilirubin and growth were evaluated with a linear mixed effects model. Neurodevelopmental outcomes were assessed at 12- and 24-months corrected gestational age. RESULTS: Twenty-one individuals were randomized (standard dose = 9, reduced dose = 12). Subjects in the reduced dose group had slower rates of direct bilirubin increase and overall levels decreased earlier than those in the standard dose group. There was a trend toward a faster direct bilirubin decrease in the reduced dose group (p = 0.07 at day 84). There were no differences in the rates of change in weight (p = 0.352 at day 84) or height Z-scores (p = 0.11 at day 84) between groups. One subject in the reduced dose group had abnormal neurodevelopmental testing at 24 months. CONCLUSIONS: Surgical neonates randomized to a reduced dose of SLE had improved trends in direct bilirubin levels without clinically significant differences in overall growth and neurodevelopment. TYPE OF STUDY: Randomized Controlled Trial. LEVEL OF EVIDENCE: II.

Autophagy protein ATG-16.2 and its WD40 domain mediate the beneficial effects of inhibiting early-acting autophagy genes in C. elegans neurons.

While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of autophagosomal degradation. Neurons can secrete protein aggregates via vesicles called exophers. Inhibiting neuronal early-acting autophagy genes, except atg-16.2, increased exopher formation and exopher events extended lifespan, suggesting exophers promote organismal fitness. Lifespan extension, reduction in PolyQ aggregates and increase in exophers were absent in atg-16.2 null mutants, and restored by full-length ATG-16.2 expression in neurons, but not by ATG-16.2 lacking its WD40 domain, which mediates noncanonical functions in mammalian systems. We discovered a neuronal role for C. elegans ATG-16.2 and its WD40 domain in lifespan, proteostasis and exopher biogenesis. Our findings suggest noncanonical functions for select autophagy genes in both exopher formation and in aging.

Silky Liquid Metal Electrodes for On-Skin Health Monitoring.

Next generation on-skin electrodes will require soft, flexible, and gentle materials to provide both high-fidelity sensing and wearer comfort. However, many commercially available on-skin electrodes lack these key properties due to their use of rigid hardware, harsh adhesives, uncomfortable support structures, and poor breathability. To address these challenges, this work presents a new device paradigm by joining biocompatible electrospun spider silk with printable liquid metal to yield an incredibly soft and scalable on-skin electrode that is strain-tolerant, conformable, and gentle on-skin. These electrodes, termed silky liquid metal (SLiM) electrodes, are found to be over five times more breathable than commercial wet electrodes, while the silk's intrinsic adhesion mechanism allows SLiM electrodes to avoid the use of harsh artificial adhesives, potentially decreasing skin irritation and inflammation over long-term use. Finally, the SLiM electrodes provide comparable impedances to traditional wet and other liquid metal electrodes, offering a high-fidelity sensing alternative with increased wearer comfort. Human subject testing confirmed the SLiM electrodes ability to sense electrophysiological signals with high fidelity and minimal irritation to the skin. The unique properties of the reported SLiM electrodes offer a comfortable electrophysiological sensing solution especially for patients with pre-existing skin conditions or surface wounds.

Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers.

Toxic protein aggregates can spread among neurons to promote human neurodegenerative disease pathology. We found that in C. elegans touch neurons intermediate filament proteins IFD-1 and IFD-2 associate with aggresome-like organelles and are required cell-autonomously for efficient production of neuronal exophers, giant vesicles that can carry aggregates away from the neuron of origin. The C. elegans aggresome-like organelles we identified are juxtanuclear, HttPolyQ aggregate-enriched, and dependent upon orthologs of mammalian aggresome adaptor proteins, dynein motors, and microtubule integrity for localized aggregate collection. These key hallmarks indicate that conserved mechanisms drive aggresome formation. Furthermore, we found that human neurofilament light chain (NFL) can substitute for C. elegans IFD-2 in promoting exopher extrusion. Taken together, our results suggest a conserved influence of intermediate filament association with aggresomes and neuronal extrusions that eject potentially toxic material. Our findings expand understanding of neuronal proteostasis and suggest implications for neurodegenerative disease progression.

Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell.

Caenorhabditis elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in C. elegans are engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor-associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease.

Neonatal pneumothorax in congenital diaphragmatic hernia: Be wary of high ventilatory pressures.

Background: Patients with congenital diaphragmatic hernia (CDH) require invasive respiratory support and higher ventilator pressures may be associated with barotrauma. We sought to evaluate the risk factors associated with pneumothorax in CDH neonates prior to repair. Methods: We retrospectively reviewed newborns born with CDH between 2014 and 2019 who developed a pneumothorax, and we matched these cases to patients with CDH without pneumothorax. Results: Twenty-six patients were included (n=13 per group). The pneumothorax group required extracorporeal life support (ECLS) more frequently (85% vs 54%, p=0.04), particularly among type A/B defects (31% vs 7%, p=0.01). The pneumothorax group had higher positive end-expiratory pressure (PEEP) within 1 hour of birth (p=0.02), at pneumothorax diagnosis (p=0.003), and at ECLS (p=0.02). The pneumothorax group had a higher mean airway pressure (Paw) at birth (p=0.01), within 1 hour of birth (p=0.01), and at pneumothorax diagnosis (p=0.04). Using multiple logistic regression with cluster robust SEs, higher Paw (OR 2.2, 95% CI 1.08 to 3.72, p=0.03) and PEEP (OR 1.8, 95% CI 1.15 to 3.14, p=0.007) were associated with an increased risk of developing pneumothorax. There was no difference in survival (p=0.09). Conclusions: Development of a pneumothorax in CDH neonates is independently associated with higher Paw and higher PEEP. A pneumothorax increases the likelihood of treated with ECLS, even with smaller defect.

Hepatic Function in Premature Lambs Supported by the Artificial Placenta and Total Parenteral Nutrition.

The artificial placenta (AP) promotes organ development and reduces organ injury in a lamb model of extreme prematurity. This study evaluates hepatic outcomes after AP support with total parenteral nutrition (TPN) administration. Premature lambs (116-121 days estimated gestational age; term = 145) were cannulated for 7 days of AP support. Lambs received TPN with SMOFlipid (n = 7) or Intralipid (n = 5). Liver function and injury were compared between the two groups biochemically and histologically. Groups were compared by ANOVA with Tukey's multiple comparisons or linear-mixed effects models. From baseline to day 7, total bilirubin (Intralipid 2.6 ± 2.3 to 7.9 ± 4.4 mg/dl; SMOFlipid 0.3 ± 0.1 to 5.5 ± 2.3 mg/dl), alanine aminotransferase, and gamma-glutamyl transferase increased in both groups ( p < 0.001 for all). Direct bilirubin (0.3 ± 0.2 to 1.8 ± 1.4 mg/dl; p = 0.006) and AST (27 ± 5 to 309 ± 242 mg/dl; p < 0.001) increased in SMOFlipid group (not measured in Intralipid group). On liver histology, Intralipid showed more cholestasis than SMOFlipid; both groups showed more than tissue controls. The Intralipid group alone showed hepatocyte injury and had more congestion than controls. Lambs supported by the AP with TPN administration maintain normal hepatic function and sustain minimal hepatic injury. SMOFlipid is associated with decreased cholestasis and hepatic injury versus Intralipid.

Management of the undescended testis in children: An American Pediatric Surgical Association Outcomes and Evidence Based Practice Committee Systematic Review.

PURPOSE: Management of undescended testes (UDT) has evolved over the last decade. While urologic societies in the United States and Europe have established some guidelines for care, management by North American pediatric surgeons remains variable. The aim of this systematic review is to evaluate the published evidence regarding the treatment of (UDT) in children. METHODS: A comprehensive search strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were utilized to identify, review, and report salient articles. Five principal questions were asked regarding imaging standards, medical treatment, surgical technique, timing of operation, and outcomes. A literature search was performed from 2005 to 2020. RESULTS: A total of 825 articles were identified in the initial search, and 260 were included in the final review. CONCLUSIONS: Pre-operative imaging and hormonal therapy are generally not recommended except in specific circumstances. Testicular growth and potential for fertility improves when orchiopexy is performed before one year of age. For a palpable testis, a single incision approach is preferred over a two-incision orchiopexy. Laparoscopic orchiopexy is associated with a slightly lower testicular atrophy rate but a higher rate of long-term testicular retraction. One and two-stage Fowler-Stephens orchiopexy have similar rates of testicular atrophy and retraction. There is a higher relative risk of testicular cancer in UDT which may be lessened by pre-pubertal orchiopexy.

Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling.

In human neurodegenerative diseases, neurons can transfer toxic protein aggregates to surrounding cells, promoting pathology via poorly understood mechanisms. In Caenorhabditis elegans, proteostressed neurons can expel neurotoxic proteins in large, membrane-bound vesicles called exophers. We investigated how specific stresses impact neuronal trash expulsion to show that neuronal exopher production can be markedly elevated by oxidative and osmotic stress. Unexpectedly, we also found that fasting dramatically increases exophergenesis. Mechanistic dissection focused on identifying nonautonomous factors that sense and activate the fasting-induced exopher response revealed that DAF16/FOXO-dependent and -independent processes are engaged. Fasting-induced exopher elevation requires the intestinal peptide transporter PEPT-1, lipid synthesis transcription factors Mediator complex MDT-15 and SBP-1/SREPB1, and fatty acid synthase FASN-1, implicating remotely initiated lipid signaling in neuronal trash elimination. A conserved fibroblast growth factor (FGF)/RAS/MAPK signaling pathway that acts downstream of, or in parallel to, lipid signaling also promotes fasting-induced neuronal exopher elevation. A germline-based epidermal growth factor (EGF) signal that acts through neurons is also required for exopher production. Our data define a nonautonomous network that links food availability changes to remote, and extreme, neuronal homeostasis responses relevant to aggregate transfer biology.

Quantitative Approaches for Scoring in vivo Neuronal Aggregate and Organelle Extrusion in Large Exopher Vesicles in C. elegans.

Toxicity of misfolded proteins and mitochondrial dysfunction are pivotal factors that promote age-associated functional neuronal decline and neurodegenerative disease across species. Although these neurotoxic challenges have long been considered to be cell-intrinsic, considerable evidence now supports that misfolded human disease proteins originating in one neuron can appear in neighboring cells, a phenomenon proposed to promote pathology spread in human neurodegenerative disease. C. elegans adult neurons that express aggregating proteins can extrude large (~4 µm) membrane-surrounded vesicles that can include the aggregated protein, mitochondria, and lysosomes. These large vesicles are called "exophers" and are distinct from exosomes (which are about 100x smaller and have different biogenesis). Throwing out cellular debris in exophers may occur by a conserved mechanism that constitutes a fundamental, but formerly unrecognized, branch of neuronal proteostasis and mitochondrial quality control, relevant to processes by which aggregates spread in human neurodegenerative diseases. While exophers have been mostly studied in animals that express high copy transgenic mCherry within touch neurons, these protocols are equally useful in the study of exophergenesis using fluorescently tagged organelles or other proteins of interest in various classes of neurons. Described here are the physical features of C. elegans exophers, strategies for their detection, identification criteria, optimal timing for quantitation, and animal growth protocols that control for stresses that can modulate exopher production levels. Together, details of protocols outlined here should serve to establish a standard for quantitative analysis of exophers across laboratories. This document seeks to serve as a resource in the field for laboratories seeking to elaborate molecular mechanisms by which exophers are produced and by which exophers are reacted to by neighboring and distant cells.

Interdisciplinary Care and a Focus on Fertility Preservation When Multi-cystic Ovaries Cause Ovarian Torsion: A Case of a 9-year-old Girl with Severe, Undiagnosed Hypothyroidism.

BACKGROUND: Ovarian torsion can occur in Van Wyk Grumbach syndrome, a disorder characterized by severe primary hypothyroidism and ovarian enlargement. To date, all documented cases of torsion in this setting describe oophorectomy, which has significant hormonal and fertility implications. CASE: A 9-year-old pubertal girl presented to the emergency room with abdominal pain. Magnetic resonance imaging demonstrated bilateral, multi-cystic ovaries. Operative laparoscopy confirmed unilateral adnexal torsion, and detorsion without oophorectomy was accomplished. Postoperative laboratory tests revealed severe primary hypothyroidism. Ovarian size was reduced with hormone replacement therapy. SUMMARY AND CONCLUSION: This case demonstrates that prompt interdisciplinary intervention and awareness of severe hypothyroidism as a cause of ovarian torsion related to enlarged, multi-cystic ovaries may reduce the rate of oophorectomy, allowing preservation of pediatric patients' future fertility, and reducing morbidity postoperatively through prompt, long-term thyroid supplementation.

Safety of delayed decannulation of venoarterial cannulas in patients with congenital diaphragmatic hernia.

BACKGROUND: The practice of "cutting-away" from venoarterial extracorporeal life support (ECLS) and leaving indwelling heparinized cannulas prior to decannulation is controversial. This study aims to determine the safety and efficacy of this strategy in patients with congenital diaphragmatic hernia (CDH) who require ECLS. METHODS: A single-center retrospective review of electronic health records was performed on all patients with CDH who underwent elective ECLS decannulation between January 2014 and September 2018. Descriptive statistics are presented as medians with interquartile range. RESULTS: Seventy-three percent (19/26) of patients who underwent venoarterial ECLS for CDH were electively decannulated. After a median ECLS run of 10.7 days [6.1-19.5], patients were "cut-away" for a median of 26 h [19.8-43] prior to decannulation. One patient required re-initiation at 36 h for a pulmonary hypertensive crisis (5%). There were no major bleeding or embolic events while "cut-away", and four (21%) patients had clots removed from the cannulas without clinical sequelae. One patient was recannulated 16 days following initial decannulation. CONCLUSIONS: Our data suggests that "cutting-away" from ECLS in patients with congenital diaphragmatic hernia is safe and allows a period of observation without significant complications. This strategy may be particularly helpful in patients at risk for recannulation, but better prognostic criteria are needed. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Treatment Study.

A standardized guideline for antibiotic prophylaxis in surgical neonates.

Infection following surgical procedures leads to increased morbidity and mortality in all populations. Guidelines to aid providers in the proper use of prophylactic antibiotics exist for adults, but are rare in the neonatal surgical population. A recent emphasis on appropriate antibiotic stewardship had led to the development of more guidelines without a coincident increase in surgical site infection. Robust data from randomized, controlled trials, however, remain sparse.

Ovarian masses in the child and adolescent: An American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee systematic review.

BACKGROUND: The treatment of ovarian masses in pediatric patients should balance appropriate surgical management with the preservation of future reproductive capability. Preoperative estimation of malignant potential is essential to planning an optimal surgical strategy. METHODS: The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee drafted three consensus-based questions regarding the evaluation and treatment of ovarian masses in pediatric patients. A search of PubMed, the Cochrane Library, and Web of Science was performed and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify articles for review. RESULTS: Preoperative tumor markers, ultrasound malignancy indices, and the presence or absence of the ovarian crescent sign on imaging can help estimate malignant potential prior to surgical resection. Frozen section also plays a role in operative strategy. Surgical staging is useful for directing chemotherapy and for prognostication. Both unilateral oophorectomy and cystectomy have been used successfully for germ cell and borderline ovarian tumors, although cystectomy may be associated with higher rates of local recurrence. CONCLUSIONS: Malignant potential of ovarian masses can be estimated preoperatively, and fertility-sparing techniques may be appropriate depending on the type of tumor. This review provides recommendations based on a critical evaluation of recent literature. TYPE OF STUDY: Systematic review of level 1-4 studies. LEVEL OF EVIDENCE: Level 1-4 (mainly 3-4).

Q&A: Trash talk: disposal and remote degradation of neuronal garbage.

Caenorhabditis elegans neurons have recently been found to throw out cellular debris for remote degradation and/or storage, adding an "extracellular garbage elimination" option to known intracellular protein and organelle degradation pathways. This Q&A describes initial insights into the biology of seemingly selective protein and organelle elimination by challenged neurons, highlighting mysteries of how garbage is distinguished and sorted in the sending neuron, how the garbage-filled "exophers" appear to elicit degradative responses as they transit neighboring tissue, and how non-digestible materials get thrown out of cells again via processes that may be highly relevant to human neurodegenerative disease mechanisms.

Time to appendectomy for acute appendicitis: A systematic review.

OBJECTIVE: The goal of this systematic review by the American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee was to develop recommendations regarding time to appendectomy for acute appendicitis in children within the context of preventing adverse events, reducing cost, and optimizing patient/parent satisfaction. METHODS: The committee selected three questions that were addressed by searching MEDLINE, Embase, and the Cochrane Library databases for English language articles published between January 1, 1970 and November 3, 2016. Consensus recommendations for each question were made based on the best available evidence for both children and adults. RESULTS: Based on level 3-4 evidence, appendectomy performed within 24h of admission in patients with acute appendicitis does not appear to be associated with increased perforation rates or other adverse events. Based on level 4 evidence, time from admission to appendectomy within 24h does not increase hospital cost or length of stay (LOS). Data are currently limited to determine an association between the timing of appendectomy and parent/patient satisfaction. CONCLUSIONS: There is a paucity of high-quality evidence in the literature regarding timing of appendectomy for patients with acute appendicitis and its association with adverse events or resource utilization. Based on available evidence, appendectomy performed within the first 24h from presentation is not associated with an increased risk of perforation or adverse outcomes. TYPE OF STUDY: Systematic Review of Level 1-4 studies.

Ovarian torsion in pediatric and adolescent patients: A systematic review.

OBJECTIVE: Ovarian torsion in pediatric patients is a rare event and is primarily managed by pediatric general surgeons. Torsion can be treated with detorsion of the ovary or oopherectomy. Oopherectomy is the most common procedure performed by pediatric general surgeons for ovarian torsion. The purpose of this systematic review by the American Pediatric Surgical Association Outcomes and Evidence Based Practice Committee was to examine evidence from the medical literature and provide recommendations regarding the optimal treatment of ovarian torsion. METHODS: Using PRISMA guidelines, six questions were addressed by searching Medline, Cochrane, Embase Central and National clearing house databases using relevant search terms. Risks of ovarian detorsion including thromboembolism and malignancy, indications for oophoropexy, benefits of detorsion including recovery of function and subsequent fertility, and recommended surveillance after detorsion were evaluated. Consensus recommendations were derived for each question based on the best available evidence. RESULTS: Ninety-six studies were included. Risks of ovarian detorsion such as thromboembolism and malignancy were reviewed, demonstrating minimal evidence for unknowingly leaving a malignancy behind in the salvaged ovary and no evidence in the literature of thromboembolic events after detorsion of a torsed ovary. There is no clear evidence supporting the benefit of oophoropexy after a single episode of ovarian torsion. The gross appearance of the ovary does not correlate with long-term ovarian viability or function. Pregnancies have occurred in patients after detorsion of an ovary both spontaneously and with harvested oocytes from previously torsed ovaries. The consensus recommendation for imaging surveillance following ovarian detorsion is an ultrasound at 3months postprocedure but sooner if there is a concern for malignancy. CONCLUSION: There appears to be overwhelming evidence supporting ovarian detorsion rather than oopherectomy for the management of ovarian torsion in pediatric patients. Ovarian salvage is safe and is the preferred treatment for ovarian torsion. Most salvaged ovaries will maintain viability after detorsion. TYPE OF STUDY: Systematic review of level 3-4 studies. LEVEL OF EVIDENCE: 3-4.

Avalon catheters in pediatric patients requiring ECMO: Placement and migration problems.

PURPOSE: The Avalon dual-lumen venovenous catheter has several advantages, but placement techniques and management have not been adequately addressed in the pediatric population. We assessed our institutional outcomes and complications using the Avalon catheter in children. METHODS: We reviewed all pediatric patients who had Avalon catheters placed for respiratory failure at our institution, excluding congenital heart disease patients, from April 2009 to March 2016. All patients were managed using our standard ECMO protocol, and cannula position was followed by daily chest x-ray and intermittent echocardiography (ECHO). Data included demographics, diagnosis, PRISM3 predicted mortality, ECMO duration, complications, and survival. The primary outcome was the need for catheter repositioning. RESULTS: Twenty-five patients were included, with mean age 8.3±6.9years and 15±22days of ECMO support. Overall survival was 68% (17/25). Fourteen patients (56%) underwent placement with fluoroscopy in addition to ultrasound and ECHO, primarily after 2013. Overall, thirteen patients (52%) had problems with cannula malposition. 9 of these (69%) required cannula repositioning. Three of 14 (21%) cannulas placed with fluoroscopy required repositioning, compared to 7/11 (64%) placed without fluoroscopy (p=0.05). CONCLUSIONS: Complications are common with the Avalon catheter in children. Safe percutaneous access requires ultrasound guidance, and use of intraoperative fluoroscopy in addition to echocardiography decreases malposition rates. LEVEL OF EVIDENCE: IV (Prognosis study).

Treatment of congenital pulmonary airway malformations: a systematic review from the APSA outcomes and evidence based practice committee.

PURPOSE: Variation in management characterizes treatment of infants with a congenital pulmonary airway malformation (CPAM). This review addresses six clinically applicable questions using available evidence to provide recommendations for the treatment of these patients. METHODS: Questions regarding the management of a pediatric patient with a CPAM were generated. English language articles published between 1960 and 2014 were compiled after searching Medline and OvidSP. The articles were divided by subject area and by the question asked, then reviewed and included if they specifically addressed the proposed question. RESULTS: 1040 articles were identified on initial search. After screening abstracts per eligibility criteria, 130 articles were used to answer the proposed questions. Based on the available literature, resection of an asymptomatic CPAM is controversial, and when performed is usually completed within the first six months of life. Lobectomy remains the standard resection method for CPAM, and can be performed thoracoscopically or via thoracotomy. There is no consensus regarding a monitoring protocol for observing asymptomatic lesions, although at least one chest computerized tomogram (CT) should be performed postnatally for lesion characterization. An antenatally identified CPAM can be evaluated with MRI if fetal intervention is being considered, but is not required for the fetus with a lesion not at risk for hydrops. Prenatal consultation should be offered for infants with CPAM and encouraged for those infants in whom characteristics indicate risk of hydrops. CONCLUSIONS: Very few articles provided definitive recommendations for care of the patient with a CPAM and none reported Level I or II evidence. Based on available information, CPAMs are usually resected early in life if at all. A prenatally diagnosed congenital lung lesion should be evaluated postnatally with CT, and prenatal counseling should be undertaken in patients at risk for hydrops.

C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress.

The toxicity of misfolded proteins and mitochondrial dysfunction are pivotal factors that promote age-associated functional neuronal decline and neurodegenerative disease. Accordingly, neurons invest considerable cellular resources in chaperones, protein degradation, autophagy and mitophagy to maintain proteostasis and mitochondrial quality. Complicating the challenges of neuroprotection, misfolded human disease proteins and mitochondria can move into neighbouring cells via unknown mechanisms, which may promote pathological spread. Here we show that adult neurons from Caenorhabditis elegans extrude large (approximately 4 µm) membrane-surrounded vesicles called exophers that can contain protein aggregates and organelles. Inhibition of chaperone expression, autophagy or the proteasome, in addition to compromising mitochondrial quality, enhances the production of exophers. Proteotoxically stressed neurons that generate exophers subsequently function better than similarly stressed neurons that did not produce exophers. The extruded exopher transits through surrounding tissue in which some contents appear degraded, but some non-degradable materials can subsequently be found in more remote cells, suggesting secondary release. Our observations suggest that exopher-genesis is a potential response to rid cells of neurotoxic components when proteostasis and organelle function are challenged. We propose that exophers are components of a conserved mechanism that constitutes a fundamental, but formerly unrecognized, branch of neuronal proteostasis and mitochondrial quality control, which, when dysfunctional or diminished with age, might actively contribute to pathogenesis in human neurodegenerative disease and brain ageing.