Internal Shunting Research Articles

Shunt dependency in supratentorial intraventricular tumors depends on the extent of tumor resection

BackgroundSupratentorial intraventricular tumors (SIVTs) are rare lesions of various entities characteristically presenting with hydrocephalus and often posing a surgical challenge due to their deep-seated localization. We aimed to elaborate on shunt dependency after tumor resection, clinical characteristics, and perioperative morbidity.MethodsWe retrospectively searched the institutional database for patients with supratentorial intraventricular tumors treated at the Department of Neurosurgery of the Ludwig-Maximilians-University in Munich, Germany, between 2014 and 2022.ResultsWe identified 59 patients with over 20 different SIVT entities, most often subependymoma (8/59 patients, 14%). Mean age at diagnosis was 41 ± 3 years. Hydrocephalus and visual symptoms were observed in 37/59 (63%) and 10/59 (17%) patients, respectively. Microsurgical tumor resection was provided in 46/59 patients (78%) with complete resection in 33/46 patients (72%). Persistent postoperative neurological deficits were encountered in 3/46 patients (7%) and generally mild in nature. Complete tumor resection was associated with less permanent shunting in comparison to incomplete tumor resection, irrespective of tumor histology (6% versus 31%, p = 0.025). Stereotactic biopsy was utilized in 13/59 patients (22%), including 5 patients who received synchronous internal shunt implantation for symptomatic hydrocephalus. Median overall survival was not reached and did not differ between patients with or without open resection.ConclusionsSIVT patients display a high risk of developing hydrocephalus and visual symptoms. Complete resection of SIVTs can often be achieved, preventing the need for long-term shunting. Stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms if resection cannot be safely performed. Due to the rather benign histology, the outcome appears excellent when adjuvant therapy is provided.

SURG-39. SURGICAL RESULTS AND LONG-TERM OUTCOME IN SUPRATENTORIAL INTRAVENTRICULAR TUMORS

Abstract BACKGROUND Intraventricular tumors (IVTs) are rare lesions of various entities, which pose a surgical challenge. We aimed to elaborate on surgical approaches and outcomes, postoperative morbidity, and elucidate whether preoperative hydrocephalus necessitates shunting despite surgical resection. METHODS We retrospectively searched the institutional database for patients with supratentorial intraventricular tumours that were treated in the Department of Neurosurgery of the Ludwig-Maximilians-University Munich, Germany between 2014 and 2022. RESULTS We identified 59 patients with supratentorial intraventricular tumors comprising over 15 different tumor entities, most often subependymoma (8/59 patients, 14%). Median age at diagnosis was 41.4 years (range 0-86 years) with 31 male patients (53%) and 28 female patients (48%). Microsurgical tumor resection was completed in 46/59 patients (78%) with incomplete tumor resection (≥ 1ml postoperative tumor volume) in 13/46 patients (28%) and complete tumor resection (< 1ml postoperative tumor volume) in 33/46 patients (72%). In cases where neurosurgical tumor resection was not feasible, stereotactic biopsy was provided in 13/59 patients (22%), often combined with stereotactic internal shunt implantation (5/59 patients, 8%). Mean follow-up was 24 months; median overall survival was not reached. Postoperative persistent hydrocephalus necessitating ventriculoperitoneal shunt placement was rare (5/59 patients, 8%). Ventriculocisternostomy was performed in one patient. New postoperative focal neurological deficits – mostly transient – were encountered in 16/59 patients (27%) at discharge with mild to moderate permanent focal neurological deficits at 3 months in 3/59 patients (5%). CONCLUSION Complete resection of IVT can often be achieved and forms the basis for favourable outcome. Permanent neurological deficits are rare, and hydrocephalus can almost always be alleviated which prevents the need for long-term shunting. If microsurgical resection is not feasible, stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms.

P11.50.A Surgical results and long-term outcome in supratentorial intraventricular tumors

Abstract Background Intraventricular tumors (IVTs) are rare lesions of various entities, which pose a surgical challenge. We aimed to elaborate on surgical approaches and outcomes, postoperative morbidity, and elucidate whether preoperative hydrocephalus necessitates shunting despite surgical resection. Material and Methods We retrospectively searched the institutional database for patients with supratentorial intraventricular tumours that were treated in the Department of Neurosurgery of the Ludwig-Maximilians-University Munich, Germany between 2014 and 2022. Results We identified 60 patients with supratentorial intraventricular tumors comprising over 10 different tumor entities, most often subependymoma (8/60 patients, 13.4%). Median age at diagnosis was 45.5 ± 3.0 years with 31 male patients (51.6%) and 29 female patients (48.3%). Microsurgical tumor resection was completed in 44 patients (45/60 patients, 75%; gross total resection: 36/45 patients, 80%; subtotal resection: 9/45 patients, 20%). In cases where neurosurgical tumor resection was not feasible, stereotactic biopsy was provided in 15/60 patients (25%), often combined with stereotactic internal shunt implantation (8/60 patients, 13.3%). Mean follow-up was 17 months; median overall survival was not reached. Postoperative persistent hydrocephalus necessitating ventriculoperitoneal shunt placement was rare (4/60 patients, 6.7%). Ventriculocisternostomy was performed in one patient. New postoperative focal neurological deficits - mostly transient - were encountered in 16/60 patients (26.6%) at discharge. Postoperative adverse events rate was 11.7%. Conclusion Complete resection of IVT can often be achieved and forms the basis for favourable outcome. Permanent neurological deficits are rare, and hydrocephalus can almost always be alleviated which prevents the need for long-term shunting. If microsurgical resection is not feasible, stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms.

Prenatally Symptomatic Suprasellar Arachnoid Cyst: When to treat? A case-base update

IntroductionSuprasellar Arachnoid Cysts (SAC) are rare heterogeneous entities. Though prenatally diagnosed, they are rarely treated pre-birth. Symptomatic cases are mainly seen in infants. Case descriptionWe describe a case of a prenatally symptomatic suprasellar arachnoid cyst treated postnatally. The cyst was diagnosed on a routine ultrasound at 22 weeks, was rapidly evolving in the ultrasounds and the MRI of the 29th week. It then became symptomatic at 30 weeks with episodes of fetal bradycardia, independent to the uterine contractions. Antenatal treatment was discussed but delivery decided in emergency despite the prematurity via C-section. Though well tolerated postnatally, the cyst continued to grow. Endoscopic ventriculo-cysto-cisternostomy was performed on the 5th day of birth. Despite progressive reduction of the cyst, residual brainstem compression and evolving ventriculomegaly lead to a transient extrathecal internal shunting. Discussion/ConclusionOur case suggests that prenatally diagnosed cysts require a close follow-up. Treatment options and timing should be adapted to anatomy, cyst evolution and symptoms whether it is before or after birth.

Stereotactic and endoscopic treatment of the trapped temporal horn

BackgroundCurrent treatment of a trapped temporal horn consists primarily of ventriculo-peritoneal (VP) shunting. ObjectiveAs a less invasive alternative, we examined an endoscopic-stereotactic approach to connect the trapped temporal horn with the prepontine cistern. MethodsSix patients with different etiology of entrapment were studied. Using frame-based stereotaxy, image fusion and endoscopy a Rickham catheter was placed connecting both compartments. ResultsAfter median follow-up of 22.1 ± 7.8 months all patients improved symptomatically and the size of the temporal horn was normalized. No morbidity was encountered. ConclusionEndoscopic-stereotactic internal shunting of trapped temporal horns into the prepontine cistern can be done with favorable risk profile, and it offers an elegant alternative to traditional VP shunting, by avoiding the inherent complications.

Stereotactic Internal Shunt Placement in Congenital Intracranial Cysts

Treatment of symptomatic intracranial cysts remains a controversial issue. We present a risk/benefit profile of a minimally invasive, not yet described, stereotactic internal shunt implantation technique. The provided data might serve as a reference against which other treatment modalities could be compared. From our prospective database, we identified a consecutive series of patients with symptomatic, untreated cysts who had undergone internal shunting from 2009 to 2017. We estimated the rates of clinical symptom improvement (RCSI), cyst reduction, total complications, and long-term complications. A minimal follow-up of 6 months was required. The prognostic factors were obtained from logistic regression models. Cyst recurrence-free survival was calculated using the Kaplan-Meier method. The outcomes data were compared with those from reported alternative treatment strategies using χ2 statistics. We included 38 patients. The cyst locations differed greatly and included the cerebellum (n= 2), brainstem (n= 5), and pineal area (n= 4). Cyst-associated hydrocephalus (n= 6) resolved after treatment. The 2-year cyst recurrence-free survival rate was 97%. The RCSI and rate of cyst reduction, total complications, and long-term complications was 91%, 97%, 11%, and 2.6%, respectively. We did not find any risk factors associated with the rate of total complications. The RCSI and rate of total and long-term complications compared favorably (P < 0.01) withthe corresponding estimates of alternative treatments (P < 0.01). The described stereotactic internal shunt implantation technique is safe and can be successfully applied for treatment of cystic formations in any location in the brain.

One-year experience in carotid endarterectomy combining general anaesthesia with preserved consciousness and sequential carotid cross-clamping.

Background and aim of the work: We report 1-year single-centre experience in carotid endarterectomy (CEA) combining general anaesthesia with preserved consciousness (GAPC) and standardized carotid sequential cross-clamping, for our protocol effectiveness evaluation in reduction of perioperative stroke, death or cardiologic complications. Methods: We considered all patients who underwent CEA in 2016. All patients underwent superficial cervical plexus block and GAPC with Remifentanil. The surgical technique consisted of common carotid artery (CCA) cross-clamping, carotid bifurcation isolation, external (ECA) and internal carotid artery (ICA) cross-clamping. After CCA cross-clamping, we performed a neurological tolerance test (NTT); this allowed selective shunting only for positive NTT. Primary end-points were: transient ischemic attack (TIA)/stroke, myocardial infarction, death in perioperative period. Secondary end-points were: carotid shunting, peripheral cranial nerves injuries (PCNI), GAPC intolerance, other complications, reintervention in perioperative period, length of hospital stay. Results: 104 consecutive patients underwent CEA with this protocol in the considered period. Twenty-seven (25.9%) patients were symptomatic. Mean clamping time was 48±13.5 minutes. Five cases (4.8%) requested internal carotid artery shunting. No TIA/stroke, myocardial infarction or death were recorded in the perioperative period. PCNI were observed in 19 cases (18.2%) in the immediate post-operative period; 16 of them (84.2%) showed complete or partial resolution at discharge. Only one patient (0.9%) showed GAPC intolerance. No other complication occurred. Three patients (2.9%) underwent reintervention for neck haematoma drainage. Mean hospital stay were 3±0.9 days. Conclusions: GAPC associated with sequential carotid cross-clamping appeared to be safe and effective in prevention of major neurological and cardiologic complications during CEA. (www.actabiomedica.it)

ENDOSCOPIC THIRD VENTRICULOSTOMY VERSUS VENTRICULOPERITONEAL SHUNT IN TREATMENT OF OBSTRUCTIVE HYDROCEPHALUS COMPLICATING PEDIATRIC POSTERIOR FOSSA TUMORS

Background:Posterior fossa tumors are the most common solid tumors found in the pediatric population. Approximately, 70–90% of patients with posterior fossa tumors present with hydrocephalus. This presents an interesting problem to pediatric neurosurgeons for which there remains no consensus: What is the best management strategy for hydrocephalus at the time of the initial presentation of the patient? Objective: This multicenter prospective cohort study compared endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in the treatment of pediatric patients with secondary obstructive hydrocephalus due to posterior fossa tumors. Patients and Methods: Sixty four patients with posterior fossa tumors (24 medulloblastoma, 12 ependymoma, 27 astrocytoma and 1 schwannoma) associated with secondary hydrocephalus were divided into two equal groups according to the treatment procedure done to the secondary hydrocephalus either ETV or VP shunts, with a follow-up period of 6 months, were prospectively studied in this work. Results: Both procedures (ETV and VP shunt) proved to be effective clinically and radiographically. Endoscopic third ventriculostomy (ETV) proved to be superior due to shorter duration of surgery (17 min versus 58 min), no mortality (0% versus 6.25%), and lower incidence of procedure failure (15.6% versus 21.9%) with highest success rate of 100% was for astrocytomas followed by 80% for ependymomas and 63.6% for medulloblastomas. Conclusion: Both procedures (ETV and VP shunt) proved to be effective clinically and radiographically in the treatment of secondary obstructive hydrocephalus in pediatric patients with posterior fossa tumors. For ETV, the safety, simplicity, a more physiological of internal shunting, a significantly shorter surgery duration, absence of mortality, lower significant complications rate, a lower rate of procedure failure, the significant advantages of not becoming shunt dependent and avoidance of hardware complications (malfunction, obstruction, infection) and making safe handling and resection of the posterior fossa tumors feasible, all the previous factors made the ETV to be recommended as the first choice in the treatment of pediatric patients with obstructive hydrocephalus due to posterior fossa tumors.

Intrinsically shunted Josephson junctions for electronics applications

Conventional Josephson metal-insulator-metal devices are inherently underdamped and exhibit hysteretic current-voltage response due to a very high subgap resistance compared to that in the normal state. At the same time, overdamped junctions with single-valued characteristics are needed for most superconducting digital applications. The usual way to overcome the hysteretic behavior is to place an external low-resistance normal-metal shunt in parallel with each junction. Unfortunately, such solution results in a considerable complication of the circuitry design and introduces parasitic inductance through the junction. This paper provides a concise overview of some generic approaches that have been proposed in order to realize internal shunting in Josephson heterostructures with a barrier that itself contains the desired resistive component. The main attention is paid to self-shunted devices with local weak-link transmission probabilities that are so strongly disordered in the interface plane that transmission probabilities are tiny for the main part of the transition region between two super-conducting electrodes, while a small part of the interface is well transparent. We discuss the possibility of realizing a universal bimodal distribution function and emphasize advantages of such junctions that can be considered as a new class of self-shunted Josephson devices promising for practical applications in superconducting electronics operating at 4.2 K.

Comprehensive Hybrid Strategy for Carotid Artery Stenosis with 8 Rules "Toyama Carotid 8"

In this paper, the preliminary results of carotid endarterectomy(CEA)and carotid artery stenting(CAS)for patients with carotid artery stenosis based on the 8 Rules "Toyama Carotid 8" are reported. This study included 104 patients who underwent CEA or CAS for carotid artery stenosis between March 2012 and January 2015. Toyama 8 Rules primarily recommend CEA and CAS for symptomatic and asymptomatic lesions, respectively. However, crossover of therapeutic options can be performed in patients at high surgical risk associated with CEA or CAS. Monitoring of platelet function is important prior to CAS. Internal shunting and near infrared spectroscopy monitoring are essential in CEA. Temporary cardiac pacing is essential in CAS. The choice of protection device and stent depends on the results of MR plaque imaging. Cerebral blood flow measurement is mandatory before and after CEA/CAS. Fifty-two CEAs and 52 CASs were performed for 55 symptomatic and 49 asymptomatic lesions. Crossover of therapeutic options was performed in 10(18%)of 55 symptomatic lesions and 7(14%)of 49 asymptomatic lesions. The 30-day morbidity rate was 1.9% in CEA and 1.9% in CAS. Postoperative diffusion-weighted magnetic resonance imaging showed fresh ischemic lesions in 5 patients who underwent CEA(10%)and 9 who underwent CAS(17%). Hyperperfusion syndrome occurred in one patient(1.0%). A management protocol for carotid artery stenosis needs to be established in hospitals to allow sharing of information and improvement in the short-term results of CEA / CAS for carotid artery stenosis. Further studies are warranted to evaluate the long-term outcome.

Corne temporale exclue, une forme rare d’hydrocéphalie obstructive : à propos de 5 cas

Objective“Entrapped temporal horn” is an unusual form of obstructive hydrocephalus which is due to an obstacle at the trigone of the lateral ventricle that seals off the temporal horn that may act as a space occupying process. In this study, our aim was to assess the clinical presentation, imaging, pathophysiology and the management of this entity. MethodsThe medical records of patients with entrapped temporal horn diagnosed between January 2003 and December 2012 were reviewed retrospectively. ResultsFive patients were identified. In four cases, the condition developed after cranial surgery; an infant having two revisions of a ventriculoperitoneal shunt; an adult operated for a glioblastoma, an infant operated on for cerebral hydatidosis and an infant operated for an occipital encephalocele. In the last patient, the entrapped temporal horn revealed sarcoidosis. ConclusionsTrapped temporal horn syndrome can act as a space occupying process and requires surgical management. Internal shunting provides good results. However, the long term outcome depends on the etiology.

Equol, an Isoflavone Metabolite, Regulates Cancer Cell Viability and Protein Synthesis Initiation via c-Myc and eIF4G

Epidemiological studies implicate dietary soy isoflavones as breast cancer preventives, especially due to their anti-estrogenic properties. However, soy isoflavones may also have a role in promoting breast cancer, which has yet to be clarified. We previously reported that equol, a metabolite of the soy isoflavone daidzein, may advance breast cancer potential via up-regulation of the eukaryotic initiation factor 4GI (eIF4GI). In estrogen receptor negative (ER-) metastatic breast cancer cells, equol induced elevated levels of eIF4G, which were associated with increased cell viability and the selective translation of mRNAs that use non-canonical means of initiation, including internal ribosome entry site (IRES), ribosome shunting, and eIF4G enhancers. These mRNAs typically code for oncogenic, survival, and cell stress molecules. Among those mRNAs translationally increased by equol was the oncogene and eIF4G enhancer, c-Myc. Here we report that siRNA-mediated knockdown of c-Myc abrogates the increase in cancer cell viability and mammosphere formation by equol, and results in a significant down-regulation of eIF4GI (the major eIF4G isoform), as well as reduces levels of some, but not all, proteins encoded by mRNAs that are translationally stimulated by equol treatment. Knockdown of eIF4GI also markedly reduces an equol-mediated increase in IRES-dependent mRNA translation and the expression of specific oncogenic proteins. However, eIF4GI knockdown did not reciprocally affect c-Myc levels or cell viability. This study therefore implicates c-Myc as a potential regulator of the cancer-promoting effects of equol via up-regulation of eIF4GI and selective initiation of translation on mRNAs that utilize non-canonical initiation, including certain oncogenes.

Ribosomal Protein S25 Dependency Reveals a Common Mechanism for Diverse Internal Ribosome Entry Sites and Ribosome Shunting

During viral infection or cellular stress, cap-dependent translation is shut down. Proteins that are synthesized under these conditions use alternative mechanisms to initiate translation. This study demonstrates that at least two alternative translation initiation routes, internal ribosome entry site (IRES) initiation and ribosome shunting, rely on ribosomal protein S25 (RPS25). This suggests that they share a mechanism for initiation that is not employed by cap-dependent translation, since cap-dependent translation is not affected by the loss of RPS25. Furthermore, we demonstrate that viruses that utilize an IRES or a ribosome shunt, such as hepatitis C virus, poliovirus, or adenovirus, have impaired amplification in cells depleted of RPS25. In contrast, viral amplification of a virus that relies solely on cap-dependent translation, herpes simplex virus, is not hindered. We present a model that explains how RPS25 can be a nexus for multiple alternative translation initiation pathways.

Non-canonical translation in RNA viruses

Viral protein synthesis is completely dependent upon the translational machinery of the host cell. However, many RNA virus transcripts have marked structural differences from cellular mRNAs that preclude canonical translation initiation, such as the absence of a 5′ cap structure or the presence of highly structured 5′UTRs containing replication and/or packaging signals. Furthermore, whilst the great majority of cellular mRNAs are apparently monocistronic, RNA viruses must often express multiple proteins from their mRNAs. In addition, RNA viruses have very compact genomes and are under intense selective pressure to optimize usage of the available sequence space. Together, these features have driven the evolution of a plethora of non-canonical translational mechanisms in RNA viruses that help them to meet these challenges. Here, we review the mechanisms utilized by RNA viruses of eukaryotes, focusing on internal ribosome entry, leaky scanning, non-AUG initiation, ribosome shunting, reinitiation, ribosomal frameshifting and stop-codon readthrough. The review will highlight recently discovered examples of unusual translational strategies, besides revisiting some classical cases.

Initiation of Translation of the FMR1 mRNA Occurs Predominantly through 5′-End-Dependent Ribosomal Scanning

The fragile X mental retardation 1 (FMR1) gene contains a CGG repeat within its 5′ untranslated region (5′UTR) that, when expanded to 55–200 CGG repeats (premutation allele), can result in the late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome. The CGG repeat is expected to form a highly stable secondary structure that is capable of inhibiting 5′-cap-dependent translation. Paradoxically, translation in vivo is only mildly impaired within the premutation range, suggesting that other modes of translation initiation may be operating. To address this issue, we translated in vitro a set of reporter mRNAs containing between 0 and 99 CGG repeats in either native (FMR1) or unrelated (heterologous) 5′UTR context. The 5′-cap dependence of translation was assessed by inserting a stable hairpin (HP) near the 5′ end of the mRNAs. The results of the current studies indicate that translation initiation of the FMR1 mRNA occurs primarily by scanning, with little evidence of internal ribosome entry or shunting. Additionally, the efficiency of translation initiation depends on transcription start site selection, with the shorter 5′UTR (downstream transcription start site I) translating with greater efficiency compared to the longer mRNA (start site III) for all CGG-repeat elements studied. Lastly, an HP previously shown to block translation gave differing results depending on the 5′UTR context, in one case initiating translation from within the HP.

Early surgical management of antenatal diagnosed cystic lesions of the foramen of Monro causing monoventricular hydrocephalus

After diagnosis of an antenatal monoventricular hydrocephalus caused by a cystic lesion of the foramen of Monro, treatment modality and time frame may be difficult to assess. Previously, this type of hydrocephalus was often treated with internal shunting. The advent of neuroendoscopy has changed the surgical management of this pathology. We report on two cases of cystic lesions of the foramen of Monro discovered on antenatal ultrasonography. A cavum veli interpositi in one case and a choroid plexus cyst in the other were responsible for unilateral hydrocephalus. In both cases, endoscopic treatment before 1 month of age was performed as the primary procedure with a successful outcome. We advise early endoscopic treatment for newborns presenting with progressive unilateral hydrocephalus caused by a cystic lesion of the foramen of Monro. It has been, in our hands, a safe and efficient procedure.

INTRAOPERATIVE DIRECT THIRD VENTRICULOSTOMY AND AQUEDUCTAL STENTING IN DEEP-SEATED MIDLINE BRAIN TUMOR SURGERY

Surgical resection of deep-seated midline brain tumors does not always resolve obstruction of cerebrospinal fluid pathways, and an additional operation--ventricular shunting--is required. To prevent postoperative obstructive hydrocephalus, we combine tumor removal and internal ventricular shunting in 1 stage. Between 2000 and 2006, 82 patients with deep-seated midline brain tumors (tumors of the third ventricle, pineal region, thalamus, upper brainstem, and superior half of the fourth ventricle) underwent 84 tumor resections with intraoperative internal ventricular shunting. Two types of intraoperative shunting were performed: direct third ventriculostomy with fenestration of the premammillary membrane of the third ventricle floor and Liliequist's membrane, 53 operations; and aqueductal stenting, 30 operations. In 1 patient, third ventriculostomy and aqueductal stenting were performed simultaneously. As most of the tumors had an infiltrative growth pattern, gross total tumor removal was achieved in only 31% of patients in this series. There were no fatal outcomes related to the surgery. Follow-up data were collected in 73 patients (89%) and ranged from 2 to 68 months (median, 16 months). Additional shunting because of inadequate function of stoma or stent was performed in 13 patients at various times after surgery (median, 30 days). The Kaplan-Meier survival analysis demonstrated that at 12 and 24 months the intraoperative direct third ventriculostomy success rates were 67 and 61%, respectively; aqueductal stenting success rates were 93% at both 12 and 24 months. Intraoperative direct third ventriculostomy and aqueductal stenting under direct visual control were found to be reliable methods of hydrocephalus management in patients with deep-seated midline brain tumors.

Anti-Static Robustness Enhancement and High-Frequency Noise Pickup Immunity by Internal Shunting for Tunneling Magnetoresistive Sensors

Internal shunting is introduced on tunneling magnetoresistive heads to enhance device anti-static robustness and external high-frequency noise pickup immunity. The details of the shunting scheme and the mechanism leading to both anti-static robustness and reduced high-frequency noise pickup are discussed.

Tethering of eIF4G to adenoviral mRNAs by viral 100k protein drives ribosome shunting.

Although most mRNAs initiate translation by 5' ribosome scanning, some small fraction of mammalian and viral mRNAs utilize either of two alternate mechanisms, known as internal ribosome entry and ribosome shunting. Ribosome shunting is a poorly understood form of initiation in which 40S ribosome subunits are loaded onto mRNA through interactions with the m7GTP cap, but then bypass large segments of the mRNA as directed by cis-acting RNA shunting elements and trans-acting protein factors. Here, we describe the molecular mechanism by which ribosome shunting occurs with high efficiency on adenovirus late mRNAs. We show that the viral 100k protein possesses a selective binding element for the 5' noncoding region (5'NCR) of viral late mRNAs (known as the tripartite leader), forms a complex with initiation factor eIF4G and poly(A)-binding protein (PABP), and strongly and selectively enhances the level of both factors and 40S ribosome subunits on viral mRNAs in polysomes. Mutational and biochemical studies demonstrate that the ability of 100k protein to bind both the tripartite leader and eIF4G are critical to promote a high level of ribosome shunting. A molecular mechanism for ribosome shunting is described by which enhanced binding of eIF4G and possibly PABP with 100k protein, and simultaneous interaction with the tripartite leader 5'NCR, drives 40S ribosome recruitment and initiation on mRNAs.

Successful management of congenital chyloperitoneum with fibrin glue

Chylous ascites in children has been treated in a variety of ways, including a low-fat diet, medium chain triglycerides, diuretics, total parental nutrition, surgical exploration, and internal peritoneo-venous shunting. The authors describe a child with persistent congenital chyloperitoneum treated successfully with the application of fibrin glue and recommend this as an effective alternative to traditional approaches.