Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

Lanthanide Luminescence and Thermochromic Emission from Soft-Atom Donor Dichalcogenoimidodiphosphinate Ligands.

The luminescence properties of two divalent europium complexes of the type Eu[N(SPPh2)2]2(THF)2 (1) and Eu[N(SePPh2)2]2(THF)2 (2) were investigated. The first complex, Eu[N(SPPh2)2]2(THF)2 (1), was found to be isomorphous with the reported structure of complex 2 and exhibited room temperature luminescence with thermochromic emission upon cooling. We found the complex Eu[N(SePPh2)2]2(THF)2 (2) was also thermochromic but the emission intensity was sensitive to temperature. Both room temperature and low temperature (100 K) single crystal X-ray structural investigation of 1 and 2 indicate geometric distortions of the metal coordination, which may be important for understanding the thermochromic behavior of these complexes. The trivalent europium complex Eu[N(SPPh2)2]3 (3) with the same ligand as 1 was also structurally characterized as a function of temperature and exhibited temperature-dependent luminescence intensity, with no observable emission at room temperature but intense luminescence at 77 K. Variable temperature Raman spectroscopy was used to determine the onset temperature of luminescence of Eu[N(SPPh2)2]3 (3), where the 615 nm (5D0 → 7F2 transition) peak was quenched above 130 K. The UV-visible diffuse reflectance of 3 provides evidence of an LMCT band, supporting a mechanism of thermally activated LMCT quenching of Eu(III) emitting states. A series of ten isomorphous, trivalent lanthanide complexes of type Ln[N(SPPh2)2]3 (Ln = Eu (3) Pr (4), Nd (5), Sm (6), Gd (7), Tb (8)) and Ln[N(SePPh2)2]3 (Ln = Pr (9), Nd (10, structure was previously reported), Sm (11), and Gd (12) for Q = Se) were also synthesized and structurally characterized. These complexes for Ln = Pr, Nd, Sm, and Tb exhibited room temperature luminescence. This study provides examples of temperature-dependent luminescence of both Eu2+ and Eu3+, and the use of soft-atom donor ligands to sensitize lanthanide luminescence in a range of trivalent lanthanides, spanning near IR and visible emitters.

Observation of an Intermediate to H2 Binding in a Metal-Organic Framework.

Coordinatively unsaturated metal sites within certain zeolites and metal-organic frameworks can strongly adsorb a wide array of substrates. While many classical examples involve electron-poor metal cations that interact with adsorbates largely through physical interactions, unsaturated electron-rich metal centers housed within porous frameworks can often chemisorb guests amenable to redox activity or covalent bond formation. Despite the promise that materials bearing such sites hold in addressing myriad challenges in gas separations and storage, very few studies have directly interrogated mechanisms of chemisorption at open metal sites within porous frameworks. Here, we show that nondissociative chemisorption of H2 at the trigonal pyramidal Cu+ sites in the metal-organic framework CuI-MFU-4l occurs via the intermediacy of a metastable physisorbed precursor species. In situ powder neutron diffraction experiments enable crystallographic characterization of this intermediate, the first time that this has been accomplished for any material. Evidence for a precursor intermediate is also afforded from temperature-programmed desorption and density functional theory calculations. The activation barrier separating the precursor species from the chemisorbed state is shown to correlate with a change in the Cu+ coordination environment that enhances π-backbonding with H2. Ultimately, these findings demonstrate that adsorption at framework metal sites does not always follow a concerted pathway and underscore the importance of probing kinetics in the design of next-generation adsorbents.

Perceptions and practices of therapeutic hypothermia in American neonatal intensive care units.

OBJECTIVE: In 2005, therapeutic hypothermia (TH) was used in few American neonatal intensive care units (NICUs) with great variability in practices. We hypothesized that TH would be used with greater frequency and uniformity today. STUDY DESIGN: We surveyed directors of 797 NICUs queried in our prior study to determine attitudes toward and practices of TH. RESULTS: Of the 781 participants with valid addresses, we received completed surveys from 330 (42.3%). There was an increase in the number of respondents who believed that TH is effective (85% versus 31%, p < 0.0001). More NICUs used TH (50% versus 6%, p < 0.0001) and nearly all not offering TH transferred eligible neonates to centers that did (97% versus 29%, p < 0.0001). There has been increased standardization of TH practices with regard to enrollment criteria, duration, and methods of monitoring. CONCLUSION: TH has become standard of care for the treatment of HIE in the United States. Most NICUs that use TH adhere to protocols, but variation still exists in TH practices.

Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates.

OBJECTIVE: To determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation. DESIGN: Retrospective analysis of prospectively collected data on intubations performed in the neonatal intensive care unit (NICU) and delivery room from the National Emergency Airway Registry for Neonates (NEAR4NEOS). SETTING: Eighteen academic NICUs in NEAR4NEOS. PATIENTS: Neonates requiring two or more attempts at intubation between October 2014 and December 2021. MAIN OUTCOME MEASURES: The primary outcome was successful intubation on the second attempt, with severe tracheal intubation-associated events (TIAEs) or severe desaturation (≥20% decline in oxygen saturation) being secondary outcomes. Multivariate regression examined the associations between these outcomes and patient characteristics and changes in intubation practice. RESULTS: 5805 of 13 126 (44%) encounters required two or more intubation attempts, with 3156 (54%) successful on the second attempt. Second attempt success was more likely with changes in any of the following: intubator (OR 1.80, 95% CI 1.56 to 2.07), stylet use (OR 1.65, 95% CI 1.36 to 2.01) or endotracheal tube (ETT) size (OR 2.11, 95% CI 1.74 to 2.56). Changes in stylet use were associated with a reduced chance of severe desaturation (OR 0.74, 95% CI 0.61 to 0.90), but changes in intubator, laryngoscope type or ETT size were not; no changes in intubator or equipment were associated with severe TIAEs. CONCLUSIONS: Successful neonatal intubation on a second attempt was more likely with a change in intubator, stylet use or ETT size.

Redesigning care to support earlier discharge from a neonatal intensive care unit: a design thinking informed pilot.

BACKGROUND: Preterm infants may remain in neonatal intensive care units (NICUs) to receive proper nutrition via nasogastric tube feedings. However, prolonged NICU stays can have negative effects for the patient, the family and the health system. AIM: To demonstrate how a patient-centred, design thinking informed approach supported the development of a pilot programme to enable earlier discharge of preterm babies. METHOD: We report on our design thinking-empathy building approach to programme design, initial outcomes and considerations for ongoing study. RESULTS: Through the use of design thinking methods, we identified unique needs, preferences and concerns that guided the development of our novel early discharge programme. We found that stable, preterm infants unable to feed by mouth and requiring nasogastric tubes can be cared for at home with remote patient monitoring and telehealth support. In addition, novel feeding strategies can help address parental preferences without compromising infant growth. CONCLUSION: A patient-centred, design thinking informed approach supported the development of a pilot programme to enable earlier discharge of preterm babies. The programme resulted in a reduced length of stay, thereby increasing NICU bed capacity and limiting hospital turn-aways.

Neonatal early onset sepsis in Middle Eastern countries: a systematic review.

BACKGROUND: Early onset neonatal sepsis (EOS) accounts for a significant portion of neonatal mortality, which accounts for 46% of global under five child mortality. OBJECTIVE: This systematic review studies the bacterial aetiology of EOS in the Middle East, susceptibility patterns to recommended empirical antibiotic therapy and whether this differs between high-income and middle-income countries in the region. METHODS: Articles were collected from Medline, Web of Science, the Cochrane Library and Index Medicus for the Eastern Mediterranean Region. The articles included in our systematic review met the following criteria: published after January 2000, data relevant to the Middle East, data specific for early onset sepsis, no language restriction. Data on aetiology and susceptibility were extracted from prospective and retrospective studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. This study focused on EOS but does include data regarding neonatal late-onset sepsis antibiotic susceptibility. The data regarding coagulase-negative Staphylococcus species were excluded from final analysis, as possible contaminants. The protocol for this systematic review was registered on PROSPERO: CRD42017060662. RESULTS: 33 articles from 10 countries were included in the analysis. There were 2215 cases of culture-positive EOS, excluding coagulase-negative Staphylococcus. In middle-income countries, Klebsiella species (26%), Staphylococcus aureus (17%) and Escherichia coli (16%) were the most common pathogens, in contrast to group B Streptococcus (26%), E. coli (24%) and Klebsiella (9%) in high-income countries. Overall susceptibility to ampicillin/gentamicin and third-generation cephalosporin were 40% and 37%, respectively, in middle-income countries versus 93% and 91%, respectively, in high-income countries. CONCLUSIONS: EOS in middle-income countries was more likely to be due to Gram-negative pathogens and less likely to be susceptible to empirical antibiotic therapy. This has important public health implications regarding neonatal mortality in the Middle East region.

Optimizing High-risk Infant Follow-up in Nonresearch-based Paradigms: The New England Follow-up Network.

OBJECTIVES: To establish the first regional quality improvement collaborative solely dedicated to follow-through care of high-risk infants after Neonatal intensive care unit (NICU) discharge and to characterize extremely low birth weight (ELBW) follow-up in New England. METHODS: Eleven of 14 follow-up programs in New England partnered with the Vermont Oxford Network (VON) ELBW project for an initial data collection project. We collected information about the health status and developmental outcomes of infants born ≤1,000 g or younger than 28 weeks 2014-2016 at the 18-24 months corrected for gestational age (CGA) follow-up visit. VON collected and compiled the data. RESULTS: Of 993 eligible infants, 516 (52.0%) had follow-up visits. The rehospitalization rate was 33.9%, mostly respiratory illness. Ninety-six children (19.3%) had weight less than 10th percentile and 44 (8.9%) had weight less than third percentile at 18-24 months. Only 170 (61.4%) children had recommended hearing screening after NICU discharge. Forty-six (9.1%) had cerebral palsy; 81 of the 441 infants that completed all 3 sections of the Bayley Scales of Infant Development, third edition (18.4%) had any composite score less than 70. Over half of the social and demographic data were missing. CONCLUSION: Most quality initiatives in neonatology stop at NICU discharge. This first project by the New England Follow-up Network showed a low rate for clinical follow-up. It demonstrated many opportunities to improve postdischarge follow-through specific to NICU-based care. Future projects will aim to improve the quality of follow-through services through collaborative learning, data sharing, and comparative outcomes.

Implementing bubble continuous positive airway pressure in a lower middle-income country: a Nigerian experience.

Bubble CPAP (bCPAP) is used for respiratory distress (RD) in neonates. The leading causes of neonatal mortality can lead to severe RD. Many neonatal deaths are preventable using evidence-based interventions like bCPAP as part of a comprehensive approach. The study aimed to assess the implementation of a multi-center, comprehensive hospital-based bCPAP program in a low-middle-income country using a low-cost bCPAP device. Seven established hospitals in three Nigerian States were selected using purposive sampling. A respiratory support program was developed and implemented using the Pumani® bCPAP. Neonates <28 days old with severe RD, birth weight >1000g and breathing spontaneously, were eligible. The program lasted 22 months. Focus group discussions and in-depth interviews of healthcare workers and hospital administrators were used in program assessment. Content analysis of qualitative data completed. The staff reported that the bCPAP device was easy to use and effective. All staff reported comfort in eligible patient identification, effective set up and bCPAP administration. All study sites experienced varying degrees of electric power interruption and oxygen availability and affordability. Staff training, staffing disruptions, data collection challenges and use of improvised bCPAP contributed to low enrollment. Advocacy, direct program support, and innovation using locally available resources improved enrollment. Professional organization collaboration, competency-based training and peer mentoring contributed to program success. Thorough pre-program assessment, with comprehensive understanding of all aspects of the existing system within the local context which are likely to impact the introduction of a new program is important to implementation success.

Transmitted Home Oximetry and Duration of Home Oxygen in Premature Infants.

OBJECTIVES: To determine if a home oxygen therapy (HOT) management strategy that includes analysis of recorded home oximetry (RHO) data, compared with standard monthly clinic visit assessments, reduces duration of HOT without harm in premature infants. METHODS: The RHO trial was an unmasked randomized clinical trial conducted in 9 US medical centers from November 2013 to December 2017, with follow-up to February 2019. Preterm infants with birth gestation ≤37 + 0/7 weeks, discharged on HOT, and attending their first pulmonary visit were enrolled. The intervention was an analysis of transmitted RHO between clinic visits (n = 97); the standard-care group received monthly clinic visits with in-clinic weaning attempts (n = 99). The primary outcomes were the duration of HOT and parent-reported quality of life. There were 2 prespecified secondary safety outcomes: change in weight and adverse events within 6 months of HOT discontinuation. RESULTS: Among 196 randomly assigned infants (mean birth gestational age: 26.9 weeks; SD: 2.6 weeks; 37.8% female), 166 (84.7%) completed the trial. In the RHO group, the mean time to discontinue HOT was 78.1 days (SE: 6.4), compared with 100.1 days (SE: 8.0) in the standard-care group (P = .03). The quality-of-life scores improved from baseline to 3 months after discontinuation of HOT in both groups (P = .002), but the degree of improvement did not differ significantly between groups (P = .75). CONCLUSIONS: RHO was effective in reducing the duration of HOT in premature infants. Parent quality of life improved after discontinuation. RHO allows physicians to determine which infants can be weaned and which need prolonged oxygen therapy between monthly visits.

Medical management of extremely low-birth-weight infants in the first week of life: a survey of practices in the United States.

We sought to determine the current practices of neonatologists in their management of extremely low-birth-weight (< 1000 g) infants. We directly mailed an anonymous survey to the medical directors of 809 neonatal intensive care units in the United States. More than one-third of those surveyed responded, with a substantial majority from intensive care (level III) nurseries or extracorporeal membrane oxygenation centers. Academic centers and private practice environments were both well represented. Some traditional practices have changed, such as beginning resuscitation with 40% rather than 100% oxygen. Many practices vary based on whether neonates are cared for in private versus academic centers, including initial resuscitation method, type of ventilation used, use of intraventricular hemorrhage prophylaxis, and routine antibiotic therapy. Parenteral nutrition composition and the use of inhaled nitric oxide differ based on the responding center's participation in clinical trials. The number of years in practice as a neonatologist does not affect practice decisions. Among all our findings, the prevalence of one potentially harmful practice, the continued use of dexamethasone for corticosteroid therapy, was particularly noteworthy. In conclusion, the strength of evidence does not always predict whether practices are adopted or abandoned. Further research is necessary to clarify the optimal management for this high-risk patient population.

Bubble CPAP therapy for neonatal respiratory distress in level III neonatal unit in Amman, Jordan: a prospective observational study.

PURPOSE: Bubble continuous positive airway pressure (bCPAP), a noninvasive respiratory support modality used to manage newborns with respiratory distress, provides continuous pressure that helps prevent derecruitment of alveoli, increasing the lungs' functional residual capacity, and thus decreasing the work of breathing. bCPAP can be used to manage various respiratory conditions in the newborn. In this prospective study, we describe our experience using bCPAP therapy as the primary respiratory support in a level III neonatal unit in Amman, Jordan. In addition to reporting therapeutic indications, durations, and side effects, we aimed to identify areas requiring improvement in bCPAP therapy in our population. PATIENTS AND METHODS: This prospective observational study investigated the usage of bCPAP in the management of respiratory distress in newborns admitted to a Jordan University Hospital in Amman. The newborns were followed until discharge. The patients' demographic and clinical data were recorded. RESULTS: A total of 143 babies (mean gestational age, 36±2.7 weeks; mean birth weight, 2,770±1,800 g) were included. All received bCPAP as the primary respiratory support. The most common underlying cause of respiratory distress was transient tachypnea of the newborn (42%), followed by prolonged respiratory transition (34%). The therapy success rate was 93.7%; only nine infants failed bCPAP. The most common side effect was physical facial injury. CONCLUSION: The use of neonatal bCPAP therapy is well established in Jordan University Hospital. The area of potential improvement was the low rate of bCPAP use as a primary respiratory support in extremely premature infants.

Cardiorespiratory function after operation for pectus excavatum.

OBJECTIVE: We performed a review of current data to determine the effect that operation has on pulmonary function, aerobic capacity, and stroke volume in patients with pectus excavatum. STUDY DESIGN: Two reviewers independently assessed clinical trials and collected data on interventions and outcomes. To qualify for inclusion, a study had to include preoperative and postoperative assessment, provide outcomes in either a published percentile or qualified matched control form to control for interval growth, and include only original patient groups. RESULTS: Postoperative total lung capacity for patients who had Ravitch repair was significantly lower (SMD, 0.71 [CI -1.06, -0.36]; I(2) = 19.6%) than preoperative. Based on 2 studies after removal of the Nuss bar, FEV(1) was significantly increased from preoperative values (SMD, 0.39 [CI, 0.03, 0.74]; I(2) = 0%). Stroke volume increased after surgery (SMD, 0.40 [CI, 0.10, 0.70]; I(2) = 0%) after Ravitch repair. There was a trend toward improved exercise tolerance, but it was not statistically significant. CONCLUSIONS: Total lung capacity was decreased after Ravitch repair, and FEV(1) was increased after Nuss bar removal. Stroke volume may be increased after Ravitch repair. Exercise tolerance was not improved after either type of surgical repair.

The optimization of home oxygen weaning in premature infants trial: Design, rationale, methods, and lessons learned.

Improved survival among preterm infants has led to an increase in diagnosis of chronic lung disease and infants discharged home from the NICU on supplemental oxygen. Despite this increased prevalence, no clearly defined guidelines for the management of home oxygen therapy (HOT) exist. This lack of consensus leads to significant variability in the duration of home oxygen therapy and a general paucity of evidence-based practice. Our team has identified recorded home oxygen therapy (RHO) as a potential new resource to guide clinical decision making in the outpatient pulmonology clinic. By recording extended O2 saturation data during the weaning process, RHO has the potential to save cost and improve the processes of HOT management. Our team is currently supporting a prospective, multi-center, randomized, controlled trial of RHO guided HOT weaning with the aims of determining effect upon duration of HOT, perceived parent quality of life and effect upon growth and respiratory outcomes. We plan to randomize 196 infants into one of two study arms evaluating standard HOT management versus RHO guided oxygen weaning. Our primary outcomes are total HOT duration and parental quality of life. This trial represents an unprecedented opportunity to test a novel home monitoring intervention for weaning within a vulnerable yet quickly growing population. If effective, the use of RHO may provide clinicians a tool for safe weaning.

A Descriptive Analysis of Occupational Fatalities Due to Felonious Assault Among U.S. Law Enforcement Officers During Tactical Incidents, 1996-2014.

INTRODUCTION: Little is known about occupational fatalities among tactical officers. A greater understanding of such injuries is needed to improve officer safety. The purpose of this study was to provide a descriptive analysis of line-of-duty deaths secondary to felonious assault during tactical incidents. METHODS: Retrospective analysis was performed of open-source de-identified Federal Bureau of Investigation Uniform Crime Reporting Law Enforcement Officers Killed and Assaulted (LEOKA) data inclusive of the years 1996-2014. Officers were included if the fatal injury occurred during operations by a Special Weapons and Tactics (SWAT) team, fugitive task force, narcotics task force, or if the LEOKA narrative described the event as a tactical situation. RESULTS: Of 1,012 officer deaths during the study period, 57 (5.6%) involved tactical officers. On average (± standard deviation), victim officers were 37.3 ± 7.8 years of age at the time of death, with 11.7 ± 6.6 years of law enforcement experience. High-risk warrant service accounted for 63.2% of fatalities. A single officer was killed in 91.2% of incidents; 49.1% of cases involved injuries to other officers. The majority of officers (59.6%) killed were the first officer(s) to enter the scene. The most commonly identified cause of death was head trauma (n = 28). Chest trauma accounted for 14 deaths; 10 (71.4%) sustained an entry wound via the ballistic vest armhole. Where recorded, 52.0% of officers died within the first hour of injury. The provision or nature of buddy care, tactical emergency medical services (EMS) care, or conventional EMS care was rarely noted. CONCLUSION: Tactical officer deaths most commonly occur during high-risk warrant service, and most often involve the first officer(s) to enter a scene, suggesting an opportunity for improved operational tactics. The frequency of fatal axillary penetration suggests the opportunity for ballistic protection redesign. Information is lacking regarding on-scene care, limiting the ability to determine optimal medical procedures for downed officers during tactical operations. Nearly 50% of victim officers survived more than 1 hour from time of injury, suggesting opportunities to intervene and potentially affect outcomes.

Diagnosis of an actively bleeding rectus sheath hematoma by Contrast- Enhanced ultrasound.

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A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymkinsT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits.

Developmental outcomes for neonatal dural arteriovenous fistulas.

Large dural arteriovenous malformations (DAVMs) accompanied by cardiac failure usually carry a poor prognosis with a high risk of morbidity and death. The authors report on the case of a male neonate with a massive DAVM who presented at birth with macrocephaly and high-output cardiac failure. The child initially underwent treatment with surgical clipping of the large main feeding artery. Hydrocephalus, thought to be due to venous hypertension, developed when the boy was 8 months old. The condition resolved after interventional embolization treatment. The patient did not require placement of a ventriculoperitoneal shunt. At 21 months of age, the child had near normal development without any focal neurological deficits.

Mutant mice with small amounts of BubR1 display accelerated age-related gliosis.

Aging is an intricate biological process thought to involve multiple molecular pathways. The spindle assembly checkpoint protein BubR1 has recently been implicated in aging since mutant mice that have small amounts of this protein (BubR1(H/H) mice) develop several early aging-associated phenotypes. The phenotype within the brain of BubR1(H/H) mice has not yet been established. Here we show that BubR1(H/H) mice exhibit features of age-related cerebral degeneration. We found that glial fibrillary acidic protein (GFAP), a marker of reactive astrogliosis, was expressed at increased levels in the cortex and thalamus of BubR1(H/H) mice as early as 1 month of age. Furthermore, CD11b, a marker of microgliosis, was markedly elevated in the cortex and hippocampus of BubR1(H/H) mice at 5 months of age. Levels of both GFAP and CD11b further increased with age. Our results demonstrate that BubR1 acts to prevent cerebral gliosis of both astrocytes and microglial cells, and suggest a role for BubR1 in the aging process of the brain.