Social prescribing for children and young people with neurodisability and their families initiated in a hospital setting: a systematic review.

OBJECTIVES: Social prescribing (SP) is a non-medical intervention in which professionals refer patients to a link worker (LW), who connects them with appropriate support. Children and young people (CYP) with neurodisability often have unmet needs and may bypass community initiatives. We undertook a review of hospital-initiated SP for CYP with neurodisability. DESIGN: Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance and using Mixed Methods Appraisal Tool. DATA SOURCES: Medline, PsycINFO, PsycARTICLES, Embase, CINAHL, Scopus, Web of Science and FutureNHS, searched from 1 January 2000 to 19 October 2023, with no language restrictions. ELIGIBILITY CRITERIA: Studies describing SP interventions for CYP (ages 0-25 years) with neurodisability/neurodivergence. EXCLUSIONS: interventions outside of secondary care; with no description; or no LW. DATA EXTRACTION AND SYNTHESIS: Two researchers independently screened references. Data were charted, summarised, quality assessments performed and narratively reviewed. RESULTS: After removal of duplicates, 518 references were identified. Following screening, eight articles (covering five SP schemes) were included. Rahi et al connected 68 families of CYP newly diagnosed with visual impairment to a community LW. Families needed information about social and educational services, and emotional support. Healthcare professionals had more time for clinical issues. Six papers described three different digital interventions supporting in total 86 CYP with traumatic brain injury and their families. Wade et al (2004, 2005a, 2005b) provided a website with core and individualised sessions, and weekly therapist support. Wade et al (2018) provided a smartphone application, website and weekly meetings with an online coach. These interventions boosted social behaviours. Wade et al (2014, 2015) found that online family problem-solving therapy improved overall child functioning compared with self-guided resources. Toutain et al (2009) provided non-medical support to 11 children with fetal alcohol syndrome and their mothers. No outcome data were provided. Studies reported benefits to health, well-being, healthcare usage, knowledge, skills, satisfaction and service delivery. CONCLUSION: Literature describing hospital-initiated SP schemes for CYP with neurodisability, while sparse, suggests potential benefit. PROSPERO REGISTRATION NUMBER: CRD42022384188.

Evaluating and operationalizing an environmental auditing program: a pilot study.

BACKGROUND: Environmental auditing is an important tool to ensure consistent and effective cleaning. Our pilot study compared an alcohol-based fluorescent marking product and an adenosine-5'-triphosphate bioluminescence product for use in an environmental auditing program to determine which product was more practical and acceptable to users. METHODS: Both products were tested on 15 preselected high touch objects in randomly selected patient rooms, following regular daily cleaning. A room was considered a "pass" if ≥80% of surfaces were adequately cleaned as defined by manufacturers' guidelines. A qualitative survey assessed user preference and operational considerations. RESULTS: Using fluorescent marking, 9 of 37 patient rooms evaluated (24%) were considered a "pass" after daily cleaning. Using adenosine-5'-triphosphate bioluminescence, 21 of 37 patient rooms passed (57%). There was great variability in results between different high touch objects. Eighty percent of users preferred the alcohol-based fluorescent marking product because it provided an effective visual aid to coach staff on proper cleaning techniques and allowed simple and consistent application. CONCLUSIONS: Environmental auditing using translucent, alcohol-based fluorescent marking best met the requirements of our organization. Our results reinforce the importance of involving a multidisciplinary team in evaluating and operationalizing an environmental auditing program.

Initiation of synapse formation by Wnt-induced MuSK endocytosis.

In zebrafish, the MuSK receptor initiates neuromuscular synapse formation by restricting presynaptic growth cones and postsynaptic acetylcholine receptors (AChRs) to the center of skeletal muscle cells. Increasing evidence suggests a role for Wnts in this process, yet how muscle cells respond to Wnt signals is unclear. Here, we show that in vivo, wnt11r and wnt4a initiate MuSK translocation from muscle membranes to recycling endosomes and that this transition is crucial for AChR accumulation at future synaptic sites. Moreover, we demonstrate that components of the planar cell polarity pathway colocalize to recycling endosomes and that this localization is MuSK dependent. Knockdown of several core components disrupts MuSK translocation to endosomes, AChR localization and axonal guidance. We propose that Wnt-induced trafficking of the MuSK receptor to endosomes initiates a signaling cascade to align pre- with postsynaptic elements. Collectively, these findings suggest a general mechanism by which Wnt signals shape synaptic connectivity through localized receptor endocytosis.

Hydrophobic oxime ethers: a versatile class of pDNA and siRNA transfection lipids.

The manipulation of the cationic lipid structures to increase polynucleotide binding and delivery properties, while also minimizing associated cytotoxicity, has been a principal strategy for developing next-generation transfection agents. The polar (DNA binding) and hydrophobic domains of transfection lipids have been extensively studied; however, the linking domain comprising the substructure used to tether the polar and hydrophobic domains has attracted considerably less attention as an optimization variable. Here, we examine the use of an oxime ether as the linking domain. Hydrophobic oxime ethers were readily assembled via click chemistry by oximation of hydrophobic aldehydes using an aminooxy salt. A facile ligation reaction delivered the desired compounds with hydrophobic domain asymmetry. Using the MCF-7 breast cancer, H1792 lung cancer and PAR C10 salivary epithelial cell lines, our findings show that lipoplexes derived from oxime ether lipids transfect in the presence of serum at higher levels than commonly used liposome formulations, based on both luciferase and green fluorescent protein (GFP) assays. Given the biological compatibility of oxime ethers and their ease of formation, this functional group should find significant application as a linking domain in future designs of transfection vectors.

A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration.

Trunk neural crest cells delaminate from the dorsal neural tube as an uninterrupted sheet; however, they convert into segmentally organized streams before migrating through the somitic territory. These neural crest cell streams join the segmental trajectories of pathfinding spinal motor axons, suggesting that interactions between these two cell types might be important for neural crest cell migration. Here, we show that in the zebrafish embryo migration of both neural crest cells and motor axons is temporally synchronized and spatially restricted to the center of the somite, but that motor axons are dispensable for segmental neural crest cell migration. Instead, we find that muscle-specific receptor kinase (MuSK) and its putative ligand Wnt11r are crucial for restricting neural crest cell migration to the center of each somite. Moreover, we find that blocking planar cell polarity (PCP) signaling in somitic muscle cells also results in non-segmental neural crest cell migration. Using an F-actin biosensor we show that in the absence of MuSK neural crest cells fail to retract non-productive leading edges, resulting in non-segmental migration. Finally, we show that MuSK knockout mice display similar neural crest cell migration defects, suggesting a novel, evolutionarily conserved role for MuSK in neural crest migration. We propose that a Wnt11r-MuSK dependent, PCP-like pathway restricts neural crest cells to their segmental path.

Salvador protein is a tumor suppressor effector of RASSF1A with hippo pathway-independent functions.

The RASSF1A tumor suppressor binds and activates proapoptotic MST kinases. The Salvador adaptor protein couples MST kinases to the LATS kinases to form the hippo pathway. Upon activation by RASSF1A, LATS1 phosphorylates the transcriptional regulator YAP, which binds to p73 and activates its proapoptotic effects. However, although serving as an adaptor for MST and LATS, Salvador can also bind RASSF1A. The functional role of the RASSF1A/Salvador interaction is unclear. Although Salvador is a novel tumor suppressor in Drosophila and mice, its role in human systems remains largely unknown. Here we show that Salvador promotes apoptosis in human cells and that Salvador inactivation deregulates the cell cycle and enhances the transformed phenotype. Moreover, we show that although the salvador gene is seldom mutated or epigenetically inactivated in human cancers, it is frequently down-regulated posttranscriptionally. Surprisingly, we also find that although RASSF1A requires the presence of Salvador for full apoptotic activity and to activate p73, this effect does not require a direct interaction of RASSF1A with MST kinases or the activation of the hippo pathway. Thus, we confirm a role for Salvador as a human tumor suppressor and RASSF1A effector and show that Salvador allows RASSF1A to modulate p73 independently of the hippo pathway.

Click assembly of magnetic nanovectors for gene delivery.

Functionalization of iron oxide nanoparticles with quaternary ammonium ion-based aminooxy and oxime ether substrates provides a flexible route for generating magnetic gene delivery vectors. Using the MCF-7 breast cancer cell line, our findings show that pDNA magnetoplexes derived from the lipid-coated nanoparticle formulation dMLP transfect in the presence of 10% serum with or without magnetic assistance at significantly higher levels than a commonly used cationic liposome formulation, based on luciferase assay. The present ion-pairing, click chemistry approach furnishes Fe(3)O(4) nanoparticles with lipid layers. The resultant magnetic nanovectors serve as transfection enhancers for otherwise transfection-inactive materials.

Xenopus sonic hedgehog guides retinal axons along the optic tract.

The role of classic morphogens such as Sonic hedgehog (Shh) as axon guidance cues has been reported in a variety of vertebrate organisms (Charron and Tessier-Lavigne [2005] Development 132:2251-2262). In this work, we provide the first evidence that Xenopus sonic hedgehog (Xshh) signaling is involved in guiding retinal ganglion cell (RGC) axons along the optic tract. Xshh is expressed in the brain during retinal axon extension, adjacent to these axons in the ventral diencephalon. Retinal axons themselves express Patched 1 and Smoothened co-receptors during RGC axon growth. Blocking Shh signaling causes abnormal ventral pathfinding, and targeting errors at the optic tectum. Misexpression of exogenous N-Shh peptide in vivo also causes pathfinding errors. Retinal axons grown in culture respond to N-Shh in a dose-dependent manner, either by decreasing extension at lower concentrations, or retracting axons in the presence of higher doses. These data suggest that Shh signaling is required for normal RGC axon pathfinding and tectal targeting in the developing visual system of Xenopus. We propose that Shh serves as a ventral optic tract repellent that helps to define the caudal boundary for retinal axons in the diencephalon, and that this signaling is also required for initial target recognition at the optic tectum.

The Ras effector RASSF2 controls the PAR-4 tumor suppressor.

RASSF2 is a novel proapoptotic effector of K-Ras. Inhibition of RASSF2 expression enhances the transforming effects of K-Ras, and epigenetic inactivation of RASSF2 is frequently detected in mutant Ras-containing primary tumors. Thus, RASSF2 is implicated as a tumor suppressor whose inactivation facilitates transformation by disconnecting apoptotic responses from Ras. The mechanism of action of RASSF2 is not known. Here we show that RASSF2 forms a direct and endogenous complex with the prostate apoptosis response protein 4 (PAR-4) tumor suppressor. This interaction is regulated by K-Ras and is essential for the full apoptotic effects of PAR-4. RASSF2 is primarily a nuclear protein, and shuttling of PAR-4 from the cytoplasm to the nucleus is essential for its function. We show that RASSF2 modulates the nuclear translocation of PAR-4 in prostate tumor cells, providing a mechanism for its biological effects. Thus, we identify the first tumor suppressor signaling pathway emanating from RASSF2, we identify a novel mode of action of a RASSF protein, and we provide an explanation for the extraordinarily high frequency of RASSF2 inactivation we have observed in primary prostate tumors.

Temporal and spatial requirements of unplugged/MuSK function during zebrafish neuromuscular development.

One of the earliest events in neuromuscular junction (NMJ) development is the accumulation of acetylcholine receptor (AChR) at the center of muscle cells. The unplugged/MuSK (muscle specific tyrosine kinase) gene is essential to initiate AChR clustering but also to restrict approaching growth cones to the muscle center, thereby coordinating pre- and postsynaptic development. To determine how unplugged/MuSK signaling coordinates these two processes, we examined the temporal and spatial requirements of unplugged/MuSK in zebrafish embryos using heat-shock inducible transgenes. Here, we show that despite its expression in muscle cells from the time they differentiate, unplugged/MuSK activity is first required just prior to the appearance of AChR clusters to simultaneously induce AChR accumulation and to guide motor axons. Furthermore, we demonstrate that ectopic expression of unplugged/MuSK throughout the muscle membrane results in wildtype-like AChR prepattern and neuromuscular synapses in the central region of muscle cells. We propose that AChR prepatterning and axonal guidance are spatio-temporally coordinated through common unplugged/MuSK signals, and that additional factor(s) restrict unplugged/MuSK signaling to a central muscle zone critical for establishing mid-muscle synaptogenesis.

NORE1A tumor suppressor candidate modulates p21CIP1 via p53.

NORE1A (RASSF5) is a proapoptotic Ras effector that is frequently inactivated by promoter methylation in human tumors. It is structurally related to the RASSF1A tumor suppressor and is itself implicated as a tumor suppressor. In the presence of activated Ras, NORE1A is a potent inducer of apoptosis. However, when expressed at lower levels in the absence of activated Ras, NORE1A seems to promote cell cycle arrest rather than apoptosis. The mechanisms underlying NORE1A action are poorly understood. We have used microarray analysis of an inducible NORE1A system to screen for physiologic signaling targets of NORE1A action. Using this approach, we have identified several potential signaling pathways modulated by NORE1A. In particular, we identify the cyclin-dependent kinase inhibitor p21(CIP1) as a target for NORE1A activation and show that it is a vital component of NORE1A-mediated growth inhibition. In primary human hepatocellular carcinomas (HCC), loss of NORE1A expression is frequent and correlates tightly with loss of p21(CIP1) expression. NORE1A down-regulation in HCC also correlates with poor prognosis, enhanced proliferation, survival, and angiogenic tumor characteristics. Experimental inactivation of NORE1A results in the loss of p21(CIP1) expression and promotes proliferation. The best characterized activator of p21(CIP1) is the p53 master tumor suppressor. Further experiments showed that NORE1A activates p21(CIP1) via promoting p53 nuclear localization. Thus, we define the molecular basis of NORE1A-mediated growth inhibition and implicate NORE1A as a potential component of the ill-defined connection between Ras and p53.

The role of complement in neurodevelopmental impairment following neonatal hypoxic-ischemic encephalopathy.

Evidence has accumulated implicating complement activation in the pathogenesis of acute post-hypoxic-ischemic cerebral injury in infants who develop hypoxic-ischemic encephalopathy (HIE). However, the relationship between complement activation and subsequent neurological impairment is not known. We tested the hypothesis that in human neonates, post-hypoxic-ischemic complement activation within the central nervous system is positively associated with the acquisition of subsequent neurodevelopmental abnormalities. This prospective study included 18 full-term infants diagnosed with HIE following resuscitation at birth and seven control infants. Cerebrospinal fluid (CSF) samples were obtained from all infants in the first 24 hours of life as part of routine investigations to exclude sepsis and meningitis. Concentrations of terminal complement complexes (TCC), complement component 9 (C9), and albumin were quantified by enzyme-linked immunosorbent assay in all CSF samples. Neurological examination and Denver Developmental Screening Test II were performed at 6 and 12 months of life. Of the 18 HIE subjects, nine died, six survived with significant neurological impairment, and three had normal neurological outcomes. In the CSF of the 15 HIE infants who died or survived with abnormal outcomes, the mean concentration of TCC was increased compared with controls (p = 0.026) and the mean C9 concentration appeared to be decreased but the difference was not statistically significant (p = 0.056). Similar to the TCC concentration, the concentration of albumin in the CSF was significantly increased in infants with abnormal outcomes (p = 0.005). This study indicates that complement activation following resuscitation at birth, as manifested by increased TCC in the CNS, is positively correlated with the combination of the development of subsequent neurological sequelae and death. Further study incorporating larger sample sizes will be required to confirm this association. This step is essential before clinical trials of complement inhibitors can be justified in human neonates who suffer birth asphyxia.

Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor.

Early during neuromuscular development, acetylcholine receptors (AChRs) accumulate at the center of muscle fibers, precisely where motor growth cones navigate and synapses eventually form. Here, we show that Wnt11r binds to the zebrafish unplugged/MuSK ectodomain to organize this central muscle zone. In the absence of such a zone, prepatterned AChRs fail to aggregate and, as visualized by live-cell imaging, growth cones stray from their central path. Using inducible unplugged/MuSK transgenes, we show that organization of the central muscle zone is dispensable for the formation of neural synapses, but essential for AChR prepattern and motor growth cone guidance. Finally, we show that blocking noncanonical dishevelled signaling in muscle fibers disrupts AChR prepatterning and growth cone guidance. We propose that Wnt ligands activate unplugged/MuSK signaling in muscle fibers to restrict growth cone guidance and AChR prepatterns to the muscle center through a mechanism reminiscent of the planar cell polarity pathway.

Eight microsatellite loci for the sexually transmitted, parasitic mite Coccipolipus hippodamiae.

Seven dinucleotide and one trinucleotide polymorphic microsatellite loci were isolated from the mite Coccipolipus hippodamiae. This mite is an ectoparasite of coccinellid beetles (ladybirds), principally the European two-spot ladybird Adalia bipunctata, where it causes sterility in the female host. Levels of genetic diversity were assessed using 32 mites from Warsaw, Poland. We observed moderate variability, with the number of alleles per locus varying between 2 and 4, and observed and expected heterozygosities ranging from 0.031 to 0.267 and between 0.062 and 0.526, respectively. This is the first description of microsatellite loci from the genus Coccipolipus and these loci are currently being employed to answer fundamental questions about the epidemiology of C. hippodamiae infections on A. bipunctata.

Genome-wide transcriptional profiling of the cyclic AMP-dependent signaling pathway during morphogenic transitions of Candida albicans.

Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis as well as superficial mucosal candidiasis. In response to the host environment, C. albicans transitions between yeast and hyphal forms. In particular, hyphal growth is important in facilitating adhesion and invasion of host tissues, concomitant with the expression of various hypha-specific virulence factors. In previous work, we showed that the cyclic AMP (cAMP) signaling pathway plays a crucial role in morphogenic transitions and virulence of C. albicans by studying genes encoding adenylate cyclase-associated protein (CAP1) and high-affinity phosphodiesterase (PDE2) (Y. S. Bahn, J. Staab, and P. Sundstrom, Mol. Microbiol. 50:391-409, 2003; and Y. S. Bahn and P. Sundstrom, J. Bacteriol. 183:3211-3223, 2001). However, little is known about the downstream targets of the cAMP signaling pathway that are responsible for morphological transitions and the expression of virulence factors. Here, microarrays were probed with RNA from strains with hypoactive (cap1/cap1 null mutant), hyperactive (pde2/pde2 null mutant), and wild-type cAMP signaling pathways to provide insight into the molecular mechanisms of virulence that are regulated by cAMP and that are related to the morphogenesis of C. albicans. Genes controlling metabolic specialization, cell wall structure, ergosterol/lipid biosynthesis, and stress responses were modulated by cAMP during hypha formation. Phenotypic traits predicted to be regulated by cAMP from the profiling results correlated with the relative strengths of the mutants when tested for resistance to azoles and subjected to heat shock stress and oxidative/nitrosative stress. The results from this study provide important insights into the role of the cAMP signaling pathway not only in morphogenic transitions of C. albicans but also for adaptation to stress and for survival during host infections.

NMI-1182, a gastro-protective cyclo-oxygenase-inhibiting nitric oxide donor.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and to provide pain relief but suffer from a major liability concerning their propensity to cause gastric damage. As nitric oxide (NO) is known to be gastro-protective we have synthesized a NO-donating prodrug of naproxen named NMI-1182. We evaluated two cyclo-oxygenase (COX)-inhibiting nitric oxide donors (CINODs), NMI-1182 and AZD3582, for their ability to be gastro-protective compared to naproxen and for their anti-inflammatory activity. NMI-1182 and AZD3582 were found to produce similar inhibition of COX activity to that produced by naproxen. Both NMI-1182 and AZD3582 produced significantly less gastric lesions after oral administration than naproxen. All three compounds effectively inhibited paw swelling in the rat carrageenan paw edema model. In the carrageenan air pouch model all three compounds significantly reduced PGE2 levels in the pouch exudate but only NMI-1182 and naproxen inhibited leukocyte influx. These data demonstrate that NMI-1182 has comparable anti-inflammatory activity to naproxen but with a much reduced likelihood to cause gastric damage.

Effects of endotoxin administration and cerebral hypoxia-ischemia on complement activity and local transcriptional regulation in neonatal rats.

It is not known whether up-regulation of complement components, either circulating or locally synthesized, contributes to an increased susceptibility to neonatal hypoxic-ischemic (HI) cerebral injury. Therefore, we tested the hypothesis that in neonatal rats subjected to a unilateral HI cerebral insult, prior administration of E. coli lipopolysaccharide (LPS) augments (1) complement-mediated serum hemolytic activity, and (2) C3 mRNA and C9 mRNA levels in hepatic and cerebral tissue. Pregnant rats were injected subcutaneously with sterile normal saline (NS) or 500 microg/kg of LPS on gestational days 18 and 19. Following birth, the pups received intraperitoneal injections of NS or 250 microg/kg of LPS on postnatal days 3 and 5. On postnatal day 7, each animal was subjected to ligation of the right common carotid artery followed by 2.5h of hypoxia (8% O(2)). At 3, 6,18, 24 and 48 h after hypoxia, the complement-mediated hemolytic activity of pooled serum was measured. Hepatic and cerebral C3 mRNA and C9 mRNA were quantified by qRT-PCR at 3, 6, and 18 h after HI. Serum hemolytic activity, hepatic C3 mRNA, and hepatic C9 mRNA were up-regulated after cerebral HI. LPS administration potentiated the effect of HI on serum hemolytic activity and increased cerebral C3 mRNA levels. Cerebral C9 mRNA was not detected and was not affected by HI, with or without the prior LPS administration. These observations support the theory that previously reported C9-mediated neurotoxicity following cerebral HI is induced by circulating, rather than locally synthesized C9.

The administration of cobra venom factor reduces post-ischemic cerebral injury in adult and neonatal rats.

The role of complement in post-ischemic cerebral injury is incompletely understood. Therefore, experiments were designed to test the effect of complement depletion on cerebral infarct volume in adult rats and cerebral atrophy in neonatal rats. Cerebral infarcts were induced in adult rats by transient filamentous occlusion of the right middle cerebral artery (MCAO). Cerebral atrophy was induced by subjecting 7-day-old rats to ligation of the right common carotid artery followed by 2.5h of hypoxia (8% O2). Forty-eight hours after MCAO, coronal sections of adult brains were obtained and stained with 2,3,5-triphenyl tetrazolium chloride. The infant rat brains were removed for analysis 6 weeks after the hypoxic-ischemic insult. Volumes of infarcts and normal hemispheric parenchyma were quantified by computer-based planimetry. Twenty-four hours prior to MCAO (adults) or hypoxia-ischemia (neonates), each animal received an i.p. injection of either 1 mcg/g body weight cobra venom factor (CVF; adult n=11; neonatal n=20) or normal saline (adult n=12; neonatal n=24). In the neonates, a second dose of CVF or saline was administered 2 days after hypoxia-ischemia. The administration of CVF significantly reduced: (1) post-ischemic cerebral infarct volume in the adults and (2) post-hypoxic-ischemic cerebral atrophy in the neonates. Therefore, complement activation augmented post-ischemic cerebral injury in adult and neonatal rats. Complement depletion induced by CVF significantly reduced post-ischemic cerebral infarct volume and atrophy in adult and neonatal rats.

Complement component 9 activation, consumption, and neuronal deposition in the post-hypoxic-ischemic central nervous system of human newborn infants.

The role of complement in neonatal hypoxic-ischemic brain injury is not known. Therefore, cerebral spinal fluid (CSF) and post-mortem cerebral tissue were analyzed to determine whether complement is activated and complement component 9 (C9) is deposited on neurons in the central nervous systems (CNS) of newborn infants who developed moderate to severe hypoxic-ischemic encephalopathy (HIE). Control CSF samples were obtained during routine evaluation for possible sepsis from infants who were not depressed at birth. In ELISA assays of CSF obtained from 16 infants with HIE, compared to CSF from 7 control infants, the mean concentration of terminal complement complexes was elevated and the mean C9 concentration was diminished. Immunofluorescence microscopy of post-mortem frozen brain tissue obtained from two infants who expired at 4-5 days of life after severe HIE revealed that activated C9 was deposited on cells in all lobes. Double label immunofluorescence microscopy demonstrated that nearly all of the C9-positive cells were neurons and essentially all of the neurons were C9-positive. Immunoperoxidase immunohistochemistry of formalin-fixed tissue also confirmed the presence of many C9-positive cells, particularly in the hippocampus. The C9-positive cells usually manifested morphology consistent with neurons, most of which contained fragmented nuclei. In summary, complement was activated in the CNS of newborn infants who developed moderate to severe HIE. C9 was deposited on neurons, including morphologically apoptotic neurons. Further investigations into a possible role of complement in the pathogenesis of neonatal hypoxic-ischemic cerebral injury are warranted.