OptiGait: Gait Monitoring Using An Ankle-Worn Stereo Camera System.

We developed an ankle-worn gait monitoring system for tracking gait parameters, including length, width, and height. The system utilizes ankle bracelets equipped with wide-angle infrared (IR) stereo cameras tasked with monitoring a marker on the opposing ankle. A computer vision algorithm we have also developed processes the imaged marker positions to estimate the length, width, and height of the person's gait. Through testing on multiple participants, the prototype of the proposed gait monitoring system exhibited notable performance, achieving an average accuracy of 96.52%, 94.46%, and 95.29% for gait length, width, and height measurements, respectively, despite distorted wide-angle images. The OptiGait system offers a cost-effective and user-friendly alternative compared to existing gait parameter sensing systems, delivering comparable accuracy in measuring gait length and width. Notably, the system demonstrates a novel capability in measuring gait height, a feature not previously reported in the literature.

Filipin complex-reactive brain lesions: a cautionary tale.

OBJECTIVE: Filipin complex is an autooxidation-prone fluorescent histochemical stain used in the diagnosis of Niemann-Pick Disease Type C (NP-C), a neurodegenerative lysosomal storage disorder. It is also widely used by researchers examining the distribution and accumulation of unesterified cholesterol in cell and animal models of neurodegenerative diseases including NP-C and Sanfilippo syndrome (mucopolysaccharidosis IIIA; MPS IIIA). Recently, it has been suggested to be useful in studying Alzheimer's and Huntington's disease. Given filipin's susceptibility to photobleaching, we sought to establish a quantitative biochemical method for free cholesterol measurement. METHODS: Brain tissue from mice with MPS IIIA was stained with filipin. Total and free cholesterol in brain homogenates was measured using a commercially available kit and a quantitative LC-MS/MS assay was developed. Gangliosides GM1, GM2 and GM3 were also quantified using LC-MS/MS. RESULTS: As anticipated, the MPS IIIA mouse brain displayed large numbers of filipin-positive intra-cytoplasmic inclusions, presumptively endo-lysosomes. Challenging the prevailing dogma, however, we found no difference in the amount of free cholesterol in MPS IIIA mouse brain homogenates cf. control tissue, using either the fluorometric kit or LC-MS/MS assay. Filipin has previously been reported to bind to GM1 ganglioside, however, this lipid does not accumulate in MPS IIIA cells/tissues. Using a fluorometric assay, we demonstrate for the first time that filipin cross-reacts with both GM2 and GM3 gangliosides, explaining the filipin-reactive inclusions observed in MPS IIIA brain cells. CONCLUSION: Filipin is not specific for free cholesterol, and positive staining in any setting should be interpreted with caution.

Nurses' perception of identity, practice and support needed in primary care: A descriptive qualitative study.

AIMS: To explore how primary care registered nurses (PCRNs) describe their professional identity, their perception of their practice, and the support they need to effectively perform the responsibilities of their role. DESIGN: A qualitative descriptive design using inductive content analysis. METHODS: Semi-structured interviews were conducted with registered nurses (n = 14) working in primary care settings in the United States between June 2018 and December 2020. Inductive content analysis was used and comprised three phases: preparation, organizing, and reporting. COREQ reporting guidelines were used. RESULTS: Three categories were discovered related to PCRN identity and practice: Wearing Multiple Hats, Practicing Within Bounds and Change is a Part of Practice. There were also three categories for support needed: Entering In, Ongoing Support and Making it a Better Place. Within each category, subcategories were identified. CONCLUSION: Primary care registered nurses have a unique professional identity and practice. When entering the setting, nurses must acquire the skills and knowledge to ask the right questions and navigate the system to meet the diverse and complex needs of their patients. PCRNs recognize change is a part of practice and have ideas and visions for what the role of PCRNs could be. IMPLICATIONS FOR PROFESSION: Recognizing the unique identity and practice of PCRNs is necessary to create an environment that leverages their skills and knowledge. IMPACT: We identified key elements of PCRN identity and practice and the support necessary to meet their needs. Healthcare organizations must ensure nurses new to the practice setting receive training and support for their unique and essential role. Additionally, leaders must partner with nurses to enhance nursing practice and achieve optimal patient outcomes. REPORTING METHOD: Adherence to COREQ guidelines were maintained. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Being fast or cautious? Sociocultural conditions influencing the sexual pathways of Black females in the United States.

BACKGROUND: Black females in the United States face unique sociocultural conditions that impact their sexual development and increase their risk for sexually transmitted infections (STI), including but not limited to chlamydia, gonorrhea, and HIV. Research has not adequately explained how sociocultural conditions contribute to this increased risk. The purpose of our investigation was to explore the sociocultural conditions that influence Black cisgender females risk for STI. METHODS: This grounded theory study involved in-depth audio-recorded interviews with 20, primarily heterosexual, Black females ages 19-62. RESULTS: Findings informed a conceptual model that builds on previous theory about the sexual development of Black females and explains how sociocultural conditions impact two, participant identified, sexual pathways: Fast and Cautious. Movement on these sexual pathways was not always a linear trajectory; some participants shifted between pathways as their sociocultural contexts changed (i.e., sexual assault, STI, and level of protection). The Fast sexual pathway often led to greater STI risk. CONCLUSIONS: This model may inform future research designed to prevent STI/HIV and promote the sexual health of Black females across the life course.

Older Adult Patients and Care Partners as Knowledge Brokers in Fragmented Health Care.

OBJECTIVE: To describe older adult patients' and care partners' knowledge broker roles during emergency department (ED) visits. BACKGROUND: Older adult patients are vulnerable to communication and coordination challenges during an ED visit, which can be exacerbated by the time and resource constrained ED environment. Yet, as a constant throughout the patient journey, patients and care partners can act as an information conduit, or knowledge broker, between fragmented care systems to attain high-quality, safe care. METHODS: Participants included 14 older adult patients (≥ 65 years old) and their care partners (e.g., spouse, adult child) who presented to the ED after having experienced a fall. Human factors researchers collected observation data from patients, care partners and clinician interactions during the patient's ED visit. We used an inductive content analysis to determine the role of patients and care partners as knowledge brokers. RESULTS: We found that patients and care partners act as knowledge brokers by providing information about diagnostic testing, medications, the patient's health history, and care accommodations at the disposition location. Patients and care partners filled the role of knowledge broker proactively (i.e. offer information) and reactively (i.e. are asked to provide information by clinicians or staff), within-ED work system and across work systems (e.g., between the ED and hospital), and in anticipation of future knowledge brokering. CONCLUSION: Patients and care partners, acting as knowledge brokers, often fill gaps in communication and participate in care coordination that assists in mitigating health care fragmentation.

Toward an Anti-Maleficent Research Agenda.

Important advances in biomedical and behavioral research ethics have occurred over the past few decades, many of them centered on identifying and eliminating significant harms to human subjects of research. Comprehensive attention has not been paid to the totality of harms experienced by animal subjects, although scientific and moral progress require explicit appraisal of these harms. Science is a public good and the prioritizing within, conduct of, generation of, and application of research must soundly address questions about which research is morally defensible and valuable enough to support through funding, publication, tenure, and promotion. Likewise, educational pathways of re-imagined science are critical.

Is SGSH heterozygosity a risk factor for early-onset neurodegenerative disease?

Lysosomal dysfunction may be an important factor in the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD). Heterozygous mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) have been found in PD patients, and some but not all mutations in other lysosomal enzyme genes, for example, NPC1 and MCOLN1 have been associated with PD. We have examined the behaviour and brain structure of mice carrying a D31N mutation in the sulphamidase (Sgsh) gene which encodes a lysosomal sulphatase. Female heterozygotes and wildtype mice aged 12-, 15-, 18- and 21-months of age underwent motor phenotyping and the brain was comprehensively evaluated for disease-associated lesions. Heterozygous mice exhibited impaired performance in the negative geotaxis test when compared with wildtype mice. Whilst the brain of Sgsh heterozygotes aged up to 21-months did not exhibit any of the gross features of PD, Alzheimer's disease or the neurodegenerative lysosomal storage disorders, for example, loss of striatal dopamine, reduced GBA activity, α-synuclein-positive inclusions, perturbation of lipid synthesis, or cerebellar Purkinje cell drop-out, we noted discrete structural aberrations in the dendritic tree of cortical pyramidal neurons in 21-month old animals. The overt disease lesions and resultant phenotypic changes previously described in individuals with heterozygous mutations in lysosomal enzyme genes such as glucocerebrosidase may be enzyme dependent. By better understanding why deficiency in, or mutant forms of some but not all lysosomal proteins leads to heightened risk or earlier onset of classical neurodegenerative disorders, novel disease-causing mechanisms may be identified.

The realities of practice change: Nurses' perceptions.

AIMS AND OBJECTIVES: To explore registered nurses' perceptions of practice change and describe factors that influence the adoption of practice changes. BACKGROUND: Nurses play a critical role in optimising patient outcomes. Healthcare organisations and nurses must do their part to achieve the Quadruple Aim, which requires nurses to change their practice. Nurses are ideally positioned to improve patient outcomes by changing their practice to align it with research evidence and organisational initiatives; however, this experience of practice change by nurses is grossly under-studied. DESIGN: A qualitative design, inductive content analysis, was used to understand nurses' perceptions of practice change. METHODS: Eleven registered nurses, who worked in one hospital system, participated in one-on-one semi-structured interviews. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) were followed. FINDINGS: The 11 participants described 63 distinct experiences with practice changes. Their experiences with and perceptions of practice change are categorised as (1) There is A History; (2) It's A Lot of Work; (3) It Happens to Nurses; and (4) Doing Right for the Patient. CONCLUSION: Nurses experience practice change as a central part of the work they do; it occurs frequently and multiple practice changes may co-occur. Nurses identify strategies, such as thoughtful planning, engaging nurses, and communicating the rationale for and the outcomes of the practice change, to facilitate changing practice. RELEVANCE TO CLINICAL PRACTICE: Involving nurses in practice changes could alleviate some inhibiting factors for adopting new practices. Local hospital and national policies should explore creative and practical ways to balance the competing needs of nurses providing direct care at the bedside and dedicated time to be engaged in practice change initiatives. With the ongoing focus on improving patient care and optimising patient safety, nurses should be viewed as highly valued members of the team when designing and implementing practice changes.

Older adults experiences with ambulation during a hospital stay: A qualitative study.

Older adults often lose their ability to independently ambulate during a hospital stay. Few studies have investigated older adults' experiences with ambulation during hospitalization. The purpose of this study was to understand older adults' perceptions of and experiences with ambulation during a hospital admission. A qualitative study using Inductive Content Analysis was conducted. Community-dwelling older adults (N = 11) were recruited to participant in five focus group meetings each lasting 90 min. All individuals participated in each focus group. Participants described high complexity in deciding whether or not they could ambulate. Six categories were identified: Uncertainty, Restriction Messaging, Non-Welcoming Space, Caring for Nurse and Self, Feeling Isolated, and Presenting Self. This study provides a detailed understanding of older adults' experiences and perceptions of a hospital stay. Findings from this study can serve as a foundation for future interventions to improve older adult patient ambulation during hospitalization.

Protecting young Black female sexuality.

In the USA, Black girls and women face significant health disparities and disproportionately experience violence, racism, discrimination, stereotype messaging and elevated STI/HIV rates. Research shows the importance of familial systems and effective communication in decreasing risky behaviours among Black girls. This grounded theory study explored the sociocultural conditions that influence the process of becoming a sexual Black woman. Analytic results of interviews with 20 Black women identified protection as a major category associated with Black female sexual development and related risk behaviour. This paper describes the role of Black women as protectors of young Black female sexuality, the sociocultural protective strategies they used across the life course and the consequences of absent protection. Findings can inform future evidence-based, culturally sensitive interventions to promote the sexual health and development of Black girls and women in the USA.

Strategies older adults use in their work to get back to normal following hospitalization.

Loss of function is a significant concern among hospitalized older adults, and prior research suggests they engage in dedicated work to regain "normal" function following hospitalization. This paper aims to describe the strategies older adults use to return to normal function and the conditions that influence their ability to do so. Recently discharged adults aged 65 and older (N = 14) completed in-depth one-on-one interviews. Data were analyzed using open, axial, and selective coding. Participants described strategies they used to regain their normal function following hospitalization: doing exercises, expanding physical space, resuming activities and daily cares, and tracking improvement with benchmarks. Several conditions, such as presence of informal and formal support, perceived threats, and poor physical or physiologic function, acted as barriers and facilitators to participants' ability to work back to normal function. Findings increase our understanding of patients' work to regain normal function and have important implications for practice.

A moral panic over cats.

Some conservationists believe that free-ranging cats pose an enormous risk to biodiversity and public health and therefore should be eliminated from the landscape by any means necessary. They further claim that those who question the science or ethics behind their arguments are science deniers (merchants of doubt) seeking to mislead the public. As much as we share a commitment to conservation of biodiversity and wild nature, we believe these ideas are wrong and fuel an unwarranted moral panic over cats. Those who question the ecological or epidemiological status of cats are not science deniers, and it is a false analogy to compare them with corporate and right-wing special interests that perpetrate disinformation campaigns over issues, such as smoking and climate change. There are good conservation and public-health reasons and evidence to be skeptical that free-ranging cats constitute a disaster for biodiversity and human health in all circumstances. Further, there are significant and largely unaddressed ethical and policy issues (e.g., the ethics and efficacy of lethal management) relative to how people ought to value and coexist with cats and native wildlife. Society is better served by a collaborative approach to produce better scientific and ethical knowledge about free-ranging cats.

Pánico Moral por los Gatos Resumen Algunos conservacionistas creen que los gatos sueltos representan un riesgo enorme para la biodiversidad y la salud pública, por lo que deberían ser eliminados del paisaje a como dé lugar. Los conservacionistas además alegan que quienes cuestionan la ciencia o la ética detrás de estos argumentos son negadores de la ciencia (mercaderes de la duda) que buscan desinformar al público. Por mucho que compartamos un compromiso con la conservación de la biodiversidad y la fauna silvestre, creemos que estás ideas están equivocadas y alimentan un pánico moral injustificado por los gatos. Aquellos que cuestionan el estado ecológico o epidemiológico de los gatos no son negadores de la ciencia y es una analogía falsa compararlos con los intereses especiales de los corporativos y de la derecha política, los cuales perpetúan las campañas de desinformación de temas como el cigarro y el cambio climático. Existen razones y evidencias de conservación y salud pública para ser escépticos sobre el argumento de que los gatos sueltos constituyen un desastre para la biodiversidad y la salud humana bajo todas las circunstancias. Además, hay temas éticos y políticos que no reciben atención (p. ej.: la ética y la eficacia del manejo letal) relativos a cómo las personas deberían valorar y coexistir con los gatos y la fauna nativa. La sociedad se beneficia más con una estrategia colaborativa para producir un mejor conocimiento científico y ético sobre los gatos que viven sueltos.

ß-Mannosidosis in German Shepherd Dogs.

A neurological disease was investigated in 3 German Shepherd pups from the same litter that failed to grow normally, appeared stiff, were reluctant to move, and were deaf. They developed intermittent seizures and ataxia and had proprioceptive defects. Histopathology showed severe vacuolation of neurons, astrocytes in nervous tissue, renal tubular epithelial cells, and macrophages in nervous tissue, spleen, and liver. Vacuoles appeared empty with no storage material stained by periodic acid-Schiff (PAS) or Sudan black stains, leading to a diagnosis of a lysosomal storage disease and in particular an oligosaccharidosis. Biochemical and genomic studies showed that this was ß-mannosidosis, not previously diagnosed in dogs. A c.560T>A transition in exon 4 of the MANBA gene was found, which segregated in these and other family members in a manner consistent with it being the causative mutation of an autosomal recessive disease. This mutation led to substitution of isoleucine to asparagine at position 187 of the 885 amino acid enzyme, a change expected to have functional significance.

Nurse-Family Communication During and After Family Meetings in the Intensive Care Unit.

PURPOSE: To explore nurse-family communication during and after family meetings. DESIGN: A cross-sectional study in which 36 family meetings were audio-recorded in two intensive care units in an urban, community hospital. METHODS: Data were analyzed using conversation analysis, a qualitative method. FINDINGS: Nurses spoke during 10 (28%) of the family meetings. During the family meetings, nurses mostly self-selected to take a turn by interrupting a physician or family member, finishing their sentences, responding to questions, and, in one instance, asking a question. Nurses were mostly selected as the next speaker to address logistical issues, but were also asked questions. Most of nurses' turns were short and simple, and aimed to provide clarification, reassurance, and information regarding the patient's status. Immediately after the family meetings, nurses offered to provide family members clarification or gestures of empathy, but these offers were met with resistance from family members. CONCLUSIONS: Despite calls for nurses to take a more active role in surrogate decision making, nurses minimally participated during family meetings. Empowering nurses to share their expertise is one solution for nurses to contribute during family meetings. Further research is needed to explore nurse-family bedside interactions to improve our understanding of the nurse's role in the surrogate decision-making process. CLINICAL RELEVANCE: Findings from this exploration of nurse communication during and after family meetings can inform how nurses may best assist families during surrogate decision making in the intensive care unit.

Measurement of function in older adults transitioning from hospital to home: an integrative review.

Older adults often experience decline in functional status during the transition from hospital to home. In order to determine the effectiveness of interventions to prevent functional decline, researchers must have instruments that are reliable and valid for use with older adults. The purpose of this integrative review is to: (1) summarize the research uses and methods of administering functional status instruments when investigating older adults transitioning from hospital to home, (2) examine the development and existing psychometric testing of the instruments, and (3) discuss gaps and implications for future research. The authors conducted an integrative review of forty research studies that assessed functional status in older adults transitioning from hospital to home. This review reveals important gaps in the functional status instruments' psychometric testing, including limited testing to support their validity and reliability when administered by self-report and limited evidence supporting their ability to detect change over time.

Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric-onset neurodegenerative disease, MPS IIIA.

Intra-cerebrospinal fluid (CSF) injection of recombinant human lysosomal enzyme is a potential treatment strategy for several neurodegenerative lysosomal storage disorders including Sanfilippo syndrome (Mucopolysaccharidosis type IIIA; MPS IIIA). Here we have utilised the MPS IIIA Huntaway dog model to compare the effectiveness of the repeated intermittent bolus injection strategy being used in the trials with an alternate approach; slow, continual infusion of replacement enzyme (recombinant human sulphamidase; rhSGSH) into the spinal CSF using a SynchroMed II® pump attached to a spinal infusion cannula. The ability of each enzyme delivery strategy to ameliorate lesions in MPS IIIA brain was determined in animals treated from ∼three- to six-months of age. Controls received buffer or no treatment. Significant reductions in heparan sulphate (primary substrate) were observed in brain samples from dogs treated via either cisternal or lumbar spinal CSF bolus injection methods and also in slow intra-spinal CSF infusion-treated dogs. The extent of the reduction differed regionally. Pump-delivered rhSGSH was less effective in reducing secondary substrate (GM3 ganglioside) in deeper aspects of cerebral cortex, and although near-amelioration of microglial activation was seen in superficial (but not deep) layers of cerebral cortex in both bolus enzyme-treated groups, pump-infusion of rhSGSH had little impact on microgliosis. While continual low-dose infusion of rhSGSH into MPS IIIA dog CSF reduces disease-based lesions in brain, it was not as efficacious as repeated cisternal or spinal CSF bolus infusion of rhSGSH over the time-frame of these experiments.

A novel conditional Sgsh knockout mouse model recapitulates phenotypic and neuropathic deficits of Sanfilippo syndrome.

Mucopolysaccharidosis (MPS) type IIIA, or Sanfilippo syndrome, is a neurodegenerative lysosomal storage disorder caused by a deficiency of the lysosomal enzyme N-sulfoglucosamine sulfohydrolase (SGSH), involved in the catabolism of heparan sulfate. The clinical spectrum is broad and the age of symptom onset and the degree of preservation of cognitive and motor functions appears greatly influenced by genotype. To explore this further, we generated a conditional knockout (Sgsh KO ) mouse model with ubiquitous Sgsh deletion, and compared the clinical and pathological phenotype with that of the spontaneous Sgsh D31N MPS-IIIA mouse model. Phenotypic deficits were noted in Sgsh KO mice prior to Sgsh D31N mice, however these outcomes did not correlate with any shift in the time of appearance nor rate of accumulation of primary (heparan sulfate) or secondary substrates (GM2/GM3 gangliosides). Other disease lesions (elevations in lysosomal integral membrane protein-II expression, reactive astrocytosis and appearance of ubiquitin-positive inclusions) were also comparable between affected mouse strains. This suggests that gross substrate storage and these neuropathological markers are neither primary determinants, nor good biomarkers/indicators of symptom generation, confirming similar observations made recently in MPS-IIIA patients. The Sgsh KO mouse will be a useful tool for elucidation of the neurological basis of disease and assessment of the clinical efficacy of new treatments for Sanfilippo syndrome.

Development and psychometric testing of a measure of older adult patients' attitudes towards mobility during hospitalization (ATM-H).

This paper describes the development and psychometric testing of a questionnaire evaluating attitudes towards mobility during hospitalization of older adults, an understudied phenomenon that lacks a valid and reliable measure. An instrument development procedure, followed by an empirical study, was conducted between December 2013 and June 2014. Instrument development included item generation and analysis of content validity, which was established by six experts. The validation study used a prospective within-patients design with a sample of 100 patients, age 70+, hospitalized in general medical units in a large medical center. Internal consistency, reliability, and divergent and predictive validity of the measure were tested. Reliability analysis revealed an acceptable estimate for the total score (0.76). Predictive validity was good. The divergent validity coefficient was in the expected direction. Preliminary psychometric properties of the measure showed acceptable results. The measure should be explored further in different cultural settings.

Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA.

Repeated replacement of sulphamidase via cerebrospinal fluid injection is an effective treatment for pathological changes in the brain in mice and dogs with the lysosomal storage disorder, mucopolysaccharidosis type IIIA (MPS IIIA). Investigational trials of this approach are underway in children with this condition, however, infusions require attendance at a specialist medical facility. We sought to comprehensively evaluate the effectiveness of sustained-release (osmotic pump-delivered) enzyme replacement therapy in murine MPS IIIA as this method, if applied to humans, would require only subcutaneous administration of enzyme once the pump was installed. Six-week-old MPS IIIA and unaffected mice were implanted with subcutaneous mini-osmotic pumps connected to an infusion cannula directed at the right lateral ventricle. Either recombinant human sulphamidase or vehicle were infused over the course of 7 weeks, with pumps replaced part-way through the experimental period. We observed near-normalisation of primarily stored substrate (heparan sulphate) in both hemispheres of the MPS IIIA brain and cervical spinal cord, as determined using tandem mass spectrometry. Immunohistochemistry indicated a reduction in secondarily stored GM 3 ganglioside and neuroinflammatory markers. A bias towards the infusion side was seen in some, but not all outcomes. The recombinant enzyme appears stable under pump-like conditions for at least 1 month. Given that infusion pumps are in clinical use in other nervous system disorders, e.g. for treatment of spasticity or brain tumours, this treatment method warrants consideration for testing in large animal models of MPS IIIA and other lysosomal storage disorders that affect the brain. Clinical trials of repeated injection of replacement enzyme into CSF are underway in patients with the inherited neurodegenerative disorder mucopolysaccharidosis type IIIA. In this pre-clinical study, we examined an alternative approach - slow, continual infusion of enzyme using pumps. We observed significant reductions in substrate accumulation and other disease-based lesions in treated mouse brain. Thus, the strategy warrants consideration for testing in large animal models of MPS IIIA and also in other neurodegenerative lysosomal storage disorders.

Determination of the role of injection site on the efficacy of intra-CSF enzyme replacement therapy in MPS IIIA mice.

MPS IIIA is an inherited neurodegenerative lysosomal storage disorder characterized by cognitive impairment, sleep-wake cycle disturbance, speech difficulties, eventual mental regression and early death. Neuropathological changes include accumulation of heparan sulfate and glycolipids, neuroinflammation and degeneration. Pre-clinical animal studies indicate that replacement of the deficient enzyme, sulfamidase, via intra-cerebrospinal fluid (CSF) injection is a clinically-relevant treatment approach, reducing neuropathological changes and improving symptoms. Given that there are several routes of administration of enzyme into the CSF (intrathecal lumbar, cisternal and ventricular), determining the effectiveness of each injection strategy is crucial in order to provide the best outcome for patients. We delivered recombinant human sulfamidase (rhSGSH) to a congenic mouse model of MPS IIIA via each of the three routes. Mice were euthanized 24h or one-week post-injection; the distribution of enzyme within the brain and spinal cord parenchyma was investigated, and the impact on primary substrate levels and other pathological lesions determined. Both ventricular and cisternal injection of rhSGSH enable enzyme delivery to brain and spinal cord regions, with the former mediating large, statistically significant decreases in substrate levels and reducing microglial activation. The single lumbar CSF infusion permitted more restricted enzyme delivery, with no reduction in substrate levels and little change in other disease-related lesions in brain tissue. While the ventricular route is the most invasive of the three methods, this strategy may enable the widest distribution of enzyme within the brain, and thus requires further exploration.