Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39≤r≤0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of sex and age explained 26±10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33±11% when body height was added into the mixture model. Age itself explained only 2±2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.

COVID-19 Stay-At-Home Orders and Secondhand Smoke in Public Housing.

INTRODUCTION: This study aimed to better understand the inequitable impact of the pandemic by examining the associations between stay-at-home orders and indoor smoking in public housing, measured by ambient particulate matter at the 2.5-micron threshold, a marker for secondhand smoke. METHODS: Particulate matter at the 2.5-micron threshold was measured in 6 public-housing buildings in Norfolk, VA from 2018 to 2022. Multilevel regression was used to compare the 7-week period of the Virginia stay-at-home order in 2020 with that period in other years. RESULTS: Indoor particulate matter at the 2.5-micron threshold was 10.29 µg/m3 higher in 2020 (95% CI=8.51, 12.07) than in the same period in 2019, a 72% increase. Although particulate matter at the 2.5-micron threshold improved in 2021 and 2022, it remained elevated relative to the level in 2019. CONCLUSIONS: Stay-at-home orders likely led to increased indoor secondhand smoke in public housing. In light of evidence linking air pollutants, including secondhand smoke, with COVID-19, these results also provide further evidence of the disproportionate impact of the pandemic on socioeconomically disadvantaged communities. This consequence of the pandemic response is unlikely to be isolated and calls for a critical examination of the COVID-19 experience to avoid similar policy failures in future public health crises.

Tralesinidase Alfa Enzyme Replacement Therapy Prevents Disease Manifestations in a Canine Model of Mucopolysaccharidosis Type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B; OMIM #252920) is a lethal, pediatric, neuropathic, autosomal recessive, and lysosomal storage disease with no approved therapy. Patients are deficient in the activity of N-acetyl-alpha-glucosaminidase (NAGLU; EC 3.2.150), necessary for normal lysosomal degradation of the glycosaminoglycan heparan sulfate (HS). Tralesinidase alfa (TA), a fusion protein comprised of recombinant human NAGLU and a modified human insulin-like growth factor 2, is in development as an enzyme replacement therapy that is administered via intracerebroventricular (ICV) infusion, thus circumventing the blood brain barrier. Previous studies have confirmed ICV infusion results in widespread distribution of TA throughout the brains of mice and nonhuman primates. We assessed the long-term tolerability, pharmacology, and clinical efficacy of TA in a canine model of MPS IIIB over a 20-month study. Long-term administration of TA was well tolerated as compared with administration of vehicle. TA was widely distributed across brain regions, which was confirmed in a follow-up 8-week pharmacokinetic/pharmacodynamic study. MPS IIIB dogs treated for up to 20 months had near-normal levels of HS and nonreducing ends of HS in cerebrospinal fluid and central nervous system (CNS) tissues. TA-treated MPS IIIB dogs performed better on cognitive tests and had improved CNS pathology and decreased cerebellar volume loss relative to vehicle-treated MPS IIIB dogs. These findings demonstrate the ability of TA to prevent or limit the biochemical, pathologic, and cognitive manifestations of canine MPS IIIB disease, thus providing support of its potential long-term tolerability and efficacy in MPS IIIB subjects. SIGNIFICANCE STATEMENT: This work illustrates the efficacy and tolerability of tralesinidase alfa as a potential therapeutic for patients with mucopolysaccharidosis type IIIB (MPS IIIB) by documenting that administration to the central nervous system of MPS IIIB dogs prevents the accumulation of disease-associated glycosaminoglycans in lysosomes, hepatomegaly, cerebellar atrophy, and cognitive decline.

Development of a Risk Behavior Diagnosis Scale for E-cigarette Use.

Objectives: Adolescent use of electronic cigarettes has risen dramatically, prompting concerns about the health effects. There is need for brief measures to assess adolescents' perceived threat and efficacy related to e-cigarette use and cessation. A 12-item Likert-type scale was modeled after the Risk Behavior Diagnosis Scale and designed to assess threat (ie, severity and susceptibility of threat) and efficacy (ie, self-efficacy and response efficacy) as they relate to e-cigarette use. Methods: The scale was administered online to a developmental sample of 674 adolescents to examine internal consistency and factor structure. Participants (52.1% female, M age = 14.6) were representative of the surrounding community (60% non-Hispanic white; 27% non-Hispanic black; 8% Hispanic). Results: Factor analysis and Velicer's minimum average partial test revealed 2 factors (as expected), which explained 68% of the variance. Analyses revealed strong internal consistency, with Cronbach's alpha of .93 overall and alphas of .92 and .87 for threat and efficacy subscales, respectively. The measure also exhibited good convergent and discriminant validity with other constructs. Conclusions: The measure demonstrates strong preliminary reliability and validity for a developmental sample of adolescents.

White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis.

OBJECTIVE: Despite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations. METHODS: Twenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls. RESULTS: Focal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T2 signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities. CONCLUSION: White matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T2 signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T2 signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.

The business case for breastfeeding: a successful regional implementation, evaluation, and follow-up.

BACKGROUND: Breastfeeding benefits the health of babies and mothers, but returning to work is a significant barrier for mothers wishing to continue breastfeeding for the recommended 12 months. A resource training kit, The Business Case for Breastfeeding (BC4BF), developed by the Health Resources and Services Administration, U.S. Department of Health and Human Services, was implemented in Southeastern Virginia to assist businesses in developing lactation support programs (LSPs) and eliminating breastfeeding barriers. MATERIALS AND METHODS: The primary goals of the 1-year project were to educate 20 businesses about breastfeeding support in the workplace, engage 10 businesses to implement the BC4BF, and assess sustainability via documented policy and environmental changes and integration of the LSP into the business infrastructure. The Transtheoretical Model of Behavior Change was adapted to assess stage of organizational change. A Centers for Disease Control and Prevention tool for measuring community-level policy, systems, and environmental change was adapted to assess worksite policy and environmental changes. EVALUATION RESULTS: Over 20 businesses were educated about the BC4BF. Seventeen engaged in the project. Fourteen significantly increased their stage of change, development of LSPs, written policies, and physical and social environment changes (p≤0.001). A brief follow-up study revealed that all 14 employers maintained their programs 8 months after the program ended, with increased stages of change, policy enforcement, and physical environment (p≤0.05). CONCLUSIONS: The BC4BF provided an effective approach to assisting employers in establishing and maintaining LSPs in the workplace across several cities.