Building Power on Mass&Cass: A Community-Centered Approach to Addressing Health Resource Gaps for Persons Experiencing Homelessness in Boston, MA, 2021.

In November 2021, two grassroots organizations in Boston, Massachusetts-a housing and health justice organization and a student-led nonprofit-established an initiative to provide persons experiencing homelessness (PEH) in Boston with access to free COVID-19 education and other wrap-around services. They partnered with hospitals, public health organizations, and advocacy groups to make this happen. This community-driven initiative serves as a model for how to enact a sustainable pipeline for PEH to receive health resources and information, with the voices of those directly impacted at the center. (Am J Public Health. Published online ahead of print June 20, 2024:e1-e4. https://doi.org/10.2105/AJPH.2024.307713).

CLASP2 facilitates dynamic actin filament organization along the microtubule lattice.

Coordination between the microtubule and actin networks is essential for cell motility, neuronal growth cone guidance, and wound healing. Members of the CLASP (cytoplasmic linker-associated protein) family of proteins have been implicated in the cytoskeletal cross-talk between microtubules and actin networks; however, the molecular mechanisms underlying the role of CLASP in cytoskeletal coordination are unclear. Here, we investigate CLASP2α's cross-linking function with microtubules and F-actin. Our results demonstrate that CLASP2α cross-links F-actin to the microtubule lattice in vitro. We find that the cross-linking ability is retained by L-TOG2-S, a minimal construct containing the TOG2 domain and serine-arginine-rich region of CLASP2α. Furthermore, CLASP2α promotes the accumulation of multiple actin filaments along the microtubule, supporting up to 11 F-actin landing events on a single microtubule lattice region. CLASP2α also facilitates the dynamic organization of polymerizing actin filaments templated by the microtubule network, with F-actin forming bridges between individual microtubules. Finally, we find that depletion of CLASPs in vascular smooth muscle cells results in disorganized actin fibers and reduced coalignment of actin fibers with microtubules, suggesting that CLASP and microtubules contribute to higher-order actin structures. Taken together, our results indicate that CLASP2α can directly cross-link F-actin to microtubules and that this microtubule-CLASP-actin interaction may influence overall cytoskeletal organization in cells.

Rescuing microtubules from the brink of catastrophe: CLASPs lead the way.

Microtubules are cytoskeletal polymers that dynamically remodel to perform essential cellular functions. Individual microtubules alternate between phases of growth and shrinkage via sudden transitions called catastrophe and rescue, driven by losing and regaining a stabilizing cap at the dynamic microtubule end. New in vitro studies now show that a conserved family of CLASP proteins specifically modulate microtubule catastrophe and rescue transitions. Further, recent cryo-electron microscopy approaches have elucidated new structural features of the stabilizing cap. Together, these new advances provide a clearer view on the complexity of the microtubule end and its regulation.

Mitochondria-cytoskeleton associations in mammalian cytokinesis.

BACKGROUND: The role of the cytoskeleton in regulating mitochondrial distribution in dividing mammalian cells is poorly understood. We previously demonstrated that mitochondria are transported to the cleavage furrow during cytokinesis in a microtubule-dependent manner. However, the exact subset of spindle microtubules and molecular machinery involved remains unknown. METHODS: We employed quantitative imaging techniques and structured illumination microscopy to analyse the spatial and temporal relationship of mitochondria with microtubules and actin of the contractile ring during cytokinesis in HeLa cells. RESULTS: Superresolution microscopy revealed that mitochondria were associated with astral microtubules of the mitotic spindle in cytokinetic cells. Dominant-negative mutants of KIF5B, the heavy chain of kinesin-1 motor, and of Miro-1 disrupted mitochondrial transport to the furrow. Live imaging revealed that mitochondrial enrichment at the cell equator occurred simultaneously with the appearance of the contractile ring in cytokinesis. Inhibiting RhoA activity and contractile ring assembly with C3 transferase, caused mitochondrial mislocalisation during division. CONCLUSIONS: Taken together, the data suggest a model in which mitochondria are transported by a microtubule-mediated mechanism involving equatorial astral microtubules, Miro-1, and KIF5B to the nascent actomyosin contractile ring in cytokinesis.

Pilot study of chronic maternal hyperoxygenation and effect on aortic and mitral valve annular dimensions in fetuses with left heart hypoplasia.

OBJECTIVE: Acute maternal hyperoxygenation (AMH) results in increased fetal left heart blood flow. Our aim was to perform a pilot study to determine the safety, feasibility and direction and magnitude of effect of chronic maternal hyperoxygenation (CMH) on mitral and aortic valve annular dimensions in fetuses with left heart hypoplasia (LHH) after CMH. METHODS: Gravidae with fetal LHH were eligible for inclusion in a prospective evaluation of CMH. LHH was defined as: sum of aortic and mitral valve annuli Z-scores < -4.5, arch flow reversal and left-to-right or bidirectional atrial level shunting without hypoplastic left heart syndrome or severe aortic stenosis. Gravidae with an affected fetus and with ≥ 10% increase in aortic/combined cardiac output flow after 10 min of AMH at 8 L/min 100% fraction of inspired oxygen were offered enrollment. Nine gravidae were enrolled from February 2014 to January 2015. The goal therapy was ≥ 8 h daily CMH from enrollment until delivery. Gravidae who were cared for from July 2012 to October 2014 with fetal LHH and no CMH were identified as historical controls (n = 9). Rates of growth in aortic and mitral annuli over the final trimester were compared between groups using longitudinal regression. RESULTS: There were no significant maternal or fetal complications in the CMH cohort. Mean gestational age at study initiation was 29.6 ± 3.2 weeks for the intervention group and 28.4 ± 1.8 weeks for controls (P = 0.35). Mean relative increase in aortic/combined cardiac output after AMH was 35.3% (range, 18.1-47.9%). Median number of hours per day on CMH therapy was 9.3 (range, 6.5-14.6) and median duration of CMH was 48 (range, 33-84) days. Mean mitral annular growth was 0.19 ± 0.05 mm/week compared with 0.14 ± 0.05 mm/week in CMH vs controls (mean difference 0.05 ± 0.05 mm/week, P = 0.33). Mean aortic annular growth was 0.14 ± 0.03 mm/week compared with 0.13 ± 0.03 mm/week in CMH vs controls (mean difference 0.01 ± 0.03 mm/week, P = 0.75). More than 9 h CMH daily (n = 6) was associated with better growth of the aortic annulus in intervention fetuses (0.16 ± 0.03 vs 0.08 ± 0.02 mm/week, P = 0.014). CONCLUSIONS: CMH is both safe and feasible for continued research. In this pilot study, the effect estimates of annular growth, using the studied method of delivery and dose of oxygen, were small. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Motor fMRI and cortical grey matter volume in adults born very preterm.

The primary aim of this study was to investigate the functional neuroanatomy of motor planning, initiation and execution in a cohort of young adults (mean age 20 years) who were born very preterm (VPT; <33 weeks of gestation), as these individuals are at increased risk of experiencing neuromotor difficulties compared to controls. A cued motor task was presented to 20 right-handed VPT individuals and 20 controls within a functional magnetic resonance imaging (fMRI) paradigm. Whole-brain grey matter volume was also quantified and associations with functional data were examined. Despite comparable task performance, fMRI results showed that the VPT group displayed greater brain activation compared to controls in a region comprising the right cerebellum and the lingual, parahippocampal and middle temporal gyri. The VPT group also displayed decreased grey matter volume in the right superior frontal/premotor cortex and left middle temporal gyri. Grey matter volume in the premotor and middle temporal clusters was significantly negatively correlated with BOLD activation in the cerebellum. Overall, these data suggest that preterm birth is associated with functional neuronal differences that persist into adulthood, which are likely to reflect neural reorganisation following early brain injury.

Exocytosis is impaired in mucopolysaccharidosis IIIA mouse chromaffin cells.

Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disorder caused by a deficiency in the activity of the lysosomal hydrolase, sulphamidase, an enzyme involved in the degradation of heparan sulphate. MPS IIIA patients exhibit progressive mental retardation and behavioural disturbance. While neuropathology is the major clinical problem in MPS IIIA patients, there is little understanding of how lysosomal storage generates this phenotype. As reduced neuronal communication can underlie cognitive deficiencies, we investigated whether the secretion of neurotransmitters is altered in MPS IIIA mice; utilising adrenal chromaffin cells, a classical model for studying secretion via exocytosis. MPS IIIA chromaffin cells displayed heparan sulphate storage and electron microscopy revealed large electron-lucent storage compartments. There were also increased numbers of large/elongated chromaffin granules, with a morphology that was similar to immature secretory granules. Carbon fibre amperometry illustrated a significant decrease in the number of exocytotic events for MPS IIIA, when compared to control chromaffin cells. However, there were no changes in the kinetics of release, the amount of catecholamine released per exocytotic event, or the amount of Ca(2+) entry upon stimulation. The increased number of large/elongated granules and reduced number of exocytotic events suggests that either the biogenesis and/or the cell surface docking and fusion potential of these vesicles is impaired in MPS IIIA. If this also occurs in central nervous system neurons, the reduction in neurotransmitter release could help to explain the development of neuropathology in MPS IIIA.

The corpus callosum and empathy in adults with a history of preterm birth.

Reduced posterior corpus callosum (CC) area has been consistently observed in children and adolescents born very preterm (VPT). CC structural differences are also observed in people diagnosed with empathy disorders. This study examined empathy in relation to CC size in VPT adults and controls. CC area was manually measured for 17 VPT adults and 9 controls. Participants completed the Interpersonal Reactivity Index (Davis, 1980) and the Empathy Quotient (Baron-Cohen & Wheelwright, 2004). VPT adults had reduced posterior CC area in contrast to controls, and a positive linear trend was observed between posterior CC size and gestational age. No between-group empathy differences were observed, although self-reported personal distress in response to social situations was higher in VPT adults, and negatively associated with anterior CC area. We conclude that VPT adults have a smaller posterior CC, which is associated with gestational age, and elevated social distress, which may be mediated by anterior CC size.

The role of 'shared representations' in social perception and empathy: an fMRI study.

Evidence suggests that we use the same mechanisms for both producing and perceiving actions. Such 'shared representations' may also underlie social perception and empathy. However, this idea raises some important and as yet unresolved questions: (i) how do we distinguish other-orientated empathic responses from a self-orientated reactions such as personal distress and (ii) what are the neural substrates underpinning these processes? We employed event-related functional magnetic resonance imaging (fMRI) to explore whether 'shared representations' were recruited to decode dynamic social stimuli in 12 healthy volunteers. We used an adapted version of the Profile of Non-Verbal Sensitivity (Rosenthal, H., Hall, J.A., DiMatteo, M.R., Rogers, P.L., Archer, D., (1979). Sensitivity to nonverbal communication: the PONS test. The Johns Hopkins University Press, Baltimore) which taps social perception using brief silent video clips. Participants chose one of two words that best described the state conveyed by the actor, or in the control condition using the same clips, the word describing which parts of the body were visible (non-social labelling). Off-line self-report measures of empathy and personal distress engendered by thoughts about others, were also given along with an experimentally-derived index of the degree of self-other overlap during social perception. Brain activation specific to the main experimental condition was found in the inferior frontal gyrus (BA44) and premotor areas (BA6) consistent with the use of 'shared representations'. Somatosensory areas such as the insula and supramarginal gyrus (BA40) were also activated suggesting that participants constructed a qualitative representation of the target state. Activity in the rostral anterior cingulate was associated with self-reports of personal distress and increased blood flow to the anterior cingulate (BA24) and inferior parietal cortex (BA40) was related to self-other overlap.

Differential effects of lesions of the amygdala and prefrontal cortex on recognizing facial expressions of complex emotions.

Humans can detect facial expressions of both simple, basic emotions and expressions reflecting more complex states of mind. The latter includes emotional expressions that regulate social interactions ("social expressions" such as looking hostile or friendly) and expressions that reflect the inner thought state of others ("cognitive expressions" such as looking pensive). To explore the neural substrate of this skill, we examined performance on a test of detection of such complex expressions in patients with lesions of the temporal lobe (n = 54) or frontal lobe (n = 31). Of the temporal group, 18 had unilateral focal lesions of the amygdala and of the frontal group, 14 patients had unilateral lesions of the ventromedial prefrontal cortex-two regions held to be pivotal in mediating social cognitive skills. Damage to either the left or right amygdala was associated with impairment in the recognition of both social and cognitive expressions, despite an intact ability to extract information relating to invariant physical attributes. Lesions to all of the right prefrontal cortex-not just the ventromedial portions-led to a specific deficit in recognizing complex social expressions with a negative valence. The deficit in the group with right prefrontal cortical damage may contribute to the disturbances in social behavior associated with such lesions. The results also suggest that the amygdala has a role in processing a wide range of emotional expressions.

Measuring empathy: reliability and validity of the Empathy Quotient.

BACKGROUND: Empathy plays a key role in social understanding, but its empirical measurement has proved difficult. The Empathy Quotient (EQ) is a self-report scale designed to do just that. This series of four studies examined the reliability and validity of the EQ and determined its factor structure. METHOD: In Study 1, 53 people completed the EQ, Social Desirability Scale (SDS) and a non-verbal mental state inference test, the Eyes Task. In Study 2, a principal components analysis (PCA) was conducted on data from 110 healthy individuals and 62 people reporting depersonalisation (DPD). Approximately 1 year later, Study 3, involved the re-administration of the EQ (n = 24) along with the Interpersonal Reactivity Index (IRI; n = 28). In the last study, the EQ scores of those with DPD, a condition that includes a subjective lack of empathy, were examined in depth. RESULTS: An association was found between the Eyes task and EQ, and only three EQ items correlated with the SDS. PCA revealed three factors: (1) 'cognitive empathy'; (2) 'emotional reactivity', and (3) 'social skills'. Test-retest reliability was good and moderate associations were found between the EQ and IRI subscales, suggesting concurrent validity. People with DPD did not show a global empathy deficit, but reported less social competence. CONCLUSIONS: The EQ is a valid, reliable scale and the different subscales may have clinical applications.

The impact of early and late damage to the human amygdala on 'theory of mind' reasoning.

There is a burgeoning interest in the neural basis of the ability to attribute mental states to others; a capacity referred to as 'theory of mind' (ToM). We examined the effects of lesions of the amygdala which arise at different stages of development on this key aspect of social cognition. Tests of ToM, executive and general neuropsychological function were given to subjects with lesions of the amygdala arising congenitally or in early childhood ('early damage', n = 15), subjects who acquired damage to the amygdala in adulthood ('late damage' n = 11) and matched clinical (n = 14) and healthy comparison groups (n = 38). Subjects with early damage to the amygdala, particularly if the lesion was associated with childhood onset of seizures, were impaired relative to all other groups on more advanced tests of ToM reasoning, such as detecting tactless or ironic comments or interpreting non-literal utterances. These deficits held for subjects with either left or right early amygdala damage and encompassed the understanding of both the beliefs and emotional states of others. In contrast, subjects who acquired damage to the amygdala in adulthood (usually as part of an anterior temporal lobectomy) were not impaired in ToM reasoning relative to both clinical and healthy controls, supporting the position that the amygdala is not part of the neural circuitry mediating the 'on-line' performance of ToM reasoning. In line with theories which claim that ToM is an independent faculty of cognition, we found that the pattern of results held after co-varying for measures of executive function, memory and general intellectual functioning. We discuss the results in the light of recent theories which link early developmental insults to the amygdala with the ToM impairments which are thought to be a core neurocognitive deficit found in disorders such as autism. We conclude that the amygdala may play an important role in the neural systems supporting the normal development of ToM reasoning.

Validity of duplex ultrasound as a diagnostic modality for internal carotid artery disease.

There is an increasing trend to rely on duplex ultrasound rather than angiography to measure an internal carotid artery stenosis. The aim of this study was to determine the validity of ultrasound assessment of carotid stenosis performed in community based vascular laboratories. We compared ultrasound with angiography in 225 patients referred to us for carotid intervention. Mild lesions were diagnosed by ultrasound with a sensitivity of 54%, specificity of 89%, and a positive predictive value of 89% compared with angiography. Severe lesions had a sensitivity of 93%, a specificity of 67%, and a positive predictive value of 45%. Receiver operator characteristic curves demonstrated the optimal ultrasound cut-off value of 66% stenosis as a predictor of >60% stenosis measured angiographically, is associated with a false positive rate of 38%, and a false negative rate of 9%. Similarly, if a cut-off of 76% on ultrasound is used to predict >70% stenosis measured angiographically, it would be associated with a 29% false positive rate and a false negative rate of 11%. Despite the value of non-invasive testing for carotid disease, duplex ultrasonography performed in non-accredited and some accredited laboratories may produce highly variable results. Using ultrasound as the sole diagnostic test to determine the severity of a carotid stenosis may result in a high number of inappropriate operations and a large proportion of patients who may not be offered treatment due to false negative diagnoses.

Outpatient carotid artery stenting: a case report.

PURPOSE: To report a case of carotid artery stenting for asymptomatic carotid restenosis performed in an outpatient setting. METHODS AND RESULTS: A 68-year-old man with right carotid restenosis after repeat carotid endarterectomy underwent carotid angioplasty and stenting on an ambulatory basis. The procedure to implant a Smart stent required 45 minutes; the femoral access site was closed with a puncture closure device. The patient experienced no sequelae to this procedure and is well 6 months after treatment. CONCLUSIONS: Outpatient delivery of percutaneous carotid stenting may be feasible in appropriately selected patients.