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Background: The early months of the coronavirus disease 19 (COVID-19) pandemic in New York City led to a rapid transition of non-essential in-person health care, including outpatient arthroplasty visits, to a telemedicine context. Questions/Purposes: Based on our initial experiences with telemedicine in an outpatient arthroplasty setting, we sought to determine early lessons learned that may be applicable to other providers adopting or expanding telemedicine services. Methods: A cross-sectional study was performed by surveying all patients undergoing telemedicine visits with 8 arthroplasty surgeons at 1 orthopedic specialty hospital in New York City from April 8 to May 19, 2020. Descriptive statistics were used to analyze demographic data, satisfaction with the telemedicine visit, and positive and negative takeaways. Results: In all, 164 patients completed the survey. The most common reasons for the telemedicine visit were short-term (less than 6 months), postoperative appointment ( n = 88; 54%), and new patient consultation ( n = 32; 20%). A total of 84 patients (51%) noted a reduction in expenses versus standard outpatient care. Several positive themes emerged from patient feedback, including less anxiety and stress related to traveling ( n = 82; 50%), feeling more at ease in a familiar environment ( n = 54; 33%), and the ability to assess postoperative home environment ( n = 13; 8%). However, patients also expressed concerns about the difficulty addressing symptoms in the absence of an in-person examination ( n = 28; 17%), a decreased sense of interpersonal connection with the physician ( n = 20; 12%), and technical difficulties ( n = 14; 9%). Conclusions: Patients were satisfied with their telemedicine experience during the COVID-19 pandemic; however, we identified several areas amenable to improvement. Further study is warranted.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene. Neuroanatomical alterations have been reported in both male and female individuals with FXS, yet the morphological underpinnings of these alterations have not been elucidated. In the current study, we found structural changes in both male and female rats that model FXS, some of which are similarly impaired in both sexes, including the superior colliculus and periaqueductal gray, and others that show sex-specific changes. The splenium of the corpus callosum, for example, was only impaired in males. We also found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Furthermore, we found that overall, male rats have higher brain-wide diffusion than female rats. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and reveal an impairment at the level of the axon that could cause structural changes in white matter regions.

Microvascular pathology and ischemic lesions contribute substantially to neuronal dysfunction and loss that lead to Alzheimer disease (AD). To facilitate recovery, the brain stimulates neovascularization of damaged tissue via sprouting angiogenesis, a process regulated by endothelial cell (EC) sprouting and the EphB4/ephrinB2 system. Here, we show that in cultures of brain ECs, EphB4 stimulates the VE-cadherin/Rok-α angiogenic complexes known to mediate sprouting angiogenesis. Importantly, brain EC cultures expressing PS1 FAD mutants decrease the EphB4-stimulated γ-secretase cleavage of ephrinB2 and reduce production of the angiogenic peptide ephrinB2/CTF2, the VE-cadherin angiogenic complexes and EC sprouting and tube formation. These data suggest that FAD mutants may attenuate ischemia-induced brain angiogenesis. Supporting this hypothesis, ischemia-induced VE-cadherin angiogenic complexes, levels of neoangiogenesis marker Endoglin, vascular density, and cerebral blood flow recovery, are all decreased in brains of mouse models expressing PS1 FAD mutants. Ischemia-induced brain neuronal death and cognitive deficits also increase in these mice. Furthermore, a small peptide comprising the C-terminal sequence of peptide ephrinB2/CTF2 rescues angiogenic functions of brain ECs expressing PS1 FAD mutants. Together, our data show that PS1 FAD mutations impede the EphB4/ephrinB2-mediated angiogenic functions of ECs and impair brain neovascularization, neuronal survival and cognitive recovery following ischemia. Furthermore, our data reveal a novel brain angiogenic mechanism targeted by PS1 FAD mutants and a potential therapeutic target for ischemia-induced neurodegeneration. Importantly, FAD mutant effects occur in absence of neuropathological hallmarks of AD, supporting that such hallmarks may form downstream of mutant effects on neoangiogenesis and neuronal survival.

Background: Mutations and deletions in the SHANK3 synaptic gene cause the major neurodevelopmental features of Phelan-McDermid syndrome (PMS). The SHANK3 gene encodes a key structural component of excitatory synapses that is important for synaptogenesis. PMS is characterized by intellectual disability, autism spectrum disorder, cognitive deficits, physical dysmorphic features, sensory hyporeactivity, and alterations in the size of multiple brain regions. Clinical assessments and limited imaging studies have revealed a reduction in volume of multiple brain regions. They have also found white matter thinning and microstructural alterations to be persistent in patients with PMS. While many of these impairments have been replicated in mouse models of PMS, the brain structure of a rat model has not yet been studied. Methods: We assessed the brain structure of haploinsufficient and homozygous Shank3-deficient rats that model the behavioral deficits of PMS with magnetic resonance and diffusion tensor imaging, and compared their brain structure to wild type littermates.Results: Both gray and white matter structures were smaller in Shank3-deficient rats, leading to an overall reduction in brain size compared to wild type littermates. The largest region to be diminished in size was the neocortex. Some regions involved in sensory processing and white matter regions were also reduced in size. Lastly, the microstructure of two white matter tracts, the external capsule and fornix, was abnormal.Conclusions: Shank3-deficient rats replicate the reduced brain volume and altered white matter phenotypes present in individuals with PMS. Therefore, the brain regions that were altered represent potential cross-species structural biomarkers that warrant further study.

The management of pelvic discontinuity in revision total hip arthroplasty can be challenging and requires a thorough understanding of the bone loss pattern as well as available treatment options. The goal of the treatment for large acetabular defects and pelvic discontinuity is to create a unitized hemipelvis by either biological healing of the discontinuity or mechanically fixing the superior and inferior aspects of the pelvis with rigid and durable fixation. This chapter discusses the indications, nuances, and considerations for various treatment approaches for pelvic discontinuities, with special attention to the use of custom triflange implants and the emerging role of 3-D printing technologies in this clinical setting. In addition, this chapter reviews the evolution of 3-D printing, and its surgical application in creating patient-specific implants to best accommodate the remaining host bone and optimize screw purchase. The rationale, manufacturing process, surgical technique, and case examples of custom triflange components, as well as the available midterm survivorship data, are also detailed.

Cognitive dysfunction after surgery under general anesthesia is a well-recognized clinical phenomenon in the elderly. Physiological effects of various anesthetic agents have been studied at length. Very little is known about potential effects of anesthesia on brain structure. In this study we used Diffusion Tensor Imaging to compare the white matter microstructure of healthy control subjects under sevoflurane anesthesia with their awake state. Fractional Anisotropy, a white mater integrity index, transiently decreases throughout the brain during sevoflurane anesthesia and then returns back to baseline. Other DTI metrics such as mean diffusivity, axial diffusivity and radial diffusivity were increased under sevoflurane anesthesia. Although DTI metrics are age dependent, the transient changes due to sevoflurane were independent of age and sex. Volumetric analysis shows various white matter volumes decreased whereas some gray matter volumes increased during sevoflurane anesthesia. These results suggest that sevoflurane anesthesia has a significant, but transient, effect on white matter microstructure. In spite of the transient effects of sevoflurane anesthesia there were no measurable effects on brain white matter as determined by the DTI metrics at 2 days and 7 days following anesthesia. The role of white matter in the loss of consciousness under anesthesia will need to be studied and MRI studies with subjects under anesthesia will need to take these results into account.

Manganese (Mn) is an essential trace metal that is neurotoxic at high levels of exposure. Disruption of brain maturation processes during the prenatal period may have lasting consequences. During this critical period, the developing human brain is uniquely vulnerable to exposure to environmental toxicants such as Mn, and prenatal Mn exposure has been associated with changes in brain areas involved in emotion processing and regulation. The goal of the present pilot study was to examine whether prenatal Mn exposure is associated with changes in the intrinsic functional connectivity (iFC) of the brain in childhood, focusing on changes in emotional brain areas. We selected 15 subjects (age 6-7 years) from an ongoing longitudinal birth cohort study to participate in a resting state functional magnetic resonance imaging (fMRI) study. Prenatal Mn exposure was determined from maternal blood collected during the 2nd and 3rd trimesters of pregnancy. We used seed-based correlation analyses and independent component analyses to examine whether prenatal Mn exposure was associated with the iFC of the brain in children. We found that the right globus pallidus showed reduced iFC with the dorsal anterior cingulate cortex and lateral prefrontal cortex in children who were exposed to higher prenatal Mn levels, after controlling for sociodemographic confounders (SES, maternal education, child sex, home environment support) and environmental confounders (prenatal lead exposure and air pollution). These findings suggest that prenatal Mn exposure is associated with reduced iFC of brain areas involved in emotion processing and regulation in children. Future studies should investigate whether this reduced iFC mediates the association between prenatal Mn exposure and emotional dysfunction in childhood.

Contains fulltext : 220137.pdf (Publisher’s version ) (Closed access) Over the last 15 years, research on canid cognition has revealed that domestic dogs possess a surprising array of complex socio-cognitive skills pointing to the possibility that the domestication process might have uniquely altered their brains; however, we know very little about how evolutionary processes (natural or artificial) might have modified underlying neural structure to support species-specific behaviors. Evaluating the degree of cortical folding (i.e., gyrification) within canids may prove useful, as this parameter is linked to functional variation of the cerebral cortex. Using quantitative magnetic resonance imaging to investigate the impact of domestication on the canine cortical surface, we compared the gyrification index (GI) in 19 carnivore species, including six wild canid and 13 domestic dog individuals. We also explored correlations between global and local GI with brain mass, cortical thickness, white and grey matter volume and surface area. Our results indicated that GI values for domestic dogs are largely consistent with what would be expected for a canid of their given brain mass, although more variable than that observed in wild canids. We also found that GI in canids is positively correlated with cortical surface area, cortical thickness and total cortical grey matter volumes. While we found no evidence of global differences in GI between domestic and wild canids, certain regional differences in gyrification were observed. 20 p.

The African wild dog is endemic to sub-Saharan Africa and belongs to the family Canidae which includes domestic dogs and their closest relatives (i.e., wolves, coyotes, jackals, dingoes, and foxes). The African wild dog is known for its highly social behavior, co-ordinated pack predation, and striking vocal repertoire, but little is known about its brain and whether it differs in any significant way from that of other canids. We employed gross anatomical observation, magnetic resonance imaging, and classical neuroanatomical staining to provide a broad overview of the structure of the African wild dog brain. Our results reveal a mean brain mass of 154.08 g, with an encephalization quotient of 1.73, indicating that the African wild dog has a relatively large brain size. Analysis of the various structures that comprise their brains and their topological inter-relationships, as well as the areas and volumes of the corpus callosum, ventricular system, hippocampus, amygdala, cerebellum and the gyrification index, all reveal that the African wild dog brain is, in general, similar to that of other mammals, and very similar to that of other carnivorans. While at this level of analysis we do not find any striking specializations within the brain of the African wild dog, apart from a relatively large brain size, the observations made indicate that more detailed analyses of specific neural systems, particularly those involved in sensorimotor processing, sociality or cognition, may reveal features that are either unique to this species or shared among the Canidae to the exclusion of other Carnivora.

Welding fume exposure has been associated with structural brain changes and a wide variety of clinical and sub-clinical outcomes including cognitive, behavioral and motor abnormalities. Respirator use has been shown to decrease exposure to welding fumes; however, the associations between respirator use and health outcomes, particularly neurologic health, have been understudied. In this preliminary study, we used diffusion tensor imaging (DTI) to investigate the effectiveness of respirator use in protecting workers’ white matter (WM) from the harmful effects related to welding fume exposure. Fractional anisotropy (FA), a common DTI measurement of water diffusion properties, was used as a marker of WM microstructure integrity. We hypothesized that FA in brain regions involved in motor and neurocognitive functions would differ between welders reporting respirator use compared to those not using a respirator. We enrolled a pilot cohort of 19 welders from labor unions in the New York City area. All welders completed questionnaires to assess welding history and occupational health. All completed a DTI acquisition on a 3 T Siemens scanner. Partial least squares discriminant analysis (PLS-DA), a bioinformatic analytical strategy, was used to model the divergence of WM microstructures in 48 regions defined by the ICBM-DTI-81 atlas between respirator users compared to non-users. This yielded an effective discrimination of respirator users from non-users, with the uncinate fasciculus, the cerebellar peduncle and the superior longitudinal fasciculus contributing most to the discrimination of these groups. These white matter tracts are involved in widespread motor and cognitive functions. To our knowledge, this study is the first to suggest a protective effect of respirator on WM microstructure, indicating that the lack of respirator may present unsafe working conditions for welders. These preliminary findings may inform a larger, longitudinal intervention study that would be more appropriate to investigate the potential protective effect of respirator usage on brain white matter in welders.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene that are known to cause neuroanatomical alterations. The morphological underpinnings of these alterations have not been elucidated. Furthermore, while alterations have been identified in both male and female individuals, neuroanatomy in female rodent models has not been assessed. We identified structural differences in regions that are also altered in FXS in male and female rat models, including the splenium of the corpus callosum. Interestingly, different sets of regions were disrupted in male and female rat models and, remarkably, male rats had higher brain-wide diffusion than female rats overall. We found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and suggest a potential mechanism for how its loss causes white matter dysfunction in FXS.

All domesticated mammals exhibit marked reductions in overall brain size, however, it is unknown whether the corpus callosum, an integral white matter fiber pathway for interhemispheric cortical communication, is affected by domestication differentially or strictly in coordination with changes in brain size. To answer this question, we used quantitative magnetic resonance imaging to compare the mid‐sagittal cross‐sectional areas of the corpus callosum in 35 carnivore species, including eight wild canids and 13 domestic dogs. We segmented rostro‐caudal regions of interest for the corpus callosum and evaluated correlations with brain mass. The results of this study indicate that under the influence of domestication in canids, the corpus callosum scales to brain size in an allometric relationship that is similar to that of wild canids and other carnivores, with relatively high correlation coefficients observed for all regions, except the rostrum. These results indicate that architectural and energetic considerations are likely to tightly constrain variation in caudal components of the corpus callosum relative to overall brain size, however fibers passing through the rostrum, putatively connecting prefrontal cortex, are less constrained and therefore may contribute more towards species‐specific differences in connectivity. Given the species diversity of the Canidae and the resurgence of interest in the brain of the domestic dog, further studies aimed at characterizing the neural architecture in domesticated species is likely to provide new insights into the effects of domestication, or artificial selection, on the brain.

Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression. Chronic social defeat stress induces loss of protein claudin-5, leading to abnormalities in blood vessel morphology, increased blood brain barrier permeability, infiltration of immune signals and depression-like behaviors.

Reviews of imaging studies assessing the brain effects of vascular risk factors typically include a substantial number of studies with subjects with a history of symptomatic cardiovascular or cerebrovascular disease and/or events, limiting our ability to disentangle the primary brain effects of vascular risk factors from those of resulting brain and cardiac damage. The objective of this study was to perform a systematic review of brain changes from imaging studies in patients with vascular risk factors but without clinically manifest cardiovascular or cerebrovascular disease or events. The 77 studies included in this review demonstrate that in persons without symptomatic cardiovascular, cerebrovascular, or peripheral vascular disease, the vascular risk factors of hypertension, diabetes mellitus, obesity, hyperlipidemia, and smoking are all independently associated with brain imaging changes before the clinical manifestation of cardiovascular or cerebrovascular disease. We conclude that the identification of brain changes associated with vascular risk factors, before the manifestation of clinically significant cerebrovascular damage, presents a window of opportunity wherein adequate treatment of these modifiable vascular risk factors may prevent the development of irreversible deleterious brain changes and potentially alter patients’ clinical course.

Background Perinatal lead (Pb) exposure is associated with adverse cognitive and behavioral outcomes that may be mediated by altered brain structure and function. Childhood Pb exposure has been ass...

Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available.