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Frontotemporal dementia (FTD) is an umbrella term covering a plethora of progressive changes in executive functions, motor abilities, behavior, and/or language. Different clinical syndromes have been described in relation to localized atrophy, informing on the functional networks that underlie these specific cognitive, emotional, and behavioral processes. These functional declines are linked with the underlying neurodegeneration of frontal and/or temporal lobes due to diverse molecular pathologies. Initially, the accumulation of misfolded proteins targets specifically susceptible cell assemblies, leading to relatively focal neurodegeneration that later spreads throughout large-scale cortical networks. Here, we discuss the most recent clinical, neuropathological, imaging, and genetics findings in FTD-spectrum syndromes affecting the temporal lobe. We focus on the semantic variant of primary progressive aphasia and its mirror image, the right temporal variant of FTD. Incipient focal atrophy of the left anterior temporal lobe (ATL) manifests with predominant naming, word comprehension, reading, and object semantic deficits, while cases of predominantly right ATL atrophy present with impairments of socioemotional, nonverbal semantic, and person-specific knowledge. Overall, the observations in FTD allow for crucial clinical-anatomic inferences, shedding light on the role of the temporal lobes in both cognition and complex behaviors. The concerted activity of both ATLs is critical to ensure that percepts are translated into concepts, yet important hemispheric differences should be acknowledged. On one hand, the left ATL attributes meaning to linguistic, external stimuli, thus supporting goal-oriented, action-related behaviors (e.g., integrating sounds and letters into words). On the other hand, the right ATL assigns meaning to emotional, visceral stimuli, thus guiding socially relevant behaviors (e.g., integrating body sensations into feelings of familiarity)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction and Aims: Oxytocin (OT) is a neuropeptide hormone secreted by the posterior pituitary gland. Deficits in OT action have been observed in patients with behavioral and mood disorders, some of which correlate with an increased risk of cardiovascular disease (CVD). Recent research has revealed a wider systemic role that OT plays in inflammatory modulation and development of atherosclerotic plaques. This study investigated the role that OT plays in cholesterol transport and foam cell formation in LPS-stimulated THP-1 human macrophages., Methods: THP-1 differentiated macrophages were treated with media, LPS (100 ng/ml), LPS + OT (10 pM), or LPS + OT (100 pM). Changes in gene expression and protein levels of cholesterol transporters were analyzed by real time quantitative PCR (RT-qPCR) and Western blot, while oxLDL uptake and cholesterol efflux capacity were evaluated with fluorometric assays., Results: RT-qPCR analysis revealed a significant increase in ABCG1 gene expression upon OT + LPS treatment, compared to LPS alone (p = 0.0081), with Western blotting supporting the increase in expression of the ABCG1 protein. Analysis of oxLDL uptake showed a significantly lower fluorescent value in LPS + OT (100pM) -treated cells when compared to LPS alone (p < 0.0001). While not statistically significant (p = 0.06), cholesterol efflux capacity increased with LPS + OT treatment., Conclusion: We demonstrate here that OT can attenuate LPS-mediated lipid accumulation in THP-1 macrophages. These findings support the hypothesis that OT could be used to reduce pro-inflammatory and potentially atherogenic changes observed in patients with heightened CVD risk. This study suggests further exploration of OT effects on monocyte and macrophage cholesterol handling in vivo., (Copyright © 2021. Published by Elsevier Inc.)

Individuals may drink or use cannabis to cope with social anxiety, and drinking or using cannabis prior to social situations (e.g., pregaming) may be a way to limit the experience of anxiety when entering social settings. However, theoretical and empirical work has reported mixed associations between social anxiety and substance use, specifically alcohol and cannabis. Little work has looked at how other variables, such as impulsivity (a central component to high risk drinking such as pregaming), may shed light onto these mixed findings. College students who reported past year pregaming (n = 363) completed self-report surveys. Supporting prior work, we found that social anxiety was associated with fewer pregaming days, even among those high in sensation seeking. However, those reporting higher social anxiety also reported higher cannabis use during pregaming, specifically among those who reported high sensation seeking and high positive urgency. Results suggest specific facets of impulsivity may affect the association between social anxiety and cannabis use during high risk drinking events., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease with high mortality that commonly occurs in middle-aged and older adults. IPF, characterized by a decline in lung function, often manifests as exertional dyspnea and cough. Symptoms result from a fibrotic process driven by alveolar epithelial cells that leads to increased migration, proliferation, and differentiation of lung fibroblasts. Ultimately, the differentiation of fibroblasts into myofibroblasts, which synthesize excessive amounts of extracellular matrix proteins, destroys the lung architecture. However, the factors that induce the fibrotic process are unclear. Diagnosis can be a difficult process; the gold standard for diagnosis is the multidisciplinary conference. Practical biomarkers are needed to improve diagnostic and prognostic accuracy. High-resolution computed tomography typically shows interstitial pneumonia with basal and peripheral honeycombing. Gas exchange and diffusion capacity are impaired. Treatments are limited, although the anti-fibrotic drugs pirfenidone and nintedanib can slow the progression of the disease. Lung transplantation is often contraindicated because of age and comorbidities, but it improves survival when successful. The incidence and prevalence of IPF has been increasing and there is an urgent need for improved therapies. This review covers the detailed cellular and molecular mechanisms underlying IPF progression as well as current treatments and cutting-edge research into new therapeutic targets., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest directly relevant to the content of this paper., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by semantic memory deficits with relatively preserved motor speech, syntax, and phonology. There is consistent evidence linking focal neurodegeneration of the anterior temporal lobes (ATL) to the semantic deficits observed in svPPA. Less is known about large-scale functional connectivity changes in this syndrome, particularly regarding the interplay between affected and spared language networks that leads to the unique cognitive dissociations typical of svPPA. Using whole-brain, seed-based connectivity on task-free Magnetic Resonance Imaging (MRI) data, we studied connectivity of networks anchored to three left-hemisphere regions crucially involved in svPPA symptomatology: ATL just posterior to the main atrophic area, opercular inferior frontal gyrus, and posterior inferior temporal lobe. First, in 32 healthy controls, these seeds isolated three networks: a ventral semantic network involving anterior middle temporal and angular gyri, a dorsal articulatory-phonological system involving inferior frontal and supramarginal regions, and a third functional connection between posterior inferior temporal and intraparietal regions likely involved in linking visual and linguistic processes. We then compared connectivity strength of these three networks between 16 svPPA patients and the 32 controls. In svPPA, decreased functional connectivity in the ventral semantic network correlated with weak semantic skills, while connectivity of the network seeded from the posterior inferior temporal lobe, though not significantly different between the two groups, correlated with pseudoword reading skills. Increased connectivity between the inferior frontal gyrus and the superior portion of the angular gyrus suggested possible adaptive changes. Our findings have two main implications. First, they support a functional subdivision of the left IPL based on its connectivity to specific language-related regions. Second, the unique neuroanatomical and linguistic profile observed in svPPA provides a compelling model for the functional interplay of these networks, being either up- or down- regulated in response to disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease associated with obesity and autoimmunity is the leading cause of death in these populations and significant residual risk remains despite current treatment approaches. Obesity, type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) are linked to chronic inflammation, and subjects with these disorders have characteristic shifts in their gut microbiome composition. Recent data suggest that alterations in gut microbial and metabolic composition may be responsible, in part, for induction of chronic inflammation, thus promoting cardiovascular disease. Common microbiome changes observed in obesity, T1DM, RA, and SLE include a decrease in the ratio of bacteria, such as Gram-positive Firmicutes to Gram-negative Bacteroidetes, as well as an overabundance or depletion of certain species, including Prevotella copri. The consequent effects of these shifts include alterations in the metabolic composition of the gut, hyper-activation of toll-like receptor 4 (TLR-4), upregulation of inflammatory pathways, e.g. c-Jun N-terminal kinase and nuclear factor-kappa B (NFκB), increased intestinal permeability, increased C-reactive protein, and increased levels of trimethylamine N-oxide (TMAO). Differential microbiome compositions may also explain sex differences observed in autoimmunity, where a male gut microbiome promotes anti-inflammatory processes as compared to a female pro-inflammatory gut microbiome. Intervention at the level of the microbiota appears to attenuate symptoms in these inflammatory syndromes with probiotic treatment, such as Lactobacilli, playing a uniquely beneficial role in restoring intestinal health, decreasing inflammation, and reducing cardiovascular disease. This review will discuss obesity, T1DM, RA, and SLE in the context of how each unique microbiome profile contributes to elevated cardiovascular risk., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive changes in behavior, personality, and language with involvement of the frontal and temporal regions of the brain. About 40% of FTD cases have a positive family history, and about 10% of these cases are inherited in an autosomal-dominant pattern. These gene defects present with distinct clinical phenotypes. As the diagnosis of FTD becomes more recognizable, it will become increasingly important to keep these gene mutations in mind. In this chapter, we review the genes with known associations to FTD. We discuss protein functions, mutation frequencies, clinical phenotypes, imaging characteristics, and pathology associated with these genes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Many patients with primary progressive aphasia (PPA) are impaired in syntactic production. Because most previous studies of expressive syntax in PPA have relied on quantitative analysis of connected speech samples, which is a relatively unconstrained task, it is not well understood which specific syntactic structures are most challenging for these patients. We used an elicited syntactic production task to identify which syntactic structures pose difficulties for 31 patients with three variants of PPA: non-fluent/agrammatic, semantic and logopenic. Neurodegenerative and healthy age-matched participants were included as controls. As expected, non-fluent/agrammatic patients made the most syntactic errors. The structures that resulted in the most errors were constructions involving third person singular present agreement, and constructions involving embedded clauses. Deficits on this elicited production task were associated with atrophy of the left posterior inferior frontal gyrus., (Published by Elsevier Inc.)

Purpose: To describe the real life challenges and HIV-risk behaviors of male-to-female (MTF) transgender youth from communities of color., Methods: A convenience sample (n = 51) of ethnic-minority MTF transgender youth aged 16-25 years completed an anonymous questionnaire including demographics, psychosocial measures, and participation in substance use and sexual risk behaviors. Descriptive analyses and analyses of association were used to interpret the data., Results: The median age of participants was 22 years, and 57% were African-American. Twenty-two percent reported being human immunodeficiency virus positive (HIV+). Prevalence of life stressors among the sample included history of incarceration (37%), homelessness (18%), sex in exchange for resources (59%), forced sexual activity (52%), difficulty finding a job (63%), and difficulty accessing health care (41%). Within the past year, 98% had sex with men, 49% had unprotected receptive anal intercourse, and 53% had sex under the influence of drugs or alcohol. Substance use within the past year was common, with marijuana (71%) and alcohol (65%) most frequently reported. Twenty-nine percent of participants had used injection liquid silicone in their lifetime. Other injection drug use and needle-sharing behaviors were rare. Compared with other racial/ethnic groups, HIV was found in higher rates among African-American youth (p < .05). HIV status was not associated with any other demographic characteristic, psychosocial measure, sexual or substance use behavior., Conclusions: These findings suggest that MTF transgender youth of color have many unmet needs and are at extreme risk of acquiring HIV. Future research is needed to better understand this adolescent subgroup and to develop targeted broad-based interventions that reduce risky behaviors.

Withdrawal effects of neuroleptics have not received much attention. Clozapine withdrawal phenomena have been attributed to psychosis arising from D2 supersensitivity, which is unlikely since it has minimal action on D2 receptors. The time course and clinical features of this phenomenon suggest that cholinergic overdrive and gamma-aminobutyric acid (GABA) supersensitivity occurs after withdrawal, since it is strongly anticholinergic and has a GABAergic action. Recently, a number of patients showed marked decompensation when they were switched from clozapine to risperidone, especially when they were rapidly tapered off clozapine. This was probably more due to withdrawal effects than the primary psychosis or a lack of efficacy of risperidone. A slow withdrawal schedule would facilitate homeostatic mechanisms; anticholinergics would be useful in clozapine withdrawal. This area has not received any attention from researchers, nor are there any guidelines for clinicians. This will be particularly important with the widespread use of atypical agents in the future.