Effects of Tobacco Usage and Antiretroviral Therapy on Biomarkers of Systemic Immune Activation in HIV-Infected Participants

Like HIV infection, smoking, which is common among HIV-infected persons, is associated with chronic, systemic inflammation. However, the possible augmentative effects of HIV infection and smoking and other types of tobacco usage on indices of systemic inflammation and the impact of combination antiretroviral therapy (cART) thereon remain largely unexplored and represent the focus of the current study. Of the total number of HIV-infected persons recruited to the study (), 100 were categorised as pre-cART and 99 as virally suppressed (HIV viral copies/mL). According to serum cotinine levels, 144 and 55 participants were categorised as nonusers and users of tobacco, respectively. In addition to cytokines (IL-6, IL-8, and TNF-α) and chemokines (IP-10, MIG, IL-8, MCP-1, and RANTES), other biomarkers of systemic inflammation included C-reactive protein (CRP), β2-microglobulin, and those of neutrophil activation [ICAM-1, L-selectin, matrix metalloproteinase-9 (MMP-9)], microbial translocation (soluble CD14, LPS-binding protein), and oxidative stress (cyclophilin A, surfactant D). These were measured using multiplex bead array, ELISA, and immunonephelometric procedures. Viral suppression was associated with significant decreases in the levels of most of the biomarkers tested (-0.0008), with the exceptions of CRP, cyclophilin A, and MMP-9. With respect to tobacco usage, irrespective of cART status, circulating levels of β2-microglobulin, cyclophilin A, and RANTES were significantly elevated (-0.012) in users vs nonusers. Additional analysis of the groups of tobacco users and nonusers according to cART status revealed high levels of RANTES in pre-cART/tobacco users relative to the three other subgroups (-0.0001), while more modest increases in cyclophilin A and MMP-9 (-0.027) were observed in comparison with the cART/tobacco user subgroup. Notwithstanding the efficacy of cART in attenuating HIV-associated, chronic systemic inflammation, the current study has identified RANTES as being significantly and seemingly selectively increased in those with active HIV infection who use tobacco, a mechanism which may underpin augmentative proinflammatory activity.

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Stereophotogrammetric analysis of labial morphology in a young adult Middle-Eastern population

Publication date: Available online 8 December 2018

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Fouad Ayoub, Maria Saadeh, Hassan Kazan-Fayad, Ramzi Haddad

Abstract

Introduction

The majority of previous research delineating the morphological characteristics of the orolabial region has been on Caucasian populations, with very minor research on Mediterranean populations, and none on the Lebanese population.

Aim

The primary aim was to collect information on the gender-specific 3D morphology of the mouth and lips in young Middle Eastern adults. The secondary aim was to explore the presence of associations between orolabial morphology and age and body mass index (BMI), and to assess correlations between linear orolabial dimensions and area/volume measures.Methods. The study used non-invasive stereophotogrammetry to collect information on gender-specific 3D labial morphology (linear distances, areas, and volumes) for 122 adult Lebanese subjects, aged 18– 30 years (47 males, 75 females). Associations between labial morphology and age and body mass index were assessed, in addition to correlations between linear orolabial dimensions and area/volume measures.

Results

All linear, angular, area, and volume lip measurements displayed significant variability. Both lip area and volume were smaller in the upper than in the lower lip. Eighteen out of the 20 linear measurements were significantly larger in males. The ratio, area, and volume measurements mostly displayed no statistically significant gender dimorphism.

Conclusions

Alongside presenting the first documented report on anthropometric labial measurements of a young Lebanese adult population, this research highlights the presence of gender dimorphism in linear and angular measurements, but not in area and volume measurements, and a strong association between certain linear labial measurements and lip area and volume. In addition, it presents pilot data on the association between labial anthropometry and body mass index.

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Age-related differences in task-induced brain activation is not task specific: Multivariate pattern generalization between metacognition, cognition and perception

Publication date: Available online 8 December 2018

Source: NeuroImage

Author(s): Esther H.H. Keulers, María Björk Birkisdóttir, Luciana Falbo, Anique de Bruin, Peter L.J. Stiers

Abstract

Adolescence is associated with widespread maturation of brain structures and functional connectivity profiles that shift from local to more distributed and better integrated networks, which are active during a variety of cognitive tasks. Nevertheless, the approach to examine task-induced developmental brain changes is function-specific, leaving the question open whether functional maturation is specific to the particular cognitive demands of the task used, or generalizes across different tasks. In the present study we examine the hypothesis that functional brain maturation is driven by global changes in how the brain handles cognitive demands. Multivariate pattern classification analysis (MVPA) was used to examine whether age discriminative task-induced activation patterns generalize across a wide range of information processing levels. 25 young (13-years old) and 22 old (17-years old) adolescents performed three conceptually different tasks of metacognition, cognition and visual processing. MVPA applied within each task indicated that task-induced brain activation is consistent and reliably different between ages 13 and 17. These age-discriminative activation patterns proved to be common across the different tasks used, despite the differences in cognitive demands and brain structures engaged by each of the three tasks. MVP classifiers trained to detect age-discriminative patterns in brain activation during one task were significantly able to decode age from brain activation maps during execution of other tasks with accuracies between 63 and 75%. The results emphasize that age-specific characteristics of task-induced brain activation have to be understood at the level of brain-wide networks that show maturational changes in their organization and processing efficacy during adolescence.

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Neural architecture supporting active emotion processing in children: A multivariate approach

Publication date: Available online 8 December 2018

Source: NeuroImage

Author(s): M. Catalina Camacho, Helmet T. Karim, Susan B. Perlman

Abstract

Background

Adaptive emotion processing is critical for nearly all aspects of social and emotional functioning. There are distinct developmental trajectories associated with improved emotion processing, with a protracted developmental course for negative or complex emotions. The specific changes in neural circuitry that underlie this development, however are still scarcely understood. We employed a multivariate approach in order to elucidate distinctions in complex, naturalistic emotion processing between childhood and adulthood.

Method

Twenty-one adults (M±SD age = 26.57 ± 5.08 years) and thirty children (age = 7.75 ± 1.80 years) completed a free-viewing movie task during BOLD fMRI scanning. This task was designed to assess naturalistic processing of movie clips portraying positive, negative, and neutral emotions. Multivariate support vector machines (SVM) were trained to classify age groups based on neural activation during the task.

Results

SVMs were able to successfully classify condition (positive, negative, and neutral) across all participants with high accuracy (61.44%). SVMs could successfully distinguish adults and children within each condition (ps < 0.05). Regions that informed the age group SVMs were associated with sensory and socio-emotional processing (inferior parietal lobule), emotion regulation (inferior frontal gyrus), and sensory regions of the temporal and occipital lobes.

Conclusions

These results point to distributed differences in activation between childhood and adulthood unique to each emotional condition. In the negative condition specifically, there is evidence for a shift in engagement from regions of sensory and socio-emotional integration to emotion regulation regions between children and adults. These results provide insight into circuitry contributing to maturation of emotional processing across development.

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Identification of novel allergic diathesis genes: are we closer to novel therapeutic targets?

Publication date: Available online 8 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Michelle Daya, Kathleen C. Barnes

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Serious Asthma Events with Mometasone Furoate Plus Formoterol Compared With Mometasone Furoate

Publication date: Available online 8 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Cindy L.J. Weinstein, Nicholas Ryan, Tulin Shekar, Davis Gates, Stephen J. Lane, Ioana Agache, Robert A. Nathan, SPIRO Investigators

Abstract

Background

The safety of long-acting beta agonists added to inhaled corticosteroids for the treatment of persistent asthma has been controversial.

Objective

To determine whether administering formoterol in combination with mometasone furoate increases the risk of serious asthma outcomes compared to mometasone furoate alone.

Methods

We conducted a 26-week, randomized, double-blind trial in adolescent and adult patients (≥12 years) with persistent asthma in 35 countries with the primary objective of evaluating whether mometasone furoate-formoterol increases the risk of serious asthma outcomes (adjudicated hospitalization, intubation, or death) compared to mometasone furoate alone. The key efficacy endpoint was asthma exacerbation (composite of hospitalizations ≥24 h, emergency visits <24 h requiring systemic corticosteroid, or systemic corticosteroid for ≥3 consecutive days).

Results

Among 11,729 patients (mometasone furoate-formoterol, n=5868; mometasone furoate, n=5861), a total of 81 serious asthma outcomes, all asthma-related hospitalizations, were observed in 71 patients; 45 events from 39 patients on mometasone furoate-formoterol and 36 events from 32 patients on mometasone furoate. The hazard ratio for the first serious asthma outcome in the mometasone furoate-formoterol versus mometasone furoate group was 1.22 (95% CI: 0.76 to 1.94, p=0.411). Asthma exacerbation occurred in 1487 patients; 708 on mometasone furoate-formoterol and 779 on mometasone furoate. The hazard ratio for the first asthma exacerbation in the mometasone furoate-formoterol versus mometasone furoate group was 0.89 (95% CI: 0.80 to 0.98, p=0.021).

Conclusions

The addition of formoterol to mometasone maintenance therapy did not increase the risk of serious asthma-related events and reduced the risk of asthma exacerbation.

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Antibody positive autoimmune encephalitis presenting with faciobrachial dystonic seizures-Case Report

63 year old male presented with new onset faciobrachial dystonic seizures. Imaging showed T2 Flair hyperintensity in left hippocampus. Possibility of autoimmune encephalitis was considered and we went for CSF autoantibody study.Result came as positive for LGI 1  (Leucine rich Glioma Inactivated-1)  antibody in CSF.

We also did a paraneoplastic work up to rule out any underlying malignancy. But was unyielding. Patient was treated with steroid pulse with methylprednisolone for 5 days. Subsequently, he was continued on oral steroids. Patient improved. No further seizure episodes.  Patient is being kept on follow up.

Final diagnosis 

Faciobrachial dystonic seizures

Autoimmune limbic encephalitis 

LGI 1 antibody positive

Case Submitted by 

Dr Rahul Rajeev, DM Neurology (Std)

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