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OBJECTIVE: Doppler tissue imaging (DTI) enables the study of the velocity of contraction and relaxation of myocardial segments. We established standards for the peak velocity of the different myocardial segments of the left ventricle in systole and diastole, and correlated them with the electrocardiogram. METHODS: We studied 35 healthy individuals (27 were male) with ages ranging from 12 to 59 years (32.9 ± 10.6). Systolic and diastolic peak velocities were assessed by Doppler tissue imaging in 12 segments of the left ventricle, establishing their mean values and the temporal correlation with the cardiac cycle. RESULTS: The means (and standard deviation) of the peak velocities in the basal, medial, and apical regions (of the septal, anterior, lateral, and posterior left ventricle walls) were respectively, in cm/s, 7.35(1.64), 5.26(1.88), and 3.33(1.58) in systole and 10.56(2.34), 7.92(2.37), and 3.98(1.64) in diastole. The mean time in which systolic peak velocity was recorded was 131.59ms (±19.12ms), and diastolic was 459.18ms (±18.13ms) based on the peak of the R wave of the electrocardiogram. CONCLUSION: In healthy individuals, maximum left ventricle segment velocities decreased from the bases to the ventricular apex, with certain proportionality between contraction and relaxation (P

Abstract Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque is the monocyte-macrophage. The behaviour of this cell type within the plaque is heterogeneous and depends on the recruitment of diverse monocyte subsets. Furthermore, the plaque microenvironment offers polarisation and activation signals which impact on phenotype. Microenvironmental signals are sensed through pattern recognition receptors, including toll-like and NOD-like receptors - the latter of which are components of the inflammasome - thus dictating macrophage behaviour and outcome in atherosclerosis. Recently cholesterol crystals and modified lipoproteins have been recognised as able to directly engage these pattern recognition receptors. The convergent role of such pathways in terms of macrophage activation is discussed in this review.

Objective: To summarize recent data on the association between gut microbiome composition and food allergy (FA) in early childhood and highlight potential host-microbiome interactions that reinforce or abrogate oral tolerance., Data Sources: PubMed search of English-language articles related to FA, other atopic disease, and the gut microbiome in pregnancy and early childhood., Study Selections: Human studies published after 2015 assessing the relationship between the gut bacteriome and virome in the first 2 years of life and FA or food sensitization development in early childhood were prioritized. Additional human studies conducted on the prenatal gut microbiome or other atopic diseases and preclinical studies are also discussed., Results: Children who developed FA harbored lower abundances of Bifidobacterium and Clostridia species and had a less mature microbiome during infancy. The early bacterial microbiome protects against FA through production of anti-inflammatory metabolites and induction of T regulatory cells and may also affect FA risk through a role in trained immunity. Infant enteric phage communities are related to childhood asthma development, though no data are available for FA. Maternal gut microbiome during pregnancy is associated with childhood FA risk, potentially through transplacental delivery of maternal bacterial metabolites, though human studies are lacking., Conclusion: The maternal and infant microbiomes throughout the first 1000 days of life influence FA risk through a number of proposed mechanisms. Further large, longitudinal cohort studies using taxonomic, functional, and metabolomic analysis of the bacterial and viral microbiomes are needed to provide further insight on the host-microbe interactions underlying FA pathogenesis in childhood., Competing Interests: Disclosures Dr Insel is a consultant for Advanced Microbiome Interventions BV, Persephone Biosciences, Inc, and Tolerance Bio, Inc. Dr Järvinen is a consultant for Janssen and Jovie and is an investigator on Aimmune, DBV, and Siolta trials., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B., Methods: HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination., Results: From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose., Conclusions: The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Depression and neurocognitive disorder continue to be the major neuropsychiatric disorders affecting persons with HIV (PWH). The prevalence of major depressive disorder is two to fourfold higher among PWH than the general population (∼6.7%). Prevalence estimates of neurocognitive disorder among PWH range from 25 to over 47% - depending upon the definition used (which is currently evolving), the size of the test battery employed, and the demographic and HIV disease characteristics of the participants included, such as age range and sex distribution. Both major depressive disorder and neurocognitive disorder also result in substantial morbidity and premature mortality. However, though anticipated to be relatively common, the comorbidity of these two disorders in PWH has not been formally studied. This is partly due to the clinical overlap of the neurocognitive symptoms of these two disorders. Both also share neurobehavioral aspects - particularly apathy - as well as an increased risk for non-adherence to antiretroviral therapy. Shared pathophysiological mechanisms potentially explain these intersecting phenotypes, including neuroinflammatory, vascular, and microbiomic, as well as neuroendocrine/neurotransmitter dynamic mechanisms. Treatment of either disorder affects the other with respect to symptom reduction as well as medication toxicity. We present a unified model for the comorbidity based upon deficits in dopaminergic transmission that occur in both major depressive disorder and HIV-associated neurocognitive disorder. Specific treatments for the comorbidity that decrease neuroinflammation and/or restore associated deficits in dopaminergic transmission may be indicated and merit study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RP declared a past co-authorship/collaboration (doi: 10.1016/j.eclinm.2021.100845 and doi: 10.1001/jamanetworkopen.2020.31190) with the author LC to the handling editor., (Copyright © 2023 Goodkin, Evering, Anderson, Ragin, Monaco, Gavegnano, Avery, Rourke, Cysique and Brew.)

In 2016 we discovered alterations in the gut bacterial and viral populations in HIV-associated AIDS (Monaco et al., 2016). Herein, I relate the background behind these developments and discuss how they advanced the field and propelled my current research endeavors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The female reproductive tract (FRT) microbiome plays a vital role in maintaining vaginal health. Viruses are key regulators of other microbial ecosystems, but little is known about how the FRT viruses (virome), particularly bacteriophages that comprise the phageome, impact FRT health and dysbiosis. We hypothesize that bacterial vaginosis (BV) is associated with altered FRT phageome diversity, transkingdom interplay, and bacteriophage discriminate taxa. Here, we conducted a retrospective, longitudinal analysis of vaginal swabs collected from 54 BV-positive and 46 BV-negative South African women. Bacteriome analysis revealed samples clustered into five distinct bacterial community groups (CGs), and further, bacterial alpha diversity was significantly associated with BV. Virome analysis on a subset of baseline samples showed FRT bacteriophages clustering into novel viral state types (VSTs), a viral community clustering system based on virome composition and abundance. Distinct BV bacteriophage signatures included increased alpha diversity along with discriminant Bacillus , Burkholderia, and Escherichia bacteriophages. Bacteriophage-bacteria transkingdom associations were also identified between Bacillus and Burkholderia viruses and BV-associated bacteria, providing key insights for future studies elucidating the transkingdom interactions driving BV-associated microbiome perturbations. In this cohort, bacteriophage-bacterial associations suggest complex interactions, which may play a role in the establishment and maintenance of BV.

The human body is inhabited by a large and complex network of commensal and predatory eukaryotic viruses and bacteriophages collectively termed the virome. Despite being the most abundant and genetically diverse biological entities on the planet, the impact of viruses on human health especially within the female reproductive tract (FRT) remains understudied. To better appreciate current knowledge regarding the dynamic role of viruses in FRT health and disease, in this review we highlight the known constituents of the FRT virome, transkingdom interactions within the FRT and their influence on gynecological disease. A better understanding of the FRT virome may pave the way toward improved outcomes in gynecological, reproductive, and neonatal health., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Herein we describe a detailed protocol for DNA virome analysis of low input human stool samples (Monaco et al. , 2016). This protocol is divided into four main steps: 1) stool samples are pulverized to evenly distribute microbial matter; 2) stool is enriched for virus-like particles and DNA is extracted by phenol-chloroform; 3) purified DNA is multiple-strand displacement amplified (MDA) and fragmented; and 4) libraries are constructed and sequenced using Illumina Miseq. Subsequent sequence analysis for viral sequence identification should be sensitive but stringent.

Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

AIDS caused by simian immunodeficiency virus (SIV) infection is associated with gastrointestinal disease, systemic immune activation, and, in cross-sectional studies, changes in the enteric virome. Here we performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in SIV-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. Progression of SIV infection to AIDS was associated with increased detection of potentially pathogenic viruses and bacterial enteropathogens. Specifically, adenoviruses were associated with an increased incidence of gastrointestinal disease and AIDS-related mortality. Viral and bacterial enteropathogens were largely absent from animals protected by the vaccine. These data suggest that the SIV-associated gastrointestinal disease is associated with the presence of both viral and bacterial enteropathogens and that protection against SIV infection by vaccination prevents enteropathogen emergence., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Genetic code redundancy would yield, on the average, the assignment of three codons for each of the natural amino acids. The fact that this number is observed only for incorporating Ile and to stop RNA translation still waits for an overall explanation. Through a Structural Bioinformatics approach, the wealth of information stored in the Protein Data Bank has been used here to look for unambiguous clues to decipher the rationale of standard genetic code (SGC) in assigning from one to six different codons for amino acid translation. Leu and Arg, both protected from translational errors by six codons, offer the clearest clue by appearing as the most abundant amino acids in protein-protein and protein-nucleic acid interfaces. Other SGC hidden messages have been sought by analyzing, in a protein structure framework, the roles of over- and under-protected amino acids.

Excessive utilization of laboratory diagnostic testing leads to increased health care costs. We evaluated criteria to reduce unnecessary nucleic acid amplification testing (NAAT) for viral pathogens in cerebrospinal fluid (CSF) samples from adults. This is a single-center split retrospective observational study with a screening cohort from 2008 to 2012 and a validation cohort from 2013. Adults with available results for herpes simplex virus 1/2 (HSV-1/2), varicella-zoster virus (VZV), cytomegalovirus (CMV), or enterovirus (EV) NAAT with CSF samples between 2008 and 2013 were included (n = 10,917). During this study, 1.3% (n = 140) of viral NAAT studies yielded positive results. The acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent subjects would have reduced HSV-1/2, VZV, CMV, and EV testing by 63%, 50%, 44%, and 51%, respectively, from 2008 to 2012. When these criteria were applied to the 2013 validation data set, 54% of HSV-1/2, 57% of VZV, 35% of CMV, and 56% of EV tests would have been cancelled. No clinically significant positive tests would have been cancelled in 2013 with this approach. The introduction of a computerized order entry set was associated with increased test requests, suggesting that computerized order sets may contribute to unnecessary testing. Acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent adults for viral CSF NAAT assays would increase clinical specificity and preserve sensitivity, resulting in significant cost savings. Implementation of these acceptance criteria led to a 46% reduction in testing during a limited follow-up period., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease and cohort specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)