Contemporaneous fluctuations in T cell responses to persistent herpes virus infections

The classical paradigm for T cell dynamics suggests that the resolution of a primary acute virus infection is followed by the generation of a long-lived pool of memory T cells that is thought to be highly stable. Very limited alteration in this repertoire is expected until the immune system is re-challenged by reactivation of latent viruses or by cross-reactive pathogens. Contradicting this view, we show here that the T cell repertoire specific for two different latent herpes viruses in the peripheral blood displayed significant contemporaneous co-fluctuations of virus-specific CD8(+) T cells. The coordinated responses to two different viruses suggest that the fluctuations within the T cell repertoire may be driven by sub-clinical viral reactivation or a more generalized 'bystander' effect. The later contention was supported by the observation that, while absolute number of CD3(+) T cells and their subsets and also the cell surface phenotype of antigen-specific T cells remained relatively constant, a loss of CD62L expression in the total CD8(+) T cell population was coincident with the expansion of tetramer-positive virus-specific T cells. This study demonstrates that the dynamic process of T cell expansion and contractions in persistent viral infections is not limited to the acute phase of infection, but also continues during the latent phase of infection.     

Histocompatibility antigens HLA-A, -B, -DR in Greek patients with Kaposi''s sarcoma

Thirty-two Greek patients with histologically documented Kaposi's sarcoma, aged 46 to 82 years, were typed for HLA-A, B and DR antigens. None of them was homosexual and they had not been subjected to any immunosuppressive therapy. The study revealed a significant increase of HLA-DR5 (53.1% vs. 21.4%, R.R. 4.1) and a decreased frequency of HLA-DR1 (3.3% vs. 16.6%, R.R. 0.16). An increased frequency of HLA-B18 was also noted (43.7% vs. 20.7% R.R. 2.96). These results indicate that the same positive association with HLA-DR5 antigen is observed in Greek patients as in other patients of Mediterranean origin and support the view that HLA linked factor(s) may have a role in the development of the disease.     

Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H

Although the importance of CD4+ T cell responses to human cytomegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4+ CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HCMV isolates revealed that the gB and gH epitope sequences recognized by human CD4+ T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4+ CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse peptide-sensitized Patr-DR7+ cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class II lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.     

Polyphasic identification and susceptibility to seven antifungals of 102 Aspergillus isolates recovered from immunocompromised hosts in Greece

In this study, the first such study in Greece, we used polyphasic identification combined with antifungal susceptibility study to analyze Aspergillus clinical isolates comprising 102 common and rare members of sections Fumigati, Flavi, Terrei, Nidulantes, Nigri, Circumdati, Versicolores, and Usti. High amphotericin B MICs (>2 μg/ml) were found for 17.6% of strains. Itraconazole, posaconazole, and voriconazole MICs of >4 μg/ml were shown in 1%, 5%, and 0% of the isolates, respectively. Anidulafungin, micafungin, and caspofungin minimum effective concentrations (MECs) of ≥2 μg/ml were correspondingly recorded for 4%, 9%, and 33%, respectively, of the strains.     

Racial disparities in early mortality in 1,134 young patients with acute stroke

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18–45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0–1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2–13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38–11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28–10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35–0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.     

Aging is not a barrier to muscle and redox adaptations: Applying the repeated eccentric exercise model

Despite the progress of analytic techniques and the refinement of study designs, striking disagreement exists among studies regarding the influence of exercise on muscle function and redox homeostasis in the elderly. The repeated eccentric exercise model was applied to produce long-lasting and extensive changes in redox biomarkers and to reveal more effectively the potential effects of aging on redox homeostasis. Ten young (20.6 ± 0.5 years) and ten elderly men (64.6 ± 1.1 years) underwent an isokinetic eccentric exercise session, which was repeated after three weeks. Muscle function/damage indices (torque, range of movement, muscle soreness and creatine kinase) and redox biomarkers (F₂-isoprostanes, protein carbonyls, glutathione, catalase, superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, uric acid, bilirubin and albumin) were assessed in plasma, erythrocytes or urine pre-exercise, immediately post-exercise and at 2 and 4 days post-exercise. As expected, the elderly group exhibited oxidative stress in baseline compared to the young group. Extensive muscle damage and extensive alterations in redox homeostasis appeared after the first bout of eccentric exercise. Noteworthy, the redox responses were similar between the age groups despite their differences in baseline values. Likewise, both age groups demonstrated blunted alterations in muscle damage and redox homeostasis after the second bout of eccentric exercise indicating adaptations from the first bout of exercise. Elderly individuals seem to be well fitted to participate in demanding physical activities without suffering detrimental effects on skeletal muscle and/or disturbances on redox homeostasis. The repeated eccentric exercise model may be a useful and practical physiological tool to study redox biology in humans.     

Congenital Zika Infection and the Risk of Neurodevelopmental,Neurological, and Urinary Track Disorders in Early Childhood. A Systematic Review

It was late 2015 when Northeast Brazil noticed a worrying increase in neonates born with microcephaly and other congenital malformations. These abnormalities, characterized by an abnormally small head and often neurological impairment and later termed Congenital Zika Syndrome, describe the severity of neurodevelopmental and nephrological outcomes in early childhood, and the implication of microcephaly at birth. The purpose of the study was to describe the neurodevelopmental outcomes in children exposed to Zika virus during fetal life, with and without microcephaly at birth. The systematic review included research studies about the neurodevelopmental outcomes with and without microcephaly, as well as nephrological outcomes in early childhood. We searched PubMed, Crossref, PsycINFO, Scopus, and Google Scholar publications and selected 19 research articles published from 2018 to 2021. Most studies have linked the severity of microcephaly in childbirth to the neurodevelopmental and urinary outcomes in early childhood. However, most children without microcephaly at birth develop typically, while others may be at risk for language impairment.     

Reference Values for Quantitative Ultrasonography (QUS) of Radius and Tibia in Healthy Greek Pediatric Population: Clinical Correlations

The aim of this study was to provide reference standards for measurements of quantitative ultrasonography (QUS) of radius and tibia in normative Greek pediatric population. Analysis was performed in 1549 healthy subjects (814 girls and 735 boys) with a mean decimal age of 11.41 ± 3.52 yr (range: 3.78–18.33 yr). Results showed a gradual increase of absolute values of radial and tibial speed of sound (SOS), with aging and with pubertal progressing, in both girls and boys. Gender comparison showed significantly increased SOS values measured both at radius and at tibia in girls more than 13 yr of age compared with aged-matched boys. Significant but mild correlation was noted between standard deviation scores (SDS) of SOS at radius and at tibia (r = 0.259, p < 0.001). Additionally, tibial SOS SDS were significantly negatively correlated with body mass index (BMI) SDS (r = −0.230, p < 0.001). Finally, subjects that spend more than 3 h of daily “screen time” (television and personal computer) showed significantly decreased SOS values measured both at radius and at tibia. On the contrary, no correlation was observed between SOS values and the amount of physical activity reported.