BackgroundNon-polio human enteroviruses are the leading cause of aseptic meningitis in children. The role of enterovirus PCR for diagnosis and management of aseptic meningitis has not been fully explored.Methodology/Principal FindingsA retrospective study was conducted to determine the epidemiological, clinical, and laboratory characteristics of aseptic meningitis and to evaluate the role of enterovirus PCR for the diagnosis and management of this clinical entity. The medical records of children who had as discharge diagnosis aseptic or viral meningitis were reviewed. A total of 506 children, median age 5 years, were identified. The annual incidence rate was estimated to be 17/100,000 children less than 14 years of age. Most of the cases occurred during summer (38%) and autumn (24%). The dominant clinical symptoms were fever (98%), headache (94%) and vomiting (67%). Neck stiffness was noted in 60%, and irritation in 46% of the patients. The median number of CSF cell count was 201/mm3 with polymorphonuclear predominance (>50%) in 58.3% of the cases. Enterovirus RNA was detected in CSF in 47 of 96 (48.9%) children tested. Children with positive enterovirus PCR had shorter hospitalization stay as compared to children who had negative PCR or to children who were not tested (P = 0.01). There were no serious complications or deaths.ConclusionsEnteroviruses accounted for approximately one half of cases of aseptic meningitis. PCR may reduce the length of hospitalization and plays important role in the diagnosis and management of children with aseptic meningitis.

The impact of viral co-infections and recently discovered viruses on the epidemiology of respiratory infections in children is still unclear. To simultaneously detect viruses that are involved in the aetiology of respiratory infections, we used a DNA/RNA microarray assay that identifies 17 different viruses or viral subtypes. Rhinopharyngeal washes were taken from 611 children (aged 1 month to 14 years) who presented in the emergency department with respiratory infections from June 2010 to June 2011 and were treated as outpatients (299, 48.9%) or hospitalized (312, 51.1%). Lower respiratory tract infection was diagnosed more often in hospitalized children (68% versus 36%, p 0.001). Of 397 children in which microarrays detected viral infection (70.1%), a single virus was found in 228 (57.4%) and two or more viruses in 169 (42.5%). The most prevalent viruses among children with positive samples were respiratory syncytial virus (RSV) in 225 (56.6%), parainfluenza virus (PIV) in 118 (29.7%), rhinovirus (RV) in 73 (18.4%), followed by influenza in 56 (14.1%), adenoviruses in 31 (7.8%), bocavirus in 25 (6.3%), human metapneumovirus in 15 (3.7%) and enteroviruses in 12 (3%). Most common viral co-infections were RSVA-RSVB in 46 children (27.2%), RSV-Influenza in 20 (11.8%), RSV-RV in 18 (10.6%) and PIV-RV in 13 (7.7%). Multiple logistic regression analysis revealed that viral co-infections were associated with increased probability for hospitalization (OR 1.52, 95% CI 1.01-2.29, p 0.04), and previous pneumococcal vaccination was associated with decreased probability for hospitalization (OR 0.52, 95% CI 0.33-0.81, p 0.004). We conclude that viral co-infections are involved in a significant proportion of children with an acute respiratory infection and may increase the severity of clinical presentation and the risk for hospitalization.

Streptolysin O (SLO) is a cholesterol-dependent cytolysin produced by the important human pathogen, group A Streptococcus (Streptococcus pyogenes or GAS). In addition to its cytolytic activity, SLO mediates the translocation of GAS NAD-glycohydrolase (NADase) into human epithelial cells in vitro. Production of both NADase and SLO is associated with augmented host cell injury beyond that produced by SLO alone, but the mechanism of enhanced cytotoxicity is not known. We have now shown that expression of NADase together with SLO dramatically enhanced the lytic activity of GAS culture supernatants for erythrocytes but had no effect on SLO-mediated poration of synthetic cholesterolrich liposomes. This result revealed a previously unknown contribution of NADase to the cytolytic activity associated with GAS production of SLO. Purified recombinant SLO bound NADase in vitro, supporting a specific, physical interaction of the two proteins. Exposure of human keratinocytes to wild-type GAS, but not to a NADase-deficient mutant strain, resulted in profound depletion of cellular NAD ؉ and ATP. Furthermore, expression of recombinant Group A Streptococcus (Streptococcus pyogenes or GAS), 2 the causative agent of streptococcal pharyngitis, skin and soft tissue infections, and severe invasive infections, produces more than 40 secreted proteins, many of which have been implicated in disease pathogenesis (1-3). Among the secreted products of GAS are streptolysin O (SLO) and NAD-glycohydrolase (NADase). SLO is a member of the pore-forming cytolysin family known as cholesterol-dependent cytolysins due to their ability to bind cholesterol in eukaryotic cell membranes (4, 5). Individual toxin molecules oligomerize and insert into the cell membrane to form transmembrane pores up to 30 nm in diameter. Sufficient doses of SLO result in cell lysis (4, 6, 7). Purified SLO is a potent toxin that is lethal within minutes of intravenous injection in animal models, primarily because of cardiotoxicity (8, 9). GASNAD-glycohydrolases are enzymes that catalyze the hydrolysis of the nicotinamide-ribose bond of NAD ϩ to yield nicotinamide and adenosine diphosphoribose. These enzymes have been described in several bacterial species and in a variety of eukaryotes (10, 11). The GAS NADase differs from most other known bacterial NAD-glycohydrolases in that it is secreted instead of being cell-associated and it possesses ADP ribosyl cyclase activity (12-14). Thus, in addition to producing adenosine diphosphoribose, the GAS NADase can convert NAD ϩ to cyclic adenosine diphosphoribose as a side reaction. Cyclic adenosine diphosphoribose is an important second messenger and signaling molecule for the regulation and mobilization of intracellular calcium stores (14 -16). The GAS genes encoding SLO (slo) and NADase (nga) are expressed from an operon that is transcribed under the control of a promoter upstream of nga. Some studies have identified downstream of nga a second weak promoter for slo (17, 18). The two proteins are functionally linked in that SLO is re...

Background Data regarding the association of antibody levels elicited after immunization with the BNT162b2 mRNA Covid-19 vaccine with epidemiological and clinical parameters are limited. Methods We prospectively measured the total (TAbs-RBD) and the neutralizing antibodies (NAbs-RBD) against the receptor binding domain (RBD) of SARS-CoV-2 spike protein in a cohort of 268 Healthcare workers before immunization, 20 days after the 1 st dose and 30 days after the 2 nd dose of the BNT162b2 vaccine. A statistical analysis for possible association of antibodies’ levels with epidemiological and clinical parameters was performed. Results The mean age (±SD) of the participants was 45.45 years (± 11.93) (range: 24-70 years) and 211 (79.9%) were females. Statistically significant differences were detected regarding both TAbs-RBD and NAbs-RBD between the first and second doses of the vaccine (P<0.001). The median (IQR) percentage (%) of NAbs-RBD after the 1 st dose was 51.07% (31.60%) and after the 2 nd dose 95.31% (3.70%) (P<0.001).The correlation between the TAbs-RBD and NAbs-RBD was after the 1 st dose, Spearman’s, rho: 0.861 ( P <0.001) and after the 2 nd dose rho: 0.989 ( P <0.001). Twenty days after the 1 st dose, 56/264 (21.2%) of the participants did not have detectable NAbs-RBD, while one month after the 2 nd dose all of them had detectable NAbs-RBD. After the 2 nd vaccine dose, a statistically significant negative association of TAbs-RBD was detected for age (P<0.001), smoking ( P =0.011), and immunosuppressive medications (P<0.001), while a positive association was detected for BMI (P=0.004) and systemic adverse events after immunization (P=0.001). Conclusion A significant correlation of TAbs-RBD and NAbs-RBD was detected after both vaccine doses. Older age, smoking, and immunosuppressive medications negatively affected the final antibody level after SARS-CoV-2 immunization. Our findings emphasize the significance of the 2 nd vaccine dose especially in the older age groups.

No abstract

The SARS-CoV-2 virus is rapidly evolving via mutagenesis, lengthening the pandemic, and threatening the public health. Until August 2021, 12 variants of SARS-CoV-2 named as variants of concern (VOC; Alpha to Delta) or variants of interest (VOI; Epsilon to Mu), with significant impact on transmissibility, morbidity, possible reinfection and mortality, have been identified. The VOC Delta (B.1.617.2) of Indian origin is now the dominant and the most contagious variant worldwide as it provokes a strong binding to the human ACE2 receptor, increases transmissibility and manifests considerable immune escape strategies after natural infection or vaccination. Although the development and administration of SARS-CoV-2 vaccines, based on different technologies (mRNA, adenovirus carrier, recombinant protein, etc.), are very promising for the control of the pandemic, their effectiveness and neutralizing activity against VOCs varies significantly. In this review, we describe the most significant circulating variants of SARS-CoV-2, and the known effectiveness of currently available vaccines against them.

The high incidence of testicular cancer in young males indicates a potential role of events during early life. Birth weight has been identified as a factor possibly associated with the risk of cancers later in life. To investigate the association between birth weight and testicular cancer, we conducted a Systematic Review and Meta-Analysis of published studies investigating the association between birth weight and testicular cancer. Data were combined using a fixed-effects model. Thirteen epidemiologic studies, published between 1983 and 2004, were included in the analysis, encompassing 5,663 patients with testicular cancer. Men weighing less than 2,500 grams at birth had a higher risk for developing testicular cancer later in life than those with normal birth weight (2,500-4,000 g) (OR 5 1.18; 95% confidence interval (CI) 1.01-1.38). A similar trend was found for men with a birth weight above 4,000 g, (OR 5 1.12; 95% CI 1.02-1.22). When seminoma and nonseminoma testicular cancer cases were considered separately, low birth weight was a risk factor specifically for seminomas (OR 5 1.44; 95% CI 1.11-1.88). A U-shaped association was observed between birth weight and the risk for testicular cancer. The underlying biological mechanisms for this phenomenon remain to be elucidated. ' 2007 Wiley-Liss, Inc.Key words: testicular cancer; birth weight; risk factors Testicular cancer is the most common cancer among young male adults, with a peak incidence among men aged 25-35 years and with a distinctive geographical and racial variation. The incidence varies 10-fold among countries, with the highest among white men in Northern Europe. 1 The incidence increased by 51% in the United States from 1973 to 1995, though it stabilized in the first half of the 1990s.2,3 An increase in incidence has been reported from other countries. 4,5 These data suggest that both genetic and environmental factors are important for the development of testicular tumors.Most testicular cancers are germ cell tumors (GCTs), with 50% being seminomas and the remaining 50% nonseminomas. 6 Nonseminomas often represent tumors of mixed histology and may include a variety of seminoma or nonseminoma histologic subtypes. The International Agency for Research on Cancer (IARC) and the WHO classify testicular GCTs into 3 types: the teratomas and yolk-sac tumors of newborns and infants; the seminomatous and nonseminomatous tumors of adolescents and young adults; and the spermatocytic seminomas of the elderly.7 Further classification beyond the 2 main histologic categories (seminomas and nonseminomas) appears to have limited relevance in etiologic or clinical settings. 8,9 Given the age incidence pattern of testicular cancer, which peaks in the third decade of life, etiologic research has focused on prenatal, perinatal and early-life exposures. A number of different factors have been identified that predispose men to testicular cancer. Cryptorchidism is the only established risk factor of etiologic significance, but it accounts for fewer than 10% of all cases. 10...

Kawasaki disease (KD) is an acute systemic vasculitis of childhood. The diagnosis is based on clinical criteria. However, the presentation of KD is incomplete/atypical for approximately 20 % of patients. Kawasaki disease is complicated with coronary artery lesions (CALs) and considered the most common cause of acquired heart disease in children. The medical records of children discharged with KD from a tertiary pediatric hospital in Athens, Greece, during a decade (2001-2010) were retrospectively analyzed. During the study period, KD was diagnosed for 86 children younger than 14 years of age. Complete diagnostic criteria were fulfilled by 64 of the children (74.4 %), whereas 25.6 % were considered incomplete cases. Cardiovascular complications were detected in 48 children (55.8 %) and CALs in 28 children (32.6 %). The prevalence of CALs did not differ significantly between complete and incomplete/atypical KD (42.2 vs 4.5 %; P = 0.001). Logistic regression analysis showed that erythema in the lips and oral cavity was associated with the development of CALs [odds ratio (OR), 3.03; 95 % confidence interval (CI), 1.051-8.783; P = 0.040]. Conversely, children with incomplete/atypical KD (OR, 0.092; 95 % CI, 0.010-0.816; P = 0.032) and previous antibiotic treatment (OR, 0.17; 95 % CI, 0.036-0.875; P = 0.034) were less likely to experience CALs. Children with an incomplete/atypical presentation of KD or before antibiotic treatment may be at lower risk for the development of CALs. Future multicenter studies may help to establish this association better.