The Importance of Lipidomic Approach for Mapping and Exploring the Molecular Networks Underlying Physical Exercise: A Systematic Review.

Maintaining appropriate levels of physical exercise is an optimal way for keeping a good state of health. At the same time, optimal exercise performance necessitates an integrated organ system response. In this respect, physical exercise has numerous repercussions on metabolism and function of different organs and tissues by enhancing whole-body metabolic homeostasis in response to different exercise-related adaptations. Specifically, both prolonged and intensive physical exercise produce vast changes in multiple and different lipid-related metabolites. Lipidomic technologies allow these changes and adaptations to be clarified, by using a biological system approach they provide scientific understanding of the effect of physical exercise on lipid trajectories. Therefore, this systematic review aims to indicate and clarify the identifying biology of the individual response to different exercise workloads, as well as provide direction for future studies focused on the body's metabolome exercise-related adaptations. It was performed using five databases (Medline (PubMed), Google Scholar, Embase, Web of Science, and Cochrane Library). Two author teams reviewed 105 abstracts for inclusion and at the end of the screening process 50 full texts were analyzed. Lastly, 14 research articles specifically focusing on metabolic responses to exercise in healthy subjects were included. The Oxford quality scoring system scale was used as a quality measure of the reviews. Information was extracted using the participants, intervention, comparison, outcomes (PICOS) format. Despite that fact that it is well-known that lipids are involved in different sport-related changes, it is unclear what types of lipids are involved. Therefore, we analyzed the characteristic lipid species in blood and skeletal muscle, as well as their alterations in response to chronic and acute exercise. Lipidomics analyses of the studies examined revealed medium- and long-chain fatty acids, fatty acid oxidation products, and phospholipids qualitative changes. The main cumulative evidence indicates that both chronic and acute bouts of exercise determine significant changes in lipidomic profiles, but they manifested in very different ways depending on the type of tissue examined. Therefore, this systematic review may offer the possibility to fully understand the individual lipidomics exercise-related response and could be especially important to improve athletic performance and human health.

JC virus infection is acquired very early in life: evidence from a longitudinal serological study.

JC virus (JCV) is a widespread member of the Polyomaviridae family. Following primary infection, which occurs asymptomatically during childhood, JCV establishes latency in the host. JCV seroprevalence can reach 80 % in healthy adults, but the age of viral exposure has not been yet characterized. This study was conducted to define JCV seroprevalence in Italian infants and to estimate the date of primary infection. A JCV viral protein 1 (VP1)-GST fusion protein was used in conjunction with a homemade indirect enzyme-linked immunosorbent assay (ELISA) to test for the presence of IgG antibodies to JCV in 981 serum samples collected from 644 Italian infants of different ages (1 day to 3 years old) and in 102 breast milk samples. IgM antibody presence was also evaluated in longitudinally collected samples from 17 selected children. JCV antibody prevalence and normalized optical density (nOD) were calculated. For the longitudinal analysis, generalized estimating equation techniques and spline functions were used to estimate the possible non-linear effects of time on antibody production kinetics. JCV IgG was detected in 71.8 % of the sera. Prevalence increased over time from 46.1 % (1 month old) to 80.7 % (12 months old), 85.9 % (24 months old), and 85.5 % (36 months old). As determined by nOD, the longitudinal analysis of serum IgG amounts in children of this study (ages 1 day to 3 years old) illustrated IgG kinetic changes with statistically significant trends (p = 0.001). One-month-old children were largely negative for JCV IgM (82.4 %), and 58.8 % of children produced JCV IgM within the second and sixth months of life. JCV IgG was detected in 27.3 % of breast milk samples. JCV primary infection likely occurs before 6 months of age, and a sizeable percentage of Italian infants will become JCV seropositive within 2 years of age. This study can be used to determine the optimal age for potential future JCV vaccination in infants.

Interaction Between Human Polyomavirus BK and Hypoxia Inducible Factor-1 alpha.

BK polyomavirus (BKV) has a worldwide seroprevalence of approximately 90%. After primary infection, BKV establishes a life-long latency within the urogenital tract. The severe immunological impairment occurring in renal transplant recipients leads to BKV reactivation, which may result in polyomavirus associated nephropathy (PVAN). While the transplanted kidney is transiently unperfused, Hypoxia Inducible Factors (HIFs) mediate the cellular response to hypoxia. The α-subunit of HIF isoform 1 (HIF-1α) may interact with several viruses, but until now, there has been no information regarding the interaction between BKV and HIF-1α. The aim of this study is to investigate the possible interaction between HIF-1α and BKV and its potential effect on the pathogenesis of PVAN. Screening of 17 kidney tissue samples revealed that HIF-1α expression was 13.6-fold higher in PVAN tissues compared to control tissues. A luminometric assay in co-transfected African green monkey kidney cells (VERO) demonstrated BKV promoter activation ranging from two to sixfold (P < 0.05) when HIF-1α was over-expressed. A Chromatin ImmunoPrecipitation (ChIP) assay showed structural binding between the BKV promoter and HIF-1α. The amount of BKV DNA increased by threefold in VERO infected cells that were exposed to simulated hypoxia, compared to the cells not subjected to hypoxia. Both ex vivo and in vitro interactions between HIF-1α and BKV were observed, suggesting that HIF-1α, stabilized during transplantation, may be able to bind the BKV promoter and enhance BKV replication. Thus, hypoxia should be considered a risk factor for the development of PVAN in kidney transplant recipients.

JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients.

The risk of developing progressive multifocal leukoencephalopathy (PML), as a consequence of infection/reactivation with JC virus (JCV), is consistent in natalizumab-treated multiple sclerosis (MS) patients, with 430 cases of PML reported so far. The risk of PML is higher in JCV seropositive patients, and it is recommended that only MS patients without JCV antibodies should be enrolled in the treatment postulating that they do not have JCV infection.We have studied forty-two natalizumab-treated MS patients, and urine and blood were collected monthly for up to 60 months. JCV and BK virus (BKV) DNA presence was verified using quantitative real-time PCR assays, and serum anti-JCV antibodies were measured with the Stratify and/or Stratify DxSelect tests.JCV and BKV DNA were not found in the blood samples, whereas they were found at least once in the urine of 21 of 42 (50 %) and of 25/42 (59.5 %) patients, respectively. JCV DNA urinary shedding increased up to month 24 of natalizumab treatment (45.2 %), and the effect of time was significant for JCV (p = 0.04), but not for BKV (p = 0.39). JCV viruria and seropositivity did not completely correlate, since three patients shedding JCV DNA in the urine were seronegative according to the serological tests.The results indicated that natalizumab therapy may increase the rate of JCV urinary shedding. Additionally, we confirmed that the identification of JCV carriers cannot solely rely on serological tests, but sensitive methods for viral DNA detection should be adopted to more precisely identify the truly JCV uninfected cases.

JC Virus Replication at the First Symptoms of Multiple Sclerosis: A Case Report.

Multiple sclerosis (MS) is an autoimmune, demyelinating disorder of unknown etiology, in which viruses have been suggested as etiological/triggering agents. The attention to the association between viruses and MS has been rekindled by the development of progressive multifocal leukoencephalopathy in natalizumab-treated MS patients. Here we report the case of a woman with JC virus (JCV) replication in the cerebrospinal fluid, blood and urine collected at the first symptoms of MS and during several follow-up visits. This observation shows that JCV can be associated with MS without a relation with natalizumab treatment, although the triggering role of JCV in some cases of MS will require further studies.

Determining the Relationship between Squat Jump Performance and Knee Angle in Female University Students.

The Squat Jump (SJ) test is widely recognized as a reliable test for assessing lower-limb explosive strength. However, uncertainty persists in the literature regarding the optimal starting positions for maximizing vertical jump performance. This uncertainty is exacerbated by a disproportionate focus on athletes in existing studies, with insufficient consideration being given to non-athletic women. To address this gap, this study investigated the influence of leg starting angle on explosive jump height in a homogeneous sample of non-athletic women. Thirty-two female students enrolled in a Sports Science master's degree program at the University of Salerno participated in the study. Descriptive statistics were employed to summarize data on various variables, and Pearson's correlations were calculated to assess the relationship between knee angle in the starting position and achieved jump height. The study revealed that different starting positions had a noteworthy impact on jump height among the participants. A strong negative correlation (-0.701) was identified between Squat Jump elevation and the knee angle in the starting position. Notably, 62.5% of the subjects opted for a starting knee position of approximately 70 degrees, with all of them consistently achieving a jump height associated with this specific angle. These findings provide valuable insights into the relationship between leg starting angle and explosive jump height in non-athletic women. The observed correlation underscores the significance of the starting position in Squat Jump performance. The prevalence of a specific knee angle choice among participants suggests potential implications for training and performance optimization in this sample.

JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a severe disease of the central nervous system (CNS), caused by infection with the Polyomavirus JC virus (JCV). Because there are no known treatments or prognostic factors, we performed a long-term study focusing mainly on cerebrospinal fluid (CSF) samples from PML patients to describe the virological features akin to the different forms of the disease. Twenty-eight PML patients were enrolled: 10 HIV-1+ patients with classical PML (CPML), 9 HIV-1+ patients with slowly progressing or stable neurological symptoms (benign PML), 3 HIV-1+ asymptomatic patients, and 6 HIV-1-negative patients. CSF, urine, and blood samples were collected at the enrollment (baseline) and every 6 months afterwards when possible. The JCV DNA and HIV-1 RNA loads were determined, and the JCV strains were characterized. At baseline, the mean CSF JCV load was log 6.0 ± 1.2 copies/ml for CPML patients, log 4.0 ± 1.0 copies/ml for benign PML patients, log 4.2 ± 0.5 copies/ml for asymptomatic PML patients, and log 5.8 ± 1.3 copies/ml for HIV-1-negative PML patients (CPML vs. benign: P < 0.01; CPML vs. asymptomatic: P < 0.05; HIV-1 negative vs. benign: P < 0.01). Organization of the JCV transcriptional control region (TCR) showed unusual archetype structures in two long-term survival patients; the NF1 sequence was found most commonly, whereas the Sp1 binding site was the most common for both CPML patients and HIV-1 negative patients. Our results suggest that the JCV load in the CSF and the organization of the TCR should be considered as indicators of PML clinical outcome.

Investigation of polyomaviruses replication in pediatric patients with nephropathy receiving rituximab.

Rituximab is a chimeric monoclonal antibody reacting with the CD20 antigen on B cells. It has been proposed as treatment for the idiopathic nephrotic syndrome, recurrent idiopathic nephropathy, and focal segmental glomerulosclerosis refractory to steroids. Rituximab influences T-cell immunity and may predispose the patients to opportunistic infections, such as progressive multifocal leukoencephalopathy caused by the polyomavirus JC (JCV). The risk of latent viruses infections/reactivations in pediatric patients receiving monoclonal antibodies is not well known yet. In this longitudinal 6-month study, the effects of rituximab on JCV and BK virus (BKV) replication have been investigated. Blood, serum, and urine samples have been collected monthly from 11 pediatric patients (mean age: 11 years) with the idiopathic nephrotic syndrome and recurrent idiopathic nephropathy, under rituximab therapy. JCV and BKV real-time PCRs and sequencing of the viral protein 1 and the non-coding control region have been conducted. The same investigations have been undertaken on samples collected from eight pediatric patients (controls, mean age: 6 years), with idiopathic nephrotic syndrome or focal segmental glomerulosclerosis, treated with conventional chemotherapy. JCV was detected in the urine of one patient (9%), and one control (12.5%); BKV was found in the urine of 7/11 patients (63.6%) and 2/8 controls (25%) and in blood samples from four patients. No significant difference was found in the mean viral loads and in the viral molecular characterizations between the two groups. The polyomaviruses replication was not associated with rituximab therapy in children.

Questionnaire of inclusion in Paralympic dance: validation and pilot study.

Purpose: The aims of this study were to assess the validity and reliability of a structured questionnaire of inclusion for Paralympic dance (PD), the association between the type of athlete about the perception of inclusion in own dance studio, and to describe knowledge and perceptions of inclusion in PD participants. Methods: Thirty-eight Italian PD participants answered a survey and a structured questionnaire of inclusion in PD (QIPD). Results: The internal consistence of the QIPD was acceptable (α = 0.79) albeit one item greater than 1 was excluded, and the test-re-test reliability was moderate to excellent (ICC 0.66-1.00). Most participants with disabilities reported to approach dancesport due to friendship and involvement of dance coach, whereas most participants without disabilities thanks to dance coach (86%). Most participants with disabilities reported to practice PD for pleasure and passion, whereas participants without disabilities because they feel emotion by dancing with a partner with disabilities (83%). A relationship was observed between the type of athlete in the coach's attempt to remove all barriers to participation (X 2 = 4.994). Conclusion: The QIPD is valid and reliable to assess knowledge and perceptions of inclusion in PD. PD participants with and without disability seem to perceive sport inclusion similarly, except for the removal of barriers to participate in PD courses.

An Exploratory Study in Non-Professional Football on the Perception of Stakeholders about the New Working Professional Profile of Sports Kinesiologist.

In Italy, recent amendments to Legislative Decree n. 36 of 28 February 2021, on sports work, may have made the application of the reform by stakeholders unclear, with the risk of generating further confusion among them. One of the most critical points concerns the possible equivalencies to the professional profile of the kinesiologist, which would be illegitimately recognized even for a different level of education, contrary to the requirements of the European qualification framework. The aim of the study was to understand the perceptions of stakeholders in the world of non-professional football regarding recent legislative provisions. A survey, divided into two sections, was administered to 112 presidents and 112 trainers of non-professional football associations of the province of Salerno. The first section presents five items common for both presidents and trainers, which seek to probe stakeholders' perceptions of the enjoyment, appropriateness, usefulness, and scientificity of kinesiologists. The second section presents five differentiated items. Validity and reliability were calculated. A chi-square analysis (χ2) was performed to test the independence within and between-subjects (trainers and presidents) on their perceptions about the new working professional profile of sports kinesiologist. From the results, it was possible to appreciate a discordance of opinion among stakeholders. Although the majority of presidents and trainers are in favour of introducing such a professional profile (p < 0.05), contradictions emerge concerning the contribution the new professional profile can make in practice (p > 0.05). The perceptual contradictions found among stakeholders' responses demonstrate how the complexity of recent regulatory provisions regarding possible equivalencies to the title of kinesiologist have inevitably generated further confusion among stakeholders.

Effect of Teaching Methods on Motor Efficiency, Perceptions and Awareness in Children.

Currently, physical inactivity and sedentariness in children are becoming increasingly common, resulting in children's poor ability to perform basic motor patterns. It is important to find strategies that instructors can adopt to improve awareness of the importance of physical activity for health and wellness, as well as motor efficiency. Two teaching methods can be used: prescriptive teaching and heuristic learning. The aim of this study was to compare these two methods to determine which is the most suitable for developing motor efficiency. An additional aim was to verify the children's level of enjoyment and self-efficacy through questions on perceptions and, subsequently, on awareness of the activity performed distinctly from perception. The sample consisted of 28 children randomly divided into two groups: HEUR-L, performing activities using heuristic learning, a basic method in ecological approach; and PRES-T, using prescriptive teaching, a basic cognitive method. A motor-efficiency test (TEM) and a survey were administered. A two-way ANOVA with repeated measures was used to test differences in motor efficiency. A Chi-square (χ2) test was used to compare differences between groups in terms of perceptions in enjoyment and self-efficacy and, on a second test, awareness of the activity performed. The results were statistically significant (p < 0.05). Both teaching methods improved motor efficiency, although HEUR-L did so to a greater extent. Differences in perception were found in terms of enjoyment and self-efficacy (p < 0.05), whereas there was no difference in terms of awareness (p > 0.05). Although both methodologies led to improvements in motor-pattern development, heuristic learning was found to be the most effective method to improve motor efficiency, relationships and self-efficacy.

Heuristic Learning as a Method for Improving Students' Teamwork Skills in Physical Education.

Transversal skills are the knowledge, skills, and personal qualities that are currently needed to meet the demands of the working world and everyday life. Schools have the task of equipping students with these skills, working not only on disciplinary goals but also on operational-behavioral goals. In 2018, the European Union adopted new recommendations on eight key competencies for lifelong learning and asked schools to implement new methods to develop these recommendations. To be successful, it is necessary to stimulate students' development of these competences, which are also called soft skills, from the earliest years of the school experience. Physical education (PE) is called upon to make its contribution. In Italy, the two teaching methods used during PE classes are prescriptive teaching and heuristic learning. It is not clear which of the two methods is the most effective in improving soft skills, especially the skills involved in teamwork. The objective of this article was to compare the effects of these two teaching methods on students' teamwork skills during PE classes in primary schools. After verifying the normality of the data, a Student's t-test for dependent samples was performed to assess pre-test and post-test differences in each of two groups, while a Student's t-test for independent samples was performed to compare the two groups after 3 months. Heuristic learning proved to be the most effective method for improving teamwork skills. The results may make an important contribution to future teacher training on the most effective teaching methods for developing students' soft skills.

Examining the Effects of Mirror Therapy on Psychological Readiness and Perception of Pain in ACL-Injured Female Football Players.

Virtual reality-guided imagery (VRGI) and mirror therapy (MT) have been used in isolation to treat patients suffering from different injuries. However, no attempts have been made to understand the effects of combined VRGI and MT added to conventional physical therapy, and no information exists regarding perceptual responses to these rehabilitation strategies in female football players. Thus, this study aimed to examine the effect of MT added to conventional rehabilitation on psychological readiness and perception of pain in ACL-injured female football players. Thirty ACL-injured female football players competing in the 2nd and 3rd Italian tier who underwent an ACL rehabilitation program from the same clinic participated in this study. Players were randomly distributed in an MT group (n = 15) and a CON group (n = 15). All participants reported their perception of pain on a VAS before and after the interventions and their psychological readiness to return to sport after ACL injury and reconstruction surgery on the ACL-RSI scale after the intervention. An independent-sample t-test was performed to assess between-group differences in post-intervention ACL-RSI, and a further independent-sample t-test to assume non-significant differences between VAS values before the intervention. A two-way repeated-measures analysis of variance was used to test the null hypothesis of no different change in VAS over time between groups. After the intervention, the MT group perceived largely greater psychological readiness (p < 0.01). MT and CON groups experienced a large reduction in VAS after the intervention (p < 0.001). However, a small time × group interaction was observed (p = 0.023). MT reported a greater perception of the psychological readiness of the soccer players and a lower perception of pain than those who performed conventional therapy.

Promoting Children's Psychomotor Development with Multi-Teaching Didactics.

This group randomized control trial examined the dose-response effect of varied combinations of linear and nonlinear pedagogy (enriched physical education with specific program led by specialist vs. conventional physical education led by generalist) for improving first-grade children's motor creativity, executive functions, self-efficacy, and learning enjoyment. We led three physical education classes per group through 12 weeks of combined instruction, based on linear and nonlinear pedagogy: mostly linear (ML; 80% linear, 20% nonlinear; n = 62); mostly nonlinear (MNL; 20% linear, 80% nonlinear; n = 61); and control (C; conventional teaching from generalists; n = 60). MNL improved in (a) motor creativity ability (DMA; 48.7%, 76.5%, and 47.6% for locomotor, stability, and manipulative tasks, respectively); (b) executive functions (working memory and inhibitory control) for RNG task (14.7%) and task errors (70.8%); (c) self-efficacy (5.9%); and (d) enjoyment (8.3%). In ML, DMA improved by 18.0% in locomotor and 60.9% in manipulative tasks. C improved of 10.5% in enjoyment, and RNG task worsened by 22.6%. MNL improvements in DMA tasks, executive functions, and self-efficacy were significantly better than those in C. ML was better than C in DMA task and in executive functions' task errors. Overall, ML and MNL approaches were more effective than conventional generalist teaching (C), and the MNL combination of 80% nonlinear and 20% linear pedagogy was optimal. We recommend that educators favor the MNL approach.

Mutations in the external loops of BK virus VP1 and urine viral load in renal transplant recipients.

Polyomavirus-associated nephropathy (PVAN) is a major complication that occurs after renal transplantation and is induced by reactivation of the human polyomavirus BK (BKV). The structure of the viral capsid protein 1 (VP1) is characterized by the presence of external loops, BC, DE, EF, GH, and HI, which are involved in receptor binding. The pathogenesis of PVAN is not well understood, but viral risk factors are thought to play a crucial role in the onset of this pathology. In an attempt to better understand PVAN pathogenesis, the BKV-VP1 coding region was amplified, cloned, and sequenced from the urine of kidney transplant recipients who did, and did not, develop the pathology. Urine viral loads were determined by using real time quantitative PCR (Q-PCR). Amino acid substitutions were detected in 6/8 patients, and 6/7 controls. The BC and EF loop regions were most frequently affected by mutations, while no mutations were found within the GH and HI loops of both patients and controls. Some mutations, that were exclusively detected in the urine of PVAN patients, overlapped with previously reported mutations, although a correlation between changes in amino acids and the development of PVAN was not found. Urine viral loads were higher than that of the proposed cut-off loads for identification of patients that are at a high risk of developing PVAN (10(7) copies/ml), both in the PVAN and control groups, thus confirming that urine viral load is not a useful predictive marker for the development of PVAN.

Naturally Degradable Photonic Devices with Transient Function by Heterostructured Waxy-Sublimating and Water-Soluble Materials.

Combined dry-wet transient materials and devices are introduced, which are based on water-dissolvable dye-doped polymers layered onto nonpolar cyclic hydrocarbon sublimating substrates. Light-emitting heterostructures showing amplified spontaneous emission are obtained on transient elements and used as illumination sources for speckle-free, full-field imaging, and transient optical labels are realized that incorporate QR-codes with stably encoded information. The transient behavior is also studied at the microscopic scale, highlighting the real-time evolution of material domains in the sublimating compound. Finally, the exhausted components are fully soluble in water thus being naturally degradable. This technology opens new and versatile routes for environmental sensing, storage conditions monitoring, and organic photonics.

Serum Gelatinases Levels in Multiple Sclerosis Patients during 21 Months of Natalizumab Therapy.

Background. Natalizumab is a highly effective treatment approved for multiple sclerosis (MS). The opening of the blood-brain barrier mediated by matrix metalloproteinases (MMPs) is considered a crucial step in MS pathogenesis. Our goal was to verify the utility of serum levels of active MMP-2 and MMP-9 as biomarkers in twenty MS patients treated with Natalizumab. Methods. Serum levels of active MMP-2 and MMP-9 and of specific tissue inhibitors TIMP-1 and TIMP-2 were determined before treatment and for 21 months of therapy. Results. Serum levels of active MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 did not differ during the treatment. The ratio between MMP-9 and MMP-2 was increased at the 15th month compared with the 3rd, 6th, and 9th months, greater at the 18th month than at the 3rd and 6th months, and higher at the 21st than at the 3rd and 6th months. Discussion. Our data indicate that an imbalance between active MMP-9 and active MMP-2 can occur in MS patients after 15 months of Natalizumab therapy; however, they do not support the use of serum active MMP-2 and active MMP-9 and TIMP-1 and TIMP-2 levels as biomarkers for monitoring therapeutic response to Natalizumab.

Upregulation of integrin expression on monocytes in multiple sclerosis patients treated with natalizumab.

Natalizumab is a humanized monoclonal antibody against the α4 subunit of VLA-4 integrin that is used to treat conditions such as multiple sclerosis (MS). Although its effects on lymphocytes have been widely described, little is known about its effects on monocytes. Here we described the effects of natalizumab treatment on peripheral blood monocytes from a small cohort of MS patients in terms of relative frequencies and surface integrin (CD49d and CD18) expression. We showed that natalizumab treatment altered the surface integrin expression on monocyte subsets in the peripheral compartment, suggesting a role for them as mediators of natalizumab effects.

Epstein-Barr Virus Specific Antibody Response in Multiple Sclerosis Patients during 21 Months of Natalizumab Treatment.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Natalizumab, a humanized anti-α4 integrin monoclonal antibody, is a highly effective treatment approved for MS. An association between MS and an exposure to Epstein-Barr Virus (EBV) sustained by the levels of antiviral capsid antigen (VCA) and anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG has been described. Our goal was to verify the utility of EBV-specific IgG as a marker in Natalizumab treated MS. Twenty patients (17 female and 3 male) in treatment with Natalizumab were enrolled. Serum levels of anti-VCA and anti-EBNA-1 IgG were determined and expressed as arbitrary units (AU) before treatment and every three months for 21 months of therapy. Anti-VCA IgG levels were increased at the 15th month (235410 ± 196712 AU) comparing with the 3rd (98146 ± 47145 AU) and the 6th (109866 ± 52270 AU) months of therapy (p < 0.05). No significant differences were found for serum anti-EBNA-1 IgG levels. Our data indicate that a transient, self-limited, EBV reactivation can occur in MS during Natalizumab therapy but our results do not support the use of serum EBV-specific antibody levels as biomarkers for monitoring therapeutic response to Natalizumab in the course of MS.

Human polyomavirus 6 DNA in the cerebrospinal fluid of an HIV-positive patient with leukoencephalopathy.

BACKGROUND: Leukoencephalopathies in HAART-treated, HIV-positive patients include progressive multifocal leukoencephalopathy (PML), a result of lytic infection oligodendrocytes by JC polyomavirus (JCV), and another form characterized by the absence of JCV genome in cerebrospinal fluid (CSF). OBJECTIVES: To test the potential viral etiology of JCV-negative leukoencephalopathy. STUDY DESIGN: CSF was collected from 43 HIV-positive patients with MRI suggestive of leukoencephalopathies. DNA was isolated and real-time PCR assays for neurotropic viruses (Herpes Simplex Viruses 1/2, Varicella Zoster Virus, Epstein Barr Virus, Human Cytomegalovirus, Human Herpesvirus 6, JCV and HIV) were conducted. CSF from 14 non-reactive cases were subjected to random nucleic acid amplification, deep sequencing, and in silico search for viral sequences. RESULTS: JCV genome was detected in the CSF of 19/43 PML patients, HIV genome in the CSF of 5 PML patients including 2 JCV negative patients, and no viruses were detected in 22 patients. Human Polyomavirus 6 (HPyV6) DNA was detected by deep sequencing in one JCV-negative leukoencephalopathy CSF sample. CONCLUSIONS: HPyV6 DNA was detected in CSF of a case of demyelinating disease. HPyV6 has not been previously reported in CSF or associated with any disease. Demonstrating a causative role will require further studies.