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A South African girl with CANDLE Syndrome is reported with emphasis on the orodental features and dental management. Clinical manifestations included short stature, wasting of the soft tissue of the arms and legs, erythematous skin eruptions and a prominent abdomen due to hepatosplenomegaly. Generalized microdontia, confirmed by tooth measurement and osteopenia of her jaws, confirmed by digitalized radiography, were previously undescribed syndromic components. Intellectual impairment posed problems during dental intervention. The carious dental lesions and poor oral hygiene were treated conservatively under local anaesthetic. Prophylactic antibiotics were administered an hour before all procedures. Due to the nature of her general condition, invasive dental procedures were minimal. Regular follow-ups were scheduled at six monthly intervals. During this period, her overall oral health status had improved markedly. The CANDLE syndrome is a rare condition with grave complications including immunosuppression and diabetes mellitus. As with many genetic disorders, the dental manifestations are often overshadowed by other more conspicuous and complex syndromic features. Recognition of both the clinical and oral changes that occur in the CANDLE syndrome facilitates accurate diagnosis and appropriate dental management of this potentially lethal condition. [ABSTRACT FROM AUTHOR]

Background: Preterm delivery is the leading cause of neonatal morbidity and mortality. Two-thirds of preterm deliveries are idiopathic. The initiating molecular mechanisms behind spontaneous preterm delivery are unclear. Umbilical cord blood DNA samples are an easy source of material to study the neonatal state at birth. DNA methylation changes can be exploited as markers to identify spontaneous preterm delivery. To identify methylation differences specific to idiopathic preterm delivery, we assessed genome-wide DNA methylation changes in 24 umbilical cord blood samples (UCB) using the 450 K Illumina methylation array. After quality control, conclusions were based on 11 term and 11 idiopathic preterm born neonates. The differentially methylated positions (DMPs) specific for preterm/term delivery, neonatal sex, use of oxytocin and mode of initiation of labor were calculated by controlling the FDR p value at 0.05. Results: The analysis identifies 1855 statistically significant DMPs between preterm and term deliveries of which 508 DMPs are also attributable to clinical variables other than preterm versus term delivery. 1347 DMPs are unique to term vs preterm delivery, of which 196 DMPs do not relate to gestational age as such. Pathway analysis indicated enrichment of genes involved in calcium signalling, myometrial contraction and relaxation pathways. The 1151 DMPs that correlate with advancing gestational age (p < 0.05) include 161 DMPs that match with two previously reported studies on UCB methylation. Additionally, 123 neonatal sex specific DMPs, 97 DMPs specific to the induction of labour and 42 DMPs specific to the mode of initiation of labor were also identified. Conclusion: This study identifies 196 DMPs in UCB DNA of neonates which do not relate to gestational age or any other clinical variable recorded and are specific to idiopathic preterm delivery. Furthermore, 161 DMPs from our study overlap with previously reported studies of which a subset is also reported to be differentially methylated at 18 years of age. A DMP on MYL4, encoding myosin light chain 4, is a robust candidate for the identification of idiopathic preterm labour as it is identified by all 3 independent studies. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the mediation of autoimmunity and regulatory T cells in patients with chromosome 22q11.2 deletion syndrome (22q11DS).

Objectives Although cognitive outcomes among perinatally infected youth have improved with highly active antiretroviral therapy ( HAART), the impact of the age of initiation of treatment and the central nervous system ( CNS) penetration effectiveness ( CPE) of the regimen on cognitive outcomes is unknown. We aimed to describe the association between initiation age/regimen CPE score and cognitive outcomes in perinatally HIV-infected youth. Methods Linear regression was used to retrospectively assess the association between full-scale IQ score ( FSIQ) and age of initiation of HAART, regimen CPE, and the presence/absence of an AIDS diagnosis before initiation of HAART in an urban US cohort. Results A total of 88 of 181 subjects (48.6%) had an AIDS diagnosis. In 69, AIDS preceded the start of HAART. Mean FSIQ (mean age 155.4 months) was 86.3 [standard deviation ( SD) 15.6]. Neither age of initiation of HAART ( P = 0.45) nor regimen CPE score ( P = 0.33) was associated with FSIQ. Mean FSIQ for patients with an AIDS diagnosis before HAART initiation [82 ( SD 17.0)] was significantly lower than for patients initiating HAART before an AIDS diagnosis [90 ( SD 13)] ( P = 0.001). Of the 129 subjects without AIDS by age 5 years, 41 (31.8%) initiated HAART before age 5 years; four of 41 later developed AIDS, compared with 32 of 88 of those who did not initiate HAART before age 5 years. The relative risk of AIDS if HAART was initiated before age 5 years was 0.19 (95% confidence interval 0.05-0.60). Conclusions Earlier age at HAART initiation and higher CPE score of a regimen did not improve cognitive outcomes. However, initiating HAART prior to AIDS protected against AIDS and was associated with a significantly higher FSIQ. [ABSTRACT FROM AUTHOR]

Background: While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation. Methods: In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself. Results: An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance. Conclusions: These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation. [ABSTRACT FROM AUTHOR]

Peste des petits ruminants (PPR), is an acute transboundary viral disease of economic importance, affecting goats and sheep. Mass vaccination programs around the world resulted in the decline of PPR outbreaks. Sungri 96 is a live attenuated vaccine, widely used in Northern India against PPR. This vaccine virus, isolated from goat works efficiently both in sheep and goat. Global gene expression changes under PPR vaccine virus infection are not yet well defined. Therefore, in this study we investigated the host-vaccine virus interactions by infecting the peripheral blood mononuclear cells isolated from goat with PPRV (Sungri 96 vaccine virus), to quantify the global changes in the transcriptomic signature by RNA-sequencing. Viral genome of Sungri 96 vaccine virus was assembled from the PPRV infected transcriptome confirming the infection and demonstrating the feasibility of building a complete non-host genome from the blood transcriptome. Comparison of infected transcriptome with control transcriptome revealed 985 differentially expressed genes. Functional analysis showed enrichment of immune regulatory pathways under PPRV infection. Key genes involved in immune system regulation, spliceosomal and apoptotic pathways were identified to be dysregulated. Network analysis revealed that the protein - protein interaction network among differentially expressed genes is significantly disrupted in infected state. Several genes encoding TFs that govern immune regulatory pathways were identified to co-regulate the differentially expressed genes. These data provide insights into the host - PPRV vaccine virus interactome for the first time. Our findings suggested dysregulation of immune regulatory pathways and genes encoding Transcription Factors (TFs) that govern these pathways in response to viral infection. [ABSTRACT FROM AUTHOR]

Regulatory T (Treg) cells play an important role in the maintenance of immune self-tolerance and homeostasis. We previously reported that neonatal CD4+ T cells have an intrinsic 'default' mechanism to become Treg (neoTreg) cells in response to T-cell receptor ( TCR) stimulation. However, the underlying mechanisms are unclear and the effects of neoTreg cells on regulating immune responses remain unknown. Due to their involvement in Foxp3 regulation, we examined the role of DNA methyltransferase 1 ( DNMT1) and DNMT3b during the induction of neoTreg cells in the Foxp3gfp mice. The function of neoTreg cells was assessed in an acute allograft rejection model established in RAG2−/− mice with allograft cardiac transplantation and transferred with syngeneic CD4+ effector T cells. Following ex vivo TCR stimulation, the DNMT activity was increased threefold in adult CD4+ T cells, but not significantly increased in neonatal cells. However, adoptively transferred neoTreg cells significantly prolonged cardiac allograft survival (mean survival time 47 days, P < 0·001) and maintained Foxp3 expression similar to natural Treg cells. The neoTreg cells were hypomethylated at the conserved non-coding DNA sequence 2 locus of Foxp3 compared with adult Treg cells. The DNMT antagonist 5-aza-2′-deoxycytidine (5-Aza) induced increased Foxp3 expression in mature CD4+ T cells. 5-Aza-inducible Treg cells combined with continuous 5-Aza treatment prolonged graft survival. These results indicate that the 'default' pathway of neoTreg cell differentiation is associated with reduced DNMT1 and DNMT3b response to TCR stimulus. The neoTreg cells may be a strategy to alleviate acute allograft rejection. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Dermatology / Turk Dermatoloji Dergisis is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The underlying cause of the enigmatic coexistence of immunodeficiency and autoimmune disorders in patients with primary immunodeficiency such as Omenn syndrome is largely due to the inefficient negative selection within thymus where T cells develop. Recent advances in molecular biology and animal models answered one of the key questions on the relationship between the partially impaired T cell development at early stages and the presence of autoreactive T cells in periphery. T cell development and thymic organogenesis are tightly coupled to each other. The maturing T cells induce thymic epithelial cell development and AIRE (Autoimmune regulator) expression in thymic medullary epithelial cells. Without thymic medullary epithelial cells and AIRE protein in the patients with primary immunodeficiency, a few autoreactive T cells survive through the complete thymic selection processes and expand to form oligoclonal T cell pools in the periphery. The induction of thymic medullary epithelial cell development may be considered as an alternative therapeutic approach in addition to the current standard therapy for primary immunodeficiency - stem cell transplantation. [ABSTRACT FROM AUTHOR]

Purpose: Syndrome diGeorge is associated amongst other clinical signs with various degrees of thymic dysplasia, related immunodeficiency and autoimmune disorders. Helios, a transcription factor from Ikaros family, has been proposed as a marker for thymus derived Tregs. We therefore examined Helios + Tregs in a cohort of patients with genetically proven diGeorge syndrome with typical T cell lymphopenia due to the thymic pathology. Methods: T cells, FoxP3+ Tregs and Helios + FoxP3+ Tregs were examined in 52 samples from 37 patients. One patient with diGeorge/CHARGE syndrome with total thymic aplasia was also included. Statistical analysis was performed using a linear regression comparison. Results: Total absolute Tregs were significantly lower in diGeorge patients as compared to controls in all age groups (0-20 years) ( p = 0.0016). The difference was more expressed in the first four years of age. Relative Treg numbers expressed as the percentage of Tregs in CD4+ T-cells, however, were not different in patients and controls in all age groups ( p = 0.661), neither could we find any significant difference in the percentage of Helios + Tregs between patients and controls ( p = 0.238). Helios + Tregs were still present in a patient with diGeorge/CHARGE syndrome with complete athymia 7 years after partially matched unrelated repeated T lymphocytes infusions. Conclusion: Our findings show that while there was a significant decrease in absolute numbers of Tregs in patients with diGeorge syndrome, the relative percentage of this population did not differ between patients and controls. Low absolute Tregs thus reflected typical T cells lymphopenia in patients. Helios expression was not affected in diGeorge syndrome. [ABSTRACT FROM AUTHOR]

Background: Objective MRI markers of central nervous system disease severity may precede subjective features of HIV encephalopathy in children. Previous work in HIV-infected adults shows that brain atrophy was associated with low CD4 and with neuropsychological impairment. Significant thinning of the corpus callosum (CC), predominantly anteriorly, was also found in HIV-infected adults and correlated with CD4 levels. These findings have not been tested in children. Purpose: The aim of this study was to determine if brain volume and midsagittal CC linear measurements (thickness and length) on MRI in children with HIV-related brain disease correlate with clinical and laboratory parameters of disease severity. Methods: Retrospective MRI analysis in children with HIV-related brain disease used a volumetric analysis software and a semi-automated tool to measure brain volume and callosal thickness/length, respectively. Each measure was correlated with clinical parameters of disease severity including Griffiths Mental Development scores (GMDS), absolute CD4 counts (cells/mm), nadir CD4 (the lowest CD4 recorded, excluding baseline), duration of HAART, and decreased brain growth. Results: Thirty-three children with HIV-related brain disease were included. Premotor segment of the CC mean thickness correlated with age ( p = 0.394). Motor CC maximum thickness correlated significantly with general developmental quotient ( p = 0.0277); CC length correlated with a diagnosis of acquired microcephaly ( p = 0.0071) and to CD4 level closest to date of the MRI scan ( p = 0.04). Conclusions: Length of the CC and the 'motor CC segment' may represent surrogate clinical biomarkers of central nervous system disease severity and with decreased level of immunity in HIV-infected patients that precede established HIV encephalopathy. [ABSTRACT FROM AUTHOR]

In this article, we examine the concept of HIV viral load and how it has evolved over time (1995-2013) in the field of HIV/AIDS. Although the term viral load is used extensively in this field, few efforts have been directed toward the conceptualization of HIV viral load, which is often left unquestioned, undertheorized, and portrayed as a neutral and objective laboratory value that has remained relatively stable over time—with the exception of progressive advancements in technology, techniques, and sensitivity. The purpose of this article is to apply the evolutionary concept analysis method developed by Rodgers (1989, 2000a) to the concept of HIV viral load. To set the stage, we establish the need for a concept analysis of HIV viral load and provide an overview of the evolutionary view. Then, drawing on the steps proposed by Rodgers (2000a), we outline the process of data collection, management, and analysis. We then offer an in-depth discussion of the findings (attributes, antecedents, and consequences) informed by Wuest’s (2000) critical approach to concept analysis. We conclude by highlighting the implications of this analysis for clinical practice, research, and theory. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the neurodevelopment of HIV-infected (HI) infants in combination with antiretroviral therapy also known as HAART (highly active antiretroviral therapy) to HIV-exposed uninfected (HEU) infants. Twenty-seven HIV infected and 29 HEU infants under the age of one year attending the Empilweni Clinic at Rahima Moosa Mother and Child Hospital were studied. HI infants were assessed prior to initiating HAART and then for six months whilst on HAART. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, 3rd ed (Bayley III). The HI infants scored significantly lower when compared to HEU infants for motor and language development at baseline, three months and six months follow up. No significant improvement in language (p= 0.46) and motor function (p= 0.91) occurred over time; however, developmental scores did not decrease. Cognitive development in the HI group was significantly lower when compared to the HEU group at visit one (p= 0.003). By six months follow-up, there were no significant differences between the two groups for cognitive development (p= 0.18). This study suggests that HIV-positive infants are delayed when compared to HEU infants. HAART may help to prevent further delay; however, it does not reverse the neurological damage already present. There is a need for therapists to be involved in pediatric HIV clinical services in order to provide early developmental screening as well as rehabilitative services to those children in need. [ABSTRACT FROM AUTHOR]

Microsporidia are ubiquitous parasites infecting all animal phyla and we present evidence that supports their zoonotic potential. Fecal samples taken from domestic (cats and dogs), farm (pigs, rabbits and ostriches) and wild animals (foxes) from different provinces of Spain were evaluated for microsporidia infection by light microscopy and PCR. After Microsporidia species identification, E. bieneusi genotypes were additionally studied by sequence analysis of the ITS region. Eighty-five samples out of 159 exhibited structures that were compatible with microsporidia spores by Webeŕs stain with 37 of them being confirmed by PCR. Microsporidia species identified included E. bieneusi, E. intestinalis and A. algerae. We report the first diagnosis of E. intestinalis and E. bieneusi in ostriches and A. algerae in pigs. We also provide new information on the molecular characterization of E. bieneusi isolates both in rabbits and ostriches. All of the E. bieneusi genotypes identified belonged to the zoonotic group of genotypes (Group I) including genotypes A (dogs), I (pigs), D (rabbits and foxes) and type IV (ostriches). Our results demonstrate that microsporidia are present in domestic, farm and wild animals in Spain, corroborating their potential role as a source of human infection and environmental contamination. [ABSTRACT FROM AUTHOR]

Sepsis is the leading cause of death in children worldwide. Although the diagnosis and management of sepsis in infants and children is largely influenced by studies done in adults, there are important considerations relevant for pediatrics. This article highlights pediatric-specific issues related to the definition of sepsis and its epidemiology and management. We review how the capacity of the immune system to respond to infection develops over early life. We also bring attention to primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms. The management of pediatric sepsis must be tailored to the child's age and immune capacity, and to the site, severity, and source of the infection. It is important for clinicians to be aware of infection-related syndromes that primarily affect children. Although children in developed countries are more likely to survive severe infections than adults, many survivors have chronic health impairments. [ABSTRACT FROM AUTHOR]

Mutations in SLC29A3 lead to pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) and H syndromes, familial Rosai-Dorfman disease, and histiocytosis-lymphadenopathy plus syndrome. We report a new association of PHID syndrome with severe systemic inflammation, scleroderma-like changes, and cardiomyopathy. A 12-year-old girl with PHID syndrome presented with shortness of breath, hepatosplenomegaly, and raised erythrocyte sedimentation rate and C-reactive protein. An echocardiogram showed biventricular myocardial hypertrophy, and cardiac magnetic resonance imaging showed circumferential late gadolinium enhancement of the myocardium. No systemic amyloid deposits were observed on a whole-body serum amyloid P scintigraphy scan. Abdominal ultrasound revealed intra-abdominal fat surrounding the solid organs, suggesting a possibility of evolving lipodystrophy with visceral adiposity. PHID syndrome is a novel monogenic autoinflammatory syndrome (AIS) associated with severe elevation of serum amyloid. Lipodystrophy, cutaneous sclerodermatous changes, and cardiomyopathy were also present in this case. In contrast to other AIS, blockade of interleukin-1 and tumor necrosis-α was ineffective. [ABSTRACT FROM AUTHOR]

Nakajo-Nishimura syndrome (NNS) is a very rare hereditary autoinflammatory disorder that generally has its onset in infancy with pernio-like rashes and gradually develops into partial lipodystrophy. A distinct homozygous PSMB8 mutation encoding an immunoproteasome subunit has recently been identified as its genetic cause. Here, we report a new case of a patient with NNS who developed exudative erythemas on his face and extremities at 2 months of age, along with high fever, elevated serum hepatic aminotransferase levels and hepatosplenomegaly. Massive infiltration of inflammatory cells was observed histologically in the dermis and subcutis without apparent leukocytoclastic vasculitis. These symptoms improved with oral corticosteroids but recurred periodically, and a thin angular face with long clubbed fingers gradually developed. Identification of the PSMB8 mutation finalized the diagnosis of NNS at 5 years of age. Understanding a variety of clinicopathological features at the developmental stages is necessary to make an early diagnosis of NNS. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article lists the authors who have submitted their abstracts in the journal including W. Aberer, J. Arnolds, and S. Baos.

The article presents abstracts on allergy and immunology which include the indices of innate immunity in children with recurrent wheezing, the predictive factors of tumor infiltrating neutrophils in patients with colorectal cancer, and the role of interleukin-10 (IL-10) in dengue infections.

The objective of the study was to determine the prevalence of pediatric human immunodeficiency virus 1 ( HIV-1) mucocutaneous manifestations in the era of highly active antiretroviral therapy ( HAART). We conducted population-based, prospective, multicenter pediatric HIV-1 surveillance in 276 children with perinatally acquired HIV-1 from 1988 to 2009. Centers for Disease Control and Prevention ( CDC)-defined HIV-1 related mucocutaneous conditions among the 276 children were: category A ( n = 152), B ( n = 60), and C ( n = 1). Nearly half of the category A and B diagnoses (43.4% [66/152] and 35.0% [21/60], respectively) occurred in the first year of life, with 59.2% (90/152) and 61.7% (37/60), respectively, occurring in the first 2 years of life. The most frequent infectious diagnosis was oropharyngeal thrush ( n = 117, 42.4%); the most common inflammatory diagnosis was diaper dermatitis ( n = 71, 25.7%). There was a temporal decline in the prevalence of A (pre- HAART cohort, 123; post- HAART cohort, 29; p < 0.01) and B (pre- HAART, 55; post- HAART, 5; p < 0.01) mucocutaneous diagnoses. In children with perinatal HIV-1, there was a significant decline in CDC category A and B mucocutaneous diagnoses by temporal cohort, consistent with the introduction of antiretroviral medications and HAART. Clinical category A and B mucocutaneous diagnoses were most common in the first 2 years of life, emphasizing the importance of early HIV-1 testing and HAART initiation. [ABSTRACT FROM AUTHOR]

Copyright of Iatreia is the property of Universidad de Antioquia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The aim of this study was to compare the effect of 2 y of antiretroviral therapy (ART) on the percentage of activated CD38+CD8+ T cells and human leukocyte antigen (HLA)-DR+CD8+ T cells, and the expression of the co-stimulatory molecule CD28 on CD4+ and CD8+ T cells in the peripheral blood of HIV-infected adults, and to assess the use of immune activation markers to predict the virological response to ART in a cohort of HIV-1-infected patients in the north-western part of China. Methods: We analyzed changes in the CD4+ T cell count, viral load, and the percentages of CD38+CD8+ T cells, HLA-DR+CD8+ T cells, CD28+CD4+ T cells, and CD28+CD8+ T cells in 48 patients with HIV diseases during 2 y of suppressive highly active antiretroviral therapy (HAART). Good virological responders ( n = 20) were defined as those who had suppressed and maintained a plasma viral load below the detection limit of the assay for at least 12 months. Poor virological responders ( n = 28) were defined as those with a detectable viral load at 6 and 12 months after beginning HAART. Results: Among the 20 good responders, baseline median levels of CD38+CD8+ T cells were elevated, but had decreased significantly at 24 months of therapy ( p < 0.0001). Median levels of HLA-DR+CD8+ T cells also decreased at 24 months of therapy ( p < 0.0001). Levels of expression of CD28+CD4+ T cells rose steadily to 6 months ( p = 0.03), and smoothly reached levels observed among HIV-negative blood donors during the 24 months of therapy ( p > 0.05). Levels of expression of CD28+CD8+ T cells increased at 24 months ( p = 0.04). Among the 28 poor responders, median levels of CD38+CD8+ T cells decreased significantly at 24 months ( p < 0.0001). Levels of HLA-DR+CD8+ T cells also decreased at 24 months ( p < 0.001). Levels of CD28+CD8+ T cells and levels of CD28+CD4+ T cells increased at 24 months remained unchanged. The percentage of CD38+CD8+ T cells appeared to provide a sensitive estimate of the overall immune recovery in comparison with the percentage of HLA-DR+CD8+ T cells, although this lacked specificity for the determination of early virological drug failure and did not appear to be a reliable surrogate for RNA viral load. Conclusions: We show that HAART can be used successfully in Chinese populations with elevated baseline immune activation markers and that the percentage of CD38+CD8+ T cells may be an additional parameter to the current criteria for estimating the antiretroviral response with HAART. [ABSTRACT FROM AUTHOR]

Preterm birth occurs in 11% of live births globally and accounts for 35% of all newborn deaths. Preterm newborns have immature immune systems, with reduced innate and adaptive immunity; their immune systems may be further compromised by various factors associated with preterm birth. The immune systems of preterm infants have a smaller pool of monocytes and neutrophils, impaired ability of these cells to kill pathogens, and lower production of cytokines which limits T cell activation and reduces the ability to fight bacteria and detect viruses in cells, compared to term infants. Intrauterine inflammation is a major contributor to preterm birth, and causes premature immune activation and cytokine production. This can induce immune tolerance leading to reduced newborn immune function. Intrauterine inflammation is associated with an increased risk of early-onset sepsis and likely has long-term adverse immune consequences. Requisite medical interventions further impact on immune development and function. Antenatal corticosteroid treatment to prevent newborn respiratory disease is routine but may be immunosuppressive, and has been associated with febrile responses, reductions in lymphocyte proliferation and cytokine production, and increased risk of infection. Invasive medical procedures result in an increased risk of late-onset sepsis. Respiratory support can cause chronic inflammatory lung disease associated with increased risk of long-term morbidity. Colonization of the infant by microorganisms at birth is a significant contributor to the establishment of the microbiome. Caesarean section affects infant colonization, potentially contributing to lifelong immune function and well-being. Several factors associated with preterm birth alter immune function. A better understanding of perinatal modification of the preterm immune system will allow for the refinement of care to minimize lifelong adverse immune consequences. [ABSTRACT FROM AUTHOR]

Recurrent fever can be the sole or leading manifestation of a variety of diseases including malignancies, autoimmune diseases and infections. Because the differential diagnoses are manifold, no formal guidelines for the approach of patients with recurrent fever exists. The newly recognized group of autoinflammatory diseases are often accompanied by repetitive fever attacks. As these episodes are frequently associated by a variety of divergent presentations, the differentiation of other causes for febrile illnesses can be difficult. In this article, we first review disease entities, which frequently present with the symptom of recurrent fever. In a next step, we summarize their characteristic pattern of disease presentation. Finally, we analyse key features of autoinflammatory diseases, which are helpful to distinguish this group of diseases from the other causes of recurrent fever. Recognizing these symptom patterns can provide the crucial clues and, thus, lead to the initiation of targeted specific diagnostic tests and therapies. [ABSTRACT FROM AUTHOR]

There are approximately from 1,100 to 1,200 HIV-infected children in a follow-up in Spain. In 2008 an open, multicentral, retrospective and prospective Cohort of the Spanish Paediatric HIV Network (CoRISpe) was founded. The CoRISpe is divided into the node 1 and node 2 representing geographically almost the whole territory of Spain. Since 2008 seventy-five hospitals have been participating in the CoRISpe. All the retrospective data of the HIV-infected children have been kept in the CoRISpe since 1995 and prospective data since 2008. In this article we are going to present the notion of CoRISpe, its role, the structure, how the CoRISpe works and the process how a child is transferred from Paediatric to Adults Units. The main objective of the CoRISpe is to contribute to furthering scientific knowledge on paediatric HIV infection by providing demographic, sociopsychological, clinical and laboratory data from HIV-infected paediatric patients. Its aim is to enable high-quality research studies on HIV-infected children. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between serum leptin levels and suppression of CD4 count in HIV-infected individuals with highly active antiretroviral therapy (HAART). Subjects and Methods: Thirty seropositive HIV male patients selected from the Infectious Disease Hospital were classified into two groups according to their immunological and virological response to HAART. The first group included 15 male patients with low viral load and low CD4 counts; the second included 15 male patients with low viral load and high CD4 counts. Morning serum leptin and tumor necrosis factor-α levels of HIV patients were measured and correlated with fasting serum insulin, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), HIV viral load and CD4 count. Results: Serum leptin levels were significantly higher in patients with high CD4 counts than in patients with low CD4 counts (mean serum leptin level 47.3 vs. 10.9 ng/ml, respectively; p < 0.0001). A positive correlation was observed between serum leptin levels and CD4 counts (r = 0.697; p < 0.0001); positive correlations were also seen between leptin levels and fasting serum insulin and HOMA-IR (r = 0.633, p < 0.0001, and r = 0.537, p < 0.003, respectively). Conclusion: Serum leptin level was higher in HIV patients with high CD4 count and correlated with fasting serum insulin and HOMA-IR, thereby indicating that HAART treatment could lead to decreased levels of leptin in HIV patients, which might lead to impaired immunological recovery. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Neurodevelopmental delay has been documented in up to 97.5% of HIV-infected children in Soweto who were not yet on antiretroviral treatment (ART). With growing numbers of children in South Africa being successfully treated with ART, the effects of ART on neurocognitive functioning in children require investigation. The objective of this study was to determine the extent of neurodevelopmental delay in stable HIV-infected preschool children (aged five to six years) receiving ART and compare it to an apparently healthy (unconfirmed HIV-status) group of preschool children. Thirty HIV-infected preschool children (virologically and immunologically stable on ART for more than one year) were conveniently sampled from 350 eligible children on ART at the Harriet Shezi Children's Clinic in Soweto, Johannesburg. The comparison group comprised 30 well-nourished preschool children attending the Lilian Ngoyi Primary Health Care Clinic in Soweto for routine immunizations. Each child was assessed using the Griffiths Mental Development Scales-Extended Revised Version (GMDS-ER), at a single point in time. The overall developmental z-scores on GMDS-ER were <−2 (indicating severe delay) in 27 (90%) children in the HIV-infected group compared to 23 (76%) in the comparison group (p = 0.166). Mental handicap (overall GQ < 70) was evident in 46.7% of children in the HIV-infected group compared to 10% in the comparison group (p = 0.002). There was a 7.88-fold increased likelihood of severe delay in the HIV infected group. The HIV-infected group and comparison group had significantly different (p = 0.001) mean overall GQ scores of 70 (95% CI: 66.0–74.0) and 78 (95% CI: 75.6–80.5), respectively, with lower mean scores in the HIV-infected group in all individual domains. Early initiation of ART in HIV-infected infants may improve cognitive functioning among this group; however, intervention strategies which optimize early cognitive development for all children in the area need to be urgently considered. [ABSTRACT FROM PUBLISHER]

Objective Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome) is an autoinflammatory syndrome recently described in children. We undertook this study to investigate the clinical phenotype, genetic cause, and immune dysregulation in 9 CANDLE syndrome patients. Methods Genomic DNA from all patients was screened for mutations in PSMB8 (proteasome subunit β type 8). Cytokine levels were measured in sera from 3 patients. Skin biopsy samples were evaluated by immunohistochemistry, and blood microarray profile and STAT-1 phosphorylation were assessed in 4 patients and 3 patients, respectively. Results One patient was homozygous for a novel nonsense mutation in PSMB8 (c.405C>A), suggesting a protein truncation; 4 patients were homozygous and 2 were heterozygous for a previously reported missense mutation (c.224C>T); and 1 patient showed no mutation. None of these sequence changes was observed in chromosomes from 750 healthy controls. Of the 4 patients with the same mutation, only 2 shared the same haplotype, indicating a mutational hot spot. PSMB8 mutation-positive and -negative patients expressed high levels of interferon-γ (IFNγ)-inducible protein 10. Levels of monocyte chemotactic protein 1, interleukin-6 (IL-6), and IL-1 receptor antagonist were moderately elevated. Microarray profiles and monocyte STAT-1 activation suggested a unique IFN signaling signature, unlike in other autoinflammatory disorders. Conclusion CANDLE syndrome is caused by mutations in PSMB8, a gene recently reported to cause 'JMP' syndrome (joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced childhood-onset lipodystrophy) in adults. We extend the clinical and pathogenic description of this novel autoinflammatory syndrome, thereby expanding the clinical and genetic disease spectrum of PSMB8-associated disorders. IFN may be a key mediator of the inflammatory response and may present a therapeutic target. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine the prevalence of intestinal parasites, with special emphasis on microsporidia and Cryptosporidium, as well as their association with human immunodeficiency virus (HIV) symptoms, risk factors, and other digestive parasites. We also wish to determine the molecular biology definitions of the species and genotypes of microsporidia and Cryptosporidium in HIV patients. Methods: In this cross-sectional study, carried out in Kinshasa, Democratic Republic of the Congo, stool samples were collected from 242 HIV patients (87 men and 155 women) with referred symptoms and risk factors for opportunistic intestinal parasites. The analysis of feces specimen were performed using Ziehl-Neelsen stainings, real-time polymerase chain reaction (PCR), immunofluorescence indirect monoclonal antibody, nested PCR-restriction fragment length polymorphism, and PCR amplification and sequencing. Odds ratio (OR) and 95% confidence intervals were used to quantify the risk. Results: Of the 242 HIV patients, 7.8%, 0.4%, 5.4%, 0.4%, 2%, 10.6%, and 2.8% had Enterocytozoon bieneusi, Encephalitozoon intestinalis, Cryptosporidium spp., Isospora belli, pathogenic intestinal protozoa, nonpathogenic intestinal protozoa, and helminths, respectively. We found five genotypes of E. bieneusi: two older, NIA1 and D, and three new, KIN1, KIN2, and KIN3. Only 0.4% and 1.6% had Cryptosporidium parvum and Cryptosporidium hominis, respectively. Of the patients, 36.4%, 34.3%, 31%, and 39% had asthenia, diarrhea, a CD4 count of <100 cells/mm3, and no antiretroviral therapy (ART), respectively. The majority of those with opportunistic intestinal parasites and C. hominis, and all with C. parvum and new E. bieneusi genotypes, had diarrhea, low CD4+ counts of <100 cells/mm3, and no ART. There was a significant association between Entamoeba coli, Kaposi sarcoma, herpes zoster, chronic diarrhea, and asthenia, and the presence of 28 cases with opportunistic intestinal parasites. Rural areas, public toilets, and exposure to farm pigs were the univariate risk factors present in the 28 cases with opportunistic intestinal parasites. In logistic regression analysis, a CD4 count of <100 cells/mm3 (OR = 4.60; 95% CI 1.70-12.20; P = 0.002), no ART (OR = 5.00; 95% CI 1.90-13.20; P < 0.001), and exposure to surface water (OR = 2.90; 95% CI 1.01-8.40; P = 0.048) were identified as the significant and independent determinants for the presence of opportunistic intestinal parasites. Conclusion: E. bieneusi and Cryptosporidium are becoming more prevalent in Kinshasa, Congo. Based on the findings, we recommend epidemiology surveillance and prevention by means of hygiene, the emphasis of sensitive PCR methods, and treating opportunistic intestinal parasites that may be acquired through fecal-oral transmission, surface water, normal immunity, rural area-based person-person and animal-human infection, and transmission of HIV. Therapy, including ART and treatment with fumagillin, is needed. [ABSTRACT FROM AUTHOR]

The otorhinolaryngological (ORL) manifestations of Human Immunodeficiency virus (HIV) are common, but remain poorly characterized among children of Sub-Saharan Africa, where 90% of new pediatric infections occur. Our objective was to compare ORL findings and hearing in HIV-positive and -negative children of Luanda, Angola, using a comparative study of 78 outpatients from the HIV polyclinic and of 78 age- and sex-matched controls in a pediatric hospital with interview, general and ORL examination, brainstem auditory evoked potentials, and at age >5 years pure tone open-air audiometry. ORL pathology emerged in 92% of HIV-positive and 78% ( p = 0.02) of control children. HIV-associated ORL findings comprised dental caries (56 vs. 32%; p = 0.0009), cervical lymphadenopathy >1 cm (45 vs. 10%; p < 0.0001), facial skin lesions (32 vs. 5.1%; p < 0.0001), chronic suppurative otitis media (26 vs. 3.8%; p = 0.0002), dry tympanic membrane perforations (9 vs. 1%; p = 0.03), tonsils of Mallampati score 0-1 (87 vs. 64%; p = 0.0009), and bilateral hearing loss of >25 dB (13 vs. 1%; p = 0.009). Other HIV-associated characteristics included ear pain (44 vs. 27%; p = 0.006), earlier otorrhea episodes (34 vs. 17%; p = 0.004), tuberculosis (29 vs. 2.6%; p < 0.0001), and pneumonia (22 vs. 2.6%; p = 0.0003). ORL pathology appeared usual in both HIV-positive and -negative children. However, the overall high frequency and severity of the findings among the HIV-positive children require regular inclusion of the ORL area in these children's clinical evaluation. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response. [ABSTRACT FROM AUTHOR]

An author index for the June 2011 issue of the journal "Allergy," is presented.

Background CD4+CD25+FoxP3+ regulatory T-cells (nTReg) have been shown to suppress immune responses to autoantigens and to other diverse antigens, this suppression is mainly mediated by a cell contact-dependent mechanism not yet fully defined. It has been reported that both human natural and induced TReg exert cytotoxic activity against autologous target cells, which suggests that the perforin/granzyme pathway may be a relevant candidate mechanism for the suppressive function of TReg. Previous reports have shown that oestradiol (E2) modulates TReg percentages and function. Methods We have evaluated in pregnant and non-pregnant subjects perforin intracellular expression in CD4+CD25+FoxP3+ regulatory T-cells by flow cytometry in whole blood, ex-vivo purified nTReg and ex-vivo purified nTReg after TCR and E2 stimulation. The expression of cellular degranulation markers was also phenotypically determined. Results We show that E2 expands TReg, enhances in vitro TReg function and induces a TReg phenotype in activated responder (CD4+CD25) T-cells, further increasing the expression of perforin on TReg than in vitro T-cell receptor activation alone. We found surface lysosomal-associated membrane glycoproteins (LAMP)-1and LAMP-2 expression by TReg, which is a sign of cell degranulation and therefore of cytotoxicity exerted by these cells. Conclusion Our data demonstrates the presence of functional TReg cytotoxic properties in biological systems and support the concept that E2 enhances the number and function of TReg suggesting the potential interaction between E2 and immunoregulatory mechanisms. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the in vitro functional profile of T cells from uninfected neonates born from HIV-1-infected pregnant women who controlled (G1) or not (G2) the virus replication. We demonstrated that the lymphoproliferation of T cell to polyclonal activators was higher in the G2 as compared with G1. Nevertheless, no detectable proliferative response was observed in response to HIV-1 antigens in both neonate groups. Cytokine dosage in the supernatants of these polyclonally activated T cell cultures demonstrated that, while IL-10 was the dominant cytokine produced in G1, Th17-related cytokines were significantly higher in G2 neonates. The higher Th17 phenotype tendency in G2 was related to high production of IL-23 by lipopolysaccharide-activated monocyte-derived dendritic cells from these neonates. Our results demonstrated immunological disorders in uninfected neonates born from viremic HIV-1-infected mothers that can help to explain why some of these children have elevated risk of clinical morbidity and mortality due to pathological hypersensitivity. [ABSTRACT FROM AUTHOR]

Objective, The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor-naïve vertically HIV-infected children on highly active antiretroviral therapy (HAART). Objective The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor-naïve vertically HIV-infected children on highly active antiretroviral therapy (HAART). Patients and methods, We carried out a multicentre retrospective study of 27 children during 48 months on HAART. Every 3 months, CD4+ T-cells, CD8+ T-cells, viral load (VL), cholesterol, triglycerides, lipoproteins and adipokines were measured. Diagnoses of lipodystrophy were based on clinical examinations. Results, We found hypercholesterolaemia (4200 mg/dL) in 9.5, 30.4, 21.7, 14.3 and 13.3% of the subjects at months 0, 12, 24, 36 and 48, respectively, and hypertriglyceridaemia (4170 mg/dL) in 14.3, 8.3, 13, 4.5 and 0% at the same time-points. During follow-up, and especially at the end of the study, we found an increase in plasma resistin levels and significant increases in total plasminogen activator inhibitor type 1, adiponectin, and leptin levels (P<0.05). We also observed slight increases in the leptin/adiponectin ratio, homeostatic model assessment, and C-peptide values during the first months of treatment followed by a moderate decrease or stabilization after 24 months on HAART. At the end of the study, 12 of the 27 children (44.4%) had lipodystrophy, 10 (37%) had lipoatrophy, and 11 (40.7%) had lipohypertrophy; and only three of the 27 children (11.1%) were diagnosed with lipoatrophy and lipohypertrophy with scores ⩾2. Conclusions, HIV-infected children showed an increase in serum adipokine levels, but this was not associated with the emergence of lipodystrophy during 48 months on HAART. [ABSTRACT FROM AUTHOR]

Immunoglobulin D (IgD) has remained a mysterious antibody class for almost half a century. IgD was initially thought to be a recently evolved Ig isotype expressed only by some mammalian species, but recent discoveries in fishes and amphibians demonstrate that IgD was present in the ancestor of all jawed vertebrates and has important immunological functions. The structure of IgD has been very dynamic throughout evolution. Mammals can express IgD through alternative splicing and class switch recombination. Active cell-dependent and T-cell-independent IgM-to-IgD class switching takes place in a unique subset of human B cells from the upper aerodigestive mucosa, which provides a layer of mucosal protection by interacting with many pathogens and their virulence factors. Circulating IgD can bind to myeloid cells such as basophils and induce antimicrobial, inflammatory, and B-cell-stimulating factors upon cross-linking, which contributes to not only immune surveillance but also inflammation and tissue damage when this pathway is overactivated under pathological conditions. Recent research shows that IgD is an important immunomodulator that orchestrates an ancestral surveillance system at the interface between immunity and inflammation. [ABSTRACT FROM AUTHOR]

Aims The human immunodeficiency virus (HIV) potentially causes a significant encephalopathy and resultant developmental delay in infected children. The aim of this study was to determine whether a home-based intervention programme could have an impact on the neurodevelopmental status of children infected with HIV. Method A longitudinal, randomized, controlled trial was conducted. A total of 122 children aged less than 2 years 6 months were assigned to either a comparison or an experimental group. Children in the experimental group were given a home stimulation programme that was updated every 3 months. The home programme included activities to promote motor, cognitive, and speech and language development. Children in the comparison group received no developmental intervention. Children were assessed by a blinded assessor at baseline, 6 months, and 12 months using the Bayley Scales of Infant Development, 2nd edition. Results The children in this study came from poor socioeconomic backgrounds and their nutritional status was suboptimal. The experimental group included 60 children (30 males, 30 females) with a mean age of 18 months (SD 8.1mo). The comparison group included 62 children (32 males, 30 females) with a mean age 19 months (SD 8.2mo). Cognitive and motor development were severely affected at baseline, with 52% of the children having severe cognitive delay and 72% having severe motor delay at baseline. Children in the experimental group showed significantly greater improvement in cognitive ( p=0.010) and motor ( p=0.020) development over time than children in the comparison group. Interpretation A home stimulation programme taught to the caregiver can significantly improve cognitive and motor development in young children infected with HIV. [ABSTRACT FROM AUTHOR]

An author index for the January 2010 issue of "Child: Care, Health & Development" is presented.

Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5narrow and R5broad resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Enfermedades Infecciosas en Pediatría is the property of Ediciones Franco S.A. de C.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article discusses research on the etiology and treatment of chronic diarrhea in children with HIV. An introduction to the medical condition is offered. Datasets reviewed include Cochrane HIV/AIDS Group Specialized Register, MEDLINE, the Global Health database and Google scholar. Identified microbiological etiologies of HIV-associated diarrhea included Cryptosporidium, Salmonella, Escherichia coli and Entamoeba histolytica, among others. Also discussed are the limitations of the research.

An author index for the October 2, 2009 issue of the journal "HIV Medicine" is presented.

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)