Benign neonatal sleep myoclonus: a review of the literature

OBJECTIVE: Neurologically normal term infants sometimes present with repetitive, rhythmic myoclonic jerks that occur during sleep. The condition, which is traditionally resolved by 3 months of age with no sequelae, is termed benign neonatal sleep myoclonus. The goal of this review was to synthesize the published literature on benign neonatal sleep myoclonus. METHODS: The US National Library of Medicine database and the Web-based search engine Google, through June 2009, were used as data sources. All articles published after the seminal description in 1982 as full-length articles or letters were collected. Reports that were published in languages other than English, French, German, Italian, Portuguese, or Spanish were not considered. RESULTS: We included 24 reports in which 164 term-born (96%) or near-term-born (4%) infants were described. Neonatal sleep myoclonus occurred in all sleep stages, disappeared after arousal, and was induced by rocking the infant or repetitive sound stimuli. Furthermore, in affected infants, jerks stopped or even worsened by holding the limbs or on medication with antiepileptic drugs. Finally, benign neonatal sleep myoclonus did not resolve by 3 months of age in one-third of the infants. CONCLUSIONS: This review provides new insights into the clinical features and natural course of benign neonatal sleep myoclonus. The most significant limitation of the review comes from the small number of reported cases.

BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination

The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.

Estimation of the risks of thermal stress due to the microclimate for manual fruit and vegetable harvesters in central Italy

Agricultural workers are exposed to various risks, including chemical agents, noise, and many other factors. One of the most characteristic and least known risk factors is constituted by the microclimatic conditions in the different phases of work (in field, in greenhouse, etc). A typical condition is thermal stress due to high temperatures during harvesting operations in open fields or in greenhouses. In Italy, harvesting is carried out for many hours during the day, mainly in the summer, with temperatures often higher than 30 degrees C. According to ISO 7243, these conditions can be considered dangerous for workers' health. The aim of this study is to assess the risks of exposure to microclimatic conditions (heat) for fruit and vegetable harvesters in central Italy by applying methods established by international standards. In order to estimate the risk for workers, the air temperature, radiative temperature, and air speed were measured using instruments in conformity with ISO 7726. Thermodynamic parameters and two more subjective parameters, clothing and the metabolic heat production rate related to the worker's physical activity, were used to calculate the predicted heat strain (PHS) for the exposed workers in conformity with ISO 7933. Environmental and subjective parameters were also measured for greenhouse workers, according to ISO 7243, in order to calculate the wet-bulb globe temperature (WBGT). The results show a slight risk for workers during manual harvesting in the field. On the other hand, the data collected in the greenhouses show that the risk for workers must not be underestimated. The results of the study show that, for manual harvesting work in climates similar to central Italy, it is essential to provide plenty of drinking water and acclimatization for the workers in order to reduce health risks. Moreover, the study emphasizes that the possible health risks for greenhouse workers increase from the month of April through July.

The risk of musculoskeletal disorders for workers due to repetitive movements during tomato harvesting

Tomatoes are the most common crop in Italy. The production cycle requires operations in the field and factory that can cause musculoskeletal disorders due to the repetitive movements of the upper limbs of the workers employed in the sorting phase. This research aims to evaluate these risks using the OCRA (occupational repetitive actions) index method This method is based firstly on the calculation of a maximum number of recommended actions, related to the way the operation is performed, and secondly on a comparison of the number of actions effectively carried out by the upper limb with the recommended calculated value. The results of the risk evaluation for workers who manually sort tomatoes during harvest showed a risk for the workers, with an exposure index greater than 20; the OCRA index defines an index higher than 3.5 as unacceptable. The present trend of replacing manual sorting onboard a vehicle with optical sorters seems to be appropriate to reduce the risk of work-related musculoskeletal disorders (WMSDs) and is supported from both a financial point of view and as a quality control measure.

Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review

BACKGROUND: Worldwide, diarrheal diseases rank second among conditions that afflict children. Despite the disease burden, there is limited consensus on how to define and measure pediatric acute diarrhea in trials. OBJECTIVES: In RCTs of children involving acute diarrhea as the primary outcome, we documented (1) how acute diarrhea and its resolution were defined, (2) all primary outcomes, (3) the psychometric properties of instruments used to measure acute diarrhea and (4) the methodologic quality of included trials, as reported. METHODS: We searched CENTRAL, Embase, Global Health, and Medline from inception to February 2009. English-language RCTs of children younger than 19 years that measured acute diarrhea as a primary outcome were chosen. RESULTS: We identified 138 RCTs reporting on 1 or more primary outcomes related to pediatric acute diarrhea/diseases. Included trials used 64 unique definitions of diarrhea, 69 unique definitions of diarrhea resolution, and 46 unique primary outcomes. The majority of included trials evaluated short-term clinical disease activity (incidence and duration of diarrhea), laboratory outcomes, or a composite of these end points. Thirty-two trials used instruments (eg, single and multidomain scoring systems) to support assessment of disease activity. Of these, 3 trials stated that their instrument was valid; however, none of the trials (or their citations) reported evidence of this validity. The overall methodologic quality of included trials was good. CONCLUSIONS: Even in what would be considered methodologically sound clinical trials, definitions of diarrhea, primary outcomes, and instruments employed in RCTs of pediatric acute diarrhea are heterogeneous, lack evidence of validity, and focus on indices that may not be important to participants.

Fatal pulmonary embolism in a premature neonate after twin-to-twin transfusion syndrome

Thrombotic events are being increasingly recognized during the neonatal period. An infant girl was born at 29 weeks' gestation after a pregnancy complicated by twin-to-twin transfusion syndrome. After an initial uncomplicated clinical course, her oxygen requirement increased, which was interpreted as an early sign of bronchopulmonary dysplasia. At 3 weeks of age, she suddenly collapsed and died of severe pulmonary hypertension. At autopsy, multiple pulmonary artery emboli and several older renal vein thromboses were found. Results of genetic analyses of the infant and her family were negative for thrombophilia. Although embolism represents a frequent emergency in adults, fatal pulmonary embolism has never, to our knowledge, been described for premature infants. This case suggests that thrombotic events are underdiagnosed and that additional studies are needed to define infants at risk and optimal treatment strategies.

CD27 signaling on chronic myelogenous leukemia stem cells activates Wnt target genes and promotes disease progression

Chronic myelogenous leukemia (CML) results from a chromosomal translocation in hematopoietic stem or early progenitor cells that gives rise to the oncogenic BCR/ABL fusion protein. Clinically, CML has a chronic phase that eventually evolves into an accelerated stage and blast crisis. A CML-specific immune response is thought to contribute to the control of disease. Whether the immune system can also promote disease progression is not known. In the present study, we investigated the possibility that the TNF receptor family member CD27 is present on leukemia stem cells (LSCs) and mediates effects of the immune system on CML. In a mouse model of CML, BCR/ABL+ LSCs and leukemia progenitor cells were found to express CD27. Binding of CD27 by its ligand, CD70, increased expression of Wnt target genes in LSCs by enhancing nuclear localization of active β-catenin and TRAF2- and NCK-interacting kinase (TNIK). This resulted in increased proliferation and differentiation of LSCs. Blocking CD27 signaling in LSCs delayed disease progression and prolonged survival. Furthermore, CD27 was expressed on CML stem/progenitor cells in the bone marrow of CML patients, and CD27 signaling promoted growth of BCR/ABL+ human leukemia cells by activating the Wnt pathway. Since expression of CD70 is limited to activated lymphocytes and dendritic cells, our results reveal a mechanism by which adaptive immunity contributes to leukemia progression. In addition, targeting CD27 on LSCs may represent an attractive therapeutic approach to blocking the Wnt/β-catenin pathway in CML.

Reproducibility of acute mountain sickness in children and adults: a prospective study

Although a history of previous acute mountain sickness (AMS) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure, the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospective controlled study.

Spa-drain entrapment complicated by suspicions of nonaccidental trauma and epilepsy onset

We present here the case of an adolescent female near-drowning victim who was reportedly discovered submerged and unconscious by family members in a whirlpool spa. Physical examination revealed extensive posterior soft tissue bruising, which raised the suspicion of nonaccidental trauma. Detailed forensic evaluation of the injuries and the scene proved that the soft tissue findings represented an unusual manifestation of whirlpool-spa suction-vent injury. Medical evaluation indicated that epilepsy onset might have contributed to the near-drowning, although forensic evaluation of this possibility was less convincing. In this article we review these rare but important injuries, which have the potential to be confused with child abuse, and detail the atypical presentation and clinically presumed etiologic event in our case.

Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated nephropathy

B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria-reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology.

Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants

Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants.