ObjectiveThe World Health Organization (WHO) has established a set of growth curves for use as international standards in children up to age 5. The WHO's position is that all economically advantaged children who were breastfed as infants grow similarly. As a result, a single set of growth charts can be used to judge growth in any child, regardless of race or ethnicity. The goal of this study was to compare mean heights, weights and head circumferences from a variety of studies with the WHO's data.DesignWe compared data from the WHO's Multicentre Growth Reference Study (MGRS) with data from studies performed in 55 countries or ethnic groups.Data sourcesPubMed, WHO Global Database on Child Growth and Malnutrition, SciELO, Google Scholar, Textbooks and Ministries of Statistics and Public Health.Eligibility criteriaLarge recent studies (1988–2013) of economically advantaged groups, including comparisons with cohorts of breastfed children wherever possible.ResultsHeight varied somewhat among different national and ethnic groups. Means were generally within 0.5 of an SD of the MGRS means. Weight varied more than height, but the low MGRS means were seen as endorsing slenderness in the midst of an obesity epidemic. The mean head circumference varied widely. In many groups, means were consistently 0.5–1 SD above the MGRS mean. Head size in breastfed children at any age examined was far closer to local norms than to the MGRS means.ConclusionsHeight and weight curves may not be optimal fits in all cases. The differences between national or ethnic group head circumference means were large enough that using the WHO charts would put many children at risk for misdiagnosis of macrocephaly or microcephaly. Our findings indicate that the use of a single international standard for head circumference is not justified.Systematic Review RegistrationPROSPERO (# CRD42013003675).

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Ataxia telangiectasia (A-T) is a rare autosomal recessive disease caused by mutations in the ataxia telangiectasia mutated ( ATM ) gene. In the absence of a family history, the diagnosis of A-T is usually not made until the child is older and symptomatic. Classic A-T is characterized by a constellation of clinical symptoms including progressive ataxia, oculocutaneous telangiectasias and sinopulmonary disease and is usually associated with absence of ATM protein. Other laboratory features associated with A-T include elevated serum levels of alpha-fetoprotein (AFP) and increased chromosomal breakage with in vitro exposure to ionizing radiation. Sinopulmonary symptoms can occur to varying degrees across the lifespan. Some children will also have hypogammaglobulinemia and impaired antibody responses requiring supplemental gamma globulin. People with hypomorphic ATM mutations are often considered to have mild A-T with onset of ataxia and neurological progression occurring later in life with less impairment of the immune system. The risk of malignancy, however, is significantly increased in people with either classic or mild A-T. While hematological malignancies are most common in the first two decades of life, solid organ malignancies become increasingly common during young adulthood. Deterioration of neurologic function with age is associated with dysphagia with aspiration, growth faltering, loss of ambulation and decline in pulmonary function, morbidities that contribute to shortened life expectancy and decreased quality of life. Premature death is often due to malignancies or chronic respiratory insufficiency. A-T is currently managed with supportive care and symptomatic treatment. Current clinical trials, however, represent progress and hope towards disease-modifying therapies for A-T.

A number of viruses replicate in macrophages, some having an obligate requirement for a macrophage host. This raised the question concerning the role of the macrophage endosomal/lysosomal compartment during such infections. Both lysosomotropic weak bases, amantadine and chloroquine, which interfere with endosomal/lysosomal pH gradients, and the macrolide antibiotic bafilomycin A1, which interferes with vacuolar H+-ATPase, inhibited African swine fever (ASF) virus replication in porcine macrophages. This inhibition was reversible: replenishment of bafilomycin, but not amantadine or chloroquine, maintained the inhibition. The characteristics of the inhibition, and the capacity of virus to escape and re-commence replication, related to the capacity of each drug to interfere with the endosomal/lysosomal proton pump. These results demonstrate that the virus actually requires macrophage endosomal/lysosomal activity for its replication. Therein, vacuolar H+-ATPase activity is particularly critical for successful virus replication, which is interesting considering the importance of this for endosomal/lysosomal activity and macrophage function.

RNA viruses with segmented genomes were the first model used for molecular analysis of viral neuropathogenesis, since they could be analysed genetically by reassortment. Four viruses with non-segmented genomes have been used as models of neurovirulence and demyelinating disease: JHM coronavirus, Theiler's virus, Sindbis virus and Semliki Forest virus (SFV). Virus gene expression in the central nervous system of infected animals has been measured by in situ hybridization and immunocytochemistry. Cell tropism has been analysed by neural cell culture. Infectious clones have been constructed for Theiler's virus, Sindbis virus and SFV, and these allow analysis of the sequences involved in the determination of neuropathogenesis, through the construction of chimeric viruses and site-specific mutagenesis. Measles and rubella viruses have been studied in animal systems because of their importance for human disease. The importance of two recently discovered mechanisms of neuropathogenesis, antibody-induced modulation of virus multiplication, and persistence of virus in the absence of multiplication, remains to be assessed.