Facilitation of school re-entry and peer acceptance of children with cancer: a review and meta-analysis of intervention studies.

Increased survival rates from childhood cancer call for efforts to reintegrate children with cancer back into their academic and social environments. The aims of this study were to: (1) review and analyse the existing literature on school re-entry interventions for children with cancer; and (2) discuss the importance of peer involvement in the treatment. Relevant databases were searched using equivalent search algorithms and six studies were selected that target children with cancer and/or their classmates. Two authors independently reviewed the literature for data extraction. The articles were reviewed using the PRISMA model for reporting reviews. Statistical calculations for the meta-analyses were done using Review Manager 5.2. The meta-analyses showed significant effects of school re-entry programmes in terms of enhancing academic achievement in children with cancer (P = 0.008) and lowering their levels of depression (P = 0.05). Increased knowledge among classmates was associated with less fear and a more positive attitude towards the child with cancer. Due to limited numbers of patients, lack of control groups, and the diversity of intervention strategies used in previous studies, there is a need for intervention programmes exploring the optimal path for the reintegration of children with cancer into the education system and into their peer groups.

Hyperbaric oxygen for neurologic indications--action plan for multicenter trials in: stroke, traumatic brain injury, radiation encephalopathy & status migrainosus.

The 2008 Toronto Hyperbaric Medicine Symposium was convened to discuss research into neurologic indications for hyperbaric oxygen therapy (HBO2T). Four topics were particularly addressed: acute ischemic stroke; acute traumatic brain injury; brain radiation necrosis; and status migrainosus. Four multicenter trials were designed and proposed to evaluate the efficacy of HBO2T for these indications and are presented here in addition to brief reviews of the rationale behind each.

Erythropoietin in thyroid cancer.

Erythropoietin (Epo) and the epo-receptor (EpoR) have been implicated in tumor growth, invasion and metastasis. We previously demonstrated Epo and EpoR expression in a small group of archived papillary thyroid cancers (PTC), but were unable to examine functional integrity using formalin-fixed tissues. In the present study, we examined the in vitro expression, induction and function of Epo and EpoR in papillary (NPA), follicular (WRO) and anaplastic (ARO-81) thyroid cancer cells. We found that all three cell lines expressed Epo and EpoR mRNA and that the hypoxia-mimetic cobalt induced Epo expression in all cell lines. None of the growth factors we examined (thyrotropin, vascular endothelial growth factor, IGF-I, or human Epo) altered Epo or EpoR gene expression. Importantly, however, administration of Epo to NPA but not WRO cells resulted in significant alterations in the expression of several mitogenic genes including cyclooxygenase-2 (COX-2), beta-casein (CSN2), wild type p53-induced gene-1 (WIG1) and cathepsin D (CTSD). Epo treated ARO-81 cells only had an increase in CSN2 expression. We conclude that Epo and EpoR are expressed by thyroid cancers and that stimulation of the Epo/EpoR signal pathway results in changes that could impact on the clinical behavior of thyroid cancers.

Standardized protocols increase organ and tissue donation rates in the neurocritical care unit.

The authors tested the effect of uncoupling and removal of the treating physician from organ and tissue donation requests on consent rates for donation in the neurocritical care unit. After a neurointensivist-led policy change, consent rates increased from 23.1 to 36.5% (odds ratio = 1.9, p = 0.01), whereas there was no change in other hospital units. This supports such a policy change and shows a positive effect of a neurointensivist on organ and tissue procurement.

Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis.

In a search for genes expressed by dendritic cells (DC), we have cloned cDNAs encoding different forms of an asialoglycoprotein receptor (ASGPR). The DC-ASGPR represents long and short isoforms of human macrophage lectin, a Ca(2+)-dependent type II transmembrane lectin displaying considerable homology with the H1 and H2 subunits of the hepatic ASGPR. Immunoprecipitation from DC using an anti-DC-ASGPR mAb yielded a major 40-kDa protein with an isoelectric point of 8.2. DC-ASGPR mRNA was observed predominantly in immune tissues. Both isoforms were detected in DC and granulocytes, but not in T, B, or NK cells, or monocytes. DC-ASGPR species were restricted to the CD14-derived DC obtained from CD34(+) progenitors, while absent from the CD1a-derived subset. Accordingly, both monocyte-derived DC and tonsillar interstitial-type DC expressed DC-ASGPR protein, while Langerhans-type cells did not. Furthermore, DC-ASGPR is a feature of immaturity, as expression was lost upon CD40 activation. In agreement with the presence of tyrosine-based and dileucine motifs in the intracytoplasmic domain, mAb against DC-ASGPR was rapidly internalized by DC at 37 degrees C. Finally, intracellular DC-ASGPR was localized to early endosomes, suggesting that the receptor recycles to the cell surface following internalization of ligand. Our findings identify DC-ASGPR/human macrophage lectin as a feature of immature DC, and as another lectin important for the specialized Ag-capture function of DC.

Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons.

Distinct classes of neurons are generated from progenitor cells distributed in characteristic dorsoventral patterns in the developing spinal neural tube. We define restricted neural progenitor populations by the discrete, nonoverlapping expression of Ngn1, Math1, and Mash1. Crossinhibition between these bHLH factors is demonstrated and provides a mechanism for the generation of discrete bHLH expression domains. This precise control of bHLH factor expression is essential for proper neural development since as demonstrated in both loss- and gain-of-function experiments, expression of Math1 or Ngn1 in dorsal progenitor cells determines whether LH2A/B- or dorsal Lim1/2-expressing interneurons will develop. Together, the data suggest that although Math1 and Ngn1 appear to be redundant with respect to neurogenesis, they have distinct functions in specifying neuronal subtype in the dorsal neural tube.

Overexpression of MATH1 disrupts the coordination of neural differentiation in cerebellum development.

An essential role for the bHLH transcription factor MATH1 in the formation of cerebellar granule cells was previously demonstrated in a Math1 null mouse. The function of regulated levels of MATH1 in granule cell development is investigated here using a gain-of-function paradigm. Overexpression of Math1 in its normal domain in transgenic mice leads to early postnatal lethality and perturbs cerebellar development. The cerebellum of the (B)MATH1 transgenic neonate is smaller with less foliation, particularly in the central vermal regions, when compared to wild-type cerebella. A detailed analysis of multiple molecular markers in brains overexpressing Math1 has revealed defects in the differentiation of cerebellar granule cells. NeuroD and doublecortin, markers normally distinguishing the discrete layered organization of granule cell maturation in the inner EGL, are aberrantly expressed in the outer EGL where MATH1-positive, proliferating cells reside. In contrast, TAG-1, a later marker of developing granule cells that labels parallel fibers, is severely diminished. The elevated MATH1 levels appear to drive expression of a subset of early differentiation markers but are insufficient for development of a mature TAG-1-expressing granule cell. Thus, balanced levels of MATH1 are essential for the correct coordination of differentiation events in granule cell development.

Self-organized patterning of an insulator-on-metal system by surface faceting and selective growth: NaCl/Cu(211)

We report experimental results on an insulator-on-metal system which is inherently unstable against lateral pattern formation on the nanometer scale. NaCl deposition on Cu(211) at substrate temperatures >300 K leads to faceting into (311) and (111) facets and selective NaCl growth on (311) facets only, thereby creating alternating stripes of bare Cu and NaCl-covered areas. The mesoscopic restructuring process is brought about by (1) the tendency to form (100)-terminated NaCl layers, (2) epitaxial matching between NaCl(100) and Cu(311), and (3) sufficient mobility of the Cu substrate surface.

Autoregulation and multiple enhancers control Math1 expression in the developing nervous system.

Development of the vertebrate nervous system requires the actions of transcription factors that establish regional domains of gene expression, which results in the generation of diverse neuronal cell types. MATH1, a transcription factor of the bHLH class, is expressed during development of the nervous system in multiple neuronal domains, including the dorsal neural tube, the EGL of the cerebellum and the hair cells of the vestibular and auditory systems. MATH1 is essential for proper development of the granular layer of the cerebellum and the hair cells of the cochlear and vestibular systems, as shown in mice carrying a targeted disruption of Math1. Previously, we showed that 21 kb of sequence flanking the Math1-coding region is sufficient for Math1 expression in transgenic mice. Here we identify two discrete sequences within the 21 kb region that are conserved between mouse and human, and are sufficient for driving a lacZ reporter gene in these domains of Math1 expression in transgenic mice. The two identified enhancers, while dissimilar in sequence, appear to have redundant activities in the different Math1 expression domains except the spinal neural tube. The regulatory mechanisms for each of the diverse Math1 expression domains are tightly linked, as separable regulatory elements for any given domain of Math1 expression were not found, suggesting that a common regulatory mechanism controls these apparently unrelated domains of expression. In addition, we demonstrate a role for autoregulation in controlling the activity of the Math1 enhancer, through an essential E-box consensus binding site.

Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic cells.

We describe a new cystatin in both mice and humans, which we termed leukocystatin. This protein has all the features of a Class II secreted inhibitory cystatin but contains lysine residues in the normally hydrophobic binding regions. As determined by cDNA library Southern blots, this cystatin is expressed selectively in hematopoietic cells, although fine details of the distribution among these cell types differ between the human and mouse mRNAs. In addition, we have determined the genomic organization of mouse leukocystatin, and we found that in contrast to most cystatins, the leukocystatin gene contains three introns. The recombinant proteins corresponding to these cystatins were expressed in Escherichia coli as N-terminal glutathione S-transferase or FLAGTM fusions, and studies showed that they inhibited papain and cathepsin L but with affinities lower than other cystatins. The unique features of leukocystatin suggests that this cystatin plays a role in immune regulation through inhibition of a unique target in the hematopoietic system.

Progenitors of dorsal commissural interneurons are defined by MATH1 expression.

MATH1 is a neural-specific basic helix-loop-helix transcription factor. Members of this family of transcription factors are involved in the development of specific subsets of neurons in the developing vertebrate nervous system. Here we examine the cells expressing MATH1 with respect to their proliferative state and co-expression of cell-type-specific differentiation markers. We localize the MATH1 protein to the nucleus of cells in the dorsal neural tube and the external germinal layer (EGL) of the developing cerebellum. Using double-label immunofluorescence, we demonstrate that MATH1-expressing cells span both the proliferating and the differentiating zones within the dorsal neural tube, but within the EGL of the cerebellum are restricted to the proliferating zone. The early differentiating MATH1-expressing cells in the dorsal neural tube co-express TAG-1, DCC-1 and LH2, markers of dorsal commissural interneurons. In addition, transgenic mice with lacZ under the transcriptional control of MATH1-flanking DNA sequences express beta-galactosidase specifically in the developing nervous system, in a manner that mimics subsets of the MATH1-expression pattern, including the dorsal spinal neural tube. Expression of the MATH1/lacZ transgene persists in differentiated dorsal commissural interneurons. Taken together, we demonstrate MATH1 expression in a differentiating population of neuronal precursors in the dorsal neural tube that appear to give rise specifically to dorsal commissural interneurons.

Characterization of a novel CC chemokine, HCC-4, whose expression is increased by interleukin-10.

We have identified and characterized a human beta (CC) chemokine, designated HCC-4, that is most closely related to HCC-1 and which demonstrates chemotactic activity for monocytes. Northern analysis of multiple tissue blots and of activated monocytes mRNA shows expression of a 500-bp mRNA. A 1,500-bp mRNA was highly expressed in monocytes activated 12 hours in the presence of interleukin-10 (IL-10) but was absent in monocytes activated for only 1 hour regardless of the presence or absence of IL-10. The upregulation of expression in the presence of IL-10 is in contrast to the downregulatory effects of IL-10 on expression of most other chemokines. Recombinant HCC-4 demonstrated chemotactic activity for human monocytes and THP-1 monocyte cells but not for resting lymphocytes or neutrophils. HCC-4 also induced a Ca2+ flux in THP-1 cells that was desensitized by prior exposure to RANTES. Taken together, these data indicate that HCC-4 is a novel chemokine whose expression is uniquely upregulated by IL-10.

XATH-1, a vertebrate homolog of Drosophila atonal, induces a neuronal differentiation within ectodermal progenitors.

XATH-1, a basic/helix-loop-helix transcription factor and a homolog of Drosophila atonal and mammalian MATH-1, is expressed specifically in the dorsal hindbrain during Xenopus neural development. In order to investigate the role of XATH-1 in the neuronal differentiation process, we have examined the effects of XATH-1 overexpression during Xenopus development. XATH-1 induces the expression of neuronal differentiation markers, such as N-tubulin, within the neural plate as well as within nonneural ectodermal progenitor populations, resulting in the appearance of process-bearing neurons within the epidermis. The related basic/helix-loop-helix genes neurogenin-related-1 and neuroD are not induced in response to XATH-1 overexpression within the embryo, suggesting that XATH-1 may activate an alternate pathway of neuronal differentiation. In further contrast to neurogenin-related-1 and neuroD, high-level expression of general neural markers expressed earlier in development, such as N-CAM, is not induced by XATH-1 overexpression. Competent ectodermal progenitors therefore respond to ectopic XATH-1 expression by initiating a distinct program of neuronal differentiation.

Protein energy malnutrition and its recognition in outpatient departments in Venda hospitals.

Between April and June 1988 the number of children under 5 years old attending outpatient departments of Venda hospitals who had protein energy malnutrition (PEM) was determined, the proportions at 3 Venda hospitals were compared, and what percentage of these children was detected by attendant health workers was determined. Approximately 6% had severe PEM; this finding was consistent for all 3 hospitals. The rates for mild PEM were 22% for Tshilidzini and Donald Fraser Hospitals and 33% for Siloam Hospital. This statistically significant difference has not been explained. Health workers failed to recognise about 25% of children with severe PEM and 50% of children with mild PEM. It is suggested that certain interventions and activities are essential if PEM is to be adequately managed: these are efficient monitoring; pre-employment and in-service education for health workers; a breast-feeding and weaning survey; and an investigation of the variation of malnutrition among Venda hospitals.

Tomato-Flavored Beverage and Onion-Flavored Chip Dip Made from Cottage Cheese Whey.

Whey from cottage cheese made by the short-set culture method was used to make tomato-flavored drink by addition of 6% dried tomato-spice flavoring material, and was found by 10 panelists to have a pleasing taste. Heat treatment of cottage cheese whey at 93 to 99 C resulted in a precipitate containing over 9% total solids. This precipitate was further concentrated by centrifugation or filtration through a cotton cloth. The precipitates were blended with xanthan gum and onion-flavoring to produce a chip dip.