Integrating the perspectives of individuals with spinal cord injuries, their family caregivers and healthcare professionals from the time of rehabilitation admission to community reintegration: protocol for a scoping study on SCI needs.

INTRODUCTION: There is fragmented information about the different needs following a spinal cord injury (SCI). Expressed SCI needs can be met or unmet, they change along the rehabilitation continuum (eg, acute, rehabilitation and reintegration into the community) and can be different for traumatic and non traumatic SCI. The general objective of this scoping study is to evaluate and integrate the needs of individuals with traumatic and non-traumatic SCI, their family caregivers and those reported by rehabilitation professionals from the time of rehabilitation admission to community reintegration. The specific objectives are to: (A) synthesise the needs of individuals with SCI as perceived by themselves, their family caregivers and rehabilitation professionals using two theoretical models, (B) classify needs as met and unmet, (C) explore the evolution of met/unmet needs from the time of rehabilitation admission to community reintegration and (D) provide recommendations to improve SCI care. METHODS AND ANALYSIS: (A) identifying the most frequent met and unmet needs reported by adults with traumatic and non-traumatic SCI, their family caregivers and their rehabilitation professionals from the time of rehabilitation admission to community reintegration; (B) identifying relevant studies with a search in electronic databases; (C) charting the data based on categories refined and adjusted with a stakeholder group; (D) collating, summarising and reporting the results using two analytical frameworks (Maslow's hierarchical model of human needs and the Ferrans et al's model of health-related quality of life) and (E) a stakeholder consultation phase. ETHICS AND DISSEMINATION: The results of this scoping study will allow understanding SCI needs from the time of rehabilitation admission to community reintegration from the perspective of different stakeholders. An integrated master report combining the needs of individuals with SCI from the perspectives of different stakeholders from the time of rehabilitation admission to community reintegration will follow the consultation meetings.

Common variants of the glial cell-derived neurotrophic factor gene do not influence kidney size of the healthy newborn.

Glial cell-derived neurotrophic factor (GDNF) plays an important role in renal development, serving as a trophic factor for outgrowth of the ureteric bud and its continued arborisation. Our previous studies have shown that common variants of the human paired-box 2 (PAX2) gene (a transcriptional activator of GDNF) and rearranged during transfection (RET) gene (encoding the cognate receptor for GDNF) are associated with a subtle reduction in the kidney size of newborns. Since heterozygosity for a mutant GDNF allele causes mild renal hypoplasia and modest hypertension in mice, we considered the possibility that common variants of the GDNF gene might also contribute to renal hypoplasia in humans. We studied the relationship between newborn renal size or umbilical cord cystatin C and 19 common GDNF gene variants [minor allele frequency (MAF) >5%], three single nucleotide polymorphisms (SNPs) related to a putative PAX binding site and one rare SNP (rs36119840 A/G) which changes an amino acid (R93W), based on data from the haplotype map of the human genome (HapMap). However, none of these 23 SNPs was associated with reduced newborn kidney size or function. Among the 163 Caucasians in our cohort, none had the R93W allele.

A common RET variant is associated with reduced newborn kidney size and function.

Congenital nephron number varies five-fold among normal humans, and individuals at the lower end of this range may have an increased lifetime risk for essential hypertension or renal insufficiency; however, the mechanisms that determine nephron number are unknown. This study tested the hypothesis that common hypomorphic variants of the RET gene, which encodes a tyrosine kinase receptor critical for renal branching morphogenesis, might account for subtle renal hypoplasia in some normal newborns. A common single-nucleotide polymorphism (rs1800860 G/A) was identified within an exonic splicing enhancer in exon 7. The adenosine variant at mRNA position 1476 reduced affinity for spliceosome proteins, enhanced the likelihood of aberrant mRNA splicing, and diminished the level of functional transcript in human cells. In vivo, normal white newborns with an rs1800860(1476A) allele had kidney volumes 10% smaller and cord blood cystatin C levels 9% higher than those with the rs1800860(1476G) allele. These findings suggest that the RET(1476A) allele, in combination with other common polymorphic developmental genes, may account for subtle renal hypoplasia in a significant proportion of the white population. Whether this gene variant affects clinical outcomes requires further study.

A common variant of the PAX2 gene is associated with reduced newborn kidney size.

Congenital nephron number ranges widely in the human population. Suboptimal nephron number may be associated with increased risk for essential hypertension and susceptibility to renal injury, but the factors that set nephron number during kidney development are unknown. In renal-coloboma syndrome, renal hypoplasia and reduced nephron number are due to heterozygous mutations of the PAX2 gene. This study tested for an association between a common haplotype of the PAX2 gene and subtle renal hypoplasia in normal newborns. A PAX2 haplotype was identified to occur in 18.5% of the newborn cohort, which was significantly associated with a 10% reduction in newborn kidney volume adjusted for body surface area. This haplotype was also associated with reduced allele-specific PAX2 mRNA level in a human renal cell carcinoma cell line. Subtle renal hypoplasia in normal newborns may be partially due to a common variant of the PAX2 gene that reduces mRNA expression during kidney development.

Effects of maternal vitamin A status on kidney development: a pilot study.

Nephron endowment ranges widely in normal human populations. Recent autopsy studies have drawn attention to the possibility that subtle congenital nephron deficits may be associated with increased risk of developing hypertension later in life. Since modest maternal vitamin A deficiency reduces nephron number in rats, we designed a pilot study to determine the prevalence of maternal vitamin A deficiency in Montreal (Canada) and Bangalore (India) and the usefulness of newborn renal volume as a surrogate for nephron endowment. Among 48 pregnant Montreal women, two (4%) had one isolated mid-gestation retinol level slightly below the accepted limit of normal (0.9 mumol/L), whereas 25 (55%) of 46 pregnant women in Bangalore had at least one sample below this limit. Average estimated retinoid intake was correlated with mean serum retinol in pregnant women from Bangalore. In Montreal where maternal vitamin A deficiency was negligible, we found that newborn renal volume (estimated by renal ultrasonography at 2-6 weeks of age) was correlated with surface area at birth and was inversely correlated with serum creatinine at 1 month. Interestingly, renal volume adjusted for body surface area in Montreal (184+/-44 ml/m(2)) was significantly greater than in Bangalore (114+/-33 ml/m(2)) (p<0.01). Definitive studies are needed to establish whether maternal vitamin A deficiency accounts for subtle renal hypoplasia in Indian newborns. If so, there may be important public health implications for regions of the world where maternal vitamin A deficiency is prevalent.