Counting the Cost of Diabetes in the Solomon Islands and Nauru

Aim

To determine the costs associated with diabetes to governments, people with diabetes and their carers, and its impact on quality of life in two Pacific Island countries—the Solomon Islands and Nauru.

Materials and Methods

This cross-sectional cost of illness study was conducted on 330 people with type 2 diabetes (197 from the Solomon Islands and 133 from Nauru) using a structured cost of illness survey questionnaire adapted from the Australian DiabCo$t study. Quality of life was measured by the EQ-5D Visual Analogue Scale.

Results

There were 330 respondents (50% female; mean duration of diabetes 10.9 years; mean age 52.6 years). The estimated annual national cost of diabetes incurred by the Solomon Islands government was AUD12.8 million (AUD281 per person/year) and by Nauru government was AUD1.2 million (AUD747 per person/year). The major contribution to the government costs was inpatient services cost (71% in the Solomon Islands and 83% in Nauru). Annual expenditure for diabetes was approximately 20% of the governments’ annual health care expenditure. Considerable absenteeism and retirement from work due to diabetes was found.

Conclusions

This study found substantial public and personal costs associated with diabetes. The findings provide objective data on which health policy, funding and planning decisions about the prevention and control of diabetes in the Solomon Islands and Nauru can be reliably based and subsequently evaluated.     

A modified static respiration assay and its relationship with an enzymatic test to assess compost stability and maturity

Despite the numerous compost stability and maturity tests, no universally accepted compost stability or maturity index exists. The fluorescein di-acetate (FDA) enzymatic assay, originating from soil studies, is examined here as a potential new compost stability test, and is compared to microbial respiration and phytotoxicity indices. Thirteen composts were used in the study from different source materials. Static microbial respiration activity indices calculated were the cumulative O₂ consumptions, O₂ consumption rates, total C-CO₂ production, the respiratory quotient and the bio C/N ratio. Compost phytotoxicity was quantified via a 7-day tomato seed germination assay. Results showed that the net fluorescein release rates correlated with all stability indices. The germination index marginally correlated with the fluorescein release rates, but not with any of the other stability indices. New limits to classify composts regarding their stability were proposed.     

Haloarchaeal myovirus φCh1 harbours a phase variation system for the production of protein variants with distinct cell surface adhesion specificities

The φCh1 myovirus, which infects the haloalkaliphilic archaeon Natrialba magadii, contains an invertible region that comprises the convergent open reading frames (ORFs) 34 and 36, which code for the putative tail fibre proteins gp34 and gp36 respectively. The inversion leads to an exchange of the C-termini of these proteins, thereby creating different types of tail fibres. Gene expression experiments revealed that only ORF34 is transcribed, indicating that φCh1 produces tail fibre proteins exclusively from this particular ORF. Only one of the two types of tail fibres encoded by ORF34 is able to bind to Nab. magadii in vitro. This is reflected by the observation that during the early phases of the infection cycle, the lysogenic strain L11 carries its invertible region exclusively in the orientation that produces that specific type of tail fibre. Obviously, Nab. magadii can only be infected by viruses carrying this particular type of tail fibre. By mutational analysis, the binding domain of gp34 was localized to the C-terminal part of the protein, particularly to a galactose-binding domain. The involvement of galactose residues in cell adhesion was supported by the observation that the addition of α-D-galactose to purified gp34 or whole virions prevented their attachment to Nab. magadii.     

Screening of MAMLD1 mutations in 70 children with 46,XY DSD: identification and functional analysis of two new mutations

More than 50% of children with severe 46,XY disorders of sex development (DSD) do not have a definitive etiological diagnosis. Besides gonadal dysgenesis, defects in androgen biosynthesis, and abnormalities in androgen sensitivity, the Mastermind-like domain containing 1 (MAMLD1) gene, which was identified as critical for the development of male genitalia, may be implicated. The present study investigated whether MAMLD1 is implicated in cases of severe 46,XY DSD and whether routine sequencing of MAMLD1 should be performed in these patients.Seventy children with severe non-syndromic 46,XY DSD of unknown etiology were studied. One hundred and fifty healthy individuals were included as controls. Direct sequencing of the MAMLD1, AR, SRD5A2 and NR5A1 genes was performed. The transactivation function of the variant MAMLD1 proteins was quantified by the luciferase method.TWO NEW MUTATIONS WERE IDENTIFIED: p.S143X (c.428C>A) in a patient with scrotal hypospadias with microphallus and p.P384L (c.1151C>T) in a patient with penile hypospadias with microphallus. The in vitro functional study confirmed no residual transactivating function of the p.S143X mutant and a significantly reduced transactivation function of the p.P384L protein (p = 0.0032). The p.P359S, p.N662S and p.H347Q variants are also reported with particularly high frequency of the p.359T- p.662G haplotype in the DSD patients.Severe undervirilization in XY newborns can reveal mutations of MAMLD1. MAMLD1 should be routinely sequenced in these patients with otherwise normal AR, SRD5A2 and NR5A1genes.     

Phenotypic switch of smooth muscle cells in paediatric chronic intestinal pseudo-obstruction syndrome

Smooth Muscle Cells (SMC) are unique amongst all muscle cells in their capacity to modulate their phenotype. Indeed, SMCs do not terminally differentiate but instead harbour a remarkable capacity to dedifferentiate, switching between a quiescent contractile state and a highly proliferative and migratory phenotype, a quality often associated to SMC dysfunction. However, phenotypic plasticity remains poorly examined in the field of gastroenterology in particular in pathologies in which gut motor activity is impaired. Here, we assessed SMC status in biopsies of infants with chronic intestinal pseudo-obstruction (CIPO) syndrome, a life-threatening intestinal motility disorder. We showed that CIPO-SMCs harbour a decreased level of contractile markers. This phenotype is accompanied by an increase in Platelet-Derived Growth Factor Receptor-alpha (PDGFRA) expression. We showed that this modulation occurs without origin-related differences in CIPO circular and longitudinal-derived SMCs. As we characterized PDGFRA as a marker of digestive mesenchymal progenitors during embryogenesis, our results suggest a phenotypic switch of the CIPO-SMC towards an undifferentiated stage. The development of CIPO-SMC culture and the characterization of SMC phenotypic switch should enable us to design therapeutic approaches to promote SMC differentiation in CIPO.     

K-Cl cotransporter gene expression during human and murine erythroid differentiation

The K-Cl cotransporter (KCC) regulates red blood cell (RBC) volume, especially in reticulocytes. Western blot analysis of RBC membranes revealed KCC1, KCC3, and KCC4 proteins in mouse and human cells, with higher levels in reticulocytes. KCC content was higher in sickle versus normal RBC, but the correlation with reticulocyte count was poor, with inter-individual variability in KCC isoform ratios. Messenger RNA for each isoform was measured by real time RT-quantitative PCR. In human reticulocytes, KCC3a mRNA levels were consistently the highest, 1-7-fold higher than KCC4, the second most abundant species. Message levels for KCC1 and KCC3b were low. The ratios of KCC RNA levels varied among individuals but were similar in sickle and normal RBC. During in vivo maturation of human erythroblasts, KCC3a RNA was expressed consistently, whereas KCC1 and KCC3b levels declined, and KCC4 message first increased and then decreased. In mouse erythroblasts, a similar pattern for KCC3 and KCC1 expression during in vivo differentiation was observed, with low KCC4 RNA throughout despite the presence of KCC4 protein in mature RBC. During differentiation of mouse erythroleukemia cells, protein levels of KCCs paralleled increasing mRNA levels. Functional properties of KCCs expressed in HEK293 cells were similar to each other and to those in human RBC. However, the anion dependence of KCC in RBC resembled most closely that of KCC3. The results suggest that KCC3 is the dominant isoform in erythrocytes, with variable expression of KCC1 and KCC4 among individuals that could result in modulation of KCC activity.     

Identification of a Murine Erythroblast Subpopulation Enriched in Enucleating Events by Multi-spectral Imaging Flow Cytometry

Erythropoiesis in mammals concludes with the dramatic process of enucleation that results in reticulocyte formation. The mechanism of enucleation has not yet been fully elucidated. A common problem encountered when studying the localization of key proteins and structures within enucleating erythroblasts by microscopy is the difficulty to observe a sufficient number of cells undergoing enucleation. We have developed a novel analysis protocol using multiparameter high-speed cell imaging in flow (Multi-Spectral Imaging Flow Cytometry), a method that combines immunofluorescent microscopy with flow cytometry, in order to identify efficiently a significant number of enucleating events, that allows to obtain measurements and perform statistical analysis.We first describe here two in vitro erythropoiesis culture methods used in order to synchronize murine erythroblasts and increase the probability of capturing enucleation at the time of evaluation. Then, we describe in detail the staining of erythroblasts after fixation and permeabilization in order to study the localization of intracellular proteins or lipid rafts during enucleation by multi-spectral imaging flow cytometry. Along with size and DNA/Ter119 staining which are used to identify the orthochromatic erythroblasts, we utilize the parameters “aspect ratio” of a cell in the bright-field channel that aids in the recognition of elongated cells and “delta centroid XY Ter119/Draq5” that allows the identification of cellular events in which the center of Ter119 staining (nascent reticulocyte) is far apart from the center of Draq5 staining (nucleus undergoing extrusion), thus indicating a cell about to enucleate. The subset of the orthochromatic erythroblast population with high delta centroid and low aspect ratio is highly enriched in enucleating cells.     

Replication and Predictive Value of SNPs Associated with Melanoma and Pigmentation Traits in a Southern European Case-Control Study

Background

Genetic association studies have revealed numerous polymorphisms conferring susceptibility to melanoma. We aimed to replicate previously discovered melanoma-associated single-nucleotide polymorphisms (SNPs) in a Greek case-control population, and examine their predictive value.

Methods

Based on a field synopsis of genetic variants of melanoma (MelGene), we genotyped 284 patients and 284 controls at 34 melanoma-associated SNPs of which 19 derived from GWAS. We tested each one of the 33 SNPs passing quality control for association with melanoma both with and without accounting for the presence of well-established phenotypic risk factors. We compared the risk allele frequencies between the Greek population and the HapMap CEU sample. Finally, we evaluated the predictive ability of the replicated SNPs.

Results

Risk allele frequencies were significantly lower compared to the HapMap CEU for eight SNPs (rs16891982 – SLC45A2, rs12203592 – IRF4, rs258322 – CDK10, rs1805007 – MC1R, rs1805008 - MC1R, rs910873 - PIGU, rs17305573- PIGU, and rs1885120 - MTAP) and higher for one SNP (rs6001027 – PLA2G6) indicating a different profile of genetic susceptibility in the studied population. Previously identified effect estimates modestly correlated with those found in our population (r = 0.72, P<0.0001). The strongest associations were observed for rs401681-T in CLPTM1L (odds ratio [OR] 1.60, 95% CI 1.22–2.10; P = 0.001), rs16891982-C in SCL45A2 (OR 0.51, 95% CI 0.34–0.76; P = 0.001), and rs1805007-T in MC1R (OR 4.38, 95% CI 2.03–9.43; P = 2×10⁻⁵). Nominally statistically significant associations were seen also for another 5 variants (rs258322-T in CDK10, rs1805005-T in MC1R, rs1885120-C in MYH7B, rs2218220-T in MTAP and rs4911442-G in the ASIP region). The addition of all SNPs with nominal significance to a clinical non-genetic model did not substantially improve melanoma risk prediction (AUC for clinical model 83.3% versus 83.9%, p = 0.66).

Conclusion

Overall, our study has validated genetic variants that are likely to contribute to melanoma susceptibility in the Greek population.     

Traumatisme du testicule chez l’enfant

Introduction

The testicular trauma is uncommon in children and the literature about this topic is very poor. The aim was to investigate the testicular trauma in children from a retrospective study.

Materials and methods

All the French pediatric surgical departments were requested to send their cases of testicular trauma reported between 2000 and 2009. The analysis was performed from the data and the operative report. Isolated scrotal wounds, testicular torsions revealed by trauma, and incomplete files were excluded.

Results

Fifteen departments sent their data and 2 had no cases. From 60 cases, 15 were excluded and 45 selected. The mean age was 12.3 years (2 days–18 years). The circumstances of the trauma were 23 knocks (foot, knee, and fist), 13 falls, 4 motorcycle accidents, 4 unknown traumas, and 1 obstetrical trauma. There were 4 wounds and 41 without wound. A color Doppler sonography was performed in 34 cases (75.5%) with an accurate diagnosis in 30 cases; 2 testicular fractures and 1 intratesticular hematoma were not confirmed at surgery, and 1 epididymal hematoma was not seen on sonography. The lesions were testicular fractures (15), intratesticular hematomas (8), benign testicular blunt traumas (6), spermatic cord hematomas (6), epididymal hematomas (6), isolated hematoceles (3), and avulsion (1). Surgical treatment was done in 33 children and 12 had nonoperative treatment. Among the 15 testicular fractures, 13 were operated (8 sutures and 5 partial orchidectomies) and 2 were only observed. For the intratesticular hematomas, a surgical treatment was performed in 5 children and a nonoperative treatment in 3, with a good evolution. Only 20 children were controlled beyond 4 months, especially the testicular fractures and no secondary testicular atrophy was seen.

Conclusion

The testicular trauma in children is rare and the prognosis is rather good. The color Doppler sonography now allows a good diagnosis in most cases and the surgery can be often avoided in benign blunt trauma. In this situation, it is important to repeat sonography 24 or 48 hours after trauma to ensure there is no fracture or other lesion necessitating a surgical treatment.