How predictive of future healthcare utilisation and mortality is data-driven population segmentation based on healthcare utilisation and chronic condition comorbidity?

BACKGROUND: In recent years data-driven population segmentation using cluster analyses of mainly health care utilisation data has been used as a proxy of future health care need. Chronic conditions patterns tended to be examined after segmentation but may be useful as a segmentation variable which, in combination with utilisation could indicate severity. These could further be of practical use to target specific clinical groups including for prevention. This study aimed to assess the ability of data-driven segmentation based on health care utilisation and comorbidities to predict future outcomes: Emergency admission, A&E attendance, GP practice contacts, and mortality. METHODS: We analysed record-linked data for 412,997 patients registered with GP practices in 2018-19 in Cwm Taf Morgannwg University Health Board (CTM UHB) area within the Secure Anonymised Information Linkage (SAIL) Databank. We created 10 segments using k-means clustering based on utilisation (GP practice contacts, prescriptions, emergency and elective admissions, A&E and outpatients) and chronic condition counts for 2018 using different variable compositions to denote need. We assessed the characteristics of the segments. We employed a train/test scheme (80% training set) to compare logistic regression model predictions with observed outcomes on follow-up in 2019. We assessed the area under the ROC curve (AUC) for models with demographic variables, with and without the segments, as well as between segmentation implementations (with/without comorbidity and primary care data). RESULTS: Adding the segments to the model with demographic covariates improved the prediction for all outcomes. For emergency admissions this increased discrimination from AUC 0.65 (CI 0.64-0.65) to 0.73 (CI 0.73-0.74). Models with the segments only performed nearly as well as the full models. Excluding comorbidity showed reduced predictive ability for mortality (similar otherwise) but most pronounced reduction when excluding all primary care variables. CONCLUSIONS: This shows that the segments have satisfactory predictive ability, even for varied outcomes and a broad range of events and conditions used in the segmentation. It suggests that the segments can be a useful tool in helping to identify specific groups of need to target with anticipatory care. Identification may be refined with selected diagnoses or more specialised tools such as risk stratification.

Demographic and socioeconomic patterns in the risk of alcohol-related hospital admission in children and young adults with childhood onset type-1 diabetes from a record-linked longitudinal population cohort study in Wales.

BACKGROUND: Little is known about alcohol-related harm in children and young adults with type 1 diabetes (T1D). Education on managing alcohol intake is provided to teenagers with T1D in paediatric clinics in Wales, but its effectiveness is unknown. We compared the patterns in risk of alcohol-related hospital admissions (ARHA) between individuals with and without childhood-onset T1D. METHODS: We extracted data for 1 791 577 individuals born during 1979 to 2014 with a general practitioner registration in Wales, and record-linked the demographic data to ARHA between 1998 and June 2016 within the Secure Anonymised Information Linkage Databank (SAIL). Linkage to a national T1D register (Brecon Cohort) identified 3575 children diagnosed aged <15 years since 1995. We estimated hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the risk of ARHA using recurrent-event models, including interaction terms. RESULTS: Individuals with T1D had a higher riskof ARHA (HR: 1.78; 95% CI: 1.60-1.98), adjusted for age group, sex, and deprivation. The risk in people with diabetes was highest aged 14 to 17 years, around three times higher than the peak in non-T1D aged 18 to 22. Females with diabetes had a lower risk generally. The association between deprivation and ARHA was weaker in the T1D group. CONCLUSION: Young people with T1D had increased risks of ARHA, particularly at school age, and smaller socioeconomic inequalities in ARHA. A review of interventions to reduce alcohol-related harm in T1D is needed, perhaps including modification of current education and guidance for teenagers on managing alcohol consumption and reviewing criteria for hospital admission.

Drinking beer, wine or spirits - does it matter for inequalities in alcohol-related hospital admission? A record-linked longitudinal study in Wales.

BACKGROUND: Alcohol-related harm has been found to be higher in disadvantaged groups, despite similar alcohol consumption to advantaged groups. This is known as the alcohol harm paradox. Beverage type is reportedly socioeconomically patterned but has not been included in longitudinal studies investigating record-linked alcohol consumption and harm. We aimed to investigate whether and to what extent consumption by beverage type, BMI, smoking and other factors explain inequalities in alcohol-related harm. METHODS: 11,038 respondents to the Welsh Health Survey answered questions on their health and lifestyle. Responses were record-linked to wholly attributable alcohol-related hospital admissions (ARHA) eight years before the survey month and until the end of 2016 within the Secure Anonymised Information Linkage (SAIL) Databank. We used survival analysis, specifically multi-level and multi-failure Cox mixed effects models, to calculate the hazard ratios of ARHA. In adjusted models we included the number of units consumed by beverage type and other factors, censoring for death or moving out of Wales. RESULTS: People living in more deprived areas had a higher risk of admission (HR 1.75; 95% CI 1.23-2.48) compared to less deprived. Adjustment for the number of units by type of alcohol consumed only reduced the risk of ARHA for more deprived areas by 4% (HR 1.72; 95% CI 1.21-2.44), whilst adding smoking and BMI reduced these inequalities by 35.7% (HR 1.48; 95% CI 1.01-2.17). These social patterns were similar for individual-level social class, employment, housing tenure and highest qualification. Inequalities were further reduced by including either health status (16.6%) or mental health condition (5%). Unit increases of spirits drunk were positively associated with increasing risk of ARHA (HR 1.06; 95% CI 1.01-1.12), higher than for other drink types. CONCLUSIONS: Although consumption by beverage type was socioeconomically patterned, it did not help explain inequalities in alcohol-related harm. Smoking and BMI explained around a third of inequalities, but lower socioeconomic groups had a persistently higher risk of (multiple) ARHA. Comorbidities also explained a further proportion of inequalities and need further investigation, including the contribution of specific conditions. The increased harms from consumption of stronger alcoholic beverages may inform public health policy.

Cell therapy with human MSCs isolated from the umbilical cord Wharton jelly associated to a PVA membrane in the treatment of chronic skin wounds.

The healing process of the skin is a dynamic procedure mediated through a complex feedback of growth factors secreted by a variety of cells types. Despite the most recent advances in wound healing management and surgical procedures, these techniques still fail up to 50%, so cellular therapies involving mesenchymal stem cells (MSCs) are nowadays a promising treatment of skin ulcers which are a cause of high morbidity. The MSCs modulate the inflammatory local response and induce cell replacing, by a paracrine mode of action, being an important cell therapy for the impaired wound healing. The local application of human MSCs (hMSCs) isolated from the umbilical cord Wharton's jelly together with a poly(vinyl alcohol) hydrogel (PVA) membrane, was tested to promote wound healing in two dogs that were referred for clinical examination at UPVET Hospital, showing non-healing large skin lesions by the standard treatments. The wounds were infiltrated with 1000 cells/µl hMSCs in a total volume of 100 µl per cm(2) of lesion area. A PVA membrane was applied to completely cover the wound to prevent its dehydration. Both animals after the treatment demonstrated a significant progress in skin regeneration with decreased extent of ulcerated areas confirmed by histological analysis. The use of Wharton's jelly MSCs associated with a PVA membrane showed promising clinical results for future application in the treatment of chronic wounds in companion animals and humans.

Isolation and characterisation of bacteria from the Eastern Mediterranean deep sea.

The Eastern Mediterranean deep sea is one of the most oligotrophic regions in the world's ocean. With the aim to classify bacteria from this special environment we isolated 107 strains affiliating to the Gammaproteobacteria, Alphaproteobacteria, Firmicutes, Actinobacteria and Bacteroidetes from sediments of the Eastern Mediterranean Sea. As determined by 16S rRNA gene sequence analysis, Actinobacteria and Firmicutes, in particular members of the genus Bacillus, were dominant and represented a remarkable diversity with 27 out of a total of 33 operational taxonomic units obtained from the untreated sediment. The considerable percentage of operational taxonomic units (42%) which may be considered to be new species underlines the uniqueness of the studied environment. In order to selectively enrich bacteria which are adapted to the deep-sea conditions and tolerate broad pressure ranges, enrichments were set up with a sediment sample under in situ pressure and temperature (28 MPa, 13.5°C) using N-acetyl-D: -glucosamine as substrate. Interestingly Gammaproteobacteria were significantly enriched and dominant among the strains isolated after pressure pre-incubation. Obviously, Gammaproteobacteria have a selective advantage under the enrichment conditions applied mimicking nutrient supply under pressure conditions and cope well with sudden changes of hydrostatic pressure. However, under the continued low nutrient situation in the Eastern Mediterranean deep-sea sediments apparently Firmicutes and Actinobacteria have a clear adaptative advantage.

Levantilides A and B, 20-membered macrolides from a Micromonospora strain isolated from the Mediterranean deep sea sediment.

Two new 20-membered macrolides, levantilide A and B, were isolated from the Micromonospora strain M71-A77. Strain M71-A77 was recovered from an Eastern Mediterranean deep-sea sediment sample and revealed to produce the levantilides under in situ salinity of 38.6 ‰. The chemical structures of the levantilides were elucidated on the basis of different one- and two- dimensional NMR experiments. Levantilide A exhibits a moderate antiproliferative activity against several tumor cell lines.

Effects of collagen membranes enriched with in vitro-differentiated N1E-115 cells on rat sciatic nerve regeneration after end-to-end repair.

Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat.

Mental health selection: common mental disorder and migration between multiple states of deprivation in a UK cohort.

OBJECTIVES: To assess whether the direction of movement along the social gradient was associated with changes in mental health status. DESIGN: Longitudinal record-linkage study using a multistate model. SETTING: Caerphilly, Wales, UK between 2001 and 2015. PARTICIPANTS: The analytical sample included 10 892 (60.8% female) individuals aged 18-74 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Deprivation change at lower super output area level using the 2008 Welsh Index of Multiple Deprivation. Mental health was assessed in 2001 and 2008 using the Mental Health Inventory subscale of the short-form 36 V.2. RESULTS: Mental health selection was shown whereby individuals with common mental health disorders were less likely to move to areas of lower deprivation but more likely to move to areas of greater deprivation. CONCLUSION: Poor mental health seems to drive health selection in a similar way to poor physical health. Therefore, funding targeted at areas of higher deprivation should consider the demand to be potentially higher as individuals with poor mental health may migrate into that area.

Tissue-associated "Candidatus Mycoplasma corallicola" and filamentous bacteria on the cold-water coral Lophelia pertusa (Scleractinia).

The cold-water coral Lophelia pertusa (Scleractinia, Caryophylliidae) is a key species in the formation of cold-water reefs, which are among the most diverse deep-sea ecosystems. It occurs in two color varieties: white and red. Bacterial communities associated with Lophelia have been investigated in recent years, but the role of the associated bacteria remains largely obscure. This study uses catalyzed reporter deposition fluorescence in situ hybridization to detect the in situ location of specific bacterial groups on coral specimens from the Trondheimsfjord (Norway). Two tissue-associated groups were identified: (i) bacteria on the host's tentacle ectoderm, "Candidatus Mycoplasma corallicola," are flasklike, pointed cells and (ii) endoderm-associated bona fide TM7 bacteria form long filaments in the gastral cavity. These tissue-bound bacteria were found in all coral specimens from the Trondheimsfjord, indicating a closer relationship with the coral compared to bacterial assemblages present in coral mucus and gastric fluid.

Epidemiology of alcohol-related emergency hospital admissions in children and adolescents: An e-cohort analysis in Wales in 2006-2011.

OBJECTIVE: Harmful levels of alcohol consumption in young people are prevalent and of increasing public concern in the western world. Rates of alcohol-related emergency hospital admissions in children and young people between 10 to 17 years were described, and the reasons for these admissions and their association with socio-demographic factors were examined. METHODS: E-cohort data were extracted from the Secure Anonymised Information Linkage Databank, which contained alcohol-related emergency hospital admissions (N = 2968) from 2006 to 2011 in children and adolescents aged 10 to 17 years in Wales. A generalised linear mixed model was fitted using a log-link with a population offset to the data to calculate incident rate ratios (IRRSs). RESULTS: There was a general decreasing trend from 2006 to 2011 in the number and rate of alcohol-related emergency hospital admissions; the mean age of admission was 15.4 (standard deviation 1.4) years. In each of the four youngest age groups (10-13,14,15,16 years), females had higher IRRs than males. Males had slightly higher IRR compared to females only in the oldest age group (17 years). IRRs increased with increasing deprivation. The majority (92%) of the admissions lasted one day and most of the admissions (70%) occured during the last three days of the week with a peak on Saturday. The length of stay in hospital was longer in cases when self-harm were present. Multiple admissions showed high prevalance of serious self-harm cases in females. The number of admissions with injuries and falls were higher for males than females. CONCLUSION: Female children and adolescents were more likely to be admitted to hospital for alcohol-related reasons. These data illustrate the significant burden of alcohol-related harm in young people and highlight the need for interventions and policies that promote safe drinking practices among young people to prevent future alcohol-related harm during the life-course.

Differences in mortality between rural and urban areas in England and Wales, 2002-04.

This article examines differences in mortality between rural and urban areas in England and Wales in the years 2002-04 using the Rural and Urban Area Classification 2004. The analysis includes adjustment using the Index of Multiple Deprivation 2004 and Welsh Index of Multiple Deprivation 2005 to investigate whether mortality differences between rural and urban areas could be explained by differences in the distribution of deprivation.

Does selective migration alter socioeconomic inequalities in mortality in Wales?: a record-linked total population e-cohort study.

Recent studies found evidence of health selective migration whereby healthy people move to less deprived areas and less healthy people move to or stay in more deprived areas. There is no consensus, however, on whether this influences health inequalities. Measures of socio-economic inequalities in mortality and life expectancy are widely used by government and health services to track changes over time but do not consider the effect of migration. This study aims to investigate whether and to what extent migration altered the observed socioeconomic gradient in mortality. Data for the population of Wales (3,136,881) registered with the National Health Service on 01/01/2006 and follow-up for 24 quarters were individually record-linked to ONS mortality files. This included moves between lower super output areas (LSOAs), deprivation quintiles and rural-urban class at each quarter, age, sex, and date of death. Cox regression models were used to estimate the hazard ratios for the deprivation quintiles in all-cause mortality, as well as deprivation change between the start and end of the study. We found evidence of health selective migration in some groups, for example people aged under 75 leaving the most deprived areas having a higher mortality risk than those they left behind, suggesting widening inequalities, but also found the opposite pattern for other migration groups. For all ages, those who lived in the most deprived quintile had a 57% higher risk of death than those in the least deprived quintile, allowing deprivation to vary with moves over time. There was little change in this risk when people were artificially kept in their deprivation quintile of origin (54% higher). Overall, migration during the six year window did not substantially alter the deprivation gradient in mortality in Wales between 2006 and 2011.

Development of a methodological approach for the characterization of bioaerosols in exhaust air from pig fattening farms with MALDI-TOF mass spectrometry.

In this paper, we evaluated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a cultivation-independent, routinely applicable approach to identify microbial fractions in bioaerosol emission samples. We developed a streamlined protocol in line with the German state-of-the-art impingement sampling guideline. Following isokinetic sampling, a fast and reliable pre-treatment methodology involving a series of cascade filtration steps was implemented, which produced fractions for spectrometric measurement devoid of interfering substances. We sampled the exhaust air from eight pig fattening farms around western Germany, which yielded two sets of samples for both method development and validation. For method development, in total 65 bacterial isolates were produced directly from the exhaust air samples, taxonomically classified by 16S rRNA-Gene sequencing, and subjected to MALDI-TOF analysis. In this way, we could assign fingerprint biomarkers to classified bacterial genera or even species to build up a preliminary reference database. For verification of the novel methodology and application of the reference database, we subjected the second set of exhaust air samples to the developed protocol. Here, 18 out of 21 bacterial species deposited in the database were successfully retrieved, including organisms classified in risk group 2, which might be used to evaluate the pathogenic potential of sampled exhaust air. Overall, this study pursues an entirely new approach to rapidly analyze airborne microbial fractions.

A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload.

BACKGROUND: It has been recently demonstrated that CD8+ T-lymphocyte numbers are genetically transmitted in association with the MHC class I region. The present study was designed with the objective of narrowing the region associated with the setting of CD8+ T-lymphocyte numbers in a population of C282Y homozygous hemochromatosis subjects, in whom a high prevalence of abnormally low CD8+ T-lymphocyte counts has been described. METHODS: The study includes 43 C282Y homozygous subjects fully characterized both phenotypically and genotypically. Clinical characterization includes measurements of iron parameters at diagnosis (transferrin saturation and serum ferritin), total body iron stores and T-cell immunophenotyping determined by flow cytometry. Genetic characterization includes HLA class I alleles (A, B and C) and four additional microsatellite markers (D6S265, D6S2222, D6S105 and D6S2239) spanning 5 Megabases in the 6p21.3 region. RESULTS: Eighty-two extended C282Y carrying haplotypes were defined. Single-locus analysis revealed that the HLA-A region was associated with CD8+ T-cell numbers. Multivariate analysis showed that the combinations of the most common HLA-A alleles (HLA-A*03, -A*02 and -A*01) were associated with significantly lower numbers of CD8+ T-lymphocytes (0.30 +/- 0.14 x 106/ml), in comparison with subjects carrying only one copy of those alleles (0.46 +/- 0.19 x 106/ml) and subjects without any copy of those alleles (0.79 +/- 0.15 x 106/ml;p = 0.0001). No differences were observed in CD8+ T-cell counts among control subjects carrying the same combinations of HLA-A alleles (0.47 +/- 0.14; 0.45 +/- 0.21 and 0.41 +/- 0.17 x 106/ml, respectively), therefore not supporting a direct effect of HLA specificity but rather an indirect association with a locus close to HLA-A. Multivariate analysis showed that the combination of the most common HLA-A alleles also have an impact on the clinical expression of HH in terms of iron stores, in males(p = 0.0009). CONCLUSION: The present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH). It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed.

Demographic and socioeconomic inequalities in the risk of emergency hospital admission for violence: cross-sectional analysis of a national database in Wales.

OBJECTIVES: To investigate the risk of emergency hospital admissions for violence (EHAV) associated with demographic and socioeconomic factors in Wales between 2007/2008 and 2013/2014, and to describe the site of injury causing admission. DESIGN: Database analysis of 7 years' hospital admissions using the Patient Episode Database for Wales (PEDW). SETTING AND PARTICIPANTS: Wales, UK, successive annual populations ∼2.8 million aged 0-74 years. PRIMARY OUTCOME: The first emergency admission for violence in each year of the study, defined by the International Classification of Diseases V.10 (ICD-10) codes for assaults (X85-X99, Y00-Y09) in any coding position. RESULTS: A total of 11 033 admissions for assault. The majority of admissions resulted from head injuries. The overall crude admission rate declined over the study period, from 69.9 per 100 000 to 43.2 per 100 000, with the largest decrease in the most deprived quintile of deprivation. A generalised linear count model with a negative binomial log link, adjusted for year, age group, gender, deprivation quintile and settlement type, showed the relative risk was highest in age group 18-19 years (RR=6.75, 95% CI 5.88 to 7.75) compared with the reference category aged 10-14 years. The risk decreased with age after 25 years. Risk of admission was substantially higher in males (RR=4.55, 95% CI 4.31 to 4.81), for residents of the most deprived areas of Wales (RR=3.60, 95% CI 3.32 to 3.90) compared with the least deprived, and higher in cities (RR=1.37, 95% CI 1.27 to 1.49) and towns (RR=1.32, 95% CI 1.21 to 1.45) compared with villages. CONCLUSIONS: Despite identifying a narrowing in the gap between prevalence of violence in richer and poorer communities, violence remains strongly associated with young men living in areas of socioeconomic deprivation. There is potential for a greater reduction, given that violence is mostly preventable. Recommendations for reducing inequalities in the risk of admission for violence are discussed.

Biocompatibility and hemocompatibility of polyvinyl alcohol hydrogel used for vascular grafting--In vitro and in vivo studies.

Polyvinyl alcohol hydrogel (PVA) is a synthetic polymer with an increasing application in the biomedical field that can potentially be used for vascular grafting. However, the tissue and blood-material interactions of such gels and membranes are unknown in detail. The objectives of this study were to: (a) assess the biocompatibility and (b) hemocompatibility of PVA-based membranes in order to get some insight into its potential use as a vascular graft. PVA was evaluated isolated or in copolymerization with dextran (DX), a biopolymer with known effects in blood coagulation homeostasis. The effects of the mesenchymal stem cells (MSCs) isolated from the umbilical cord Wharton's jelly in the improvement of PVA biocompatibility and in the vascular regeneration were also assessed. The biocompatibility of PVA was evaluated by the implantation of membranes in subcutaneous tissue using an animal model (sheep). Histological samples were assessed and the biological response parameters such as polymorphonuclear neutrophilic leucocytes and macrophage scoring evaluated in the implant/tissue interface by International Standards Office (ISO) Standard 10993-6 (annex E). According to the scoring system based on those parameters, a total value was obtained for each animal and for each experimental group. The in vitro hemocompatibility studies included the classic hemolysis assay and both human and sheep bloods were used. Relatively to biocompatibility results, PVA was slightly irritant to the surrounding tissues; PVA-DX or PVA plus MSCs groups presented the lowest score according to ISO Standard 10993-6. Also, PVA was considered a nonhemolytic biomaterial, presenting the lowest values for hemolysis when associated to DX.

Perspectives of employing mesenchymal stem cells from the Wharton's jelly of the umbilical cord for peripheral nerve repair.

Mesenchymal stem cells (MSCs) from Wharton's jelly present high plasticity and low immunogenicity, turning them into a desirable form of cell therapy for the injured nervous system. Their isolation, expansion, and characterization have been performed from cryopreserved umbilical cord tissue. Great concern has been dedicated to the collection, preservation, and transport protocols of the umbilical cord after the parturition to the laboratory in order to obtain samples with higher number of viable MSCs without microbiological contamination. Different biomaterials like chitosan-silicate hybrid, collagen, PLGA90:10, poly(DL-lactide-ɛ-caprolactone), and poly(vinyl alcohol) loaded with electrical conductive materials, associated to MSCs have also been tested in the rat sciatic nerve in axonotmesis and neurotmesis lesions. The in vitro studies of the scaffolds included citocompatibility evaluation of the biomaterials used and cell characterization by imunocytochemistry, karyotype analysis, differentiation capacity into neuroglial-like cells, and flow cytometry. The regeneration process follow-up has been performed by functional analysis and the repaired nerves processed for stereological studies permitted the morphologic regeneration evaluation. The MSCs from Wharton's jelly delivered through tested biomaterials should be regarded a potentially valuable tool to improve clinical outcome especially after trauma to sensory nerves. In addition, these cells represent a noncontroversial source of primitive mesenchymal progenitor cells, which can be harvested after birth, cryogenically stored, thawed, and expanded for therapeutic uses. The importance of a longitudinal study concerning tissue engineering of the peripheral nerve, which includes a multidisciplinary team able to develop biomaterials associated to cell therapies, to perform preclinical trials concerning animal welfare and the appropriate animal model is here enhanced.

Widespread occurrence of two carbon fixation pathways in tubeworm endosymbionts: lessons from hydrothermal vent associated tubeworms from the mediterranean sea.

Vestimentiferan tubeworms (siboglinid polychetes) of the genus Lamellibrachia are common members of cold seep faunal communities and have also been found at sedimented hydrothermal vent sites in the Pacific. As they lack a digestive system, they are nourished by chemoautotrophic bacterial endosymbionts growing in a specialized tissue called the trophosome. Here we present the results of investigations of tubeworms and endosymbionts from a shallow hydrothermal vent field in the Western Mediterranean Sea. The tubeworms, which are the first reported vent-associated tubeworms outside the Pacific, are identified as Lamellibrachia anaximandri using mitochondrial ribosomal and cytochrome oxidase I (COI) gene sequences. They harbor a single gammaproteobacterial endosymbiont. Carbon isotopic data, as well as the analysis of genes involved in carbon and sulfur metabolism indicate a sulfide-oxidizing chemoautotrophic endosymbiont. The detection of a hydrogenase gene fragment suggests the potential for hydrogen oxidation as alternative energy source. Surprisingly, the endosymbiont harbors genes for two different carbon fixation pathways, the Calvin-Benson-Bassham (CBB) cycle as well as the reductive tricarboxylic acid (rTCA) cycle, as has been reported for the endosymbiont of the vent tubeworm Riftia pachyptila. In addition to RubisCO genes we detected ATP citrate lyase (ACL - the key enzyme of the rTCA cycle) type II gene sequences using newly designed primer sets. Comparative investigations with additional tubeworm species (Lamellibrachia luymesi, Lamellibrachia sp. 1, Lamellibrachia sp. 2, Escarpia laminata, Seepiophila jonesi) from multiple cold seep sites in the Gulf of Mexico revealed the presence of acl genes in these species as well. Thus, our study suggests that the presence of two different carbon fixation pathways, the CBB cycle and the rTCA cycle, is not restricted to the Riftia endosymbiont, but rather might be common in vestimentiferan tubeworm endosymbionts, regardless of the habitat.

Use of hybrid chitosan membranes and human mesenchymal stem cells from the Wharton jelly of umbilical cord for promoting nerve regeneration in an axonotmesis rat model.

Many studies have been dedicated to the development of scaffolds for improving post-traumatic nerve regeneration. The goal of this study was to assess the effect on nerve regeneration, associating a hybrid chitosan membrane with non-differentiated human mesenchymal stem cells isolated from Wharton's jelly of umbilical cord, in peripheral nerve reconstruction after crush injury. Chromosome analysis on human mesenchymal stem cell line from Wharton's jelly was carried out and no structural alterations were found in metaphase. Chitosan membranes were previously tested in vitro, to assess their ability in supporting human mesenchymal stem cell survival, expansion, and differentiation. For the in vivo testing, Sasco Sprague adult rats were divided in 4 groups of 6 or 7 animals each: Group 1, sciatic axonotmesis injury without any other intervention (Group 1-Crush); Group 2, the axonotmesis lesion of 3 mm was infiltrated with a suspension of 1 250-1 500 human mesenchymal stem cells (total volume of 50 µL) (Group 2-CrushCell); Group 3, axonotmesis lesion of 3 mm was enwrapped with a chitosan type III membrane covered with a monolayer of non-differentiated human mesenchymal stem cells (Group 3-CrushChitIIICell) and Group 4, axonotmesis lesion of 3 mm was enwrapped with a chitosan type III membrane (Group 4-CrushChitIII). Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index, static sciatic index, extensor postural thrust, and withdrawal reflex latency. Stereological analysis was carried out on regenerated nerve fibers. Results showed that infiltration of human mesenchymal stem cells, or the combination of chitosan membrane enwrapment and human mesenchymal stem cell enrichment after nerve crush injury provide a slight advantage to post-traumatic nerve regeneration. Results obtained with chitosan type III membrane alone confirmed that they significantly improve post-traumatic axonal regrowth and may represent a very promising clinical tool in peripheral nerve reconstructive surgery. Yet, umbilical cord human mesenchymal stem cells, that can be expanded in culture and induced to form several different types of cells, may prove, in future experiments, to be a new source of cells for cell therapy, including targets such as peripheral nerve and muscle.

Rural/urban mortality differences in England and Wales and the effect of deprivation adjustment.

Perceptions that rural populations are inevitably healthier and live longer than urban populations are increasingly being challenged. But very few publications have investigated the extent to which these putative differences can be explained by variation in area composition. Existing publications have tended to use conventional deprivation measures, often thought to mask rural deprivation by favourable averages. Further, they have typically been based on large and variably-sized geographical units, or confined to studies of a single region or cause of death. This study examines differences in mortality between rural and urban areas in the entire population of England and Wales for 2002-2004. It uses the most up-to-date small geographical units of similar size and homogeneity of population together with the recently-introduced Rural and Urban Area Classification, and adjusts for five different deprivation measures (including modern composite indices). The causes of death investigated were all-cause mortality, cancer, lung cancer, respiratory disease, circulatory disease, suicide and accidents. Particular points of focus for the study were the potential for interaction between deprivation and rurality, and the importance of choice of deprivation measure in quantifying the relationships between mortality, rurality and deprivation. Choice of deprivation measure was not found to alter the substantive conclusions of any analysis, and little evidence for differential effects of deprivation in rural and urban areas was uncovered. Differences between rural and urban areas in all-cause, circulatory disease and cancer mortality could largely be accounted for by adjusting for deprivation. For these causes of death, therefore, rural populations were not found to be inherently healthier than their urban counterparts. However, substantial residual differences between rural and urban areas were found in comparisons of mortality from lung cancer and respiratory disease, mortality being lower in rural areas. Stronger relationships between rurality and mortality were found in 'village and dispersed' settlements.