Role of nutritional therapy on dietary habits and glycemic control in insulin-treated kidney transplant patients with diabetes.

AIMS: To evaluate the effect of nutritional therapy on glycemic compensation and key cardio-renal risk markers in patients with diabetes and kidney transplant, on insulin treatment by Multiple Daily Injection (MDI) or Continuous Subcutaneous Insulin Infusion (CSII). METHODS: 34 patients with diabetes on insulin treatment and kidney transplant recipients were enrolled;12 participated in the structured nutritional program (intervention group), 22 patients (control group) did not receive nutritional protocol. Both groups were then divided into subgroups according to the method of insulin administration (MDI and CSII). RESULTS: Statistically significant reduction in fasting blood glucose values, glycosylated hemoglobin (HbA1c) and glycosuria were observed in both groups at the end of the study. The intervention group, significantly reduced total cholesterolemia and the glycemic index, together with reduced dietary intake of lipids, cholesterol, soluble carbohydrates and increased consumption of carbohydrates and fiber. These improvements were even more pronounced in patients treated with CSII. CONCLUSIONS: A proper nutritional approach optimize glycometabolic outcomes and contribute significantly to the reduction of the major cardiovascular risk factors in renal transplant patients.

Attitudes and perceptions of Italian Students in Healthcare Settings on COVID-19 vaccines and vaccinations strategies, one year after the immunization campaign.

Background: The topic of vaccine confidence is increasingly relevant, particularly due to the COVID-19 pandemic and the global distribution of COVID-19 vaccines. This issue is even more critical for students in healthcare settings, given their future role not only as vaccine recipients but also as advocates for vaccination. In light of this, achieving a good level of vaccine acceptance is crucial. Hence, the aim of our study was to evaluate the attitudes and perceptions of healthcare students regarding vaccines and COVID- 19 vaccination. Methods: Medical and pharmaceutical area students attended an Elective Teaching Activity on COVID-19 vaccines and vaccination campaign, organized at the University of Florence (Italy) and participated in filling two anonymous questionnaires. The first questionnaire was submitted before the Elective Teaching Activity was focused on students' attitudes and perceptions toward vaccines. The second questionnaire was designed to evaluate the students' satisfaction with the course topics. Both descriptive and inferential analyses were performed on the results. In addition, the Vaccine Confidence Index was calculated to evaluate the propensity of students toward vaccinations. Results: A total of 423 students attended the Elective Teaching Activity in the early beginnings of 2022. Overall, students have shown greater confidence in vaccines, compared to COVID-19 vaccines, especially as regards the safety profile. Students' Vaccine Confidence Index was very close to 0.25 value, which indicates being in favor of vaccinations. Nevertheless, in the satisfaction questionnaire filled in at the end of the course, the percentage of students in favor of COVID-19 vaccination increased for both medical (from 94% to 99%) and pharmaceutical area students (from 81% to 97%). Conclusions: Our study suggests that educational activities such as this Elective Teaching Activity, could be considered an effective teaching strategy to improve vaccine acceptance rates among students in healthcare settings.

Gut microbiome dynamics in index patients colonized with extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales after hospital discharge and their household contacts.

IMPORTANCE: Colonization with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) often precedes infections and is therefore considered as a great threat for public health. Here, we studied the gut microbiome dynamics in eight index patients colonized with ESBL-PE after hospital discharge and the impact of exposure to this index patient on the gut microbiome dynamics of their household contacts. We showed that the microbiome composition from index patients is different from their household contacts upon hospital discharge and that, in some of the index patients, their microbiome composition over time shifted toward the composition of their household contacts. In contrast, household contacts showed a stable microbiome composition over time irrespective of low-level extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) or extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) gut colonization, suggesting that, in healthy microbiomes, colonization resistance is able to prevent ESBL-PE expansion.

Author Correction: Hyaluronic acid accelerates re-epithelialization and healing of acute cutaneous wounds.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27(3 Suppl): 37-45. doi: 10.26355/eurrev_202304_31320-PMID: 37129334-published online on April 27, 2023. After publication, the authors found some transcription mistakes and applied minor corrections to the Abstract and Discussion sections. The sections have been amended as follows: -       Abstract section: "an average 80% decrease" has been corrected in "an average 86% decrease"; "a small amount of exudate was noted in 91% of wounds" has been corrected in "a small amount of exudate was noted in 10% of wounds". -       Discussion section: "by a reduced wound surface area of 80% at six weeks and a reduced surface area of 95% after eight weeks" has been corrected to "by a reduced wound surface area of 80% at four weeks and a reduced surface area of 86% after six weeks". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31320.

A novel collagenase from Vibrio Alginolyticus: experimental study for Dupuytren's disease.

OBJECTIVE: Dupuytren contracture (DC) is a highly prevalent hand affection in which contracted fingers compromise hand function. It is a benign fibroproliferative condition affecting the hand palmar fascia with a deposition of excess matrix proteins in the extracellular space of the palmar aponeurosis. In particular type III over type I collagen V. Alginolyticus collagenase (CVA), is a new enzyme that is fully active on the collagen filaments and inactive on other components of the dermal extracellular matrix. The aim of this study is to evaluate the safety and effectiveness of an intra-lesional injection of CVA on an animal model of subcutaneous fibrosis mimicking the pathological anatomy of the cord of Dupuytren's disease. MATERIALS AND METHODS: We performed an in vivo study on 27 rats that were randomized into four groups, and we evaluated macroscopic and microscopic analysis examining the inflamed cell population and the extracellular matrix. RESULTS: In all cases, no skin necrosis, skin tears or wound dehiscence were recorded, demonstrating the safety of the CVA in contrast to group D which had full-thickness skin necrosis, and this is confirmed by the microscopic analysis of the samples treated with CVA, where no hematomas are found around the fibrotic area with the absence of leukocyte infiltrates and macrophages. CONCLUSIONS: CVA is confirmed to be selective for collagens I and III, reducing the risk of vascular lesions or skin ulcerations.

Hyaluronic acid accelerates re-epithelialization and healing of acute cutaneous wounds.

OBJECTIVE: Hyaluronic acid has been efficient in ameliorating and supporting recovery in both chronic and acute lesions. The aim of this study was to assess the effectiveness of hyaluronic acid-based cream and gauze pads in cutaneous wounds. PATIENTS AND METHODS: This retrospective and prospective study examines the use of a 0.2% hyaluronic acid cream or gauze-pads application (Connettivina Bio®). 85 patients participated in the study and were affected by wounds of different etiologies, comprising superficial trauma wounds (20), surgical sutures (15), first- and second-degree burns (15), dermabrasions (30) and ulcers of different etiologies (5). We analyzed the healing process in terms of progression and wound quality. Moreover, we performed biopsies (not on all patients) to evaluate the grade of re-epithelialization. RESULTS: We observed a reduction in the mean surface area of the wounds, precisely 456 mm2 at baseline to 147 mm2 after six weeks with an average 86% [corrected] decrease in the wound surface area. No fibrin tissue was observed, and a small amount of exudate was noted in 10% [corrected] of wounds. Hyaluronic acid cream and gauze-pads-based treatments were well tolerated by patients. All groups showed a decrease of inflammation with a progressive increase of collagen fibers and granulation tissue. CONCLUSIONS: The treatment with hyaluronic acid 0.2% yielded remarkable outcomes in the re-epithelialization of superficial wounds and provided favorable recovery and tolerance for patients.

Impact of Built Environment and Neighborhood on Promoting Mental Health, Well-being, and Social Participation in Older People: an Umbrella Review.

Background: The built environment, especially in the context of the neighborhood, affects older people's health. This umbrella review aims to summarize the associations between factors and interventions in the built environment as regards modifying or improving mental health, well-being, social inclusion and participation in the elderly. Methods: We searched articles in the following databases: PubMed, Embase, Cochrane Library, Scopus, Avery Index, Sage, Web of Science, Health Evidence, and Google Scholar, without any time limits. The factors and interventions examined have been classified into three categories (urban infrastructure, green infrastructure, built environment), and we have assessed their relationships with each of the health outcomes. Results: Eight reviews have been included. The results show a positive association between factors and interventions and health outcomes, even though this tends to differ with respect to some of the elements (study design, sample size, built environment and health outcome measurements, and the quality of the primary studies included in the reviews) in the selected studies. Conclusions: In conclusion, the present study suggests and confirms that acting on the built environment has a positive impact on mental health and social inclusion.

Populations of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae are different in human-polluted environment and food items: a multicentre European study.

OBJECTIVES: To assess the extent to which food items are a source of extended-spectrum ß-lactamase (ESBL) -producing Escherichia coli (ESBL-Ec) and ESBL-producing Klebsiella pneumoniae (ESBL-Kp) for humans in five European cities. METHODS: We sampled 122 human polluted (hp)-environments (sewers and polluted rivers, as a proxy of human contamination) and 714 food items in Besançon (France), Geneva (Switzerland), Sevilla (Spain), Tübingen (Germany) and Utrecht (The Netherlands). A total of 254 ESBL-Ec and 39 ESBL-Kp isolates were cultured. All genomes were fully sequenced to compare their sequence types (ST) and core genomes, along with the distribution of blaESBL genes and their genetic supports (i.e. chromosome or plasmid). RESULTS: Sequence data revealed that ESBL-Ec and ESBL-Kp isolates from hp-environments were genetically different from those contaminating food items. ESBL-Ec ST131 was widespread in the hp-environment (21.5% of the isolates) but absent from the food items tested. ESBL-Ec ST10 was in similar proportions in hp-environments and food items (15 and 10 isolates, respectively) but mostly carried reservoir-specific blaESBL. blaCTX-M-1 and blaSHV-12 predominated in food-related E. coli isolates (32% and 34% of the isolates, respectively), whereas blaCTX-M-15 and blaCTX-M-27 predominated in isolates from hp-environments (52% and 15% of the isolates, respectively). CONCLUSIONS: We found a very limited connection between ESBL-Ec and ESBL-Kp populations retrieved in food items and from hp-environments and blaESBL. This suggests that human-to-human contamination, rather than the food chain, is possibly the most frequent route of ESBL-Ec and ESBL-Kp transmission in high-income countries.

Fosfomycin residues in colostrum: Impact on morpho-physiology and microbiology of suckling piglets.

Fosfomycin is a broad-spectrum bactericidal antibiotic widely used in pig farms for the treatment of a wide variety of bacterial infections. In this study, the elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of this antibiotic on the microbiota and intestinal morpho-physiology of suckling piglets were analyzed. The average amount of fosfomycin eliminated in colostrum (after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85 µg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The elimination profile of fosfomycin concentrations in colostrum occurs at a time of profound changes in the morpho-physiology of the gastrointestinal tract of the piglet. However, the studied concentrations did not produce imbalances on the microbiota or on the morpho-physiology of the gastrointestinal tract of the piglet. Concentrations of fosfomycin were maintained in the mammary gland above the MIC for more than 8 hr for pathogenic bacteria of productive importance. This would indicate that fosfomycin may be considered safe for the specific treatment of bacterial infectious processes in sows during the peri- and postpartum period. This first study with disodium fosfomycin stimulates awareness in the proper use of antimicrobials at farrowing.

Soft-tissue defects of the Achilles tendon region: Management and reconstructive ladder. Review of the literature.

INTRODUCTION: Defects of the Achilles tendon region represent a challenge for reconstructive surgeons. Several options are available but there is still no reconstructive ladder for this specific and tricky area. An up-to-date reconstructive ladder according to local and general conditions is proposed based on our multicentre experience and an extensive review of the English literature on PubMed. MATERIALS AND METHODS: An extensive review of the English literature was performed on PubMed using the following key-words: "Achilles region", "heel", "soft-tissue reconstruction", "flaps", "grafts" and "dermal substitutes". RESULTS: A total of 69 complete papers were selected, covering the last thirty years' literature. Although most of the studies were based on limited case-series, local and general conditions were always reported. A comprehensive reconstructive ladder of all the available reconstructive techniques for the Achilles region has been created based on our personal multicentre experience and the results of the literature review. CONCLUSIONS: The reconstructive ladder is a concept that is still a mainstay in plastic surgery and guides decisions in the repair strategy for soft tissue defects. The optimal solution, according to the experience of the surgeon and the wishes of the patient, is the one that implies less sacrifice of the donor site. Perforator flaps should be the first-line option for small-to-moderate defects; the distally-based sural flap is the most reported for moderate-to-large defects of the Achilles region, and free flaps should be reserved mainly for complex and wide reconstructions.

The MRI as a valid help for oncoplastic surgery: esthetic and oncologic results analysis in a group of 489 patients.

AIM: There is an increased expectation from breast cancer patients to retain their "normal breast appearance". To help to achieve this expectation, many radiologic exams have been created to get the exact extension and position of the tumor. MRI is effective to obtain correct information about neoplasms, especially those with shaded edges, like DCIS. MRI might change the surgical project, thus avoiding second operations for cancer relapses. METHODS: We have performed MRI to all the patients except those with big lesions or adypous breasts. We have chosen for reconstruction various oncoplastic techniques. We have had early complications in 98/489 (20%) cases. RESULTS: As late complications, we have found scar retractions and minus areas in 20/489 cases (4.08%), while we have found asymmetries and bigger deformities in 34/489 cases (6.95%). We have not found any cancer relapse after one year, we have had 3 cases of relapse (0.6%) after five years of follow-up, after 5, 4 and 2 years. Our good oncologic and plastic results have to be attributed to many factors, among which stands out the MRI done in all the cases. CONCLUSION: We think that an immediate breast reshaping following quadrantectomy is the best esthetic and psychologic option for breast cancer patients.

Failure by congestion of pedicled and free flaps for reconstruction of lower limbs after trauma: the role of negative-pressure wound therapy.

Lower limb reconstruction with pedicled or free flaps can be commonly compromised by venous insufficiency. This complication often leads to partial/complete flap necrosis and increases the risk of superinfection. Negative-pressure wound therapy (NPWT) is known to increase local blood flow, decrease edema, promote tissue granulation, and reduce the likelihood of soft tissue infection. This study aims to evaluate the effectiveness of NPWT in the treatment of congested pedicled and free flaps of the lower limb after reconstructions in lower limb traumas. A retrospective analysis was performed on four congested (pedicled and free) flaps on the lower limbs. NPWT was applied in all cases after partial flap debridement. NPWT was able to improve and resolve tissue edema and venous insufficiency, avoid further flap necrosis, and promote granulation. On NPWT removal, a split-thickness skin graft was applied on the wound, achieving complete and uneventful healing. NPWT is a useful instrument in managing flaps affected by venous insufficiency in lower limb reconstruction, although larger studies are necessary to better define the effectiveness and indications of NPWT in this setting.

16(th) IHIW: analysis of HLA population data, with updated results for 1996 to 2012 workshop data (AHPD project report).

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.

Strategies to work with HLA data in human populations for histocompatibility, clinical transplantation, epidemiology and population genetics: HLA-NET methodological recommendations.

HLA-NET (a European COST Action) aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations, with an expected strong impact on both public health and fundamental research. Such improvements involve finding consensual strategies to characterize human populations and samples and report HLA molecular typings and ambiguities; proposing user-friendly access to databases and computer tools and defining minimal requirements related to ethical aspects. The overall outcome is the provision of population genetic characterizations and comparisons in a standard way by all interested laboratories. This article reports the recommendations of four working groups (WG1-4) of the HLA-NET network at the mid-term of its activities. WG1 (Population definitions and sampling strategies for population genetics' analyses) recommends avoiding outdated racial classifications and population names (e.g. 'Caucasian') and using instead geographic and/or cultural (e.g. linguistic) criteria to describe human populations (e.g. 'pan-European'). A standard 'HLA-NET POPULATION DATA QUESTIONNAIRE' has been finalized and is available for the whole HLA community. WG2 (HLA typing standards for population genetics analyses) recommends retaining maximal information when reporting HLA typing results. Rather than using the National Marrow Donor Program coding system, all ambiguities should be provided by listing all allele pairs required to explain each genotype, according to the formats proposed in 'HLA-NET GUIDELINES FOR REPORTING HLA TYPINGS'. The group also suggests taking into account a preliminary list of alleles defined by polymorphisms outside the peptide-binding sites that may affect population genetic statistics because of significant frequencies. WG3 (Bioinformatic strategies for HLA population data storage and analysis) recommends the use of programs capable of dealing with ambiguous data, such as the 'gene[rate]' computer tools to estimate frequencies, test for Hardy-Weinberg equilibrium and selective neutrality on data containing any number and kind of ambiguities. WG4 (Ethical issues) proposes to adopt thorough general principles for any HLA population study to ensure that it conforms to (inter)national legislation or recommendations/guidelines. All HLA-NET guidelines and tools are available through its website http://hla-net.eu.

Endocytosis and intracellular localisation of type 1 ribosome-inactivating protein saporin-s6.

Saporin-S6 is a single-chain ribosome-inactivating protein (RIP) that has low toxicity in cells and animals. When the protein is bound to a carrier that facilitates cellular uptake, the protein becomes highly and selectively toxic to the cellular target of the carrier. Thus, saporin-S6 is one of the most widely used RIPs in the preparation of immunoconjugates for anti-cancer therapy. The endocytosis of saporin-S6 by the neoplastic HeLa cells and the subsequent intracellular trafficking were investigated by confocal microscopy that utilises indirect immunofluorescence analysis and transmission electron microscopy that utilises a direct assay with gold-conjugated saporin-S6 and an indirect immunoelectron microscopy assay. Our results indicate that saporin-S6 was taken up by cells mainly through receptor-independent endocytosis. Confocal microscopy analysis showed around 30% co-localisation of saporin-S6 with the endosomal compartment and less than 10% co-localisation with the Golgi apparatus. The pathway identified by the immunofluorescence assay and transmission electron microscopy displayed a progressive accumulation of saporin-S6 in perinuclear vesicular structures. The main findings of this work are the following: i) the nuclear localisation of saporin-S6 and ii) the presence of DNA gaps resulting from abasic sites in HeLa nuclei after intoxication with saporin-S6.

Developmental evolution in a patient with multiple acyl-coenzymeA dehydrogenase deficiency under pharmacological treatment.

PURPOSE: evaluate the psychomotor evolution of a child with Multiple acyl-CoA dehydrogenase deficiency after treatment with L-carnitine, ubiquinone and riboflavin. METHODS: an assessment of psychomotor development was performed before the start of farmacological treatment using the Assessment Scale of Mental Development Griffiths (GMDS-R, 0-2 years). The same assessment was performed after a month and after six months of treatment to evaluate the possible benefits of treatment. RESULTS: we noticed a quick and dramatic improvement in muscular tone and motor performances after pharmacological treatment. We also observed a substantial improvement in the personal/social and hearing/language areas, suggesting the presence of intellectual/cognitive improvement. The clinical improvement correlated with the biochemical response. CONCLUSION: In our patient early therapy resulted in a optimal response in psychomotor development, motor function and muscole hypotonia. Evaluation with GMDS-R, a simple, non-invasive and multidimensional tool, represents a useful instrument to monitor the clinical response to treatment.

Simultaneous care and melanoma: preliminary report about the psychoncological approach.

AIM: The main aim of the study was to investigate the efficacy of a "take-in- charge" model of advanced stage melanoma patients by a multidisciplinary team and highlight the psychological patterns of the disease. METHODS: The study sample involved 44 patients, 27 females and 17 males, who were given a "Questionnaire on Health Status SF-12" which provides two synthetic indexes, one related to physical health PCS-12, and the other to mental health MCS-12. The statistical data was collected through a preliminary analysis of principal components P.C. A., carried out with SPSS software. RESULTS: Comparing the scores obtained by the PCS and MCS indexes, the mean score is low: 6.52 out of 10 for PCS and 3.23 out of 10 for MCS. At first consultation, there is evidence which supports patients' need for psycho-oncological support. By dividing the sample patients into two subgroups, cutaneous melanoma and visceral melanoma, it should be noted that the first group obtained a mean of 4.75 for PCS and 3.77 for MCS and the second group 7.53 for PCS and 2.92 for MCS respectively. Therefore, the results show, at first consultation, a more complex situation for patients with cutaneous melanoma. CONCLUSION: The results of the study highlight the need to supply some form of psycho-oncological support to help patients while they adapt to the disease. Furthermore, different problems and different coping styles also emerged depending on whether the patient has cutaneous or visceral melanoma. The study therefore demonstrates the need to take into account such variables when devising a personal care system centered on the patient.

Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report).

During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy-Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1-7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.

Norwegian Sami differs significantly from other Norwegians according to their HLA profile.

This study reports extensive genomic data for both human leukocyte antigen (HLA) class I and II loci in Norwegian Sami, a native population living in the northwest of Europe. The Sami have a distinct culture and their own languages, which belong to the Uralic linguistic family. Norwegian Sami (n = 200) were typed at the DNA level for the HLA-A, -C, -B, -DRB1 and -DQB1 loci, and compared with a non-Sami Norwegian population (n = 576). The two populations exhibited some common genetic features but also differed significantly at all HLA loci. The most significantly deviating allele frequencies were an increase of HLA-A*03, -B*27, -DRB1*08 and -DQB1*04 and a decrease of HLA-A*01, C*01, -DRB1*04 and -DQB1*02 among Sami compared with non-Sami Norwegians. The Sami showed no deviation from Hardy-Weinberg equilibrium. The hypothesis of selective neutrality was rejected at all loci except for the A- and C- loci for the Sami. HLA haplotype frequencies also differed between the two populations. The most common extended HLA haplotypes were A*02-B*27-C*01-DR*08-DQB1*04 in the Sami and A*01-B*08-C*07-DR*03-DQB1*02 in the other Norwegians. Genetic distance analyses indicated that the Norwegian Sami were highly differentiated from other Europeans and were most closely related to Finns whose language also belongs to the Uralic linguistic family. In conclusion, the Norwegian Sami and the non-Sami Norwegians were significantly different at all HLA loci. Our results can be explained by the fact that the two populations have different origins and that the Sami population has remained smaller and more isolated than its neighbors.

Human dental pulp stem cells produce mineralized matrix in 2D and 3D cultures.

The aim of this study was to characterize the in vitro osteogenic differentiation of dental pulp stem cells (DPSCs) in 2D cultures and 3D biomaterials. DPSCs, separated from dental pulp by enzymatic digestion, and isolated by magnetic cell sorting were differentiated toward osteogenic lineage on 2D surface by using an osteogenic medium. During the differentiation process, DPSCs express specific bone proteins like Runx-2, Osx, OPN and OCN with a sequential expression, analogous to those occurring during osteoblast differentiation, and produce extracellular calcium deposits. In order to differentiate cells in a 3D space that mimes the physiological environment, DPSCs were cultured in two distinct bioscaffolds, Matrigel™ and Collagen sponge. With the addition of a third dimension, osteogenic differentiation and mineralized extracellular matrix production significantly improved. In particular, in Matrigel™ DPSCs differentiated with osteoblast/osteocyte characteristics and connected by gap junction, and therefore formed calcified nodules with a 3D intercellular network. Furthermore, DPSCs differentiated in collagen sponge actively secrete human type I collagen micro-fibrils and form calcified matrix containing trabecular-like structures. These neo-formed DPSCs-scaffold devices may be used in regenerative surgical applications in order to resolve pathologies and traumas characterized by critical size bone defects.