On color adjustment potential and color blending threshold of dental composite resins.

OBJECTIVE: Color Adjustment Potential evaluates the color blending of dental Composite Resins. While Color Adjustment Potential is simple, its clinical relevance is unclear. This research aims to understand it better and to create an index for Composite Resins with meaningful clinical interpretation. MATERIALS AND METHODS: Single and double shade composite disks of various diameters and opacities were created to test the indices. Color measurements used a dental colorimeter, avoiding subjective assessments. Color Adjustment Potential analysis of each material revealed insights, leading to the creation of a new Color Blending Threshold, providing a clinically relevant numerical value for Composite Resins. RESULTS: Color Adjustment Potential's numerical significance was clarified and introduced a new index for clinical applications. Color adaptation of each test shade to all Vita shades was also calculated, useful for single-shade restorations in open and closed cavity types. CONCLUSIONS: The proposed Color Blending Threshold defines the open/closed cavity dimension that can be adequately restored with a single shade of resin composite. CLINICAL SIGNIFICANCE: Understanding how dental materials adapt to surrounding tooth colors enhances esthetic restorations, simplifies shade matching, and optimizes resin composite production. The proposed Color Blending Threshold is a parameter that directly relates to the clinical significance of a material's true color blending ability. It defines the cavity dimension that can be adequately restored with a single shade of resin composite while ensuring that the resulting color difference falls below a predetermined threshold, meeting the clinical requirements for an esthetic restoration.

Spatially resolved, high-dimensional transcriptomics sorts out the evolution of biphasic malignant pleural mesothelioma: new paradigms for immunotherapy.

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place. METHODS: We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis. RESULTS: Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability. CONCLUSIONS: Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.

Abordaje institucional de la infancia desde la protección integral de derechos en centro de acción familiar N°25 de Santa Fe / Institutional approach to childhood from the comprehensive protection of rights in Family Action Center No. 25 of Santa Fe

INTRODUCCIÓN Es necesario profundizar el conocimiento sobre las prácticas en relación con la nueva ley de infancia, puesta al servicio de un cambio de paradigma que considera al niño como sujeto de derechos. OBJETIVOS Explorar y describir las prácticas y opiniones sobre niñez de los trabajadores del Centro de Acción Familiar (CAF) N° 25 de Santa Fe y analizar desde qué paradigma y qué nociones de infancia se realiza el abordaje institucional. Métodos Se realizó un estudio exploratorio cualitativo, con una muestra no probabilística de carácter intencional. Los datos se recabaron a partir de entrevistas semiestructuradas y revisión de legislación, documentos oficiales e institucionales. RESULTADOS Subyace la idea del niño como sujeto de derechos. En cuanto a las prácticas realizadas a diario en el CAF, consisten en actividades lúdicas orientadas a promover el desarrollo integral de los niños y proporcionarles un ambiente de protección, confianza y seguridad. Por otro lado, aún falta profundizar el trabajo en red y con la comunidad. En relación con la implementación de la Ley Provincial 12697 en el CAF, hay en general una necesidad de participar de espacios de capacitación y de formación respecto al nuevo paradigma de protección de derechos. DISCUSIÓN Existe en los trabajadores una concepción de niñez acorde a los postulados de la Ley de Protección de Derechos, donde se piensa a los niños como sujetos de derechos. Asimismo, dentro de la institución se encuentra arraigado el espíritu de la ley y las prácticas con niños se encuentran orientadas a promover su desarrollo integral. Existen diferencias significativas con las prácticas que se realizaban en años anteriores; sin embargo, el equipo se encuentra en un proceso de cambio, donde se debe profundizar el trabajo comunitario y en red. Para afianzar una estrategia de abordaje integral de la infancia, es necesario implementar espacios de capacitación con los lineamientos de la Ley y de reflexión sobre la práctica.

Draft Genome Sequence of Clostridium difficile Belonging to Ribotype 018 and Sequence Type 17.

Clostridium difficile, belonging to ribotype 018 (RT018), is one of the most prevalent genotypes circulating in hospital settings in Italy. Here, we report the draft genome of C. difficile CD8-15 belonging to RT018, isolated from a patient with fatal C. difficile-associated infection.

Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men.

OBJECTIVES: To study the impact of obesity, age and varicocele on sexual hormones of adult and elderly men. MATERIALS AND METHODS: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. RESULTS: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. CONCLUSIONS: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.

Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men

ABSTRACT Objectives: To study the impact of obesity, age and varicocele on sexual hormones fof adult and elderly men. Materials and Methods: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. Results: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. Conclusions: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.

Automated urinalysis with expert review for incidental identification of atypical urothelial cells: An anticipated bladder carcinoma diagnosis.

BACKGROUND: The most common diagnostic technique for the detection of malignant/atypical urothelial cells (m/AUC) is urinary cytology (Ucytol). Urinary sediment (Used) examination, often prescribed for asymptomatic, healthy subjects, can incidentally identify suspicious/AUC (s/AUC) in routine daily practice. METHODS: Unstained, unfixed and uncentrifuged urine samples were analyzed with an automated intelligent microscopy (AIM) system. From January 2010, any incidental identification of s/AUC through expert revision of unclassified cell images was reported, according to internal protocols, as an additional note on the patients' laboratory report. Patients' symptomatology or previous history was unknown to the pathologist. All referrals from January 2010 to December 2014, with the s/AUC note, were reviewed and cross-referenced with Ucytol and histology data from a central database. RESULTS: Of the 162 patients identified with s/AUC (0.1/1000 samples), 84% (n=136) performed further Ucytol and/or histological examinations. The sensitivity of the identification of non-transitory AUC at Used was 87.5%. Positive histological examinations were 91.2% classified as high-grade urothelial carcinoma. CONCLUSIONS: Routine Used examination, with an AIM and expert revision, can identify the presence of AUC in a clinical laboratory setting, and for some subjects, may anticipate bladder carcinoma diagnosis.

A novel BRAF mutation in association with primary amelanotic melanoma with oral metastases.

BACKGROUND: In the context of amelanotic melanoma, little is known on the genetic or molecular background that determines the onset of this peculiar phenotype of melanoma and its sites of metastatic spread. However, it appears that amelanotic melanomas frequently lack BRAF mutations. OBJECTIVE: To report the genetical analysis of one case amelanotic melanoma developing oral metastasis. METHODS: The BRAF mutational status of the primary lesion was assessed by both Sanger sequencing and pyrosequencing. RESULTS: Both methodologies showed changes in three nucleotides: C1796T; G1798A and T1799A. These mutations should result in a rare double aminoacid substitution in codons 599 and 600 of the BRAF protein (BRAF T599I/V600K). CONCLUSION: This unusual mutation was associated with an uncommon clinical phenotype of the primary tumour and with an unusual site of metastatic spread. In the lack of comparable data, a potential association between the unusual mutation and clinical findings remains a matter of further studies.

Allele frequencies for 26 STR loci in a population of Tuscany (Central Italy).

Allele frequencies for 26 short tandem repeats (STRs) were obtained from a sample of 203 unrelated individuals living in the area of Florence, Prato and Pistoia (Tuscany, Central Italy). These 26 loci are in addition to the existing 13 U.S. core loci and can help provide assistance in complex kinship testing when, for example, the alleged father is not available for testing. The results were compared with U.S. Caucasian, African American and Hispanic populations.

Single center experience with elective surgical patients as living kidney donors.

PURPOSE: To report a single center experience with elective surgical patients as living kidney donors. METHODS: We retrospectively analyzed a prospective database of 458 living kidney donors from September 2005 to May 2011. Fifteen (3.2%) of them were elective surgical patients simultaneously undergoing living donor nephrectomy. We reviewed age, gender, operative time, intraoperative blood transfusion, intra- and postoperative complications, as well as length of hospital stay. Recipients were evaluated for delayed graft function. Four hundred forty-three patients undergoing living donor nephrectomy alone composed the control group. RESULTS: Among the elective surgical patients group, the mean (range) operative time was 155 (90 to 310) minutes and mean (range) length of hospital stay was 3 (2 to 9) days. One (6.7%) recipient displayed delayed graft function. Among the regular living kidney donors group, the mean (range) operative time was 100 (70 to 150) minutes, mean (range) length of hospital stay was 3 (2 to 5) days, and delayed graft function was observed in 5.6% of recipients. Only operative time (P = .03) was significantly different between the groups. CONCLUSIONS: Elective surgical patients are potential donors who may be treated at the same time as the living donor nephrectomy.

[Deep Oscillation: therapeutic-rehabilitative experiences with a new electrostatic device]. / Deep Oscillation®: esperienze terapeutico-riabilitative con un nuovo innovativo strumento ad azione elettrostatica.

AIM: Deep Oscillation® is an apparatus that produces low frequency electromagnetic radiations able to modulate immune reactions and, therefore, applicable to pain, tumour and inflammation treatments. The aim of this study is to evaluate how the Deep Oscillation® therapy works on conventional therapy resistant patients as the apparatus can be applied either to trauma derived fom surgical wounds or on sports post-traumatic oedema, low back pain and/or sciatalgic pain and cervicobrachial pain. METHODS: In the first part of the study, 34 cases of recent surgical wounds have been treated with Deep Oscillation® with 3 times a week visits for 20 minutes. In the same way 30 cases of sports post-traumatic oedema, 20 cases of low back pain and/or sciatalgic pain and 10 cases of cervicobrachial pain were treated. Among these patients, 15 cases had also undergone contemporaneous nonsteroidal anti-inflammatory drugs intravenous drip, electrolytes and vitamins to verify the probable synergetic efficacy of both treatments. RESULTS: The results confirm that in some cases the Deep Oscillation® treatment is effective since the first/third therapy up to the restitutio ad integrum. It has also been demonstrated that the maximum efficiency of the Deep Oscillation® and nonsteroidal anti-inflammatory drugs synergetic treatment is probably due to the electromagnetic radiations able to facilitate the pharmacological uptake. CONCLUSION: This study confirms the capacity of the electrostatic energy, released by Deep Oscillation®, to stimulate the patient's neurosensory system, raising his pain threshold and facilitating his pharmacological uptake and restoring his functional recovery more quickly.

Use of patch testing for the diagnosis of abacavir-related hypersensitivity reaction in HIV patients.

BACKGROUND: The use of antiretroviral drug abacavir (ABC) has been often associated with cutaneous hypersensitivity reactions, the majority being severe. OBJECTIVE: The present study discusses the issues of patch testing associated with pharmacogenetic screening in light of the development of abacavir hypersensitivity reactions (HSRs). METHODS: The present authors classified 100 patients into three groups: 20 patients (group A) had experienced a hypersensitivity reaction when treated with highly active antiretroviral therapy (HAART) including ABC; 60 HIV-positive patients (group B) were receiving HAART scheme including ABC; 20 HIV-negative patients acted as control group (group C). Patients of group A and B were patch tested with ABC as such, then with an ABC extract diluted to 1 and 10% in petrolatum. Group C patients underwent patches with petrolatum only. A biopsy of the lesion was performed in those patients who showed a positive skin reaction. All patients had been tested for HLA-B5701. RESULTS: A correlation between positive ABC-patch testing and HLA-B5701 was found in 50% of patients enrolled in group A, while in group B and C, all patients tested negative for both genetic marker and ABC-patch testing. Histopathology findings confirmed a vigorous CD4+ and CD8+ cellular response that is compatible with HSR. CONCLUSIONS: Patch testing is a safe and sensitive method that can be used for to confirm or exclude any correlation between abacavir and hypersensitivity skin reactions in patients who have been previously treated with abacavir during HAART. Correlation between patch test, immunohistochimical, and genetic tests results shows that genetic testing increases the possibility to identify patients with a true reaction.

Novel mutations in of the ABCR gene in Italian patients with Stargardt disease.

PURPOSE: Stargardt disease (STGD) is the most prevalent juvenile macular dystrophy, and it has been associated with mutations in the ABCR gene, encoding a photoreceptor-specific transport protein. In this study, we determined the mutation spectrum in the ABCR gene in a group of Italian STGD patients. METHODS: The DNA samples of 71 Italian patients (from 62 independent pedigrees), affected with autosomal recessive STGD, were analysed for mutations in all 50 exons of the ABCR gene by the DHPLC approach (with optimization of the DHPLC conditions for mutation analysis) and direct sequencing techniques. RESULTS: In our group of STGD patients, 71 mutations were identified in 68 patients with a detection rate of 95.7%. Forty-three mutations had been already reported in the literature, whereas 28 mutations had not been previously described and were not detected in 150 unaffected control individuals of Italian origin. Missense mutations represented the most frequent finding (59.2%); G1961E was the most common mutation and it was associated with phenotypes in various degrees of severity. CONCLUSIONS: Some novel mutations in the ABCR gene were reported in a group of Italian STGD patients confirming the extensive allelic heterogeneity of this gene-probably related to the vast number of exons that favours rearrangements in the DNA sequence.

A normal electro-oculography in a family affected by best disease with a novel spontaneous mutation of the BEST1 gene.

AIMS: To describe clinical and genetic findings in an Italian family affected by Best disease. METHODS: Five related patients underwent a complete ophthalmological assessment; genetic testing was performed by single-strand conformation polymorphism analysis and direct sequencing of the BEST1 gene. RESULTS: In three of five family members, the sequence analysis of the BEST1 gene revealed a single Phe-to-Leu transition at nucleotide 305 associated with clinical evidence of Best disease. Surprisingly, the electro-oculogram was normal in all affected patients. CONCLUSION: This study reveals a de novo mutation in the BEST1 gene never described before, sustaining the autosomal-dominant pattern of inheritance of the disease. Clinical evaluation showed phenotypic variability between affected members. In addition, these data suggest that a normal electro-oculography (EOG) does not rule out a diagnosis of Best disease, supporting instead the crucial role of molecular analysis.

Modelling the pharmacokinetics of tramadol: on the difference between CYP2D6 extensive and poor metabolizers.

In this work we propose a mathematical model for the kinetics of tramadol, a synthetic opioid commonly used for treating moderate to severe pain. This novel theoretical framework could result in an objective criterion on how to adjust the assigned dose, depending on the genetic polymorphisms of CYP2D6. The model describes the coupled dynamics of tramadol and the metabolite O-desmethyltramadol. The effect of diffusion of the drug in the blood is here accounted for and we further hypothesize the existence of a time delay in the process of chemical translation from tramadol into metabolites. The system of coupled differential equations is solved numerically and the free parameters adjusted so to interpolate the experimental time series for the intravenous injection setting. Theoretical curves are shown to reproduce correctly the experimental profiles obtained from clinical trials. This enables in turn to extract an estimate of the metabolization rate. A difference in metabolization rate between CYP2D6 poor and extensive metabolizers is also found, and the stereoselectivity in the O-demethylation of tramadol highlighted. Our results allow one to quantify the dose of (+)-tramadol (resp. (-)-tramadol) administered to poor or extensive metabolizers, if the same effect is sought. The latter is here quantified through the blood concentration of (+)-metabolites (resp. (-)-metabolites).

Phenotypic intrafamilial variability associated with S212G mutation in the RDS/peripherin gene.

PURPOSE: To describe an Italian family in which two separate phenotypes (retinitis pigmentosa and adult onset vitelliform macular dystrophy) are associated with an identical mutation (S212G) in the peripherin/RDS gene. This mutation has already been reported in patients with retinitis pigmentosa, but it has never been previously detected in association with adult onset vitelliform macular dystrophy. METHODS: A 38-year-old woman complained of bilateral mild metamorphopsias and on ophthalmologic examination she showed the clinical phenotype of adult onset vitelliform macular dystrophy. Her 62-year-old mother was clinically diagnosed with a retinitis pigmentosa, with a severe clinical course. RESULTS: In both patients, molecular genetic analysis revealed a 874A-->G transition in the exon 2 of the RDS gene leading to the amino acid change of S212G. CONCLUSIONS: Peripherin/RDS S212G mutation may have damaging effects on the formation and stability of the photoreceptors' disk structure and may be associated with different clinical phenotypes, even in the same family. Intrafamilial phenotypic variability has been reported for other RDS mutations; this supports the possible influence of modifier genes or environmental factors in the clinical expression of RDS gene variants. Moreover, it suggests that in patients with retinal degeneration and peripherin/RDS mutation, caution should be taken both in using molecular genetic results to predict the clinical course of the disease and in offering genetic counseling.

A novel mutation in the VMD2 gene in an Italian family with Best maculopathy.

Vitelliform macular dystrophy (Best disease) is an inherited macular degeneration in which the primary defect is thought to occur at the level of the retinal pigment epithelium. The VMD2 gene, considered responsible for the disease, mapped to the long arm of chromosome 11, and it codifies the bestrophin protein, probably acting as a transmembrane ionic channel. In the present study, we screened for mutations the VMD2 gene in Italian patients with Best maculopathy. Five families with Best disease were recruited from central and southern Italy, and family members were evaluated by complete ophthalmologic examination and DNA analysis by means of DHPLC technology. Some mutations of the VMD2 gene were identified and among them there was a novel mutation (R218G), probably involving a functionally active region of the bestrophin protein. In spite of the small number of families considered, it was possible to note a significant phenotypic heterogeneity. First, in one family the R218C mutation was associated with early onset of choroidal neovascularization (CNV) in the affected mother and her son, while no CNV was reported in another family sharing the same mutation. Then a patient with the R25W mutation showed a multifocal location of the vitelliform deposits, while another family with the same mutation showed a typical isolated vitelliform disc in the macular area.

Pancreas retransplantation: outcomes of 20 cases.

The objective of this paper was to evaluate our initial experience with pancreas retransplantation. From January 26, 1996 to February 2005, 285 pancreas transplantations were performed, including 20 (7%) retransplants. The causes of primary graft loss were graft thrombosis in 11 (55%, 7 venous and 4 arterial); 4 (20%) chronic rejections; 2 (10%) ischemia/reperfusion injury; 1 severe graft pancreatitis; 1 primary nonfunction; and 1 sepsis. Venous drainage was placed in the iliac vessels in 14 (70%), vena cava in 5 (25%), and portal drainage in 1. The exocrine drainage was vesical in 16 (80%) and enteric in 4 (20%). In 14 cases (70%), the primary graft was removed before and in 6 (30%) at the time of retransplantation. Immunosuppression was based on antilymphocyte induction, tacrolimus, mycophenolate mofetil, and steroids in all patients. One-year patient and graft survivals were 95% and 85%. In conclusion, pancreas retransplants were feasible with results comparable to a primary pancreas transplantation.

Occurrence of full-thickness macular hole complicating Stargardt disease with ABCR mutation.

PURPOSE: To report an unusual episode of full-thickness macular hole complicating Stargardt disease with an ABCR mutation. METHODS: Case report . RESULTS: Fundus examination of a 20-year-old healthy man showed typical fundus manifestation with yellowish-round or fish-like flecks associated with vitreous macular adhesion and a round punched-out area in the right eye. Optical coherence tomography (OCT) illustrated a full-thickness macular hole. Molecular genetic examination of the ABCR gene showed two heterozygous missense mutations: R1108C (CGC-->TGC) in exon 22 and a splicing mutation IVS6--> 1GT - described in the literature in association with Stargardt disease. CONCLUSIONS: Macular hole was once described in other inherited retinal degenerations (Best disease and Bietti crystal line retinopathy). The pathogenesis gives rise to a host of speculations: widespread alteration of the retinal pigment epithelium; inflammatory mechanisms; a minor trauma which might cause subretinal fibrosis. Surgical procedures were not performed on our patient after his ophthalmologic history and findings were considered.

Pharmacogenomics education: International Society of Pharmacogenomics recommendations for medical, pharmaceutical, and health schools deans of education.

Pharmacogenomics would be instrumental for the realization of personalized medicine in coming decades. Efforts are evident to clarify the potential bioethical, societal, and legal implications of key pharmacogenomics-based technologies projected to be soon introduced into the core practice of medicine. In sharp contrast, a lack of sufficient attention to educational aspects of pharmacogenomics, both for professionals and for society at large, is evident. In order to contribute to this discussion, a 'Pharmacogenomics Education Forum' was held on October 2, 2004 during the 3rd Annual Meeting of the International Society of Pharmacogenomics (ISP) at Santorini, Greece. The participants, members of the ISP Pharmacogenomics Education Forum, after deliberate discussions, proposed a document of 'Background Statement' and 'Recommendations and Call for Action' addressed to Deans of Education at Medical, Pharmaceutical, and Health Schools globally. This document has been considered by the education committee of the International Society of Pharmacogenomics and the result is presented here. We hope that this call would be listened to, and soon followed by beneficial action, ultimately leading to enhanced implementation of personalized medicine into core medical education and practice.