CARDIOCARE: An integrated platform for the management of elderly multimorbid patients with breast cancer therapy induced cardiac toxicity.

Breast cancer (BC) remains the most diagnosed cancer in women, accounting for 12% of new annual cancer cases in Europe and worldwide. Advances in surgery, radiotherapy and systemic treatment have resulted in improved clinical outcomes and increased survival rates in recent years. However, BC therapy-related cardiotoxicity, may severely impact short- and long-term quality of life and survival. This study presents the CARDIOCARE platform and its main components, which by integrating patient-specific data from different categories, data from patient-oriented eHealth applications and wearable devices, and by employing advanced data mining and machine learning approaches, provides the healthcare professionals with a valuable tool for effectively managing BC patients and preventing or alleviating treatment induced cardiotoxicity.Clinical Relevance- Through the adoption of CARDIOCARE platform healthcare professionals are able to stratify patients for their risk for cardiotoxicity and timely apply adequate interventions to prevent its onset.

Medical legislation - educational needs assessment for dental students.

Rationale (hypothesis): Many studies have highlighted the vulnerabilities in medical practice due to the legislation ignorance. Therefore, developing special programs for students training is needed and has become imperative. Objective: This research aimed to identify the educational needs for the 5th year students in "Carol Davila" School of Dentistry in Bucharest, related to the legislation in dentistry and its area of application. Methods and results: 199 students were invited to respond to a specially designed questionnaire. The questionnaire had 11 closed-response questions and the answers were statistically analyzed. The results indicated many educational needs in all the areas of investigation. Discussion: "Carol Davila" University of Medicine and Pharmacy is the first university in Romania that created a new discipline in the School of Dentistry, called Work Organization and Legislation in Medicine and Dentistry.

Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter - Case Report.

Cherubism is a particular form of fibrous dysplasia of the jaws. Familial occurrence was reported in most cases. The condition is a rare hereditary disorder with autosomal dominant inheritance, with complete penetrance in males and incomplete penetrance in females and variable expressivity. It is known to be caused by mutations in the gene encoding SH3-domain binding protein 2, SH3BP2 gene. Major diagnostic criteria are cherubic facial appearance, painless hard enlargement of the jaws, and frequently associated dental abnormalities. The aim of the study was to analyze clinical and genetic features of cherubism in a family with 3 daughters in which the youngest one was affected. Clinical and radiographic examinations, hematological and biochemical evaluations and biopsy were performed. Molecular genetic analysis consisted of PCR amplification and direct sequencing of selected exons of the SH3BP2 gene. Cherubism was suspected based on clinical and radiographic examinations of the 9-year-old daughter. She presented asymmetrical enlargement of the mandible, speech and swallowing problems and dental abnormalities on the lower jaw. There was no history of similar clinical findings in any of the daughters or the parents of the affected girl. Abnormal results were obtained by genetic analysis. A c.1244G>A mutation was identified in exon 9 of the SH3BP2 gene in the asymptomatic mother and her affected daughter. The identified mutation in the SH3BP2 gene is probably disease-causing. The asymptomatic mother transmitted the gene mutation to her affected daughter. Our results confirm the reduced penetrance and variable expression of the gene mutation.

[Correlations between the occlusal plane angle and the risk of relapse after surgical orthodontic treatment of Angle Class III anomalies]. / Corelatii intre orientarea planului de ocluzie si riscul de recidiva in tratamentul chirurgical al anomaliilor dento-maxilare de clasa a III-a.

An important criterion in the diagnostic and therapeutic assessment of severe true mandibular prognathia (characterized by excessive growth of the mandible and hiperdivergent facial growth pattern) is the orientation of the occlusal plane compared with the facial benchmark represented by the Frankfurt horizontal line. This is because orthognatic surgery in this pathology (sagittal bilateral osteotomy) envisages not only the shortening of the mandible, but also the counterclockwise rotation of the mandible to restore facial and dento-alveolar harmony in the three planes (sagittal, transverse, vertical). The aim of the study is the analysis of the evolution of the maxillo-mandibular complex in relation to the occlusal plane after orthognatic surgery (sagittal osteotomy of the mandible and bilateral Le Fort I of the maxilla), in a group of 15 patients with a mean age 22+3 years diagnosed with skeletal class III malocclusion, hiperdivergent facial pattern, initial average value of the occlusal plane angle 130+0.60. t test applied for comparative statistical analysis for the linear and angular parameters considered in four therapeutic stages (initial presurgical, post surgical, one year post surgical) show statistically significant changes in parameters related to the mandibular length and rotation, without significant variations one year after the surgical phase.

[Computed tomography investigation of temporomandibular joint in surgery of dento-maxillary anomalies]. / Metoda de evaluare tomografica a articulatiei temporo-mandibulare in chirurgia anomaliilor dento-maxilare scheletale severe.

The aim of this study was to evaluate changes in the temporomandibular joint morphology, regarding the relation between mandibular condyle and fossa, after bilateral sagittal split osteotomy in Angle class III dentomaxillary anomalies. Preserving the preoperative position of the condyle during sagittal split osteotomy is considered important to obtain skeletal and occlusal stability. Cone-beam computed tomography of 20 class III patients with mandibular prognathism were assessed before and 6 weeks after operation to evaluate changes of the condylar position. We propose a protocol for head posture and computed tomography investigation, which makes possible the comparison between cone-beam computed tomography (CBCT) in different moments at the same patient. There are no significant changes after bilateral sagittal split osteotomy regarding joint relations.

[Clinical and therapeutical considerations regarding odontogenic acute mediastinitis]. / Consideratii clinico-terapeutice în mediastinitele acute de cauza dentara.

Odontogenic acute mediastinitis is an polymicrobial infections caused in most cases by gram negative and anaerobic germs. The odontogenic origin of the cases in this study was based on anamnestic inquiry of the patients, which reveales a dental treatment 7-15 days before the diagnosis of acute mediastinitis was established. Clinical features are often nonspecific at the debut of this affection; septic shock could appear suddenly associated with multiple systems and organs failure. This is the explication why, some of these patients presented septic shock when are diagnosed. In this situations, when acute mediastinitis is suspected, based on clinical and imaging findings, it must be confirmed by surgical exploration and perioperative bacteriological evaluations. Positive diagnosis is based on clinical features associated with labs and imaging studies. Surgery plays an important role in therapy of acute mediastinitis: debridement and drainage of mediastinum with subsequently lavage of it, using antiseptic solutions. Broad spectrum antibiotherapy should be administrated immediately, before antibiogram is ready.

Oxidative stress markers in oral lichen planus.

Oral lichen planus (OLP) is a relatively common disorder whose cause is still unknown. Oral cancer is preceded in most cases by pre malignant lesions-leukoplasia, submucous fibrosis and lichen planus. Free radicals and reactive oxygen species play important roles in both pathogenesis of lichen planus and carcinogenesis. Thus monitoring systemic and saliva compounds important for the antioxidant defence (oxidative balance) could be important for the clinician's treatment strategy. Thorough medical management and early active treatment are necessary to improve symptoms and might also be a relevant prevention strategy from squamous cell carcinoma risk, although data to fully support this statement still need investigation. The principal aim of this study was to determine the systemic uric acid, GGT, and albumin levels as well as the levels of uric acid and albumin in 20 patients diagnosed with lichen planus and 20 controls. Extensive medline search failed to reveal any study of this type. Our results showed a significant decrease of saliva (p < 0.005) uric acid and an increase in serum gamma glutamyl transpherase (GGT) (p < 0.01) as well as in the total antioxidant capacity of saliva in patient group with respect to the control one. The preliminary conclusion of our study is that uric acid, the most important salivary antioxidant and GGT could be considered in the future as useful markers of oxidative stress for elaboration of treatment strategy and monitoring.

Comparison of two strategies of background-accommodation: influence on the metabolite concentration estimation from in vivo Magnetic Resonance Spectroscopy data.

Localized proton Magnetic Resonance Spectroscopy brain signals acquired at short echo-time contain contributions from metabolites, water and a ;background' which mainly originates from macromolecules and lipids. The purpose of the present study was to compare the influence of the background-accommodation strategy on the metabolite concentration estimates. Two strategies were investigated to accommodate the background, 1) the measured background signal was incorporated in the metabolite basis-set; and 2) the background signal was estimated and subtracted from the in vivo signal using Subtract-QUEST. The influence of the background-accommodation strategy was addressed with the aid of Monte Carlo and in vivo studies. For the considered signals of this study, the concentration estimates obtained using the first approach were below those obtained with Subtract-QUEST. Indeed, the presence of residual contribution of metabolite signals with short longitudinal relaxation times (T1) in the measured background led to an underestimation of metabolite concentration estimates. Conversely, the observed underestimation of the background contribution using Subtract-QUEST led to an overestimation of the metabolite estimates.

[Inferior hemiarthroplasty of the temporo-mandibular joint with articulated condylar prosthesis type Stryker]. / Hemiartroplastia inferioara a articulatiei temporo-mandibulare cu proteza de condil articular articulata tip Stryker.

The optimal reconstruction of the mandible and of the temporo-mandibular joint after mandibular hemi-resection with disarticulation is still controversial in literature. This paperwork presents our experience on four cases in the reconstruction of the mandible together with the inferior arthroplasty of the temporo-mandibular joint, after the resection of extended benign tumors of the mandible, based on fibular free vascularized grafts having attached a Stryker titanium condylar prosthesis reconstructing the inferior segment of the temporo-mandibular joint. Our results for the this technique were excellent, with a functional rehabilitation very close to normal. After reviewing the various techniques and their arguments in literature, with accent on the TMJ reconstruction, we consider this method to be optimal for the reconstruction of mandibular defects in patients with neoplastic conditions.

[Giant parotid pleomorphic adenoma--presentation of a case and review of the literature]. / Adenom pleomorf parotidian gigant--prezentare de caz si recenzia datelor din literatura de specialitate.

This is a case presentation of a 51-year-old patient, with a giant parotid tumor on the right side (18 x 11 cm on the longer, cranio-caudal axis, 950 g), with an extremely slow evolution, since 1978. There are no clinical signs of malignancy within the tumor. A total parotidectomy with conservation of the facial nerve and a cervico-facial plasty were performed. The pathological result indicated a pleomorphic adenoma with central malignant foci. Such cases are rare in the literature, approximately 12 similar cases.

[Progress of surgical treatment in the last 10 years. Comparative study of surgical interventions performed between 1993-1995 versus between 2003-2005]. / Evolutia terapiei chirurgicale în ultima decada. Studiu comparativ al interventiilor 1993-1995 vs. 2003-2005.

In the last decade of the past century, as laparoscopy was introduced in our clinic in 1993, minimal access therapy (MAT--endoscopy, angiography, interventional imagery) had a positive and constant evolution. Our paper retrospectively evaluates the interventions performed between 2003-2005 (group A) compared to those performed between 1993-1995 (group B). We observed a 17.08% (7056 vs 6026 interventions/year) raise in the total number of interventions in group A, with a significant 66% decrease (195 vs. 588 interventions/year) of interventions for gastro-duodenal ulcer and a 18% decrease (1211 vs 1490 interventions/year) of appendectomies, but a 63% increase (1560 vs. 955 interventions/year) of cholecystectomies, 53% increase (1186 vs. 773 interventions/year) of interventions for parietal defects and a 62% (626 vs. 325 interventions/year) increase of oncological interventions. The most frequent interventions were, in the order of frequencies: cholecystectomies (79.8% laparoscopically), appendectomies, interventions for hernia and eventrations, oncological operations and trauma surgery. The incidence of laparoscopic interventions was greater in group A, counting for 19% of the total number of interventions. In group A were performed 2334 endoscopies, 149 diagnostic and therapeutic angiographies. Postoperative mortality dropped with 29.64% and hospital stay dropped to 4.7 days. We believe that the incidence of MAT should rise, by performing more laparoscopic interventions and this change should lead to a revision of the surgical residents training program.

Developing a European grid infrastructure for cancer research: vision, architecture and services.

Life sciences are currently at the centre of an information revolution. The nature and amount of information now available opens up areas of research that were once in the realm of science fiction. During this information revolution, the data-gathering capabilities have greatly surpassed the data-analysis techniques. Data integration across heterogeneous data sources and data aggregation across different aspects of the biomedical spectrum, therefore, is at the centre of current biomedical and pharmaceutical R&D.This paper reports on original results from the ACGT integrated project, focusing on the design and development of a European Biomedical Grid infrastructure in support of multi-centric, post-genomic clinical trials (CTs) on cancer. Post-genomic CTs use multi-level clinical and genomic data and advanced computational analysis and visualization tools to test hypotheses in trying to identify the molecular reasons for a disease and the stratification of patients in terms of treatment.The paper provides a presentation of the needs of users involved in post-genomic CTs and presents indicative scenarios, which drive the requirements of the engineering phase of the project. Subsequently, the initial architecture specified by the project is presented, and its services are classified and discussed. A range of such key services, including the Master Ontology on sCancer, which lie at the heart of the integration architecture of the project, is presented. Special efforts have been taken to describe the methodological and technological framework of the project, enabling the creation of a legally compliant and trustworthy infrastructure. Finally, a short discussion of the forthcoming work is included, and the potential involvement of the cancer research community in further development or utilization of the infrastructure is described.

Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation.

The suppressors of cytokine signaling (SOCS) are critically involved in the regulation of cellular proliferation, survival, and apoptosis via cytokine-induced JAK/STAT signaling. SOCS-1 silencing by aberrant DNA methylation contributes to oncogenesis in various B-cell neoplasias and carcinomas. Recently, we showed an alternative loss of SOCS-1 function due to deleterious SOCS-1 mutations in a major subset of primary mediastinal B-cell lymphoma (PMBL) and in the PMBL line MedB-1, and a biallelic SOCS-1 deletion in PMBL line Karpas1106P. For both cell lines our previous data demonstrated retarded JAK2 degradation and sustained phospho-JAK2 action leading to enhanced DNA binding of phospho-STAT5. Here, we analysed SOCS-1 in laser-microdissected Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). We detected SOCS-1 mutations in HRS cells of eight of 19 cHL samples and in three of five Hodgkin lymphoma (HL)-derived cell lines by sequencing analysis. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells of cHL tumor tissue (P < 0.01). Collectively, these findings support the concept that PMBL and cHL share many overlapping features, and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.

[Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation]. / Mutationen des Tumorsuppressorgens SOCS-1 treten im klassichen Hodgkin Lymphom häufig auf und sind assoziiert mit einer Kernakkumulation des phospho-STAT5 Proteins.

AIMS: Suppressors of cytokine signaling (SOCS) negatively regulate Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling involved in proliferation, survival, and apoptosis. We previously showed a loss of SOCS-1 function due to deleterious mutations in a major subset of mediastinal B-cell lymphoma (MBL). In MBL cell lines this leads to retarded JAK2 degradation and sustained phospho-STAT5 action results in enhanced DNA binding of phospho-STAT5. METHODS: To investigate the SOCS-1 gene we laser-microdissected Hodgkin-and Reed-Sternberg (HRS) cells of 19 classical Hodgkin lymphoma (cHL) and performed sequencing analysis. To assess phospho-STAT5 status immunohistochemistry on the corresponding paraffin-embedded cHL tumor tissue was done. RESULTS: We detected mutations of the SOCS-1 gene in HRS cells of 8 of 19 cHL samples and in 3 of 5 cHL-derived cell lines. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells (P <0.01). CONCLUSIONS: In conclusion, these findings support the concept that MBL and cHL share overlapping features and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas.

[The reconstruction of the oral and maxillofacial defects with free vascularized flaps and microsurgical anastomoses]. / Plastia reconstructiva a defectelor oro-maxilo-faciale prin lambouri liber vascularizate si anastomozate microchirurgical.

The reconstruction of the oral and maxillofacial defects is difficult, because of the high specialisation of the tissues. In cancer resection, the post-operatory defects are quite important, because of the oncological principle of assuring free margins. The free flap is a modem and nowadays very used method in oral and maxillofacial reconstruction, after the removal of the malignant tumors with this localisation. These flaps are indicated for large defects, when the reconstruction with local or regional flaps is not possible. The wide variety of the raised tissues allows better results, making them the flaps of choice for large defects of the lip and cheek. The main advantages are related to the tri-dimensional extension of the free margins, assuring the quality of life and allowing early initiation of the radiotherapy in oncological patients.

[Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in MedB-1 mediastinal lymphoma line]. / Die biallelische Mutation von SOCS-1 verhindert den Abbau von JAK2 und prolongiert die Wirkung von phospho-JAK2 in der mediastinalen B-Zell Lymphomlinie MedB-1.

Primary mediastinal B-cell lymphoma (PMBL) is a well-defined subtype of diffuse large B-cell lymphoma. Molecular cytogenetics revealed frequent gains of 9 p24. JAK2, mapping in this region, is presently regarded as a candidate oncogene since expression profiling showed high JAK2 transcript levels and JAK2 was found to be constitutively phosphorylated in mediastinal B-cell lymphomas. We confirm that in the MedB-1 mediastinal B-cell line, harbouring a trisomy 9, JAK2 transcription is elevated and the product is highly phosphorylated. However, JAK2 is not over-expressed at the protein level. On top, JAK2 protein turnover is even delayed. This unexpected finding coincides with a biallelic mutation of the SOCS-1 gene in this cell, which abrogates SOCS box function of the protein. Ectopic expression of wt-SOCS-1 in MedB-1 leads to growth arrest, dramatic reduction of phospho-JAK2 and its downstream partner phospho-STAT5. We conclude that, in MedB-1, action of phospho-JAK2 is sustained due to defective SOCS-1. Hence, SOCS-1 qualifies as a novel tumor suppressor. Of note, the SOCS-1 mutations are also present in the parental tumor of MedB-1 and were detected in 9 of 20 PMBL.

[Comparative study of clinical effectiveness of antibiotic prophylaxis in aseptic mouth-jaw- and facial surgery]. / Vergleichende Studie zur klinischen Effizienz der Antibiotikaprophylaxe in der aseptischen Mund-, Kiefer- und Gesichtschirurgie.

METHODS: This study evaluates the clinical efficiency of four regimens of antibiotic prophylaxis against wound infection in aseptic oral and maxillofacial surgery that does not involve implantation of foreign material and included 140 adult patients randomly distributed into four groups. Patients from two groups received prophylactic amoxicillin/clavulanate in a single-dose regimen or a 5-day regimen, respectively. Subjects from the other two groups received cefazolin in a single-dose regimen or a 5-day regimen, respectively. RESULTS: Clinical prophylactic efficiency proved to be equal for the four types of antibiotic regimens. DISCUSSION: Single-dose regimens are more economical, easier to administer, and carry a lower risk of inducing bacterial resistance. Amoxicillin/clavulanate is more expensive than cefazolin. For aseptic maxillofacial surgery that does not involve implantation of foreign material, we recommend preoperative single-dose antibiotic prophylaxis with cefazolin 2 g i.v. (in adult patients).

A prospective study of the effect of fracture on measured physical performance: results from the MacArthur Study--MAC.

OBJECTIVE: To examine the impact of fractures on measured physical performance and to assess whether specific fractures have unique sequelae. SUBJECTS: 762 men and women, aged 70 to 79 at baseline, who were part of the MacArthur Study of Successful Aging. DESIGN: A longitudinal case-cohort: those with prevalent fractures at baseline were excluded; cases were persons with a medically diagnosed hip, arm, spine, or wrist fracture during the follow-up period (1988-1995). MEASURES: Eight physical performance tests: turning a circle, walking fast, chair stands, timed tap, tandem stand, grip strength, single leg stand, and balance (average of single leg and tandem stands) measured at baseline and follow-up. ANALYSIS: Two fracture groups were defined: (1) those with incident wrist fractures (n = 7) and (2) those with a fracture of the hip, arm, or spine (combined fractures group, n = 16). Change in physical performance was analyzed using crude, age-adjusted, and multiply-adjusted ANCOVA models. RESULTS: The combined fracture group demonstrated statistically significant (P < .05) declines seven of eight of the performance tests compared with individuals without fractures. In contrast, individuals with wrist fractures did not experience a statistically significant decline in any performance measure compared with the no fracture group. CONCLUSIONS: Relative to those without fractures, individuals with a hip, arm, or clinical spinal fracture show similar global declines in physical performance, whereas those with wrist fracture demonstrate no physical performance decrements.

Eight years of experience in the first Romanian center of family planning and contraception.

This study describes 8 years of experience (1990-97) in the first Romanian center for family planning and contraception, which started in Bucharest at the Clinic Hospital of Obstetrics and Gynecology 'Prof. Dr. P. Sirbu' on 27 February 1990. A total of 14,258 women had attended the clinic by 1 January 1998. Trends in the use of contraceptives and the number of births and abortions at the center are described. During the 8 years, the induced abortions decreased by 65% and the uncompleted abortions (illegal abortions) by 45%. Hormonal contraception was the most commonly used contraceptive method (61.5%), followed by intrauterine devices (28.8%) and local contraception (barrier methods: condoms, diaphragms, spermicides) (9%).

How do older netcitizens compare with their younger counterparts?

The Internet is modifying the lives of people around the world. Although many talk about the democratization of knowledge and information, differences remain among users as older netcitizens are under-represented and less involved. We use national and representative U.S. data, the Current Population Survey, to show age-based differences. We complement our analysis with web-based data, the Georgia Tech World Wide Web User Surveys, to show Internet characteristics and trends by age for netcitizens. Results show that older users compose a lower share of Internet users than that of the total U.S. population; however, once they join the ranks of avid Internet users, older netcitizens are similar to their younger counterparts.