Possible role of oral ibandronate administration in Osteonecrosis of the Jaw: a case report.

We describe a case of Osteonecrosis of the Jaw (ONJ) that developed in a 65-year-old Caucasian woman with osteopenia and other risk factors who was receiving low doses of oral bisphosphonate therapy (ibandronate, 150 mg monthly). Computed tomography (CT), panoramic radiographs (OPT), 99mTc-Sn-MDP scintigraphy, and magnetic resonance imaging (MRI) were performed to study the diseased area; cytological examination also revealed the presence of suppurative material around the area of exposed bone. A diagnosis of bisphosphonate-related osteonecrosis of the jaw complicated by osteomyelitis was made. The patient was prescribed a drug protocol consisting of metronidazole 250 mg 2 times daily, chlorhexidine mouthwashes 3 times daily and chewing exercises for two months. Ibandronate was stopped and replaced with strontium ranelate. The symptoms improved and the patient is still under close follow-up. Assessment of the benefits versus risks is particularly necessary in patients with several risk factors to ascertain their eligibility for treatment with antiresorptive drugs and when this is not possible to choose alternative medications

Action of combined magnetic fields on aqueous solution of glutamic acid: the further development of investigations

In the present work the results of the known investigation of the influence of combined static (40 μT) and alternating (amplitude of 40 nT) parallel magnetic fields on the current through the aqueous solution of glutamic acid, were successfully replicated. Fourteen experiments were carried out by the application of the combined magnetic fields to the solution placed into a Plexiglas reaction vessel at application of static voltage to golden electrodes placed into the solution. Six experiments were carried out by the application of the combined magnetic fields to the solution placed in a Plexiglas reaction vessel, without electrodes, within an electric field, generated by means of a capacitor at the voltage of 27 mV. The frequency of the alternating field was scanned within the bounds of 1.0 Hz including the cyclotron frequency corresponding to a glutamic acid ion and to the applied static magnetic field. In this study the prominent peaks with half-width of ~0.5 Hz and with different heights (till 80 nA) were registered at the alternating magnetic field frequency equal to the cyclotron frequency (4.2 Hz). The general reproducibility of the investigated effects was 70% among the all solutions studied by us and they arose usually after 40–60 min. after preparation of the solution. In some made-up solutions the appearance of instability in the registered current was noted in 30–45 min after the solution preparation. This instability endured for 20–40 min. At the end of such instability period the effects of combined fields action appeared practically every time. The possible mechanisms of revealed effects were discussed on the basis of modern quantum electrodynamics

A Reaction-Diffusion Numerical Model to Predict Cardiac Tissues Regeneration Via Stem Cell Therapy

Myocardial infarction is a leading cause of morbidity and mortality in the industrialized world. Extensive loss of cardiomyocytes, substituted by scarred tissue, is the key pathological mechanism leading to post infarc- tion heart failure [1]. The use of exogenous cells to replace lost cardiomy- ocytes has been demonstrated in animal models and in clinical trials by transplanting mesenchymal stem cells (MSCs) into the infarcted area. To optimize the initial conditions of the stem cell therapy, many experimen- tal studies are focused on determining the number and the localization of stem cells that must be implanted near the necrotic area. In this work we develop a quantitative numerical model able to simulate substrate con- centration profile, stem cells distribution and their proliferation near the ischemic area. The model describes the cell growth, the nutrient transport and its consumption through reaction-diffusion equations. The shrinking of the necrotic area leads in fact to a moving boundary problem. Some preliminary results, obtained in a 3D framework, are shown and discuss

Learning models for classifying Raman spectra of genomic DNA from tumor subtypes

An early and accurate detection of different subtypes of tumors is crucial for an effective guidance to personalized therapy and in predicting the ability of tumor to metastasize. Here we exploit the Surface Enhanced Raman Scattering (SERS) platform, based on disordered silver coated silicon nanowires (Ag/SiNWs), to efficiently discriminate genomic DNA of different subtypes of melanoma and colon tumors. The diagnostic information is obtained by performing label free Raman maps of the dried drops of DNA solutions onto the Ag/NWs mat and leveraging the classification ability of learning models to reveal the specific and distinct physico-chemical interaction of tumor DNA molecules with the Ag/NW, here supposed to be partly caused by a different DNA methylation degree

Right ventricle involvement in patients with breast cancer treated with chemotherapy

Background Anthracyclines can cause left ventricular (LV) dysfunction. There is little data about right ventricular (RV) damage during chemotherapy. Aim This study aimed to investigate the toxic effects of chemotherapy, analyzing its impact on right ventricular function. Material and Methods A prospective study was conducted, enrolling 83 female patients (55 +/- 11 years old) affected by breast cancer treated with anthracyclines. Cardiological evaluation, HFA risk score assessment and comprehensive echocardiogram, including speckle tracking analysis and 3D analysis, were performed before starting chemotherapy (T0) and at 3 (T1), 6 (T2) and 12 months (T3) after beginning treatment. RV function was assessed with tricuspid annular plane excursion (TAPSE), S' wave of the tricuspid annulus, fractional area change (FAC), RV global longitudinal strain (RV-GLS), free wall strain (RV-FWLS) and RV 3D ejection fraction (RV-3DEF). Subclinical LV CTRCD was defined as a reduction of GLS > 15% compared to baseline. Subclinical RV cardiotoxicity was defined as the co-presence of a relative decrease of 10% from baseline in RV-3DEF and a relative reduction of 15% from baseline RV-FWLS. Results After chemotherapy, we found a significant reduction in 2D-LVEF (p = < 0.001) and 3D-LVEF (p = < 0.001), in LV-GLS and RVLS (p = < 0.001), in FAC and TAPSE, also RV-3DEF reduced significantly (p = 0.002). 39% of patients developed LV subclinical CTRCD; 28% of patients developed RV subclinical cardiotoxicity. LV and RV changes occurred concomitantly, and no RV echocardiographic parameters were found to predict the development of LV CTRCD and vice-versa. Conclusion After anthracyclines-based chemotherapy, LV and RV subclinical damage occurs, and it can be detected early by speckle-tracking and 3D echocardiography

Hereditary Transthyretin Amyloidosis: How to Differentiate Carriers and Patients Using Speckle-Tracking Echocardiography

Background: Hereditary transthyretin amyloidosis is a rare disease caused by transthyretin (TTR) gene mutations. The aim of our study was to identify early signs of cardiac involvement in patients with a TTR gene mutation in order to differentiate carriers from patients with neurological or cardiac disease. Methods: A case-control study was carried out on 31 subjects with the TTR mutation. Patients were divided into three groups: 23% with cardiac amyloidosis and polyneuropathy (group A), 42% with only polyneuropathy (group B) and 35% carriers (group C). Speckle-tracking echocardiography (left-ventricular global longitudinal strain-GLS, atrial stiffness) was performed in all patients. The apical/basal longitudinal strain ratio (SAB) and relative apical sparing (RAS) were assessed in all subjects. Results: Analyzing groups C and B, we only found a significant difference in the SAB (p-value 0.001) and RAS (p-value 0.039). These parameters were significantly more impaired in group A compared to group B (SAB p-value 0.008; RAS p-value 0.002). Also, atrial stiffness was significantly impaired in groups A and B compared to group C. Conclusions: Our study suggests the diagnostic role of the SAB and RAS in cardiac amyloidosis. The SAB and RAS showed a gradual increase from carriers to patients with neurological and cardiac diseases. Thus, these parameters, in addition to atrial stiffness, could be used to monitor carriers. More extensive data are needed

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Learning models for classifying Raman spectra of genomic DNA from tumor subtypes

An early detection of different tumor subtypes is crucial for an effective guidance to personalized therapy. While much efforts focus on decoding the sequence of DNA basis to detect the genetic mutations related to cancer, it is becoming clear that physical properties, including structural conformation, stiffness, and shape, as well as biological processes, such as methylation, can be pivotal to recognize DNA modifications. Here we exploit the Surface Enhanced Raman Scattering (SERS) platform, based on disordered silver coated--silicon nanowires, to investigate genomic DNA from subtypes of melanoma and colon cancers and to efficiently discriminate tumor and healthy cells, as well as the different tumor subtypes. The diagnostic information is obtained by performing label--free Raman maps of the dried drops of DNA solutions onto the Ag/NWs mat, and leveraging the classification ability of learning models to reveal the specific and distinct interaction of healthy and tumor DNA molecules with nanowires

Novel sensitive, specific and rapid pharmacogenomic test for the prediction of abacavir hypersensitivity reaction: HLA-B*57:01 detection by real-time PCR.

Aim: International HIV treatment guidelines recommend HLA-B*57:01 typing before abacavir administration, in order to reduce the incidence of abacavir hypersensitivity reactions, the major cause of early therapy discontinuation. A fast, sensitive and specific test for HLA-B*57:01 detection has been developed in the present study. Materials & methods: Two sets of sequence-specific primers were designed, and amplification rapidly detected by real-time PCR. Results: A total of 108 samples were analyzed in a single-blind fashion, and 41 samples were identified as positive. Complete agreement, with k = 1 (standard error = 0.0962, p < 0.0001), was found, with a validated methodology used in the EPI109367 clinical trial funded by GlaxoSmithKline, and consisting of low-resolution sequence-specific oligonucleotide PCR, followed by high-resolution sequence-specific oligonucleotide PCR carried out on the HLA-B*57-positive samples. Conclusion: We provided a detailed characterization of a novel HLA-B*57:01 screening test, which can be easily implemented by those laboratories already involved in the detection of viral load and virus genotyping

Expression of iNOS, CD163 and ARG-1 taken as M1 and M2 markers of microglial polarization in human glioblastoma and the surrounding normal parenchyma

Microglia and macrophages appear to be the most common cells in the GBM microenvironment. In the present study we investigated the status of macrophages/microglia activation in surgical specimens from 41 patients diagnosed with grade IV GBM. For each patient we analyzed both the center of tumor and the parenchyma surrounding the tumor. The specimens were stained for: i) IBA1, a 17-kDa EF hand protein specifically expressed in microglia/macrophages ii) CD163, a cell surface antigen associated with M2 phenotype; iii) iNOS, taken as a functional marker of M1 phenotype, and iv) ARG-I, taken as a functional marker of M2 phenotype. Staining was scored in a double-blinded score on a scale from 0 to 5. Our results suggest that CD163 expression is higher within the tumor than in surrounding periphery in both male and female patients; while iNOS is higher within the tumor in males, no significant difference was found for ARG-1. In addition, analyzing the data in TGCA database, we found that CD163 expression was significantly and inversely correlated with mean survival times, with average survival times ranging from 448&nbsp;days in patients having low expression, to 319 in mid, and 353 in patients with high CD163 expressing tumors. In contrast, no significant association was found between survival time and ARG-1 or iNOS expression