ABSTRACT
Aims: The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients' logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Methods: Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. Results: From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10-30%, 30-50% and 50-70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country's Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient's access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Conclusions: Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.
ABSTRACT
Abstract: Psoriasis is a immune-mediated, chronic, inflammatory skin dis-ease. In HIV positive (HIV+) patients we usually observe more serious clinical features and recalcitrant course. Furthermore, therapeutic man-agement of HIV+ patient is complex and requires collaboration with the infectious disease specialist. We report the case of a patient affected by severe psoriasis who contracted HIV infection during biological therapy and, subsequently, succesfully treated with ixekizumab.
Subject(s)
HIV Infections , Psoriasis , Antibodies, Monoclonal, Humanized/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Humans , Male , Psoriasis/complications , Psoriasis/drug therapy , Severity of Illness Index , Skin , Treatment OutcomeABSTRACT
Abstract: Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical , dermoscopic and histolopathologic features of a case of proliferative nodule arising within blue nevus is discussed. Running title: Blue nevi are an heterogeneous group of melanocytic lesions blue tinctorial properties. Proliferative nodules are rare benign lesions often present at birth as a component of a large congenital melanocytic nevi, congenital or acquired nevi. We first report a case of proliferative nodule arising within blue nevus.
Subject(s)
Melanoma , Nevus, Blue , Nevus, Pigmented , Skin Neoplasms , Humans , Infant, Newborn , Nevus, Blue/pathology , Nevus, Pigmented/congenital , Nevus, Pigmented/pathologySubject(s)
COVID-19 , Administration, Cutaneous , Adult , Child , Humans , Mucous Membrane , SARS-CoV-2 , SkinABSTRACT
Hu proteins are members of the RNA-binding protein (RBP) family and play a pivotal role in the regulation of post-transcriptional processes. Through interaction with selected mRNAs, RBPs regulate their function and stability; as a consequence, RBP dysregulation can cause abnormal translation of key proteins involved in several pathologies. In the past few years, this observation has sparked interest to develop new treatments against these pathologies by using small molecules able to modulate RBP activity. Among the four Hu proteins, we have directed our efforts towards the isoform HuR, which is mainly involved in cancer, inflammation and retinopathy. Aimed at developing compounds able to modulate the stability of HuR-mRNA complexes, in the present work, we applied a biophysical fragment screening by assessing a library of halogen-enriched heterocyclic fragments (HEFLibs) via Surface Plasmon Resonance (SPR) and Saturation Transfer Difference (STD) NMR to select promising fragments able to interact with HuR. One selected fragment and a few commercially available congeners were exploited to design and synthesize focused analogues of compound N-(3-chlorobenzyl)-N-(3,5-dihydroxyphenethyl)-4-hydroxybenzamide (1), our previously reported hit. STDNMR spectroscopy, molecular modeling, and SPR offered further insight into the HuR-small molecule interaction and showed that fragment-based approaches represent a promising and yet underexplored strategy to tackle such unusual targets. Lastly, fluorescence polarization (FP) studies revealed the capability of the new compounds to interfere with the formation of the HuR-mRNA complex. This is, to our knowledge, the first fragment-based campaign performed on the Hu protein class, and one of the few examples in the larger RBP field and constitutes an important step in the quest for the rational modulation of RBPs and related RNA functions by small molecules.
Subject(s)
Picolinic Acids/chemistry , RNA-Binding Proteins/chemistry , Humans , Models, Molecular , Molecular Structure , Picolinic Acids/chemical synthesis , Surface Plasmon ResonanceABSTRACT
The aesthetic goals of implant dentistry should be similar to those of conventional prostheses. In implant-prosthetic rehabilitations of the anterior sectors, the quantity and quality of hard and soft tissue play a fundamental role in achieving the desired aesthetics and in integrating the restoration in a complete and harmonious way into the existing anterior dentition. Post-extraction implantology is a treatment option for implant therapy after the extraction of a single tooth in the anterior jaw. This article presents some key factors to analyze and follow in order to achieve a predictable and acceptable aesthetic result. The creation of a predictable peri-implant aesthetics requires adequate preservation of the bone and soft tissues around the teeth that will be extracted and a correct positioning of the 3D implant. Furthermore, aesthetic success requires the creation of a correct transmucosal path, during the provisional prosthetic phases, which must be replicated and maintained with the definitive crowns.
Subject(s)
Immediate Dental Implant Loading , Crowns , Esthetics , Esthetics, Dental , Tooth Extraction , Treatment OutcomeABSTRACT
BACKGROUND: The outbreak of coronavirus disease-2019 (COVID-19) is a public health crisis of global proportion. In psoriatic patients treated with biologic agents, evidence is not yet available on susceptibility to infection with the novel SARS-CoV-2 coronavirus, and data about the perception of COVID-19 and its impact on these patients are lacking. AIMS: The aim of this observational, spontaneous study was the evaluation of the impact of anti COVID-19 measures in "fragile population" such as patients with a chronic inflammatory disease. Thus, we evaluated the impact of perceived risk on quality of life of patients with moderate to severe psoriasis, in our outpatient clinic, and how their perceptions changed before and after the adoption of Covid-19 emergency measures following the Italian Ministerial Decree in March 9, 2020. METHODS: Using a series of questions, our study surveyed adult patients with moderate to severe psoriasis receiving treatment with biologic agents (n = 591), before and after the adoption of COVID-19 emergency measures. RESULTS: Most patients (97%) had been sufficiently informed by healthcare staff about COVID-19 spread. A significant change was observed in social activity reduction before and after the adoption of the measures (18% vs. 90% of patients; P < 0.0001). Similarly, patients were more likely to suspend ongoing therapy after the measures were adopted than before (87% vs. 34% of patients; P < 0.0001). Following the measures, older patients were significantly more inclined to suspend therapy and reduce social activities than younger patients. CONCLUSIONS: Government COVID-19 emergency measures further curtailed already reduced social activities in psoriatic patients, and led to a greater inclination to suspend biologic therapy, more so in older patients, despite there being no evidence to support this suspension. These vulnerable patients may need support from clinicians in order to maintain treatment adherence.
Subject(s)
COVID-19 , Pandemics , Adult , Aged , Biological Therapy , Communicable Disease Control , Humans , Italy/epidemiology , Perception , Quality of Life , SARS-CoV-2ABSTRACT
Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.
Subject(s)
Carcinoma, Squamous Cell/diagnostic imaging , Magnetic Resonance Imaging , Neoplasm Recurrence, Local , Oropharyngeal Neoplasms/diagnostic imaging , Humans , Neoplasm Recurrence, Local/diagnostic imaging , Prognosis , Retrospective StudiesABSTRACT
Soft tissue sarcomas (STS) are uncommon, heterogeneous malignant tumors of mesodermal origin. Other than conservative surgery (CS), neoadjuvant or adjuvant radiotherapy (RT) is recommended when the risk of local recurrence is high. The aim of this study is to present our Institutional experience in adjuvant RT for treatment of STS of extremities and trunk (with either brachytherapy (BRT), external beam RT (EBRT), or both) and to provide an insight of toxicity and oncological outcomes for each RT modality. According to the RT treatment approach, patients were divided into three categories: 1) BRT alone; 2) EBRT alone; 3) combined BRT+EBRT. Differences among the three groups were assessed by the Chi-squared test. Patients' follow-up was performed every 6 months for the first two years after the end of RT and then once a year. Data from 90 patients were analyzed. The overall 3-year distant relapse-free survival (DRFS), progression-free survival (PFS), and overall survival (OS) were 84%, 80%, and 97%, respectively. Acute erythema was the most frequent side effect, although severe grade 3 toxicity was present in 5 patients. Chronic toxicity of any grade was reported in 14 patients. The incidence of chronic toxicity did not show any association with treatment modality. Multivariate analysis suggested a significant correlation between acute toxicity and tumor size, RT modality, and RT dose. In conclusion, good local control and toxicity profile were observed, despite negative patients' selection at baseline. Further investigation on wider series is warranted in order to define the optimal combination with systemic therapy.
Subject(s)
Radiotherapy, Adjuvant , Sarcoma , Disease-Free Survival , Extremities/pathology , Humans , Retrospective Studies , Sarcoma/radiotherapyABSTRACT
BACKGROUND: Psoriasis is a multifactorial chronic inflammatory skin disease characterized by erythemato-squamous lesions with a chronic relapsing course. The desease clinical activity (PASI) and the patient's quality of life (DLQI) are the main elements to assess for setting up a correct therapeutic management. OBJECTIVES: The aim of the study was to evaluate the management of the patient with moderate-severe psoriasis in therapy with biological drugs and to establish the difference in the achievement of PASI 90 and DLQI 0-1 between a group of patients treated with only biological drugs and a group of patients receiving biologic therapy in combination with a topical ointment. METHODS: We conducted a prospective, observational real-life study enrolling 60 patients with moderate to severe psoriasis and divided in two groups: Group A patients treated with biological drugs, Group B patiens treated with biological drugs in association with an ointment composed of betamethasone, salicylic acid and ammonium sulpho-ichtyolate, applied 2 times a day. PASI and DLQI were evaluated at study beginning (T0) for both study groups, after 12 weeks (T3) for sample in therapy with biological drugs and after 24 weeks (T6) for sample in co-medication therapy. RESULTS: The two-way ANOVA method was used to evaluate the standard deviations (SD): at T3 and T6 Group B obtained a significant PASI reduction and improvement of DLQI (* p value <0.05) compared to Group A. CONCLUSIONS: Our study shown that the patients treated with biologics in co-medication with topical therapy reached a significantly higher PASI and DQLI compared with those treated with only biologics. Furthermore we observed that the association with topical oinment showed more efficacy in the treatment of areas such as palm-plantar region, that is often difficult-to-treat region, even for biologic drugs.
Subject(s)
Biological Products/therapeutic use , Ointments/therapeutic use , Psoriasis/drug therapy , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Severity of Illness Index , Skin/pathologyABSTRACT
Heat Shock Proteins are chaperones primary involved in the repair of cellular damages induced by temperature. The harmful effect of temperature on the male gonad is well known, on the contrary knowledge on the effects of the environment on semen quality are still insufficient. The aim of this paper was to learn more about the role of HSPs and the environment in modulating the physiology of equine male gonads. We showed a detailed analysis of equine semen characteristic and the expression level of three HSPs (60-70-90) over a one-year period analyzing the effects of temperature and humidity and the correlation among the different variables. We showed also that the interpretation of results depends strongly on the way in which data are assembled and analyzed, therefore we compared results obtained from three different ways of grouping: according to single months, to weather seasons and to mare reproductive periods. Results showed that the expression of the three HSPs is correlated to the environment through temperature and humidity and that it reaches the highest level in the breeding season and in summer. We found also that HSPs expression is correlated to some variables describing the quality of equine semen (concentration) and the kinetic of spermatozoa (total motility-MOT, %, average path velocity -VAP, µm/s- and lateral head displacement -ALH, µm). No correlation was found between HSPs expression and the mitochondrial membrane potential; while viability and HSP90 expression resulted positively correlated. The month-by-month analysis evidenced that in February equine semen has the highest kinetic characteristics (increased linearity -LIN, %-, straightness -STR, % -and average path velocity -VAP, µm/s) with the highest number of motile, progressive motile and rapid cells. These results may have a great impact in the comprehension of functional aspects of the physiology of equine semen and may have potential implications for breeders who want to understand the period (and/or month) of the year in which equine semen reaches the best characteristics with increased chances for better results in reproductive practice.
Subject(s)
Semen Analysis , Sperm Motility , Animals , Female , Heat-Shock Proteins/genetics , Horses , Male , Semen , Semen Analysis/veterinary , SpermatozoaABSTRACT
The aim is to present the technical feasibility and efficacy of multiple re-irradiation (re-EBRT) for local recurrence of prostate cancer (PCa) using retrospective analysis of an updated series of patients who received ablative re-EBRT with stereotactic image-guided technique for isolated local recurrence of PCa. Eight patients received three RT courses (2 re-RTs); of those 2 received 4 RT courses (3 re-RTs). Local relapse in the prostate was assessed by multiparametric magnetic resonance and/ or choline positron emission tomography. Before treatment planning, all patients had been evaluated for late toxicity from previous RT according to RTOG/EORTC. Biochemical control was assessed according to Phoenix definition. Mean age at the third RT course was 68 (standard deviation, SD: 7.2); all patients had a good performance status. At diagnosis, four cases were classified as high risk PCa, three as intermediate and one as low per NCCN 2017. Biochemical progression free interval after first and second RT-course were 74 (IQR: 59.3-133.6) months and 33 (IQR: 20.8-53.1) months, respectively. Biochemical and radiological response was registered in all patients. At present, seven out of eight patients are disease free. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Multiple RT courses with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent, low-burden PCa recurrence in adequately selected patients. Deeper understanding of radiobiological effects of hypofractionation and larger series of patients are warranted to fully evaluate the applicability of multiple RT courses in the setting of locally recurrent PCa.
Subject(s)
Neoplasm Recurrence, Local/radiotherapy , Prostatic Neoplasms/radiotherapy , Re-Irradiation , Humans , Male , Retrospective StudiesABSTRACT
To report toxicity and efficacy outcome of moderately hypofractionated image-guided external-beam radiotherapy in a large series of patients treated for prostate cancer (PCa). Between 10/2006 and 12/2015, 572 T1-T3N0M0 PCa patients received 70.2 Gy in 26 fractions at 2.7 Gy/fraction: 344 patients (60%) with three-dimensional conformal radiotherapy (3D-CRT) and 228 (40%) with intensity-modulated radiotherapy (IMRT). Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median age was 74 years (interquartile range 69-77). Compared with 3D-CRT, in IMRT group more high-risk patients (29% vs 18%; P = 0.002) and more high-volume target (75% vs 60%; P < 0.001) were included. Acute gastro-intestinal (GI) toxicity G > 1 were registered in 8% and in 11% IMRT and 3D-CRT patients, respectively, whereas late GI G > 1 were observed in 2% and 16% IMRT and 3D-CRT patients, respectively. Acute genito-urinary (GU) toxicity G > 1 were registered in 26% and 40% IMRT and 3D-CRT patients, respectively, whereas late GU G > 1 occurred in 5% IMRT and 15% 3D-CRT patients. Multivariate proportional hazard Cox models confirmed significantly greater risk of late toxicity with 3D-CRT compared to IMRT for GU > 1 (P = 0.004) and for GI > 1 (P < 0.001). With a median 4-year follow-up, overall survival (OS), clinical progression-free survival (cPFS) and biochemical PFS (bPFS) for the whole series were 91%, 92% and 91%, respectively. cPFS and bPFS were significantly different by risk groups. Multivariate Cox models for bPFS and cPFS showed no difference between irradiation techniques and a significant impact of risk group and initial PSA. Moderately hypofractionated radiotherapy is a viable treatment option for localized PCa with excellent tumour control and satisfactory toxicity profile. IMRT seems associated with a reduction in toxicity, whereas tumour control was equal between IMRT and 3D-CRT patients and depended mainly on the risk category.
Subject(s)
Prostatic Neoplasms/radiotherapy , Radiotherapy, Image-Guided/adverse effects , Radiotherapy, Image-Guided/methods , Adult , Aged , Aged, 80 and over , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Progression-Free Survival , Prostatic Neoplasms/mortality , Radiation Dose Hypofractionation , Radiation Injuries/epidemiology , Radiation Injuries/etiology , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Conformal/adverse effects , Radiotherapy, Conformal/methods , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Retrospective StudiesABSTRACT
The ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumulating evidences indicate that miR-205-5p is significantly downregulated in breast tumors compared with normal breast tissue and acts as a tumor suppressor directly targeting oncogenes such as Zeb1 and ErbB3. In this study, we report that miR-205-5p is highly expressed in BCSCs and represses directly ERBB2 and indirectly EGFR leading to resistance to targeted therapy. Furthermore, we show that miR-205-5p directly regulates the expression of p63 which is in turn involved in the EGFR expression suggesting a miR-205/p63/EGFR regulation.
Subject(s)
Breast Neoplasms/drug therapy , ErbB Receptors/genetics , MicroRNAs/genetics , Receptor, ErbB-2/genetics , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/genetics , ErbB Receptors/biosynthesis , Female , Gene Expression Regulation, Neoplastic , Humans , Lapatinib , MicroRNAs/biosynthesis , Molecular Targeted Therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/drug effects , Quinazolines/administration & dosage , Receptor, ErbB-2/biosynthesis , Transcription Factors/biosynthesis , Trastuzumab/administration & dosage , Tumor Suppressor Proteins/biosynthesisABSTRACT
Incorporation of novel agents into auto-SCT for patients with multiple myeloma has led to improvement in their outcomes. However, the effects of new drugs, either single or combined, on PBSC mobilization have not been fully evaluated, particularly in phase 3 clinical studies. We analyzed the impact of two novel agent-based induction treatments in patients enrolled in the GIMEMA MMY-3006 study comparing bortezomib, thalidomide and dexamethasone (VTD) versus thalidomide and dexamethasone (TD) in preparation for double auto-SCT. Results showed that a short-term induction therapy with VTD did not adversely affect CD34(+) cell yields as compared with TD (9.75 vs 10.76 × 10(6) CD34(+) cells/kg, P=0.220). For poor mobilizers (<4 × 10(6) CD34(+) cells/kg), 5-year rates of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were significantly shorter than for successful mobilizers (TTP:17 vs 48%, P<0.0001; PFS: 16 vs 46%, P<0.0001; OS: 50 vs 80%, P<0.0001). These differences were retained across patients randomized to the TD arm; conversely, no differences in outcomes were seen in patients treated with VTD, irrespective of the number of harvested CD34(+) cells. The number of collected PBSCs predicted better outcomes after auto-SCT and VTD overcame the negative impact of a poor stem cell mobilization.
Subject(s)
Bortezomib/administration & dosage , Dexamethasone/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation , Thalidomide/administration & dosage , Autografts , Female , Humans , Induction Chemotherapy/methods , Male , Middle AgedABSTRACT
A number of studies suggest that cancer stem cells are essential for tumour growth, and failure to target these cells can result in tumour relapse. As this population of cells has been shown to be resistant to radiation and chemotherapy, it is essential to understand their biology and identify new therapeutic approaches. Targeting cancer metabolism is a potential alternative strategy to counteract tumour growth and recurrence. Here we applied a proteomic and targeted metabolomic analysis in order to point out the main metabolic differences between breast cancer cells grown as spheres and thus enriched in cancer stem cells were compared with the same cells grown in adherent differentiating conditions. This integrated approach allowed us to identify a metabolic phenotype associated with the stem-like condition and shows that breast cancer stem cells (BCSCs) shift from mitochondrial oxidative phosphorylation towards fermentative glycolysis. Functional validation of proteomic and metabolic data provide evidences for increased activities of key enzymes of anaerobic glucose fate such as pyruvate kinase M2 isoform, lactate dehydrogenase and glucose 6-phopshate dehydrogenase in cancer stem cells as well as different redox status. Moreover, we show that treatment with 2-deoxyglucose, a well known inhibitor of glycolysis, inhibits BCSC proliferation when used alone and shows a synergic effect when used in combination with doxorubicin. In conclusion, we suggest that inhibition of glycolysis may be a potentially effective strategy to target BCSCs.
Subject(s)
Breast Neoplasms/metabolism , Deoxyglucose/metabolism , Glycolysis , Neoplastic Stem Cells/metabolism , Breast Neoplasms/enzymology , Cell Line, Tumor , Female , Humans , L-Lactate Dehydrogenase/metabolism , Neoplastic Stem Cells/enzymology , Oxidative Phosphorylation , Pyruvate Kinase/metabolismABSTRACT
The process evaluation of HEALTHY, a large multi-center trial to decrease type 2 diabetes mellitus in middle school children, monitored the implementation of the intervention to ascertain the extent that components were delivered and received as intended. The purpose of this article is to report the process evaluation findings concerning the extent to which the HEALTHY nutrition intervention was implemented during the HEALTHY trial. Overall, the observed fidelity of implementing nutrition strategies improved from baseline to the end of the study. By the last semester, all but two nutrition process evaluation goals were met. The most challenging goal to implement was serving high fiber foods, including grain-based foods and legumes. The easiest goals to implement were lowering the fat content of foods offered and offering healthier beverages. The most challenging barriers experienced by research dietitians and food service staff were costs, availability of foods and student acceptance. Forming strong relationships between the research dietitians and food service staff was identified as a key strategy to meet HEALTHY nutrition goals.
Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Food Services/organization & administration , Health Promotion/organization & administration , Pediatric Obesity/prevention & control , Process Assessment, Health Care , School Health Services/organization & administration , Adolescent , Adolescent Nutritional Physiological Phenomena , Child , Energy Intake , Feeding Behavior , Female , Food Preferences , Health Education , Humans , Interviews as Topic , Male , Nutrition Surveys , Program EvaluationABSTRACT
Regulatory T cells (Tregs) are considered to be key immunomodulatory cells of the immune system and are increased in chronic lymphocytic leukemia (CLL). Rai stage 0 identifies patients with early stage CLL for which there is no effective intervention at the present time and a "wait and see" policy is usually adopted. Some biological and clinical studies have reported that green tea constituents, such as epigallocatechin-gallate (EGCG), have antitumor effects on hematologic malignancies including CLL. We report data on a clinical trial in which green tea extracts were given orally to 12 patients with stage 0 CLL and 12 healthy subjects. Ten patients and 10 controls completed the 6-month scheduled therapy. Two patients and 2 controls stopped therapy within 1 month because of tachycardia and epigastralgia. Eight out 10 evaluable patients (80 percent) showed a reduction of lymphocytosis and absolute number of circulating Tregs, as well. One patient (10 percent) had a stabilization of lymphocytosis and a reduction of Tregs, and 1 patient (10 percent) showed an increase of both lymphocytosis and Tregs. Only the non-responding patient progressed after 5 months from the end of green tea administration and chemotherapy was given. Interestingly, both IL-10 and TGF-beta serum levels declined throughout the green tea intake period, in both patients and controls. These data seem to indicate that green tea is able to modulate circulating Tregs in CLL patients with early stage of the disease. This can result in the control of lymphocytosis as well as in the prevention of disease progression.
Subject(s)
Camellia sinensis , Immunologic Factors/pharmacology , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Plant Extracts/pharmacology , T-Lymphocytes, Regulatory/drug effects , Adult , Aged , Aged, 80 and over , CD4 Lymphocyte Count , Caffeine/analysis , Catechin/analogs & derivatives , Catechin/analysis , Female , Humans , Immunologic Factors/chemistry , Interleukin-10/blood , Male , Middle Aged , Plant Extracts/chemistry , T-Lymphocytes, Regulatory/immunology , Transforming Growth Factor beta/bloodABSTRACT
This in vitro investigation was conducted to study the relationship between resonance frequency analysis (RFA) and lateral displacement measurements of dental implants. A total of 30 implant sites were prepared in nine fresh bovine bone specimens. The bone density around each preparation was determined by using cone beam computerized tomography (CBCT) and imaging software. Dental implants were then inserted during continuous registration of insertion torque. RFA measurements were performed in perpendicular and parallel to the long axis of the specimens. The bone blocks were embedded in plaster and fixated in a specially designed rig for displacement measurements. A lateral force of 25 N was applied via an abutment perpendicular and parallel to each implant and the displacement measured in µm. In addition, a flex constant (µm N(-1) ) was calculated for each measurement. There was a significant inverse correlation between RFA and lateral implant displacement (µm) measurements and between RFA measurements and the flex constant in both perpendicular and parallel directions in bone (P ≤ 0·001). Moreover, both RFA and displacement measurements correlated with bone density (P ≤ 0·001). It is concluded that RFA measurements reflect the micromobility of dental implants, which in turn is determined by the bone density at the implant site.