The Effect of Denture Adhesives on Denture Quality and Occlusal Force.

INTRODUCTION: Complete dentures (CDs) have been associated with substantial problems regarding edentulous patient's function. Denture adhesives seem to be useful adjuncts to improving retention and stability. METHODS: A clinical study was undertaken to investigate the effect of a denture adhesive (DA) on function in complete denture wearers along with the quality of their CDs. Thirty complete denture wearers participated in the study. The first phase of the experimental procedure comprised 3 groups of measurements performed at 3 distinct time points: the initial measurement (T1), a 2nd measurement after 15 days of DA daily application (T2), and a 3rd measurement following a 15-day washout period (T3). The second phase consisted of the follow-up measurements. The measurements included: recording of relative occlusal force (ROF), distribution of occlusal contacts (DOC) and center of force (COF) using the T-Scan 9.1 device and functional assessment of dentures using the FAD index. RESULTS: The DA use induced a statistically significant increase in ROF (p-value=0.003) and decrease in COF (p-value⟨0.001) and DOC (p-value=0.001). The overall FAD score significantly improved (p-value⟨0.001). CONCLUSIONS: The use of the DA improved the occlusal force, the distribution of occlusal contacts as well as the qualitative characteristics of CDs.

Lateral gain is impaired in macular degeneration and can be targeted to restore vision in mice.

Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss of central vision affects lateral feedback to spared areas of the human retina. We identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in macular degeneration. This finding provides an insight into the negative effects of geographic atrophy on vision. Therefore, we develop a strategy to restore this feedback mechanism, through activation of laterally projecting cells. This results in improved vision in Cnga3-/- mice, which lack cone function, as well as a mouse model of geographic atrophy. Our work shows that a loss of lateral gain control contributes to the vision deficit in macular degeneration. Furthermore, in mouse models we show that lateral feedback can be harnessed to improve vision following retinal degeneration.

ß-eye: A benchtop system for in vivo molecular screening of labeled compounds.

Preclinical nuclear molecular imaging speeds up the mean time from synthesis to market, in drug development process. Commercial imaging systems have in general high cost, require high-cost service contracts, special facilities and trained staff. In the current work, we present ß-eye, a benchtop system for in vivo molecular screening of labeled compounds with Positron Emission Tomography (PET) isotopes. The developed system is based on a dual-head geometry, offering simplicity and decreased cost. The goal of the design is to provide 2D, real-time radionuclide images of mice, allowing the recording of fast frames and thus perform fast kinetic studies, with spatial resolution of ∼2 mm. Performance evaluation demonstrates the ability of ß-eye to provide quantitative results for injected activities lower than 1.5 MBq, which is adequate for pharmacodynamic studies in small mice.

Benchtop systems for in vivo molecular screening of labeled compounds, as a tool to speed up drug research.

BACKGROUND: For every new drug, >10,000 candidate molecules are tested for ~15 years. This is the daily mission of thousands research teams worldwide. It is well proven that small animal imaging speeds up this work, increases accuracy and decreases costs. However, commercial imaging systems have high purchase cost, require high service contracts, special facilities and trained staff. Thus, they are affordable to only few large research centres and not to the majority of small and medium research teams internationally. There are two main reasons that urge the addressing of this problem at large scale now: Firstly, small animal imaging started in 2000 and quickly research community and pharma industry understood its value, which opened preclinical imaging market (>2.5 Bil $). Continuous evolution in medicine and biology clearly shows the need to speed up research using new tools. Asian countries rapidly invest funds in drug research, enlarging existing market. Secondly, until recently such systems were based on complicated electronics and expensive components. Evolution in detector technology, electronics, software and 3D printing, made feasible the development of benchtop imaging systems, with attractive end user price. MATERIALS AND METHODS: Being an active partner of numerous international and national projects, we tried to identify the main requirements that an imaging system should have, in order to become a screening tool for daily use. Thus, we recently developed a new generation of affordable, but high-performance imaging systems, which can fulfil the daily needs of all research labs activated in preclinical research. Our technology covers the field of SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) imaging, while an optical and x-ray imaging system is under development. The systems are based on well tested technology, including pixeliated scintillators, Position Sensitive Photomultipliers, programmable ADCs (Analog to Digital Converters) and FPGAs (Field Programmable Gate Arrays) and are connected with a standard laptop through USB and Ethernet connection. The systems are named "eyes-series" and have been already tested for fast screening of small animals injected with labeled compounds including peptides, antibodies and nanoparticles. Besides their performance, they are offered at a fraction of the cost of the commercial ones, comparable to standard lab equipment such as HPLC, gamma counter etc, opening new prospects in preclinical research. The first system is called "γ-eye™" and it is a dedicated system for imaging photons (γ-rays) which are emitted from radiolabelled biomolecules (2D-SPECT). The second system is called "ß-eye™" and detects positrons (ß-rays) from similar biomolecules (2D-PET). They both have dimensions which are 35x35x30cm and weight which is less that 30kgr. The spatial resolution of both systems is <2mm and their energy resolution <20%. Their sensitivity allows real time imaging for the first second post injection, while images are shown in real time during acquisition. They allow recording of fast frames, down to 1min, thus it is possible to perform fast kinetic studies. Finally, they are both provided along with a laptop that has preinstalled the required software, named "VISUAL-eyes". RESULTS: The technical specifications and performance evaluation of our technology will be presented. Different applications including oncology, regenerative medicine, nanomedicine and lung imaging will be given. Finally, the results of the comparison against high performance systems and a typical workflow for optimizing throughput will be demonstrated.

An international study to revise the EORTC questionnaire for assessing quality of life in lung cancer patients.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 was the first module to be used in conjunction with the core questionnaire, the QLQ-C30. Since the publication of the LC13 in 1994, major advances have occurred in the treatment of lung cancer. Given this, an update of the EORTC QLQ-LC13 was undertaken. METHODS: The study followed phases I to III of the EORTC Module Development Guidelines. Phase I generated relevant quality-of-life issues using a mix of sources including the involvement of 108 lung cancer patients. Phase II transformed issues into questionnaire items. In an international multicenter study (phase III), patients completed both the EORTC QLQ-C30 and the 48-item provisional lung cancer module generated in phases I and II. Patients rated each of the items regarding relevance, comprehensibility, and acceptance. Patient ratings were assessed against a set of prespecified statistical criteria. Descriptive statistics and basic psychometric analyses were carried out. RESULTS: The phase III study enrolled 200 patients with histologically confirmed lung cancer from 12 centers in nine countries (Cyprus, Germany, Italy, Israel, Spain, Norway, Poland, Taiwan, and the UK). Mean age was 64 years (39 - 91), 59% of the patients were male, 82% had non-small-cell lung cancer, and 56% were treated with palliative intent. Twenty-nine of the 48 questions met the criteria for inclusion. CONCLUSIONS: The resulting module with 29 questions, thus currently named EORTC QLQ-LC29, retained 12 of the 13 original items, supplemented with 17 items that primarily assess treatment side-effects of traditional and newer therapies.

Perceived effectiveness and mechanisms of community peer-based programmes for Spinal Cord Injuries-a systematic review of qualitative findings.

STUDY DESIGN: Systematic review and meta-synthesis of qualitative findings. OBJECTIVES: To establish the perceived effectiveness and mechanisms of community peer-based programmes based on narratives of consumers with spinal cord injury (SCI). METHODS: Scopus, Academic Search Complete, CINAHL, Health Source, Medline, PsycARTICLES, PsychINFO, SPORTSDiscus and ProQuest were searched for articles published in English between January 1990 and December 2015. Qualitative studies referring to community peer-based interventions were included if most cases had a SCI. The results section of included studies was extracted and entered in NVivo. Data were inductively coded and analysed according to the three phases of Thematic Synthesis. RESULTS: The search yielded 1402 unique records, out of which 126 were scrutinised in full. Four studies were appraised based on eight criteria and were finally included in the analysis. Three analytical themes emerged: (1) a unique learning environment created by the right mixture of learning resources, learning processes and a can-do attitude; (2) peer mentors-a unique learning resource with high level of relatedness that eases and empowers participants; and (3) an intervention that responds to important unmet needs and unrealised potential. CONCLUSIONS: Community peer-based programmes for people with SCI provide individualised training in important life areas, using a variety of learning resources and a plethora of learning processes. The high level of perceived effectiveness suggests that this type of intervention is an important tool of health systems post discharge from initial rehabilitation. Community organisations should be supported with evaluating their programmes through quality research.

Evaluation of a SiPM array coupled to a Gd3Al2Ga3O12:Ce (GAGG:Ce) discrete scintillator.

PURPOSE: In this study, we present the results of the evaluation of the SensL ArraySL-4 photo-detector, coupled to a 6 × 6 GAGG:Ce scintillator array, with 2 × 2 × 5 mm(3) crystal size elements for possible applications in medical imaging detectors with focus in PET applications. Experimental evaluation was carried out with (22)Na and (137)Cs radioactive sources and the parameters studied were energy resolution and peak to valley ratio. METHODS: ArraySL-4 is a commercially available, 4 × 4 array detector covering an active area of 13.4 mm(2). The GAGG:Ce scintillator array used in this study has 0.1 mm thickness BaSO4 reflector material between the crystal elements. A symmetric resistive voltage division matrix was applied, which reduces the 16 outputs of the array to 4 position signals. A Field Programmable Gate Array was used for triggering and digital processing of the signal pulses acquired using free running Analog to Digital Converters. RESULTS: Raw images and horizontal profiles of the 6 × 6 GAGG:Ce scintillator array produced under 511 keV and 662 keV excitation are illustrated. Moreover, the energy spectra obtained with (22)Na and (137)Cs radioactive sources from a single 2 × 2 × 5 mm(3) GAGG:Ce scintillator are shown. The peak to valley ratio and the mean energy resolution values are reported. CONCLUSIONS: The acquired raw image of the GAGG:Ce crystal array under 511 keV excitation shows a clear visualization of all discrete scintillator elements with a mean peak to valley ratio equal to 40. The mean energy resolution was measured equal to 10.5% and 9% respectively under 511 keV and 662 keV irradiation.

DAPK2 regulates oxidative stress in cancer cells by preserving mitochondrial function.

Death-associated protein kinase (DAPK) 2 is a serine/threonine kinase that belongs to the DAPK family. Although it shows significant structural differences from DAPK1, the founding member of this protein family, DAPK2 is also thought to be a putative tumour suppressor. Like DAPK1, it has been implicated in programmed cell death, the regulation of autophagy and diverse developmental processes. In contrast to DAPK1, however, few mechanistic studies have been carried out on DAPK2 and the majority of these have made use of tagged DAPK2, which almost invariably leads to overexpression of the protein. As a consequence, physiological roles of this kinase are still poorly understood. Using two genetically distinct cancer cell lines as models, we have identified a new role for DAPK2 in the regulation of mitochondrial integrity. RNA interference-mediated depletion of DAPK2 leads to fundamental metabolic changes, including significantly decreased rate of oxidative phosphorylation in combination with overall destabilised mitochondrial membrane potential. This phenotype is further corroborated by an increase in the production of mitochondrial superoxide anions and increased oxidative stress. This then leads to the activation of classical stress-activated kinases such as ERK, JNK and p38, which is observed on DAPK2 genetic ablation. Interestingly, the generation of oxidative stress is further enhanced on overexpression of a kinase-dead DAPK2 mutant indicating that it is the kinase domain of DAPK2 that is important to maintain mitochondrial integrity and, by inference, for cellular metabolism.

DAPK2 is a novel modulator of TRAIL-induced apoptosis.

Targeting molecules involved in TRAIL-mediated signalling has been hailed by many as a potential magic bullet to kill cancer cells efficiently, with little side effects on normal cells. Indeed, initial clinical trials showed that antibodies against TRAIL receptors, death receptor (DR)4 and DR5, are well tolerated by cancer patients. Despite efficacy issues in the clinical setting, novel approaches to trigger TRAIL-mediated apoptosis are being developed and its clinical potential is being reappraised. Unfortunately, as observed with other cancer therapies, many patients develop resistance to TRAIL-induced apoptosis and there is thus impetuous for identifying additional resistance mechanisms that may be targetable and usable in combination therapies. Here, we show that the death-associated protein kinase 2 (DAPK2) is a modulator of TRAIL signalling. Genetic ablation of DAPK2 using RNA interference causes phosphorylation of NF-κB and its transcriptional activity in several cancer cell lines. This then leads to the induction of a variety of NF-κB target genes, which include proapoptotic DR4 and DR5. DR4 and DR5 protein expression is correspondingly increased on the cell surface and this leads to the sensitisation of resistant cells to TRAIL-induced killing, in a p53-independent manner. As DAPK2 is a kinase, it is imminently druggable, and our data thus offer a novel avenue to overcome TRAIL resistance in the clinic.

Oral Mucositis: understanding the pathology and management.

Oral Mucositis is a common complication of cancer therapy which may limit the completion of treatment and affect the quality of life of the patient. As we have come to understand its pathogenesis new developments in its management and prevention have allowed us minimize this side effect.

Early posttransplantation hemoglobin level corresponds with chronic renal dysfunction in heart transplant recipients.

BACKGROUND: The risk factors for moderate or severe chronic renal dysfunction (MSCRD) among heart transplant recipients may be distinct from those previously recognized owing to recently improved clinical care. METHODS: We examined the clinical records of 88 adult patients who underwent first heart transplantations from 2000 to 2005 and survived 2 years. MSCRD was defined as a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) at 2 years after transplantation. Fifty patients were included in the MSCRD group and 38 in the non-MSCRD group. RESULTS: Loss of renal function was observed largely during the first 9 months after transplantation in the MSCRD group. The pretransplantation GFR was lower in the MSCRD group. Besides older age in the MSCRD group, there were no differences in baseline characteristics, immunosuppressive regimens, incidences of acute rejection episodes, cardiac allograft vasculopathy, or severe infections. The MSCRD group showed permanent lower posttransplantation hemoglobin levels. In multivariate logistic regression analysis, recipient age, pretransplantation GFR, postoperative intensive care unit stay and hemoglobin level at 9 month were unfavorable factors for posttransplantation MSCRD. CONCLUSIONS: In addition to recipient age and pretransplantation GFR as well established risk factors, our results suggest a prognostic value of a low early hemoglobin level for the development of chronic renal dysfunction after heart transplantation.

Outbreak of Salmonella Enteritidis phage type 13a: case-control investigation in Hertsmere, United Kingdom.

Cases of illness were reported to Hertsmere Borough Council among attendees of a children's charity event in June 2006. Initial laboratory investigation identified Salmonella Enteritidis PT13a as a possible cause of the outbreak. We carried out an unmatched case-control investigation. The population at risk included all individuals who attended the event. Self-completion questionnaires were sent to 53 presumptive cases and 212 randomly selected potential controls. Information was available for 49 cases and 128 controls (overall response rate=75%). We calculated odds ratios from single and multivariable analysis and tested for all two-way interactions. Risk factors for diarrhoea were eating egg mayonnaise bagels (OR=34.1, 95%CI 10.5 - 111.3) and drinking apple juice (OR=16.1, 95% CI 3.5 - 74.2). There was weak statistical evidence to suggest that the risk of diarrhoea after eating egg mayonnaise bagels was greater in the afternoon. No food samples were available to confirm which food item might have caused this outbreak. Eggs from Spain were used by the caterer. The ecology of salmonella, experience from previous outbreaks and epidemiological findings from this case-control investigation suggest that the most likely cause of the outbreak was contaminated eggs.

Changes in serum sodium concentration after transurethral procedures.

The aim of this study is to evaluate the changes in serum sodium concentration and the degree of correlation with factors such as the amount of intravenous fluid intake, the kind and the amount of irrigating fluids and the duration of the procedure. In this framework, 98 male patients who underwent transurethral procedure were studied and the correlation between the magnitude of hyponatraemia and the above-mentioned parameters was evaluated. All procedures were performed under spinal anesthesia and a solution of either manitol-sorbitol or sterilized water was used as irrigation fluid. Serum sodium concentration was measured before and after the procedure, while the kind and amount of the irrigating fluids, the amount of fluid intake and the duration of the procedure were also recorded. The patients were divided into three groups according to the duration of the procedure (i) <30 min, (ii) 30-60 min, and (iii) >60 min. Significant reduction in serum sodium concentration was found postoperatively (P < 0.001) and this was more profound in procedures longer than 1 h. This reduction was strongly correlated only with the duration of the transurethral procedure (P < 0.01). In conclusion, in transurethral procedures the reduction in serum sodium is postoperatively related to the duration of the procedure, while the intravenous and irrigating fluids to play no role on it.

Spontaneous rupture of the rectosigmoid with small bowel evisceration through the anus.

Spontaneous rupture of the rectosigmoid with small bowel evisceration through the anus is a rare and acute condition of the gastrointestinal tract. After Brodie's first description, only 52 such cases have been reported in the literature. An 83-year-old woman experienced a sudden, spontaneous rectosigmoid rupture and protrusion of small bowel loops, through the ruptured colon and out of the anus. After an immediate management, an emergency operation was performed, and a small bowel resection and suturing of the ruptured rectosigmoid were carried out for restoration of bowel continuity. On the 41st postoperative day, a massive cerebro-vascular accident (CVA) was the cause of the patient's death. Discussion of the aetiology and treatment of this rare condition.

Preincisional local infiltration of levobupivacaine vs ropivacaine for pain control after laparoscopic cholecystectomy.

BACKGROUND: Postoperative pain is less intense after laparoscopic surgery than after open surgery. However, patients may gain additional benefit from a preincisional local infiltration of anesthetic. The aim of this study was to compare the analgesic efficacy of two local anesthetics, ropivacaine and levobupivacaine, for tissue infiltration as a means of improving postoperative pain control after laparoscopic cholecystectomy. METHODS: Using a randomized, double-blind study design, 57 American Society of Anesthesiologists (ASA) I and II patients scheduled for laparoscopic cholecystectomy were randomly assigned to receive local infiltration with 0.9% saline solution (Placebo group, n = 18), ropivacaine 1% (Rop group, n = 20), or levobupivacaine 0.5% (Lev group, n = 19). The local anesthetic was administered, prior to trocar placement, using the same technique and delivering the same volume (20 ml) for all three groups. The anesthetic technique was standardized for all groups. Postoperative pain was rated at 2 h, 4 h, and 24 h postoperatively by visual analogue scale (VAS) score. Cumulative analgesic consumption and adverse effects were also recorded. Data were analyzed by analysis of variance (ANOVA), followed by a post hoc test. RESULTS: The Lev and Rop groups did not differ significantly in their VAS scores at 2 h postoperatively, but the Lev group experienced significantly ( p < 0.001) less pain than the Placebo and Rop groups at 4 h and 24 h postoperatively. The Rop group registered significantly lower VAS scores ( p < 0.001) than the Placebo group at 4 h postoperatively. Additionally, the consumption of analgesics was significantly lower in the Lev group than in the Rop ( p < 0.01) and Placebo ( p < 0.001) groups, and patients in the Rop group consumed significantly less analgesics ( p < 0.001) than the to patients in the Placebo group. CONCLUSION: Local tissue infiltration with levobupivacaine is more effective than ropivacaine in reducing the postoperative pain associated with laparoscopic cholecystectomy.

Sufentanil or clonidine for blunting the increase in intraocular pressure during rapid-sequence induction.

BACKGROUND AND OBJECTIVE: The aim was to determine if the intravenous administration of sufentanil or clonidine before the induction of anaesthesia could obtund the increase of intraocular pressure associated with rapid-sequence induction. METHODS: Thirty-two ASA I-II patients with no history of eye illness scheduled for elective non-ophthalmic surgery were randomly assigned to receive either sufentanil 0.05 microg kg(-1) i.v. (Group A, n = 15) or clonidine 2 microg kg(-1) i.v. (Group B, n = 17) prior to induction. General anaesthesia was induced with thiopental (5 mg kg(-1)) followed by succinylcholine 1 mg kg(-1) to facilitate tracheal intubation. The general anaesthetic technique was standardized in both groups. Intraocular pressure was measured using the Schioetz tonometer just before the succinylcholine administration (t0), just before tracheal intubation (t1) and immediately after intubation (t2). Mean arterial pressure and heart rate were recorded at the same time intervals. RESULTS: Intraocular pressures were similar in both groups at t0, but the sufentanil group had significantly lower values compared with the clonidine group just before (t1) and immediately after tracheal intubation (t2). CONCLUSIONS: Sufentanil is effective in blunting the increase in intraocular pressure caused by rapid-sequence induction with succinylcholine, while clonidine did not seem to have any effect in intraocular pressures just before (t1) and just after (t2) intubation.