Dynamic image acquisition protocols are increasingly used in emission tomography, for drug development and clinical research. As such, there is a need for computational phantoms accurately describing both the spatial as well as temporal distribution of the radiotracer, taking into account periodic and non-periodic physiological processes during the course of the acquisition, such as tracer kinetics and respiratory motion. To this end, we developed a new 5D anthropomorphic digital phantom for accurate parametric imaging simulation studies in emission tomography. The proposed phantom is comprised of 3 spatial and 2 temporal dimensions and is based on high spatial and temporal information derived from 4D MR data. The envisaged applications of this digital phantom include development and evaluation of motion correction and image reconstruction algorithms in PET and SPECT, development of protocols and methods for tracer and drug development and new kinetic parameter estimation algorithms amongst others. Example applications are shown in parametric [18F]FDG and [15O]H2O PET imaging.

Introduction: Dynamic image acquisition protocols are increasingly used in emission tomography for drug development and clinical research. As such, there is a need for computational phantoms to accurately describe both the spatial and temporal distribution of radiotracers, also accounting for periodic and non-periodic physiological processes occurring during data acquisition. Methods: A new 5D anthropomorphic digital phantom was developed based on a generic simulation platform, for accurate parametric imaging simulation studies in emission tomography. The phantom is based on high spatial and temporal information derived from real 4D MR data and a detailed multi-compartmental pharmacokinetic modelling simulator. Results: The proposed phantom is comprised of three spatial and two temporal dimensions, including periodic physiological processes due to respiratory motion and non-periodic functional processes due to tracer kinetics. Example applications are shown in parametric [18F]FDG and [15O]H2O PET imaging, successfully generating realistic macro- and micro-parametric maps. Conclusions: The envisaged applications of this digital phantom include the development and evaluation of motion correction and 4D image reconstruction algorithms in PET and SPECT, development of protocols and methods for tracer and drug development as well as new pharmacokinetic parameter estimation algorithms, amongst others. Although the simulation platform is primarily developed for generating dynamic phantoms for emission tomography studies, it can easily be extended to accommodate dynamic MR and CT imaging simulation protocols.

In 3D PET scatter degrades image quality and quantification. The currently most popular scatter estimation method is the single scatter simulation (SSS) which accommodates for multiple scattering by scaling the single scatter estimation. However, it has not been clear yet how accurate this approximation is for cases where multiple scatter is significant, raising the specific questions: "How important double scatter correction is, and how accurately do we simulate the total scatter events by appropriate scaling?" This project aims to clarify the improvements in terms of quantification due to scatter correction, using: (i) single scatter events only, (ii) single and double scatter events, (iii) total scatter events, or (iv) scaled single scatter, and evaluate the analytic scatter estimation algorithm as implemented in the open source reconstruction software STIR. The analytic SSS scatter estimation implemented in STIR is compared with the SimSET Monte Carlo package. Scatter correction accuracy is examined for different levels of scattering and scaling approaches. A large anthropomorphic phantom was reconstructed with FBP. The images have been compared quantitatively: Areas with high scatter fraction are compared with single scatter corrected images and show a 50% bias reduction after performing single and double scatter correction. Scaled single scatter correction results are in good agreement with SimSET true events, less than 10% difference. Total-fit and tail-fit scaled single scatter results in approximately equal mean values. SSS correction with tail-fit scaling in STIR is very close with SimSET true events, 10% difference. The results show that multiple scatter correction improves accuracy and scaling single scatter is an efficient method to compensate for multiple scattering for standard PET scanning acquisitions.

Background: The use of ice as a supplement to an exercise programme has been recommended for the management of lateral elbow tendinopathy (LET). No studies have examined its effectiveness. Objectives: To investigate whether an exercise programme supplemented with ice is more successful than the exercise programme alone in treating patients with LET. Methods: Patients with unilateral LET for at least four weeks were included in this pilot study. They were sequentially allocated to receive five times a week for four weeks either an exercise programme with ice or the exercise programme alone. The exercise programme consisted of slow progressive eccentric exercises of wrist extensors and static stretching of the extensor carpi radialis brevis tendon. In the exercise programme/ice group, the ice was applied after the exercise programme for 10 minutes in the form of an ice bag to the facet of the lateral epicondyle. Patients were evaluated at baseline, at the end of treatment, and three months after the end of treatment. Outcome measures used were the pain visual analogue scale and the dropout rate. Results: Forty patients met the inclusion criteria. At the end of treatment there was a decline in visual analogue scale of about 7 units in both groups compared with baseline (p<0.0005, paired t test). There were no significant differences in the magnitude of reduction between the groups at the end of treatment and at the three month follow up (p<0.0005, independent t test). There were no dropouts. Conclusions: An exercise programme consisting of eccentric and static stretching exercises had reduced the pain in patients with LET at the end of the treatment and at the follow up whether or not ice was included. Further research to establish the relative, absolute, and cost effectiveness as well as the mechanism of action of the exercise programme is needed.

Modern Wearable Medical Devices (WMDs), implement capabilities that have contributed significantly to patient outcomes, as well as quality of life. Using such devices can be beneficial for many patients, especially during the time of the pandemic where everyone had to isolate at home. This paper presents a proof of concept of a new low-cost technology-based approach to support home-based rehabilitation for people with hemiplegia aiming to assess the effectiveness of their home-based exercises thus making telerehabilitation sessions more effective.

Background: The Children's Color Trails Test (CCTT) is a neuropsychological test that measures attention, divided attention, and speed of mental processing. It has been increasingly used in the assessment of children in cross-cultural environments for neurological and psychiatric disorders such as seizures and closed head injuries, learning and/or language disabilities, attention deficit/hyperactivity disorder, children with manganese exposure, and children diagnosed with HIV virus. However, there is a paucity of studies presenting normative data. The aim of the present study was to provide normative data for the CCTT in the Cypriot population. Methods: A total of 709 native Cypriot children aged 7-16 years, recruited from various public schools across the island, took part in the study. Exclusion criteria involved the existence of neurological, psychiatric, cardiological, and metabolic diseases, premature birth, history of maternal alcohol and drug abuse during pregnancy, low birth weight, hearing loss, visual problems, native language other than Greek, and abnormality in fine-motor movements. Results: Age and gender were found to be important factors for the interpretation of scores in all CCTT variables. Older children required less time and exhibited fewer errors, near misses, and prompts compared to younger children. There was a consistent pattern of a 3-4 seconds improvement (less time in seconds) in the CCTT completion time as age increased. Conclusions: CCTT is a promising tool for the measurement of attention in the native Cypriot population. Further research is needed in children diagnosed with various neurological and psychiatric diseases in order to estimate validity of the CCTT in clinical populations.

Swimming is an advantageous exercise modality since it induces limited muscle damage. Performance is a crucial endpoint measurement of physiological relevance in exercise physiology and clinical settings alike. To our knowledge, the literature lacks a comprehensive and widely accepted swimming performance protocol without suffering from high variability in time to exhaustion. Thus, the present study presents an easily carried out, two-phased swimming performance incremental test exhibiting low variability in the time to exhaustion among rats. All nine rats managed to complete the first 12 min-part of the test (phase 1) with gradually increased loads attached at the base of their tails equal to 2%, 3.5% and 5% (for 4 min each). All rats reached exhaustion at the 10% final load (phase 2). The mean swimming time until exhaustion, as a measure for defining exercise performance, was 865 ± 59 s. In conclusion, we have presented in detail a novel protocol for practically and satisfactorily measuring swimming performance in rats characterized by low variability in the time to exhaustion. This protocol, with the appropriate modifications, can be applied to a wide spectrum of experimental treatments.

Speech and voice symptomatology (dysarthrophonia) are often reported by patients with myasthenia gravis (MG). However, they have been poorly investigated despite their significant impact on quality of life. Quantitative methods for the assessment of dysarthrοphonia could facilitate the evaluation of these common MG symptoms. The goal of this study was to investigate the phonatory (sustained phonation and reading) and speech (diadochokinesis) function in MG patients using quantitative measures. The voice/speech of 12 MG patients (7 with anti-AchR and 5 with anti-MuSK antibodies) and 24 age-matched healthy controls was recorded and analyzed using electroglottography (EGG) and speech acoustics. For the analysis of voice, the variables that were found to distinguish MG patients compared to healthy controls were a higher average fundamental frequency (P<0.05), a higher standard deviation of the average fundamental frequency (P<0.001), a higher mean fundamental frequency of the vibrating vocal folds (P<0.005) and a higher fundamental frequency range (P<0.005). The analysis of diadochokinesis showed that MG patients had a higher mean duration of the silent interval between a series of repetitive /pa/ syllables (P<0.05), of the sound /t/ (P=0.05) and of the silent interval between a series of repetitive /ka/syllables (P<0.05). No statistical differences were found in any of these variables between the MG subgroups with anti-AchR or anti-MuSK antibodies. This study demonstrates that non-invasive physiological methods (EGG and speech acoustics) offer essential tools for the assessment of dysarthrophonia in MG patients.

ObjectiveLaboratory tests have progressively acquired a dominant role in screening, diagnosis, disease monitoring and outcome assessment. This trend has also adversely led to the inappropriate ordering of laboratory tests, the results of which are highly unlikely to establish or change diagnosis, and, in extent, influence the treatment decision-making of a specific disease. This practice raises the cost of healthcare while it exposes patients to unjustified risk as healthcare professionals may be led to perform unnecessary procedures. Study DesignA quasi-experimental study in the form of an interrupted time series analysis was performed to assess the potential impact of introduction of co-payment on cholesterol test ordering. MethodsThis study was performed using public health care sector data from Nicosia General Hospital and Nicosia primary health care centers. Daily ordering for all outpatient cholesterol tests were tracked for 43 consecutive months; 33 months prior to, and 10 months after the introduction of this measure. ResultsCo-payment resulted in an instant and significant reduction in cholesterol test ordering. The measure's impact remained unchanged throughout the observation period. ConclusionCo-payment can be considered to be a potent and durable measure to successfully contain inappropriate laboratory ordering. However, the long–term effect of this measure must be assessed to ensure that co-payment does not exert a negative effect on public health.

Abscess of the spleen is a rare discovery, with about 600 cases in the international literature so far. Although it may have various causes, it is most usually associated with trauma and infections of the spleen. The latter are more common in the presence of a different primary site of infection, especially endocarditis or in cases of ischemic infarcts that are secondarily infected. Moreover, immunosuppression is a major risk factor. Clinical examination usually reveals a combination of fever, left-upper-quadrant abdominal pain and vomiting. Laboratory findings are not constant. Imaging is a necessary tool for establishing the diagnosis, with a choice between ultrasound and computed tomography. Treatment includes conservative measures, and surgical intervention. In children and in cases of solitary abscesses with a thick wall, percutaneous catheter drainage may be attempted. Otherwise, splenectomy is the preferred approach in most centers. Here, we present three cases of splenic abscess. In all three, splenectomy was performed, followed by rapid clinical improvement. These cases emphasize that current understanding of spleen abscess etiology is still limited, and a study for additional risk factors may be necessary

OBJECTIVE To create a composite image of accidents in Greece from 2003 to 2013, with a view to drawing conclusions about the main categories, proportion and trends. METHOD Review and meta-analysis of data produced by relevant investigations. The data were drawn mainly from the Greek Statistical Office, the Greek Police and the Ministry of Health and Social Security. RESULTS Road traffic, workplace, home environment and leisure accidents were the main categories of accidents in Greece, with a reduction in incidence over the decade from 2003 to 2012. CONCLUSIONS The ratio of industrial to traffic accidents was approximately 1:1 at the beginning of the study decade, but in 2012 it was 1:3. In conclusion, it appears that in Greece progress has been made in reducing accidents in general, but further efforts are clearly needed.

Purpose: Older individuals suffer from low NADH levels. We have previously shown that nicotinamide riboside [NR; a NAD(P)(H) precursor] administration impaired exercise performance in young rats. It has been suggested that supplementation of redox agents exerts ergogenic effect only in deficient individuals. We hypothesized that old individuals would more likely benefit from NR supplementation. We investigated the effect of acute NR supplementation on redox homeostasis and physical performance in young and old individuals. Methods: Twelve young and twelve old men received NR or placebo in a double-blind cross-over design. Before and 2 h after NR or placebo supplementation, blood and urine samples were collected, while physical performance (VO2max, muscle strength, and fatigue) was assessed after the second blood sample collection. Results: At rest, old individuals exhibited lower erythrocyte NAD(P)H levels, higher urine F2-isoprostanes and lower erythrocyte glutathione levels compared to young (P < 0.05). NR supplementation increased NADH (51% young; 59% old) and NADPH (32% young; 38% old) levels in both groups (P < 0.05), decreased F2-isoprostanes by 18% (P < 0.05), and tended to increase glutathione (P = 0.078) only in the old. NR supplementation did not affect VO2max and concentric peak torque, but improved isometric peak torque by 8% (P = 0.048) and the fatigue index by 15% (P = 0.012) in the old. In contrast, NR supplementation did not exert any redox or physiological effect in the young. Conclusions: NR supplementation increased NAD(P)H levels, decreased oxidative stress, and improved physical performance only in old subjects, substantiating that redox supplementation may be beneficial only in individuals with antioxidant deficiencies.

This article describesmethods for efficient posterior simulation for Bayesian variable selection in generalized linear models with many regressors but few observations. The algorithms use a proposal on model space that contains a tuneable parameter. An adaptive approach to choosing this tuning parameter is described that allows automatic, efficient computation in these models. The method is applied to examples from normal linear and probit regression. Relevant code and datasets are posted online as supplementary materials.

Maximal velocity (Vmax) is a well established biomarker for the assessment of tissue redox status. There is scarce evidence, though, that it does not probably reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis constant (Km) could more adequately image tissue oxidative stress and, thus, be a more physiologically relevant redox biomarker. Therefore, the aim of the present study was to side-by-side compare Vmax and Km of an antioxidant enzyme after implementing an in vivo set up that induces alterations in tissue redox status. Forty rats were divided into two groups including rats injected with blood plasma originating from rats that had previously swam until exhaustion and rats injected with blood plasma originating from sedentary rats. Tail-vein injections were performed daily for 21 days. Catalase Vmax and Km measured in gastrocnemius muscle were increased after administration of the exercise-conditioned plasma, denoting enhancement of the enzyme activity but impairment of its affinity for the substrate, respectively. These alterations are potential adaptations stimulated by the administered plasma pointing out that blood is an active fluid capable of regulating tissue homeostasis. Our findings suggest that Km adequately reflects in vivo modifications of skeletal muscle catalase and seems to surpass Vmax regarding its physiological relevance and biological interpretation. In conclusion, Km can be regarded as an in vivo-like biomarker that satisfactorily images the intracellular environment, as compared to Vmax that could be aptly parallelized with a biomarker that describes tissue oxidative stress in an in vitro manner.

Purpose: To screen hearing and evaluate outcomes in community-dwelling older adults. Method: Three thousand and twenty-five adults responded to an invitation to be screened by questionnaire, otoscopy, and pure-tone audiometry. Pure-tone average (PTA) >35 dB HL in the worse ear, unilateral hearing loss, or otoscopic findings were the criteria for referral for services. A questionnaire related to compliance with referral recommendations was completed by telephone interview for 160 randomly selected participants after 1-2 years from referral. Results: The referral rate for audiologic/hearing aid evaluation was 46%, and referral for cerumen removal/medical evaluation was 17%. Of the people referred for audiologic/hearing aid evaluation, 18% tried a hearing aid; 2 years later, 11% were using a hearing aid. Screening recommendations affected participants' decision to seek help. Study participants stated that the screening was helpful, it should be offered to everybody, and they would participate in future screenings. Conclusion: Although adult hearing screening offered timely identification of hearing loss for adults seeking help, follow-up with hearing aid treatment was low.

Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of renal cell carcinoma (RCC). It is one of the most therapy-resistant carcinomas, responding very poorly or not at all to radiotherapy, hormonal therapy and chemotherapy. A more comprehensive understanding of the deregulated pathways in ccRCC can lead to the development of new therapies and prognostic markers. We performed a metaanalysis of 5 publicly available gene expression datasets and identified a list of coderegulated genes, for which we performed extensive bioinformatic analysis coupled with experimental validation on the mRNA level. Gene ontology enrichment showed that many proteins are involved in response to hypoxia/oxygen levels and positive regulation of the VEGFR signaling pathway. KEGG analysis revealed that metabolic pathways are mostly altered in ccRCC. Similarly, Ingenuity Pathway Analysis showed that the antigen presentation, inositol metabolism, pentose phosphate, glycolysis/gluconeogenesis and fructose/mannose metabolism pathways are altered in the disease. Cellular growth, proliferation and carbohydrate metabolism, were among the top molecular and cellular functions of the co-deregulated genes. qRT-PCR validated the deregulated expression of several genes in Caki-2 and ACHN cell lines and in a cohort of ccRCC tissues. NNMT and NR3C1 increased expression was evident in ccRCC biopsies from patients using immunohistochemistry. ROC curves evaluated the diagnostic performance of the top deregulated genes in each dataset. We show that metabolic pathways are mostly deregulated in ccRCC and we highlight those being most responsible in its formation. We suggest that these genes are candidate predictive markers of the disease.

Hemorrhoids is a common disorder and a leading cause of rectal bleeding, with unpleasant discomfort and pain for the patient. Medication and surgery are the standard treatments of hemorrhoids. In this study, we are investigating an alternative herbal treatment of hemorrhoids using the Arum maculatum L. (Araceae). A randomized controlled trial was conducted with a test treatment period of 2 weeks using a sample of 53 diagnosed patients from Greece to assess the efficacy of Arum maculatum in treating symptomatic hemorrhoids. The patients randomly assigned to consume a liquid mixture of Arum maculatum or a standard antihemorrhoid cream. The primary outcome was the health-related quality of life measured by the SF-36 health survey at the baseline and 2 weeks after the end of treatment. The mixed ANOVA statistical method was used to compare the groups. Participants in the treatment group had significantly greater improvement in all measures of the SF-36. Particularly the treatment effect for the physical health summary was 5.0 [95% confidence interval (CI): 0.9-9.1] while for the mental health summary was 4.7 (95% CI: 1.3-8.0). This trial shows that treatment with Arum maculatum improves the quality of life of patients with hemorrhoids, but further studies are needed to confirm these results.

Introduction: The duration of the nuclei is a crucial factor for the shift of prelexical to mature speech, since control of duration is closely related with improved speech intelligibility. Objectives: This work records the suprasegmental feature of duration in infants with normal hearing (NH) compared to those with cochlear implants (CI) based on vocant productions (quasivowels and full vowels). Materinals and Methods: In this longitudinal study, 102 vocant productions were analyzed from cases of congenitally hearing-impaired infants (implantation ages 1:4 and 1:11 years; post-implant ages 0:6 months and 1:3 years) who were matched with three NH infants of similar hearing experience (ages 0:8–0:11 months). Current methodology analyzes vocants using a combination of acoustical and auditory analyses. Vegetative data or reflexive sounds were excluded. Participants had had unknown deafness etiology and no other disabilities. Duration was measured using wideband spectrographic analysis, from voice onset to the loss of audible signal and the decrease of higher formant’s energy. Results: The results showed that the mean vocant duration of young CI users was longer, compared to hearing matched peers during the first six months after cochlear implantation. Conclusions: This recorded weakness for CI users' speech production is a challenge for future work in speech processing strategies. This is the first study measuring production of vocants during the pre-linguistic stage in CI recipients.

Background: Home exercise programmes and exercise programmes carried out in a clinical setting are commonly advocated for the treatment of lateral elbow tendinopathy (LET), a very common lesion of the arm with a well-defined clinical presentation. The aim of this study is to describe the use and effects of strengthening and stretching exercise programmes in the treatment of LET. Eccentric exercises: Slow progressive eccentric exercises for LET should be performed with the elbow in extension, forearm in pronation, and wrist in extended position (as high as possible). However, it is unclear how the injured tendon, which is loaded eccentrically, returns to the starting position without experiencing concentric loading and how the "slowness" of eccentric exercises should be defined. Nor has the treatment regimen of the eccentric exercises of a supervised exercise programme been defined. Stretching exercises: Static stretching is defined as passively stretching a given muscle-tendon unit by slowly placing and maintaining it in a maximal position of stretch. We recommend the position should be held for 30-45 s, three times before and three times after eccentric exercises during each treatment session with a 30 s rest interval between each procedure. The treatment region of static stretching exercises when a supervised exercise programme is performed is unknown. Discussion: A well designed trial is needed to study the effectiveness of a supervised exercise programme for LET consisting of eccentric and static stretching exercises. The issues relating to the supervised exercise programme should be defined so that therapists can replicate the programme.