University faculty on student motivation to use medical education apps and barriers to their usage.

OBJECTIVE: University teachers, who primarily provide guidance and advice to their students, can play a significant role in educational process transformation. As there is no particular e-learning framework, it is important to understand the factors and variables that may impact both its effective usage and further successful implementation. The current study aims to outline the influence of university faculty, and possible barriers preventing medical students from using apps for learning purposes. SUBJECTS AND METHODS: Α cross-sectional study was conducted with an online survey questionnaire. The population of the study included 1,458 students from all the seven Greek schools of medicine. RESULTS: University faculty (51.7%), followed by fellow students and friends (55.6%), constitute the second most common source of information on adopting apps for medical education. 45.8% of students rated their educational guidance as insufficient/inadequate, 33.0% as moderate, 18.6% as quite good, and only 2.7% as sufficient/complete. University professors have proposed certain apps to 25.5% of students. PubMed (41.7%), Medscape (20.9%), and Complete Anatomy (12.2%) were the leading suggestions. The main barriers to app usage were the lack of knowledge of apps' benefits (28.8%), insufficient updates of their content (21.9%), their cost-effectiveness (19.2%), and financial reasons (16.2%). Most students preferred using free apps (51.4%) and 76.7% preferred universities to cover apps' expenses. CONCLUSIONS: University faculty represent the main source of information regarding the adaptation of medical apps in the educational process. However, students need improved and enhanced guidance. The main barriers are ignorance about apps and financial reasons. The majority prefer free apps and universities to cover their cost.

Effectiveness of a Robot-Assisted Psychological Intervention for Children with Autism Spectrum Disorder.

Difficulties with social interaction characterise children with Autism Spectrum Disorders and have a negative impact in their everyday life. Integrating a social-humanoid robot within the standard clinical treatment has been proven promising. The main aim of this randomised controlled study was to evaluate the effectiveness of a robot-assisted psychosocial intervention and the secondary aim was to investigate potential differences between a robot-assisted intervention group and a control group receiving intervention by humans only. The analysis of the results showed that robot-assisted intervention could be beneficial by improving children's psychosocial skills. This improvement was highlighted by neuropsychological testing and parent reporting. Group comparison only presented minimal statistically significant differences. The study underpins the potential of robot-assisted interventions to augment standard care.

Human decidual gamma/delta T cells possess unique effector and TCR repertoire profiles during pregnancy.

Human γδ T cells are enriched at the maternal-fetal interface (MFI, decidua basalis) showing a highly differentiated phenotype. However, their functional potential is not well-known and it is not clear whether this decidua-enrichment is associated with specific γδ T cell receptors (TCR) as is observed in mice. Here we addressed these open questions by investigating decidual γδ T cells during early and late gestation, in comparison with paired blood samples, with flow cytometry (cytotoxic mediators, cytokines) and TCR high-throughput sequencing. While decidual γδ T cells expressed less perforin than their counterparts in the blood, they expressed significant more granulysin during early pregnancy. Strikingly, this high granulysin expression was limited to early pregnancy, as it was reduced at term pregnancy. In contrast to this granulysin expression pattern, decidual γδ T cells produced reduced levels of IFNγ and TNFα (compared to paired blood) in early pregnancy that then increased by term pregnancy. TCR repertoire analysis indicated that human decidual γδ T cells are not generated early in life as in the mouse. Despite this, a specific enrichment of the Vγ2 chain in the decidua in early pregnancy was observed that disappeared later onwards, reflecting dynamic changes in the decidual γδ TCR repertoire during human gestation. In conclusion, our data indicate that decidual γδ T cells express a specific and dynamic pattern of cytotoxic mediators, Th1 cytokines and TCR repertoire suggesting an important role for these unconventional T cells in assuring a healthy pregnancy in human.

Medical application usage traits by students in Greece.

OBJECTIVE: Medical applications ("apps") can offer innovative educational capabilities, facilitating the acquisition of learning objectives and enhancing decision making. The present study aims at demonstrating the usage characteristics and relevant perceptions among students in seven medical schools in Greece. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted through an online survey. Popularity, usage patterns and medical student perceptions regarding medical apps were studied. RESULTS: A total of 1,458 undergraduate medical students participated, 99.2% owned a smartphone, 72.8% were aware of medical apps' existence, although only 53.9% used them. Apps awareness was higher in higher-ranked universities. Overall, 46% used 1-3 apps, 7.9% more than four apps. 40.3% stated apps' usage at least 1-3 times a month, followed by 16.0% using them 1-3 times per week. Only 2.5% reported daily usage. Students who used more apps tend to use them more frequently. 77.3% used at least half of the downloaded apps. Awareness of medical apps, number of apps in use and frequency of usage tend to increase in each succeeding year of study. The most popular apps and the main reasons of usage are presented in this study. Current and future perceptions have been investigated. No disparities have been observed between genders. CONCLUSIONS: Overall medical apps usage was relatively low, despite the high percentage of smartphone ownership. Quantitative traits are enhanced across the progression of medical studies. Utilization frequency is higher in those using more apps. Distinct utilization patterns were identified between preclinical and clinical students, possibly depicting particular needs, portraying apps as a special adjunctive educational tool.

Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic.

The Black Death (1347-1352 CE) is the most renowned pandemic in human history, believed by many to have killed half of Europe's population. However, despite advances in ancient DNA research that conclusively identified the pandemic's causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, 'big data palaeoecology', which, starting from palynological data, evaluates the scale of the Black Death's mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death's mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics.

Computed-tomography-guided transforaminal intrathecal nusinersen injection in adults with spinal muscular atrophy type 2 and severe spinal deformity. Feasibility, safety and radiation exposure considerations.

BACKGROUND AND PURPOSE: The purpose was to investigate our centre's experience on computed-tomography-guided (CT-guided), transforaminal, intrathecal administration of nusinersen in adult subjects with spinal muscular atrophy (SMA) type 2 and severe spinal deformity. METHOD: This is a retrospective, single-centre study investigating the feasibility and safety of CT-guided, transforaminal, lumbar puncture for the intrathecal administration of nusinersen (Spinranza®; Biogen; Cambridge, MA, USA) in a cohort of adult subjects with SMA type 2, severe neuromuscular scoliosis and previous spinal surgery. Between January 2019 and October 2019, five male, adult, SMA type 2 subjects were eligible to be treated in our centre with nusinersen. The mean age of the patients was 31 ± 9 years (range 19-43 years). The study's outcome measures were technical success, adverse events and radiation exposure. RESULTS: In total, four patients completed the four loading doses, whilst the fifth patient received only one loading dose; two patients also received their first maintenance doses. Overall, 20 consecutive transforaminal, intrathecal treatments were analysed. Technical success was 100% (20/20 intrathecal infusions). No adverse events were documented following the procedures. Mean dose-length product (DLP) value per injection was 665.4 ± 715.5 mGy*cm. Estimated mean effective dose per injection was 12.7 ± 12.9 mSv. Subgroup analysis between the chronologically first 10 versus subsequent 10 procedures demonstrated a clear trend towards less radiation exposure in the latter, although this difference did not reach statistical significance (DLP: 984.7 ± 903.3 vs. 436.7 ± 321.5 mGy*cm, P = 0.165; respectively). CONCLUSIONS: In this retrospective series, CT-guided transforaminal access for intrathecal injection of nusinersen was proven feasible and safe. A decrease in radiation dose over time was noted. Protocols to minimize radiation exposure are essential.

Benthic community indicators over a long period of monitoring (2000-2012) of the Saronikos Gulf, Greece, Eastern Mediterranean.

An analysis of the results of the 12-year regular monitoring (2000-2012) of benthic communities in Saronikos Gulf and Elefsis Bay (Eastern Mediterranean, Greece) in relation to the functioning of the Psittalia Wastewater Treatment Plant (WWTP) and advances in treatment is presented. Benthic community indicators applied include the Bentix index adopted for the implementation of the Water Framework Directive (WFD); the diversity and species richness proposed in combination with the Bentix index for the evaluation of certain attributes of the Sea-floor Integrity descriptor for the marine waters of Greece, under the Marine Strategy Framework Directive (MSFD), and the evenness index. The benthic and environmental data were treated according to the distance from the outfall, largely accounting for the variance of the indicators, to investigate trends along the monitoring. Results showed an upgrade of the condition of the benthic communities of Saronikos Gulf throughout the monitoring period mostly demonstrated by the Bentix and diversity indices. A change in the trends of most indices was especially evident after 2004, especially in the areas more adjacent to the outfall zones, when the advanced secondary biological treatment plant was completed and commissioned. Sediment parameters' trend patterns indicate a delayed reaction to recovery processes in relation to benthic indices. An evaluation of the current status of the benthic communities based on the indices applied showed a gradient from a moderate ecological status at stations up to a distance of 8,000 m from the outfalls to good environmental and ecological status at more remote stations. At shallower stations located at a distance of more than 4,000 m from the outfall, benthic communities also present good environmental status. In Elefsis Bay, the enclosed physiography, shallower depth and local pressures result in more adverse environmental conditions for benthic communities and a more complex influence from WWTP advances.

Effect of previous anesthesia experience on patients' knowledge and desire for information about anesthesia and the anesthesiologist: a 500 patients' survey from Greece.

BACKGROUND: This study aimed at assessing the effect of previous anesthesia experience on patients' knowledge of anesthesia and the role of anesthesiologists, on what they would want to know about anesthesia and the way they would like to be informed. METHODS: Questionnaires with fixed questions were distributed to consenting, consecutive surgical patients before the pre-anesthetic visit. Patients were divided into two groups: patients with previous anesthesia experience (Group A) and patients without previous anesthesia experience (Group B). The questionnaires included patients' demographics, questions related to their knowledge about the anesthesiologists' role and about their desire for information. RESULTS: 500 questionnaires were analyzed. The majority of patients (94.2%) know that the anesthesiologist is a specialized doctor and 89.2% believe that the anesthesiologist watches over the patient throughout surgery. These results were similar in both groups. The majority of patients (98.2%) also want to meet the anesthesiologist before surgery and 78% want even more information. Only 65.6% want to be aware of all possible complications, in both groups, while 17.6% do not want to know anything about complications. In general, answers to specific questions regarding what the patients want to know about anesthesia did not differ between groups. The vast majority of patients wish to talk with the anesthesiologist before surgery. CONCLUSION: Previous anesthesia experience did not seem to influence patients' desire for meeting the anesthesiologist and seeking information. A strong desire to personally meet the anesthesiologist is expressed and patients' desire for even more information is noted.

Concurrent bilateral projection and activation of motor cortices in a patient with congenital mirror movements: a TMS study.

OBJECTIVES: Mirror movements (MMs) are unintended and unnecessary movements accompanying voluntary activity in homologous muscles on the opposite side of the body, particularly in distal arm muscles. Congenital MMs may be sporadic or familial. Several mechanisms have been proposed to explain persistent congenital MMs. Hypothesis 1 assumes the existence of an ipsilateral corticospinal pathway, and Hypothesis 2 the activation of both motor cortices. We report a new case of congenital mirror movements in a healthy woman. METHODS: Electromyographic recordings and focal transcranial magnetic stimulation (TMS) were used for neurophysiological evaluation. RESULTS: Voluntary contraction of either abductor pollicis brevis (APB) elicited mirror activation of the other APB. Focal TMS of either M1 elicited motor evoked potential (MEP) of normal latency and amplitude in both resting APB. TMS of the left cortex upon maximal contraction of the right APB and mirror contraction of the left APB produced interhemispheric inhibition (IHI) in the former and silent period (SP) in the later. CONCLUSIONS: The electrophysiological evaluation using transcranial magnetic stimulation provides evidence of the concurrent action of both mechanisms in this patient. SIGNIFICANCE: The combination of more than one hypothesis could be more appropriate for understanding the underlying mechanism in some MM cases.

The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy.

BACKGROUND: Metastases cause most cancer-related deaths. We investigated the use of hypoxia-selective cytotoxins as adjuvants to radiotherapy in the control of metastatic tumour growth. METHODS: The NLCQ-1, RB6145 and tirapazamine were assessed against the spontaneously metastasising KHT model. Subcutaneous KHT tumours (250 mm(3)) were irradiated with 25 Gy (single fraction) to control primary growth. Equitoxic drug treatments (NLCQ-1 (10 mg kg(-1)) once daily; RB6145 (75 mg kg(-1)) and tirapazamine (13 mg kg(-1)) twice daily) were administered 3-6 days post-radiotherapy when hypoxic cells were evident in lung micrometastases. Mice were culled when 50% of controls exhibited detrimental signs of lung metastases. RESULTS: In total, 95% of control mice presented with lung disease. This was significantly reduced by NLCQ-1 (33%; P=0.0002) and RB6145 (60%; P=0.02). Semi-quantitative grading of lung disease revealed a significant improvement with all treatments, with NLCQ-1 proving most efficacious (median grades: control, 4; NLCQ, 0 (P<0.0001); RB6145, 1 (P<0.001), tirapazamine, 3 (P=0.007)). Positron emission tomography (PET) was evaluated as a non-invasive means of assessing metastatic development. Primary and metastatic KHT tumours showed robust uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG). Metastatic burden discernable by [(18)F]FDG PET correlated well with macroscopic and histological lung analysis. CONCLUSION: The hypoxia-selective cytotoxin NLCQ-1 controls metastatic disease and may be a successful adjuvant to radiotherapy in the clinical setting.

Pharmacodynamics of amoxicillin against Mannheimia haemolytica and Pasteurella multocida and pharmacokinetic/pharmacodynamic (PK/PD) correlation in sheep.

Silicone-made tissue cages were implanted in sheep. Blood serum (SBS) and tissue cage fluid (TCF) samples were collected after amoxicillin intravenous and intramuscular administrations, at the dose of 15 mg/kg. Amoxicillin pharmacodynamics were studied in an artificial culture medium, SBS and TCF with use of a Mannheimia haemolytica and a Pasteurella multocida strain. A concentration-independent antimicrobial activity of amoxicillin was confirmed for levels higher than 0.79-1.75×MIC. This result favored the use of the percentage of the 24 h dosing interval during which drug levels remain above MIC as the appropriate pharmacokinetic/pharmacodynamic index. The subsequent correlation revealed that intravenous administration could be considered effective against "deep" infections caused by bacteria with MICs<1 µg/mL or "shallow" infections caused by bacteria with MICs<0.1 µg/mL. Intramuscular administration could be safely considered effective against both "deep" and "shallow" infections when the MICs of the targeted pathogens are lower than 1 µg/mL.

Influence of the injection site on the pharmacokinetics of amoxicillin after intramuscular administration of a conventional and a long-acting formulation in sheep.

The pharmacokinetics of amoxicillin (AMX) were investigated in sheep following intravenous (i.v.) and intramuscular (i.m) injection, comparing two different drug formulations, a conventional and a long-acting AMX-trihydrate suspension. For the i.m. application two different injections sites, the neck area and the hind limb were used to identify possible differences in the kinetic parameters related to the site of injection. A three-compartment open model could best describe AMX disposition after i.v. administration. Data analysis after i.m. administration of the conventional suspension at both injection sites revealed the occurrence of a flip-flop phenomenon, clearly indicating that absorption of AMX is the rate-limiting step of its overall disposition. A moderate effect of the injection site was observed with a tendency for the neck area to be advantageous, mainly in terms of rate rather than extent of absorption. Injection of the long-acting formulation led to a focal depot formation, thus yielding lower but remarkably prolonged serum AMX levels reflected in the respective terminal half-lives. The concentration-time profile of AMX after administration of the long-acting formulation was less affected by the injection site, but the low serum levels justify its use only in cases in which a high susceptibility of the involved bacterial population is confirmed.

Milrinone and theophylline act as lower oesophageal sphincter relaxing agents: a comparative pharmacodynamic study in the rabbit.

This study demonstrates that the inotropic agent milrinone and the bronchodilator drug theophylline exert a relaxing effect on the rabbit lower oesophageal sphincter in vitro. The relaxing effect of milrinone and theophylline, which is concentration-dependent, involves a second messenger 3',5'-cyclic adenosine monophosphate pathway and most probably it is accomplished through inhibition of phosphodiesterase (PDE) type III, as according to the obtained results it is not significantly modified either by nicotinic acid, an inhibitor of adenylate cyclase, or by the inhibitor of nitric oxide-synthetase N(omega)-nitro-L-arginine methylester and the purinergic antagonist suramin; moreover, it persists under non-adrenergic non-cholinergic conditions and it is both hexamethonium- and tetrodotoxin-insensitive. Both milrinone and theophylline display equal efficacy, comparable to that of the calcium blocker verapamil and the non-selective PDE inhibitor papaverine, but milrinone appears 50 times more potent than theophylline and three times less potent than verapamil, as, according to the pIC(50) values the potency rank of order is found to be verapamil (5.56) > milrinone (5.12) > theophylline (3.42). The here obtained pharmacodynamic profiles of the drugs suggest that both milrinone and theophylline may be considered as potent relaxing agents of the lower oesophageal sphincter.

Gene therapy approaches to enhance bioreductive drug treatment.

Hypoxia, or a lack of oxygen, occurs in 50-60% of solid human tumours. Clinical studies have shown that the presence and extent of hypoxia in a tumour cannot be predicted by size or histopathological stage but it is predictive of a poor outcome following radiotherapy, chemotherapy and surgery. However, as a physiological feature of tumours, it can be exploited and researchers have developed many hypoxia-selective chemotherapies or bioreductive drugs that are in varying stages of clinical development. These agents are prodrugs that have two key requirements for their biological activation: they require the reductive environment of a hypoxic tumour cell and the appropriate complement of cellular reductase enzymes. To overcome tumour heterogeneity in reductase enzyme levels and enhance bioreductive drug metabolism a gene therapy strategy can be employed. We have reviewed this field and also present our own pre-clinical research using gene therapy to enhance bioreductive drug treatment for the treatment of cancer. We have specifically focused on studies enhancing lead clinical bioreductive drugs. We consider the metabolic requirements for their activation and we highlight the key in vivo studies supporting the future clinical development of hypoxia-targeted gene-directed enzyme prodrug therapy.

Theophylline and its metabolites produce a stimulating cholinergic effect on the small intestine and a nonadrenergic noncholinergic relaxing effect on the colon: a comparative study in the rabbit intestine.

The present study examines comparatively the effects of theophylline and its metabolites, 1-methylxanthine (1-MX), 3-methylxanthine (3-MX), 1,3-dimethyluric acid (1,3-DMU) and 1-methyluric acid (1-MU) along the rabbit intestine, and explores the underlying mechanism(s). In the small intestine, theophylline produces atropine- and hexamethonium-sensitive increases in both the amplitude of phasic contractions and the basal tone. All metabolites mimic the theophylline's stimulating effect. In particular, concerning the phasic contractions, all metabolites are more potent than theophylline in the duodenum and jejunum, while in the ileum, only 1-MU is more potent. Regarding the basal tone, the metabolites show, in most cases, higher efficacy in all small intestinal regions, the maximum effects of 3-MX and 1-MU on the duodenum and ileum being double or triple the one of theophylline. In the ascending colon, while lower concentrations of theophylline produce an atropine- and hexamethonium-sensitive increase in the basal tone, higher ones produce a postsynaptic, nonadrenergic noncholinergic (NANC) relaxing effect. 1-MU mimics, in a weaker manner, theophylline's effect, while the other metabolites produce only relaxation, the potency rank of order being 3-MX>1-MX=1,3-DMU>theophylline. It is suggested that the theophylline and its metabolites stimulatory effect involves a cholinergic pathway, while the relaxing one is due to 3('),5(')-cyclic adenosine monophosphate (cAMP) elevation mediated by the theophylline and its metabolites inhibitory action on phosphodiesterases (PDEs).