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Abstract Background Patients with cirrhosis and portal hypertension may have alterations in intestinal barrier resulting in increased susceptibility for infections. We investigated the effect of propranolol in gastrointestinal motility, permeability and bacterial overgrowth in cirrhosis. Methods Patients with cirrhosis and esophageal varices were studied before and after a build-up dose of propranolol according to standard guidelines. Serum TNF-a, IL-6, IL-1b, LPS and bacterial DNA were measured before and during propranolol therapy. Oro-caecal transit time (OCTT) and bacterial overgrowth (BO) have been evaluated with H2 breath testing. Intestinal paracellular (IP), cellular passive non-carrier (ICNC), cellular passive carrier-mediated (ICCM), and gastric permeability (GP) were evaluated by measurement of lactulose, mannitol, D-xylose and sucrose respectively in urine, with high performance liquid chromatography (HPLC). Results 35 patients with cirrhosis and portal hypertension with median age was 59.6 years (range 42–86) were included in the study. Twenty one had viral hepatitis and 25 were classified as having advanced cirrhosis (Child-Pugh B: 14 or C: 11). Median dose of administrated propranolol was 40 mg/day. After 7 days propranolol treatment BO was resolved in 15 out of 16 patients (93.7%, p = 0.0001) and OCTT was reduced significantly from 180 min to 139 min (SD 58.5, difference − 4 1 min, p = 0.0001). Serum IL-6 levels were reduced in 21/35 (60%) patients from 41.1 to 19 pg/ml (p = 0.01), TNF-a in 10/35 (28.5%) patients from 10.7 to 5.6 pg/ml (p = 0.007) and LPS in 20/35 (57%) from 7.1 to 5.2 mg/L (p = 0.1). No bacterial DNA was detected in serum of all patients either baseline or under propranolol treatment. IP was significantly reduced (0.2 to 0.16, p = 0.04) whereas ICNC (p = 0.9), ICCM (p = 0.4) and GP (p = 0.7) were not affected significantly. Intestinal Permeability (PI) index (Lactulose to Mannitol ratio) was significantly reduced (0.027 to 0.02, p = 0.03). Conclusion In patients with cirrhosis and portal hypertension, propranolol use is associated with reduction in BO, increase in intestinal motility and amelioration in intestinal permeability. Moreover IL-6 and LPS levels are being decreased in the majority of patients under propranolol.

Abstract Patient‐reported outcome measures (PROMs) are used to assess a patient's health status at a particular point in time. They are essential in the development of person‐centred care. This paper reviews studies performed on PROMs for assessing AR and asthma control, in particular VAS scales that are included in the app MASK‐air® (Mobile Airways Sentinel networK) for asthma and rhinitis. VASs were initially developed on paper and pencil and tested for their criterion validity, cut‐offs and responsiveness. Then, a multicentric, multinational, double‐blind, placebo‐controlled, randomised control trial (DB‐PC‐RCT) using an electronic VAS form was carried out. Finally, with the development of MASK‐air® in 2015, previously validated VAS questions were adapted to the digital format and further methodologic evaluations were performed. VAS for asthma, rhinitis, conjunctivitis, work and EQ‐5D are included in the app. Additionally, two control‐medication scores for allergic symptoms of asthma (e‐DASTHMA) were validated for their criterion validity, cut‐offs and responsiveness.

ABSTRACT Pseudomonas aeruginosa infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current advances on phage-host studies. As a mucosal pathogen, we hypothesize that P. aeruginosa and its phages are linked to the bacteriophage adherence to mucus (BAM) model. This means that phage-host interactions could be influenced by mucin presence, impacting the success of phage infections on the P. aeruginosa host and consequently leading to the protection of the metazoan host. By using a group of four different phages, we tested three important phenotypes associated with the BAM model: phage binding to mucin, phage growth in mucin-exposed hosts, and the influence of mucin on CRISPR immunity of the bacterium. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. Improved phage growth was likely the result of phage exploitation of mucin-induced physiological changes in the host. We could not detect CRISPR activity in our system but identified two putative anti-CRISPR proteins coded by the phage. Overall, the differential responses seen for the phages tested show that the same bacterial species can be targeted by mucosal-associated phages or by phages not affected by mucus presence. In conclusion, the BAM model is relevant for phage-bacterium interactions in P. aeruginosa, opening new possibilities to improve phage therapy against this important pathogen by considering mucosal interaction dynamics.IMPORTANCESome bacteriophages are involved in a symbiotic relationship with animals, in which phages held in mucosal surfaces protect them from invading bacteria. Pseudomonas aeruginosa is one of the many bacterial pathogens threatening humankind during the current antimicrobial resistance crisis. Here, we have tested whether P. aeruginosa and its phages are affected by mucosal conditions. We discovered by using a collection of four phages that, indeed, mucosal interaction dynamics can be seen in this model. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. These results link P. aeruginosa and its phages to the bacteriophage adherence to the mucus model and open opportunities to explore this to improve phage therapy, be it by exploiting the phenotypes detected or by actively selecting mucosal-adapted phages for treatment.

Allergic rhinitis (AR) is a chronic respiratory condition that internationally continues to be burdensome and impacts quality of life. Despite availability of medicines and guidelines for healthcare providers for the optimal management of AR, optimisation of its management in the community continues to be elusive. The reasons for this are multi-faceted and include both environmental and healthcare related factors. One factor that we can no longer ignore is that AR management is no longer limited to the domain of healthcare provider and that people with AR make their own choices when choosing how to manage their condition, without seeking advice from a health care provider. We must build a bridge between healthcare provider knowledge and guidelines and patient decision-making. With this commentary, we propose that a shared decision-making approach between healthcare professionals and people with AR be developed and promoted, with a focus on patient health literacy. As custodians of AR knowledge, we have a responsibility to ensure it is accessible to those that matter most—the people with AR.

Hepatitis B virus reactivation (HBVr) is a well-described result of immunosuppressive therapy initiation in various diseases, with the dose and duration of treatment being the main factors determining the probability for reactivation. Such cases have also been described in COVID-19 patients treated with immunosuppressive therapies. Nevertheless, cases of COVID-19 infection that led to HBVr with no concurrent immunosuppressive treatment or any other related cause have also been reported. By that observation, we present a patient followed for a period spanning 20 years with HBeAg negative chronic HBV infection and non-detectable HBV DNA who, after a mild COVID-19 infection treated only with low-dose and short-duration-inhaled corticosteroids (ICS), developed elevated AST and ALT as well as elevated HBV DNA levels. Other etiologies of abnormal liver biochemistries during the diagnostic workout were excluded; thus, the diagnosis of HBV reactivation was established. Treatment with entecavir was initiated, leading to the normalization of AST and ALT levels and a decreasing trend of HBV DNA levels. Since other causes of reactivation were excluded, and the ICS dose and duration were found baring only a very low risk (

Abstract Background Protein annotation is a major goal in molecular biology, yet experimentally determined knowledge is typically limited to a few model organisms. In non-model species, the sequence-based prediction of gene orthology can be used to infer protein identity; however, this approach loses predictive power at longer evolutionary distances. Here we propose a workflow for protein annotation using structural similarity, exploiting the fact that similar protein structures often reflect homology and are more conserved than protein sequences. Results We propose a workflow of openly available tools for the functional annotation of proteins via structural similarity (MorF: MorphologFinder) and use it to annotate the complete proteome of a sponge. Sponges are highly relevant for inferring the early history of animals, yet their proteomes remain sparsely annotated. MorF accurately predicts the functions of proteins with known homology in $${>}90\%$$ > 90 % cases and annotates an additional $$50\%$$ 50 % of the proteome beyond standard sequence-based methods. We uncover new functions for sponge cell types, including extensive FGF, TGF, and Ephrin signaling in sponge epithelia, and redox metabolism and control in myopeptidocytes. Notably, we also annotate genes specific to the enigmatic sponge mesocytes, proposing they function to digest cell walls. Conclusions Our work demonstrates that structural similarity is a powerful approach that complements and extends sequence similarity searches to identify homologous proteins over long evolutionary distances. We anticipate this will be a powerful approach that boosts discovery in numerous -omics datasets, especially for non-model organisms.

Hepatitis D virus (HDV) globally affects nearly 5% of people with chronic hepatitis B virus (HBV) infection. Bulevirtide (BLV) is an HDV/HBV entry inhibitor recently approved for adult patients with chronic hepatitis delta (CHD). In this real-life case report, we describe the virological efficacy, the safety, and the liver function amelioration of one patient with liver compensated cirrhosis with esophageal varices after one-year combo treatment with BLV (2 mg/day in sub-cutaneous injection) and tenofovir disoproxil fumarate (TDF) (245 mg/day). The patient had HDV RNA levels of 9300 IU/mL, 1100 IU/mL, and undetectable at baseline, after three months, and after six months of treatment, respectively. In addition, the model for end-stage liver disease (MELD) score has declined from 11 at baseline to 8 after twelve months of treatment accompanied by alanine aminotransferase (ALT) normalization. Moreover, the treatment significantly improved the liver stiffness measurement (LSM) since a reduction from 34.3 kPa to 24.5 kPa was observed after twelve months of treatment. Furthermore, the treatment was well tolerated, and no dose reduction was needed.

Background: The prevalence of hepatitis B varies (HBV) among countries. Although an overall reduction has been described in Greece, data are limited. Methods: We reviewed the HBsAg/anti-HBc/anti-HBs seroprevalence among military recruits and compared data between 2005 and 2019. The study included 2001 (group 1) and 1629 (group 2) male recruits in 2019 and 2005, respectively. Age and descent were recorded. Results: The prevalence of HBsAg, anti-HBc and anti-HBs positivity in group1 vs. group 2 was estimated as: 0.2%, 1.3% and 67% vs. 0.4%, 1.6% and 62%, respectively. Only anti-HBs positivity achieved a statistically significant difference between the two groups (p = 0.007). HBsAg and anti-HBc were more frequently positive in non-Greeks than in Greeks (9/237 (4%) vs. 2/3393 (0.06%), p < 0.001), (26/237 (11%) vs. 26/3393 (0.8%), p < 0.001 respectively), while anti-HBs was more frequently positive in Greeks than in non-Greeks (84/164 (51%) vs. 1461/2213 (66%), p < 0.001). Conclusions: Our data suggest a further reduction in HBV prevalence in Greece about 20 years after the adoption of the National HBV Immunization Program, with Greek participants experiencing a more effective HBV Immunization Program than non-Greeks.

PurposeThe Catquest-9SF questionnaire is a tool measuring visual disability and vision-related limitation in patients' daily activities. The primary objective of this study was the validation of Catquest-9SF in a Greek-speaking cataract population.MethodsThe questionnaire was translated into Greek and translated back into English. A pre-final Greek version was formed and tested by 10 Greek-English bilingual participants and by the translation team, and the final version was produced. Patients scheduled for cataract surgery completed the questionnaire preoperatively and postoperatively. Rasch analysis was performed for the assessment of the Catquest-9SF psychometric properties, including response category ordering, item fit statistics, principal components analysis, precision, differential item functioning and targeting for preoperative and postoperative data collectively.ResultsA total of 100 (55 men, 45 women, mean age = 71.94±6.63) cataract patients completed the Greek version of Catquest-9SF questionnaire preoperatively and postoperatively. Rasch analysis showed a significant improvement in the median person Rasch score from -1.49 preoperatively to -4.71 logits postoperatively, while the effect size was 1.3. Unidimensionality was confirmed since infit and outfit mean square values varied between 0.66 and 1.37. Rasch analysis showed good precision and separation ability (Person Separation Index of 3.28, and Person Reliability of 0.92). Four response categories were found for all items. The item-person means difference was -1.83 logits. The difference between preoperative and postoperative Catquest-9SF logit score was positively correlated with preoperative Catquest-9SF logit score (coeff. = 0.798, pConclusionThe Greek version of Catquest-9SF proved to be reliable, valid, unidimensional and responsive to changes after cataract surgery presenting good psychometric properties for cataract patients. Some postoperative mistargeting was found indicating that the tasks were easily performed by respondents after cataract surgery.Trial registrationNCT05323526 -retrospectively registered.

Bronchiolitis is the most common cause of hospitalization in infancy and is associated with a higher risk for the development of childhood asthma. However, not all children hospitalized with bronchiolitis will develop asthma. The mechanisms underlying asthma development following bronchiolitis hospitalization are complex. Immune responses to respiratory viruses may underlie both bronchiolitis severity and long-term sequela (such as asthma). Interferons (IFNs) are important components of innate immune responses to respiratory viruses and could influence both asthma development and asthma exacerbations. However, the nature of the relationship between interferon production and wheezing illnesses is controversial. For example, low peripheral blood IFN responses at birth have been linked with recurrent wheeze and asthma development. In contrast, there is evidence that severe illnesses (e.g., hospitalization for bronchiolitis) are associated with increased IFN responses during acute infection (bronchiolitis hospitalization) and a higher risk for subsequent asthma diagnosis. Furthermore, mechanistic studies suggest that bronchial epithelial cells from asthmatic children have impaired IFN responses to respiratory viruses, which may enable increased viral replication followed by exaggerated secondary IFN responses. This review aims to discuss controversies around the role of IFNs as drivers of susceptibility to asthma development following bronchiolitis hospitalization. Past evidence from both mechanistic and cohort studies are discussed. We will highlight knowledge gaps that can inform future research study design.

Abstract Following a request from the European Commission, the EFSA Panel on Plant Health examined evidence as to whether the import of fruits of Musa (bananas and plantains) could provide a pathway into the EU for Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) or other non‐EU Tephritidae for which Musa is a host. Relevant scientific and technical information, including unpublished information provided to the EFSA Panel on Plant Health by the European Commission from research conducted in Cabo Verde, were taken into account. The majority of EU imports of Musa fruit comes from Ecuador, Colombia and Costa Rica where B. dorsalis does not occur. Commercial Musa fruits are harvested at ‘green stage one’ before they begin to ripen naturally. Postharvest processes are designed to ensure that only high quality, unripe fruit are exported. Green stage one fruit are transported to the EU in controlled conditions and stimulated to ripen when exposed to exogenous ethylene in ripening rooms in the EU. There is no evidence that any Tephritidae can naturally infest commercial varieties of Musa fruit at green stage one or earlier. When experimentally infested with eggs of Tephritidae, larvae fail to develop in green stage one fruit. Physical and chemical changes that occur during fruit ripening enable B. dorsalis and 11 other species of Tephritidae to oviposit and develop in Musa at later stages of fruit development. Reports of B. dorsalis or other Tephritidae infesting bunches of Musa fruit are a consequence of the fruit being left to develop beyond green stage one in the field. There is no evidence that commercially grown fruits of Musa, for export to the EU, provide a pathway for the entry of non‐EU Tephritidae. Passengers bringing Musa fruit from countries where Tephritidae can infest ripened Musa fruit do however provide a potential pathway for the entry of non‐EU Tephritidae into the EU territory.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) constitute highly malignant forms of primary liver cancers. Hepatocellular and bile duct carcinogenesis is a multiplex process, caused by various genetic and epigenetic alterations, the influence of environmental factors, as well as the implication of the gut microbiome, which was undervalued in the previous years. The molecular and immunological analysis of the above malignancies, as well as the identification of the crucial role of intestinal microbiota for hepatic and biliary pathogenesis, opened the horizon for novel therapeutic strategies, such as immunotherapy, and enhanced the overall survival of cancer patients. Some of the immunotherapy strategies that are either clinically applied or under pre-clinical studies include monoclonal antibodies, immune checkpoint blockade, cancer vaccines, as well as the utilization of oncolytic viral vectors and Chimeric antigen, receptor-engineered T (CAR-T) cell therapy. In this current review, we will shed light on the recent therapeutic modalities for the above primary liver cancers, as well as on the methods for the enhancement and optimization of anti-tumor immunity.

Background: In this retrospective study, records of patients with thalassemia major (TM) diagnosed with hepatocellular carcinoma (HCC) from 2008‐2018 were reviewed in order to determine the survival rate and evaluate possible etiological factors associated with survival. Methods: Forty-two TM patients who were diagnosed with HCC have been included in the study. Most of our patients (78.5%) were anti-HCV positive, while 16.5% had evidence of resolved HBV infection. At the time of HCC diagnosis, 78.5% of our patients were diagnosed with cirrhosis, while the vast majority (98%) had normal or mild elevated liver iron concentration (LIC) values. According to Barcelona Clinic Liver Cancer (BCLC) grading system patients were classified as 0-A: 28.5%, B: 57% and as C-D: 14.5%. HCC has been treated with loco-regional treatment in 78.5% of our patients, while the rest have been treated with sorafenib. Results: Twenty-eight patients (66.5%) have eventually died with a median survival time of 6 months (range: 2-60). Using the Cox proportional hazard model, the only factors who have been associated with poor survival were BCLC stages C and D. Conclusions: In conclusion, BCLC staging is the main prognostic factor of survival in patients with TM who develop HCC, with a median survival time of six months.

Abstract The Panel on Plant Health performed a group pest categorisation of non‐EU Tephritidae, a large insect family containing well‐studied and economically important fruit fly species and little studied species with scarce information regarding their hosts and species that do not feed on plants. Information was saught on the distribution of each species and their hosts. Tephritidae occur in all biogeographic regions except in extreme desert and polar areas, where their hosts are scarce or absent. Non‐European Tephritidae are listed in 2000/29 EC as Annex 1/A1 pests whose introduction into the EU is prohibited. Non‐EU Tephritidae are regularly intercepted in the EU. Interceptions mainly occur on fruits although there is potential for entry on other plant parts. Beginning with over 5,000 recognised species, factors relevant for pest categorisation were sequentially used to narrow down the list of species to create a list of Tephritidae not known to be established in the EU yet which occur in countries with some EU climate types and which feed on plants that occur in the EU. Following the introduction of pest species, impacts on cultivated host plants could result in yield and quality losses; harmful impacts on wild hosts are uncertain. Phytosanitary measures are available to prevent the entry of non‐EU Tephritidae. Results are presented in a series of appendices listing species screened during the process. Of 4,765 species regarded as non‐EU Tephritidae, 257 species satisfy the criteria assessed by EFSA such that they can be considered as potential quarantine pests for the EU. Lack of information of the distribution of hosts and/or impact on wild hosts means 1,087 species of non‐EU Tephritidae do not satisfy all criteria to be considered as potential quarantine pests for the EU. Non‐EU Tephritidae do not meet the criteria assessed by EFSA for consideration as regulated non‐quarantine pests, as members of the group are not present in the EU and plants for planting are not the main means of spread.

Seasonal patterns of mosquito population density and their vectorial capacity constitute major elements to understand the epidemiology of mosquito-borne diseases. Using adult mosquito traps, we compared the population dynamics of major mosquito species (Culex pipiens, Aedes albopictus, Anopheles spp.) in an urban and a wetland rural area of Attica Greece. Pools of the captured Cx. pipiens were analyzed to determine infection rates of the West Nile virus (WNV) and the Usutu virus (USUV). The data provided were collected under the frame of the surveillance program carried out in two regional units (RUs) of the Attica region (East Attica and South Sector of Attica), during the period 2017–2018. The entomological surveillance of adult mosquitoes was performed on a weekly basis using a network of BG-sentinel traps (BGs), baited with CO2 and BG-Lure, in selected, fixed sampling sites. A total of 46,726 adult mosquitoes were collected, with larger variety and number of species in East Attica (n = 37,810), followed by the South Sector of Attica (n = 8916). The collected mosquitoes were morphologically identified to species level and evaluated for their public health importance. Collected Cx. pipiens adults were pooled and tested for West Nile virus (WNV) and Usutu virus (USUV) presence by implementation of a targeted molecular methodology (real-time PCR). A total of 366 mosquito pools were analyzed for WNV and USUV, respectively, and 38 (10.4%) positive samples were recorded for WNV, while no positive pool was detected for USUV. The majority of positive samples for WNV were detected in the East Attica region, followed by the South Sector of Attica, respectively. The findings of the current study highlight the WNV circulation in the region of Attica and the concomitant risk for the country, rendering mosquito surveillance actions and integrated mosquito management programs as imperative public health interventions.

Cow's milk allergy is one of the most commonly reported childhood food allergies, with increasing incidence, persistence and severity in many countries across the world. The World Allergy Organization Special Committee on Food Allergy has identified cow's milk allergy as an area in need of a rationale-based approach in order to make progress against what it considered an onerous problem, with worldwide public health impact. There is growing interest in the potential role of the gut microbiota in the early programming and development of immune responses and allergy. This discussion paper considers the rationale and available evidence for modulation of the gut microbiota and for the use of synbiotics in the management of infants at risk of, or living with cow's milk allergy and summarizes remaining research questions that need to be answered for the development of evidence-based recommendations. Keywords: Cow's milk allergy, Allergy, Microbiota, Bifidobacteria, Lactobacilli, Synbiotic, Probiotic, Prebiotic, IgE, World Allergy Organization, Anaphylaxis, Dysbiosis

The objectives of this experimental work were the evaluation of the potential role of Salmonella enterica subsp. diarizonae in diarrhoeic syndrome in lambs and the investigation of facets of the pathogenesis of the infection. In total, 12 lambs were challenged orally on the first day of life, with a S. enterica subsp. diarizonae isolate from a clinical case of diarrhoeic syndrome. Sequential blood, faecal and buccal samples were collected from lambs and faecal and milk samples were taken from their dams. Lambs were euthanised 1, 2, 4, 7, 10, 14 and 21 days after challenge. Samples were processed for recovery of the challenge organism; they were also subjected to examination by PCR for detection of the invA gene. Tissue samples from lambs were also examined as above and histopathologically. S. enterica subsp. diarizonae was recovered from faecal samples of all lambs, in total, from 45/77 samples (median duration: 2.4 days post-inoculation). It was also recovered from buccal samples (10/77) from seven lambs (median duration: 0.8 days), and from tissue samples (small intestine, abomasum, liver, gallbladder) of nine lambs. It was recovered from two consecutive milk samples from the same ewe, but not from any faecal sample from ewes. The invA gene was detected in samples from all lambs (median duration: 5.5 days in faecal and 1.3 days in buccal samples), as well as in milk samples from three ewes. Histopathological findings included abomasitis with subepithelial presence of eosinophils, lymphocytes and plasma cells, consistently observed in all lambs. In the small intestine, salient lesions initially included distension and oedema of intestinal villi, leucocytic infiltration and hyperplasia of lymphoid nodules with apparent germinal centres; this was followed at later stages by atrophy and/or degeneration of the lymphoid tissue of the intestine with marked subepithelial infiltration of lymphocytes, plasma cells and eosinophils.

The objectives of the study were (a) to study the characteristics of uterine involution in ewes that had developed subclinical uterine infection in the immediately post-partum period and (b) to evaluate effects of the infection in the subsequent reproductive performance of ewes. Uterine infection was induced in ewes (I, n = 10) by intrauterine inoculation of Escherichia coli; uninoculated controls were included (C, n = 12). Animals were examined at regular intervals before and post-inoculation. Clinical and ultrasonographic examinations were performed. Vaginal swab samples and biopsy uterine tissue samples were collected for bacteriological, cytological and histological examination. Finally, ewes were put to rams and reproductive performance was monitored. After challenge, it was ultrasonographically found that caruncular dimensions, myometrial thickness and diameter of uterine lumen were greater in I ewes. In these ewes, particular reduction of dimensions occurred during the second week post-partum, whilst in C ewes during the first week. The uterine artery diameter and the blood flow into the uterus were also greater in I than in C ewes. E. coli infection was more frequent and of longer duration in I than in C ewes: in 68.1% and 50.0% of ewes and 19.5 and 14 days, respectively. There was lower proportion of neutrophils and higher of lymphocytes in group I than in C. In inoculated ewes, there was histological evidence of uterine epithelial destruction, increased cellular infiltration, hyperaemia and extracasation, which persisted up to 42 days post-partum. During the subsequent reproductive season, all ewes in group I lambed normally and produced healthy and viable lambs. No significant difference in reproductive performance parameters were seen in I comparison to C ewes. It is concluded that the innate immunity of the uterus sufficed to counteract the bacterial infection, although the process of involution took longer than in healthy animals; moreover, the ultrasonographic examination is a useful means for assessment of the genital tract of ewes post-partum; finally, no adverse effects were noted in the subsequent reproductive performance of ewes.

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder where motor dysfunction gradually increases. PD-specific dopaminergic drugs can ameliorate symptoms, but neurologists also strongly recommend physiotherapy combined with regular exercise. As there is no known cure for PD, traditional rehabilitation programs eventually tire and bore patients to the point of losing interest and dropping out of those programs just because of the predictability and repeatability of the exercises. This can be avoided with the help of current technology, character-based, interactive 3D games promote physical training in a nonlinear fashion, and can provide experiences that change each time the game is played. Such “exergames” (a combination of the words “exercise” and “game”) challenge patients into performing exercises of varying complexity in a playful and interactive environment. In this work we present a Unity3D-based platform hosting two exergames tailored to PD patients with mild to moderate symptoms. The platform employs Microsoft Kinect, an affordable off-the-shelf motion capture sensor that can be easily installed in both home and clinical settings. Platform navigation and gameplay rely on a collection of gestures specifically developed for this purpose and are based upon training programs tailored to PD. These gestures employ purposeful, large-amplitude movements intended to improve postural stability and reflexes and increase upper and lower limb mobility. When the patient’s movements, as detected by Kinect, “match” a preprogrammed gesture, an onscreen 3D cartoon avatar responds according to the game context at hand. In addition, ingame decision-making aims at improving cognitive reaction.

Background and Aim. Extended liver radiofrequency ablation (RFA) has been shown to disrupt gut barrier integrity with subsequent bacterial translocation. The aim of the present project was to study the immune and inflammatory responses of the intestinal mucosa after extended RFA of the liver. Methods. Twelve Wistar rats were either subjected to RFA of the left lateral hepatic lobe (approximately 30% of the liver mass) after midline laparotomy (group RFA, n=6) or sham operation (group Sham, n=6). Forty-eight hours later, ileal tissue specimens were excised for immunohistochemical assessment of CD68+ macrophages, CD4+ T-lymphocytes, CD8+ T-lymphocytes, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and nuclear factor-κB (NFκB) expression. Results. Immune response biomarkers were upregulated in the RFA group. Expression of CD4+ and CD8+ T-lymphocytes was moderate, while that of CD68+ macrophages and MAdCAM-1 was high. Inflammatory response biomarkers were also upregulated in the RFA group. TNFα, IL-6, and NFκB expression was low, moderate, and high, respectively. Conclusions. Extended liver RFA evokes both immune and inflammatory responses of the gut mucosa.

Modern agriculture requires technology to give precise measures about relevant parameters such as pest control. Here, we developed a decision support system (DSS) based on semi-automatic pest monitoring for managing the olive fruit fly Bactrocera oleae (Rossi), in Mallorca (Balearic Islands, Spain). The DSS was based on an algorithm that took into account spatial and temporal patterns of olive fruit fly population in an orchard where all trees were georeferenced, thus precise treatments against the pest were conducted through a location aware system (LAS). The olive fruit fly adult population was monitored by using ad hoc off-the-grid autonomous electronic traps.The results were compared with those obtained with conventional methods. For a pilot trial, we selected an olive-producing orchard, where from June to October 2015, three plots using LAS management and three plots under conventional control (NO-LAS plots) were compared. Spray threshold considered both adult population and fruit damage. An additional non-sprayed plot was selected for assessing biological control due to the parasitoid, Psyttalia concolor (Szépligeti). Results showed that the use of DSS reduced by 36.84% the volume of insecticide used in LAS compared to NO-LAS plots. Accordingly, time and distance needed for spraying were also reduced. Adult olive fruit fly population was lower in the LAS plots when compared with the NO-LAS plots; conversely, fruit infestation was higher in LAS compared with NO-LAS. The implementation of LAS and DSS at field level allowed real-time monitoring of adult olive flies, thereby increasing the accuracy and precision of sprays in time and space and decreasing impact on natural enemies.

Background and Aims: Acute hepatitis C is rarely diagnosed due to its predominantly asymptomatic course. However, early treatment results in viral eradication in a high number of patients thus, preventing chronicity. The aim of our study was to describe our experience with patients with acute hepatitis C virus (HCV) infection who presented and followed-up in our liver unit, pointing on treatment strategy, and outcome. Patients and Methods: Retrospective, descriptive study of 30 patients with acute HCV infection (26 males and 4 females) with a mean age of 32 years. Results: The source of infection was mainly injection drug use in 17/30 (56.7) and medical procedures 6/30 (20%). Twenty patients (66.6%) were symptomatic. HCV-ribonucleic acid (RNA) was detectable at presentation in 26 (86.7%) patients. The genotype distribution was: 13/26 (50%) genotype 1, 3/26 (11.5%) genotype 2, 8/26 (30.8%) genotype 3 and 2/26 (7.7%) genotype 4. Totally, 9 patients (30%) experienced spontaneous viral eradication. No significant differences could be documented between patients who spontaneously cleared the virus and those who had viral persistence. Thirteen patients (44%) were treated with peginterferon-based regimen. All patients (100%) achieved non-detectable HCV-RNA and had normal serum alanine aminotransferase levels at the end of the treatment. Eleven patients achieved sustained virologic response (SVR), one relapsed and one was lost to follow-up. The overall SVR rate was 84.6%. None of the patients required dose reduction or stopped the treatment due to side effects. Conclusion: In conclusion, early initiation of anti-viral treatment in patients with acute hepatitis C results in high-SVR rates (independently of genotype) and is well-tolerated.

Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment.

Aim: Polymorphous low grade adenocarcinoma of the salivary glands (PLGA) is a low grade neoplasm that predominantly occurs in the minor salivary glands. In this site is amenable to biopsy and histologic diagnosis. However, experience with cytological findings in these tumors is limited. We describe the cytology of this entity. Experimental design: Touch imprint cytology of a primary parotid PLGA is specified and correlated with histology. Results: Smears were hypercellular showing branching papillae, sheets and clusters of uniform cells with bland nuclei, dispersed chromatin and no nucleoli. The cells had a scant to moderate amount of eosinophilic cytoplasm. They formed tubular structures containing hyaline globules. Conclusions. The cytologic differential diagnosis of PLGA includes adenoid cystic carcinoma, pleomorphic adenoma, and monomorphic adenoma. PLGA should be considered in the differential diagnosis of head and neck tumors, where the cytology suggests on of the above mentioned tumors, even when the clinical findings (involvement of a major salivary gland, lymph node metastasis) is not typical of PLGA.

Aim: To determine the immunoreactivity of pancreatic-polypeptide (PP) during the development of the human fetal pancreas and ductal pancreatic adenocarcinoma, given that, PP positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. Methods: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed. Results: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal – endocrine) and pure ductal type (p1=0.001, p2

Aim: The maturation of most T- lymphocyte precursors takes place within the meshwork of thymic epithelial cells. Different steps of this process can be defined by immunologic phenotyping. The prothymocytes are positive for the terminal deoxynucleotidyl transferase (TdT) and give rise to cortical thymocytes, which express CD1, CD2, CD3, CD5, and both CD4 and CD8. These CD4 and CD8 double-positive cortical thymocytes differentiate into two lineages: CD4+ or CD8+ lymphocytes of the thymic medulla, by the tenth week of gestation. Our study points towards the determination of the CD8 cytotoxic/suppressor capacity of the fetal thymus in Down’s syndrome. Experimental design: A quantitative comparison of T-lymphocytes (CD3, CD4, and CD8) in the thymic parenchyme in embryos after voluntary abortion during 2nd trimester of gestation and embryos with Down’s syndrome, respectively, was performed. Results: Our results showed: 1) A statistically significant depletion in the total number of T-cells (CD3 positive) in the cases of embryos with Down’s syndrome over those after voluntary abortion, during the second trimester of gestation (p

Unfortunately this article [1] was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below: Funding EAACI and the BM4SIT project (Grant Number 601763) in the European Union’s Seventh Framework Programme FP7.

Unfortunately this article [1] was published with an error in the Funding section. The BM4SIT project is not acknowledged. This section should be corrected to the below: Funding EAACI and the BM4SIT project (Grant Number 601763) in the European Union’s Seventh Framework Programme FP7.

West Nile Virus (WNV) is the causative agent of a vector-borne, zoonotic disease with a worldwide distribution. Recent expansion and introduction of WNV into new areas, including southern Europe, has been associated with severe disease in humans and equids, and has increased concerns regarding the need to prevent and control future WNV outbreaks. Since 2010, 524 confirmed human cases of the disease have been reported in Greece with greater than 10% mortality. Infected mosquitoes, wild birds, equids, and chickens have been detected and associated with human disease. The aim of our study was to establish a monitoring system with wild birds and reported human cases data using Geographical Information System (GIS). Potential distribution of WNV was modelled by combining wild bird serological surveillance data with environmental factors (e.g. elevation, slope, land use, vegetation density, temperature, precipitation indices, and population density). Local factors including areas of low altitude and proximity to water were important predictors of appearance of both human and wild bird cases (Odds Ratio = 1,001 95%CI = 0,723-1,386). Using GIS analysis, the identified risk factors were applied across Greece identifying the northern part of Greece (Macedonia, Thrace) western Greece and a number of Greek islands as being at highest risk of future outbreaks. The results of the analysis were evaluated and confirmed using the 161 reported human cases of the 2012 outbreak predicting correctly (Odds = 130/31 = 4,194 95%CI = 2,841-6,189) and more areas were identified for potential dispersion in the following years. Our approach verified that WNV risk can be modelled in a fast cost-effective way indicating high risk areas where prevention measures should be implemented in order to reduce the disease incidence.

Regional Student Groups (RSGs) of the International Society for Computational Biology Student Council (ISCB-SC) have been instrumental to connect computational biologists globally and to create more awareness about bioinformatics education. This article highlights the initiatives carried out by the RSGs both nationally and internationally to strengthen the present and future of the bioinformatics community. Moreover, we discuss the future directions the organization will take and the challenges to advance further in the ISCB-SC main mission: “Nurture the new generation of computational biologists”.

The Student Council of the International Society for Computational Biology (ISCB-SC) is a student-focused organization for researchers from all early career levels of training (undergraduates, masters, PhDs and postdocs) that organizes bioinformatics and computational biology activities across the globe. Among its activities, the ISCB-SC organizes several symposia in different continents, many times, with the help of the Regional Student Groups (RSGs) that are based on each region. In this editorial we highlight various key moments and learned lessons from the 14th Student Council Symposium (SCS, Chicago, USA), the 5th European Student Council Symposium (ESCS, Athens, Greece) and the 3rd Latin American Student Council Symposium (LA-SCS, Viña del Mar, Chile).