Anexelekto (AXL) no more: microRNA-155 (miR-155) controls the "Uncontrolled" in SARS-CoV-2.

AXL is the gene that encodes the Anexelekto (AXL) receptor tyrosine kinase that demonstrates significant roles in various cellular processes, including cell growth, survival, and migration. Anexelekto is a Greek word meaning excessive and uncontrolled, semantically implying the crucial involvement of AXL in cancer and immune biology, and in promoting cancer metastasis. AXL overexpression appears to drive epithelial to mesenchymal transition, tumor angiogenesis, decreased antitumor immune response, and resistance to therapeutic agents. Recently, AXL has been reported to play important roles in several viral infections, including SARS-CoV-2. We have previously outlined the importance of microRNAs (miRNAs, miRs) and especially miR-155 in SARS-CoV-2 pathophysiology through regulation of the Renin-Angiotensin Aldosterone System (RAAS) and influence on several aspects of host innate immunity. MiRNAs are negative regulators of gene expression, decreasing the stability of target RNAs or limiting their translation and, enthrallingly, miR-155 is also involved in AXL homeostasis-both endogenously and pharmaceutically using repurposed drugs (e.g., metformin)-highlighting thrifty evolutionary host innate immunity mechanisms that successfully can thwart viral entry and replication. Cancer, infections, and immune system disturbances will increasingly involve miRNA diagnostics and therapeutics in the future.

Live to die another day: novel insights may explain the pathophysiology behind smoker's paradox in SARS-CoV-2 infection.

The severe acute respiratory coronavirus 2 (SARS-CoV-2) infection demonstrates a highly variable and unpredictable course. Several reports have claimed a smoker's paradox in coronavirus disease 2019 (COVID-19), in line with previous suggestions that smoking is associated with better survival after acute myocardial infarction and appears protective in preeclampsia. Several plausible physiological explanations exist accounting for the paradoxical observation of smoking engendering protection against SARS-CoV-2 infection. In this review, we delineate novel mechanisms whereby smoking habits and smokers' genetic polymorphism status affecting various nitric oxide (NO) pathways (endothelial NO synthase, cytochrome P450 (CYP450), erythropoietin receptor (EPOR); ß-common receptor (ßcR)), along with tobacco smoke modulation of microRNA-155 and aryl-hydrocarbon receptor (AHR) effects, may be important determinators of SARS-CoV-2 infection and COVID-19 course. While transient NO bioavailability increase and beneficial immunoregulatory modulations through the above-mentioned pathways using exogenous, endogenous, genetic and/or therapeutic modalities may have direct and specific, viricidal SARS-CoV-2 effects, employing tobacco smoke inhalation to achieve protection equals self-harm. Tobacco smoking remains the leading cause of death, illness, and impoverishment.

Beauty and the beast: host microRNA-155 versus SARS-CoV-2.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection in the young and healthy usually results in an asymptomatic or mild viral syndrome, possibly through an erythropoietin (EPO)-dependent, protective evolutionary landscape. In the old and in the presence of co-morbidities, however, a potentially lethal coronavirus disease 2019 (COVID-19) cytokine storm, through unrestrained renin-angiotensin aldosterone system (RAAS) hyperactivity, has been described. Multifunctional microRNA-155 (miR-155) elevation in malaria, dengue virus (DENV), the thalassemias, and SARS-CoV-1/2, plays critical antiviral and cardiovascular roles through its targeted translational repression of over 140 genes. In the present review, we propose a plausible miR-155-dependent mechanism whereby the translational repression of AGRT1, Arginase-2 and Ets-1, reshapes RAAS towards Angiotensin II (Ang II) type 2 (AT2R)-mediated balanced, tolerable, and SARS-CoV-2-protective cardiovascular phenotypes. In addition, it enhances EPO secretion and endothelial nitric oxide synthase activation and substrate availability, and negates proinflammatory Ang II effects. Disrupted miR-155 repression of AT1R + 1166C-allele, significantly associated with adverse cardiovascular and COVID-19 outcomes, manifests its decisive role in RAAS modulation. BACH1 and SOCS1 repression creates an anti-inflammatory and cytoprotective milieu, robustly inducing antiviral interferons. MiR-155 dysregulation in the elderly, and in comorbidities, allows unimpeded RAAS hyperactivity to progress towards a particularly aggressive COVID-19 course. Elevated miR-155 in thalassemia plausibly engenders a favorable cardiovascular profile and protection against malaria, DENV, and SARS-CoV-2. MiR-155 modulating pharmaceutical approaches could offer novel therapeutic options in COVID-19.

Mitochondrial neurogastrointestinal encephalomyopathy: Clinical and biochemical impact of allogeneic stem cell transplantation in a Greek patient with one novel TYMP mutation.

We describe the case of a Greek female patient with the Classic form of the ultra- rare and fatal autosomal recessive disorder Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and the impact of allogeneic hematopoietic stem cell transplantation on the biochemical and clinical aspects of the disease. The patient presented at the age of 15 years with severe gastrointestinal symptoms, cachexia, peripheral neuropathy and diffuse leukoencephalopathy. The diagnosis of MNGIE disease was established by the increased levels of thymidine and deoxyuridine in plasma and the complete deficiency of thymidine phosphorylase activity. The novel c.[978dup] (p.Ala327Argfs*?) variant and the previously described variant c.[417 + 1G > A] were identified in TYMP. The donor for the allogeneic hematopoietic stem cell transplantation was her fully compatible sister, a carrier of the disease. The patient had a completely uneventful post- transplant period and satisfactory PB chimerism levels. A marked and rapid decrease in thymidine and deoxyuridine plasma levels and an increase of the thymidine phosphorylase activity to the levels measured in her donor sister was observed and is still present sixteen months post-transplant. Disease symptoms stabilized and some improvement was also observed both in her neurological and gastrointestinal symptoms. Follow up studies will be essential for determining the long term impact of allogeneic hematopoietic stem cell transplantation in our patient.

Electron-beam energy reconstruction for neutrino oscillation measurements.

Neutrinos exist in one of three types or 'flavours'-electron, muon and tau neutrinos-and oscillate from one flavour to another when propagating through space. This phenomena is one of the few that cannot be described using the standard model of particle physics (reviewed in ref. 1), and so its experimental study can provide new insight into the nature of our Universe (reviewed in ref. 2). Neutrinos oscillate as a function of their propagation distance (L) divided by their energy (E). Therefore, experiments extract oscillation parameters by measuring their energy distribution at different locations. As accelerator-based oscillation experiments cannot directly measure E, the interpretation of these experiments relies heavily on phenomenological models of neutrino-nucleus interactions to infer E. Here we exploit the similarity of electron-nucleus and neutrino-nucleus interactions, and use electron scattering data with known beam energies to test energy reconstruction methods and interaction models. We find that even in simple interactions where no pions are detected, only a small fraction of events reconstruct to the correct incident energy. More importantly, widely used interaction models reproduce the reconstructed energy distribution only qualitatively and the quality of the reproduction varies strongly with beam energy. This shows both the need and the pathway to improve current models to meet the requirements of next-generation, high-precision experiments such as Hyper-Kamiokande (Japan)3 and DUNE (USA)4.

Exploring genetic resistance to infectious salmon anaemia virus in Atlantic salmon by genome-wide association and RNA sequencing.

BACKGROUND: Infectious Salmonid Anaemia Virus (ISAV) causes a notifiable disease that poses a large threat for Atlantic salmon (Salmo salar) aquaculture worldwide. There is no fully effective treatment or vaccine, and therefore selective breeding to increase resistance to ISAV is a promising avenue for disease prevention. Genomic selection and potentially genome editing can be applied to enhance host resistance, and these approaches benefit from improved knowledge of the genetic and functional basis of the target trait. The aim of this study was to characterise the genetic architecture of resistance to ISAV in a commercial Atlantic salmon population and study its underlying functional genomic basis using RNA Sequencing. RESULTS: A total of 2833 Atlantic salmon parr belonging to 194 families were exposed to ISAV in a cohabitation challenge in which cumulative mortality reached 63% over 55 days. A total of 1353 animals were genotyped using a 55 K SNP array, and the estimate of heritability for the trait of binary survival was 0.13-0.33 (pedigree-genomic). A genome-wide association analysis confirmed that resistance to ISAV was a polygenic trait, albeit a genomic region in chromosome Ssa13 was significantly associated with resistance and explained 3% of the genetic variance. RNA sequencing of the heart of 16 infected (7 and 14 days post infection) and 8 control fish highlighted 4927 and 2437 differentially expressed genes at 7 and 14 days post infection respectively. The complement and coagulation pathway was down-regulated in infected fish, while several metabolic pathways were up-regulated. The interferon pathway showed little evidence of up-regulation at 7 days post infection but was mildly activated at 14 days, suggesting a potential crosstalk between host and virus. Comparison of the transcriptomic response of fish with high and low breeding values for resistance highlighted TRIM25 as being up-regulated in resistant fish. CONCLUSIONS: ISAV resistance shows moderate heritability with a polygenic architecture, but a significant QTL was detected on chromosome 13. A mild up-regulation of the interferon pathway characterises the response to the virus in heart samples from this population of Atlantic salmon, and candidate genes showing differential expression between samples with high and low breeding values for resistance were identified.

A commercial autogenous injection vaccine protects ballan wrasse (Labrus bergylta, Ascanius) against Aeromonas salmonicida vapA type V.

Atypical Aeromonas salmonicida (aAs) and Vibrionaceae related species are bacteria routinely recovered from diseased ballan wrasse used as cleaner fish in the Atlantic salmon farming industry. Autogenous (i.e. farm specific inactivated) multivalent vaccines formulated from these microorganisms are widely used to protect farmed wrasse despite limited experimental proof that they are primary pathogens. In this study, the components of a commercial multivalent injection vaccine containing four strains of Aeromonas salmonicida and one strain of Vibrio splendidus previously isolated from ballan wrasse in Scotland, were tested for infectivity, pathogenicity and virulence via intra peritoneal injection at pre-deployment size (25-50 g) and the efficacy of the vaccine for protection against aAs assessed. Injection with 3.5 × 109, 8 × 109 1.8 × 109 and 5 × 109 cfu/fish of Vibrio splendidus, V. ichthyoenteri, Aliivibrio logeii and A. salmonicida, respectively, did not cause significant mortalities, lesions or clinical signs after a period of 14 days. IP injection with both aAs and Photobacterium indicum successfully reproduced the clinical signs and internal lesions observed during natural outbreaks of the disease. Differences in virulence (LD50 at day 8-post infection of 3.6 × 106 cfu/fish and 1.6 × 107 cfu/fish) were observed for two aAs vapA type V isolates. In addition, the LD50 for Photobacterium indicum was 2.2 × 107 cfu/fish. The autogenous vaccine was highly protective against the two aAs vapA type V isolates after 700-degree days of immunisation. The RPSFINAL values for the first isolate were 95 and 91% at 1 × 106 cfu/fish and 1 × 107 cfu/fish, respectively, and 79% at 1 × 107 cfu/fish for the second isolate tested. In addition, significantly higher anti aAs seral antibodies (IgM), were detected by ELISA in vaccinated fish in contrast with control (mock vaccinated) fish. These results suggest wrasse can be effectively immunised and protected against aAs infection by injection with oil adjuvanted vaccines prepared with inactivated homologous isolates.

Aspergillus peritonitis in peritoneal dialysis patients: A systematic review.

Fungal peritonitis in patients undergoing peritoneal dialysis (PD) is very difficult to treat and is associated with significant morbidity and mortality. Among fungal pathogens, Aspergillus peritonitis presents a higher mortality rate when compared to Candida peritonitis and its identification as well as appropriate treatment remains a challenge for the physicians. We critical reviewed all published cases in literature of Aspergillus peritonitis in PD patients. The results showed that a total of 55 cases (51% males) of Aspergillus peritonitis in PD patients were reported from 1968 to 2019. Mean patient age was 49.54±19.63years and mean PD duration prior to fungal infection was 33.31±32.45months. Aspergillus fumigatus was isolated in 17/55 patients, Aspergillus niger in 15, Aspergillus terreus in 9, unidentified Aspergillus spp. in 6, Aspergillus flavus in 4, whereas sporadic cases of other Aspergillus spp. were reported. As far as predisposing factors are concerned, 75% of patients suffered from prior bacterial peritonitis receiving antimicrobial therapy. Initial antifungal treatment was intravenous and/or intraperitoneal administration of amphotericin B formulations monotherapy in 47.2% of patients or in combination with fluconazole in 13.2%, or with itraconazole in 13.2%, or with caspofungin in 3.8%, or with ketoconazole or with 5-FC in 1.9%, each. Peritoneal catheter removal was performed in 85.5% of cases. Mortality rate was 38.2%, while 81.8% of the survived patients switched to hemodialysis. Conclusively, Aspergillus peritonitis diagnosis can be difficult, due to unspecific symptoms. Early treatment with appropriate antifungal agents can be determinant for patient prognosis. Despite appropriate treatment, reported mortality remains high.

Atypical Aeromonas salmonicida vapA type V and Vibrio spp. are predominant bacteria recovered from ballan wrasse Labrus bergylta in Scotland.

Healthy and/or moribund farmed and wild ballan wrasse Labrus bergylta (>0.5 to 900 g) were sampled from hatcheries (n = 2) and Atlantic salmon Salmo salar cage sites (n = 8) in Scotland between February 2016 and October 2018. Less than half of the sampled individuals (n = 43; 32.3%) had been vaccinated (autogenous polyvalent vaccine; dip and/or injection) against atypical furunculosis (type V and VI), while 20 (15.0%) fish were not vaccinated, and the rest (70 individuals, 52.7%) were of unknown vaccination status. Swab samples from skin lesions, gill, liver, spleen and kidney were inoculated onto a variety of bacteriological agar plates, and bacteriology identification and sequencing analysis was performed on significant bacterial colonies. Atypical Aeromonas salmonicida (aAs) vapA type V was the predominant bacterial species (70/215 bacterial isolates, 32.5% of bacterial samples; 43/117 positive individual fish, 36.8%) isolated in this survey followed by Vibrio species, which were the most geographically prevalent bacteria. Photobacterium indicum/profundum was also isolated from L. bergylta for the first time during this study. The collection of these bacterial isolates provides useful information for disease management. Identifying the aAs isolates involved in disease in ballan wrasse could provide vital information for improving/updating existing autogenous vaccines.

Effectiveness and easiness of adherence to behavioural guidelines for diet and lifestyle changes for cholesterol-lowering: the Increasing Adherence of Consumers to Diet & Lifestyle Changes to Lower (LDL) Cholesterol (ACT) randomised controlled trial.

BACKGROUND: The present study aimed to assess perceived effectiveness and easiness of behavioural diet and lifestyle changes related to dyslipidaemia given by physicians or dieticians as a result of diet and lifestyle modifications being difficult to maintain. METHODS: One-hundred hypercholesterolaemic individuals were enrolled in a parallel, randomised 6-week study. Fifty were advised by dietitians (dietitian group: DG) in six weekly face-to-face behavioural therapy sessions and 50 received standard advice from physicians (physician group: PG). All individuals were followed-up for another 6 weeks under real-life conditions. Questionnaires regarding perceived effectiveness, easiness of adhering, forecasted and actual adherence to specific cholesterol-lowering advice were completed. RESULTS: Scores of perceived effectiveness of advice for sufficient exercise, limiting saturated fat (SFA) intake, eating fish twice a week, consuming plenty of fresh fruit and vegetables, and limiting salt intake different scientifically (all P < 0.05) in PG and DG between study phases. Scores of the individuals' perception of effectiveness at all study phases were higher in the DG compared to PG for sufficient exercise, limiting SFA intake, eating fish twice a week, eating plenty of fruits and vegetables, and limiting salt intake, whereas scores of easiness were significant only for fish consumption (P = 0.008) and using foods with added plant sterols (all P < 0.05). DG and PG significantly differed in forecasted (week 6) versus actual adherence (week 12) to various chances, with DG reporting higher adherence. CONCLUSIONS: Lifestyle and dietary changes related to dyslipidaemia can be achieved with continuous education, monitoring and follow-ups by dieticians, as well as potentially other trained healthcare professionals.

Structured advice provided by a dietitian increases adherence of consumers to diet and lifestyle changes and lowers blood low-density lipoprotein (LDL)-cholesterol: the Increasing Adherence of Consumers to Diet & Lifestyle Changes to Lower (LDL) Cholesterol (ACT) randomised controlled trial.

BACKGROUND: Evidence from healthcare professionals suggest that consumer compliance to healthy diet and lifestyle changes is often poor. The present study investigated the effect of advice provided by a physician or dietitian on consumer adherence to these measures combined with consuming foods with added plant sterols (PS) with the aim of lowering low-density lipoprotein cholesterol (LDL-C). METHODS: One hundred mildly-to-moderately hypercholesterolaemic individuals were enrolled into a parallel, randomised, placebo-controlled study. Dietitians (dietitian group; DG) advised 50 individuals in six weekly face-to-face behavioural therapy sessions, whereas the other 50 received standard advice from physicians (physician group, PG). Both groups consumed foods with added PS (three servings a day) for 6 weeks. Subsequently, all individuals were followed-up for another 6 weeks under real-life conditions. Blood lipids were measured at baseline and weeks 6 and 12 and 3-day diet diaries were taken at weeks 1, 6 and 12. RESULTS: Individuals in the DG significantly improved their dietary habits, physical activity and increased PS intake compared to the PG. After 6 weeks, LDL-C decreased in both groups compared to baseline without any significant differences between groups. At week 12, LDL-C was further significantly improved only in the DG (P = 0.006) compared to week 6. Total cholesterol, LDL-C and triglycerides were significantly lower in the DG compared to the PG at week 12 after adjusting for levels at week 6 (P < 0.001, P < 0.001 and P = 0.009, respectively). CONCLUSIONS: Although structured counselling by dietitians and common standard advice by physicians were equally effective with respect to improving blood cholesterol after 6 weeks, dietitians were more effective in the longer-term (i.e. 6 weeks after the end of the intervention period).

Psychotic (delusional) depression and suicidal attempts: a systematic review and meta-analysis.

OBJECTIVE: It still remains unclear whether psychotic features increase the risk of suicidal attempts in major depressive disorder. Thus, we attempted, through a systematic review coupled with a meta-analysis, to elucidate further whether unipolar psychotic depression (PMD) compared to non-PMD presents higher levels of suicidal attempts. METHOD: A systematic search was conducted in PubMed, EMBASE, PsycINFO as well as in various databases of the so-called gray literature for all studies providing data on suicidal attempts in PMD compared to non-PMD, and the results were then subjected to meta-analysis. RESULTS: Twenty studies met our inclusion criteria, including in total 1,275 PMD patients and 5,761 non-PMD patients. An elevated risk for suicide attempt for PMD compared to non-PMD patients was found: The total (lifetime) fixed-effects pooled OR was 2.11 (95% CI: 1.81-2.47), and the fixed-effects pooled OR of the five studies of the acute phase of the disorder was 1.93 (95% CI: 1.33-2.80). This elevated risk of suicidal attempt for PMD patients remained stable across all age groups of adult patients. CONCLUSION: Despite data inconsistency and clinical heterogeneity, this systematic review and meta-analysis showed that patients with PMD are at a two-fold higher risk, both during lifetime and in acute phase, of committing a suicidal attempt than patients with non-PMD.

Effects of different endurance exercise modalities on migraine days and cerebrovascular health in episodic migraineurs: A randomized controlled trial.

Aerobic exercise training is a promising complementary treatment option in migraine and can reduce migraine days and improve retinal microvascular function. Our aim was to elucidate whether different aerobic exercise programs at high vs moderate intensities distinctly affect migraine days as primary outcome and retinal vessel parameters as a secondary. In this randomized controlled trial, migraine days were recorded by a validated migraine diary in 45 migraineurs of which 36 (female: 28; age: 36 (SD:10)/BMI: 23.1 (5.3) completed the training period (dropout: 20%). Participants were assigned (Strata: age, gender, fitness and migraine symptomatology) to either high intensity interval training (HIT), moderate continuous training (MCT), or a control group (CON). Intervention groups trained twice a week over a 12-week intervention period. Static retinal vessel analysis, central retinal arteriolar (CRAE) and venular (CRVE) diameters, as well as the arteriolar-to-venular diameter ratio (AVR) were obtained for cerebrovascular health assessment. Incremental treadmill testing yielded maximal and submaximal fitness parameters. Overall, moderate migraine day reductions were observed (ηP2 = .12): HIT revealed 89% likely beneficial effects (SMD = 1.05) compared to MCT (SMD = 0.50) and CON (SMD = 0.59). Very large intervention effects on AVR improvement (ηP2 = 0.27), slightly favoring HIT (SMD=-0.43) over CON (SMD=0), were observed. HIT seems more effective for migraine day reduction and improvement of cerebrovascular health compared to MCT. Intermittent exercise programs of higher intensities may need to be considered as an additional treatment option in migraine patients.

Substance abuse and cancer.

Substance abuse is a health problem with serious psychological and psychiatric dimensions and multiple social and economic consequences. Cancer is a disease that threatens not only life and physical integrity but mental health as well. Oncology patients suffer from mental disorders in high rates, especially from depression and anxiety. The role of substance abuse in the pathogenesis of cancer is studied systematically, since there are research data supporting the mutagenic effects of certain substances. It has been supported that a possible dysregulation of the immune system is linked to the oncogenic processes induced by substances of abuse. Specifically, opioids are the first addictive substances that have been identified as oncogenic factors. However, conflicting results have been offered by experimental animal studies, which showed that opioids, such as morphine, depending on the dosage administered, may not only enhance the process of tumor growth, but also inhibit it. Additionally, research data indicate that the use of cannabis may be associated with cancer, either as an independent factor or in relation to other mutagenics, although it is not yet clear to which extent these effects may be connected to the disease, especially once the consumption of tobacco and alcohol by these patients are taken into account. However, it has been argued that certain cannabinoids may have biological -anticancer- activities which could be used therapeutically without being accompanied by the corresponding 9-tetrahydrocannabinol psychoactive effects. It is well known that alcohol is a risk factor for developing head and neck cancer, and epidemiological studies indicate that the higher the consumption of alcohol, the more mortality due to cancer increases. In addition, it is suggested that there is no safety level for alcohol consumption regarding the risk of developing cancer; that is even a minimum daily consumption is associated with the occurrence of certain types of cancer. Specific components have been identified in tobacco, which are considered to be carcinogenic and responsible for tumor development in various sites. Moreover, complicated psychiatric problems arise due to substance abuse in cancer patients, either in the context of pain treatment, or under pre-existing dependence. The rational use of opioid analgesics, when it is medically required as suggested by the health professionals specialized in the treatment of acute pain in cancer patients, could be a therapeutic option. Substance abuse reduces treatment compliance, worsens cancer prognosis and seems to be a negative factor for the quality of life of these patients. Current literature highlights the importance of appropriate psychiatric interventions to address substance abuse in cancer patients.

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology

BACKGROUND AND PURPOSE: Current guidelines on cerebral venous thrombosis (CVT) diagnosis and management were issued by the European Federation of Neurological Societies in 2010. We aimed to update the previous European Federation of Neurological Societies guidelines using a clearer and evidence-based methodology. METHOD: We followed the Grading of Recommendations, Assessment, Development and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews and writing recommendations based on the quality of available scientific evidence. RESULTS: We suggest using magnetic resonance or computed tomographic angiography for confirming the diagnosis of CVT and not routinely screening patients with CVT for thrombophilia or cancer. We recommend parenteral anticoagulation in acute CVT and decompressive surgery to prevent death due to brain herniation. We suggest preferentially using low-molecular-weight heparin in the acute phase and not direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that, in women who have suffered a previous CVT, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular-weight heparin should be considered throughout pregnancy and puerperium. CONCLUSIONS: Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of CVT.

Lactobacillus reuteri DSM 17938 and a placebo both significantly reduced symptoms in children with functional abdominal pain.

AIM: Lactobacillus reuteri is a Gram-positive bacterium that naturally inhabits the human intestinal tract. This study assessed how effectively the probiotic L. reuteri DSM 17938 managed childhood functional abdominal pain (FAP). METHODS: We recruited 54 children with a mean age 9.1 ± 3.8 years, who were diagnosed with FAP in the outpatient clinics of three university hospitals in Greece, Slovenia and Poland, according to the Rome III criteria, from January 2013 to December 2015. They were randomly assigned to receive either 2 × 108 colony-forming units of L. reuteri (n = 27) or a placebo (n = 27) for four weeks. RESULTS: Both L. reuteri and the placebo significantly reduced the frequency and intensity of abdominal pain episodes at four and eight weeks compared to baseline (all p < 0.001). L. reuteri decreased the use of pain relieving drugs at four weeks and the number of child school and adult work absences at four and eight weeks, unlike the placebo, which achieved nonsignificant results. However, the difference between the groups did not reach significance. No side effects were recorded. CONCLUSION: Both L. reuteri and the placebo were effective in alleviating pain in children with FAP, but only L. reuteri improved the child's and family's normal activities.

Joint ESPGHAN/NASPGHAN guidelines for the management of helicobacter pylori in children and adolescents (Update 2016)

BACKGROUND: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. METHODS: A systematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. RESULTS: The consensus group recommended that invasive diagnostic testing for H pylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. CONCLUSIONS: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child.

In vivo adherence of Flavobacterium psychrophilum to mucosal external surfaces of rainbow trout (Oncorhynchus mykiss) fry.

The adherence of Flavobacterium psychrophilum to surfaces of epithelial tissues has been inconclusively suggested as a mechanism, which enables the bacterium to invade the host. Hence, the present study aimed to examine the adherence of the cells of two colony phenotypes, smooth and rough, of F. psychrophilum to mucosal tissues of rainbow trout fry and to test the skin mucus as a nutrient for the growth of F. psychrophilum. Fish were immersed in water containing 106  CFU  mL-1 F. psychrophilum for each colony phenotype. Mucosal tissue samples from fins, gills, skin and eyes, and swab samples from spleen and kidney were taken and inoculated onto TYES agar plates. Colony phenotypes of F. psychrophilum were identified and number of colonies counted. The results showed that cells of both phenotypes initially (0 h) adhered to all mucosal surfaces, but only the rough cells were still present on tissues 1 h post-immersion. Both phenotypes showed a tissue tropism with the fin tissue being the most adhered. Furthermore, skin mucus promoted the growth of both colony phenotypes. We suggest that the growth of F. psychrophilum cells in skin mucus apparently facilitates the bacterial adherence to mucosal surfaces, and the subsequent invasion into the host.

Role of Cathepsin S in Periodontal Inflammation and Infection.

Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1ß and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1ß and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.