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Summary In agriculture, antibiotics are used for the treatment and prevention of livestock disease. Antibiotics perturb the bacterial gut composition but the extent of these changes and potential consequences for animal and human health is still debated. Six calves were housed in a controlled environment. Three animals received an injection of the antibiotic florfenicol (Nuflor), and three received no treatment. Faecal samples were collected at 0, 3 and 7 days, and bacterial communities were profiled to assess the impact of a therapy on the gut microbiota. Phylogenetic analysis (16S‐rDNA) established that at day 7, antibiotic‐treated microbiota showed a 10‐fold increase in facultative anaerobic Escherichia spp, a signature of imbalanced microbiota, dysbiosis. The antibiotic resistome showed a high background of antibiotic resistance genes, which did not significantly change in response to florfenicol. However, the maintenance of Escherichia coli plasmid‐encoded quinolone, oqxB and propagation of mcr‐2, and colistin resistance genes were observed and confirmed by Sanger sequencing. The microbiota of treated animals was enriched with energy harvesting bacteria, common to obese microbial communities. We propose that antibiotic treatment of healthy animals leads to unbalanced, disease‐ and obese‐related microbiota that promotes growth of E. coli carrying resistance genes on mobile elements, potentially increasing the risk of transmission of antibiotic resistant bacteria to humans., Antibiotic treatment leads to expansion of facultative anaerobic Escherichia spp. (proteobacteria) in calves, a signature of imbalanced microbiota, dysbiosis. This in turn enhances a risk of the growth of bacteria that carry highly mobile clinically relevant resistances that can be transmitted to humans.

A 38y. old woman was admitted to a Cardiology Department due to increased exertional dyspnea and decreased exercise tolerance. Echocardiography performed in an outpatient setting has found a substantial enlargement of the right ventricle and severe tricuspid regurgitation. Physical examination significantly enlarged liver, pulsation of jugular veins and numerous scars in the pits elbow. ECG sinus rhythm 85 / min. Right axis deviation. LPH. Hypertrophy of the right atrium. QS in V1-V4. Transthoracic and Transesophageal Echocardiography (TTE,TEE) EF 64%, a significant increase in a right heart chambers (RVDD 4.1 cm, severe tricuspid regurgitation with completely disappearing of tricuspid valve ( only part of septal leaflet was present, which was a consequence of pressure equalization between the right atrium and the right ventricle). In addition, it revealed the structure connected with the pulmonary valve leaflet and moving between the right ventricular outflow tract and pulmonary trunk (most probably healed vegetation, 1.2 x 0.5 cm ). Computed tomography (CT) confirmed the significant enlargement of right heart chambers (EDV 335 ml, ESV 143 ml, SV 192 ml, EF ∼ 58%) with displacement of interatrial septum to the left and the flattening of the interventricular septum . Complete destruction of the tricuspid valve leaflets, with the remaining residual part of septal leaflet was observed. The pulmonary valve was connected mobile irregular structure 2,5 cm x 0,5 cm. Laboratory tests revealed a history of cytomegalovirus infection (p / body IgG> 500,000U / ml). Other tests (HIV, hepatitis B, reaction W-R) - were negative. There was no laboratory and clinical signs of active infection at present. Patient demanded to be discharged from the hospital and refused operation. DISCUSSION Echocardiography did not confirm diagnosis of pulmonary hypertension. D-dimer values of 396 ng / ml (normal This case deserves attention because it documents severe right heart endocarditis by the person using drugs intravenously with an extremely rare takeover of both right heart valves and septic pulmonary embolism. Despite such a large morphological change in the heart of a patient remains in a relatively good clinical condition (NYHA class II/ III). The observed structure of the pulmonary trunk should be considered as healed vegetation. In the absence of consent to the surgery the patient is still treated pharmacologically. Abstract P855 Figure. Pic.1

Aim: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown. Methods: A prospective cohort study in 243 Neonatal Intensive Care Units (NICUs) from 18 European countries recorded frequency of pain assessments, use of mechanical ventilation, sedation, analgesia, or neuromuscular blockade for each neonate upto 28 days after NICU admission. Results: Only 2113/6648 (31·8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46·0%), noninvasive ventilation (NiV, 35·0%), and no ventilation (NoV, 20·1%) groups (p, Neoopiod, EUROPAIN - EUROpean-Pain-Audit-In-Neonates

Breastfeeding induces a different metabolic and endocrine response than feeding conventional infant formula, and it has also been associated with slower weight gain and reduced disease risk in later life. The underlying programming mechanisms remain to be explored. Breastfeeding has been reported to induce lower levels of insulin, insulin-like growth factor-1 and some amino acids (AAs) than formula feeding. In the Childhood Obesity Project (CHOP), infants fed a conventional protein-rich formula had a higher BMI at 2 and 6 years than those fed a protein-reduced formula. At 6 months, higher protein intakes induced increased plasma concentrations of branched-chain AAs (BCAAs) and their oxidation products, short-chain acylcarnitines. With increasing BCAA levels, these short-chain acylcarnitines increased proportionally only until a break point was reached, after which BCAAs seemed to escape their degradation. The resulting marked elevation in BCAA levels with high-protein (HP) intakes appears to contribute to increased insulin levels and to affect β-oxidation of fatty acids. The ratios of long-chain acylcarnitines to free carnitine decreased in infants who received a HP formula, which indicates a reduced initiation of β-oxidation. We conclude that HP intakes inducing high BCAA plasma levels may inhibit fat oxidation and thereby enhance body fat deposition and adiposity.

Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder in which an error in cholesterol biosynthesis results in congenital anomalies/mental deficits. The results of our previous newborn screening, based on the carrier frequency of the two most common SLOS-causing mutations in Poland (p.W151X and p.V326L), would make SLOS one of the most frequent recessive disorders in our country (with an incidence of 1:2,300 - 1:3,937). This prompted us to carry out a 3-year (2006-2008) national surveillance program in which about 2,000 physicians were asked to identify potential SLOS patients pre- and postnatally based on clinical identification forms. The incidence of SLOS in Poland was estimated to be from 1:60,941 to 1:105,395 (1: 83,168 ± 22,227) live births, and its 3-year prevalence 1:866,273 ± 16,242. The mean carrier frequency was calculated to be from 1:123 to 1:165. The notable discrepancy between our previous carrier newborn screening and these prospective data may result from reduced fertility in SLOS carriers, intrauterine death of affected fetuses, or underdiagnosis in postnatal life. Since we did not notice significant data supporting the first two aspects, our study may support the suggestion that screening for the most frequent DHCR7 alleles does not reflect the true disease rates in the Polish population. Hence, further studies in which maternal urinary steroids (7-dehydroestriol/estriol and 8-dehydropregnanetriol/pregnanetriol ratios) would serve as screening markers in early pregnancies may be justified.

Since the concept of lasting programming effects on disease risk in human adults by the action of hormones, metabolites, and neurotransmitters during sensitive periods of early development was proposed >3 decades ago, ample supporting evidence has evolved from epidemiologic and experimental studies and clinical trials. For example, numerous studies have reported programming effects of infant feeding choices on later obesity. Three meta-analyses of observational studies found that obesity risk at school age was reduced by 15-25% with early breastfeeding compared with formula feeding. We proposed that breastfeeding protects against later obesity by reducing the occurrence of high weight gain in infancy and that one causative factor is the lower protein content of human milk compared with most infant formula (the early protein hypothesis). We are testing this hypothesis in the European Childhood Obesity Project, a double-blind, randomized clinical trial that includes > 1000 infants in 5 countries (Belgium, Germany, Italy, Poland, and Spain). We randomly assigned healthy infants who were born at term to receive for the first year infant formula and follow-on formula with higher or lower protein contents, respectively. The follow-up data obtained at age 2 y indicate that feeding formula with reduced protein content normalizes early growth relative to a breastfed reference group and the new World Health Organization growth standard, which may furnish a significant long-term protection against later obesity. We conclude that infant feeding practice has a high potential for long-term health effects, and the results obtained should stimulate the review of recommendations and policies for infant formula composition. ©2009 American Society for Nutrition., SCOPUS: cp.j, info:eu-repo/semantics/published

Background: Neonates who are in pain or are stressed during care in the intensive care unit (ICU) are often given sedation or analgesia. We investigated the current use of sedation or analgesia in neonatal ICUs (NICUs) in European countries. Methods: EUROPAIN (EUROpean Pain Audit In Neonates) was a prospective cohort study of the management of sedation and analgesia in patients in NICUs. All neonates admitted to NICUs during 1 month were included in this study. Data on demographics, methods of respiration, use of continuous or intermittent sedation, analgesia, or neuromuscular blockers, pain assessments, and drug withdrawal syndromes were gathered during the first 28 days of admission to NICUs. Multivariable linear regression models and propensity scores were used to assess the association between duration of tracheal ventilation (TV) and exposure to opioids, sedatives-hypnotics, or general anaesthetics in neonates (O-SH-GA). This study is registered with ClinicalTrials.gov, number NCT01694745. Findings: From Oct 1, 2012, to June 30, 2013, 6680 neonates were enrolled in 243 NICUs in 18 European countries. Mean gestational age of these neonates was 35∙0 weeks (SD 4∙6) and birthweight was 2384 g (1007). 2142 (32%) neonates were given TV, 1496 (22%) non-invasive ventilation (NIV), and 3042 (46%) were kept on spontaneous ventilation (SV). 1746 (82%), 266 (18%), and 282 (9%) neonates in the TV, NIV, and SV groups, respectively, were given sedation or analgesia as a continuous infusion, intermittent doses, or both (p, NeoOpioid, EUROPAIN

Aim. To identify the reasons that may have contributed to the emergency readmission of older people to a medical unit, within 28 days of hospital discharge. Background. The current UK Government has initiatives in place to monitor quality and service delivery of NHS organizations. This is achieved by setting, delivering and monitoring standards, one of which is ‘emergency readmission to hospital within 28 days of discharge (all ages), as a percentage of live discharges’. Design/method. A year-long study examined reasons for unplanned readmission of patients (aged 77 and over) within 28 days of hospital discharge. The population was patients, registered with North Bradford PCT General Practitioners, readmitted to one of five care of older people wards in two local acute trust NHS hospitals. Patient records were scrutinized and data related to demography, diagnosis and readmission were collected using a structured extraction tool. Data analysis was undertaken using descriptive statistics and identification of differences and correlations within the data. Results. A pilot study indicated patients readmitted from home vs. other sources and patients discharged to home vs. other sources had a significantly shorter stay on readmission. The main study showed other significant findings. Patients who lived in care were readmitted sooner than those who lived at home: those discharged home vs. other sources and agreeing to increased social service provision had longer stays on readmission. Shorter length of stay on index admission (up to 72 hours) was associated with increased likelihood of earlier readmission. Conclusions. A framework of factors was identified and could be used to target resources to meet patients’ needs more flexibly. Relevance to clinical practice. It is possible that the process of targeting resources to ‘at-risk’ patients might enable services to be delivered in a more cost-efficient and cost-effective way.

Hypoxic ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in full-term newborns, and neurologic handicaps develop in ∼25–28% of these infants (1)(2). The postasphyxia period is crucial because brain damage may be at a subclinical stage or its symptoms may be hidden by the effects of sedation, and radiologic assessment may still be unrevealing (3)(4). Because activin A is a growth factor produced in the central nervous system (CNS) (5)(6), mainly after brain injury to modulate neuronal survival against toxicity (7)(8)(9)(10)(11)(12)(13)(14), in the present study we investigated whether its concentrations in cerebrospinal fluid (CSF) collected from asphyxiated full-term newborns were higher in those developing HIE and whether this measurement could be useful for the early detection of postasphyxia HIE. We conducted a longitudinal cohort study, recruiting any infants consecutively admitted (April 1998 through June 2002) to our Neonatal Intensive Care Units (NICUs), who underwent a lumbar puncture in the first 24-h from birth for clinical indications. We expected approximately one third of asphyxiated infants to exhibit moderate/severe HIE; we therefore planned to enroll 30 infants in the asphyxiated group (full-term infants with a gestational age >36 weeks), with at least 8 of them in the HIE subgroup, which would assure a statistical power of 90% to detect differences ≥10% between group means with a significance level of 95%. Considering that

H. pylori infection and peptic ulcerations and their complications such as bleeding are causally related, but the available methods used in bleeding to confirm active H. pylori lack accuracy. AIM To evaluate the usefulness of 13C-urea breath test (UBT) in diagnosing of H. pylori infection in bleeding patients.Eighty-one patients with upper gastrointestinal bleeding and 258 matched controls without bleeding were enrolled to the study. UBT was performed using low-dose capsulated 13C-urea and IgG antibodies to H. pylori were determined by ELISA.UBT performed in bleeding patients was positive in 77.7%. In this group anti Hp IgG was positive in 79% of cases and among them gastroscopy showed 40.7% of bleeding duodenal ulcer, 38% bleeding gastric ulcer, and 86% hemorrhagic gastritis. UBT was positive in 90.9%, 77.4%, and in 52.97% cases, respectively, and it was not statistically different from that in non-bleeding controls, duodenal and gastric ulcers and gastritis. All patients with blood or "coffee grounds" in the stomach had both UBT and serology positive.The UBT is simple and non-invasive method, which can be successively applied also in patients with upper gastrointestinal bleeding to detect active H. pylori infection prior to emergency endoscopy.

Background. Helicobacter pylori infection might, in some instances, be considered as zoonosis. Aim. The aim of this study was to assess the H. pylori prevalence in Polish shepherds and in their families as compared to controls. Patients and methods. A total of 42 shepherds from Polish Tatra Mountains with regular contact with sheep, 28 members of their families with incidental contacts and 61 age- and gender-matched farmer controls without such contacts were involved in this study. H. pylori status was determined by 13C-urea breath test. Serology was used to measure anti-H. pylori and anti-CagA IgG. Plasma gastrin, interleukin-8 and tumor necrosis factor-α were also determined. Results. The H. pylori prevalence reached 97.6% in shepherds, 86% in their family members, but significantly less, 65.1%, in controls without contact with sheep. Anti-H. pylori IgG, anti-CagA in contact groups were significantly higher than in controls. Also, plasma gastrin, interleukin-8 and tumor necrosis factor-α had significantly higher values as compared to controls. Conclusions. Shepherds showed almost 100% H. pylori prevalence and higher incidence of CagA seropositivity, plasma gastrin and pro-inflammatory cytokine levels. Considering 100% positive 13C-urea breath test in sheep, it may be reasonable to suggest that H. pylori infection in shepherds and their family members originates from sheep and H. pylori infection might, therefore, be considered as zoonosis.

Background: Nutrition in childhood has an influence on the cardiovascular function later on in life. European Childhood Obesity Project is a multicenter, randomized clinical intervention trial examining the effect of early protein intake on later health outcomes, particularly adiposity and related disorders. The aim of the study was to examine the effect of nutritional intervention - different protein intake in infancy on carotid intima-media thickness (cIMT) at 5 years. The association of cardiovascular risk factors with cIMT was also assessed. Methods: Healthy term formula-fed infants in five European countries were enrolled either to the higher (HP) or to the lower (LP) protein group. Observational group consisted of breastfed infants. Plasma insulin, glucose, lipid profile, IGF-1, apolipoprotein A1 and B were measured as well as anthropometric parameters of parents and a child, blood pressure and physical activity. Results: No difference in cIMT between HP and LP group was observed. Insulin, HOMA-IR index and total IGF-1 were positively associated with cIMT but after adjustment for confounders only an inverse association between ApoA1 and positive between ApoB/ApoA1 and cIMT were significant. Conclusion: High versus low protein intake in infancy does not influence cIMT at 5 years. cIMT in healthy children at 5 years is associated with their apolipoprotein profile.

Prognostic relevance of serum p53 antibodies was assessed in 96 patients with microscopically proven small cell lung cancer (SCLC). The study group included 67 males and 29 females; mean age 58 years; range 35‐86 years; 60 with limited disease (LD), and 36 with extensive disease (ED). The control group consisted of 41 patients with non-malignant diseases. The presence of p53 antibodies was assayed by the immunoenzymatic method (P53 ELISA kit, PharmaCell, France). Antibodies were present in 26 SCLC cases (27%); 15 (25%) in LD and 11 (31%) in ED. Antibodies were also found in one out of 41 control subjects (2%). There was no correlation between the level of antibodies and clinical characteristics of SCLC patients including age, gender and extent of disease. The median follow-up for the entire group was 30 months (range: 11‐39 months). By the time of analysis, 78 patients (82%) had deceased. Median survival in SCLC patients with and without antibodies was 42 and 39 weeks, respectively (log rank, P0.81). These results indicate the lack of clinical relevance of serum p53 antibodies in SCLC. © 2001 Elsevier Science Ireland Ltd. All rights reserved.

Background: Protein intake during infancy was associated with rapid early weight gain and later obesity in observational studies. Objective: The objective was to test the hypothesis that higher protein intake in infancy leads to more rapid length and weight gain in the first 2 y of life. Design: In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow milk‐based infant and follow-on formula with lower (1.77 and 2.2 g protein/100 kcal) or higher (2.9 and 4.4 g protein/100 kcal) protein contents for the first year. For comparison, 619 exclusively breastfed children were also followed. Weight, length, weight-for-length, and BMI were determined at inclusion and at 3, 6, 12, and 24 mo of age. The primary endpoints were length and weight at 24 mo of age, expressed as length and weight-for-length z scores based on World Health Organization growth standards 2006. Results: Six hundred thirty-six children in the lower (n ¼ 313) and higher (n ¼ 323) protein formula groups and 298 children in the breastfed group were followed until 24 mo. Length was not different between randomized groups at any time. At 24 mo, the weight-forlength z score of infants in the lower protein formula group was 0.20 (0.06, 0.34) lower than that of the higher protein group and did not differ from that of the breastfed reference group. Conclusions: A higher protein content of infant formula is associated with higher weight in the first 2 y of life but has no effect on length. Lower protein intake in infancy might diminish the later risk of overweight and obesity. This trial was registered at clinicaltrials.gov as NCT00338689. Am J Clin Nutr 2009;89:1‐10.

Objective Family unit is generally accepted as one of the contributors to Helicobacter pylori infection that is most frequently acquired in childhood, so it seems logical to diagnose and treat this infection in childhood. This study was designed to assess H. pylori prevalence in children from shepherd families having contacts with sheep. Material and methods This study involved 146 children (58 M/88 F, age 6–17 years; mean: 10.2 years) from families living in Polish Tatra Mountains with contact (group A, n = 58) or without contact with sheep (group B, n = 88). H. pylori status was determined by 13 C-urea breath test and was compared to 141 age- and gender-matched urban controls (group C). In both groups of mountain children, the anti- H. pylori and anti-CagA IgG were measured by ELISA and serum gastrin, ghrelin and leptin concentrations by RIA. Results The H. pylori prevalence in group A was significantly higher (58.6%) than that in group B (21.6%) and urban controls (26%). Serum gastrin concentrations were significantly higher in H. pylori -positive than in H. pylori -negative mountain children (52.2 ± 5.8 pmol/L versus 22.7 ± 2.1 pmol/L), while serum ghrelin and leptin concentrations were significantly lower in H. pylori -infected (741 ± 112 pg/mL and 3.6 ± 0.8 ng/mL) than in non-infected children (1323 ± 104 pg/mL and 8.6 ± 2.4 ng/mL). Conclusions Children with sheep contact show about twice higher H. pylori prevalence and higher serum gastrin but lower ghrelin and leptin levels than those without H. pylori infection. Considering almost 100% positive 13 C-urea breath test in sheep, it is reasonable to propose that H. pylori infection in shepherd children may originate from sheep and the infection might, therefore, be considered as zoonosis.

Perinatal infections such as bacterial meningitis (BM) are one of the major factors associated with perinatal brain damage (1)(2)(3)(4). Despite accurate monitoring, the early stages of meningitis are crucial because brain damage may occur at a subclinical stage when ultrasound assessment is still silent (5)(6). Laboratory assessment is based on chemical analysis of cerebrospinal fluid (CSF) and the detection of bacteria, and the possibility of detecting cases at risk of brain damage is to date limited. The measurement of brain constituents able to diagnose subclinical lesions at this stage could therefore be useful. S100B is a calcium-binding protein primarily present in nervous tissue (7)(8)(9). Increased S100B in biological fluids has been shown to be a marker of brain damage both in adults and during the antenatal and postnatal periods (10)(11)(12)(13)(14)(15)(16). The present case–control study is aimed at investigating whether the measurement of S100B in CSF could also be useful in infants with BM for the early detection of cases at risk of encephalitis. Samples of CSF were collected from infants consecutively admitted between April 1998 and June 2000 to our tertiary referral center for intensive care for infectious diseases. For the present study we identified from our database 44 patients with BM and matched them for gestational age at sampling with 44 patients without BM (1 BM case vs 1 control). We retrieved clinical, laboratory, and routine CSF test data and CSF S100B concentrations. Eligibility criteria for infants with BM were as follows: clinical (respiratory distress, lethargy, presence/absence of minor/major neurologic symptoms, feeding and abdominal distension problems, temperature instability or increases, unexplained recurrent hypoglycemia, poor vascular perfusion) and laboratory signs of septicemia with altered CSF …

A feature that distinguishes chronic idiopathic myelofibrosis (CIM) from other chronic myeloproliferative disorders is the progression to bone marrow fibrosis and osteosclerosis. Because osteoclast formation can be inhibited by osteoprotegerin (OPG), we investigated its megakaryocytes’ expression and serum concentration in patients (pts) with CIM (n=20, median age 64 years, range 46–81) and in 20 controls showing no evidence of neoplastic disease (median age 62 years, range 46–82). The study group comprised 10 pts with prefibrotic cellular CIM and 10 with severe fibrosis. Assessment of OPG concentration in serum was performed using Osteoprotegerin ELISA Kit (Biomedica, Austria). EnVision (DAKO) kit with monoclonal anti-human osteoprotegerin/TNFRSF11B antibody - MAB8051 (R&D Systems, USA) was used to evaluate OPG expression in megakaryocytes. Gomori silver staining technique was applied for semi-quantitative assessment of bone marrow fibrosis according to increased amount of reticulin fibers. OPG serum levels in pts with CIM were significantly higher than in controls (105.78 vs 85.14 pg/ml, p=0.02), and showed positive correlation with age in both groups (r=0.61, p=0.0037 and r=0.55, p=0.012, respectively). Serum levels of OPG in pts with CIM patients were not associated with erythrocyte, leukocyte, platelet numbers and with the Visani, Lille or Cervantes prognostic scores. There was no correlation between serum levels of OPG and its expression in megakaryocytes in pts and controls. In megakaryocytes derived from patients with CIM as well as from controls, OPG expression was detected, but in those derived from CIM hematopoiesis (at any stage of the disease) were significantly higher. OPG expression in megakaryocytes derived from prefibrotic CIM was significantly lower than from advanced stages of the disease (p=0.007). We conclude that OPG appears to be involved in bone marrow fibrosis in CIM through overexpression by megakariocyte.