A European perspective on nosocomial urinary tract infections I. Report on the microbiology workload, etiology and antimicrobial susceptibility (ESGNI−003 study)

Objectives   To obtain information on the microbiology workload, etiology and antimicrobial susceptibility of urinary tract infection (UTI) pathogens isolated in European hospitals.
Materials and methods   We collected data available in the microbiology units of a large sample of European hospitals regarding the laboratory workload, diagnostic criteria, and etiology and antimicrobial resistance of the urinary isolates collected on one day (the study day).
Results   Data were received from a total of 228 hospitals from 29 European countries. The average rate of urine samples cultured per 1000 admissions in 1999 was 324. The criteria to consider a positive urine culture as significant were quite variable; ≥10⁴ colony-forming units (CFU)/mL for bacteria or ≥10³ CFU/mL in the case of yeasts were the most used cut-off points. On the study day, a total of 607 micro-organisms from 522 patients with nosocomial UTI were isolated. The six most commonly isolated micro-organisms were, in decreasing order: Escherichia coli (35.6%), Enterococci (15.8%), Candida (9.4%), Klebsiella (8.3%), Proteus (7.9%) and Pseudomonas aeruginosa (6.9%). Pseudomonas was isolated more frequently in non-EU countries. The study data reveal high rates of antimicrobial resistance in UTI pathogens, especially in non-EU countries, where Pseudomonas aeruginosa presented rates of aminoglycoside resistance as high as 72% to gentamicin, 69.2% to tobramycin and 40% to amikacin.
Conclusions   Nosocomial UTI accounts for an important proportion of the workload in microbiology laboratories. A consensus on the practice and interpretation of urine cultures in Europe is needed. The levels and patterns of resistance of UTI pathogens must be a serious cause for concern and a clear reason for stricter guidelines and regulations in antimicrobial policy.     

Clinical-epidemiological characteristics and outcome of patients with catheter-related bloodstream infections in Europe (ESGNI-006 Study)

This study analysed 89 episodes of catheter-related bloodstream infection (CR-BSI) occurring during one week in 107 hospitals from 21 European countries (1.02 episodes/1,000 admissions). Patients from European Union (EU) countries had a higher incidence of CR-BSI than patients from non-EU countries (1.55 vs. 0.33/1,000 admissions). Most (67%) catheters were non-tunneled central venous catheters, were in the jugular vein (44%), had been implanted for > 7 days (70%), were made of polyurethane (61%) and were multi-lumen (67%). In 36% of cases, catheters were implanted by physicians other than anaesthetists or surgeons, and 50% were inserted by junior staff.     

OxyR contributes to the virulence of a Clonal Group A Escherichia coli strain (O17:K+:H18) in animal models of urinary tract infection,subcutaneous infection,and systemic sepsis

The oxidative stress response regulator OxyR was assessed as both a urinary and extra-urinary virulence factor in Escherichia coli strain UCB34 (O17:K+:H18), a representative of the emergent Clonal Group A (CGA). Compared to UCB34, the isogenic oxyR mutant exhibited increased H₂O₂ sensitivity, indistinguishable in vitro growth, and attenuated virulence in rodent models of urinary tract, subcutaneous infection, and systemic sepsis. Complemented mutants showed virulence levels comparable to parent strains in all models. These findings uniquely fulfill molecular Koch's postulates for a putative virulence factor of CGA, provide experimental evidence of an extra-urinary virulence promoting trait in CGA, and document a role for OxyR in local and systemic extra-urinary E. coli infections.     

Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland)

BACKGROUND: Environmental, cultural and health care differences may account for variation among countries in the prevalence of asthma and respiratory symptoms in teenagers. OBJECTIVE: To examine the prevalence of respiratory symptoms and the level of diagnosis, and to compare determinants of asthma and severe wheeze in two countries. METHODS: Self-completion questionnaires based on the International Study of Asthma and Allergies in Childhood (ISAAC) protocol were provided to school children in Ireland (Republic and Northern Ireland). In the Republic of Ireland, all children in classes largely aged 13-14 years from 30 post-primary schools were selected by random sampling stratified by school size, composition and Health Board in Spring 1995. In Northern Ireland, all children largely aged 13-14 years of age from 26 post-primary schools were selected by random sampling stratified by school type, composition and Education and Library Board in Spring 1996. RESULTS: Questionnaires were completed by 2,364 children from Northern Ireland and 2,671 from the Republic, about 90% of those eligible to participate. The prevalences of wheeze at various levels of severity, of diagnosed asthma and of treated wheeze were very similar in Northern Ireland and the Republic of Ireland. A significant proportion of those reporting more severe symptomatology (four or more attacks of wheeze in the past 12 months and/or one or more nights disturbed and/or moderate or greater disruption of daily activities and/or speech restriction due to wheeze) had been neither diagnosed nor treated for asthma (20-37%). To investigate the determinants of the more severe symptomatology of asthma or treated wheeze a series of stepwise multiple regression analyses was performed. A history of atopy, cigarette smoking, the possession of a furry pet other than a dog or cat and age were each independently associated with severe wheeze, whilst atopy, a furry pet (as above) and gender were each independently associated with asthma or treated wheeze. CONCLUSIONS: Cigarette smoking is closely associated with the reporting of significant respiratory symptoms together with atopy and exposure to furry pets. Some 20-37% of severe symptoms were neither diagnosed nor treated as asthma.     

European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015)

The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA), and the Respiratory Effectiveness Group (REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision‐making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost‐effective treatment strategies.     

Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA2LEN

Aims:  To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis.
Methods:  The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation.
Results:  The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete.
Conclusions:  The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.     

The influence of gender on clinical and social characteristics of patients at psychosis onset: A report from the Psychosis Incident Cohort Outcome Study (PICOS)

BACKGROUND. This paper examined the hypothesis that males with first-episode psychosis (FEP) experience lower pre-morbid adjustment, greater social disability and more self-perceived needs at illness onset than females(by controlling for duration of untreated psychosis, diagnosis, age and symptoms at onset). Results disconfirming this hypothesis were thought to suggest the potentially mediating role of social context in determining the impact of symptoms and disability on the everyday lives of male patients in the early phase of psychosis. METHOD. A large epidemiologically representative cohort of FEP patients (n=517) was assessed within the Psychosis Incident Cohort Outcome Study (PICOS) framework – a multi-site research project examining incident cases of psychosis in Italy's Veneto region. RESULTS. Despite poorer pre-morbid functioning and higher social disability at illness onset, males reported fewer unmet needs in the functioning domain than females did. An analysis of help provided by informal care givers showed that males received more help from their families than females did. This finding led us to disconfirm the second part of the hypothesis and suggest that the impact of poorer social performance and unmet needs on everyday life observed in male patients might be hampered by higher tolerance and more support within the family context.CONCLUSIONS. These findings shed new light on rarely investigated sociocultural and contextual factors that may account for the observed discrepancy between social disability and needs for care in FEP patients. They also point to a need for further research on gender differences, with the ultimate aim of delivering gender-sensitive effective mental health care.     

The Role of Endogenous Histamine on the Pathogenesis of the Lipopolysaccharide (LPS)-Induced, Acute Lung Injury: A Pilot Study

Abstract —Histamine is widely distributed in the lungs and increases capillary permeability and P-selectin expression. To observe the role of histamine in acute lung injury (ALI), we measured the histamine and protein concentrations and cell numbers in the bronchoalveolar lavage (BAL) of LPS-induced ALI in rats. We instilled LPS (3 mg/kg) intratracheally, in conjunction with the intravenous histamine receptor antagonists (mepyramine, a H1-receptor antagonist, or ranitidine, a H2-receptor antagonist). LPS increased protein concentration and neutrophil numbers in the BAL as well as myeloperoxidase (MPO) activity in lungs after 6 h. LPS also increased histamine concentration in BAL after 2 h. Mepyramine and ranitidine attenuated the increased histamine concentrations. Total cell number in the BAL and MPO activity in the lungs were significantly decreased and neutrophil numbers and protein concentration in the BAL seemed to decrease with the administration of ranitidine at 6 h. In conclusion, endogenous histamine might be involved in the recruitment of neutrophils and protein leaks in LPS-induced ALI via the H2 receptors.     

Self- or parent report of (co-occurring) internalizing and externalizing problems,and basal or reactivity measures of HPA-axis functioning: A systematic evaluation of the internalizing-hyperresponsivity versus externalizing-hyporesponsivity HPA-axis hypothesis

Background

Previous research findings on the link between adolescents’ psychopathology and hypothalamic–pituitary–adrenal (HPA) axis activity have been heterogeneous.

Method

Adolescents (n = 211) with a preadolescent DSM-IV diagnosis participated in a lab-based social stress task. Saliva cortisol was assessed at awakening and during social stress. It was investigated if continuous measures of internalizing and externalizing problems and their interaction, using both self- and parent report, were associated with basal or reactivity measures of HPA-axis functioning

Results

During social stress, an enhanced total release of cortisol was associated with self-reported internalizing problems and a blunted total release of cortisol with self-reported externalizing problems. Post hoc analyses revealed that the association between enhanced cortisol output and internalizing problems held for boys but not for girls. Associations with morning cortisol measures were overall weak

Conclusions

Only in the context of stress, and particularly when based on self-report, blunted cortisol output was associated with externalizing and enhanced cortisol output with internalizing problems. Our broad approach demonstrates the importance of who reports on psychopathology, the use of dimensional measures of psychopathology, simultaneous analysis of internalizing and externalizing problems, and the use of awakening and social stress related measures of cortisol.     

Effects of Propyithiouracil (PTU) Administration on the Synthesis and Secretion of Thyroglobulin in the Rat Thyroid Gland: A Quantitative Immuno-electron Microscopic Study Using Immunogold Technique

To clarify the effects of an antithyroid drug on the kinetics of thyroglobulin synthesis, secretion, and reabsorption in the thyroid follicles, propylthiouracil (PTU) was administered to rats and the thyroid glands were examined by a refined post-embedding immunogold technique during and after withdrawal of PTU. Seven-wk-old male Wistar rats were administered with 5 mg of PTU/d through a gastric tube, and sacrificed at 1 and 2 wk of administration and at 1, 2, and 3 d, and 1, 2, 3, and 4 wk, after discontinuation. The administration of PTU caused a remarkable dilatation of the rER and Golgi apparatus, but these areas gradually recovered after withdrawal of PTU. During the experiment, no significant change in the density of thyroglobulin (Tg) was observed except for a transient increase immediately after withdrawal of PTU. The expression of Tg on subapical vesicles (SV) and follicular colloid took a relatively parallel course; increasing during administration of PTU and decreasing with a transient peak immediately after treatment was discontinued. In contrast to the remarkable changes in the morphology of compartments involved in Tg synthesis, the development of colloid droplets and formation of secondary lysosomes were suppressed during and after discontinuing administration of PTU. However, the basic pattern of the gradient of Tg density among the cellular compartments was essentially retained in the experimental group. Thus the present immunoelectron-microscopic study provided evidence that administration of PTU stimulates the synthesis and secretion of Tg in the follicular epithelium in vivo, and, also, suppresses reabsorption and degradation of Tg. Further, it was speculated that the density gradient of Tg among the compartments involved in Tg synthesis, secretion and storage is regulated by an unknown constitutive mechanism and not by the thyroid-stimulating hormone (TSH)-TSH receptor-mediated system.     

The stimulatory role of human cytochrome b5 in the bioactivation activities of human CYP1A2, 2A6 and 2E1: a new cell expression system to study cytochrome P450-mediated biotransformation (a corrigendum report on Duarte et al. (2005) Mutagenesis 20, 93-100)

This corrigendum report describes the study of the comparison of human cytochrome b(5) (b(5)) with rat b(5) when coupled with human cytochrome P450 CYP1A2, 2A6 or 2E1. Results indicate a role of the N-terminal part of b(5) in the coupling with CYP. Indeed, the plasmid pLCM-b(5)-RED used in our former study on b(5) [Duarte et al. (2005) Mutagenesis, 20(2), 193-100] erroneously contained rat b(5). Plasmid pLCM-b(5)-RED was corrected with human b(5) and subsequently all experimental work was repeated as was described for the rat b(5) plasmid. Although absolute values of contents and activities were lower, all key-findings as found for rat b(5) could be confirmed using human b(5). The physiological relevant co-expression of the members of the cytochrome P450 complex, CYP, NADPH-cytochrome P450 oxidoreductase (RED) and human b(5) could be demonstrated in the different BTC strains, as was found before. The stimulatory effect of human b(5) on the activity of CYP1A2, CYP2A6 and CYP2E1 was in general similar, when compared with rat b(5), though less quantitatively pronounced. This was both the case when using membrane preparations as well as by the bioactivation of procarcinogens using the bacterial mutagenicity assay. Human b(5) stimulated the bioactivation of all compounds as described for rat b(5), except for CYP1A2 mediated bioactivation of 2-aminoanthracene (2AA), which was not stimulated by human b(5). All other main findings of the effect of rat b(5) were confirmed with human b(5), i.e. for CYP2A6: N-nitrosodiethylamine (NNdEA): approximately 14-fold increase ( approximately 23-fold with rat b(5)) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK): approximately 3-fold ( approximately 9-fold with rat b(5)); for CYP2E1: NNdEA: approximately 1.5-fold increase ( approximately 3-fold with rat b(5)); NNK: no mutagenicity with or without human b(5). Both CYP2A6 and CYP2E1 demonstrated total dependence on the presence of human b(5) for N-nitrosodi-n-propylamine (NNdPA) mutagenicity, as was shown before with rat b(5).     

Correlation Between the Allelic Distribution of STRs in a Finnish Population and Phenotypically Different Gastrointestinal Tumours: A Study Using Four X-Chromosomal Markers (DXS7423, DXS8377, ARA, DXS101)

Microsatellite instability in tumours has been suggested as a model to study the process of short tandem repeat (STR) mutations. In the present study we have determined the allelic variation of four X‐STRs (DXS7423, DXS8377, DXS101 and ARA) in a Finnish population of 103 individuals, and assessed whether a comparable allelic distribution could be found in a series of gastrointestinal cancers differing by the level of microsatellite instability. Fifty‐seven gastric and colorectal cancers were stratified by autosomal STRs, and the mononucleotide marker BAT‐26 into stable, low‐level unstable and high‐level unstable microsatellite (MSI‐H) cancers, of which the last produced the majority of X‐STR alleles. For the four markers analysed, a significant correlation of allele distribution between our Finnish population sample and MSI‐H tumours was noted. Together, the eight MSI‐H tumours found represented 80%, 66–80% and 100% of the DXS101 alleles in the Finnish, and in previously described Caucasian and Korean population samples, respectively. Of the ARA, DXS7423 and DXS8377 alleles in the Finnish population, 42%, 75% and 79% were found in the MSI‐H cancers, respectively. The results suggest that analysis of STR variation in a relatively small number of MSI‐H cancers may aid in pre‐evaluation of their allelic distribution in a population.     

A research agenda for ageing in China in the 21st century (2nd edition): Focusing on basic and translational research,long-term care,policy and social networks

One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the ‘one child policy’ and the ‘empty-nest elderly’ phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of ‘exercising more, eating less’, while other anti-ageing molecules from molecular gerontologists could help to improve ‘healthspan’ in the elderly. Machine learning, ‘Big Data’, and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).