The importance of study duration and spatial scale in pathogen detection - evidence from a tick-infested island

Ticks (Acari: Ixodoidea) are among the most common vectors of zoonotic pathogens worldwide. While research on tick-borne pathogens is abundant, few studies have thoroughly investigated small-scale spatial differences in their occurrence. Here, we used long-term cloth-dragging data of Ixodes ricinus and its associated, known and putative pathogens (Borrelia burgdorferi s.l., Borrelia miyamotoi, Anaplasma phagocytophilum, Rickettsia spp., Candidatus Neoehrlichia mikurensis, Bartonella spp., Babesia spp., and tick-borne encephalitis virus, TBEV) from a small, well-studied island in southwestern Finland to analyze potential temporal and spatial differences in pathogen prevalence and diversity between and within different biotopes. We found robust evidence indicating significant dissimilarities in B. burgdorferi s.l., A. phagocytophilum, Rickettsia, and Ca. N. mikurensis prevalence, even between proximal study areas on the island. Moreover, during the 6 years of the ongoing study, we witnessed the possible emergence of TBEV and Ca. N. mikurensis on the island. Finally, the stable occurrence of a protozoan pathogen that has not been previously reported in Finland, Babesia venatorum, was observed on the island. Our study underlines the importance of detailed, long-term tick surveys for public health. We propose that by more precisely identifying different environmental factors associated with the emergence and upkeep of enzootic pathogen populations through rigorous longitudinal surveys, we may be able to create more accurate models for both current and future pathogen distributions

Tick-borne bacterial pathogens in southwestern Finland

Background: Ixodes ricinus and Ixodes persulcatus are the main vectors of Lyme borreliosis spirochetes and several other zoonotic bacteria in northern Europe and Russia. However, few studies screening bacterial pathogens in Finnish ticks have been conducted. Therefore, reports on the occurrence and prevalence of several bacterial pathogens detected from ticks elsewhere in Europe and Russia are altogether missing from Finland. The main aim of the current study was to produce novel data on the occurrence and prevalence of several tick-borne bacterial pathogens in ticks collected from southwestern Finland. Methods: Ticks were collected in 2013–2014 by blanket dragging from 25 localities around southwestern Finland, and additionally from a dog in Lempäälä. Collected ticks were molecularly identified and screened for Borrelia burgdorferi s.l., Borrelia miyamotoi, Rickettsia, Bartonella and Candidatus Neoehrlichia mikurensis using quantitative PCR. Furthermore, detected Rickettsia spp. were sequenced using conventional PCR to determine species. Results: A total of 3169 ticks in 1174 DNA samples were screened for the listed pathogens. The most common bacteria detected was B. burgdorferi (s.l.) (18.5 % nymphal and 23.5 % adult ticks), followed by Rickettsia spp. (1.1 %; 5.1 %) and B. miyamotoi (0.51 %; 1.02 %). B. miyamotoi and Rickettsia spp. were also detected in larval samples (minimum infection rates 0.31 % and 0.21 %, respectively). Detected Rickettsia spp. were identified by sequencing as R.helvetica and R.monacensis. All screened samples were negative for Bartonella spp. and Ca. N. mikurensis. Conclusions: In the current study we report for the first time the presence of Rickettsia in Finnish ticks. Furthermore, Rickettsia spp. and B. miyamotoi were found from larval tick samples, emphasizing the importance they may have as vectors of these pathogens. Comparisons of tick density estimates and B. burgdorferi (s.l.) prevalence made between the current study and a previous study conducted in 2000 in ten out of the 25 study localities suggest that an increase in tick abundance and B. burgdorferi (s.l.) prevalence has occurred in at least some of the study localities. Keywords: Ixodes ricinus, Ixodes persulcatus, Tick-borne diseases, Borrelia burgdorferi, Borrelia miyamotoi, Rickettsia, Bartonella, Candidatus Neoehrlichia mikurensis, Finland</p

Divergent expression of claudin -1, -3, -4, -5 and -7 in developing human lung

<p>Abstract</p> <p>Background</p> <p>Claudins are the main components of tight junctions, structures which are associated with cell polarity and permeability. The aim of this study was to analyze the expression of claudins 1, 3, 4, 5, and 7 in developing human lung tissues from 12 to 40 weeks of gestation.</p> <p>Methods</p> <p>47 cases were analyzed by immunohistochemisty for claudins 1, 3, 4, 5 and 7. 23 cases were also investigated by quantitative RT-PCR for claudin-1, -3 and -4.</p> <p>Results</p> <p>Claudin-1 was expressed in epithelium of bronchi and large bronchioles from week 12 onwards but it was not detected in epithelium of developing alveoli. Claudin-3, -4 and -7 were strongly expressed in bronchial epithelium from week 12 to week 40, and they were also expressed in alveoli from week 16 to week 40. Claudin-5 was expressed strongly during all periods in endothelial cells. It was expressed also in epithelium of bronchi from week 12 to week 40, and in alveoli during the canalicular period. RT-PCR analyses revealed detectable amounts of RNAs for claudins 1, 3 and 4 in all cases studied.</p> <p>Conclusion</p> <p>Claudin-1, -3, -4, -5, and -7 are expressed in developing human lung from week 12 to week 40 with distinct locations and in divergent quantities. The expression of claudin-1 was restricted to the bronchial epithelium, whereas claudin-3, -4 and -7 were positive also in alveolar epithelium as well as in the bronchial epithelium. All claudins studied are linked to the development of airways, whereas claudin-3, -4, -5 and -7, but not claudin-1, are involved in the development of acinus and the differentiation of alveolar epithelial cells.</p

Effects of childhood and adolescence physical activity patterns on psychosis risk—a general population cohort study

Schizophrenia spectrum disorders are associated with high morbidity and mortality in somatic diseases. The risk factors of this excess mortality include, e.g., obesity, dietary factors, and physical inactivity, especially after the onset of psychosis, but there are limited early developmental data on these factors in individuals who later develop psychosis. A population-based cohort study “Cardiovascular Risk of Young Finns” started in 1980 with 3596 children and adolescents from six different age groups (3, 6, 9, 12, 15, and 18 years). Cardiovascular health parameters, including questionnaire of physical activity before first hospitalization (≤18 years), were studied in 1980, 1983, and 1986. All psychiatric diagnoses of the participants were derived from the Finnish Hospital Discharge Register up to the year 2012. We identified diagnostic groups of non-affective psychosis (n = 68, including a schizophrenia subgroup, n = 41), personality disorders (n = 43), affective disorders (n = 111), and substance-related disorders (n = 49), based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Groups were compared with controls with no psychiatric diagnoses (n = 3325). Sex, age, body mass index, birth weight, non-preterm birth, and mother’s mental disorders were included in the statistical model. Low physical activity in childhood and adolescence (9–18 years) independently predicted later development of non-affective psychosis. Lower physical activity index (relative risk 1.26 [1.1–1.5]), lower level of common activity during leisure time (relative risk 1.71 [1.2–2.5]), and non-participation in sports competitions (relative risk 2.58 [1.3–5.3]) were associated with a higher risk for later non-affective psychosis (expressed as increase in relative risk per physical activity unit). The findings were even stronger for schizophrenia, but no such link was observed for other diagnoses. The cause of low physical activity in premorbid/prodromal phase is likely to be multifactorial, including deviant motor and cognitive development. The results provide a rationale for including exercise and physical activity interventions as a part of psychosis prevention programs.</p

Crowdsourcing-based nationwide tick collection reveals the distribution of Ixodes ricinus and I. persulcatus and associated pathogens in Finland

A national crowdsourcing-based tick collection campaign was organized in 2015 with the objective of producing novel data on tick distribution and tick-borne pathogens in Finland. Nearly 20 000 Ixodes ticks were collected. The collected material revealed the nationwide distribution of I. persulcatus for the first time and a shift northwards in the distribution of I. ricinus in Finland. A subset of 2038 tick samples containing both species was screened for Borrelia burgdorferi sensu lato (the prevalence was 14.2% for I. ricinus and 19.8% for I. persulcatus), B. miyamotoi (0.2% and 0.4%, respectively) and tick-borne encephalitis virus (TBEV; 0.2% and 3.0%, respectively). We also report new risk areas for TBEV in Finland and, for the first time, the presence of B. miyamotoi in ticks from mainland Finland. Most importantly, our study demonstrates the overwhelming power of citizen science in accomplishing a collection effort that would have been impossible with the scientific community alone

Collagen XIII secures pre- and postsynaptic integrity of the neuromuscular synapse

© The Author 2017. Published by Oxford University Press. All rights reserved. Both transmembrane and extracellular cues, one of which is collagen XIII, regulate the formation and function of the neuromuscular synapse, and their absence results in myasthenia. We show that the phenotypical changes in collagen XIII knock-out mice are milder than symptoms in human patients, but the Col13a1 -/- mice recapitulate major muscle findings of congenital myasthenic syndrome type 19 and serve as a disease model. In the lack of collagen XIII neuromuscular synapses do not reach full size, alignment, complexity and function resulting in reduced muscle strength. Collagen XIII is particularly important for the preterminal integrity, and when absent, destabilization of the motor nerves results in muscle regeneration and in atrophy especially in the case of slow muscle fibers. Collagen XIII was found to affect synaptic integrity through binding the ColQ tail of acetylcholine esterase. Although collagen XIII is a muscle-bound transmembrane molecule, it also undergoes ectodomain shedding to become a synaptic basal lamina component. We investigated the two forms' roles by novel Col13a1 tm/tm mice in which ectodomain shedding is impaired. While postsynaptic maturation, terminal branching and neurotransmission was exaggerated in the Col13a1 tm/tm mice, the transmembrane form's presence sufficed to prevent defects in transsynaptic adhesion, Schwann cell invagination/retraction, vesicle accumulation and acetylcholine receptor clustering and acetylcholinesterase dispersion seen in the Col13a1 -/- mice, pointing to the transmembrane form as the major conductor of collagen XIII effects. Altogether, collagen XIII secures postsynaptic, synaptic and presynaptic integrity, and it is required for gaining and maintaining normal size, complexity and functional capacity of the neuromuscular synapse

Social- and Health Care Educators’ Cultural Competence

Introduction and aim: Cultural differences have significant impacts on classroom behaviours and communication in teaching. The aim of this study is to explore social and healthcare educators’ cultural competence in transcultural education. Methodology: Data was collected from semi-structured focus group interviews at universities of applied sciences and vocational colleges. Inductive content analysis was used in the analysis process. Results: Educators’ cultural competence in transcultural education emerges as generic categories: transcultural education, educatorship and ethical attitudes, and underpins by the sub-categories: language and linguistics, different learning styles, integrating multicultural students, cultural knowledge and sensitivity, collaborating and cooperating, self-awareness and openness, and respecting and caring. Conclusion: Cultural competence represents a core competence for social-and health care educators. Educators need to know students’ background, master different learning styles, be flexible in their pedagogical approaches and have an open and ethical attitude.  </p

Activation Status of Wnt/ß-Catenin Signaling in Normal and Neoplastic Breast Tissues: Relationship to HER2/neu Expression in Human and Mouse

Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS), and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001), consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04) and estrogen receptor-negative status (P = 0.03), both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%), similar to that in carcinomas (35%). Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%), suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02). Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary glands from bigenic MMTV/neu, Axin2NLSlacZ mice, highlighted by robust ß-catenin/TCF signaling, likely represent the earliest stage of mammary intraepithelial neoplasia in MMTV/neu mice. Our study thus provides provocative evidence for Wnt/ß-catenin signaling as an early, HER2/neu-inducible event in breast neoplasia