Human Babesia odocoilei and Bartonella spp. co-infections in the Americas.

BACKGROUND: In recent years, Babesia and Bartonella species co-infections in patients with chronic, nonspecific illnesses have continued to challenge and change the collective medical understanding of "individual pathogen" vector-borne infectious disease dynamics, pathogenesis and epidemiology. The objective of this case series is to provide additional molecular documentation of Babesia odocoilei infection in humans in the Americas and to emphasize the potential for co-infection with a Bartonella species. METHODS: The development of improved and more sensitive molecular diagnostic techniques, as confirmatory methods to assess active infection, has provided increasing clarity to the healthcare community. RESULTS: Using a combination of different molecular diagnostic approaches, infection with Babesia odocoilei was confirmed in seven people suffering chronic non-specific symptoms, of whom six were co-infected with one or more Bartonella species. CONCLUSIONS: We conclude that infection with Babesia odocoilei is more frequent than previously documented and can occur in association with co-infection with Bartonella spp.

A case of mistaken identity: a systematic review, meta-analysis, and reinvestigation of hemotropic Mycoplasma spp. infection in Ctenocephalides felis (cat flea).

BACKGROUND: Feline-associated hemotropic Mycoplasma (hemoplasmas) are believed to be transmitted by two primary mechanisms: (1) direct transmission via fighting and (2) vector-borne transmission by the cat flea (Ctenocephalides felis). While the efficiency of transmission by C. felis appears low, most manuscripts focus on the prevalence of hemoplasmas in wild-caught fleas and report either a very low (< 3%) or a high (> 26%) prevalence. Therefore, we aimed to assess the influence of sample processing and PCR methods on C. felis hemoplasma infection prevalence. METHODS: A systemic review of PubMed articles identified 13 manuscripts (1,531 fleas/flea pools) that met the inclusion criteria (performed PCR for >1 hemoplasma on C. felis collected from cats). Risk of bias was assessed utilizing the ROBINS-E tool. Meta-analysis performed in R of these manuscripts found that not washing samples and a common set of 16S rRNA primers first published in Jensen et al. 2001 were associated with increased hemoplasma prevalence. To evaluate the influence of washing on newly collected fleas, we assessed the hemoplasma status of 20 pools of 5 C. felis each, half of which were washed and half not washed. RESULTS: Flea washing did not influence the detection of hemoplasma but instead amplified Spiroplasma. To assess non-specific amplification with the Jensen et al. 2001 primers, 67 C. felis samples (34% previously reported hemoplasma infected) were subject to PCR and sequencing. By this method, hemoplasma was detected in only 3% of samples. In the remaining "hemoplasma infected" fleas, PCR amplified Spiroplasma or other bacteria. CONCLUSIONS: Therefore, we concluded that hemoplasma infection in C. felis is rare, and future flea prevalence studies should sequence all positive amplicons to validate PCR specificity. Further investigation of alternative methods of feline-associated hemoplasma transmission and the ability of C. felis to maintain hemoplasma infection is necessary.

Vector biology of the cat flea Ctenocephalides felis.

Ctenocephalides felis, the cat flea, is among the most prevalent and widely dispersed vectors worldwide. Unfortunately, research on C. felis and associated pathogens (Bartonella and Rickettsia spp.) lags behind that of other vectors and vector-borne pathogens. Therefore, we aimed to review fundamental aspects of C. felis as a vector (behavior, epidemiology, phylogenetics, immunology, and microbiome composition) with an emphasis on key techniques and research avenues employed in other vector species. Future laboratory C. felis experimental infections with Bartonella, Rickettsia, and Wolbachia species/strains should examine the vector-pathogen interface utilizing contemporary visualization, transcriptomic, and gene-editing techniques. Further environmental sampling will inform the range and prevalence of C. felis and associated pathogens, improving the accuracy of vector and pathogen modeling to improve infection/infestation risk assessment and diagnostic recommendations.

Wordform variability in infants' language environment and its effects on early word learning.

Most research regarding early word learning in English tends to make the simplifying assumption that there exists a one-to-one mapping between concrete objects and their labels. In the current work, we provide evidence that runs counter to this assumption, aligning English with more morphologically-rich languages. We suggest that even in a morphologically-poor language like English, real world language input to infants does not provide tidy 1-to-1 mappings. Instead, infants encounter many variant wordforms for familiar nouns (e.g. dog∼doggy∼dogs). We explore this wordform variability in 44 English-learning infants' naturalistic environments using a longitudinal corpus of infant-available speech. We look at both the frequency and composition of wordform variability. We find two broad categories of variability: referent-changing alterations, where words were pluralized or compounded (e.g. coat∼raincoats); and wordplay, where words changed form without a notable change in referent (e.g. bird∼birdie). We further find that wordplay occurs with a limited number of lemmas that are usually early-learned, high-frequency, and shorter. When looking at all wordform variability, we find that individual words with higher levels of wordform variability are learned earlier than words with fewer wordforms, over and above the effect of frequency.

Functional analysis reveals driver cooperativity and novel mechanisms in endometrial carcinogenesis.

High-risk endometrial cancer has poor prognosis and is increasing in incidence. However, understanding of the molecular mechanisms which drive this disease is limited. We used genetically engineered mouse models (GEMM) to determine the functional consequences of missense and loss of function mutations in Fbxw7, Pten and Tp53, which collectively occur in nearly 90% of high-risk endometrial cancers. We show that Trp53 deletion and missense mutation cause different phenotypes, with the latter a substantially stronger driver of endometrial carcinogenesis. We also show that Fbxw7 missense mutation does not cause endometrial neoplasia on its own, but potently accelerates carcinogenesis caused by Pten loss or Trp53 missense mutation. By transcriptomic analysis, we identify LEF1 signalling as upregulated in Fbxw7/FBXW7-mutant mouse and human endometrial cancers, and in human isogenic cell lines carrying FBXW7 mutation, and validate LEF1 and the additional Wnt pathway effector TCF7L2 as novel FBXW7 substrates. Our study provides new insights into the biology of high-risk endometrial cancer and suggests that targeting LEF1 may be worthy of investigation in this treatment-resistant cancer subgroup.

The association of host and vector characteristics with Ctenocephalides felis pathogen and endosymbiont infection.

Surveillance of the fleas and flea-borne pathogens infecting cats is important for both human and animal health. Multiple zoonotic Bartonella and Rickettsia species are known to infect the most common flea infesting cats and dogs worldwide: Ctenocephalides felis, the cat flea. The ability of other flea species to transmit pathogens is relatively unexplored. We aimed to determine cat host and flea factors independently associated with flea Bartonella and Rickettsia infection. We also assessed flea and cat infection by flea-host pair and location. To accomplish these aims, we performed qPCR for the detection of Bartonella, hemotropic Mycoplasma, Rickettsia, and Wolbachia DNA using paired cat and flea samples obtained from free-roaming cats presenting for spay or neuter across four locations in the United States. A logistic regression model was employed to identify the effect of cat (sex, body weight, geographic location, and Bartonella, hemotropic Mycoplasma, and Rickettsia spp., infection) and flea (clade and Rickettsia and Wolbachia infection) factors on C. felis Bartonella clarridgeiae infection. From 189 free roaming cats, we collected 84 fleas: Ctenocephalides felis (78/84), Cediopsylla simplex (4/84), Orchopeas howardi (1/84), and Nosopsyllus fasciatus (1/84). Ctenocephalides felis were phylogenetically assigned to Clades 1, 4, and 6 by cox1 gene amplification. Rickettsia asembonensis (52/84) and B. clarridgeiae (16/84) were the most common pathogenic bacteria detected in fleas. Our model identified host cat sex and weight as independently associated with B. clarridgeiae infection in fleas. Rickettsia asembonensis (52/84), Rickettsia felis (7/84) and Bartonella henselae (7/84) were detected in specific clades: R. felis was detected only in Clades 1 and 6 while B. henselae and R. asembonensis were detected only in Clade 4. Wolbachia spp., also displayed clade specificity with strains other than Wolbachia wCfeT only infecting fleas from Clade 6. There was poor flea and host agreement for Bartonella spp., infection; however, there was agreement in the Bartonella species detected in cats and fleas by geographic location. These findings reinforce the importance of considering reservoir host attributes and vector phylogenetic diversity in epidemiological studies of flea-borne pathogens. Widespread sampling is necessary to identify the factors driving flea-borne pathogen presence and transmission.

Feeding on a Bartonella henselae Infected Host Triggers Temporary Changes in the Ctenocephalides felis Microbiome.

The effect of Bartonella henselae on the microbiome of its vector, Ctenocephalides felis (the cat flea) is largely unknown, as the majority of C. felis microbiome studies have utilized wild-caught pooled fleas. We surveyed the microbiome of laboratory-origin C. felis fed on B. henselae-infected cats for 24 h or 9 days to identify changes to microbiome diversity and microbe prevalence compared to unfed fleas, and fleas fed on uninfected cats. Utilizing Next Generation Sequencing (NGS) on the Illumina platform, we documented an increase in microbial diversity in C. felis fed on Bartonella-infected cats for 24 h. These changes returned to baseline (unfed fleas or fleas fed on uninfected cats) after 9 days on the host. Increased diversity in the C. felis microbiome when fed on B. henselae-infected cats may be related to the mammalian, flea, or endosymbiont response. Poor B. henselae acquisition was documented with only one of four infected flea pools having B. henselae detected by NGS. We hypothesize this is due to the use of adult fleas, flea genetic variation, or lack of co-feeding with B. henselae-infected fleas. Future studies are necessary to fully characterize the effect of endosymbionts and C. felis diversity on B. henselae acquisition.

IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer.

Breast cancer bone metastasis is currently incurable, ~75% of patients with late-stage breast cancer develop disease recurrence in bone and available treatments are only palliative. We have previously shown that production of the pro-inflammatory cytokine interleukin-1B (IL-1B) by breast cancer cells drives bone metastasis in patients and in preclinical in vivo models. In the current study, we have investigated how IL-1B from tumour cells and the microenvironment interact to affect primary tumour growth and bone metastasis through regulation of the immune system, and whether targeting IL-1 driven changes to the immune response improves standard of care therapy for breast cancer bone metastasis. Using syngeneic IL-1B/IL1R1 knock out mouse models in combination with genetic manipulation of tumour cells to overexpress IL-1B/IL1R1, we found that IL-1B signalling elicited an opposite response in primary tumours compared with bone metastases. In primary tumours, IL-1B inhibited growth, by impairing the infiltration of innate immune cell subsets with potential anti-cancer functions but promoted enhanced tumour cell migration. In bone, IL-1B stimulated the development of osteolytic metastases. In syngeneic models of breast cancer, combining standard of care treatments (Doxorubicin and Zoledronic acid) with the IL-1 receptor antagonist Anakinra inhibited both primary tumour growth and metastasis. Anakinra had opposite effects on the immune response compared to standard of care treatment, and its anti-inflammatory signature was maintained in the combination therapy. These data suggest that targeting IL-1B signalling may provide a useful therapeutic approach to inhibit bone metastasis and improve efficacy of current treatments for breast cancer patients.

Monolingual and bilingual children's processing of coarticulation cues during spoken word recognition.

Bilingual children cope with a significant amount of phonetic variability when processing speech, and must learn to weigh phonetic cues differently depending on the cues' respective roles in their two languages. For example, vowel nasalization is coarticulatory and contrastive in French, but coarticulatory-only in English. In this study, we extended an investigation of the processing of coarticulation in two- to three-year-old English monolingual children (Zamuner, Moore & Desmeules-Trudel, 2016) to a group of four- to six-year-old English monolingual children and age-matched English-French bilingual children. Using eye tracking, we found that older monolingual children and age-matched bilingual children showed more sensitivity to coarticulation cues than the younger children. Moreover, when comparing the older monolinguals and bilinguals, we found no statistical differences between the two groups. These results offer support for the specification of coarticulation in word representations, and indicate that, in some cases, bilingual children possess language processing skills similar to monolinguals.

Point, walk, talk: Links between three early milestones, from observation and parental report.

Around their first birthdays, infants begin to point, walk, and talk. These abilities are appreciable both by researchers with strictly standardized criteria and caregivers with more relaxed notions of what each of these skills entails. Here, we compare the onsets of these skills and links among them across two data collection methods: observation and parental report. We examine pointing, walking, and talking in a sample of 44 infants studied longitudinally from 6 to 18 months. In this sample, links between pointing and vocabulary were tighter than those between walking and vocabulary, supporting a unified sociocommunicative growth account. Indeed, across several cross-sectional and longitudinal analyses, pointers had larger vocabularies than their nonpointing peers. In contrast to previous work, this did not hold for walkers' versus crawlers' vocabularies in our sample. Comparing across data sources, we find that reported and observed estimates of the growing vocabulary and of age of walk onset were closely correlated, while agreement between parents and researchers on pointing onset and talking onset was weaker. Taken together, these results support a developmental account in which gesture and language are intertwined aspects of early communication and symbolic thinking, whereas the shift from crawling to walking appears indistinct from age in its relation with language. We conclude that pointing, walking, and talking are on similar timelines yet distinct from one another, and discuss methodological and theoretical implications in the context of early development. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Toddlers' sensitivity to within-word coarticulation during spoken word recognition: Developmental differences in lexical competition.

To understand speech, listeners need to be able to decode the speech stream into meaningful units. However, coarticulation causes phonemes to differ based on their context. Because coarticulation is an ever-present component of the speech stream, it follows that listeners may exploit this source of information for cues to the identity of the words being spoken. This research investigates the development of listeners' sensitivity to coarticulation cues below the level of the phoneme in spoken word recognition. Using a looking-while-listening paradigm, adults and 2- and 3-year-old children were tested on coarticulation cues that either matched or mismatched the target. Both adults and children predicted upcoming phonemes based on anticipatory coarticulation to make decisions about word identity. The overall results demonstrate that coarticulation cues are a fundamental component of children's spoken word recognition system. However, children did not show the same resolution as adults of the mismatching coarticulation cues and competitor inhibition, indicating that children's processing systems are still developing.

Health Care Use During Transfer to Adult Care Among Youth With Chronic Conditions.

OBJECTIVE: To compare health care use and costs for youth with chronic health conditions before and after transfer from pediatric to adult health care services. METHODS: Youth born in Ontario, Canada, between April 1, 1989, and April 1, 1993, were assigned to 11 mutually exclusive, hierarchically arranged clinical groupings, including "complex" chronic conditions (CCCs), non-complex chronic conditions (N-CCCs), and chronic mental health conditions (CMHCs). Outcomes were compared between 2-year periods before and after transfer of pediatric services, the subjects' 18th birthday. RESULTS: Among 104,497 youth, mortality was highest in those with CCCs, but did not increase after transfer (1.3% vs 1.5%, P = .55). Costs were highest among youth with CCCs and decreased after transfer (before and after median [interquartile range]: $4626 [1253-21,435] vs $3733 [950-16,841], P < .001);Costs increased slightly for N-CCCs ($569 [263-1246] vs $589 [262-1333], P < .001), and decreased for CMHCs ($1774 [659-5977] vs $1545 [529-5128], P < .001). Emergency department visits increased only among youth with N-CCCs (P < .001). High-acuity emergency department visits increased CCCs (P = .04) and N-CCCs (P < .001), but not for CMHC (P = .59), who had the highest visit rate. Among the 11 individual conditions, costs only increased in youth with asthma (P < .001), and decreased (P < .05) in those with neurologic impairment, lupus, inflammatory bowel disease, and mood/affective disorders. CONCLUSIONS: Pediatric transfer to adult care is characterized by relatively stable short-term patterns of health service use and costs among youth with chronic conditions.

A care pathway: delayed active management of the third stage of labour.

Challenging the current National Institute for Clinical Excellence guidelines (NICE 2007), this paper will identify and discuss the evidence to support a care pathway for delayed active management of the third stage of labour, which promotes a delay in the administration of the uterotonic drug and delayed cord clamping (DCC). Current evidence highlights that clamping and cutting the umbilical cord once pulsation has ceased allows the baby to receive additional blood from the placenta, which in turn increases the baby's blood volume and significantly reduces instances of anaemia. The research available to support DCC and the benefits this provides to the newborn with little adverse effect to the mother could possibly be enough to change current practice to create Delayed Active Management as a third stage option for women.

Fibropolycystic liver disease in children.

Fibropolycystic liver diseases are a group of associated congenital disorders that present most often in childhood. These disorders include congenital hepatic fibrosis, biliary hamartomas, autosomal dominant polycystic liver disease, choledochal cysts and Caroli disease. We present a discussion and illustrations of the embryology, genetics, anatomy, pathology, imaging approach and key imaging features that distinguish fibropolycystic liver disease in children. The pathogenesis of these disorders is believed to be abnormal development of the embryonic ductal plates, which ultimately form the liver and biliary systems. An understanding of the abnormal embryogenesis helps to explain the characteristic imaging features of these disorders.

Sonography of the neonatal spine: part 1, Normal anatomy, imaging pitfalls, and variations that may simulate disorders.

OBJECTIVE: Our objective is to discuss neonatal spine sonography with emphasis on imaging pitfalls and normal variants that may simulate disease and to distinguish them from true spinal disorders. CONCLUSION: Sonography of the neonatal spine is now accepted as a highly sensitive, readily available screening study that can be used to evaluate various anomalies of the lumbar spine in most infants younger than 4 months.

Sonography of the neonatal spine: part 2, Spinal disorders.

OBJECTIVE: The objective of part 2 of this article is to focus on key imaging features of common skin-covered spinal anomalies (spina bifida occulta) and to distinguish them from normal variants (previously discussed in part 1). CONCLUSION: Modern imaging technology allows accurate neonatal spinal sonographic screening and the characterization of spinal abnormalities within the first few days of life. It is useful to determine the type of lesion present and to guide the type and timing of therapy.

The transition from student to qualified nurse: a military perspective.

This article explores some of the issues surrounding my transition from student nurse to qualified Royal Air Force staff nurse. It supports much of the research showing that the transition to staff nurse is stressful, with the time for preceptorship and supernumerary status varying. The education and support received during this period is still largely dependent on staff availability and this remains an area of concern. For military nurses the transition period is extra challenging, as there are military as well as nursing demands. This includes working predominantly in a civilian environment, while being aware that we may be deployed overseas with the military. However, the ability to adapt and adjust to changing circumstances is what essentially makes military nurses unique and distinctive. Provided that support is in place and appropriate clinical experience is obtained, we can fulfil our primary military roles.

The effects of chronic intracochlear electrical stimulation on inferior colliculus spatial representation in adult deafened cats.

Previous studies have shown that chronic electrical stimulation through a cochlear implant causes significant alterations in the central auditory system of neonatally deafened cats. The goal of this study was to investigate the effects of chronic stimulation in the mature auditory system. Normal hearing adult animals were deafened by ototoxic drugs and received daily electrical stimulation over periods of 4-6 months. In terminal physiology experiments, response thresholds to pulsatile and sinusoidal signals were recorded within the inferior colliculus (IC). Using previously established methods, spatial tuning curves (STCs; threshold vs. IC depth functions) were constructed, and their widths measured to infer spatial selectivity. The IC spatial representations were similar for pulsatile and sinusoidal stimulation when phase duration was taken into consideration. However, sinusoidal signals consistently elicited much lower thresholds than pulsatile signals, a difference not solely attributable to differences in charge/phase. The average STC width was significantly broader in the adult deafened/stimulated animals than in controls (adult deafened/unstimulated cats), suggesting that electrical stimulation can induce spatial expansion of the IC representation of the chronically stimulated cochlear sector. Further, results in these adult animals were not significantly different from results in neonatally deafened, early stimulated animals, suggesting that a similar degree of plasticity was induced within the auditory midbrains of mature animals.

Temperature Classification of the Spectra of Dysprosium (Dy i, Dy ii).

The Temperature Classifications are listed for 4584 lines of Dy i and Dy ii, as taken from an unpublished manuscript of the late A. S. King. In recording his observations, King used a wavelength list compiled mostly from the early literature. A homogeneous and extensive line list based on new observations has been prepared at the Lawrence Radiation Laboratory (LRL). King's data have been edited and adjusted by the present authors to fit the new wavelength list. In the Table, King's estimated intensities of Dy lines in the spectra of the Arc, Spark, and Furnace are given along with the Temperature Classification. Some of his earlier published work has been used to fill the gaps in this manuscript, which was forwarded to the late W. F. Meggers in 1956.