Early first trimester uteroplacental flow and the progressive disintegration of spiral artery plugs: new insights from contrast-enhanced ultrasound and tissue histopathology.

STUDY QUESTION: Does the use of a vascular contrast agent facilitate earlier detection of maternal flow to the placental intervillous space (IVS) in the first trimester of pregnancy? SUMMARY ANSWER: Microvascular filling of the IVS was demonstrated by contrast-enhanced ultrasound from 6 weeks of gestation onwards, earlier than previously believed. WHAT IS KNOWN ALREADY: During placental establishment and remodeling of maternal spiral arteries, endovascular trophoblast cells invade and accumulate in the lumen of these vessels to form 'trophoblast plugs'. Prior evidence from morphological and Doppler ultrasound studies has been conflicting as to whether the spiral arteries are completely plugged, preventing maternal blood flow to the IVS until late in the first trimester. STUDY DESIGN, SIZE, DURATION: Uteroplacental flow was examined across the first trimester in human subjects given an intravenous infusion of lipid-shelled octofluoropropane microbubbles with ultrasound measurement of destruction and replenishment kinetics. We also performed a comprehensive histopathological correlation using two separately archived uteroplacental tissue collections to evaluate the degree of spiral artery plugging and evaluate remodeling of the upstream myometrial radial and arcurate arteries. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women (n = 34) were recruited in the first trimester (range: 6+3 to 13+6 weeks gestation) for contrast-enhanced ultrasound studies with destruction-replenishment analysis of signal intensity for assessment of microvascular flux rate. Histological samples from archived in situ (Boyd Collection, n = 11) and fresh first, second, and third trimester decidual and post-hysterectomy uterine specimens (n = 16) were evaluated by immunohistochemistry (using markers of epithelial, endothelial and T-cells, as well as cell adhesion and proliferation) and ultrastructural analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Contrast agent entry into the IVS was visualized as early as 6+3 weeks of gestation with some variability in microvascular flux rate noted in the 6-7+6 week samples. Spiral artery plug canalization was observed from 7 weeks with progressive disintegration thereafter. Of note, microvascular flux rate did not progressively increase until 13 weeks, which suggests that resistance to maternal flow in the early placenta may be mediated more proximally by myometrial radial arteries that begin remodeling at the end of the first trimester. LIMITATIONS REASONS FOR CAUTION: Gestational age was determined by crown-rump length measurements obtained by transvaginal ultrasound on the day of contrast-enhanced imaging studies, which may explain the variability in the earliest gestational age samples due to the margin of error in this type of measurement. WIDER IMPLICATIONS OF THE FINDINGS: Our comprehensive in situ histological analysis, in combination with the use of an in vivo imaging modality that has the sensitivity to permit visualization of microvascular filling, has allowed us to reveal new evidence in support of increasing blood flow to the IVS from 6 weeks of gestation. Histologic review suggested the mechanism may be blood flow through capillary-sized channels that form through the loosely cohesive 'plugs' by 7 weeks gestation. However, spiral artery remodeling on its own did not appear to explain why there is significantly more blood flow at 13 weeks gestation. Histologic studies suggest it may be related to radial artery remodeling, which begins at the end of the first trimester. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by the Oregon Health and Science University Knight Cardiovascular Institute, Center for Developmental Health and the Struble Foundation. There are no competing interests

Vibrio parahemolyticus septicaemia in a liver transplant patient: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Vibrio parahemolyticus </it>is the leading cause of vibrio-associated gastroenteritis in the United States of America, usually related to poor food handling; only rarely has it been reported to cause serious infections including sepsis and soft tissue infections. In contrast, <it>Vibrio vulnificus </it>is a well-known cause of septicaemia, especially in patients with cirrhosis. We present a patient with <it>V. parahemolyticus </it>sepsis who had an orthotic liver transplant in 2007 and was on immunosuppression for chronic rejection. Clinical suspicion driven by patient presentation, travel to Gulf of Mexico and soft tissue infection resulted in early diagnosis and institution of appropriate antibiotic therapy.</p> <p>Case presentation</p> <p>A 48 year old Latin American man with a history of chronic kidney disease, orthotic liver transplant in 2007 secondary to alcoholic end stage liver disease on immunosuppressants, and chronic rejection presented to the emergency department with fever, vomiting, abdominal pain, left lower extremity swelling and fluid filled blisters after a fishing trip in the Gulf of Mexico. Samples from the blister and blood grew <it>V. parahemolyticus</it>. The patient was successfully treated with ceftriaxone and ciprofloxacin.</p> <p>Conclusion</p> <p>Febrile patients with underlying liver disease and/or immunosuppression should be interviewed regarding recent travel to a coastal area and seafood ingestion. If this history is obtained, appropriate empiric antibiotics must be chosen. Patients with liver disease and/or immunosuppresion should be counselled to avoid eating raw or undercooked molluscan shellfish. People can prevent <it>Vibrio </it>sepsis and wound infections by proper cooking of seafood and avoiding exposure of open wounds to seawater or raw shellfish products.</p

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

Compulsory admission at first presentation to services for psychosis: does ethnicity still matter? Findings from two population-based studies of first episode psychosis

Objectives Compared with the majority population, those from minority ethnic groups in the UK are more likely to be admitted compulsorily during a first episode of psychosis (FEP). We investigated whether these disparities in pathways in to care continue. Methods We analysed data from two first episode psychosis studies, conducted in the same geographical area in south London 15 years apart: the Aetiology and Ethnicity in Schizophrenia and Other Psychosis (AESOP) and the Clinical Record Interactive Search-First Episode Psychosis (CRIS-FEP) studies. The inclusion/exclusion criteria for case ascertainment for first episode psychosis were identical across the two studies. We performed multivariable logistic regression to estimate odds of compulsory admission by ethnic group, controlling for confounders. Participants Two hundred sixty-six patients with first episode psychosis, aged 18–64 years, who presented to mental health services in south London in 1997–1999 and 446 with FEP who presented in 2010–2012. Results When the two samples were compared, ethnic differences in compulsory admission appear to have remained the same for black African patients, i.e. three times higher than white British in both samples: AESOP (adj. OR = 3.96; 95% CI = 1.80–8.71) vs. CRIS-FEP (adj. OR = 3.12; 95% CI = 1.52–6.35). Black Caribbean patients were three times more likely to be compulsorily admitted in AESOP (adj. OR = 3.20; 95% CI = 1.56–6.54). This was lower in the CRIS-FEP sample (adj. OR = 1.68; 95% CI = 0.71–3.98) and did not meet conventional levels for statistical significance. Conclusion Ethnicity is strongly associated with compulsory admissions at first presentation for psychosis with evidence of heterogeneity across groups, which deserves further research

Molecular characterisation of protist parasites in human-habituated mountain gorillas (Gorilla beringei beringei), humans and livestock, from Bwindi impenetrable National Park, Uganda

Over 60 % of human emerging infectious diseases are zoonotic, and there is growing evidence of the zooanthroponotic transmission of diseases from humans to livestock and wildlife species, with major implications for public health, economics, and conservation. Zooanthroponoses are of relevance to critically endangered species; amongst these is the mountain gorilla (Gorilla beringei beringei) of Uganda. Here, we assess the occurrence of Cryptosporidium, Cyclospora, Giardia, and Entamoeba infecting mountain gorillas in the Bwindi Impenetrable National Park (BINP), Uganda, using molecular methods. We also assess the occurrence of these parasites in humans and livestock species living in overlapping/adjacent geographical regions

Ethnic variations in duration of untreated psychosis: report from the CRIS-FEP study

Objectives:  There is inconsistent evidence on the influence of ethnicity on duration of untreated psychosis (DUP). We investigated ethnic differences in DUP in a large epidemiological dataset of first episode psychosis patients in an inner city area of south London, UK. Methods:  We analysed data on 558 first episode psychosis patients at the South London and Maudsley NHS Trust, between 2010 and 2012. We performed multivariable logistic regression to estimate the odds of a short DUP (≤ 6 months) by ethnic group, controlling for confounders. Results:  There was no evidence that ethnicity is associated with duration of untreated psychosis. However, we found evidence that a short DUP was strongly associated with age, living circumstances, and pathways to care variables (involuntary admission, out of office hour contact, accident and emergency referral, criminal justice agency referral and family involvement in help-seeking). Conversely, a long DUP was associated with report of social isolation, living alone, being single and General Practitioner referral. Conclusion:  Our findings suggest that indicators of social isolation were associated with long DUP. Our data also show that pathways into care characteristics play significant role in DUP. Thus, the challenge of tackling the issue of timely access to EI under the new Access and Waiting Time standard for psychosis requires a multilevel approach, including joint working with communities, public awareness of psychosis, less restrictive referral pathways and adequate resourcing of early intervention for psychosis services. These will go a long way in addressing patients’ needs rather than be determined by service structures

Editorial Board

Source at http://dx.doi.org/10.1186/s12888-017-1345-8 Background: The duration of untreated psychosis is determined by both patient and service related factors. Few studies have considered the geographical accessibility of services in relation to treatment delay in early psychosis. To address this, we investigated whether treatment delay is co-determined by straight-line distance to hospital based specialist services in a mainly rural mental health context. Methods: A naturalistic cross-sectional study was conducted among a sample of recent onset psychosis patients in northern Norway (n = 62). Data on patient and service related determinants were analysed. Results: Half of the cohort had a treatment delay longer than 4.5 months. In a binary logistic regression model, straight-line distance was found to make an independent contribution to delay in which we controlled for other known risk factors. Conclusions: The determinants of treatment delay are complex. This study adds to previous studies on treatment delay by showing that the spatial location of services also makes an independent contribution. In addition, it may be that insidious onset is a more important factor in treatment delay in remote areas, as the logistical implications of specialist referral are much greater than for urban dwellers. The threshold for making a diagnosis in a remote location may therefore be higher. Strategies to reduce the duration of untreated psychosis in rural areas would benefit from improving appropriate referral by crisis services, and the detection of insidious onset of psychosis in community based specialist services

The influence of ethnic group composition on focus group discussions.

BACKGROUND: Focus groups are commonly used to explore participants' experiences in health and social care research. Although it is suggested that having demographically homogenous groups may help put participants at ease, the evidence is sparse.The aims of the paper are to: explore the impact of relative ethnic homogeneity and heterogeneity of focus group participants on the group discussions; improve understanding of homogeneity and heterogeneity in focus groups; suggest ways to operationalise concepts such as being 'more comfortable' with other focus group participants. METHOD: Digitally recorded focus groups were undertaken with family carers of stroke survivors and were later transcribed and analysed using framework analysis. Groups were designated as more or less ethnically homogenous. More homogenous groups included, for example, only White British or Asian Indian participants whilst more heterogeneous groups comprised a mixture of, for example, Asian, White British and Black Caribbean participants. RESULTS: Forty-one carers participated in seven focus groups. Analysis revealed differences in discussions around ethnicity between the more or less ethnically homogenous groups. For example, participants in more ethnically homogenous focus groups were more likely to say ethnicity might influence perceptions of social care services. On the other hand, more heterogeneous groups emphasised similarity in carers' experiences, irrespective of ethnicity. Participants in the more homogenous groups were also more likely to make potentially controversial comments relating to ethnic differences. Additionally they appeared to be more at ease with each other discussing the topic. For example, they spontaneously mentioned ethnic differences earlier in these groups.In contrast, analysis of topics not specifically related to ethnicity, such as the difficult experiences of being a carer, produced no discernible patterns when comparing more and less homogenous focus groups. CONCLUSION: Considerations around focus group participant demographic homogeneity and heterogeneity are complex and these terms may be most usefully applied only in relative terms. Data derived from more homogenous groups complement data from more heterogeneous groups providing different perspectives. Depending on the focus of the discussion, having characteristics in common, such as being a carer can override other differences

Identification of the Transgenic Integration Site in Immunodeficient tgε26 Human CD3ε Transgenic Mice

A strain of human CD3ε transgenic mice, tgε26, exhibits severe immunodeficiency associated with early arrest of T cell development. Complete loss of T cells is observed in homozygous tgε26 mice, but not in heterozygotes, suggesting that genomic disruption due to transgenic integration may contribute to the arrest of T cell development. Here we report the identification of the transgenic integration site in tgε26 mice. We found that multiple copies of the human CD3ε transgene are inserted between the Sstr5 and Metrn loci on chromosome 17, and that this is accompanied by duplication of the neighboring genomic region spanning 323 kb. However, none of the genes in this region were abrogated. These results suggest that the severe immunodeficiency seen in tgε26 mice is not due to gene disruption resulting from transgenic integration