Transmission of Babesia microti in Minnesota through four blood donations from the same donor over a 6-month period

BACKGROUND: Babesiosis is a tick-borne zoonosis caused by intraerythrocytic protozoa. More than 40 US cases of Babesia microti infection acquired by blood transfusion have been reported. This report describes the identification of a transfusion-associated case of babesiosis and the subsequent identification of the infected blood donor and three other infected recipients of cellular blood components from three other donations by this donor. STUDY DESIGN AND METHODS: Serum specimens from the donors of blood that had been made into cellular components received by the index recipient and from other recipients of such components from the implicated donor were tested by the indirect fluorescent antibody (IFA) assay for antibodies to B. microti. Whole blood from IFA-positive persons was tested by PCR for B. microti DNA. RESULTS: IFA testing of serum from 31 of 36 donors implicated a 45-year-old man (titer, 1 in 256), whose donation had been used for RBCs. He likely became infected when bitten by ticks while camping in Minnesota in June 1999 and had donated blood four times thereafter. As demonstrated by PCR, he remained parasitemic for at least 10 months. Of the five other surviving recipients of cellular blood components from the implicated donor, three recipients (one for each of the three other donations) had become infected through either RBC or platelet transfusions. CONCLUSIONS: Babesiosis should be included in the differential diagnosis of posttransfusion febrile illness, and effective means for preventing transmission by blood transfusion are needed.     

Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy

The risk of mycobacterial disease is significantly increased in drug abusers as well as in immunocompromised HIV-1-infected individuals. The essential trace element selenium has an important function in maintaining immune processes and may, thus, have a critical role in clearance of mycobacteria. The impact of selenium status on the development of mycobacterial diseases in HIV-1-seropositive drug users was investigated over a 2-year period (1999-2001). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections who were matched on age, sex, and HIV status. Significant risk for development of mycobacterial disease was associated with a CD4 cell count of <200/mm 3, malnutrition, and selenium levels of 相似文献   

Substance P primes lipoteichoic acid- and Pam3CysSerLys4-mediated activation of human mast cells by up-regulating Toll-like receptor 2

We investigated the distribution of natural killer (NK) cell subsets, their activating and inhibitory receptors, and their cytolytic potential, in primary human immunodeficiency virus (HIV)-infected (PHI) individuals at baseline and during 1 year of follow-up with or without antiretroviral therapy, and compared the results with those obtained in treatment-naïve, chronically HIV-infected (CHI) individuals, and HIV-seronegative (HN) healthy individuals. The proportion of the CD56^dim and CD56^bright subsets decreased with disease progression, whereas that of the CD56⁻ CD16⁺ subset increased. In the CD56^dim subset, the proportion of cells with natural cytotoxicity receptors (NCRs) decreased with disease progression, and their cytolytic potential was reduced. Conversely, the CD56^bright subset was characterized by a high proportion of NCR-positive, killer cell immunoglobulin-like receptor (KIR)-positive NKG2A⁺ cells in both CHI and PHI individuals, which was associated with an increase in their cytolytic potential. During the 1 year of follow-up, the PHI individuals with high viraemia levels and low CD4⁺ T-cell counts who received highly active antiretroviral therapy (HAART) had a similar proportion of NK subsets to CHI individuals, while patients with low viraemia levels and high CD4⁺ T-cell counts who remained untreated had values similar to those of the HN individuals. Our results indicate a marked perturbation of the NK cell compartment during HIV-1 infection that is multifaceted, starts early and is progressive, primarily involves the CD56^bright subset, and is partially corrected by effective HAART.     

Recovery from central nervous system oxygen toxicity in the rat at oxygen pressures between 100 and 300 kPa

No symptoms related to central nervous system (CNS) oxygen toxicity have been reported when diving with oxygen rebreathers at depths shallower than 3 msw. We hypothesised that recovery from CNS oxygen toxicity will take place when the PO₂ is less than 130 kPa. We exposed rats to a high PO₂ (mainly 608 kPa) to produce CNS oxygen toxicity. The latency to the first electrical discharge (FED) preceding convulsions was determined as the animal’s control latency. Thereafter, the rat was exposed to the same PO₂ for 60% of its latency, then to a lower PO₂ for 15 min (sufficient time for full recovery in normoxia), and finally to the high PO₂ again until appearance of the FED. If recovery from CNS oxygen toxicity takes place during the interim period, the latency for the final exposure to the high oxygen pressure should not be shorter than the control. The latencies to CNS oxygen toxicity for exposure to the high oxygen pressure after a 15-min interim period at 21, 101, 132, 203, 304, 405, and 456 kPa were 110, 110, 125, 94, 85, 54 and 38% of the control value, respectively. Only after the last two interim pressures were the latencies significantly shorter than control values. The remaining latencies were not significantly different from 100%. Recovery from CNS oxygen toxicity in the rat takes place at a PO₂ anywhere between 21 and 304 kPa. The present findings support our previous suggestion that recovery from CNS oxygen toxicity in humans will take place at a PO₂ below 130 kPa. If our findings are corroborated by further human studies, this will justify including recovery in the algorithm for CNS oxygen toxicity in closed-circuit oxygen divers.     

CRIPTO promotes an aggressive tumour phenotype and resistance to treatment in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Despite increasing treatment options for this disease, prognosis remains poor. CRIPTO (TDGF1) protein is expressed at high levels in several human tumours and promotes oncogenic phenotype. Its expression has been correlated to poor prognosis in HCC. In this study, we aimed to elucidate the basis for the effects of CRIPTO in HCC. We investigated CRIPTO expression levels in three cohorts of clinical cirrhotic and HCC specimens. We addressed the role of CRIPTO in hepatic tumourigenesis using Cre‐loxP‐controlled lentiviral vectors expressing CRIPTO in cell line‐derived xenografts. Responses to standard treatments (sorafenib, doxorubicin) were assessed directly on xenograft‐derived ex vivo tumour slices. CRIPTO‐overexpressing patient‐derived xenografts were established and used for ex vivo drug response assays. The effects of sorafenib and doxorubicin treatment in combination with a CRIPTO pathway inhibitor were tested in ex vivo cultures of xenograft models and 3D cultures. CRIPTO protein was found highly expressed in human cirrhosis and hepatocellular carcinoma specimens but not in those of healthy participants. Stable overexpression of CRIPTO in human HepG2 cells caused epithelial‐to‐mesenchymal transition, increased expression of cancer stem cell markers, and enhanced cell proliferation and migration. HepG2‐CRIPTO cells formed tumours when injected into immune‐compromised mice, whereas HepG2 cells lacking stable CRIPTO overexpression did not. High‐level CRIPTO expression in xenograft models was associated with resistance to sorafenib, which could be modulated using a CRIPTO pathway inhibitor in ex vivo tumour slices. Our data suggest that a subgroup of CRIPTO‐expressing HCC patients may benefit from a combinatorial treatment scheme and that sorafenib resistance may be circumvented by inhibition of the CRIPTO pathway. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Molecular events underlying interleukin‐6 independence in a subclone of the CMA‐03 multiple myeloma cell line

We explored the molecular mechanisms involved in the establishement of CMA‐03/06, an IL‐6‐independent variant of the multiple myeloma cell line CMA‐03 previously generated in our Institution. CMA‐03/06 cells grow in the absence of IL‐6 with a doubling time comparable with that of CMA‐03 cells; neither the addition of IL6 (IL‐6) to the culture medium nor co‐culture with multipotent mesenchymal stromal cells increases the proliferation rate, although they maintain the responsiveness to IL‐6 stimulation as demonstrated by STAT1, STAT3, and STAT5 induction. IL‐6 independence of CMA‐03/06 cells is not apparently due to the development of an autocrine IL‐6 loop, nor to the observed moderate constitutive activation of STAT5 and STAT3, since STAT3 silencing does not affect cell viability or proliferation. When compared to the parental cell line, CMA‐03/06 cells showed an activated pattern of the NF‐κB pathway. This finding is supported by gene expression profiling (GEP) analysis identifying an appreciable fraction of modulated genes (28/308) in the CMA‐03/06 subclone reported to be involved in this pathway. Furthermore, although more resistant to apoptotic stimuli compared to the parental cell line, CMA‐03/06 cells display a higher sensibility to NF‐κB inhibition induced by bortezomib. Finally, GEP analysis suggests an involvement of a number of cytokines, which might contribute to IL‐6 independence of CMA‐03/06 by stimulating growth and antiapoptotic processes. In conclusion, the parental cell‐line CMA‐03 and its variant CMA‐03/06 represent a suitable model to further investigate molecular mechanisms involved in the IL‐6‐independent growth of myeloma cells. © 2013 Wiley Periodicals, Inc.     

Masked priming and ERPs dissociate maturation of orthographic and semantic components of visual word recognition in children

This study examined the time‐course of reading single words in children and adults using masked repetition priming and the recording of event‐related potentials. The N250 and N400 repetition priming effects were used to characterize form‐ and meaning‐level processing, respectively. Children had larger amplitude N250 effects than adults for both shorter and longer duration primes. Children did not differ from adults on the N400 effect. The difference on the N250 suggests that automaticity for form processing is still maturing in children relative to adults, while the lack of differentiation on the N400 effect suggests that meaning processing is relatively mature by late childhood. The overall similarity in the children's repetition priming effects to adults' effects is in line with theories of reading acquisition, according to which children rapidly transition to an orthographic strategy for fast access to semantic information from print.     

Long Working Hours and Sleep Disturbances: The Whitehall II Prospective Cohort Study

Study Objective:

To examine whether exposure to long working hours predicts various forms of sleep disturbance; short sleep, difficulty falling asleep, frequent waking, early waking and waking without feeling refreshed.

Design:

Prospective study with 2 measurements of working hours (phase 3, 1991–1994 and phase 5, 1997–1999) and 2 measurements of subjective sleep disturbances (phase 5 and phase 7, 2002–2004).

Setting:

The Whitehall II study of British civil servants.

Participants:

Full time workers free of sleep disturbances at phase 5 and employed at phases 5 and 7 (n = 937–1594) or at phases 3, 5, and 7 (n = 886–1510).

Measurements and Results:

Working more than 55 hours a week, compared with working 35–40 hours a week, was related to incident sleep disturbances; demographics-adjusted odds ratio (95% CI) 1.98 (1.05, 3.76) for shortened sleeping hours, 3.68 (1.58, 8.58) for difficulty falling asleep; and 1.98 (1.04, 3.77) for waking without feeling refreshed. Repeat exposure to long working hours was associated with odds ratio 3.24 (1.45, 7.27) for shortened sleep, 6.66 (2.64, 16.83) for difficulty falling asleep, and 2.23 (1.16, 4.31) for early morning awakenings. Some associations were attenuated after adjustment for other risk factors. To a great extent, similar results were obtained using working hours as a continuous variable. Imputation of missing values supported the findings on shortened sleep and difficulty in falling asleep.

Conclusion:

Working long hours appears to be a risk factor for the development of shortened sleeping hours and difficulty falling asleep.

Citation:

Virtanen M; Ferrie JE; Vahtera J; Elovainio M; Singh-Manoux A; Marmot MG; Kivimäki M. Long working hours and sleep disturbances: the whitehall II prospective cohort study. SLEEP 2009;32(6):737–745.     

Early adolescent outcomes of institutionally deprived and non-deprived adoptees. III. Quasi-autism

BACKGROUND: Some young children reared in profoundly depriving institutions have been found to show autistic-like patterns, but the developmental significance of these features is unknown. METHODS: A randomly selected, age-stratified, sample of 144 children who had experienced an institutional upbringing in Romania and who were adopted by UK families was studied at 4, 6, and 11 years, and compared with a non-institutionalised sample of 52 domestic adoptees. Twenty-eight children, all from Romanian institutions, for whom the possibility of quasi-autism had been raised, were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) at the age of 12 years. RESULTS: Sixteen children were found to have a quasi-autistic pattern; a rate of 9.2% in the Romanian institution-reared adoptees with an IQ of at least 50 as compared with 0% in the domestic adoptees. There were a further 12 children with some autistic-like features, but for whom the quasi-autism designation was not confirmed. The follow-up of the children showed that a quarter of the children lost their autistic-like features by 11. Disinhibited attachment and poor peer relationships were also present in over half of the children with quasi-autism. CONCLUSIONS: The findings at age 11/12 years confirmed the reality and clinical significance of the quasi-autistic patterns seen in over 1 in 10 of the children who experienced profound institutional deprivation. Although there were important similarities with 'ordinary' autism, the dissimilarities suggest a different meaning.