Summary We describe the transmission of hepatitis C virus (HCV) to two patients from a thoracic surgeon who was unaware of his hepatitis C infection. By partial sequencing of the non-structural 5B ...gene and phylogenetic analysis, the viruses from both patients were found to be closely related to genotype 1a strain from the surgeon. Two further hepatitis C cases were found in relation to the thoracic clinic. Their HCV sequences were related to each other but were of genotype 2b and the source of infection was never revealed. To elucidate the magnitude of the problem, we conducted a prospective study for a period of 17 months in which patients who were about to undergo thoracic surgery were asked to participate. Blood samples were drawn prior to surgery and at least four months later. The postoperative samples were then screened for anti-HCV and, if positive, the initial sample was also analysed. The only two patients (0.4%) identified were confirmed anti-HCV positive before surgery, and none out of 456 evaluable cases seroconverted to anti-HCV during the observation period. Despite the retrospectively identified cases, nosocomial hepatitis C is rare in our thoracic unit. The study points out the risk of transmission of hepatitis C from infected personnel and reiterates the need for universal precautions.
Aims: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell cytoplasm (ICA) in combination with human ...leukocyte antigen (HLA) would improve the diagnostic sensitivity of childhood type 1 diabetes by detecting the children who otherwise would have been autoantibody-negative.Methods: A total of 686 patients diagnosed in 1996-2005 in Skåne were analyzed for all the seven autoantibodies arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA in addition to HLA-DQ genotypes.Results: Zinc transporter 8 autoantibody to either one or all three amino acid variants at position 325 (ZnT8RWQA) was found in 65% (449/686) of the patients. The frequency was independent of age at diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients from 7.5 to 5.4%-a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 years of age had no autoantibody at diagnosis. Diagnosis without any islet autoantibody increased with increasing age at onset. DQA1-B1*X-0604 was associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with IAA.Conclusions: This study revealed that (1) the ZnT8RWQA was common, independent of age; (2) multiple autoantibodies were common among the young; (3) DQA1-B1*X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between autoantibody pairs was common for all combinations except IAA. These results suggest that ZnT8RWQA is a necessary complement to the classification and prediction of childhood type 1 diabetes as well as to randomize the subjects in the prevention and intervention of clinical trials.
The Internet is becoming a new erotic oasis for obtaining sex online or in person. We reviewed the literature on cybersex and compared differences in data from samples of homosexually active men ...obtained on identical questionnaires from a conventional written questionnaire, distributed through the mailing and contact lists of a large national gay organization in Sweden, and through the same organization’s website and chat room. A total of 716 written questionnaires and 678 Internet questionnaires were obtained. The Internet sample was younger, more likely to live in small towns or cities, live with parents or a girlfriend, and have lower formal education. They are less likely to have previous sexual experience solely with other men (one in three of the Internet sample vs. 1 in 14 of the written sample defined themselves as bisexual) and more likely to visit erotic oases such as bathhouses, video clubs and erotic movie houses. They also visited Internet chat rooms more frequently (86% of the Internet sample vs. 50% of the written sample). One third of the Internet sample wanted the opportunity to talk with an expert about HIV compared with a quarter of the written sample. Sexual practices between the two samples were generally similar, although the Internet sample reported significantly less body contact, kissing, hugging, mutual masturbation, and more condom use for anal intercourse with steady partners. Over four times as many of the Internet samples reported sex with women in the past year as the written sample. These data indicate that Internet data collection is feasible and that this mode of data collection, despite the nonrandom and self-selected nature of both types of samples, is likely to be more significantly oriented toward the young, geographically more isolated, and more behaviorally and self-identified bisexual respondent than conventionally distributed written questionnaires.
•CXCL14 is lost in BM stromal cells in patients with CML, and restoring CXCL14 suppresses CML LSC engraftment in vivo and survival in vitro.•CXCL14 treatment inhibits mTOR and oxidative ...phosphorylation signaling pathways in CML LSCs.
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Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38– cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
An Internet study of cybersex participants Daneback, Kristian; Cooper, Al; Månsson, Sven-Axel
Archives of sexual behavior,
06/2005, Letnik:
34, Številka:
3
Journal Article
Recenzirano
Cybersex is a subcategory of online sexual activities (OSA) and is defined as when two or more people are engaging in sexual talk while online for the purposes of sexual pleasure and may or may not ...include masturbation. Cybersex is a growing phenomenon with a significant impact on participants but very little research has been done on this subject to date. This study is the first to attempt to delineate characteristics of those who engage in cybersex. Data were collected through an online questionnaire in Swedish, administered through the Swedish web portal Passagen.se. Out of the total sample (N = 1828), almost a third, both men and women, reported to have engaged in cybersex. A logistic regression analysis showed that age, sex, and sexual orientation were important demographic variables to consider when investigating cybersex. A comparison of interval data showed those engaging in cybersex to have a higher likelihood of spending more time online for OSA and having more offline sex partners than those not engaging in cybersex.
The internet is becoming a favored technology for carrying out survey research, and particularly sexual health research. However, its utility is limited by unresolved sampling questions such as how ...biased internet samples may be. This paper addresses this issue through comparison of a ‘gold standard’ random selection population-based sexual survey (The Swedish Sexual Life Survey) with an internet-based survey in Sweden which used identical demographic, sexual and relationship questions, to ascertain the biases and degree of comparability between the recruitment methods. On the internet questionnaire, there were significant differences between males and females on all the measured indices. There were no significant differences in proportions of males and females, or nationality, between the two samples. However, the internet samples for both males and females were significantly more likely to be younger, originally from and currently living in a major city, better educated, and more likely to be students and less likely to be retired. Relationship variables were less likely to be significantly different between samples: there were no differences for males or females between the SSS and the internet samples on having been in a committed relationship, and how they met their present partner, nor for males in having discussed separation in the past year. However, there was a higher proportion of people attracted to the same sex, and higher numbers of sex partners (as well as a higher proportion of people reporting no sex) in the past year, in the internet sample. These data suggest that apart from the demographics of age, location, and education, currently being in a committed relationship, and the number of sex partners in the past year, internet samples are comparable for relationship characteristics and history with a national sexual life survey. Comparison of internet data with random survey data in other western countries should occur to determine if these patterns are replicated.
Dose integration properties were investigated for normoxic polymer gels based on methacrylic acid (nMAG) and acrylamide/N, N'-methylenebisacrylamide (nPAG). The effect of sequential irradiation was ...studied for different fractionation schemes and varying amounts of methacrylic acid for the nMAG gels. Magnetic resonance imaging (MRI) was used for read out of the absorbed dose response. The investigated gels exhibited a dependence on the fractionation scheme. The response when the total dose was divided into fractions of 0.5 Gy was compared with the response when the total dose was delivered in a single fraction. The slope of the R2 versus the absorbed dose response decreased when the absorbed dose per fraction was increased. Also, for higher amounts of methacrylic acid in the nMAG system the difference in the response increased. For gels containing 2, 4, 6 and 8% methacrylic acid, the R2 versus the absorbed dose response increased by 35, 37, 63 and 93%, respectively. Furthermore, the effect of the fractionation was larger when a higher total absorbed dose was given. The effect was less pronounced for the investigated nPAG, containing 3% acrylamide and 3% N, N'-methylenebisacrylamide, than for the nMAG systems. Consequently, this study indicates that the nPAG system has preferable beam integration characteristics compared with the nMAG system.
The development of B cells relies on an intricate network of transcription factors critical for developmental progression and lineage commitment. In the B cell developmental trajectory, a temporal ...switch from predominant
to
expression occurs at the CLP stage. Utilizing VAV-iCre mediated conditional deletion, we found that the loss of FOXO3 impaired B cell development from LMPP down to B cell precursors, while the loss of FOXO1 impaired B cell commitment and resulted in a complete developmental block at the CD25 negative proB cell stage. Strikingly, the combined loss of FOXO1 and FOXO3 resulted in the failure to restrict the myeloid potential of CLPs and the complete loss of the B cell lineage. This is underpinned by the failure to enforce the early B-lineage gene regulatory circuitry upon a predominantly pre-established open chromatin landscape. Altogether, this demonstrates that FOXO3 and FOXO1 cooperatively govern early lineage restriction and initiation of B-lineage commitment in CLPs.
Summary
Objectives
X‐linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all ...known cases of X‐linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease.
Study design
Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21‐hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48–200) were selected. Sera from subjects included were analysed for levels of very long‐chain fatty acids, which are diagnostic for X‐linked adrenoleukodystrophy in men.
Results
Eighteen subjects had negative indices and 17 had low indices for 21‐hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X‐linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X‐linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%.
Conclusions
We found X‐linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far‐reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long‐chain fatty acids.
Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and ...maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model. These AML cells could regenerate AML after transplantation. Prospective niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs protected AML-initiating stem cells (LSCs) from chemotherapy in vitro partially via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs appeared to be retained in Lama4-/- mouse skin after cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining and protecting AML LSCs during chemotherapy, meriting future exploration of their impact on AML relapse.
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