Prevalence of hepatitis C infection and its associated factors in healthy adults without identifiable route of transmission.

While hepatitis C virus (HCV) infection is long known to be associated with parenteral exposure, the specific route of transmission is not identified in a proportion of infected patients. Taking blood donors as the surrogate of healthy adults in the community in Hong Kong, we identified 91 HCV-infected donors (≤0.02% positive rate) in 2014-2016, of whom 46 were recruited in a mixed-method study to examine their transmission routes. A majority (75%) of the recruited donors were HCV RNA positive, with the predominant subtypes being 1b and 6a. From the results of the structured self-administered questionnaire and in-depth interviews, only 14 (30%) recruited donors could be traced to past history of contaminated blood transfusion (n = 9) or injection drug use (n = 5). Case-control analyses with 3 different control groups were performed to examine factors associated with HCV infection in multivariable analyses. High-risk sexual behaviour, body piercing, intramuscular injection and vaccine inoculation abroad, having lived abroad for >3 months were significantly associated with HCV in donors with otherwise nonidentifiable source of infection. While the specific route of transmission cannot be established for each person, associations with multiple parenteral exposures outside Hong Kong were observed. The World Health Organization has advocated for the global elimination of HCV by 2030. With a high proportion of HCV-infected persons who are unaware of their infections, HCV elimination could be hard to achieve.

Endothelial chimerism in chronic sclerotic-type chronic graft-versus-host disease (GVHD) and GVHD-associated angiomatosis.

Graft-versus-host disease-associated angiomatosis (GVHD-AA) is an uncommon manifestation of chronic GVHD consisting of friable vascular proliferations. Using fluorescence in situ hybridization, we demonstrate the presence of donor-derived endothelial cells within areas of GVHD-AA. This is the first documented occurrence of a benign neoplastic growth in relationship to a form of chronic GVHD.

Differential CTLA-4 expression in human CD4+ versus CD8+ T cells is associated with increased NFAT1 and inhibition of CD4+ proliferation.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a costimulatory molecule that negatively regulates T-cell activation. Originally identified in murine CD8(+) T cells, it has been found to be rapidly induced on human T cells. Furthermore, CTLA-4 is expressed on regulatory T cells. Clinically, targeting CTLA-4 has clinical utility in the treatment of melanoma. Whether the expression of CTLA-4 is differentially regulated in CD8(+) vs CD4(+) human T cells is unclear. Here, we analyzed CTLA-4 in normal human CD4(+) and CD8(+) T-cell subsets and show for the first time that CTLA-4 is expressed significantly higher in the CD4(+) T cells than in CD8(+) T cells. CTLA-4 is higher at the protein and the transcriptional levels in CD4(+) T cells. This increase is due to the activation of the CTLA-4 promoter, which undergoes acetylation at the proximal promoter. Furthermore, we show that blocking CTLA-4 on CD4(+) T cells permits greater proliferation in CD4(+) vs CD8(+) cells. These findings demonstrate a differential regulation of CTLA-4 on CD4(+) and CD8(+) T-cell subsets, which is likely important to the clinical efficacy for anti-CTLA-4 therapies. The findings hint to strategies to modulate CTLA-4 expression by targeting epigenetic transcription to alter the immune response.

Diagnostic accuracy of the BACs-on-Beads™ assay versus karyotyping for prenatal detection of chromosomal abnormalities: a retrospective consecutive case series.

OBJECTIVE: To evaluate the diagnostic performance of the BACs-on-Beads(™) (BoBs(™)) assay for prenatal detection of chromosomal abnormalities. DESIGN: Retrospective study. SETTING: Tertiary prenatal diagnosis centre. POPULATION: Women referred for prenatal diagnosis. METHODS: We retrieved 2153 archived DNA samples collected between January 2010 and August 2011 for the BoBs(™) assay. These samples had previously been tested by quantitative fluorescence polymerase chain reaction (QF-PCR) and karyotyping. In the BoBs(™) assay a sample was defined as normal disomic when the ratio of the fluorescence intensities in a chromosome locus lay within the threshold (mean ratio ± 2SD), and as deleted or duplicated when the ratio was below the lower threshold (0.6-0.8) or above the upper threshold (1.3-1.4), respectively. The BoBs(™) results were further validated by microarray and compared in a blinded manner with the original QF-PCR and karyotyping results. MAIN OUTCOME MEASURES: Concordance of any numerical, structural, and submicroscopic chromosomal abnormalities between the methods. RESULTS: BACs-on-Beads(™) was similar to karyotyping and QF-PCR in detecting trisomy 13, trisomy 18, trisomy 21, and sex chromosomal aneuploidies, and superior to QF-PCR in detecting major structural abnormalities (53.3 versus 13.3%) and mosaicism (28.6 versus 0%) involving chromosomal abnormalities other than the common aneuploidies. BoBs(™) detected six microdeletion syndromes missed by karyotyping and QF-PCR; however, BoBs(™) missed two cases of triploidy identified by QF-PCR. Therefore, the sensitivity of BoBs(™) is 96.7% (95% CI 92.6-98.7%), and its specificity is 100% (95% CI 99.8-100%). CONCLUSIONS: BACs-on-Beads(™) can replace QF-PCR for triaging in prenatal diagnosis, and gives a better diagnostic yield than current rapid aneuploidy tests.

Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract.

Poor human-to-human transmission of influenza A H5N1 virus has been attributed to the paucity of putative sialic acid alpha2-3 virus receptors in the epithelium of the human upper respiratory tract, and thus to the presumed inability of the virus to replicate efficiently at this site. We now demonstrate that ex vivo cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected with H5N1 viruses in spite of an apparent lack of these receptors.

Reduction in vasovagal reaction rate in young first-time blood donors by collecting 350 mL rather than 450 mL.

BACKGROUND: There is a paucity of studies on the magnitude of reduction of vasovagal reaction by reduced collection volume. This study was thus conducted to determine the difference in reaction rates between two collection volumes among the young first-time donors who are at particular risk of reaction. STUDY DESIGN AND METHODS: This retrospective study analyzed 38,436 whole blood donations made by young (aged 16 to 18 years) first-time donors. The effect of collection volume on vasovagal reaction was compared among different weight subgroups for both sexes by chi-square test. RESULTS: For females in all weight subgroups and two of the male lower-weight subgroups, the reduction percentages ranged from 35% to 58% (p < 0.05). It was also noted that, among the females, a higher weight was associated with a higher percent reduction in the reaction rate. CONCLUSION: With reduced collection volume, this study detected large and significant reduction in reaction rates among all females, as well as lower-weight males.

A study of the predonation hemoglobin and iron status among Hong Kong Chinese blood donors.

BACKGROUND: Predonation hemoglobin (PDH) is used to safeguard donors' welfare, and low hemoglobin (Hb) is known to be the most frequent reason for donor deferral. A study was initiated to assess the PDH and iron status of blood donors in Hong Kong. STUDY DESIGN AND METHODS: This observational study was designed with four groups of whole blood donors invited (group 1-eligible first time donors, group 2-eligible repeat donors with zero or one donation in preceding 12 months, group 3-eligible repeat donors with at least two donations in preceding 12 months, group 4-repeat donors being deferred for low PDH). Predonation blood samples were obtained for blood counts and iron status. Mann-Whitney test, Kruskal-Wallis test, and chi-square test for trend were applied for statistical analysis. RESULTS: A total of 836 donors were recruited, of which 35 were excluded because of hemoglobinopathy. An inverse relationship between serum ferritin level and number of donations in the preceding 12 months was observed in both sexes. Iron deficiency was significantly seen in 35.1% of male and 65.3% of female deferred donors. More importantly, up to 7.2, 5.8, and 29.5% of the female donors in groups 1, 2, and 3 were found to be iron deficient despite having a high enough PDH. CONCLUSION: This is the first study to assess PDH and iron status in Chinese blood donors. Iron depletion is noted with increasing number of blood donations in the preceding 12 months. Advice on iron repletion is a necessary step for donor welfare and strategies should be developed to ensure that donors have adequate PDH.

Long-term clinical outcomes after Streptococcus bovis isolation in asymptomatic blood donors in Hong Kong.

BACKGROUND: Risk of transfusion-transmitted bacterial sepsis has been substantially reduced by a bacterial surveillance program (BST). However, new problems emerge as asymptomatic bacteremia is detected in blood donors. Streptococcus bovis bacteremia, which is known to associate with infective endocarditis and colonic carcinoma, is an example. STUDY DESIGN AND METHODS: A retrospective study was conducted to examine the demographic and clinical outcome of this group of donors. All confirmed culture-positive cases under the BST were retrieved and those donors with S. bovis bacteremia were contacted for follow-up. Viable culture samples were sent for detailed microbiologic analysis. RESULTS: From 1998 to 2012, a total of 16 donors were found to have S. bovis bacteremia, giving an estimated prevalence of 1 in 110,800 donations. They consisted of nine men and seven women with median age of 43.5 years. Eight donors had undergone colonoscopy with colonic carcinoma detected in two and benign adenoma in four. Five of the 16 isolates could be retrieved for 16S DNA sequencing. Four were identified as S. gallolyticus ssp. pasteurianus and one as S. gallolyticus ssp. gallolyticus. The two patients with colonic carcinoma had one each of subspecies pasteurianus and gallolyticus. CONCLUSION: The findings highlight a close association of S. bovis and colonic carcinoma. We recommend prompt donor follow-up if S. bovis bacteremia is detected. Besides, all confirmed S. bovis should be fully characterized by molecular technique.

Use of electroacupuncture to accelerate the antidepressant action of selective serotonin reuptake inhibitors: a single-blind, randomised, controlled study.

1. Patients treated with dense cranial electroacupuncture stimulation (DCEAS) had a significantly greater reduction in the 17-item Hamilton Rating Scale for Depression scores and clinically significant response to treatment than those having sham acupuncture (19.4% vs.8.8%). 2. Neither sham acupuncture nor DCEAS had effects on the platelet serotonin system. 3. In the early phase of selective serotonin reuptake inhibitor treatment for depressed patients, DCEAS could be used as an additional therapy. 4. Neurobiological mechanisms responsible for DCEAS effects warrant further investigation using neuroimaging.

The relationship between body dissatisfaction and attentional bias to thin bodies in Malaysian Chinese and White Australian women: a dot probe study.

Studies suggest that an attentional bias to thin bodies is common among those with high levels of body dissatisfaction, which is a risk factor for, and symptom of, various eating disorders. However, these studies have predominantly been conducted in Western countries with body stimuli involving images of White people. In a preregistered study, we recruited 150 Malaysian Chinese women and 150 White Australian women for a study using standardized images of East Asian and White Australian bodies. To measure attentional bias to thin bodies, participants completed a dot probe task which presented images of women who self-identified their ethnicity as East Asian or as White Australian. Contrary to previous findings, we found no evidence for an association between body dissatisfaction and attentional bias to thin bodies. This lack of association was not affected by participant ethnicity (Malaysian Chinese versus White Australian) or ethnic congruency between participants and body stimuli (own-ethnicity versus other-ethnicity). However, the internal consistency of the dot probe task was poor. These results suggest that either the relationship between body dissatisfaction and attentional bias to thin bodies is not robust, or the dot probe task may not be a reliable measure of attentional bias to body size.

Current-pulse-induced enhancement of transient photodetective effect in tilted manganite film.

A current-pulse-induced enhancement effect of transient photovoltage has been discovered in tilted manganite La(2/3)Ca(1/3)MnO(3) film at room temperature. Here, by applying a pulsed current stimulus before pulse laser irradiation, we observed a significant enhancement of more than 50% in photovoltaic sensitivity. The current-pulse-induced photovoltaic enhancement can be tuned not only by the stimulating current value but also by the stimulating time. Such enhancement is time-sensitive and reproducible. This electrically induced effect, observed at room temperature, has both the benefit of a discovery in materials properties and the promise of applications for thin film manganites in photodetectors.

Risk factor analysis of hepatitis C virus infection among Chinese blood donors in Hong Kong.

BACKGROUND: Hepatitis C virus (HCV) infection can result in serious hepatic complications and hence potentially significant burden to the society. Despite advances in technology, transfusion-transmitted HCV infection still exists. To further minimise the risk, a review on the epidemiology of HCV infection among Chinese blood donors in Hong Kong was conducted. METHODS: All donations associated with HCV infection confirmed by positive serologic diagnosis with or without molecular confirmation during the period from 2003 to 2010 were studied. Demographic data were retrieved and risk factors were identified. RESULTS: HCV infection was more commonly seen in first time donors and donors with blood transfusion history before the availability of HCV testing, whereas its association with intravenous drug use was noted to be decreasing. Interestingly, half of the HCV positive donors in 2008-2010 were young donors aged below 21, which was also the group with the highest rate of no known source of infection. CONCLUSION: A subgroup of younger age donors was found to have no known risk factor. To develop better screening strategy, it is recommended that a more detailed analysis of this group of donors is required.

Significant bacterial contamination risk reduction with the use of diversion pouch.

BACKGROUND: Significant efforts have been made towards bacterial risk minimization by limiting the chance of bacteria entering into collected blood, detecting its presence and eliminating them by pathogen reduction technology. Improved skin disinfection and the use of diversion pouch are effective upstream measures to reduce the risk of bacterial sepsis. Here we report on our experience with the use of blood bags with diversion pouch. MATERIALS AND METHODS: An observational study was performed to compare the bacterial contamination rate for two periods of time, i.e. before and after introduction of diversion pouch into blood bags. The incidence of bacterial contamination was monitored by the existing bacterial surveillance programme using pooled samples from 5 units of random donor platelets underwent aerobic culture in the BacT/ALERT 3D system. RESULTS: Between 1 June 2004 and 31 May 2006 (blood bag without diversion pouch), 50 (0·0213%) out of 234,252 units of random donor platelets were found to have bacteria on culture whereas 15 (0·0057%) isolates out of 262,156 units were found from 1 June 2007 to 31 May 2009 (after diversion pouch was introduced). Overall, there was an 85% reduction in bacterial contaminated risk due to skin flora (P < 0·0001) but an increasing trend of detection of non skin flora such as Streptococcus bovis was noted. CONCLUSION: Integration of diversion pouch into blood bags to divert the first 30 mL blood during blood collection on top of the current skin disinfection protocol can significantly reduce the risk of bacterial contamination.

Enhanced lateral photovoltaic effect in the p-n heterojunction composed of manganite and silicon by side irradiation for position sensitive detecting.

Lateral photovoltaic effect has been studied in p-La0.67Ca0.33MnO3/n-Si heterojunction. Under illumination of continuous 808 nm laser beam on the film surface, a transient photovoltaic overshoot accompanied with the steady signal was observed when the laser turned off and on. The open-circuit photovoltage had a linear dependence on illuminated position, and the sensitivity reached 0.75 mV mW(-1) mm(-1) for steady value and 6.25 mV mW(-1) mm(-1) for the transient peak value. Especially, an enhancement in position detecting sensitivity was observed when the interface of this heterojunction was irradiated, which were 1.25 mV mW(-1) mm(-1) (steady value) and 26.0 mV mW(-1) mm(-1) (peak value). This work demonstrates a novel way to increase sensitivity for manganite-based position sensitive detectors.

Human skin Langerhans cells are targets of dengue virus infection.

Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine. Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by mosquitoes of the genus Aedes, we undertook experiments to determine whether human dendritic cells (DCs) were permissive for the growth of DV. Initial experiments demonstrated that blood-derived DCs were 10-fold more permissive for DV infection than were monocytes or macrophages. We confirmed this with human skin DCs (Langerhans cells and dermal/interstitial DCs). Using cadaveric human skin explants, we exposed skin DCs to DV ex vivo. Of the human leukocyte antigen DR-positive DCs that migrated from the skin, emigrants from both dermis and epidermis, 60-80% expressed DV antigens. These observations were supported by histologic findings from the skin rash of a human subject who received an attenuated tetravalent dengue vaccine. Immunohistochemistry of the skin showed CD1a-positive DCs double-labeled with an antibody against DV envelope glycoprotein. These data demonstrate that human skin DCs are permissive for DV infection, and provide a potential mechanism for the transmission of DV into human skin.

High-sensitivity photovoltaic responses in manganite-based heterojunctions on Si substrates for weak light detection.

We have fabricated and characterized a weak light photodetector in a heterojunction composed of manganite La0.4Ca0.6MnO3 and n-type Si. High-sensitivity photoresponse properties were investigated. The responsivities of open-circuit photovoltage and short-circuit photocurrent reach ∼1000 V/mJ and ∼30 A/mJ, respectively, without any amplification bias under irradiation by 20-ps-wide and 355, 532, and 1064-nm-wavelength laser pulses in nanojoule to microjoule order. The present results demonstrate that the manganite-based heterojunction on Si substrate has potential applications in weak light detection from ultraviolet to near-infrared light.