Sampling Males Who Inject Drugs in Haiphong,Vietnam: Comparison of Time-Location and Respondent-Driven Sampling Methods

Accurate measurements of HIV prevalence and associated risk factors among hidden and high-risk groups are vital for program planning and implementation. However, only two sampling methods are purported to provide representative estimates for populations without sampling frames: time-location sampling (TLS) and respondent-driven sampling (RDS). Each method is subject to potential biases and questionable reliability. In this paper, we evaluate surveys designed to estimate HIV prevalence and associated risk factors among people who inject drugs (PWID) sampled through TLS versus RDS. In 2012, males aged ≥16 years who reported injecting drugs in the previous month and living in Haiphong, Vietnam, were sampled using TLS or RDS. Data from each survey were analyzed to compare HIV prevalence, related risk factors, socio-demographic characteristics, refusal estimates, and time and expenditures for field implementation. TLS (n = 432) and RDS (n = 415) produced similarly high estimates for HIV prevalence. Significantly lower proportions of PWID sampled through RDS received methadone treatment or met an outreach worker. Refusal estimates were lower for TLS than for RDS. Total expenditures per sample collected and number of person-days of staff effort were higher for TLS than for RDS. Both survey methods were successful in recruiting a diverse sample of PWID in Haiphong. In Vietnam, surveys of PWID are conducted throughout the country; although the refusal estimate was calculated to be much higher for RDS than TLS, RDS in Haiphong appeared to sample PWID with less exposure to services and required fewer financial and staff resources compared with TLS.     

Synthesis and antibacterial properties of a novel magnetic nanocomposite prepared from spent pickling liquors and polyguanidine

Magnetic nanoparticles have received much interest for their application in wastewater treatment because of their easy retrieval and reuse. However, the methods used to synthesise high saturation magnetization magnetic nanoparticles require expensive and pure precursors. In the current study, we explore the potential for using spent pickling liquor, a wastewater solution from steel factories, as the iron precursor for preparing iron oxide nanoparticles. Here, magnetic Fe₃O₄ nanoparticles were synthesized via the oxidation–precipitation of spent pickling liquors using a saturated solution of calcium hydroxide at room temperature. The Fe₃O₄ nanoparticles were then modified with antibacterial polyguanidine to form a nanocomposite. It was found that monodisperse magnetic Fe₃O₄ nanoparticles with a size in the range 20–30 nm and a high saturation magnetization value of 73.9 emu g⁻¹ were synthesised. The Fe₃O₄ nanoparticles were successfully encapsulated with polyguanidine to form an Fe₃O₄/polyguanidine nanocomposite. FT-IR and TGA analysis results indicated the presence of the polymer on the Fe₃O₄ surface and the polymer content in the nanocomposite was about 15% (w/w). The Fe₃O₄/polyguanidine nanocomposite exhibited strong antibacterial activity against Escherichia coli (E. coli), demonstrating its potential for use in disinfecting wastewater.

An Fe₃O₄/polyguanidine nanocomposite with strong antibacterial activity was prepared from Fe₃O₄ nanoparticles, using spent pickling liquors as the iron source, which were then encapsulated with polyguanidine.     

Lowering platelet count threshold to 10,000/µL for peripherally inserted central catheter placement safely conserves blood products

Annals of Hematology - Despite the low risk of peripherally inserted central catheter (PICC) insertion-related bleeding, the practice of administering prophylactic platelets varies greatly....     

Gallbladder motility in Crohn disease: influence of disease localization and bowel resection

BACKGROUND: Patients with Crohn disease (CD) have an increased risk of developing gallstones. Among other factors, gallbladder motility may have a role in the pathogenesis of gallstone formation. We have evaluated whether gallbladder motor function is affected in Crohn disease with special emphasis on the influence of disease localization and previous bowel resection. METHODS: Thirty-seven patients (20 females and 17 males, age 36 +/- 2 years) with inactive Crohn disease (CDAI < 150) were studied: 15 patients after ileocecal resection and 22 non-operated patients; 12 had small bowel disease and 10 had large bowel disease. Nineteen healthy subjects (10 female; 9 male, age 30 +/- 2 years) served as controls. Gallbladder volumes were measured in the fasting state and at regular intervals for 2 h after ingestion of a solid meal (780 kcal). Blood samples were drawn at regular intervals for determination of cholecystokinin (CCK) and peptide YY (PYY). RESULTS: Fasting gallbladder volumes were significantly (P < 0.05) reduced in patients with large bowel disease (20.8 +/- 2.1 ml) or after ileocecal resection (18.3 +/- 2.4 ml) compared to patients with small bowel disease (28.0 +/- 2.1 ml) and controls (27.2 +/- 1.8 ml). Fasting plasma CCK levels were significantly (P < 0.05) higher in patients with large bowel disease or after ileocecal resection compared to patients with small bowel disease and controls. Postprandial gallbladder emptying and endogenous plasma CCK and PYY secretion in patients with Crohn disease were not different from controls. CONCLUSIONS: Fasting gallbladder volume is decreased and fasting plasma CCK levels are increased in patients with Crohn disease of the large bowel and patients after ileocecal resection. Postprandial gallbladder motility, CCK and PYY release were not affected in patients with Crohn disease.     

Transplant of rhesus-positive bone marrow in a rhesus-negative woman having anti-rhesus D alloantibodies

A woman affected by acute myeloblastic leukemia was grafted with HLA A, B and D compatible rhesus-positive bone marrow from her brother. Before grafting, she had anti-D alloantibodies (1/512 IAT, 2.9 micrograms/ml). To prevent the destruction of donor red blood cells, four plasma exchanges and a conditioning regimen (total-body irradiation 800 rad, cyclophosphamide, methotrexate) were carried out to decrease anti-D from 2.9 to less than 0.02 micrograms/ml on day 0. The anti-D level was 0.8 micrograms/ml on day 12 and was decreased to 0.2 micrograms/ml by eight plasma exchanges until day 35. Anti-D antibodies were undetectable with Lalezari's technique on day 45. Engraftment was obtained on day 25 (3,000 leukocytes/mm3 and 50% erythroblasts in bone marrow). The patient died from aspergillosis and graft-versus-host disease on day 54. This observation shows that an engraftment of rhesus-positive bone marrow in a recipient with anti-D antibody is possible.     

Transthyretin Is Dysregulated in Preeclampsia,and Its Native Form Prevents the Onset of Disease in a Preclinical Mouse Model

Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinol, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia.Preeclampsia occurs in 5% to 8% of pregnancies worldwide and is a major cause of fetal and maternal morbidity and mortality.^1–3 It is a heterogeneous disease with varied presentations from mild self-limited hypertension and proteinuria to severe forms with significant end-organ dysfunction and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets).³ Although the cause of preeclampsia and its appropriate treatment remain elusive, this syndrome has been proposed to reflect at least two stages of complications during pregnancy. These begin with preclinical manifestations at the maternal-fetal interface, followed by systemic clinical symptoms.^1,2 Hypertension, proteinuria, and edema, with a variable degree of fetal growth restriction, are the cardinal features of preeclampsia.³ Because the placenta is the nutritional and immunological gateway to normal fetal development and pregnancy outcome, placenta-related events are believed to be central to the pathogenesis of this disease. Evidence exists for the release of disease-initiating molecules into maternal circulation that triggers the clinical symptoms.^1,4 Placental and systemic anomalies reflected by circulating placental debris, inflammation, impaired remodeling of spiral arteries, placental hypoxia/ischemia, excess production of anti-angiogenic factors [soluble fms-like tyrosine kinase-1 (sFlt-1)], and soluble endoglin (sEng), and angiotensin receptor autoantibodies have all emerged as contributors to the pathophysiological characteristics of preeclampsia.^2,4–14Preeclampsia has remained enigmatic because of lack of well-defined etiology and animal models. Although normal mice do not develop preeclampsia spontaneously, mouse models have been judged to be particularly useful to uterine diseases and pregnancy complications because many similarities in female reproduction and placentation have been identified between the two species.¹⁵ Moreover, their tractable genetics provide an effective way to probe mechanisms more deeply than many other species.^15–17 We recently showed that sera from preeclamptic women could function as a source of novel causative factors that induced hypertension, proteinuria, and kidney pathological characteristics, as well as intrauterine growth restriction (IUGR), in IL-10^−/− mice in a pregnancy-specific manner.¹⁸ IL-10 functions as a potent vascular and anti-inflammatory cytokine and has been shown to be present at significantly reduced levels in preeclampsia placental tissue.^19,20 Preeclampsia serum (PES) was found to disrupt endovascular cross talk between trophoblasts and endothelial cells and to induce placental hypoxia and excess production of sFlt-1 and sEng,¹⁸ soluble factors known to precipitate maternal symptoms.^21,22 These results from our serum-based humanized mouse model suggest that the pathophysiological characteristics of preeclampsia are more complex than previously thought and are likely to involve interactions and dysregulation of multiple factors. By using serum proteomic screening by surface-enhanced laser-desorption ionization-time-of-flight (SELDI-TOF), our results suggest that PES contains a reduced abundance of transthyretin, a plasma transport protein for the thyroid hormone, thyroxine, and retinol-binding protein.²³ More important, transthyretin has been widely studied for its role in amyloid diseases associated with protein misfolding and aggregation, resulting in deposits of toxic, fibrillar aggregates in specific organs.^24–26 Dysregulated or reduced transthyretin has also been implicated in Alzheimer disease, and overexpression of a wild-type human transthyretin transgene has been shown to ameliorate the disease in the transgenic murine model of human Alzheimer disease.^27,28 Transthyretin in its native form assumes a homotetrameric quaternary configuration (approximately 14 kDa per monomer). Post-translational modifications of the monomer result in detection of several isoforms.²⁹ Circulating transthyretin is also a validated marker of malnutrition and has a putative role in oocyte maturation and inflammation.^30–32 Although the presence of transthyretin during implantation in mice and in the placenta and trophoblasts in humans has been reported,^33,34 its functional role in normal pregnancy or adverse pregnancy outcomes has not been recognized. We hypothesize that transthyretin in preeclampsia is structurally and functionally dysregulated and contributes to the onset of this serious pregnancy complication. Herein, we present complementary in vitro and in vivo approaches, which show that endogenously altered transthyretin is a preeclampsia-causing agent and that native transthyretin has the ability to block the onset of preeclampsia-like features.     

Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam

The antigenicity of the influenza A virus hemagglutinin is responsible for vaccine efficacy in protecting pigs against swine influenza virus (SIV) infection. However, the antigenicity of SIV strains currently circulating in Japan and Vietnam has not been well characterized. We examined the antigenicity of classical H1 SIVs, pandemic A(H1N1)2009 (A(H1N1)pdm09) viruses, and seasonal human-lineage SIVs isolated in Japan and Vietnam. A hemagglutination inhibition (HI) assay was used to determine antigenic differences that differentiate the recent Japanese H1N2 and H3N2 SIVs from the H1N1 and H3N2 domestic vaccine strains. Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus. A Vietnamese H1N2 SIV, whose H1 gene originated from a human strain in the mid-2000s, reacted poorly with post-infection ferret serum against human vaccine strains from 2000-2010. These results provide useful information for selection of optimal strains for SIV vaccine production.     

Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association with Viral Load,Independent of Symptoms

Background

SARS-CoV-2 infection leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches.

Methods

SARS-CoV-2-infected patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal wash and serum specimens from a subset of patients were collected to measure viral load, IgA specific for the S1 domain of the spike protein, and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms.

Results

Samples from 13 SARS-CoV-2-infected patients and six controls were analyzed. We found an increase in CXCL10 and IL-6, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection also induced CCL2 and GM-CSF, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia. Some patients had S1-specific IgA in the nasal cavity while almost none had IgG.

Conclusion

The nasal epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this mild COVID-19 cohort, anosmia was not associated with increases in any locally produced cytokines.

     

Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study

Group A Streptococcus (GAS) M protein is an important virulence factor and potential vaccine antigen, and constitutes the basis for strain typing (emm-typing). Although >200 emm-types are characterized, structural data were obtained from only a limited number of emm-types. We aim to evaluate the sequence diversity of near-full-length M proteins from worldwide sources and analyse their structure, sequence conservation and classification. GAS isolates recovered from throughout the world during the last two decades underwent emm-typing and complete emm gene sequencing. Predicted amino acid sequence analyses, secondary structure predictions and vaccine epitope mapping were performed using MUSCLE and Geneious software. A total of 1086 isolates from 31 countries were analysed, representing 175 emm-types. emm-type is predictive of the whole protein structure, independent of geographical origin or clinical association. Findings of an emm-type paired with multiple, highly divergent central regions were not observed. M protein sequence length, the presence or absence of sequence repeats and predicted secondary structure were assessed in the context of the latest vaccine developments. Based on these global data, the M6 protein model is updated to a three representative M protein (M5, M80 and M77) model, to aid in epidemiological analysis, vaccine development and M protein-related pathogenesis studies.