Systemic lupus erythematosus in a multiethnic US cohort: XXXIV. Deficient mannose‐binding lectin exon 1 polymorphisms are associated with cerebrovascular but not with other arterial thrombotic events

Objective

To study the association between deficient mannose‐binding lectin (MBL) genotypes and arterial thrombotic events in systemic lupus erythematosus (SLE).

Methods

Patients with SLE of Hispanic, African American, and Caucasian ethnicity from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Arterial thrombotic events (myocardial infarction, angina, coronary artery bypass graft surgery, stroke, claudication, gangrene, or tissue loss and/or peripheral arterial thrombosis) that occurred after diagnosis were recorded. Genotyping for MBL gene polymorphisms was performed and their distribution was compared between patients who did and did not have thrombotic events.

Results

There were 58 events (21 cardiovascular, 27 cerebrovascular, and 10 peripheral vascular) in 48 patients. Patients who had thrombotic events were older and were more likely to be smokers, to have more severe disease, and to have accrued more damage overall. Also, a larger proportion of these patients had C‐reactive protein values in the highest quintile of distribution. No significant difference in arterial thrombotic events was found in patients homozygous for MBL‐deficient alleles compared with others. Similar results were seen within ethnic groups. Caucasians who developed potential thrombotic events exhibited a higher frequency of MBL‐deficient alleles, but the difference was not statistically significant for all events together or for cardiovascular and cerebrovascular events combined. However, when only the cerebrovascular events were considered, the difference became statistically significant.

Conclusion

Age, smoking, and measures of activity and damage were associated with arterial thrombotic events in patients with SLE, but MBL‐deficient genotypes were not, with cerebrovascular events in Caucasians being the exception. The relationship between MBL‐variant alleles and arterial thrombotic events may exist only within select ethnic groups and event types.

     

Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon,Nicaragua

Noroviruses are associated with one fifth of diarrheal illnesses globally and are not yet preventable with vaccines. Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. Metagenomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. Taxonomic and functional diversities of gut microbiomes were profiled at time points before, during, and after norovirus infection. Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. When disturbed by AGE, Gammaproteobacteria dominated, particularly Pseudomonas species. Alpha diversity increased but the genes involved in carbohydrate metabolism and glycan biosynthesis decreased. After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness.     

Global Trends in Norovirus Genotype Distribution among Children with Acute Gastroenteritis

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016–2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.     

Primary culture of venom glands from the Brazilian armed spider, Phoneutria nigriventer (Araneae, Ctenidae).

Phoneutria spider venoms are a rich source of bioactive components. The limited amounts of crude material available, however, can be considered as a major hindrance for a faster development in the field. In the present study, we attempted to establish primary cultures of venom glands of Phoneutria nigriventer as an alternative, in vitro source of venom. Three different developmental stages were tried as starting materials: whole embryo (inside the cocoon), nymph (early after cocoon hatching) and young adult (1 year after cocoon hatching). The embryonic cells remained in suspension in the primary cultures, with no signs of adhesion or differentiation, for about 6 months. Nevertheless, this culture was useful for the first chromosome C-banding of Phoneutria. An average of 29+/-1 acrocentric chromosomes were found. Striated muscle cells were the only kind of cells in the culture of venom glands from Phoneutria nymphs. The most promising results were achieved with 1-year-old specimens. Besides muscle, adherent epithelial cells were also obtained in culture. Although these cells remained in culture for a short time (up to 48 h) immunochemical analysis of the culture supernatant evidenced the presence of Phoneutria venom components. This can be considered as a first step toward the functional cultures of venom glands of Phoneutria spiders.     

Effects of government registration on unprotected sex amongst female sex workers in Tijuana; Mexico

BackgroundSex work is partially regulated in Tijuana, but little is known of its health effects. A recent behavioural intervention amongst female sex workers (FSWs) decreased incidence of HIV/STIs by 40%. We evaluated effects of sex worker regulation on condom use amongst FSWs randomized to this intervention.MethodsFSWs aged ≥18 years who reported unprotected sex with ≥1 client in the last 2 months and whether they were registered with Tijuana's Municipal Health Department underwent a brief, theory-based behavioural intervention to increase condom use. At baseline and 6 months, women underwent interviews and testing for HIV, syphilis, Chlamydia trachomatis and Neisseria gonorrhoeae. Negative binomial regression was used to determine the effect of registration on numbers of unprotected sex acts and cumulative HIV/STI incidence.ResultsOf 187 women, 83 (44%) were registered. Lack of registration was associated with higher rates of unprotected sex (rate ratio: 1.7, 95% CI: 1.2–2.3), compared to FSWs who were registered, after controlling for potential confounders.ConclusionsRegistration predicted increased condom use amongst FSWs enrolled in a behavioural intervention. Public health programmes designed to improve condom use amongst FSWs may benefit from understanding the impact of existing regulation systems on HIV risk behaviours.     

Solid Tumor Differentiation Therapy – Is It Possible?

Genetic and epigenetic events within a cell which promote a block in normal development or differentiation coupled with unregulated proliferation are hallmarks of neoplastic transformation. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells. The promise of differentiation-based therapy as a viable treatment modality is perhaps best characterized by the addition of retinoids in the treatment of acute promyelocytic leukemia (APML) revolutionizing the management of APML and dramatically improving survival. However, interest and application of differentiationbased therapy for the treatment of solid malignancies have lagged due to deficiencies in our understanding of differentiation pathways in solid malignancies. Over the past decade, a differentiation-based developmental model for solid tumors has emerged providing insights into the biology of various solid tumors as well as identification of targetable pathways capable of re-activating blocked terminal differentiation programs. Furthermore, a variety of agents including retinoids, histone deacetylase inhibitors (HDACI), PPARγ agonists, and others, currently in use for a variety of malignancies, have been shown to induce differentiation in solid tumors. Herein we discuss the relevancy of differentiation-based therapies in solid tumors, using soft tissue sarcomas (STS) as a biologic and clinical model, and review the preclinical data to support its role as a promising modality of therapy for the treatment of solid tumors.