A Population-Based Study of Pregnancy and Delivery Characteristics Among Women with Vulvodynia

Introduction: To examine pregnancy and delivery characteristics of women with and without vulvodynia. Methods: The authors analyzed 227 vulvodynia cases that were less than 45 years old at pain onset; controls were age matched 1:1 to cases and had no history of vulvar pain. Pregnancy and delivery events were assessed after age at first vulvar pain onset (the reference age) in cases and a matched age in controls. Results: The authors observed no significant difference between cases and controls in achieving pregnancy after reference age. Also, no difference in pregnancy outcome was observed between cases and controls (P = 0.87). There was an indication that cases were more likely to receive a Cesarean section delivery (P = 0.07). In addition, 37.1% of cases who had vaginal delivery versus 11.3% of controls (P < 0.01) reported pain at 2 months postpartum. Comparing only women with vulvodynia, women who had intermittent pain versus constant pain were more than twice as likely to have a pregnancy (adjusted odds ratio 2.26, 95% CI 1.10–4.60). Conclusions: Women with vulvodynia may be as likely as other women to carry their pregnancy to birth; however, they may experience higher rates of Cesarean section delivery and could reflect a selection towards those women with vulvodynia who have inconsistent pain

Mucosal versus muscle pain sensitivity in provoked vestibulodynia

An estimated 8.3%—16% of women experience vulvovaginal discomfort during their lifetime. Frequently these patients report provoked pain on contact or with attempted intercourse, commonly referred to as provoked vestibulodynia (PVD). Despite the burden of this condition, little is known about its potential etiologies including pelvic floor muscular dysfunction and mucosal components. This knowledge would be beneficial in developing targeted therapies including physical therapy

Effect of Treatment, during Primary Infection, on Establishment and Clearance of Cellular Reservoirs of HIV-1

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatmen

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one&nbsp;kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways

Human plasmacytoid dendritic cells secrete high levels of IFNα and are thus implicated in the activation of NK cells. Activated NK cells are characterised by the up-regulation of CD69 and MHC class II DR expression, secretion of IFN γ and enhanced cytotoxicity. We show that pDC mediate these processes by different mechanisms, some of which overlap. Human NK cells were analysed after co-culture with immature or CpG-matured blood pDC or with supernatant from these cells. Maximal CD69 expression by NK cells was mediated by supernatant from mature pDC and did not require pDC contact. Up-regulation was due in part to IFNα but also to factors in IFNα negative supernatant from immature DC. HLA-DR expression was independent of secreted molecules but required contact with immature or mature DC. Enhanced NK cytotoxicity, measured by killing of K562 targets and expression of CD107a, was mediated by multiple factors including type I IFN, supernatant from immature pDC cultures and contact with immature or mature pDC. These factors act cumulatively to enhance cytotoxcity. Thus different parameters of pDC mediated NK cell activation are regulated by distinct pathways

Special considerations for studies of extracellular vesicles from parasitic helminths: A community‐led roadmap to increase rigour and reproducibility

Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found in the phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function and physiology. Emerging evidence supports a role for helminth-derived EVs in these processes and highlights EVs as an important participant in cross-phylum communication. While the mammalian EV field is guided by a community-agreed framework for studying EVs derived from model organisms or cell systems [e.g., Minimal Information for Studies of Extracellular Vesicles (MISEV)], the helminth community requires a supplementary set of principles due to the additional challenges that accompany working with such divergent organisms. These challenges include, but are not limited to, generating sufficient quantities of EVs for descriptive or functional studies, defining pan-helminth EV markers, genetically modifying these organisms, and identifying rigorous methodologies for in vitro and in vivo studies. Here, we outline best practices for those investigating the biology of helminth-derived EVs to complement the MISEV guidelines. We summarise community-agreed standards for studying EVs derived from this broad set of non-model organisms, raise awareness of issues associated with helminth EVs and provide future perspectives for how progress in the field will be achieved

Religiosity, materialism, consumer environmental predisposition. Some insights on vegan purchasing intentions in Italy

This paper explores the effects of environmental predisposition on purchasing intentions. The proposed model considers religiosity as a determinant of consumer environmental predisposition, adopting a multidimensional view entailing both intrinsic and extrinsic religiosity. Further, the effects of materialism are investigated, as it has been recognized as one of the most relevant hampering factors in determining consumer environmental predispositions and behaviors. Such factors appear intimately related, as materialism has been indicated as largely antithetical with respect to religion. Literature has suggested religiosity to be a key determinant of consumer environmental predispositions and behaviors. This might be even more important for specific, environmentally relevant consumer lifestyles. This work is hence set within vegan consumption. Veganism has been mostly related to specific religious beliefs (like Buddhism), according to which it represents a core component of larger worldviews. A structural equation model is proposed, based on a sample of 842 Italian consumers. Results show that religiosity exerts some effect on consumer environmental predisposition, and that, in turn, such predisposition determines vegan purchasing intentions. A split model is then proposed considering Christian and Buddhist consumers. Results of multigroup analysis show that religious influxes on consumer environmental predispositions might vary according to different religious faiths. Given the lack of previous empirical research, results of this study require further validation; still, they might provide some insights for managers, as markets related to environmentally relevant products and services are exhibiting a sustained growth