The Role of Gender Empowerment on Reproductive Health Outcomes in Urban Nigeria

To date, limited evidence is available for urban populations in sub-Saharan Africa, specifically research into the association between urban women’s empowerment and reproductive health outcomes. The objective of this study is to investigate whether women’s empowerment in urban Nigerian settings is associated with family planning use and maternal health behaviors. Moreover, we examine whether different effects of empowerment exist by region of residence. This study uses baseline household survey data from the Measurement, Learning and Evaluation Project for the Nigerian Urban Reproductive Health Initiative being implemented in six major cities. We examine four dimensions of empowerment: economic freedom, attitudes towards domestic violence, partner prohibitions and decision-making. We determine if the empowerment dimensions have different effects on reproductive health outcomes by region of residence using multivariate analyses. Results indicate that more empowered women are more likely to use modern contraception, deliver in a health facility and have a skilled attendant at birth. These trends vary by empowerment dimension and by city/region in Nigeria. We conclude by discussing the implications of these findings on future programs seeking to improve reproductive health outcomes in urban Nigeria and beyond.     

Telemental health training in the Veterans Administration Puget Sound Health Care System

As a pioneer of training in the field of psychology, the Veterans Affairs (VA) HealthCare System serves as a leader in the training in and provision of Telemental Health (TMH) services in the United States. To meet goals toward continued expansion of these services, the VA TMH training program includes both web-based didactic courses and a skills competency test at a basic level with supervision and consultation in TMH for more advanced training and is available to staff psychologists and psychologist trainees. Despite these efforts, barriers for training in and implementation of TMH occur at the provider, system, and patient level. At the national level, the VA is actively working to resolve these barriers and we share site-specific examples implemented by the VA Puget Sound Health Care System promoting access through TMH team to further address barriers to training and implementation.     

N‐chlorotaurine and its analogues N,N‐dichloro‐2,2‐dimethyltaurine and N‐monochloro‐2,2‐dimethyltaurine are safe and effective bactericidal agents in ex vivo corneal infection models

Purpose: N‐chlorotaurine (NCT) and its analogues N‐monochloro‐2,2‐dimethyltaurine (NVC‐612) and N‐dichloro‐2,2‐dimethyltaurine (NVC‐422) are new anti‐infectives for topical treatment for conjunctivitis. The aim of this study was to show that these compounds are safe in an EpiOcular model and effective in corneas infected ex vivo. Methods: Corneal buttons were excised from porcine eyes. In 183 of the 229 corneas, erosion and artificial superficial stromal incision were induced. They were bathed in suspensions of Pseudomonas aeruginosa or Staphylococcus aureus for 24 hr at 37°C and incubated in solutions of the test substances at 37°C and pH 7.1. Subsequently, they were subjected to histology (n = 20) or homogenized followed by quantitative bacterial cultures (n = 209). Ocular irritation was tested using the EpiOcular? tissue system (MatTek Corporation). Results: Bacterial accumulations were detected histologically both on the corneal surface and also in the anterior third of the stroma of incised corneal buttons. All three test compounds at a concentration of 55 mm (equals 1% NCT) reduced the bacterial counts of P. aeruginosa and S. aureus by approximately 5 log10 after 60‐ and 120‐min incubation, respectively. Significant killing was observed as early as after 5‐min incubation. Also intrastromal bacteria were inactivated. In the EpiOcular? tissue model, NCT, NVC‐422 and NVC‐612 had no or very low potential to irritate corneal tissue. Conclusion: N‐chlorotaurine, NVC‐422 and NVC‐612 are non‐irritating in cornea and kill P. aeruginosa and S. aureus, even following penetration into the deeper corneal stromal layers.     

Acute kidney injury in paediatric patients with sickle cell disease is associated with increased morbidity and resource utilization

Renal disease is a common complication experienced by patients with sickle cell disease (SCD), though the epidemiology of acute kidney injury (AKI) in paediatric patients and its impact on long-term renal outcomes is unclear. We utilized the Pediatric Health Information System (PHIS) to identify inpatient encounters of paediatric patients with SCD admitted for vaso-occlusive pain crisis (VOC). Overall, 1·4% of patients experienced at least one episode of AKI and 2·5% of admissions were complicated by AKI. Patients with at least one episode of AKI were more likely to be adolescents or young adults at the time of their initial admission, had increased rates of admission to the ICU, longer lengths of stay, increased costs of hospitalization, increased risk of readmission and increased rates of SCD-related comorbidities. Generalized estimating equation modelling demonstrated that increasing age, history of hypertension, history of haematuria and history of chronic kidney disease were associated with increased odds of developing AKI, though hydroxycarbamide use (OR 0·64, 95% CI 0·44–0·94) was protective. Episodes of AKI during hospitalization in children with SCD are associated with increased morbidity and utilization of hospital resources. Increasing the use of hydroxycarbamide may decrease the likelihood of this complication.     

Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling

Toll-like receptor signaling and subsequent activation of NF-κB– and MAPK-dependent genes during infection play an important role in antimicrobial host defense. The YopJ protein of pathogenic Yersinia species inhibits NF-κB and MAPK signaling, resulting in blockade of NF-κB–dependent cytokine production and target cell death. Nevertheless, Yersinia infection induces inflammatory responses in vivo. Moreover, increasing the extent of YopJ-dependent cytotoxicity induced by Yersinia pestis and Yersinia pseudotuberculosis paradoxically leads to decreased virulence in vivo, suggesting that cell death promotes anti-Yersinia host defense. However, the specific pathways responsible for YopJ-induced cell death and how this cell death mediates immune defense against Yersinia remain poorly defined. YopJ activity induces processing of multiple caspases, including caspase-1, independently of inflammasome components or the adaptor protein ASC. Unexpectedly, caspase-1 activation in response to the activity of YopJ required caspase-8, receptor-interacting serine/threonine kinase 1 (RIPK1), and Fas-associated death domain (FADD), but not RIPK3. Furthermore, whereas RIPK3 deficiency did not affect YopJ-induced cell death or caspase-1 activation, deficiency of both RIPK3 and caspase-8 or FADD completely abrogated Yersinia-induced cell death and caspase-1 activation. Mice lacking RIPK3 and caspase-8 in their hematopoietic compartment showed extreme susceptibility to Yersinia and were deficient in monocyte and neutrophil-derived production of proinflammatory cytokines. Our data demonstrate for the first time to our knowledge that RIPK1, FADD, and caspase-8 are required for YopJ-induced cell death and caspase-1 activation and suggest that caspase-8–mediated cell death overrides blockade of immune signaling by YopJ to promote anti-Yersinia immune defense.The innate immune response forms the first line of defense against pathogens. Microbial infection triggers the activation of pattern recognition receptors, such as Toll-like receptors (TLRs) on the cell surface or cytosolic nucleotide binding domain leucine-rich repeat family proteins (NLRs) (1). TLRs induce NF-κB and MAPK signaling to direct immune gene expression, whereas certain NLRs direct the assembly of multiprotein complexes known as inflammasomes that provide platforms for caspase-1 or -11 activation (2). Active caspase-1 and -11 mediate cleavage and secretion of the IL-1 family of proteins and a proinflammatory cell death termed pyroptosis. However, microbial pathogens can interfere with various aspects of innate immune signaling, and the mechanisms that mediate effective immune responses against such pathogens remain poorly understood. Pathogenic Yersiniae cause diseases from gastroenteritis to plague and inject a virulence factor known as YopJ, which inhibits NF-κB and MAPK signaling pathways in target cells (2–4). YopJ activity inhibits proinflammatory cytokine production (4) and induces target cell death (5). YopJ activity induces processing of multiple caspases, including caspases-8, -3, -7, and -1 (6–8). Nevertheless, Yersinia-infected cells exhibit properties of both apoptosis and necrosis (9, 10), and no specific cellular factors have been identified as being absolutely required for YopJ-induced caspase activation and cell death. We previously found that the inflammasome proteins NLR CARD 4 (NLRC4), NLR Pyrin 3 (NLRP3), and apoptosis-associated speck-like protein containing a CARD (ASC), are dispensable for YopJ-induced caspase-1 processing and cell death (11). Thus, additional pathways likely mediate YopJ-induced caspase-1 activation and cell death.Death receptors, such as TNF receptor and Fas, mediate caspase-8–dependent apoptosis via a death-inducing signaling complex containing receptor-interacting serine/threonine kinase 1 (RIPK1), caspase-8, and Fas-associated death domain (FADD) (12, 13). Whether these proteins are required for Yersinia-induced cell death, and whether this death contributes to antibacterial immune responses, is not known. The Ripoptosome complex, which contains RIPK1, FADD, caspase-8, as well as RIPK3 and cFLIP, regulates apoptosis, programmed necrosis, and survival in response to various stimuli including signaling by the TLR adaptor TRIF (14, 15). Because YopJ-induced cell death is inhibited in the absence of either TLR4 or TRIF (17) we sought to determine whether YopJ-dependent cell death and caspase-1 activation is regulated by caspase-8 or RIPK3 and to define the role of YopJ-dependent cell death in host defense. Here, we describe a previously unappreciated requirement for RIPK1, FADD, and caspase-8, but not RIPK3, in YopJ-induced caspase-1 activation and cell death. Critically, loss of caspase-8 in the hematopoietic compartment resulted in a failure of innate immune cells to produce proinflammatory cytokines in response to Yersinia infection and severely compromised resistance against Yersinia infection. Our data suggest that caspase-8–mediated cell death in response to blockade of NF-κB/MAPKs by YopJ allows for activation of host defense against Yersinia infection. This cell death may thus enable the immune system to override inhibition of immune signaling by microbial pathogens.