Experiences of the Flint Water Crisis Among Reproductive-Age Michigan Women in Communities Outside of Flint: Differences by Race and Ethnicity

We sought to understand how women in Michigan communities outside of Flint experienced the Flint water crisis, an avoidable public health disaster widely attributed to structural racism. Using survey data from 950 Michigan women aged 18–45 from communities outside of Flint, we examined racial and ethnic differences in personal connections to Flint, perceived knowledge about the water crisis, and beliefs about the role of anti-Black racism in the water crisis factors that could contribute to poor health via increased psychological stress. We found that White (OR = 0.32; 95% CI: 0.22, 0.46) and Hispanic (OR = 0.21; 95% CI: 0.09, 0.49) women had lower odds than Black women of having family or friends who lived in Flint during the water crisis. Compared to Black women, White women were less likely to be moderately or very knowledgeable about the water crisis (OR = 0.58; 95% CI: 0.41, 0.80). White women (OR = 0.26; 95% CI: 0.18, 0.37), Hispanic women (OR = 0.38; 95% CI: 0.21, 0.68), and women of other races (OR = 0.28; 95% CI: 0.15, 0.54) were less likely than Black women to agree that the water crisis happened because government officials wanted to hurt Flint residents. Among those who agreed, White women (OR = 0.47; 95% CI: 0.30, 0.74) and women of other races (OR = 0.33; 95% CI: 0.12, 0.90) were less likely than Black women to agree that government officials wanted to hurt people in Flint because most residents are Black. We conclude that the Flint water crisis was a racialized stressor, with potential implications for the health of reproductive-age Black women

Value of hospital antimicrobial stewardship programs [ASPs]:a systematic review

Abstract Background Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods An update to the Dik et al. systematic review (2000–2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014–31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500–1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range:$2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention

Exacerbated leishmaniasis caused by a viral endosymbiont can be prevented by immunization with Its viral capsid

Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as a potent innate immunogen, aggravating lesional inflammation and development in mice. In humans, the presence of LRV in Leishmania guyanensis and in L. braziliensis was significantly correlated with poor treatment response and symptomatic relapse. So far, no clinical effort has used LRV for prophylactic purposes. In this context, we designed an original vaccine strategy that targeted LRV nested in Leishmania parasites to prevent virus-related complications. To this end, C57BL/6 mice were immunized with a recombinant LRV1 Leishmania guyanensis viral capsid polypeptide formulated with a T helper 1-polarizing adjuvant. LRV1-vaccinated mice had significant reduction in lesion size and parasite load when subsequently challenged with LRV1+ Leishmania guyanensis parasites. The protection conferred by this immunization could be reproduced in naïve mice via T-cell transfer from vaccinated mice but not by serum transfer. The induction of LRV1 specific T cells secreting IFN-γ was confirmed in vaccinated mice and provided strong evidence that LRV1-specific protection arose via a cell mediated immune response against the LRV1 capsid. Our studies suggest that immunization with LRV1 capsid could be of a preventive benefit in mitigating the elevated pathology associated with LRV1 bearing Leishmania infections and possibly avoiding symptomatic relapses after an initial treatment. This novel anti-endosymbiotic vaccine strategy could be exploited to control other infectious diseases, as similar viral infections are largely prevalent across pathogenic pathogens and could consequently open new vaccine opportunities

Societal-level versus individual-level predictions of ethical behavior: a 48-society study of collectivism and individualism

Is the societal-level of analysis sufficient today to understand the values of those in the global workforce? Or are individual-level analyses more appropriate for assessing the influence of values on ethical behaviors across country workforces? Using multi-level analyses for a 48-society sample, we test the utility of both the societal-level and individual-level dimensions of collectivism and individualism values for predicting ethical behaviors of business professionals. Our values-based behavioral analysis indicates that values at the individual-level make a more significant contribution to explaining variance in ethical behaviors than do values at the societal-level. Implicitly, our findings question the soundness of using societal-level values measures. Implications for international business research are discussed

Effect of sex and fatigue on single leg squat kinematics in healthy young adults

Background: The single-leg squat (SLS) test is widely used in screening for musculoskeletal injury risk. Little is known, however, of lower limb, pelvis, and trunk kinematics of SLS performance or the effect of sex and fatigue. Our aim was to determine sex differences and the influence of fatigue on SLS kinematics in healthy young adults. Methods: We recruited 60 healthy men and women between the ages of 20 and 40 years. Three-dimensional kinematic data was collected for SLSs with a ten-camera VICON motion analysis system (Oxford Metrics, UK) before and after a lower limb fatiguing exercise regime. One-way ANCOVA was used to make sex comparisons of kinematic parameters and repeated measures ANOVA was used to determine the effect of fatigue and the interaction with sex. Results: 30 men (25.6 ± 4.8 years) and 30 women (25.1 ± 3.8 years) volunteered to participate. Peak pelvic rotation (3.9 ± 4.1 vs. 7.7 ± 6.2 deg, P = 0.03), peak hip internal rotation (−1.8 ± 5.7 vs. 3.0 ± 7.3 deg, P = 0.02), hip adduction range (11.7 ± 4.8 vs. 18.3 ± 6.7 deg, P = 0.004), and hip rotation range (10.7 ± 3.9 vs. 13.0 ± 4.2 deg, P = 0.04) were smaller for men than for women. Likewise, distance of mediolateral knee motion (180 ± 51 vs. 227 ± 50 mm, P = 0.001) was shorter for men than for women. The kinematic response to fatigue was an increase in trunk flexion, lateral flexion and rotation, an increase in pelvic tilt, obliquity and rotation, and an increase in hip flexion and adduction range (P ≤0.05). Conclusions: Sex differences in SLS kinematics appear to apply only at the hip, knee, and pelvis and not at the trunk. Fatiguing exercise, however, produces changes at the trunk and pelvis with little effect on the knee.Griffith Health, School of Allied Health SciencesFull Tex

In Vitro Downregulation of Matrix Metalloproteinase-9 in Rat Glial Cells by CCR5 Antagonist Maraviroc: Therapeutic Implication for HIV Brain Infection

BACKGROUND: Matrix metalloproteinases (MMPs) released by glial cells are important mediators of neuroinflammation and neurologic damage in HIV infection. The use of antiretroviral drugs able to combat the detrimental effect of chronic inflammation and target the exaggerated MMP activity might represent an attractive therapeutic challenge. Recent studies suggest that CCR5 antagonist maraviroc (MVC) exerts immunomodulant and anti-inflammatory activity beyond its anti-HIV properties. We investigated the in vitro effect of MVC on the activity of MMPs in astrocyte and microglia cultures. METHODOLOGY/PRINCIPAL FINDINGS: Primary cultures of rat astrocytes and microglia were activated by exposure to phorbol myristate acetate (PMA) or lypopolysaccharide (LPS) and treated in vitro with MVC. Culture supernatants were subjected to gelatin zymography and quantitative determination of MMP-9 and MMP-2 was done by computerized scanning densitometry. MMP-9 levels were significantly elevated in culture supernatants from both LPS- and PMA-activated astrocytes and microglia in comparison to controls. The treatment with MVC significantly inhibited in a dose-dependent manner the levels and expression of MMP-9 in PMA-activated astrocytes (p<0,05) and, to a lesser extent, in PMA-activated microglia. By contrast, levels of MMP-2 did not significantly change, although a tendency to decrease was seen in PMA-activated astrocytes after treatment with MVC. The inhibition of levels and expression of MMP-9 in PMA-activated glial cells did not depend on cytotoxic effects of MVC. No inhibition of MMP-9 and MMP-2 were found in both LPS-activated astrocytes and microglia. CONCLUSIONS: The present in vitro study suggests that CCR5 antagonist compounds, through their ability to inhibit MMP-9 expression and levels, might have a great potential for the treatment of HIV-associated neurologic damage

Structural basis for inhibition of homologous recombination by the RecX protein

The RecA/RAD51 nucleoprotein filament is central to the reaction of homologous recombination (HR). Filament activity must be tightly regulated in vivo as unrestrained HR can cause genomic instability. Our mechanistic understanding of HR is restricted by lack of structural information about the regulatory proteins that control filament activity. Here, we describe a structural and functional analysis of the HR inhibitor protein RecX and its mode of interaction with the RecA filament. RecX is a modular protein assembled of repeated three-helix motifs. The relative arrangement of the repeats generates an elongated and curved shape that is well suited for binding within the helical groove of the RecA filament. Structure-based mutagenesis confirms that conserved basic residues on the concave side of RecX are important for repression of RecA activity. Analysis of RecA filament dynamics in the presence of RecX shows that RecX actively promotes filament disassembly. Collectively, our data support a model in which RecX binding to the helical groove of the filament causes local dissociation of RecA protomers, leading to filament destabilisation and HR inhibition