Inhibition of sialidase activity and cellular invasion by the bacterial vaginosis pathogen Gardnerella vaginalis.

Bacterial vaginosis is a genital tract infection, thought to be caused by transformation of a lactobacillus-rich flora to a dysbiotic microbiota enriched in mixed anaerobes. The most prominent of these is Gardnerella vaginalis (GV), an anaerobic pathogen that produces sialidase enzyme to cleave terminal sialic acid residues from human glycans. Notably, high sialidase activity is associated with preterm birth and low birthweight. We explored the potential of the sialidase inhibitor Zanamavir against GV whole cell sialidase activity using methyl-umbelliferyl neuraminic acid (MU-NANA) cleavage assays, with Zanamavir causing a 30% reduction in whole cell GV sialidase activity (p < 0.05). Furthermore, cellular invasion assays using HeLa cervical epithelial cells, infected with GV, demonstrated that Zanamivir elicited a 50% reduction in cell association and invasion (p < 0.05). Our data thus highlight that pharmacological sialidase inhibitors are able to modify BV-associated sialidase activity and influence host-pathogen interactions and may represent novel therapeutic adjuncts.

Variation in Access to Kidney Transplantation Across Renal Programs in Ontario, Canada.

In the United States, kidney transplant rates vary significantly across end-stage renal disease (ESRD) networks. We conducted a population-based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1-, 5-, and 10-year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for "healthy" dialysis patients (aged 18-50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow-up of 11 years). Among 23 022 chronic dialysis patients, the 10-year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8-10.7%) to 31.4% (95% CI 16.5-47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2-0.5) to 1.5 (95% CI 1.4-1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.

Trabecular bone score in kidney transplant recipients.

SUMMARY: It is uncertain whether bone mineral density (BMD) can accurately predict fracture in kidney transplant recipients. Trabecular bone score (TBS) provides information independent of BMD. Kidney transplant recipients had abnormal bone texture as measured by lumbar spine TBS, and a lower TBS was associated with incident fractures in recipients. INTRODUCTION: Trabecular bone score (TBS) is a texture measure derived from dual energy X-ray absorptiometry (DXA) lumbar spine images, providing information independent of bone mineral density. We assessed characteristics associated with TBS and fracture outcomes in kidney transplant recipients. METHODS: We included 327 kidney transplant recipients from Manitoba, Canada, who received a post-transplant DXA (median 106 days post-transplant). We matched each kidney transplant recipient (mean age 45 years, 39% men) to three controls from the general population (matched on age, sex, and DXA date). Lumbar spine (L1-L4) DXA images were used to derive TBS. Non-traumatic incident fracture (excluding hand, foot, and craniofacial) (n = 31) was assessed during a mean follow-up of 6.6 years. We used multivariable linear regression models to test predictors of TBS, and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) per standard deviation decrease in TBS to express the gradient of risk. RESULTS: Compared to the general population, kidney transplant recipients had a significantly lower lumbar spine TBS (1.365 ± 0.129 versus 1.406 ± 0.125, P < 0.001). Multivariable linear regression revealed that receipt of a kidney transplant was associated with a significantly lower mean TBS compared to controls (-0.0369, 95% confidence interval [95% CI] -0.0537 to -0.0202). TBS was associated with fractures independent of the Fracture Risk Assessment score including BMD (adjusted HR per standard deviation decrease in TBS 1.64, 95% CI 1.15-2.36). CONCLUSION: Kidney transplant recipients had abnormal bone texture as assessed by TBS and a lower lumbar spine TBS was associated with fractures in recipients.

The laws that affect abortion in the United States and their impact on women's health.

Abortion has been a hotly contested political issue since the mid 1960s, when states began liberalizing their abortion laws. Recent Supreme Court rulings, such as Rust vs. Sullivan, the retirement of two liberal Supreme Court justices and the battle over Louisiana's abortion legislation have created new fervor on both fronts of the battle. All health care providers who care for women need to be cognizant of the current abortion laws and the factors that influence the abortion decision. These factors include the different levels of health risk and financial implications posed by continued pregnancy or abortion. Historically, numerous court cases have influenced women's health care, and reviews of several significant cases are provided. The Webster vs. Reproductive Health Services decision was the first case that directly challenged the Roe vs. Wade decision. The Webster decision enables states to have greater authority in writing their own abortion laws. Individual state laws can vary greatly, so it is vitally important for providers to know and understand the laws of their state.

PIP: Changing abortion laws means changing medical practices. Roe v. Wade (1973) established and absolute constitutional protection against state regulation in 1st trimester abortions, increasing abortion safety by allowing professionals working in sterile environments to perform abortions. In Planned Parenthood of Central Missouri v. Danforth (1976) the Supreme Court invalidated a spousal/parental consent requirement. In Harris v. McRae (1980) the Court upheld the Hyde Amendment prohibiting the use of Medicaid funds for abortions. In City of Akron v. Akron Center for Reproductive Health Inc. (1983) the Court held as unconstitutional the requirement of hospitalization for all 2nd and 3rd trimester abortions, that unmarried minors under 15 obtain parental consent, that physicians give detailed lectures on fetal status, and that women wait 24 hours before an abortion. In Thornburgh v. American College of Obstetricians and Gynecologists (1986) the Court held as unconstitutional mandatory statements about alternatives to abortion, and particularized medical risks. Webster v. Reproductive Health Service (1989) upheld a state's right to protect life beginning at conception, withhold use of public employees, facilities, and funds for counseling a woman about, or performing, a nontherapeutic abortion, to encourage birth over abortion. Subsequent cases established a state's right to require parental notification for minor's abortion when a judicial hearing exists as an alternative. Rust v. Sullivan (1991) upheld regulations prohibiting medical staff from talking about abortion with family planning patients when the facility receives funding under Title X of the Public Health Service Act, and requires objective physical and financial separation of facilities from programs that offer abortion information. These regulations have been denounced by medical groups for compromising ethics. While the Senate passed a bill allowing such talk about abortion, President Bush promises a veto. Abortion is still legal in every state, but each state has its own laws.