Strain-Specific Targeting and Destruction of Cells by Prions.

Prion diseases are caused by the disease-specific self-templating infectious conformation of the host-encoded prion protein, PrPSc. Prion strains are operationally defined as a heritable phenotype of disease under controlled conditions. One of the hallmark phenotypes of prion strain diversity is tropism within and between tissues. A defining feature of prion strains is the regional distribution of PrPSc in the CNS. Additionally, in both natural and experimental prion disease, stark differences in the tropism of prions in secondary lymphoreticular system tissues occur. The mechanism underlying prion tropism is unknown; however, several possible hypotheses have been proposed. Clinical target areas are prion strain-specific populations of neurons within the CNS that are susceptible to neurodegeneration following the replication of prions past a toxic threshold. Alternatively, the switch from a replicative to toxic form of PrPSc may drive prion tropism. The normal form of the prion protein, PrPC, is required for prion formation. More recent evidence suggests that it can mediate prion and prion-like disease neurodegeneration. In vitro systems for prion formation have indicated that cellular cofactors contribute to prion formation. Since these cofactors can be strain specific, this has led to the hypothesis that the distribution of prion formation cofactors can influence prion tropism. Overall, there is evidence to support several mechanisms of prion strain tropism; however, a unified theory has yet to emerge.

Not Speaking the Same Language-Lower Portal Use for Limited English Proficient Patients in the Los Angeles Safety Net.

BACKGROUND: With the expansion of online patient portals linked to electronic health records in safety-net health care settings, we need more data on the use of these websites by patients with limited English proficiency (LEP) in order to guide their continued design, implementation, and evaluation as portals for the underserved. METHODS: Cross-sectional portal data for the Los Angeles County Department of Health Services, the second largest safety-net system in the nation. We examined differences in portal use across language (English vs. non-English/LEP), covering four years since implementation. RESULTS: Of 425,281 patients assigned to primary care as of March 2019, 55,190 (13%) unique portal enrollments were registered. Among 54,981 portal users, LEP users had lower adjusted odds of using an active portal function (e.g., medication refill) vs. English-speakers. CONCLUSIONS: Even among those registered to access portals, these websites are underused, particularly by LEP patients. All systems must facilitate use for these populations, especially for time-saving active functions, which can improve outcomes. Health systems must prioritize design/usability as a factor to counter LEP underuse.

Portals of Change: How Patient Portals Will Ultimately Work for Safety Net Populations.

Despite the implementation of internet patient portals into the safety net after the introduction of the Affordable Care Act in the United States, little attention has been paid to the process of engaging vulnerable patients into these portals. The portal is a health technology tool that was developed with a mainstream, English-speaking audience in mind. Thus, there are valid concerns that such technologies will actually exacerbate health care disparities, conferring further advantages to the already advantaged. In this paper, we describe a framework for portal engagement (awareness, registration, and use) among safety net patients. We incorporate the experiences in the Los Angeles County Department of Health Services to illustrate important contextual factors for portal outreach in our safety net. Finally, we discuss considerations for moving forward with health technology in the safety net as the next version of patient portals are being developed.

Long-Term Consequences of Intimate Partner Abuse on Physical Health, Emotional Well-Being, and Problem Behaviors.

This study examines the physical health, emotional well-being, and problem behavior outcomes associated with intimate partner abuse (IPA) victimization and perpetration experiences by analyzing a nationally representative, prospective, and longitudinal sample of 879 men and women collected from the National Youth Survey Family Study (NYSFS) and assessed across a period of 9 years from 1993 to 2003. Using multivariate regression techniques, it was found that both men and women experience numerous negative outcomes associated with their IPA victimization and perpetration experiences. Implications of these findings are discussed, as are the study's limitations, and future research directions.

Life Course and Intergenerational Continuity of Intimate Partner Aggression and Physical Injury: A 20-Year Study.

The objective of this study is to examine continuity of intimate partner aggression (IPA), which is defined as repeated annual involvement in IPA, across respondents' life course and into the next generation, where it may emerge among adult children. A national, longitudinal, and multigenerational sample of 1,401 individuals and their adult children is analyzed. Annual data on IPA severity and physical injury were collected by the National Youth Survey Family Study across a 20-year period from 1984 to 2004. Three hypotheses and biological sex differences are tested and effect sizes are estimated. First, findings reveal evidence for life course continuity (IPA is a strong predictor of subsequent IPA), but the overall trend decreases over time. Second, intergenerational continuity is documented (parents' IPA predicts adult children's IPA), but the effect is stronger for female than for male adult children. Third, results from combined and separate, more restrictive, measures of victimization and perpetration are nearly identical except in the intergenerational analyses. Fourth, evidence for continuity is not found when assessing physical injury alone. Together, these findings imply that some but not all forms of IPA are common, continuous, and intergenerational. Life course continuity appears stronger than intergenerational continuity.

Parental predictors of children's animal abuse: findings from a national and intergenerational sample.

This study examines the intra- and intergenerational links between intimate partner violence (IPV) and animal abuse by analyzing a national, longitudinal, and multigenerational sample of 1,614 individuals collected by the National Youth Survey Family Study from 1990 to 2004. Using multilevel random-intercept regression modeling, parents' own history of animal abuse is predictive of their later involvement in IPV perpetration and victimization, net of important controls. In turn, parents' IPV violent perpetration (but not violent victimization) is predictive of their children's history of animal abuse-measured 14 years later. Intergenerational continuity of animal abuse, however, is not significant. Implications of these findings are discussed, as are the study's limitations, and future research directions.

Intergenerational continuity of substance use.

Guided by rigorous methodology and a life-course perspective, the goal of this research is to address a gap in current knowledge on whether, when, and how strongly intergenerational continuity of substance use exists when examining age-equivalent and developmentally specific stages of the life course. Annual self-reported substance use measures were analyzed from a prospective, longitudinal, and nationally representative sample that originally consisted of 1,725 respondents and their families, who were then interviewed over a 27-year period from 1977 to 2004. Findings from multilevel random-intercept regression models provide support for intergenerational continuity when substance use occurs in emerging adulthood but not when limited to adolescence. Implications, limitations, and future research directions are discussed.

Educational strategies for rural new graduate registered nurses.

Rural health care facilities are geographically remote, tend to be small, and often possess limited resources. Although newly graduated registered nurses are important to the work force of many rural communities, maintaining a formal preceptorship/mentorship program within a rural hospital may prove difficult as a result of limited resources. Unfortunately, the new graduate may become overwhelmed by the many expectations for clinical practice and the facility can experience high turnover rates of new graduate hires. This article explores the unique traits of the rural hospital and the new graduate nurse as well as the pros and cons of a formal preceptorship program within a rural setting. Constructivist learning theory is used to develop practical teaching strategies that can be used by the preceptor and the new graduate. These strategies are inexpensive, yet effective, and are feasible for even the smallest of facilities.

Gliding resistance and triggering after venting or A2 pulley enlargement: a study of intact and repaired flexor tendons in a cadaveric model.

PURPOSE: This study compared the effect of 2 techniques of pulley management--venting and pulley enlargement (complete A2 incision with pulley repair and sheath closure using a retinacular graft)--on gliding resistance and on the incidence of triggering following zone 2 flexor tendon repairs in human cadaver specimens. METHODS: In vitro gliding resistance and the incidence of triggering were determined in 10 human cadaver specimens under 5 progressive conditions: (1) intact, (2) tendon repair (both tendons cut and repaired with the sheath intact), (3) condition 2 plus 50% venting of the distal A2 pulley, (4) condition 2 with venting extended to 66% of distal A2, and (5) condition 4 plus pulley enlargement. Triggering was determined in the same specimens by 2 computational algorithms that detected force changes in the load cells used to measure gliding resistance. RESULTS: Tendon repair increased gliding resistance from the intact condition by an average of 229%. Gliding resistance was reduced in conditions 3, 4, and 5 from the repair condition by 15%, 25%, and 22%, respectively. Triggering commenced with tendon repair in some specimens, and its incidence increased with 50% venting. Further venting reduced triggering, but not as effectively as pulley enlargement did. CONCLUSIONS: In this cadaveric study, venting and pulley enlargement reduce gliding resistance by equivalent amounts. Triggering persisted despite venting. The surgeon should carefully examine tendon repairs for free gliding. Pulley enlargement might be more effective than venting in reducing the incidence of triggering.

Primary tendon sheath enlargement and reconstruction in zone 2: an in vitro biomechanical study on tendon gliding resistance.

PURPOSE: To investigate our hypothesis that primary pulley enlargement and repair using an extensor retinaculum graft will reduce tendon repair gliding resistance. The benefit of pulley enlargement has been tested in experimental animals, but its effect on gliding resistance in vitro using human fingers is not known. METHODS: In vitro gliding resistance in the proximal tendon sheaths (A1 through A3) was measured and compared in 7 cadaver fingers using the method of Uchiyama and colleagues at a fixed 50 degrees over the proximal sheath under 3 conditions: (1) intact tendons with intact proximal sheath; (2) laceration and 2-strand core plus running epitenon repair of the tendons with intact sheath; and (3) repaired tendons with enlargement of the A2 pulley and adjacent proximal sheath by incision and repair with an extensor retinacular graft. Results were analyzed statistically. RESULTS: Gliding resistance increased from an average of 0.44 N +/- 0.07 in the intact condition to an average of 1.51 N +/- 0.23 (a mean increase of 243%) when the tendons were cut and repaired. Enlarging the proximal sheath by sheath incision and graft repair reduced the gliding resistance from the repair condition to 1.04 N +/- 0.15 (a mean decrease of 31%). These changes are statistically significant. CONCLUSIONS: In vitro, repaired tendons had a greater resistance to gliding than that of the intact tendons through the proximal sheath when tested by the method of Uchiyama and colleagues. Enlargement and repair with an extensor retinacular graft of the A2 pulley and adjacent sheath significantly reduced resistance to repaired tendon gliding. These findings support further investigation into the concept that primary pulley enlargement may improve tendon function after repair.

Lunate revascularization with artery implantation and bone grafting.

Treatment of Kienböck's disease encompasses a wide array of options. Proper staging is the first step to successful treatment. Revascularization of the lunate remains a viable option for the treatment of Lichtman stage II or IIIA Kienböck's disease. In this article, we review the indications for and the surgical technique used with a modified Hori procedure (vascular pedicle insertion with structural distal radius graft) for revascularization of the lunate.