Two Coselected Distal Mutations in HIV-1 Reverse Transcriptase (RT) Alter Susceptibility to Nonnucleoside RT Inhibitors and Nucleoside Analogs.

Two mutations, G112D and M230I, were selected in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) by a novel nonnucleoside reverse transcriptase inhibitor (NNRTI). G112D is located near the HIV-1 polymerase active site; M230I is located near the hydrophobic region where NNRTIs bind. Thus, M230I could directly interfere with NNRTI binding but G112D could not. Biochemical and virological assays were performed to analyze the effects of these mutations individually and in combination. M230I alone caused a reduction in susceptibility to NNRTIs, while G112D alone did not. The G112D/M230I double mutant was less susceptible to NNRTIs than was M230I alone. In contrast, both mutations affected the ability of RT to incorporate nucleoside analogs. We suggest that the mutations interact with each other via the bound nucleic acid substrate; the nucleic acid forms part of the polymerase active site, which is near G112D. The positioning of the nucleic acid is influenced by its interactions with the "primer grip" region and could be influenced by the M230I mutation.IMPORTANCE Although antiretroviral therapy (ART) is highly successful, drug-resistant variants can arise that blunt the efficacy of ART. New inhibitors that are broadly effective against known drug-resistant variants are needed, although such compounds might select for novel resistance mutations that affect the sensitivity of the virus to other compounds. Compound 13 selects for resistance mutations that differ from traditional NNRTI resistance mutations. These mutations cause increased sensitivity to NRTIs, such as AZT.

Daily Spiritual Experiences of Nurse Educators and Relationship to Depression and Health.

This research describes the first reported assessment of spirituality in nurse educators. Faculty members at a public university in a southern U.S. state participated in a study to investigate the relationship between daily spiritual experiences (DSE), self-reported health, and depression. All participants viewed themselves as spiritual, had a religious affiliation, and recognized a difference between spirituality and religiosity. Many who reported spiritual experiences at least daily rated their health as good or excellent; those reporting less frequent DSE reported more depressive symptoms. Nurse educators' self-awareness of spirituality is important as they prepare future nursing professionals who will integrate spirituality into healthcare.

Mutations in the thumb allow human immunodeficiency virus type 1 reverse transcriptase to be cleaved by protease in virions.

Although human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has been extensively studied, there are still significant questions about the effects of mutations on the maturation and stability of RT. We show here that a significant fraction (>80%) of the single point mutations we generated in the thumb subdomain of HIV-1 (RT) affect the stability of RT in virions. Fragments of the unstable mutant RTs can be detected in Western blots of virion proteins; however, the degree of degradation varies. The titers of the mutants whose virions contain degraded RTs are reduced. Some, but not all, of the unstable RT thumb subdomain mutants we analyzed have a temperature-sensitive phenotype. A preliminary survey of mutations in other subdomains of RT shows that some of these mutations also destabilize RT. The stability of the RT mutants is enhanced by the addition of a protease inhibitor, suggesting that the viral protease plays an important role in the degradation of the mutant RTs. These results confirm and extend earlier reports of mutations that affect the stability of RT in virions. The data suggest that the stability of a mutant RT in virions could be a major factor in determining the virus titer and, by extension, viral fitness, which could affect whether a mutation in RT is acceptable to the virus.

Making a difference: initiating and maintaining a faith-based free health clinic.

This article is a summary of the challenges, struggles, and barriers that a group of churches encountered in developing a faith-based free health clinic. From the inception, this clinic has existed for the uninsured whose total household income aligns with the 2009 Fedral Poverty Guidelines. A voluntary interview with the executive director of The Good Samaritan Clinic revealed the experiential evolvement of this free health clinic. Numerous examples are shared that depict how this clinic has made a difference in the lives of many people.

The provision of spiritual care by registered nurses on a maternal-infant unit.

PURPOSE: This study explores the spirituality, spiritual well-being (SWB), and spiritual care provision of registered nurses on a maternal-infant unit. METHODS: Data collection instruments included a demographic and spiritual care form, Spiritual Perspective Scale (SPS), and Spiritual Well-Being Scale (SWBS) to address the study's research questions. FINDINGS: Significant positive correlations were found between SPS and SWBS as well as religious well-being (RWB) and existential well-being (EWB; subscales of SWBS). Religious attendance was significantly correlated with SPS, SWBS, and RWB but not EWB. Frequency of spiritual assessment themes was first encounter and when needed, whereas reaching up and reaching out described their provision of spiritual care. CONCLUSION: The sample was highly spiritual, spiritually well, and provided varied spiritual care. IMPLICATIONS: More spiritual care research is needed. Content on providing spiritual care must be enhanced within nursing curricula as well as with nurses in practice.

Mutations in human immunodeficiency virus type 1 reverse transcriptase that make it sensitive to degradation by the viral protease in virions are selected against in patients.

Mutations in the thumb subdomain of reverse transcriptase (RT) of HIV-1 can cause this enzyme to be degraded in virions by the viral protease (PR). Many of these mutations confer a temperature-sensitive phenotype on RT and viral replication. The degradation of RT by PR appears to take place after Gag-Pol has been processed. We show here that mutations in other parts of RT, including the RNase H domain, can make RT PR-sensitive and temperature-sensitive. These data explain why some mutations in the RNase H domain, which had little or no effect on the polymerase activity of purified recombinant RT, had a profound effect on viral titer. Because the PR-sensitive phenotype significantly reduced viral titer, we previously suggested that these mutations would be selected against in patients. We also show that RT mutations that are known to confer a temperature sensitive phenotype are rarely found in the Stanford database.

Prenatal predictors of intimate partner abuse.

OBJECTIVE: To determine the prevalence of physical abuse and to identify predictors of abuse in a sample of pregnant women in Alabama. DESIGN: A prospective, correlational design was used. SETTING: Participants were drawn from four unrelated public and private prenatal clinics in Tuscaloosa, Alabama. PARTICIPANTS: The sample consisted of pregnant women between 20 and 34 years of age who had no high-risk health conditions and who initiated prenatal care during the 1st trimester. Four hundred thirty-nine ethnically diverse women completed interviews during the 1st and 3rd trimesters and had available birth outcomes. MAIN OUTCOME MEASURE: Physical abuse during pregnancy was measured by a modified version of the Abuse Assessment Screen. Bivariate and multiple logistic regressions yielded significant associations between individual predictors and physical abuse during pregnancy. RESULTS: The findings showed that 10.9% of the sample experienced physical abuse during the current pregnancy and 62% reported the intimate partner or former intimate partner to be the perpetrator. The best predictive model included stressful life events, depression, lack of faith in God or a higher power, and lack of contraceptive use.

Can senior volunteers deliver reminiscence and creative activity interventions? Results of the legacy intervention family enactment randomized controlled trial.

CONTEXT: Palliative care patients and their family caregivers may have a foreshortened perspective of the time left to live, or the expectation of the patient's death in the near future. Patients and caregivers may report distress in physical, psychological, or existential/spiritual realms. OBJECTIVES: To conduct a randomized controlled trial examining the effectiveness of retired senior volunteers (RSVs) in delivering a reminiscence and creative activity intervention aimed at alleviating palliative care patient and caregiver distress. METHODS: Of the 45 dyads that completed baseline assessments, 28 completed postintervention and 24 completed follow-up assessments. The intervention group received three home visits by RSVs; control group families received three supportive telephone calls by the research staff. Measures included symptom assessment and associated burden, depression, religiousness/spirituality, and meaning in life. RESULTS: Patients in the intervention group reported a significantly greater reduction in frequency of emotional symptoms (P=0.02) and emotional symptom bother (P=0.04) than the control group, as well as improved spiritual functioning. Family caregivers in the intervention group were more likely than control caregivers to endorse items on the Meaning of Life Scale (P=0.02). Only improvement in intervention patients' emotional symptom bother maintained at follow-up after discontinuing RSV contact (P=0.024). CONCLUSION: Delivery of the intervention by RSVs had a positive impact on palliative care patients' emotional symptoms and burden and caregivers' meaning in life. Meaningful prolonged engagement with palliative care patients and caregivers, possibly through alternative modes of treatment delivery such as continued RSV contact, may be necessary for maintenance of therapeutic effects.

Mutations in HIV-1 reverse transcriptase cause misfolding and miscleavage by the viral protease.

Previous work on mutations in the thumb of HIV-1 reverse transcriptase (RT) showed that the majority of the mutant RTs were degraded (by the viral protease) to various extents in virions. This degradation was, in most cases, temperature sensitive, and presumably was due to a partial unfolding of the protein at 37°C. We used recombinant proteins to investigate the effects of the mutations on the thermal stability and proteolytic degradation of RT. Both subunits contribute to the stability of RT. In general, the differences in stability between the mutants and WT were greater if the mutation was in p51 rather than p66. Expressing the Pol polyprotein containing the RT mutants in Escherichia coli produced results similar to what was seen in virions; the mutant RTs were misfolded and/or degraded at 37°C, but were better folded and processed at 30°C.

Spiritual well-being, anxiety, and depression in antepartal women on bedrest.

This descriptive correlational study examined relationships among anxiety, depression, and spiritual well-being (SWB) in three groups of women (non-pregnant, normal pregnancy, high-risk pregnancy on bedrest). Women in each group completed a demographic survey, a Spiritual Well-Being Scale, and depression and anxiety subscales from the Abbreviated Scale for the Assessment of Psychosocial Status in Pregnancy. All groups (N = 180) demonstrated significant, inverse relationships among SWB, anxiety, and depression. Findings emphasize the importance of obstetrical nurses screening pregnant women to evaluate emotional health, especially in high risk pregnancies. Collaboration with mental health nurses may be useful in developing interventions to improve a woman's SWB, reduce anxiety and depression, and improve pregnancy outcomes.