Family Caregiving of Patients With Heart Failure and Vascular Dementia in Rural Appalachia: A Mixed-Methods Study.

INTRODUCTION: Vascular dementia and heart failure (HF) are common co-existing conditions among adult populations. Each condition requires extensive home caregiving from family caregivers, especially those in rural Appalachia. This study aimed to assess caregivers' burden and their physical and mental health status, as well as explore their experiences and needs. METHODS: This study used an exploratory mixed-methods design combining quantitative and qualitative research (N = 20 caregivers). We collected data using questionnaires, short-answered interviews, and focus group discussions. The multivariable generalized linear model (GLiM) was used to analyze quantitative data; content analysis was used for qualitative data. RESULTS: The average age of family caregivers was 64.95 years. The generalized linear model showed that the caregiving burden was associated with caregivers' depression/anxiety (r = 0.68, P < .001) and their number of dementia caregiving years (r = 0.54, P < .05). Caregivers' poor physical health status was associated with better preparedness for HF and dementia home caregiving (r = 0.52, P < .05) and male caregivers (r = -0.46, P < .01). Caregivers' mental health status was associated with depression/anxiety (r = -0.80, P < .001). The qualitative data identified key caregiving themes: emotional impact and physical demands of caregiving, lack of help in rural areas, dealing with multiple disease progression, and relationship changes with their loved ones. CONCLUSION: Caregiving burden was associated with caregivers' home care responsibilities and the need for support. Nurse-led home caregiving preparedness interventions tailored for family caregivers of patients with HF and dementia in rural areas are recommended.

You're Not Who You Used to Be: A Case Report of a Family Living with Heart Failure and Vascular Dementia.

Heart failure and vascular dementia have similar underlying pathologies, so it is not uncommon for one condition to exist in the presence of the other. In-home management of each condition is challenging for patients and their family caregivers, but when both conditions are present, those challenges are amplified. The purpose of this case report is to describe one family's experience managing heart failure and vascular dementia at home. A mixed method of semistructured interviews and short surveys was used to examine the health status and well-being of the patient and family caregiver. Data were derived from individual interviews and standardized measures. Survey results revealed the patient had worsening dementia, poor heart failure-related quality of life, poor spiritual well-being, depression, and diminished self-care. The caregiver reported poor physical and mental health. Interview data revealed frustration dealing with worsening symptoms, inadequate information about disease progression, and fear of an unknown future. Additionally, the patient suggested strategies to deal with challenges. Families managing heart failure and vascular dementia need easy-to-understand education from healthcare providers, on-going assessments, and early referrals to support services including those provided by social workers and chaplains.

Being treated with compassion by nursing students in their baccalaureate program.

BACKGROUND/PURPOSE: Compassion is an essential component of nursing education. Having nursing students describe situations in which they were treated with compassion may offer guidance for faculty. The purpose of the study was to uncover themes in descriptions of undergraduate nursing students who described self as being treated with compassion during their Baccalaureate nursing education. METHOD: Conventional content analysis was the method used in the study. RESULTS: Four themes represent the findings. These are: 1) compassion began in situations where students were lost, confused, frightened, and discouraged; 2) emerged in a relationship focused on being recognized, valued, and understood; 3) developed with the other taking charge, listening carefully, remaining patient, and maintaining presence; and 4) ended with feelings of success, comfort, and belonging. CONCLUSION: The findings offer a description of compassion from the students' point of view. An approach for teaching compassion based on the study findings is proposed.

Orchestration of ErbB3 signaling through heterointeractions and homointeractions.

Members of the ErbB family of receptor tyrosine kinases are capable of both homointeractions and heterointeractions. Because each receptor has a unique set of binding sites for downstream signaling partners and differential catalytic activity, subtle shifts in their combinatorial interplay may have a large effect on signaling outcomes. The overexpression and mutation of ErbB family members are common in numerous human cancers and shift the balance of activation within the signaling network. Here we report the development of a spatial stochastic model that addresses the dynamics of ErbB3 homodimerization and heterodimerization with ErbB2. The model is based on experimental measures for diffusion, dimer off-rates, kinase activity, and dephosphorylation. We also report computational analysis of ErbB3 mutations, generating the prediction that activating mutations in the intracellular and extracellular domains may be subdivided into classes with distinct underlying mechanisms. We show experimental evidence for an ErbB3 gain-of-function point mutation located in the C-lobe asymmetric dimerization interface, which shows enhanced phosphorylation at low ligand dose associated with increased kinase activity.

Resources, mortality, and disease ecology: Importance of positive feedbacks between host growth rate and pathogen dynamics.

Resource theory and metabolic scaling theory suggest that the dynamics of a pathogen within a host should strongly depend upon the rate of host cell metabolism. Once an infection occurs, key ecological interactions occur on or within the host organism that determine whether the pathogen dies out, persists as a chronic infection, or grows to densities that lead to host death. We hypothesize that, in general, conditions favoring rapid host growth rates should amplify the replication and proliferation of both fungal and viral pathogens. If a host population experiences an increase in mortality, to persist it must have a higher growth rate, per host, often reflecting greater resource availability per capita. We hypothesize that this could indirectly foster the pathogen, which also benefits from increased within-host resource turnover. We first bring together in a short review a number of key prior studies which illustrate resource effects on viral and fungal pathogen dynamics. We then report new results from a semi-continuous cell culture experiment with SHIV, demonstrating that higher mortality rates indeed can promote viral proliferation. We develop a simple model that illustrates dynamical consequences of these resource effects, including interesting effects such as alternative stable states and oscillatory dynamics. Our paper contributes to a growing body of literature at the interface of ecology and infectious disease epidemiology, emphasizing that host abundances alone do not drive community dynamics: the physiological state and resource content of infected hosts also strongly influence host-pathogen interactions.

Filaggrin gene mutations in African Americans with both ichthyosis vulgaris and atopic dermatitis.

Atopic dermatitis (AD) and ichthyosis vulgaris (IV) are two common disorders of epidermal homeostasis resulting in dry skin. The profilaggrin gene, located on chromosome 1q22, encodes a keratin filament aggregating protein (filaggrin) that is essential to forming the epidermal barrier and maintaining hydration. Null mutations in filaggrin have been found to underlie IV and are common in patients with AD, but the minority of African Americans with AD or IV show these mutations in filaggrin. We have selectively studied African Americans with both AD and IV to maximize the possibility of finding filaggrin null mutations in this population. DNA was collected using buccal swabs from 18 African American children with both AD and IV and 17 African American controls without either of these diseases. Purified genomic DNA was amplified using polymerase chain reaction from three regions of the filaggrin gene, exon 3, including R501X, 2282del4, E2554X, R2447X, 1249insG, R826X, 2767insT, and E2422X. Of the African American children with both AD and IV, 22.2% were heterozygous for filaggrin null mutations. Out of the control group, one carried a null mutation and was later discovered to have a history of asthma. Null mutations found in this population included R501X (n = 1), 2282del4 (n = 2), and R826X (n = 2, including the control patient). Our data demonstrate a prevalence of filaggrin mutations in the African American population that exceeds previously published data, although the overall prevalence is still lower than in other populations. It is likely that factors other than known FLG mutations are involved in African American patients.

Intimate partner violence and the meaning of love.

Despite physical, emotional, verbal, and sexual abuse from their partner, many women remain in an abusive relationship, often proclaiming to love the one who is hurting them. Nineteen females who had experienced intimate partner violence were interviewed and asked to share their experiences and describe their meaning of love. An analysis of the transcripts was done using qualitative content analysis. With this approach, the contents of the verbal data were summarized and arranged in three major categories: (1) What love is not; (2) Attributes of a loving relationship; and (3) Attachment to the relationship. The findings demonstrate a woman's clear recognition of being in an abusive relationship, yearning to be truly loved, but often finding herself unable to detach from the relationship.

Elders' experiences of the death of an adult child.

The death of a child can result in complicated grief. Thirty-one adults, 60 years of age or older, who lost an adult child, participated in a qualitative study using a focus group format that allowed them to discuss their experience. A hermeneutical approach was used to develop an overall thematic description of what it meant to an older person to lose an adult child. Four major themes emerged: losses, limited influence/decision making power, regrets, and decreased quality of life. Suggested interventions to prevent complicated grief in elders who experienced the death of an adult child include attentive listening, storytelling, and the use of metaphors.

Correlations between in situ denitrification activity and nir-gene abundances in pristine and impacted prairie streams.

Denitrification is a process that reduces nitrogen levels in headwaters and other streams. We compared nirS and nirK abundances with the absolute rate of denitrification, the longitudinal coefficient of denitrification (i.e., Kden, which represents optimal denitrification rates at given environmental conditions), and water quality in seven prairie streams to determine if nir-gene abundances explain denitrification activity. Previous work showed that absolute rates of denitrification correlate with nitrate levels; however, no correlation has been found for denitrification efficiency, which we hypothesise might be related to gene abundances. Water-column nitrate and soluble-reactive phosphorus levels significantly correlated with absolute rates of denitrification, but nir-gene abundances did not. However, nirS and nirK abundances significantly correlated with Kden, as well as phosphorus, although no correlation was found between Kden and nitrate. These data confirm that absolute denitrification rates are controlled by nitrate load, but intrinsic denitrification efficiency is linked to nirS and nirK gene abundances.

Homicide of an intimate male partner: the impact on the woman.

Using existential-phenomenological interview procedures, two women who killed their husbands during an altercation were asked to share their experiences. Analysis of individual transcripts was done within the context of a hermeneutical approach. Their stories are divided into three distant phases of their life: (1) choosing to fight back in order to live, (2) dealing with the legal system, and (3) the emotional aftermath. Hopefully, these women's stories will help healthcare providers become more diligent in assessing for intimate partner violence, more cognizant of the emotional needs of women who have killed their intimate partners, and more understanding when women continue to proclaim their love for their abusive partner.

Electroconvulsive therapy: the struggles in the decision-making process and the aftermath of treatment.

The perceptions of patients and their family members about electroconvulsive therapy (ECT) are crucial to understanding the meaning attached to having ECT and the impact it has on quality of life. Thus, in this qualitative study, patients and their family members described their perceptions of having electroconvulsive therapy (ECT). The experience occurred in two distinct periods in the patient's life: making the decision to have ECT and the physical and emotional aftermath of treatment. One of the most important themes in the study was a need for patients and families to be better informed about the risks of ECT.

Energetic effects for observed and unobserved HIV-1 reverse transcriptase mutations of residues L100, V106, and Y181 in the presence of nevirapine and efavirenz.

The effect of mutations on amino acid residues L100, V106, and Y181 for unbound HIV-1 reverse transcriptase (RT) and RT bound to nevirapine and efavirenz was investigated using Monte Carlo/free energy perturbation calculations. Using both native and bound crystal structures of RT, mutation of the amino acid residues to both those observed and unobserved in patients was carried out. The results of the calculations revealed that the variant that survives in patients dosed with either nevirapine or efavirenz had a more positive Delta Delta G value than other variants that were not observed in patients. These data suggest that the mutation observed in patients is the most effective (the one that binds the drug most weakly) of all possible codon change mutations.

Protection of macaques against AIDS with a live attenuated SHIV vaccine is of finite duration.

Using background data that live vaccines against several viral pathogens are effective in inducing life-long protection against disease, we undertook studies in macaques to determine the duration of protection that two live SHIV vaccines could induce against AIDS. Earlier studies had established that macaques immunized once with a live vaccine and challenged 6 months later were protected, and that other macaques given two sequential inoculations of live vaccines were protected for at least 1 year. Protection was associated with persistence of the vaccine viruses. In this study, we sought to determine whether the duration of protection in macaques given a single inoculation of replication competent live vaccines would extend beyond 3 years. Two groups of four rhesus macaques were inoculated with two live SHIV vaccines, respectively. The viruses replicated transiently in all animals but at the 3-year time point, PCR analysis of PBMC did not detect DNA of either virus in any of the animals, and all were negative for CMI responses in the blood. All 8 animals succumbed to disease when challenged with pathogenic viruses.

Biological stoichiometry in human cancer.

BACKGROUND: A growing tumor in the body can be considered a complex ecological and evolutionary system. A new eco-evolutionary hypothesis (the "Growth Rate Hypothesis", GRH) proposes that tumors have elevated phosphorus (P) demands due to increased allocation to P-rich nucleic acids, especially ribosomal RNA, to meet the protein synthesis demands of accelerated proliferation. METHODOLOGY/PRINCIPAL FINDINGS: We determined the elemental (C, N, P) and nucleic acid contents of paired malignant and normal tissues from colon, lung, liver, or kidney for 121 patients. Consistent with the GRH, lung and colon tumors were significantly higher (by approximately two-fold) in P content (fraction of dry weight) and RNA content and lower in nitrogen (N):P ratio than paired normal tissue, and P in RNA contributed a significantly larger fraction of total biomass P in malignant relative to normal tissues. Furthermore, patient-specific differences for %P between malignant and normal tissues were positively correlated with such differences for %RNA, both for the overall data and within three of the four organ sites. However, significant differences in %P and %RNA between malignant and normal tissues were not seen in liver and kidney and, overall, RNA contributed only approximately 11% of total tissue P content. CONCLUSIONS/SIGNIFICANCE: Data for lung and colon tumors provide support for the GRH in human cancer. The two-fold amplification of P content in colon and lung tumors may set the stage for potential P-limitation of their proliferation, as such differences often do for rapidly growing biota in ecosystems. However, data for kidney and liver do not support the GRH. To account for these conflicting observations, we suggest that local environments in some organs select for neoplastic cells bearing mutations increasing cell division rate ("r-selected," as in colon and lung) while conditions elsewhere may select for reduced mortality rate ("K-selected," as in liver and kidney).

Batterer intervention program: the victim's hope in ending the abuse and maintaining the relationship.

In this existential-phenomenological investigation, women whose partners were mandated to attend a batterers' intervention program (BIP) were interviewed about their experiences before their partner attended his first class. The goal of this study was to gain an understanding of the woman's expectations of the BIP in the aftermath of her experience of abuse and her reasons for maintaining the relationship. Women described their experience as one of living in a dangerous environment that keeps them nervous, confused, fearful, and feeling bad about themselves, but yet hopeful that the abuse will stop now that their partner is being sent to treatment. BIP was, in fact, the "last hope," an optimism unsupported by current research data.

Self-deception among men who are mandated to attend a batterer intervention program.

TOPIC: Intimate partner violence continues to be a confounding national health problem, especially for women and children. Certified batterers' intervention programs are one means currently being used to combat intimate partner violence. METHOD: Existential phenomenology was utilized in this qualitative study to gain an understanding of the perceptions of the perpetrator prior to beginning a batterer intervention program. FINDINGS: The batterer's experience is divided into two major themes: lack of justification of behaviors toward him and minimization and justification of his behaviors toward the victim and others. CONCLUSIONS: It is hoped that obtaining this understanding will encourage program personnel working in the area of batterers' intervention programs to include more emotional skills training within such programs, thus improving the quality of life for victims, perpetrators, and their families.

Synthesis, biological activity, and crystal structure of potent nonnucleoside inhibitors of HIV-1 reverse transcriptase that retain activity against mutant forms of the enzyme.

In an ongoing effort to develop novel and potent nonnucleoside HIV-1 reverse transcriptase (RT) inhibitors that are effective against the wild type (WT) virus and clinically observed mutants, 1,2-bis-substituted benzimidazoles were synthesized and tested. Optimization of the N1 and C2 positions of benzimidazole led to the development of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methylbenzimidazole (1) (IC50 = 0.2 microM, EC50 = 0.44 microM, and TC50 >/= 100 against WT). This paper describes how substitution on the benzimidazole ring profoundly affects activity. Substituents at the benzimidazole C4 dramatically enhanced potency, while at C5 or C6 substituents were generally detrimental or neutral to activity, respectively. A 7-methyl analogue did not inhibit HIV-1 RT. Determination of the crystal structure of 1 bound to RT provided the basis for accurate modeling of additional analogues, which were synthesized and tested. Several derivatives were nanomolar inhibitors of wild-type virus and were effective against clinically relevant HIV-1 mutants.