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Making a difference: women of action in the community.

This qualitative study documents the contributions of 21 Hispanic women who were identified as being active in the community. Through the use of the grounded theory approach to data collection and analysis, being active in the community emerged as a dynamic system of making a difference, defined as promoting changes to improve circumstances for people; creating, providing, and maintaining tangible human services; developing and sustaining individual and collective approaches to assuming responsibility for the well-being of self and community; promoting ethnic appreciation within one's own culture and among other cultures; and continuing change efforts. The integrative theme in this article concurs with primary components of self-in-relation theory. Because the research was exploratory, the findings point to a broad range of topics for further study related to social work education, knowledge, ethics, and practice.

Acculturation↗

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients.

Although obesity promotes tidal expiratory flow limitation (EFL), with concurrent dynamic hyperinflation (DH), intrinsic PEEP (PEEPi) and risk of low lung volume injury, the prevalence and magnitude of EFL, DH and PEEPi have not yet been studied in mechanically ventilated morbidly obese subjects. In 15 postoperative mechanically ventilated morbidly obese subjects, we assessed the prevalence of EFL [using the negative expiratory pressure (NEP) technique], PEEPi, DH, respiratory mechanics, arterial oxygenation and PEEPi inequality index as well as the levels of PEEP required to abolish EFL. In supine position at zero PEEP, 10 patients exhibited EFL with a significantly higher PEEPi and DH and a significantly lower PEEPi inequality index than found in the five non-EFL (NEFL) subjects. Impaired gas exchange was found in all cases without significant differences between the EFL and NEFL subjects. Application of 7.5 +/- 2.5 cm H2O of PEEP (range: 4-16) abolished EFL with a reduction of PEEPi and DH and an increase in FRC and the PEEPi inequality index but no significant effect on gas exchange. The present study indicates that: (a) on zero PEEP, EFL is present in most postoperative mechanically ventilated morbidly obese subjects; (b) EFL (and concurrent risk of low lung volume injury) is abolished with appropriate levels of PEEP; and (c) impaired gas exchange is common in these patients, probably mainly due to atelectasis.

Adult↗

Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly.

The p21-activated kinase PAK is targeted to focal complexes (FCs) through interactions with the SH3 domains of the PAK-interacting exchange factor PIX and Nck. PIX is a Rac GTP exchange factor that also binds the G-protein-coupled receptor kinase-interacting protein known as GIT1. Overexpression of GIT1 in fibroblasts or epithelial cells causes a loss of paxillin from FCs and stimulates cell motility. This is due to the direct interaction of a C-terminal 125-residue domain of GIT1 with paxillin, under the regulation of PIX. In its activated state, GIT1 can promote FC disassembly independent of actin-myosin contractile events. Additionally, GIT directly couples to a key component of FCs, focal adhesion kinase (FAK), via a conserved Spa2 homology domain. We propose that GIT1 and FAK cooperate to promote motility both by directly regulating focal complex dynamics and by the activation of Rac.

Adaptor Proteins, Signal Transducing↗

Barrier role of actin filaments in regulated mucin secretion from airway goblet cells.

Airway goblet cells secrete mucin onto mucosal surfaces under the regulation of an apical, phospholipase C/G(q)-coupled P2Y(2) receptor. We tested whether cortical actin filaments negatively regulate exocytosis in goblet cells by forming a barrier between secretory granules and plasma membrane docking sites as postulated for other secretory cells. Immunostaining of human lung tissues and SPOC1 cells (an epithelial, mucin-secreting cell line) revealed an apical distribution of beta- and gamma-actin in ciliated and goblet cells. In goblet cells, actin appeared as a prominent subplasmalemmal sheet lying between granules and the apical membrane, and it disappeared from SPOC1 cells activated by purinergic agonist. Disruption of actin filaments with latrunculin A stimulated SPOC1 cell mucin secretion under basal and agonist-activated conditions, whereas stabilization with jasplakinolide or overexpression of beta- or gamma-actin conjugated to yellow fluorescent protein (YFP) inhibited secretion. Myristoylated alanine-rich C kinase substrate, a PKC-activated actin-plasma membrane tethering protein, was phosphorylated after agonist stimulation, suggesting a translocation to the cytosol. Scinderin (or adseverin), a Ca(2+)-activated actin filament severing and capping protein was cloned from human airway and SPOC1 cells, and synthetic peptides corresponding to its actin-binding domains inhibited mucin secretion. We conclude that actin filaments negatively regulate mucin secretion basally in airway goblet cells and are dynamically remodeled in agonist-stimulated cells to promote exocytosis.

Actin Cytoskeleton↗

Neurotropism and Therapeutic Targeting of Brain Metastases in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is an aggressive malignancy marked by rapid progression, early dissemination, and a pronounced propensity for brain metastases (BM), which develop in up to 80% of patients. SCLC is defined by profound genomic instability, lineage plasticity, and rapid drug resistance. The establishment of BM is promoted by neuronal mimicry, enhanced intercellular adhesion, and dynamic cross-talk with astrocytes and microglia. Emerging therapies targeting delta-like ligand 3 and B7H3 have demonstrated encouraging intracranial activity. Despite these advances, treatment resistance and limited brain drug penetration remain major unmet needs. This review highlights recent advances in SCLC BM biology and precision therapeutic strategies.

Humans↗

Relaxin increases calcium efflux from rat myometrial cells in culture.

Relaxin and isoproterenol treatment rapidly increased 45Ca2+ efflux from mature rat myometrial cells in culture in a time- and concentration-dependent manner. This effect on Ca2+ efflux was specific for myometrial cells and was not observed in stromal cells isolated from the same uteri. This rapidly exchangeable Ca2+ may be mobilized from a loosely bound peripheral Ca2+ pool in myometrial cells. Relaxin may promote uterine relaxation in part by affecting Ca2+ dynamics in the myometrium.

Animals↗

Adiposity signaling and biological defense against weight gain: absence of protection or central hormone resistance?

An abundant and compelling literature supports the existence of a homeostatic system that dynamically adjusts energy intake and energy expenditure to promote stability of body fat mass. In the context of this system, the ease with which many individuals gain weight is difficult to explain. Some have argued that energy homeostasis operates primarily to defend against weight loss and that, over the course of evolution, biological defense against weight gain was not selected for. According to this Absence of Protection model, obesity is seen as the natural result of living in an obesigenic environment. An alternative hypothesis, termed the Central Resistance model, proposes that under normal circumstances, the energy homeostasis system provides an effective defense against weight gain as well as weight loss and that common forms of obesity involve genetic or acquired defects (or interactions between them) that impair the function of this system. Here, we discuss these dichotomous possibilities within the context of current literature regarding energy homeostasis and suggest a strategy for distinguishing between them.

Animals↗

Introducing students to research: the road to success.

Introduction of the terminology associated with research can overwhelm both students and faculty. In this article, I describe an interactive method for teaching undergraduate nursing students about the concepts involved in the research process. The "Research Road to Success" is a board game created to promote active learning using repetition, peer collaboration, group dynamics, and questioning. The game has been part of the curriculum for 3 years, with positive results. Nurse educators and students can benefit from the incorporation of creative methods to stimulate interest in and understanding of nursing research.

Education, Nursing↗

Astrocyte-targeted expression of IL-12 induces active cellular immune responses in the central nervous system and modulates experimental allergic encephalomyelitis.

The role of IL-12 in the evolution of immunoinflammatory responses at a localized tissue level was investigated. Transgenic mice were developed with expression of either both the IL-12 subunits (p35 and p40) or only the IL-12 p40 subunit genes targeted to astrocytes in the mouse CNS. Glial fibrillary acidic protein (GF)-IL-12 mice, bigenic for the p35 and p40 genes, developed neurologic disease which correlated with the levels and sites of transgene-encoded IL-12 expression. In these mice, the brain contained numerous perivascular and parenchymal inflammatory lesions consisting of predominantly CD4+ and CD8+ T cells as well as NK cells. The majority of the infiltrating T cells had an activated phenotype (CD44high, CD45Rblow, CD62Llow, CD69high, VLA-4 high, and CD25+). Functional activation of the cellular immune response was also evident with marked cerebral expression of the IFN-gamma, TNF, and IL-1alphabeta genes. Concomitant with leukocyte infiltration, the CNS expression of immune accessory molecules was induced or up-regulated, including ICAM-1, VCAM-1, and MHC class II and B7-2. Glial fibrillary acidic protein-p40 mice with expression of IL-12 p40 alone remained asymptomatic, with no inflammation evident at any age studied. The effect of local CNS production of IL-12 in the development of experimental autoimmune encephalomyelitis was studied. After immunization with myelin oligodendrocyte glycoprotein-peptides, GF-IL-12 mice had an earlier onset and higher incidence but not more severe disease. We conclude that localized expression of IL-12 by astrocytes can 1) promote the spontaneous development of activated type 1 T cell and NK cellular immunity and cytokine responses in the CNS, and 2) promote more effective Ag-specific T cell dynamics but not activity in experimental autoimmune encephalomyelitis.

Animals↗

The critical attributes of leadership.

The final decade of this century is a period of unprecedented change that by all indicators will continue unabated well into the next millennium. This article explored some elemental and immutable truths about leadership, management, communication, and negotiation essential to organizational success, particularly during periods of accelerated change. The case is made for a level of integrity, ethical conduct, and self-control to match the technical competence essential for managerial success in a technologically intensive work environment. These attributes and skills coupled with a widening scope of institutional vision are critical to sustained leadership and growth in an unstable world. Those without these abilities will be diminished in their capacity to communicate or negotiate. Hence, they will be thwarted or powerless to create task attraction, to effect change, or to promote excellence. These lessons are applicable to the dynamic changes occurring within the health care industrial complex, including health information management.

Communication↗

[Study of the quasispecies dynamics of serum hepatitis B virus in a patient with acute exacerbations of chronic hepatitis B].

OBJECTIVES: To investigate the quasispecies dynamics of hepatitis B virus (HBV) during the course of exacerbation and resolution of chronic hepatitis B in a patients. METHODS: Five serum samples were collected from a patient with two episodes of exacerbation and resolution of chronic hepatitis B. A method of PCR-TA cloning-conformation sensitive gel electrophoresis (CSGE)-sequencing was performed to study the dynamic changes of HBV quasispecies in basal core promoter (BCP), precore and core regions of HBV genome. RESULTS: Quasispecies complexity was 10 and 12 at the points of exacerbations, and 14 and 17 at the points of resolutions (t = 3.133, P < 0.05). Ratio of dominant quasispecies in HBV population was high (42.4% and 51.5%) during exacerbations and low (30.3% and 21.2%) during resolutions (t = 3.295, P < 0.05). All dominant quasispecies, except the one during the second resolution, carried core P5T, L60V, S155T, and precore G1896A mutations. CONCLUSION: The composition of HBV quasispecies changes due to the change of host immune status, and immune pressure might lead to the selection of immune escape mutants.

Adolescent↗

Cultural competence in the assessment of poor Mexican families in the rural southeastern United States.

Increasing numbers of poor Mexican immigrant families are settling in the rural southeastern United States. Most of these families are from isolated agrarian communities in Mexico and are headed by unskilled laborers or displaced farm workers with little education. Child welfare workers and other service providers in rural communities may be poorly prepared to address the needs of this population. This article provides an overview of the cultural, social, and family dynamics of first generation, working class Mexicans to promote cultural competency among helping professionals. An ecological perspective is used to examine the strengths that poor Mexicans bring from their culture of origin, stresses of the migratory experience and ongoing adaptation, shifts that may occur in family structure and functioning, disruptions in the family life cycle, the role of social supports in family adaptation, and effect of institutional discrimination on family well-being. Suggestions also are made for essential components of adequate in-service education.

Child↗

When families cannot "let go": ethical decision-making at the bedside.

Shared decision-making at the bedside is now a regular feature of medical practice. When disagreements arise between a patient and family members caregivers sometimes find themselves caught in a complex tangle of human relationships that strains monochrome ethical thinking. The patient's expressed wishes are often compromised for the sake of the family's needs. Conversely, a unilateral appeal for patient autonomy may prove insensitive to the hurt and the needs of the family. We describe a relatively unsuccessful attempt by a patient's caregivers to buy time to maximize the interests of the patient and her family and discuss the way in which the family dynamics militated against the rather obvious solution of promoting the patient's right to refuse treatment. The purpose of this article is not to evoke sympathy for health care professionals in dealing with such conflicts but rather to heighten awareness of the issues at stake and to stimulate thinking about ways and means to bring about a more favourable outcome than the one described here.

Decision Making↗

Effect of latissimus dorsi dynamic cardiomyoplasty on ventricular function.

In our approach to dynamic cardiomyoplasty, which consists of wrapping a skeletal muscle around the heart and stimulating the former in synchrony with heart contractions to augment ventricular contractility, we have transferred a latissimus dorsi muscle flap to the heart by way of a partial resection of the second rib and subsequently suturing the muscle flap around the ventricles. The muscle flap is stimulated by a Cardio-Myostimulator burst-pulse generator (Medtronic SP 1005) connected to intramuscular electrodes. In preclinical animal research, the latissimus dorsi muscle flap was shown to maintain adequate contractile force and to increase its fatigue resistance by gradual conversion of glycolytic-fatigue-sensitive-to-oxidative-fatigue-resistant muscular fibers (100%). Histochemical and biochemical studies of chronically stimulated muscles showed a total transformation of muscle fast myosin to slow myosin with characteristics similar to those of myocardium. Electron microscopy showed preserved myofibrillar cytoarchitecture and increased mitochondrial density in the cell. At 9 months, cardiac output and ultrasonic Doppler studies showed a significant increase in ventricular function (cardiac output, +21%; peak blood velocity, +40% -80%; and stroke volume, +98% -102%) during muscle stimulation. In the clinical situation, long-term (range of follow-up interval, 4-42 months) beneficial cardiac effects of cardiomyoplasty have been documented in eight patients with various pathologies (ventricular tumor, left ventricular aneurysm, ischemic disease, and dilated cardiomyopathy). Our current understanding of this process is that dynamic cardiomyoplasty acts in two ways: 1) it promotes more vigorous systolic contraction, and 2) it appears to limit heart dilatation.

Animals↗

[Antithrombin III determination in horses. Reference values and acquired antithrombin III deficiency].

Antithrombin III (AT III) determinations were done in healthy and sick horses using the chromogenic substrate Chromozym TH. Reference values for adult horses at 25 degrees C were 18-25 IU AT III per ml plasma and 84-118% AT III activity of normal horse plasma, respectively. Precision and accuracy were good (intra assay coefficient of variation less than 2%, accuracy 10%). Surgical operations on healthy horses led to a biphasic decrease in AT III activity touching the lower border of the reference values on the second postoperative day. Other reasons for acquired AT III deficiencies included disseminated intravascular coagulation (DIC), liver disease and glomerulonephritis. Using follow-up studies, differences in the dynamics of acquired AT III deficiency and coagulation promoting factors were demonstrated. 12 of 35 horses with decreased AT III values suffered from phlebothrombosis of the jugular veins. It was presumed that acquired AT III deficiencies promote development and progression of phlebothrombosis/thrombophlebitis in horses.

Animals↗

Accelerated Ostwald ripening by chemical activity.

Phase separation of biomolecular condensates promotes membrane-free compartmentalization in cells. The dynamics of these biocondensates is routinely regulated by energy-consuming processes. Here, we devise a theory pinpointing how active chemical reactions, interconverting molecules between phase-separating and inert forms, can drive faster condensate coarsening. We find that mass conservation limits droplet volume growth to being linear in time regardless of activity, resembling the passive Lifshitz-Slyozov law. However, if reactions are restricted to occur only outside droplets, the rate of Ostwald ripening can be increased by an arbitrarily large factor. Our theory is quantitatively supported by recent experiments on ripening in the presence of fueled interconversion reactions, under precisely the predicted conditions. We posit that the ability to induce rapid biocondensate coarsening can be advantageous in synthetic-biological contexts, e.g., as a regulator of metabolic channeling.

Journal Article↗

[Antibacterial therapy of liver abscesses of varying etiology].

The investigation of microbial flora and its sensitivity in 196 patients with the kidney abscesses of various etiology showed expediency of the use of aminoglycosides, ampicillin and lincomycin. The local use of colloid iodine promoted rapid inhibition of the microbial flora. The dynamic observations showed an increase in the number of gramnegative pathogens by the 7th--10th day of the treatment. Rational surgical intervention, the antibiotic use with control of the microbial flora sensitivity, specific chemotherapy provided a decrease in the lethality up to 6.7 per cent.

Anti-Bacterial Agents↗