Experimental bacterial meningitis in the rabbit: cerebrospinal fluid changes and its relation to leukocyte response

This study was focused on cerebrospinal fluid (CSF) manifestations in experimental Streptococcus pneumoniae and Escherichia coli meningitis in rabbits. An increased (p less than 0.001) CSF lactate concentration was found in infected animals, mostly not accompanied by a decrease in CSF glucose concentrations. Despite a marked difference in CSF cellular response between the 2 etiological groups no significant difference in CSF lactate levels was found. Neither did CSF lactate levels correlate to CSF polymorphonuclear cell counts. CSF concentrations of albumin were with large variations above control levels in all infected animals. Also a small or moderate increase in CSF albumin levels was generally associated with a marked increase in CSF lactate concentration. The concentration of total amino acids in the CSF was above control values (mean + 2 SD) in 9/21 infected animals. Halothane/N2O anesthesia for 25 min increased (p less than 0.05) CSF levels of glucose, partly independent of alterations in plasma glucose concentrations, in both infected rabbits and in controls.     

INAUGURAL ARTICLE by a Recently Elected Academy Member:In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone

In the highly concentrated environment of the cell, polypeptide chains are prone to aggregation during synthesis (as nascent chains await the emergence of the remainder of their folding domain), translocation, assembly, and exposure to stresses that cause previously folded proteins to unfold. A large and diverse group of proteins, known as chaperones, transiently associate with such folding intermediates to prevent aggregation, but in many cases the specific functions of individual chaperones are still not clear. In vivo, Hsp90 (heat shock protein 90) plays a role in the maturation of components of signal transduction pathways but also exhibits chaperone activity with diverse proteins in vitro, suggesting a more general function. We used a unique temperature-sensitive mutant of Hsp90 in Saccharomyces cerevisiae, which rapidly and completely loses activity on shift to high temperatures, to examine the breadth of Hsp90 functions in vivo. The data suggest that Hsp90 is not required for the de novo folding of most proteins, but it is required for a specific subset of proteins that have greater difficulty reaching their native conformations. Under conditions of stress, Hsp90 does not generally protect proteins from thermal inactivation but does enhance the rate at which a heat-damaged protein is reactivated. Thus, although Hsp90 is one of the most abundant chaperones in the cell, its in vivo functions are highly restricted.     

The elongation of yeast prion fibers involves separable steps of association and conversion

A self-perpetuating change in the conformation of the translation termination factor Sup35p is the basis for the prion [PSI+], a protein-based genetic element of Saccharomyces cerevisiae. In a process closely allied to in vivo conversion, the purified soluble, prion-determining region of Sup35p (NM) converts to amyloid fibers by means of nucleated conformational conversion. First, oligomeric species convert to nuclei, and these nuclei then promote polymerization of soluble protein into amyloid fibers. To elucidate the nature of the polymerization step, we created single-cysteine substitution mutants at different positions in NM to provide unique attachment sites for various probes. In vivo, the mutants behaved like wild-type protein in both the [psi-] and [PSI+] states. In vitro, they assembled with wild-type kinetics and formed fibers with the same morphologies. When labeled with fluorescent probes, two mutants, NMT158C and NME167C, exhibited a change in fluorescence coincident with amyloid assembly. These mutants provided a sensitive measure for the kinetics of fiber elongation, and the lag phase in conversion. The cysteine in the mutant NMK184C remained exposed after assembly. When labeled with biotin and bound to streptavidin beads, it was used to capture radiolabeled soluble NM in the process of conversion. This process established the existence of a detergent-susceptible intermediate in fiber elongation. Thus, the second stage of nucleated conformational conversion, fiber elongation, itself contains at least two steps: the association of soluble protein with preformed fibers to form an assembly intermediate, followed by conformational conversion into amyloid.     

Nurse attitudes towards the use of complementary and alternative therapies in critical care

BACKGROUND: There is increasing demand for complementary/alternative therapies (CAT) in critical care, however, critical care nurses' perspectives regarding CAT are unknown. OBJECTIVES: This study was conducted to determine critical care nurses' knowledge, attitudes, and use of CAT. SAMPLE/SETTING: A total of 348 critical care registered nurses working at least 40% in medical, surgical, cardiac, neurological, and pediatric ICUs at 2 tertiary-level hospitals in a large Midwestern city were surveyed. One hospital is a 926-bed private, urban hospital and the second is an 1868-bed academic-affiliated medical center. METHODS: A survey was distributed to all critical care nurses described above. RESULTS: The level of knowledge reported by 138 nurse respondents was greatest for diet, exercise, massage, prayer, and music therapy. Use of therapies was related to knowledge and training and consistent with beliefs of legitimacy and perceptions of beneficial effects. Despite barriers including lack of knowledge, time, and training, 88% of respondents were open or eager to use CAT, and 60% reported moderate or greater desire to use CAT. CONCLUSIONS: Critical care nurses are open to CAT use and many use them in their own practice. Because use was associated with knowledge, recommendations for future research include increasing the scientific base and enhancing knowledge to promote evidence-based incorporation of CAT in practice.     

Pattern of microbial translocation in patients living with HIV-1 from Vietnam,Ethiopia and Sweden

Introduction

The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.

Methods

Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.

Results

All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.

Conclusions

Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.     

A retrospective study on telephone follow-up of anterior colporrhaphy by a specialized nurse

Introduction and hypothesis

The aim of the study was to evaluate a new follow-up practice after anterior colporrhaphy for central cystocele involving nurse telephone follow-up.

Methods

A retrospective follow-up of all 84 patients with an anterior colporrhaphy operation during 2011 was performed. Standard postoperative procedure in uncomplicated cases of cystocele operation (first-time cystocele operation, no preoperative incontinence or voiding difficulties, and no immediate postoperative complications) was a telephone interview performed by a continence nurse 3 months after patient surgery. A local checklist comprising questions concerning complications, voiding dysfunction, and sexual life, as well as questions from the International Consultation on Incontinence Vaginal Symptoms (ICIQ-VS) and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) were used. Complex cases were followed by the surgeon with a consultation including gynecological examination after 3 months.

Results

Out of 84 patients with a cystocele operation, 59 were uncomplicated and had a telephone follow-up. Forty-four (75 %) were satisfied and needed no further consultation in the hospital. One patient could not be contacted. Fourteen patients had a consultation, three before the telephone consultation because of bleeding, five because of anxiety, and one each because of voiding dysfunction and prolapse symptoms. Four patients had persisting urinary incontinence and were incorrectly scheduled for a telephone interview.

Conclusions

Selecting uncomplicated cases for a nurse telephone follow-up after cystocele operation is feasible in a majority of cases. This allows doctors to see more new patients and focus on difficult cases, as well as saving time and money.     

Evaluation of dyskerin expression and the Cajal body protein WRAP53β as potential prognostic markers for patients with primary vaginal carcinoma

Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53β), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53β in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53β was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53β was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.     

Emotion depends on context,culture and their interaction: evidence from effective connectivity

Situated models of emotion hypothesize that emotions are optimized for the context at hand, but most neuroimaging approaches ignore context. For the first time, we applied Granger causality (GC) analysis to determine how an emotion is affected by a person’s cultural background and situation. Electroencephalographic recordings were obtained from mainland Chinese (CHN) and US participants as they viewed and rated fearful and neutral images displaying either social or non-social contexts. Independent component analysis and GC analysis were applied to determine the epoch of peak effect for each condition and to identify sources and sinks among brain regions of interest. We found that source–sink couplings differed across culture, situation and culture × situation. Mainland CHN participants alone showed preference for an early-onset source–sink pairing with the supramarginal gyrus as a causal source, suggesting that, relative to US participants, CHN participants more strongly prioritized a scene’s social aspects in their response to fearful scenes. Our findings suggest that the neural representation of fear indeed varies according to both culture and situation and their interaction in ways that are consistent with norms instilled by cultural background.     

Comparison of health-related quality-of-life outcomes of men and women after coronary artery bypass surgery through 1 year: findings from the POST CABG Biobehavioral Study

Background

Women undergoing coronary artery bypass graft (CABG) surgery have a worse medical condition and fewer social and financial resources than men. Some studies have found that women recover less well than men after CABG, whereas others have found women's outcomes comparable to those of men. Past studies of health-related quality of life after CABG have too few women for adequate comparison with men and have not included patients whose data are not available at baseline (eg, emergency CABG), limiting generalizability.

Methods

A longitudinal study of symptoms and health-related quality of life was conducted among patients from four clinical centers enrolling both men (n = 405) and women (n = 269) in the Post CABG Biobehavioral Study in the United States and Canada.

Results

After 6 weeks from CABG (average 81 days), both men and women had less anxiety and symptoms related to depression than before surgery (P < .001). After 6 months (average 294 days), both men and women improved in physical and social functioning (P < .001). Although changes in scale scores were similar for men and women at each time point, women scored lower than men on these domains (P < .001, adjusted for baseline medical and sociodemographic differences) and had more symptoms related to depression through 1 year after CABG (P = .003).

Conclusions

Both male and female patients improve in physical, social, and emotional functioning after CABG, and recovery over time is similar in men and women. However, women's health-related quality-of-life scale scores remained less favorable than men's through 1 year after surgery.