Cyanobacterial diversity and activity in modern conical microbialites.

Modern conical microbialites are similar to some ancient conical stromatolites, but growth, behavior and diversity of cyanobacteria in modern conical microbialites remain poorly characterized. Here, we analyze the diversity of cyanobacterial 16S rRNA gene sequences in conical microbialites from 14 ponds fed by four thermal sources in Yellowstone National Park and compare cyanobacterial activity in the tips of cones and in the surrounding topographic lows (mats), respectively, by high-resolution mapping of labeled carbon. Cones and adjacent mats contain similar 16S rRNA gene sequences from genetically distinct clusters of filamentous, non-heterocystous cyanobacteria from Subsection III and unicellular cyanobacteria from Subsection I. These sequences vary among different ponds and between two sampling years, suggesting that coniform mats through time and space contain a number of cyanobacteria capable of vertical aggregation, filamentous cyanobacteria incapable of initiating cone formation and unicellular cyanobacteria. Unicellular cyanobacteria are more diverse in topographic lows, where some of these organisms respond to nutrient pulses more rapidly than thin filamentous cyanobacteria. The densest active cyanobacteria are found below the upper 50 µm of the cone tip, whereas cyanobacterial cells in mats are less dense, and are more commonly degraded or encrusted by silica. These spatial differences in cellular activity and density within macroscopic coniform mats imply a strong role for diffusion limitation in the development and the persistence of the conical shape. Similar mechanisms may have controlled the growth, morphology and persistence of small coniform stromatolites in shallow, quiet environments throughout geologic history.

Aberrant hypermethylation in primary tumours and sentinel lymph node metastases in paediatric patients with cutaneous melanoma.

BACKGROUND: Debate on how to manage paediatric patients with cutaneous melanoma continues, particularly in those with sentinel lymph node (SLN) metastases who are at higher risk of poor outcomes. Management is often based on adult algorithms, although differences in clinical outcomes between paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences. OBJECTIVES: We investigated the epigenetic (methylation) regulation of several tumour-related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance. METHODS: Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I-III cutaneous melanoma were analysed. Gene promoter methylation of the TRGs RASSF1A, RARß2, WIF1 and APC was evaluated. RESULTS: Hypermethylation of RASSF1A, RARß2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow-up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease-free (P = 0·02) and overall survival (P = 0·02). CONCLUSIONS: Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow-up.

FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling.

Human basal-like breast cancer (BLBC) is an enigmatic and aggressive malignancy with a poor prognosis. There is an urgent need to identify therapeutic targets for BLBC, because current treatment modalities are limited and not effective. The forkhead box transcription factor FOXC1 has recently been identified as a critical functional biomarker for BLBC. However, how it orchestrates BLBC cells was not clear. Here we show that FOXC1 activates the transcription factor nuclear factor-κB (NF-κB) in BLBC cells by increasing p65/RelA protein stability. High NF-κB activity has been associated with estrogen receptor-negative breast cancer, particularly BLBC. The effect of FOXC1 on p65/RelA protein stability is mediated by increased expression of Pin1, a peptidyl-prolyl isomerase. FOXC1 requires NF-κB for its regulation of cell proliferation, migration and invasion. Notably, FOXC1 overexpression renders breast cancer cells more susceptible to pharmacological inhibition of NF-κB. These results suggest that BLBC cells may rely on FOXC1-driven NF-κB signaling. Interventions of this pathway may provide modalities for the treatment of BLBC.

Formation and stability of oxygen-rich bubbles that shape photosynthetic mats.

Gas release in photic-zone microbialites can lead to preservable morphological biosignatures. Here, we investigate the formation and stability of oxygen-rich bubbles enmeshed by filamentous cyanobacteria. Sub-millimetric and millimetric bubbles can be stable for weeks and even months. During this time, lithifying organic-rich laminae surrounding the bubbles can preserve the shape of bubbles. Cm-scale unstable bubbles support the growth of centimetric tubular towers with distinctly laminated mineralized walls. In environments that enable high photosynthetic rates, only small stable bubbles will be enclosed by a dense microbial mesh, while in deep waters extensive microbial mesh will cover even larger photosynthetic bubbles, increasing their preservation potential. Stable photosynthetic bubbles may be preserved as sub-millimeter and millimeter-diameter features with nearly circular cross-sections in the crests of some Proterozoic conical stromatolites, while centrimetric tubes formed around unstable bubbles provide a model for the formation of tubular carbonate microbialites that are not markedly depleted in (13)C.

Basic cardiac life support education for non-medical hospital employees.

BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) recommends that strategies should be implemented that promote cardiopulmonary resuscitation (CPR) training in the workplace. Non-medical employees at a hospital were therefore trained to conduct basic life support (BLS). Subject background information, test results and survey findings were examined and factors affecting BLS skill acquisition were studied. METHODS: Of 1432 non-medical employees at a hospital trained to conduct BLS, 880 agreed to participate in the survey. The training course consisted of a single session of 3 h of lectures, practice and testing. Skill acquisition was assessed using a 13-item skill checklist and a 5-point overall competency scale. The effects of age, gender, type of job, educational status, a previous history of CPR training and level of subject-perceived training difficulty were examined. RESULTS: According to total checklist scores, subjects achieved a mean (SD) score of 8.66 (3.57). 22.3% performed all 13 skills. Based on 5-point overall competency ratings, 43.7% of subjects were rated as "competent", "very good" or "outstanding". Age (<40 years and >or=40 years) was the only factor that significantly affected skill acquisition (skill acquisition by those >or=40 years of age was poorer than by those aged <40 years). CONCLUSION: Traditional BLS training is less effective in individuals aged >or=40 years.

Smad4 expression in gastric adenoma and adenocarcinoma: frequent loss of expression in diffuse type of gastric adenocarcinoma.

Smads are signal transducers for the members of the TGF-beta superfamily. Of these Smads, Smad4 is essential for TGF-beta signaling. The purpose of this study was to elucidate Smad4 expression and localization in 65 gastric adenomas, 49 intestinal-type and 39 diffuse type of gastric adenocarcinomas (including 12 cases of fresh frozen tissue) using Real-time RT-PCR and immunohistochemistry. Real-time RT-PCR showed that intestinal type gastric adenocarcinomas have higher Smad4 mRNA expression than diffuse type gastric adenocarcinomas. Immunohistochemical stain for Smad4 revealed that expression of Smad4 was significantly lower in diffuse-type gastric adenocarcinoma than intestinal-type gastric adenocarcinomas. Also, higher Smad4 protein expression in intestinal type gastric adenocarcinomas than overall gastric adenoma was noted. The rate of reduced Smad4 expression was higher in advanced gastric cancer than early gastric cancer. These results suggest that Smad4 might play different roles in human gastric carcinogenesis, especially between intestinal type and diffuse type of gastric adenocarcinoma.

Post-prandial plasma ghrelin levels in people with different breakfast hours.

OBJECTIVES: To investigate the changes in post-meal plasma ghrelin levels in people with different breakfast hours. DESIGN AND INTERVENTIONS: The subjects adhered to strict breakfast times starting 2 weeks before the study. Blood was drawn hourly from 0530 or 0630 until 1130. Plasma ghrelin, leptin, and insulin levels were measured by radioimmunoassay. SETTING: Medical Research Institute, Pusan National University Hospital, Korea. SUBJECTS: A total of 16 healthy volunteers. RESULTS: The mean plasma ghrelin level in subjects consuming breakfast was 548.7 +/- 239.6 fmol/ml before breakfast and 384.8 +/- 168.7 fmol/ml 1 h after breakfast, with leptin levels of 6.8 +/- 2.6 and 6.5 +/- 2.5 ng/ml, respectively. Plasma ghrelin levels were lowest 1 h after the meal, although the breakfast times differed. The plasma ghrelin level was lowest at 0730 in subjects not eating breakfast. CONCLUSIONS: These findings suggest that the plasma ghrelin levels are lowest 1 h after breakfast despite the variance in breakfast times. This timing might best reflect an individual's plasma ghrelin level and enable reasonable comparisons.

Correlation of Ultrasonographic Findings and Pathologic Prognostic Predictions in Breast Cancer.

PURPOSE: Increased technologic capabilities have allowed for the expanded use of ultrasound beyond simple differentiation of a lesion as solid versus cystic nature, allowing us to classify lesions into various categories based on a number of descriptive features. The purpose of this study was to investigate whether to predict the preoperative prognosis of breast cancer through the correlation between ultrasonographic images and the grade of malignancy. MATERIALS AND METHODS: The patient population for this study consisted of 107 patients with infiltrative ductal carcinoma who were evaluated using ultrasound technology. Ultrasonographic findings were divided as follows: Type I, round or oval shape and regular border; Type II, partially round or oval shape and partially irregular border; and Type III, irregular shape and irregular border. RESULTS: 1. The frequency of grade 1 (G1) was significantly higher in the Type I group than the othergroups. 2. In the 2.0 cm sized mass, the lymph node metastasis rate was significantly lower in the Type I group than the other groups. 3. In all the groups, Estrogen receptor (ER) positivity was insignificant regardless of tumor size and type. 4. In the 2.0 cm sized mass, c-erbB-2 positivity was significantly lower in the Type I than the other groups. There was no clear difference among the three groups in tumors greater than 2.0 cm in size. CONCLUSION: These results show that our classification of ultrasonographic images reflect the grade of malignancy in terms of clinicopathological features in breast cancers less than 2.0 cm in size. Therefore, ultrasonographic findings may help predict the preoperative prognosis in T1 size breast cancer, although further study is required.

Recovery of replication-competent virus from CD4 T cell reservoirs and change in coreceptor use in human immunodeficiency virus type 1-infected children responding to highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) suppresses plasma viremia in most patients with human immunodeficiency virus (HIV) infection. Prospective study of HIV-infected children (n=27) shows that, in 8 of 12 who responded to HAART (>/=0.5 log reduction in plasma HIV RNA), HAART restricted the number of coreceptors used by the predominant HIV isolate (mean number of coreceptors used at baseline was 4, vs. 1 coreceptor used at 6 months after treatment). This decrease was most striking in 6 of 8 children whose HIV coreceptor tropism changed from X4-tropic at baseline to R5-tropic. In 6 of 10 children tested, with plasma HIV RNA levels of <50 copies/mL, R5-tropic virus was isolated from CD4 T cell reservoirs. All the responding children had a significant increase in naive CD4 T cells (P<.05). These results show that persistent HIV T cell reservoirs are present in children and that HAART may influence the number and type of coreceptors used by the predominant virus isolate.

Antiperistaltic ileostomy using the long terminal ileal segment.

PURPOSE: This study was undertaken to determine whether reversed terminal ileal segments can be used to decrease ileostomy output in patients who have undergone total proctocolectomy and ileostomy for ulcerative colitis or familial adenomatous polyposis. METHODS: An approximately 25-cm length of terminal ileum was reversed in an antiperistaltic manner, and the new terminal ileal end was used for the ileostomy constructed in the usual manner. Six patients underwent this procedure and were compared with six patients who had conventional total proctocolectomy and ileostomy. Variables studied included weight of ileostomy output and the weight of the filtered fluid component. Data were obtained on seven different occasions during a two-month period beginning three months after the operation. Analysis was done using Student's t-test. RESULTS: There was a statistically significant decrease in the weight of the average 24-hour ileostomy effluent in those patients undergoing reversed antiperistaltic loop procedures. There was also a statistically significant decrease in the filterable liquid proportions. CONCLUSIONS: The antiperistaltic ileostomy is effective in reducing the daily amount of ileostomy effluent and facilitates stoma care, owing to its diminished liquid component.

Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load.

OBJECTIVE: To determine if there are levels of human immunodeficiency virus type 1 (HIV-1) associated with a high or low risk of perinatal transmission and to ascertain the mechanism by which zidovudine treatment reduces perinatal transmission. DESIGN: A nonrandomized prospective cohort study. SETTING: University medical center and two general hospital affiliates from May 1989 to September 1994. PATIENTS: Ninety-two HIV-1-seropositive women (95 pregnancies) and their 97 infants. INTERVENTION: Forty-two mothers (43 pregnancies) received zidovudine therapy during pregnancy and/or during labor and delivery. Eleven infants received prophylactic zidovudine for the first 6 weeks after delivery. MAIN OUTCOME MEASURE: HIV-1 infection status of the infant. RESULTS: Twenty of the 97 infants were perinatally infected with HIV-1. Transmitting mothers were more likely to have plasma HIV-1 RNA levels higher than 50000 copies per milliliter at delivery than nontransmitting mothers (15 [75.0%] of 20 transmitters vs four [5.3%] of 75 nontransmitters; P < .001). None of the 63 women with less than 20000 HIV-1 RNA copies per milliliter transmitted. Twenty-two women treated with open-label oral zidovudine during gestation showed an eightfold median decrease in plasma RNA levels (median [25th and 75th percentile], 43043 [5699 and 63053] copies per milliliter before zidovudine vs 4238 [603 and 5116] HIV-1 RNA copies per milliliter at delivery; P < .001) and none transmitted. Four zidovudine-treated women with high HIV-1 levels transmitted despite the presence of zidovudine-sensitive virus in vitro in both the mothers and their infants. CONCLUSIONS: Maternal HIV-1 RNA levels were highly predictive of perinatal transmission risk and suggest that certain levels of virus late in gestation and/or during labor and delivery are associated with both a high risk and a low risk of transmission. Our results also suggest that zidovudine exerts a major protective effect by reducing maternal HIV-1 RNA levels prior to delivery and that further strategies are needed to prevent perinatal transmission in women with high or increasing virus levels and/or zidovudine-resistant virus.

Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay.

A rapid method for determination of zidovudine resistance was developed and results were correlated with clinical outcome in human immunodeficiency virus (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from 34 children were determined through a direct quantitative peripheral blood lymphocyte assay and compared with results of the AIDS Clinical Trials Group resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and cocultured with donor lymphocytes and varying concentrations of zidovudine. Isolates were defined as sensitive if inhibited by < or = 1.0 microM zidovudine and resistant at > 1.0 microM. Children (n = 21) with zidovudine-resistant virus had greater evidence of disease progression than did those with zidovudine-sensitive virus (n = 11) as demonstrated by failure to thrive (57% vs. 9%, P = .01) and opportunistic infections (48% vs. 0, P = .006). This assay may be useful as a screening tool for development of clinically relevant zidovudine resistance.

Quality of life in adult survivors of lung, colon and prostate cancer.

In a cross-sectional study design, a disease free sample of 57 lung, 117 colon, and 104 prostate cancer survivors who represented short, intermediate and long-term survivors completed a detailed assessment of quality of life (QOL) and rehabilitation needs using the CAncer Rehabilitation Evaluation System (CARES). Demographic and medical data, social support, and a global QOL rating were also assessed. Lung cancer patients showed no differences in QOL with respect to their period of survival. QOL improved for survivors of colon cancer as they lived for longer periods, but declined with time for survivors of prostate cancer. The best predictor of QOL for all groups was KPS, although other variables such as type of hospital, gender, and work status were predictive for survivors of colon cancer. For survivors of prostate cancer comorbidity with other medical illnesses, time since diagnosis and comorbidity due to psychiatric difficulties were predictive of QOL. All groups had significant rehabilitation problems in the domains of physical, psychosocial, sexual, medical interaction, and marital relationships. Lung cancer survivors had more problems than the other cancer survivors. We conclude that patients who survive cancer do not return to a state of normal health. They demonstrate a variety of difficulties with which they must cope as they continue to survive. Greater efforts need to be made early in diagnosis and treatment to understand rehabilitation problems and target interventions in the hope of reducing later sequelae.

Predicting psychosocial risk in patients with breast cancer.

Breast cancer is the most common neoplasm in North American women. The psychosocial impact of breast cancer has been extensively studied, and a number of investigators have attempted to characterize women who are at high risk for increased psychosocial morbidity. Although a detailed interview performed by a professional is the clinical standard for psychosocial assessment, such interviews are usually time-consuming and expensive, and thus are rarely performed. This study was designed to develop a strategy for the rapid identification of newly-diagnosed breast cancer patients at risk for psychosocial morbidity. A sample of 227 newly diagnosed breast cancer patients were interviewed systematically by a clinical social worker and were subsequently classified for risk of psychosocial distress in the year after diagnosis. In addition, these women completed a battery of standardized instruments designed to assess quality of life, rehabilitation needs and psychological distress. A logistic regression procedure was used to examine a wide range of variables for their ability to correctly classify the risk of psychosocial distress in this sample. The final model included the Cancer Rehabilitation Evaluation System (CARES) Psychosocial Summary Scale, the Karnofsky Performance Status score and age as the best predictors of psychosocial risk. Subsequently these three variables were used to construct a clinically usable risk prediction model. Additional research should be performed to validate this predictive model.

Exploring the influence of multiple variables on the relationship of age to quality of life in women with breast cancer.

This paper explores the relationship between age, psychosocial status and quality of life in a community based sample (n = 229) of newly-diagnosed breast cancer patients. A casement display methodology is used to examine the influence of demographic and medical variables on the outcome variables of interest (psychosocial status and quality of life) and their relationship to age. Based on the literature, a positive relationship between age and psychosocial status was predicted, but the relationship between age and quality of life was uncertain. For the whole sample, a weakly positive relationship between age and measures of psychosocial status and quality of life was observed. In the exploratory studies using the casement plots, the positive relationship between age and quality of life was most strong and significant in married women and in women who had received segmental mastectomy. Among sub-groups examined according to marital status and type of surgery, a positive relationship between age, psychosocial status and quality of life was observed only in married women who received segmental mastectomy. Additional preliminary observations were made about the relationship of household income and age to the outcome variables being studied. The casement plot methodology permits the simultaneous evaluation of multiple variables as a preliminary step before hypothesis development and should be considered when complex clinical problems are being evaluated.

The CARES: a generic measure of health-related quality of life for patients with cancer.

In spite of the prevalence of neoplastic disorders as a cause of chronic illness, very few of the currently available generic measures of health-related quality of life or health status have been utilized with cancer patients. In this paper we reviewed our studies with the Cancer Rehabilitation Evaluation System (CARES), a cancer-specific measure of rehabilitation needs and quality of life. We present data to demonstrate that the CARES is a generic measure of health-related quality of life, suitable for use in the many different diseases called cancer. The data that form the basis for this paper were collected during a decade of research on the CARES. This paper represents the first discussion of the performance of the CARES across separate cancer sites and phases of the disease. In addition, we demonstrated that the CARES is responsive to changes in health-related quality of life over time. Finally, we will discuss the application of the CARES in clinical and research settings.