Education as Risk Factor of Mild Cognitive Impairment: The Link to the Gut Microbiome.

BACKGROUND: With differences apparent in the gut microbiome in mild cognitive impairment (MCI) and dementia, and risk factors of dementia linked to alterations of the gut microbiome, the question remains if gut microbiome characteristics may mediate associations of education with MCI. OBJECTIVES: We sought to examine potential mediation of the association of education and MCI by gut microbiome diversity or composition. DESIGN: Cross-sectional study. SETTING: Luxembourg, the Greater Region (surrounding areas in Belgium, France, Germany). PARTICIPANTS: Control participants of the Luxembourg Parkinson's Study. MEASUREMENTS: Gut microbiome composition, ascertained with 16S rRNA gene amplicon sequencing. Differential abundance, assessed across education groups (0-10, 11-16, 16+ years of education). Alpha diversity (Chao1, Shannon and inverse Simpson indices). Mediation analysis with effect decomposition was conducted with education as exposure, MCI as outcome and gut microbiome metrics as mediators. RESULTS: After exclusion of participants below 50, or with missing data, n=258 participants (n=58 MCI) were included (M [SD] Age=64.6 [8.3] years). Higher education (16+ years) was associated with MCI (Odds ratio natural direct effect=0.35 [95% CI 0.15-0.81]. Streptococcus and Lachnospiraceae-UCG-001 genera were more abundant in higher education. CONCLUSIONS: Education is associated with gut microbiome composition and MCI risk without clear evidence for mediation. However, our results suggest signatures of the gut microbiome that have been identified previously in AD and MCI to be reflected in lower education and suggest education as important covariate in microbiome studies.

Randomized study of the influence of two-dimensional versus three-dimensional imaging using a novel 3D head-mounted display (HMS-3000MT) on performance of laparoscopic inguinal hernia repair.

BACKGROUND: 3D laparoscopy has proven to be superior to the 2D approach in experimental settings. The aim of the present study was to investigate the influence of 3D laparoscopy using a novel head-mounted display on the performance of defined steps within a laparoscopic inguinal hernia repair. This effect was investigated both in laparoscopically advanced surgeons and in beginners. METHODS: Patients suffering from symptomatic inguinal hernia were randomly assigned to laparoscopic hernia repair using either a head-mounted 3D display or a conventional 2D laparoscopic approach. Operative performance of both groups was compared in terms of the time taken for mesh placement and for peritoneal suturing. Additionally, quality of imaging and physical discomfort were assessed. RESULTS: The use of a head-mounted 3D display was able to shorten the time required for placement of the mesh as well as that for peritoneal suturing, both for experienced and novice surgeons when compared to the conventional 2D approach. 3D laparoscopy was significantly superior to 2D laparoscopy in terms of depth perception, image sharpness and image contrast. Additionally, increased impairment caused by ghosting effects could not be detected in 3D laparoscopy. Evaluation of image quality was independent of experience in laparoscopic surgery. However, use of a head-mounted 3D display resulted in a significant impairment of surgeon's comfort when compared to 2D laparoscopy. Thereby, the greatest impairment was caused by ear discomfort. CONCLUSIONS: This is the first study examining the effect of a head-mounted 3D system on the performance of laparoscopy in a randomized controlled trial (RCT) showing a clear advantage of this system in surgical performance as well as in depth perception and image quality.

A high-throughput screening for mammalian cell death effectors identifies the mitochondrial phosphate carrier as a regulator of cytochrome c release.

Functional annotation of complex genomes requires the development of novel experimental platforms with increased capacity. Here, we describe a high-throughput system designed to identify cDNAs whose overexpression induces morphologically distinct cell death modalities. The methodology incorporates two robotized steps, and relies on coexpression of library clones with GFP to reveal the morphological features presented by the dying cells. By using this system we screened 135 000 cDNA clones and obtained 90 independent molecules. Interestingly, three death categories were identified, namely; apoptotic, vacuolated and autophagic. Among the pro-apoptotic clones, we found four members of the mitochondrial carrier family: the phosphate and adenine nucleotide (type 3) transporters, and the mitochondrial carrier homologs (MTCHs) 1 and 2. Expression of these molecules induced cytochrome c release and caspase-9-dependent death. One of them, the phosphate carrier, was able to interact with members of the permeability transition pore complex ANT1 and VDAC1, and its binding to ANT1 was stabilized in the presence of apoptotic activators. Depletion of this carrier by siRNA delayed cytochrome c mobilization and apoptosis. These results attribute a previously undescribed apoptotic function to the phosphate carrier and, more generally, suggest that a common property of various mitochondrial transporters was exploited during evolution to regulate apoptosis.

The Southeast Minnesota Fetal and Infant Mortality Reduction Project.

Using linked birth and death certificates, researchers collected information on the events surrounding and potentially contributing to all fetal and infant deaths in an 11-county southeast Minnesota area May 1, 1996, through May 31, 1998. Data were collected from medical record reviews and maternal interviews. Information was collated and presented to county review teams consisting of health, human services, and education personnel. These teams identified factors associated with potentially preventable deaths and gaps in services for women, infants, and families. A regional team then grouped and prioritized the factors.

Elution parameters in constant-pressure, single-ramp temperature-programmed gas chromatography.

The dependence of the degree of interaction of a solute with the stationary phase at the time of its elution from the column in temperature-programmed GC is best described by interaction level of the solute. The latter represents the fraction of a solute residing in the stationary phase relative to the total amount of the solute. A simple approach to the evaluation of interaction levels of eluting solutes in a single-ramp temperature program is proposed. In a single-ramp temperature program having no preceding temperature plateau, all solutes that elute at temperatures that are about 60 degrees C higher than the initial temperature of the heating ramp elute with nearly the same interaction levels that can be found as exp(-r), where r is dimensionless heating rate. A specially designed temperature plateau preceding the ramp causes all solutes eluting during the entire time of the ramp to elute with nearly the same interaction levels equal to exp(-r). A transformation of the interaction level of a solute into its retention factor or mobility factor (a fraction of a solute in a mobile phase in relation to the total amount of the solute) and vice versa is also described.

Ovarian carcinoma: care and survival in a community-based population.

BACKGROUND: Previous studies of the management and costs of ovarian cancer have been based on data from oncology practices. Such studies may exclude patients who are not candidates for treatment and may not account for costs incurred during diagnosis or primary treatment. OBJECTIVE: The purpose of this study was to describe the epidemiology, management, and costs of care of ovarian cancer in a geographically defined population to better reflect the total spectrum of the disease and its care. METHODS: We conducted a retrospective review of the medical records of all residents of Olmsted County, Minnesota, who received a first diagnosis of epithelial ovarian carcinoma (including postmortem diagnoses) between 1985 and 1997. RESULTS: Of the 107 women with a new diagnosis of ovarian cacinoma, 42 (39%) had stage I or II tumors at the time of diagnosis. The mean age of the patients at the time of diagnosis was 64.7 years, and 20% were nulliparous. The diagnostic assessment for ovarian carcinoma was initiated by a family physician or internist in 50% of cases and by an obstetrician or gynecologist in 16% of cases. One hundred two patients (95%) underwent surgical treatment, and 80 (75%) received primary chemotherapy. The 5-year survival rate was 88% in those with stage I or II tumors and 17% in those with stage III or IV tumors. The mean charges for secondary care were higher than those for primary care ($36,110 vs $32,367; P < 0.05) in those receiving both types of therapy. Fifty percent of those dying of ovarian cancer received hospice care for a mean of 39.0 days before death. CONCLUSIONS: Most assessments leading to a diagnosis of ovarian carcinoma were initiated by primary care physicians. In this community-based population, early-stage and low-grade tumors were common (> or = 30%) and were associated with lower costs of care and higher 5-year survival rates. Total treatment costs for those requiring secondary therapy were approximately twice the costs for those requiring primary treatment only, with approximately 50% of costs associated with inpatient care.

Correlation of characteristic thermal constant and elution temperature in GC.

In a temperature-programmed analysis, the solutes that elute at higher temperatures have generally larger characterisitic thermal constants, theta(char). The change approximately matches the temperature-related increase in a carrier gas viscosity. Accounting for the effect allows reduction in the uncertainty of prediction of theta(char) by a factor or f approximately 2 and, in a constant-pressure mode, description of a linear heating ramp by the same dimensionless rate for all solutes.

Quantitative comparison of performance of isothermal and temperature-programmed gas chromatography.

As a basic metric of separation for comparing isothermal and temperature-programmed GC (gas chromatography), we used the separation measure. S (defined elsewhere). We used this metric as both a measure of separation of any two peaks, and a measure of separation capacity of arbitrary intervals where peaks can potentially exist. We derived several formulae for calculation of S for any pair of peaks regardless of their shape and the distance from each other in isothermal and temperature-programmed GC. The formulae for isothermal GC can be viewed as generalizations of previously known expressions while, in the case of temperature-programmed GC, no equivalents for the new formulae were previously known from the literature. In all formulae for S. we identified similar key component-metrics (solute separability, intrinsic efficiency of separation, specific separation measure, separation power) that helped us to identify and better understand the key factors affecting the separation process. These metrics also facilitated the quantitative comparison of separation capacities and analysis times in isothermal and temperature-programmed GC. Some of these metrics can be useful beyond GC. In the case of GC, we have shown that, if the same complex mixture was analyzed by the same column, and the same separation requirements were used then isothermal analysis can separate more peaks than its temperature-programmed counterpart can. Unfortunately, this advantage comes at the cost of prohibitively longer isothermal analysis time. The latter is a well know fact. Here, however, we provided a quantitative comparison. In a specific example, we have shown that a single-ramp temperature program with a typical heating rate yields about 25% fewer peaks than the number of peaks available from isothermal analysis of the same mixture using the same column. However, that isothermal analysis would last 1000 times longer than its temperature-programmed counterpart. Using twice as longer column in the case of a temperature-programmed analysis, allows one to recover the 25% disadvantage in the number of separated peaks, while still retaining a 500-fold advantage in the speed of analysis.

Health-related quality of life of patients with endometrial cancer who are disease-free following external irradiation.

Health-related quality of life (HQoL) is assessed through the patients' own evaluation of the impact that a disease and its treatment may have on some of the physical, psychological and social aspects of their lives. The purpose of this study is to describe the HQoL of patients with endometrial cancer who are free of disease after undergoing external irradiation. An HQoL questionnaire was designed and validated, and consisted of the EORTC QLQ-C30 and 80 additional questions. The patients provided self-reported assessments at the end of radiotherapy, and 1, 3, 6, 12, 18 and 24 months later. Forty-nine out of 66 potential subjects participated in the study, which was confined to the period during which the, women were disease free. Most patients experience physical side effects at the end of treatment and up to 6 months thereafter; 10% of the patients have chronic local symptoms and a large number of the patients think about their treatment even two years later. The patients' overall evaluation of their quality of life is lower than that of a matched population of healthy women.

A clinical model for quality of life assessment in cancer patients receiving chemotherapy.

BACKGROUND: The pattern of symptoms experienced by cancer patients during chemotherapy is very complex. Consequently, quality of life (QOL) assessment has to be carefully planned to capture clinically relevant changes. PATIENTS AND METHODS: A clinical model of changes in symptoms experienced by symptomatic metastatic patients during several courses of chemotherapy has been developed. The model differentiates cancer-related symptoms, acute side-effects, chronic side-effects and symptoms not related to cancer. The model was used to predict changes in each of these four symptom groups. Three time points were selected (post-cycle 2, pre-cycle 3, post-cycle 5) and an appropriate window around each time point was set. The model predictions were tested empirically with 56 patients with advanced ovarian cancer who completed the EORTC QLQ-C30 plus disease specific items during a six-cycle course of chemotherapy. RESULTS: The changes observed in the sample were in accordance with the changes predicted by the clinical model. Results from patients who did not complete the questionnaire within the specified time windows tended to dilute the findings from the group who did. CONCLUSIONS: A clinical model is useful in the planning of QOL assessments in order to capture clinically relevant effects. Such models also facilitate the interpretation of QOL studies, particularly when cyclic short-term effects and chronic side-effects are overlaid on disease symptoms, as is the case with chemotherapy for cancer.

Life after radiotherapy: the psychological and social effects experienced by women treated for advanced stages of cervical cancer.

PURPOSE: The aim of this study was to describe the psychological and social reactions of women with advanced stages of cancer of the cervix during and after radiotherapy. METHODS: A questionnaire about health-related quality of life was used, which consisted of the EORTC QLQ-C30 and additional specific questions. One-hundred eighteen patients filled out the questionnaire at the end of treatment and 1, 3, 6, 12, 18, and 24 months later. The scores from the disease-free patients were compared to those from 236 healthy controls. RESULTS: Many patients experience psychological and social consequences at the end of treatment and 1 to 3 months later. Patients continue to think about their illness and treatment throughout the 24-month study period, but find it increasingly hard to share their worries with others. Their score on overall quality of life never reaches that of the controls. CONCLUSION: Disease-free patients treated for cancer of the cervix with radiotherapy have psychological reactions. The interpretation of the results should take into consideration that the patients change their personal frame of reference over the course of time. Professionals should be aware of patients' needs to talk about their disease long after treatment. Patients should be informed about the risk of psychological reactions. The more information about possible symptoms they receive the better their ability to cope with them should they arise.

The patients' perspective on physical symptoms after radiotherapy for cervical cancer.

PURPOSE: The aim of this study was to describe the physical symptoms experienced by patients with advanced stages of cervical cancer during the first 2 years after radiotherapy. METHODS: A questionnaire about health-related quality of life was used. It consisted of the EORTC QLQ-C30 and additional specific questions. The patients were assessed at the end of treatment and 1, 3, 6, 12, 18, and 24 months later. The scores from the 118 patients were compared to those from 236 healthy controls. RESULTS: Most patients had acute physical symptoms at the end of treatment and up to 3 months later. Local symptoms such as frequent voiding and diarrhea may become chronic symptoms. CONCLUSION: Assessment of health-related quality of life includes information about milder side effects that is not usually included in physician scoring of morbidity. Information about possible side effects improves the patient's ability to cope with the symptoms should they occur.

Anxiety and depression in breast cancer patients at low risk of recurrence compared with the general population: a valid comparison?

Breast cancer and its treatment have been associated with psychological morbidity. In this study our aim was to quantify the excess anxiety and depression resulting from breast cancer. We compared 538 newly diagnosed breast cancer patients at low risk of recurrence (87.0% responded) to 872 women randomly selected from the Danish general population (69.7% responded) using the Hospital Anxiety and Depression Scale (HADS). Contrary to expectations, the proportions classified as "cases" of anxiety and depression were not significantly different in the two groups. The breast cancer patients' mean HADS scores were significantly lower than those in the general population sample (anxiety, P = 0.021; depression, P < 0.001), indicating less anxiety and depression. However, we question the validity of this comparison. The HADS may not be suitable for use in the general population and there may be methodological problems in comparisons of groups whose life situations are very different.

Using data from studies of health-related quality of life to describe clinical issues examples from a longitudinal study of patients with advanced stages of cervical cancer.

The focus of the paper is to describe how to present data from studies on health-related quality of life (H-QoL) in a way that is simple and clinically relevant. Data from a longitudinal study of patients with advanced stages of cervix cancer are used. One hundred and eighteen patients filled out questionnaires (including EORTC QLQ-C30) 7 times over a period of 2 years. The following issues are considered: (1) The use of a panel for an initial overview of data. (2) The visual difference between using mean and median values. (3) Box-whisker plots to illustrate the variability of the data. (4) The effect of combining categorical data into fewer categories. (5) Individual patient profiles showing the wide variability among patients. (6) A table showing the change of scores over a one-year period. (7) "Prognostic plots" dividing the initial scores and the following scores. (8) Plotting changes over time. (9) Illustration of the impact of non-random dropout. (10) The effect of drop-out for the patients who fill out two sequential assessments. (11) The use of healthy controls to help answer the question "what is normal?".

Validation of the EORTC QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreement.

Patient-rated questionnaires are increasingly used to assess health-related quality of life. We studied one aspect of the validity of such measures that has rarely been investigated do patients interpret questionnaires in the same way as do the researchers reporting the results? If not, there may be a problem. We employed the EORTC QLQ-C30 quality-of-life questionnaire to study 95 cancer patients and measured the agreement between (1) the patient's self-assessment and (2) an observer's rating of the patient's open-ended responses to the same questionnaire administered as an interview. The observer made qualitative recordings describing potential misinterpretations. The agreement between patients' and observers' ratings was high (median kappa = 0.85, range 0.49-1.00). The qualitative data revealed a few minor validity problems. One of these, selective reporting, may lead to systematic errors; some patients reported only what they considered "relevant" symptoms. The combination of quantitative and qualitative methods proved useful for questionnaire validation.

[Treatment of cancer pain in Denmark. A questionnaire survey]. / Behandling af cancersmerter i Danmark. En spørgeskemaundersøgelse.

A questionnaire survey was carried out with the aim of evaluating knowledge about and practice of cancer pain treatment in Denmark. A questionnaire was sent to a 10% random sample of Danish physicians. Of these 1411 physicians, 1068 (76%) returned the questionnaires and after the exclusion of those doctors who never treated cancer patients, 577 (54%) were analyzed. Their knowledge of the principles and practice of cancer pain treatment was evaluated by means of 14 multiple-choice and open questions. Their ability to apply their knowledge in practice was evaluated by analyzing their suggested treatment of three simulated patient cases. Ninety-seven percent of the physicians recognized difficulties in cancer pain treatment, the most frequent being side effects of drugs and inadequate pain relief. It appeared from the proposals for pain treatment of the patient cases that the majority of the physicians could treat both pain from bone metastasis (75%) and visceral pain (78%) satisfactorily, while very few suggested coanalgesics for neuropathic pain (20%). Older physicians performed less satisfactorily than did their younger colleagues. Basic pain treatment skills have been acquired by the Danish physicians. However, in the future emphasis should be placed on the treatment of neuropathic pain with coanalgesics and the management of opioid side-effects.