Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased muscle protein breakdown in chronic hemodialysis patients with type 2 diabetes mellitus.

BACKGROUND The presence of diabetes mellitus (DM) in chronic hemodialysis (CHD) patients has potential to increase body protein losses and muscle wasting. METHODS In this study, we examined whole-body and skeletal muscle protein metabolism in 6 CHD patients with type 2 (T2) DM (2 male, 44.4 +/- 6.1 years old, 2 white/4 African American HbA(1)C = 9.5 +/- 1.1%), and 6 non-DM CHD patients (2 male, 43.3 +/- 6.7 years old, 2 white/4 African American) in a fasting state, using a primed-constant infusion of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. RESULTS CHD patients with T2DM had significantly increased (83%) skeletal muscle protein breakdown (137 +/- 27 vs. 75 +/- 25 microg/100 mL/min). There was no significant difference in muscle protein synthesis between groups (78 +/- 27 vs. 66 +/- 21 microg/100 mL/min, for DM and non-DM respectively), resulting in significantly more negative net protein balance in the muscle compartment in the DM group (-59 +/- 4 vs. -9 +/- 6 microg/100 mL/min, P < 0.05). A similar trend was observed in whole-body protein synthesis and breakdown. Plasma glucose levels were 113 +/- 16 and 71 +/- 2 mg/dL, P < 0.05, and insulin levels were 25.3 +/- 9.6 and 7.3 +/- 1.0 uU/mL, for DM versus non-DM, respectively, P < 0.05. No significant differences between DM and non-DM were found in other metabolic hormones. CONCLUSION The results of this study demonstrate that CHD patients with T2DM under a suboptimal metabolic control display accelerated muscle protein loss compared with a matched group of non-DM CHD patients.
Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans

Significance Vaccination is the most effective means of attaining protection against influenza viruses. However, the constantly evolving nature of influenza viruses enables them to escape preexisting immune surveillance, and thus thwarts public health efforts to control influenza annual epidemics and occasional pandemics. One solution is to elicit antibodies directed against highly conserved epitopes, such as those within the stem region of influenza HA, the principal target of virus-neutralizing antibody responses. This study shows that annual influenza vaccines induce antibody responses that are largely directed against the highly variable HA head region. In contrast, heterologous immunization with HA derived from influenza strains that are currently not circulating in humans (e.g. H5N1) can substantially increase HA stem-specific responses. The emergence of pandemic influenza viruses poses a major public health threat. Therefore, there is a need for a vaccine that can induce broadly cross-reactive antibodies that protect against seasonal as well as pandemic influenza strains. Human broadly neutralizing antibodies directed against highly conserved epitopes in the stem region of influenza virus HA have been recently characterized. However, it remains unknown what the baseline levels are of antibodies and memory B cells that are directed against these conserved epitopes. More importantly, it is also not known to what extent anti-HA stem B-cell responses get boosted in humans after seasonal influenza vaccination. In this study, we have addressed these two outstanding questions. Our data show that: (i) antibodies and memory B cells directed against the conserved HA stem region are prevalent in humans, but their levels are much lower than B-cell responses directed to variable epitopes in the HA head; (ii) current seasonal influenza vaccines are efficient in inducing B-cell responses to the variable HA head region but they fail to boost responses to the conserved HA stem region; and (iii) in striking contrast, immunization of humans with the avian influenza virus H5N1 induced broadly cross-reactive HA stem-specific antibodies. Taken together, our findings provide a potential vaccination strategy where heterologous influenza immunization could be used for increasing the levels of broadly neutralizing antibodies and for priming the human population to respond quickly to emerging pandemic influenza threats.
Systemic Monocyte-Derived Dendritic Cells and Associated Th2 Skewing in Chronic Rhinosinusitis

Introduction Monocyte-derived dendritic cells (moDCs) are antigen-presenting cells capable of directing immune responses toward T-helper 1 (Th1) or T-helper 2 (Th2) phenotypes. The systemic profile of moDCs and their association with Th1/Th2 skewing in chronic rhinosinusitis (CRS) is unclear. The purpose of this study is to characterize circulating moDCs in controls, CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP) and correlate moDCs with Th1/Th2 skewing, mucosal inflammation on computed tomography (CT), and quality of life (QoL). Study Design Cross-sectional study. Setting Tertiary care hospital. Subjects Blood was drawn from control (n = 12), CRSsNP (n = 18), and CRSwNP (n = 15) patients during endoscopic sinus surgery. Methods Peripheral blood moDCs were analyzed with flow cytometry for expression of HLA-DR, CD209, and CD14. Th1 and Th2 cells were identified by CXCR3 and CCR8 expression, respectively. Lund-Mackay CT scores were assigned by blinded graders. Sino-Nasal Outcome Test 22 (SNOT-22) surveys were completed by patients before surgery. Results CRSsNP and CRSwNP displayed elevations in systemic moDCs compared with controls. In CRSwNP, systemic Th2 skewing was observed and circulating CD4+ Th2 cells correlated with percent moDCs. MoDCs strongly correlated with higher Lund-Mackay CT scores in CRSsNP but not in CRSwNP. No relationship between moDCs and SNOT-22 scores was observed for either subset of CRS. Conclusion These data support that CRSwNP and CRSsNP display alterations in systemic immune profiles. CRSwNP is characterized by significant elevations in circulating moDCs, which is associated with systemic Th2-biased inflammation. Circulating moDCs are associated with mucosal inflammation on CT imaging in CRSsNP. No association between moDCs and QoL is evident in either CRS subset.
Treatment results of carcinoma in situ of the glottis: an analysis of 82 cases.

OBJECTIVES To evaluate the results of different treatment modalities for carcinoma in situ of the glottis, and to identify important prognostic factors for outcome. DESIGN Review of 82 cases treated definitively for glottic carcinoma in situ between 1958 and 1998. The median follow-up for all patients was 112 months, and 90% had more than 2 years of follow-up. SETTING Academic tertiary care referral centers. INTERVENTION Fifteen patients were treated with vocal cord stripping (group 1), 13 with more extensive surgery (group 2) including endoscopic laser resection (11 patients) and hemilaryngectomy (2 patients), and 54 with radiotherapy (group 3). Thirty patients had anterior commissure involvement and 9 had bilateral vocal cord involvement. Radiotherapy was delivered via opposed lateral fields at 1.5 to 2.4 Gy per fraction per day (median fraction size, 2 Gy), 5 days per week. The median total dose was 64 Gy, and the median overall time was 47 days. MAIN OUTCOME MEASURES Initial locoregional control (LRC), ultimate LRC, and larynx preservation. RESULTS The 10-year initial LRC rates were 56% for group 1, 71% for group 2, and 79% for group 3. Of those who failed, the median time to relapse was 11 months for group 1, 17 months for group 2, and 41 months for group 3. Univariate analysis showed that the difference in initial LRC rates between groups 1 and 3 was statistically significant (P =.02), although it was not statistically significant on multivariate analysis (P =.07). Anterior commissure involvement was an important prognostic factor for LRC on both univariate (P =.03) and multivariate (P =.04; hazard ratio, 1.6) analysis, and its influence appeared to be mainly confined to the surgically treated patients (groups 1 and 2). The 10-year larynx preservation rates were 92% for group 1, 70% for group 2, and 85% for group 3. Anterior commissure involvement was the only important prognostic factor for larynx preservation (P =. 01) on univariate analysis. All but 2 patients in whom treatment failed underwent successful salvage surgery. Voice quality was deemed good to excellent in 73% of the patients in group 1, 40% in group 2, and 68% in group 3. CONCLUSIONS Treatment of carcinoma in situ of the glottis with vocal cord stripping or more extensive surgery or radiotherapy provided excellent ultimate LRC and comparable larynx preservation rates. Anterior commissure involvement was associated with poorer initial LRC and larynx preservation, particularly in the surgically treated patients. The choice of initial treatment should be individualized, depending on patient age, reliability, and tumor extent. Pretreatment and posttreatment objective evaluation of voice quality should be helpful in determining the best therapy for these patients.
The long-term impact of bereavement upon spouse health: a 10-year follow-up

Jones MP, Bartrop RW, Forcier L, Penny R. The long-term impact of bereavement upon spouse health: a 10-year follow-up. Objectives: This study is the first to examine the effect of bereavement of a first-degree family member on subsequent morbidity over a 10-year follow-up period. Methods: A sample of bereaved subjects (n = 72) were compared with a control group (n = 80) recruited in the same period with respect to morbidity experience during follow-up. Morbidity events were ascertained from the subject themselves, their health care providers and these sources were also compared. Results: Bereavement was associated with an elevated total burden of illness as well as with mental health and circulatory system categories diagnosed according to the International Classification of Diseases - Clinically Modified (ICD-9) classification system. The elevation ranged from approximately 20% for any illness to 60–100% among circulatory system disorders. Although in an earlier study there was a downregulation of T-cell function in the bereaved during the first 8 weeks, there was no evidence that the bereavement was associated with increased morbidity in the respiratory or immune system ICD-9 categories long-term. Conclusions: Past epidemiological research has indicated that bereavement of a close family member is associated with adverse health consequences of a generalised morbidity. Our study suggests an increase in mental health and circulatory system effects in particular. Further research is required to determine whether other systems are also affected by bereavement.
Palliation of Nonresectable Bile Duct Cancer: Improved Survival After Photodynamic Therapy

OBJECTIVES:Preliminary uncontrolled studies of photodynamic therapy (PDT) of bile duct cancer (BDC) have shown astonishingly good results in the reduction of cholestasis, improvement of life quality, and potential improvement of survival time. Therefore, we investigated the influence of PDT on survival time in advanced BDC in a randomized controlled study.METHODS:Thirty-two patients with nonresectable BDC were randomized. In the PDT group 48 h after intravenous application of 2 mg/kg body weight of Photosan-3®, light activation was performed. In the control group, patients were treated with endoprostheses but no PDT.RESULTS:PDT group and the control group were comparable due to age, gender, performance status, bilirubin level, and BDC stage (Bismuth classification). The median survival time after randomization was 7 months for the control group and 21 months for the PDT group (p = 0.0109). In half of the initially percutaneously treated patients, we could change from percutaneous to transpapillary drainage after PDT. Four patients showed infectious complications after PDT versus one patient in the control group.DISCUSSION:PDT is minimally invasive but shows a considerable postinterventional cholangitis rate. PDT has the potential to result in a changeover of current palliative treatment of BDC.
Genome‐wide scan for prostate cancer susceptibility genes using families from the University of Michigan prostate cancer genetics project finds evidence for linkage on chromosome 17 near BRCA1

Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses.
Patient Empowerment through Personal Medical Recommendations

Patients today have ample opportunities to inform themselves about their disease and possible treatments using the Internet. While this type of patient empowerment is widely regarded as having a positive influence on the treatment, there exists the problem that the quality of information that can be found on online is very diverse. This paper presents a platform which empowers patients by allowing searching in a high quality document repository. In addition, it automatically provides intelligent and personalized recommendations according to the individual preferences and medical conditions.
Possible Detrimental Effects of Cognitive Behaviour Therapy for Chronic Fatigue Syndrome

Background: Cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) can decrease the level of fatigue and disabilities, but it has been suggested that during therapy some patients experience a deterioration of their symptoms rather than an improvement. The aim of this study is to examine the frequency and severity of symptom deterioration during CBT for CFS. Methods: Data from 3 randomised controlled trials on CBT for CFS were pooled and reanalysed. Symptom deterioration during the trial was rated by patients and measured as deterioration in fatigue, pain, functional impairment and psychological distress. Both the frequency and severity of deterioration in these domains were compared between the patients receiving CBT and those in the control group. Predictors of symptom deterioration were identified by comparing their means in patients with and without an increase in fatigue. Statistically significant predictors were then combined in a logistic regression model. Results: The frequency of symptom deterioration varied from 2 to 12% in patients receiving CBT and from 7 to 17% in the control group. None of the measures showed a significantly higher frequency of symptom deterioration in the CBT group. The severity of deterioration was also comparable in the CBT and in the control group. No predictors of symptom deterioration specific to CBT were found. Conclusion: Patients receiving CBT do not experience more frequent or more severe symptom deterioration than untreated patients. The reported deterioration during CBT seems to reflect the natural variation in symptoms. Thus, CBT is not only a helpful, but also a safe treatment for CFS.
Cytotoxicity of and DNA adduct formation by ellipticine and its micellar form in human leukemia cells in vitro.

OBJECTIVES The improvements of cancer treatment are the major challenge in oncology research. Nanocarriers are one of the promising approaches to selectively target tumor cells, frequently leading to improve drug therapeutic index. Ellipticine is an anticancer agent that functions through multiple mechanisms. Here, the toxic effects of an anticancer drug ellipticine encapsulated in a micellar nanotransporter and free ellipticine on human HL-60 leukemia cells and formation of ellipticine-derived DNA adducts by both forms of the drug in these cells were investigated. METHODS The toxicity of modified ellipticine on cells was compared to that of free ellipticine using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide cytotoxicity assay. 32P-postlabeling was utilized to determine ellipticine-DNA adducts in treated cells. RESULTS The comparison of efficiencies of free ellipticine and ellipticine-micelles [the poly(ethylene oxide)-block-poly(allyl glycidyl ether) block copolymer] to form ellipticine-derived DNA adducts in leukemia HL-60 cells and to act as cytotoxic agent on these cells was performed. Exposure of HL-60 cells to ellipticine in micelles resulted in formation of ellipticine-DNA adducts and caused the cytotoxic effect on these cells. The influence of ellipticine in micelles on HL-60 cells was very similar to that of free ellipticine. The ellipticine half maximal inhibition concentration was determined as 1.3±0.3 µmol. L(-1) and 1.4±0.3 µmol. L(-1) for ellipticine and ellipticine in micelles, respectively. Likewise, the levels of ellipticine-DNA adducts generated in HL-60 cells by both forms of ellipticine were analogous. CONCLUSION The results found in this work demonstrate similar cytotoxicity and DNA-damaging effects of ellipticine and its micellar form on leukemia HL-60 cells in vitro.
Evolutionary and functional analyses of cytochrome P4501A promoter polymorphisms in natural populations

The functional importance of variable, transcriptional regulatory sequences within and among natural populations is largely unexplored. We analysed the cytochrome P4501A (CYP1A) promoter in three populations of the minnow, Fundulus heteroclitus, because two SNPs in the promoter and first intron of CYP1A are under selection in populations adapted to pollutants. To define the importance of these SNPs, 1630 bp of the CYP1A promoter and first intron and exon were sequenced in eight individuals from three populations: a population from a polluted environment resistant to some aromatic pollutants and two flanking reference populations. CYP1A is induced by many aromatic pollutants, but in populations adapted to pollutants, CYP1A has been shown to be refractory to induction. We were interested in understanding whether variation in the CYP1A promoter explains mechanism(s) of adaptation to these aromatic pollutants. The CYP1A promoter was extremely variable (an average of 9.3% of the promoter nucleotides varied among all populations) and exhibited no fixed differences between populations. As CYP1A is poorly inducible in adapted fish, we hypothesized that CYP1A promoter regions might vary functionally between populations. Unexpectedly, in vitro analysis showed significantly greater transcription from CYP1A promoters found in the population from the polluted environment relative to promoters found in both reference populations. Thus, despite extensive variation among populations and lack of fixed differences between populations, individuals from a polluted environment have significantly enhanced promoter activity. These data demonstrate that intraspecific variation, which provides the raw material for natural selection to act on, can occur while maintaining promoter function.
Direct visualization and quantitation of cytomegalovirus-specific CD8+ cytotoxic T-lymphocytes in liver transplant patients.

BACKGROUND CMV infection remains a significant clinical problem in the context of LT. Changes in the magnitude of the CMV-specific CTL response after LT have not previously been assessed but may be important in determining the outcome of CMV infection. METHOD We used a fluorescent HLA-B*0702-CMV peptide tetrameric complex to directly visualize and quantitate CMV-specific CD8+ CTL both in immunosuppressed patients after LT and in immunocompetent controls. RESULTS CMV-specific CD8+ CTL, at a frequency ranging from 0.1 to 5.8% of CD8+, were detected in the peripheral blood of 22 of 25 B*0702, CMV immunoglobulin G seropositive individuals, with no difference observed between immunocompetent controls and patients >3 years after LT. In CMV seropositive LT recipients who did not have symptomatic CMV infection during the first 3 months after LT, CMV-specific CD8+ CTL magnitude initially decreased, then increased up to 5 times higher than pre-LT levels within 3 months. Two CMV seronegative recipients of seropositive donors had symptomatic CMV infection in association with high viral load. In both patients, no CD8+ CTL response was detected before the onset of symptoms, and a reduction in viral load was observed during antiviral therapy. However, polymerase chain reaction negativity was achieved only when a demonstrable CMV-specific CD8+ CTL response was generated. Responses were never observed in asymptomatic CMV seronegative patients. CONCLUSIONS We suggest that the generation of CMV-specific CD8+ CTL may be driven by, and seems to coincide with the suppression of, viral reactivation. Direct monitoring of CMV-specific CD8+ CTL using an HLA-peptide tetramer may prove to be of value in the management of patients after LT.
Trauma and stress response among Hurricane Katrina evacuees.

OBJECTIVES Hurricane Katrina's impact on public health has been significant and multifaceted, with trauma-related psychological sequelae likely to result in a sizable burden of disease. Data were collected that assessed acute stress disorder (ASD) prevalence and factors related to ASD symptomatology among sheltered evacuees. METHODS On days 12 to 19 after Katrina, evacuees at a major emergency shelter completed surveys that assessed demographics, Katrina-specific experiences, and ASD symptomatology. RESULTS Sixty-two percent of the sample met ASD threshold criterion. Projections based on the predictive power of ASD to posttraumatic stress disorder (PTSD) suggest that 38% to 49% of the sample will meet PTSD criteria 2 years post-disaster. Female gender (odds ratio [OR] = 4.08), positive psychiatric history (OR=5.84), injury (OR=2.75), increased life-threat perception (OR=1.37), and decreased sense of personal control (OR=1.56) were significantly related to ASD. Black race was associated with greater symptom severity (B=7.85, SE[B]=3.50). CONCLUSIONS Katrina-related trauma and its psychological sequelae will remain a significant public health issue for years to come. The identification of several vulnerability factors related to ASD and PTSD provides a brief sketch of those at greatest risk.
Improved signal to noise in proton spectroscopy of the human calf muscle at 7 T using localized B1 calibration

Large variations of tip angle within a slice can lead to suboptimal pulse power optimization using standard techniques, which measure the average tip angle over a slice; this effect is especially pronounced at fields of 7 T and above. A technique was introduced that performed a volume‐selective power optimization in less than 10 sec and automatically calibrates the radiofrequency pulses for subsequent spectroscopy scans. Using this technique, MR spectra were acquired in the human calf of seven healthy volunteers with a partial volume Tx/Rx coil. Increases in signal‐to‐noise ratio based upon the unsuppressed water signal between 22 ± 5% and 166 ± 42%, compared to spectra obtained with the conventional power calibration technique, were measured in different regions of the calf muscle. This new technique was able to measure the inhomogeneous radiofrequency field at 7 T and its use resulted in a considerable signal‐to‐noise ratio increase. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.