Miracle-dz/UniFAR-FTUs huggingface dataset:
Preserved Central Memory and Activated Effector Memory CD4+ T-Cell Subsets in Human Immunodeficiency Virus Controllers: an ANRS EP36 Study

ABSTRACT Human immunodeficiency virus (HIV) controllers are rare individuals who spontaneously control HIV type 1 replication for 10 years or more in the absence of antiretroviral treatment. In the present study, HIV controllers (n = 11) maintained potent HIV-specific CD4 responses in spite of very low antigenic loads. Their CD4+ central memory T (TCM) cells were characterized by near-normal numbers and preserved interleukin-2 (IL-2) secretion in response to HIV antigens and uniformly high expression of the survival receptor IL-7 receptor α (IL-7Rα). Controllers expressed CCR7 at higher levels than uninfected controls, suggesting differences in TCM-cell homing patterns. CD4+ effector memory T (TEM)-cell responses were polyfunctional in HIV controllers, while IL-2 secretion was lost in viremic patients. Cytokine production was three times higher in controllers than in treated patients with undetectable viral loads, suggesting an intrinsically more efficient response in the former group. The total CD4+ TEM-cell pool underwent immune activation in controllers, as indicated by increased HLA-DR expression, decreased IL-7Rα expression, a bias towards gamma interferon production upon polyclonal stimulation, and increased macrophage inflammatory protein 1β secretion associated with chronic CCR5 down-regulation. Thus, HIV controllers showed a preserved CD4+ TCM-cell compartment and signs of potent functional activation in the CD4+ TEM-cell compartment. While controllers did not show the generalized immune activation pattern associated with disease progression, they had signs of immune activation restricted to the effector compartment. These findings suggest the induction of an efficient, nondetrimental type of immune activation in patients who spontaneously control HIV.
Who owns the child in hospital? A preliminary discussion.

AIM To 'own' a person is considered an infringement of human rights, but we suggest that concepts of ownership influence interactions between parents and staff when a child is admitted to hospital. This paper aims to stimulate debate and contains an explanation of the exploration of the literature for research and discussion of ownership of the child. METHOD A wide variety of library indexes, databases and populist media were examined although it was impossible to examine all literature which may have contained references to this topic, and, apart from databases which contained abstracts in English, we could not include literature written in any language other than English, Swedish, and Icelandic. FINDINGS We found no research that examines how concepts of ownership of a child affects communication between health professionals and parents and, ultimately, the delivery of health care. This paper begins discussion on the issues. DISCUSSION Historical literature shows that ownership of humans has been a part of many cultures, and parents were once considered to own their children. Ownership of another has legal connotations, for instance in guardianship struggles of children during marriage breakup and in ethical debates over surrogacy and products of assisted conception. Within health care, it becomes a contentious issue in transplantation of body parts, in discourse on autonomy and informed consent, and for religious groups who refuse blood transfusions. In health care, models such as family centred care and partnership in care depend on positive communication between parents and staff. If a hospital staff member feels that he/she owns a child for whom he/she is caring, then conflict between the staff member and the parents over who has the 'best interests of the child' at heart is possible. CONCLUSION We encourage debate about concepts of who owns the hospitalized child - the parents or the staff? Should it be argued at all? Is the whole concept of ownership of another, be it adult or child, the ethical antithesis to modern beliefs about human rights? Comment on this issue is invited.
Role of Tumor Pericytes in the Recruitment of Myeloid-Derived Suppressor Cells.

BACKGROUND Pericytes are members of the tumor stroma; however, little is known about their origin, function, or interaction with other tumor components. Emerging evidence suggest that pericytes may regulate leukocyte transmigration. Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with powerful inhibitory effects on T-cell-mediated antitumor reactivity. METHODS We generated subcutaneous tumors in a genetic mouse model of pericyte deficiency (the pdgfb (ret/ret) mouse) and littermate control mice (n = 6-25). Gene expression profiles from 253 breast cancer patients (stage I-III) were evaluated for clinic-pathological parameters and survival using Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) based on a two-sided Wald test. RESULTS We report that pericyte deficiency leads to increased transmigration of Gr1(+)/CD11b(+) cells in experimentally induced tumors. Pericyte deficiency produced defective tumor vasculature, resulting in a more hypoxic microenvironment promoting IL-6 upregulation in the malignant cells. Silencing IL-6 expression in tumor cells attenuated the observed differences in MDSC transmigration. Restoring the pericyte coverage in tumors abrogated the increased MDSC trafficking to pericyte-deficient tumors. MDSC accumulation in tumors led to increases in tumor growth and in circulating malignant cells. Finally, gene expression analysis from human breast cancer patients revealed increased expression of the human MDSC markers CD33 and S100A9 with concomitant decreased expression of pericyte genes and was associated with poor prognosis (HR = 1.88, 95% CI = 1.08 to 3.25, P = .03). CONCLUSIONS Our data uncovers a novel paracrine interaction between tumor pericytes and inflammatory cells and delineates the cellular events resulting in the recruitment of MDSC to tumors. Furthermore, we propose for the first time a role for tumor pericytes in modulating the expression of immune mediators in malignant cells by promoting a hypoxic microenvironment.
Early Life and Postnatal Western Diet Feeding and Susceptibility to Chemically Induced Colonic Aberrant Crypt Foci in Male Rats Offspring

ABSTRACT The modifying effects of a Western diet (WD) during early life on the susceptibility to colon carcinogenesis induced by dimethylhydrazine (DMH) were examined in male rats as later adults. Three groups were studied: a lifetime control diet-fed group, a test group fed WD since pregnancy from dams until postnatal day (PND) 42, and a group fed WD at adulthood. At PND 70, all groups received the carcinogen DMH and were euthanized 10 wk later. Colonic aberrant crypt foci (ACF) were scored (number and crypt multiplicity) and the altered pattern of β-catenin expression was evaluated in the colonic lesions. ACF multiplicity (≥4 crypts) was significantly higher in the group fed WD at early life than in the group fed the control diet. ACF number, crypt multiplicity, and the number of high-grade dysplastic lesions were significantly higher in the group fed WD at adulthood than in the groupfed the control diet. The number of lesions with altered β-catenin expression was higher in the groups receiving WD at early life or at adulthood than in the lifetime control-diet-fed group. These findings indicate that WD exposure at early life increased the susceptibility to colon carcinogenesis at adulthood.
A Tailored Curriculum of Alcohol Screening, Brief Intervention, and Referral to Treatment (SBIRT) for Nurses in Inpatient Settings

AbstractA package of clinical strategies known as alcohol screening, brief intervention, and referral to treatment (SBIRT) is increasingly recommended for reducing unhealthy alcohol use, the spectrum of alcohol consumption from at-risk drinking (defined as consumption above recommended guidelines) to alcohol abuse and alcohol dependence. The United States’ Joint Commission issued new SBIRT-related hospital accreditation measures for alcohol. Ongoing initiatives aim to promote, support, and sustain SBIRT implementation in hospital settings. In hospital settings, nurse-delivered SBIRT may be a particularly viable and efficient model for SBIRT implementation. However, like physicians, most nurses have not been trained in how to perform SBIRT, and few authors have described alcohol-related curricula specifically for nurses. In addition, historical differences in nurse and physician professional scopes of practice, role perceptions, and patterns of care delivery suggest the need for effective SBIRT initial and continuing education and training that are tailored to the nursing profession and inpatient environments. In this article, we provide an in-depth description of the registered nurse SBIRT curriculum and describe its development and contents as well as various nurse- and setting-specific adaptations. In addition, we describe how we engaged nursing stakeholders in the development and implementation of the curriculum and discuss potential implications for future SBIRT training and delivery by nurses. SBIRT continuing education and training for nurses represents one of the first steps in expanded SBIRT implementation. Comprehensive workforce and organizational development of inpatient and nurse-delivered SBIRT may provide the means to address the entire spectrum of unhealthy alcohol use across healthcare settings.
Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings.

PURPOSE To assess degree of macrovesicular steatosis with unenhanced computed tomography (CT) and correlate it with histologic findings in potential donors for living related liver transplantation. MATERIALS AND METHODS Forty-two candidates underwent unenhanced CT within 4 weeks of core liver biopsy. An experienced liver pathologist, blinded to both CT and surgical findings, retrospectively reviewed biopsy specimens and determined degree of macrovesicular steatosis. A radiologist blinded to histologic grading calculated mean hepatic attenuation in each donor liver by averaging 25 region-of-interest (ROI) measurements on five sections (five ROIs per section). Mean splenic attenuation was calculated with three separate ROI measurements. Liver attenuation index (LAI) was derived and defined as the difference between mean hepatic and mean splenic attenuation. Body mass index (BMI) was determined for each patient. Linear regression analysis was used to correlate degree of macrovesicular steatosis with both LAI and BMI. RESULTS LAI correctly predicted degree of macrovesicular steatosis in 38 (90%) of 42 cases. In four of four livers, LAI below -10 HU correlated with greater than 30% macrovesicular steatosis (unacceptable for liver transplantation). In nine of 11 livers, LAI was between -10 and 5 HU and correctly predicted 6%-30% steatosis (relative contraindication). In two of 11 cases, LAI overestimated degree of hepatic steatosis. LAI above 5 HU correctly predicted 0%-5% steatosis in 25 of 27 livers. In two of 27 cases, parenchymal hemosiderin deposition led to an increase in LAI into the normal range, despite mild histologically confirmed steatosis. Degree of histologic macrovesicular steatosis correlated well with LAI (r = 0.92) and marginally with BMI (r = 0.45). Of 27 potential donors with normal livers at CT and acceptable LAI levels, four (15%) were deemed poor donor candidates because core biopsy revealed subtle hepatic necrosis and nonspecific hepatitis. CONCLUSION Although unenhanced CT quantifies the degree of macrovesicular steatosis relatively well, it may preclude a liver biopsy only in a small percentage of potential donors with low LAI (unacceptable degree of steatosis). Core liver biopsy is still necessary in the majority of donors with normal LAI to identify those with both fatty liver and coexistent hemosiderin deposition or radiologically occult diffuse liver diseases.
CONGESTIVE HEART FAILURE ASSOCIATED WITH PREGNANCY IN OKAPI (OKAPIA JOHNSTONI)

Abstract Acute signs associated with cardiovascular disease occurred in three pregnant okapi (Okapia johnstoni) during early to midgestation and progressed to congestive heart failure. Congestive heart failure was diagnosed antemortem using echocardiography and plasma cardiac troponin levels. Clinical signs included decreased activity, hyporexia, tachypnea, dyspnea, flared nostrils, and productive coughing with copious amounts of foamy nasal discharge. Parenteral and oral treatment with furosemide, enalapril, and spironolactone controlled clinical signs in the three okapi allowing each to carry out one pregnancy to term. Two okapi carried the first pregnancy to term after showing signs, while one okapi aborted the first calf and gave birth to a healthy calf in a subsequent pregnancy. Subsequent pregnancy in one okapi ended with abortion and associated dystocia and endometritis. Following parturition, clinical signs associated with heart failure resolved in all three individuals; serial echocardiography in two individuals showed improvement in fractional shortening and left atrial size and all three okapi showed markedly decreased pleural effusion and resolution of pulmonary edema. However, subsequent pregnancies in all three okapi induced respiratory distress and recurrence of congestive heart failure; one okapi died from congestive heart failure associated with subsequent pregnancy. This case series describes the clinical presentation and pathologic findings of congestive heart failure during pregnancy in adult okapi.
A randomized comparative study on the safety and efficacy of clarithromycin and erythromycin in treating community-acquired pneumonia.

BACKGROUND Clarithromycin, a new macrolide, has distinct microbiological and pharmacokinetic advantages compared with erythromycin. This study was designed to compare the safety and efficacy of clarithromycin and erythromycin in the treatment of community-acquired pneumonia. METHODS Forty adult patients, diagnosed with community-acquired pneumonia, were randomly arranged to received either clarithromycin 250 mg twice daily (20 patients) or erythromycin 500 mg four times daily (20 patients), over a period of 14 days each. RESULTS There were no statistically significant differences between the two groups in terms of clinical cure (65% for clarithromycin, 65% for erythromycin), clinical success (clinical cure and improvement: 95% for clarithromycin, 90% for erythromycin) and radiological response (95% for clarithromycin, 90% for erythromycin). However, adverse effects, mainly gastrointestinal, were significantly higher among patients treated with erythromycin than among patients treated with clarithromycion (p < 0.05). CONCLUSIONS These results demonstrate that clarithromycin 250 mg twice daily is at least as effective as erythromycin 500 mg four times daily for the treatment of community-acquired pneumonia, and is much better tolerated.
Non-Tunneled Central Venous Catheters in Adult Stem Cell Transplantation Recipients: An Effective Option

Stem cell transplantation (SCT) recipients require central venous catheter (CVC) insertion for the administration of chemotherapy, antibiotics and total parenteral nutrition. Traditionally, tunneled CVC have been considered as the golden standard although they require surgery for both insertion and removal. We prospectively evaluated the use of a non-tunneled CVC in 182 consecutive patients who had undergone allogenic or autologous SCT. The median duration of CVC was 4 weeks (range 1–24) with a significant difference between allogenic (8 weeks, range 2–24) and autologous SCT (4 weeks, range 1–24) (p<0.0001). The life expectancy of the CVC was significantly influenced by spontaneous removal, which occurred in 26 patients (13.8%). There was a significant increase of this complication in allogenic SCT (p=0.039). The overall incidence of sepsis was 24.5%, although catheter-related sepsis was microbiologically documented by positive culture of the tip only in 17 cases (9%). Non-tunneled CVC in adult SCT recipients allowed (a) bedside insertion and removal, (b) guidewire replacement for diagnostic or therapeutic purposes (dialysis or pheresis procedures) thus reducing the need for repeated venipunctures.
Implementation of chemometrics in quality evaluation of food and beverages

ABSTRACT Conventional methods for food quality evaluation based on chemical or microbiological analysis followed by traditional univariate statistics such as ANOVA are considered insufficient for some purposes. More sophisticated instrumental methods including spectroscopy and chromatography, in combination with multivariate analysis—chemometrics, can be used to determine food authenticity, identify adulterations or mislabeling and determine food safety. The purpose of this review is to present the current state of knowledge on the use of chemometric tools for evaluating quality of food products of animal and plant origin and beverages. The article describes applications of several multivariate techniques in food and beverages research, showing their role in adulteration detection, authentication, quality control, differentiation of samples and comparing their classification and prediction ability.
Reprogramming of avian neural crest axial identity and cell fate

Versatile embryonic neural crest cells Neural crest cells wander far and wide through the developing vertebrate embryo to build tissues such as the jaw and peripheral nerves. Simoes-Costa et al. show, studying chick embryos, that not all neural crest cells are alike. The expression of a handful of transcription factors identifies cranial neural crest cells as distinct from trunk neural crest cells. Ectopic expression of some of these factors caused trunk neural crest cells to function as cranial neural crest cells. Thus, embryonic neural crest cells carry subspecialties that are defined but malleable. Science, this issue p. 1570 Neural crest cells that build the trunk differ from those that build craniofacial structures, but they can be coaxed into switching programs. Neural crest populations along the embryonic body axis of vertebrates differ in developmental potential and fate, so that only the cranial neural crest can contribute to the craniofacial skeleton in vivo. We explored the regulatory program that imbues the cranial crest with its specialized features. Using axial-level specific enhancers to isolate and perform genome-wide profiling of the cranial versus trunk neural crest in chick embryos, we identified and characterized regulatory relationships between a set of cranial-specific transcription factors. Introducing components of this circuit into neural crest cells of the trunk alters their identity and endows these cells with the ability to give rise to chondroblasts in vivo. Our results demonstrate that gene regulatory circuits that support the formation of particular neural crest derivatives may be used to reprogram specific neural crest–derived cell types.
Lessons from the War on Dietary Fat

Conventional dietary guidelines put forth by health care institutions and providers for the past 40 years have stressed the importance of reducing the amount of dietary fat consumed. Such a diet is purported to mitigate metabolic risk factors and optimize the ability to achieve or maintain a healthy body weight. However, over the past 35 years obesity rates in the United States have risen dramatically though the level of dietary fat consumed by U.S. adults has fallen. This review examines the potential reasons for this paradox. Various meta-analyses, controlled trials, and cohort studies have demonstrated that reducing dietary fat intake provides for very little weight loss unless accompanied by equal or greater reductions in total energy intake. Due to both psychological (e.g., the tendency for people to eat more of what they consider low fat) and physiological (e.g., the low satiety that accompanies carbohydrate intake) factors, reducing total caloric intake while simultaneously reducing fat intake is a difficult challenge. Further, reductions in total carbohydrate intake, increases in protein intake, and adoption of a Mediterranean diet seem to be more effective in inducing weight loss than reductions in fat intake. Traditional claims that simply reducing dietary fat will improve metabolic risk factors are also not borne out by research. There is some evidence that replacing dietary saturated fat with unsaturated fat may improve metabolic risk factors, but that research is not conclusive. Teaching Points: • Over the past 40 years, Americans have decreased the percentage of calories they get from dietary fat while rates of overweight and obesity have risen dramatically. • It appears that a decrease in total dietary fat in ad libitum diets may induce a very small decrease in body weight. • Evidence suggests that reductions in total dietary fat intake often occur in conjunction with an increase in total caloric intake. • It seems reasonable to conclude that guiding the public to simply reduce dietary fat intake is an ineffective method to mitigate the rise in obesity and improve public health.
Structural and Functional Dynamics of Sulfate-Reducing Populations in Bacterial Biofilms

ABSTRACT We describe the combined application of microsensors and molecular techniques to investigate the development of sulfate reduction and of sulfate-reducing bacterial populations in an aerobic bacterial biofilm. Microsensor measurements for oxygen showed that anaerobic zones developed in the biofilm within 1 week and that oxygen was depleted in the top 200 to 400 μm during all stages of biofilm development. Sulfate reduction was first detected after 6 weeks of growth, although favorable conditions for growth of sulfate-reducing bacteria (SRB) were present from the first week. In situ hybridization with a 16S rRNA probe for SRB revealed that sulfate reducers were present in high numbers (approximately 108 SRB/ml) in all stages of development, both in the oxic and anoxic zones of the biofilm. Denaturing gradient gel electrophoresis (DGGE) showed that the genetic diversity of the microbial community increased during the development of the biofilm. Hybridization analysis of the DGGE profiles with taxon-specific oligonucleotide probes showed thatDesulfobulbus and Desulfovibrio were the main sulfate-reducing bacteria in all biofilm samples as well as in the bulk activated sludge. However, different Desulfobulbus andDesulfovibrio species were found in the 6th and 8th weeks of incubation, respectively, coinciding with the development of sulfate reduction. Our data indicate that not all SRB detected by molecular analysis were sulfidogenically active in the biofilm.