Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulatory B Cells (B10 Cells) and Regulatory T Cells Have Independent Roles in Controlling Experimental Autoimmune Encephalomyelitis Initiation and Late-Phase Immunopathogenesis

Experimental autoimmune encephalomyelitis (EAE) is a T lymphocyte-mediated autoimmune disease of the CNS. Significant roles for B cells and a rare IL-10–producing CD1dhighCD5+ regulatory B cell subset (B10 cells) have been identified during the initiation and progression of EAE. Whether and how the regulatory functions of B10 cells and FoxP3+ T regulatory cells (Tregs) overlap or influence EAE immunopathogenesis independently has remained unanswered. This study demonstrates that the number of endogenous or adoptively transferred B10 cells directly influenced EAE pathogenesis through their production of IL-10. B10 cell numbers expanded quickly within the spleen, but not CNS following myelin oligodendrocyte glycoprotein35–55 immunization, which paralleled B10 cell regulation of disease initiation. The adoptive transfer of myelin oligodendrocyte glycoprotein33–35-sensitized B10 cells into wild-type mice reduced EAE initiation dramatically. However, B10 cells did not suppress ongoing EAE disease. Rather, Treg numbers expanded significantly within the CNS during disease progression, which paralleled their negative regulation of late-phase disease. Likewise, the preferential depletion of B10 cells in vivo during disease initiation enhanced EAE pathogenesis, whereas Treg depletion enhanced late-phase disease. B10 cells did not regulate T cell proliferation during in vitro assays, but significantly altered CD4+ T cell IFN-γ and TNF-α production. Furthermore, B10 cells downregulated the ability of dendritic cells to act as APCs and thereby indirectly modulated T cell proliferation. Thus, B10 cells predominantly control disease initiation, whereas Tregs reciprocally inhibit late-phase disease, with overlapping B10 cell and Treg functions shaping the normal course of EAE immunopathogenesis.
Leishmania and human immunodeficiency virus coinfection: the first 10 years

Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack of randomized prospective treatment trials; therefore, coinfected patients are treated by conventional regimens. Prophylactic therapy is suggested to be helpful in preventing relapses.
Sustained vasoconstriction associated with daily cyclosporine dose in heart and lung transplant recipients: potential pathophysiologic role of endothelin.

Transient decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) have been associated with each daily dose of cyclosporine (CYA) in patients with renal allografts. We examined the differential dose effects of CYA on native renal function in 24 recipients of heart or lung transplants (treated with 7.3 +/- 0.5 mg/kg/day [mean +/- SEM]) and in seven patients with psoriasis (treated with 4.2 +/- 0.7 mg/kg/day). GFR and RPF were measured by urinary inulin and para-aminohippuric acid clearances 2 hours before the morning CYA dose and for 6 hours after. The age of heart and lung transplant recipients at renal study (2 months after transplantation) was 47 +/- 2.0 years. Their serum creatinine levels rose from 80 +/- 4.0 mumol/L during the first week after transplantation to 120 +/- 4.0 mumol/L at renal study (p < 0.0001). Their GFR and RPF were decreased before the CYA dose at 64 +/- 2.4 and 340 +/- 16 ml/min per 1.73 m2 and did not vary during the study. In comparison, the age of patients with psoriasis was 51 +/- 4.6 years at renal study (24 +/- 4.0 months after CYA treatment). Their serum creatinine levels rose from 80 +/- 4.0 mumol/L before treatment to 100 +/- 10 mumol/L at renal study (p = 0.07). Transient decreases of their baseline GFR and RPF (85 +/- 7.4 and 380 ml/min per 1.73 m2) with a nadir occurring during the first 2 hours of CYA ingestion were observed together with the recovery of these parameters toward baseline by the end of the study. (ABSTRACT TRUNCATED AT 250 WORDS)
IGF-1 and survival in ESRD.

BACKGROUND AND OBJECTIVES IGF-1 deficiency links to malnutrition in CKD patients; however, it is not clear to what extent it associates with survival among these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Serum IGF-1 and other biochemical, clinical (subjective global assessment), and densitometric (dual energy x-ray absorptiometry) markers of nutritional status and mineral and bone metabolism were measured in a cohort of 365 Swedish clinically stable CKD stage 5 patients (median age of 53 years) initiating dialysis between 1994 and 2009; in 207 patients, measurements were also taken after 1 year of dialysis. Deaths were registered during a median follow-up of 5 years. Associations of mortality with baseline IGF-1 and changes of IGF-1 after 1 year of dialysis were evaluated by Cox models. RESULTS At baseline, IGF-1 concentrations associated negatively with age, diabetes mellitus, cardiovascular disease, poor nutritional status, IL-6, and osteoprotegerin and positively with body fat mass, bone mineral density, serum phosphate, calcium, and fibroblast growth factor-23. At 1 year, IGF-1 had increased by 33%. In multivariate regression, low age, diabetes mellitus, and high serum phosphate and calcium associated with IGF-1 at baseline, and in a mixed model, these factors, together with high fat body mass, associated with changes of IGF-1 during the first 1 year of dialysis. Adjusting for calendar year of inclusion, age, sex, diabetes mellitus, cardiovascular disease, IL-6, and poor nutritional status, a 1 SD higher level of IGF-1 at baseline associated with lower mortality risk (hazard ratio, 0.57; 95% confidence interval, 0.32 to 0.98). Persistently low or decreasing IGF-1 levels during the first 1 year on dialysis predicted worse survival (adjusted hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.50). CONCLUSION In incident dialysis patients, low serum IGF-1 associates with body composition and markers of mineral and bone metabolism, and it predicts increased mortality risk.
Enzymatic grafting of hexyloxyphenol onto chitosan to alter surface and rheological properties.

An enzymatic method to graft hexyloxyphenol onto the biopolymer chitosan was studied. The method employs tyrosinase to convert the phenol into a reactive o-quinone, which undergoes subsequent nonenzymatic reaction with chitosan. Reactions were conducted under heterogeneous conditions using chitosan films and also under homogeneous conditions using aqueous methanolic mixtures capable of dissolving both hexyloxyphenol and chitosan. Tyrosinase was shown to catalyze the oxidation of hexyloxyphenol in such aqueous methanolic solutions. Chemical evidence for covalent grafting onto chitosan was provided by three independent spectroscopic approaches. Specifically, enzymatic modification resulted in (1) the appearance of broad absorbance in the 350-nm region of the UV/vis spectra for chitosan films; (2) changes in the NH bending and stretching regions of chitosan's IR spectra; and (3) a base-soluble material with (1)H-NMR signals characteristic of both chitosan and the alkyl groups of hexyloxyphenol. Hexyloxyphenol modification resulted in dramatic changes in chitosan's functional properties. On the basis of contact angle measurements, heterogeneous modification of a chitosan film yielded a hydrophobic surface. Homogeneously modified chitosan offered rheological properties characteristic of associating water-soluble polymers.
A study of the impact of discharge information for surgical patients.

AIM OF THE STUDY To establish whether the routine information surgical patients receive about the management of pain and wound care during their hospitalization is sufficient for them to care for themselves without seeking assistance from a health professional or health care agency. BACKGROUND While there has been considerable evidence suggesting cost benefits of discharge information the health care environment is constantly changing. Contemporary issues such as increased patient participation, extensive use of technology, reduction in health care expenditure, and greater awareness of consumer rights necessitate further inquiry into the appropriateness of discharge information. METHOD One hundred and fifty-eight adult patients discharged within a week of their operation participated in the study. A written questionnaire was distributed within 24 hours prior to discharge and a telephone interview conducted 1 to 2 weeks after discharge. At the time of discharge the majority of patients had received information. FINDINGS Those patients who had received information were less likely to access a health facility than those who had not received information. However, the telephone interview, revealed that there was no evidence that patients who believed they were well informed within 24 hours of discharge about the management of their wound, still felt well informed 1 to 2 weeks later. CONCLUSION Nurses need to be aware that patients who leave the hospital with little or no discharge information may not be confident in the management of their health condition and therefore may access a health facility, if even just for reassurance.
Circumvention of regulatory CD4+ T cell activity during cross‐priming strongly enhances T cell‐mediated immunity

Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8+ T cell‐mediated protection against intracellular pathogens. Most efforts to improve the CD8+ T cell immunogenicity of these vaccines have focused on co‐administration of adjuvant to support cross‐presentation and dendritic cell maturation. In addition, it has been shown that CD4+ T cell help during the priming phase contributes to the generation of protective CD8+ memory T cells. In this report we demonstrate that the depletion of CD4+ T cells paradoxically enhances long‐lasting CD8‐mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II‐restricted CD4+ regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long‐living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4+ T cell help, even the absence of all CD4+ T cells or lack of MHC class II‐mediated interactions on priming dendritic cells result in enhanced CD8+ T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.
Sarcopenic obesity: definition, cause and consequences

Purpose of reviewOlder obese persons with decreased muscle mass or strength are at special risk for adverse outcomes. We discuss potential pathways to muscle impairment in obese individuals and the consequences that joint obesity and muscle impairment may have on health and disability. Tantamount to this discussion is whether low muscle mass or, rather, muscle weakness should be used for the definition. Recent findingsExcess energy intake, physical inactivity, low-grade inflammation, insulin resistance and changes in hormonal milieu may lead to the development of so-called ‘sarcopenic obesity’. It was originally believed that the culprit of age-related muscle weakness was a reduction in muscle mass, but it is now clear that changes in muscle composition and quality are predominant. We propose that the risk of adverse outcomes, such as functional limitation and mortality, is better estimated by considering jointly obesity and muscle strength rather than obesity and muscle mass and the term ‘sarcopenic obesity’ should be revisited. SummaryRecognition of obese patients who have associated muscle problems is an essential goal for clinicians. Further research is needed to identify new target for prevention and cure of this important geriatric syndrome.
Mycobacterial proteomics: analysis of expressed proteomes and post-translational modifications to identify candidate virulence factors

The Mycobacterium tuberculosis bacillus has a number of unique features that make it a particularly effective human pathogen. Although genomic analysis has added to our current understanding of the molecular basis by which M. tuberculosis damages its host, proteomics may be better suited to describe the dynamic interactions between mycobacterial and host systems that underpin this disease. The M. tuberculosis proteome has been investigated using proteomics for over a decade, with increasingly sophisticated mass spectrometry technology and sensitive methods for comparative proteomic profiling. Deeper coverage of the M. tuberculosis proteome has led to the identification of hundreds of putative virulence determinants, as well as an unsurpassed coverage of post-translational modifications. Proteomics is therefore uniquely poised to contribute to our understanding of this pathogen, which may ultimately lead to better management of the disease.
Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure-lowering effects of vitamin C in clinical trials is inconsistent. OBJECTIVE The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP. DESIGN We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance. RESULTS Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were -3.84 mm Hg (95% CI: -5.29, -2.38 mm Hg; P < 0.01) and -1.48 mm Hg (95% CI: -2.86, -0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were -4.85 mm Hg (P < 0.01) and -1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant. CONCLUSIONS In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed.
Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia.

The protein products of proto‐oncogenes implicated in T cell acute lymphoblastic leukemia include two distinct families of presumptive transcription factors. RBTN1 and RBTN2 encode highly related proteins that possess cysteine‐rich LIM motifs. TAL1, TAL2 and LYL1 encode a unique subgroup of basic helix‐loop‐helix (bHLH) proteins that share exceptional homology in their bHLH sequences. We have found that RBTN1 and RBTN2 have the ability to interact with each of the leukemogenic bHLH proteins (TAL1, TAL2 and LYL1). These interactions occur in vivo and appear to be mediated by sequences within the LIM and bHLH domains. The LIM‐bHLH interactions are highly specific in that RBTN1 and RBTN2 will associate with TAL1, TAL2 and LYL1, but not with other bHLH proteins, including E12, E47, Id1, NHLH1, AP4, MAX, MYC and MyoD1. Moreover, RBTN1 and RBTN2 can interact with TAL1 polypeptides that exist in assembled bHLH heterodimers (e.g. TAL1‐E47), suggesting that the RBTN proteins can influence the functional properties of TAL1. Finally, we have identified a subset of leukemia patients that harbor tumor‐specific rearrangements of both their RBTN2 and TAL1 genes. Thus, the activated alleles of these genes may promote leukemia cooperatively, perhaps as a result of bHLH‐LIM interactions between their protein products.
Modeling protein density of states: Additive hydrophobic effects are insufficient for calorimetric two‐state cooperativity

A well‐established experimental criterion for two‐state thermodynamic cooperativity in protein folding is that the van't Hoff enthalpy ΔHvH around the transition midpoint is equal, or very nearly so, to the calorimetric enthalpy ΔHcal of the entire transition. This condition is satisfied by many small proteins. We use simple lattice models to provide a statistical mechanical framework to elucidate how this calorimetric two‐state picture may be reconciled with the hierarchical multistate scenario emerging from recent hydrogen exchange experiments. We investigate the feasibility of using inverse Laplace transforms to recover the underlying density of states (i.e., enthalpy distribution) from calorimetric data. We find that the constraint imposed by ΔHvH/ΔHcal ≈ 1 on densities of states of proteins is often more stringent than other “two‐state” criteria proposed in recent theoretical studies. In conjunction with reasonable assumptions, the calorimetric two‐state condition implies a narrow distribution of denatured‐state enthalpies relative to the overall enthalpy difference between the native and the denatured conformations. This requirement does not always correlate with simple definitions of “sharpness” of a transition and has important ramifications for theoretical modeling. We find that protein models that assume capillarity cooperativity can exhibit overall calorimetric two‐state‐like behaviors. However, common heteropolymer models based on additive hydrophobic‐like interactions, including highly specific two‐dimensional Gō models, fail to produce proteinlike ΔHvH/ΔHcal ≈ 1. A simple model is constructed to illustrate a proposed scenario in which physically plausible local and nonlocal cooperative terms, which mimic helical cooperativity and environment‐dependent hydrogen bonding strength, can lead to thermodynamic behaviors closer to experiment. Our results suggest that proteinlike thermodynamic cooperativity may require a cooperative interplay between local and nonlocal interactions. The prospect of using calorimetric data to constrain Z‐scores of knowledge‐based potentials is discussed. Proteins 2000;40:543–571. © 2000 Wiley‐Liss, Inc.
Origin and Diversity of Metabolically Active Gut Bacteria from Laboratory-Bred Larvae of Manduca sexta (Sphingidae, Lepidoptera, Insecta)

ABSTRACT Cultivation-independent analyses based on genetic profiling of partial bacterial 16S rRNA genes by PCR-single-strand conformation polymorphism (PCR-SSCP), reverse transcriptase (RT)-PCR-SSCP of the 16S rRNA itself, and stable isotope probing (SIP), followed by RT-PCR-SSCP, were applied to characterize the diversity of metabolically active bacteria in the larval gut of Manduca sexta bred on tobacco leaves under greenhouse conditions. For SIP, hatching larvae were fed with leaves from tobacco plants grown in a 13CO2-enriched atmosphere. Dominant SSCP bands were sequenced and phylogenetically analyzed. Only one major gut colonizer, an Enterococcus relative, was detected; it occurred in the heavy RNA fraction, demonstrating its metabolic activity, and it originated from eggs, where its metabolic activity was also indicated by rRNA-based SSCP profiles. In contrast, a Citrobacter sedlakii relative was detected on eggs by DNA-SSCP, but rRNA-SSCP and SIP-rRNA-SSCP were negative, suggesting that these bacterial cells were inactive. A Burkholderia relative was dominant and metabolically active on the tobacco leaves but inactive inside the gut, where it was also quantitatively reduced, as suggested by lower band intensities in the DNA-based SSCP profiles. SIP-RNA-SSCP detected another metabolically active gut bacterium (Enterobacter sp.) and more bacteria in the light RNA fraction, indicating low or no metabolic activity of the latter inside the gut. We conclude that the larval gut supported only a low diversity of metabolically active bacteria.
Carbon‐coated Stents in Patients with Acute Coronary Syndromes

For patients with ST elevation myocardial infarction (STEMI) or non‐ST elevation myocardial infarction (NSTEMI), rapid restoration of coronary blood flow is the primary therapeutic goal. Because of the acute nature of this clinical presentation, bleeding risks may not be adequately evaluated, limiting the use of drug‐eluting stents, since premature discontinuation of antiplatelet therapy strongly predicts stent thrombosis. We evaluated angiographic and clinical results of non‐drug‐eluting carbon‐coated stents.
Functional magnetic resonance imaging of human hypothalamic responses to sweet taste and calories 1 – 3

Background: Evidence exists that beverages do not trigger appropriate anticipatory physiologic responses, such as cephalic phase insulin release. Therefore, it is of interest to elucidate the food properties necessary for triggering adaptive responses. Previously, we found a prolonged dose-dependent decrease in the hypothalamic functional magnetic resonance imaging signal after ingestion of a