Miracle-dz/UniFAR-FTUs huggingface dataset:
Illness Intrusiveness Mediates the Relationship Between Heart Failure Severity and Depression in Older Adults

Depression frequently co-occurs in heart failure (HF) patients, causing significant interference and negative health outcomes. This case-controlled study explored the construct of illness intrusiveness and examined its relationship to HF severity and depression. Older veterans (n = 104) with an HF diagnosis completed a one-time assessment that included demographics, depressive symptoms (Geriatric Depression Scale), the Illness Intrusiveness Rating Scale (IIRS), and HF quality of life and functional abilities (Kansas City Cardiomyopathy Questionnaire [KCCQ]). Analyses included exploratory correlations between IIRS and KCCQ items, a confirmatory factor analysis (IIRS), and formal mediational analyses. Results indicated that the IIRS had adequate internal consistency and concurrent validity, with support for its established three-factor model. Regression analyses indicated that illness intrusiveness mediated HF illness severity and depression. In conclusion, illness intrusiveness may be a better indicator of depression than illness severity (HF symptoms); thus research methods and interventions targeted at reducing illness intrusiveness merit further investigation.
Novel Teleost CD4-Bearing Cell Populations Provide Insights into the Evolutionary Origins and Primordial Roles of CD4+ Lymphocytes and CD4+ Macrophages

Tetrapods contain a single CD4 coreceptor with four Ig domains that likely arose from a primordial two-domain ancestor. Notably, teleost fish contain two CD4 genes. Like tetrapod CD4, CD4-1 of rainbow trout includes four Ig domains, whereas CD4-2 contains only two. Because CD4-2 is reminiscent of the prototypic two-domain CD4 coreceptor, we hypothesized that by characterizing the cell types bearing CD4-1 and CD4-2, we would shed light into the evolution and primordial roles of CD4-bearing cells. Using newly established mAbs against CD4-1 and CD4-2, we identified two bona-fide CD4+ T cell populations: a predominant lymphocyte population coexpressing surface CD4-1 and CD4-2 (CD4 double-positive [DP]), and a minor subset expressing only CD4-2 (CD4-2 single-positive [SP]). Although both subsets produced equivalent levels of Th1, Th17, and regulatory T cell cytokines upon bacterial infection, CD4-2 SP lymphocytes were less proliferative and displayed a more restricted TCRβ repertoire. These data suggest that CD4-2 SP cells represent a functionally distinct population and may embody a vestigial CD4+ T cell subset, the roles of which reflect those of primeval CD4+ T cells. Importantly, we also describe the first CD4+ monocyte/macrophage population in a nonmammalian species. Of all myeloid subsets, we found the CD4+ population to be the most phagocytic, whereas CD4+ lymphocytes lacked this capacity. This study fills in an important gap in the knowledge of teleost CD4-bearing leukocytes, thus revealing critical insights into the evolutionary origins and primordial roles of CD4+ lymphocytes and CD4+ monocytes/macrophages.
The association between symptoms and microbiologically defined response to tuberculosis treatment.

RATIONALE The lack of consistent associations between clinical outcomes and microbiological responses to therapy for some infectious diseases has raised questions about the adequacy of microbiological endpoints for tuberculosis treatment trials. OBJECTIVES To evaluate the association between symptoms and microbiological response to tuberculosis treatment. METHODS We performed a retrospective analysis of four clinical trials in which participants had culture-positive tuberculosis, standardized symptom assessment, and follow-up mycobacterial cultures. Two trials (studies 22 and 23) followed participants to identify recurrent tuberculosis; participants in studies 27 and 28 were only followed to treatment completion. MEASUREMENTS AND MAIN RESULTS This analysis included 1,978 participants; 39 (2.0%) had culture-confirmed treatment failure, and 75 (3.9%) had culture-confirmed recurrence. Productive cough was associated with indices of increased mycobacterial burden at diagnosis (acid-fast smear grade, severity of radiographic abnormalities). Fever and sweats improved rapidly with treatment, whereas productive cough decreased more slowly and was present in 20% of visits after treatment completion. During treatment, study participants with productive cough more often had concurrent culture positivity compared with those without productive cough (studies 22 and 23: adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.33-2.44). Finally, symptoms during the latter part of treatment and follow-up were associated with culture-confirmed treatment failure and recurrence in studies 22 and 23 (for cough: adjusted hazard ratio, 2.07; 95% CI, 1.23-3.49; for fever: adjusted hazard ratio, 5.05; 95% CI, 2.76-9.19). CONCLUSIONS There are consistent relationships between symptoms and microbiological indices of tuberculosis, including measures of mycobacterial burden at baseline, culture positivity during treatment, and time to culture-confirmed treatment failure and recurrence.
Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease.

RATIONALE There is a need to identify clinically meaningful predictors of mortality following hospitalized COPD exacerbation. OBJECTIVES The aim of this study was to systematically review the literature to identify clinically important factors that predict mortality after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS Eligible studies considered adults admitted to hospital with COPD exacerbation. Two authors independently abstracted data. Odds ratios were then calculated by comparing the prevalence of each predictor in survivors versus nonsurvivors. For continuous variables, mean differences were pooled by the inverse of their variance, using a random effects model. MEASUREMENTS AND MAIN RESULTS There were 37 studies included (189,772 study subjects) with risk of death ranging from 3.6% for studies considering short-term mortality, 31.0% for long-term mortality (up to 2 yr after hospitalization), and 29.0% for studies that considered solely intensive care unit (ICU)-admitted study subjects. Twelve prognostic factors (age, male sex, low body mass index, cardiac failure, chronic renal failure, confusion, long-term oxygen therapy, lower limb edema, Global Initiative for Chronic Lung Disease criteria stage 4, cor pulmonale, acidemia, and elevated plasma troponin level) were significantly associated with increased short-term mortality. Nine prognostic factors (age, low body mass index, cardiac failure, diabetes mellitus, ischemic heart disease, malignancy, FEV1, long-term oxygen therapy, and PaO2 on admission) were significantly associated with long-term mortality. Three factors (age, low Glasgow Coma Scale score, and pH) were significantly associated with increased risk of mortality in ICU-admitted study subjects. CONCLUSION Different factors correlate with mortality from COPD exacerbation in the short term, long term, and after ICU admission. These parameters may be useful to develop tools for prediction of outcome in clinical practice.
The safety of thoracentesis in patients with uncorrected bleeding risk.

BACKGROUND Thoracentesis is commonly performed to evaluate pleural effusions. Many medications (warfarin, heparin, clopidogrel) or physiological factors (elevated International Normalized Ratio [INR], thrombocytopenia, uremia) increase the risk for bleeding. Frequently these medications are withheld or transfusions are performed to normalize physiological parameters before a procedure. The safety of performing thoracentesis without correction of these bleeding risks has not been prospectively evaluated. METHODS This prospective observational cohort study enrolled 312 patients who underwent thoracentesis. All patients were evaluated for the presence of risk factors for bleeding. Hematocrit levels were obtained pre- and postprocedure, and the occurrence of postprocedural hemothorax was evaluated. MEASUREMENTS AND MAIN RESULTS Thoracenteses were performed in 312 patients, 42% of whom had a risk for bleeding. Elevated INR, secondary to liver disease or warfarin, and renal disease were the two most common etiologies for bleeding risk, although many patients had multiple potential bleeding risks. There was no significant difference in pre- and postprocedural hematocrit levels in patients with a bleeding risk when compared with patients with no bleeding risk. No patient developed a hemothorax as a result of the thoracentesis. CONCLUSIONS This single-center, observational study suggests that thoracentesis may be safely performed without prior correction of coagulopathy, thrombocytopenia, or medication-induced bleeding risk. This may reduce the morbidity associated with transfusions or withholding of medications.
Blood-Borne Lipopolysaccharide Is Rapidly Eliminated by Liver Sinusoidal Endothelial Cells via High-Density Lipoprotein

During Gram-negative bacterial infections, excessive LPS induces inflammation and sepsis via action on immune cells. However, the bulk of LPS can be cleared from circulation by the liver. Liver clearance is thought to be a slow process mediated exclusively by phagocytic resident macrophages, Kupffer cells (KC). However, we discovered that LPS disappears rapidly from the circulation, with a half-life of 2–4 min in mice, and liver eliminates about three quarters of LPS from blood circulation. Using microscopic techniques, we found that ∼75% of fluor-tagged LPS in liver became associated with liver sinusoidal endothelial cells (LSEC) and only ∼25% with KC. Notably, the ratio of LSEC-KC–associated LPS remained unchanged 45 min after infusion, indicating that LSEC independently processes the LPS. Most interestingly, results of kinetic analysis of LPS bioactivity, using modified limulus amebocyte lysate assay, suggest that recombinant factor C, an LPS binding protein, competitively inhibits high-density lipoprotein (HDL)–mediated LPS association with LSEC early in the process. Supporting the previous notion, 3 min postinfusion, 75% of infused fluorescently tagged LPS-HDL complex associates with LSEC, suggesting that HDL facilitates LPS clearance. These results lead us to propose a new paradigm of LSEC and HDL in clearing LPS with a potential to avoid inflammation during sepsis.
Rpl22 Loss Selectively Impairs αβ T Cell Development by Dysregulating Endoplasmic Reticulum Stress Signaling

Although ribosomal proteins (RP) are thought to primarily facilitate biogenesis of the ribosome and its ability to synthesize protein, emerging evidence suggests that individual RP can perform critical regulatory functions that control developmental processes. We showed previously that despite the ubiquitous expression of the RP ribosomal protein L22 (Rpl22), germline ablation of Rpl22 in mice causes a selective, p53-dependent block in the development of αβ, but not γδ, T cell progenitors. Nevertheless, the basis by which Rpl22 loss selectively induces p53 in αβ T cell progenitors remained unclear. We show in this study that Rpl22 regulates the development of αβ T cells by restraining endoplasmic reticulum (ER) stress responses. In the absence of Rpl22, ER stress is exacerbated in αβ, but not γδ, T cell progenitors. The exacerbated ER stress in Rpl22-deficient αβ T lineage progenitors is responsible for selective induction of p53 and their arrest, as pharmacological induction of stress is sufficient to induce p53 and replicate the selective block of αβ T cells, and attenuation of ER stress signaling by knockdown of protein kinase R–like ER kinase, an ER stress sensor, blunts p53 induction and rescues development of Rpl22-deficient αβ T cell progenitors. Rpl22 deficiency appears to exacerbate ER stress by interfering with the ability of ER stress signals to block new protein synthesis. Our finding that Rpl22 deficiency exacerbates ER stress responses and induces p53 in αβ T cell progenitors provides insight into how a ubiquitously expressed RP can perform regulatory functions that are selectively required by some cell lineages but not others.
Operative complications and fetal morbidity encountered in 300 prophylactic transabdominal cervical cerclage procedures by one obstetric surgeon

This retrospective cohort study identifies complications associated with transabdominal cerclage (TAC). In 300 procedures performed over a 24 year time span, 11 (3.7%) surgical complications were encountered. Fetal loss (prior to 20 weeks) occurred in 4.1% of pregnancies. The median estimated blood loss among patients was 100 ml, with blood loss sufficient to require transfusion only once. Considering patients with classical indications, the gestational age at delivery was greater (37 weeks) after TAC than in the latest pre-TAC pregnancy (24 weeks) (p < 0.001). Lower uterine dehiscence in four patients and uterine rupture in one, underscore the advisability of early term delivery after fetal lung maturity is assured. A survival rate of 98.0% was calculated among infants that were delivered at >24 weeks’ gestation. Our results demonstrate that complications encountered in placing a TAC were unusual and generally manageable. This communication may assist the surgeon to balance risks in individual clinical circumstances more adequately.
Clinical significance of a first positive nontuberculous mycobacteria culture in cystic fibrosis.

RATIONALE Little is known about outcomes of infection with nontuberculous mycobacteria (NTM) in cystic fibrosis (CF) or about the significance of a positive NTM culture. Determining which patients are at risk for active NTM disease is clinically valuable. OBJECTIVES To examine the clinical course of subjects with CF with an initial positive NTM culture and identify characteristics associated with active NTM disease. METHODS We performed a retrospective study of pediatric and adult subjects with CF with at least one positive NTM culture at the Colorado CF Center from 2000 to 2010. MEASUREMENTS AND MAIN RESULTS Mycobacterium avium complex was the first identified NTM in the majority of subjects (73%). The frequency of growing a second NTM species was 26% at 5 years. Clinical characteristics and distribution of NTM species between pediatric and adult subjects were similar except for differences in baseline FEV1 (89% vs. 71%; P < 0.001) and coinfection with Pseudomonas aeruginosa (33% vs. 55%; P = 0.04). Over 60% of subjects had transient or persistent infection but not active NTM disease. Subjects who developed active NTM disease were distinguished from those with transient or persistent infection, respectively, by FEV1 at the time of first positive NTM culture (72% vs. 84 or 86%; P = 0.02) and FEV1 decline in the prior year (-5.8%/yr vs. -0.7%/yr [P = 0.009] or -0.4%/yr [P = 0.001]). CONCLUSIONS The majority of patients with CF with a first positive NTM culture do not progress to active disease. Lower lung function and accelerated lung function decline appear to be indicators of the significance of an initial positive NTM culture.
Eritromelalgia primária: relato de caso

Erythromelalgia is a rare clinical syndrome characterized by heat, redness and intermittent pain in the extremities, being most frequent the bilateral development in the lower extremities. Local cooling brings relief to symptoms, while heating, physical exercises and use of stockings/socks intensify the discomfort. This condition can be primary or idiopathic or secondary to haematological disorders and vascular inflammatory and degenerative diseases. It is reported the case of an eighteen-year-old male who presented, at the early age of two, development of the symptoms of erythema ,heat and pain followed by desquamation of hands and feet, in outbreaks, with intervals 4 to 5 years long between the crises.
Cyproterone Acetate Versus Hydrocortisone Treatment in Late-Onset Adrenal Hyperplasia

Thirty late-onset adrenal hyperplasia patients consulting for isolated hirsutism were randomly divided into two groups; group 1 (n = 16) was treated with hydrocortisone in order to suppress androgen adrenal secretion, and group 2 (n = 14) received cyproterone acetate (CPA) antiandrogen therapy to inhibit peripheral androgen activity. The clinical and hormonal effects of each type of treatment were evaluated. Before treatment, the clinical and hormonal profiles of the two patient groups did not differ significantly. Excellent clinical evolution in terms of the regression of hirsutism was observed in the CPA-treated patients (54% decrease in the clinical score in 1 yr), in contrast with the slight decrease in hirsutism (26%) after hydrocortisone treatment. In hydrocortisone-treated patients, plasma androgen decreased to normal levels: testosterone from 3.05 ± 1.45 to 1.46 ± 0.42 nmol/L and Δ4-androstenedione from 13.6 ± 4.1 to 6.33 ± 1.47 nmol/L. Conversely, in CPAtreated patients, only a slight decrease in.
The Bacterial Peptidoglycan-Sensing Molecules NOD1 and NOD2 Promote CD8+ Thymocyte Selection

Nucleotide-binding and oligomerization domain (NOD)–like receptors NOD1 and NOD2 are cytosolic innate immune receptors that recognize microbial peptidoglycans. Although studies have addressed the role of NOD proteins in innate immune responses, little attention has been given to their impact on the developing adaptive immune system. We have assessed the roles of NOD1 and NOD2 deficiency on T cell development in mice. Our results demonstrate that NOD1 and NOD2 promote the positive selection/maturation of CD8 single-positive thymocytes in a thymocyte-intrinsic manner. TCR-mediated ERK phosphorylation is significantly reduced in the absence of NOD proteins, but receptor-interacting protein 2 is not involved in CD8 single-positive thymocyte selection or ERK signaling. Commensal bacteria–free animals have thymocyte maturation defects, and exogenous NOD ligands can enhance thymocyte maturation in culture. These results raise the intriguing possibility that abnormal lymphocyte responses observed in NOD-dependent inflammatory diseases are not driven solely by microbial signals in the gut, but may also involve intrinsic lymphocyte defects resulting from impaired CD8 T cell thymic development.
Antibody Distance from the Cell Membrane Regulates Antibody Effector Mechanisms

Immunotherapy using mAbs, such as rituximab, is an established means of treating hematological malignancies. Abs can elicit a number of mechanisms to delete target cells, including complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity, and Ab-dependent cellular phagocytosis. The inherent properties of the target molecule help to define which of these mechanisms are more important for efficacy. However, it is often unclear why mAb binding to different epitopes within the same target elicits different levels of therapeutic activity. To specifically address whether distance from the target cell membrane influences the aforementioned effector mechanisms, a panel of fusion proteins consisting of a CD20 or CD52 epitope attached to various CD137 scaffold molecules was generated. The CD137 scaffold was modified through the removal or addition of cysteine-rich extracellular domains to produce a panel of chimeric molecules that held the target epitope at different distances along the protein. It was shown that complement-dependent cytotoxicity and Ab-dependent cellular cytotoxicity favored a membrane-proximal epitope, whereas Ab-dependent cellular phagocytosis favored an epitope positioned further away. These findings were confirmed using reagents targeting the membrane-proximal or -distal domains of CD137 itself before investigating these properties in vivo, where a clear difference in the splenic clearance of transfected tumor cells was observed. Together, this work demonstrates how altering the position of the Ab epitope is able to change the effector mechanisms engaged and facilitates the selection of mAbs designed to delete target cells through specific effector mechanisms and provide more effective therapeutic agents.
Decline in tuberculosis among Mexico-born persons in the United States, 2000-2010.

BACKGROUND In 2010, Mexico was the most common (22.9%) country of origin for foreign-born persons with tuberculosis in the United States, and overall trends in tuberculosis morbidity are substantially influenced by the Mexico-born population. OBJECTIVES To determine the risk of tuberculosis disease among Mexico-born persons living in the United States. METHODS Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined tuberculosis case counts and case rates stratified by years since entry into the United States and geographic proximity to the United States-Mexico border. We calculated trends in case rates over time measured by average annual percent change. RESULTS The total tuberculosis case count (-14.5%) and annual tuberculosis case rate (average annual percent change -5.1%) declined among Mexico-born persons. Among those diagnosed with tuberculosis less than 1 year since entry into the United States (newly arrived persons), there was a decrease in tuberculosis cases (-60.4%), no change in tuberculosis case rate (average annual percent change of 0.0%), and a decrease in population (-60.7%). Among those living in the United States for more than 5 years (non-recently arrived persons), there was an increase in tuberculosis cases (+3.4%), a decrease in tuberculosis case rate (average annual percent change of -4.9%), and an increase in population (+62.7%). In 2010, 66.7% of Mexico-born cases were among non-recently arrived persons, compared with 51.1% in 2000. Although border states reported the highest proportions (>15%) of tuberculosis cases that were Mexico-born, the highest Mexico-born-specific tuberculosis case rates (>20/100,000 population) were in states in the eastern and southeastern regions of the United States. CONCLUSIONS The decline in tuberculosis morbidity among Mexico-born persons may be attributed to fewer newly arrived persons from Mexico and lower tuberculosis case rates among non-recently arrived Mexico-born persons. The extent of the decline was dampened by an unchanged tuberculosis case rate among newly arrived persons from Mexico and a large increase in the non-recently arrived Mexico-born population. If current trends continue, tuberculosis morbidity among Mexico-born persons will be increasingly driven by those who have been living in the United States for more than 5 years.
IL-13–Mediated Regulation of Learning and Memory

The role of proinflammatory cytokines in cognitive function has been investigated with both beneficial and possible detrimental effects, depending on the cytokine. More recently, the type 2 IL-4 has been demonstrated to play a role in cognition. In this study, using the Morris water maze task, we demonstrate that IL-13–deficient mice are significantly impaired in working memory as well as attenuated reference memory, both functions essential for effective complex learning. During the learning process, wild-type mice increased the number of CD4+ T cells in the meninges and production of IL-13, whereas neither Morris water maze–trained IL-4 nor trained IL-13–deficient mice were able to increase CD4+ T cells in the meninges. Mechanistically, we showed that IL-13 is able to stimulate primary astrocytes to produce brain-derived neurotrophic factor, which does foster cognitive functions. Moreover, Morris water maze–trained wild-type mice were able to increase astrocyte-produced glial fibrillary acidic protein in the hippocampus, which was impaired in Morris water maze–trained IL-4– and IL-13–deficient mice. Collectively, this study strongly suggests that the Th2 cytokines, not only IL-4 but also IL-13, are involved in cognitive functions by stimulating astrocytes from the meninges and hippocampus. These results may be important for future development of therapeutic approaches associated with neurologic disorders such as Parkinson disease–associated dementia and HIV-associated dementia among others.