Miracle-dz/UniFAR-FTUs huggingface dataset:
Survey of video laryngoscopy use by U.S. critical care fellowship training programs.

RATIONALE Recent studies on video laryngoscopy have demonstrated improvements in both safety and success of endotracheal intubation in the critically ill. OBJECTIVES We assessed the use of video laryngoscopy among internal medicine fellowship programs training physicians in critical care medicine. METHODS A 19-question survey was e-mailed to program directors of pulmonary/critical care and internal medicine critical care fellowship training programs. MEASUREMENTS AND MAIN RESULTS A completed survey was returned by 36% of invited program directors. Sixty-nine percent of respondents reported a change in their approach to intubation training over the prior 3 years, with 56% of changes attributed to the adoption of a video laryngoscope. Other reported changes include new training methods (23%) and adoption of a checklist (10%). A video laryngoscope is available for clinical use in 89% of the responding programs. The video scope is used as the primary device in 16% and is never used in 9%. In the remainder of programs, the video laryngoscope is only used for difficult intubations or after failure of direct laryngoscopy (32%) or the primary device is determined by the preference of the operator (32%). CONCLUSIONS The majority of internal medicine critical care program directors who recently responded to an e-mail survey reported that they have changed their approach to teaching endotracheal intubation, driven largely by the adoption of video laryngoscopy for upper airway visualization. Nevertheless, despite widespread availability, video laryngoscopy is used uncommonly as the primary visualization device for intubation at the programs represented by the respondents to this survey.
Notch Ligand Delta-like 4 Promotes Regulatory T Cell Identity in Pulmonary Viral Infection

Regulatory T (Treg) cells establish tolerance, prevent inflammation at mucosal surfaces, and regulate immunopathology during infectious responses. Recent studies have shown that Delta-like ligand 4 (Dll4) was upregulated on APC after respiratory syncytial virus (RSV) infection, and its inhibition leads to exaggerated immunopathology. In the present study, we outline the role of Dll4 in Treg cell differentiation, stability, and function in RSV infection. We found that Dll4 was expressed on CD11b+ pulmonary dendritic cells in the lung and draining lymph nodes in wild-type BALB/c mice after RSV infection. Dll4 neutralization exacerbated RSV-induced disease pathology, mucus production, group 2 innate lymphoid cell infiltration, IL-5 and IL-13 production, as well as IL-17A+ CD4 T cells. Dll4 inhibition decreased the abundance of CD62LhiCD44loFoxp3+ central Treg cells in draining lymph nodes. The RSV-induced disease was accompanied by an increase in Th17-like effector phenotype in Foxp3+ Treg cells and a decrease in granzyme B expression after Dll4 blockade. Finally, Dll4-exposed induced Treg cells maintained the CD62LhiCD44lo central Treg cell phenotype, had increased Foxp3 expression, became more suppressive, and were resistant to Th17 skewing in vitro. These results suggest that Dll4 activation during differentiation sustained Treg cell phenotype and function to control RSV infection.
Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus

Systemic lupus erythematosus (lupus) is characterized by autoantibody-mediated organ injury. Follicular Th (Tfh) cells orchestrate physiological germinal center (GC) B cell responses, whereas in lupus they promote aberrant GC responses with autoreactive memory B cell development and plasma cell–derived autoantibody production. IL-21, a Tfh cell–derived cytokine, provides instructional cues for GC B cell maturation, with disruption of IL-21 signaling representing a potential therapeutic strategy for autoantibody-driven diseases such as systemic lupus erythematosus. We used blockade of IL-21 to dissect the mechanisms by which this cytokine promotes autoimmunity in murine lupus. Treatment of lupus-prone B6.Sle1. Yaa mice with an anti–IL-21 blocking Ab reduced titers of autoantibodies, delayed progression of glomerulonephritis and diminished renal-infiltrating Tfh and Th1 cells, and improved overall survival. Therapy inhibited excessive accumulation of Tfh cells coexpressing IL-21 and IFN-γ, and suppressed their production of the latter cytokine, albeit while not affecting their frequency. Anti–IL-21 treatment also led to a reduction in GC B cells, CD138hi plasmablasts, IFN-γ–dependent IgG2c production, and autoantibodies, indicating that Tfh cell–derived IL-21 is critical for pathological B cell cues in lupus. Normalization of GC responses was, in part, caused by uncoupling of Tfh–B cell interactions, as evidenced by reduced expression of CD40L on Tfh cells and reduced B cell proliferation in treated mice. Our work provides mechanistic insight into the contribution of IL-21 to the pathogenesis of murine lupus, while revealing the importance of T–B cellular cross-talk in mediating autoimmunity, demonstrating that its interruption impacts both cell types leading to disease amelioration.
Frequency of Mycoplasma hominis and Ureaplasma urealyticum in Females With Urogenital Infections and Habitual Abortion History in Ahvaz, Iran; Using Multiplex PCR

Results: The results of the current study showed that the presence of M. hominis in urine (P = 0.006) and genital samples (P = 0.01) was associated with urogenital infections. Statistical analysis based on the age, revealed that the highest prevalence of M. hominis (71.4%) and U. urealyticum (60%) were in females within 30-34 and 35-39 years old, respectively. Similarly, in genital samples, the highest incidence of M. hominis (54.5%) and U. urealyticum (53.8%) was found in females within 28-33 and 34-39 years old. Interestingly, further analyses revealed direct strong relation between the mollicutes used in this study and habitual abortion as well as urogenital infections. Conclusions: There was a strong relation between the presence of the studied M. hominis and U. urealyticum with urogenital infection in the females under study in comparison with those of control groups. The studied mollicutes were highly associated with habitual abortion in symptomatic females. The multiplex PCR was developed for simultaneous, early, and easy detection of these potential pathogens.
High Prevalence of Obstructive Sleep Apnea in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease.

RATIONALE When obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in the so-called "overlap" syndrome, a high risk for mortality and morbidity has been reported. There is controversy about the prevalence of OSA in people affected by COPD. OBJECTIVES The purpose of this study was to investigate objective meaures of sleep-disordered breathing in patients with moderate to severe COPD to test the hypothesis that COPD is associated with an increased prevalence of OSA. METHODS Fifty-four patients (54% men) with moderate to severe COPD were enrolled prospectively (mean ± SD, FEV1 = 42.8 ± 19.8% predicted, and FEV1/FVC = 42.3 ± 13.1). Twenty patients (37%) were on supplemental oxygen at baseline. Exercise tolerance; questionnaires related to symptoms, sleep, and quality of life; and home polysomnography were obtained. MEASUREMENTS AND MAIN RESULTS Forty-four patients had full polysomnography suitable for analysis. OSA (apnea-hypopnea index > 5/h) was present in 29 subjects (65.9%). Sleep efficiency was poor in 45% of subjects. CONCLUSIONS OSA is highly prevalent in patients with moderate to severe COPD referred to pulmonary rehabilitation. Sleep quality is also poor among this selected group. These patients have greater-than-expected sleep-disordered breathing, which could be an important contributory factor to morbidity and mortality. Pulmonary rehabilitation programs should consider including a sleep assessment in patients with moderate to severe COPD and interventions when indicated to help reduce the impact of OSA in COPD.
Multitasking Immune Sp185/333 Protein, rSpTransformer-E1, and Its Recombinant Fragments Undergo Secondary Structural Transformation upon Binding Targets

The purple sea urchin, Strongylocentrotus purpuratus, expresses a diverse immune response protein family called Sp185/333. A recombinant Sp185/333 protein, previously called rSp0032, shows multitasking antipathogen binding ability, suggesting that the protein family mediates a flexible and effective immune response to multiple foreign cells. Bioinformatic analysis predicts that rSp0032 is intrinsically disordered, and its multiple binding characteristic suggests structural flexibility to adopt different conformations depending on the characteristics of the target. To address the flexibility and structural shifting hypothesis, circular dichroism analysis of rSp0032 suggests that it transforms from disordered (random coil) to α helical structure. This structural transformation may be the basis for the strong affinity between rSp0032 and several pathogen-associated molecular patterns. The N-terminal Gly-rich fragment of rSp0032 and the C-terminal His-rich fragment show unique transformations by either intensifying the α helical structure or changing from α helical to β strand depending on the solvents and molecules added to the buffer. Based on these results, we propose a name change from rSp0032 to rSpTransformer-E1 to represent its flexible structural conformations and its E1 element pattern. Given that rSpTransformer-E1 shifts its conformation in the presence of solvents and binding targets and that all Sp185/333 proteins are predicted to be disordered, many or all of these proteins may undergo structural transformation to enable multitasking binding activity toward a wide range of targets. Consequently, we also propose an overarching name change for the entire family from Sp185/333 proteins to SpTransformer proteins.
Chest computed tomography predicts the frequency of pulmonary exacerbations in children with cystic fibrosis.

RATIONALE Abnormalities on chest computed tomography (CT) in children with cystic fibrosis (CF) have been shown to correlate with short-term measures of lung disease. Chest CT scores offer promise as a potential surrogate end point in CF; however, there is limited information available on the ability of chest CT scores to predict future morbidity. OBJECTIVES Determine whether chest CT scores are associated with the rate of pulmonary exacerbations over the next 10 years. METHODS Ten years of follow-up data were obtained from the CF Foundation Patient Registry for 60 children enrolled in the Pulmozyme Early Intervention Trial and who had chest CT scans at baseline. MEASUREMENTS AND MAIN RESULTS Multivariable Poisson regression was used to compare Brody CT scores and the number of pulmonary exacerbations in the following 10 years. At the time of the chest CT, the mean (SD) age was 10.6 (1.7) years. A 1-point increase in the Brody CT score was associated with an increase in the mean (95% confidence interval) rate of pulmonary exacerbations of 1.39 (1.15, 1.67) (P < 0.001). Brody CT scores were more strongly associated with the number of pulmonary exacerbations than FEV1 % predicted at the time of the chest CT (P = 0.037 by chi-square test). CONCLUSIONS There is a significant association between Brody CT scores and the rate of pulmonary exacerbations up to 10 years later. This association is stronger than for FEV1 obtained at the time of the CT, suggesting that chest CT scores offer improved ability to predict future outcomes.
Bach2 Promotes B Cell Receptor–Induced Proliferation of B Lymphocytes and Represses Cyclin-Dependent Kinase Inhibitors

BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling. Following BCR engagement in vitro, B cells from Bach2-deficient (Bach2−/−) mice showed lower incorporation of BrdU and reduced cell cycle progression compared with wild-type cells. Bach2−/− B cells also underwent increased apoptosis, as evidenced by an elevated frequency of sub-G1 cells and early apoptotic cells. Transcriptome analysis of BCR-engaged B cells from Bach2−/− mice revealed reduced expression of the antiapoptotic gene Bcl2l1 encoding Bcl-xL and elevated expression of cyclin-dependent kinase inhibitor (CKI) family genes, including Cdkn1a, Cdkn2a, and Cdkn2b. Reconstitution of Bcl-xL expression partially rescued the proliferation defect of Bach2−/− B cells. Chromatin immunoprecipitation experiments showed that Bach2 bound to the CKI family genes, indicating that these genes are direct repression targets of Bach2. These findings identify Bach2 as a requisite factor for sustaining high levels of BCR-induced proliferation, survival, and cell cycle progression, and it promotes expression of Bcl-xL and repression of CKI genes. BCR-induced proliferation defects may contribute to the impaired GC formation observed in Bach2−/− mice.
Primary Percutaneous Coronary Intervention in Acute ST-Elevation Myocardial Infarction: The Experience of "Evagelismos" General Hospital of Athens

We report our experience from treating a large number of patients who presented to the Emergency Department of our Hospital with ST-elevation acute myocardial infarction (AMI) with primary percutaneous coronary intervention (PCI). Of the 196 patients who presented with ST elevation AMI over a period of 12 months, 100 (51%) patients underwent primary PCI. Clinical and angiographic data were collected and patients were followed up for 9 months. Technical details of the primary PCI, including use of balloon, use of thrombus aspiration catheter, stent implantation, use of drug eluting stents, and use of GP IIb/IIIa inhibitors were recorded and correlated to clinical and angiographic patient data. Our results are in keeping with those published by other groups performing primary PCI. We demonstrated the importance of time interval from onset of symptoms until PCI is started. We found that the use of GP IIb/IIIa inhibitors was beneficial and emphasized the predictive value of left ventricular ejection fraction >50% and the importance of achieving TIMI 3 flow in the AMI related artery at the end of the procedure.
Four cases of fetal intra-abdominal umbilical vein varix: A single centre's approach to management

Fetal intra-abdominal umbilical vein (FIUV) varix is a rare prenatal abnormality characterised by a focal intrahepatic or extrahepatic dilatation of the intra-abdominal portion of the umbilical vein. Usually, it is an isolated finding, but in some cases it can be associated to other fetal anomalies. Thrombosis is a possible complication of FIUV varix and it can lead to poor fetal or neonatal outcome. We describe four consecutive cases of FIUV varix diagnosed in our Unit and managed with low-dose aspirin (LDA) prophylaxis until the 35th week of gestation. None of the fetuses developed thrombosis of the varix and the neonatal outcomes were good in all the cases.
CD40L-Dependent Pathway Is Active at Various Stages of Rheumatoid Arthritis Disease Progression

The inflammatory CD40–CD40L pathway is implicated in various autoimmune diseases, but the activity status of this pathway in various stages of rheumatoid arthritis (RA) progression is unknown. In this study, we used gene signatures of CD40L stimulation derived from human immature dendritic cells and naive B cells to assess the expression of CD40-downstream genes in synovial tissues from anti-citrullinated protein Ab–positive arthralgia, undifferentiated arthritis (UA), early RA, and established RA cohorts in comparison with healthy donors. Interestingly, the expression of CD40LG and active full-length CD40 was increased in the disease tissues, whereas that of a dominant-negative CD40 isoform was decreased. Gene set variation analysis revealed that CD40L-responsive genes in immature dendritic cells and naive B cells were significantly enriched in synovial tissues from UA, early RA, and established RA patients. Additionally, CD40L-induced naive B cell genes were also significantly enriched in synovial tissues from arthralgia patients. In our efforts to characterize downstream mediators of CD40L signaling, we have identified GPR120 and KDM6B as novel components of the pathway. In conclusion, our data suggest that therapeutic CD40–CD40L blocking agents may prove efficacious not only in early and established RA, but also in inhibiting the progression of the disease from arthralgia or UA to RA.
Preferential Blockade of CD8+ T Cell Responses by Administration of Anti-CD137 Ligand Monoclonal Antibody Results in Differential Effect on Development of Murine Acute and Chronic Graft-Versus-Host Diseases1

We investigated the effect of CD137 costimulatory blockade in the development of murine acute and chronic graft-vs-host diseases (GVHD). The administration of anti-CD137 ligand (anti-CD137L) mAb at the time of GVHD induction ameliorated the lethality of acute GVHD, but enhanced IgE and anti-dsDNA IgG autoantibody production in chronic GVHD. The anti-CD137L mAb treatment efficiently inhibited donor CD8+ T cell expansion and IFN-γ expression by CD8+ T cells in both GVHD models and CD8+ T cell-mediated cytotoxicity against host-alloantigen in acute GVHD. However, a clear inhibition of donor CD4+ T cell expansion and activation has not been observed. On the contrary, in chronic GVHD, the number of CD4+ T cells producing IL-4 was enhanced by anti-CD137L mAb treatment. This suggests that the reduction of CD8+ T cells producing IFN-γ promotes Th2 cell differentiation and may result in exacerbation of chronic GVHD. Our results highlight the effective inactivation of CD8+ T cells and the lesser effect on CD4+ T cell inactivation by CD137 blockade. Intervention of the CD137 costimulatory pathway may be beneficial for some selected diseases in which CD8+ T cells are major effector or pathogenic cells. Otherwise, a combinatorial approach will be required for intervention of CD4+ T cell function.
Effect of oral supplementation of Aloe vera extract on haematology indices and immune cells of blood in rabbit

Aloe vera is being widely used in herbal medicine as antibacterial, antiviral, antifungal, and antiinflammatory agent. It is also used as topical application for many skin diseases; its antidiabetic effect in rats is also reported. Looking at its enormous medicinal effects, the present study was conducted to investigate the effects of oral supplements of Aloe vera extract on hemotology indices and immune cells of rabbit. Total of twenty (n=20) rabbits were selected and divided into 4 group’s i-e A, B, C and D with n=5 in each group. Group A was kept as control while B, C and D were given 400, 500 and 600 mg/kg of Aloe vera extract, respectively daily for 21 days. Blood samples were collected from central ear vein transferred into test tubes containing ethylene diamine tetra acetate (EDTA) on 0 day, 7th day, 14th day and 21st day and analysed for complete blood count (CBC). Results revealed that oral supplementation of A. vera extract significantly increase mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and lymphocytes at level (p< 0.05) and decrease neutrophils in normal domestic rabbits. Results of this study concluded that A. vera has hematopoetic and immunomodulatory effects; thus its extract can be used for the treatment of anemia and immune deficiency problems. Key words: Aloe vera, biological active, anaemia, immunodeficiency.
Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections

Dengue is a global public health problem and is caused by four dengue virus (DENV) serotypes (DENV1-4). A major challenge in dengue vaccine development is that cross-reactive anti-DENV Abs can be protective or potentially increase disease via Ab-dependent enhancement. DENV nonstructural protein 1 (NS1) has long been considered a vaccine candidate as it avoids Ab-dependent enhancement. In this study, we evaluated survival to challenge in a lethal DENV vascular leak model in mice immunized with NS1 combined with aluminum and magnesium hydroxide, monophosphoryl lipid A + AddaVax, or Sigma adjuvant system+CpG DNA, compared with mice infected with a sublethal dose of DENV2 and mice immunized with OVA (negative control). We characterized Ab responses to DENV1, 2, and 3 NS1 using an Ag microarray tiled with 20-mer peptides overlapping by 15 aa and identified five regions of DENV NS1 with significant levels of Ab reactivity in the NS1 + monophosphoryl lipid A + AddaVax group. Additionally, we profiled the Ab responses to NS1 of humans naturally infected with DENV2 or DENV3 in serum samples from Nicaragua collected at acute, convalescent, and 12-mo timepoints. One region in the wing domain of NS1 was immunodominant in both mouse vaccination and human infection studies, and two regions were identified only in NS1-immunized mice; thus, vaccination can generate Abs to regions that are not targeted in natural infection and could provide additional protection against lethal DENV infection. Overall, we identified a small number of immunodominant regions, which were in functionally important locations on the DENV NS1 protein and are potential correlates of protection.
Rehabilitation of atrophic maxilla: a review of 101 zygomatic implants.

Introduction: Zygomatic implants are a good rehabilitation alternative for upper maxilla with severe bone reabsorption. These implants reduce the need for onlay-type bone grafting in the posterior sectors and for maxillary sinus lift procedures - limiting the use of bone grafts to the anterior zone of the upper jaw in those cases where grafting is considered necessary. Objective: To evaluate the survival of 101 zygomatic implants placed in upper maxilla presenting important bone reabsorption, with a follow-up of 1-72 months. Patients and methods: A retrospective study was made of 101 Zygoma® implants (Nobel Biocare, Goteborg, Sweden) placed in 54 patients with totally edentulous and atrophic upper maxilla, in the period between 1998-2004. There were 35 women and 19 men, subjected to rehabilitation in the form of fixed prostheses and overdentures using 1-2 zygomatic implants and 2-7 implants in the anterior maxillary zone. The principal study variables were smoking, a history of sinusitis, the degree of bone reabsorption, and peri-implant bone loss, among others. Results: The descriptive analysis of the 101 zygomatic implants placed in 54 patients with a mean age of 56 years (range 38-75) yielded a percentage survival of 96.04%, with four failed implants that were removed (two before and two after prosthetic loading). Nine patients were smokers, and none of the 54 subjects reported a history of sinus disorders. Discussion and conclusions: Zygomatic implants are designed for use in compromised upper maxilla. They allow the clinician to shorten the treatment time, affording an interesting alternative for fixed prosthetic rehabilitation. This study confirms that zygomatic bone offers predictable anchorage and acceptable support function for prostheses in atrophic jaws. However, these implants are not without complications. Longer-term evaluations are needed of zygomatic implant survival in order to establish a correct clinical prognosis.