Miracle-dz/UniFAR-FTUs huggingface dataset:
Akt-Dependent Enhanced Migratory Capacity of Th17 Cells from Children with Lupus Nephritis

Th17 cells infiltrate the kidneys of patients with lupus nephritis (LN) and are critical for the pathogenesis of this disease. In this study, we show that enhanced activity of Stat3 in CD4+CD45RA−Foxp3− and Foxp3low effector T cells from children with LN correlates with increased frequencies of IL-17–producing cells within these T cell populations. The levels of retinoic acid-related orphan receptor c and IL-17 mRNA are significantly higher in PBMCs from children with LN than in those from controls. Mammalian target of rapamycin inhibition by rapamycin reduces both Stat3 activation in effector T cells and the frequency of IL-17–producing T cells in lupus patients. Complement factor C5a slightly increases the expression of IL-17 and induces activation of Akt in anti-CD3–activated lupus effector T cells. Th17 cells from children with LN exhibit high Akt activity and enhanced migratory capacity. Inhibition of the Akt signaling pathway significantly decreases Th17 cell migration. These findings indicate that the Akt signaling pathway plays a significant role in the migratory activity of Th17 cells from children with LN and suggest that therapeutic modulation of the Akt activity may inhibit Th17 cell trafficking to sites of inflammation and thus suppress chronic inflammatory processes in children with LN.
Prevalence of Orofacial Complications in Iranian Patients with β -Thalassemia Major

Background: Majorβ -thalassemia is the most common monogenic known disorder in Iran and about 15000 persons are affected. The purpose of this study was to evaluate the prevalence of orofacial complications. Methods: In this cross-sectional study during 2003-2004, 300 patients with major β -thalassemia referring to 8 hospitals for routine examinations, blood infusion and treatment in cities of Tehran, Isfahan, Sari, Zahedan, Shahre Kord and Sanandag were studied. The questionnaires included general information, medical and dental history. Results: The prevalence of orofacial complications in major β -thalassemia was: saddle nose (67%), maxillary protrusion (49/7%), color change of oral mucousa (41/7%), rodent face (34/7%), deep bite (21/7%), spacing (20/7%), and open bite (8/7%), respectively. There was not any relationship between the complications and sex. Most of the patients (91%) were in the first and second decade of life. Early diagnosis and blood infusion caused less prevalence of rodent face. The most observed type of occlusion was class 1, 2 and 3, respectively. Conclusion: Knowing the prevalence of complication can help the dentists to do properly for these patients to solve their problems and improve knowledge of the parents about their children’s dental health.
The use of endostatin in the treatment of solid tumors

Background: Endostatin represents the most studied endogenous anti-angiogenesis peptide that has been found to inhibit angiogenesis and exhibit broad-spectrum antitumor activity in animal models. Clinical trials evaluating endostatin alone or in combination with other currently used strategies for the treatment of solid tumors has generated debatable efficacy results, albeit with low toxicity, immunogenicity and resistance. Objective/methods: We delineate the current knowledge regarding endostatin's mechanism of action during carcinogenesis, spotlight already reported and ongoing research concerning its clinical development, and discuss future perspectives and challenges for its potential therapeutic utility. Results/conclusions: After more than a decade of intense basic and clinical research since its original discovery it is still unclear whether endostatin has any clinically meaningful role in cancer therapeutics and more questions than answers have emerged.
Tetherin Promotes the Innate and Adaptive Cell–Mediated Immune Response against Retrovirus Infection In Vivo

Tetherin/BST-2 is a host restriction factor that could directly inhibit retroviral particle release by tethering nascent virions to the plasma membrane. However, the immunological impact of Tetherin during retrovirus infection remains unknown. We now show that Tetherin influences antiretroviral cell-mediated immune responses. In contrast to the direct antiviral effects of Tetherin, which are dependent on cell surface expression, the immunomodulatory effects are linked to the endocytosis of the molecule. Mice encoding endocytosis-competent C57BL/6 Tetherin exhibited lower viremia and pathology at 7 d postinfection with Friend retrovirus (FV) compared with mice encoding endocytosis-defective NZW/LacJ Tetherin. Notably, antiretroviral protection correlated with stronger NK cell responses. In addition, Friend retrovirus infection levels were significantly lower in wild-type C57BL/6 mice than in Tetherin knockout mice at 2 wk postinfection, and antiretroviral protection correlated with stronger NK cell and virus-specific CD8+ T cell responses. The results demonstrate that Tetherin acts as a modulator of the cell-mediated immune response against retrovirus infection in vivo.
Using a Delphi process to establish consensus on emergency medicine clerkship competencies

Background: Currently, there is no consensus on the core competencies required for emergency medicine (EM) clerkships in Canada. Existing EM curricula have been developed through informal consensus or local efforts. The Delphi process has been used extensively as a means for establishing consensus. Aim: The purpose of this project was to define core competencies for EM clerkships in Canada, to validate a Delphi process in the context of national curriculum development, and to demonstrate the adoption of the CanMEDS physician competency paradigm in the undergraduate medical education realm. Methods: Using a modified Delphi process, we developed a consensus amongst a panel of expert emergency physicians from across Canada utilizing the CanMEDS 2005 Physician Competency Framework. Results: Thirty experts from nine different medical schools across Canada participated on the panel. The initial list consisted of 152 competencies organized in the seven domains of the CanMEDS 2005 Physician Competency Framework. After the second round of the Delphi process, the list of competencies was reduced to 62 (59% reduction). Conclusion: This study demonstrated that a modified Delphi process can result in a strong consensus around a realistic number of core competencies for EM clerkships. We propose that such a method could be used by other medical specialties and health professions to develop rotation-specific core competencies.
Static and dynamic balance in school children with and without hearing impairment

Objective: Balance control and motor assessments are not a routine procedure in children with hearing impairment. This study compared static and dynamic balance of school children with and without hearing impairment. Methods: This two-group study involved 160 school children, i.e. 80 hearing impaired having stimulus intensity values of 30 dB or greater and 80 control, aged between 8 and 17 years. One leg stance test and functional reach test were used to assess static and dynamic balance, respectively. Data were summarized using both descriptive and inferential statistics. Alpha level was set at 0.05. Results: Both eyes closed and eyes opened static balances were significantly lower among hearing impaired than the normal hearing subjects. Dynamic balance was higher among the hearing impaired but was not statistically significant. There was no significant correlation between eyes closed and eyes opened static balance among the hearing impaired and the normal hearing subjects, respectively. No significant correlation was found between dynamic and static balance among the hearing impaired and normal hearing subjects, respectively. Conclusion: Children with hearing impairment perform poorly on static balance tests compared with their normal hearing subjects, while dynamic balance was comparable between both groups of subjects. Balance training program is recommended for children with hearing impairment who present movement and stability deficits.
Genome-Wide Transcriptional Analyses of Islet-Specific CD4+ T Cells Identify Idd9 Genes Controlling Diabetogenic T Cell Function

Type 1 diabetes (T1D) is a polygenic disease with multiple insulin-dependent diabetes (Idd) loci predisposing humans and NOD mice to disease. NOD.B10 Idd9 congenic mice, in which the NOD Idd9 chromosomal region is replaced by the Idd9 from T1D-resistant C57BL/10 mice, are significantly protected from T1D development. However, the genes and pathways conferring T1D development or protection by Idd9 remain to be fully elucidated. We have developed novel NOD.B10-Idd9 (line 905) congenic mice that predominantly harbor islet-reactive CD4+ T cells expressing the BDC2.5 TCR (BDC-Idd9.905 mice). To establish functional links between the Idd9 genotype and its phenotype, we used microarray analyses to investigate the gene expression profiles of ex vivo and Ag-activated CD4+ T cells from these mice and BDC2.5 (BDC) NOD controls. Among the differentially expressed genes, those located within the Idd9 region were greatly enriched in islet-specific CD4+ T cells. Bioinformatics analyses of differentially expressed genes between BDC-Idd9.905 and BDC CD4+ T cells identified Eno1, Rbbp4, and Mtor, all of which are encoded by Idd9 and part of gene networks involved in cellular growth and development. As predicted, proliferation and Th1/Th17 responses of islet-specific CD4+ T cells from BDC-Idd9.905 mice following Ag stimulation in vitro were reduced compared with BDC mice. Furthermore, proliferative responses to endogenous autoantigen and diabetogenic function were impaired in BDC-Idd9.905 CD4+ T cells. These findings suggest that differential expression of the identified Idd9 genes contributed to Idd9-dependent T1D susceptibility by controlling the diabetogenic function of islet-specific CD4+ T cells.
Post-competition lactate levels in canoe slalomists

During the "Pre-World" international canoe slalom championships held at Bala, in North Wales in 1980, post competition blood samples were drawn from 19 competitors in four events. The events were:1. Mens Kayak singles in which the competitor uses a double blade paddle. 2. Mens Canadian singles in which a kneeling competitor uses a single blade paddle. 3. Mens Canadian doubles in which two canoeists each with a single paddle propel one canoe. 4. Womens Kayak singles as mens K1.
IgG4 and IgE Transcripts in Childhood Allergic Asthma Reflect Divergent Antigen-Driven Selection

The physiologic function of the “odd” Ab IgG4 remains enigmatic. IgG4 mediates immunotolerance, as, for example, during specific immunotherapy of allergies, but it mediates tissue damage in autoimmune pemphigus vulgaris and “IgG4-related disease. ” Approximately half of the circulating IgG4 molecules are bispecific owing to their unique ability to exchange half-molecules. Better understanding of the interrelation between IgG4 and IgE repertoires may yield insight into the pathogenesis of allergies and into potential novel therapies that modulate IgG4 responses. We aimed to compare the selective forces that forge the IgG4 and IgE repertoires in allergic asthma. Using an IgG4-specific RT-PCR, we amplified, cloned, and sequenced IgG4 H chain transcripts of PBMCs from 10 children with allergic asthma. We obtained 558 functional IgG4 sequences, of which 286 were unique. Compared with previously published unique IgE transcripts from the same blood samples, the somatic mutation rate was significantly enhanced in IgG4 transcripts (62 versus 83%; p < 0.001), whereas fewer IgG4 sequences displayed statistical evidence of Ag-driven selection (p < 0.001). On average, the hypervariable CDRH3 region was four nucleotides shorter in IgG4 than in IgE transcripts (p < 0.001). IgG4 transcripts in the circulation of children with allergic asthma reflect some characteristics of classical Ag-driven B2 immune responses but display less indication of Ag selection than do IgE transcripts. Although allergen-specific IgG4 can block IgE-mediated allergen presentation and degranulation of mast cells, key factors that influence the Ag-binding properties of the Ab differ between the overall repertoires of circulating IgG4- and IgE-expressing cells.
Sterile DJH Rearrangements Reveal that Distance Between Gene Segments on the Human Ig H Chain Locus Influences Their Ability To Rearrange

Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B cells from 110 healthy adult donors. We found that DJH rearrangements and nonproductive VHDJH rearrangements share many features but differ significantly in their use of D genes and propensity for somatic hypermutation. In D to JH gene rearrangements, the D genes proximal to the JH locus are used more frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus.
Is running a Problem-Based Learning curriculum more expensive than a traditional Subject-Based Curriculum?

Background: Running a problem-based learning (PBL) curriculum has been considered to be more expensive than a traditional Subject-Based Curriculum? This claim has not been well substantiated. Aim: To identify faculty educational activities (FEA) related to PBL, calculate its cost (faculty number and time) and compare it with a traditional Subject-Based Curriculum. Methods: A structured questionnaire was developed through focused group discussion using a Delphi method to identify FEA and ensure face and content validity. For cost comparison, a hypothetic model was developed based on “what if” the curriculum was traditional subject-based, and running within the frame of the current regulations of University of Sharjah. Results: A total of 23 faculty (16 full-time basic medical sciences and 7 clinical tutors) equal to 19.5 full-time equivalent (FTE) responded to the questionnaire. About five major domains and 26 sub-domains of FEA were identified. The calculated number of faculty needed for the hypothetical Subject-Based Curriculum should have been 19 FTEs. The average FEA hours per faculty per week per student in PBL was 17.41 and for the Subject-Based Curriculum would have been 17.85. Conclusion: PBL does not require an increase in number of faculty. The time spent by faculty on educational activities was similar in the two curriculum models. Although the cost of two strategies was similar, but the educational roles and the faculty engagement in education in a PBL curriculum is broader than in the traditional curriculum.
Reaching the limits of mandated self-reporting: Clinical logbooks do not predict clerkship performance

Background: Logbooks are used by US medical schools to evaluate curricular objectives and meet accreditation requirements, but research supporting their utility is conflicting. Aims: The goal of our study was to examine the relationship between volume of clinical rotation experiences as reported in a logbook and clerkship grades within a longitudinal integrated clerkship. Methods: We conducted a retrospective cohort study of third-year (clinical) medical students during academic year 2008–2009. We tracked student entries in a pocket-sized logbook (number of clinical encounters per clerkship, total number of exams, and procedures over the academic year). We performed correlation analyses between logbook entries and clerkship grades. Results: We enrolled 36 students, who reported a total of 2992 encounters, 2262 exams, and 2342 procedures. Correlation coefficients between volume of clinical experience and clerkship grades were less than 0.4, indicating low correlation. We found borderline statistical significance for the Neurology, OB/Gyn, and Surgery clerkships. Sensitivity analyses showed little correlation between low-reporting activity and clerkship grades. Conclusions: Even within an integrated longitudinal clerkship framework, our findings are consistent with previous studies showing a negligible relationship between logbooks as an educational process measure and how they relate to educational outcomes.
THE ANTIGENIC STRUCTURE OF THE POLYPEPTIDE CHAINS OF HUMAN γ-GLOBULIN

The antigenic properties of the polypeptide chains of human 7S γ-globulin have been related to two major non-cross-reacting antigenic determinants of the whole molecule. These determinants, called S and F, were obtained by hydrolysis of γ-globulin with papain. Antisera against whole γ-globulin and against S and F fragments were used in techniques of immune diffusion. Light (L) chains of γ-globulin showed reactions of partial identity with S fragments, and thus are antigenically deficient with respect to these fragments. Antisera directed against F determinants did not react with L chains but did react with heavy (H) polypeptide chain preparations. In addition, the major component of H chain fractions did not appear to contain determinants in common with the S fragments. L chains of a γ-myeloma protein were shown to be antigenically deficient with respect to the whole myeloma molecule, and antigenically identical with the Bence-Jones protein of the same patient. Correlation of these results with those of previous investigations have led to the conclusions that the S fragment which is known to contain the combining region of antibody molecules, consists in part of L chains or portions of L chains, and that the F fragment, which mediates several other functions of the whole molecule, is composed in part of portions of H chains.
Improving the accuracy of self-assessment of practical clinical skills using video feedback – The importance of including benchmarks

Introduction: Isolated video recording has not been demonstrated to improve self-assessment accuracy. This study examines if the inclusion of a defined standard benchmark performance in association with video feedback of a student's own performance improves the accuracy of student self-assessment of clinical skills. Methods: Final year medical students were video recorded performing a standardised suturing task in a simulated environment. After the exercise, the students self-assessed their performance using global rating scales (GRSs). An identical self-assessment process was repeated following video review of their performance. Students were then shown a video-recorded ‘benchmark performance’, which was specifically developed for the study. This demonstrated the competency levels required to score full marks (30 points). A further self-assessment task was then completed. Students’ scores were correlated against expert assessor scores. Results: A total of 31 final year medical students participated. Student self-assessment scores before video feedback demonstrated moderate positive correlation with expert assessor scores (r = 0.48, p < 0.01) with no change after video feedback (r = 0.49, p < 0.01). After video feedback with benchmark performance demonstration, self-assessment scores demonstrated a very strong positive correlation with expert scores (r = 0.83, p < 0.0001). Conclusions: The demonstration of a video-recorded benchmark performance in combination with video feedback may significantly improve the accuracy of students’ self-assessments.
GATA2 Germline Mutations Impair GATA2 Transcription, Causing Haploinsufficiency: Functional Analysis of the p.Arg396Gln Mutation

Germline GATA2 mutations have been identified as the cause of familial syndromes with immunodeficiency and predisposition to myeloid malignancies. GATA2 mutations appear to cause loss of function of the mutated allele leading to haploinsufficiency; however, this postulate has not been experimentally validated as the basis of these syndromes. We hypothesized that mutations that are translated into abnormal proteins could affect the transcription of GATA2, triggering GATA2 deficiency. Chromatin immunoprecipitation and luciferase assays showed that the human GATA2 protein activates its own transcription through a specific region located at −2.4 kb, whereas the p.Thr354Met, p.Thr355del, and p.Arg396Gln germline mutations impair GATA2 promoter activation. Accordingly, GATA2 expression was decreased to ∼58% in a patient with p.Arg396Gln, compared with controls. p.Arg396Gln is the second most common mutation in these syndromes, and no previous functional analyses have been performed. We therefore analyzed p.Arg396Gln. Our data show that p.Arg396Gln is a loss-of-function mutation affecting DNA-binding ability and, as a consequence, it fails to maintain the immature characteristics of hematopoietic stem and progenitor cells, which could result in defects in this cell compartment. In conclusion, we show that human GATA2 binds to its own promoter, activating its transcription, and that the aforementioned mutations impair the transcription of GATA2. Our results indicate that they can affect other GATA2 target genes, which could partially explain the variability of symptoms in these diseases. Moreover, we show that p.Arg396Gln is a loss-of-function mutation, which is unable to retain the progenitor phenotype in cells where it is expressed.
Twelve tips for writing educational research grant proposals

Background: The need to promote educational research and faculty development grants and assist medical educators with grant writing is well documented in the medical education literature. Aims: To assist medical educators with writing educational research grant proposals, we propose a set of 12 tips for writing competitive grant proposals. Methods: We distilled challenges and effective strategies and approaches from our experience in writing and assisting with education research grant proposals. We presented these challenges and approaches at faculty development workshops on writing educational research grant proposals conducted over the past 3 years and evaluated the outcomes of these presentations and the participant's experiences with educational research grant writing. Results: Approximately 100 participating faculty provided feedback, affirming that these sessions were very useful for developing grant proposals and for reaching out to funding agencies and that these faculty development efforts in grant writing are much needed. Conclusions: Based on our experiences with education grants and workshop efforts, we propose a set of strategies for faculty to seek grant sources and write promising education research grant proposals.
Assessment of the lactate and ventilatory thresholds by breathing frequency in runners

The aim of this study was to establish the validity of the breakpoint in breathing frequency for the assessment of the lactate threshold and the ventilatory threshold during incremental running exercise. Twelve trained runners (mean +/- s: age 29 +/- 8 years; body mass 68.7 8.8 kg; V O 2m ax 57.9 +/- 4.1 ml . kg -1 . min -1 ) performed randomly assigned incremental treadmill tests on separate days. In addition to the assessment of the V O 2m ax (Test 1), the subjects performed two standard multi-stage treadmill tests (4-min stages) for the assessment of the lactate threshold while wearing (Test 2) and not wearing (Test 3) a standard mouthpiece and noseclip arrangement. Breathing frequency was measured by a thermistor, which was positioned in the back of the mouthpiece for Test 2, and fixed 3 cm in front of the mouth using a headband and flexible wiring for Test 3. All exercise tests were recorded on videotape and mean breathing frequency and stride rate were calculated for the last minute of each stage fr.