Miracle-dz/UniFAR-FTUs huggingface dataset:
The case-crossover study design in pharmacoepidemiology

In the study of the association of transient drug exposures with acute outcomes, the case-crossover design is an efficient alternative to the case-control approach. This design based exclusively on the case series uses within-subject comparisons of drug exposures over time to estimate the rate ratio of the outcome associated with the drug under study. This design inherently removes the biasing effects of unmeasured, time-invariant confounding factors from the estimated rate ratio, but is sensitive to several assumptions. We illustrated the case-crossover design and explored its sensitivity using data from 4028 cases of gastrointestinal bleeding from the General Practice Research Database in assessing the effects of the drug warfarin. We compared the use of different time window lengths to assess exposure and considered the use of a case-time-control design to account for exposure time trends. The case-crossover approach found no excess risk of bleeding with warfarin exposure [rate ratio 0.98; 95% confidence interval (CI): 0.74—1.28] using a 1-month time window. When we restricted the analysis to subjects with truly transient drug exposure, defined by 1 to 3 prescriptions in the previous year, the rate ratio was 2.59 (95% CI: 1.42—4.74). To consider the longer 1-year exposure time window, the case-time-control approach was used and resulted in a rate ratio of 1.72 (95% CI: 1.08—2.43). In conclusion, the case-crossover design is potentially a powerful approach to assess the risk of drugs. This design is, however, highly sensitive to assumptions about intermittency of drug use and the length of the exposure time window, as demonstrated with the example of bleeding associated with warfarin use.
Assessment of thermal alteration during class V cavity preparation using the Er:YAG laser.

OBJECTIVE The aim of this study was to evaluate in vitro the pulp thermal alterations during class V cavity preparations using the Er:YAG laser and high-speed water flow. MATERIALS AND METHODS Forty human teeth were selected and prepared for the thermocouple adaptation in the pulp chamber. The specimens were assigned to four groups: (1) laser 300 mJ/3 Hz, (2) laser 300 mJ/4 Hz, (3) high-speed 9 mL/min water flow, and (4) high-speed 100 mL/min water flow. The temperature was measured before the beginning and at the end of the preparation, as well as during the procedures. The groups were analyzed by scanning electron microscopy. RESULT Data analysis disclosed temperature reduction at high-speed drilling with the high-speed total water flow group, and these values were statistically different from the other groups. The results of the 9-mL/min water flow group were similar to those of the 300-mJ/3-Hz group and different from the 300-mJ/4-Hz laser group. CONCLUSION The laser promoted a greater increase in temperature only when compared with high-speed handpiece and water flow rate of 100 mL/min.
The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization.

BACKGROUND With continuous exposure to beta2-adrenergic agonists, vascular tissue becomes desensitized to agonist-mediated vasodilatation. We studied the effects of two common polymorphisms of the beta2-adrenergic receptor, one at codon 16 and one at codon 27, on agonist-mediated vasodilatation and desensitization in the vascular bed. METHODS We studied 26 healthy subjects who were selected to represent three genotypes: 7 were homozygous for the alleles encoding Arg16 and Gln27, 8 were homozygous for the alleles encoding Gly16 and Gln27, and 11 were homozygous for the alleles encoding Gly16 and Glu27. Vascular responses were assessed by measuring changes in the diameter of a dorsal hand vein. A dose-response curve of the effect of the beta2-adrenergic-receptor agonist isoproterenol was constructed (dose range, 4 to 480 ng per minute). Desensitization was then induced by a 2-hour continuous infusion of isoproterenol, and venodilatation was measured 30, 60, 90, and 120 minutes after the start of the infusion. RESULTS Subjects who were homozygous for Arg16 had almost complete desensitization; venodilatation in response to isoproterenol in this group decreased from a mean (+/-SE) of 44+/-11 percent to 8+/-4 percent (P=0.006). In contrast, subjects who were homozygous for Gly16 did not have significant desensitization, irrespective of the amino acid encoded by codon 27. Subjects who were homozygous for Glu27 had higher maximal venodilatation in response to isoproterenol than those who were homozygous for Gln27 (86+/-13 percent vs. 54+/-8 percent, P=0.03). CONCLUSIONS The Arg16 polymorphism of the beta2-adrenergic receptor is associated with enhanced agonist-mediated desensitization in the vasculature, and the Glu27 polymorphism is associated with increased agonist-mediated responsiveness. Therefore, polymorphisms of the beta2-adrenergic receptor are potentially important determinants of the vascular response to stress.
Passively transferred anti‐MUC1 antibodies cause neither autoimmune disorders nor immunity against transplanted tumors in MUC1 transgenic mice

C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to investigate the autoimmune consequences of producing MUC1 tumor immunity in an animal that expresses MUC1 as a self‐protein on normal ductal epithelia. Previous work showed that MUC1.Tg mice challenged with MUC1‐bearing syngeneic tumors (B16.MUC1) developed progressively growing MUC1‐expressing tumors and no detectable MUC1‐specific antibody (Ab) response. In contrast, wild‐type C57BL/6 (wt) mice developed MUC1‐negative tumors at a significantly slower rate and produced approximately 50 μg IgG1 Ab reactive with the MUC1 tandem repeat (TR)/ml of sera. One milliliter of these sera was administered passively to MUC1.Tg or wt mice and the concentration of the MUC1 TR‐reactive IgG1 Abs was monitored over time. The results indicate that circulating MUC1‐reactive Abs were detectable in MUC1.Tg mice and that significant amounts of these Abs were not absorbed by organs that endogenously express MUC1. No evidence of autoimmune disease, either gross or histological, was observed in the MUC1.Tg recipients of sera suggesting that MUC1, an organ‐specific protein expressed primarily by secretory epithelia, is inaccessible to circulating MUC1‐reactive Abs. Additional studies showed that polyclonal sera containing IgG1 Abs reactive with MUC1 TR were unable to provide protection against the growth of syngeneic tumors expressing MUC1 in the MUC1.Tg animal model. Int. J. Cancer 80:595–599, 1999. © 1999 Wiley‐Liss, Inc.
Extensive White Matter Dysfunction in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis

BACKGROUND AND PURPOSE: Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI. MATERIALS AND METHODS: Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement. RESULTS: Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (pcorr < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (pcorr > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status. CONCLUSIONS: Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.
Reduced renal function in patients with simple renal cysts.

BACKGROUND Sporadic renal cysts not associated with genetic polycystic disorders are common and generally thought to be of no clinical significance. Since multiple cysts frequently develop in end-stage renal disease (ESRD), we tested the hypothesis that cysts that are solitary or few in number are an early manifestation of reduced renal function. METHODS We evaluated 561 hospitalized patients who underwent contrast-enhanced, abdominal computed tomography (CT) and correlated clinical characteristics and parameters of renal function with the presence or absence of renal cysts. RESULTS Age ranged from 16 to 100 years, mean serum creatinine concentration was 0.88 mg/dL (range 0.4 to 2.1 mg/dL), and mean estimated creatinine clearance was 94 mL/min/1.73 m(2) (range 22 to 218 mL/min/1.73 m(2)). The presence of cysts was significantly correlated with older age (P < 0.001), higher serum creatinine concentration (P < 0.002), and lower estimated creatinine clearance (P < 0.001). In a multivariate analysis, including age and gender, estimated creatinine clearance still correlated with the presence of cysts (P= 0.009). When patients were grouped by age, estimated creatinine clearance correlated with cysts in patients <40 years and 40 to 59 years, but not in patients 60 to 79 years or > or =80 years. There was no association of cysts with hypertension or proteinuria. In patients with cysts, serum creatinine increased progressively but not significantly with cyst number, and did not correlate with size or distribution of cysts. Renal parenchymal volume was slightly but not significantly reduced in patients with cysts. CONCLUSION The presence of kidney cysts, even single cysts, is associated with reduced renal function in hospitalized patients younger than 60 years. This relationship may be obscured by the reduced renal function and the high incidence of cysts in older patients. These results suggest that acquired cystic kidney disease may begin early in the course of renal disease and that underlying renal disease should be considered in individuals with renal cysts prior to age 60 years.
IL2RA gene polymorphism rs2104286 A>G seen in multiple sclerosis is associated with intermediate uveitis: possible parallel pathways?

PURPOSE Uveitis is a major cause for visual impairment. Inflammation-related gene polymorphisms have previously been shown to confer susceptibility to different types of uveitis. Recently, IL-2 receptor alpha (IL2RA, also called CD25) and IL-7 receptor alpha (IL7RA) gene variants (rs2104286, rs12722489, and rs6897932) have been identified to play an essential role in the pathogenesis of immune-mediated diseases. Their role in uveitis, however, has not yet been studied. The present study was set to investigate a hypothesized association of these gene polymorphisms and the presence of either intermediate or HLA-B27-associated acute anterior uveitis. METHODS One hundred forty-five patients with HLA-B27-associated acute anterior uveitis (AAU), 84 patients with intermediate uveitis, 132 HLA-B27-negative controls, and 61 HLA-B27-positive controls were enrolled. Determination of genotypes was done by polymerase chain reaction. RESULTS The frequency of carriers of the minor allele for rs2104286 was significantly lower in patients with intermediate uveitis compared with HLA-B27 positive and negative controls combined (P = 0.006). Frequencies of the minor allele for rs2104286 did not differ significantly in patients with HLA-B27-associated uveitis (28.3%) when compared with HLA-B27-negative controls (24.2%; P = 0.29) and HLA-B27-positive controls (30.3%; P = 0.72). The rs12722489 and rs6897932 polymorphisms were not significantly associated with either investigated uveitis entity (P > 0.005). CONCLUSIONS These findings suggest an association of the rs2104286 polymorphism with intermediate uveitis, but not with HLA-B27-associated acute anterior uveitis. Because this polymorphism was associated with multiple sclerosis in previous studies, the authors suggest possible parallel pathways between multiple sclerosis and intermediate uveitis but not HLA-B27-associated uveitis.
Analysis of Independent Risk Factors for Death Among Pediatric Patients With Candidemia and a Central Venous Catheter in Place

Objective. To use multivariate analysis to determine risk factors for death among pediatric patients with candidemia and a central venous catheter in place. Design. Retrospective cohort study conducted at Santa Casa Complexo Hospitalar, a 1,200-bed teaching hospital in southern Brazil. Methods. All cases of candidemia in pediatric patients (age, ≤ 13 years) at our medical center over a 9-year period were reviewed. A diagnosis of sepsis was required for inclusion in the study. Severity of illness was confirmed by the presence of hypotension requiring inotropes and according to the following scores: the Pediatric Risk of Mortality (PRISM) II score, the PRISM III score, and the Pediatric Logistic Organic Dysfunction score. The following 2 outcomes were evaluated: early death, defined as death occurring within 7 days after candidemia was diagnosed, and late death, defined as death 8-30 days after candidemia was diagnosed. Results. A total of 61 patients were included in the study, including 14 neonates. Most (63.9%) of these patients were girls, and the median age was 0.3 years. A total of 80.3% of candidemia cases were due to species other than Candida albicans, primarily Candida parapsilosis (32.8% of cases) and Candida tropicalis (24.6% of cases). Using multivariate analysis, we demonstrated that failure to remove the central venous catheter was an independent risk factor for early death among pediatric patients with candidemia. However, patients whose catheters were retained were sicker than patients whose catheters were removed, and catheter removal had no impact on late death. Instead, severity of illness determined using the PRISM III score was also an independent predictor of late death. Conclusions. Results from this study suggest that systematic removal of catheters from pediatric patients with candidemia does not reduce the occurrence of late death.
Cytokine Evaluation in Throat Infections

Inflammatory cytokines have been shown to play an important role in the pathogenesis of various inflammatory processes. In throat infections, intracellular inflammatory cytokines have been detected from the sites of inflammation. The present study aimed to evaluate serum cytokine levels of patients with throat infections and correlate them to the inflammatory parameters and type of inflammation. Significantly higher inflammatory cytokine levels (interleukin [IL]–6 >7 pg/mL, IL-1 >1β pg/mL, tumor necrosis factor a >1 pg/mL) were detected in most of the patients as opposed to healthy controls. Clinical parameters of infection (fever >38°C, leukocytosis >11,000 white blood cells per cubic millimeter, polymorphonuclear neutrophils >75%) were significantly correlated with high levels of inflammatory cytokines: mainly IL-6 and tumor necrosis factor α, and to a lesser degree with IL-1β. No correlation, however, was found between the type of inflammation and cytokine levels. The present study indicates a role of inflammatory cytokines in the pathogenesis of throat infections and the need for an anti-inflammatory and anticytokine therapeutic approach.
Room for Improvement: Mixed Portrayal of Young People with Mental Illness on Australian Television News

Objective: The aim of the present study was to review television news depiction of mental illness in children and adolescents to test the hypothesis that positive portrayals of adults with mental illness also apply to young people. Methods: Content and frame analysis of first-person depictions and overall news angle was carried out to determine whether depictions were positive, neutral or negative. Results: The media portrayal of young people with mental illnesses was mixed. Overall, 10 items (29%) of news angles were positive, 13 items (37%) neutral and nine items (26%) negative. Positive themes were significantly less frequent for young people compared to adults (10 items, 29% compared to 151 items, 66%), and negative themes were more frequent (nine items, 26% vs 21 items, 9%). First-person depictions, however, were similar for young people and adults (24 items, 69% vs 150 items, 66%). An anti-medication sub-theme was notable. Conclusions: Overall the portrayal of young people with mental illnesses on television news is not as positive as that for adults. Similar to adults, however, first-person depictions resulted in a more positive representation of young people. Fewer first-person depictions in combination with an anti-medication theme and historically less access to appropriate services for young people may have contributed to the less positive results for young people with mental illnesses.
Cooperation of Matrix Metalloproteinases with the RhoA/Rho Kinase and Mitogen‐Activated Protein Kinase Kinase‐1/Extracellular Signal‐Regulated Kinase Signaling Pathways Is Required for the Sphingosine‐1‐Phosphate‐Induced Mobilization of Marrow‐Derived Stromal Cells

The ease of isolation and ex vivo culture of marrow‐derived stromal cells (MSCs) from adult bone marrow renders them a very promising source of adult stem cells for gene transfer and cell therapy. However, little is known about the signaling pathways that control their in vivo mobilization and subsequent biodistribution. Platelet‐derived sphingosine‐1‐phosphate (S1P), a bioactive lipid that acts via G‐protein‐coupled‐receptors, exerts strong chemoattraction upon MSCs through yet‐uncharacterized signaling pathways. We show that the S1P‐induced migration and morphological changes of MSCs in vitro require the activities of extracellular signal‐regulated kinase (ERK), Rho kinase (ROCK), and matrix metalloproteinase (MMP) signaling molecules. Specifically, S1P‐induced remodeling of the MSC cytoskeleton led to the rapid (<1 minute) formation of actin stress fibers via activation of the RhoA/ROCK pathway and required the catalytic activity of MMPs. S1P‐induced activation of the mitogen‐activated protein kinase kinase‐1 (MEK1)/ERK pathway also contributed to the induction of the actin stress fibers and to the redistribution of paxillin at the focal adhesions through tyrosine phosphorylation of focal adhesion kinase in an MMP‐dependent manner. Moreover, MMP‐ and ROCK‐dependent molecular events are implicated in the regulation of the S1P‐induced activation of ERK. Our results demonstrate that MSC mobilization in response to S1P requires cooperation between MMP‐mediated signaling events and the RhoA/ROCK and MEK1/ERK intracellular pathways. Therefore, the characterization of the cellular factors and the intracellular signaling pathways underlying MSC mobilization is crucial to achieve high efficacy in therapeutic use.
Ready or Not? Obstetrics and Gynecology Resident Preparedness for Female Pelvic Medicine and Reconstructive Surgery Training

Objective The aim of this study was to assess the perception of female pelvic medicine and reconstructive surgery (FPMRS) program directors (PDs) and obstetrics and gynecology (OG) FMPRS fellows regarding the adequacy of OG residency as preparation for FPMRS fellowship. Methods Electronic invitations to complete a modified version of a validated survey were extended to FPMRS PDs and their second- and third-year OG FPMRS fellows who had just completed their first or second year of FPMRS fellowship, respectively. The survey consisted of 5 domains; qualitative questions and recommendations for improvement were elicited. Results Program directors (33%, 16/48) and second-year (64%, 29/45) and third-year (53%, 26/49) fellows completed the surveys. While incoming fellows were deemed professional, serious surgical skill competency issues were identified: (1) PDs felt they could not leave their incoming fellow to operate independently on a major case for 30 minutes while in the next room compared with fellow responses (PDs: 33.3% vs second-year fellows: 67.9%; P = 0.03); (2) no PDs felt their fellows could suture laparoscopically; and (3) there was group consensus that incoming fellows were not proficient at cystoscopy (PDs: 40.0%, second-year fellows: 39.3%, third-year fellows: 32.0%; P = 0.82). Mostly, fellows could clinically evaluate and manage patients. Program directors thought their fellows had better understanding of statistics than fellows believed of themselves (P = 0.05). Increasing FPMRS exposure during residency was favored as the method to better prepare OG residents for fellowship. Conclusions Quantitative and emerging qualitative outcomes highlight that fellows are professional and are largely able to evaluate and care for patients but that achieving independence, surgical skills, and scholarship requires further training.
Effect of Membrane Charge on Flow and Protein Transport during Ultrafiltration

Although several recent studies have demonstrated the importance of electrostatic interactions in ultrafiltration, there have been few quantitative studies of the effects of membrane charge density on protein transport and membrane hydraulic permeability. Data were obtained using a series of charge‐modified cellulose membranes, with the surface charge density controlled by varying the extent of addition of a quaternary amine functionality. The membrane charge was evaluated from streaming potential measurements. Protein transmission decreased by a factor of 100 as the membrane ζ potential increased from 0.3 to 6.6 mV. The protein sieving data were in good agreement with a partitioning model accounting for electrostatic effects, while the hydraulic permeability data were consistent with a flow model accounting for the effects of counter‐electroosmosis. The results provide the first quantitative analysis of the effects of membrane charge density on the performance of ultrafiltration membranes.