The purpose of our study was to determine which wrist fractures are not prospectively diagnosed at radiography using CT as a gold standard and to identify specific fracture patterns.
Through a search ...of radiology records from January 1 to December 31, 2005, 103 consecutive patients were identified as having radiographic and CT examinations of the wrist. After excluding incomplete or nondiagnostic examinations and those with a greater than 6-week interval between imaging studies, the final study group consisted of 61 wrist examinations in 60 patients. Two musculoskeletal radiologists and one emergency radiologist blindly reviewed CT examinations, and each bone (scaphoid, lunate, triquetrum, pisiform, trapezium, trapezoid, capitate, hamate, metacarpals, distal radius, distal ulna) was categorized as normal or fractured, with agreement reached by consensus. Each prospective radiographic report was categorized as either normal or fracture/equivocal for each osseous structure. Results were compared using the chi-square and Fisher's exact tests.
In the proximal carpal row, lunate and triquetrum fractures were often radiographically occult (0% and 20%, respectively, detected at radiography); whereas in the distal carpal row, trapezoid, capitate, and hamate fractures were often occult (0%, 0%, and 40% detected at radiography, respectively). Hamate fractures were significantly associated with metacarpal fractures, and distal radius fractures were associated with scaphoid and ulna fractures.
Thirty percent of wrist fractures were not prospectively diagnosed on radiography, suggesting that CT should be considered after a negative radiographic finding if clinically warranted. The location of a dorsal scaphoid avulsion fracture emphasizes the need for specific radiographic views or cross-sectional imaging for diagnosis.
Solid-state electrochemical cells with dense oriented thin film electrodes of La0.5Sr0.5CoO3-delta (LSCO) were prepared on (100) surfaces of single-crystal disCs of yttria-stabilised zirconia (YSZ) ...by the pulsed laser deposition technique. Oxygen exchange at the electrodes was studied with ac impedance spectroscopy under various temperature and oxygen partial pressure conditions. Three distinctive features were observed in the impedance spectra from high to low frequency corresponding to contributions from the ionic conduction of the YSZ electrolyte, ionic transfer at the LSCO/YSZ interface, and the oxygen exchange on the LSCO electrode surface. An equivalent circuit model of the electrode process is used to fit the impedance data. The time constant for the oxygen surface exchange was derived from the impedance simulation. The surface chemical exchange coefficients, kchem, were calculated from the time constants as a function of temperature and pO2. kchem is 7 x 10 exp(-4) cm/s at T = 700 C and pO2 = 1 atm. The activation energy at pO2 = 1 atm is approximately 1.1 eV. The interfacial conductivity data were also derived from the impedance simulations as a function of temperature and pO2. The activation energy for the interfacial transport at pO2 = 1 atm is approximately 1.6 eV. 44 refs.
Neelapu and colleagues report a post hoc subgroup analysis from the ZUMA-1 trial of chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B cell lymphoma. In comparison ...with younger patients, those ≥65 years old have similar rates of complete response and durable response at 2 years, but higher rates of neurological toxicity.
Aims/hypothesis
We previously identified the
G6PC2
locus as a strong determinant of fasting plasma glucose (FPG) and showed that a common
G6PC2
intronic single nucleotide polymorphism (SNP) ...(rs560887) and two common
G6PC2
promoter SNPs (rs573225 and rs13431652) are highly associated with FPG. However, these promoter SNPs have complex effects on
G6PC2
fusion gene expression, and our data suggested that only rs13431652 is a potentially causative SNP. Here we examine the effect of rs560887 on
G6PC2
pre-mRNA splicing and the contribution of an additional common
G6PC2
promoter SNP, rs2232316, to the association signal.
Methods
Minigene analyses were used to characterise the effect of rs560887 on
G6PC2
pre-mRNA splicing. Fusion gene and gel retardation analyses characterised the effect of rs2232316 on
G6PC2
promoter activity and transcription factor binding. The genetic association of rs2232316 with FPG variation was assessed using regression adjusted for age, sex and BMI in 4,220 Europeans with normal FPG.
Results
The rs560887-G allele was shown to enhance
G6PC2
pre-mRNA splicing, whereas the rs2232316-A allele enhanced
G6PC2
transcription by promoting Foxa2 binding. Genetic analyses provide evidence for association of the rs2232316-A allele with increased FPG (
β
= 0.04 mmol/l;
p
= 4.3 × 10
−3
) as part of the same signal as rs560887, rs573225 and rs13431652.
Conclusions/interpretation
As with rs13431652, the in situ functional data with rs560887 and rs2232316 are in accord with the putative function of
G6PC2
in pancreatic islets, and suggest that all three are potentially causative SNPs that contribute to the association between
G6PC2
and FPG.
Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. ...Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice.
We examined whether heparin and enoxaparin influence APP processing and inhibit Aβ production in primary cortical cell cultures. Heparin and enoxaparin were incubated with primary cortical cells derived from Tg2576 mice, and the level of APP and proteolytic products of APP (sAPPα, C99, C83 and Aβ) was measured by western blotting. Treatment of the cells with heparin or enoxaparin had no significant effect on the level of total APP. However, both GAGs decreased the level of C99 and C83, and inhibited sAPPα and Aβ secretion. Heparin also decreased the level of β-secretase (BACE1) and α-secretase (ADAM10). In contrast, heparin had no effect on the level of ADAM17.
The data indicate that heparin and enoxaparin decrease APP processing via both α- and β-secretase pathways. The possibility that GAGs may be beneficial for the treatment of AD needs further study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
P2Y receptors (P2YRs), a family of purinergic G-protein-coupled receptors (GPCRs), are activated by extracellular nucleotides. There are a total of eight distinct functional P2YRs expressed in human, ...which are subdivided into P2Y1-like receptors and P2Y12-like receptors. Their ligands are generally charged molecules with relatively low bioavailability and stability in vivo, which limits our understanding of this receptor family. P2Y12R regulates platelet activation and thrombus formation, and several antithrombotic drugs targeting P2Y12R--including the prodrugs clopidogrel (Plavix) and prasugrel (Effient) that are metabolized and bind covalently, and the nucleoside analogue ticagrelor (Brilinta) that acts directly on the receptor--have been approved for the prevention of stroke and myocardial infarction. However, limitations of these drugs (for example, a very long half-life of clopidogrel action and a characteristic adverse effect profile of ticagrelor) suggest that there is an unfulfilled medical need for developing a new generation of P2Y12R inhibitors. Here we report the 2.6 Å resolution crystal structure of human P2Y12R in complex with a non-nucleotide reversible antagonist, AZD1283. The structure reveals a distinct straight conformation of helix V, which sets P2Y12R apart from all other known class A GPCR structures. With AZD1283 bound, the highly conserved disulphide bridge in GPCRs between helix III and extracellular loop 2 is not observed and appears to be dynamic. Along with the details of the AZD1283-binding site, analysis of the extracellular interface reveals an adjacent ligand-binding region and suggests that both pockets could be required for dinucleotide binding. The structure provides essential insights for the development of improved P2Y12R ligands and allosteric modulators as drug candidates.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pediatric brain tumor survivors demonstrate weaknesses in adaptive functioning, most notably practical adaptive skills; however, the specific areas of weakness within practical skills are unknown. ...This study examined the aspects of practical adaptive functions that are most impacted in brain tumor survivors, and identified medical and socio-demographic variables that predicted outcomes. The sample included 117 pediatric brain tumor patients seen for a clinical neuropsychological evaluation and whose parents completed the Adaptive Behavior Assessment System, Second or Third Edition. T-tests compared practical adaptive skills to normative means. Correlations examined associations between medical and socio-demographic variables and each of the practical adaptive subscales (Community Use, Home Living, Health & Safety, Self-Care). Significant correlations were entered into linear regression models for each practical adaptive skill. All practical subscales were significantly below the normative mean. Community Use was positively correlated with age at diagnosis and negatively correlated with treatment burden, time since diagnosis, and neighborhood deprivation. Health and Safety was positively correlated with age at diagnosis. Home Living was positively correlated with neighborhood deprivation. Self-Care was positively correlated with age at diagnosis and parental education. Specific medical and socio-demographic factors predicted practical adaptive functioning, highlighting the importance of considering the role of medical and socio-demographic determinants of health on adaptive functioning outcomes in pediatric brain tumors.
To develop an automated, physiologic metric of immune effector cell-associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor-T cell therapy.
We conducted a retrospective ...observational cohort study from 2016 to 2020 at two tertiary care centers among patients receiving chimeric antigen receptor-T cell therapy with a CD19 or B-cell maturation antigen ligand. We determined the daily neurotoxicity grade for each patient during EEG monitoring via chart review and extracted clinical variables and outcomes from the electronic health records. Using quantitative EEG features, we developed a machine learning model to detect the presence and severity of neurotoxicity, known as the EEG immune effector cell-associated neurotoxicity syndrome score.
The EEG immune effector cell-associated neurotoxicity syndrome score significantly correlated with the grade of neurotoxicity with a median Spearman's R
of 0.69 (95% CI of 0.59-0.77). The mean area under receiving operator curve was greater than 0.85 for each binary discrimination level. The score also showed significant correlations with maximum ferritin (R
0.24, p = 0.008), minimum platelets (R
-0.29, p = 0.001), and dexamethasone usage (R
0.42, p < 0.0001). The score significantly correlated with duration of neurotoxicity (R
0.31, p < 0.0001).
The EEG immune effector cell-associated neurotoxicity syndrome score possesses high criterion, construct, and predictive validity, which substantiates its use as a physiologic method to detect the presence and severity of neurotoxicity among patients undergoing chimeric antigen receptor T-cell therapy.
Introduction Labels considered normatively appropriate for specific social identity groups change. Researchers have examined the effects of censorship and slur usage, but minimal research examines ...the psychological consequences of imposing new language constraints on people. Methods Across four samples of university students ( N total = 997), we sought participants' compliance in avoiding usage of numerous commonplace group labels while they wrote essays about obese people (Sample 1) or specific ethnic groups (Samples 2-4). Results We observed consistently high compliance rates: participants either invented novel terminology to describe the group or avoided group labels entirely. We observed a substantial absence of task discomfort, attitudinal shifts regarding the group, or motivational shifts, according to Bayesian analyses. Nor did we detect negative effects of language constraint among people who saw themselves as opposed to censorship. Discussion Although free speech and respectful language remain a multifaceted social debate, our findings show that university students are willing to follow even completely contrived language directives when describing social identity groups and to do so without substantial discomfort or backlash against those groups.
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