Miracle-dz/UniFAR-FTUs huggingface dataset:
Durability of Response to Zoledronate Treatment and Competing Mortality in Paget's Disease of Bone

There has been a marked secular trend in recent decades toward patients with Paget's disease presenting at a greater age and having less extensive skeletal involvement. Over a similar time frame more potent bisphosphonates with a long duration of effect have been developed, raising the prospect of many patients needing only once in a lifetime treatment. We studied a cohort of 107 patients who had been treated with intravenous zoledronate for the first time at a mean age of 76 years. Sequential measurements of the bone turnover marker procollagen‐1 NT‐peptide (P1NP) were made for up to 10 years. By 9 years, 64% showed some loss of zoledronate effect (defined as a doubling of P1NP from the nadir value after treatment), but only 14% had a biochemical relapse (defined as a P1NP value >80 μg/L). The mortality rate was substantially greater than the relapse rate—by 10 years more than half the cohort had died (p < 0.0001). We conclude that for the majority of older people with Paget's disease a single intravenous infusion of zoledronate will provide disease suppression for the remainder of their lives. © 2016 American Society for Bone and Mineral Research.
Flow Re-direction Endoluminal Device in treatment of cerebral aneurysms: initial experience with short-term follow-up results.

OBJECT Flow diverter (FD) stents are relatively new and important devices in the treatment of cerebral aneurysms. The Flow Re-Direction Endoluminal Device has been recently released for clinical use. The authors' aim in this paper is to report their initial single-center FRED experience with short-term results. METHODS Between February 2012 and May 2013, 33 patients with 37 aneurysms (35 unruptured and 2 previously ruptured aneurysms) were treated with the FRED. Clinical and radiological data of the patients were retrospectively reviewed. RESULTS In all patients only 1 device was used without any additional device or material, such as a stent or coil. All procedures were successfully performed. The procedural complication rate was 3% (1 of 33). Thirty patients underwent clinical and radiological follow-up. During the follow-up period, changes in stent morphology, such as "fish mouth" and "foreshortening" phenomena, occurred in 5 patients. The mortality and permanent morbidity rates were 0%. The complete occlusion rates were 32% (6 of 19) at 0-1 month, 67% (8 of 12) at 2-3 months, 80% (4 of 5) at 4-6 months, and 100% (8 of 8) at 7-12 months. The rates for some aneurysms were assessed at more than one time point. CONCLUSIONS The FRED has an ability to serve neurointerventionalists in the treatment of cerebral aneurysms with its different technical advantages. The occlusion rates with FRED are similar to those with other FD devices. However, these short-term results need to be confirmed with mid- and long-term follow-up results of multicenter large series.
A phase II study of daily afatinib (BIBW 2992) with or without temozolomide (21/28 days) in the treatment of patients with recurrent glioblastoma.

2010 Background: Epidermal growth factor receptor (EGFR) is over-expressed in ~50% of glioblastoma (GBM); approximately half express the constitutively active mutant receptor EGFRvIII. Afatinib (A), an irreversible erbB family blocker (including EGFRvIII), has high levels of in vitro activity in tumor cell lines resistant to reversible EGFR inhibitors.Temozolomide (T) can overcome O6-methylguanine methyltransferase (MGMT) resistance. We hypothesized that daily A or daily A+T (AT, 21/28 days) may be an effective treatment for recurrent GBM. METHODS The trial's primary objectives were to evaluate efficacy and safety of A and AT compared to T in recurrent GBM, and to assess molecular determinants of response to A. Patients (pts) with histologically-confirmed GBM at first recurrence after prior combined chemoradiotherapy were randomized 1:1:1 to receive A, AT or T. Randomization was stratified by age (≤50 vs. >50 years) and Karnofsky Performance Status (KPS; 70, 80 vs. 90, 100). A was dosed daily at 40 mg; T was dosed at 75 mg/m2 for 21/28 days. The primary endpoint was 6-month progression-free survival rate (PFS-6). Independent imaging and pharmacokinetic assessments were obtained. Archival tumor samples were assessed for EGFR, EGFRvIII, PTEN, pAKT and MGMT. Patients were treated until undue toxicity or disease progression. RESULTS Enrolment was completed in June 2010. 119 pts were randomized (median age 58 years [range 22-81]) and 54% had a KPS of 70-80. The most frequent AEs in pts A-treated pts were diarrhea (70% and 68% in A and AT, respectively) and rash (80% and 69%). PFS-6 by investigator assessment was 3%, 17% and 22% in the A, AT and T arms, respectively. A was statistically worse compared to T (p=0.008); AT was comparable to T (p =0.59). Best overall response included partial response in one, five and six pts and SD in 22, 20 and 21 pts in A, AT and T, respectively. Preliminary biomarker data in 54 pts suggested durable disease control in EGFRvIII-positive pts treated with A/AT. Updated biomarker data will be presented. CONCLUSIONS Afatinib has limited single-agent activity in recurrent GBM; however, potential activity in biomarker-selected pts warrants further evaluation.
Molecular modelling, synthesis and biological evaluation of peptide inhibitors as anti-angiogenic agent targeting neuropilin-1 for anticancer application

Vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) are important targets of many pro-angiogenic factors. In this study, nine peptides were synthesized and evaluated for their molecular interaction with NRP-1 and compared to our previous peptide ATWLPPR. Docking study showed that the investigated peptides shared the same binding region as shown by tuftsin known to bind selectively to NRP-1. Four pentapeptides (DKPPR, DKPRR, TKPPR and TKPRR) and a hexapeptide CDKPRR demonstrated good inhibitory activity against NRP-1. In contrast, peptides having arginine residue at sites other than the C-terminus exhibited low activity towards NRP-1 and this is confirmed by their inability to displace the VEGF165 binding to NRP-1. Docking study also revealed that replacement of carboxyl to amide group at the C-terminal arginine of the peptide did not affect significantly the binding interaction to NRP-1. However, the molecular affinity study showed that these peptides have marked reduction in the activity against NRP-1. Pentapeptides having C-terminal arginine showed strong interaction and good inhibitory activity with NRP thus may be a good template for anti-angiogenic targeting agent.
Intrinsic association fiber system of the piriform cortex: A quantitative study based on a cholera toxin B subunit tracing in the rat

By using retrograde and anterograde transport of the B subunit of cholera toxin (CTb), we examined quantitatively the association fiber systems, i.e., the collaterals of pyramidal cell axons, that reciprocally connect both the rostral and the caudal parts of the piriform cortex (PC). Well‐defined CTb injections were obtained in layers Ib or II‐III of the rostral and the caudal parts of the PC. Using precision counting, we determined the proportion of cellular profiles in layers II and III that gave rise to association fibers and thus demonstrated a predominance of rostrocaudal fibers over the caudorostral ones. Our data also support a precise laminar organization of the PC in which the rostrocaudal fibers originated mainly from layer II and the caudorostral fibers primarily from layer III. Cholera toxin injections into layer Ib produced a peak of labeled profiles 2 mm from the site, indicating that a large proportion of the association fibers from layer II travel for at least 2 mm and then synapse in layer Ib. At either end of the PC, the association projections are concentrated laterally. The functional significance of these anatomical features is discussed with respect to olfactory processing, propagation of the activity within the PC, and the possible role of intrinsic fibers in olfactory memory. © 1996 Wiley‐Liss, Inc.
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay in Two Unrelated Turkish Families

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is an early onset form of hereditary spastic paraplegia with a peculiar clinical presentation. In addition to cerebellar findings which manifest first with ataxic gait in early life and spasticity, on an evolutionary basis, there is axonal neuropathy, prominent myelinated fibers in the optic fundus, and evidence of cerebellar atrophy that can be detected by cranial MRI. Intelligence is usually normal, however lower IQs have also been documented. This disorder mainly originates from the Charlevoix-Saguenay region of Quebec. Here, we report two Turkish families linked to the disease locus on chromosome 13 q12. There was homozygosity and segregation of disease haplotypes in both families. This form of spastic ataxia may be more common than originally presumed.
Technical Note: Magnetic field effects on Gafchromic-film response in MR-IGRT.

PURPOSE Magnetokinetic changes may affect crystal orientation and polymerization within the active layer of radiochromic film (RCF). This effect is investigated in a magnetic resonance image-guided radiotherapy unit within the context of film dosimetry. METHODS Gafchromic EBT2 RCF was irradiated in a 30 × 30 × 30 cm3 solid water phantom using a Co-60 MRI guided radiotherapy system (B = 0.35 T) under normal operating conditions, and under the exact conditions and setup without a magnetic field. Fifteen 20.3 × 25.4 cm2 EBT2 film sheets were placed at three different depths (d = 0.5, 5, and 10 cm) using five different treatment plans. The plans were computed using the MRIdian (ViewRay, Inc.) treatment planning system to deliver doses between 0 and 17.6 Gy. Films were analyzed before and after irradiation to obtain the net optical density (netOD) for each color channel separately. Scanning electron microscope (SEM) images were obtained to compare the active layer of selected samples. RESULTS The results indicated that the red channel netOD decreased between 0.013 and 0.123 (average of 0.060 ± 0.033) for doses above 2.8 Gy, with a linear increase in this effect for higher doses. Green channel netOD showed similar results with a decrease between 0.012 and 0.105 (average of 0.041 ± 0.027) for doses above 3.5 Gy. The blue channel showed the weakest effect with a netOD decrease between 0.013 and 0.029 (average of 0.020 ± 0.006) for doses above 8.0 Gy. SEM images show changes in crystal orientation within active layer in RCF exposed in a magnetic field. CONCLUSIONS The presence of a magnetic field affects crystal orientation and polymerization during irradiation, where netOD decreased by an average of 8.7%, 8.0%, and 4.3% in the red, green, and blue channels, respectively. The under response was dependent on dose and differed by up to 15% at 17.6 Gy.
Restoration of thrombosed Brescia-Cimino dialysis fistulas by using percutaneous transluminal angioplasty.

PURPOSE To evaluate the authors' experience with a technique for management of thrombosed Brescia-Cimino arteriovenous fistula. MATERIALS AND METHODS Forty patients with 42 thrombosed arteriovenous fistulas were percutaneously treated. Thrombosis occurred within 24 hours of attempted angioplasty in five fistulas, between 24 and 72 hours in 27, and longer than 72 hours in 10. Thrombosed fistulas were approached in a retrograde fashion followed by direct balloon dilation with 5-8-mm balloon catheters. If retrograde catheterization failed to cross the arterial anastomosis, an antegrade puncture directly into the thrombosed drainage vein close to the anastomosis was performed with ultrasonographic guidance, as an aid to catheterize the arterial inflow. Thrombolytic therapy with infusion of urokinase directly into the thrombus was performed in selected patients with visible thrombus that had compromised blood flow in the partially restored vascular access. Postintervention primary and secondary patency was calculated by using Kaplan-Meier analysis. Patency rates between patients without and with urokinase infusion were examined by using the log-rank test. RESULTS Anatomic success was achieved in 39 (93%) of 42 fistulas; and clinical patency, in 38 (90%) of 42 fistulas. Postintervention primary and secondary patencies (including initial technical failure) at 6, 12, and 18 months were 81% and 84%, 70% and 80%, and 63% and 80%, respectively. No significance of patency rate between patients without and with urokinase infusion was found (P =.912). Three patients died of unrelated causes at 1, 2, and 5 months after the procedures. No major complications were encountered. CONCLUSION High anatomic success and excellent clinical patency can be achieved in the salvage of thrombosed arteriovenous fistulas. Percutaneous restoration of arteriovenous fistulas should be attempted before surgical recreation to optimize outcome in patients undergoing hemodialysis.
Juvenile myoclonic epilepsy: clinical and EEG features

We aimed to characterize the clinical profile and EEG features of 43 patients with juvenile myoclonic epilepsy. In a retrospective design we studied the records of, and re‐interviewed, 43 patients diagnosed with JME from the epilepsy clinic data base. Furthermore, available EEGs were re‐evaluated. Of the patients 72% were female and 28% male. Average age of onset was 13 (5.5–22) years for absences, 16 (5.2–25) years for myoclonic seizures, and 16 (8–29) years for generalized tonic–clonic seizures. Forty‐two percent reported asymmetric or unilateral myoclonic jerks. Commonly reported precipitating factors were sleep deprivation (84%), stress (70%), and alcohol consumption (51%). EEG findings included rapid spike‐wave and polyspike‐wave.
[Investigation of pathogenic bacteria for pulmonary infections and their drug resistance in neurological intensive care unit].

OBJECTIVE To investigate the pathogenic bacterial spectrum responsible for pulmonary infections and their drug resistance in patients admitted to neurological care unit. METHODS Sputum specimens were obtained from patients who developed pulmonary infections in neurological intensive care unit between January, 2001 and June, 2002 for bacterial culture and isolation. K-B paper disc method was employed for determination of the drug sensitivity of the bacterial isolates. RESULTS In the 207 strains obtained from the patients, the majority (68.51%) were Gram-negative and 30.91/ Gram-positive bacteria, with fungi detected in one case (0.48%). The major pathogenic bacteria for pulmonary infection were, in the order of frequency, Staphylococcus aureus(14.49%), Pseudomonas aeruginosa (14.49%), Klebsiella pneumoniae (8.7%), Enterobacter cloacae (6.76%), and Enterobacter aerogenes (6.28%). Drug sensitivity tests showed increased drug resistance of the bacteria, but Staphylococcus aureus still remained sensitive to vancomycin and most of the Gram-negative bacillus sensitive to imipenem. CONCLUSION The major pathogenic bacteria causing pulmonary infections in neurological intensive care unit are Staphylococcus aureus and Pseudomonas aeruginosa, and their drug resistance is obviously increased, suggesting the necessity of strengthening bacterial surveillance and more adequate clinical use of antibiotics.
Antioxidant activity of five vegetables traditionally consumed by south‐Asian migrants in Bradford, Yorkshire, UK

Five vegetables traditionally consumed among South‐Asian migrants in Bradford (Yorkshire, UK) were tested for their free radical scavenging activity (FRSA) in the DPPH (1,1‐diphenyl‐2‐picrylhydrazil radical) screening assay (using extracts prepared both by cold maceration and also by boiling the plant in the solvent under reflux) and for their in vitro non‐enzymatic inhibition of bovine brain lipid peroxidation.
Validity of a Prescription Claims Database to Estimate Medication Adherence in Older Persons

Background:Prescription claims data have been used to estimate refill medication adherence through calculations of cumulative medication acquisition (CMA) and cumulative medication gap (CMG) values. Few studies have assessed the validity of these calculated rates. Objectives:We sought to assess the validity of CMA and CMG calculated from the Manitoba prescription claims database (DPIN) against pill count medication adherence, targeting overall medications and angiotensin converting enzyme inhibitors (ACEIs). Methods:Using a survey of a convenience sample of subjects recruited through community pharmacies, subjects who were eligible for study (ie, 65 years or older, noninstitutionalized, taking 2 or more “discrete” prescribed medications, including an ACEI, and willing to provide informed consent) were studied. Pill counts were conducted on all prescribed medicines during 3 home interviews over the course of 4 months. Ten months of DPIN data also were collected on each subject. Results:The concordance between CMA and pill count for overall medications was 411/522 (79%) and for ACEIs was 89/101 (88%) with no systematic differences (McNemar's P = 0.68 and P = 0.097, respectively). CMG and pill count showed even better concordance of 438/514 (85%) for overall medications and 96/101 (95%) for ACEIs, although systematic differences were noted for overall medications (McNemar's P = 0.0012) but not for ACEIs (McNemar's P = 0.500). Spearman's rank correlations were weak for all comparisons. Conclusions:The high concordance between prescription claims database and pill counts suggested that the rate with which patients refill their medications usually is consistent with the rate they consume them. DPIN is not accurate for nondiscrete dosage forms or medications prescribed for “as-required” use.
Distribution of aromatase mRNA and protein in the brain and pituitary of female rainbow trout: Comparison with estrogen receptor α

Recent data indicate that estrogens locally produced in the brain by aromatization of androgens could be important for neurogenesis and brain repair. In this respect, fish are interesting because of the extremely high aromatase activity of their brain. In this study, the rainbow trout brain aromatase was cloned and riboprobes were used to map the distribution of cells expressing the corresponding mRNAs. A very strong hybridization signal was detected in the pituitary and in cells bordering the ventricles in the telencephalon and ventral diencephalon, with the highest expression in the preoptic area and hypothalamus. A weaker signal was detected in the ependymal layer bordering the torus semicircularis and optic tectum. This localization was fully confirmed by immunohistochemistry using antibodies against a teleost aromatase. In addition, this antibody showed that aromatase expression in fact corresponds to radial glial cells because immunoreactive cells had long cytoplasmic processes extending toward the pial surface. Because brain aromatase was shown to be upregulated by estradiol in fish, the distribution of aromatase mRNAs was compared with that of rainbow trout estrogen receptor α (rtERα) on adjacent sections. Although the highest aromatase expression was found in regions expressing rtERα, no obvious coexpression was found, as rtERα was never observed in radial cells. However, reverse transcriptase‐polymerase chain reaction experiments performed on brain cell cultures enriched in glial cells suggest that a weak expression of rtERα in glial cells cannot be excluded. The possible role of the high brain aromatase content in fish could be related to the continuous growth of their central nervous system during adulthood. J. Comp. Neurol. 462:180–193, 2003. © 2003 Wiley‐Liss, Inc.
Epinephrine Fails to Enhance Performance of Food-Deprived Rats on a Delayed Spontaneous Alternation Task

Increases in blood glucose levels after epinephrine injection appear to contribute to the hormone's effects on learning and memory. The present experiment evaluated whether epinephrine-induced enhancement of spontaneous alternation performance would be attenuated in fasted rats that had blunted increases in circulating glucose levels after injections of epinephrine. Rats deprived of food for 24 h prior to injection of epinephrine exhibited significant attenuation of the increase in blood glucose levels seen in fed rats. When the rats were tested on a delayed spontaneous alternation task, epinephrine enhanced performance in fed rats but not in rats deprived of food for 24 h. These findings are consistent with the view that hyperglycemia subsequent to epinephrine injections contributes to the memory-enhancing effects of epinephrine.
Corneal transplantation in antibody-deficient hosts.

PURPOSE To examine the role of donor-specific antibodies, with or without complement, in rejection of orthotopic corneal transplants by using mice as recipients in which the genes for the heavy chain of immunoglobulin or the third complement component have been eliminated by homologous recombination. METHODS BALB/c corneas were transplanted into eyes of B-cell-deficient (n=17) or wild-type control C57BL/6 (n=30) mice and into eyes of complement (C3)-deficient (n=15) or wild-type control 129-C57BL/6 (n=13) mice. After surgery all grafts were evaluated over 8 weeks in a masked manner by biomicroscopy for signs of rejection. RESULTS The rates of corneal transplant rejection were similar among B-cell-deficient and C3-deficient mice compared with rejection rates in their respective wild-type control subjects. This similarity applied to the time course of rejection and to cumulative survival rates. CONCLUSIONS Neither donor-specific antibody nor the third component of complement play essential roles in acute rejection of orthotopic corneal allografts in mice.
Ontogeny of the female femur: geometric morphometric analysis applied on current living individuals of a Spanish population

In this study we describe the development of the female femur based on the analysis of high‐resolution radiographic images by means of geometric morphometrics, while assessing the usefulness of this method in these kinds of studies. The material analysed consisted of digital images in DICOM format (telemetries), corresponding to 184 left femora in anterior view, obtained from the database of the Hospital Sant Joan de Déu of Barcelona (Spain). Bones analysed corresponded to individuals from 9 to 14 years old. Size and shape variation of the entire femur was quantified by 22 two‐dimensional landmarks. Landmark digitisation errors were assessed using Procrustes anova test. Centroid size (CS) variation with age was evaluated by an anova test. Shape variation was assessed by principal component analysis. A mancova test between the first five principal components and age, using the CS as covariable, was applied. Results indicated that both size and shape vary significantly with age. Several age‐related shape changes remained significant after removing the allometric effect. In general, an increase in the robustness of the bone and noticeable phenotypic changes in certain areas of the femur were observed. During growth in the proximal region of the femur, the collo‐diaphyseal angle decreases, the neck of the femur widens and the fovea moves to a lower position, standing more in line with the plane of the neck. Likewise, the size of the greater and lesser trochanters increase. In the distal region, a significant increase of epiphyseal dimensions was recorded, mainly in the medial condyle. The angular remodelling of the neck and the bicondylar region of the femur in females continues until 13 years old. The information provided in the present study increases our knowledge on the timing and morphology of the femur during development, and in particular the morphology of the different femoral ossification centres during development.