Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanoparticle transport across the blood brain barrier

ABSTRACT While the role of the blood-brain barrier (BBB) is increasingly recognized in the (development of treatments targeting neurodegenerative disorders, to date, few strategies exist that enable drug delivery of non-BBB crossing molecules directly to their site of action, the brain. However, the recent advent of Nanomedicines may provide a potent tool to implement CNS targeted delivery of active compounds. Approaches for BBB crossing are deeply investigated in relation to the pathology: among the main important diseases of the CNS, this review focuses on the application of nanomedicines to neurodegenerative disorders (Alzheimer, Parkinson and Huntington's Disease) and to other brain pathologies as epilepsy, infectious diseases, multiple sclerosis, lysosomal storage disorders, strokes.
Progenitor cells and vascular function are impaired in patients with chronic kidney disease.

BACKGROUND Endothelial dysfunction contributes to accelerated atherosclerosis in chronic kidney disease (CKD). Bone marrow-derived endothelial progenitor cells (EPC) constitute an endogenous vascular repair system protecting against atherosclerosis. Smooth muscle progenitor cells (SPC) may stimulate atherosclerosis development. We hypothesized that an imbalance in EPC and SPC occurs in CKD, which may contribute to the increased cardiovascular disease (CVD) risk. METHODS EPC and SPC outgrowth from mononuclear cells (MNC), EPC migratory function and circulating CD34(+)KDR(+)-EPC were measured in 49 patients with varying degrees of CKD on regular therapy and 33 healthy volunteers. Renal function, CKD cause, CVD history and endothelial dysfunction parameters were determined as factors of influence on progenitor cells. RESULTS Patients had reduced EPC outgrowth compared to controls [9 (2-22) vs 12 (1-38) cells/10(3) MNC, P = 0.026], independent of CKD cause and degree, whereas SPC outgrowth levels were higher in patients with more impaired kidney function (r = -0.397, P = 0.008). Patients had lower CD34(+)KDR(+)-EPC compared to controls [9 (0-52) vs 19 (4-110) cells/10(5) granulocytes, P = 0.004]. CVD history and increased endothelial dysfunction markers were related to lower EPC levels. Progenitor cell outgrowth was shifted towards SPC with progression of endothelial damage. Reduction in EPC could not be attributed to decreases in progenitor cell-mobilizing factors SDF-1 alpha and VEGF as levels increased with progressive kidney and endothelial dysfunction, while EPC remained low. CONCLUSIONS Our data suggest that, already in mild CKD, EPC-mediated endogenous vascular regeneration is impaired, while SPC levels increase with declining kidney function.
Folklore Linked to Pregnancy and Birth in Nigeria

As a part of a safe motherhood project implemented in eastern Nigeria between 1992 and 1996, in-house interviews were conducted with rural women and traditional birth attendants in the seven states of eastern Nigeria. The overall project was designed to contribute toward the reduction of maternal mortality and morbidity through the involvement of community leaders and women’s organizations in women’s health activities in rural Nigeria. It also focused on identifying and addressing some of the underlying cultural factors in maternal mortality and morbidity in Nigeria. Findings from the interview show that women in rural eastern Nigeria still hold many folklore beliefs about pregnancy and childbirth, and some of these beliefs lead to delay in the referral of complications to hospitals.
Towards the optimum cost of ownership of switched-mode power supplies: Early stage cost management with life-cycle costing

In order to minimize the total life-cycle ownership cost, selection should be based on the optimum trade-off between spending on design and manufacturing cost with the price of lost energy. This study shows that it is advantageous to use power supplies with higher efficiencies even when the initial development and manufacturing costs are higher. It is critical to make the correct decision at an early stage of design. This study uses life-cycle costing to analyze whether electronic products are designed optimally. We explore life-cycle ownership cost and identify corresponding efficiency levels. The study uses a cost-efficiency model that is based on industry cases and empirical data. Application is made of an early stage cost management method, used prior to, and during, product development and design. Two power supply types were analyzed. To identify the trade-off between higher development and manufacturing cost with running cost having energy losses, three different configurations (with efficiencies between 80% and 91%) were analyzed. The findings were evaluated through a sensitivity analysis to illustrate the robustness of results
The Argument from Design

Abstract: This article offers a brief overview of the argument for God's existence grounded in the evidence of design. It pays particular attention to the way the argument has evolved over time and in relation to changing scientific perspectives. The argument from design has in fact been formulated and reformulated in response to the discoveries and challenges it has encountered from the field of science. The conclusion of the article explores the theological importance of this argument with respect to its extent and its limits
Ameliorative effects of a neuroprotective agent, T‐817MA, on place learning deficits induced by continuous infusion of amyloid‐β peptide (1–40) in rats

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline due to neuronal loss and neural network dysfunction. It has been postulated that progressive neuronal loss in AD is consequence of the neurotoxic properties of the amyloid‐β peptide (Aβ). In the present study, we investigated the effect of T‐817MA (1‐{3‐[2‐(1‐benzothiophen‐5‐yl)ethoxy] propyl}‐3‐azetidinol maleate), a newly synthesized neurotrophic compound, on place learning deficits in rats with hippocampal damages. To induce granule cell loss in the dentate gyrus (DG) of the hippocampus, Aβ (1–40) was continuously infused (300 pmol/day) into the cerebral ventricle using a mini‐osmotic pump for 5 weeks. Three weeks after the Aβ infusion, the rats were tested in a place learning task, which required them to alternatively visit two diametrically opposed areas in an open field to obtain intracranial self‐stimulation reward. The results indicated that the Aβ‐infused rats without treatment of T‐817MA displayed learning impairment in the task; their performance level was significantly inferior to that of the vehicle rats. Treatment of T‐817MA (8.4 mg/kg/day, p.o.) significantly improved the task performance of the Aβ‐infused rats. Furthermore, T‐817MA prevented granule cell loss due to Aβ‐infusion, which was correlated to task performance of the rats. However, other cognitive enhancer, an acetylcholinesterase inhibitor, had no such effects. The results demonstrated that T‐817MA ameliorated learning deficits induced by Aβ infusion, which might be attributed to neuroprotection in the hippocampus. © 2007 Wiley‐Liss, Inc.
Age‐related Changes in Blood Pressure and Duration of Motor Block in Spinal Anesthesia

Changes in blood pressure, heart rate and the time necessary for recovery from motor block after spinal anesthesia were compared in 65 children, aged 8 months to 15 years, and 17 adult patients. All patients had similar levels of sensory anesthesia (T5-T3) following tetracaine, 0.3 mg/kg, plus phenylephrine, 0.075 mg/kg. Children less than 5 years of age showed little or no change in blood pressure and heart rate following spinal anesthesia, but children more than 6 years old had widely variable decreases in blood pressure. The decreases of blood pressure in the older children resembled those in adults. The time needed to regain motor function increase with age; in children less than 2 years of age, motor function returned in about a fifth of the time needed in adults. It is suggested that 1) the small proportions of the lower extremities and immaturity of the sympathetic nervous system in young children are responsible for the cardiovascular stability observed in these children during spinal anesthesia; 2) age-related differences in duration of motor block reflect physical and physiologic differences, including amount of cerebrospinal fluid, diameter and surface area of the spinal cord and nerve roots, and rate of absorption of local anesthetics from the subarachnoid space.
Dorzolamide in situ Gel Forming System: Characterization and Evaluation for Glaucoma Treatment

The objective of the present study was to develop an efficient in situ gel forming system of Dorzolamide for the treatment of glaucoma. The in situ gel was formulated using alginate and hydroxyl propyl methyl cellulose (HPMC) polymer combination. The developed formulation was characterized for various in vitro parameters e.g. drug content, pH, isotonicity, surface tension, rheological behavior, drug release profile and transcorneal permeation. The rheological behavior of all formulations was not affected by the incorporation of the drug. The bioadhesive strength of the developed formulation was found to be 0.311 Nmm. The optimized formulation was stable and non-irritant to rabbit eyes. In vitro drug release was found to be 91.27 ± 0.61 % over a period of 10 hours. The best-fit kinetic model (Korsmeyer model) for the optimized formulation DIG 8 suggests that the drug release via Fickian-diffusion mechanism. A maximum mean difference of 27.4% in lowering intra ocular pressure was observed between control and treated eyes with optimized formulation after water loading (p<0.01). The in situ alginate/HPMC gel forming system could be a potential approach for Dorzolamide formulation to enhance ocular bioavailability for the treatment of glaucoma, ultimately improving the patient compliance.
A molecular characterization of Clostridium difficile isolates from humans, animals and their environments

Summary It is generally accepted that most patients with Clostridium difficile-associated diarrhoea acquire the organism from the environment. Recently we demonstrated that household pets may constitute a significant reservoir of C. difficile through gastrointestinal carriage in up to 39% of cats and dogs. These findings suggested that direct transmission from household pets, or contamination of the environment by them, may be a factor in the pathogenesis of C. difficile-associated diarrhoea. To investigate this possibility, we examined isolates of C. difficile from humans, pets and the environment by restriction enzyme analysis (REA) and restriction fragment length polymorphism (RFLP) typing using enhanced chemiluminescence. Both REA and RFLP typing methods used Hind III digests of chromosomal DNA. A total of 116 isolates of C. difficile from pets (26), veterinary clinic environmental sites (33), humans (37) and hospital environmental sites (20) was examined. REA was far more discriminatory than RFLP typing and for all isolates there were 34 REA types versus 6 RFLP types. There was good correlation between the REA types found in isolates from pets and from the veterinary clinic environment, and between isolates from humans and from those found in the hospital environment. There was, however, no correlation between REA type of C. difficile found in pets and isolates of human origin. We conclude that there may still be a risk of humans acquiring C. difficile from domestic pets as these findings may be the result of geographical variation.
Postpartum positioning and attachment education for increasing breastfeeding: a randomized trial.

BACKGROUND Although lactation experts suggest that a correct positioning and attachment technique reduces breastfeeding problems and enhances long-term breastfeeding, evidence from randomized trials is lacking. The objective of this study was to evaluate the effect of postpartum positioning and attachment education on breastfeeding outcomes in first-time mothers. METHOD A randomized trial was performed in a public hospital in Adelaide, South Australia, where 160 first-time mothers were randomly allocated to receive either structured one-to-one education (experimental group) or usual postpartum care (control group) within 24 hours of birth. The primary outcome was breastfeeding at 6 weeks and 3 and 6 months postpartum; other outcomes were nipple pain and trauma in hospital and at 6 weeks and 3 and 6 months, and satisfaction with breastfeeding. RESULTS No significant differences occurred in breastfeeding rates between the groups at each endpoint, although a trend in the direction of lower rates was seen at each endpoint in the experimental group. This group reported less nipple pain on days 2 (p = 0.004) and 3 (p = 0.04), but this was not sustained on follow-up. No differences were observed in nipple trauma in hospital or in self-reported nipple pain and/or trauma at the three endpoints. Experimental group women were less satisfied with breastfeeding at 3 and 6 months postpartum when using a one-item measure; however, a multiple-item measure showed no significant differences at the three endpoints. CONCLUSIONS The intervention did not increase breastfeeding duration at any assessment time or demonstrate any differences between the groups on secondary outcomes. The trend toward lower breastfeeding rates in the experimental group suggests a need for a larger trial to evaluate whether or nor postpartum positioning and attachment education may negatively affect breastfeeding.
The Acute Effect of Acupuncture on 20-km Cycling Performance

Objective:To examine acupuncture's effect on cycling performance. Design:This was a prospective, single-blind, patient as own control (repeated measures), crossover design. Subjects underwent 3 tests a week, riding a stationary bike for 20-km as fast as able. Before each test, they received acupuncture (test A), "sham" acupuncture (test B), and no intervention (control, test C) once each in a random order. Setting:University of Alberta, Faculty of Rehabilitation Medicine. Participants:20 male cyclists (age, 18 to 30 years) were recruited via convenience sampling of students and general public. Athletic ability was assessed through a questionnaire and modified Par-Q. Interventions:Acupuncture, sham acupuncture, and no intervention in random order with each subject before each test. Acupuncture points were chosen on the basis of Traditional Chinese Medicine and administered immediately before cycling. Sham was shallow needling of known acupoints. Main Outcome Measurements:The outcome measures of each of the tests were time to completion, VAS for lower extremity/exercise-induced pain, Borg rating of perceived exertion (RPE), and blood lactate concentrations, recorded immediately following each test. Results:Mean times to Test A, B, and C completion were 36.19 ± 5.23, 37.03 ± 5.66, and 37.48 ± 6.00 minutes, respectively, P = 0.76. Mean RPE scores after tests A, B, and C were 17.65 ± 0.67, 16.95 ± 0.99, and 16.85 ± 0.88, respectively, P = 0.0088. Mean VAS scores after tests A, B, and C were 7.72 ± 0.86, 7.94 ± 0.78, and 8.08 ± 0.69, respectively, P = 0.76. Conclusions:The only statistically significant finding was that acupuncture gave higher RPE scores compared to the other tests. The clinical significance was that the higher RPE scores gave lower time and VAS scores.
The dura causes spinal cord compression after spinal cord injury

Abstract MR scans from 65 patients with traumatic spinal cord injury were analysed; on admission 95% had evidence of cord compression – in 26% due to the dura, and in the remaining 74% due to extradural factors. Compression due to dural factors resolved with a half-life of 5.5 days. These findings suggest that bony decompression alone may not relieve spinal cord compression in the quarter of patients in whom dural factors are significant.
The Utility of PAX-2 in Distinguishing Metastatic Clear Cell Renal Cell Carcinoma From its Morphologic Mimics: An Immunohistochemical Study With Comparison to Renal Cell Carcinoma Marker

PAX-2 is a homeogene expressed during kidney development. Although immunohistochemical expression of PAX-2 has been described in a variety of primary renal cell carcinoma (RCC) subtypes and in metastatic RCC, its specificity as a marker of renal lineage in a metastatic setting has not been fully evaluated. In addition, its utility has not been directly compared with the most widely used antibody in this setting, renal cell carcinoma marker (RCCma). We studied PAX-2 expression in metastatic clear cell renal cell carcinoma (CC-RCC) and in a variety of nonrenal neoplasms with clear cytoplasm that may potentially mimic CC-RCC. Archival material from 27 CC-RCCs metastatic to various organs and 50 close morphologic mimics of CC-RCC were retrieved. Immunohistochemistry with PAX-2 and RCCmaπ antibodies was performed on each case. Nuclear staining (PAX-2) or membranous staining (RCCma) was scored semiquantitatively. Twenty-three of 27 (85%) metastatic CC-RCCs showed nuclear immunoreactivity for PAX-2, whereas RCCma reactivity was found in 19 of 27 (70%). The immunoprofiles of the metastatic CC-RCC were PAX-2+/RCCma+: 19 of 27 (70%), PAX-2+/RCCma−: 5 of 27 (19%), PAX-2−/RCCma+: 2 of 27 (7%), and PAX-2-/RCCma-: 1 of 27 (4%). Five of the 50 mimics of CC-RCC (10%) had at least focal nuclear reactivity with PAX-2, including 1 of 3 parathyroid carcinomas (33%), 3 of 7 clear cell carcinomas of the ovary (43%), and the 1 clear cell papillary cystadenoma of the epididymis. Membranous RCCma reactivity was identified in 26 of the 50 mimics (52%). We conclude that PAX-2 is a useful marker for distinguishing metastatic CC-RCC from its potential morphologic mimics, but caution must be used in certain differential diagnostic settings where nonrenal tumors such as parathyroid carcinoma, ovarian clear cell carcinoma, and clear cell papillary cystadenoma of the epididymis were shown to express both PAX-2 and RCCma.
Signal transduction pathways involved in PPARβ/δ‐induced neuronal differentiation

Neuroblastomas are pediatric tumors originating from neuroblasts in the developing peripheral nervous system. The neurotrophin brain‐derived neurotrophic factor (BDNF) is a key regulator of survival and differentiation of specific neuronal populations in the central and peripheral nervous system. Patients whose neuroblastoma tumors express high levels of BDNF and TrkB have an unfavorable prognosis. We have previously reported on the neuronal differentiating activity of peroxisome proliferator‐activated receptors (PPAR)β/δ natural and synthetic ligands by modulating BDNF/TrkB pathway, suggesting their potential use as new therapeutic strategies for neuroblastoma. The validation of new therapeutic agents implies the understanding of their mechanisms of action. Herein, we report the effects of activated‐PPARβ/δ on signal transduction pathways known to be involved in neuronal differentiation, such as ERK1,2 and BDNF pathways. The results obtained, using also PPARβ/δ silencing, indicating a neuronal differentiating effect PPARβ/δ‐dependent through BDNF‐P75‐ERK1,2 pathways, further support a role for PPARβ/δ in neuronal differentiation and pointing towards PPARβ/δ as a modulator of pathways crucial for neuronal differentiation. These findings open new perspectives in the formulation of potential therapeutic approaches to be used as adjuvant treatment with the standard therapies. J. Cell. Physiol. 226: 2170–2180, 2011. © 2010 Wiley‐Liss, Inc.
Refining esophageal cancer staging.

OBJECTIVE Cancer staging is dynamic, reflecting accrual of knowledge and experience in treatment. The objectives of this study were to assess current esophageal cancer staging and to determine whether refinements of classification and stage grouping are necessary. METHODS From 1983 through November 2000, 480 patients underwent esophagectomy without induction therapy. Depth of tumor invasion (T), regional lymph node status (N), distant status (M), number of metastatic regional lymph nodes, and histopathologic type and grade were subjected to survival-tree analysis, multivariable Cox and hazard function analysis, and residual misclassification risk analysis. RESULTS Inhomogenity of survival was found within and lack of distinction was found between current American Joint Committee on Cancer staging groups, supporting the need for refinement. T1 and N1 were redefined on the basis of survival differences. T1a is intramucosal cancer, T1b is submucosal cancer (P =.008), N1 is 1 or 2 metastatic regional lymph nodes, and N2 is 3 or more metastatic regional lymph nodes (P =.01). Current subclassification of M1 is not warranted (P =.9). Histopathologic type (P =.17) and grade (P =.3) minimally refined staging. Reassignment of staging groups constrained by American Joint Committee on Cancer definitions of stages 0 and IV produced less monotonic, distinctive, and homogeneous survival than free assignment of staging groups. CONCLUSIONS Current American Joint Committee on Cancer staging of esophageal cancer is inadequate. Refinement requires redefinition of T1, N1, and M1 classifications. Stage grouping within the constraints of American Joint Committee on Cancer definitions produces less accurate prognosis than free assignment based on survival data.
Spatial Patterns of Spontaneous Local Field Activity in the Monkey Visual Cortex

Spontaneous activity among visually responsive neurons is often considered to consist of random neural events, or perhaps to reflect an irrelevant by-product of brain homeostasis. However, recent studies have emphasized that such ongoing activity is strongly synchronized over large cortical distances, and can have a marked impact on the responsiveness of neurons to visual stimuli, suggesting that such activity may indeed be highly relevant to the brain's interpretation of its sensory input. In the current study, we examined the spatiotemporal nature of local field potential (LFP) fluctuations in the visual cortex of two macaque monkeys that were awake, but in a state of relaxation with minimal visual stimulation. Using an array of 16 electrodes spaced by several millimeters, we simultaneously monitored the LFP at many sites over a large region of the visual cortex. In agreement with the literature, we found that the coherence in the raw LFP signal fell off quickly with both frequency and distance. However, when we examined slower fluctuations in the LFP power, we found that power signals, including those derived from the high y-range frequencies, had high coherence that fell off only very slowly with cortical distance. Finally, we performed an additional experiment, with several electrodes placed on either side of a sulcus, to demonstrate that the decline in local field synchrony with cortical distance was so reliable that the interruption in the cortical sheet corresponding to the opening of the sulcus could be easily identified by monitoring just a few minutes of spontaneous LFP activity. These experiments reveal that a significant portion of spontaneous LFP fluctuations in the visual cortex is contributed by global mechanisms, imposing synchrony that is, first and foremost, a function of cortical separation between any two points.