Miracle-dz/UniFAR-FTUs huggingface dataset:
The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review.

AIMS To carry out a systematic review to assess the effectiveness of cannabis extracts and cannabinoids in the management of chronic nonmalignant neuropathic pain. METHODS Electronic database searches were performed using Medline, PubMed, Embase, all evidence-based medicine reviews, and Web of Science, through communication with the Canadian Consortium for the Investigation of Cannabinoids (CCIC), and by searching printed indices from 1950. Terms used were marijuana, marihuana, cannabis, cannabinoids, nabilone, delta- 9-tetrahydrocannabinol, cannabidiol, ajulemic acid, dronabinol, pain, chronic, disease, and neuropathic. Randomized placebo-controlled trials (RCTs) involving cannabis and cannabinoids for the treatment of chronic nonmalignant pain were selected. Outcomes considered were reduction in pain intensity and adverse events. RESULTS Of the 24 studies that examined chronic neuropathic pain, 11 studies were excluded. The 13 included studies were rated using the Jadad Scale to measure bias in pain research. Evaluation of these studies suggested that cannabinoids may provide effective analgesia in chronic neuropathic pain conditions that are refractory to other treatments. CONCLUSION Cannabis-based medicinal extracts used in different populations of chronic nonmalignant neuropathic pain patients may provide effective analgesia in conditions that are refractory to other treatments. Further high-quality studies are needed to assess the impact of the duration of the treatment as well as the best form of drug delivery.
Antimicrobial Resistance Patterns In Community Acquired Urinary Tract Infections.

BACKGROUND Urinary tract infection (UTI) is the most frequent disease for which patients seek medical care. The antimicrobial agents causing UTI and their sensitivity patterns have remarkably changed throughout the world over the past few years. Hence, the present study was designed to explore the uropathogens and their susceptibility to various molecules in our region. METHODS This descriptive cross sectional study was conducted at Medical C Unit of Ayub Teaching Hospital, Abbottabad from January 2015 to January 2016. Patients with clinical features of UTI were evaluated using Urine R/E and Urine culture and sensitivity. Ten antibiotics were checked for susceptibility. Results were analysed using SPSS 17. RESULTS A total of 630 patients presented with urinary complaints. Of these, 236 patients had more than 8-10 pus cells on urine R/E. They were further evaluated using culture and sensitivity and positive culture was obtained in 75 patients. Of these 34 (45.3%) were males and 41 (54.7%) were females. E Coli was the predominant isolate being present in 49 (65.3%) patients. This was followed by Klebsiella in 9 (12%) patients. Tazobactam-piperacillin and cefoperazone-sulbactam were the most sensitive drugs having overall sensitivity of 96% and 93.3% respectively. The isolates were highly resistant to Fluoroquinolones 77.3% followed by Penicillins 72% and TMP-SMX 69.3%. CONCLUSIONS Antibiotic sensitivity patterns have enormously changed over the past decade. Newer agents are quite efficacious but their use should be highly judicious to prevent the development of resistance to these molecules.
Structure-function mapping: variability and conviction in tracing retinal nerve fiber bundles and comparison to a computational model.

PURPOSE We evaluated variability and conviction in tracing paths of retinal nerve fiber bundles (RNFBs) in retinal images, and compared traced paths to a computational model that produces anatomically-customized structure-function maps. METHODS Ten retinal images were overlaid with 24-2 visual field locations. Eight clinicians and 6 naïve observers traced RNFBs from each location to the optic nerve head (ONH), recording their best estimate and certain range of insertion. Three clinicians and 2 naïve observers traced RNFBs in 3 images, 3 times, 7 to 19 days apart. The model predicted 10° ONH sectors relating to each location. Variability and repeatability in best estimates, certain range width, and differences between best estimates and model-predictions were evaluated. RESULTS Median between-observer variability in best estimates was 27° (interquartile range [IQR] 20°-38°) for clinicians and 33° (IQR 22°-50°) for naïve observers. Median certain range width was 30° (IQR 14°-45°) for clinicians and 75° (IQR 45°-180°) for naïve observers. Median repeatability was 10° (IQR 5°-20°) for clinicians and 15° (IQR 10°-29°) for naïve observers. All measures were worse further from the ONH. Systematic differences between model predictions and best estimates were negligible; median absolute differences were 17° (IQR 9°-30°) for clinicians and 20° (IQR 10°-36°) for naïve observers. Larger departures from the model coincided with greater variability in tracing. CONCLUSIONS Concordance between the model and RNFB tracing was good, and greatest where tracing variability was lowest. When RNFB tracing is used for structure-function mapping, variability should be considered.
Genetic score of multiple risk‐associated single nucleotide polymorphisms is a marker for genetic susceptibility to bladder cancer

Genome‐wide association studies have identified 13 single nucleotide polymorphisms (SNPs) that are associated with bladder cancer; three of these SNPs were validated in the Chinese population. This study assessed the performance of these three SNPs, in combination, to predict genetic susceptibility to bladder cancer in Chinese. Three previously established bladder cancer risk‐associated SNPs (rs798766 in TACC3, rs9642880 in MYC, and rs2294008 in PSCA) were genotyped in 1,210 bladder cancer patients and 1,008 control subjects in Shanghai, China. A genetic score was calculated for each subject based on these three SNPs. Each of these three SNPs was significantly associated with bladder cancer risk in this independent study population, P < 0.05. The genetic score based on these three SNPs was significantly higher in cases than controls, with a mean of 1.05 and 0.99, respectively, P = 1.03E‐05. Compared with subjects with a genetic score <= 1.00, subjects with an elevated genetic score (>1.00) had a significantly increased risk for bladder cancer after adjusting for age, gender, and smoking status, OR = 1.58, 95% Confidence Interval (CI) = 1.21 − 2.06, P = 0.0007. When tested separately for lower (Ta) or higher (Tis, T1‐T4) tumor stage, the association was significantly stronger for lower (OR = 2.24, 95% CI = 1.66 − 3.01, P = 1.02E‐07) than higher tumor stage (OR = 1.33, 95% CI = 1.00 − 1.78, P = 0.05), P = 0.001. In conclusion, A combination of three previously implicated bladder cancer risk‐associated SNPs is a significant predictor of genetic susceptibility to bladder cancer in Chinese. © 2013 Wiley Periodicals, Inc.
Do Novel Risk Biomarkers Reflect the Severity of Peripheral Arterial Disease?

The association between novel atherosclerotic risk biomarkers and severity of peripheral arterial disease (PAD) was assessed. Patients (n = 133) with PAD were recruited. Established risk biomarkers including low- and high-density cholesterol, triglycerides, and blood pressure were measured. Novel risk biomarkers including plasma C-reactive protein, von Willebrand factor (vWF), interleukin 6, red cell folate (RCF), vitamin B12, total homocysteine (tHcy), and Hcy genotypes were also determined. The severity of PAD was evaluated, using ankle—brachial pressure index (ABPI), brachial—knee, and brachial—ankle pulse wave velocity (bk- and ba-PWV). Plasma tHcy and systolic blood pressure had a positive independent correlation with bk-PWV (β = +0.56, P = .02 and β = +0.38, P < .001, respectively). Red cell folate had an independent inverse correlation with bk-PWV (β = —0.01, P = .01). Systolic blood pressure showed an independent positive correlation with ba-PWV only after adjustment for other risk biomarkers (β = +0.1, P = .04). Novel markers, plasma tHcy, and RCF levels correlated with the severity of PAD.
Mitochondria respond to Ca2+ already in the submicromolar range: correlation with redox state.

Rapid formation of high-Ca2+ perimitochondrial cytoplasmic microdomains has been shown to evoke mitochondrial Ca2+ signal and activate mitochondrial dehydrogenases, however, the significance of submicromolar cytoplasmic Ca2+ concentrations in the control of mitochondrial metabolism has not been sufficiently elucidated. Here we studied the mitochondrial response to application of Ca2+ at buffered concentrations in permeabilized rat adrenal glomerulosa cells, in an insulin-producing cell line (INS-1/EK-3) and in an osteosarcoma cell line (143BmA-13). Mitochondrial Ca2+ concentration was measured with the fluorescent dye rhod-2 and, using an in situ calibration method, with the mitochondrially targeted luminescent protein mt-aequorin. In both endocrine cell types, mitochondrial Ca2+ concentration increased in response to elevated cytoplasmic Ca2+ concentration (between 60 and 740 nM) and an increase in mitochondrial Ca2+ concentration could be revealed already at a cytoplasmic Ca2+ concentration step from 60-140 nM. Similar responses were observed in the osteosarcoma cell line, although a clearcut response was first observed at 280 nM extramitochondrial Ca2+ only. As examined in glomerulosa cells, graded increases in cytoplasmic Ca2+ concentration were associated with graded increases in the reduction of mitochondrial pyridine nucleotides, consistent with Ca2+-dependent activation of mitochondrial dehydrogenases. Our data indicate that in addition to the recognized role of high-Ca2+ cytoplasmic microdomains, also small Ca2+ signals may influence mitochondrial metabolism.
Placental Growth Hormone and Lactogen Production by Perifused Ovine Placental Explants: Regulation by Growth Hormone-Releasing Hormone and Glucose

Abstract The factors controlling normal placental development are poorly understood. We have previously reported the presence of ovine placental growth hormone (oPGH) and growth hormone receptors in ovine placenta, and oPGH production by the trophectoderm and syncitium during the second month of pregnancy. To identify factors regulating oPGH production, we developed a perifusion system to measure oPGH and ovine placental lactogen (oPL) production by Day 45 ovine placental explants. The mRNAs for both hormones were quantitated by real-time polymerase chain reaction in explants collected after perifusion periods of up to 8 h. Ovine PGH and oPL were released into the medium at mean rates of 2.45 ± 0.2 and 353.6 ± 13.6 ng/g/h, respectively. Ovine placenta produces growth hormone-releasing hormone (GHRH), but addition of GHRH to the perifusion medium did not modify either oPGH or oPL production. In vivo, oPGH production occurs between Days 30 and 60 of pregnancy. Because modulation of the maternal diet during this period affects placental development, the potential regulation of oPGH and oPL production by glucose was evaluated. Glucose supplementation of the perifusion medium resulted in a concentration-dependent decrease in oPGH release after 4 h, but oPGH mRNA levels were not affected. Production of oPL was not affected by glucose. Thus, oPGH and oPL belong to the same growth hormone/prolactin family but are differentially regulated by glucose. Ovine PGH modulations should be taken into account in metabolic experiments performed during the first trimester of pregnancy in sheep.
Deficits in dopamine clearance and locomotion in hypoinsulinemic rats unmask novel modulation of dopamine transporters by amphetamine

Insulin affects brain reward pathways and there is converging evidence that this occurs through insulin regulation of the dopamine (DA) transporter (DAT). In rats made hypoinsulinemic by fasting, synaptosomal DA uptake is reduced. Interestingly, [3H]DA uptake is increased in hypoinsulinemic rats with a history of amphetamine self‐administration. The possibility that amphetamine and insulin act in concert to regulate DAT activity prompted this study. Here we show that [3H]DA uptake, measured in vitro and clearance of exogenously applied DA in vivo, is significantly reduced in rats made hypoinsulinemic by a single injection of streptozotocin. Strikingly, amphetamine (1.78 mg/kg, given every other day for 8 days) restored DA clearance in streptozotocin‐treated rats but was without effect on DA clearance in saline‐treated rats. Basal locomotor activity of streptozotocin‐treated rats was lower compared to control rats; however, in streptozotocin‐treated rats, hyperlocomotion induced by amphetamine increased over successive amphetamine injections. In saline‐treated rats the locomotor stimulant effect of amphetamine remained stable across the four amphetamine injections. These results provide exciting new evidence that actions of amphetamine on DA neurotransmission are insulin‐dependent and further suggest that exposure to amphetamine may cause long‐lasting changes in DAT function.
Temperature- and frequency-dependent dielectric properties of biological tissues within the temperature and frequency ranges typically used for magnetic resonance imaging-guided focused ultrasound surgery

Abstract Purpose: This study aimed to obtain the temperature- and frequency-dependent dielectric properties of tissues subjected to magnetic resonance (MR) scanning for MR imaging-guided focused ultrasound surgery (MRgFUS). These variables are necessary to calculate radio frequency electromagnetic fields distribution and specific radio frequency energy absorption rate (SAR) in the healthy tissues surrounding the target tumours, and their variation may affect the efficacy of advanced RF pulses. Materials and methods: The dielectric properties of porcine uterus, liver, kidney, urinary bladder, skeletal muscle, and fat were determined using an open-ended coaxial probe method. The temperature range was set from 36 °C to 60 °C; and the frequencies were set at 42.58 (1 T), 64 (1.5 T), 128 (3 T), 170 (4 T), 298 (7 T), 400 (9 T), and 468 MHz (11 T). Results: Within the temperature and frequency ranges, the dielectric constants were listed as follows: uterus 49.6–121.64, liver 44.81–127.68, kidney 37.3–169.26, bladder 42.43–125.95, muscle 58.62–171.7, and fat 9.2327–20.2295. The following conductivities were obtained at the same temperature and frequency ranges: uterus 0.5506–1.4419, liver 0.5174–0.9709, kidney 0.8061–1.3625, bladder 0.6766–1.1817, muscle 0.8983–1.3083, and fat 0.1552–0.2316. Conclusions: The obtained data are consistent with the temperature and frequency ranges typically used in MRgFUS and thus can be used as reference to calculate radio frequency electromagnetic fields and SAR distribution inside the healthy tissues subjected to MR scanning for MRgFUS.
Culprit plaque morphology in STEMI - an optical coherence tomography study: insights from the TOTAL-OCT substudy.

AIMS Our aim was to compare stenosis severity and plaque content between STEMI culprit lesions with intact fibrous cap (IFC) and those with plaque rupture (PR) in a prospective study. METHODS AND RESULTS We evaluated 93 patients undergoing OCT and thrombectomy as part of a prospective substudy of the TOTAL (ThrOmbecTomy versus PCI ALone) trial. Culprit lesion morphology was assessable by OCT in 70/93 (75.3%). IFC was found in 31 (44.3%), PR in 34 (48.6%) and calcified nodule in five (7.1%) patients. Following thrombectomy, OCT demonstrated similar lumen area stenosis in IFC (79.3%) and PR (79.6%) (p=0.88). Lumen area stenosis <50% was observed in none of the patients with PR and in one patient with IFC. IFC had fewer quadrants with lipid plaque as compared to PR (28.16±15.02 vs. 39.12±14.23, p=0.004). However, in both lesion types, lipid was the predominant plaque type (83.9 vs. 63.7% of diseased quadrants). CONCLUSIONS In a prospective study of STEMI patients treated with thrombectomy, mild residual stenoses were uncommon in IFC lesions. Although lipid content was lower than in PR lesions, lipid composed the majority of the diseased segments in IFC.
Systemically delivered insulin-like growth factor-I enhances mesenchymal stem cell-dependent fracture healing

In this study, we examined the effectiveness of systemic subcutaneous delivery of recombinant Insulin-like growth factor (IGF)-I concurrently with primary cultured bone marrow-derived mesenchymal stem cell (MSC) transplant on fracture repair. We found that the fracture callus volume increased in mice with a stabilized tibia fracture that received IGF-I+MSC when compared with that in either untreated or MSC alone treated mice. In evaluating the callus tissue components, we found that the soft and new bone tissue volumes were significantly increased in IGF-I+MSC recipients. Histological and in-situ hybridization analyses confirmed a characteristic increase of newly forming bone in IGF-I+MSC recipients and that healing progressed mostly through endochondral ossification. The increase in soft and new bone tissue volumes correlated with increased force and toughness as determined by biomechanical testing. In conclusion, MSC transplant concurrent with systemic delivery of IGF-I improves fracture repair suggesting that IGF-I+MSC could be a novel therapeutic approach in patients who have inadequate fracture repair.
A search for circumstellar dust disks with ADONIS

We present results of a coronographic imaging search for circumstellar dust disks with the Adaptive Optics Near Infrared System (ADONIS) at the ESO 3.6 m telescope in La Silla (Chile). 22 candidate stars, known to be orbited by a planet or to show infrared excess radiation, were examined for circumstellar material. In the PSF-subtracted images no clear disk was found. We further determine the detection sensitivities and outline how remaining atmospheric fluctuations still can hamper adaptive optics observations.
Coronary Artery Disease and Reticular Macular Disease, a Subphenotype of Early Age-Related Macular Degeneration

ABSTRACT Purpose: Reticular macular disease (RMD) is the highest risk form of early age-related macular degeneration and also specifically confers decreased longevity. However, because RMD requires advanced retinal imaging for adequate detection of its characteristic subretinal drusenoid deposits (SDD), it has not yet been completely studied with respect to coronary artery disease (CAD), the leading cause of death in the developed world. Because CAD appears in middle age, our purpose was to screen patients aged 45–80 years, documented either with or without CAD, to determine if CAD is associated with RMD. Design: A prospective cohort study of patients with documented CAD status and no known retinal disease in a clinical practice setting at one institution. Subjects and Controls: A number of 76 eyes from 38 consecutive patients (23 with documented CAD, 15 controls documented without CAD; 47.4% female; mean age 66.7 years). Methods: Patients were imaged with near-infrared reflectance/spectral domain optical coherence tomography and assessed in masked fashion by two graders for the presence of SDD lesions of RMD and soft drusen. Main Outcome Measures: Presence or absence of RMD/SDD and soft drusen. Results: RMD was more frequent in patients with CAD versus those without (Relative Risk [RR] = 2.1, CI = 1.08–3.95, P = 0.03). There was no association of CAD with soft drusen. Conclusions: A specific relationship between CAD and RMD suggests common systemic causes for both and warrants further study.
Prebiotics and resistance to gastrointestinal infections

Acute gut disorder is a cause for significant medicinal and economic concern. Certain individual pathogens of the gut, often transmitted in food or water, have the ability to cause severe discomfort. There is a need to manage such conditions more effectively. The route of reducing the risk of intestinal infections through diet remains largely unexplored. Antibiotics are effective at inhibiting pathogens; however, these should not be prescribed in the absence of disease and therefore cannot be used prophylactically. Moreover, their indiscriminate use has reduced effectiveness. Evidence has accumulated to suggestthat some of the health-promoting bacteria in the gut (probiotics) can elicit a multiplicity of inhibitory effects against pathogens. Hence, an increase in their numbers should prove effective at repressing pathogen colonisation if/when infectious agents enter the gut. As such, fortification of indigenous bifidobacteria/lactobacilli by using prebiotics should improve protection. There are a number of potential mechanisms for lactic acid bacteria to reduce intestinal infections. Firstly, metabolic endproducts such as acids excreted by these micro-organisms may lower the gut pH to levels below those at which pathogens are able to effectively compete. Also, many lactobacilli and bifidobacteria species are able to excrete natural antibiotics, which can have a broad spectrum of activity. Other mechanisms include an improved immune stimulation, competition for nutrients and blocking of pathogen adhesion sites in the gut. Many intestinal pathogens like type 1 fimbriated Escherichia coli, salmonellae and campylobacters utilise oligosaccharide receptor sites in the gut. Once established, they can then cause gastroenteritis through invasive and/or toxin forming properties. One extrapolation of the prebiotic concept is to simulate such receptor sites in the gut lumen. Hence, the pathogen is ‘decoyed’ into not binding at the host mucosal interface. The combined effects of prebiotics upon the lactic acid flora and anti-adhesive strategies may lead towards new dietary interventions against food safety agents.
Comparison between a newly developed PC-based Doppler umbilical artery waveform analyser and a commercial unit.

OBJECTIVES To determine the accuracy of the resistance index (RI) of flow velocity waveforms of the umbilical artery measured using a newly developed PC-based continuous wave Doppler device (Umbiflow) with regard to systematic and random variations when compared with a commercial standard (Vasoflow). DESIGN A cohort study. SETTING The fetal evaluation clinic (FEC) at Tygerberg Hospital. SUBJECTS Patients referred to the FEC at Tygerberg Hospital with suspected chronic placental insufficiency. OUTCOME MEASURES The correlation coefficients indicating the strength of the relationship between the two devices and their agreement using the method of Bland and Altman. RESULTS A total of 248 patients were studied. The mean RIs of the first Doppler assessment were 0.69 (standard deviation (SD) 0.11) and 0.67 (SD 0.11) using the Vasoflow and Umbiflow respectively. The Pearson's correlation coefficient comparing the RI of the first test was 0.85. The degree of agreement between the two methods was excellent, the mean differences being very small (< 0.024) with tight confidence intervals. One hundred and ninety-four patients (78.2%) of patients remained in the same percentile category with both the Vasoflow and Umbiflow. CONCLUSIONS The accuracy of the Umbiflow has been proved. A non-significant trend towards slightly lower values needs to be considered. This could be addressed by changing the percentile cut-off to slightly lower values.