Miracle-dz/UniFAR-FTUs huggingface dataset:
Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype: a randomised, double-blind, and placebo-controlled, phenotype panel study

Abstract In neuropathic pain with irritable nociceptor (IN) phenotype, upregulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype panel, crossover study with 4-week treatment periods of lidocaine 5% patch and placebo was performed to search for phenotype differences in effect. The primary efficacy measure was the total pain intensity on an 11-point numeric rating scale, and the primary objective was to compare the effect of lidocaine in patients with and without IN phenotype as defined by hypersensitivity and preserved small-fibre function determined by quantitative sensory testing. Forty-six patients with neuropathic pain due to nerve injury or postherpetic neuralgia were randomised. The modified intention-to-treat population comprised 15 patients with irritable nociceptor and 25 patients with nonirritable nociceptor. In the total sample, lidocaine reduced pain by 0.3 numeric rating scale points (95% confidence interval [CI]: 0.1-0.5) and pain-related sleep disturbance by 0.6 points (95% CI: 0.4-0.8) more than placebo (P = 0.007 and P < 0.001) and relieved pain by 0.4 verbal score (−1-5) points more (P = 0.036). For these measures, there was no significant interaction between treatment and phenotype, but there was a significant interaction for pain paroxysms (0.8, 95% CI: 0.4-1.2, P < 0.001) and deep aching pain (0.6, 95% CI: 0.1-1.0, P = 0.013). In conclusion, lidocaine 5% patch had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with IN phenotype. The lack of significant phenotype differences may be caused by too low statistical power.
Visible-light-induced annihilation of tumor cells with platinum-porphyrin conjugates.

Despite the extensive use of porphyrins in photodynamic therapy (PDT), tetraplatinated porphyrins have so far not been studied for their anticancer properties. Herein, we report the synthesis of such novel platinum-porphyrin conjugates as well as their photophysical characterization and in vitro light-induced anticancer properties. These conjugates showed only minor cytotoxicity in the dark, but IC50 values down to 19 nM upon irradiation with light at 420 nm.These values correspond to an excellent phototoxic index (PI=IC50 in the dark/IC50 in light), which reached 5000 in a cisplatin-resistant cell line. After incubation with HeLa cells, nuclear Pt concentrations were 30 times higher than with cisplatin. All of these favorable characteristics imply that tetraplatinated porphyrin complexes are worthy of exploration as novel PDT anticancer agents in vivo.
Effects of alcohol withdrawal on blood pressure in hypertensive heavy drinkers

Background Epidemiological investigations have demonstrated a close association between heavy alcohol consumption and hypertension. The mechanisms of this association, however, remain elusive. We studied the effects of alcohol withdrawal on blood pressure, hormonal parameters, and circulating markers of endothelial activity. Methods In 14 hypertensive heavy alcohol consumers (> 200 g/day) who agreed to participate in a hospital withdrawal programme we monitored, for 30 days, blood pressure, plasma levels of renin, aldosterone, cortisol, endothelin, and plasminogen activator inhibitor 1 (PAI-1), and urinary levels of catecholamines. Patients in the withdrawal group were compared with eight hypertensive heavy drinkers who refused to participate in the programme and maintained regular alcohol consumption and 11 normotensive teetotalers. Results By the third day after withdrawal, blood pressure was significantly decreased and the normalization of levels was obtained in 13 of 14 patients by the end of the study. Alcohol withdrawal significantly decreased plasma aldosterone and cortisol levels, but did not affect levels of active renin and fractionated urinary catecholamines. At baseline, plasma endothelin and PAI-1 levels were significantly higher in alcoholic individuals than in teetotalers, and after the cessation of alcohol intake decreased progressively, reaching levels different from baseline within 1 week. A significant correlation was found between changes in endothelin and PAI-1, and blood pressure variations during alcohol abstinence that remained significant only for endothelin with the multivariate approach. Conclusion Hypertension is rapidly reversible in the majority of heavy drinkers after the withdrawal of alcohol consumption. In these patients, hypertension is associated with an increased release of endothelial factors that might contribute to the increase in blood pressure.
Investigation of the effect of probiotic exposure on filaggrin expression in an experimental model of canine atopic dermatitis.

BACKGROUND Atopic dermatitis (AD) results from complex interactions between an impaired skin barrier and immunological stimulation. Filaggrin is a key protein for the skin barrier, and its expression is decreased in subsets of atopic dogs and can be modified by inflammation; thus, immunomodulatory approaches may alter its expression. Probiotics have been explored for the prevention and treatment of allergies, owing to their immunomodulatory properties; however, it is currently unknown whether they can modulate filaggrin expression. OBJECTIVE The purpose of this study was to evaluate whether probiotics can modulate filaggrin expression in an experimental model of canine AD. ANIMALS AND METHODS Eighteen atopic (11 probiotic exposed and seven control) and five normal beagles were challenged for three consecutive days with Dermatophagoides farinae. Skin biopsies were taken before (day 0), at the peak (day 3) and after the end of the allergen challenge (day 10). Immunohistochemistry for filaggrin was done using a polyclonal antibody specific for canine filaggrin, and staining was scored both subjectively (for intensity, granularity and continuity) and objectively, by tracing the stratum granulosum and calculating the percentage of filaggrin per unit traced area. RESULTS Analysis of variance of the percentage of filaggrin in the stratum granulosum showed a significant effect of group (P = 0.0414, AD < normal), time (P = 0.0066, days 3 and 10 > day 0) and marginal group × time interaction (P = 0.0606). Within the atopic group, exposure to probiotics did not change filaggrin expression. No significant differences were found in the subjective scores among groups. CONCLUSIONS AND CLINICAL IMPORTANCE It is concluded that probiotic exposure early in life does not alter filaggrin expression in this AD model.
Role of peripheral CRF signalling pathways in stress‐related alterations of gut motility and mucosal function

Central corticotrophin releasing‐factor (CRF) signalling pathways are involved in the endocrine, behavioural and visceral responses to stress. Recent studies indicate that peripheral CRF‐related mechanisms also contribute to stress‐induced changes in gut motility and intestinal mucosal function. Peripheral injection of CRF or urocortin inhibits gastric emptying and motility through interaction with CRF2 receptors and stimulates colonic transit, motility, Fos expression in myenteric neurones and defecation through activation of CRF1 receptors. With regard to intestinal epithelial cell function, intraperitoneal CRF increases ion secretion and mucosal permeability to macromolecules. The motility and mucosal changes induced by peripheral CRF mimic those induced by acute stress. In addition, CRF receptor antagonists given peripherally prevent acute restraint and water avoidance stress‐induced delayed gastric emptying, stimulation of colonic motor function and mucosal permeability. Similarly, early trauma enhanced intestinal mucosal dysfunction to an acute stressor in adult rats and the response is prevented by peripheral injection of CRF antagonist. Chronic psychological stress results in reduced host defence and initiates intestinal inflammation through mast cell‐dependent mechanisms. These findings provide convergent evidence that activation of peripheral CRF receptors and mast cells are important mechanisms involved in stress‐related alterations of gut physiology.
An outbreak of forty five cases of Pseudomonas aeruginosa acute endophthalmitis after phacoemulsification.

PURPOSE To describe an outbreak of Pseudomonas aeruginosa endophthalmitis post cataract surgery. Clinical findings, treatment and outcome are discussed. METHODS Clinical charts review of forty-five patients treated for endophthalmitis in a two-day period. The patients underwent primary vitrectomy, anterior chamber irrigation and intravitreous antibiotic injection. Cultures from vitreous and anterior chamber samples were performed in all patients. RESULTS Forty-five patients (twenty-three men and twenty-two women) were identified. The average age was 71.2 years (range, 56-83 years). The right eye (62%) was affected more often than the left eye (38%). The median interval between surgery and endophthalmitis onset was 5.5 days (range, 5-6 days). The visual acuity at the diagnosis was better than 20/40 in one patient (2%), from 20/40 to 20/200 in one patient (2%), from 20/400 to counting fingers in two patients (4%), hand movements in eleven patients (24%), and light perception in thirty patients (68%). Pseudomonas aeruginosa was the isolated agent in twenty-six vitreous samples and in three anterior chamber samples. Overall, one patient (2%) achieved a final visual acuity better than 20/40; eight patients (18%) achieved a final visual acuity from 20/40 to 20/200; six patients (13%) achieved a final visual acuity from 20/400 to counting fingers; eleven patients (25%) achieved a final acuity of hand movements; thirteen patients (29%) achieved a final acuity of light perception and six (13%) patients had no light perception at the last examination. None of these eyes underwent evisceration or enucleation in a three-month follow-up period. CONCLUSION Even with all the safety that cataract surgery has achieved, today, endophthalmitis remains a risk and a fearful complication of this procedure. In the present study, it was impossible to identify the source of the outbreak.
MDM2 and CDKN1A gene polymorphisms and risk of Kaposi’s sarcoma in African and Caucasian patients

A single-nucleotide polymorphism in the MDM2 promoter (SNP309; rs2279744) causes elevated transcription of this major negative regulator of p53 in several cancer types. We investigated MDM2 SNP309 and CDKN1A (p21/Waf1/Cip1) codon 31 (rs1801270) polymorphisms in 86 cases of cutaneous Kaposi’s sarcoma (KS) from African and Caucasian patients, and 210 healthy controls. A significant increase of the MDM2 SNP309 T/G genotype was observed among classic KS cases (odds ratio 2.38, 95% confidence interval 1.0–5.5). Frequencies of CDKN1A codon 31 genotypes were not significantly different between cases and controls. The results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene for the development of classic KS in Caucasian patients.
Painless, Nonablative, Immediate Skin Contraction Induced by Low‐Fluence Irradiation with New Infrared Device: A Report of 25 Patients

BACKGROUND Nonablative radiofrequency (NARF) has been the only method for producing noninvasive skin tightening. Nevertheless, significant pain during the procedure is an important downside of this technology. A new nonablative medical device, Titan (Cutera, Inc., Brisbane, CA, USA), capable of fluences much lower than those possible with NARF, was tested as a less painful alternative. OBJECTIVES To produce skin contraction leading to lifting of eyebrows and/or improvement of lower face and neck skin laxity using fluences below pain levels. PATIENTS AND METHODS Twenty-five patients were treated. Standardized photographs were obtained preoperatively, after a few days, a few weeks, and up to 12 months after the procedure. RESULTS Immediate changes were obtained in 22 of 25 patients. Examination of photographs revealed that the initial improvement was maintained throughout the follow-up period. CONCLUSION Immediate true skin contraction persisting through the immediate, intermediate, and long-term follow-up was found in the vast majority of patients in this group. Edema as an artifact simulating immediate improvement was excluded by serial photographs taken during the follow-up period. Skin contraction occurred at low fluences, below the threshold of pain. This, to the best of our knowledge, has not been previously described in the medical literature.
Corruption, Political Instability and Sustainable Development: The Interlinkages

The study empirically probed the interdependence among corruption, political instability and sustainable development for a panel of 28 developing economies and disaggregated sample of lower-middle and upper-middle income economies for the time period 2000-2014. The three stage least square (3SLS) estimation revealed that corruption negatively affects sustainable development and political instability. The political instability impedes sustainable development and corruption. The sustainable development reduces political instability and corruption. It explains that corruption enhances political stability and political stability increases corruption. The disaggregated estimates of developing economies are almost same as aggregate estimates of developing economies, however political instability has statistically insignificant effect on sustainable development in upper-middle-income economies. To go forward for sustainable development, the elimination of corruption is imperative.
Evidence of noncovalent dimerization of calmodulin.

Calcium-binding proteins, such as S-100, dimerize readily, and this phenomenon plays an important role in their regulation of target enzymes [Krebs, J., Quadroni, M. & Van Eldik, L.J. (1995) Nat. Struct. Biol. 2, 711-714; Kilby, P.M. , Van Eldik, L.J. & Roberts, G. C. (1996) Structure 4, 1041-1052]. We have investigated by Fourier-transform ion cyclotron resonance (FTICR) MS the conformational states of the calcium-binding protein calmodulin, and present clear evidence for a calmodulin dimer formed as a result of noncovalent interactions between folded monomers. Ultra-high-resolution electrospray ionization (ESI) mass spectra for calmodulin, obtained with a 9.4 T FTICR mass spectrometer, are presented. With the use of denaturing solutions (1 : 1 acetonitrile/water + 1% formic acid), relatively high charge states (20 < z < 10) of monomeric calmodulin ions were detected, whereas when calmodulin was electrosprayed from buffer, monomers ions with only 5-10 charges were detected. CD measurements for calmodulin in buffered solution revealed that its alpha-helical content was significantly higher than that for calmodulin in acetonitrile/water solutions, consistent with a proposition that changes in charge state distributions observed in the MS experiments reflect differing states of calmodulin folding. Under buffered conditions, noncovalently bound calmodulin dimers were observed by ESI FTICR MS. Analytical ultracentrifugation experiments carried out in the same solution conditions as those used in the MS experiments were consistent with the proposed calmodulin dimer-monomer equilibrium. The ultra-high mass resolution achieved with the 9.4 T FTICR mass spectrometer allowed unequivocal identification of the noncovalent, as opposed to covalent, character of the calmodulin dimer.
Clinical significance of the preoperative serum-soluble intercellular adhesion molecule-1 in non-small cell lung cancer.

BACKGROUND The serum-soluble intercellular adhesion molecule-1 (sICAM-1) is reported to correlate with both the metastatic potential and a poor prognosis. We analyzed the sICAM-1 concentrations and investigated whether or not the serum levels of these adhesion molecules in the peripheral venous blood could help predict the clinical staging in patients with NSCLC. METHODS From January to December 1999, 66 patients (79.5%) underwent either a lobectomy or a pneumonectomy with a mediastinal lymph node dissection at the National Sanatorium Nishi-Gunma Hospital. RESULTS The sICAM-1 concentration in the NSCLC patients was a mean value of 212.0+/-106.6 ng/ml. In contrast, the concentration of sICAM-1 in 20 healthy controls was a mean value of 117.9+/-64.1 ng/ml. In patients with NSCLC, the sICAM-1 concentrations were significantly higher than in the normal control group (p=0.002). In addition, the difference in the serum concentrations was significant between the patients with T1 and T2 disease (p=0.042), and N0 and N2 patients (p=0.042). No significant differences were observed in aging, smoking history, histological type, or pathological staging. CONCLUSIONS The sICAM-1 concentrations in lung cancer patients are thus suggested to play a role in staging, and may also serve as a useful indicator of advanced disease.
Three major haplotypes of the β2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder

Adrenergic receptor β2 (ADRB2) is a primary target for epinephrine. It plays a critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with a complex array of psychological and physiological phenotypes. These genetic variants should also interact with environmental factors such as physical or emotional stress to produce a phenotype vulnerable to pathological states. In this study, we determined whether common genetic variants of ADRB2 contribute to the development of a common chronic pain condition that is associated with increased levels of psychological distress and low blood pressure, factors which are strongly influenced by the adrenergic system. We genotyped 202 female subjects and examined the relationships between three major ADRB2 haplotypes and psychological factors, resting blood pressure, and the risk of developing a chronic musculoskeletal pain condition—Temporomandibular Joint Disorder (TMD). We propose that the first haplotype codes for lower levels of ADRB2 expression, the second haplotype codes for higher ADRB2 expression, and the third haplotype codes for higher receptor expression and rapid agonist‐induced internalization. Individuals who carried one haplotype coding for high and one coding for low ADRB2 expression displayed the highest positive psychological traits, had higher levels of resting arterial pressure, and were about 10 times less likely to develop TMD. Thus, our data suggest that either positive or negative imbalances in ADRB2 function increase the vulnerability to chronic pain conditions such as TMD through different etiological pathways that imply the need for tailored treatment options. © 2006 Wiley‐Liss, Inc.
A spatial analysis of air pollution and environmental inequality in Beijing, 2000–2010

Whilst air pollution is a major problem in China, little is known about how it is distributed socially and how such distributions are changing over time. We use a fine-grained population census and air quality data for 2000 and 2010 to explore socio-spatial and temporal inequalities in air pollution for Beijing, using distributional analyses and spatial regression models. We find that environmental inequalities exist with respect to measures of social disadvantage, such as hukou migrant status, very young children (0–4 years), and the elderly (≥65 years). Our temporal analysis reveals that environmental inequality increases for migrants and the elderly, who bear a disproportionate and increasing share of declining air quality from 2000 to 2010. Regression results emphasise the spatial and temporal variations in environmental inequality, as the associations between air pollution and social demographics differ between different urban zones of Beijing; and their geographic patterns change significantly over time.
5‐HT3 receptors promote colonic inflammation via activation of substance P/neurokinin‐1 receptors in dextran sulphate sodium‐induced murine colitis

5‐HT (serotonin) regulates various physiological functions, both directly and via enteric neurons. The present study investigated the role of endogenous 5‐HT and 5‐HT3 receptors in the pathogenic mechanisms involved in colonic inflammation, especially in relation to substance P (SP) and the neurokinin‐1 (NK1) receptor.
Quantitative models for assessment of respiratory diseases

Experienced dynamic demographic growth of many cities, especially in the last three decades, has often resulted in a replacement of areas with vegetation and crops by industrial parks and residential areas, exposing areas to erosion. Mexicali, which is located in an arid region, is experiencing such transformations which are paralleled by a significant increase in respiratory diseases and allergies especially in children. In particular, adverse health effects of PM10 particles and asthma can be observed. The focus of this paper is to present a method for a quantitative assessment of patient health as it relates to respiratory disorders utilizing lung sounds. In order to accomplish this, applicable traditional techniques within the speech processing domain were utilized to evaluate lung sounds obtained with a digital stethoscope. Traditional methods utilized in the evaluation of asthma involve auscultation and spirometry, but utilization of more sensitive electronic stethoscopes, which are currently available, and application of quantitative signal analysis methods offer opportunities of improved diagnosis. In particular we propose acoustic evaluation methodology based on the Gaussian Mixed Models (GMM) which should assist in broader analysis, identification, and diagnosis of asthma based on the frequency domain analysis of wheezing and crackles.
Detection of Cell‐CAM 105 in the pericanalicular domain of the rat hepatocyte plasma membrane

Cell‐CAM 105 has been identified as a cell adhesion molecule based on the ability of anti‐cell‐CAM 105 monospecific Fab fragments to inhibit the reaggregation of rat hepatocytes. Because of its adhesive properties, it was expected that cell‐CAM 105 would be present on the lateral cell surface where adhesive interactions predominate. Paradoxically, however, immunofluorescence analysis of frozen sections of rat liver using specific monoclonal antibodies indicated that cell‐CAM 105 was present exclusively in the bile canalicular domain of the rat hepatocyte where there is no intercellular adhesion. To more precisely define the in situ localization of cell‐CAM 105, immunoperoxidase labeling and electron microscopy were used to examine intact and mechanically dissociated liver tissue. Results showed that when accessibility was provided by mechanical dissociation of perfusion fixed liver tissue, cell‐CAM 105 could be detected in the pericanalicular region of lateral membranes. In contrast, when hepatocytes were labeled after incubation in vitro under conditions used during adhesion assays to induce reaggregation, cell‐CAM 105 rapidly redistributed to all areas of the plasma membrane. Immunofluorescence analysis of primary hepatocyte cultures further revealed that cell‐CAM 105 and two other bile canalicular proteins relocalized to discrete domains reminiscent of bile canaliculi, whereas cell‐CAM 105 was also present in areas of intercellular contact. Serial section electron microscopy analysis of well‐defined, cross‐sectional profiles of bile canaliculi suggested the presence of cell‐CAM 105—positive membrane folds that extended along the length of the bile canalicular border. In sections from livers in which calcium‐dependent adhesive contacts had been disrupted by treatment with ethylenediamine tetraacetate, intact bile canaliculi were found that remained attached only by these border folds. The implications of these results are discussed with regard to a possible role for cell‐CAM 105 in bile canalicular formation. (HEPATOLOGY 1991; 13:47–56).