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pubmed_456_8563 | INTRODUCTION
The aim of this study was to investigate complication rates and types following allograft reconstruction and discuss unique considerations for management.
METHODS
Seventy-four consecutive patients underwent large segment allograft reconstruction following resection of primary musculoskeletal tumors from 1991 to 2016. Mean patient age was 32 ± 20 years (range, 5-71 years). Minimum follow-up was 2 years unless patients were lost to disease prior. Mean follow-up was 105 months.
RESULTS
Thirty-five patients had complications requiring subsequent surgery at a mean of 30 months (range, 1-146 months) post-operatively. Individual complication rates were 29%, 50%, and 42% for Allograft Prosthetic Composite, Intercalary, and Osteoarticular allograft reconstruction, respectively. Risk factors for complication included age less than 30 (OR 4.5; p = 0.002), male gender (OR 2.8; p = 0.031), chemotherapy (OR 4.4; p = 0.003), lower extremity disease (OR 3.4; p = 0.025). In patients with complications, limb-retention rate was 91% and mean MSTS scores were 23.6.
CONCLUSION
Despite considerable complication rates, management with a systematic approach results in successful outcomes with limb-retention greater than 90% and mean MSTS scores of 79%. In carefully selected patients, allografts provide a reliable method of reconstruction with treatable complications occurring at a mean of 30 months. | 10.1016/j.jor.2018.12.013 |
pubmed_937_18042 | This article summarizes the potential role of evolved brain emotional systems in the mediation of music appreciation. A variety of examples of how music may promote behavioral change are summarized, including effects on memory, mood, brain activity as well as autonomic responses such as the experience of 'chills'. Studies on animals (e.g. young chicks) indicate that musical stimulation have measurable effects on their behaviors and brain chemistries, especially increased brain norepinephrine (NE) turnover. The evolutionary sources of musical sensitivity are discussed, as well as the potential medical-therapeutic implications of this knowledge. | 10.1016/s0376-6357(02)00080-3 |
pubmed_351_20081 | The authors describe a technique for the gross examination of postmortem eyes of children who are suspected to have been the victims of deliberate trauma. By removing the anterior segment (cornea, iris, lens and pars plicata of the ciliary body) en bloc by a coronal incision through the pars plana just anterior to the ora serrata, the pathologist may view and photograph the fundus exactly as it would have been seen clinically. The photographs obtained with this technique correlate more closely with antemortem clinical examinations and photographs than conventional gross examination procedures and have been introduced as evidence in trials concerning the issue of retinal hemorrhages in injured children. The anterior segment and optic nerve are also examined to facilitate a comprehensive description of ocular findings. | 10.1016/0379-0738(92)90149-q |
pubmed_189_16234 | Crystalline KOH undergoes an antiferroelectric (AFE) proton ordering phase transition at low temperatures, which results in a monoclinic bilayer structure held together by a network of weak hydrogen bonds (HBs). The Curie temperature shifts up when the compound is deuterated, an effect that classical MD is not able to catch. For deeper insights into the transition mechanism, we carry out ab initio MD simulations of KOH and KOD crystals by including quantum effects on the nuclei through Feynman path integrals. The geometric isotope effect and the evolution of the lattice parameters with temperature agree with the experimental data, while the purely classical description is not appropriate. Our results show that deuteration strengthens the HBs in the low-T AFE ordered phase. The transition is characterized by the flipping of OH/OD groups along a bending mode. Above the transition, the system is driven into a dynamical disordered paraelectric phase. | 10.1021/acs.jpcc.1c06953 |
pubmed_733_9293 | This paper describes recent developments in the Stradx freehand 3D ultrasound system. Unlike other systems, Stradx works directly from the raw B-scans and their relative positions, without first resampling this unstructured data onto a regular voxel array. The paper discusses the many advantages of this unique approach, and presents new developments in the visualisation and quantitative analysis of freehand 3D ultrasound data, including novel volume rendering schemes and a robust method to compensate for the effects of varying probe pressure. | 10.1016/s0041-624x(02)00103-8 |
pubmed_143_5866 | : A 64-year-old man, whose medical history was significant only for locally advanced squamocellular carcinoma of the right palatine tonsil treated with extended neck radiotherapy 9 years before, was evaluated for traumatic cerebral haemorrhage secondary to syncope after a postural change. The selective angiographic study of cerebral vessels was negative. No heart arrhythmias were recorded at ECG monitoring. The 24-h ABPM revealed sudden pressor and depressor episodes during day-time and a reverse dipper pattern during night-time. Noninvasive autonomic nervous system function testing showed supine hypertension and orthostatic hypotension caused by afferent baroreflex failure. According to literature, even if only few cases are described, neck irradiation can be assumed to be the major cause of baroreflex failure. No treatment is currently approved. The patient was treated with a selective beta-blocker (bisoprolol) administered at bedtime. Repeated ABPM after 1 month of therapy showed absence of sudden pressor and depressor episodes and no dipper pattern during night-time. | 10.1097/HJH.0000000000002286 |
pubmed_146_18208 | The human glycoprotein hormone alpha-subunit (alphaGSU) gene is transcriptionally regulated by glucocorticoids in a cell type-specific fashion. In direct contrast to repression of alphaGSU by glucocorticoids in placenta, glucocorticoid receptor (GR) modulation in the pituitary is little understood. We show that glucocorticoids stimulate the alphaGSU promoter in immortalized pituitary gonadotrope-derived LbetaT2 cells, whereas estrogens, androgens, and progestins have no significant effect. Moreover, GR acts in a dose-dependent manner at physiological concentrations of glucocorticoids. Transient transfection of GR with dexamethasone (Dex) treatment further stimulates the alphaGSU promoter, but this induction is severely diminished using a receptor mutated in the DNA-binding domain. Truncation and cis mutations demonstrate that glucocorticoid response element 2 (GRE2) and cAMP-response element 2 (CRE2) within -168 bp of the human alphaGSU promoter are critical for induction. Moreover, dominant-negative CRE-binding protein markedly inhibits basal but also Dex induction of alphaGSU promoter activity. Additionally, GR specifically binds to GRE2 in the human alphaGSU promoter in vitro and to the 5' region of the endogenous mouse alphaGSU gene in vivo. Furthermore, overexpression of the homeobox factor, Distal-less 3 that regulates this gene in placental cells through a site partially overlapping GRE2, blocks Dex induction of alphaGSU in gonadotrope cells, indicating that placenta-specific expression of Dlx3 may interfere with GR, resulting in repression in placental cells vs. induction in gonadotrope cells. These results demonstrate the stimulatory role played by glucocorticoids in alphaGSU gene expression in the pituitary gonadotrope, in contrast to repression in placental cells, and highlight the tissue-specific nature of steroid hormone action. | 10.1210/en.2007-1100 |
others_384_8961 | The main objective of this research is to investigate the growth rates and CO2 sequestration potential of local and commercial strains of microalgae. Two local strains used were Chlorella Sorokiniana (UKM 2) and Characium sp. (UKM 1), both isolated from Palm Oil Mill Effluent (POME) and two commercial strains used were Chlorella Vulgaris and Ankistrodesmus sp.. The highest performance showed by C.Vulgaris where its growth rates was µm=0.47d-1 followed by Ankistrodesmus sp. µm=0.43d-1, C. sorokiniana µm=0.4d-1 and Characium spµm=0.37-1. Based on the yield, Ankistrodesmus sp. had highest yield which is 3g/L, followed by C.Vulgaris 2.72g/L, C.Sorokiniana 2.52g/L and Characium sp. 2.27g/L. CO2 sequestration rate was calculated based on the microalgae’s yield where Ankistrodesmus sp. showed highest CO2 sequestration, at 5.64g/L. © 2015, Journal of Pure and Applied Microbiology. All rights reser | others_384_8961 |
pubmed_1074_11990 | The glycoprotein P-selectin belongs to the selectin family of cell adhesion molecules. In this study, we cloned the full-length cDNA of P-selectin from zebrafish (Danio rerio) by the method of rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR). Zebrafish P-selectin cDNA is 2,800 bp and encodes a putative 868 amino acid protein with a theoretical molecular weight of 122.36 kDa and isoelectric point of 6.27. A signal peptide of 25 amino acids is predicted at the N-terminus of the putative protein. All structural domains involved in P-selectin function are conserved in the putative protein. The amino acid sequence of zebrafish P-selectin is 37% to 39% identical to that of mammalian P-selectins. Real-time quantitative PCR and whole-mount in situ hybridization analysis revealed that P-selectin was expressed in early embryonic development, the expression increased from 0.2 hpf (1-cell stage) to 72 hpf, and the expression significantly upregulated within 30 minutes of ADP induction. The results indicate that the structure of P-selectin protein is highly conserved among species and zebrafish P-selectin plays an important role in early embryonic development and probably has similar biological function to mammalian P-selectins. | 10.3390/ijms11114618 |
pubmed_983_19415 | In cycling, proper saddle height is important because it contributes to the mechanical work of the lower limb joints, thus altering pedaling efficiency. The appropriate method to select optimal saddle height is still unknown. This study was conducted to compare a static (anthropometric measurements) vs. a dynamic method (2D analysis) to adjust saddle height. Therefore, an examination of the relationship between saddle height, anthropometrics, pedaling angles, and hamstring flexibility was carried out. Saddle height outside of the recommended range (106-109% of inseam length) was observed in 56.5% of the subjects. Inappropriate knee flexion angles using the dynamic method were observed in 26% of subjects. The results of this study support the concept that adjusting saddle height to 106-109% of inseam length may not ensure an optimal knee flexion (30-40°). To solve these discrepancies, we applied a multiple linear regression to study the relationship between anthropometrics, pedaling angles, and saddle height. The results support the contention that saddle height, inseam length, and knee angle are highly related (R = 0.963, p < 0.001). We propose a novel equation that relates these factors to recommend an optimal saddle height (108.6-110.4% of inseam length). | 10.1519/JSC.0b013e318245c09d |
pubmed_265_10595 | PURPOSE
An extensive study was conducted to identify and enumerate staphylococcal microbiota found on ocular sites during asymptomatic soft contact lens (SCL) wear.
METHODS
A biochemical identification system separately grouped the eight clinically relevant staphylococci. Total counts and isolation frequencies from SCLs and ocular sites were evaluated.
RESULTS
The epidermidis group was the most numerous isolate from extended wear (EW) lenses; the capitis/warneri group was the most numerous (p < 0.05) from daily wear (DW) lenses. In both DW and EW, the greatest isolation frequency (p < 0.05) was recorded for the capitis/warneri group. The remaining six groups were isolated infrequently and in low numbers.
DISCUSSION
These results show that, in addition to Staphylococcus epidermidis, other staphylococcal species may be important members of the normal microbiota of the ocular surface during SCL wear. Furthermore, an increase and a shift in staphylococcal microbiota between DW and EW regimes was highlighted. | 10.1097/00006324-199804000-00022 |
pubmed_660_25350 | OBJECTIVE
To optimize the prescription dose of Mahuang decoction in a multi-target manner, in order to provide reference for the quantitative optimization of the prescription dose of the traditional Chinese medicine compound.
METHOD
The number of diaphoretic spots in rats, the tracheal antispasmodic rate in guinea pigs and the writhing times by acetic acid in mice were taken as the indexes for evaluating the diaphoretic, antispasmodic and analgesic effects. According to the experimental results of the 16 orthogonal combination prescriptions, a mathematical dose-effect model was built by support vector regression (SVR) and quadratic response surface regression (RSR) respectively. The multi-target optimization was achieved by elitist non-dominated sorting genetic algorithm (NSGA-II) and entropy weight TOPSIS method.
RESULT
The optimal dose of Mahuang decoction after being optimized by SVR modeling contained 17.71 g of Ephedrae Herba, 9.57 g of Cinnamomi Ramulus, 11.75 g of Armeniacae Semen Amarum and 4.39 g of Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle. The optimized result by RSR modeling contained 13.37 g of Ephedrae Herba, 11.61 g of Cinnamomi Ramulus, 11.98 g of Armeniacae Semen Amarum and 5.67 g of Glycyrrhizae Radix et Rhizoma Praeparate Cum Melle. SVR was superior to RSR in both of the forecast capacity and optimization results.
CONCLUSION
SVR-NSGA-II-TOPSIS method could be adopted for the multi-target optimization for the dose of Mahuang decoction and other traditional Chinese medicine compounds. It is proved to be the optimal prescription with the best efficacy, and could provide scientific quantitative basis for determining the dose of traditional Chinese medicine compound prescriptions and developing new traditional Chinese medicines. | pubmed_660_25350 |
others_342_5520 | Congenital heart disease (CHD) represents the most frequent developmental deformity in human beings and accounts for substantial morbidity and mortality worldwide. Accumulating investigations underscore the strong inherited basis of CHD, and pathogenic variations in >100 genes have been related to CHD. Nevertheless, the heritable defects underpinning CHD remain elusive in most cases, mainly because of the pronounced genetic heterogeneity. In this investigation, a four-generation family with CHD was recruited and clinically investigated. Via whole-exome sequencing and Sanger sequencing assays in selected family members, a heterozygous variation in the SMAD4 gene (coding for a transcription factor essential for cardiovascular morphogenesis), NM_005359.6: c.285T > A; p.(Tyr95*), was identified to be in co-segregation with autosomal-dominant CHD in the entire family. The truncating variation was not observed in 460 unrelated non-CHD volunteers employed as control subjects. Functional exploration by dual-reporter gene analysis demonstrated that Tyr95*-mutant SMAD4 lost transactivation of its two key downstream target genes NKX2.5 and ID2, which were both implicated with CHD. Additionally, the variation nullified the synergistic transcriptional activation between SMAD4 and GATA4, another transcription factor involved in CHD. These data strongly indicate SMAD4 may be associated with CHD and shed more light on the molecular pathogenesis underlying CHD, implying potential implications for antenatal precise prevention and prognostic risk stratification of the patients affected with CHD. © 2022 Elsevier Masson SAS | 10.1016/j.ejmg.2022.104677 |
pubmed_869_8564 | BACKGROUND AND OBJECTIVE
It has been proposed that genotypes reflective of polymorphisms in cytokine genes can predispose individuals to disease by enhancing inflammatory processes. The C/T polymorphism at position -889 of the IL1A gene influences interleukin-1alpha expression, with the T allele inducing higher expression. The aim of this study was to evaluate the association of the IL1A (-889) gene polymorphism in Brazilian individuals with different clinical forms of periodontitis and severity of disease.
MATERIAL AND METHODS
DNA was obtained from oral swabs of 163 Brazilian individuals and was amplified using the polymerase chain reaction (PCR). Products were submitted to digestion and were analyzed by electrophoresis to distinguish the C and T alleles.
RESULTS
A significant difference in the genotype distribution was observed when comparing the chronic periodontitis group with the control group, evaluating only nonsmokers (chi-squared analysis = 9.91; p = 0.007), as well as when smokers were included (chi-squared analysis = 6.36; p = 0.04). Moreover, we observed a higher incidence of the T allele in the chronic periodontitis group (37.8%) when compared with the control group (18.4%) in nonsmokers (p = 0.006, odds ratio = 2.69, confidence interval = 1.27-5.68) and also when smokers were included (p = 0.03, odds ratio = 1.87, confidence interval = 0.98-3.56). No statistical difference was observed when the aggressive periodontitis group was compared with the control group. With regard to severity of disease, no statistical difference was observed.
CONCLUSION
These data show an association of the IL1A (-889) polymorphism with chronic periodontitis in Brazilian individuals. | 10.1111/j.1600-0765.2006.00910.x |
pubmed_1015_14133 | The synthesis and structural characterization of a six-coordinate (carbonmonoxy)(porphyrin)iron(II), carbonyl(deuteroporphinato)(tetrahydrofuran)iron(II), is described. The choice of tetrahydrofuran as the sixth ligand represents one of the weakest field and weakest binding ligands possible and leads to stronger than usual bonding of CO to the heme. The Fe--C(CO) bond distance is 1.706 A, unusually short. The Fe--O(THF) bond distance in the low-spin complex is 2.127 A. The Fe--C--O and O--Fe--C groups are essentially linear with angles of 178.3 degrees and 177.4 degrees, respectively. The iron atom is displaced out of plane 0.10 A toward the tightly bound CO. The results suggest that the different CO stretching frequencies observed in myoglobin might result from modulating the bonding of the histidine trans to CO. Crystal data are as follows: a = 11.524 (3) A, b = 14.915 (5) A, c = 10.583 (2) A; alpha = 91.51 (2) degrees, beta = 108.99 (2) degrees, gamma = 102.86 (3) degrees; triclinic, space group P1, Z = 2; rho calcd = 1.363 g/cm3, rho obsd = 1.370 g/cm3. | 10.1021/bi00515a054 |
pubmed_288_6762 | Cyclodextrins (CyDs) were employed as protective stabilizers for the preparation of surfactant-free nanocrystals of indomethacin (IMC) by using the emulsion solvent diffusion method. The effect of changing the type and concentration of CyDs on the formation of IMC nanocrystals was investigated. Dispersions were freeze-dried to characterize the size, shape, nanoparticle yield, crystallinity, and dissolution behavior of the obtained particles. Submicron-sized particles of IMC with average diameters in the range of 300-500 nm were obtained by incorporating alpha-, beta-, or gamma-CyD in the outer phase of the primary emulsions. Quantitative determination demonstrated that more than 80% of IMC was recovered as fine particles smaller than 0.8 microm. The powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses of the freeze-dried samples confirmed the polymorphic change of IMC to the meta-stable form. A significant enhancement in the dissolution rate of IMC nanocrystals was observed when compared to the commercial powder. | 10.1016/j.ijpharm.2008.01.025 |
pubmed_152_11356 | A 43-year-old man with common variable immune deficiency underwent liver transplantation for cirrhosis caused by hepatitis C virus (HCV). HCV had been acquired from a contaminated batch of immunoglobulin. He developed cirrhosis within 3 years of infection with the virus, then liver failure requiring liver transplantation. The immediate post-transplant course was uncomplicated. Five months after transplantation he developed liver failure, and the histological appearances were those of severe cholestatic hepatitis. Withdrawal of immunosuppression resulted in recovery from liver failure. Clearance of the HCV from serum was also observed and has been sustained during follow-up (despite the subsequent reintroduction of low-dose immunosuppression). The patient is alive and well more than 5 years after transplantation. His post-transplant course has been remarkable for the aggressive recurrence then clearance of the HCV. | 10.1007/s00147-002-0420-2 |
pubmed_340_14514 | BACKGROUND
There is no obvious link between qualitative descriptors and overall intensity of dyspnea during bronchoconstriction in patients with asthma.
AIMS
To determine whether qualitative and quantitative perception of methacholine-induced bronchoconstriction independently contribute to characterizing clinically stable asthma.
MATERIAL AND METHODS
We assessed changes in inspiratory capacity, and quantitative (by Borg scale) and qualitative (by a panel of eight dyspnea descriptors) sensations of dyspnea at 20 to 30% fall in FEV(1) during methacholine inhalation in 49 asthmatics. Furthermore, we calculated the level of perception of bronchoconstriction at 20% fall in FEV(1) (PB(20)).
RESULTS
Descriptors selected by patients during methacholine inhalation allowed us to define three language subgroups: (1) chest tightness (subgroup A, n = 21); (2) work/effort (subgroup B, n = 7); and (3) both descriptors (subgroup C, n = 13). Eight of the 49 patients (subgroup D) were not able to make a clear-cut distinction among descriptors. The subgroups exhibited similar function at baseline and during methacholine inhalation. Most importantly, patients selected chest tightness to a greater extent (42.85%), and work/effort (14.3%) and both descriptors (26.5%) to a lesser extent at the lowest level of bronchoconstriction (FEV(1) fall < 10%) as at 20% fall in FEV(1). Thirty-two patients were normoperceivers (PB(20) > or = 1.4 to < 5 arbitrary units [au]), 7 patients were hyperperceivers (PB(20) > or = 5 au), and 10 patients were hypoperceivers (PB(20) < 1.4 au). Language subgroups were equally distributed across the perceiver subgroups.
CONCLUSIONS
In patients with clinically stable asthma, PB(20) and language of dyspnea independently contribute to defining the condition of the disease. However, the possibility that this independence may be due to a beta-error should be taken into account. | 10.1378/chest.130.2.436 |
pubmed_626_9771 | CONTEXT
The pituitary-adrenal ensemble of obese humans is marked by increased urinary excretion of cortisol and its metabolites in the face of normal circulating cortisol levels. For better understanding of the (patho) physiological meaning of these changes, the mechanistic underpinnings need to be clarified.
INTERVENTION AND METHODS
We investigated 17 obese women [body mass index (BMI) 30-39.4 kg/m(2)] and 14 normal women (BMI, 18.3-24.8 kg/m(2)) who underwent 24-h blood sampling at 10-min intervals, and plasma ACTH and cortisol concentrations were measured with sensitive assays. Data were analyzed with a new deconvolution program, approximate entropy (ApEn) analyses, and cosinor regression.
OUTCOME
ACTH and cortisol production rates were higher in obese women than in controls and correlated with BMI. Secretion of ACTH correlated with leptin (R = 0.63; P = 0.0001) and insulin (R = 0.67; P = 0.0001). ACTH ApEn and forward ACTH-cortisol cross-ApEn were diminished in obese women. The half-maximal effective concentration (ED(50)) of ACTH pulses vs. cortisol pulses was higher in obese women (38.3 +/- 4.9 vs. 25.1 +/- 3.7 ng/liter; P = 0.03), indicating decreased potency of ACTH. The diurnal properties of ACTH and cortisol secretion were unchanged in obese females.
CONCLUSION
Obese women exhibit enhanced ACTH and cortisol 24-h production compared with lean controls. The amplified ACTH drive is accompanied by decreased secretory regularity and diminished forward coupling between ACTH and cortisol. In addition, the potency of ACTH is decreased in obesity. | 10.1210/jc.2009-0350 |
others_121_375 | Purpose: The implementation of electron beam radiation coupled with the use of probiotics is one of the newest food processing technologies that may be used to ensure food safety and improve shelf life of food products. The purpose of this study was to evaluate the effect of 50–150-Gy electron beam irradiation on the antimicrobial activity of the putative probiotic strain Lactobacillus rhamnosus Vahe. Methods: Low-dose electron beam irradiation of lactobacilli cells was performed using the Advanced Research Electron Accelerator Laboratory’s electron accelerator, and the agar well diffusion method and Verhulst logistic function were used to evaluate the effect of radiation on anti–Klebsiella pneumoniae activity of the cell free supernatant of L. rhamnosus Vahe cells in vitro. Results: Our results suggest that 50–150-Gy electron beam irradiation decreases the viability of the investigated lactobacilli, but does not significantly change the probiotic’s activity against K. pneumoniae. Conclusions: Results indicate that the combined use of irradiation and L. rhamnosus Vahe might be suggested for non-thermal food sterilizing technologies. © 2019, The Author(s) | 10.1007/s13213-019-01522-2 |
pubmed_786_5801 | Vesicle affinity capillary electrophoresis (VCE), a newly developed technique, was designed to assess the effect of physicochemical properties of apolipoprotein (apo) on the binding to lipoproteins, under physiological conditions (phosphate-saline buffer system at pH 7.4 and 37 degrees C), using vesicle as a model. The technique results in similar lipid binding properties of apo CIII (CIII) and its peptides compared to other techniques. It also offers a fast and more sensitive tool in determining the lipid affinity of apos in a unique system simulating the dynamic binding properties of apo in vivo. A noncompetitive binding model is used to determine the multiple binding properties of CIII and its peptides to vesicle. The VCE binding constants are dependent on temperature, physicochemical properties of the protein (hydrophobicity and charge), and nature of the vesicle. The vesicles used in the VCE experiments described here have been fully characterized and found to be stable under different temperatures (4 and 37 degrees C) and voltage conditions. Migration behavior of CIII and related peptides is reported in terms of relative mobility in order to correct for variability in viscosity at different vesicle concentrations. The VCE method provides very precise data on the migration time from 0.1 to 3.3% RSD at the highest concentration of vesicle. The model and current data have been used to determine VCE binding constants and protein-to-lipid binding ratios. The model predicts that higher lipid affinity (K(B)), protein-lipid binding ratio (n), and lower protein concentration result in a shift of the binding isotherm toward a lower concentration range of vesicle. A higher vesicle mobility, reflecting the size and charge of the vesicle, results in a larger separation window between the migration time of the free protein and the complex. The value of VCE for structure-function studies and drug design for peptides and proteins that are strongly bound to lipids has been illustrated. | 10.1021/ac030085x |
pubmed_580_25133 | This study sought to evaluate platform-switched implants for immediate placement. A total of 136 implants were placed in 58 patients using either an immediate or delayed implant protocol. Bone level changes of the implants were measured mesially and distally and statistically analyzed with linear mixed models. No implant was lost. There was no significant difference between immediate and delayed implants in approximal bone level changes during the first year (95% confidence interval: -0.10 to -0.01 for immediate versus -0.14 to -0.07 for delayed implants). Subsequent bone resorption was negligible in both groups. | 10.11607/prd.1276 |
pubmed_433_3943 | The purpose of this research is to determine the efficiency of energy usage and its role in carbon dioxide emissions (CI) and economic-environmental efficiency (EEE) for some countries Organization for Economic Co-operation and Development (OECD) economies. For environment quality assessment, data envelopment analysis (DEA) is used to assess the data cover the period from 2013 to 2017. In this study, primary energy consumption (PEC) and population are two basic inputs along with gross domestic product (GDP) and carbon dioxide emissions that are desirable and undesirable outputs, respectively. The practical outcomes illustrate that Brunei, Australia, Singapore, and Hong Kong are the most effective and efficient states for the 5 years periods (2013-2017) in terms of energy efficiency and to reduce emission of carbon dioxide. In addition, other states in the OECD region shows greater economic proficiency than environmental proficiency. Furthermore, the results shows that energy efficiency has strong bonding with carbon emissions; however there is a weaker association between economic-environmental efficiency. Thus, the attainment of optimal level of energy efficiency could be more pivotal than economic efficiency to improve environmental efficiency in countries from the OECD region. | 10.1007/s11356-019-07020-x |
pubmed_718_15183 | The retroviral genome consists of two homologous RNA molecules associated close to their 5' ends. We studied the spontaneous dimerization of four HIV-1 RNA fragments (RNAs 1-707, 1-615, 311-612, and 311-415) containing the previously defined dimerization domain, and a RNA fragment (RNA 1-311) corresponding to the upstream sequences. Significant dimerization of all RNAs is observed on agarose gels when magnesium is included in the electrophoresis buffer. In contrast to dimerization of RNAs 311-612 and 311-415, dimerization of RNAs 1-707, 1-615 and 1-311 strongly depends on the size of the monovalent cation present in the incubation buffer. Also, dimerization of RNAs 1-707, 1-615, and 1-311 is 10 times faster than that of RNAs 311-612 and 311-415. The dimers formed by the latter RNAs are substantially more stable than that of RNA 1-615, while RNA 1-311 dimer is 5-7 degrees C less stable than RNA 1-615 dimer. These results indicate that dimerization of HIV-1 genomic RNA involves elements located upstream of the splice donor site (position 305), i.e. outside of the previously defined dimerization domain. | 10.1093/nar/22.2.145 |
pubmed_468_21790 | Growth factors are essential in cellular signaling for migration, proliferation, differentiation and maturation. Sustainable delivery of therapeutic as well as functional proteins is largely required in the pharmacological and regenerative medicine. Here we have prepared chitosan nanoparticles (CNP) and incorporated growth factors such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), either individually or in combination, which could ultimately be impregnated into engineered tissue construct. CNP was characterized by Fourier transform infrared (FTIR) spectroscopy, Zeta sizer and high resolution transmission electron microscope (HRTEM). The particles were in the size range of 50-100 nm with round and flat shape. The release kinetics of both EGF and FGF incorporated CNP showed the release of growth factors in a sustained manner. Growth factors incorporated nanoparticles did not show any toxicity against fibroblasts up to 4 mg/ml culture medium. Increased proliferation of fibroblasts in vitro evidenced the delivery of growth factors from CNP for cellular signaling. Western blotting results also revealed the poor inflammatory response showing less expression of proinflammatory cytokines such as IL-6 and TNFα in the macrophage cell line J774 A-1. | 10.1016/j.ijpharm.2011.02.065 |
pubmed_290_24627 | Cells of the adaptive and innate immune systems in the brain parenchyma and in the meningeal spaces contribute to physiologic functions and disease states in the central nervous system (CNS). Animal studies have demonstrated the involvement of immune constituents, along with major histocompatibility complex (MHC) molecules, in neural development and rare genetic disorders (e.g., colony stimulating factor 1 receptor [CSF1R] deficiency). Genome wide association studies suggest a comparable role of the immune system in humans. Although the CNS can be the target of primary autoimmune disorders, no current experimental model captures all of the features of the most common human disorder placed in this category, multiple sclerosis (MS). Such features include spontaneous onset, environmental contributions, and a recurrent/progressive disease course in a genetically predisposed host. Numerous therapeutic interventions related to antigen and cytokine specific therapies have demonstrated effectiveness in experimental autoimmune encephalomyelitis (EAE), the animal model used to define principles underlying immune-mediated mechanisms in MS. Despite the similarities in the two diseases, most treatments used to ameliorate EAE have failed to translate to the human disease. As directly demonstrated in animal models and implicated by correlative studies in humans, adaptive and innate immune constituents within the systemic compartment and resident in the CNS contribute to the disease course of neurodegenerative and neurobehavioral disorders. The expanding knowledge of the molecular properties of glial cells provides increasing insights into species related variables. These variables affect glial bidirectional interactions with the immune system as well as their own production of "immune molecules" that mediate tissue injury and repair. | 10.1002/glia.23746 |
pubmed_549_10395 | Multiple stable isotope analysis can be a powerful technique in forensic sciences. Oxygen and nitrogen isotopes were used to determine the source of nitrate that was responsible for the poisoning deaths of 71 wild horses in the Nevada desert. The nitrate was present in a water-filled hole known as 'the Main Lake depression.' Nitrate from the Main Lake depression had delta(18)O and delta(15)N values that were very positive (+32 per thousand, +37 per thousand), and Delta(17)O values of approximately +2 per thousand. The isotopic data suggested that the most probable source of the nitrate was nitrification of nitrogen from horse manure and urine that had leached into the pond. The delta(18)O signal suggested that extreme evaporative concentration had occurred, resulting in toxic levels of nitrate accumulating in the Main Lake depression. The study demonstrates the utility of the multiple stable isotope analysis approach for characterizing sources of nitrate. | 10.1016/j.forsciint.2010.01.012 |
pubmed_612_25350 | This study evaluated the antibacterial efficacy of methanolic extracts of isolated endophytic fungi from stem barks and leaves of Alstonia boonei De Wild and Greenwayodendron suaveolens (Engl. and Diels) Verdc. subsp. Suaveolens against Klebsiella pneumoniae ATCC 43816, Haemophilus influenzae ATCC 49247, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 35218, responsible for causing pneumonia. The endophytic fungi were isolated and characterized in the Potato Dextrose Agar (PDA), Sabouraud Dextrose Agar (SDA), and Czapek Dox Agar (CDA) media. The fungi and their methanolic extracts were tested for in vitro antibacterial potential by antagonistic assay for endophytic fungi against bacterial pathogens and microdilution method. The phytochemical screening of extracts was carried out according to the colorimetric and precipitation methods to reveal the presence of secondary metabolites. The results showed that 24 macroscopically and microscopically distinct endophytic fungi were isolated, identified, and stored. These endophytic fungi possessed antibacterial activity against the selected bacterial strains with inhibition zones ranging from 7.00 to 25.00 mm. The endophytic fungi GS15 and AB24 have presented the inhibitions zones of 20.33 mm and 25.00 mm, respectively, and these were better than the ones obtained for Levofloxacin®. The endophytes with inhibition zones greater than 10 mm were used for extraction of their secondary metabolites. The endophytic fungi extracts showed antibacterial activity with the minimum inhibitory concentrations (MICs) ranging from 6.25 × 10-4 to 2 × 10-2 g/L and the minimum bactericidal concentrations (MBCs) ranging from 2.5 × 10-3 to 2 × 10-2 g/L. The endophytic fungi GS15 extract was the most effective extract; it showed bactericidal effects on the tested bacterial strains. The phytochemical screening of the extracts revealed the presence of secondary metabolites classes, responsible for causing the obtained antibacterial activity. Thus, the endophytic fungi methanolic extracts from A. boonei and G. suaveolens have the potential to inhibit the growth of bacteria responsible for nosocomial pneumonia. | 10.1155/2021/9966323 |
pubmed_1091_10740 | BACKGROUND
Young people with attention deficit hyperactivity disorder (ADHD) often have learning and behavioral control difficulties.
AIM
The aim of this review is analyse the acute and chronic effect of physical activity (PA) on the cognition and behaviour of children and adolescents with ADHD.
METHODS
Studies were identified in five databases (PubMed, SPORTDiscus, ProQuest, Web of Science, and SCOPUS), from January 2000 through to January 2017. A total of 16 interventional studies met the inclusion criteria.
RESULTS/CONCLUSIONS
PA practice of 20-30 min (intensity 40-75%) produces a positive acute effect on processing speed, working memory, planning and problem solving in young people with ADHD. However, these effects on behaviour are contradictory and vary depending on age. Chronic PA practice (≥30 min per day, ≥40% intensity, ≥three days per week, ≥five weeks) further improves attention, inhibition, emotional control, behaviour and motor control. The results must be treated with caution, because only 25% of the studies used confounders.
IMPLICATION
More research is needed to justify the causes of these effects. It is necessary to establish programs with regard to the duration, intensity, kind of exercise, and time of PA to improve cognition and behaviour in young people with ADHD taking into account potential confounders. | 10.1016/j.ridd.2018.03.015 |
pubmed_826_14209 | The optimal management strategy for neonates with congenital aortic stenosis, two balanced ventricles, and duct-dependent systemic circulation (critical aortic stenosis) is still controversial. Thirteen patients with critical aortic stenosis underwent balloon aortic valvotomy (BAV) between 1996 and 2013, at the median age of 1 day old (range 0-28). Since 2010, bilateral pulmonary artery banding with ductal stenting following BAV was conducted for patients with reduced left ventricular (LV) function as a hybrid stage I palliation for the bridge to decision for further treatment. A follow-up was completed on all patients and the median follow-up period was 3.3 years (max 16.0). The overall survival rate at 15 years was 67.1 %. Six of the seven patients with maintained LV function could go on to the definitive Ross or Konno-aortic valve replacement at the median duration of 311 days after initial BAV, without any mortality. Three of four patients with reduced LV function died before 2010 with conventional treatment. With use of a hybrid stage I palliation, one of two patients ultimately underwent Fontan completion at 38 months of age and the other successfully underwent the definitive Ross-Konno operation at 9 months of age after recovery of the LV function. Although a statistically significant improvement has not been observed yet, the application of hybrid stage I palliation following BAV would be a favorable alternative for patients with reduced LV function to avoid a high-risk neonatal Ross or Norwood-type operation, and also to determine further treatment carefully. | 10.1007/s00246-014-1074-4 |
pubmed_635_4861 | In present study, a novel phospholipid complex loaded cucurbitacin B modified with berberine hydrochloride (CUB-PLC-BER) was prepared by a simple solvent evaporation method with the aim of improving bile duct-targeted drug delivery and therapeutic efficacy for cholangiocarcinoma (CC). The complex's physicochemical properties were systemically investigated in terms of scanning electron microscopy (SEM), x-ray diffraction (XRD) and infrared absorption spectroscopy (IR). In vivo and in vitro antitumor studies, CUB-PLC-BER and the unmodified cucurbitacin B-phospholipid complex (CUB-PLC) presented stronger antitumor efficacy against human cholangiocarcinoma cells (QBC939 cells) than free cucurbitacin B (CUB), while phospholipids (PL) itself had no significant toxicity. Besides that, CUB-PLC showed the advantage over the free CUB and CUB-PLC-BER with regard to the inhibition of tumor growth in vivo antitumor study. Failure to establish the orthotopic CC model, the study attempted to measure the level of CUB in plasma and in bile to explore bile duct-targeted effect indirectly. In the pharmacokinetics study in rats, the average values of Cmax and AUC0-8h of CUB-PLC-BER group in rat bile were higher than those of CUB-PLC, while an opposite result was found in plasma. Meanwhile, the Cmax, AUC0-8h and AUC0-24h of CUB were the least both in plasma and in bile. The results indicated that the CUB-PLC-BER tended to provide a high and prolonged drug concentration to bile duct, and PL played a central role in internalizing CUB into cells to improve the water insoluble drug's permeability, which was of great benefit to enhance the bioavailability of CUB and improve therapeutic efficacy of CC. These results elucidated the potential of CUB-PLC-BER as drug delivery system for improving bile duct-targeted and therapeutic efficacy for CC. | pubmed_635_4861 |
pubmed_528_7955 | The results of MCSS therapy for patients with severe heart failure are improving, and there are increasing numbers of implants as device therapy enters the era of permanent use (i.e., destination therapy). Device-related infection of implanted pumps and sepsis remain important risk factors for death, and once infections are established on biomaterial surfaces they usually persist despite prolonged antimicrobial therapy. This paper covers the topic of infection in mechanical circulatory support. Methods to prevent and manage infection are described. Recent information from the field of microbiology that is relevant to understanding device-related infection is reviewed, including the mechanisms for microbial adhesion to prosthetic surfaces, quorum sensing, and biofilm formation. Characteristics that are important to antimicrobial resistance of microbes dwelling in biofilms are described (e.g. responses to microenvironmental conditions that result in resistance to antibiotics). This information may lead to new therapies that further diminish rates of device infection, and allow complete eradication of infections when they occur. | 10.1177/039139880703000904 |
pubmed_522_4380 | OBJECTIVES
The anticryptococcal activity of chloroquine was assessed after incorporation in phosphatidylserine (PS)-containing negatively charged liposomes in a murine model.
METHODS
In the present study, we investigated the antifungal activity of chloroquine entrapped in PS liposomes against Cryptococcus neoformans in the macrophage cell line J 774 and in a murine model. Mice were treated with free as well as liposomal formulations of chloroquine before and after challenging with C. neoformans infection. The anticryptococcal activity of chloroquine was also evaluated in combination with fluconazole in the treatment of systemic murine cryptococcosis. The efficacy of chloroquine treatment was assessed by continued survival as well as by colony forming units (cfu) in liver and brain of treated mice.
RESULTS
Chloroquine entrapped in PS liposomes shows increased activity against C. neoformans infection both in in vitro and in vivo studies. Moreover, the antifungal activity of fluconazole increases when used in combination with liposomal chloroquine. Chloroquine in PS liposomes was found to be more effective in comparison with the same dose of free chloroquine or chloroquine entrapped in neutral liposomes.
CONCLUSIONS
The enhanced anticryptococcal activity of chloroquine in PS liposomes seems to be due to uptake of drug-containing PS liposomes by macrophages. It can be assumed that liposome-mediated delivery of chloroquine to macrophages results in an unfavourable (alkaline) environment for the growth of C. neoformans inside macrophages. | 10.1093/jac/dkh522 |
pubmed_908_11606 | This research addressed adults' health check-ups through the lens of Role Transportation Theory. This theory is applied to narrative advertising that lures adults into seeking health check-ups by causing audiences to empathize with the advertisement's character. This study explored the persuasive mechanism behind narrative advertising and reinforced the Protection Motivation Theory model. We added two key perturbation variables: optimistic bias and truth avoidance. To complete the verification hypothesis, we performed two experiments. In Experiment 1, we recruited 77 respondents online for testing. We used analyses of variance to verify the effectiveness of narrative and informative advertising. Then, in Experiment 2, we recruited 228 respondents to perform offline physical experiments and conducted a path analysis through structural equation modelling. The findings showed that narrative advertising positively impacted participants' disease prevention intentions. The use of Role Transportation Theory in advertising enables the audience to be emotionally connected with the character, which enhances persuasiveness. In Experiment 2, we found that the degree of role transference can interfere with optimistic bias, improve perceived health risk, and promote behavioral intentions for health check-ups. Furthermore, truth avoidance can interfere with perceived health risks, which, in turn, reduce behavioral intentions for health check-ups. | 10.1080/10410236.2018.1473706 |
pubmed_20_19446 | OBJECTIVE
To evaluate the accuracy and safety of pedicle screw insertion with the aid of novel patient-specific drill-guide templates in scoliosis cases.
METHODS
Ten patients with scoliosis were selected to participate in the research (the observation group) from December 2013 to December 2014. The data was obtained from CT scanning, and put into the computer to perform reconstruction of spine, simulation of pedicle screw insertion, and design of patient-specific drill-guide templates with software. The templates were made with rapid prototyping technique. After sterilization, the templates were used to aid the pedicle screw insertion intraoperatively. The blood loss, operation duration, change of creatinine level pre- and post-operation, and complications related to pedicle screw insertion were recorded. The location of pedicle screws were graded so as to evaluate the accuracy. A comparative study was then performed with the data of ten scoliosis cases operated with free-hand method during the same period (control group). There were 5 cases of idiopathic scoliosis and 5 cases of congenital scoliosis in the observation group, including 3 males and 7 females. Their average age was 11.9 years old (ranged, 4 to 18 years old), and the average Cobb angle of main curve was 54.9° (ranged, 42.1° to 78.4°). There were also 5 cases of idiopathic scoliosis and 5 cases of congenital scoliosis in the control group,including 2 males and 8 females. Their average age was 12.6 years old (ranged, 6 to 17 years old), and the average Cobb angle of main curve was 56.6° (ranged, 38.2° to 93.4°).
RESULTS
A total of 167 pedicle screws were inserted intraoperatively, with 138 screws (82.6%) in grade I, 26 screws (15.0%) in grade II, 4 screws in grade III (2.4%), but no screws in grade IV according to the CT image. There were 29 (17.4%) screws perforated, and 163 (97.6%) screws could be accepted. In the control group, a total of 165 pedicle screws were inserted intraoperatively, with 98 screws (59.4%) in grade I, 39 screws (23.6%) in grade II, 21 screws in grade III (12.7%), and 7 screws in grade IV (4.2%). There were 67 (40.6%) screws perforated, and 137 (83.0%) screws could be accepted. The grade distribution of screw position, ratio of perforated and accepted screws were significantly different between the two groups respectively (Z=-5.013, P=0.000; χ2=9.347, P=0.002; χ2=20.242, P=0.000). The correction rate of Cobb angle were (74.1±10.0)% vs (69.7±17.6)%; blood loss were (455±447) ml vs (415±389) ml; operation duration were (163.5±53.7) min vs (164.0±48.7) min; and the changes of creatinine level pre- and post-operatively were (-5.3±3.2) μmol/L vs (-3.4±3.1) μmol/L; all above data had no significant differences respectively (t=0.696, P=0.496; t=0.214, P=0.833; t=0.022, P=0.983; t=1.375, P=0.192). There were no complications related to pedicle screw insertion in each group.
CONCLUSION
The novel patient-specific drill guide template can be used to assist the insertion of pedicle screws in scoliosis cases with much higher accuracy than that of freehand method and fair safety. | pubmed_20_19446 |
pubmed_381_25006 | BACKGROUND
There is a high carrying rate of α-thalassemia in Fujian province. However, there are few large-scale studies on the correlation between genotype and phenotype in Fujian province. The purpose of this study was to analyze the phenotype and genotype in a cohort of 2923 patients with α-thalassemia in Fujian province, so as to provide reference data for screening and diagnosis of α-thalassemia in Fujian province.
METHODS
The genotype of α-thalassemia was detected by PCR reverse dot blot assay, gap-PCR, single PCR, nested PCR, and sequencing. Clinical and hematological indices of 2923 patients were collected, and the correlation between genotype and phenotype was analyzed.
RESULTS
Among 10,350 patients, 2923 cases were found with α-thalassemia, with a detection rate of 28.24%. Among them, --SEA /αα was the most common genotype, accounting for 64.80%. In addition, rare α-thalassemia genotypes were detected in Fujian province, including --THAI /αα (0.41%), HKαα/--SEA (0.03%), and the novel α-thalassemia gene mutation CD5 (GCC>ACC) (HGVS named HBA1: c.16G>A) (0.03%). Patients with deletional genotypes of α-thalassemia were found to have higher RBC and lower Hb, MCV, MCH, and HbA2 than patients with non-deletional genotypes of α-thalassemia (p < 0.05).
CONCLUSION
The clinical phenotype of α-thalassemia is influenced by molecular mechanisms. HBA1: c.16G>A mutation is a novel mutation that was first reported in Fujian province, which enriches the human hemoglobin mutation spectrum. | 10.1002/jcla.24696 |
pubmed_752_17725 | WHAT IS KNOWN AND OBJECTIVE
Pain is a prevalent, and due to the ageing population, increasing medical problem. Opioids are frequently prescribed to meet the unmet medical need. Unfortunately, with the increase in the legitimate use of opioids, there has been a corresponding increase in abuse. A practical way to retain the pain relief afforded by opioids while decreasing opportunities for abuse is to make it more difficult to extract the opioid from the product or to make it less desirable to do so by designing an abuse-deterrent formulation (ADF). We provide a brief overview of the strategies and early evidence related to opioid ADFs.
METHODS
Published and unpublished literature, websites, and other sources were searched for current opioid formulation options, including immediate-release and extended-release products. Each was summarized, reviewed and assessed.
RESULTS
The strategies that have been used to design the current opioid ADFs involve one or more of four approaches: a physical barrier; incorporation of an opioid receptor antagonist (e.g. naloxone) that self-limits opioid action when taken in excess amount; inclusion of a noxious agent that is released during inappropriate use; or a pro-drug.
WHAT IS NEW AND CONCLUSIONS
Legitimate use of opioid analgesics carries with it certain risks, including the risk of abuse. The new ADFs utilize four major strategies and provide innovative additions to the armamentarium. They likely will become an important part of a comprehensive approach to limiting, although not eliminating, opioid misuse and abuse. | 10.1111/jcpt.12337 |
pubmed_468_17542 | BACKGROUND
The aim of this study was to investigate if immunohistochemical expression and mutational status of KIT and PDGFRA in GISTs are associated with the clinical course and disease-free survival after curative resection of the primary tumor without adjuvant systemic therapy.
METHODS
Paraffin-embedded tumor sections of 95 GISTs were analyzed for KIT and PDGFRA expression by immunohistochemistry. PDGFRA expression was judged using a scoring system subdividing tumors in negative/weak and strong immunoreactivity groups. For mutation analysis, exons 9, 10, 11, 13, and 17 of KIT and exons 10, 12, 14, and 18 of PDGFRA were sequenced.
RESULTS
Of 95 R0-resected GISTs, 69% showed strong PDGFRA immunoreactivity. Gastric GISTs revealed a significantly higher rate of strong PDGFRA immunoreactivity (P = 0.01) and longer DFS (P = 0.015) than GISTs of the small intestine. KIT mutations were detected in 43 of 63 (68.3%) completely sequenced cases while PDGFRA mutations were identified in 6 cases (10%). In multivariate analysis, neither KIT/PDGFRA expression nor mutational status of KIT or PDGFRA were independent prognostic factors. Only mitotic rate predicted recurrence independently.
CONCLUSION
Our data do not support the notion that expression of PDGFRA or mutations in KIT or PDGFRA are independent prognostic factors after curative resection of primary GIST. | 10.1002/jso.21905 |
pubmed_1093_23716 | Multiple sclerosis (MS) is a degenerative autoimmune disease of the CNS. Experimental autoimmune encephalomyelitis (EAE) is a commonly used murine model for MS. Here we report that CD137 ligand (CD137L, 4-1BB ligand, TNFS9), a member of the TNF superfamily, is critical for the development of EAE. EAE symptoms were significantly ameliorated in CD137L(-/-) mice. In the absence of CD137L, myelin oligodendrocyte glycoprotein (MOG)-specific T-cells secreted lower levels of T(h)1/T(h)17 cell-associated cytokines. MOG-specific T-cells also trafficked less efficiently to the CNS in CD137L(-/-) mice, possibly as a consequence of reduced expression of vascular cell adhesion molecule-1 (VCAM-1), which regulates leukocyte extravasation. Thus, CD137L regulates many functions of MOG-specific T-cells that contribute to EAE and may represent a novel therapeutic target for the treatment of MS. | 10.1523/JNEUROSCI.2473-12.2012 |
pubmed_85_25344 | The effective defense against parasite infections requires the ability to mount an appropriate and controlled specific immune response able to eradicate the invading pathogen while limiting the collateral damage to self-tissues. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. Ligation of dendritic cell pattern recognition receptors by pathogen-associated molecular pattern present in the parasites initiates signaling pathways that lead to the production of surface and secreted proteins that are required, together with the antigen, to induce an appropriate and timely regulated immune response. There is evidence showing that parasites can influence and regulate dendritic cell functions in order to promote a more permissive environment for their survival. In this review, we will focus on new insights about the ability of protozoan and helminth parasites or their products to modify dendritic cell function and discuss how this interaction is crucial in shaping the host response. | 10.1007/s00281-016-0588-7 |
others_115_5257 | When covered by a layer of soil, seedling development follows a dark-specific program (skotomorphogenesis). In the dark, seedlings consist of small, non-green cotyledons, a long hypocotyl, and an apical hook to protect meristematic cells. We recently highlighted the role played by mitochondria in the high energy-consuming reprogramming of Arabidopsis skotomorphogenesis. Here, the role played by plastids, another energy-supplying organelle, in skotomorphogenesis is investigated. This study was conducted in dark conditions to exclude light signals so as to better focus on those produced by plastids. It was found that limitation of plastid gene expression (PGE) induced an exaggerated apical hook bending. Inhibition of PGE was obtained at the levels of transcription and translation using the antibiotics rifampicin (RIF) and spectinomycin, respectively, as well as plastid RPOTp RNA polymerase mutants. RIF-treated seedlings also showed expression induction of marker nuclear genes for mitochondrial stress, perturbation of mitochondrial metabolism, increased ROS levels, and an augmented capacity of oxygen consumption by mitochondrial alternative oxidases (AOXs). AOXs act to prevent overreduction of the mitochondrial electron transport chain. Previously, we reported that AOX1A, the main AOX isoform, is a key component in the developmental response to mitochondrial respiration deficiency. In this work, we suggest the involvement of AOX1A in the response to PGE dysfunction and propose the importance of signaling between plastids and mitochondria. Finally, it was found that seedling architecture reprogramming in response to RIF was independent of canonical organelle retrograde pathways and the ethylene signaling pathway. © 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons L | 10.1111/tpj.16134 |
pubmed_118_24235 | Trichobezoars are hairballs or hair-like fibers formed by chewing and swallowing hair or any other indigestible materials. Trichobezoars usually form in the gastric body and are thus prepyloric. However, trichobezoars may rarely pass through the pylorus into the duodenum, jejunum, ileum, and even the colon, in a condition referred to as Rapunzel syndrome. Here, we present a case of a 13-year-old girl with this rare syndrome and discuss the diagnosis and treatment of the disease. | 10.1177/2058460115627660 |
pubmed_204_13162 | BACKGROUND
Integration of mental health and psychosocial support (MHPSS) into primary health care in the Gaza Strip involves the delivery of mental health services within the essential service package provided by UNRWA, as recommended by WHO to fill the treatment gap. In early 2016, a successful pilot demonstrated that the integration is achievable in limited resource settings, and resulted in the adoption of a stepped care model to screen, identify, support, and treat patients. This study aimed to evaluate the MHPSS integration process and outcomes at UNRWA health centres in the Gaza Strip.
METHODS
We used a descriptive analytical study design, with quantitative and qualitative data collected from records, and individual feedback from patients and health care providers (HCPs). The study was performed in the 22 UNRWA health centres of the Gaza Strip and all participants agreed to participate either verbally or by written consent. Approval was also obtained from the UNRWA Health Program Gaza Field Office.
FINDINGS
The integration process started with the comprehensive training of 460 medical and nursing HCPs, in accordance with the Mental Health Gap Action Programme (mhGAP) Intervention Guide. On completion of training, the HCPs put into practice their learning, under close supervision for the first month and with only technical support thereafter. During the period of technical support, MHPSS activities, referral pathways, and proper reporting were ensured and standardised in all health centres. Overall, the integration process achieved success in training, implementation, and supervision. The success of training was assessed with an evaluation form and participants' feedback, the success of implementation by the numbers of people who benefitted, their response to the intervention, and their feedback, and the success of supervision by the standardisation of the process and the technical validity of the intervention. By the end of September, 2018, 80 857 high-risk patients were screened using the General Health Questionnaire 12 (GHQ-12) and 9·0% (7327) were identified as requiring intervention and support, and were assisted using the UNRWA stepped care approach. Of the individuals who were assisted, 30·2% (2212 of 7327) showed significant improvement and 38·9% (2849) were identified as having mental health issues according to the mhGAP. In the same period, 1020 patients benefited from 113 support groups, with excellent effects on their physical and mental health as assessed with qualitative data, patients' testimonies and, in some cases, laboratory investigations. The challenges that were faced were due to manual documentation and reporting, sociopolitical uncertainty, an increase in the number and needs of patients, and the imposed burden on HCPs. In addition, during implementation many individuals who were screened and identified required an urgent response: individuals who were suicidal and individuals whose mental health had been affected by the Great March of Return.
INTERPRETATION
The integration showed remarkable success in a short time as a result of the collective effort of all participants. However, there are challenges to overcome, and observation, further evaluation, and refinement of the process are needed to stabilise and sustain the integration of MHPSS services into primary health care for maximum benefit.
FUNDING
WHO, and UNRWA resources. | 10.1016/S0140-6736(21)01537-3 |
pubmed_909_18543 | Application of benzyladenine to dry pea seed delayed the production of amylase and the concomitant breakdown of starch. The utilization of nitrogenous reserve food material was also delayed. Shoot growth was correlated with breakdown of reserve food.Benzyladenine given to one of the cotyledons did not affect the senescence of the other. Cotyledonary axillary shoots were released from apical dominance, but only those originating from the benzyladenine treated cotyledon continued to develop. The pattern of growth initiated by benzyladenine was not altered by gibberellic acid although this substance caused increased elongation of all growing shoots. | 10.1007/BF00385517 |
others_331_16814 | A bacterium, Klebsiella pneumoniae CBL-1, was isolated from heavy metal laden industrial wastewater and could tolerate Cd2+ (1500?g/mL), Cr 6+ (800?g/mL), Cu 2+ (600?g/mL), Pb 2+ (700?g/mL), Zn 2+ (800?g/mL) and Ni 2+ (1000?g/mL). K. pneumoniae showed optimum growth at 30°C and pH at 7. K. pneumoniae could decrease 46%, 68%, 83% and 93% of cadmium (100?g/mL) from the medium after 24, 48, 72 and 96 hours, respectively. K. pneumoniae was also capable to remove 54% and 82% cadmium from the industrial effluents after 4 and 8 days of incubation at room temperature. Multiple metal tolerance and high Cd accumulation by K. pneumoniae indicates its potential application in biological treatment of wastewaters contaminated with heavy metals. © 2012 Zoological Society of Pakis | others_331_16814 |
pubmed_917_13231 | Long-chain fatty acyl-CoA esters (LCFACoAE) were extracted from freeze-clamped powdered brown adipose tissue (BAT) obtained from thermoneutral control and cold-acclimated hamsters and the CoA esters individually separated by high-performance liquid chromatography. LCFACoAE of carbon chain length C12 to C20 were identified by increasing column retention time in the following order: C12:0, C14:1, C14:0, C16:1, C18:2, C16:0, C18:1, C18:0, and C20:4. The mean total LCFACoAE concentrations were 235 +/- 40 nmol/g protein for the control hamsters and 648 +/- 105 nmol/g protein for the 22-day cold-acclimated hamsters. A rapid fourfold increase in the levels of C16:0, C18:0, and C18:1 occurred within hours after initiation of the cold temperature, whereas the concentrations of the other six LCFACoAE either increased only slightly or remained unchanged. Almost 50% of the total LCFACoAE in the BAT of cold-acclimated hamsters was made up of C16:0, C18:0, and C18:1. These results, which demonstrate some dynamic changes in adipose tissue LCFACoAE, are consistent with their proposed role in the initiation and maintenance of BAT thermogenesis. | 10.1152/ajpendo.1988.254.2.E181 |
pubmed_912_6406 | Many aging male suffer various andropause symptoms including loss of physical and mental activities. This study evaluated the putative alleviative effects of CRS-10 dandelion and rooibos extract complex (CRS-10) on the symptoms of andropause. The survival rate of TM3 Leydig cells (TM3 cells) treated with CRS-10 was measured based on typical physiological stress. After daily intake of CRS-10 for 4 weeks, the level of testosterone, physical activity and both the number and activity of sperm in older rats (18 weeks) were measured. Furthermore, thirty males were surveyed with AMS (Aging Males' Symptoms) questionnaire after intake of 400 mg of CRS-10. Overall, CRS-10 protected TM3 cells from serum restriction and oxidative stress via activation of ERK and Akt pathways. The level of testosterone and activation of spermatogenesis in rats were significantly enhanced. In addition, physical locomotion was markedly improved. Daily intake of 400 mg of CRS-10 improved the quality of life among agingmale respondents, according to a clinical survey using the AMS. The results indicate the potential of CRS-10 as a safe and efficacious natural substance for reducing or alleviating andropause symptoms. | 10.4162/nrp.2012.6.6.505 |
pubmed_482_20999 | OBJECTIVE
Patients with depression frequently experience persistent residual symptoms even with optimal interventions. These patients often use complementary treatments, including yoga, as a preferred alternative or adjunctive treatment. There is evidence for the benefit of yoga for depression, but this has not been rigorously evaluated, particularly in bipolar depression. We aimed to determine the feasibility and benefit of manualized breathing-focused yoga in comparison to psychoeducation as augmentation to pharmacotherapy for improving residual symptoms of depression in unipolar and bipolar patients.
METHODS
Using a randomized single-blind crossover design, 72 outpatients with unipolar or bipolar depression were augmented with the two 8-week interventions at separate times, as add-ons to current first-line antidepressants and mood stabilizers. The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). Due to the high dropout of participants after crossover at Week 8, analysis focused on between-group comparisons of yoga and psychoeducation during the initial 8 weeks of the study.
RESULTS
There was a significant decline in depressive symptoms, as measured by the MADRS, following 8 weeks of yoga. However, there was no significant difference in MADRS ratings between intervention groups. Similar improvements in self-rated depressive symptoms and well-being were also observed across time.
CONCLUSIONS
Both yoga and psychoeducation may improve residual symptoms of unipolar and bipolar depression as add-on to medications. In-class group sessions and long study durations may reduce feasibility for this population. Larger trials with parallel group design and shorter duration may be more feasible. | 10.1177/0706743720940535 |
pubmed_152_4056 | Many companies are now prioritizing the development of dry powder inhalers (DPIs) above pressurized formulations of asthma drugs. A well-designed DPI and an appropriate powder formulation can optimize the effectiveness of inhaled drug therapy. A DPI must be able to deliver medications effectively for most patients, and an ideal inhaler would provide a dose that does not vary with inspiratory flow rate. Recent regulatory guidelines, among which the U.S. FDA draft guidance is the most stringent, demand consistent dose delivery from an inhaler throughout its life and consistency of doses from one inhaler to another. However, the properties of free micronized powders often interfere with drug handling and with drug delivery reducing dose consistency. Recent advances in formulation technology can increase lung dose and reduce its variability. While a perfect DPI may never exist, both device and formulation technology are evolving to rectify perceived deficiencies in earlier systems. | 10.1053/rmed.2001.1276 |
pubmed_321_13791 | Primary percutaneous coronary interventions (PCI) have been developed to improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). In primary PCI, the door-to-balloon time (DTBT) is closely associated with mortality and morbidity. The purpose of this study was to find determinants of short and long DTBT. From our hospital record, we included 214 STEMI patients, and divided into the short DTBT group (DTBT < 60 min, n = 60), the intermediate DTBT group (60 min ≤ DTBT ≤ 120 min, n = 121) and the long DTBT group (DTBT > 120 min, n = 33). In-hospital mortality was highest in the long DTBT group (24.2%), followed by the intermediate DTBT group (5.8%), and lowest in the short DTBT group (0%) (< 0.001). Transfers from local clinics or hospitals (OR 3.43, 95% CI 1.72-6.83, P < 0.001) were significantly associated with short DTBT, whereas Killip class 3 or 4 (vs. Killip class 1 or 2: OR 0.20, 95% CI 0.06-0.64, P = 0.007) was inversely associated with short DTBT in multivariate analysis. In conclusion, transfer from local clinics/hospitals was associated with short DTBT. Our results may suggest the current limitation of ambulance system, which does not include pre-hospital ECG system, in Japan. The development of pre-hospital ECG system would be needed for better management in STEMI. | 10.1007/s00380-017-1089-x |
pubmed_723_2281 | Evidence accumulated over the past decade provides support for liquid-liquid phase separation as the mechanism underlying the formation of biomolecular condensates, which include not only 'membraneless' organelles such as nucleoli and RNA granules, but additional assemblies involved in transcription, translation and signaling. Understanding the molecular mechanisms of condensate function requires knowledge of the structures of their constituents. Current knowledge suggests that structures formed via multivalent domain-motif interactions remain largely unchanged within condensates. Two different viewpoints exist regarding structures of disordered low-complexity domains within condensates; one argues that low-complexity domains remain largely disordered in condensates and their multivalency is encoded in short motifs called 'stickers', while the other argues that the sequences form cross-β structures resembling amyloid fibrils. We review these viewpoints and highlight outstanding questions that will inform structure-function relationships for biomolecular condensates. | 10.1016/j.sbi.2019.09.007 |
pubmed_269_1140 | Background
The United Nations defines violence against women as "any act of gender-based violence that results in, or is likely to result in, physical, sexual or mental harm or suffering to women, including threats of such acts, coercion or arbitrary deprivation of liberty, whether occurring in public or in private life".[1] Violence can take many forms, including physical, sexual or emotional and varies in its severity. Gender discrimination, norms and practices mean that adolescent girls are likely to experience certain forms of violence, such as sexual violence, at much higher rates than boys.
Methods
This cross-sectional study was conducted in a rural block of North India. A total of 500 adolescent girls in the age group of 13-19 years studying in class VIII to class XII in 10 government and private senior secondary schools of the Lakhanmajra block were included in the study. A pre-designed pre-tested semi-structured interview schedule was used.
Results
In this study, we found the prevalence of physical, sexual and emotional violence among adolescent girls as 6.6, 5.4 and 5.2%, respectively. The most frequent perpetrator of physical violence was the parent and of sexual violence was the neighbour followed by friends or relatives. Higher emotional violence was experienced by adolescent girls from middle-class families (P < 0.05). The prevalence of physical violence among adolescent girls was maximum in the younger age group 13-14 years (10.2%), followed by 15-17 years (4.0%). This association was found statistically significant (P < 0.05).
Conclusions
There are several restrictions on free communication about violence-related topics in our highly conservative society. Blaming the victim is the rule rather than the exception and sexual abuse is usually linked to a loss of virginity and family honour in our patriarchal society. Hence, girls may be more reluctant to disclose their experience of violence. | 10.4103/jfmpc.jfmpc_533_21 |
pubmed_845_22284 | Airway management during cardiac arrest has undergone several advancements. Endotracheal intubation (ETI) often is considered the gold standard for airway management in cardiac arrest; however, other options exist. Recent prospective randomized trials have compared outcomes in bag-valve mask ventilation and supraglottic airways to ETI in out-of-hospital cardiac arrest. ETI, if performed early in resuscitation, is associated with worse patient outcomes and has been de-emphasized so as not to interfere with other aspects of the resuscitation. Hyperventilation has multiple theoretic harms during cardiac arrest, and methods, such as compression-adjusted ventilation, may be utilized to help reduce the incidence of hyperventilation. | 10.1016/j.ccc.2020.07.008 |
pubmed_608_10038 | INTRODUCTION
The previous studies suggested an association between osteoporosis and sudden sensory neural hearing loss (SSNHL). The aim of the present study was to evaluate the association between osteoporosis and benign paroxysmal positional vertigo (BPPV).
MATERIALS AND METHODS
Data from the Korean National Health Insurance Service-National Sample Cohort of participants who were ≥ 50 years old were collected from 2002 to 2013. A total of 13,484 BPPV participants were matched with respect to age group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia to 53,936 controls. In both the BPPV and control groups, the previous histories of osteoporosis were evaluated. Crude (simple) and adjusted odds ratios (ORs) of osteoporosis for BPPV were analyzed using unconditional logistic regression analyses. Subgroup analyses were conducted according to age, sex, and BPPV frequency.
RESULTS
A total of 18.64% (2514/13,464) of the BPPV group and 12.21% (6589/53,936) of the control group had a history of osteoporosis (P < 0.001). The adjusted OR of osteoporosis for BPPV was 1.29 (95% CI = 1.23-1.35, P < 0.001). In the subgroup analysis according to age and sex, the ≥ 70-year-old men did not demonstrate a high adjusted OR of osteoporosis for BPPV. All other age and sex subgroups demonstrated high adjusted ORs of osteoporosis for BPPV.
CONCLUSIONS
Osteoporosis increased the risk of BPPV in the population aged ≥ 50 years. The OR of osteoporosis was higher in the frequent BPPV group than in the less frequent BPPV group. | 10.1007/s00405-018-5230-y |
pubmed_896_9652 | Whilst research has largely focused on the recognition of emotional items, emotion may be a more subtle part of our surroundings and conveyed by context rather than by items. Using ERPs, we investigated which effects an arousing context during encoding may have for item-context binding and subsequent familiarity-based and recollection-based item-memory. It has been suggested that arousal could facilitate item-context bindings and by this enhance the contribution of recollection to subsequent memory judgements. Alternatively, arousal could shift attention onto central features of a scene and by this foster unitisation during encoding. This could boost the contribution of familiarity to remembering. Participants learnt neutral objects paired with ecologically highly valid emotional faces whose names later served as neutral cues during an immediate and delayed test phase. Participants identified objects faster when they had originally been studied together with emotional context faces. Items with both neutral and emotional context elicited an early frontal ERP old/new difference (200-400 ms). Neither the neurophysiological correlate for familiarity nor recollection were specific to emotionality. For the ERP correlate of recollection, we found an interaction between stimulus type and day, suggesting that this measure decreased to a larger extend on Day 2 compared with Day 1. However, we did not find direct evidence for delayed forgetting of items encoded in emotional contexts at Day 2. Emotion at encoding might make retrieval of items with emotional context more readily accessible, but we found no significant evidence that emotional context either facilitated familiarity-based or recollection-based item-memory after a delay of 24 h. | 10.3758/s13415-021-00944-3 |
pubmed_527_8121 | Cyclin-dependent kinase 5 (Cdk5) is activated by binding to its activators, p35 and p39. The level of Cdk5 activity is determined by the amount of p35 and p39, which is regulated not only by transcription but also via proteasomal degradation. Alternatively, calpain-induced cleavage of p35 to p25 can induce aberrant Cdk5 activation. As the regulation of p35 and p39 proteolysis is not well understood, we have studied here the mechanisms governing their degradation and cleavage. We find that p35 and p39 undergo proteasomal degradation in neurons, with p39 showing a slower degradation rate than p35. Degradation of the activators is dependent on their respective N-terminal p10 region, as indicated by experiments in which cognate p10 regions were swapped between p35 and p39. The effect of the p10 region on degradation and cleavage could be assigned to its membrane binding properties, mediated predominantly by myristoylation. Together, these results indicate that both proteasomal degradation and calpain cleavage of p35 and p39 are stimulated by membrane association, which is in turn mediated via myristoylation of their p10 regions. However, p35 and p39 show differences in degradation and cleavage rates, which may in fact underlie the distinct physiological and pathological functions of these two Cdk5 activators. | 10.1021/bi100631f |
pubmed_4_532 | Two new Ru(II) polypyridyl complexes containing fluorine substituents, [Ru(bpy)2(o-fpip)]2+ (Ru1, bpy=2,2'-bipyridine, o-fpip=2-(2-fluorophenyl)imidazo[4,5-f] [1,10]phenanthroline) and [Ru(bpy)2(p-fpip)]2+ (Ru2, p-fpip=2-(4-fluorophenyl)imidazo[4,5-f] [1,10]phenanthroline) have been synthesized as binders for poly(U)•poly(A)∗poly(U) triplex RNA. The binding of the two complexes with the triplex RNA has been investigated by spectroscopic methods and viscosity measurements. Analysis of the electronic absorption spectra indicates that the association of intercalating Ru2 with the triplex RNA is greater than that of Ru1, which is also supported by spectroscopic titrations and viscosity measurements. Thermal denaturation studies reflect that third-strand stabilization depend on the nature of the two complexes and Ru2 is more effective for stabilization of the triplex RNA. Circular dichroism spectra of the triplex RNA in the presence of metal complexes indicate that the binding-induced CD perturbation of the triplex structure is more obvious by Ru2. The main results obtained here suggest that the positions of fluorine substituent in the intercalating ligands have a significant effect on the two complexes stabilizing the third strand. | 10.1016/j.jinorgbio.2017.08.004 |
pubmed_325_10269 | OBJECTIVE
To assess the impact of simulation training on complications associated with femoral arterial access obtained by first year cardiology fellows.
BACKGROUND
Prior studies demonstrate a higher incidence of arterial access related complications among patients undergoing invasive cardiac procedures.
METHODS
First year cardiology fellows at four teaching hospitals in Michigan tracked their femoral access experience and any associated complications between July 2011 and June 2013. Fellows starting their academic training in July 2012 were first trained on a specially developed simulator before starting their rotation in the catheterization laboratory. The primary outcome was access proficiency, defined as five successful femoral access attempts without any complication or need to seek help from a more experienced team member.
RESULTS
A total of 1,278 femoral access attempts were made by 21 fellows in 2011-2012 compared with 869 femoral access attempts made by 21 fellows in 2012-2013. There was a lower rate of access related complications in patients undergoing access attempts by first year fellows in year 2 compared with year 1 (2.1% versus 4.5%, P = 0.003). The number of procedures to achieve procedural proficiency was significantly higher in year 1 compared with year 2 (median 20 versus 10, P = 0.007).
CONCLUSIONS
Incorporation of simulation in the training of first year fellows was associated with an improvement in proficiency and a clinically meaningful reduction in vascular complications. | 10.1002/ccd.26256 |
pubmed_530_23695 | The purpose of this study was to evaluate the effect of air-blowing duration on the bonding performance of all-in-one systems using the same pressure (0.25 MPa). Three all-in-one systems were: EB (Easy Bond, 3M ESPE, USA), BB (BeautiBond, Shofu Inc., Japan) and GBp (G-Bond plus, GC Corporation, Japan). After adhesive application, the 3 systems were air-blown thereafter using 7 different durations (5 s, 10 s, 15 s, 20 s, 25 s, 30 s and 35 s). Bond strengths to dentin were determined using µTBS test after 24 h water storage. In addition, evaluation of both the resin-dentin interface and the fractured surface on the dentin side were performed by SEM. The maximum µTBS for each system, BB (40.4±14.8 MPa), EB (79.8±16.5 MPa), and GBp (47.3±17.6 MPa), were recorded with 15 s, 15 s and 25 s air-blowing duration respectively. Under the same air-pressure, the air-blowing duration could affect evaporation and the thickness of the adhesive layer, which contributed to the different bond strengths. | 10.4012/dmj.2012-205 |
pubmed_776_13440 | Otoconia from the peripheral portion of the vestibular system contain specific proteins and are mineralized by several polymorphs of calcium carbonate. To infer the internal distribution of their mineral and protein components, we have measured the densities, by equilibrium centrifugation, and the lengths of aragonitic otoconia from the African clawed frog (Xenopus laevis) and calcitic otoconia from the Norway rat (Rattus norvegicus). The densities are statistically dependent on the length of the otoconia. Further, this dependence is not the same for aragonitic and calcitic otoconia. Aragonitic otoconia are statistically more dense when smaller and less dense when larger. For calcitic otoconia the opposite is true; the smaller otoconia are statistically less dense than larger otoconia. Because the organic and inorganic phases have different densities, this indicates that the otoconial proteins and the mineral phases have different distributions within these two types of otoconia. | 10.1016/0378-5955(93)90142-n |
pubmed_801_13255 | Listeria monocytogenes is a foodborne pathogen that can cause serious invasive illness, mainly in certain well-defined high-risk groups, including elderly and immunocompromised patients, pregnant women, newborns and infants. In India, this pathogen has been isolated from humans, animals and foods. The incidence of Listeria is generally comparable to those reported elsewhere in the world. In humans, maternal/neonatal listeriosis is the most common clinical form reported. Among animal populations, spontaneous abortions, subclinical mastitis, meningoencephalitis and endometritis were the commonest forms reported. The disease largely remains undiagnosed and under reported. From reported analyses of a variety of foods for Listeria, milk and milk products, meat and meat products, seafood and vegetables have been reported to be contaminated in India. The legal framework for microbiological safety of foods against microbes including L. monocytogenes is summarised. The epidemiological studies would help in understanding of the sources of infection and persistence and their risk assessment, routes of transmission, clinical forms and allow for better management of the infection. | 10.1016/j.ijfoodmicro.2011.08.030 |
pubmed_368_25374 | PURPOSE OF REVIEW
This article focuses on recent advances in Charcot-Marie-Tooth disease, in particular additions to the genetic spectrum, novel paradigms in molecular techniques and an update on therapeutic strategies.
RECENT FINDINGS
Several new Charcot-Marie-Tooth disease-causing genes have been recently identified, further enlarging the genetic diversity and phenotypic variability, including: SBF1, DHTKD1, TFG, MARS, HARS, HINT1, TRIM1, AIFM1, PDK3 and GNB4. The increasing availability and affordability of next-generation sequencing technologies has ramped up gene discovery and drastically changed genetic screening strategies. All large-scale trials studying the effect of ascorbic acid in Charcot-Marie-Tooth 1A have now been completed and were negative. Efforts have been made to design more robust outcome-measures for clinical trials. Promising results with lonaprisan, curcumin and histone deacetylase 6 inhibitors have been obtained in animal models.
SUMMARY
Charcot-Marie-Tooth is the most common form of inherited peripheral neuropathy and represents the most prevalent hereditary neuromuscular disorder. The genetic spectrum spans more than 70 genes. Gene discovery has been revolutionized recently by new high-throughput molecular technologies. In addition, the phenotypic diversity has grown tremendously. This is a major challenge for geneticists and neurologists. No effective therapy is available for Charcot-Marie-Tooth. Several large trials with ascorbic acid were negative but research into novel compounds continues. | 10.1097/WCO.0000000000000131 |
pubmed_1045_22560 | OBJECTIVE
Extraventricular drains (EVDs) are intended to control intracranial pressure for patients with acute disorders of the cerebrospinal fluid circulation. We tested five commercially available EVDs to assess their fundamental hydrodynamic properties, which determine the quality of this control.
METHODS
The five most frequently used drainage systems were tested. The pressure responses to water flow from a computer-controlled infusion pump were studied in the rig constructed in the UK Shunt Evaluation Laboratory (Cambridge, England). EVDs were studied under normal conditions and after brief (20-s) contact of the vent located in the drip chamber with the test reagent. Pure water and water with 10% rat blood content were used for testing.
RESULTS
All of the tested EVDs demonstrated low hydrodynamic resistance [<3.5 mm Hg/(ml/min)], indicating their ability to control intracranial pressure. When the drip chamber vents were in brief contact with the reagent, the hydrodynamic properties of two models were unaffected. For the three other EVDs, blockage of the drip chamber was observed, leading to increases in the inlet pressure to more than 150 mm Hg. All three models that demonstrated obstruction have the same vent configuration, which allows cerebrospinal fluid to accumulate close to the filter when the drip chamber is held horizontally. This feature was confirmed to be the cause of the blockage.
CONCLUSION
In clinical practice, special care should be taken to avoid contact of the drip chamber vents with cerebrospinal fluid, which causes obstruction and may lead to the development of gross intracranial hypertension. Specific configurations, as identified in this testing program, are safer than others in this respect. | 10.1227/01.neu.0000049956.11888.6d |
pubmed_669_5182 | Fucoxanthin (Fx) is a marine carotenoid with anti-inflammatory and anti-cancer properties in various animal models of carcinogenesis. However, there is currently no information on the effects of Fx in animal models of pancreatic cancer. We investigated the chemopreventive effects of Fx in C57BL/6J mice that received allogenic and orthotopic transplantations of cancer cells (KMPC44) derived from a pancreatic cancer murine model (Ptf1aCre/+; LSL-kras). Using microarray, immunofluorescence, western blot, and siRNA analyses, alterations in cancer-related genes and protein expression were evaluated in pancreatic tumors of Fx-administered mice. Fx administration prevented the adenocarcinoma (ADC) development of pancreatic and parietal peritoneum tissues in a pancreatic cancer murine model, but not the incidence of ADC. Gene and protein expressions showed that the suppression of chemokine (C-C motif) ligand 21 (CCL21)/chemokine receptor 7 (CCR7) axis, its downstream of Rho A, B- and T-lymphocyte attenuator (BTLA), N-cadherin, αSMA, pFAK(Tyr397), and pPaxillin(Tyr31) were significantly suppressed in the pancreatic tumors of mice treated with Fx. In addition, Ccr7 knockdown significantly attenuated the growth of KMPC44 cells. These results suggest that Fx is a promising candidate for pancreatic cancer chemoprevention that mediates the suppression of the CCL21/CCR7 axis, BTLA, tumor microenvironment, epithelial mesenchymal transition, and adhesion. | 10.3390/ijms222413620 |
pubmed_465_9733 | This work is a contribution to the discussion of the polymorphism of class I histocompatibility antigens (H-2 antigens in the mouse). Specially, the involvement of gene conversion in H-2 polymorphism has been explored through the use of a simplified computer model. It thus appears that in a population of limited size, gene conversion can promote allelic polymorphism while homogenizing the DNA sequences in a multigene family, only if it acts as a directional process. The DNA sequences of the preferential targets are then polymorphic and evolutionary versatile, while other genes of the family mostly behave as sequence donors, have more stable DNA sequences and are much less polymorphic. The characteristics of such a polymorphism generator are discussed with respect to their functional and evolutionary implications. | 10.1016/s0300-9084(83)80274-0 |
pubmed_750_21916 | Knowledge about the identity of parasites in vertebrates is relevant because of their influence on ecological processes and health of their hosts. This is particularly important for groups of animals currently facing conservation issues, such as reptiles. The diversity of species and supra-specific taxa of microparasites and macroparasites (such as helminths and arthropods) present in non-avian reptiles in Chile was analyzed through a systematic review. A total of 49 scientific documents (thesis projects, abstracts in congresses, book chapters and peer-reviewed articles) concerning parasites, taxonomic descriptions and parasite ecology were included in this review. The suborder Iguania was among the most studied group with 35 native species recognized as hosts of parasites and 39 species of parasites reported up to the category of species or genus. Liolaemus tenuis was the species with the most taxa of recorded parasites (11 taxa, and only three to species level), but Liolaemus chillanensis had the highest number of identified species of parasites. In addition, only one native species of Serpentes, one of Gymnophthalmoidea, and two of Gekkota, as well as some reports of exotic species, were recorded as hosts. Among parasites, Trombidiformes was the richest order with 10 species from the superfamily Pterygosomatoidea and 16 species from Trombiculoidea. Current knowledge about the richness of helminths is very limited and there were only a few records of microparasites. In general, there is an urgent need for the development of collaborative works between specialists in reptile taxonomy and epidemiology in parasitology destined to evaluate the consequences that reptiles and their parasites will suffer due to the ongoing processes of habitat loss, climate change and the still present taxonomic issues of the native reptiles. | 10.11646/zootaxa.4543.3.1 |
pubmed_63_8770 | The vast majority of patients with supraventricular tachycardias present with specific 12-lead surface ECG characteristics allowing the diagnosis of the underlying mechanisms prior to the invasive electrophysiological study. However, an accurate diagnosis remains challenging in a subset of patients, even when using well-established stimulation maneuvers and sophisticated conventional mapping methods. Thus, the aim of the present manuscript is to describe some cases with uncommon entities of supraventricular tachycardias where the combined interpretation of 12-lead ECG presentation and invasive electrophysiological characteristics revealed the correct diagnoses. | 10.1007/s00399-009-0028-7 |
pubmed_842_4596 | We describe a white emitting coordination network solid that can be conveniently applied as a thin film onto a commercial UV-LED lamp for practical white lighting applications. The solid state material was discovered in an exercise of exploring molecular building blocks equipped with secondary groups for fine-tuning the structures and properties of coordination nets. Specifically, CH(3)SCH(2)CH(2)S- and (S)-CH(3)(OH)CHCH(2)S- (2-hydroxylpropyl) were each attached as secondary groups to the 2,5- positions of 1,4-benzenedicarboxylic acid (bdc), and the resultant molecules (L1 and L2, respectively) were crystallized with Pb(II) into the topologically similar 3D nets of PbL1 and PbL2, both consisting of interlinked Pb-carboxyl chains. While the CH(3)S- groups in PbL1 are not bonded to the Pb(II) centers, the hydroxy groups in PbL2 participate in coordinating to Pb(II) and thus modify the bonding features around the Pb(II), but only to a slight and subtle degree (e.g., Pb-O distances 2.941-3.116 Å). Interestingly, the subtle change in structure significantly impacts the properties, i.e., while the photoluminescence of PbL1 is yellowish green, PbL2 features bright white emission. Also, the homochiral side group in PbL2 imparts significant second harmonic generation, in spite of its seemingly weak association with the main framework (the NLO-phore). In a broad perspective, this work showcases the idea of secondary group participation (SGP) in the construction of coordination networks, an idea that parallels that of hemilabile ligands in organometallics and points to an effective strategy in developing advanced functions in solid state framework materials. | 10.1021/ja2073559 |
pubmed_617_19733 | Tuberous sclerosis complex 1 (TSC1) inhibits mammalian target of rapamycin (mTOR), a central promotor of cell growth and proliferation. The protein product of the TSC1 gene, hamartin (referred to as TSC1) is known to interact with Polo-like kinase 1 (Plk1) in a cell cycle regulated, phosphorylation-dependent manner. We hypothesized that the p53 target gene, Plk2, is a tumor suppressor, mediating its tumor suppressor function through interactions with TSC1 that facilitate TSC1/2 restraint of mTOR under hypoxic stress. We found that human lung tumor cells deficient in Plk2 grew larger than control tumors, and that Plk2 interacts with endogenous TSC1 protein. Additionally, C-terminal Plk2-GST fusion protein bound both TSC1 and TSC2 proteins. TSC1 levels were elevated in response to Adriamycin and cells transiently overexpressing Plk2 demonstrated decreased phosphorylation of the downstream target of mTOR, ribosomal protein p70S6 kinase during hypoxia. Plk2 levels were inversely correlated with cytoplasmic p70S6K phosphorylation. Plk2 levels did not increase in response to DNA damage (Adriamycin, CPT -11) when HCT 116 and H460 cells were exposed to hypoxia. TSC1-deficient mouse embryonic fibroblasts with TSC1 added back demonstrated decreased S6K phosphorylation, which was further decreased when Plk2 was transiently overexpressed. Interestingly, under normoxia, Plk2 deficient tumor cells demonstrated increased apoptosis in response to various chemotherapeutic agents including CPT -11 but increased resistance to apoptotic death after CPT-11 treatment under hypoxia, and tumor xenografts comprised of these Plk2-deficient cells were resistant to CPT -11. Our results point to a novel Plk2-TSC1 interaction with effects on mTOR signaling during hypoxia, and tumor growth that may enable targeting Plk2 signaling in cancer therapy. | 10.4161/cc.8.24.10800 |
pubmed_1088_1915 | Electronic Health Records (EHRs) maintain information of sensitive nature. Security requirements in this context are typically multilateral, encompassing the viewpoints of multiple stakeholders. Two main research questions arise from a security assurance point of view, namely how to demonstrate the internal correctness of EHRs and how to demonstrate their conformance in relation to multilateral security regulations. The above notions of correctness and conformance directly relate to the general concept of system verification, which asks the question "are we building the system right?" This should not be confused with the concept of system validation, which asks the question "are we building the right system?" Much of the research in the medical informatics community has been concerned with the latter aspect (validation). However, trustworthy security requires assurances that standards are followed and specifications are met. The objective of this paper is to contribute to filling this gap. We give an introduction to fundamentals of security assurance, summarize current assurance standards, and report on experiences with using security assurance methodology applied to the EHR domain, specifically focusing on case studies in the Canadian context. | pubmed_1088_1915 |
others_399_6847 | A high-efficiency, nondestructive, rapid, and automatic crop disease classification method is essential for the modernization of agriculture. To more accurately extract and fit citrus disease image features, we designed a new 13-layer convolutional neural network (CNN13) consisting of multiple convolutional layer stacks and dropout in this study. To address the problem created by the uneven number of disease images in each category, we used the VGG16 network module for transfer learning, which we combined with the proposed CNN13 to form a new joint network, which we called OplusVNet. To verify the performance of the proposed OplusVNet network, we collected 1869 citrus pest and disease images and 202 normal citrus images from the field. The experimental results showed that the proposed OplusVNet can more effectively solve the problem caused by uneven data volume and has higher recognition accuracy, especially for image categories with a relatively small data volume. Compared with the state of the art networks, the generalization ability of the proposed OplusVNet network is stronger for classifying diseases. The classification accuracy of the model prediction results was 0.99, indicating the model can be used as a reference for crop image classification. © 2022 by the authors | 10.3390/agriculture12091487 |
pubmed_788_15388 | AIM
To obtain better survival estimates for the individual than is provided by placement in an NPI group.
METHOD
Consecutive primary operable breast cancers treated at Nottingham City Hospital 1990-1999. Ten year % actuarial survivals plotted for 10 ranges of NPI from 2.0 to 6.9. There is an excellent inverse correlation between median NPI value for each range and survival at 10 years. To enable estimation of survival for all individual values of NPI, a curve fitting technique applied to these results (by G.B.) gave the formula to estimate survival from the individual's NPI score: 10 year % survival for the individual=-3.0079 x NPI(2)+12.30 x NPI+83.84. This gave an r(2) of 0.98.
RESULTS AND CONCLUSION
Greater accuracy in individual survival prediction is obtained by dividing women into 10 groups by NPI scores than in the originally described six groups; rank order of survival in relation to NPI score is preserved. A curve fitting technique has been applied to these data to give a formula for the prediction of 10 year survival for every 0.1 value of NPI. | 10.1016/j.ejca.2007.01.003 |
pubmed_714_21370 | Our objective was to evaluate a new concept for assessment and treatment of urinary incontinence in an open-access, interdisciplinary incontinence clinic. A standardized program for investigation and treatment of incontinence was based on minimal relevant investigations, primarily non-surgical treatment with a limited consumption of resources ("minimal care"). This was a prospective observational study of 408 consecutive women examined and treated in the clinic. The main characteristics of the women were a high median age and a high prevalence of severe concomitant diseases with possible influence on lower urinary tract function. More than half of the patients had urge or mixed incontinence. Most of the patients were managed with conservative treatment. Fifteen percent were referred to in-hospital treatment, with 5% to incontinence surgery. In total 44% felt cured or very much improved. Before and after treatment one third of the women completed quality-of-life questions and voiding charts, while 43% completed the pad tests. Quality of life improved significantly. Objectively leakage on pad test and voiding charts was significantly improved. The patients were in general very satisfied with clinic's program. Almost one fourth of the women were followed up for 6 months after discharge. No significant deterioration in the subjective results were found compared to status at discharge. In conclusion, the results highlight the need for advice and treatment of patients with incontinence. The minimal care program and interdisciplinary structure in the incontinence clinic offer effective and low cost treatment for urinary incontinence. The open-access, interdisciplinary incontinence clinic model is recommended. Neurourol. Urodynam. 18:9-17, 2000. | 10.1002/(sici)1520-6777(2000)19:1<9::aid-nau3>3.0.co;2-m |
pubmed_352_9740 | Abdominal fetal electrocardiography (AFECG) as a means of intrapartum fetal heart rate (FHR) monitoring was studied in 700 consecutive labors in a small hospital. Sixty-eight pregnancies were excluded from the study because of the elective cesarean section or because labor was too short for electronic monitoring. AFECG succeeded (at least 30% of fetal heart intervals obtained) throughout labor in 99 of 632 monitored labors (16%). Ultrasound was needed in six cases (1%). The rest (527) were monitored first with the use of AFECG, and later with the use of direct FECG. The mean beat-to-beat variation of FHR (differential index) during last two hours of labor measured from AFECG signal was similar to that measured from AFECG and direct FECG. Hence the same reference values of the differential indices for both methods can be used. The mean long term variation (interval index) measured from AFECG was lower than that measured from abdominal and direct FECGs consecutively. Ultrasound is rarely needed during labor, and it should be avoided except in breech presentations, in association with low placentas and twins, if recording of AFECG fails. | pubmed_352_9740 |
pubmed_937_6753 | Five isoforms of tropomyosin, designated as TMa, TMb, TMc, TMd, and TMe, were detected in the sea anemone, Anthopleura japonica. The apparent molecular weights of these isoforms were estimated to be approximately 30 kD to 37.5 kD, and their pI values were approximately 4.55 (TMa and TMb) and 4.65 (TMc, TMd, and TMe). Although sea anemone tropomyosin isoforms have the ability to bind to rabbit skeletal muscle actin, they preferably bind to actin at higher concentrations of Mg(2+) (10-20 mM) and slightly lower pH (6.2-7.2) than those used in conventional conditions. Antigenic properties of sea anemone tropomyosin seemed to be considerably specific to each isoform. Distribution of tropomyosin isoforms in the sea anemone body was somewhat portion-specific. TMa, TMb, and TMe were detected similarly in the extracts from tentacle, oral disc, column, mouth, and pedal disc. Although TMc and TMd were detected abundantly in the tentacle extract and moderately in the column and mouth extracts, these components were not contained in the pedal disc extract and detected only faintly in the oral disc extract. | 10.1002/jez.10180 |
pubmed_109_4405 | Henri de Mondeville details a method of wound healing that emphasizes early debridement and primary closure. In Guy de Chauliac's advice on the treatment of groin hernias, he demonstrates an early if unsophisticated understanding of the principles of high ligation of the sac and repair of the direct defect. | 10.1016/0002-9610(76)90018-0 |
pubmed_129_740 | A classic equation that has frequently been used to estimate the fraction of glucose metabolized by the pentose phosphate pathway, using 14CO2 data, is more simply re-derived with careful consideration of the assumptions involved and the conditions under which it is applicable. The equation is shown to be unreliable for non-homogeneous tissues, depending on the fraction of triose phosphate converted to CO2. The formula in question is as follows: ([1]CO2/G-[6]CO2/G)/(1-[6]CO2/G) = 3Fmet./(1 + 2Fmet.) where [1]CO2 and [6]CO2 are output rates of carbons 1 and 6 of glucose respectively to CO2, G is the rate of glucose uptake and Fmet. is the fraction of the glucose that is metabolized to CO2 and triose phosphate by the pentose phosphate pathway, allowing for recycling of an appropriate fraction of the fructose-6-phosphate produced by the pathway. This analysis illustrates the importance of suitably testing any equation that assumes homogeneity before application to non-homogeneous tissues. | 10.1042/bj2720127 |
pubmed_1124_10529 | Anti-estrogen (anti-E2) therapy with E2 receptor antagonists has a significant benefit in women with breast cancer, but it may also increase the risk for developing hormone-independent breast cancer for which there is no therapy similar to that used in hormone-dependent breast cancer. Therefore, there is a significant interest in the development of compounds that may provide therapeutic benefit for hormone-independent breast cancer without untoward risks and adverse effects. The estrogen receptor (ER) modulators with both agonistic as well as antagonistic properties may, thus, be exploited for the development of the next generation of compounds for the prevention and/or treatment of breast cancer. In this article, we have discussed the clinical indications, risks, benefits and mechanisms of action of ER modulators and related compounds, particularly indole-3-carbinol (I3C), which may open new avenues for the prevention and/or treatment of breast cancer. | 10.1016/s0960-0760(01)00186-8 |
pubmed_879_23228 | OBJECTIVE
To describe electrocorticographic, electromyographic and electrocardiographic profiles to report the electrophysiological effects of caffeine in Wistar rats.
METHODS
Male adult Wistar rats weighing 230g to 250g were used. Rats were allocated to one of two groups, as follows: Group 1, Control, intraperitoneal injection of 0.9% saline solution (n=27); and Group 2, treated with intraperitoneal injection of caffeine (50mg/kg; n=27). The rats were submitted to electrocorticographic, electromyographic and electrocardiographic assessment.
RESULTS
Brain oscillations (delta, theta, alpha, beta and gamma) in the frequency range up to 40Hz varied after caffeine administration to rats. Powers in delta and theta oscillations ranges were preponderant. The contractile force of the skeletal striated and cardiac muscles increased. Electrocardiogram analysis revealed shorter RR, QRS and QT intervals under the effect of caffeine.
CONCLUSION
In the central nervous system, there was an increase in the delta, theta and alpha amplitude spectrum, which are related to memory encoding and enhanced learning. With regard to skeletal muscle, increased contraction of the gastrocnemius muscle was demonstrated, a clear indication of how caffeine can be used to enhance performance of some physical activities. Electrocardiographic changes observed after caffeine administration are primarily related to increased heart rate and energy consumption. | 10.31744/einstein_journal/2021AO6417 |
pubmed_12_4465 | Fourteen patients with cluster headache (13 with the episodic and 1 with the chronic form; 11 males and 3 females) were studied. One patient was in remission at the time of investigation; no one was studied during an ongoing attack. The cavernous sinus and its immediate surroundings were studied at 0.5 Tesla (n = 7) and 1.5 Tesla (n = 7). No definite pathological changes were found in the area of particular interest. Since the evidence implicating the cavernous sinus in cluster headache pathogenesis is rather strong, the search for abnormalities in this area should continue. | 10.1111/j.1526-4610.1990.hed3006350.x |
pubmed_714_22213 | The morphology of the gastroenteropancreatic (GEP) system of fish was reviewed with the objective of providing the phylogenetic and ontogenetic development of the system in this vertebrate group, which includes agnathans and gnathostome cartilaginous, actinoptyerygian, and sarcopterygian fish. Particular emphasis is placed on the fish homolog of the endocrine pancreas of other vertebrates, which is referred to as the islet organ. The one-hormone islet organ (B cells) of larval lampreys is the most basic pattern seen among a free-living vertebrate, with the two-hormone islet organ (B and D cells) of hagfish and the three-hormone islet organ (B, D, and F cells) of adult lampreys implying a phylogenetic trend toward the classic four-hormone islet tissue (B, D, F, and A cells) in most other fish. An earlier stage in the development of this phylogenetic sequence in vertebrates may have been the restriction of islet-type hormones to the alimentary canal, like that seen in protochordates. The relationship of the islet organ to exocrine pancreatic tissue, or its equivalent, is variable among bony, cartilaginous, and agnathan fishes and is likely a manifestation of the early divergence of these piscine groups. Variations in pancreatic morphology between individuals of subgroups within both the lamprey and chondrichthyan taxa are consistent with their evolutionary distance. A comparison of the distribution and degree of concentration of the components of the islet organ among teleosts indicates a diffuse distribution of relatively small islets in the generalized euteleosts and the tendency for the concentration into Brockmann bodies of large (principal) islets (with or without secondary islets) in the more derived forms. The holostean actinopterygians (Amiiformes and Semiontiformes) share with the basal teleosts (osteoglossomorphs, elopomorphs) the diffuse arrangement of the components of the islet organ that is seen in generalized euteleosts. Since principal islets are also present in adult lampreys the question arises whether principal islets are a derived or a generalized feature among teleosts. There is a paucity of studies on the ontogeny of the GEP system in fish but it has been noted that the timing of the appearance of the islet cell types parallels the time that they appear during phylogeny; the theory of recapitulation has been revisited. It is stressed that the lamprey life cycle provides a good opportunity for studying the development of the GEP system. There are now several markers of cell differentiation in the mammalian endocrine pancreas which would be useful for investigating the development of the islet organ and cells of the remaining GEP system in fish. | 10.1006/gcen.1999.7376 |
pubmed_379_5203 | Recombinant human nidogen was obtained from transfected kidney cell clones as a 150-kDa protein with a three-globule structure. It was modified by sulfation and O-glycosylation and a lower level of N-glycosylation than mouse nidogen. Recombinant nidogens of both species were, however, indistinguishable in their affinities for laminin-1 and a recombinant laminin gamma 1 chain fragment and showed a similar binding to collagen IV and the heparan sulfate proteoglycan perlecan. The two nidogens were also equivalent in the promotion of ternary complex formation between these ligands, indicating that this function has been conserved during mammalian evolution. Fewer zinc-binding sites could be identified in human nidogen and correlated with a lower capacity of zinc to prevent binding to laminin and collagen IV. Most remarkable was the greater sensitivity of human nidogen to endogenous proteolysis in cell culture, yielding fragments of 90-145 kDa. Studies with several exogenous proteases, including thrombin and leucocyte elastase, showed lack of stability of the N-terminal globular domain G1 in contrast to what was found for mouse nidogen. Since such degradation could be important for basement membrane remodelling, this difference between human and mouse may be biologically significant. | 10.1111/j.1432-1033.1995.tb20188.x |
pubmed_878_24929 | The phosphorescence properties of Trp-59 of ribonuclease T1 fromAspergillus oryzae were monitored as a function of temperature, pH, salt concentration, and complex formation with substrate analogues and, also, in the presence of glycerol as viscogenic cosolvent. The results establish a rough correlation between the internal flexibility of the macromolecule, as derived from the triplet lifetime, and its stability (ΔG orT m ) toward unfolding. Below 10°C or in 70% glycerol the triplet probe distinguishes at least two gross conformations for the protein, which are characterized by a large difference in phosphorescence lifetime. It is pointed out that such structural heterogeneity does not correspond with the heterogeneity inferred from fluorescence decays and acrylamide quenching rates. Further, implications of the phosphorescence data with regard to the interpretation of acrylamide quenching of fluorescence are discussed. | 10.1007/BF00866930 |
pubmed_807_19425 | OBJECTIVE
To evaluate the contingent use of fetal fibronectin (fFN) testing and cervical length (CL) measurement to predict preterm delivery, and to validate the use of phosphorylated IGFBP-1 as a predictor of preterm delivery.
METHODS
We recruited 71 women with a clinical diagnosis of preterm labour between 24 and 34 weeks, and tested for the presence of fFN and IGFBP-1 in the cervicovaginal secretions of all women immediately before CL measurement.
RESULTS
Among the 66 women with complete outcome, four were excluded from the final analysis as two had assessment for fFN but no CL measurement, and another two had CL measured but no screening for fFN. Among 62 women with complete results, the mean gestational age at recruitment was 29.4 +/- 2.5 weeks. Six women (9.6%) delivered within two weeks of assessment, and 14 (22.5%) delivered before 34 weeks. A positive fFN test resulted in a sensitivity of 83%, a specificity of 84%, a positive predictive value of 36%, and a negative predictive value of 98% for delivery within two weeks; for CL < 25 mm, these figures were 50%, 52%, 10%, and 91%, respectively, and for a positive IGFBP-1, they were 17%, 93%, 20%, and 91%, respectively. A policy of contingent use of fFN (in which the test was assumed to be positive if CL < or = 15 mm, and fFN was only measured if the CL was between 16 and 30 mm) gave sensitivity, specificity, positive and negative predictive values of 80%, 61%, 17%, and 97%, respectively for delivery within two weeks. Using this contingent use protocol, only one third of women needed fFN screening after CL measurement.
CONCLUSION
In this study, IGFBP-1 screening did not predict preterm delivery and fFN screening provided the best predictive capacity. A policy of contingent use of testing for fFN after CL measurement, or contingent use of CL measurement after fFN screening (depending on available resources) is a promising approach to limit use of resources. | 10.1016/s1701-2163(16)34473-5 |
pubmed_341_7869 | Lactobacilli have been evaluated as probiotics against Candida infections in several clinical trials, but with variable results. Predicting and understanding the clinical efficacy of Lactobacillus strains is hampered by an overall lack of insights into their modes of action. In this study, we aimed to unravel molecular mechanisms underlying the inhibitory effects of lactobacilli on hyphal morphogenesis, which is a crucial step in C. albicans virulence. Based on a screening of different Lactobacillus strains, we found that the closely related taxa L. rhamnosus, L. casei and L. paracasei showed stronger activity against Candida hyphae formation compared to other Lactobacillus species tested. By exploring the activity of purified compounds and mutants of the model strain L. rhamnosus GG, the major peptidoglycan hydrolase Msp1, conserved in the three closely related taxa, was identified as a key effector molecule. We could show that this activity of Msp1 was due to its ability to break down chitin, the main polymer in the hyphal cell wall of C. albicans. This identification of a Lactobacillus-specific protein with chitinase activity having anti-hyphal activity will assist in better strain selection and improved application in future clinical trials for Lactobacillus-based Candida-management strategies. | 10.1038/s41598-019-39625-0 |
pubmed_918_18766 | OBJECTIVES
To determine the characteristics of children who met the risk criteria for potential neurotoxicity defined by the US Food and Drug Administration (FDA; 2016 warning) in a procedural sedation (PS) service.
STUDY DESIGN
A single-center retrospective review of all infants and children aged <3 years receiving PS outside the operating room from 2014 to 2016. Demographics, duration of, and the reason for PS were analyzed.
RESULTS
A total of 2950 patients with 3653 sedation encounters were included. Median age was 19 (range, 11-26) months. Most PS (86.4%) were for magnetic resonance imaging (MRI). The median number of sedation procedures per patient was 1 (25th-75th: 1-7), and median duration of sedation was 72 minutes (25th-75th: 55-98 minutes). Forty patients (1.4%) required prolonged sedations >3 hours, in a single encounter (median, [25th-75th] of 196 minutes [185-214 minutes]), and 298 patients (10.1%) had multiple sedation exposures during the study period. Overall, 327 patients, 11.1% (95% confidence interval, 10.0%-12.3%) required repeated and/or prolonged sedation. The most common reasons for repeated or prolonged sedation were MRI of the brain and neurologic concerns.
CONCLUSIONS
Multiple and prolonged PS commonly occurs outside the operating room in this young and potentially vulnerable population. Although certain imaging cannot be avoided, other cases may have the potential to be delayed until the child is >3 years old or to have alternate imaging that may not require prolonged PS. Family and provider awareness of the FDA warnings regarding potential neurotoxicity of sedation in all settings, both inside and outside the operating room, is critical. | 10.1016/j.acap.2019.02.011 |
pubmed_731_20628 | This guest editorial introduces the special section on Medical Image Perceptions and Observer Performance. | 10.1117/1.JMI.5.3.031401 |
pubmed_0_4532 | Novel high-throughput (Deep) sequencing technology methods have redefined the way genome sequencing is performed. They are able to produce tens of millions of short sequences (reads) in a single experiment and with a much lower cost than previous sequencing methods. In this paper, we present a new algorithm for addressing the problem of efficiently mapping millions of short reads to a reference genome. In particular, we define and solve the Massive Approximate Pattern Matching problem for mapping short sequences to a reference genome. | 10.1007/978-1-4419-5913-3_45 |
pubmed_95_18140 | Recently, a human homologue of the Drosophila patched gene, PTCH, was identified as a putative tumor suppressor mutated in both hereditary and sporadic basal cell carcinomas. Because PTCH controls its own transcription, inactivating mutations in PTCH may lead to overexpression of mutant PTCH mRNA due to loss of autoregulation. The present study is aimed at evaluating whether deregulation of PTCH mRNA expression is a general feature of BCCs of varying histological growth pattern and malignant potential. Irrespective of histological subtype, PTCH mRNA was overexpressed consistently as determined by in situ hybridization in all of the sporadic (n = 16) and hereditary (n = 20) tumors examined. PTCH expression was found in all of the tumor cells but appeared stronger in the peripheral palisading cells. PTCH mRNA was not detected in adjacent nontumor epidermal cells or in other parts of the epidermis. In the majority of tumors (20 of 36), nuclear immunostaining for p53 was found in scattered cells, whereas seven tumors completely lacked p53 immunoreactivity. Our finding of an up-regulation of PTCH mRNA levels in all of the BCCs analyzed indicates that deregulation of the PTCH signaling pathway constitutes an early rate-limiting event in BCC development. | pubmed_95_18140 |
pubmed_912_16340 | BACKGROUND
Diagnosis of pulmonary TB by conventional smear microscopy requires patient attendance on 2 consecutive days. We investigated whether collecting sputum on-the-spot for smear microscopy on the day the patient presented was as sensitive and specific for diagnosis as the conventional spot-morning-spot scheme.
METHOD
We enrolled 412 adults who presented between January 2009 and October 2010 at the National Centre for TB Control in Tripoli, Libya, with cough of >2 weeks' duration, into a cross-sectional survey collecting four sputum specimens: on-the-spot and Xspot on Day 1; morning and on-the-spot on Day 2.
RESULTS
97 (24%) of 401 culture results were culture positive. Spot-Xspot and spot-morning smear microscopy had, respectively, 65% and 66% sensitivity and 97% and 96% specificity (p > 0.5). Spot-Xspot-morning and Spot-morning-spot smear-microscopy had, respectively, 67% and 66% sensitivity and 96% and 96% specificity (p > 0.5).
CONCLUSION
For the diagnosis of pulmonary TB, the sensitivity and specificity of front-loaded (same-day) smear microscopy is similar to that of the standard smear microscopy scheme. | 10.1093/trstmh/trs023 |
pubmed_624_18686 | A rare case of sacrococcygeal teratoma (SCT) associated with hydrops diagnosed on prenatal ultrasound and subsequently confirmed on parturition is presented. | 10.1111/j.1440-1673.1989.tb03292.x |
pubmed_1064_959 | According to the new chemicals policy of the European Union (EU), most chemicals, i.e. the 20,000 chemicals manufactured or imported at 1-10 tons annually, should be tested primarily by using in vitro methods. Also, for other chemicals, the use of in vitro methods is encouraged in the testing strategies given in the draft EU legislation. However, the validation and international acceptance of in vitro tests has been slow. Only recently has the OECD approved four new in vitro test methods, validated by the European Centre for the Validation of Alternative Methods. An analysis of ten randomly selected risk assessment reports of the EU Existing Chemicals Risk Assessment Programme showed that in vitro studies, for example, on cytotoxicity to different cell cultures, cell transformation, metabolism and skin penetration (a total of 115 studies) were used for the assessments. Key metabolic pathways and mechanisms of toxicity have been elucidated, for some chemicals, by using in vitro methods. On the other hand, the results of in vitro studies were regarded as secondary or unreliable in some cases. For several toxic endpoints, in vitro methods will probably serve as screening tools and for mechanistic studies, while target organ toxicity or physiologically regulated adverse effects caused by long-term exposure are difficult to observe without the use of animal models. | 10.1177/026119290403200416 |
pubmed_806_16178 | PURPOSE
To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT).
DESIGN
Prospective interventional case series.
METHODS
setting: Clinical practice.
STUDY POPULATION
Thirty patients (31 eyes) with treatment-naïve neovascular AMD.
OBSERVATION PROCEDURES
Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings.
MAIN OUTCOME MEASURES
RPE response, geographic atrophy (GA) progression.
RESULTS
Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm(2) at 12 months to 1.10 mm(2) (standard deviation = 1.09 mm(2)) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased.
CONCLUSIONS
Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. | pubmed_806_16178 |
others_18_10782 | 1. 1. Glyceraldehyde-3-phosphate dehydrogenase with a specific activity of 153 units/mg protein was isolated from bovine heart muscle. 2. 2. Its relative molecular mass was found to be 144,000. 3. 3. The tryptic peptide map and amino acid analysis were obtained. 4. 4. The N-terminal sequence was established as Val-Lys-Val-Gly-Val-Asn-Gly-... and C-terminal as ...-Ala-Ser-Lys-Glu. 5. 5. Fluorescence and optimal rotation dispersion measurements were performed. 6. 6. The data were compared with other glyceraldehyde-3-phosphate dehydrogenases. © 1986 | 10.1016/0305-0491(86)90180-X |
pubmed_558_17143 | In this study, the annual cycle of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), 17β-oestradiol (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) was determined using radioimmunoassay and then compared, for XY males (n=35) and sex-reversed XX males (n=27) rainbow trout, to establish possible endocrinology differences. Both in XY males and sex-reversed XX males, significant correlation was shown between body weight and T (r=0.5046 and 0.34078, respectively; p<0.0001) or KT (r=0.52494 and 0.43545, respectively; p<0.0001) concentrations. Plasma androgen levels in XY and sex-reversed XX males were similar and showed an intense seasonal variation. The highest levels for T and 11-KT were detected from December to April with a peak in January (51.67 ± 5.11 and 61.95 ± 4.25 ng/ml, for XY males and 57.1 ± 5.82 and 59.27 ± 4.84 ng/ml, respectively, for XX males). In addition, there was a positive correlation (p<0.0001) between T and 11-KT levels for XY males (r=0.7533) and sex-reversed XX males (r=0.6019). Concentrations of DHP in XY males also showed seasonal variation with a peak in February (25.18 ± 12.99 ng/ml). However, DHP levels in sex-reversed XX males were undetectable (<0.1 ng/ml) over the year. Levels of E2 were undetectable through the year in both groups of trout. In conclusion, the androgenic and oestrogenic profiles of sex-reversed XX males were similar to those observed in XY males. The only difference in the annual gonadal steroid cycle between XY and sex-reversed XX males was in the DHP profile. | 10.1111/j.1439-0531.2009.01512.x |
pubmed_306_17874 | UNLABELLED
In recent years, implementation of (68)Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of (44)Sc (half-life = 3.97 h, average β(+) energy [Eβ(+)av] = 632 keV) as a valuable alternative to (68)Ga (half-life = 68 min, Eβ(+)av = 830 keV) for imaging and dosimetry before (177)Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotron-produced (44)Sc and its in vitro and in vivo comparison with the (177)Lu-labeled pendant.
METHODS
(44)Sc was produced via the (44)Ca(p,n)(44)Sc nuclear reaction at a cyclotron (17.6 ± 1.8 MeV, 50 μA, 30 min) using an enriched (44)Ca target (10 mg (44)CaCO3, 97.00%). Separation from the target material was performed by a semiautomated process using extraction chromatography and cation exchange chromatography. Radiolabeling of a DOTA-folate conjugate (cm09) was performed at 95°C within 10 min. The stability of (44)Sc-cm09 was tested in human plasma. (44)Sc-cm09 was investigated in vitro using folate receptor-positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice
RESULTS
Under the given irradiation conditions, (44)Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (>99%). Semiautomated isolation of (44)Sc from (44)Ca targets allowed formulation of up to 300 MBq of (44)Sc in a volume of 200-400 μL of ammonium acetate/HCl solution (1 M, pH 3.5-4.0) within 10 min. Radiolabeling of cm09 was achieved with a radiochemical yield of greater than 96% at a specific activity of 5.2 MBq/nmol. In vitro, (44)Sc-cm09 was stable in human plasma over the whole time of investigation and showed folate receptor-specific binding to KB tumor cells. PET/CT images of mice injected with (44)Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with (44)Sc and (177)Lu revealed almost identical pharmacokinetics.
CONCLUSION
This study presents a high-yield production and efficient separation method of (44)Sc at a quality suitable for radiolabeling of DOTA-functionalized biomolecules. An in vivo proof-of-concept study using a DOTA-folate conjugate demonstrated the excellent features of (44)Sc for PET imaging. Thus, (44)Sc is a valid alternative to (68)Ga for imaging and dosimetry before (177)Lu-radionuclide tumor therapy. | 10.2967/jnumed.113.123810 |
pubmed_419_18264 | Previously reported (S)-5'-C-aminopropyl-2'-arabinofluoro-thymidine (5ara-T) and newly synthesized (S)-5'-C-aminopropyl-2'-arabinofluoro-5-methyl-cytidine (5ara-) analogs were incorporated into a series of antisense gapmers containing multiple phosphorothioate (PS) linkages and locked nucleic acids (LNAs) in their wing regions. The functional properties of the gapmers were further evaluated in vitro. Compared with the positive control, for the LNA-wing full PS gapmer without 5ara modification, it was revealed that each gapmer could have a high affinity and be thermally stable under biological conditions. Although the cleavage pattern was obviously changed; gapmers with 5ara modification could still efficiently activate E. coli RNase H1. In addition, incorporating one 5ara modification into the two phosphodiester linkages could reverse the destabilization in enzymatic hydrolysis caused by fewer PS linkages. In vitro cellular experiments were also performed, and the Lipofectamine® 2000 (LFA)+ group showed relatively higher antisense activity than the LFA-free group. KN5ara-10, which contains fewer PS linkages, showed similar or slightly better antisense activity than the corresponding full PS-modified KN5ara-3. Hence, KN5ara-10 may be the most promising candidate for KNTC2-targeted cancer therapy. | 10.3390/molecules27217384 |
pubmed_921_22491 | Four recently discovered homologues of the brown adipose tissue-specific mitochondrial uncoupling protein (UCP1) vary from 29% to 58% in their similarity to UCP1. Although these homologues share important structural features with UCP1 and like UCP1 can reduce the mitochondrial membrane potential when expressed in yeast, there is no clear evidence that they can function thermogenically in vivo. On the other hand, evidence continues to accumulate indicating that the up-regulation of Ucp1 reduces excessive adiposity. | 10.1146/annurev.nutr.20.1.339 |
pubmed_21_2438 | IMPORTANCE
The cervicofacial rotation-advancement flap is commonly used for facial defects. Decreasing the rate of distal edge necrosis (DEN) encountered with this flap would help prevent complications in sensitive areas such as the eyelid, lip, and nose.
OBJECTIVE
To compare the untoward occurrence of DEN between 2 surgical dissection methods for reconstructive cervicofacial rotation-advancement flaps. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: A review was conducted of 88 patients who underwent cervicofacial flap reconstruction for Mohs ablative surgery between January 1, 2003, and June 30, 2012, by the senior author (A.A.J.). All patients had periorbital, midfacial, cervical, and/or lateral temporal/forehead defects following Mohs surgical ablation. Patients were categorized into 1 of 2 groups on the basis of the surgical technique used: subcutaneous (SC) cervicofacial elevation or deep-plane (DP) cervicofacial elevation. Subcategories of smokers and nonsmokers within each group were further reviewed. Statistical analysis of DEN between categories and subcategories was performed.
RESULTS
Sixty-nine patients were in the SC group and 19 were in the DP group. The mean defect size among both groups was 14.3 cm(2). The rate of active or recent smokers was 23% in the SC group and 11% in the DP group. The rate of DEN among nonsmokers in the SC group was 23% (n = 53) compared with 0% in the 17 DP nonsmokers (P = .03). The rate of smokers with DEN in the SC group was 75% and 0% in the DP group (P = .09). The mean area of DEN in the SC group was 0.8 cm(2).
CONCLUSIONS AND RELEVANCE
Our statistically significant data indicate that DP dissection is a superior technique for avoiding DEN in nonsmokers. We found better outcomes in smokers as well. Thus, we strongly advocate the use of the DP approach as the criterion standard in cervicofacial flap elevation.
LEVEL OF EVIDENCE
3. | 10.1001/jamafacial.2013.20 |
pubmed_924_2114 | BACKGROUND
Scant data exist on factors that may identify outcome in patients with severe left ventricular (LV) dysfunction early after coronary artery bypass graft surgery (CABG).
DESIGN
This study was designed to determine the prognostic value of clinical, operative, and postoperative factors in patients with LV dysfunction early after CABG.
METHODS
In 333 consecutive patients with ejection fraction < or =35% on admission to residential cardiac rehabilitation after isolated CABG, potential preoperative, perioperative, and postoperative predictors of outcome, including 6-month LV remodeling, were recorded and patients followed up for a median of 3 years. The study end points were cardiovascular (CV) mortality and the combination of CV mortality and nonfatal CV events requiring hospitalization.
RESULTS
The 3-year CV mortality-free survival and survival free of nonfatal CV event rates were 87 and 73%, respectively. Independent predictors of CV mortality were history of congestive heart failure [hazard ratio, HR: 2.8; 95% Confidence Interval (CI): 1.51-5.21], low ejection fraction on admission to cardiac rehabilitation (HR: 0.9; 95% CI: 0.87-0.96), and early complications after CABG (HR: 2.5; 95% CI: 1.23-5.15). When the combined end points were considered, postoperative left atrial size (HR: 1.07; 95% CI: 1.01-1.11), New York Heart Association class III or IV (HR: 1.69; 95% CI: 1.04-2.74), and 6-month remodeling (HR: 2.12; 95% CI: 1.33-3.36) were independent predictors.
CONCLUSION
Simple preoperative and postoperative variables may help identify patients with LV dysfunction early after CABG who are still at risk of major CV events. In this setting, 6-month LV remodeling is a strong predictor of a poor prognosis. | 10.1097/HJR.0b013e3282f73501 |
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