Atypical ductal hyperplasia bordering on DCIS on core biopsy is associated with higher risk of upgrade than conventional atypical ductal hyperplasia.
Upgrade rates of conventional ADH are reported at 10-30%; however, rates for ADH bordering on DCIS (ADH-BD) are largely unknown. We examined the upgrade rate of ADH-BD and core needle biopsy (CNB) features associated with upgrade. Surgical management in patients with concurrent ipsilateral breast cancer (BC) was also examined. From 2000 to 2018, women with CNB diagnosis of ADH-BD were prospectively identified. Women with pure ADH-BD and concurrent ipsilateral ADH-BD/BC were analyzed separately, and upgrade rates were calculated. CNB features associated with upgrade and type of surgery were examined in women with pure ADH-BD; CNB features and concurrent pathology associated with upgrade were examined in women with ipsilateral BC. 108/236 (46%) patients with pure ADH-BD on CNB had DCIS (40%) or invasive carcinoma (6%) on surgical excision. DCIS or invasive carcinoma was more frequently found on excision of a mass that yielded ADH-BD on biopsy than excision of calcifications (65% vs 38%; p < 0.001). The breast conservation success rate was high (80%) in patients who upgraded, despite a high re-excision rate of 46%. The upgrade rate of ADH-BD in women with concurrent ipsilateral BC was 41%. Most women (94%) with ADH-BD in the same quadrant as the BC were candidates for breast conserving surgery, with a success rate of 89%. The upgrade rate for pure ADH-BD is significantly higher than that reported for women with conventional ADH, especially in women with a mass on imaging. The upgrade rate of concurrent ipsilateral ADH-BD and BC is similarly high. Excision with a margin of normal tissue and specimen inking should be routine to minimize the need for re-excision.


Cellular Membranes, a Versatile Adaptive Composite Material.
Cellular membranes belong to the most vital yet least understood biomaterials of live matter. For instance, its biomechanical requirements substantially vary across species and subcellular sites, raising the question how membranes manage to adjust to such dramatic changes. Central to its adaptability at the cell surface is the interplay between the plasma membrane and the adjacent cell cortex, forming an adaptive composite material that dynamically adjusts its mechanical properties. Using a hypothetical composite material, we identify core challenges, and discuss how cellular membranes solved these tasks. We further muse how pathological changes in material properties affect membrane mechanics and cell function, before closing with open questions and future challenges arising when studying cellular membranes.


Remarkable Temperature Sensitivity of Partially Carbonized Carbon Fibers with Different Microstructures and Compositions.
In order to explore effect of structure on the temperature sensitivity of partially carbonized carbon fibers, different heat treatment temperatures (700, 750 and 800 °C) and heat treatment times (3 and 9 min) were used to prepare fibers with different structures. The electrical resistivities were monitored whilst the room temperature was increased from 30 to 100 °C, which was used to characterize the temperature sensitivity. The fibers showed negative temperature coefficients in the temperature range. Infrared spectra, an element analysis, a scanning electron microscope (SEM), Raman spectroscopy and X-ray diffraction measurements were used to study the microstructure of the fibers. Through the analysis, the proportions of the graphite-like structure, graphitization degree and size of the graphite-like structure crystallite influenced the temperature sensitivity. The main electron transfer method used for the fibers was variable-range hopping. This indicated that the fibers had a potential application of preparing thermistors in polymer composites.


[Guidelines for the diagnosis and management of hepatic encephalopathy in cirrhosis].
Current guideline developed by the Chinese Society of Hepatology on the management of hepatic encephalopathy in cirrhosis is grounded on the published evidences and panelists' consensus. This guideline presents recommendations for diagnosis and management of covert and overt hepatic encephalopathy, and underline the importance of screening minimal hepatic encephalopathy in patients with end-stage liver diseases. In addition, it also stresses that early identification and timely treatments are the means to know the prognosis. The principles of treatment are primary and secondary prevention, prompt removal of the cause, and recovery of acute neuropsychiatric abnormalities to baseline status.


Successful chemotherapy with modified FOLFIRINOX for pancreatic acinar cell carcinoma.
Abdominal ultrasonography revealed a pancreatic mass in a 67-year-old man with diabetes mellitus. Endoscopic ultrasound-guided fine needle aspiration led to the histological diagnosis of acinar cell carcinoma. The clinical stage was determined to be IVb based on findings of multiple metastatic lesions in the liver and lymph nodes, as well as splenic vein infiltration. Because the patient was not a surgical candidate, he underwent chemotherapy with modified FOLFIRINOX. In the absence of any severe adverse events, 12 courses of chemotherapy were delivered, resulting in marked shrinkage of both the primary and metastatic lesions. The outcome was judged to be a partial response, which was maintained even 9 months from the introduction of the chemotherapy. The results of this case suggest that modified FOLFIRINOX is safe and effective in the treatment of pancreatic acinar cell carcinoma.


Flavonoids of St. John's Wort reduce HPA axis function in the rat.
A common biological alteration in patients with major depression is the activation of the hypothalamic-pituitary-adrenal (HPA) axis, manifested as hypersecretion of adrenocorticotropic hormone (ACTH) and cortisol. The hyperactivity of the HPA axis in depressed patients can be corrected during clinically effective therapy with standard antidepressant drugs such as imipramine, indicating that the HPA axis may be an important target for antidepressant action. We previously showed that a methanolic extract of St. John's Wort (SJW) and hypericin, one of its active constituents, both have delayed effects on the expression of genes that are involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis , whereas the phloroglucinol derivative hyperforin was inactive in the same model . Since flavonoids of SJW are also discussed as active constituents it was of interest to determine whether these compounds can modulate HPA axis function. Imipramine (15 mg/kg), hypericin (0.2 mg/kg), hyperoside (0.6 mg/kg), isoquercitrin (0.6 mg/kg) and miquelianin (0.6 mg/kg) given daily by gavage for two weeks significantly down-regulated circulating plasma levels of ACTH and corticosterone by 40 - 70 %. However, none of the compounds tested had an effect on plasma ACTH and corticosterone levels after chronic treatment (daily gavage for 8 weeks). Our data suggest that besides hypericin, flavonoids of SJW play an important role in the modulation of HPA axis function. Furthermore, the results support the hypothesis that flavonoids are involved in the antidepressant effects of SJW.


Mapping of the bovine blood group systems J, N', R', and Z show evidence for oligo-genetic inheritance.
Genes determining the bovine erythrocyte antigens were mapped by linkage analysis. In total 9591 genotypes of 20 grandsire families with 1074 sires from a grand-daughter design were elucidated for the genes determining the erythrocyte antigens EAA, EAB, EAC, EAF, EAJ, EAL, EAM, EAN', EAR', EAS, EAT', and EAZ according to standard paternity testing procedures in the blood typing laboratories. Linkage analyses were performed with 248 microsatellite markers, eight SSCP markers and four polymorphic proteins and enzymes covering the 29 autosomes and the pseudoautosomal region of the sex chromosomes. The number of informative meioses for the blood group systems ranged from 76 to 947. Blood group systems EAM and EAT' were non-informative. Most of the erythrocyte antigen loci showed significant linkage to a single chromosome and were mapped unequivocally. The genes determining erythrocyte antigen EAA, EAB, EAC, EAL, and EAS were mapped to chromosomes 15, 12, 18, 3, and 21, respectively. Lod-score values ranged from 11.43 to 107.83. Moreover, the EAF system could be mapped to chromosome 17. However, the EAN' system previously known as part of the EAF system could be mapped to chromosome 5. In addition, the blood group systems EAJ, the new EAN', EAR', and EAZ, showed significant linkage to microsatellite markers on various chromosomes and also to other blood groups. The appearance of a single blood group system might be therefore either dependent on the existence of other blood group systems or because of an interaction between different loci on various chromosomes as is known in humans and in pigs.


Identification of isoform-specific dynamics in phosphorylation-dependent STAT5 dimerization by quantitative mass spectrometry and mathematical modeling.
STAT5A and STAT5B are important transcription factors that dimerize and transduce activation signals of cytokine receptors directly to the nucleus. A typical cytokine that mediates STAT5 activation is erythropoietin (Epo). Differential functions of STAT5A and STAT5B have been reported. However, the extent to which phosphorylated STAT5A and STAT5B (pSTAT5A, pSTAT5B) form homo- or heterodimers is not understood, nor is how this might influence the signal transmission to the nucleus. To study this, we designed a concept to investigate the isoform-specific dimerization behavior of pSTAT5A and pSTAT5B that comprises isoform-specific immunoprecipitation (IP), measurement of the degree of phosphorylation, and isoform ratio determination between STAT5A and STAT5B. For the main analytical method, we employed quantitative label-free and -based mass spectrometry. For the cellular model system, we used Epo receptor (EpoR)-expressing BaF3 cells (BaF3-EpoR) stimulated with Epo. Three hypotheses of dimer formation between pSTAT5A and pSTAT5B were used to explain the analytical results by a static mathematical model: formation of (i) homodimers only, (ii) heterodimers only, and (iii) random formation of homo- and heterodimers. The best agreement between experimental data and model simulations was found for the last case. Dynamics of cytoplasmic STAT5 dimerization could be explained by distinct nuclear import rates and individual nuclear retention for homo- and heterodimers of phosphorylated STAT5.


MicroRNA-144 regulates proliferation, invasion, and apoptosis of cells in malignant solitary pulmonary nodule via zinc finger E-box-binding homeobox 1.
This study was to investigate the expression of microRNA (miR)-144 in malignant solitary pulmonary nodule (SPN) tissues and peripheral blood, as well as the biological function of miR-144 in the occurrence and development of lung cancer. In this study, 39 malignant and 30 benign SPN patients were included. The expression of miR-144 was examined using quantitative real-time polymerase chain reaction. Receiver operating characteristic (ROC) curve was used to identify the clinical value of miR-144 in the early diagnosis of malignant SPN. MTT assay was performed to determine A549 cell proliferation and Transwell assay was used to detect changes in A549 cell invasion and migration ability. Flow cytometry was performed to monitor cell apoptosis, while Western blotting assay was used to measure protein expression levels. At last, dual-luciferase reporter assay was employed to test whether miR-144 regulates zinc finger E-box-binding homeobox 1 (ZEB1) gene expression. Expression of miR-144 was reduced in patients with malignant SPN. miR-144 had diagnostic value for malignant SPN. Proliferation of A549 cells was inhibited by miR-144. Invasion ability of A549 cells was reduced by miR-144. Apoptosis of A549 cells was promoted by miR-144. miR-144 induced A549 cell apoptosis by targeting ZEB1 protein. miR-144 regulated the expression of ZEB1 by interacting with its 3'-UTR region. Expression of miR-144 is reduced in malignant SPN tissues and peripheral blood, being of clinical value in the diagnosis of malignant SPN. miR-144 promotes the apoptosis of lung cancer cells, and inhibits the proliferation, invasion and migration of lung cancer by regulating ZEB1 gene.


[Differentiation of benign from malignant pulmonary nodules with the digital analysis of computed radiography].
To differentiate benign pulmonary nodules from malignant nodules, digital analysis of computed radiography (CR) was performed retrospectively. A total of 142 histologically or clinically proved cases were studied. Digital analysis was performed using the method of gradient processing reported by Sherrier et al. Gradient number with and without background trend correction and gradient number corrected by L-value were obtained from the raw data of CR. The mean gradient of 93 malignant nodules was significantly different from that of 49 benign nodules. The analysis of gradient number without background trend correction and L-value correction was most sensitive. Seven radiologists evaluated these nodules as to benign or malignant, status, degree of calcification and homogeneity. A correlation was found between the detectability of benign nodules and degree of calcification. In conclusion, CR-gradient analysis is useful as a screening test to differentiate benign nodules from malignant ones.


Seasonal changes in cell proliferation in the adult sheep brain and pars tuberalis.
To adapt to seasonal variations in the environment, most mammalian species exhibit seasonal cycles in their physiology and behavior. Seasonal plasticity in the structure and function of the central nervous system contributes to the adaptation of this physiology in seasonal mammals. As part of these plasticity mechanisms, seasonal variations in proliferation rate and neuron production have been extensively studied in songbirds. In this report, we investigated whether this type of brain plasticity also occurs in sheep, a seasonal species, by assessing variations in cell proliferation in the sheep diencephalon. We administered the cell birth marker 5'-bromodeoxyuridine (BrdU) to adult female sheep in July and December, during long and short photoperiod, respectively. The BrdU incorporation was analyzed and quantified in the hypothalamus, a key center for neuroendocrine regulations, as well as in other structures involved in relaying neuroendocrine and sensory information, including the median eminence, the pars tuberalis of the pituitary gland, and the thalamus. In December, 2-fold and 6-fold increases in the number of BrdU+ nuclei were observed in the hypothalamus and thalamus, respectively, when compared with July. This variation is independent of the influence of peripheral gonadal estradiol variations. An inverse seasonal regulation of cell proliferation was observed in the pars tuberalis. In contrast, no seasonal variation in cell proliferation was seen in the subventricular zone of the lateral ventricle. Many of the newborn cells in the adult ovine hypothalamus and thalamus differentiate into neurons and glial cells, as assessed by the expression of neuronal (DCX, NeuN) and glial (GFAP, S100B) fate markers. In summary, we show that the estimated cell proliferation rates in the sheep hypothalamus, thalamus, and pars tuberalis are different between seasons. These variations are independent of the seasonal fluctuations of peripheral estradiol levels, unlike the results described in the brain nuclei involved in song control of avian species.


Characterization of abscisic Acid-induced ethylene production in citrus leaf and tomato fruit tissues.
Abscisic acid (ABA) significantly stimulated ethylene production in citrus (Citrus sinensis [L.] Osbeck, cv Shamouti orange) leaf discs. The extent of stimulation was dependent upon the concentration of ABA (0.1-1 milimolar) and the duration of treatment (15-300 minutes). Aging the discs before applying ABA increased ABA-induced ethylene production due to enhancement of both ethylene-forming enzyme activity and the responsiveness of ABA. Discs excised from mature leaves were much more responsive to ABA than discs excised from young or senescing leaves. ABA stimulated ethylene production shortly after application, suggesting that ABA does not enhance ethylene production via the acceleration of senescence. The stimulating effect of ABA on ethylene production resulted mainly from the enhancement of 1-aminocylopropane-1-carboxylic acid synthesis. Stimulation of ethylene production by ABA in intact citrus leaves and tomato (Lycopersicon esculentum Mill., cv Castlemart) fruit was small but could be increased by various forms of wounding.


Prevalence of antibodies against respiratory viruses in children of Koulikoro (Mali).
The prevalence of antibodies to viruses associated with respiratory illnesses (influenza, corona, R.S., adeno, parainfluenza Mycoplasma pneumoniae) has been investigated in 119 children under 3 years of age (Koulikoro region Mali) and 50 persons 15-19 years of age (Bamako/Mali). In the surveillance period (March 1982-September 1982) an outbreak of respiratory disease in association with RS virus took place. A rise of CF titer has been found in 90.8% of the children; 59.1% of them presented a fourfold or greater increase of titer. The GMT values rose from 1:7 to 1:48. Concerning influenza viruses a higher incidence of positive reactions has been observed only for H3N2 viruses. A fourfold CF rise of titer has been observed for adenovirus and mycoplasma pneumoniae in 3 cases each, for parainfluenza type I and III in 2 cases each, and for parainfluenza II in 1 case. In persons 15-19 years of age the incidence of positive CF reactions was relatively high (68%-98%), but the GMT values were moderate (1:12-1:25). These data confirm that the frequency of viral respiratory diseases is the same in tropical countries as in countries with a temperate climate.


[Obesity and metabolic syndrome in children and adolescents].
Obesity and the metabolic syndrome are closely related to the cases of cardiovascular disease; they are usually regarded as belonging to the adult population but are seen with increasing frequency in children and adolescents. There is evidence that atherosclerotic lesions occur most often in young people with obesity. The factors involved in this pandemic are manifold and range from genetic-biological to cultural changes. The family and the environment in which the child develops play a key role in the adoption of habits related to diet and physical activity. This problem does not respect borders and cultures but all countries are being affected, even more those of middle-income. State and Society as a whole can play a role oriented to modify this environment. The restriction on sales of unhealthy food and the fight against the sedentary lifestyle are urgently needed to be applied. The impact that these disorders will have in terms of cardiovascular disease, has not yet reached its true dimension.


Reduced intrinsic heart rate is associated with reduced arrhythmic susceptibility in guinea-pig heart.
In the clinical setting, patients with slower resting heart rate are less prone to cardiovascular death compared with those with elevated heart rate. However, electrophysiological adaptations associated with reduced cardiac rhythm have not been thoroughly explored. In this study, relationships between intrinsic heart rate and arrhythmic susceptibility were examined by assessments of action potential duration (APD) rate adaptation and inducibility of repolarization alternans in sinoatrial node (SAN)-driven and atrioventricular (AV)-blocked guinea-pig hearts perfused with Langendorff apparatus. Electrocardiograms, epicardial monophasic action potentials, and effective refractory periods (ERP) were assessed in normokalemic and hypokalemic conditions. Slower basal heart rate in AV-blocked hearts was associated with prolonged ventricular repolarization during spontaneous beating, and with attenuated APD shortening at increased cardiac activation rates during dynamic pacing, when compared with SAN-driven hearts. During hypokalemic perfusion, the inducibility of repolarization alternans and tachyarrhythmia by rapid pacing was found to be lower in AV-blocked hearts. This difference was ascribed to prolonged ERP in the setting of reduced basal heart rate, which prevented ventricular capture at critically short pacing intervals required to induce arrhythmia. Reduced basal heart rate is associated with electrophysiological changes that prevent electrical instability upon an abrupt cardiac acceleration.


Best practice in primary care pathology: review 14.
This 14th best practice review is the second of a pair that examines tumour marker requesting primary care situations. This review considers carbohydrate antigen 125, α-fetoprotein and human chorionic gonadotropin. It is presented in question-answer format, referenced for each question. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They will be updated periodically to take into account new information.


Random strain effects in optical and EPR spectra of electron-nuclear excitations in CaWO4:Ho(3+) single crystals.
We study paramagnetic Ho(3+) centers in CaWO4, a promising material for applications in quantum electronics and quantum information devices. Oriented single crystals with nominal holmium concentrations 0.05, 0.5, and 1 at% were investigated at 4.2 K using EPR spectroscopy in the frequency range 37-850 GHz at temperatures 5-40 K and high-resolution optical transmission spectroscopy in the infrared and visible wave-length ranges. Along with the tetragonal Ho(3+) centers of the S4 point symmetry, four different types of low-symmetry centers were identified in the EPR spectra and their spectral parameters were determined. A well resolved hyperfine structure exhibiting holmium concentration dependent features was observed in optical spectra. Modeling of the spectra taking into account random lattice strains gave a possibility of reproducing satisfactorily the measured hyperfine structure of the EPR signals, in particular, at anticrossings of the electron-nuclear sublevels of the ground non-Kramers doublet, and the envelopes of the hyperfine structure of optical transitions. The widths of the probability distribution of random deformations related to the point lattice defects in the samples with different concentrations of the impurity Ho(3+) ions were estimated from a comparison of the simulated spectra with the experimental data.


Carcinoma of the papilla of Vater following treatment of pancreaticobiliary maljunction.
Pancreaticobiliary maljunction (PBM) is frequently associated with biliary cancer due to reflux of pancreatic enzymes into the choledochus, and even after surgery to correct the PBM such patients still have a risk of residual bile duct cancer. Here, we report the case of a 59-year-old female with carcinoma of the papilla of Vater which developed 2.5 years after choledochoduodenostomy for PBM. During the postoperative follow-up period, computed tomography obtained 2 years after the first operation demonstrated a tumor in the distal end of the choledochus, although she did not have jaundice and laboratory tests showed no abnormalities caused by the previous operation. As a result, carcinoma of the papilla of Vater was diagnosed at an early stage, followed by surgical cure. For early detection of periampullary cancer in patients undergoing surgery for PBM, careful long-term follow-up is needed.


Treatment persistence of biologics among patients with psoriatic arthritis.
Persistence of biologic therapy in psoriatic arthritis (PsA) patients is an important factor in individualized patient treatment planning and healthcare policy and guideline development. To estimate the persistence of biologic agents prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients. Patients with PsA from a large healthcare provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1, 2002, until December 31, 2018, were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a permissible lag time of 6 months from the time of prescription issuance until medication filling date was exceeded. Treatment changes were based on physician decisions and patient preferences. Demographic data including age, sex, body mass index (BMI), ethnicity, smoking history, and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence. A total of 2301 PsA patients with 2958 treatment periods were identified and included in the analyses. Mean age of the study population was 50.9 ± 14 years, 54% were females, 70.4% were with BMI > 25, 40% were current smokers, and 76% were with a Charlson comorbidity index > 1. The most commonly prescribed drug was etanercept (33%), followed by adalimumab (29%), golimumab (12%), secukinumab (10%), ustekinumab (8%), and infliximab (8%). While approximately 40% of patients persisted on therapy following 20 months of treatment, only about 20% of patients remained on any particular biologic agent after 5 years. Analyzing the data for all treatment periods while taking into account all lines of therapy revealed that secukinumab had a higher persistency than adalimumab, infliximab, and ustekinumab, with a log rank of 0.022, 0.047, and 0.001, respectively. Female sex and smoking were associated with lower drug persistence (HR = 1.25, 95% CI = 1.13-1.38 and HR = 1.109, 95% CI = 1.01-1.21, respectively). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-tumor necrosis factor-alpha (anti-TNFα) agent was observed, while secukinumab was found to be superior as second line therapy to adalimumab, etanercept, infliximab, and ustekinumab but not to golimumab with a log rank P value of 0.001, 0.004, 0.025, and 0.002, respectively. In this large observational cohort studied in the era of biologic therapy, a relatively low drug persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents was found to be more persistent than others as first line therapy, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.


Hydrophilic nanowire modified polymer ultrafiltration membranes with high water flux.
Germanate nanowires/nanorods with different lengths were synthesized and used as additives for the fabrication of polymer composite membranes for high-flux water filtration. We for the first time demonstrated that at a small nanowire/nanorod loading (e.g., <0.5 wt % on the basis of poly(ether sulfone)), the length of germinate nanowires was a key parameter in determining their migration and diffusion in the polymer solution, and thus affecting polymer precipitation in the membrane formation process. In particular, short Ca2Ge7O16 nanowires with an average length of 138.7 nm and an average diameter of 12.7 nm, and Zn2GeO4 nanorods with an average length of 400 nm and an average diameter of 18.7 nm quickly diffused out of the membrane, leading to a higher pore density on the active layer in comparison with the pristine membranes. The addition of short Ca2Ge7O16 nanowires resulted in greater pore sizes than the addition of Zn2GeO4 nanorods because the out-diffusion of the former was faster than that of the latter. In contrast, the addition of long Ca2Ge7O16 nanowires with lengths of several tens to hundreds of micrometers and an average of 27.3 nm was not effective in promoting the pore formation because of partial embedment of nanowires. Poly(ether sulfone) composite membranes prepared by adding a small amount of Zn2GeO4 nanorods exhibited dramatically enhanced water permeation without losing rejection property. For example, the poly(ether sulfone) (PES) composite membrane prepared with 0.3 wt % Zn2GeO4 nanorods exhibited the highest flux, 1294.5 LMH, which was 3.5 times of the pristine (PES) membrane (384.2 LMH). Our work provides a new strategy for developing high-performance ultrafiltration membranes for practical industrial filtration applications.


[How to improve efficacy of onychomycosis treatment?].
Onychomycosis is a public health concern because of its high world wide prevalence, and its potential for spread of fungal elements to others. About one half of all patients presenting to dermatologists' offices for nail disorders have onychomycosis. This kind of infection may impact upon physical, functional, and emotional aspects of life. Onychomycosis can be treated with the new generation of oral antifungals. Efficacy rates for fingernail onychomycosis are high; however, for toenail onychomycosis, efficacy rates may range from 60% to 80%. Relapse rates have been estimated to be 15% to 20% measured at 2 years following therapy initiation. Because many factors may be associated with a suboptimal clinical response, consideration to measures that reflect the most appropriate pharmacologic and supportive regimens must be made in order to meet the challenge of onychomycosis cure. In some situations supplemental therapy consisting of extra antifungal or adjunctive (topical/surgical) therapy may be beneficial.


New developments in ultrasound systems for contrast echocardiography.
Contrast echocardiography (CE) has evolved significantly in the past decade. Contrast agents and the hardware and software used to detect them and display optimal images have developed in tandem. Not only are hardware and contrast agents available that allow left ventricular cavity enhancement, but recent research points to the usefulness of CE for the evaluation of myocardial perfusion in the cardiac catheterization laboratory and operating room. Advances in ultrasound technology, such as transient harmonic imaging and integrated backscatter, coupled with the development of newer contrast agents that contain smaller, more stable microbubbles capable of transpulmonary passage for intravenous injection, promise a vast increase in the applications of CE in clinical practice.


[Therapeutic effect of electroacupuncture combined with medicine on acute rheumatoid arthritis at active stage].
To explore a treatment program for increasing therapeutic effect on rheumatoid arthritis at active stage. One hundred and forty-six cases were randomly divided into treatment group (n = 74) and medicine control group (n = 72). The treatment group were treated by electroacupuncture at Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), etc. , combined with meloxicam, sulfasalazine and MTX. The control group treated by simple the Western medicines. Their therapeutic effects were compared. The effective rate was 79.73% in the treatment group and 51.39% in the control group with a significant difference between the two groups (P< 0. 05). Electroacupuncture combined with medicine has a better therapeutic effect than the simple medicine on rheumatoid arthritis at active stage.


Primary leiomyosarcoma of the anterior mediastinum.
Primary mediastinal leiomyosarcoma are extremely rare tumors, which develop from smooth muscle, usually in the esophagus or main vessels. Very few cases have been reported in the literature and only two of these developed from small vessels in the soft tissue of the anterior mediastinum. We report on a 45-year-old man who presented with a huge anterior mediastinal tumor. The tumor was surgically removed with right thoracotomy and the diagnosis of well-differentiated leiomyosarcoma was established. It probably originated from the anterior mediastinal tissue, so at operation a continuity was not found between the tumor and neighboring structures. This rare and interesting histopathology is discussed and the literature is reviewed.


Cell-to-cell and cell-to-matrix interactions mediate chemokine expression: an important component of the inflammatory lesion.
Although many studies have characterized soluble factors that stimulate or inhibit chemokine secretion, in this review we focus on the event of cellular adhesion as a novel mechanism for stimulating chemokine expression. Recent work has demonstrated chemokine expression following cell-to-cell and cell-to-matrix adhesion. The specificity of this finding was demonstrated utilizing various techniques that illustrate that adhesion, and not a soluble stimulus, is in some cases responsible for initiating or augmenting chemokine expression. For example, co-cultures of peripheral blood monocytes and endothelial cells secreted elevated levels of IL-8 and MCP-1 compared with either cell type alone. When co-cultured in transwells, this effect was significantly attenuated. In other experiments, neutralizing monoclonal antibodies to various adhesion molecules inhibited chemokine expression. The effects of adhesion were not limited to leukocytes. Both immune and non-immune cell types were evaluated as potential sources of adhesion-mediated chemokine expression. Not suprisingly, expression of some chemokines was associated with adhesion, whereas others were not, supporting the notion that adhesion differentially signals chemokine secretion during the inflammatory response. We hypothesize that as a recruited leukocyte encounters different adhesion substrates such as endothelial cells, basement membrane, extracellular matrix, and fibroblasts, the expression of chemokines from both the leukocyte and the substrate may be initiated, inhibited, or augmented. Careful characterization of the contribution of adhesion to regulation of chemokine expression will provide insight into the pathogenesis of many human diseases where chemokines have a central role.


Monoclonal gammopathy of undeterminated significance and endoneurial IgG deposition: A case report.
Monoclonal gammopathy of undeterminated significance is the most common form of plasma cell dyscrasia, usually considered as benign. In rare cases it may have a malignant course, sometimes limited to an organ such as peripheral nerves. We describe clinical, electrophysiological and pathological findings in a patient presenting a immunoglobulin G (IgG) paraproteinemic polyneuropathy clinically mimicking a chronic inflammatory demyelinating polyneuropathy. Immuno-electron microscopy (immune-EM) demonstrated that the widenings of the myelin lamellae resulted from the infiltration of IgG between a significant number of myelin lamellae (with absence of inflammatory cells in the epineurium, endoneurium, and perineurium, and the lack signs of vasculitis). This patient was finally treated successfully with lenalidomide then mycophenolate mofetil. In polyneuropathies associated to a monoclonal gammopathy, a nerve biopsy may clinch the diagnosis. Immuno-EM may be required to determine the role of the pathological immunoglobulin in the destruction of the peripheral nerve parenchyma. Diagnosis of such a direct involvement of peripheral nerve can endorse more aggressive treatment of real efficiency.


Postural orthostatic tachycardia syndrome: a rare complication following electrical injury.
We report on two previously healthy patients who developed severe form of postural orthostatic tachycardia syndrome (POTS) following an electric injury. Both the patients developed symptoms of orthostatic intolerance in the form of dizziness, fatigue, lightheadedness, and palpitations, weeks to months after electrical injury. Orthostatic intolerance produced considerable functional impairment in these patients. Early recognition of POTS when it occurs after an electrical injury allows for prompt evaluation and management to occur.


A conserved acetyl esterase domain targets diverse bacteriophages to the Vi capsular receptor of Salmonella enterica serovar Typhi.
A number of bacteriophages have been identified that target the Vi capsular antigen of Salmonella enterica serovar Typhi. Here we show that these Vi phages represent a remarkably diverse set of phages belonging to three phage families, including Podoviridae and Myoviridae. Genome analysis facilitated the further classification of these phages and highlighted aspects of their independent evolution. Significantly, a conserved protein domain carrying an acetyl esterase was found to be associated with at least one tail fiber gene for all Vi phages, and the presence of this domain was confirmed in representative phage particles by mass spectrometric analysis. Thus, we provide a simple explanation and paradigm of how a diverse group of phages target a single key virulence antigen associated with this important human-restricted pathogen.


Artificial intelligence for a personalized diagnosis and treatment of atrial fibrillation.
Although atrial fibrillation (AF) is the most common cardiac arrhythmia, its early identification, diagnosis, and treatment is still challenging. Due to its heterogeneous mechanisms and risk factors, targeting an individualized treatment of AF demands a large amount of patient data to identify specific patterns. Artificial intelligence (AI) algorithms are particularly well suited for treating high-dimensional data, predicting outcomes, and eventually, optimizing strategies for patient management. The analysis of large patient samples combining different sources of information such as blood biomarkers, electrical signals, and medical images opens a new paradigm for improving diagnostic algorithms. In this review, we summarize suitable AI techniques for this purpose. In particular, we describe potential applications for understanding the structural and functional bases of the disease, as well as for improving early noninvasive diagnosis, developing more efficient therapies, and predicting long-term clinical outcomes of patients with AF.


Cardiorenal Syndrome: New Pathways and Novel Biomarkers.
Cardiorenal syndrome (CRS) is a multi-organ disease characterized by the complex interaction between heart and kidney during acute or chronic injury. The pathogenesis of CRS involves metabolic, hemodynamic, neurohormonal, and inflammatory mechanisms, and atherosclerotic degeneration. In the process of better understanding the bi-directional pathophysiological aspects of CRS, the need to find precise and easy-to-use markers has also evolved. Based on the new pathophysiological standpoints and an overall vision of the CRS, the literature on renal, cardiac, metabolic, oxidative, and vascular circulating biomarkers was evaluated. Though the effectiveness of different extensively applied biomarkers remains controversial, evidence for several indicators, particularly when combined, has increased in recent years. From new aspects of classic biomarkers to microRNAs, this review aimed at a 360-degree analysis of the pathways that balance the kidney and the heart physiologies. In this delicate system, different markers and their combination can shed light on the diagnosis, risk, and prognosis of CRS.


Bimetallic anilido-aldimine Al or Zn complexes for efficient ring-opening polymerization of epsilon-caprolactone.
Four bimetallic Al or Zn complexes supported by anilido-aldimine ligands (o-C6H4(NHAr)-CH=N)2CH2CH2 (Ar = 2,6-Me2C6H3,L1H2; Ar = 2,6-iPr2C6H3, L2H2) have been synthesized and characterized. Treatment of L1H2 or L2H2 with two equiv. of AlMe3 gives bimetallic complex L1(AlMe2)2 1 or L2 (AlMe2)2 2, respectively. Reaction of L1H2 or L2H2 with two equiv. of ZnEt2 leads to bimetallic complex L1(ZnEt)2 3 or L2(ZnEt)2 4, respectively. All of the complexes 1-4 are efficient catalysts for ring-opening polymerization of epsilon-caprolactone (CL) in the presence of benzyl alcohol and catalyze the polymerization of CL in living fashion yielding polymers with a narrow polydispersity index. The activity of bimetallic Zn complexes 3 and 4 is higher than bimetallic Al complexes 1 and 2.


[Expression of tumor suppressor gene PTEN in laryngeal carcinoma and its clinical significance].
To investigate the expression of tumor suppressor gene PTEN in laryngeal carcinoma and study its clinical-pathological implication and its clinical significance. The expression of PTEN was detected by immunohistochemistry SP(Streptavidin peroxidase) method in 68 cases of laryngeal carcinoma, 33 cases of adjacent normal laryngeal mucosa. (1) There was 61.8% (42 of 68) of cases with expression of PTEN in the tumor tissues, and 100.0% of cases (33 of 33) with the expression of PTEN in the normal mucosa. The positive expression of PTEN in the laryngeal carcinoma gorp was remarkably lower than that in the control group. ( P <0.01). (2) The positive expression of PTEN in high and middle degree of differentiation group was significantly higher than that in low degree of differentiation(79.3% vs 48.7%). Tumors with lymph node metastases(55.0%) had less PTEN protein expression than those without metastasis(71.4%) (P <0.05). As for the PTEN expression between I + II stage and III + IV stage, the difference was significant (76.0% vs 53.5%)(P <0.05). The positive rates of PTEN decreased with clinical stage, the poor differentiation, deep invasion and lymph nodes metastasis ( P <0.05). PTEN protein expression had no relation to the patients' age, sex, tumor size and location (P >0.05). PTEN gene plays an important role in the occurrence and development of laryngeal carcinoma. It is suggested that PTEN can be a useful marker for predicting invasion and metastasis ability of laryngeal carcinoma.


Determination of the primary structure of an alpha-amylase inhibitor from wheat kernel by Edman degradation and fast atom bombardment mass spectrometry.
The primary structure of an alpha-amylase inhibitor (coded 0.39) from wheat kernel was determined by fast atom bombardment mass spectrometry and Edman degradation. The sequence is similar to an extent of 97% compared to the other major component of the monomeric isoinhibitor family coded 0.28. The differences consist of the substitution of a single residue and the deletion of two residues in inhibitor 0.39. Neither heterogeneity nor polymorphism were observed in the primary structures of the inhibitors.


Comparative Transcriptomics Reveals the Expression Differences Between Four Developmental Stages of American Cockroach (Periplaneta americana).
The globally distributed American cockroach (Periplaneta americana) is considered a pest, but it has been widely used in traditional Chinese medicine. In the past, the American cockroach's genome and transcriptomes were sequenced, but the differential expression transcripts between developmental stages were unavailable. We performed the de novo assembly and analysis of American cockroach transcriptomes from four developmental stages. Approximately 200 million high-quality paired-end reads were generated by using Illumina Hiseq 2000 sequencer. The assembly produced 291,250 transcripts with an average length of 714 bp. In addition, 38,052 microsatellites and 11,060,020 transposable elements were identified. Based on sequence homology, 53,262 transcripts were annotated. After calculating the expression levels of all the transcripts, we found that 13 transcripts were highly expressed in all the samples and at least two, p10 and actin-related protein 1, played important roles during development. A total of 7954 differentially expressed transcripts (DETs) were identified. The adult had the largest number of DETs when compared to other samples (4818), while the 3rd and 8th larva had the least number of DETs (1332). We performed gene enrichment analysis with the DETs, and some interesting results were detected in the different groups. For example, chitin is the major component of the insect exoskeleton, and the chitin-related genes in larvae and new molted samples had higher expression levels than in adults. In addition, the enrichment analysis detected many chitin-related pathways. Our study performed the first large-scale comparative transcriptomics between the developmental stages of American cockroach, which could provide useful gene expression data for future studies.


Abrasive wear on the atomic scale.
A scanning force microscope in ultrahigh vacuum has been used to realize and detect atomic-scale abrasion on KBr(001). The continuous time evolution of the lateral force under scratching reveals that the wear mechanism is due to the removal and the rearrangement of single ion pairs. The debris is reorganized in regular terraces with the same periodicity and orientation as the unscratched surface, as in local epitaxial growth. The applied load has a strong influence on the abrasive process, whereas the scan velocity is less relevant.


Small intestinal submucosa plug for closure of dilated nephrostomy tracts: a pilot study in swine.
The aim of this study was to evaluate efficacy of a plug made of small intestinal submucosa (SIS) for closure of dilated nephrostomy tract in the kidney after nephroscopy. Ten kidneys in 5 swine had nephrostomy tracts dilated up to 8 mm. The SIS plug was placed into the dilated renal cortex under nephroscopic control. Follow-up arteriograms, retrograde pyelograms, and macroscopic and histologic studies at 24 h (n = 4), 6 weeks (n = 2), and 3 months (n = 4) were performed to evaluate the efficacy of the plug. The SIS plug effectively closed the dilated nephrostomy tract. Follow-up studies showed minimal changes of the kidneys, except for 1 small infarction, regarding inflammatory and foreign-body reactions and progressive scarring of the SIS. SIS plug is effective for occlusion of dilated nephrostomy tract after nephroscopy. Its efficacy should be compared with other therapeutic options.


Evaluation of acute coronary syndromes by cardiac magnetic resonance imaging.
The use of cardiovascular magnetic resonance (CMR) imaging for the evaluation of patients with acute chest pain and acute coronary syndromes has great potential. The strength of CMR relies on its ability to provide information on anatomy, physiology, and function in a single scanning session in a noninvasive manner without the need for iodinated contrast, radiation, or the need to undergo invasive procedures. Specifically, with regard to imaging patients with acute chest pain and/or myocardial infarction (MI), CMR has the ability to qualitatively and quantitatively evaluate global and regional right and left ventricular systolic functions, myocardial edema, myocardial perfusion, and myocardial infarct size and transmurality/viability. This review will focus on CMR imaging for the following applications: (1) imaging for the evaluation of ventricular function and infarct size in patients with acute chest pain and/or acute MI, (2) for triage and prognosis of patients presenting to the emergency department with acute chest pain, (3) for evaluating patients after sustaining an acute MI, and (4) for stem cell research.


Prophylactic and therapeutic effects of phosphonoformate against feline leukemia virus in vitro.
Phosphonoformate (PFA), a noncompetitive inhibitor of reverse transcriptase (RT), inhibited feline leukemia virus (FeLV) infection of 2 feline cell lines and inhibited progeny virus RT activity in a chronically FeLV-infected cell line. Feline leukemia virus infection of 3201 cells, an FeLV-negative lymphoma cell line, was inhibited by greater than 70% at a concentration of only 1 microM PFA and by greater than 90% at concentrations of 64 to 256 microM PFA, as evidenced by RT activity. However, FeLV antigen expression by 3201 cells remained relatively constant over noncytotoxic concentrations of PFA. Because the persistence of viral antigen expression with concomitant suppression of RT activity appears to be unique and because 3201 cells express small amounts of an endogenous retrovirus (RD-114) and contain endogenous FeLV proviral sequences, a possible role of endogenous retroviruses acting as helper viruses was suggested. Feline leukemia virus infection of 81C cells, a sarcoma-positive, leukemia-negative fibroblast cell line, was inhibited by greater than 50% at a concentration of 64 microM PFA and by greater than 98% at concentrations of 256 to 512 microM PFA, as indicated by suppression of focus formation. The feline lymphoid cell line FL-74 is a large producer of FeLV. When FL-74 cells were cultured in the presence of 256 microM PFA, virus production (virus budding and viral antigen) was not affected, but progeny virus lost RT activity and infectivity. Direct addition of PFA (256 microM) to FeLV also reduced RT activity and infectivity. These data indicate that PFA can directly and rapidly inactivate retrovirus independent of cellular processing, presumably by inhibiting RT.(ABSTRACT TRUNCATED AT 250 WORDS)


Endoplasmic reticulum stress in UMOD-related kidney disease: a human pathologic study.
Mutations of the UMOD gene, which encodes the uromodulin protein, are associated with tubulointerstitial nephritis and hyperuricemia. UMOD mutations impair uromodulin folding, resulting in its retention within the endoplasmic reticulum (ER) of renal tubular cells. The aim of this study was to investigate whether mutant uromodulin accumulation in epithelial tubular cells is associated with ER stress. We characterized tubular expression of uromodulin and the ER stress surrogate marker Grp78 by immunohistochemistry in kidney biopsy specimens from 7 patients with UMOD-related kidney disease. We compared this population with 5 patients with familial tubulointerstitial nephritis not related to UMOD mutation. All biopsy specimens from patients carrying the UMOD mutation showed strong heterogeneous cytoplasmic expression of uromodulin in cells of the thick ascending limb of the loop of Henle. In the same tubules, Grp78 was highly expressed in a perinuclear pattern. In contrast, in all kidney biopsy specimens from patients without UMOD mutations, uromodulin staining showed normal apical expression and Grp78 expression was not increased. Our observations support the hypothesis that ER accumulation of mutant uromodulin may cause ER stress, providing a potential mechanism for the progression of UMOD-related kidney disease.


Friends of adolescent suicide attempters and completers.
Friends of adolescent suicide attempters and suicide completers were compared with students who had low exposure to suicide on a range of preexposure, concurrent, and outcome variables. Subjects who were friends of both suicide attempters and completers (N = 84) differed significantly from the low-exposure group (N = 554) on most variables examined. Friends of suicide completers only (N = 68) and attempters only (N = 92) did not differ from one another; however, the latter group reported significantly higher levels of current depression and suicidal behavior than the low-exposure group. Greater attention needs to be paid to friends of suicide attempters in the development and evaluation of suicide prevention strategies.


Effects of NO-donors on thrombus formation and microcirculation in cerebral vessels of the rat.
Sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 micrograms/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 micrograms/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction.


Evaluating the reliability of specific and global methods to assess the phenolic content of virgin olive oil: Do they drive to equivalent results?
Despite the huge number of different published methodologies, there is an open debate regarding which one is the most convenient analytical strategy for the determination of phenolic compounds from virgin olive oils. Diverse technical issues together with the disparity of criteria regarding results expression cause a lot of confusion. Herewith, a systematic comparison between specific (a powerful and LC-MS method) and global methodologies (the Folin-Ciocalteau (FC) colorimetric assay, the International Olive Council (IOC) method and hydrolysis plus HPLC-DAD) has been carried out. Thus, these strategies have been applied to the analysis of 50 extra virgin olive oils (covering all the possible quantitative ranges of these substances). This is the first time in which the individual LC-MS quantification of so many phenolic substances is included in this kind of comprehensive comparison. The outcomes of all the strategies have been thoroughly confronted and their equivalence (or divergence) has been carefully evaluated, establishing possible correspondence factors. The LC-MS individual determination with the pure standard of every analyte represented the ideal situation; when only the commercially available standards were used, a drastic change was observed in the absolute concentrations of oleuropein derivatives (in terms of hydroxytyrosol). Total phenolic content (summing individual levels) proved to be higher (1.9-3.0 times when data was expressed in mg/kg) than the values given by the three non-specific methods (with R2 from 0.84 to 0.90). In any case, the IOC method, the FC assay and the hydrolysis approach could be considered as feasible strategies when a global value is pursued. Good correlations between their results were found (R2 > 0.89), with the following equivalence factors: FC(mg caffeic acid/kg) ≈ 0.60 IOC(mg TY/kg); IOC(mg TY/kg) ≈ 1.27 Sum acid hydrolysis(mg TY+HTY/kg); FC(mg HTY/kg) ≈ 1.04 Sum acid hydrolysis(mg TY+HTY/kg).


The era of biomarkers and precision medicine in colorectal cancer: an interview with Ajay Goel.
In this interview, Professor Ajay Goel speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of epigenetic biomarkers in colorectal cancer. Ajay Goel, PhD, is a Professor and Founding Chair of the Department of Molecular Diagnostics, at the Beckman Research Institute and Associate Director of Basic Science at the City of Hope comprehensive Cancer Center. He also serves as Director of Biotech Innovations at the City of Hope, Duarte, CA, USA. Dr Goel has spent more than 25 years researching cancer and has been the lead author or contributor to more than 350 scientific articles published in peer-reviewed international journals and several book chapters. He is also a primary inventor on more than 40 international patents aimed at developing various disease biomarkers or therapeutic targets for gastrointestinal cancers. He is currently using advanced genomic, epigenomic and transcriptomic approaches to develop novel circulating, liquid biopsy-based biomarkers (e.g., cell-free nucleic acids, exosomes) for the early detection, prognosis and determination of predictive responses to chemotherapy and targeted drugs in gastrointestinal (GI) cancers. In addition, his group is interested in the identification of novel therapeutic targets, particularly immune therapy, for various GI cancers. His research also involves understanding the role of gut microbiome, health disparities and the prevention of GI cancers using integrative and alternative approaches. Dr Goel is a member of the American Association for Cancer Research, American Society of Clinical Oncology and the American Gastroenterology Association. He is on the international editorial boards of several journals, including Gastroenterology, Clinical Cancer Research, Carcinogenesis, PLoS ONE, Molecular Carcinogenesis, Scientific Reports, Epigenomics, Future Oncology, Alternative Therapies in Heath and Medicine, Digestive Diseases and Sciences, and Molecular Therapy Oncolytics. He is also actively involved in peer-reviewing activities for more than 100 international scientific journals and various grant review panels of various national and international funding organizations. His research has been actively funded by various private and federal organizations, including the National Cancer Institute at the NIH, American Cancer Society and state organizations. He has won more than a dozen national and international awards and honors and has been invited for visiting professorships by various national and international academic institutions and academic bodies.


Antiproliferative effects of antisense oligonucleotides directed to the RNA of c-myc oncogene.
Several groups have reported the use of antisense oligonucleotides to inhibit c-myc gene expression and study its biological role. However high concentrations of free oligonucleotides were generally needed. To lower their concentration and stabilize the antisense effect against c-myc, oligonucleotides were covalently linked to poly(L-lysine) and administered in ternary complexes formed with heparin (100 micrograms/ml). A sequence specific growth inhibition was observed at concentrations lower than 1 microM, while oligonucleotide-poly(L-lysine) conjugates alone were inefficient. Similar results occurred with other polyanionic compounds. Inhibition of proliferation was correlated to a reduction of c-myc protein and to a transient decrease in c-myc mRNA level. However, implication of RNase H in this process could not be demonstrated.


Tonsil-derived stem cells as a new source of adult stem cells.
Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, T-SCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.


Zooming in and zooming out of the attentional focus: an FMRI study.
Visuospatial attention can either be "narrowly" focused on (zooming in) or "widely" distributed to (zooming out) different locations in space. In the current functional magnetic resonance imaging study, we investigated the shared and differential neural mechanisms underlying the dynamic "zooming in" and "zooming out" processes while potential distance confounds from visual inputs between zooming in and zooming out were controlled for. When compared with zooming out, zooming in differentially implicated left anterior intraparietal sulcus (IPS), which may reflect the functional specificity of left anterior IPS in focusing attention on local object features. By contrast, zooming out differentially activated right inferior frontal gyrus, which may reflect higher demands on cognitive control processes associated with enlarging the attentional focus. A conjunction analysis between zooming in and zooming out revealed significant shared activations in right middle temporal gyrus, right superior occipital gyrus, and right superior parietal cortex. The latter result suggests that the right posterior temporal-occipital-parietal system, which is known to be crucial for the control of spatial attention, is involved in updating the internal representation of the spatial locations that attentional processing is associated with.


Validation of Three-dimensional Electronic Portal Imaging Device-based PerFRACTION™ Software for Patient-Specific Quality Assurance.
PerFRACTION™ is a three-dimensional (3D) in vivo electronic portal imaging device-based dosimetry software. To validate the software, three phantoms with different inserts (2D array, ionization chamber, and inhomogeneity materials) were constructed to evaluate point dose and fluence map. Phantoms underwent independent computed tomography simulation for planning and received repetitive fractions of volumetric modulated arc therapy, simulating prostate treatment. Fluence and absolute point dose measurements, PerFRACTION™ reconstructed doses, and the dose predictions of the planning system were compared. There was concordance between ionization chamber and PerFRACTION™ 3D absolute point dose measurements. Close agreement was also obtained between X- and Y-axis dose profiles with PerFRACTION™ calculated doses, MapCHECK measured doses, and planning system predicted doses. Setup shifts significantly influenced 2D gamma passing rates in PerFRACTION™ software. PerFRACTION™ appears reliable and valid under experimental conditions in air and with phantoms.


Dual-competitive lateral flow aptasensor for detection of aflatoxin B1 in food and feedstuffs.
A novel dual-competitive lateral flow aptasensor (LFA) benefited from aptamer and lateral flow strips was first designed by using aflatoxin B1 (AFB1) as the model target. In this LFA assay, the target AFB1 competed with AFB1-hapten at T line for binding to Cy5-labeled AFB1 aptamer and the complementary strand competed with the target AFB1 for binding to Cy5-labeled AFB1 aptamer at C line. The ratio of their fluorescent intensities at the T line and C line (ST/SC ratio) was employed in order to increase the sensitivity for target AFB1 detection. This technique has the limit of detection (LOD) of 0.1ng/mL for AFB1 within the linear range from 0.1ng/mL to 1000ng/mL. Subsequently, the LFA approach was validated using 11 kinds of food and feedstuff samples with a simple aqueous extraction protocol. The test results with different naturally contaminated feedstuffs indicated a good correlation between this LFA and a commercial ELISA kit. The assay can be completed within 20min and its sensitivity, specificity and reproducibility are highly satisfactory. This is the first LFA that has been rigorously validated, which will be greatly beneficial to development of commercial aptamer-based biosensors for food safety, environmental analysis, particularly in clinical diagnosis.


[Textual study of ginseng in Wupu Bencao].
In the study of materia medica literature, we found of ginseng in Wupu Bencao that "Leaf is a little sharp, root is black and stem is pilous" had been ignored by its subsequent literatures. In this study, the variety of ginseng in Wupu Bencao was researched. We believed the remaining records of ginseng in Wupu Bencao referred to Oplopanax elatus instead of Panax ginseng. The origin of this species was in Handan during the period of three-kingdom dynasty, but distributed in the area of Changbai mountain nowadays.


[Strategy of points, lines and layers in needle assisted laparoscope functional modified neck dissection through bilateral breast approach].
The incidence of papillary thyroid carcinoma is growing rapidly. Especially in young patients, the patients have high demand for better cosmetic effect and less psychological trauma. The application of laparoscope technique in papillary thyroid carcinoma surgery should meet the needs of patients. The development of needle assisted technique make it easy to access the neck potential fascial spaces, and provide the basic instrument for laparoscope modified neck dissection. The application of needle assisted techniques mainly include suture suspension and V type needle retractor, MiniLap, 3 mm laparoscopic apparatus. Indications of this procedure is very important, and it is necessary to make full use of the "critical points" , "mark lines" and "fascia layers" to precise positioning in the operation. Furthermore, the levels of dissection must be determined based on the pattern of cervical lymph node metastasis in differentiated thyroid carcinoma, that will make the surgical procedures more safety.


Feasibility of closed-loop controller for righting seated posture after spinal cord injury.
Spinal cord injury (SCI) can compromise the ability to maintain an erect seated posture. This study examined the feasibility of a sensor-based threshold controller to automatically modulate stimulation to paralyzed hip and trunk extensor muscles to restore upright sitting from forward leaning postures. Forward trunk tilt was estimated from the anterior-posterior component of gravitational acceleration sensed by a sternum-mounted wireless accelerometer. Stimulation increased if trunk tilt exceeded a specified flexion threshold and ceased once upright sitting was resumed. The controller was verified experimentally in five volunteers with SCI and successfully returned all subjects to upright postures from forward leaning positions. Upper-limb effort exerted while returning to erect posture was significantly reduced (to 7.4% +/- 3.7% of body mass) pooled across all volunteers while using the controller compared with using continuous and no stimulation (p < 0.03). Controller response times were consistent among subjects when applied while sitting with (0.30 +/- 0.05 s) or without a backrest (0.34 +/- 0.11 s). The controller enabled volunteers to lean farther forward (59.7° +/- 16.4°) in wheelchairs without upper-limb effort than with no stimulation. Clinical utility of the system for facilitating reach or preventing falls remains to be determined in future studies.


The Effects of Manual Acupuncture on Mitochondrial Fusion and Fission Gene Expression in Rat Spleen.
A significant amount of research has been conducted to establish the validity of acupuncture, and it has been demonstrated through animal disease model studies that acupuncture influences mitochondrial changes. However, to more accurately examine the mechanisms of acupuncture treatment effectiveness in pathological models, it is crucial to investigate changes in disease-free animals. Among various hypotheses regarding the effects of acupuncture on the body, we focused on the result that acupuncture stimulation is related to mitochondria. We examined the effects of acupuncture mitochondrial fission and fusionrelated mediators in disease-free Sprague Dawley (SD) rats' spleen meridian acupoints. SD rats were divided into control, SP1, SP2, SP3, SP5, and SP9 acupuncture groups. Acupuncture was performed at each point for 10 minutes daily for four days. Peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC-1α) and fission protein 1 (Fis1) levels were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), while dynamin-related protein 1 (DRP1), optic atrophy-1 (OPA1), mitofusin-1 (MFN1), and mitofusin-2 (MFN2) levels were assessed via western blotting. Mitochondria protein concentrations and NADH dehydrogenase activity in spleen tissues were measured using enzyme-linked immunosorbent assay (ELISA). PGC-1α expression decreased in the SP1 (p < 0.01), SP5 (p < 0.05), and SP9 (p < 0.05) groups, while Fis1 expression increased in the SP1 (p < 0.01), SP5 (p < 0.01), and SP9 (p < 0.05) groups. DRP1, OPA1, MFN1, and MFN2 levels exhibited no significant changes. Mitochondrial protein concentrations decreased in the SP2 (p < 0.01), SP3 (p < 0.01), SP5 (p < 0.01), and SP9 (p < 0.01) groups, while NADH dehydrogenase activity decreased in the SP2 (p < 0.05) and SP9 (p < 0.05) groups. Acupuncture at the SP9 acupoint influenced the mitochondrial fission pathway by modulating PGC-1α and Fis1 mediators in the rat spleen under non-disease conditions.


Soil Temperature Influences on Root Resistance of Pinus contorta Seedlings.
The influence of low temperature in the root zone on water uptake in lodgepole pine (Pinus contorta Dougl. ex Loud.) was studied under laboratory conditions. To remove soil hydraulic influences, two-year-old seedlings were transferred to solution cultures and maintained in temperature controlled water baths. Short term measurements of leaf conductance, leaf water potential and tritiated water movement were taken at root temperatures from 22 C down to 0 C. Root resistance was calculated to be 67% of total plant resistance at 7 C and 93% at 0 C. In addition an Arrhenius break was found in a plant resistance versus temperature plot, suggesting a significant change with temperature in the membrane pathway in the root water uptake system.


Spacers' role in the dynamics of hyperbranched polymers.
We investigate hyperbranched polymers (HBPs) and highlight the relation between their architecture and their viscoelastic behavior, while paying special attention to the role of the chainlike spacer segments between branching points. For this we study the dynamics of HBP in solution, based on the generalized Gaussian structure formalism, an extension of the Rouse model, which disregards hydrodynamical and excluded volume effects. For HBP the dynamical effects display, beside the obvious contributions of localized modes on the spacers, also remarkable features, as we highlight based on the exact renormalization procedure recently developed by us in J. Chem. Phys. 123, 034907 (2005). We exemplify these features by analyzing the dynamics of randomly linked star polymers and study the impact both of the length and of the spacers' mobility on the normal modes' spectra. We compute these modes both by numerical diagonalization and also by employing our renormalization procedure; the excellent agreement between these methods allows us to extend the range of investigations to very large HBP.


Endovascular treatment of idiopathic intracranial hypertension caused by multiple venous sinus stenoses.
Idiopathic intracranial hypertension (IIH) shows symptoms by elevating intracranial pressure. Although sinus stenosis has been detected in many patients with IIH, the role of sinus stenosis in IIH remains obscure. Endovascular treatment for IIH due to transverse sinus stenosis has been frequently documented; however, IIH due to multiple sinus stenoses including the superior sagittal sinus (SSS) is rare. Here, we report a case of IIH due to multiple sinus stenoses treated by sinus stenting. A 47-year-old woman suffered from intractable headache with IIH presented with stenosis of the right transverse and SSS. Stent placement was carried out since intracranial hypertension and trans-stenotic cerebral venous pressure gradient (CVPG) were presented, and her intractable headache disappeared. IIH can be caused by venous sinus stenoses and stent placement could be an appropriate treatment in patients who demonstrated a CVPG.


The co-ordination chemistry of bis(2,2'-bipyrid-6'-yl)ketone with first row transition metals: the reversible interconversion of a mononuclear complex and a dinuclear hemiketal containing species.
Bis(2,2'-bipyrid-6'-yl)ketone has been shown to co-ordinate to Zn(II) to form either a dinuclear hemiketal complex in methanol solutions or mononuclear complexes in acetonitrile. The ligand readily complexes to the late transition metals in acetonitrile to yield mononuclear complexes (Mn(II), Co(II), Ni(II),Zn(II) and Cd(II)) however for Fe(II) only dinuclear complexes [Fe(2){(2-bipy)(2)C(OMe)O(-)}(2)][ClO(4)](2) could be isolated. The solid state structures of the mononuclear complexes exhibit varying degrees of distortion compared to an anticipated planar array of bipyridyl donors.


Liver Transplantation as Definitive Treatment of Post-cholecystectomy Bile Duct Injury: Experience in a High-volume Repair Center.
To analyze the perioperative and long-term outcomes of patients undergoing LT due to BDI in a tertiary care center. BDI is associated with significant morbidity and long-term impact on quality of life. LT represents the only possibility of a cure in patients with BDI who develop SBC. Retrospective cohort study from a prospective LT database. Between 2008 and 2019, patients with SBC due to BDI after cholecystectomy and requiring LT were identified. Perioperative and long-term outcomes were analyzed. Among 354 LT, 12 patients underwent LT to treat post-cholecystectomy BDI and accounted for 3.4% of all LT. The median time from BDI to SBC diagnosis was 9.3 years (2.4-14). The mean time from SBC to inclusion on the waitlist was 2.4years (± 2.2). Postoperative complications occurred in 11 patients (91.6%); mainly infectious (9/12 patients, 75%), followed by renal complications (4/12 patients, 33.3%). Only 2 patients developed major complications, which were the patients who died, resulting in a 90-day mortality of 16.7%. After a mean follow-up of 40.3 months (± 42.2) survival at 1, 3, and 5 years was 83%. Although BDI is an unusual indication for LT worldwide, it accounted for 3.4% of all LT in our center. Although postoperative mortality remains high, LT is the only possibility of a cure, with acceptable long-term outcomes. Early referral to a tertiary care center is essential to avoid long-term complications of BDI, such as SBC.


Metabolism and distribution of cyclohexanecarboxylic Acid, a plant growth stimulant, in bush bean.
A foliar spray of 10 mm cyclohexanecarboxylic acid (CHC), a component of the growth stimulant naphthenic acid, to primary leaves of 14-day-old plants of bush bean, Phaseolus vulgaris L., cv Top Crop, resulted in increased vegetative growth and pod production. One minute after the application of 0.5 mm CHC-7-(14)C (CHC(*)) to a primary leaf, CHC(*) was present within it. The chief conversion of the CHC(*) in the leaf during the interval 15 minutes to 4 hours after the acid had been applied appeared to be CHC(*) to its glucose conjugate (CHC(*)-G), and during 4 to 48 hours, CHC(*)-G to CHC(*)-aspartate and an unknown metabolite. Radioactivity was confined to the leaf for at least 1 hour, but by the 12th hour was detected throughout the plant. In the interval 1 to 4 weeks after CHC(*) application, the mean percentage distribution of radioactivity was: treated leaf, 65.3; roots, 18.8; stem, 7.7; trifoliate leaves, 5.9; flower buds-flowers-pods, 2.3. During this period CHC(*)-G was the most prominent metabolite in all organs; no free CHC(*) was detected. Light favored the movement of CHC(*) conjugates out of the leaf; glucose fed to dark-grown plants substituted for light to some extent but aspartate was relatively ineffective, suggesting the dependence of outward movement on ATP. The presence of the glucose and aspartate conjugates of the acid in all organs of CHC-treated plants and the absence of free CHC from them suggest that one or both conjugates, rather than the acid itself, are involved in growth stimulation.


Levamisole synergizes experimental F4ac+ Escherichia coli oral vaccine in stimulating ileal Peyer's patch T cells in weaned pigs.
Recent findings demonstrate that priming by levamisole of weaned pigs experimentally vaccinated against postweaning colibacillosis (PWC) contributes to immune protection from challenge-induced clinical disease through stimulation of the mesenteric lymph node cells that participate in cell-mediated immunity. With the objective of better understanding the mechanisms by which levamisole induces protective mucosal cell-mediated immune response to vaccination against PWC, it was tested whether the drug synergizes experimental F4ac+ Escherichia coli oral vaccine in stimulating T cells also in the jejunal lamina propria (JLP) and ileal Peyer's patch (IPP) upon virulent challenge. Commercial crossbred pigs weaned at 4 weeks were allocated into two equal groups. The experimental group was i.m. primed with levamisole at an immunostimulatory dose of 2.5 mg/kg once daily, for 3 consecutive days, and controls received saline. Both groups were vaccinated orally with the vaccinal E. coli strain on day 0 and challenged with the virulent E. coli strain 7 days later. All pigs were killed on postchallenge day 6. The results determined by immunophenotyping of isolated cells indicate that priming by levamisole of the vaccinated weaned pigs selectively recruited and activated T cells in the IPP, a lymphoid organ-generating B lymphocytes. The pig IPP is normally populated with up to 5% of CD3+ T cells and CD6 is an activation antigen expressed exclusively by T cells in swine. Therefore, a significantly higher number of CD3+ (P < 0.01) and CD6+ (P < 0.001) cells observed within the IPP follicles of the primed-vaccinated vs. unprimed-vaccinated challenge-infected pigs suggest enhanced T cell-mediated immunity in this B-cell compartment induced by the potentiating action of the drug and vaccine. The ability of levamisole to influence interaction between activated T cells and B cells in the IPP of primed-vaccinated weaned pigs, and the possibility that this interaction plays a role in regulating B-cell maturation within the IPP follicles, are discussed.


Phenolic fraction extracted from Kedrostis foetidissima leaves ameliorated isoproterenol-induced cardiotoxicity in rats through restoration of cardiac antioxidant status.
In this study, the cardioprotective effects of partially purified phenolic fraction of Kedrostis foetidissima leaves (PFK) were evaluated in isoproterenol (ISO)-induced myocardial infarction rat model. ISO induction to experimental rats for two consecutive days significantly increased the levels of triglycerides, cholesterol, phospholipids, free fatty acids, low-density lipoproteins, and cardiac biomarker enzymes, and decreased the levels of high-density lipoproteins and antioxidant enzyme activity. Pretreatment of experimental rats with PFK for 45 days led to a significant elevation in antioxidant enzyme activity. PFK-pretreated rats exhibited significantly reduced levels of circulating lipids and cardiac-specific biomarker enzymes compared to ISO-treated rats. Thus, the present study demonstrated that PFK ameliorated ISO-induced cardiotoxicity through the augmentation of the endogenous cardiac antioxidant system, thereby modulating the lipid peroxidation caused by ISO-induced free radicals, and prevented the myocardial damage, which was confirmed through histopathological analysis. PRACTICAL APPLICATIONS: Kedrostis foetidissima is edible medicinal plant and phenolic fraction extracted from the leaves of this plant may help the common man in the protection of heart. The phenolic fraction shows significant antioxidant activity, so this might be referred to as dietary supplement and also helps to develop new pharmaceutical formulations.


Future directions of CAM research in pediatric oncology.
Children with cancer are using complementary and alternative medicine (CAM) to relieve symptoms, reduce side effects of treatment, and cope with the emotional aspects of having a life-threatening illness. Parental decisions about using CAM should be based on studies of efficacy and safety. Unfortunately, little evidence of efficacy is available for the majority of CAM therapies. This article discusses the methodological challenges to conducting CAM research in children and the evidence needed to support integrative medicine in pediatric oncology.


An exchange-Coulomb model potential energy surface for the Ne-CO interaction. II. Molecular beam scattering and bulk gas phenomena in Ne-CO mixtures.
Four potential energy surfaces are of current interest for the Ne-CO interaction. Two are high-level fully ab initio surfaces obtained a decade ago using symmetry-adapted perturbation theory and supermolecule coupled-cluster methods. The other two are very recent exchange-Coulomb (XC) model potential energy surfaces constructed by using ab initio Heitler-London interaction energies and literature long range dispersion and induction energies, followed by the determination of a small number of adjustable parameters to reproduce a selected subset of pure rotational transition frequencies for the (20)Ne-(12)C(16)O van der Waals cluster. Testing of the four potential energy surfaces against a wide range of available experimental microwave, millimeter-wave, and mid-infrared Ne-CO transition frequencies indicated that the XC potential energy surfaces gave results that were generally far superior to the earlier fully ab initio surfaces. In this paper, two XC model surfaces and the two fully ab initio surfaces are tested for their abilities to reproduce experiment for a wide range of nonspectroscopic Ne-CO gas mixture properties. The properties considered here are relative integral cross sections and the angle dependence of rotational state-to-state differential cross sections, rotational relaxation rate constants for CO(v=2) in Ne-CO mixtures at T=296 K, pressure broadening of two pure rotational lines and of the rovibrational lines in the CO fundamental and first overtone transitions at 300 K, and the temperature and, where appropriate, mole fraction dependencies of the interaction second virial coefficient, the binary diffusion coefficient, the interaction viscosity, the mixture shear viscosity and thermal conductivity coefficients, and the thermal diffusion factor. The XC model potential energy surfaces give results that lie within or very nearly within the experimental uncertainties for all properties considered, while the coupled-cluster ab initio surface gives results that agree similarly well for all but one of the properties considered. When the present comparisons are combined with the ability to give accurate spectroscopic transition frequencies for the Ne-CO van der Waals complex, only the XC potential energy surfaces give results that agree well with all extant experimental data for the Ne-CO interaction.


Primary intracranial amelanotic melanoma--report of an autopsy case.
Primary intracranial amelanotic melanoma was verified at autopsy in a 38-year-old male. Correct diagnosis of amelanotic melanoma needs electron microscopy or immunohistochemistry, since Masson staining is negative due to the absence of melanin pigment. We adopted the following criteria for clinical use: macroscopically not dark and microscopically negative for Masson staining, but ultrastructurally various melanoma types present. Although the clinical profile of this case is consistent with melanotic melanoma, the more detailed features of primary intracranial amelanotic melanoma require future study.


[Effect of diet therapy using horse meat on liver function of patients with metabolic-alimentary obesity].
The data are provided for the first time about the use of the national food, horse meat, in dietetic management of patients with metabolic-alimentary obesity. Horse meat is characterized by low caloricity, considerable content of full-value protein with an optimally balanced amino acid composition, high content of essential polyunsaturated fatty acids, vitamins, mineral substances. Dietetic management with the use of horse meat, a product that possesses lipotropic and choleretic properties, made in possible to reduce markedly the patients' body mass, with the reduction amounting to 54% of the excess body weight. Furthermore, such a management led to a considerable improvement of liver function. The research data permit the authors to recommend the inclusion of horse meat, a product having a high biological value, into the diets of patients suffering from metabolic-alimentary obesity.


Synthesis of new tetracyclic benzodiazepine-fused isoindolinones using recyclable mesoporous silica nanoparticles.
Pseudo natural products (NPs) feature structural novelty and diversity and thus are a new source of lead compounds for drug discovery. We first report the mesoporous silica nanoparticles (MSNs)-catalyzed de novo combination of benzodiazepine and isoindolinone, giving tetracyclic benzodiazepine-fused isoindolinone pseudo natural products (21 examples, 55-91% yields). The work also demonstrates that MSNs are efficient acidic catalysts for multi-component reactions.


RAS, FLT3, and TP53 mutations in therapy-related myeloid malignancies with abnormalities of chromosomes 5 and 7.
Oncogenic mutations in the KRAS2, NRAS, or FLT3 gene are detected in more than 50% of patients with de novo acute myeloid leukemia (AML). RAS mutations are also prevalent in de novo myelodysplastic syndrome (MDS), especially chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia. However, few studies have examined these genetic lesions in therapy-related myeloid malignancies. Monosomy 7/del(7q) and monosomy 5/del(5q) represent the most common cytogenetic abnormalities in therapy-related MDS and AML (t-MDS/t-AML) and are strongly associated with prior exposure to alkylating agents. Mutational analysis of bone marrow specimens from a well-characterized cohort of 26 t-MDS/t-AML patients with abnormalities of chromosomes 5 and/or 7 revealed 3 with RAS mutations. Further analyses of 23 of these cases uncovered one FLT3 internal tandem duplication and five TP53 mutations. The four patients with RAS or FLT3 mutations had monosomy 7, including one with abnormalities of chromosomes 5 and 7. One specimen demonstrated mutations in both KRAS2 and TP53. RAS and FLT3 mutations, which are thought to stimulate the proliferation of leukemia cells, appear to be less common in t-MDS/t-AML than in de novo AML, whereas TP53 mutations are more frequent.


[Hydrostatic toe pressure measurement: a noninvasive screening method in the diagnosis of arterial occlusive diseases in diabetics and nondiabetics].
To assess whether the hydrostatic toe pressure measurement is a reliable method for diagnosing peripheral arterial vascular disease (PAVD) in diabetics. The systolic anterior tibial artery pressure was measured hydrostatically and by sphygmomanometry in 245 legs of 133 patients (94 males, 39 females; mean age 65 [61-68] years) with PAVD, stages II-IV (staging after Fontaine). 106 were diabetics. In addition the systolic toe pressure was measured hydrostatically and by sphygmomanometry in 155 legs. The sensitivity and specificity of the results in stages III/IV were calculated. Up to 27% of sphygmomanometric anterior tibial pressure measurements (including PAVD stage III/IV) stages could not be evaluated because they were above the measuring limit of 300 mm Hg. 81% of hydrostatic measurements (including PAVD III/IV) were above the 60 mm Hg measuring limit. The hydrostatic systolic pressure was outside the measuring limit of 70 mm Hg only in healthy subjects and those with PAVD < III. Hydrostatically measured systolic pressure < 50 mm Hg in the large toe indicated PAVD > II with a sensitivity of 83% (87% in diabetics) and a specificity of 82% (94% in diabetics). Hydrostatically measured systolic pressure in the large toe of < 50 mm Hg is suitable as a diagnostic criterion for PAVD, stages III -IV.


[Effects of atorvastatin on plasma hypersensitive C-reactive protein and interleukin-6 in patients with acute cerebral infarction].
To observe the effects of different doses of atorvastatin on the plasma hypersensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with acute cerebral infarction. 131 patients with acute cerebral infarction, 73 males and 58 females, aged 63 +/- 11, were randomly divided into 3 groups: Group A (n = 47), with basal treatment; Group B (n = 42), atorvastatin 10 mg was added every night; and Group C (n = 42), atorvastatin 20 mg was added every night. Before the treatment and 7 and 14 days after the treatment the plasma levels of hsCRP and IL-6, fasting plasma levels of lipid, such as total cholesterol (TC) and low density lipoprotein-C (LDL-C), liver functions, such as aspartate aminotransferase (ALT) and alanine transaminase (ALT), creatine kinase (CK), urea nitrogen, were detected. Neurological function deficit was determined. The survival condition was surveyed 6 months after. (1) The TC and LDL-C decreased after treatment in the 3 groups with significant differences between Group A and Group C, Group B and Group C, and Group B and Group C (all P < 0.05). (2) The plasma level of hsCRP decreased by 9.1%, 33.9%, and 30.1% respectively 7 days after treatment in Groups A, B, and C with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. The level of hsCRP decreased by 34.3%, 56.0%, and 52.9% respectively 14 days after treatment in the 3 groups with significant differences between Groups A and B and between Groups A and C (both P < 0.05), however, without significant difference between Group B and Group C. (3) The level of IL-6 decreased 7 and 14 days after treatment in all 3 groups, however, without significant differences between any 2 groups (all P > 0.05). (4) The decrease of hsCRP and decrease of IL-6 were not correlated with the percentage of TC decrease (both P > 0.05) in Group B. The decrease of hsCRP was not correlated with the changes of blood lipids in Group C. (5) Both the plasma hsCRP and IL-6 before treatment were positively correlated with the infection volume and neurological function score (all P < 0.01). Atorvastatin has an anti-inflammatory action benefiting the alleviation of secondary inflammatory damaged in acute cerebral infarction that is independent of lipid lowering.


Septic pulmonary embolism complicated by pyogenic spondylitis and psoas abscesses in a patient with methicillin-sensitive Staphylococcus aureus bacteraemia.
Septic pulmonary embolism (SPE) is a rare condition, indicating bacteraemia. We report a rare case of Staphylococcus aureus bacteraemia causing SPE and multiple abscesses in a previously healthy patient. A previously healthy 33-year-old man presented to our hospital with fever and back pain for 3 weeks. Chest contrast-enhanced computed tomography image was suggestive of SPE, and the blood culture showed methicillin-susceptible S. aureus. Additional focus identification revealed pyogenic spondylitis and abscesses in the psoas muscles. After the 6-week antimicrobial treatment, his clinical condition and image findings improved, and he was discharged. SPE should be considered as a critical consequence of bacteraemia, and early focus identification is essential for appropriate treatment.


The effects of inspiratory muscle training on balance and functional mobility: a systematic review.
Inspiratory muscle training (IMT) has been widely used in both healthy and diseased populations especially in older adults, and its effects have been proven not only on inspiratory muscle strength but also on dyspnea, exercise capacity, quality of life, and other health parameters. This study aims to review the effects of IMT on balance and functional ability of healthy and diseased populations. A systematic literature search was conducted on MEDLINE, EMBASE, AMED, and Cochrane Central Register of Controlled Trials (CENTRAL). Randomized control trials having participants > 18 years of age and having balance and functional mobility as primary or secondary outcomes were included. Two independent reviewers screened studies against the eligibility criteria, extracted the data, and assessed the quality of evidence. The protocol was prospectively registered on PROSPERO: CRD42021261652. Ten studies were included in the review out of which eight had balance and six had functional mobility as an outcome measure. There was a significant improvement in balance of the participants after treatment with IMT, however the effect on functional mobility was inconclusive. The review provided evidence of improvement in balance and functional mobility following inspiratory muscle training in both healthy and diseased adults. Future studies should be conducted to determine the optimal protocol and dosage of treatment.


Haemodialysis before emergency surgery in a patient treated with dabigatran.
Novel oral anticoagulants (NOAs) which directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban and apixaban) have recently been developed. We report the first case of perioperative management of a patient treated with dabigatran requiring haemodialysis before emergency surgery. A 62-yr-old woman visited the emergency department for a left bi-malleolar ankle fracture; she had a past medical history of severe ischaemic cardiomyopathy, alcoholic cirrhosis Child B, and moderate chronic renal insufficiency. The patient was treated with dabigatran for a left ventricular aneurysm with thrombus. Cutaneous manifestation of a voluminous haematoma required emergency surgery. Blood tests revealed dabigatran anticoagulant activity of 123 ng ml(-1) (therapeutic values: 85-200 ng ml(-1)), activated partial thromboplastin time of 63 s, and a prothrombin ratio of 68%, indicating that dabigatran disturbed coagulation. We decided to perform emergency haemodialysis before surgery. After 2 h, the anticoagulant activity of dabigatran was 11 ng ml(-1), allowing surgery. Surgery proceeded without any problems and the postoperative period was unremarkable. This case highlights the difficulties for the anaesthesiologist regarding emergency perioperative management of patients treated with NOAs and confirms the efficacy of haemodialysis in cases of dabigatran treatment. NOAs should be prescribed with caution, especially for patients with renal or hepatic disease, at least as long as no antagonist is available. In cases of deferred operative urgency in haemodynamically stable patients treated with dabigatran, haemodialysis should be considered to reverse dabigatran's anticoagulant effects.


Nanofluidic Trapping of Faceted Colloidal Nanocrystals for Parallel Single-Particle Catalysis.
Catalyst activity can depend distinctly on nanoparticle size and shape. Therefore, understanding the structure sensitivity of catalytic reactions is of fundamental and technical importance. Experiments with single-particle resolution, where ensemble-averaging is eliminated, are required to study it. Here, we implement the selective trapping of individual spherical, cubic, and octahedral colloidal Au nanocrystals in 100 parallel nanofluidic channels to determine their activity for fluorescein reduction by sodium borohydride using fluorescence microscopy. As the main result, we identify distinct structure sensitivity of the rate-limiting borohydride oxidation step originating from different edge site abundance on the three particle types, as confirmed by first-principles calculations. This advertises nanofluidic reactors for the study of structure-function correlations in catalysis and identifies nanoparticle shape as a key factor in borohydride-mediated catalytic reactions.


Tobramycin for nebulisation: new formulation. A high price for a small improvement in formulation.
(1) In patients with cystic fibrosis, chronic bronchial infection with Pseudomonas aeruginosa is a major factor in the development of chronic respiratory failure and premature death. (2) Over the last two decades, such patients have commonly received long-term treatment with antibiotic aerosols (mainly tobramycin or colistin, in off-licence uses). (3) Tobramycin solution for nebulisation is the first antibiotic preparation to be licensed in the EU for this indication. (4) Comparative evaluation of antibiotic aerosol therapy for chronic bronchial infections due to P. aeruginosa includes two large trials of nebulised tobramycin. (5) A combined analysis of these two placebo-controlled trials, both lasting 20 weeks, showed that tobramycin aerosol delayed the deterioration of respiratory function and reduced the number of hospitalisations. However, an increase in P. aeruginosa resistance to tobramycin was reported. (6) The file on tobramycin includes no precise criteria for stopping treatment, and no data on the long-term impact of the observed increase in bacterial resistance. (7) The main adverse effects of tobramycin aerosol are tinnitus and voice changes. Deafness has also been reported. (8) The available assessment file does not show whether the risk-benefit ratio of tobramycin aerosol differs from that of other nebulised antibiotics used (off-licence) in this setting. However, tobramycin is the best-assessed nebulised antibiotic for this indication. (9) In practice, tobramycin solution for nebulisation may be considered the reference long-term treatment for chronic pulmonary infections due to P. aeruginosa in patients with cystic fibrosis. Assessment should continue, however, especially regarding the possible impact on mortality and the selection of resistant strains.