Formulation and Evaluation of Naringenin Nanosuspensions for Bioavailability Enhancement.
The clinical potential of naringenin (NRG) is compromised due to its poor aqueous solubility and low oral bioavailability. The study is aimed at addressing these issues by means of naringenin nanosuspensions (NRG-NS) formulated using polyvinylpyrrolidone (PVP K-90) as stabiliser via antisolvent sonoprecipitation method. Optimisation of sonication time, drug concentration and stabilisers was done based on particle size. Characterisation of pure NRG and NRG-NS was carried out by scanning electron microscopy, differential scanning calorimetry (DSC), x-ray powder diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR). In vitro dissolution, intestinal absorption by non-everted rat intestinal sac model and in situ single pass intestinal perfusion techniques were performed for further investigation. Nanosuspensions prepared using PVP K-90 lead to minimum particle size (117 ± 5 nm) with zeta potential of -14.6 ± 5.6 mV. The particle size was affected by increasing sonication time, concentration of stabiliser and drug. Nanosizing process converted the crystalline drug into amorphous form as predicted from DSC and XRD patterns. FTIR demonstrated the formation of hydrogen bonds between drug and polymer. NRG-NS displayed a higher dissolution amount (91 ± 4.4% during 60 min) compared to NRG powder (42 ± 0.41%). The apparent and effective permeability of NRG-NS was increased as compared to the pure NRG. The in vivo pharmacokinetics demonstrated that the C max and AUC0-24 h values of NRG-NS were approximately 2- and 1.8-fold superior than the pure drug. Hence, overall results confirmed nanosuspensions as promising approach for NRG delivery with high absorption in gastrointestinal tract, improved dissolution and oral bioavailability.


Arthroscopic-assisted first metatarsophalangeal joint arthrodesis.
This is the first report of a successful first metatarsophalangeal joint arthrodesis using great toe arthroscopy and percutaneous internal fixation. The surgical trauma associated with open operative arthrodesis can be minimized using minimally invasive techniques under arthroscopic control. The authors describe the principles of the surgery and discuss the advantages compared with traditional surgery.


Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study.
There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings. To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment. This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability. Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors. Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.


Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques.
Atherosclerosis is a leading cause of mortality in the Western world, and plaque diagnosis is still a challenge in cardiovascular medicine. The main focus of this study was to make atherosclerotic plaques visible using targeted nanoparticles for improved imaging. Today various biomarkers are known to be involved in the pathophysiologic scenario of atherosclerotic plaques. One promising new candidate is the globular domain of the adipocytokine adiponectin (gAd), which was used as a targeting sequence in this study. gAd was coupled to two different types of nanoparticles, namely protamine-oligonucleotide nanoparticles, known as proticles, and sterically stabilized liposomes. Both gAd-targeted nanoparticles were investigated for their potency to characterize critical scenarios within early and advanced atherosclerotic plaque lesions using an atherosclerotic mouse model. Aortic tissue from wild type and apolipoprotein E-deficient mice, both fed a high-fat diet, were stained with either fluorescent-labeled gAd or gAd-coupled nanoparticles. Ex vivo imaging was performed using confocal laser scanning microscopy. gAd-targeted sterically stabilized liposomes generated a strong signal by accumulating at the surface of atherosclerotic plaques, while gAd-targeted proticles became internalized and showed more spotted plaque staining. Our results offer a promising perspective for enhanced in vivo imaging using gAd-targeted nanoparticles. By means of nanoparticles, a higher payload of signal emitting molecules could be transported to atherosclerotic plaques. Additionally, the opportunity is opened up to visualize different regions in the plaque scenario, depending on the nature of the nanoparticle used.


[Evaluation of hepatic encephalopathy and portal hemodynamics by Doppler ultrasonography after a transjugular intrahepatic portosystemic shunt].
TIPS (transjugular intrahepatic portosystemic shunt) is an efficacious treatment for esophagogastric varices, ascites and hypertensive gastrointestinal vasculopathy associated with portal hypertension. The main complication after the procedure is hepatic encephalopathy. We tried to elucidate the correlation between hepatic encephalopathy and changes in portal hemodynamics after TIPS, based on observation by Doppler ultrasonography. We carried out Doppler ultrasonography in 28 cases of TIPS to assess hepatopetal and hepatofugal blood flow in the right and left portal branches. Hepatic encephalopathy occurred after TIPS in 9 cases out of 28 (32%), and new onset of disease was observed in 6 of 9. Doppler ultrasonography revealed hepatofugal blood flow in both right and left portal branches in 6 cases, 5 of which showed encephalopathy. Hepatopetal blood flow of the right and left portal branches was observed in 17 of 28 cases after TIPS. Hepatic encephalopathy occurred in only 2 of 17 cases. The changes in portal vein hemodynamics after TIPS were investigated by color Doppler ultrasonography, which were considered to be very useful for prediction of hepatic encephalopathy and indication of medical treatment to prevent the occurrence of this disease.


Nestin contributes to laser choroidal and retinal neovascularization.
Choroidal and retinal neovascularization plays an essential role in various ocular diseases. In this study, we examined the role of nestin in this process. Nestin is an intermediate filament protein known to play several roles, including as a marker of neural progenitor and proliferating endothelial cells. We used Brown Norway rats, in which choroidal and retinal neovascularization was induced using intraocular laser impacts. The role of nestin was examined using angiography, western blot from the second to the 14th day after laser impacts, and intraocular injection of nestin siRNA. The localization of the protein was specified by co-immunoreactivity with glial fibrillary protein (GFAP), glutamine synthetase (GS), and von Willebrand factor (vWF). In the control retina, nestin was found principally in glial structures in the ganglion cell layer, as confirmed by nestin/GFAP immunolabeling. Two days after the laser impacts, the nestin expression extended to numerous radial processes at the site of the impacts. With Bruch's membrane ruptured, these processes penetrated into the choroid. Nestin immunolabeling remained high from the third to the seventh day but appeared reduced on the 14th day. The nature of these processes was not clearly defined, but co-immunolabeling with GFAP suggested that they were principally in activated Müller cells from the third day after the laser impacts. However, the co-immunoreactivity of nestin and GS, a marker of mature functional Müller cells, could be observable only from the seventh day. Nestin was also observed in some vascular cells, as demonstrated by the co-immunoreactivity of the protein with vWF in the choroid and retina. As observed on angiography, the numbers of choroidal and retinal blood vessels were significantly increased (principally on the seventh day) after the laser impacts. An intraocular injection of nestin siRNAs led to a significant decrease in the number of blood vessels. Our results confirmed the presence of nestin in glial (e.g., astrocytes), reactive Müller, and endothelial cells. They demonstrated their critical involvement in a rat model of retinal and choroidal neovascularization experimentally induced using ocular laser impacts.


Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis.
In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.


Myrcia splendens (Sw.) DC. (syn. M. fallax (Rich.) DC.) (Myrtaceae) Essential Oil from Amazonian Ecuador: A Chemical Characterization and Bioactivity Profile.
In this study, we performed the chemical characterization of Myrcia splendens (Sw.) DC. (Myrtaceae) essential oil from Amazonian Ecuador and the assessment of its bioactivity in terms of cytotoxic, antibacterial, and antioxidant activity as starting point for possible applicative uses. M. splendens essential oil, obtained by hydro-distillation, was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Gas Chromatography-Flame Ionization Detector (GC-FID): the major components were found to be trans-nerolidol (67.81%) and α-bisabolol (17.51%). Furthermore, we assessed the cytotoxic activity against MCF-7 (breast), A549 (lung) human tumor cell lines, and HaCaT (human keratinocytes) non-tumor cell line through 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test: promising results in terms of selectivity and efficacy against the MCF-7 cell line (IC50 of 5.59 ± 0.13 μg/mL at 48 h) were obtained, mainly due to α-bisabolol. Furthermore, antibacterial activity against Gram positive and negative bacteria were performed through High Performance Thin Layer Chromatography (HPTLC) bioautographic assay and microdilution method: trans-nerolidol and β-cedren-9-one were the main molecules responsible for the low antibacterial effects against human pathogens. Nevertheless, interesting values of Minimum Inhibitory Concentration (MIC) were noticeable against phytopathogen strains. Radical scavenging activity performed by HPTLC bioautographic and spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH) approaches were negligible. In conclusion, the essential oil revealed a good potential for plant defense and anti-cancer applications.


Fine needle aspiration vs. mTESE in non-obstructive azoospermia.
This study was carried out on 100 patients with non-obstructive azoospermia (NOA) to compare between results and complications of fine needle aspiration (FNA) vs. microdissection testicular sperm extraction (mTESE) sperm retrieval. They underwent history taking, clinical examination, semen analysis, serum follicle stimulating hormone estimation and scrotal Duplex. One testis was subjected to FNA screening whereas the other testis was subjected to mTESE and histopathology. Follow-up was by ultrasonography at 1, 3 and 6 months. The overall sperm retrieval rate was 54% by mTESE and 10% by FNA. Spermatozoa were retrieved by mTESE from all cases with hypospermatogenesis, severe hypospermatogenesis, 30% of Sertoli cell only (SCO), 16.7% of germ cell arrest and in 28.6% of tubular hyalinization. Sperms were retrieved by FNA in 33.3% of hypospermatogenesis, 9% in severe hypospermatogenesis, 5% in SCO, 16.7% in germ cell arrest, while no sperms were retrieved in the tubular hyalinization group. The total complication rate following mTESE was 10% in the early phase and none in the long-term follow-up compared to 24% of FNA side. It is concluded that mTESE is superior to FNA as regards sperm retrieval rate and lower incidence of complications in NOA patients.


Evaluating information transfer between auditory cortical neurons.
Transfer entropy, presented as a new tool for investigating neural assemblies, quantifies the fraction of information in a neuron found in the past history of another neuron. The asymmetry of the measure allows feedback evaluations. In particular, this tool has potential applications in investigating windows of temporal integration and stimulus-induced modulation of firing rate. Transfer entropy is also able to eliminate some effects of common history in spike trains and obtains results that are different from cross-correlation. The basic transfer entropy properties are illustrated with simulations. The information transfer through a network of 16 simultaneous multiunit recordings in cat's auditory cortex was examined for a large number of acoustic stimulus types. Application of the transfer entropy to a large database of multiple single-unit activity in cat's primary auditory cortex revealed that most windows of temporal integration found during spontaneous activity range between 2 and 15 ms. The normalized transfer entropy shows similarities and differences with the strength of cross-correlation; these form the basis for revisiting the neural assembly concept.


[Psychedelics and quasi-psychedelics in the light of contemporary research: medical cannabis, MDMA, salvinorin A, ibogaine and ayahuasca].
In lack of professional research and appropriate concepts our scientific knowledge of psychedelic agents is limited. According to the long-held official view these drugs are entirely harmful and have no medical use. However, a recent surge of clinical and pharmacological studies in the field indicates that many psychedelic-like agents have therapeutic potentials under proper circumstances. In this paper, from a biomedical and psychological perspective, we provide a brief review of the general effects and promising treatment uses of medical cannabis, 3,4-methylenedioxy-methamphetamine (MDMA), salvinorin A, ibogaine and the dimethyltryptamine-(DMT)-containing ayahuasca. In Hungary - similarly to many other countries - these compounds are classified as "narcotic drugs" and their research is difficult due to strict regulations.


Burnout, Engagement, and Organizational Culture: Differences between Physicians and Nurses.
Burnout results from a prolonged response to chronic emotional and interpersonal workplace stressors. The focus of research has been widened to job engagement. Purpose of the study was to examine associations between burnout, job engagement, work demands, and organisational culture (OC) and to demonstrate differences between physicians and nurses working in general hospital in Skopje, Republic of Macedonia. Maslach Burnout Inventory and Utrecht Work Engagement Scale were used for assessment of burnout and job engagement. Work demands and OC were measured with Hospital Experience Scale and Competing Values Framework, respectively. Higher scores of dedication, hierarchy OC, and organizational work demands were found in physicians. Nurses demonstrated higher scores of clan OC. Burnout negatively correlated with clan and market OC in physicians and nurses. Job engagement positively correlated with clan and market OC in nurses. Different work demands were related to different dimensions of burnout and/or job engagement. Our findings support job demands-resources (JD-R) model (Demerouti and Bakker). Data obtained can be used in implementation of specific organizational interventions in the hospital setting. Providing adequate JD-R interaction can lead to prevention of burnout in health professionals (HPs) and contribute positively to better job engagement in HPs and higher quality of patient care.


The standardization of pancreatic donors for islet isolations.
Islet transplantation has proven to be a successful treatment for type 1 diabetes mellitus. The aim of this study was to establish an algorithm by which the combination of the donor quality and pancreas quality was given a numerical score from 0 to 100 for use in determining the quality of a pancreas for islet isolation. We retrospectively analyzed 326 pancreases and the outcomes of their respective isolations. Specific donor variables and physical characteristics were identified and weighted according to their influence on the success of the isolation. For each variable, ranges and point weightings were established based on our laboratory experience and literature review. Analysis of the data showed a strong association of the donor point with isolation outcome. Pancreases with lower donor point scores had lower transplant success rates, whereas higher donor point scores in turn produced higher transplant rates. This scoring system has proven to be useful in guiding the decision process as to whether to accept a particular pancreas for a favorable isolation outcome.


Temporomandibular Joint Ankylosis Leading to Obstructive Sleep Apnea.
Temporomandibular joint ankylosis in children commonly lead to difficulty in feeding, poor oral hygiene, retrognathic mandible and obstructive sleep apnea. Surgical release of the ankylosis has always been the standard treatment. The authors report a 12 year old boy with unilateral temporomandibular joint ankylosis and obstructive sleep apnea underwent surgical release of the ankylosis with successful gain in mouth opening. However, he continued to suffer from obstructive sleep apnea as confirmed by post-operative polysomnography. Orthognathic surgery for mandibular advancement is not favorable due to his young age and mandibular distraction osteogenesis was not a choice. A mandibular advancement device similar to orthodontic myofunctional appliance was the preferred choice in the post-operative period while waiting for definitive retrognathia surgical treatment after skeletal maturity. Surgical release of temporomandibular joint ankylosis corrects the oral problem but does not adequately address the narrow pharyngeal airway space. Assessment of pharyngeal airway with a high suspicion of obstructive sleep apnea is mandatory in the management of TMJ ankylosis.


C. elegans ankyrin repeat protein VAB-19 is a component of epidermal attachment structures and is essential for epidermal morphogenesis.
Elongation of the epidermis of the nematode Caenorhabditis elegans involves both actomyosin-mediated changes in lateral epidermal cell shape and body muscle attachment to dorsal and ventral epidermal cells via intermediate-filament/hemidesmosome structures. vab-19 mutants are defective in epidermal elongation and muscle attachment to the epidermis. VAB-19 is a member of a conserved family of ankyrin repeat-containing proteins that includes the human tumor suppressor Kank. In epidermal cells, VAB-19::GFP localizes with components of epidermal attachment structures. In vab-19 mutants, epidermal attachment structures form normally but do not remain localized to muscle-adjacent regions of the epidermis. VAB-19 localization requires function of the transmembrane attachment structure component Myotactin. vab-19 mutants also display aberrant actin organization in the epidermis. Loss of function in the spectrin SMA-1 partly bypasses the requirement for VAB-19 in elongation, suggesting that VAB-19 and SMA-1/spectrin might play antagonistic roles in regulation of the actin cytoskeleton.


Development and validation of the GAIN Short Screener (GSS) for internalizing, externalizing and substance use disorders and crime/violence problems among adolescents and adults.
The Global Appraisal of Individual Needs (GAIN)1 is a 1-2 hour standardized biopsychosocial that integrates clinical and research assessment for people presenting to substance abuse treatment. The GAIN - Short Screener (GSS) is 3-5 minute screener to quickly identify those who would have a disorder based on the full 60-120 minute GAIN and triage the problem and kind of intervention they are likely to need along four dimensions (internalizing disorders, externalizing disorders, substance disorders, and crime/violence). Data were collected from 6,177 adolescents and 1,805 adults as part of 77 studies in three dozen locations around the United States that used the GAIN. For both adolescents and adults the 20-item total disorder screener (TDScr) and its four 5-item sub-screeners (internalizing disorders, externalizing disorders, substance disorders, and crime/violence) has good internal consistency (alpha of .96 on total screener), is highly correlated (r = .84 to .94) with the 123-item longer scales in the full GAIN. The GSS also does well in terms of its receiver operator characteristics (90% or more under the curve in all analyses) and has clinical decision-making cut points with excellent sensitivity (90% or more) for identifying people with a disorder and excellent specificity (92% or more) for correctly ruling out people who did not have a disorder. The GSS has good potential as an efficient screener for identifying people with co-occurring disorders across multiple systems and routing them to the right services and more detailed assessments.


The effect of oligohydramnios on detection of fetal anomalies with sonography.
The sonographic examination of fetuses is generally thought to be compromised when oligohydramnios is present because of the subjective impression of less adequate visualization of fetal anatomy. The aim of this study was to evaluate the extent to which oligohydramnios limits our ability to detect major anomalies on sonograms. Records from the University of California, San Francisco from March 4, 1989 through January 4, 1994, were reviewed to identify all cases of premature rupture of the membranes in patients who then underwent nontargeted sonography. Sonographic results in pregnancies with oligohydramnios and without oligohydramnios (control population) were compared. Follow-up was obtained from a perinatal database, autopsy reports, and medical records. We found 345 patients with a history of premature rupture of the membranes (175 with oligohydramnios, 170 without oligohydramnios). Gestational age of fetuses was 16-38 weeks. Major congenital anomalies, including hydronephrosis, ventriculomegaly, intestinal atresias, hydrops, congenital diaphragmatic hernia, skeletal dysplasias, cloacal malformations, and gastroschisis, were revealed on sonography in 13 of 175 pregnancies with oligohydramnios and in 17 of the 170 pregnancies in the control group. Major anomalies missed in the oligohydramnios group included cardiac anomalies, club foot, small ventral hernia, limb reduction defect, and anal atresia. Major anomalies missed in the control group were club foot, anal atresia, and tracheoesophageal fistula. All of the major anomalies missed in both groups were of the type that are known to be difficult to diagnose before birth and that are frequently missed on sonography. Although oligohydramnios subjectively degrades image resolution, sonography still reveals important fetal anatomic landmarks. Major anomalies can be detected on sonography even when the pregnancy has less than the normal amount of amniotic fluid.


Incidence, predictors, and prognostic implications of bleeding and blood transfusion following percutaneous coronary interventions.
Bleeding related to percutaneous coronary intervention (PCI) occurs relatively frequently. We retrospectively investigated the incidence, predictors, and prognostic impact of periprocedural bleeding and transfusion in 10,974 patients who underwent PCI. Bleeding definitions were based on Thrombolysis In Myocardial Infarction (TIMI) criteria: (1) major bleeding (n = 588; 5.4%): if patients had a hemorrhagic stroke or if hematocrit decreased >15 points or by 10 to 15 points with clinical bleeding; (2) minor bleeding (n = 1,394; 12.7%): if hematocrit decreased <10 points with clinical bleeding or by 10 to 15 points without clinical bleeding; and (3) no bleeding (n = 8,992; 81.9%): if hematocrit decreased <10 points without clinical bleeding. Patients with major bleeding were older than patients with minor or no bleeding (67.8 +/- 11 vs 65.9 +/- 11 vs 63.6 +/- 11 years, respectively; p <0.001) and more often experienced intraprocedural complications, such as emergency use of an intra-aortic balloon pump (13.6% vs 6.5% vs 2.3%, respectively; p <0.001). Multivariate logistic regression analysis identified the use of an intra-aortic balloon pump (odds ratio [OR] 3.0, p <0.0001), procedural hypotension (OR 2.9, p <0.001), and age >80 years (OR 1.9 compared with age <50 years, p = 0.001) as the strongest predictors for major bleeding. Patients who had major bleeding had higher in-hospital and 1-year mortality compared with patients with minor or no bleeding. Bleeding was an independent predictor of in-hospital death. Thus, periprocedural major bleeding occurs relatively frequently and is associated with adverse outcomes. Patients >80 years of age who experience intraprocedural complications are at particularly high risk.


Parathyroid Hormone as a Predictor of Post-Thyroidectomy Hipocalcemia: A Prospective Evaluation of 100 Patients.
Hypocalcemia is a frequent complication after total thyroidectomy and the main reason for prolonged hospitalization of these patients. We studied prospectively 112 patients who underwent total or completation thyroidectomy between June 2012 and November 2013. Twelve patients with preoperative changes in parathyroid function were excluded. Parathyroid hormone and calcium levels were determined pre-operatively, immediately after surgery, on 1st day and on 14th day after surgery. Of the 100 patients enrolled, 60 have developed hypocalcaemia (60%) but only 14 patients had symptomatic hypocalcaemia. It mostly occurs 24 hours after surgery (76.7%). It was permanent in 3 patients and temporary in the others. In the 60 patients with hypocalcaemia, it has been found hypoparathyroidism in 19 patients immediately after surgery, in 14 patients on 1st day but only 3 had hypoparathyroidism (patients with permanent hypocalcaemia). Comparing the group of patients with and without hypocalcaemia we found a decrease of parathyroid hormone in both (immediately after surgery and on 1st day) but was more important in the hypocalcaemia group (p = 0.004 and p < 0.001). The decrease of PTH levels was more pronounced in the hypocalcaemia group, with significance on the first day (22.29% vs 50.29%, p < 0.001). The best predictor of hypocalcaemia identified was the decrease of parathyroid hormone levels > 19.4% determined on the 1st day (sensitivity = 82%; specificity = 63%). In our study there was a high incidence of hypocalcemia (60%), expressed predominantly 24 hours after surgery and conditioned, in these patients, a longer hospital stay. However, only 3 patients (3%) had permanent hypocalcemia. We still found a match in the oscillation of serum calcium levels and parathyroid hormone which identified the decrease in parathyroid hormone on the first day after surgery as a reliable predictor of hypocalcemia. Decrease of parathyroid hormone levels > 19.4% determined on 1st day is a good predictor of hypocalcemia after total / completation thyroidectomy, allowing to identify patients at higher risk of hypocalcemia, medicate them prophylactically and get early and safe discharges.


Two-dimensional ultrasound shear wave elastography for identifying and staging liver fibrosis in pediatric patients with known or suspected liver disease: a clinical effectiveness study.
Ultrasound shear wave elastography (SWE) measures liver stiffness noninvasively, but few studies have defined cutoff values for detecting liver fibrosis in pediatric patients using 2-D ultrasound SWE. To evaluate the diagnostic performance of 2-D ultrasound SWE and define cutoff values for liver fibrosis in pediatric patients, using Canon (Toshiba) Aplio ultrasound systems. This was an institutional review board-approved retrospective study of patients (≤18 years old) who had undergone both liver 2-D ultrasound SWE and percutaneous liver biopsy within 6 months. Liver biopsies were staged using the METAVIR (fibrosis) scoring system. Continuous data were compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic performance. Forty-six patients, with a median age of 11.5 years (interquartile range: 8.0-14.3 years), were included. Twenty-three patients were male (50%). Twenty-seven patients had a METAVIR fibrosis score of F0-1, and 19 patients had a score of F2-4. For differentiating METAVIR F0-1 from F2--4, the area under the ROC (AuROC) was 0.75 (95% confidence interval [CI]: 0.60-0.90). A cutoff of >1.89 m/s yielded sensitivity of 73.7% (95% CI: 51.2-88.2) and specificity of 77.8% (95% CI: 59.2-89.4). For the subset of patients without histological hepatic steatosis (n=35), the AuROC was 0.86 (95% CI: 0.71-1.0). The same cutoff of >1.89 m/s yielded a sensitivity of 80.0% (95% CI: 54.8-93.0) and specificity of 95.0% (95% CI 76.4-99.7). Two-dimensional ultrasound SWE distinguishes patients with no/mild fibrosis from those with moderate/severe fibrosis with good sensitivity and specificity. Diagnostic performance is comparable to that published for magnetic resonance elastography and is likely adversely impacted by steatosis.


The association between non-biting midges and Vibrio cholerae.
Vibrio cholerae is a natural inhabitant of aquatic ecosystems, yet its interactions within this habitat are poorly understood. Here we describe the current knowledge on the interaction of V. cholerae with one group of co-inhabitants, the chironomids. Chironomids, non-biting midges (Chironomidae, Diptera), are an abundant macroinvertebrate group encountered in freshwater aquatic habitats. As holometabolous insects, chironomids start life when their larvae hatch from eggs laid at the water/air interface; through various feeding strategies, the larvae grow and pupate to become short-lived, non-feeding, adult flying insects. The discovery of the connection between V. cholerae and chironomids was accidental. While working with Chironomus transavaalensis, we observed the disintegration of its egg masses and searched for a possible microbial agent. We identified V. cholerae as the primary cause of this phenomenon. Haemagglutinin/protease, a secreted extracellular enzyme, degraded the gelatinous matrix surrounding the eggs, enabling bacterial growth. Observation of chironomids in relation to V. cholerae continuously for 7 years in various types of water bodies in Israel, India, and Africa revealed that environmental V. cholerae adhere to egg-mass surfaces of various Chironomini ('bloodworms'). The flying adults' potential to serve as mechanical vectors of V. cholerae from one water body to another was established. This, in turn, suggested that these insects play a role in the ecology of V. cholerae and possibly take part in the dissemination of the pathogenic serogroups during, and especially between, epidemics.


Polychlorinated biphenyls have inhibitory effect on testicular steroidogenesis by downregulation of P450(17alpha) and P450(scc).
Polychlorinated biphenyls (PCBs) are environmental pollutants that are quite toxic to biological systems. This study examined the inhibitory effect of PCB126 and PCB114 on testicular steroidogenesis in male rats. Male Sprague Dawley rats received weekly intraperitoneal injections of PCB126 (0.2 mg/kg) or PCB114 (20 mg/kg) or vehicle (corn oil). Animals from each group were sacrificed at 2, 5 and 8 weeks after the injections. Blood and testis tissue samples were collected for the hormone assay, Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). The testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were assayed, and the expression levels of the mRNA and proteins associated with the testosterone biosynthesis pathway were measured to determine the effect of PCB126 and PCB114 on testicular steroidogenesis. The results showed that the testis weight was significantly higher in the PCB126-treated rats given eight shots. Moreover, the serum testosterone levels were significantly lower in the PCB126 and PCB114-treated groups than the control. The transcription and translation levels of P450(17alpha) and P450(scc) were significantly lower in the PCB126-treated groups than the control. These results suggest that PCB126 may affect testicular steroidogenesis by downregulating P450(17alpha), P450(scc) and have inhibitory effect on the testicular functions.


[Observation on the clinical effect of self-designed modified rhomboid skin flap in facial wound repair].
Objective: To investigate the clinical effect of self-designed modified rhomboid flap in repairing rhomboid, round, and teardrop-shaped wounds on the face. Methods: A retrospective observational study was conducted. From August 2018 to April 2020, 30 patients with facial lesions admitted into Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the People's Hospital of Jianchuan County in Yunnan province met the inclusion criteria, including 16 males and 14 females, aged 23 to 88 years. The wound area ranged from 1.0 cm×1.0 cm to 7.0 cm×5.0 cm, with 10 cases of rhomboid wounds, 12 cases of round wounds, and 8 cases of teardrop-shaped wounds. The self-designed modified rhomboid flaps were applied to repair the wounds and after that, the patients were followed up for 1 to 18 months to record the survival of flaps, wound tension, scar formation and complications after surgery. Results: No necrosis or blackening was observed at the tip of the flaps after surgery. All the flaps survived and the wounds healed well with little tension, minimal scars, and no complications. Conclusions: The self-designed modified rhomboid flap is especially suitable for facial wounds with multiple important organs, multiple anatomical subunits, and areas with large changes in soft tissue tension, which can reduce not only the rotation of the flap, but also unnecessary excision of normal skin and soft tissue.


DNA polymerase in virions of a reptilian type C virus.
A study was made of the DNA polymerase of reptilian type C virus isolated from Russell's viper spleen cells. Simultaneous detection experiments demonstrated the presence of 70S RNA and RNA-dependent DNA polymerase activity in reptilian type C virions. The endogenous activity was dependent on the addition of all four deoxynucleotide triphosphates and demonstrated an absolute requirement for a divalent cation. The reptilian viral DNA polymerase elutes from phosphocellulose at 0.22 M salt. In this respect, it is similar to the avian (avian myeloblastosis virus; AMV) viral enzyme but is different from the mammalian (Rauscher leukemia virus; RLV) viral enzyme which elutes at 0.4 M salt. The molecular weight of the viper DNA polymerase as estimated from glycerol gradient centrifugation is 109,000. It is a smaller enzyme than the AMV DNA polymerase (180,000 daltons) and somewhat larger than the RLV enzyme (70,000 daltons). A comparison of other properties of the type C reptilian DNA polymerase with the enzyme found in other type C oncogenic viruses is made.


Cell contact during expression of radiation mutation in Chinese hamster V79 spheroids.
The influence of cell to cell contact during expression of radiation mutation at the HGPRT locus was examined using Chinese hamster V79 spheroids. Spheroids left intact for up to 6 days following 7.5 Gy (and then dissociated into single cells for selection in 6-thioguanine) showed no significant decrease in radiation-induced mutation frequency compared to cells of spheroids dissociated immediately following irradiation and passaged in monolayers during the expression interval. These results suggest that the intimate cell contact which occurs between cells in spheroids does not inhibit mutant expression. However, the cell selection process did appear to reduce mutation frequency when spheroids were left intact for 8 days of expression, or when spheroids received 10 Gy.


Asymmetric Synthesis of the Tetraponerine Alkaloids.
The asymmetric syntheses of all eight tetraponerine alkaloids (T1-T8) were achieved using the diastereoselective conjugate additions of lithium amide reagents in the key stereodefining steps. Conjugate addition of either lithium (R)-N-allyl-N-(α-methylbenzyl)amide or lithium (R)-N-(but-3-en-1-yl)-N-(α-methylbenzyl)amide to tert-butyl sorbate was followed by ring-closing metathesis of the resultant N-alkenyl β-amino esters, reduction to the corresponding aldehydes, and reaction with tert-butyl (triphenylphosphoranylidene)acetate. Subsequent conjugate addition of the requisite antipode of lithium N-benzyl-N-(α-methylbenzyl)amide to the resultant α,β-unsaturated esters gave a range of diamines for elaboration to T1-T8 via a sequence involving reduction of the ester moiety to give the corresponding aldehyde, olefination, tandem hydrogenation/hydrogenolysis, and cyclization upon reaction with 4-bromobutanal to give the tricyclic skeleton.


Synthesis and regulation of chlorogenic acid in potato: Rerouting phenylpropanoid flux in HQT-silenced lines.
Chlorogenic acid (CGA) is the major phenolic sink in potato tubers and can constitute over 90% of total phenylpropanoids. The regulation of CGA biosynthesis in potato and the role of the CGA biosynthetic gene hydroxycinnamoyl CoA:quinate hydroxycinnamoyl transferase (HQT) was characterized. A sucrose induced accumulation of CGA correlated with the increased expression of phenylalanine ammonia-lyase (PAL) rather than HQT. Transient expression of the potato MYB transcription factor StAN1 (anthocyanin 1) in tobacco increased CGA. RNAi suppression of HQT resulted in over a 90% reduction in CGA and resulted in early flowering. The reduction in total phenolics and antioxidant capacity was less than the reduction in CGA, suggesting flux was rerouted into other phenylpropanoids. Network analysis showed distinct patterns in different organs, with anthocyanins and phenolic acids showing negative correlations in leaves and flowers and positive in tubers. Some flavonols increased in flowers, but not in leaves or tubers. Anthocyanins increased in flowers and showed a trend to increase in leaves, but not tubers. HQT suppression increased biosynthesis of caffeoyl polyamines, some of which are not previously reported in potato. Decreased PAL expression and enzyme activity was observed in HQT suppressed lines, suggesting the existence of a regulatory loop between CGA and PAL. Electrophysiology detected no effect of CGA suppression on potato psyllid feeding. Collectively, this research showed that CGA in potatoes is synthesized through HQT and HQT suppression altered phenotype and redirected phenylpropanoid flux.


Indirect Effects of Field Management on Pollination Service and Seed Set in Hybrid Onion Seed Production.
Pollination in crops, as in native ecosystems, is a stepwise process that can be disrupted at any stage. Healthy pollinator populations are critical for adequate visitation, but pollination still might fail if crop management interferes with the attraction and retention of pollinators. Farmers must balance the direct benefits of applying insecticide and managing irrigation rates against their potential to indirectly interfere with the pollination process. We investigated these issues in hybrid onion seed production, where previous research has shown that high insecticide use reduces pollinator attraction. We conducted field surveys of soil moisture, nectar production, pollinator visitation, pollen-stigma interactions, and seed set at multiple commercial fields across 2 yr. We then examined how management actions, such as irrigation rate (approximated by soil moisture), or insecticide use could affect the pollination process. Onions produced maximum nectar at intermediate soil moisture, and high nectar production attracted more pollinators. Insecticide use weakly affected pollinator visitation, but when applied close to bloom reduced pollen germination and pollen tube growth. Ultimately, neither soil moisture nor insecticide use directly affected seed set, but the high correlation between pollinator visitation and seed set suggests that crop management will ultimately affect yields via indirect effects on the pollination process.


Quantum conditional generative adversarial network based on patch method for abnormal electrocardiogram generation.
To address the scarcity and class imbalance of abnormal electrocardiogram (ECG) databases, which are crucial in AI-driven diagnostic tools for potential cardiovascular disease detection, this study proposes a novel quantum conditional generative adversarial algorithm (QCGAN-ECG) for generating abnormal ECG signals. The QCGAN-ECG constructs a quantum generator based on patch method. In this method, each sub-generator generates distinct features of abnormal heartbeats in different segments. This patch-based generative algorithm conserves quantum resources and makes QCGAN-ECG practical for near-term quantum devices. Additionally, QCGAN-ECG introduces quantum registers as control conditions. It encodes information about the types and probability distributions of abnormal heartbeats into quantum registers, rendering the entire generative process controllable. Simulation experiments on Pennylane demonstrated that the QCGAN-ECG could generate completely abnormal heartbeats with an average accuracy of 88.8%. Moreover, the QCGAN-ECG can accurately fit the probability distribution of various abnormal ECG data. In the anti-noise experiments, the QCGAN-ECG showcased outstanding robustness across various levels of quantum noise interference. These results demonstrate the effectiveness and potential applicability of the QCGAN-ECG for generating abnormal ECG signals, which will further promote the development of AI-driven cardiac disease diagnosis systems. The source code is available at github.com/VanSWK/QCGAN_ECG.


Spatial Cues Provided by Sound Improve Postural Stabilization: Evidence of a Spatial Auditory Map?
It has long been suggested that sound plays a role in the postural control process. Few studies however have explored sound and posture interactions. The present paper focuses on the specific impact of audition on posture, seeking to determine the attributes of sound that may be useful for postural purposes. We investigated the postural sway of young, healthy blindfolded subjects in two experiments involving different static auditory environments. In the first experiment, we compared effect on sway in a simple environment built from three static sound sources in two different rooms: a normal vs. an anechoic room. In the second experiment, the same auditory environment was enriched in various ways, including the ambisonics synthesis of a immersive environment, and subjects stood on two different surfaces: a foam vs. a normal surface. The results of both experiments suggest that the spatial cues provided by sound can be used to improve postural stability. The richer the auditory environment, the better this stabilization. We interpret these results by invoking the "spatial hearing map" theory: listeners build their own mental representation of their surrounding environment, which provides them with spatial landmarks that help them to better stabilize.


Smoking, APOE Genotype, and Cognitive Decline: The Rotterdam Study.
The association of smoking with preclinical cognitive decline remains unclear and may be modified by the APOEɛ4 genotype. In 5,705 participants (mean age: 63.9±9.1 years; 57.4% women) from the population-based Rotterdam Study, we investigated the relationship between smoking and cognitive decline over a 5.5-year period and examined potential effect modification by APOEɛ4 genotype. We found that current smoking was related to decline in global cognition [difference compared to never smoking: -0.06 (95% C.I.-0.10;-0.01)], as well as decline on specific cognitive tests including the Letter Digit Substitution Task, the 15-Word Learning Test, and the Purdue Pegboard. We found no evidence for effect modification by APOEɛ4 genotype on this relation.


Evidence that pulsatile follicle-stimulating hormone secretion is independent of endogenous luteinizing hormone-releasing hormone.
Although LHRH can stimulate the release of both LH and FSH from the pituitary, there are a number of instances in which the secretion of LH and FSH are divergent. Previous studies from our laboratory have indicated that pulsatile LH and FSH secretion are independently regulated by gonadal factors. We have, therefore, reexamined the role of LHRH in regulating pulsatile gonadotropin secretion by evaluating the effect of passive LHRH immunoneutralization on LH and FSH secretion in castrate adult male rats. Injection of 500 microliters ovine anti-LHRH serum no. 772 (LHRH-AS) into 2-week-castrate rats caused an 85% suppression of mean plasma LH levels by 2 h, which lasted through 48 h. Mean plasma FSH, however, was reduced by only 19% after 2 h and by only 59% after 48 h. When cannulated 2-week-castrate rats were bled every 10 min, both LH and FSH were secreted in a pulsatile manner. Injection of 500 microliters LHRH-AS caused an immediate abolishment of LH pulses and a rapid reduction in mean plasma LH through 24 h. Pulsatile FSH secretion, as characterized by the parameters of pulse frequency and amplitude, was unaffected by LHRH-AS, although mean plasma FSH levels were significantly reduced. Collectively, the results suggest that pulsatile FSH secretion is regulated by a separate factor(s) distinct from LHRH, but that LHRH is required for the maintenance of elevated FSH levels.


Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion.
Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 +/- 15 years versus 62 +/- 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 +/- 9 to 95 +/- 16 fl, serum ferritin levels from 4 +/- 2 to 37 +/- 41 microg/L, gastrin level from 166 +/- 118 to 382 +/- 299 pM/L (349 +/- 247 to 800 +/- 627 pg/mL), and a decrease in cobalamin level from 392 +/- 179 to 108 +/- 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.


Mycophenolate Mofetil in Severe Atopic Dermatitis: A Review.
Atopic Dermatitis (AD) is a chronic inflammatory skin disease that is a significant cause of morbidity, quality-of-life impairment and health-care costs. Although many patients can be treated satisfactorily with topical medications and phototherapy, a smaller subset requires more aggressive systemic therapies. Multiple studies have shown promise for the use of mycophenolate mofetil (MMF) to treat refractory AD. This report summarizes the evidence for use of MMF in the treatment of recalcitrant AD for both children and adults. Familiarity with these studies on the benefits and risks of MMF will enable the clinician and patient to select the most appropriate therapy.

 J Drugs Dermatol. 2016;15(6):715-718.


Role of the Polymorphisms of Uncoupling Protein Genes in Childhood Obesity and Their Association with Obesity-Related Disturbances.
Obesity, one of the most common disorders observed in clinical practice, has been associated with energy metabolism-related protein genes such as uncoupling proteins (UCPs). Herein, we evaluated UCPs as candidate genes for obesity and its morbidities. A total of 268 obese and 185 nonobese children and adolescents were enrolled in this study. To determine dyslipidemia, hypertension, and insulin resistance, laboratory tests were derived from fasting blood samples. UCP1-3826 A/G, UCP2 exon 8 deletion/insertion (del/ins), and UCP3-55C/T variants were also genotyped, and the relationships among the polymorphisms of these UCPs and obesity morbidities were investigated. The mean ages of the obese and control groups were 11.61 ± 2.83 and 10.74 ± 3.36 years, respectively. The respective genotypic frequencies of the AA, AG, and GG genotypes of UCP1 were 46.3%, 33.2%, and 20.5% in obese subjects and 46.5%, 42.2%, and 11.4% in the controls (p = 0.020). G alleles were more frequent in obese subjects with hypertriglyceridemia (42.9%; p = 0.048) than in those without, and the GG genotype presented an odds ratio for obesity of 2.02 (1.17-3.47; p = 0.010). The polymorphisms of UCP2 exon 8 del/ins and UCP3-55C/T did not influence obesity risk (p > 0.05). The I (ins) allele was associated with low HDL cholesterolemia (p = 0.023). The GG genotype of the UCP1-3826 A/G polymorphism appears to contribute to the onset of childhood obesity in Turkish children. The GG genotype of UCP1, together with the del/del genotype of the UCP2 polymorphism, may increase the risk of obesity with synergistic effects. The ins allele of the UCP2 exon 8 del/ins polymorphism may contribute to low HDL cholesterolemia.


Preparing social workers to address HIV/AIDS prevention and detection: implications for professional training and education.
The social work profession remains an untapped resource within the community for addressing HIV/AIDS prevention and early detection. This study investigated social workers' knowledge and practices relating to HIV prevention education, risk assessment, and case finding. A six page questionnaire was mailed to a random sample of 600 licensed social workers and licensed clinical social workers in Illinois. The sample was drawn from a list provided by the state department of professional regulation, stratified by geographic location. The final response rate for the survey was 51.3% (N = 308). Social work knowledge concerning HIV and AIDS was significantly related to the variables of age, geographic location, and practice setting. Respondents scored lower on knowledge items pertaining to their ability to perform a comprehensive sexual and drug risk assessment and to appropriately advise clients on HIV antibody testing. Most of the social workers in the sample provided minimal to no HIV-related services in their clinical practice. HIV-related behaviors were also significantly related to the variables of age, geographic location, and practice setting. Multiple logistic regression was used to test whether prior HIV/AIDS training predicted the presence of HIV-related practice behaviors, controlling for potential confounding factors. Both prior HIV-related training and education and prior work experience with HIV-infected clients were statistically significant and independent predictors of current HIV-related practice behaviors reported by social workers.


[Epidemiological pattern of scarlet fever in recent years].
During the period of 1953-2001 scarlet fever morbidity level fluctuated from 670.3 to 65.9 per 100,000 of the population in Moscow and from 531.9 to 35.0 per 100,000 of the population of the Russian Federation. In recent years an increased morbidity was more pronounced in Moscow than in the Russian Federation as a whole. Children formed the greater part of scarlet fever patients, the cases of scarlet fever among children in Moscow occurring more often than, on the average, in Russia. As before, annual morbidity among children attending children's institutions was higher 3- to 4-fold than among children brought up at home. This difference was most sharply pronounced among young children during the first two years of their life. In contrast to morbidity observed during previous 20-30 years, a drop in morbidity among children during the first two years of their life was registered, while morbidity level among children aged 3-6 years and 7-14 years increased. Scarlet fever morbidity had a pronounced seasonal (autumn-winter) pattern. In a group of children aged 3-5 years who attended organized groups, on the average, 78.6% of scarlet fever cases fell on seasonal morbidity, the most prolonged one.


Tailoring subunit vaccine immunity with adjuvant combinations and delivery routes using the Middle East respiratory coronavirus (MERS-CoV) receptor-binding domain as an antigen.
The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund's adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.


Development of a measure (ICECAP-Close Person Measure) through qualitative methods to capture the benefits of end-of-life care to those close to the dying for use in economic evaluation.
End-of-life care affects both the patient and those close to them. Typically, those close to the patient are not considered within economic evaluation, which may lead to the omission of important benefits resulting from end-of-life care. To develop an outcome measure suitable for use in economic evaluation that captures the benefits of end-of-life care to those close to the dying. To develop the descriptive system for the outcome measure, in-depth qualitative interviews were conducted with the participants and constant comparative analysis methods were used to develop a descriptive system for the measure. Twenty-seven individuals bereaved within the last 2 years or with a close-person currently receiving end-of-life care were purposively recruited into the study. Participants were recruited through newsletters, adverts, snowball sampling and a local hospice. Twenty-seven individuals were recruited. A measure of capability with six attributes, each with five levels, was developed based on themes arising from the analysis. Attributes comprise the following: good communication with services, privacy and space to be with the loved one, emotional support, practical support, being able to prepare and cope and being free from emotional distress related to the condition of the decedent. This measure is designed to capture the benefits of end-of-life care to close-persons for use in economic evaluation. Further research should value the measure and develop methods for incorporating outcomes for close-persons into economic evaluation.


[Laryngeal actinomycosis].
Actinomycosis is a rare infectious disease in our practice and clinically it is charactherized by the presence of granulomatous lesions of subacute or chronic evolution. Most of the cases of actinomycosis are localised in the cervico-facial area, being the laryngeal one uncommon. We present a clinical case of a 53 years-old male diagnosed of primary laryngeal actinomycosis and we realise a bibliographic revision on this subject emphazising the diagnosis techniques and the differential diagnosis of this kind of lesions.


Composite glandular and endocrine tumors of the stomach with pancreatic acinar differentiation.
Composite tumors of the stomach consisting of mixed glandular and endocrine components are rare. We report 3 cases of composite glandular and endocrine tumors with pancreatic acinar differentiation in the stomach with their clinicopathologic findings. The patients' presenting symptoms were variable and included abdominal pain, gastrointestinal hemorrhage, and weight loss. One patient with abdominal pain also had an elevated serum lipase level, clinically mimicking acute pancreatitis. The histology of these tumors was similar. They showed admixture of well-differentiated endocrine components with acinar and glandular components. The glandular component consisted of columnar epithelial cells resembling gastric foveolar or intestinal goblet cells, consistent with a well-differentiated adenocarcinoma. A panel of histochemical and immunohistochemical stains was performed, which included PAS, Alcian blue, Mib1, CEA, cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, chromogranin, synaptophysin, trypsin, chymotrypsin, lipase, insulin, gastrin, serotonin, and pancreatic polypeptide. While the immunoreactivity for cytokeratin 7, cytokeratin 20, Muc2, Muc5AC, and CEA was largely restricted to the glandular component, the endocrine and pancreatic acinar markers showed marked variability and overlap. All cases showed immunoreactivity for at least one of the exocrine pancreatic enzymes, and all expressed endocrine differentiation. Some degree of amphicrine differentiation was suggested in all cases. Two cases showed metastases in perigastric lymph nodes, which histologically resembled the primary tumor. In summary, these tumors represent another distinct type of composite glandular and endocrine gastric neoplasm with pancreatic acinar differentiation.


Using electrocapillarity to measure the zeta potential of a planar hydrophobic surface in contact with water and nonionic surfactant solutions.
A method is introduced for determining the zeta potential of planar surfaces by combining electroosmosis and capillarity. In this method, an electric field is applied across the channel, which is filled with aqueous solution seeded with fluorescent tracer particles. Some excess liquid is applied on both ends of the channel, which bulges out and modulates the capillary force across the channel by adjusting its curvature. While the velocity profile in the channel approaches steady state, a balance of the electroosmotic stress and Laplace pressure difference is achieved across the channel. However, as soon as the electric field is turned off, a Poiseuille flow develops in the channel due to the difference in the curvatures of the liquid bulges. We show that the measurement of the centerline velocity of the liquid inside the channel is enough to deduce the zeta potential of the surface. Utilizing this technique, the zeta potential of a hydrophobic glass surface (silanized by n-hexadecyltrichlorosilane, HC-16) has been measured to be -52.2 +/- 7.7 mV in distilled deionized water, which is in close agreement with the literature values. This technique has also been used to estimate the zeta potential of the HC-16 surface (zeta w(HC-16)), in the presence of the aqueous solutions of polyoxyethylene (23) lauryl ether (Brij 35). The zeta potential here at first becomes more negative than that in pure water, it stays flat for a while, and then it continues to become less negative as the concentration of the surfactant increases above the critical micelle concentration (CMC). This effect, where changes take place beyond the CMC but not below it, leads to a complementary Gibbs plot, where all the changes occur below the CMC but not above it. It is conjectured that the scavenging of hydroxyl ions by the Brij 35 micelles may be responsible for the observed effect.


Double rib penetration of the spinal canal in a patient with neurofibromatosis.
Rib head penetration into the spinal canal in patients with severe kyphoscoliosis secondary to neurofibromatosis type-1 (NF-1) is extremely rare. Double rib head penetration has only been reported once earlier. We are reporting on an adolescent male with NF-1 and severe thoracic kyphoscoliosis with adjacent double rib head penetration into the spinal canal without neurological deficits. Only one was recognized on the initial radiographic imaging. A 14-year-old with NF-1 and 74 degrees left thoracic scoliosis and 75 degrees kyphosis was treated at our institution. Preoperative computed tomography (CT) demonstrated protrusion of the left T6 rib head into the spinal canal on the convexity of the curve, compressing the spinal cord. Staged surgical procedures for resection of the rib head and correction of the spinal deformity were planned. After presumed successful resection of the penetrated rib head, a postoperative CT revealed the presence of a second adjacent left T7 rib head in the spinal canal. This was not initially recognized owing to the severe deformity and image obliquity of the CT gantry. Another procedure was performed to remove this rib head. He was then placed in halo traction until anterior and posterior spinal fusion and segmental spinal instrumentation were performed. He achieved good deformity correction and had no neurological deficits throughout his treatment. Rib head protrusion into the spinal canal can occur with spine deformity in NF-1. If present, the imaging should be carefully reviewed for the possibility of an adjacent rib head penetration that may have been obscured by the limitations of CT in the context of a dysplastic spinal deformity. Level V. Case study.


Bilateral subgaleal hematoma after a robot-assisted radical prostatectomy: an uncommon complication.
Robot-assisted radical prostatectomy is a relatively recent technique. Its advantages include less invasiveness and better pain management, but has specific anesthesia requirements, such as steep Trendelenburg position and pneumoperitoneum. Mild complications are common, e.g., transient hypotension or soft tissue edema. We present a case of a 62-year old male who developed subgaleal hematoma associated with transient neurologic impairment after surgery. Jugular vein insufficiency was suspected as the most likely cause. The patient recovered fully. Robot-assisted radical prostatectomy can be a challenging procedure due to the anesthesia requirements, but most complications are mild and transient. However, patients should be carefully assessed before surgery. We identified potential factors that may have led to this complication: the abnormal prolonged surgical time, the steep Trendelenburg, a non-assessed jugular vein insufficiency, and/or patient`s obesity.


The role of epithelial integrin receptors in recognition of pulmonary pathogens.
Integrins are a large family of heterodimeric transmembrane cell adhesion receptors. During the last decade, it has become clear that integrins significantly participate in various host-pathogen interactions involving pathogenic bacteria, fungi, and viruses. Many bacteria possess adhesins that can bind either directly or indirectly to integrins. However, there appears to be an emerging role for integrins beyond simply adhesion molecules. Given the conserved nature of integrin structure and function, and the diversity of the pathogens which use integrins, it appears that they may act as pattern recognition receptors important for the innate immune response. Several clinically significant bacterial pathogens target lung epithelial integrins, and this review will focus on exploring various structures and mechanisms involved in these interactions.


Changes of the wax contents in mixtures of olive oils as determined by gas chromatography with a flame ionization detector.
Mixing of refined olive-pomace oil with virgin olive oil is a fraud that has been tried often. Normally, the tests that detected the fraud were determinations of wax esters, erythrodiol+uvaol, and stigmastadienes contents. The most common is the determination of wax esters content (extra virgin olive oil is very poor in wax esters, usually less than 100 mg/kg). In this work, the variations of individual wax esters (C40, C42, C44, and C46), with different degrees of unsaturation content, and total wax esters were studied when extra virgin olive oil and refined pomace-olive oil were mixed. The following mixtures were prepared: extra virgin olive oil plus 1, 2, 4, 6, 8, 10, 12, 15, 18, 25, 35, 45, 50, and 80% of refined olive-pomace oil. In all cases, individual and total wax ester content variation was linear with increasing percentage of refined olive-pomace oil in the mixture. The variation of the total wax esters content can be adjusted according to the equation: Total wax esters, mg/kg = 14.3 x (% refined olive-pomace oil) + 83.9.


Total Atrial Conduction Time as a Predictor of Atrial Fibrillation Recurrence: A Systematic Review and Meta-Analysis.
This systematic review and meta-analysis aims to evaluate the predictive value of total atrial conduction time (TACT) assessed by tissue Doppler echocardiography (PA-TDI) in atrial fibrillation (AF) recurrence in patients following a rhythm-control strategy. A systematic approach following Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines was applied in electronic databases (Pubmed, Cochrane Library, and Web of Science), supplemented by scanning through studies' references. TACT was compared using a random-effects model and presented as a difference in means (MD). The primary endpoint was AF recurrence. Seven publications were included in this systematic review. The mean age of the patients ranged from 55 years to 72 years. Prolonged TACT was associated with AF recurrence [MD, 23.12 msec; 95% confidence interval (CI), 11.54-34.71; I2 = 95%]. Subgroup analysis showed that prolonged TACT was strongly associated with AF recurrence in persistent AF cohorts undergoing electrical cardioversion (MD, 26.56; 95% CI, 15.51-37.6; I2 = 86%), while in patients with paroxysmal AF (PAF) undergoing catheter ablation, the results were not statistically significant (MD, 11.48; 95% CI, -1.19 to 24.14; I2 = 90%). The summary area under the curve (sAUC) using a random-effects model was 0.89 (95% CI, 0.80-0.99). TACT is a valuable echocardiographic parameter that can predict AF recurrence in patients following a rhythm-control strategy. Protocol registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022353018.


Monitoring carbonyl-amine reaction between pyruvic acid and alpha-amino alcohols by FTIR spectroscopy--a possible route to Amadori products.
The carbonyl-amine reaction between pyruvic acid and alpha-amino alcohols was monitored by Fourier transform infrared spectroscopy at a temperature range between 20 and 100 degrees C and under acidic and basic conditions. To avoid interference, the reactions were conducted in the absence of solvent using liquid reactants such as methyl pyruvate, pyruvic acid, ethanolamine, and 1-amino-2,3-propanediol. Analysis of the time- and temperature-dependent spectra indicated that under basic conditions and at room temperature, the initial imine formation and its subsequent isomerization through a 1,3-prototropic shift occur very rapidly and the reaction goes to completion within 12 min. Interestingly, the isomerization product of the initial imine is the so-called Schiff base intermediate formed when the corresponding amino acid and the reducing sugar react during a typical Maillard reaction. Furthermore, the detailed studies also indicated that during the first 30 s, the rate of formation of the initial imine was faster than the rate of its isomerization; however, after 60 s, its rate of isomerization becomes faster than the rate of its formation. The data also indicated that under acidic conditions, this isomerization was prevented from occurring and the reaction was terminated at the initial imine formation stage. In addition, temperature-dependent spectra indicated that the isomerization of the Schiff's base into eneaminol can be achieved at or above 60 degrees C and its subsequent rearrangement into Amadori product can be attained at temperatures above 80 degrees C even under basic conditions, thus providing a novel route to Maillard reaction products starting from a keto acid and an amino alcohol. This observation was also confirmed through identification of the common Amadori product in both keto acid/amino alcohol and sugar/amino acid mixtures, by the application of tandem mass spectrometry and chemical ionization techniques.


Patient-therapist convergence in alliance ratings as a predictor of outcome in psychotherapy for generalized anxiety disorder.
Although patients and therapists aligning over time on their perceptions of alliance quality is regarded as clinically important, few studies have examined the influence of such dyadic convergence on psychotherapy outcomes. This study tested whether early treatment convergence in patient-therapist alliance ratings was associated with subsequent worry and distress reduction in psychotherapy for generalized anxiety disorder (GAD), and whether treatment type and the dyad members' initial alliance perceptions moderated these associations. Data derived from a randomized trial for which patients with severe GAD received either 15 sessions of standard cognitive-behavioral therapy (CBT; n = 43) or CBT integrated with motivational interviewing (n = 42). Patients and therapists rated the alliance after each session. Patients rated worry after each session, and their distress multiple times. As predicted, dyadic multilevel modeling revealed that early alliance convergence was associated with greater subsequent worry (p = .03) and distress (p = .01) reduction, and the combination of low initial patient-rated alliance and low convergence was associated with the worst outcome for the distress variable (p = .04). Results suggest that alliance convergence may be an important clinical process that bears on outcome, rendering it an important marker for therapist responsiveness.


Velocity and cluster distributions in a bottleneck system.
Velocity and cluster distributions for particles with unidirectional motion in one dimension are studied. The particles never pass each other, like cars on a narrow road that does not allow overtaking. As a result, particles cluster behind slow particles (queues are formed behind slow cars). Thus, the actual velocity of each particle is to a large extent determined by slow particles further ahead. Considering all possible permutations of N particles with initial velocities {vi}, the average number of particles with actual velocity vi is (N+1)/[i(i+1)] (in the sequence {vi}, the initial velocities are listed with monotonically increasing values). For i large and vi proportional, variant i the average number of actual velocities is thus a power law in vi, even though the average cluster density is found to be independent of cluster size, L. On the other hand, the cluster density varies significantly with cluster velocity; we obtain [(N-i)!(N-L)!]/[NN!(N-L-i+1)!]. The average velocity at a given position in the sequence of N particles, and the average global velocity are determined. Explicit results for several distributions of the initial velocities show that the global velocity depends sensitively on the form of this distribution.


Dorsal inlay graft urethroplasty for primary hypospadiac repair.
Tubularized incised plate urethroplasty has become a popular technique for repairing distal and proximal hypospadias in many institutions. Dorsal inlay graft urethroplasty has been used in our institution since 2003 to reduce the risk of meatal stenosis. In the present study, we evaluated the results of the dorsal inlay graft procedure. A total of 28 patients with no deep groove and no severe curvature underwent one-stage urethroplasty using an inner preputial-based dorsal inlay graft. The medical records of all patients were retrospectively reviewed with regard to complication rate and cosmetic appearance. Mean patient age at surgery was 21 months (range, 14 months to 4.6 years). Preoperatively the urethral meatus was coronal in two cases, distal shaft in 17, proximal shaft in six and penoscrotal in three. Nine patients required testosterone therapy before surgery. Mean operative time was 200 min (range, 154-249 min). Mean length of inlay graft was 20.9 mm (range, 12-30 mm). In all patients, a straight penis was achieved without dorsal plication of the corposa cavernosa, and the neomeatus with a slit-like appearance was positioned at the glans tip. At a mean of 22 months of follow up, a urethrocutaneous fistula developed in only one patient (3.6%), requiring repair surgery 6 months after urethroplasty. No patient had meatal stenosis, neourethral stricture or urethral diverticulum along the inlay graft. Dorsal inlay graft urethroplasty is an effective method for hypospadiac repair and leads to good cosmetic outcome with low risk of complications.


Alexithymia, Illness Perception and Self-management Competency in Psoriasis.
Alexithymia, defined as difficulty in describing or recognizing emotions, has been shown to be connected with psoriasis, but its relationship with self-management of psoriasis has not been explored. The aim of this study was to assess the frequency of alexithymia and its relationship with self-management and illness perception in the context of psoriasis. A total of 163 patients participating in 3 weeks of climate heliotherapy (CHT) at Gran Canaria were assessed for alexithymia using the Toronto Alexithymia Scale (TAS-20) at baseline. Self-reported measures for self-management (Health Education Impact Questionnaire; heiQ), and disease severity and illness perception (Brief Illness Perception Questionnaire; BIPQ) were assessed twice. Of all patients, 14.1% were characterized as alexithymic and 22.1% scored in the intermediate range. Alexithymic patients scored significantly worse in all heiQ domains, and reported worse illness perception. However, there were no between-group differences in heiQ or BIPQ change from baseline to after CHT. In conclusion, this study shows that alexithymia indicates inferior self-management and reaffirms the associations with illness perception. Further research is required into these relationships.


Correlation between clinical and histopathological diagnoses in periapical inflammatory lesions.
The purpose of the present study was to evaluate the correlation between clinical and histopathological diagnoses of periapical inflammatory lesions, focusing mainly on cystic conditions. Files dating from 1998 to 2006 at the Oral Pathology Laboratory, School of Dentistry, Alfenas Federal University, Brazil, were reviewed to identify cases with histopathological diagnoses of periapical inflammatory lesions. A total of 1788 files were analyzed, and 255 cases were identified with clinical diagnoses of periapical inflammatory lesions. The most prevalent clinical diagnosis was apical periodontal cyst (59%), followed by periapical granuloma (20%), and dentoalveolar abscess (2%). After histopathological analysis, 53% of the cases represented apical periodontal cyst, 42% periapical granuloma, and 5% dentoalveolar abscess. The outcomes of the present study show a high prevalence of periapical cysts among periapical inflammatory lesions. Moreover, this study highlights the importance of histopathological evaluation for the correct diagnosis of periapical inflammatory lesions.


Sharing data under the 21st Century Cures Act.
On 13 December 2016, President Obama signed the 21st Century Cures Act ("the Act") into law. Many of its provisions support the creation of an "Information Commons," an ecosystem of separate but interconnected initiatives that facilitate open and responsible sharing of genomic and other data for research and clinical purposes. For example, the Act supports the National Institutes of Health in mandating data sharing, provides funding and guidance for the large national cohort program now known as All of Us, expresses congressional support for a global pediatric study network, and strengthens patient access to health information. The Act also addresses potential barriers to data sharing. For example, it makes the issuance of certificates of confidentiality automatic for federally funded research involving "identifiable, sensitive" information and strengthens the associated protections. At the same time, the Act exacerbates or neglects several challenges, for example, increasing complexity by adding a new definition of "identifiable" and failing to address the financial sustainability of data sharing and the scope of commercialization. In sum, the Act is a positive step, yet there is still much work to be done before the goals of broad data sharing and utilization can be achieved.


Non-word repetition and non-word discrimination in Swedish preschool children.
By looking at data on expressive phonology, non-word repetition, non-word discrimination and phonological sensitivity in two groups of Swedish children, the common basis for tasks tapping into different levels of phonological processing is discussed. Two studies were performed, one including children with language impairment (LI) and one including children with normal language development (NL). A discrimination task consisting of non-word pairs differing in one phoneme was developed. In both groups there was a significant correlation between non-word repetition and phoneme identification. In children with LI phoneme identification was significantly correlated with expressive phonology. In children with NL non-word repetition correlated significantly with non-word discrimination, which was linked both to rhyme recognition and phoneme identification. Non-word discrimination might be equally useful as non-word repetition as an early screening tool and would circumvent the confounding factor of an expressive phonological impairment as well as decrease the amount of complicating factors involved in scoring procedures.


Opinion piece: genomics and crop plant science in Europe.
Recent report reviews and funding initiatives in the field of plant genomic research are considered in the context of their translation into practical and economic value via plant breeding. It is concluded that there is a deficit in investment and that a change in working styles towards knowledge sharing and connectivity is required.


Nerve Growth Factor Levels in Term Human Infants: Relationship to Prenatal Growth and Early Postnatal Feeding.
Nerve growth factor (NGF) plays a key role in neuroprotection and developmental maturity. We assessed longitudinally the circulating concentrations of NGF in term healthy human newborns and infants as well as their association with prenatal growth and early postnatal feeding patterns. Circulating NGF and anthropometric measures (weight, length, body mass index, and ponderal index) were assessed longitudinally-at birth and at age 4 months-in 86 term infants born appropriate (AGA), small (SGA), or large for gestational age (LGA). Cord blood NGF levels in SGA newborns were higher than those in AGA newborns (1.41 ± 0.2 pg/mL vs. 0.66 ± 0.1 pg/mL; p = 0.02) and not different from those in LGA neonates (0.79 ± 0.2 pg/mL). At age 4 months, SGA-breastfed infants showed the highest NGF concentrations (p = 0.02 and p = 0.01 vs. AGA and SGA-formula-fed infants, respectively), while LGA infants depicted a marginal increase. NGF levels in cord blood correlated negatively with the ponderal index at birth (r = -0.36; p = 0.0008). Circulating NGF is related to both prenatal growth and early postnatal nutrition. The maintenance of increased NGF concentrations in SGA-breastfed infants at age 4 months might be a potential mechanism to counterbalance potential risks for developing cognitive and psychomotor disadvantages.


Aiding Adherence to Glaucoma Medications: A Systematic Review.
To provide a comprehensive assessment of the strategies studied to date that focus on improving glaucoma medication adherence. A systematic review of the literature was conducted in MEDLINE (PubMed), Embase (Elsevier), and Scopus (Elsevier) from inception to March 1, 2021, of publications describing a device or strategy used to improve glaucoma medication adherence. 42 studies described by 50 papers were included. Five categories were identified: reminder systems, medication simplifications, behavioral change programs, education, and alternative engagement strategies. Most studies (40 of the 42) addressed the question of improved adherence directly, with 26 finding improved adherence. Notably, 14 examined the clinical effects of the intervention, either in terms of intraocular pressure (IOP) or visual fields. Only three found an improvement in IOP. None demonstrated a between group difference in visual field progression.


Distortions of temporal integration and perceived order caused by the interplay between stimulus contrast and duration.
Stimulus contrast and duration effects on visual temporal integration and order judgment were examined in a unified paradigm. Stimulus onset asynchrony was governed by the duration of the first stimulus in Experiment 1, and by the interstimulus interval in Experiment 2. In Experiment 1, integration and order uncertainty increased when a low contrast stimulus followed a high contrast stimulus, but only when the second stimulus was 20 or 30ms. At 10ms duration of the second stimulus, integration and uncertainty decreased. Temporal order judgments at all durations of the second stimulus were better for a low contrast stimulus following a high contrast one. By contrast, in Experiment 2, a low contrast stimulus following a high contrast stimulus consistently produced higher integration rates, order uncertainty, and lower order accuracy. Contrast and duration thus interacted, breaking correspondence between integration and order perception. The results are interpreted in a tentative conceptual framework.


A serological study of the age distribution of endemic treponematoses in children from Mali, Africa.
Using the Treponema Pallidum Haemagglutination Assay (TPHA) for the demonstration of treponema-specific antibodies, 444 children in age groups between 5 months and 10 years from different parts of Mali (Africa) were investigated for endemic treponematoses. The rate of seroreactivity (1,85%) in the age groups under four years (n = 270) indicates a low incidence of treponemal infections. From these observations it can be concluded that treponemal infections in infants are not caused by suckling of the babies on infectious nipples of their mothers. The high rate of TPHA-reactive children (17,8%) in the age groups between 5 and 10 years (n = 174) can be explained by the assumption of nonvenereal transmission of the disease. Furthermore, 101 mothers from Bamako and their newborn babies, were investigated serologically. In 17 mothers (17%) the TPHA was reactive. Treponema-specific antibodies were transmitted to the children in all cases and with nearly identical antibody titres.


Distribution of antigen presenting cells in the human cornea: correlation of in vivo confocal microscopy and immunohistochemistry in different pathologic entities.
The purpose of this study was to determine the quantity and distribution of antigen presenting cells (APC) in various inflammatory and non-inflammatory corneal diseases, comparing in vivo confocal microscopy (IVCM) and immunohistochemistry. Corneae of 41 eyes, composed of group 1 (status post herpes-keratitis), group 2 (keratoconus) and group 3 (graft rejection after keratoplasty) were investigated. IVCM was used preoperatively to assess the distribution and density of dendritic cells in the corneal center versus the paracentral area. Afterwards, all patients underwent penetrating keratoplasty. The host corneas were analyzed by immunohistochemistry for antigen presenting cell distribution, density and characterization by using specific markers for CD207/Langerin, CD209/DC-SIGN and HLA-DR. The IVCM findings were compared with immunohistochemistry results in the corneal epithelium. Cells with branching dendritic morphology were visualized by IVCM mainly in the basal epithelial layer and subepithelial nerve plexus of the central and paracentral cornea. The density of APC in IVCM decreased in all groups towards the central part of the cornea. The highest gradient was observed in group 2, followed by groups 1 and 3. The corneal paracenter showed similiar distribution of APC in group 1 and 2 (76.7 cells/mm(2) and 74.4 cells/mm(2)). The highest density of central APC was observed in group 1 (53.76 cells/mm(2)), followed by group 3 (27.0 cells/mm(2)) and group 2 (24.2 cells/mm(2)). In immunohistochemistry positive stained, APC were distributed similarly to IVCM but with a higher density (p < 0.05). Distribution, density and stage of maturation of corneal epithelial APCs can be evaluated on morphological basis by IVCM. However, the corneal APCs density was about three-fold lower compared to immunohistochemistry findings.


Effect of protein provision via milk replacer or solid feed on protein metabolism in veal calves.
The current study evaluated the effects of protein provision to calves fed a combination of solid feed (SF) and milk replacer (MR) at equal total N intake on urea recycling and N retention. Nitrogen balance traits and [(15)N2]urea kinetics were measured in 30 calves (23 wk of age, 180±3.7kg of body weight), after being exposed to the following experimental treatments for 11 wk: a low level of SF with a low N content (SF providing 12% of total N intake), a high level of SF with a low N content (SF providing 22% of total N intake), or a high level of SF with a high N content (SF providing 36% of total N intake). The SF mixture consisted of 50% concentrates, 25% corn silage, and 25% straw on a dry matter basis. Total N intake was equalized to 1.8g of N·kg of BW(-0.75)·d(-1) by adjusting N intake via MR. All calves were housed individually on metabolic cages to allow for quantification of a N balance of calves for 5 d, and for the assessment of urea recycling from [(15)N2]urea kinetics. Increasing low-N SF intake at equal total N intake resulted in a shift from urinary to fecal N excretion but did not affect protein retention (0.71g of N·kg of BW(-0.75)·d(-1)). Increasing low-N SF intake increased urea recycling but urea reused for anabolism remained unaffected. Total-tract neutral detergent fiber digestibility decreased (-9%) with increasing low-N SF intake, indicating reduced rumen fermentation. Increasing the N content of SF at equal total N intake resulted in decreased urea production, excretion, and return to ornithine cycle, and increased protein retention by 17%. This increase was likely related to an effect of energy availability on protein retention due to an increase in total-tract neutral detergent fiber digestion (>10%) and due to an increased energy supply via the MR. In conclusion, increasing low-N SF intake at the expense of N intake from MR, did not affect protein retention efficiency in calves. Increasing the N content of SF at equal total N intake decreased urea production, increased protein retention, and coincided with improved fiber degradation. Therefore, results suggest that low N availability in the rumen limits microbial growth and rumen fermentation in calves fed low-N SF (93g of CP/kg of DM), and this effect cannot be compensated for by recycling of urea originating from MR.


[Historical study of the moth repellent, "Fujisawa Camphor" (7) - selling price and packaging.].
The selling price of "Fujisawa Camphor" has increased 1,000-fold in the 100 years since it first went on sale. This 1,000-fold increase is not high at all. The price of "Fujisawa Camphor" was not low in the 1980s, one of grounds for setting the price was the damage caused by moths to expensive Japanese clothes and curios. For packaging in the Edo era, being wrapped in paper was the mainstream form, but modern-age packaging shifted to a cardboard box. As for "Fujisawa Camphor", a beautiful design was created for the cardboard.


Could Endothelin-1 Be a Promising Neurohormonal Biomarker in Acute Heart Failure?
Acute heart failure (AHF) is a life-threatening condition with high morbidity and mortality. Even though this pathology has been extensively researched, there are still challenges in establishing an accurate and early diagnosis, determining the long- and short-term prognosis and choosing a targeted therapeutic strategy. The use of reliable biomarkers to support clinical judgment has been shown to improve the management of AHF patients. Despite a large pool of interesting candidate biomarkers, endothelin-1 (ET-1) appears to be involved in multiple aspects of AHF pathogenesis that include neurohormonal activation, cardiac remodeling, endothelial dysfunction, inflammation, atherosclerosis and alteration of the renal function. Since its discovery, numerous studies have shown that the level of ET-1 is associated with the severity of symptoms and cardiac dysfunction in this pathology. The purpose of this paper is to review the existing information on ET-1 and answer the question of whether this neurohormone could be a promising biomarker in AHF.


Functional analysis of the finO distal region of plasmid R1.
The intergenic region linking conjugative transfer and replication copy control modules of IncF plasmids shows conservation of gene homology and organization. Genes distal to finO are coordinately expressed with the upstream transfer operon encoding the majority of conjugation genes in related plasmids. Here we investigate potential functions for these genes in copy number control and in processes related to conjugation: gene transfer, pilus specific phage infection and plasmid-promoted biofilm formation by an Escherichia coli host. We find that insertional inactivation of genes in the finO distal region reduced transcriptional read through into the downstream copB gene of plasmid R1. The mutant plasmid derivatives exhibited a reduced copy number compared to the wild type. Moreover all insertion mutant derivatives of plasmid R1-16 with aberrantly low copy numbers conferred poor biofilm forming ability to their hosts. The general mutagenesis thus identified plasmid stability genes as the only plasmid functions besides conjugation genes linked to plasmid-promoted biofilm production under these laboratory conditions. Our findings imply that a novel component of cis- or trans-regulation on the transcriptional level is important to normal R1 plasmid copy number regulation.


Expression of the human gamma-globin gene after retroviral transfer to transformed erythroid cells.
Regulation of the human fetal (gamma) globin gene and a series of mutant gamma-globin genes was studied after retroviral transfer into erythroid cells with fetal or adult patterns of endogenous globin gene expression. Steady-state RNA from a virally transferred A gamma-globin gene with a normal promoter increased after induction of erythroid maturation of murine erythroleukemia cells and comprised from 2% to 23% of the mouse beta maj-globin RNA level. RNA expression from the virally transferred A gamma-globin gene comprised 23% of the endogenous G gamma- + A gamma-globin expression in K 562 cells after treatment with hemin. Expression from a virally transferred gamma- or beta-globin gene exceeded endogenous gamma- or beta-globin expression by a factor of 6 or more in the human erythroleukemia line KMOE, in which the endogenous globin genes are weakly inducible. In these experiments, no difference in expression was observed between the gene with the normal promoter and an A gamma-globin gene with a point mutation in its promoter (-196 C-to-T) that has been associated with hereditary persistence of fetal hemoglobin (HPFH). To test for cis-acting determinants located within the introns of the gamma-globin gene, expression was measured from a set of gamma-globin genes configured with either intron alone or with neither intron. In contrast to an intronless beta-globin gene, which is not expressed in MEL cells, the intronless gamma-globin gene was expressed in MEL cells at 24% of the level of an intron-containing gene.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinicopathological significance and function of miR-135b in the occurrence and development of gastric cancer].
To explore the function and clinicopathological significance of miR-135b in the occurrence and development of gastric cancer. Seventy-two pairs of fresh gastric cancer tissues and corresponding normal gastric epithelium were collected at our department from September 2007 to March 2011. Six of them were randomly selected and miRNA microarray was applied to study the miRNA expression profiles of gastric cancer. Quantitative real-time PCR was used to validate the reliability of microarray and detect miR-135b expression in the above clinical samples, as well as cell lines GES-1, BGC-823 and SGC-7901. The methods of cell transfection, thiazolyl blue tetrazolium bromide (MTT) and flow cytometry were used to study the impact of miR-135 on cell proliferation, cell cycle and apoptosis of gastric cancer cells. Real-time quantitative PCR and Western blot were used to explore the relationship between miR-135b and adenomatous polyposis coli (APC). Compared with normal gastric tissues, 7 miRNA were significantly up-regulated and 9 miRNA significantly down-regulated for over 2 folds in gastric cancer tissues (P < 0.05). The results of microarray were verified by quantitative real-time PCR. MiR-135b expression was up-regulated in most clinical samples compared with their corresponding epithelium (n = 66, 91.67%). The average expression level of miR-135b in gastric cancer tissues was significantly higher than normal epithelium (3.42 ± 2.62 vs 1.00 ± 0.07, P < 0.05). MiR-135b was related to Laurén classification, tumor differentiation, invasion and pathologic tumor-node-metastasis (pTNM) stage of gastric cancer (all P < 0.05). The worse differentiation degree of gastric cell lines, the higher miR-135b expression level (P < 0.05). MiR-135b promoted gastric cancer cell proliferation, inhibited its apoptosis and directly regulated the expression of APC in gastric cancer cell. Special miRNA expression profiles of gastric cancer are found. MiR-135b is closely correlated with the biological behavior of human gastric cancer. And its regulation of APC may be one of the pathogenic mechanisms of gastric cancer.