Accelerated loss of diastase in mānuka honey: Investigation of mānuka specific compounds.
Diastase is used internationally as a quality monitor for excessive heat treatment and prolonged storage of honey; honey must contain an activity of at least 8 diastase numbers (DN) for it to be considered export quality. Freshly harvested mānuka honey can have diastase activity close to the export threshold of 8 DN without excess heating, increasing susceptibility for export failure. This research investigated the effect of compounds unique to or high in concentration in mānuka honey on diastase activity. Investigation of the effect of methylglyoxal, dihydroxyacetone, 2-methoxybenzoic acid, 3-phenyllatic acid, 4-hydroxyphenyllactic acid and 2'-methoxyacetophenone on diastase activity was carried out. Mānuka honey was stored at 20 and 27 °C and clover honey spiked with compounds of interest were stored at 20, 27 and 34 °C and monitored overtime. Methylglyoxal and 3-phenyllactic acid were found to accelerate the loss of diastase above the loss normally observed with time and elevated temperature.


Physiologic disposition of nabilone, a cannabinol derivative, in man.
Nabilone is a cannabinoid that is being evaluated in man as a potentially useful psychoactive drug. We found that nabilone was readily absorbed from the human gastrointestinal tract when administered orally as a coprecipitate with polyvinyl-pyrrolidone. The absorbed drug disappeared from plasma rather rapidly (half-life, approximately 2 hr), evidently due to extensive tissue distribution and rapid metabolism. The metabolites of nabilone persist in plasma for extended periods (half-life of total radioactivity exceeds 20 hr). Circulating metabolites include isomeric carbinols formed by reduction of the ketone in the 9-position of nabilone. Nabilone is eliminated in feces (about 65% of dose) and urine (20%). The excretory products in urine have not been identified, but metabolites that are labile to hydrolysis by beta-glucuronidase or sulfatase do not appear to be formed in significant amounts. A metabolite of nabilone in feces has been identified as a diol formed by reduction of the 9-keto group plus oxidation at the penultimate carbon of the dimethylheptyl side chain. The long duration of action of nabilone in the face of rapid and extensive metabolic elimination suggests that the pharmacologic effects, at least in part, may be exerted by one or more active metabolites.


Effects of drug-induced changes in brain monoamines on aggression and motor behavior in mice.
Mice maintained on a basal casein diet supplemented with 4% L-tyrosine potentiated L-DOPA effects on aggression. At low doses (12.5-25 mg/kg) L-DOPA increased aggression whereas at high doses (50-100 mg/kg) it decreased aggression. 5-HTP (50-200 mg/kg) produced a dose-dependent decrease in aggression and motor activity which was antagonized by pretreatment with dietary L-tyrosine (4%) or L-DOPA (50 mg/kg). L-DOPA induced reductions in motor activity were, in turn, antagonized by 5-HTP. Increases in motor activity following d-amphetamine (3 mg/kg) were sharply reduced by 5-HTP (50-100 mg/kg), but 5-HTP potentiated reductions in aggression following d-amphetamine. The concentration in brain of tyrosine, DOPA, dopamine (DA), noradrenaline (NA), DOPAC, HVA, tryptophan, serotonin (5-HT), and 5-HIAA were obtained following drug and diet treatments. The changes observed, particularly in DA and 5-HT metabolites, provide further evidence for an inhibitory role of brain 5-HT systems in the mediation of the behavioral effects of d-amphetamine and the catecholamine precursors, L-tyrosine and L-DOPA.


A novel HPLC method for the concurrent analysis and quantitation of seven water-soluble vitamins in biological fluids (plasma and urine): a validation study and application.
An HPLC method was developed and validated for the concurrent detection and quantitation of seven water-soluble vitamins (C, B(1), B(2), B(5), B(6), B(9), B(12)) in biological matrices (plasma and urine). Separation was achieved at 30°C on a reversed-phase C18-A column using combined isocratic and linear gradient elution with a mobile phase consisting of 0.01% TFA aqueous and 100% methanol. Total run time was 35 minutes. Detection was performed with diode array set at 280 nm. Each vitamin was quantitatively determined at its maximum wavelength. Spectral comparison was used for peak identification in real samples (24 plasma and urine samples from abstinent alcohol-dependent males). Interday and intraday precision were <4% and <7%, respectively, for all vitamins. Recovery percentages ranged from 93% to 100%.


Isolation and propagation of primary human and rodent embryonic neural progenitor cells and cortical neurons.
The research on human neural progenitor cells holds great potential for the understanding the molecular programs that control differentiation of cells of glial and neuronal lineages and pathogenetic mechanisms of neurological diseases. Stem cell technologies provide also opportunities for pharmaceutical industry to develop new approaches for regenerative medicine. Here we describe the protocol for isolation and maintenance of neural progenitor cells and cortical neurons using human fetal brain tissue. This protocol can be successfully adapted for preparation of rodent neural and oligodendrocyte progenitor cells. While several methods for isolation of neural and oligodendrocyte progenitors from rodent brain tissue have been described, including techniques which use gene transfer and magnetic resonance beads, few methods are focused on derivation of human oligodendrocyte progenitor cells. Development of human culture provides the most physiologically relevant system for investigation of mechanisms which regulate function of oligodendrocyte, specifically of human origin.


Prediction of fluid responsiveness following liver compression in pediatric patients with single ventricle physiology.
The role of liver compression in predicting fluid responsiveness in children with a single ventricle has never been evaluated. The purpose of this study was to assess whether blood pressure changes during liver compression predict fluid responsiveness in children with single ventricle physiology. This prospective, interventional study included children aged 3 months to 5 years who underwent surgery for bidirectional cavopulmonary shunt or extracardiac Fontan operation. Before fluid loading, the right upper abdomen was compressed at 30 mmHg for 10 s, and changes in the blood pressure waves were recorded before administering 10 ml kg-1 of crystalloid solution. Systolic arterial pressure, diastolic arterial pressure, central venous pressure, pleth variability index, respiratory variation in aortic blood flow peak velocity, and stroke volume were measured before and after fluid loading. A volume responder was defined as a patient with >15% increase in stroke volume index. Thirty patients underwent bidirectional cavopulmonary shunt (15 responders and 15 non-responders), and 32 underwent Fontan surgery (17 responders and 15 non-responders). In children with bidirectional cavopulmonary shunt, Δsystolic arterial pressure > 8 mmHg (sensitivity 76.9% and specificity 93.3%), Δdiastolic arterial pressure > 7 mmHg (sensitivity 69.2% and specificity 93.3%), and Δmean arterial pressure > 7 mmHg (sensitivity 69.2% and specificity 100%) during liver compression predicted fluid responsiveness. The areas under the receiver operating characteristic curves of Δsystolic arterial pressure, Δdiastolic arterial pressure, and Δmean arterial pressure were 0.928, 0.859, and 0.874 (all p < .001). In children who underwent Fontan surgery, only Δsystolic arterial pressure > 16 mmHg was predictive of fluid responsiveness (sensitivity of 41.2% and specificity of 100%), with the areas under the receiver operating characteristic curves curve of 0.786 (p < .001). Pleth variability index and respiratory variation in aortic blood flow peak velocity had no predictive value for fluid responsiveness after both types of surgeries. In BCPS patients, liver compression increases the inferior vena cava flow which directly leads to an increase in preload. On the other hand, blood flow from the liver drains directly into the pulmonary arteries in Fontan circulation. Because of this characteristics for preload determination, the clinical application of liver compression to monitor hemodynamic changes might be more useful in patients with bidirectional cavopulmonary shunt than those with Fontan circulation. Increase in blood pressure induced by liver compression is predictive of fluid responsiveness in children with single ventricle physiology.


CT scan does not predict optimal debulking in stage III-IV epithelial ovarian cancer: a multicentre validation study.
Our aim was to design and validate a model of CT findings that predict suboptimal cytoreduction in primary surgery (PS) for Stage III-IV epithelial ovarian cancer (EOC). We performed a retrospective review of preoperative CT scans of patients undergoing PS for EOC in a cancer centre in London, UK, between November 1995 and October 2003 (n = 91). Radiological features predictive of suboptimal cytoreduction were identified and the model tested in a second cohort undergoing PS in Manchester, June 2005 - March 2007 (n = 35). In the London cohort, liver surface disease and infrarenal para-aortic lymph node involvement predicted suboptimal cytoreduction with 80% accuracy. Accuracy of these predictors dropped to 63% when applied to the Manchester cohort. We concluded that CT prediction of suboptimal cytoreduction is unreliable and may not be reproducible. In the absence of favourable data from larger, prospective trials, it should not be used to guide management.


Variable wind directions and anemotactic strategies of searching for an odour plume.
This paper deals with anemotactic strategies of searching for odour plumes under conditions of variation in wind direction and equal energy costs involved in moving a unit path length in any direction in the x, y plane. It is generally accepted that cross-wind searching is the best searching strategy to acquire a maximum amount of information. This is of course true, if the wind is unidirectional. A geometrical model of anemotactic searching is presented that takes into account variation in wind direction. It is shown, that, if wind direction fluctuates over a range larger than 30 degrees from the mean wind direction, then upwind or downwind searching is the best strategy and cross-wind searching is the worst of all possibilities.


Visualization of oxidative processes at the cellular level during neutrophil-mediated cytotoxicity against a human hepatoma cell line, HCC-M.
Human neutrophil-mediated oxidative processes against a human hepatoma cell line, HCC-M, was visualized at the cellular level by using a silicon-intensified target camera and subsequently processing with a computer-assisted digital-imaging processor. Neutrophils were activated by a streptococcal preparation, OK-432. A hydroperoxide-sensitive tracer, dichlorofluorescein diacetate, was loaded in HCC-M and temporal and spatial changes of lipid peroxides in this cell after addition of stimulated neutrophils were analyzed. The luminol-dependent chemiluminescence activity of neutrophils was significantly enhanced and continued for at least 2 hr by stimulation with OK-432, and its activity was shown to be accumulated at the site where a neutrophil attached with HCC-M. The intensity of dichlorofluorescein fluorescence in HCC-M rapidly increased after adding stimulated neutrophils, and their reaction was significantly attenuated by superoxide dismutase. The number of non-viable cells was increased as the dichlorofluorescein fluorescence increase. It is suggested that oxidative stress may play an important role in neutrophil-mediated tumor-cell damage.


Development of a proteomic approach to monitor protein synthesis in mycotoxin producing moulds.
In general, proteome studies compare different states of metabolism to investigate external or internal influences on protein expression. In the context of mycotoxin production the method could open another view on this complex and could be helpful to gain knowledge about proteins which are involved in metabolism (enzymes, transporters). In this short technical report, we describe a new protocol suitable for protein preparation for whole proteome analysis ofFusarium graminearum. Cell lysis was performed by grinding the mycelium with liquid nitrogen. Proteins were extracted with TCA/acetone and then cleaned; the isolated proteins were separated in a 2D-gel electrophoresis system (BioRad) using different pH gradients. The protocol established seems also generally applicable for other mycotoxin producing fungi.


Genetic association study of the HLA class II alleles DRB1, DQA1, and DQB1 in patients with pharmacoresistant temporal lobe epilepsy associated with mesial hippocampal sclerosis.
Temporal lobe epilepsy (TLE) is the most common variety of focal epilepsy among adults. The neuroinflammatory mechanisms of epilepsies may be involved in the genesis of seizures and refractory epilepsies, particularly in the case of progressive syndromes such as TLE associated with mesial hippocampal sclerosis (TLE-HS). The goal of the present study is investigate the genetic profile of susceptibility of individuals with TLE-HS by analyzing the possible association of TLE-HS with human leukocyte antigen (HLA) DRB1, DQA1 and DQB1 alleles. Peripheral blood samples were collected from 42 individuals with pharmacoresistant TLE-HS and 89 healthy controls. The typing of the HLA class II alleles from DRB1, DQB1, and DQA1 loci were analyzed using sequence-specific primer-polymerase chain reaction (SSP-PCR) and identified through sequencing. Statistical analysis of relative allele frequencies was performed using an Excel spreadsheet; p-value, relative risk (RR), and odds ratio (OR) were calculated using the software Epi Info 6.0. p-values <0.05 following Bonferroni's method correction were considered statistically significant. HLA-DRB1*13:02 was the only allele with a statistically significant difference (p=0.01) in frequency between patients and controls. However, the significance was lost following Bonferroni's method correction (p=0.44). The remainder of the alleles in the HLA-DRB1, HLA-DQB1 and HLA-DQA1 regions did not exhibit any significant association. The allele HLA DRB1*13:02 has exhibited a tendency to behave as a susceptibility factor for TLE-HS.


Serum hyperviscosity syndrome responding to therapeutic plasmapheresis in a patient with primary Sjögren's syndrome.
Hyperviscosity syndrome is a disorder first described in patients with Waldenström's macroglobulinemia and is not commonly seen in rheumatic diseases. Its association with Sjögren's syndrome is very rare and it has been reported in very few patients. We report the case of a patient with primary Sjögren's syndrome presenting as hyperviscosity syndrome who was successfully treated with therapeutic plasma exchange.


A direct radioimmunoassay for estriol-16-glucuronide in urine for monitoring pregnancy and induction of ovulation.
Antibodies to estriol-16alpha-[beta-D-glucuronide] were raised in sheep with the use of keyhold limpet hemocyanin and bovine serum albumin conjugates of estriol-16alpha-[beta-D-glucuronide]. A simple, rapid method is presented for direct radioimmunoassay of estriol-16alpha-[beta-D-glucuronide] in urine with dextran-coated charcoal used for separation of free from bound and deionized water used for dilutions. The method is thrifty in its use of reagents. The assay has been evaluated in the pregnancy range, and the sensitivity has been extended into the range necessary for monitoring induction of ovulation with Pergonal.


Data augmentation using generative adversarial networks (CycleGAN) to improve generalizability in CT segmentation tasks.
Labeled medical imaging data is scarce and expensive to generate. To achieve generalizable deep learning models large amounts of data are needed. Standard data augmentation is a method to increase generalizability and is routinely performed. Generative adversarial networks offer a novel method for data augmentation. We evaluate the use of CycleGAN for data augmentation in CT segmentation tasks. Using a large image database we trained a CycleGAN to transform contrast CT images into non-contrast images. We then used the trained CycleGAN to augment our training using these synthetic non-contrast images. We compared the segmentation performance of a U-Net trained on the original dataset compared to a U-Net trained on the combined dataset of original data and synthetic non-contrast images. We further evaluated the U-Net segmentation performance on two separate datasets: The original contrast CT dataset on which segmentations were created and a second dataset from a different hospital containing only non-contrast CTs. We refer to these 2 separate datasets as the in-distribution and out-of-distribution datasets, respectively. We show that in several CT segmentation tasks performance is improved significantly, especially in out-of-distribution (noncontrast CT) data. For example, when training the model with standard augmentation techniques, performance of segmentation of the kidneys on out-of-distribution non-contrast images was dramatically lower than for in-distribution data (Dice score of 0.09 vs. 0.94 for out-of-distribution vs. in-distribution data, respectively, p < 0.001). When the kidney model was trained with CycleGAN augmentation techniques, the out-of-distribution (non-contrast) performance increased dramatically (from a Dice score of 0.09 to 0.66, p < 0.001). Improvements for the liver and spleen were smaller, from 0.86 to 0.89 and 0.65 to 0.69, respectively. We believe this method will be valuable to medical imaging researchers to reduce manual segmentation effort and cost in CT imaging.


V1 neurons respond differently to object motion versus motion from eye movements.
How does the visual system differentiate self-generated motion from motion in the external world? Humans can discern object motion from identical retinal image displacements induced by eye movements, but the brain mechanisms underlying this ability are unknown. Here we exploit the frequent production of microsaccades during ocular fixation in the primate to compare primary visual cortical responses to self-generated motion (real microsaccades) versus motion in the external world (object motion mimicking microsaccades). Real and simulated microsaccades were randomly interleaved in the same viewing condition, thereby producing equivalent oculomotor and behavioural engagement. Our results show that real microsaccades generate biphasic neural responses, consisting of a rapid increase in the firing rate followed by a slow and smaller-amplitude suppression that drops below baseline. Simulated microsaccades generate solely excitatory responses. These findings indicate that V1 neurons can respond differently to internally and externally generated motion, and expand V1's potential role in information processing and visual stability during eye movements.


Efficacy and safety of ciprofloxacin in the treatment of UTIs and RTIs in patients affected by liver diseases.
The clinical efficacy and the safety of ciprofloxacin was studied in 92 patients (aged 26 to 83 years; mean 57.5 years) affected by urinary tract infections (UTI) and respiratory tract infections (RTI) suffering also with various liver diseases. Ciprofloxacin was given orally at different dose regimens: 500 mg b.i.d. (22 cases), 250 mg b.i.d. (20 cases), 500 mg s.i.d. (20 cases) for the treatment of UTIs; 500 mg b.i.d. (ten cases) and 250 mg b.i.d. (20 cases) for the treatment of RTIs. The doses were not correlated to the severity of the infections. Patients were treated for five to 15 days. All the bacteria isolated from sputum or urine before treatment were sensitive to ciprofloxacin (MIC range less than or equal to 0.015 mg/l to 8 mg/l). The clinical and bacteriological responses were favourable in a high percentage of patients both for RTIs and UTIs, irrespective of the dose. Side effects were infrequent (7%) and mild (nausea, gastralgia, oral candidosis), never requiring the interruption of the treatment. No change in the blood chemistry tests was observed at any dose.


Gold nanolayer-encapsulated silica particles synthesized by surface seeding and shell growing method: near infrared responsive materials.
Gold nanolayer-encapsulated silica particles whose optical resonance is located in 750-900 nm spectral region were synthesized by combining Sn (tin)-surface seeding and a shell growing process. The synthesized composite particles can be potentially used in wide biological fields, due to biocompatibility and a well-known bioconjugation technique of gold layer. Sn atoms, which can act not only as a catalytic surface for reduction of gold but also as a linker between silica surface and gold nanoparticles, were chemically deposited on hydroxylated silica particles. Then, we introduced another reductant with gold chloride in order to produce a multilayer of Au shell. In the process, Au shells grew by the reduction of additional gold ions on the Sn-functionalized silica surface and resulted in the subsequent coalescence and growth of the deposited gold nanoparticles. Finally, a complete gold nanoshell was formed on the silica surface by the one-step method, without a repeated coating process. The deposition of a gold nanolayer on the silica particles was easily controlled by the concentration ratio of Sn-functionalized silica particles and gold chloride solutions. Transmission electron microscopy (TEM) images and optical extinction spectra clearly showed that gold nanolayers were successfully deposited on the silica surface by the novel method. As the gold colloids attached on the silica surface grew, their optical plasmon peak became red-shifted until complete a gold shell was formed. After the gold shell was completed, the optical plasmon resonance became blue-shifted and the extinction spectra were functions of a relative ratio of the core to shell thickness.


Tissue safety in view of CJD and variant CJD.
Epidemiological studies on human transmissible spongiform encephalopathies (Creutzfeldt-Jakob Disease, CJD) have shown that the agent could be transmitted by highly infectious tissues like brain, spinal cord or retina and medicinal products derived from these tissues (i.e. human growth hormone, dura mater). A few cases of transmission of CJD by neurosurgical instruments have been reported. The transmission of the agent of variant CJD, which is suspected to be transmitted by BSE-contaminated food, by blood transfusion implies that in contrast to the agent of classical CJD this agent can also be transmitted by organs and tissues other than nerve tissues. Health authorities have implemented guidelines to reduce the risk of transmission of human and animal TSE by human and veterinary medicinal products. The high resistance of TSE agents against physical or chemical treatment hamper the development of highly efficient inactivation steps in the production of medicinal products. Donor selection is considered as an efficient measure to reduce the risk of TSE transmission. However, the development of rapid, sensitive and specific diagnostic test systems is urgently required to test blood, organs and tissue of donors.


Diffusion Mechanisms of Dissolved Gases in Transformer Oil Influenced with Moisture Based on Molecular Dynamics Simulation.
Dissolved Gas Analysis (DGA) of insulating oil is widely used for diagnosing transformer incipient faults. Moisture is a major contaminant and degradation byproduct of transformer insulating oil. In this paper, molecular dynamics simulation was used to study the influence of moisture on the diffusion movement of dissolved gases in the insulating oil. Cycloalkanes (C20H42), alkanes (C20H38), and aromatic hydrocarbons (C20H26) are selected as the basic structural units in the constructed transformer oil simulation system. 0%, 1%, 3%, and 5% moisture molecules are added to insulating oil, respectively, and the insulating oil generates seven kinds of gas molecules through cracking. With an anhydrous model used as a benchmark, we researched the diffusion trajectory, the diffusion coefficient (D), free volume (V F), and the moisture-gas interaction energy of each gas molecule as a function of moisture content. Through this study, we found that the increase of moisture content enlarges the V F value of dissolved gas in insulating oil, which makes the gas in oil easier to diffuse. Besides, the moisture can also alter the mean square displacement (MSD) of dissolved gases; the mutual energy of molecules is mainly affected by the electrostatic interaction energy. This study can contribute to a better understanding of the influence of different moisture contents on the diffusion movement of dissolved gas in transformer oil from the micro level.


Cat 'P300' and cholinergic septohippocampal neurons: depth recordings, lesions, and choline acetyltransferase immunohistochemistry.
The role of septohippocampal circuits in the generation of the P300 response in cats (n = 12) was explored in a series of depth recording, tract-tracing and lesion experiments. Systematic mapping of the hippocampus in 1-mm increments from rostral to caudal extent revealed large positive potentials, greater in amplitude to rare than to frequent stimuli, within the 200-500 ms range. Each map revealed maximal amplitude responses at diverse, widely distributed hippocampus loci. Furthermore, these electrical responses displayed polarity inversion within the hippocampus that was generally localized to the pyramidal cell layer; polarity inversion was also observed in the adjacent entorhinal cortex and amygdala. Injections of propidium iodide, a tract-tracing agent, into these inversion sites resulted in retrograde labeling of small clusters of choline acetyltransferase (ChAT)-positive neurons in the medial septal nucleus and vertical limb of the diagonal band. Aspiration lesions that bilaterally destroyed large amounts of caudal hippocampus from stereotaxic levels A4 to A1 resulted in a decreased number of cells expressing ChAT in the rostral basal nuclear complex. In only 2 cats was the preoperative presence of a significant vertex P300 absent postoperatively. In the majority of cases (5 of 8 animals), hippocampal aspiration produced an enhancement of the preoperative P300 potential. We conclude that cholinergic mechanisms are importantly, albeit not exclusively, involved in the mediation of P300 potentials in cats. Neurons mediating P300 responses appear to be organized in diverse clusters of septal and diagonal band cells. These septal cells may facilitate, and in turn be facilitated or inhibited as a function of hippocampal, or other, allocortical feedback loops.


Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study.
To determine the efficacy and tolerability of gemcitabine (GEM)-concurrent chemoradiotherapy (CCRT) vs. 5-fluorouracil (5-FU) CCRT for locally advanced pancreatic cancer. Thirty-four patients with locally advanced pancreatic cancer were studied. Eighteen patients were randomized to receive GEM CCRT (600 mg/m(2)/wk for 6 weeks) and 16 patients to receive bolus 5-FU CCRT (500 mg/m(2)/d for 3 days repeated every 2 weeks for 6 weeks). All patients were to receive 3D-CRT 50.4-61.2 Gy at 1.8-Gy/d fractions and GEM (1000 mg/m(2) weekly for 3 weeks repeated every 4 weeks) after RT. The median survival and median time to progression were 14.5 months and 7.1 months for the GEM CCRT group and 6.7 months and 2.7 months for the 5-FU CCRT group (p = 0.027 and p = 0.019, respectively). The quality-adjusted life month survival time was 11.2 +/- 0.5 months for GEM CCRT and 6.0 +/- 0.3 months for 5-FU CCRT patients (p <0.001). The response rate was 50% (four complete responses and five partial responses) for GEM CCRT and 13% (two partial responses) for 5-FU CCRT (p = 0.005). Pain control was 39% for GEM CCRT and 6% for 5-FU CCRT (p = 0.043). Grade 3-4 neutropenia (34% vs. 19%), thrombocytopenia (0% vs. 7%), nausea (33% vs. 31%), vomiting (17% vs. 19%), hospitalization days per month of survival (7.4 +/- 1.7 days vs. 8.0 +/- 1.3 days), and full dose of RT received (78% vs. 75%) were not significantly different between the GEM CCRT and 5-FU CCRT patients. GEM CCRT appears more effective than 5-FU CCRT for locally advanced pancreatic cancer and has comparable tolerability.


Analysis of ceramide and monohexaosyl glycolipid derivatives by high-performance liquid chromatography and its application to the determination of the molecular species in tissues.
Several molecular species of monohexaosyl glycolipids and ceramides were analyzed as their benzoyl derivatives by high-performance liquid chromatography on a silica column with mixtures of dioxane and hexane as eluents. Monohexaosyl glycolipid derivatives were classified according to their hydrophobic structures, and ceramides were separated based on the fatty acid groups and the long-chain bases. The method allowed us to observe the heterogeneities in the molecular species of cerebrosides and ceramides from the epidermis and dermis of the guinea pig, and clear differences in the molecular species were observed between the different regions.


Yoga and Cardiovascular Health Trial (YACHT): a UK-based randomised mechanistic study of a yoga intervention plus usual care versus usual care alone following an acute coronary event.
To determine the effects of yoga practice on subclinical cardiovascular measures, risk factors and neuro-endocrine pathways in patients undergoing cardiac rehabilitation (CR) following acute coronary events. 3-month, two-arm (yoga +usual care vs usual care alone) parallel randomised mechanistic study. One general hospital and two primary care CR centres in London. Assessments were conducted at Imperial College London. 80 participants, aged 35-80 years (68% men, 60% South Asian) referred to CR programmes 2012-2014. A certified yoga teacher conducted yoga classes which included exercises in stretching, breathing, healing imagery and deep relaxation. It was pre-specified that at least 18 yoga classes were attended for inclusion in analysis. Participants and partners in both groups were invited to attend weekly a 6- to 12-week local standard UK National Health Service CR programme. (i) Estimated left ventricular filling pressure (E/e'), (ii) distance walked, fatigue and breathlessness in a 6 min walk test, (iii) blood pressure, heart rate and estimated peak VO2 following a 3 min step-test. Effects on the hypothalamus-pituitary-adrenal axis, autonomic function, body fat, blood lipids and glucose, stress and general health were also explored. 25 participants in the yoga + usual care group and 35 participants in the usual care group completed the study. Following the 3-month intervention period, E/e' was not improved by yoga (E/e': between-group difference: yoga minus usual care:-0.40 (-1.38, 0.58). Exercise testing and secondary outcomes also showed no benefits of yoga. In this small UK-based randomised mechanistic study, with 60 completing participants (of whom 25 were in the yoga + usual care group), we found no discernible improvement associated with the addition of a structured 3-month yoga intervention to usual CR care in key cardiovascular and neuroendocrine measures shown to be responsive to yoga in previous mechanistic studies. NCT01597960; Pre-results.


Parathyroid disorders of pregnancy.
Diseases of the parathyroid gland are uncommon in women of childbearing age. However, total serum calcium is lower in normal pregnancy, but ionized serum calcium remains within normal limits. Serum parathyroid levels are slightly decreased in the second half of pregnancy. Primary hyperparathyroidism, if unrecognized, may increase maternal and fetal morbidity, which is related to the level of serum calcium. The most common cause is a single parathyroid adenoma, accounting for about 80% of cases. Maternal complications include acute pancreatitis, hypercalcemia crisis, and toxemia. An increased incidence of prematurity and neonatal hypocalcemia has been reported when maternal hypercalcemia is significantly elevated. Other causes of hypercalcemia are rare in pregnancy. Hypoparathyroidism is seldom seen in pregnancy; the most common cause is after surgical throidectomy. The doses of vitamin D and calcium do not change during pregnancy; however, hypercalcemia may develop in the postpartum period. Serum calcium should be determined at every trimester of pregnancy and at regular intervals after delivery, and in a significant number of patients, the dose of vitamin D should be reduced. Osteoporosis has been recognized most frequently in the last few years. It appears that those patients with a family history of osteoporosis and those on heparin therapy have a tendency to develop symptoms of the disease in pregnancy. Finally, lactation is not contraindicated in women with osteoporosis; although there is a slight decrease in bone density in the few months after delivery, this is a transient event and bone densitometry returns to prepregnancy levels in most women. Recent studies indicate that there is no need for calcium therapy during lactation with few exceptions, such as lactating adolescents, mothers nursing more than one child, and mothers with closely-spaced pregnancies.


Bilateral chemodectoma: medicolegal considerations on a case report of aeromedical concern.
The authors describe a case of bilateral carotid chemodectoma occurring in a military pilot who was assessed and evaluated in terms of aeromedical and medico-legal aspects for his fitness to fly. In view of the lack of specific guidelines and/or regulations, both national and international, we choose to follow a multidisciplinary clinical approach that included aero-physiological tests in the hypobaric chamber, in order to identify a standard protocol that could be used as reference for similar future cases, where this kind of assessment is necessary.


Therapy with intermittent pulse cyclophosphamide for pulmonary hypertension associated with systemic lupus erythematosus.
The aim of this study was to compare the efficacy of intravenous cyclophosphamide (IVCYC) versus oral enalapril in mild or moderate pulmonary hypertension (PH) in systemic lupus erythematosus (SLE). Thirty-four patients with SLE who had systolic pulmonary artery pressure (SPAP) > 30 mmHg by Doppler echocardiography were randomized to receive IVCYC (0.5 g/mt2 body surface area, monthly), or oral enalapril (10 mg/day) for six months. The primary outcome was the significant decrease in SPAP. An additional outcome measure included the improvement in the heart functional class (NYHA). Sixteen patients received cyclophosphamide and 18 enalapril. IVCYC decreased the median values of SPAP from 41 to 28 mmHg (P < 0.001), and enalapril from 35 to 27 mmHg (P = 0.02). IVCYC reduced more than twice as much SPAP than enalapril (P = 0.04). In those patients with SPAP > or = 35 mmHg, cyclophosphamide decreased from 43 to 27 mmHg (P = 0.003), but enalapril was not effective (P = 0.14). The NYHA functional class improved only in those with cyclophosphamide (P = 0.021). Also IVCYC had a higher frequency of side effects including infections (RR = 1.6; 95% CI, 1.001-2.47), and gastrointestinal side effects (RR = 14.6; 95% CI, 2.15-99.68). We concluded that IVCYC was effective in mild and moderate PH associated with SLE. Further research is needed to evaluate its long-term efficacy.


Prognostic value of left ventricular blood stasis in patients with acute myocardial infarction: A cardiac magnetic resonance study.
Cerebrovascular accidents (CVAs) can complicate the follow-up of patients with acute myocardial infarction (AMI). Intracavitary blood stasis evaluation can be useful to stratify cardioembolic risk and optimize medical therapy. Cardiac magnetic resonance (CMR) imaging is increasingly used in AMI patients for prognostic purposes. Slow-flow artefact is common on T2-weighted images in presence of left ventricular (LV) blood stasis. In this observational retrospective study, all patients with AMI undergoing CMR in our hospital were included. T2-weighted images were used to assess the presence of LV blood stasis. Among the 209 patients enrolled (males 72%, mean age 61 ± 12 years), LV blood stasis was detected in 48 (23%) and was significantly more prevalent in patients with extensive anterior or antero-apical AMI, lower LV ejection fraction, greater infarct size and microvascular obstruction. During follow-up (54 months, IQR 41-70), 8 CVAs and 6 cardiovascular deaths occurred. LV blood stasis emerged as a significant risk factor for both endpoints (logRank p < 0.001 and p = 0.008, respectively) and remained independent predictor of CVAs (HR 9.819, 95% CI 1.733-55.617, p = 0.010). LV blood stasis identified with CMR predicts the occurrence of CVAs in patients with AMI. These results may be helpful to personalize antithrombotic therapy for prevention strategies.


Asthma in the workplace.
Occupational asthma (OA) refers to asthma that occurs as a result of workplace inhalation exposures. Most workers exposed to antigens and irritants will not develop OA. Although much more study focused on OA needs to be completed, it can be stated with some surety that identification of IgE-mediated sensitization and bronchial hyperresponsiveness occurs with OA. Also, extreme short-term chemical exposures versus a cumulative effect of chemical exposures will need continued evaluation to determine tolerable levels that do not cause harm. Health care providers often seek guidance from NIOSH, which sponsors ongoing research and training related to workplace exposures.


Endothelial G protein-coupled receptor kinase 2 regulates vascular homeostasis through the control of free radical oxygen species.
The role of endothelial G protein-coupled receptor kinase 2 (GRK2) was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2(fl/fl)). Aortas from Tie2-CRE/GRK2(fl/fl) presented functional and structural alterations as compared with control GRK2(fl/fl) mice. In particular, vasoconstriction was blunted to different agonists, and collagen and elastic rearrangement and macrophage infiltration were observed. In primary cultured endothelial cells deficient for GRK2, mitochondrial reactive oxygen species was increased, leading to expression of cytokines. Chronic treatment with a reactive oxygen species scavenger in mice corrected the vascular phenotype by recovering vasoconstriction, structural abnormalities, and reducing macrophage infiltration. These results demonstrate that GRK2 removal compromises vascular phenotype and integrity by increasing endothelial reactive oxygen species production.


In vivo study on cross talk between inducible nitric-oxide synthase and cyclooxygenase in rat gastric mucosa: effect of cyclooxygenase activity on nitric oxide production.
The integrity of gastric mucosa during endotoxemia is maintained by the balance of inflammatory mediators, such as prostanoids originated from cyclooxygenase-2 (COX-2) and nitric oxide (NO) from inducible nitric-oxide synthase (iNOS). Thus, we elucidated in vivo cross talk between prostanoids and NO in gastric mucosa during endotoxemia, using an iNOS-specific inhibitor, N-(3-(aminomethyl)benzyl)acetamidine (1400W); a nonspecific COX inhibitor, indomethacin; and a COX-2-specific inhibitor, N-(2-[cyclohexyloxy]-4-nitrophenyl)methanesulfonamide (NS-398). Gastric mucosal NO and prostaglandin E2 (PGE2), a predominant product of COX, expressed as mean +/- S.D. of five rats per group, were assayed by electron paramagnetic resonance spectrometry and enzyme immunoassay technique, respectively. The levels of NO and PGE2 increased gradually up to 6 h after administration of bacterial lipopolysaccharide (LPS) (NO: control, 0.35 +/- 0.16; 6 h, 13.3 +/- 3.3 nmol/g tissue/30 min; and PGE2: control, 288 +/- 16; 6 h, 806 +/- 15 pg/g tissue). Pretreatment with 1400W decreased the increase in NO level without any effect on the PGE2 level (NO, 4.0 +/- 0.4 nmol/g tissue/30 min; PGE2, 788 +/- 26 pg/g tissue). In contrast, treatment with indomethacin and NS-398 inhibited not only PGE2 level but also NO level in a dose-dependent manner without any significant effect on both iNOS and COX protein and mRNA expression. These results demonstrate that in the LPS-treated rat gastric mucosa, PGE2 enhances the release of NO after activation of iNOS, although NO produced by iNOS does not stimulate the release of PGE2 by COXs. The effect of COX activity on iNOS-NO pathway can be important in the regulation of gastric mucosal integrity in inflammatory states.


A region in the steroid binding domain determines formation of the non-DNA-binding, 9 S glucocorticoid receptor complex.
This work was initiated to determine if a specific region of the glucocorticoid receptor determines the formation of the inactive (i.e. non-DNA-binding) 9 S form of the receptor recovered in cytosol preparations. It is known that the murine glucocorticoid receptor of the nti phenotype, which consists of only the carboxyl-terminal 40-kDa peptide containing the DNA-binding and steroid-binding domains separated by a short linker region, is recovered in hypotonic lysates as a 9 S heteromeric complex (Gehring, U., and Arndt, H. (1985) FEBS Lett. 179, 138-142). To further localize the domain required for formation of the 9 S complex, we have determined the sedimentation coefficients of receptors produced in COS-7 cells transfected with several mutants of the human glucocorticoid receptor gene. Deletion of the DNA-binding domain results in a 9 S complex that is somewhat less stable than the wild type receptor during sucrose gradient centrifugation. Deletion of the linker region yields a molybdate-stabilized 9 S complex, but deletion of the entire steroid-binding domain or internal deletion of the amino-terminal two-thirds of this domain yields receptors that are constitutive transcriptional activators and are present in cytosol only in the 4 S form. Taken together, these observations demonstrate that the steroid-binding domain contains the features required for formation of the 9 S heteromeric complex, and they are consistent with the proposal that the steroid-binding domain normally represses receptor function.


Valproic acid reduces insulin-resistance, fat deposition and FOXO1-mediated gluconeogenesis in type-2 diabetic rat.
Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage. Insulin-resistance, dyslipidemia and glycemia were evaluated by biochemical estimations, while fat accumulation and structural alteration were assessed by histopathology. Protein expression and insulin signaling were evaluated by western blot and immunohistochemistry. VPA treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, fat deposition in brown adipose tissue, white adipose tissue and liver, which are comparable to metformin treatment. Further, VPA inhibited the gluconeogenesis and glucagon expression as well as restored the histopathological alterations in pancreas and liver. Our findings provide new insights on the anti-diabetic role of VPA in type-2 diabetes mellitus by the modulation of insulin signaling and forkhead box protein O1 (FOXO1)-mediated gluconeogenesis. Since VPA is a well established clinical drug, the detailed molecular mechanisms of the present findings can be further investigated for possible clinical use.


To screen or not to screen: Are we asking the right question? In response to considering de-implementation of universal perinatal depression screening.
This Editorial is a response to the Canadian Task Force on Preventive Health Care's recent recommendation "against instrument-based depression screening using a questionnaire with cut-off score to distinguish 'screen positive' and 'screen negative' administered to all individuals during pregnancy and the postpartum period (up to 1 year after childbirth)." While we acknowledge the gaps and limitations in research on perinatal mental health screening, we have concerns regarding the potential impact of a recommendation against screening and for "de-implementation" of existing perinatal depression screening practices, particularly if there is not careful attention to the specificity as well as limitations of the recommendation, or if there are not clear alternative systems put in place to support the detection of perinatal depression. In this manuscript, we highlight some of our key concerns and suggest considerations for perinatal mental health practitioners and researchers.


Effect of Citrulline and Leucine Intake with Exercises on Body Composition, Physical Activity, and Amino Acid Concentration in Older Women: A Randomized Double-Blind Placebo-Controlled Study.
The combined intake of citrulline (CIT) and leucine (LEU) can stimulate protein synthesis. Therefore, this study aimed to investigate the effect of combined intake of CIT and LEU accompanied by exercise for 20 weeks on body composition, physical activity (PA), and amino acid concentrations in older Japanese women with low body mass index (BMI) (16 to 21 kg/m2) using a randomized, double-blind, placebo-controlled design. The supplement was administered twice a day for 20 weeks (Ex (exercise) + CIT·LEU group, n = 10: mainly 0.8 g CIT and 1.6 g LEU; Ex + Placebo group, n = 13: mainly 3.5 g carbohydrate). Additionally, both groups exercised (weight-bearing exercise, square stepping exercise) once a week for 75 min. Body composition, PA, and amino acid concentrations in the plasma were measured. Body weight, BMI, body mass, household PA, total PA, and phenylalanine significantly increased in the Ex + CIT·LEU group (p < 0.05) post intervention. This study suggests that the combined intake of CIT and LEU accompanied by exercise can improve body weight, BMI, body mass, and PA in older women with low BMI, which may prevent sarcopenia and frailty.


Effect of SO4 2-/Al3+ ratio and OH-/Al3+ value on the characterization of coagulant poly-aluminum-chloride-sulfate (PACS) and its coagulation performance in water treatment.
A poly-aluminum-chloride-sulfate (PACS) was prepared at various experimental conditions. It was found that the coagulation performance of PACS in water treatment was affected by the PACS particle size distribution and zeta potential value. The experimental results indicated that the PACS particle size distribution and zeta potential value were highly influenced by SO(4)(2-)/Al(3+) molar ratio and bacicities (gamma,gamma=[OH]/[Al]) value. At a fixed gamma value of 2.0, the average PACS particle size increased from 25 to 80nm with the increase of SO(4)(2-)/Al(3+) ratio from 0 to 0.1. Further increase of the SO(4)(2-)/Al(3+) ratio resulted in acute increment particle size of PACS extremely, which can be attributed to its aggregation. At a fixed SO(4)(2-)/Al(3+) ratio of 0.0664, the largest average size of PACS occurred at gamma=2.0. It was also found that the zeta potential value of PACS was strongly influenced by the SO(4)(2-)/Al(3+) ratio, gamma value and pH of the aquatic solution. The zeta potential value of PACS increased with increasing of SO(4)(2-)/Al(3+) ratio. At a fixed SO(4)(2-)/Al(3+) ratio of 0.0664, PACS achieved greatest zeta potential value at gamma value of around 2.0. The maximum positive zeta potential value of PACS was found at pH5.3. At a fixed gamma value of 2.0 and SO(4)(2-)/Al(3+) ratio of 0.0664, the PACS achieved an optimum natural organic matter and turbidity removal efficiency.


Medical Student Assessment in the Time of COVID-19.
Medical student education in the era of the COVID-19 outbreak is vastly different than the standard education we have become accustomed to. Medical student assessment is an important aspect of adjusting curriculums in the era of increased virtual learning. Students took our previously validated free response clinical skills exam (CSE) at the end of the scheduled clerkship as an open-book exam to eliminate any concern for breaches in the honor code and then grades were adjusted based on historic norms. The National Board of Medical Examiners (NBME) shelf exam was taken with a virtual proctor. Students whose clerkship was affected by the COVID-19 pandemic were compared to the students from a similarly timed surgery block the previous 3 years. Primary outcomes included CSE and NBME exam scores. Secondary outcomes included clinical evaluations and the percentage of students who received grades of Honors, High Pass, and Pass. After the surgery clerkship was completed, we surveyed all students who participated in the surgery clerkship during the COVID-19 crisis. There were 19 students during the COVID-interrupted clerkship and 61 students in similarly timed clerkships between 2017 and 2019. Prior to adjustment and compared to historic scores, the COVID-interrupted clerkship group scored higher on the CSE, NBME exam, and performance evaluations (median, CSE:75.2 vs 68.7, shelf:68.0 vs 64.0, performance evaluation mean: 2.96 vs 2.78). The percentage of students with an honors was marginally higher in the group affected by COVID (42% vs 32%). Out of 19 students surveyed, 9 students responded. Seven students stated they would have preferred a closed-book CSE, citing a few drawbacks of the open-book format such as modifying their exam preparation, being discouraged from thinking prior to searching online during the test, and second guessing their answers. During the initial outbreak of COVID-19, we found that an open book exam and a virtually proctored shelf exam was a reasonable option. However, to avoid adjustments and student dissatisfaction, we would recommend virtual proctoring if available.


PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation.
Peroxisome proliferator-activated receptor δ (PPARδ) belongs to the nuclear receptor family and is involved in metabolic diseases. Although PPARδ is known to attenuate hepatic lipid deposition, its mechanism remains unclear. Here, we show that PPARδ is a potent stimulator of hepatic autophagic flux. The expression levels of PPARδ and autophagy-related proteins were decreased in liver tissues from obese and ageing mice. Pharmacological and adenovirus-mediated increases in PPARδ expression and activity were achieved in obese transgenic db/db and high fat diet-fed mice. Using genetic, pharmacological and metabolic approaches, we demonstrate that PPARδ reduces intrahepatic lipid content and stimulates β-oxidation in liver and hepatic cells by an autophagy-lysosomal pathway involving AMPK/mTOR signalling. These results provide novel insight into the lipolytic actions of PPARδ through autophagy in the liver and highlight its potential beneficial effects in NAFLD.


Phage adsorption and lytic propagation in Lactobacillus plantarum: could host cell starvation affect them?
Bacteriophages constitute a great threat to the activity of lactic acid bacteria used in industrial processes. Several factors can influence the infection cycle of bacteriophages. That is the case of the physiological state of host cells, which could produce inhibition or delay of the phage infection process. In the present work, the influence of Lactobacillus plantarum host cell starvation on phage B1 adsorption and propagation was investigated. First, cell growth kinetics of L. plantarum ATCC 8014 were determined in MRS, limiting carbon (S-N), limiting nitrogen (S-C) and limiting carbon/nitrogen (S) broth. L. plantarum ATCC 8014 strain showed reduced growth rate under starvation conditions in comparison to the one obtained in MRS broth. Adsorption efficiencies of > 99 % were observed on the starved L. plantarum ATCC 8014 cells. Finally, the influence of cell starvation conditions in phage propagation was investigated through one-step growth curves. In this regard, production of phage progeny was studied when phage infection began before or after cell starvation. When bacterial cells were starved after phage infection, phage B1 was able to propagate in L. plantarum ATCC 8014 strain in a medium devoid of carbon source (S-N) but not when nitrogen (S-C broth) or nitrogen/carbon (S broth) sources were removed. However, addition of nitrogen and carbon/nitrogen compounds to starved infected cells caused the restoration of phage production. When bacterial cells were starved before phage infection, phage B1 propagated in either nitrogen or nitrogen/carbon starved cells only when the favorable conditions of culture (MRS) were used as a propagation medium. Regarding carbon starved cells, phage propagation in either MRS or S-N broth was evidenced. These results demonstrated that phage B1 could propagate in host cells even in unfavorable culture conditions, becoming a hazardous source of phages that could disseminate to industrial environments.


Novel c-Myc G4 stabilizer EP12 promotes myeloma cytotoxicity by disturbing NF-κB signaling.
Multiple myeloma (MM) is a B-cell malignancy characterized by the excessive proliferation of bone marrow plasma cells and the production of abnormal immunoglobulins. Despite advances in therapeutic strategies, it remains an incurable disease. Recently, innovative anticancer drugs have been developed and approved, leading to improvements in MM therapy; however, drug resistance continues to be a major obstacle that results in treatment failure. Therefore, the development of novel agents is imperative to achieve superior therapeutic outcomes for relapsed/refractory multiple myeloma (MM) patients. Previously, we identified EP12 as a c-Myc G4 stabilizer that could induce cytotoxicity in MM cells in vitro. However, further investigation is required to elucidate the underlying molecular mechanisms and anti-MM activity of EP12 in vivo. In this study, we have discovered that the compound EP12 effectively inhibits primary myeloma growth in vivo by destabilizing c-Myc and disrupting the canonical nuclear factor-κB (NF-κB) signaling pathway. Overall, our findings suggest that EP12, as a potent c-Myc inhibitor, holds great promise as a therapeutic agent for MM.


Oral and sublingual immunotherapy for food allergy: current progress and future directions.
Food allergies are increasing in prevalence and present an emerging epidemic for westernized countries. Strict dietary avoidance is the only approved management for food allergy, but accidental exposures regularly occur, leading to significant patient anxiety and decreased quality of life. Over the past decade, oral and sublingual immunotherapies have emerged as potential treatments for food allergy. While several small clinical trials have demonstrated that immunotherapy can desensitize food-allergic individuals, strategies for further enhancing safety and definitively establishing long-term efficacy are needed. This review presents an overview of recent oral and sublingual immunotherapy trials, and provides a glimpse into what the next generation of food immunotherapy may entail.


The effects of Crocus sativus L. (Saffron) and its ingredients on dietary intakes in cardiovascular disease in Iranian population: A systematic review and meta-analysis.
Cardiovascular disease (CVD) is one of the most common causes of mortality around the world. The aim of this study is to summarize and conclude the clinical evidence regarding the use of Crocus sativus (C. sativus) and its ingredients on cardiovascular risk factors. A systematic search was conducted with PubMed, Web of Science (ISI), and Scopus in the English language from 2015 until September 2021. A fixed-effect or random-effects model were applied to pool standard mean difference (SMD) and its 95 % confidence intervals (CI). Randomized controlled studies that assessed the clinical effects of C. sativus and its ingredients on dietary intake (Energy, Carbohydrate, Protein, and total Fat) in human subjects were included. Seven studies comprising 421 participants were included in the meta-analysis. Pooling of results showed significant effect of saffron on total fat (-0.14; 95% CI: -0.49 to 0.20; I2 = 57.3%) and significant effect of crocin on Energy (0.94; 95% CI: -0.77 to 2.65; I2 = 95.9%), Carbohydrate (0.44; 95% CI: -0.74 to 1.62; I2 = 92.6%), and Protein (-0.04; 95% CI: -0.26 to 0.34; I2 = 0.0%). Present meta-analysis suggests that treatment with crocins is more effective than saffron in energy, carbohydrate, and protein, while saffron is more effective than crocins in fat. However, further studies are needed to confirm these findings.


Increased flow in the superior mesenteric artery in dumping syndrome.
Transcutaneous Doppler ultrasound was used to measure resting and postprandial blood flow in the superior mesenteric artery (SMABF) in nine patients with dumping syndrome and in ten normal volunteers of matching age and sex. All nine patients experienced signs and symptoms of dumping during the investigation, but none of the controls did so. At rest, SMABF in the dumping patients (567 +/- 47 ml/min) (mean +/- s.e.m.) did not significantly differ from that of the normal volunteers (493 +/- 72 ml/min). Five minutes from the end of a balanced liquid meal, flow had approximately doubled in each group (1232 +/- 140 and 941 +/- 128 ml/min). Compared with controls, increased SMABF was observed in patients with dumping syndrome at 10 min (76 per cent), 15 min (66 per cent), 30 min (55 per cent) and 45 min (42 per cent) (P = 0.05-0.01). Splanchnic pooling and abnormal redistribution of blood probably contribute to the pathogenesis of the early dumping syndrome.


Heterogeneity of a human isolate of Coxsackie B4: biological differences.
Evidence is presented to demonstrate existence of virion heterogeneity within the human isolate, Edwards, of Coxsackievirus B4 (CB4-Edw). Three virion types (E1, E2 and E3) were cloned by repeated plaque purification of CB4-Edw and then all were compared relative to their effects on the pancreas of mice during acute infection. Seventy-two hours post-infection blood glucose, plasma amylase and insulin levels were monitored in mice of the SWR/J strain (previously classified susceptible to other diabetogenic picornaviruses), and the C57B1/6J strain (resistant). While all the viruses caused pancreatitis none of the animals infected with any of the clones showed as dramatic an increase in plasma amylase levels (four- vs 20-fold) as is characteristic of C57B1/6J mice inoculated with the original CB4 Edw virus. Greatest differences were expressed between the clones and CB4-Edw while less substantiative differences were found among the clones. For instance, clone E1 depressed blood glucose levels in C57B1/6J mice without affecting insulin levels. Likewise, the clone E2 depressed blood glucose levels without affecting insulin levels but only in SWR/J animals. This study demonstrates the heterogeneity of a human isolate of CB4. The subpopulation of virions contained within this isolate differ in the biological responses they elicit, specifically with regard to diabetogenic potential.


LncRNA Malat1 inhibition of TDP43 cleavage suppresses IRF3-initiated antiviral innate immunity.
Long noncoding RNAs (lncRNAs) involved in the regulation of antiviral innate immune responses need to be further identified. By functionally screening the lncRNAs in macrophages, here we identified lncRNA Malat1, abundant in the nucleus but significantly down-regulated after viral infection, as a negative regulator of antiviral type I IFN (IFN-I) production. Malat1 directly bound to the transactive response DNA-binding protein (TDP43) in the nucleus and prevented activation of TDP43 by blocking the activated caspase-3-mediated TDP43 cleavage to TDP35. The cleaved TDP35 increased the nuclear IRF3 protein level by binding and degrading Rbck1 pre-mRNA to prevent IRF3 proteasomal degradation upon viral infection, thus selectively promoting antiviral IFN-I production. Deficiency of Malat1 enhanced antiviral innate responses in vivo, accompanying the increased IFN-I production and reduced viral burden. Importantly, the reduced MALAT1, augmented IRF3, and increased IFNA mRNA were found in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Therefore, the down-regulation of MALAT1 in virus-infected cells or in human cells from autoimmune diseases will increase host resistance against viral infection or lead to autoinflammatory interferonopathies via the increased type I IFN production. Our results demonstrate that the nuclear Malat1 suppresses antiviral innate responses by targeting TDP43 activation via RNA-RBP interactive network, adding insight to the molecular regulation of innate responses and autoimmune pathogenesis.


Erratum: Benefit of rituximab maintenance is associated with Follicular Lymphoma International Prognostic Index in patients with follicular lymphoma.
[This corrects the article DOI: 10.1097/BS9.0000000000000144.].


Prevalence of heart disease diagnosed de novo in pregnancy in a West London population.
To determine the prevalence of heart disease diagnosed de novo in pregnancy in a West London population and to re-examine the current role of routine cardiovascular examination in antenatal care in the UK. Retrospective study. Obstetric medical clinics at Queen Charlotte's and Chelsea Hospital, University College Hospital and Northwick Park Hospital. Three hundred and twenty women referred for cardiac evaluation during pregnancy. The majority of the 139 women referred specifically for evaluation of murmurs during pregnancy were found to have physiological murmurs (97%). Only four women (3%) were found to have significant cardiac lesions de novo in their pregnancy. Three of these four women were immigrants who had no previous history of heart disease. The only woman from the UK was already known to have a murmur from childhood. Our study shows that heart disease diagnosed de novo in pregnancy in a West London population is an uncommon problem with low prevalence. It also appears to be a problem seen mainly in the immigrant population. The results emphasise the importance of taking a thorough medical history in all pregnant women. However, our results if they are confirmed, would suggest that only immigrants and those with significant symptoms or a known history of heart murmur or heart disease need undergo cardiovascular examination during pregnancy. These findings need to be confirmed in a larger group in other parts of the UK before further recommendations on selective cardiovascular examination can be made. This will have significant implications for midwifery-led care.


[Behavior of artificially produced defects in the epiphyseal plate of rabbits after transplantation of autologous and homologous rib cartilage].
In the first part of this study one could demonstrate that a defined mechanical traumatization of the distal epiphyseal plate of femur produced a constant development of bone fossilization which united the epiphysis to the metaphysis as a histopathological substract. In the second part--a correspondingly set-up defect--on the opposite side of the distal epiphyseal plate femur was filled up either by an autogeneous or homogeneous cartilage from the rib of a rabbit. The autogeneous rib transplantations were in this connection in a good position to prevent a partial bone-bridge-development between the epiphysis and metaphysis. The homogeneous transplantations showed some bone fossilizations, on the whole though satisfactory results with regard to the prevention of a partial obstruction could be obtained.


FCGR2A and FCGR3A Genotypes in Human Immunodeficiency Virus Mother-to-Child Transmission.
Background. Fc-mediated effector functions have been suggested to influence human immunodeficiency virus (HIV) acquisition and disease progression. Analyzing the role of host Fc gamma receptor (FcγR) polymorphisms on HIV outcome in mother-to-child transmission (MTCT) will increase our understanding of how host genetics may alter immune responses in prevention, therapy, and disease. This study analyzed the impact of FCGR2A and FCGR3A genotypes on MTCT in a cohort in which Fc-mediated antibody functions are predictive of infant HIV outcome. Methods. Human immunodeficiency virus-positive mothers and their infants from a historical MTCT cohort were genotyped for FCGR2A and FCGR3A. We assessed the impact of these genotypes on transmission and acquisition of HIV and disease progression using χ(2) tests, survival analyses, and logistic regression. Results. Among 379 mother-infant pairs, infant FCGR2A and FCGR3A genotypes were not associated with infant HIV infection or disease progression. Maternal FCGR2A was not associated with transmission, but there was a trend between maternal FCGR3A genotype and transmission (P = .07). When dichotomizing mothers into FCGR3A homozygotes and heterozygotes, heterozygotes had a 64.5% higher risk of transmission compared with homozygotes (P = .02). This risk was most evident in the early breastfeeding window, but a trend was only observed when restricting analyses to breastfeeding mothers (hazards ratio, 1.64; P = .064). Conclusions. Infant FCGR2A and FCGR3A genotypes were not associated with HIV infection or disease progression, and, thus, host FcγR genotype may not significantly impact vaccination or therapeutic regimens that depend on Fc-mediated antibody functions. Maternal FCGR3A genotype may influence early breastfeeding transmission risk, but more studies should be conducted to clarify this association and its mechanism.


Switch to tacrolimus for cyclosporine-induced gynecomastia in liver transplant recipients.
We report herein on two male liver transplant (LT) recipients who presented with cyclosporine (CsA)-related gynecomastia 6 and 10 months after transplantation. The clinical workup showed increased luteinizing hormone (LH), associated with a slight reduction in testosterone blood levels in one patient and increased prolactin levels in the other. After excluding concomitant primary endocrine and/or malignant disease, conversion to tacrolimus (TAC) was performed resulting in clinical improvement of gynecomastia and return of hormone blood levels to normal range within 3 months. Our report confirms a putative role of CsA in post-LT gynecomastia, reversible however upon conversion to TAC.


Long-term culture of functional hepatocytes on chemically modified collagen gels.
For long-term maintenance of functional hepatocytes in primary culture, a new culture system with chemically modified type-I collagen gel was developed. Isolated hepatocytes spread as flat cells and rapidly lost their viability and functions when cultured on native collagen gel. In contrast, they survived for several weeks when cultured on collagen gels that had been modified by treatment with sodium-borohydride (NaBH(4)) or by digestion with pepsin, which resulted in destruction of crosslinking of collagen fibers and marked decrease in meachanical strength of the gels. These long-lived cells were round and aggregated and maintained high levels of various differentiated liver functions including albumin secretion and activities of tyrosine aminotransferase and P450. Moreover on collagen gels modified by treatment with NaBH(4) or pepsin, the cell showed less DNA synthesis in response to mitogenic stimulation than cells cultures on gel containing native collagen. Interestingly, crosslinking of these chemically modified gels with D-ribose resulted in changes in various phenotypes of hepatocytes cultures on them including shape, longevity, and functions expressed when the cells were cultured on native collagen gel, suggesting that the effect of modification of the collagen gel is reversible. Thus the structure of collagen gels, probably due to the degree of crosslinking, seems to affect the morphology, maintenance of differentiated functions, and growth of primary cultured hepatocytes.


Gonococcal infection within Scotland: antigenic heterogeneity and antibiotic susceptibility of infecting strains.
Two panels of monoclonal antibody reagents were used to serotype all strains of Neisseria gonorrhoeae isolated from four separate geographical areas serving two million of the five million Scottish population. Serotype 1B isolates accounted for 60% of the 869 strains examined and were more prevalent than 1A isolates in each geographical area. A total of 11 1A serovars and 47 1B serovars were recognised. Only two of the 11 1A serovars (Aedgkih/Arost and Aedih/Arst) were found in every centre but these accounted for over 90% of the 1A isolates. Although there was a total of 47 different 1B serovars over 80% of the isolates were accounted for by the ten most commonly encountered serovars. There were, however, marked geographical differences within both major and minor serovars. There was a highly significant difference (P less than 0.001) between protein 1A and 1B serovars with respect to their susceptibility to penicillin. Within each protein 1 type there were also differences in antibiotic susceptibility. Penicillinase-producing N. gonorrhoeae (PPNG) were found in all centres and accounted for 24 (2.8%) of the 869 isolates. The majority of the PPNG (71%) were serotype 1A and with one exception were serovar Aedih/Arst. PPNG strains accounted for 37% (16) of the 43 Aedih/Arst isolates. Epidemiological, diagnostic and therapeutic implications arising from the distinct geographical differences in the pool of circulating gonococci are discussed.


A hydroxyapatite-coated total knee replacement: prospective analysis of 1000 patients.
We prospectively reviewed 1000 consecutive patients who underwent a cementless, hydroxyapatite-coated, stemless, total knee replacement over a period of nine years. Regular post-operative clinical follow-up was performed using the Knee Society score. The mean pre-operative score was 96, improving to 182 and 180 at five and ten years, respectively. To date, there have been seven (0.5%) cases which required revision, primarily for septic loosening (four cases), with low rates of other post-operative complications. The cumulative survival at ten years with revision as the end-point, was 99.14% (95% confidence interval 92.5 to 99.8). These results support the use of hydroxyapatite in a cementless total knee replacement since it can give reliable fixation with an excellent clinical and functional outcome.


Health Literacy in Transitions of Care: An Innovative Objective Structured Clinical Examination for Fourth-Year Medical Students in an Internship Preparation Course.
Low health literacy is associated with adverse health outcomes, especially during transitions of care. Competency-based assessments may improve communication during this time. To develop an Objective Structured Clinical Examination (OSCE) for medical students to demonstrate communication skills to be used during the hospital discharge process with patients of low health literacy. The OSCE was integrated into the curriculum of an internship preparatory clerkship. One hundred and one fourth-year medical students participated. Students received a skills-based health literacy workshop. In the OSCE, learners counseled standardized patients regarding initiation of anticoagulation at discharge and wrote discharge instructions. Fifty-seven students completed the workshop prior to the OSCE, and 44 participated in the workshop after the completing the OSCE. Participants who completed the workshop first outperformed their peers on the checklist (15.1 vs. 13.4, p < 0.0001) and on the reading level of their written instructions (9.9 vs. 10.6, p = 0.01); 82% felt confident communicating with patients of low health literacy after the workshop and OSCE. This OSCE is a tool to train and evaluate future interns' ability to communicate with patients of limited health literacy levels at hospital discharge. Such innovations may make this period of time safer for patients, improving health outcomes.


Changes in connectivity of the posterior default network node during visual processing in mild cognitive impairment: staged decline between normal aging and Alzheimer's disease.
Visual processing difficulties are often present in Alzheimer's disease (AD), even in its pre-dementia phase (i.e. in mild cognitive impairment, MCI). The default mode network (DMN) modulates the brain connectivity depending on the specific cognitive demand, including visual processes. The aim of the present study was to analyze specific changes in connectivity of the posterior DMN node (i.e. the posterior cingulate cortex and precuneus, PCC/P) associated with visual processing in 17 MCI patients and 15 AD patients as compared to 18 healthy controls (HC) using functional magnetic resonance imaging. We used psychophysiological interaction (PPI) analysis to detect specific alterations in PCC connectivity associated with visual processing while controlling for brain atrophy. In the HC group, we observed physiological changes in PCC connectivity in ventral visual stream areas and with PCC/P during the visual task, reflecting the successful involvement of these regions in visual processing. In the MCI group, the PCC connectivity changes were disturbed and remained significant only with the anterior precuneus. In between-group comparison, we observed significant PPI effects in the right superior temporal gyrus in both MCI and AD as compared to HC. This change in connectivity may reflect ineffective "compensatory" mechanism present in the early pre-dementia stages of AD or abnormal modulation of brain connectivity due to the disease pathology. With the disease progression, these changes become more evident but less efficient in terms of compensation. This approach can separate the MCI from HC with 77% sensitivity and 89% specificity.


Primary pulmonary lymphoepithelioma-like carcinoma: a rare type of lung cancer with a favorable outcome in comparison to squamous carcinoma.
Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare tumor and often misdiagnosed as squamous carcinoma. In the current study, clinical characteristics and outcome of primary pulmonary LELC were systematically compared with pulmonary squamous carcinoma. Forty-two cases of primary pulmonary LELC and 134 squamous carcinomas were enrolled retrospectively. Characteristic and prognosis difference between the two groups was compared, and the independent prognostic factor for pulmonary LELC was identified as well. In comparison to squamous carcinoma, pulmonary LELC was more common in women with a younger median age and less smokers. LELC seemed to be smaller in diameter on computed tomography (CT) scans than squamous carcinoma, with scarce spiculation and vascular convergence signs. Epstein-Bar virus-encoded RNA (EBER) by in-situ hybridization was detected in 33 LELC cases, among whom 27 ones were positive in serum EBV-DNA examination. LELC patients presented a much longer median progression-free survival (PFS) than squamous carcinoma. Positive serum EBV-DNA, distant lymph node invasion, advanced clinical stage and receiving radiotherapy were correlated with the shorter PFS in LELC patients. However, only positive serum EBV-DNA was the independent PFS predictor. Pulmonary LELC looks like distinct from squamous carcinoma. Middle-aged women and nonsmokers are comparatively predominated. CT features of pulmonary LELC are relatively less-malignant. Correspondently, the progression of pulmonary LELC is seemingly favorable than squamous carcinoma and the positive serum EBV-DNA appears to be the predictor of PFS.


Political quarrel overshadows vaccination advocacy: How the vaccine debate on Brazilian Twitter was framed by anti-vaxxers during Bolsonaro administration.
Despite Brazil's tradition of successful mass immunization programs, the country has been experiencing alarming declines in vaccination coverage, especially among children. That is aggravated by the growth of anti-vaccine movements and the spread of health misinformation in social media in the last decade, which have worsened during the COVID-19 outbreak. Several reports link populism and far-right politicians to anti-vaccination support worldwide, which was also the case in Brazil during president Jair Bolsonaro's administration. This project aimed to identify the circulating pro and anti-vaccine narratives in Portuguese on Twitter, during a crucial decision-making period regarding childhood vaccination in Brazil, from December 9, 2021, until February 9, 2022. From the over one million tweets and four million retweets collected, we identified two well-defined groups, one in favor and another against vaccination. Within the sample, we selected 1500 influencer tweets with the highest impact (>500 retweets) and conducted content analysis. Although the pro-vaccine influencers were more retweeted than anti-vaxxer ones, we observed that anti-vaccine movements were more succesful in framing discussions on Twitter. The subject of COVID-19 was the target of political polarization embedded in populist, anti-science and anti-traditional media discourses promoted by anti-vaxxers. As a counterpart, the pro-vaccine influencers reacted inarticulately, focusing on criticizing the anti-vaccination actors, attitudes, and policies instead of promoting vaccines. Based on reults, we claim that a well-coordinated network of health communicators from science centers and health institutions, in partnership with properly briefed social media influencers and fact-checking sources, would more efectively pre-tempt the public about vaccine misinformation.


Dialysis of saliva improves accuracy of saliva lithium determinations.
Saliva lithium (Li) determinations have been explored as a potential alternative to plasma levels. Unfortunately, this method has been shown to be unreliable. Saliva has two major components: the aqueous and the mucopolysaccharide portions. Since Li is likely to distribute only in the aqueous fraction, we dialyzed the saliva through a 3000 Da filter to isolate the aqueous component and determine the Li level in it. Lithium levels in the dialyzed saliva agreed more closely with plasma levels (Spearman's rho = 0.901, p < 0.001) than did whole saliva (Spearman's rho = 0.775, p = 0.012). Dialysis of saliva may contribute to more accurate saliva Li levels.


Cytokines, adipocytokines and inflammatory markers in patients on continuous ambulatory peritoneal dialysis and hemodialysis.
Cytokines are essential mediators of immune response. Chronic renal failure patients suffer from chronic inflammation that results from factors such as impaired renal function, accumulation of uremic toxins and bio incompatibility of dialyzer membranes. These patients are also at increased risk of cardiovascular diseases. We have evaluated cytokines, adipocytokines and inflammatory markers in patients with chronic renal failure undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). We have determined serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), leptin and ghrelin levels of chronic renal failure patients treated with either HD (n = 20) or CAPD (n = 20). TNF-α, IL-6, ghrelin and leptin measurements were performed by commercially available kits based on enzyme-linked immunosorbent assay (ELISA) method. hsCRP levels were determined by turbidimetric methods. Serum TNF-α and IL-6 levels of patients on HD were significantly higher than those of the ones on CAPD (p < 0.05). Ghrelin, leptin and hsCRP concentrations were similar in both groups. We can conclude that cytokine production is more obvious in HD process.


The fracture strength of endocrowns manufactured from different hybrid blocks under axial and lateral forces.
This in vitro study was conducted to compare the fracture strength of endocrowns manufactured from different hybrid blocks under axial and lateral forces. Following root-canal treatment, 100 permanent mandibular first molars were randomly distributed among 5 groups according to restoration material. Endocrown restorations were produced from IPS e.max CAD (IPS), Vita Enamic (VE), GC Cerasmart (GC), Shofu (SH), and Brilliant Crios (BC) using CAD/CAM technology. Specimens were cemented, subjected to artificial aging, and further divided into 2 subgroups (n = 10) per group for fracture testing. Each specimen was placed on a universal testing machine and subjected to axial or lateral forces applied at a crosshead speed of 1 mm/min. Fracture data were analyzed using one-way ANOVA, Tukey, Tamhane T2, and Weibull tests. Statistically significant differences in fracture-strength (FS) values under axial and lateral forces were observed among the groups (P < 0.05). Group BC had the highest FS value under axial forces, whereas group IPS had the highest FS value under lateral forces. According to Weibull analysis, VE exhibited the highest reliability under axial forces (7.62), whereas IPS exhibited the highest reliability under lateral forces (4.68). No statistically significant differences were detected in the distribution of failure types under either axial or lateral forces among the groups (P > 0.05). All of the hybrid blocks tested showed sufficient fracture strength for use as CAD/CAM-fabricated endocrowns. Hybrid blocks can be used as an alternative to lithium disilicate blocks in endocrown restorations.


Novel Vigna subterranea (L.) Verdc Soluble Dietary Fibre-Starch Nanocomposite: Functional and Antioxidant Characteristics.
Bambara groundnut (Vigna subterranea (L.) Verdc.) is a great source of soluble dietary fibre and starch. Bambara groundnut soluble dietary fibre is rich in bioactive compounds, namely, uronic acids (11.8%) and hydrolysable polyphenols (expressed as gallic acid equivalents (GAE) 20 mg/g), with crucial physiological and functional benefits. The industrial use of native starch is limited because of the inherent undesirable attributes that render it unstable. The aim of this study is to characterise the antioxidant, functional and physicochemical properties of Bambara groundnut starch-soluble dietary fibre nanocomposite (hereafter groundnut nanocomposite). The pasting properties by rapid visco analysis, chemical composition, hydration properties, oil-binding capacity, emulsifying activity index (EAI), emulsion stability index (ESI) and antioxidant properties of Bambara groundnut starch, soluble fibre and nanocomposite were studied. The Bambara groundnut soluble dietary fibre and nanocomposite did not exhibit typical pasting properties. The nanocomposite had high mass fraction of carbohydrates (78.7%) and proteins (7.0%), low mass fraction of fat (0.8%) and had a considerable mass fraction of ash (4.9%). The Bambara groundnut starch, soluble dietary fibre and nanocomposite showed significant (p<0.001) differences in solubility. Their EAI values were 23.2, 85.7 and 90.6%, respectively, and the ESI values were 23.3, 87.1 and 87.5%, respectively. The three biopolymers differed significantly (p<0.001) in all colour characteristics: lightness (L*), redness/greenness (a*), yellowness/blueness (b*), chroma and hue angles. Their polyphenolic mass fraction, expressed as GAE, was 0.10, 6.6 and 0.46 mg/g, respectively, and their ferric reducing antioxidant power values, expressed as ascorbic acid equivalents (AAE), were 1.2, 4.8 and 1.4 μmol/g, respectively. The phenolic compounds (in mg/g): chlorogenic acid 18, monocrotaline 20, luteolin 7-O-(6''-malonylglucoside) 4 and casuarine 6-α-d-glucoside 27 were present in the dietary fibre but absent from the starch and nanocomposite. The Bambara groundnut nanocomposite possesses desirable physicochemical and antioxidant properties, making it suitable as an ingredient in various food systems. Nanocomposites have the potential to revolutionise the food industry but their study as food ingredients is very limited. Furthermore, nothing is known about the physicochemical, functional and antioxidant characteristics of Bambara groundnut nanocomposite, thus investigating these properties will address this knowledge gap.


Relationship between thyroid function and ICU mortality: a prospective observation study.
Although nonthyroidal illness syndrome is considered to be associated with adverse outcome in ICU patients, the performance of thyroid hormone levels in predicting clinical outcome in ICU patients is unimpressive. This study was conducted to assess the prognostic value of the complete thyroid indicators (free triiodothyronine (FT3), total triiodothyronine; free thyroxine, total thyroxine, thyroid-stimulating hormone and reverse triiodothyronine) in unselected ICU patients. A total of 480 consecutive patients without known thyroid diseases were screened for eligibility and followed up during their ICU stay. We collected each patient's baseline characteristics, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and thyroid hormone, N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels. The primary outcome was ICU mortality. Potential predictors were analyzed for possible association with outcomes. We also evaluated the ability of thyroid hormones together with APACHE II score to predict ICU mortality by calculation of net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. Among the thyroid hormone indicators, FT3 had the greatest power to predict ICU mortality, as suggested by the largest area under the curve (AUC) of 0.762±0.028. The AUC for FT3 level was less than that for APACHE II score (0.829±0.022) but greater than that for NT-proBNP level (0.724±0.030) or CRP level (0.689±0.030). Multiple regression analysis revealed that FT3 level (standardized β=-0.600, P=0.001), APACHE II score (standardized β=0.912, P<0.001), NT-proBNP level (standardized β=0.459, P=0.017) and CRP level (standardized β=0.367, P=0.030) could independently predict primary outcome. The addition of FT3 level to APACHE II score gave an NRI of 54.29% (P<0.001) and an IDI of 36.54% (P<0.001). The level of FT3 was significantly correlated with NT-proBNP levels (r=-0.344, P<0.001) and CRP levels (r=-0.408, P<0.001). In unselected ICU patients, FT3 was the most powerful and only independent predictor of ICU mortality among the complete indicators. The addition of FT3 level to the APACHE II score could significantly improve the ability to predict ICU mortality.


[The influence of amplitude modulation on the structure of call spectrum in marmots (Marmota, rodentia, sciuridae)].
A relationship was established between the amplitude modulation and the structure of call spectrum in animals by the example of alarm call in three marmots (Marmota sibirica, M. menzbieri, and M. caudata). In the case of amplitude modulation, side frequencies are produced higher and lower than the carrier frequencies. In the absence of amplitude modulation, no side frequencies are produced.


Transperineal ultrasound is a good alternative for intra-fraction motion monitoring for prostate stereotactic body radiotherapy.
To report our experience in a prospective study of implementing a transperineal ultrasound system to monitor intra-fractional prostate motion for prostate stereotactic body radiotherapy (SBRT). This IRB-approved prospective study included 23 prostate SBRT patients treated between 04/2016 and 11/2019 at our institution. The prescription doses were 36.25 Gy to the Low-Dose planning target volume (LD-PTV) and 40 Gy to the High-Dose PTV (HD-PTV) in five fractions with 3 mm planning margins. The transperineal ultrasound system was successfully used in 110 of the 115 fractions. For intra-fraction prostate motion, the real-time prostate displacements measured by ultrasound were exported for analysis. The percentage of time prostate movement exceeded a 2 mm threshold was calculated for each fraction of all patients. T-test was used for all statistical comparisons. Ultrasound image quality was adequate for prostate delineation and prostate motion tracking. The setup time for each fraction under ultrasound-guided prostate SBRT was 15.0 ± 4.9 min and the total treatment time per fraction was 31.8 ± 10.5 min. The presence of an ultrasound probe did not compromise the contouring of targets or critical structures. For intra-fraction motion, prostate movement exceeded 2 mm tolerance in 23 of 110 fractions for 11 of 23 patients. For all fractions, the mean percentage of time when the prostate moved more than 2 mm in any direction during each fraction was 7%, ranging from 0% to 62% of a fraction. Ultrasound-guided prostate SBRT is a good option for intra-fraction motion monitoring with clinically acceptable efficiency.


Improved cryopreservation protocol for Blanca-Celtibérica buck semen collected by electroejaculation.
The collection of sperm samples by electroejaculation (EE) leads to an increase of the production of seminal plasma which could modify the tolerance of spermatozoa to the cryopreservation procedure. This study aims to compare a standard sperm cryopreservation protocol for samples collected by artificial vagina (AV) with the same protocol and modifications to this for samples obtained by EE. Semen from six males of Blanca-Celtibérica goat breed was collected by AV (control) and EE, and three experiments were conducted. In Experiment 1, it was examined the effects of egg yolk concentration contained in freezing extender (0%, 1.5%, 10% and 20% of egg yolk); in Experiment 2, it was evaluated the cooling rate from 30 to 5 °C (fast: 10 min and slow: 90 min) and the temperature of glycerol addition (30 and 5 °C); and in Experiment 3, it was examined the time of equilibration at 5 °C (0, 1, 2 or 3h). A heterologous in vitro fertilization test was carried out in order to compare the fertility of control samples with that resulting from the EE protocol which showed the highest sperm quality. Results showed greater sperm motility parameters after thawing for control samples cryopreserved in standard conditions in the three experiments. For samples collected by EE, extender with 20% egg yolk, a slow cooling rate and a longer equilibration time (3h) provided higher sperm quality, and no differences were observed between temperatures of glycerol addition. Samples collected by EE and cryopreserved with the protocol which yielded the best sperm quality after thawing showed higher fertility compared to AV.


Optimal conditions for detection of reverse transcriptase activity in human placentas.
Optimal conditions for detecting reverse transcriptase activity in human placental extracts are described. They vary with the state of the placenta at birth and are influenced by relative amounts of detergent, monovalent cation, and protein in the reaction mixture. Demonstrating activity of the placental enzyme requires detergent, but the enzyme is sensitive to high detergent concentrations. This sensitivity can be be altered by lowering the monovalent cation concentration from 0.154 to 0.034 M and by adding protein to the reaction mixture. The detection of reverse transcriptase in Rauscher murine leukemia virus and baboon endogenous type C virus, but not in the Mason-Pfizer monkey type D virus, shows similar requirements.


Strategies for Successful Catheterization Laboratory Recovery From the COVID-19 Pandemic.
As the world slowly starts to recover from the coronavirus disease-2019 pandemic, health care systems are now thinking about resuming elective cardiovascular procedures, including procedures in cardiac catheterization laboratories. Rebooting catheterization laboratories will be an arduous process, in part because of limited health care resources, new processes, and fears stemming from the coronavirus disease-2019 pandemic. The authors propose a detailed phased-in approach that considers clinical, patient-centered, and operational strategies to safely and effectively reboot catheterization laboratory programs during these unprecedented times. This model balances the delivery of essential cardiovascular care with reduced exposure and preservation of resources. The guiding principles detailed in this review can be used by catheterization laboratory programs when restarting elective interventional procedures.


A Mathematical Model for the Release, Transport, and Retention of Per- and Polyfluoroalkyl Substances (PFAS) in the Vadose Zone.
Per- and Polyfluoroalkyl Substances (PFAS) are emerging contaminants of critical concern. As surfactants, PFAS tend to accumulate at air-water interfaces and may stay in the vadose zone for long times before contaminating groundwater. Yet not well understood, the extent of retention in the vadose zone has critical implications for risk management and remediation strategies. We present the first mathematical model that accounts for surfactant-induced flow and solid-phase and air-water interfacial adsorption. We apply the model to simulate PFOS (a PFAS compound of primary concern) transport in the vadose zone at a model fire-training area site impacted by Aqueous Film-Forming Foam (AFFF). Air-water interfacial adsorption is shown to have a significant impact-amplified by the low water content due to gravity drainage-total retardation factors range from 233 to 1355 for the sand and 146 to 792 for the soil used in the study. The simulations illustrate it can take several decades or longer for PFOS to reach groundwater. Counterintuitively, the lower water content in the sand-due to stronger drainage and weaker capillary retention-leads to retardation factors greater than for the soil. Also, most PFOS is adsorbed at air-water interfaces with only 1-2% in the aqueous phase. The implications include 1) fine-texture materials could have lower retardation factors than sand due to higher retained water content, 2) soil PFAS concentrations are likely to be orders of magnitude higher than those in groundwater at source zones. Both implications are consistent with recent field observations at hundreds of AFFF-impacted sites.


Ancillary therapies to enhance success of non-invasive modes of respiratory support - Approaches to delivery room use of surfactant and caffeine?
During recent decades, non-invasive respiratory support has become popular for treating neonates with respiratory failure. Several prospective randomized controlled trials have been performed to compare use of continuous positive airway pressure (CPAP) as primary respiratory support in preterm infants with respiratory distress syndrome (RDS) to endotracheal intubation, mechanical ventilation and surfactant therapy. Systematic reviews of these studies suggest that routine CPAP at delivery is efficacious in decreasing bronchopulmonary dysplasia (BPD), death, or both. This led to the recommendation to consider CPAP to avoid endotracheal intubation. As surfactant therapy is known to reduce BPD and death, several ways to combine CPAP with surfactant have been described. With the increasing use of CPAP immediately after birth, the early use of caffeine to stimulate respiration has become a point of discussion. This review focuses on different modes of surfactant application during CPAP and on the early use of caffeine as ancillary therapies to enhance CPAP success.


Novel theranostic approaches to neovascularized atherosclerotic plaques.
As the global burden of atherosclerotic cardiovascular disease continues to rise, there is an increased demand for improved imaging techniques for earlier detection of atherosclerotic plaques and new therapeutic targets. Plaque lesions, vulnerable to rupture and thrombosis, are thought to be responsible for the majority of cardiovascular events, and are characterized by a large lipid core, a thin fibrous cap, and neovascularization. In addition to supplying the plaque core with increased inflammatory factors, these pathological neovessels are tortuous and leaky, further increasing the risk of intraplaque hemorrhage. Clinically, plaque neovascularization has been shown to be a significant and independent predictor of adverse cardiovascular outcomes. Microvessels can be detected through contrast-enhanced ultrasound (CEUS) imaging, however, clinical assessment in vivo is generally limited to qualitative measures of plaque neovascularization. There is no validated standard for quantitative assessment of the microvessel networks found in plaques. Advances in our understanding of the pathological mechanisms underlying plaque neovascularization and its significant role in the morbidity and mortality associated with atherosclerosis have made it an attractive area of research in translational medicine. Current areas of research include the development of novel therapeutic and diagnostic agents to target plaque neovascularization stabilization. With recent progress in nanotechnology, nanoparticles have been investigated for their ability to specifically target neovascularization. Contrast microbubbles have been similarly engineered to carry loads of therapeutic agents and can be visualized using CEUS. This review summarizes the pathogenesis, diagnosis, clinical significance of neovascularization, and importantly the emerging areas of theranostic tool development.


The effects of process-focused versus experience-focused narratives in a breast cancer treatment decision task.
To examine the effect of patient narratives that discuss decision processes versus patient experiences on decisions about treatments for early stage breast cancer. We recruited 300 women with no previous history of breast cancer to imagine that they had been diagnosed with early stage breast cancer and to choose between mastectomy and lumpectomy with radiation. Before learning about their treatment options, participants were randomly assigned to one of four conditions with videotaped stories from fictitious cancer survivors, using a 2 (content: experience versus process) × 2 (emotional valence: positive only vs. positive and negative) factorial design, or a control condition with no stories. We measured information search, treatment intentions, and decision satisfaction. Participants viewing process narratives spent more time searching for information. Participants viewing experience narratives reported a greater ability to imagine what it was like to experience the treatments; they also evaluated their decision more positively on several dimensions. Process narratives appeared to guide information search, and experience narratives improved evaluations of the decision process. There is no evidence that process and experience narratives 'bias' decisions in the same manner as outcome narratives. Further, their potential to focus patient attention on key information and increase patient confidence in decision making appears significant.