COPD management costs according to the frequency of COPD exacerbations in UK primary care.
The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown. We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK. A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database. Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009). Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale. Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations. Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011. The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%). The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively. General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively. Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly.


[Respiratory diseases in European farmers-II. Part of the European farmers' project].
The aim of the European Farmers' Project was to estimate the prevalence of respiratory diseases in farmers across Europe. Furthermore, risk factors for respiratory symptoms in different parts of agricultural production should be assessed. In the first part of the study, 7496 farmers from four European countries answered a written questionaire. Of these, 229 were visited at their farms in the second part of the survey. On site, spirometry, allergy tests, as well exposure measurements were performed. Farmers with animal production had a significantly lower prevalence of allergic diseases than the general population. In contrast, the prevalence of chronic phlegm was higher in animal farmers. Organic dust toxic syndrome (ODTS) was a major predictor of chronic bronchitis. It was indicated that allergens found in the working environment could be transfered to the living environment of the farmer. Poor ventilation as well as high temperatures inside the animal buildings were shown to have a negative impact on respiratory symptoms and lung function parameters. Animal farmers are at high risk of chronic bronchitis. Intervention studies on the efficacy of different types of ventilation are now warranted. Furthermore, prospective studies on the associaton between ODTS and COPD should be done.


Saliva-based PCR tests for SARS-CoV-2 detection.
The outbreak of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Nasopharyngeal swabs are widely used in polymerase chain reaction (PCR) test to detect SARS-CoV-2. However, the collection of nasopharyngeal swabs has a series of drawbacks concerning exposure of healthcare staff, difficulty in collection, and discomfort of patients. Therefore, an alternative noninvasive sample for diagnostic of emerging viral diseases is required. The usefulness of saliva screening tests is compared to conventional swab tests in this report. The results suggest that saliva could be a reliable sample for detecting SARS-CoV-2.


Heterogeneous and epitaxial nucleation of protein crystals on mineral surfaces.
Fifty different mineral samples were tested as potential heterogeneous or epitaxial nucleants for four commonly crystallized proteins. It was found, by conventional protein crystallization techniques, that for each protein there was a set of mineral substrates that promoted nucleation of crystals at lower critical levels of supersaturation than required for spontaneous growth. Numerous examples, involving all four proteins, were observed of modification of crystal habit and, in some cases, unit cell properties promoted by the presence of the mineral nucleants. In at least one case, the growth of lysozyme on the mineral apophyllite, it was shown by lattice analysis and x-ray diffraction that the nucleation and growth of the protein crystal on the mineral was likely to involve a direct lattice match.


A naturalistic evaluation of the financial benefits of employing a mental health pharmacist to work with child and adolescent mental health services.
To demonstrate that employing a mental health pharmacist in child and adolescent mental health services can significantly reduce medication expenditure, while assisting optimising medication use. The financial evaluation was undertaken by comparing annual expenditure on medication between years 2004-2005 and 2014-2015, and examining any financial impact arising from the employment of the first pharmacist in 2007-2008. The current postholder and the chief pharmacist identified expenditure reduction initiatives undertaken or led by the pharmacist and agreed which key medicines optimisation roles the postholder had also undertaken. Prior to the appointment of the pharmacist, annual drug expenditure over the preceding 3 years had remained steady at approximately £250 000. Since the first appointment in 2007, there has been a gradual and sustained reduction in expenditure and by March 2015, the annual reduction from baseline was approximately £133 000. This is significantly more than the £36 000 per annum that it cost to employ the pharmacist for six sessions a week and represents a net saving of £97 000 per annum. Eight key expenditure reduction initiatives were identified that were introduced and facilitated by the pharmacist. The period covered by this naturalistic evaluation was unusually stable with regard to the range and model of services provided, prescribing practice, medication prices and the medications available. It provided a rare opportunity to assess the financial impact of employing a pharmacist. These savings were pivotal in persuading Sussex Partnership NHS Foundation Trust to invest another £200 000 in 2016 in the employment of four additional pharmacists to work with the trust's community adult mental health teams.


Prognostic impact of preoperative tumor marker levels and lymphovascular invasion in pathological stage I adenocarcinoma and squamous cell carcinoma of the lung.
Some unfavorable prognostic factors for stage I non-small-cell lung cancers have been reported; however, they are not reflected in the current Tumor-Node-Metastasis classification. We retrospectively reviewed 629 patients who underwent complete resection of pathological stage I adenocarcinomas (ADs) or squamous cell carcinomas (SQs) at two institutes between 1996 and 2011. The correlation between clinicopathological characteristics and survival rates was analyzed to identify prognostic factors. Multivariate analysis indicated that among ADs, high serum carcinoembryonic antigen levels (p = 0.04 for overall survival [OS]; p < 0.01 for recurrence-free survival [RFS]; p = 0.02 for disease-specific survival [DSS]), lymphatic permeation (p < 0.01 for RFS and DSS), and vascular invasion (p < 0.01 for OS and RFS; p = 0.03 for DSS) were independent prognostic factors. Among SQs, high squamous cell carcinoma antigen (SCC) (p < 0.05 for OS), and vascular invasion (p < 0.05 for RFS and DSS) were independently prognostic. We suggest that among completely resected tumors less than or equal to 5 cm without lymph node metastasis, the current stages IA and IB AD with high serum carcinoembryonic antigen levels, lymphatic permeation, or vascular invasion should be upgraded to stage IB and IIA, respectively. The current stage IA SQ with high SCC antigen levels or vascular invasion should be upgraded to stage IB. These reclassifications accurately reflect survival status (p < 0.04 in all comparisons). Some important differences in prognostic factors were observed between AD and SQ. High preoperative serum tumor marker levels and lymphovascular invasion should be included as additional criteria in the forthcoming Tumor-Node-Metastasis staging.


Comparative Study between 2-Furonitrile and 2-Cyanopyridine as Dehydrants in Direct Synthesis of Dialkyl Carbonates from CO2 and Alcohols over Cerium Oxide Catalyst.
The shift of equilibrium by removing water with nitrile dehydrants is crucial for CeO2 -catalyzed synthesis of dialkyl carbonates from CO2 and alcohols. Two nitriles - 2-cyanopyridine and 2-furonitrile - were previously found as effective dehydrants, yet their detailed comparison as well as exploration of potential of 2-furonitrile remain insufficient. Herein, the performance of 2-cyanopyridine and 2-furonitrile was compared in the synthesis of various dialkyl carbonates. 2-furonitrile was found to be superior to 2-cyanopyridine in the synthesis of dialkyl carbonates from CO2 and bulky or long-chain (≥C3) alcohols. Namely, the yield of diisopropyl carbonate (up to 50 %) achieved using CeO2 and 2-furonitrile is comparable to or even higher than previously reported ones. Meanwhile, 2-cyanopyridine acted as a better dehydrant than 2-furonitrile in the synthesis of dimethyl carbonate and diethyl carbonate. The adsorption experiments and density functional theory calculations have indicated that the better performance of 2-furonitrile compared to 2-cyanopyridine in the synthesis of dialkyl carbonates from bulky or long-chain alcohols is due to the weaker interaction of 2-furonitrile with the CeO2 surface. Such weak interaction of 2-furonitrile offers a larger reaction field on the catalyst surface for both CO2 and alcohols.


Ozone inhibits guard cell K+ channels implicated in stomatal opening.
Ozone (O3) deleteriously affects organisms ranging from humans to crop plants, yet little is understood regarding the underlying mechanisms. In plants, O3 decreases CO2 assimilation, but whether this could result from direct O3 action on guard cells remained unknown. Potassium flux causes osmotically driven changes in guard cell volume that regulate apertures of associated microscopic pores through which CO2 is supplied to the photosynthetic mesophyll tissue. We show in Vicia faba that O3 inhibits (i) guard cell K+ channels that mediate K+ uptake that drives stomatal opening; (ii) stomatal opening in isolated epidermes; and (iii) stomatal opening in leaves, such that CO2 assimilation is reduced without direct effects of O3 on photosynthetic capacity. Direct O3 effects on guard cells may have ecological and agronomic implications for plant productivity and for response to other environmental stressors including drought.


Detection of Enzyme Inhibitors in Crude Natural Extracts Using Droplet-Based Microfluidics Coupled to HPLC.
Natural product screening for new bioactive compounds can greatly benefit from low reagents consumption and high throughput capacity of droplet-based microfluidic systems. However, the creation of large droplet libraries in which each droplet carries a different compound is a challenging task. A possible solution is to use an HPLC coupled to a droplet generating microfluidic device to sequentially encapsulate the eluting compounds. In this work we demonstrate the feasibility of carrying out enzyme inhibiting assays inside nanoliter droplets with the different components of a natural crude extract after being separated by a coupled HPLC column. In the droplet formation zone, the eluted components are mixed with an enzyme and a fluorogenic substrate that permits to follow the enzymatic reaction in the presence of each chromatographic peak and identify those inhibiting the enzyme activity. Using a fractal shape channel design and automated image analysis, we were able to identify inhibitors of Clostridium perfringens neuraminidase present in a root extract of the Pelargonium sidoides plant. This work demonstrates the feasibility of bioprofiling a natural crude extract after being separated in HPLC using microfluidic droplets online and represents an advance in the miniaturization of natural products screening.


Ethanol and acetate production by Clostridium ljungdahlii and Clostridium autoethanogenum using resting cells.
Combined gasification and fermentation technologies can potentially produce biofuels from renewable biomass. Gasification generates synthesis gas consisting primarily of CO, CO(2), H(2), N(2), with smaller amounts of CH(4), NO(x), O(2), C(2) compounds, ash and tars. Several anaerobic bacteria species can ferment bottled mixtures of pure synthesis gas constituents. However, there are challenges to maintaining culture viability of synthesis gas exposed cells. This study was designed to enhance culture stability and improve ethanol-to-acetate ratios using resting (non-growing) cells in synthesis gas fermentation. Resting cell states were induced in autotrophic Clostridium ljungdahlii cultures with minimal ethanol and acetate production due to low metabolic activity compared to growing cell production levels of 5.2 and 40.1 mM of ethanol and acetate. Clostridium autoethanogenum cultures were not induced into true resting states but did show improvement in total ethanol production (from 5.1 mM in growing cultures to 9.4 in one nitrogen-limited medium) as well as increased shifts in ethanol-to-acetate production ratios.


Microcrustaceans in rice fields: A scientometric analysis from 1977 to 2019.
We evaluated the worldwide trends in studies of the active and dormant forms of microcrustaceans in rice fields, and the potential of this environment as a stock of diversity through a scientometric analysis. Web of Science and Scopus databases were used to compile the 77 studies published before 2019. Publications were distributed over 35 years, with a positive correlation between the number of studies and the year of publication (rho = 0.34). The identified studies were from 18 countries, and 58.4% were conducted in Japan, Italy, the United States, and Spain. Most studies addressed more than two groups of microcrustaceans (37.6%), followed by those focused on Cladocera (27.2%) and Ostracoda (18.1%). We quantified 301 species from six groups of microcrustaceans, the majority of which were Cladocera (41.5%) and Ostracoda (39.8%). The greatest richness of microcrustaceans identified in studies were found in Italy, Thailand, Malaysia, Spain, France, Japan, and Brazil. Of the studies, 87% were centered on the active forms of microcrustaceans rather than dormant forms. We found that 15.5% of the countries that grow rice have identified the richness of microcrustaceans, and even though they are artificial environments, rice fields have high potential to store a high diversity of microcrustaceans.


Heel-ball (HB) index: sexual dimorphism of a new index from foot dimensions.
The present research is aimed to introduce Heel-ball (HB) index from foot dimensions and determine whether this index exhibits sexual dimorphism. The study was conducted on a sample of 303 North Indian individuals (154 men, and 149 women) aged between 13 and 18 years. The stature, body weight, foot breadth at the ball (BBAL), and foot breadth at heel (BHEL) were measured. The HB index was derived by the formula BHEL × 100/BBAL. Although the mean HB index was larger in women in both feet it showed statistically significant sex differences in the right foot only. The study shows that while the foot dimensions show a positive correlation with stature and weight, the HB index is independent of the stature and weight of an individual. This novel index (HB index) may be utilized in sex determination when a part of the foot is brought for medico-legal investigation.


Vitamin B6: a molecule for human health?
Vitamin B6 is an intriguing molecule that is involved in a wide range of metabolic, physiological and developmental processes. Based on its water solubility and high reactivity when phosphorylated, it is a suitable co-factor for many biochemical processes. Furthermore the vitamin is a potent antioxidant, rivaling carotenoids or tocopherols in its ability to quench reactive oxygen species. It is therefore not surprising that the vitamin is essential and unquestionably important for the cellular metabolism and well-being of all living organisms. The review briefly summarizes the biosynthetic pathways of vitamin B6 in pro- and eukaryotes and its diverse roles in enzymatic reactions. Finally, because in recent years the vitamin has often been considered beneficial for human health, the review will also sum up and critically reflect on current knowledge how human health can profit from vitamin B6.


Promoting Healthy Eating among Young People-A Review of the Evidence of the Impact of School-Based Interventions.
Globally, the prevalence of overweight and obesity is increasing among children and younger adults and is associated with unhealthy dietary habits and lack of physical activity. School food is increasingly brought forward as a policy to address the unhealthy eating patterns among young people. This study investigated the evidence for the effectiveness of school-based food and nutrition interventions on health outcomes by reviewing scientific evidence-based intervention studies amongst children at the international level. This study was based on a systematic review using the PRISMA guidelines. Three electronic databases were systematically searched, reference lists were screened for studies evaluating school-based food and nutrition interventions that promoted children's dietary behaviour and health aiming changes in the body composition among children. Articles dating from 2014 to 2019 were selected and reported effects on anthropometry, dietary behaviour, nutritional knowledge, and attitude. The review showed that school-based interventions in general were able to affect attitudes, knowledge, behaviour and anthropometry, but that the design of the intervention affects the size of the effect. In general, food focused interventions taking an environmental approach seemed to be most effective. School-based interventions (including multicomponent interventions) can be an effective and promising means for promoting healthy eating, improving dietary behaviour, attitude and anthropometry among young children. Thus, schools as a system have the potential to make lasting improvements, ensuring healthy school environment around the globe for the betterment of children's short- and long-term health.


Effects of 8 wk of voluntary unloaded wheel running on K+ tolerance and excitability of soleus muscles in rat.
During intense exercise, efflux of K(+) from working muscles increases extracellular K(+) ([K(+)](o)) to levels that can compromise muscle excitability and hence cause fatigue. In this context, the reduction in the exercise-induced elevation of [K(+)](o) observed after training in humans is suggested to contribute to the increased performance after training. Although a similar effect could be obtained by an increase in the tolerance of muscle to elevated [K(+)](o), this possibility has not been investigated. To examine this, isolated soleus muscles from sedentary (sedentary) rats and from rats that had voluntarily covered 13.1 ± 0.7 km/day in an unloaded running wheel for 8 wk (active) were compared. In muscles from active rats, the loss of force induced by exposure to an elevated [K(+)](o) of 9 mM was 42% lower than in muscles from sedentary rats (P < 0.001). This apparent increase in K(+) tolerance in active rats was associated with an increased excitability as evident from a 33% reduction in the electrical current needed to excite individual muscle fibers (P < 0.0009). Moreover, muscles from active rats had lower Cl(-) conductance, higher maximal rate of rise of single-fiber action potentials (AP), and higher Na(+)/K(+) pump content. When stimulated intermittently at 6.5 mM K(+), muscles from active rats displayed better endurance than muscles from sedentary rats, whereas no difference was found when the muscles were stimulated continuously at 30 or 120 Hz. We conclude that voluntary running increases muscle excitability, leading to improved tolerance to elevated [K(+)](o).


FACTORS OF AGGRESSION AT THE STAGES OF OPEN SURGICAL TREATMENT OF SEVERE FORMS OF PERITONITIS.
There are many unresolved questions regarding the features of surgical aggression in the open method of treatment of severe forms of peritonitis. There are isolated publications in the literature on the risk features of these interventions, despite the high prevalence of the problem. The purpose of this study was to study the features of surgical aggression in the open method of treatment of severe forms of peritonitis. The study included 205 patients with severe forms of purulent peritonitis treated at the Emergency Hospital in Aktobe (n=205). To assess the factors of surgical aggression, the reliability of the results was evaluated by variational statistics according to the Student's t-criterion, taking into account the degree of freedom, at p<0.05 and p<0.01, with the calculation of arithmetic averages and their average errors (M+m). The data are presented as an average value±standard deviation or median and percentiles, p-values less than 0.05 were considered significant. Based on the results obtained, it was found that the frequency of repeated laparosanation surgical interventions in one patient was 2.8±0.3 times against the background of purulent-inflammatory process in the abdominal cavity, a high degree of stress index of the regulatory systems of the body during sanitation was revealed - up to 1460.9±101.5 units, postural reactions of blood circulation and respiration in 7.55% and metabolic disorders homeostasis. Aggressive factors affecting patients and causing the risk of multiple laparosanation interventions at the stages of open surgical treatment of severe forms of peritonitis have been identified. The data obtained can be used to develop therapeutic and preventive measures to improve the results of treatment of severe peritonitis.


[Continuous inhalation administration of surfactant-BL for control of adult respiratory distress syndrome after reconstruction of the abdominal aorta].
A 62-year-old patient with Leriche's syndrome and critical ischemia of the low extremities has undergone the surgery of aortofemoral grafting. A patient has developed the severe ARDS on the second day of reperfusion (bilateral diffuse infiltrates, PO2/FiO2 < 100, lung injury score was 3). Different ways of administration of bovine surfactant (SURFACTANT BL, Russia) were used during the treatment. Total application time was 84 hours, total dose was 4000 mg (50 mg/kg). Considerable improvement of lung function occurred after start of the continuous inhalation of surfactant with a constant rate of 63 mg/h. Two hours after this step PO2/FiO2 reached 400 mm Hg and remained stable 12 hours more, up to the end of surfactant administration. The patient was soon successfully extubated and discharged on the 25th day after surgery. It is supposed that in spite of a small total dose of bovine surfactant the success was achieved due to an early start of the surfactant replacement, continuous inhalation and its definite rate.


Effect of drying temperatures on starch-related functional and thermal properties of acorn flours.
The application of starchy flours from different origins in food systems depends greatly on information about the chemical and functional properties of such food materials. Acorns are important forestry resources in the central and southern regions of Portugal. To preserve these fruits and to optimize their use, techniques like drying are needed. The effects of different drying temperatures on starch-related functional properties of acorn flours obtained from dried fruits of Quercus rotundifolia (QR) and Quercus suber (QS) were evaluated. Flours were characterized for amylose and resistant starch (RS) contents, swelling ability, and gelatinization properties. Drying temperature mainly affected amylose content and viscoamylographic properties. Amylograms of flours from fruits dried at 60 °C displayed higher consistency (2102 B.U. and 1560 B.U., respectively, for QR and QS). The transition temperatures and enthalpy were less affected by drying temperature, suggesting few modifications in starch structure during drying. QR flours presented different functional properties to those obtained from QS acorn flours. The effect of drying temperatures were more evident in QR.


Buckling the equatorial anion plane: octahedral anion distortions in ferroic perovskites and related systems resolved via neutron diffraction.
A framework for describing anion displacements from perfect octahedra in perovskites has been developed for use with neutron diffraction data sets. We describe the distortions as noncoplanar arrangements, or buckling, of oxygen ions in any central plane of the octahedron, ignoring the central cation. Nonplanar distortions of octahedra have been calculated for perovskite structures contained within the Inorganic Crystal Structure Database. We find that antiferroelectric materials have buckling angles larger than ~2° and ferroelectric materials have buckling angles between 0° and 1°. The trend is found as a function of solid solution composition and temperature for common antiferroelectrics. For example, the described method resolves a structural difference between the end members PbTiO(3) and PbZrO(3), which exhibit ferroelectric and antiferroelectric responses, respectively. This technique is applicable to other structures containing anion octahedra, e.g., pyrochlores, spinels, and tungsten bronzes.


Prospective controlled trial comparing colostomy irrigation with "spontaneous-action" method.
Thirty randomly selected patients with permanent colostomies entered a prospective controlled trial comparing colostomy irrigation with spontaneous action. Each patient was interviewed and examined before irrigation was begun and again after the technique had been used for three months. Each then reverted to spontaneous action for a further three months and was then reassessed. Eight patients abandoned irrigation and 22 (73%) adhered to the protocol. Irrigation caused no mishaps or complications. The mean time spent managing the stoma was 45 +/- SEM 9 min/24 hours during spontaneous action and 53 +/- 9 min/24 hours during irrigation. This difference was not significant. The numbers of bowel actions weekly were 13 +/ SEM 2 during spontaneous action and 6 +/- 1 during irrigation (p < 0.01). Irrigation reduced odour and flatus in 20 patients and enabled 12 out of 18 to stop using drugs and seven to discard their appliance. Irrigation also improved the social life of 18 patients and the working conditions of eight out of 14. These finding show that some patients may not be suitable for irrigation but that for many it is better than the conventional British method of colostomy management. With modern apparatus the technique is safe.


Breakthrough COVID-19 infections and perceived vaccine effectiveness.
While SARS-CoV-2 vaccines provide significant protection against severe COVID-19 illness, breakthrough infections have sparked confusion among patients about the effectiveness of vaccination. It's unclear if (or to what extent) breakthrough infection experiences impact public perceptions of COVID-vaccine effectiveness, though the answer may have significant implications for public health communications and ongoing vaccine acceptance. We conducted a survey of 2,500 adults in the United States (February 27 - March 9, 2023) in order to better understand the relationship between breakthrough COVID-19 infections and perceived vaccine effectiveness. Survey respondents were selected using a stratified, quota sampling approach to ensure representativeness; analysis was conducted on responses from 1,928 participants who received a COVID-19 vaccine. Among those who tested positive for COVID-19 after being vaccinated, 21.18 % said that COVID-19 vaccines had been "less effective" than they initially expected, compared with 10.0 % of those who did not experience any breakthrough infections (X2 = 75.551; φ = 0.198; p ≤ 0.001). Those who experienced their own breakthrough infection were 1.37 times less likely to report perceived vaccine efficacy, while those whose family members experienced a breakthrough infection were 1.64 times less likely to report the same, ceteris paribus. The largest effect was observed among those who experienced both a personal and familial breakthrough infection. This group was almost two times less likely to describe COVID-19 vaccines as "very effective". Breakthrough infections correlated with lower overall levels of perceived vaccine effectiveness, even after accounting for demographic and political considerations. Moving forward, public officials and health professionals should work proactively to ensure that breakthrough infections are understood in the broader context of overall vaccine effectiveness.


[Localized syringoma of the vulva].
A 26-year-old woman developed papular lesions symmetrically located on both labia majora during several years duration. Histopathological examination showed typical features of syringomas. In the literature, only 15 patients have been previously described.


Deletions of the terminal sequences in the genomes of the white pock (u) and host-restricted (p) mutants of rabbitpox virus.
The DNAs of wild-type rabbitpox virus (u+.p+), and selected u (white pock, u.p+) and p (white pock, PK-15 cell non-permissive, u.p) mutants were compared by restriction enzyme analysis. The cleavage fragments produced by digestion with HindIII or EcoRI endonucleases were separated by agarose gel electrophoresis. Deletions of approx. 10 x 10(6) were recognized at the right-hand terminus of each u mutant (three isolates), whereas deletions of 5 x 10(6) to 20 x 10(6) were detected at the left-hand terminus of each p mutant (nine isolates), Rapidly renaturing terminal restriction fragments, indicative of the covalent cross-links, were only found at the terminus unaffected by deleted sequences. Recombinant viruses that were wild-type in both genetic characters and in restriction pattern were recovered from mixed infections involving u and p mutants, but no genetic interaction was detected between crosses involving only u or p mutants. The p mutants were divided into two non-permissive classes dependent on their biochemical expression in PK-15 cells: the 'early' class which failed to replicate virus DNA and synthesized only the 'early' polypeptides and the 'late' class which appeared to be normal both in virus DNA and polypeptide synthesis. There was no correlation between the extent of the left-hand terminal deletion and the extent of permissiveness of the p mutants in PK-15 cells.


Age-related difference in muscle metabolism patterns during upper limb's encircling exercise: a near-infrared spectroscopy study.
Aging is usually accompanied by decrease in limb motor function and change in muscle metabolism patterns. However, few studies have investigated the aging effect on muscle hemodynamics of the upper extremity. This study aims to explore the aging effect on muscle metabolism patterns during upper limb's exercise. Twelve middle-aged and elderly subjects and 12 young subjects were recruited, and muscle oxygenation signals from these subjects' biceps brachii muscles were collected during active and passive upper limb's encircling exercise with near-infrared spectroscopy (NIRS). The old group showed stronger muscle hemodynamic metabolism than the young group. The multiscale fuzzy approximate entropy and multiscale transfer entropy analyses indicated higher complexity and stronger interlimb coupling of the muscle oxygenation signals for the old group. Based on the selected muscle metabolism features, the constructed support vector machine model showed a high accuracy rate for classifying the two groups of subjects: 91.6% for the passive mode and 87.5% for the active mode. Our results proved the specific muscle metabolism patterns in the upper limb's exercise for old subjects, promoting the understanding of the aging effect on muscle hemodynamics.


The Arabidopsis abscisic acid response gene ABI5 encodes a basic leucine zipper transcription factor.
The Arabidopsis abscisic acid (ABA)-insensitive abi5 mutants have pleiotropic defects in ABA response, including decreased sensitivity to ABA inhibition of germination and altered expression of some ABA-regulated genes. We isolated the ABI5 gene by using a positional cloning approach and found that it encodes a member of the basic leucine zipper transcription factor family. The previously characterized abi5-1 allele encodes a protein that lacks the DNA binding and dimerization domains required for ABI5 function. Analyses of ABI5 expression provide evidence for ABA regulation, cross-regulation by other ABI genes, and possibly autoregulation. Comparison of seed and ABA-inducible vegetative gene expression in wild-type and abi5-1 plants indicates that ABI5 regulates a subset of late embryogenesis-abundant genes during both developmental stages.


Making mesoderm--upstream and downstream of Xbra.
The mesoderm of the amphibian embryo is formed through an inductive interaction in which cells of the vegetal hemisphere of the embryo act on overlying equatorial cells. My laboratory is studying the Brachyury gene, which plays a key role in this interaction, being both necessary and sufficient for normal mesoderm formation. In this article I describe our attempts to understand how Xenopus Brachyury (Xbra) is activated in the right cells at the right time, and then to understand how Xbra exerts its effects.


Point-of-Care Ultrasound-Guided Versus Conventional Bladder Catheterization for Urine Sampling in Children Aged 0 to 24 Months.
It can be difficult to obtain urine samples, especially in children aged 0 to 24 months who have not yet completed toilet training. Bladder catheterization is a common method for urine sampling in this age group. However, if the bladder is not adequately filled, this process fails and repeat catheterization is necessary. Point-of-care ultrasonography (POCUS) is often used to assist invasive procedures in the pediatric emergency department. This study aimed to compare success rates of bladder catheterization in patients with and without POCUS to guide the timing of the procedure. This was a prospective cohort study of children 0 to 24 months presenting to a pediatric emergency department in a tertiary center hospital. Patients were divided into 2 groups; the one group received conventional catheterization (CC group) without POCUS and the other group had catheterization after POCUS (POCUS group). The transverse and anterior-posterior diameter measurements of the bladder were obtained from one view in the transverse orientation using the (6-3 MHz) convex probe. Successful catheterization was defined by obtaining 3 mL or more of urine. A total of 110 patients were included in the study, with 56 in the POCUS group and 54 in the CC group. There was no difference between the mean age and sex of the groups. The success rates of obtaining urine samples were 93% and 78% in the POCUS group and CC group, respectively. This difference was statistically significant (P = 0.03). No significant difference was found between measurements of bladder catheterizations with and without obtaining 3 mL or greater urine volumes in the ultrasound group (P > 0.05). The use of POCUS during bladder catheterization in children was found to be effective and successful. In addition, the detection of any amount of urine in the bladder using POCUS increases the success rate of bladder catheterization.


Hyperspectral and Radar Airborne Imagery over Controlled Release of Oil at Sea.
Remote sensing techniques are commonly used by Oil and Gas companies to monitor hydrocarbon on the ocean surface. The interest lies not only in exploration but also in the monitoring of the maritime environment. Occurrence of natural seeps on the sea surface is a key indicator of the presence of mature source rock in the subsurface. These natural seeps, as well as the oil slicks, are commonly detected using radar sensors but the addition of optical imagery can deliver extra information such as thickness and composition of the detected oil, which is critical for both exploration purposes and efficient cleanup operations. Today, state-of-the-art approaches combine multiple data collected by optical and radar sensors embedded on-board different airborne and spaceborne platforms, to ensure wide spatial coverage and high frequency revisit time. Multi-wavelength imaging system may create a breakthrough in remote sensing applications, but it requires adapted processing techniques that need to be developed. To explore performances offered by multi-wavelength radar and optical sensors for oil slick monitoring, remote sensing data have been collected by SETHI (Système Expérimental de Télédection Hyperfréquence Imageur), the airborne system developed by ONERA (the French Aerospace Lab), during an oil spill cleanup exercise carried out in 2015 in the North Sea, Europe. The uniqueness of this dataset lies in its high spatial resolution, low noise level and quasi-simultaneous acquisitions of different part of the EM spectrum. Specific processing techniques have been developed to extract meaningful information associated with oil-covered sea surface. Analysis of this unique and rich dataset demonstrates that remote sensing imagery, collected in both optical and microwave domains, allows estimating slick surface properties such as the age of the emulsion released at sea, the spatial abundance of oil and the relative concentration of hydrocarbons remaining on the sea surface.


Effect of laparotomy on respiratory muscle activation pattern.
Muscular tone of the abdominal wall is important in maintaining transdiaphragmatic pressures and its loss can lead to decreased lung volumes. Patients who are status postlaparotomy are at risk of developing atelectasis. The compensatory role of respiratory muscle activity in postlaparotomy is not well studied. Normally, inspiratory muscles are active during inspiration and passive during expiration to allow for lung recoil. However, electrical activities of the inspiratory muscles continue during early expiratory phase to prevent rapid loss of lung volume. This activity is known as post-inspiratory inspiratory activity (PIIA). In this study, we hypothesized that laparotomy will elicit an increase in PIIA, which is enhanced by respiratory chemical loading. Experiments were conducted in cats under three different conditions: intact abdomen (n = 3), open abdomen (n = 10), and post abdominal closure (n = 10) during eupnea and hypercapnia (10% CO2). Electromyography (EMG) activities of the diaphragm and parasternal muscles were recorded and peak EMG amplitude, PIIA time, and area under the curve were measured. Intraesophageal pressure was also obtained. PIIA was significantly higher under open abdominal conditions in comparison to intact abdomen during eupnea. Our data indicates that PIIA is increased during open abdomen and may be an important compensatory mechanism for altered respiratory mechanics induced by laparotomy. Also, PIIA remained elevated after abdominal closure. However, under hypercapnia, PIIA was significantly higher during intact abdomen in comparison to open abdomen, which is thought to be due to respiratory muscle compensation under chemical loading.


Unveiling professional and personal preferences of early career dentists during first year of employment at the Thai dental public sector: a one-year cross-sectional study.
Despite the implementation of various government policies to retain Thai dentists in public sector, a high turnover rate among early career dentists has persisted for decades. This study aims to explore factors relating to early career dentists' choice of the public sector as their preferred workplace and decisions relating to staying, resigning, or relocating from the workplace after one-year employment. A one-year cross-sectional survey was conducted among Thai early career dentists who began working in 2020 using two sets of online questionnaires. The first survey assessed factors influencing dentists' decision to choose the public sector as their preferred workplace at the beginning of the year. The second survey investigated factors influencing dentists' decision to stay, resign, or relocate from the same workplace at one-year after employment. Descriptive statistics and multivariable binary logistic regression were used for data analysis. A total of 198 early career dentists completed the online survey questionnaire at the starting point (December 2020-January 2021), and 186 dentists completed the one-year employment questionnaire. The living environment and provided amenities and facilities were the most influential factors in their decision to choose and remain in the public sector. Conversely, their attitude toward unrelated job descriptions and an increased opportunity to pursue postgraduate studies were the most relevant factors when deciding to relocate to a new workplace. Factors such as delayed authority in bureaucracy, hometown location, and being in relationship status were the most significant contributors to resignation from the public sector. The major factors influencing dentists' choice and retention in the public sector include the living environment, supportive supervisors and colleagues, and the availability of opportunities for further postgraduate education. Meanwhile, factors impacting retention after one year of work are related to hometown location and the bureaucracy system. Collaborations among ministries, tailored to each local community's specific requirements, may enhance dentists' retention in public sectors.


Elovanoid-N32 or RvD6-isomer decrease ACE2 and binding of S protein RBD after injury or INFγ in the eye.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic tall around the world. Effective treatments to mitigate this virus infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation as well as human corneal epithelial cells in culture challenged with IFNγ to study this issue. We explore ways to block the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to angiotensin-converting enzyme 2 (ACE2). Elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i), among the lipid mediators studied, consistently decreased the expression of the ACE2 receptor, furin, and integrins in damaged corneas or IFNγ stimulated human corneal epithelial cells (HCEC). There was also a concomitant decrease in the binding of spike RBD with the lipid treatments. Concurrently, we uncovered that the lipid mediators also attenuated the expression of cytokines that participate in the cytokine storm, hyper-inflammation and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to opening therapeutic avenues for COVID-19 by counteracting virus attachment and entrance to the eye and other cells and the ensuing disruptions of homeostasis.


Determination of Seed Soundness in Conifers Cryptomeria japonica and Chamaecyparis obtusa Using Narrow-Multiband Spectral Imaging in the Short-Wavelength Infrared Range.
Regeneration of planted forests of Cryptomeria japonica (sugi) and Chamaecyparis obtuse (hinoki) is the pressing importance to the forest administration in Japan. Low seed germination rate of these species, however, has hampered low-cost production of their seedlings for reforestation. The primary cause of the low germinability has been attributed to highly frequent formation of anatomically unsound seeds, which are indistinguishable from sound germinable seeds by visible observation and other common criteria such as size and weight. To establish a method for sound seed selection in these species, hyperspectral imaging technique was used to identify a wavelength range where reflectance spectra differ clearly between sound and unsound seeds. In sound seeds of both species, reflectance in a narrow waveband centered at 1,730 nm, corresponding to a lipid absorption band in the short-wavelength infrared (SWIR) range, was greatly depressed relative to that in adjacent wavebands on either side. Such depression was absent or less prominent in unsound seeds. Based on these observations, a reflectance index SQI, abbreviated for seed quality index, was formulated using reflectance at three narrow SWIR wavebands so that it represents the extent of the depression. SQI calculated from seed area-averaged reflectance spectra and spatial distribution patterns of pixelwise SQI within each seed area were both proven as reliable criteria for sound seed selection. Enrichment of sound seeds was accompanied by an increase in germination rate of the seed lot. Thus, the methods described are readily applicable toward low-cost seedling production in combination with single seed sowing technology.


Variations of electroanatomic substrates and markers of successful ablation in idiopathic left ventricular tachycardia: role of electroanatomic substrates and potential mechanism of tachycardia.
The variation of the substrates of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) was not understood. The purpose of this study was to investigate the variation of electroanatomic substrate [slow conduction zone (SCZ) and left ventricular conduction system (LVCS)] in ILVT and control individuals and markers of successful ablation. Electroanatomical mapping was performed during sinus rhythm in 20 ILVT patients and 26 control individuals with paroxysmal supraventricular tachycardia. LVCS and SCZ were tagged in geometry and the anatomic aspects were investigated. According to the distribution of Purkinje potential, LVCS was distinguished into three types: left bundle branch (LBB) was divided into two discrete fascicles without interconnections; divided into three separate fascicles; and fanlike structure distribution over septum broadly. The length of LBB and its fascicles in patients with ILVT were slightly longer than those of controls (P > 0.05). In the ILVT group, the SCZ was located at the inferoposterior septum in 17, inferior apical septum in one and two SCZs were located at the posterior and mid-septal in the other two patients, which were greater in size and longer in length than those of six controls (P < 0.05). At the crossover junction area with diastolic potential and Purkinje potential, with the size of 1.5 ± 0.4 cm(2), concealed entertainment and ablation were obtained successfully in all patients with ILVT. The anatomy of the LVCS and SCZ is highly variable in patients with ILVT, and the crossover junction area with diastolic potential and Purkinje potential might be a marker of ablation.


Clinicopathological and Molecular Characteristics of Early-Onset Stage III Colon Adenocarcinoma: An Analysis of the ACCENT Database.
Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing. Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided. Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers. Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.


CT appearance of the adolescent and preadolescent pituitary gland.
Coronal computed tomographic scans of the pituitary gland in 27 normal children, adolescents, and young adults (ages, 8-21 years) and in a comparison group of adults (ages, 24-91 years) were evaluated retrospectively to test the applicability of published criteria for size and configuration of normal adult pituitary glands to younger patients. Statistically significant differences were found between the two groups, indicating that the pituitary gland in adolescents, particularly girls, is larger than in younger or older patients. The authors suggest that pubertal pituitary hyperplasia accounts for these findings. They conclude that standards for normal pituitary glands are probably inappropriate for adolescents.


Interventions for Concerning Patient-Reported Outcomes in Routine Cancer Care: A Systematic Review.
Collecting patient-reported outcomes (PROs) in routine cancer care improves patient-clinician communication, decision making, and overall patient satisfaction. Recommendations exist regarding standardized ways to collect, store, and interpret PRO data. However, evidence on incorporating PROs into cancer process of care, especially the type of HIs that are warranted after observing a concerning PRO and the effectiveness of these HIs are lacking. This study summarizes HIs triggered after PRO completion and their effectiveness in improving patient outcomes for adults being treated for cancer types that are resource intensive and associated with high symptom burden [i.e., gastrointestinal (GI), lung, and head and neck cancer (HNC)]. Secondary outcomes included factors associated with poor implementation of PROs. A literature search of peer-reviewed publications on MEDLINE, CINAHL Plus, APA PsycInfo, Scopus, and Cochrane was conducted following PRISMA guidelines from 1 January 2012, to 31 July 2022. Trial and real-world studies describing HIs after PRO completion for adult patients being treated for GI, lung, and HNC were included. Sixteen studies involving 144,496 patients were included. The Joanna Briggs Institute critical appraisal checklist was used to assess risk of bias. Of the 16 included studies, 5 included patients with HNC. Commonly used PRO measurement tools were the PRO-CTCAE and ESAS. Only three studies reported specific HIs delivered in response to concerning PROs and measured their effectiveness on patient outcomes. In all three studies, these HIs significantly improved cancer-related care. The most common HIs undertaken in response to concerning PROs were referrals to other specialists/allied healthcare professionals, medication changes, or self-management advice. Provider-related barriers to PRO measurement and delivery included the overwhelming number of alerts, the time required to address each PRO and the unclear role of healthcare providers in response to these alerts. Patient-related barriers included lower digital literacy and socioeconomic status, older age, rural living, and patients suffering from GI and HNC. This review highlights that PRO-triggered HIs are heterogenous and can improve patient quality of life. Further studies are necessary to determine the types of interventions with the greatest impact on patient care and outcomes.


Hypoxia regulates VEGF expression and cellular proliferation by osteoblasts in vitro.
Numerous studies have demonstrated the critical role of angiogenesis for successful osteogenesis during endochondral ossification and fracture repair. Vascular endothelial growth factor (VEGF), a potent endothelial cell-specific cytokine, has been shown to be mitogenic and chemotactic for endothelial cells in vitro and angiogenic in many in vivo models. Based on previous work that (1) VEGF is up-regulated during membranous fracture healing, (2) the fracture site contains a hypoxic gradient, (3) VEGF is up-regulated in a variety of cells in response to hypoxia, and (4) VEGF is expressed by isolated osteoblasts in vitro stimulated by other fracture cytokines, the hypothesis that hypoxia may regulate the expression of VEGF by osteoblasts was formulated. This hypothesis was tested in a series of in vitro studies in which VEGF mRNA and protein expression was assessed after exposure of osteoblast-like cells to hypoxic stimuli. In addition, the effects of a hypoxic microenvironment on osteoblast proliferation and differentiation in vitro was analyzed. These results demonstrate that hypoxia does, indeed, regulate expression of VEGF in osteoblast-like cells in a dose-dependent fashion. In addition, it is demonstrated that hypoxia results in decreased cellular proliferation, decreased expression of proliferating cell nuclear antigen, and increased alkaline phosphatase (a marker of osteoblast differentiation). Taken together, these data suggest that osteoblasts, through the expression of VEGF, may be in part responsible for angiogenesis and the resultant increased blood flow to fractured bone segments. In addition, these data provide evidence that osteoblasts have oxygen-sensing mechanisms and that decreased oxygen tension can regulate gene expression, cellular proliferation, and cellular differentiation.


SIRT3 Regulates Clearance of Apoptotic Cardiomyocytes by Deacetylating Frataxin.
Efferocytosis is an activity of macrophages that is pivotal for the resolution of inflammation in hypertension. The precise mechanism by which macrophages coordinate efferocytosis and internalize apoptotic cardiomyocytes remains unknown. The aim of this study was to determine whether SIRT3 (sirtuin-3) is required for both apoptotic cardiomyocyte engulfment and anti-inflammatory responses during efferocytosis. We generated myeloid SIRT3 knockout mice and FXN (frataxin) knock-in mice carrying an acetylation-defective lysine to arginine K189R mutation (FXNK189R). The mice were given Ang II (angiotensin II) infusion for 7 days. We analyzed cardiac macrophages' mitochondrial iron levels, efferocytosis activity, and phenotype both in vivo and in vitro. We showed that SIRT3 deficiency exacerbated Ang II-induced downregulation of the efferocytosis receptor MerTK (c-Mer tyrosine kinase) and proinflammatory cytokine production, accompanied by disrupted mitochondrial iron homeostasis in cardiac macrophages. Quantitative acetylome analysis revealed that SIRT3 deacetylated FXN at lysine 189. Ang II attenuated SIRT3 activity and enhanced the acetylation level of FXNK189. Acetylated FXN further reduced the synthesis of ISCs (iron-sulfur clusters), resulting in mitochondrial iron accumulation. Phagocytic internalization of apoptotic cardiomyocytes increased myoglobin content, and derived iron ions promoted mitochondrial iron overload and lipid peroxidation. An iron chelator deferoxamine improved the levels of MerTK and efferocytosis, thereby attenuating proinflammatory macrophage activation. FXNK189R mice showed improved macrophage efferocytosis, reduced cardiac inflammation, and suppressed cardiac fibrosis. The SIRT3-FXN axis has the potential to resolve cardiac inflammation by increasing macrophage efferocytosis and anti-inflammatory activities.


Increasing threat of Gram-negative bacteria.
The widespread use of broad-spectrum antibiotics has led to emergence of antibiotic-resistant strains of many Gram-negative organisms. This problem is particularly serious in critically ill patients, especially those with ventilator-associated pneumonia. Extensive antibiotic resistance has developed in Gram-negative bacteria, due both to innate resistance in some species and the fact that they are highly adept at acquiring antibiotic-resistant determinants from each other. Antibiotic resistance develops through the following three basic mechanisms: alteration of the drug target, prevention of drug access to the target (including actively removing the drug from the bacteria), and drug inactivation. Certain Gram-negative microorganisms are particular problems in the intensive care unit, including Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia, and the Enterobacteriaceae. The combination of an increasing population at risk, and the natural virulence and adaptability of Gram-negative bacteria guarantees that critical care physicians will face a persistent and increasing challenge from these pathogens.


Retroperitoneal fibrosis in feline renal transplant recipients: 29 cases (1998-2011).
To evaluate features, treatment, and prognosis associated with retroperitoneal fibrosis that developed after renal transplantation in cats. Retrospective case series. 29 cats. Medical records of cats that developed retroperitoneal fibrosis after renal transplantation at the College of Veterinary Medicine, University of Pennsylvania, between 1998 and 2011 were reviewed for signalment, date of transplantation, age, results of urine and blood analyses, blood pressure at the time of diagnosis, infectious disease and medication anamneses, anesthetic protocols, and intraoperative complications. Of 138 transplant recipients, 29 (21%) developed clinically important retroperitoneal fibrosis. Nineteen (66%) were male, and median age at the time of renal transplantation was 8 years (range, 4 to 13 years). Median number of days after transplantation to diagnosis of retroperitoneal fibrosis was 62 (range, 4 to 730 days; mean, 125 days). The most common clinical signs were lethargy and anorexia. All affected cats were azotemic (BUN concentration > 32 mg/dL; creatinine concentration > 2.0 mg/dL) and anemic (PCV < 35%) at the time of retroperitoneal fibrosis diagnosis, although cats were nonazotemic at the time of discharge following transplantation, and anemia was less pronounced. Twenty-five cats successfully underwent surgical ureterolysis in which scar tissue was dissected away from the allograft ureter to relieve extraluminal compression. Retroperitoneal fibrosis recurred in 6 (22%) cats a median of 180 days (range, 8 to 343 days) following the original diagnosis and was treated successfully by repeated ureterolysis. Retroperitoneal fibrosis occurred in a substantial percentage of feline renal transplant recipients and should be considered a differential diagnosis in any feline renal transplant recipient with clinicopathologic findings, imaging abnormalities, or signs suggestive of obstructive uropathy.


The effects of aquatic exercise on body composition and nonspecific low back pain in elderly males.
[Purpose] The purpose of this study was to investigate the effect of aquatic exercises on nonspecific low back pain (LBP) in elderly males. [Subjects and Methods] Thirty-two elderly men aged 65 or older were recruited and randomly allocated to two groups: aquatic training (3 d/wk for 12 wk) or a control group. Body mass index (BMI), percentage of body fat (PBF), waist-hip ratio (WHR), and trunk muscle mass were measured before and after training. [Results] The results suggested that all obesity variables including BMI, WHR, and PBF of the aquatic training group were decreased significantly, while the trunk muscle mass of the aquatic training group was increased significantly. Furthermore, low back pain was decreased in the subjects after the intervention. [Conclusion] The water-based program improved LBP and body composition in the elderly men.


Fluorescence-based bacterial overlay method for simultaneous in situ quantification of surface-attached bacteria.
For quantification of bacterial adherence to biomaterial surfaces or to other surfaces prone to biofouling, there is a need for methods that allow a comparative analysis of small material specimens. A new method for quantification of surface-attached biotinylated bacteria was established by in situ detection with fluorescence-labeled avidin-D. This method was evaluated utilizing a silicon wafer model system to monitor the influences of surface wettability and roughness on bacterial adhesion. Furthermore, the effects of protein preadsorption from serum, saliva, human serum albumin, and fibronectin were investigated. Streptococcus gordonii, Streptococcus mitis, and Staphylococcus aureus were chosen as model organisms because of their differing adhesion properties and their clinical relevance. To verify the results obtained by this new technique, scanning electron microscopy and agar replica plating were employed. Oxidized and poly(ethylene glycol)-modified silicon wafers were found to be more resistant to bacterial adhesion than wafers coated with hydrocarbon and fluorocarbon moieties. Roughening of the chemically modified surfaces resulted in an overall increase in bacterial attachment. Preadsorption of proteins affected bacterial adherence but did not fully abolish the influence of the original surface chemistry. However, in certain instances, mostly with saliva or serum, masking of the underlying surface chemistry became evident. The new bacterial overlay method allowed a reliable quantification of surface-attached bacteria and could hence be employed for measuring bacterial adherence on material specimens in a variety of applications.


Demonstration of an abnormality of C apoprotein of very low density lipoprotein in patients with gout.
The very low density (VLDL) apolipoproteins of 12 male patients with gout have been studied by analytical isoelectric focusing. The relative percentage distribution of the C apolipoproteins was calculated and compared with that from 12 normolipidaemic and 12 'lipid-matched' controls. In the gout patients apolipoprotein CII (apo CII) represented 19.6% of the VLDL C proteins and the CII/CIII2 ratio was 0.57. In the normolipidaemic controls apo CII represented 28.8% and in the lipid-matched controls 33.1% of VLDL apo C, and the CII/CIII2 ratio approached one in each control group. These differences were significant. This suggests that a reduction in VLDL apo CII may predispose to the hypertriglyceridaemia that is commonly found in patients with gout.


Prevalence and predictors of herbal medication use in veterans with chronic hepatitis C.
Herbal therapies are used by a substantial proportion of persons in the United States, and use of these supplements may be even higher in those with chronic liver disease. The aims of this study were to prospectively determine the proportion of US veterans with chronic hepatitis C that are currently taking vitamins and herbal medications and to evaluate factors associated with use of herbal preparations. Patients with hepatitis C who were seen in the gastroenterology, infectious disease, and primary care clinics at the VA New York Harbor Healthcare System were invited to participate in this prospective study. For comparison, healthy patients without hepatitis C were enrolled from the primary care clinics at the same medical center. Patients were interviewed by trained research coordinators who obtained detailed demographic and clinical data, as well as information on the use of antioxidants (vitamin C and E), multivitamins, and herbal medications. Use of vitamin C (34.8% vs. 19.6%, P < 0.001), vitamin E (25.8% vs. 13.2%, P < 0.001), multivitamins (43.6% vs. 28.0%, P < 0.001), and herbal therapies (21.0% vs. 10.4%, P < 0.001) was significantly higher in the 500 patients with hepatitis C compared with the 250 healthy controls. The most common herbal medications taken by hepatitis C patients were milk thistle (12.2%), ginseng (4.6%), and echinacea (3.0%). After adjusting for age and gender, multivariate logistic regression identified 12 or more years of education (OR 2.7; 95% CI 1.6-4.3; P < 0.001) and annual income of at least 20,000 US dollars (OR 2.0; 95% CI 1.3-3.2; P = 0.004) as the only significant predictors of herbal medication use in patients with hepatitis C. The use of herbal preparations is prevalent among veterans with chronic hepatitis C, especially those with higher levels of education and higher incomes. Obtaining a detailed medical history and documentation of the use of these supplements is critical to determine the potential for herbal-drug interactions and hepatotoxicity.


NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors.
By applying the 'recognition mask' strategy to 300 mammalian sequences containing NotI sites we demonstrated that 5' ends of genes are highly enriched in NotI sites. A NotI linking clone NL2-252 (D3S1678) containing transferrin receptor (TFRC) gene was used as an initial point for chromosomal jumping. One of the jumping clones, J21-045 traverses 210 kbp and links NL2-252 to NL26 (D3S1632), a NotI linking clone containing highly polymorphic sequences. The TFRC gene was mapped to 3q29, close to the telomeric marker D3S2344, by linkage analysis, a panel of hybrid cell lines, GeneBridge 4 panel and FISH. Clone NLM-007 (D3S4302) was found to contain ras-homologous gene RAB7. By FISH and a panel of hybrid cell lines this gene was mapped to 3q21. This region is of particular interest due to frequent rearrangements in different types of leukemia. Clone L2-081 (D3S4283) containing new member of ubiquitin-specific proteases (HAUSP gene) was localized in 3p21 inspiring further investigation of involvement of this gene in development of lung and renal carcinomas.


Carbon dioxide evolution during the cell cycle of the fission yeast Schizosaccharomyces pombe.
The rate of CO2 evolution was measured in synchronous cultures of the fission yeast Schizosaccharomyces pombe growing in a minimal medium. The rate of CO2 evolution was found to double sharply at about the time of nuclear division (0.75 of the way through the cell cycle). For the remainder of the cell cycle the rate remained constant. Addition of inhibitors of DNA synthesis or nuclear division did not affect the pattern of CO2 evolution in synchronous cultures. Similarly, in an induced synchronous culture, in which DNA synthesis, nuclear division and cell division--but not growth, were synchronized, CO2 evolution showed a continuous pattern and not the step-wise increase associated with the normal synchronous cultures. When S. pombe was grown in a complete medium, the evolution of CO2 in a synchronous cultures was shown to increase in a continuous manner but at a rate faster than the growth of the culture.


I know It's false, but I keep thinking as if it were true: A replication study of Johnson and Seifert's (1994) continued influence effect.
False Information (FI) is a critical societal issue, made even more pressing by our inability to mitigate its influence through correction. Researchers Johnson and Seifert (1994, Experiment 1A) penned a seminal paper on this "Continued Influence Effect" (CIE), which they observed in English-speaking participants. In their experiments, one group read a text containing FI that was later retracted (FI group), while another read the same text without FI (control group). Interestingly, even after receiving corrections, participants who read the FI were more likely than their peers to form FI-related inferences about the text. To the best of our knowledge, this finding has never been successfully directly replicated. Given the current replicability crisis plaguing the human sciences, the influence of culture on CIE and the importance of Johnson and Seifert's paradigm in this literature, the reassessment of their findings within a non-English-speaking population appears crucial. The present research investigated the direct replicability of their study with a French-speaking sample, comparing the inferences drawn by an FI group (n = 21) to those made by a control group (n = 23). The results confirm those of the original study, supporting the validity of Johnson and Seifert's paradigm (1994) and extending its applicability to a French-speaking population.


Evidence for independent modulation of human 11-HSD and 5 alpha/5 beta reductase activities.
The increased ratio of 5 alpha to 5 beta reduced steroids associated with apparent mineralocorticoid excess (AME) may be a necessary consequence of altered 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity. In order to test this hypothesis we have compared changes in 11-HSD activity and 5 alpha/5 beta reduction in a variety of clinical and experimental conditions. The ratio of 11-oxo/11 beta-hydroxy metabolites of cortisol (11-oxo/11-OH FM) was used as an index of 11-HSD activity and the ratio of allotetrahydrocortisol/ tetrahydrocortisol (allo THF/THF) was used as an index of 5 alpha/5 beta reduction. Ratios were derived from 24 hour urinary steroid profiles measured by high resolution gas chromatography. The clinical conditions studied were Cushing's Syndrome, Major Depression and hirsutism. In each study, the patient group were compared with age-matched healthy controls. For the experimental conditions, subjects treated with either hydrocortisone, dexamethasone, metyrapone or finasteride acted as their own controls. No consistent relationship was found between changes in the ratios of 11-oxo/11-OH FM and allo THF/THF. We conclude that there is no evidence of consistent metabolic interaction between 11-HSD and 5 alpha/5 beta reductase activities under a wide range of conditions. Furthermore, the patterns of metabolic changes seen in these conditions are no less characteristic, although more subtle, than the well-documented metabolic changes seen in inborn errors of steroid metabolism.


[Clinicopathologic features of infant dysembryoplastic neuroepithelial tumor: a case report and literature review].
Dysembryoplastic neuroepithelial tumor (DNT) has traditionally been viewed as rare benign tumors that present with seizure widely considered curable with surgery alone. Most DNTs occur in childhood and young adults. However, rare reported cases occur in infants. This paper reported an infant case of DNT and its diagnosis, differential diagnosis, treatment, molecular features and prognosis based on the review of current literatures. The age onset of this patient was only 11 months old. The clinical manifestations were partial seizures and the imaging data untypical; CT and MRI were all supportive of astrocytoma. Typical glioneuronal element histologic features could be seen, which contained oligodendrocyte-like cells attached to bundles of axons and neurons floating in a myxoid interstitial fluid. Meanwhile, some atypical regions could also be seen. These atypical regions showed a mixture of oligodendrocyte-like cells and neurons without a myxoid interstitial fluid, which were easily misdiagnosed. The BRAFV600E mutation was not detected. This patient had a good response to drug therapy. Totally surgical resection of the tumor was conducted. The patient had been seizures free for 6 months. In conclusion, DNT is a rare and well prognostic tumor (WHO grade I), which most often arise in children in the setting of medically refractory epilepsy. The most common tumor location was temporal. Because clinical symptoms, imaging and histological features of DNT and other low-grade gliomas broadly overlap such as ganglioglioma, pilocytic astrocytomas and oligodendroglioma et al., differential diagnosis should be made carefully. The glioneuronal element was the histopathological hallmark of DNT. In addition, some untypical regions should also be called attention. Although BRAFV600E mutation didn't exist in this case, it played a role in differential diagnosis because it has been previously recorded that BRAFV600E mutation was a common feature of DNT. Infant patients have their own characteristics. For example, drug therapy worked well and the imaging data was untypical. Doctors should improve the understanding of this disease to avoid unnecessary radiotherapy or chemotherapy.


Clinical and molecular approaches to well differentiated and dedifferentiated liposarcoma.
Liposarcoma, a rare disease, is classified into five histologic subtypes. These include well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS), both characterized by chromosome 12q13-15 amplification. This review will focus on the clinical management of WDLS and DDLS and examine recent molecular studies that have the potential to affect clinical management. Outcome of patients with WDLS and DDLS depends on completeness of surgical resection as well as tumor location and histologic subtype. Risk of recurrence is high for patients with dedifferentiated histology or retroperitoneal location. We now understand that surgical outcomes are poor for patients with rapidly growing or incompletely resectable tumors, so these patients should be managed nonoperatively. Radiation and chemotherapy have low response rates in WDLS and DDLS, but novel agents targeted at chromosome 12 gene products MDM2 and CDK4 have shown promise in preclinical studies and are being tested in clinical trials. Cell line, tissue microarray, and genomic analyses have identified additional targets including ZIC1, TOP2A, AURKA, and IGF-1R, which could form the basis of future therapies. Although complete surgical resection is currently the most effective treatment for WDLS and DDLS, the majority of patients with retroperitoneal liposarcoma will eventually have recurrence and die of disease. It is hoped that a multimodality approach, which incorporates targeted therapies and complete surgical resection, will significantly improve patient outcomes.


Cessation of Antibiotics for Complicated Appendicitis at Discharge Does Not Increase Risk of Post-operative Infection.
The utilization of home antibiotic therapy following surgery for complicated pediatric appendicitis is highly variable. In 2019, we stopped home antibiotic therapy in this cohort at our institution. We sought to evaluate our outcomes following this protocol change. We queried our institutional NSQIP Pediatrics data for all children undergoing appendectomy for complicated appendicitis between January 2015 and May 2022. We identified two cohorts: those discharged with home antibiotics (1/1/15-4/30/19) and those discharged with no home antibiotics (5/1/19-4/30/22). Both groups were treated with response based parenteral antibiotics while hospitalized and discharged when clinically well. Our primary outcome was postoperative deep organ space infection requiring intervention (drainage, aspiration, reoperation, or antibiotics). Secondary outcomes included length of stay, superficial site infection, Clostridium difficile colitis, ER visits, post-operative CT imaging, and readmission. There were 185 patients in the home antibiotic group (83% discharged with antibiotics) and 121 patients in the no home antibiotic group (8.3% discharged with antibiotics). There were no significant differences in deep organ space infection requiring intervention (7% vs. 7.4%, p = 1.0). Our length of stay was not different (4.5 days vs. 3.95 days, p = 0.32), nor were other secondary outcomes or patient characteristics. All patients had documented follow-up. We did not identify differences in deep organ space infections, length of stay or other events after eliminating home antibiotic therapy in our complicated appendicitis cohort. The use of home antibiotics following surgery for complicated appendicitis should be reconsidered. III.


Ouabain binding and potassium relaxation in aortas from renal hypertensive rabbits.
This study was designed to characterize the electrogenic sodium pump in vascular smooth muscle from one-kidney one-clip (1K-1C), renal hypertensive rabbits. Two measures of the electrogenic pump were used: 1) [3H]ouabain binding and 2) potassium-induced relaxation. The binding study indicated a significant increase in the affinity of pump sites for ouabain in aortic strips from hypertensive rabbits compared with those from normotensive rabbits (Scatchard analysis). The maximal binding capacity of the binding sites was similar in the two groups of animals, whereas the concentration of ouabain at which half-maximal binding occurred was lower in the aortic strips from hypertensive rabbits. Aortic strips from hypertensive rabbits showed greater sensitivity to the relaxant effect of potassium after incubation in potassium-free solution. The potassium-induced relaxation in aortic strips from hypertensive rabbits was more sensitive to the inhibitory effect of ouabain than that in strips from normotensive rabbits. These results suggest that the increased sensitivity to potassium and ouabain in vascular smooth muscle from hypertensive rabbits is due to an increased affinity of the pump sites for these substances.


Design and synthesis of doublecortin-like kinase 1 inhibitors and their bioactivity evaluation.
Doublecortin-like kinase 1 (DCLK) is a microtubule-associated serine/threonine kinase that is upregulated in a wide range of cancers and is believed to be related to tumour growth and development. Upregulated DCLK1 has been used to identify patients at high risk of cancer progression and tumours with chemotherapy-resistance. Moreover, DCLK1 has been identified as a cancer stem cell (CSC) biomarker in various cancers, which has received considerable attention recently. Herein, a series of DCLK1 inhibitors were prepared based on the previously reported XMD8-92 structure. Among all the synthesised compounds, D1, D2, D6, D7, D8, D12, D14, and D15 showed higher DCLK1 inhibitory activities (IC50 40-74 nM) than XMD8-92 (IC50 161 nM). Compounds D1 and D2 were selective DCLK1 inhibitors as they showed a rather weak inhibitory effect on LRRK2. The antiproliferative activities of these compounds were also preliminarily evaluated. The structure-activity relationship revealed by our compounds provides useful guidance for the further development of DCLK1 inhibitors.


Effect of Baseline Nutritional Status on Long-term Multivitamin Use and Cardiovascular Disease Risk: A Secondary Analysis of the Physicians' Health Study II Randomized Clinical Trial.
Long-term multivitamin use had no effect on risk of cardiovascular disease (CVD) in the Physicians' Health Study II. Baseline nutritional status may have modified the lack of effect. To investigate effect modification by various baseline dietary factors on CVD risk in the Physicians' Health Study II. The Physicians' Health Study II was a randomized, double-blind, placebo-controlled trial testing multivitamin use (multivitamin [Centrum Silver] or placebo daily) among US male physicians. The Physicians' Health Study II included 14 641 male physicians 50 years or older, 13 316 of whom (91.0%) completed a baseline 116-item semiquantitative food frequency questionnaire and were included in the analyses. This study examined effect modification by baseline intake of key foods, individual nutrients, dietary patterns (Alternate Healthy Eating Index and Alternate Mediterranean Diet Score), and dietary supplement use. The study began in 1997, with continued treatment and follow-up through June 1, 2011. Multivitamin or placebo daily. Major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Secondary outcomes included myocardial infarction, total stroke, CVD mortality, and total mortality individually. In total, 13 316 male physicians (mean [SD] age at randomization, 64.0 [9.0] years in those receiving the active multivitamin and 64.0 [9.1] years in those receiving the placebo) were observed for a mean (SD) follow-up of 11.4 (2.3) years. There was no consistent evidence of effect modification by various foods, nutrients, dietary patterns, or baseline supplement use on the effect of multivitamin use on CVD end points. Statistically significant interaction effects were observed between multivitamin use and vitamin B6 intake on myocardial infarction, between multivitamin use and vitamin D intake on CVD mortality, and between multivitamin use and vitamin B12 intake on CVD mortality and total mortality. However, there were inconsistent patterns in hazard ratios across tertiles of each dietary factor that are likely explained by multiple testing. The results suggest that baseline nutritional status does not influence the effect of randomized long-term multivitamin use on major CVD events. Future studies are needed to investigate the role of baseline nutritional biomarkers on the effect of multivitamin use on CVD and other outcomes. clinicaltrials.gov Identifier: NCT00270647.


Control group bias in randomized atypical antipsychotic medication trials for schizophrenia.
It has been suggested that the need for concurrent placebo control groups in new schizophrenia studies might be minimized by making comparisons with external placebo. This strategy requires an assumption of constancy, that the novel medication will perform the same way in a study with only active controls as it would have in a placebo-controlled trial. To test this constancy assumption in active- and low dose-controlled trials vs placebo-controlled trials of atypical antipsychotic medications. A comprehensive search of bibliographic databases, conference proceedings, and Food and Drug Administration databases through November 24, 2003. English-language, randomized, double-blind clinical trials of newer atypical antipsychotic medications in otherwise unselected acutely ill adults with schizophrenia or schizoaffective disorder that reported baseline and intent-to-treat end point change values for the Brief Psychiatric Rating Scale. Study number, sample size, reported dosage for each arm, trial duration, percentage of men, average age, trial arm treatment completion rate, baseline and within-arm end point change in the Brief Psychiatric Rating Scale, method of scoring the Brief Psychiatric Rating Scale, and date of publication were extracted from each study independently by 2 of us (S.W.W. and C.B.B.) each. There were 32 studies comprising 66 risperidone, olanzapine, quetiapine, and ziprasidone arms including 7264 patients. Random-effects analysis revealed that in atypical antipsychotic medication arms, the degree of improvement was nearly double in active-controlled trials than that seen with the same drugs and dosages in placebo-controlled studies. An effect of design was also observed in low dose-controlled studies vs placebo-controlled studies in ineffective and intermediate antipsychotic medication dose ranges. The observed control group bias indicates that the constancy assumption does not hold in recent antipsychotic medication trials. These results suggest that caution is indicated when considering active- or low dose-controlled studies requiring comparisons with external placebo as alternatives to placebo-controlled trials for establishing efficacy of new medications for schizophrenia.


Effects of Dickkopf-1 (DKK-1) on Prostate Cancer Growth and Bone Metastasis.
Osteoblastic bone metastases are commonly detected in patients with advanced prostate cancer (PCa) and are associated with an increased mortality rate. Dickkopf-1 (DKK-1) antagonizes canonical WNT/β-catenin signaling and plays a complex role in bone metastases. We explored the function of cancer cell-specific DKK-1 in PCa growth, metastasis, and cancer-bone interactions using the osteoblastic canine PCa cell line, Probasco. Probasco or Probasco + DKK-1 (cells transduced with human DKK-1) were injected into the tibia or left cardiac ventricle of athymic nude mice. Bone metastases were detected by bioluminescent imaging in vivo and evaluated by micro-computed tomography and histopathology. Cancer cell proliferation, migration, gene/protein expression, and their impact on primary murine osteoblasts and osteoclasts, were evaluated in vitro. DKK-1 increased cancer growth and stimulated cell migration independent of canonical WNT signaling. Enhanced cancer progression by DKK-1 was associated with increased cell proliferation, up-regulation of NF-kB/p65 signaling, inhibition of caspase-dependent apoptosis by down-regulation of non-canonical WNT/JNK signaling, and increased expression of epithelial-to-mesenchymal transition genes. In addition, DKK-1 attenuated the osteoblastic activity of Probasco cells, and bone metastases had decreased cancer-induced intramedullary woven bone formation. Decreased bone formation might be due to the inhibition of osteoblast differentiation and stimulation of osteoclast activity through a decrease in the OPG/RANKL ratio in the bone microenvironment. The present study indicated that the cancer-promoting role of DKK-1 in PCa bone metastases was associated with increased growth of bone metastases, reduced bone induction, and altered signaling through the canonical WNT-independent pathway. DKK-1 could be a promising therapeutic target for PCa.


Estrogenic activity of lignin-derivable alternatives to bisphenol A assessed via molecular docking simulations.
Lignin-derivable bisphenols are potential alternatives to bisphenol A (BPA), a suspected endocrine disruptor; however, a greater understanding of structure-activity relationships (SARs) associated with such lignin-derivable building blocks is necessary to move replacement efforts forward. This study focuses on the prediction of bisphenol estrogenic activity (EA) to inform the design of potentially safer BPA alternatives. To achieve this goal, the binding affinities to estrogen receptor alpha (ERα) of lignin-derivable bisphenols were calculated via molecular docking simulations and correlated to median effective concentration (EC50) values using an empirical correlation curve created from known EC50 values and binding affinities of commercial (bis)phenols. Based on the correlation curve, lignin-derivable bisphenols with binding affinities weaker than ∼-6.0 kcal mol-1 were expected to exhibit no EA, and further analysis suggested that having two methoxy groups on an aromatic ring of the bio-derivable bisphenol was largely responsible for the reduction in binding to ERα. Such dimethoxy aromatics are readily sourced from the depolymerization of hardwood biomass. Additionally, bulkier substituents on the bridging carbon of lignin-bisphenols, like diethyl or dimethoxy, were shown to weaken binding to ERα. And, as the bio-derivable aromatics maintain major structural similarities to BPA, the resultant polymeric materials should possess comparable/equivalent thermal (e.g., glass transition temperatures, thermal decomposition temperatures) and mechanical (e.g., tensile strength, modulus) properties to those of polymers derived from BPA. Hence, the SARs established in this work can facilitate the development of sustainable polymers that maintain the performance of existing BPA-based materials while simultaneously reducing estrogenic potential.


Evidence that secondary rat Schwann cells in culture maintain their differentiated phenotype.
Schwann cells, on receiving the correct signal, will encircle an axon and wrap it with a myelin sheath. To begin examining some of the mechanisms underlying the process of myelination in vitro, we isolated Schwann cells from the sciatic nerves of neonatal rats and generated large cell populations with cholera toxin. The immunological and biochemical properties of these secondary Schwann cells were characterized after five to seven passages in the absence of axonal contact. These cells continued to express antigens found in both myelinating (P0 and 2',3'-cyclic nucleotide phosphohydrolase) and nonmyelinating cells in vivo (A5E3 and glial fibrillary acidic protein) in addition to the markers common to both types of cells (Ran-1, 217c, S-100, and laminin). Biochemical analyses showed that these cells synthesize the very-long-chain fatty acids (22-26 carbon atoms) found in myelin membranes. Moreover, the enzymes required for the synthesis of myelin glycolipids (including sphingosine acyltransferase, UDP-galactose:ceramide galactosyltransferase, and cerebroside sulfotransferase) were still active, and metabolic labeling studies showed that galactocerebroside and sulfatide were synthesized even though the galactocerebroside pool was insufficient to be detected by immunostaining. Secondary Schwann cells also synthesized four species of myelin basic protein and the major structural glycoprotein in myelin, P0. The pathway necessary for glycosylation of P0 protein remained active, and an analysis of the oligosaccharide chain revealed that approximately 70% was processed to a complex form. In summary, we found that secondary Schwann cells still express most of the immunological markers of differentiated cells and continue to synthesize low levels of myelin components. Therefore, Schwann cells do not dedifferentiate in culture, as previously believed.


3D Spheroids Versus 3D Tumor-Like Microcapsules: Confinement and Mechanical Stress May Lead to the Expression of Malignant Responses in Cancer Cells.
As 2D surfaces fail to resemble the tumoral milieu, current discussions are focused on which 3D cell culture strategy may better lead the cells to express in vitro most of the malignant hints described in vivo. In this study, this question is assessed by analyzing the full genetic profile of MCF7 cells cultured either as 3D spheroids-considered as "gold standard" for in vitro cancer research- or immobilized in 3D tumor-like microcapsules, by RNA-Seq and transcriptomic methods, allowing to discriminate at big-data scale, which in vitro strategy can better resemble most of the malignant features described in neoplastic diseases. The results clearly show that mechanical stress, rather than 3D morphology only, stimulates most of the biological processes involved in cancer pathogenicity, such as cytoskeletal organization, migration, and stemness. Furthermore, cells entrapped in hydrogel-based scaffolds are likely expressing other physiological hints described in malignancy, such as the upregulated expression of metalloproteinases or the resistance to anticancer drugs, among others. According to the knowledge, this study represents the first attempt to answer which 3D experimental system can better mimic the neoplastic architecture in vitro, emphasizing the relevance of confinement in cancer pathogenicity, which can be easily achieved by using hydrogel-based matrices.


Predictor of a negative tilt-table test result based on early heart rate variation in patients with a history of syncope.
Lack of early sympathetic overreactivity measured by early increase in heart rate has been shown to predict a negative tilt-table (TT) test result. The goal of this study was to evaluate this observation in patients with a history of syncope. The author retrospectively identified 27 patients with a history of syncope undergoing TT testing. The difference between maximal heart rate during the first 10 minutes of the tilting and baseline heart rate was used for early heart rate change. There was a significant association between the probability of a negative TT test result and failure to increase early heart rate over 19 beats per minute. The sensitivity of a negative TT test result was 93.3%, with a specificity of 66.7% (odds ratio, 0.1; confidence interval, 0.14-0.69; P=.001). This study confirms previous findings that failure to increase the heart rate early during a TT test can predict low probability of syncope.


Cellular and Humoral Immune Responses in Mice Immunized with Vaccinia Virus Expressing the SARS-CoV-2 Spike Protein.
The COVID-19 pandemic is a global health emergency, and the development of a successful vaccine will ultimately be required to prevent the continued spread and seasonal recurrence of this disease within the human population. However, very little is known about either the quality of the adaptive immune response or the viral Ag targets that will be necessary to prevent the spread of the infection. In this study, we generated recombinant Vaccinia virus expressing the full-length spike protein from SARS-CoV-2 (VacV-S) to evaluate the cellular and humoral immune response mounted against this viral Ag in mice. Both CD8+ and CD4+ T cells specific to the SARS-CoV-2 spike protein underwent robust expansion, contraction, and persisted for at least 40 d following a single immunization with VacV-S. Vaccination also caused the rapid emergence of spike-specific IgG-neutralizing Abs. Interestingly, both the cellular and humoral immune responses strongly targeted the S1 domain of spike following VacV-S immunization. Notably, immunization with VacV-expressing spike conjugated to the MHC class II invariant chain, a strategy previously reported by us and others to enhance the immunogenicity of antigenic peptides, did not promote stronger spike-specific T cell or Ab responses in vivo. Overall, these findings demonstrate that an immunization approach using VacV or attenuated versions of VacV expressing the native, full-length SARS-CoV-2 spike protein could be used for further vaccine development to prevent the spread of COVID-19.


An economic analysis of tolvaptan compared with fluid restriction among hospitalized patients with hyponatremia.
The vasopressin-receptor antagonist tolvaptan is used for the treatment of hyponatremia (HN) in hospitalized patients with congestive heart failure (CHF) or syndrome of inappropriate antidiuretic hormone secretion (SIADH). The objective of this economic modeling study was to assess the potential cost and health outcomes associated with tolvaptan in comparison with fluid restriction (FR). A decision-analytic model was developed to estimate potential cost and health outcomes associated with tolvaptan compared with FR among hospitalized CHF and SIADH patients with severe HN (serum sodium [SS] levels < 125 mEq/L). The model, which was populated with data from the published literature, assumes that response to treatment influences hospital length of stay, probability of an intensive care unit (ICU) admission, and probability of a 30-day all-cause hospital readmission. One-way and probabilistic sensitivity analyses (PSAs) assessed the influence of parameter uncertainty on model results. Model results suggest that, among hospitalized CHF patients with severe HN, the use of tolvaptan compared with FR may lead to reductions of 7.2% and 4.6% in ICU admissions and 30-day readmissions, respectively. Compared with FR, tolvaptan may result in total cost-savings of $156 per hospitalized CHF patient. Among hospitalized SIADH patients with severe HN, the model suggested reductions of 14.6% and 5.1% in ICU admissions and 30-day readmissions, respectively. Compared with FR, tolvaptan may result in total cost-savings of $135 per hospitalized SIADH patient. PSAs found that the probabilities of net cost-savings from the use of tolvaptan compared with FR were 64% and 59% among patients with severe HN with CHF and SIADH, respectively. Decision-analytic modeling based on published data for hospitalized CHF and SIADH patients with severe HN, indicates that tolvaptan compared with FR has the potential to improve health outcomes and produce cost-savings that more than offset the cost of tolvaptan.


Development and Reliability of an Appropriateness and Prioritization Instrument for Eye Care Practice: A Modified Delphi Process.
Purpose: To modify the Western Canada Waiting List Project (WCWLP) cataract prioritization criteria into measurement instruments for assessing appropriateness and prioritization emphasizing health-related quality of life (HRQoL) and examining reliability.Methods: A modified Delphi process was conducted using two rounds of online surveys and a face-to-face meeting. A panel of eye care experts rated the relevancy of criteria on a 5-point scale. Patient narratives highlighted the patient experience. A G-theory framework was used to assess inter- and intra-rater agreement using the criteria.Results: Nine Ophthalmologists, three Optometrists, and one General Practitioner participated in the modified Delphi process. Consensus to include/exclude was reached on all criteria. Seventeen criteria were included and 16 were excluded. The most significant changes were related to the categorization of comorbidities and expansion of HRQoL questions. The overall reliability was good (ϕ = 0.852).Conclusion: The WCWLP was modified to include appropriateness and to better reflect HRQoL. Having achieved consensus and demonstrated reliability of the criteria, the next step is to estimate weights for criteria and to validate against patient health outcomes data.


Metabolic signals influence cell-fate decisions in Dictyostelium discoideum.
Nutrient-sensing plays a crucial role in maintaining cellular energy and metabolic homeostasis. Perturbations in sensing pathways are associated with a wide variety of pathologies, especially metabolic diseases. Very little is understood about sensing fluctuations in nutrients and how this information is integrated into physiological and metabolic adaptation that could further affect cell-fate decisions during differentiation in Dictyostelium discoideum (henceafter, Dictyostelium). Glucose is the primary metabolic fuel among all nutrients. Carbohydrates, lipids and proteins ultimately breakdown into glucose, which is further used for providing energy. The maintenance of optimum glucose levels is important for efficient cell-survival. Glucose is not only a nutrient, but also a signaling molecule influencing cell growth and differentiation in Dictyostelium. Modulation of endogenous glucose levels either by varying exogenous glucose levels or genetic overexpression or deletion of genes involved in glucose signaling lead to changes in endogenous metabolite levels such as ADP/ATP ratio, NAD+ /NADH ratio, cAMP and ROS levels which further influence cell-fate decisions. Here, we show that AMPKα and Sir2D are components of glucose-signaling pathway in Dictyostelium which adjust cell metabolism interdependently in response to nutrient-status and promote cell-fate decisions.