Topographical distribution of antimicrobial genes in the zebrafish intestine.
The zebrafish is increasingly being utilized to study aspects of the conserved innate intestinal immunity of vertebrates. In mammals, some antimicrobial proteins are synthesised by specialised immune cells that appear to have no equivalent in zebrafish. To delineate foci of antimicrobial protein production along the zebrafish intestine, we examined the antero-posterior expression gradients of antimicrobial genes. Quantitative PCR revealed distinct expression gradient profiles, with the mid-intestine exhibiting elevated expression of several genes such as dual oxidase and the defensin beta-like and peptidoglycan recognition protein families. This region also presented with the most numbers of leukocytes and endocytic cells, supporting a specialised immunological role. Conversely, expression of the Dr-RNase family was prominent in the anterior intestine. Expression of the zebrafish β-defensin family was examined in adult zebrafish tissues. Strong expression of defensin beta-like 1 was detected in the swim bladder of zebrafish from the larval stage of development through to adults.


Revascularization versus medical therapy in patients aged 80 and older with stable ischemic heart disease.
Older patients are underrepresented in landmark randomized trials for stable ischemic heart disease (SIHD). Therefore, we sought to evaluate the benefits of revascularization in patients ≥80 years old with SIHD. Retrospective study of patients undergoing invasive coronary angiography (ICA) for SIHD between 2009 and 2019. Patients were grouped according to treatment: revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) versus initial medical therapy alone. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analyses were performed. Outcomes evaluated were all-cause mortality, non-fatal myocardial infarction (MI), and repeat revascularization. A total of 1015 patients (median age 83.0, interquartile range [IQR] 81.3-85.2 years; 29% female) underwent ICA for SIHD. Of these, 557 (55%) were treated with revascularization and 458 (45%) with initial medical therapy alone. Baseline characteristics were well balanced after IPTW adjustment. At median follow-up of 3.5 years (IQR 1.7-5.9 years), there were no differences in all-cause mortality and non-fatal MI between treatment groups; but there was an increased need for repeat revascularization (IPTW adjusted hazard ratio 2.22, 95% confidence interval 1.53-3.22) with revascularization. Separately comparing PCI or CABG alone versus medical therapy yielded similar results; as well as in subgroup analysis (except for patients ≥90 years old and those without prior CABG). There were no differences in all-cause mortality and non-fatal MI with invasive revascularization (either PCI or CABG) versus medical therapy alone in patients ≥80 years old with SIHD. Large randomized trials focusing on older patients are warranted to guide clinical practice in this growing population.


Integrated services for chronic mental patients: theoretical perspective and experimental results.
The theoretical basis of an integrated service approach to the care of chronic mental patients is discussed. An experiment testing the Treatment Network Team (TNT) program, based on that approach, is described and results are reported. Although TNT and control patients exhibited minimal differences in symptomatology and psychopathology, those in the experimental group showed substantive improvement in psychosocial functioning. The authors conclude that flexible service systems that deemphasize locus of care and offer a range of treatment modalities have the potential for enriching the social lives of chronic mental patients.


The traumatic and the work of the après-coup in Freud's opus.
This text explores the evolution of the notion of trauma in Freud's work and of its decisive import for the organization of psychic functioning through a two-stage process called the après-coup. By following the three steps of Freud's theory of the drives, the author shows that the conception of the traumatic is gradually internalized to become a basic quality of all drives as a tendency to return to an earlier state, and ultimately an organic, inanimate state. An open question remains in Freud about this tendency's relation to Eros, and therefore to the links between Eros and the traumatic state. This question has remained latent within the psychoanalytic community. The author proposes to conceive of Eros as an infinitely extensible tendency that needs containing in order for it to contribute to evolving inscriptions. Thus is outlined one traumatic state as a return to the inorganic and another traumatic state as an infinite extensibility, both being transformed by the superego and its imperatives in order to generate all life forms.


Networking and Applying to Radiation Oncology During A Pandemic: Cross-Sectional Survey of Medical Student Concerns.
We assessed the effectiveness of a virtual networking session tailored for third- and fourth-year medical students interested in radiation oncology, and report students' concerns about applying to radiation oncology during the pandemic. A multi-institutional networking session was hosted on Zoom and included medical students, faculty, and residents from across the country. The breakout room feature was used to divide participants into smaller groups. Participants were randomly shuffled into new groups every 10 to 15 minutes. Students completed pre- and post-session surveys. Among the 134 students who registered, 69 students participated in the session, and 53 students completed a post-session survey. Most students reported the session was valuable or very valuable (79%), and it was easy or very easy to network through the virtual format (66%). After the session, 18 (33.9%) students reported their interest in radiation oncology increased, and 34 (64.2%) reported their interest remained the same. Most students believed COVID-19 (55%) and virtual interviews and platforms (55%) negatively or somewhat negatively affected their ability to select a residency program. Most students (62%) were concerned they will be inaccurately evaluated as an interviewee on a virtual platform. Although 30% agreed or strongly agreed the cost-savings and convenience of virtual interviews outweigh potential downsides, 66% of students were planning to visit cities of interest in person before rank list submission. Medical students reported significant concerns with their ability to be accurately evaluated and to choose among residency programs on a virtual platform. Students found the networking session to be a valuable resource for most students, and programs could continue similar efforts during the residency application cycle to better represent their program while maintaining certain financial and geographic advantages of a virtual environment.


Morphological studies of the pigment present in the seminal vesicles of orchidectomized hamsters, and the preventive action of vitamin E and methylene blue.
Authors studies the histological and electromicroscopical picture of the seminal vesicles of hamsters after orchidectomy, after orchidectomy and Vitamin E feeding and after orchidectomy and Methylene Blue treatment. They states that 120 days after orchidectomy large amounts of lipofuscin and lamellar structures, myelin-like forms developed in the cytoplasm of the epithelial cells and macrophages of the seminal vesicles. Vitamin E feeding inhibited the appearance of lipofuscin, while Methylene Blue significantly reduced the amount of lipofuscin.


A Clinical and Budgetary Impact Analysis of Introducing Sugammadex for Routine Reversal of Neuromuscular Blockade in a Hypothetical Cohort in the US.
Sugammadex rapidly reverses the effects of rocuronium- and vecuronium-induced neuromuscular blockade (NMB), offering a more complete and predictable NMB recovery than cholinesterase inhibitors. Despite clinical benefits, cost pressures on hospital budgets influence the choice of the NMB reversal method. This study evaluated clinical and healthcare system payer's budget impacts associated with sugammadex in the US for routine reversal of moderate or deep rocuronium- or vecuronium-induced NMB in adults undergoing surgery. A 1-year decision analytic model was constructed reflecting a set of procedures using rocuronium or vecuronium that resulted in moderate or deep NMB at the end of surgery. Two scenarios were considered for a hypothetical cohort of 100,000 patients: without sugammadex versus with sugammadex. Comparators included neostigmine (+glycopyrrolate) and no neuromuscular blocking agents (NMBAs). Total costs (in 2019 US dollars) to a healthcare system [net of costs of reversal agents and overall cost offsets via reduction in postoperative pulmonary complications (PPC)] were compared. A total of 9971 surgical procedures utilized rocuronium or vecuronium, resulting in moderate (91.0% of cases) or deep (9.0%) blockade at the end of surgeries. In the with sugammadex scenario, sugammadex replaced neostigmine in 4156 of 9585 procedures versus the without sugammadex scenario that used only neostigmine for NMB reversal. Introducing sugammadex reduced PPC events by 12% (58 cases) among the modeled procedures, leading to a budget impact of -$3,079,703 (-$309 per modeled procedure, or a 10.9% reduction in total costs). The results did not vary qualitatively in one-way sensitivity analyses. The additional costs of sugammadex for the reversal of rocuronium- or vecuronium-induced NMB could be offset by improved outcomes (i.e., reduced PPC events), and potentially lead to overall healthcare budgetary savings versus reversal with neostigmine or spontaneous recovery. This study provides insights into savings that can be obtained beyond the anesthesia budget, reducing the broader clinical and budgetary burden on the hospital.


Effect of CH4, Pressure, and Initial Temperature on the Laminar Flame Speed of an NH3-Air Mixture.
Ammonia (NH3) is not only expected to be used as a hydrogen energy carrier but also expected to become a carbon-free fuel. Methane (CH4) can be used as a combustion enhancer for improving the combustion intensity of NH3. In addition, it is important to understand the flame characteristics of NH3-air at elevated pressures and temperatures. The laminar flame speed of NH3-CH4-air is numerically investigated, where the mole fraction of CH4 ranges from 0 to 50% in binary fuels and the pressure and initial temperature are up to 10 atm and 1000 K, respectively. The calculated value from the Okafor mechanism is in excellent agreement with experimental data. The CH4 in the fuel affects the flame speed by changing the main species of free radicals in the flame; the high pressure not only increases the rate-limiting reaction rate in the flame but also reduces the amount of H, O, and OH radicals in the flame, so as to restrain the propagation of the flame. At a higher initial temperature, the faster flame speed is mainly due to the higher adiabatic flame temperature. The laminar flame speed correlation equation has a consistent trend with the simulation results, though with a slight underestimation at higher pressures and temperatures. It is a more effective way to calculate the laminar flame speeds of NH3-air for a given pressure and temperature.


Search for OIE-listed ruminant mycoplasma diseases in Afghanistan.
Little is known about the occurrence of important diseases of ruminants in Afghanistan because of the conflict affecting the country over the last 40 years. To address this discrepancy, ruminant herds in Afghanistan were screened for OIE-listed mycoplasma diseases, contagious bovine (CBPP) and caprine pleuropneumonias (CCPP). Of the 825 samples from 24 provinces tested for serological evidence of CBPP caused by Mycoplasma mycoides subsp.mycoides, 20 (3.4%) had ELISA values greater than the positive threshold of 50% though all were less than 55%. Repeat testing of these suspect sera gave values below 50. A smaller number of sera (330) from cattle in nine provinces were also tested by the rapid latex agglutination test (LAT) for CBPP, 10 of which were considered suspect. However, no positive bands were seen when immunoblotting was carried out on all sera that gave suspect results. Serological evidence of Mycoplasma bovis was detected in half of 28 herds in eight provinces. The cause of CCPP, M. capricolum subsp. capripneumoniae was not detected in any of the 107 nasal swabs and lung tissue collected from goats in seven provinces though sample handling and storage were not optimal. However, strong serological evidence was detected in goat herds in several villages near Kabul some of which were over 50% seropositive by LAT and ELISAs for CCPP; immunoblotting confirmed positive results on a selection of these sera. The data presented here provide a first assessment of the occurrence of the two OIE listed mycoplasma diseases in Afghanistan. From the results of the testing bovine sera from the majority of provinces there is no evidence of the presence of CBPP in Afghanistan. However the samples tested represented only 0.03% of the cattle population so a larger survey is required to confirm these findings. Serological, but not bacterial, evidence was produced during this investigation to show that CCPP is highly likely to be present in parts of Afghanistan.


No or only population-specific effect of PON1 on human longevity: a comprehensive meta-analysis.
Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE epsilon4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet).


Structure of bovine parietal pericardium and of unimplanted Ionescu-Shiley pericardial valvular bioprostheses.
To obtain a basis for the evaluation of postimplantation changes in bioprostheses made of parietal pericardium, we conducted comparative histologic, scanning and transmission electron microscopic studies of the structure of (1) normal bovine parietal pericardium, (2) glutaraldehyde-treated pericardial patches to be used for repair of cardiac defects, and (3) pericardial tissue cusps of unimplanted Ionescu-Shiley valves. Bovine parietal pericardium has three layers: (1) the serosa, or mesothelial cell layer; (2) the fibrosa, formed by diversely oriented, wavy bundles of collagen and by elastic fibers, and (3) the epipericardial connective tissue layer, which is partly continuous with the pericardiosternal ligaments. Pericardial patches and pericardial bioprosthetic cusps differ from normal pericardium by being denuded of mesothelium but they have normal degrees of waviness in their collagen. In Ionescu-Shiley valves, the inflow and outflow surfaces of each cusp correspond to the epipericardial and serosal surfaces of parietal pericardium, respectively. The inflow surfaces have a coarse texture, characterized by large bundles of collagen, and the outflow surfaces have numerous grooves, 10 to 30 mu in width and 20 mu in depth, which probably result from pressure exerted on the cuspidal surfaces by cotton material either during manufacturing or packing of the valves. Comparisons of the structure of bioprosthetic pericardial cusps and porcine aortic valve cusps show that the latter have reduced degrees of collagen waviness and a different layered structure: A layer similar to the spongiosa of aortic valve cusps is not present in pericardium. The functional implications of these observations are discussed in detail.


Dynamics of the interactions of basic proteins with polyribonucleotides.
Pancreatic ribonuclease was irradiated in the dried state with electrons and then added to acetate buffer solutions that contained different concentrations of polyribonucleotides. Qualitatively similar results were obtained by adding a combination of unirradiated ribonuclease and lysozyme to such solutions. Such solutions scatter light strongly, and the intensity of the scattered light changes with time after mixing. The angular distribution of the scattered light was obtained as a function of time and compared with the rates at which hydrolysis products were formed. The turbidity of the solutions increases rapidly with time at the lower polyribonucleotide concentrations, and seems to result from a complex between inactive ribonuclease, or lysozyme, and oligonucleotides that appear during enzymic hydrolysis of the polynucleotides. The dissymmetry of the scattered light is approximately 5, indicating that the scattering centers are, if spherical, about 1500 A in diameter. The turbidities are remarkably high when one considers the low concentrations of protein and nucleic acid materials that are used.


Bioremediation potential of new cadmium, chromium, and nickel-resistant bacteria isolated from tropical agricultural soil.
Soil management using fertilizers can modify soil chemical, biochemical and biological properties, including the concentration of trace-elements as cadmium (Cd), chromium (Cd) and nickel (Ni). Bacterial isolates from Cd, Cr, and Ni-contaminated soil were evaluated for some characteristics for their use in bioremediation. Isolates (592) were obtained from soil samples (19) of three areas used in three maize cultivation systems: no-tillage and conventional tillage with the application of mineral fertilizers; minimum tillage with the application of sewage sludge. Four isolates were resistant to Cr3+ (3.06 mmol dm-3) and Cd2+ (2.92 mmol dm-3). One isolate was resistant to the three metals at 0.95 mmol dm-3. All isolates developed in a medium of Cd2+, Cr3+ and Ni2+ at 0.5 mmol dm-3, and removed Cd2+ (17-33%) and Cr6+ (60-70%). They were identified by sequencing of the gene 16S rRNA, as bacteria of the genera Paenibacillus, Burkholderia, Ensifer, and two Cupriavidus. One of the Cupriavidus isolate was able to remove 60% of Cr6+ from the culture medium and showed high indole acetic acid production capacity. We evaluated it in a microbe-plant system that could potentially be deployed in bioremediation by removing toxic metals from contaminated soil.


Amyloid inhibitors enhance survival of cultured human islets.
Amyloid fibrils created by misfolding and aggregation of proteins are a major pathological feature in a variety of degenerative diseases. Therapeutic approaches including amyloid vaccines and anti-aggregation compounds in models of amyloidosis point to an important role for amyloid in disease pathogenesis. Amyloid deposits derived from the beta-cell peptide islet amyloid polypeptide (IAPP or amylin) are a characteristic of type 2 diabetes and may contribute to loss of beta-cells in this disease. We developed a cellular model of rapid amyloid deposition using cultured human islets and observed a correlation between fibril accumulation and beta-cell death. A series of overlapping peptides derived from IAPP was generated. A potent inhibitor (ANFLVH) of human IAPP aggregation was identified. This inhibitory peptide prevented IAPP fibril formation in vitro and in human islet cultures leading to a striking increase in islet cell viability. These findings indicate an important contribution of IAPP aggregation to beta-cell death in situ and point to therapeutic applications for inhibitors of IAPP aggregation in enhancing beta-cell survival. Anti-amyloid compounds could potentially reduce the loss of beta-cell mass in type 2 diabetes and maintain healthy human islet cultures for beta-cell replacement therapies.


Use of an abnormal laboratory value-drug combination alert to detect drug-induced thrombocytopenia in critically Ill patients.
The aim of this study was to assess the performance of a commercially available clinical decision support system (CDSS) drug-laboratory result alert in detecting drug-induced thrombocytopenia in critically ill patients. Adult patients admitted to the medical and cardiac intensive care unit during an 8-week period and identified by 1 of 3 signals in the CDSS, TheraDoc, were eligible. Alerts were generated when the patient had a low platelet count and was ordered a potentially causal drug. Patients were evaluated in real time for the occurrence of an adverse drug reaction using 3 causality instruments. Positive predictive values were calculated for the alert. Sixty-four patients with a mean age of 54 years met the inclusion criteria, generating 350 alerts. Positive predictive values were 0.36, 0.83, and 0.40 for signals 1, 2, and 3, respectively. Overall, there were 137 adverse drug reactions identified in the 350 alerts, with heparin, vancomycin, and famotidine as the 3 most common potential causes. A commercial CDSS drug-laboratory alert is effective at identifying drug-induced thrombocytopenia in the intensive care unit and may improve patient safety. Compared with previous studies, the combination alert performs better than alerts based exclusively on laboratory values and should be considered to reduce alert fatigue.


Peripheral airway involvement in asthma assessed by single-breath SF6 and He washout.
The aim of the study was to assess how deep into the acinar region the airway response to cold dry-air hyperventilation challenge (CACh) reaches in subjects with asthma of different severity. Peripheral airway function was measured using a single-breath sulphur hexafluoride (SF6) and helium (He) washout test and overall airway function by forced expiratory volume in one second (FEV1) at rest, after CACh and beta2-therapy in 55 adults with a history of asthma. The normalised phase-III slopes (SnIII) for SF6 and He were used to assess peripheral airway obstruction and the (SF6-He) SnIII difference to indicate where obstruction occurred. While a greater He versus SF6 slope increase indicates a response close to the acinar entrance, the reverse indicates a response deeper into the acinar airspaces. Twelve subjects had a major fall in FEV1 (> or = 20%) after CACh, 16 a minor fall (10-19%), and 27 did not react. Resting He and SF6 SnIII were significantly greater in major responders with respect to minor and nonresponders, while resting FEV1 did not differ between the three groups. The major responders showed marked increases of He and SF6 SnIII after CACh, with greater increase for He resulting in a negative (SF6-He) SnIII difference. To conclude, airways close to the acinar entrance participate in the overall airway response to cold-air challenge in asthmatic adults with marked airway hyperresponsiveness to cold, dry air.


Photochemical Electrocyclization of Poly(phenylacetylene)s: Unwinding Helices to Elucidate their 3D Structure in Solution.
Photochemical electrocyclization of poly(phenylacetylene)s (PPAs) is used for the structural elucidation of a polyene backbone. This method not only allows classification of PPAs in cis-cisoidal (ω1 <90°) or cis-transoidal structures (ω1 >90°), but also approximating ω1 . A PPA solution is illuminated with visible light and monitoring the photochemical electrocyclization of the PPA helix by measuring the ECD spectra at different times. PPAs with a cis-cisoidal structure show a reduction of the ECD signal of at least 50 % before 30 min of irradiation, while cis-transoidal helices need much longer time because the transoidal bond must be isomerized. The different cis-cisoidal and cis-transoidal helices require different times to decrease their ECD signal by 50 % (t1/2 ), depending on the degree of compression or stretching of the helix, establishing a relationship between the secondary structure adopted by PPA (ω1 ) and the time required to lose the ECD vinylic signal by light irradiation.


Experiences of women with hypertensive disorders of pregnancy: a scoping review.
Hypertensive disorders of pregnancy (HDP) constitute one of the leading causes of maternal and perinatal mortality worldwide, and are associated with an increased risk of recurrence and future cardiovascular disease. HDP affect women's health condition, mode of birth and timing, length of hospital stay, and relationship with their newborn and family, with future life repercussions. To explore the experiences of women with HDP from pregnancy to postpartum, and to identify (a) their perceptions and understanding of HDP, (b) their understanding of future health risks, and (c) the possible interventions by healthcare providers. A scoping review was conducted following the Joanna Briggs Institute method and in accordance with the PRISMA-ScR checklist. The following databases were searched from 1990 to 2020 (October): MEDLINE (PubMed), EMBASE, Cochrane Library, CINAHL, PsycINFO, and Google Scholar database. The Critical Appraisal Skills Programme (CASP) checklist was used as a guide for the qualitative analysis. Content analysis and synthesis of findings were conducted using Nvivo12. Of the 1971 articles identified through database searching, 16 articles met the inclusion criteria. After data extraction, content analysis yielded six categories: 'Life-threatening disorder', 'Coping with HDP', 'Concerns for baby and challenges of motherhood', 'Fear of recurrence and health problems', 'Necessity of social and spiritual support', and 'Positive and negative experiences in the healthcare context'. Women faced complex difficulties from the long treatment process while transitioning to motherhood. Our findings revealed the perceptions and understanding of women regarding HDP as a life-threatening disorder to both mothers and their babies which mothers need to cope with. Recovery of physical condition and the long-term psychological effects of HDP on women should be given attention by mothers and HCP to reduce future health risks. Importantly, a lifelong follow-up system is recommended for women with HDP.


A war of coefficients or a meaningless wrangle over practical unessentials?
The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.


Can recognition of living things be selectively impaired?
Brain damage sometimes seems to impair recognition of living things, despite relatively preserved recognition of nonliving things. The most straightforward interpretation of this dissociation is that the recognition of living things depends on some specialized mechanisms that are not needed for the recognition of nonliving things. However, there are alternative interpretations of the dissociation in terms of the greater complexity or inter-item similarity of living things, or the more specific, within-category identifications that are usually required for living things. Surprisingly, the relevant tests to discriminate among these rival hypotheses have never been performed. We took the factors of visual complexity, inter-item similarity, specificity of identification, as well as others, into account in analyzing the visual recognition performance of two head-injured visual agnosic patients. In each case we found that recognition of living things was still disproportionately impaired when the effects of the other factors were accounted for.


Education, APOE ε4, and Cognition in Individuals with Subjective Cognitive Decline with Worry in the SILCODE Study.
Education could offer a protective effect on cognition in individuals with Subjective Cognitive Decline (SCD), which is considered to be the early stage of Alzheimer's Disease (AD). However, the effect of education on cognition in SCD individuals with SCD-plus features is not clear. The aim of the study was to explore the effect of education on cognition in SCD individuals with SCD-plus features. A total of 234 individuals with SCD were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Cognition was assessed across 4 domains (memory, executive, language, and general cognitive functions). Multiple linear regression models were constructed to examine the effect of education on cognitive scores in individuals without worry (n=91) and with worry (n=143). Furthermore, we assessed differences in effects between APOE ε4 noncarriers and APOE ε4 carriers in both groups. Multiple linear regression analysis showed a positive effect of education on memory, executive, and language cognition in individuals without worry and all cognitive domains in individuals with worry. Furthermore, we found a positive effect of education on executive cognition in APOE ε4 noncarriers without worry and language and general cognition in APOE ε4 carriers without worry. Meanwhile, education had a positive effect on all cognitive domains in APOE ε4 noncarriers with worry and executive, language, and general cognition in APOE ε4 carriers with worry. This study indicates that education has the potential to delay or reduce cognitive decline in SCD individuals with SCD-plus features.


[Investigations on localization and synthesis of egg proteins during early development ofDermestes frischi (Coleoptera)].
1. UV-irradiation, of the entire ectoplasm during intravitelline cleavage stages causes the formation of a pseudoblastoderm. The damaged superficial areas remain free of cleavage nuclei, which contact with their cytoplasm and form a blastodermlike layer inside the yolk-entoplasm. However there is no visible differentiation in the pseudoblastoderm before its death. 2. Disc-electrophoresis was performed on normal developing eggs and on those in pseudoblastoderm stages in order to find out whether the protein pattern of the egg is affected by the loss of cortical regions. Normally with blastoderm formation 2 new protein fractions occur in the electrophoretic pattern. But in the pseudoblastoderm egg they are absent. Three other fractions, which will be removed in the normal blastoderm egg were also not detected in the pattern of the pseudoblastoderm egg. One protein fraction synthetized during intravitelline cleavage and always present in later development could not be observed in pseudoblastoderm stages. 3. Micro-disc-electrophoresis of isolated yolk-entoplasm material was carried out to locate certain protein fractions in the egg system. The same protein fraction, which could be damaged by UV-treatment of the ectoplasm is not detectable in the electrophoretic pattern of the underlying yolk-entoplasm. Therefore this fraction must be situated in superficial regions of the egg confirming reported results of autoradiographic investigations. 4. This leads to the conclusions, that the synthesis of certain protein fractions depends on the functional condition of cortical egg components. Other physiological processes, which are not affected by the loss of the periplasm take place without influence of superficial regions. Beside their role as egg areas in which physiological ooplasmatic factors are located the superficial egg components contain special protein structures.


Supercritical fluid extract of Lycium chinense Miller root inhibition of melanin production and its potential mechanisms of action.
The mode of action of Lycium chinense Miller root extract in skin care has never been explored. In the present study, Lycium chinense Miller root was extracted by the supercritical fluid CO2 extraction method. In the present study, the components of the root extract were analyzed by HPLC. The effects of the extract on tyrosinase activity and melanin content were determined spectrophotometrically; the expression of melanogenesis-related proteins was determined by Western blotting; the possible signaling pathways involved in the root extract-mediated depigmentation were also investigated using specific inhibitors. The results revealed that the SFE of Lycium chinense Miller root (2.37-7.11 mg/mL) effectively suppressed intracellular tyrosinase activity and decreased the melanin content in B16F10 cells. The root extract also effectively decreased intracellular reactive oxygen species (ROS) levels. Furthermore, the root extract decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related protein-1 (TRP-1) and then inhibited melanogenesis in B16F10 cells. The root extract also showed antioxidant capacities and depleted cellular ROS. Our results indicate that the SFE of Lycium chinense Miller root inhibited melanogenesis in B16F10 cells by down-regulation of both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways or through its antioxidant properties.


Implementation assessment of a patient personalized clinical pharmacy programme (5P project) into orthogeriatric care pathway.
The orthogeriatric path (hip-fractured elderly patients) is composed of several transition points (emergency surgery, orthopaedic, geriatric and rehabilitation units). The intervention of clinical pharmacists can ensure the continuity of patients' drug management during their hospital stay. The aim of the study was to assess the implementation of clinical pharmacy activities in an orthogeriatric pathway, regarding its impact on medication error prevention, the healthcare professionals' and patients' satisfaction, and the estimated associated pharmaceutical workload. Participants were aged 75 or older and managed for proximal femoral fracture. Their admission prescription was reviewed. If they were evaluated at high risk of adverse event (AE), medication reconciliation (MedRec) and pharmaceutical interviews (admission, discharge, and targeted on oral anticoagulant) were added at different steps of their care pathway. The achievement and duration of each clinical pharmacy activity were recorded. The number of pharmaceutical interventions (PI) made during prescription review, and unintentional discrepancies (UID) identified during MedRec were collected. A satisfaction questionnaire was sent to patients and healthcare professionals. Among 455 included patients, 284 patients were considered at high risk of AE. Clinical pharmacy activity achievement rates varied between 12% and 98%. A total of 622 PI and 333 UID were identified. The overall patients' and healthcare professionals' satisfaction was rated from 63% to 100%. The total workload was estimated at 376 h: on average 16 min per prescription review, 43 min per admission MedRec, 26 min per discharge MedRec and 17 to 25 minutes per interview. The implementation of the programme showed a high potential of drug management securing. To sustain it, additional pharmaceutical human resources and high-performance computing tools are needed.


A model of evolution and learning.
We study a model of evolving populations of self-learning agents and analyze the interaction between learning and evolution. We consider an agent-broker that predicts stock price changes and uses its predictions for selecting actions. Each agent is equipped with a neural network adaptive critic design for behavioral adaptation. We discuss three cases in which either evolution or learning, or both, are active in our model. We show that the Baldwin effect can be observed in our model, viz. originally acquired adaptive policy of best agent-brokers becomes inherited over the course of the evolution. We also compare the behavioral tactics of our agents to the searching behavior of simple animals.


Treatment of multiple sclerosis - success from bench to bedside.
The modern era of multiple sclerosis (MS) treatment began 25 years ago, with the approval of IFNβ and glatiramer acetate for the treatment of relapsing-remitting MS. Ten years later, the first monoclonal antibody, natalizumab, was approved, followed by a third important landmark with the introduction of oral medications, initially fingolimod and then teriflunomide, dimethyl fumarate and cladribine. Concomitantly, new monoclonal antibodies (alemtuzumab and ocrelizumab) have been developed and approved. The modern era of MS therapy reached primary progressive MS in 2018, with the approval of ocrelizumab. We have also learned the importance of starting treatment early and the importance of clinical and MRI monitoring to assess treatment response and safety. Treatment decisions should account for disease phenotype, prognostic factors, comorbidities, the desire for pregnancy and the patient's preferences in terms of acceptable risk. The development of treatment for MS during the past 25 years is a fantastic success of translational medicine.


Evaluation of bovine cervical mucus penetration as a test of human spermatozoal function for an in vitro fertilization programme.
Thirty-two couples participating in an in vitro fertilization (IVF) programme were evaluated as regards the prognostic value on fertilization of spermatozoal performance through flat capillary tubes filled with standardized midcycle bovine cervical mucus (Penetrak, Serono Diagnostics, Surrey, UK). A statistically significant correlation (P < 0.033) was observed between the distance travelled by the neat spermatozoa in the mucus and the % penetration of oocytes at IVF. There were also significant correlations between motility and progression (P < 0.004) and a borderline correlation between progression and the Penetrak results (P < 0.098). There was no significant difference between the Penetrak distances travelled between the 9 who conceived (33.4 mm) and the 23 who did not (29.9 mm). While the test does add to the knowledge of fertilization potential, the results extrapolated to a larger series would give false positive rates of 25% and false negative rates of 11%. The absence of a clear end point renders the Penetrak mucus penetration test insufficiently accurate to be used as a main measure of the male factor when advising for or against IVF therapy.


Solid waste management in western Canadian First Nations.
This research examined solid waste management on First Nations communities in western Canada to provide information and insight into programs, practices, policies, and activities, as well as to help bridge an identified gap related to these in the literature. Utilizing a qualitative case study approach, we examined twelve First Nations communities in Canada's western provinces, which relative to other communities, had 'advanced' solid waste management systems in place. Interviews conducted in each of the communities yielded information on six themes grounded in the data, including solid waste facilities and infrastructure, solid waste programs, local capacity, provincial stewardship programs, regulation and enforcement, and funding/finance. Our analysis show that majority of the communities examined are advancing their waste management systems and now have infrastructure/facilities, such as transfer stations and recycling depots, and have implemented recycling programs, which they previously did not have. As well, we learned that implementing such programs has reduced practices, such as open dumping, which the literature highlights as a common way of managing waste in First Nations communities. Most of the communities attributed the success of their programs to regular residential curbside pickups, ability to transport waste out of the community, and community involvement and interest in programs. Despite these improvements, inadequate funding hampers the efforts of communities to sustain and/or expand their programs and maintain facilities. Additionally, most communities face challenges partnering with provincial stewardship programs, and some communities are not clear whether they even qualify to participate in these programs.


Selective stimulation of brush border glutamine transport in the tumor-bearing rat.
Intestinal extraction of circulating glutamine across the basolateral membrane is diminished in the tumor-bearing rat (TBR). This study was designed to investigate the effects of progressive malignant growth on brush border glutamine transport in order to gain further insight into the adaptive/regulatory changes in intestinal glutamine metabolism that occur in the tumor-bearing rat. Fischer 344 rats (225 +/- 5 g) were implanted with fibrosarcoma cells and were studied at various time points after implantation when the tumors comprised 7%, 20%, and 29% of total body weight. Control and tumor-bearing rats were pair-fed throughout the study. Jejunal brush border membrane vesicles (BBMVs) were prepared by magnesium aggregation/differential centrifugation and transport of radioactively labeled L-glutamine, L-leucine, L-alanine, and D-glucose by BBMVs was measured using a Millipore filtration technique. BBMVs were enriched 15-fold in alkaline phosphatase, indicating brush border vesicle purity. Uptake of all substrates occurred into an osmotically active space, exhibited overshoots, and had similar 1-hr equilibrium values. The rate of glutamine uptake by BBMVs from all tumor-bearing rats was significantly greater than controls, regardless of tumor size. The increase in transport activity was not due to a change in carrier affinity but rather to an increase in maximal transport velocity. In rats with small tumors (7% of body weight), the Vmax was 431 +/- 40 pmole/mg protein/10 sec compared to 259 +/- 30 in control animals (P less than 0.01). In marked contrast, the mean transport of alanine was diminished in BBMVs from TBR (31 +/- 3 pmole/mg protein/10 sec in TBR vs 23 +/- 2 in controls, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


E2→E1 transition and Rb(+) release induced by Na(+) in the Na(+)/K(+)-ATPase. Vanadate as a tool to investigate the interaction between Rb(+) and E2.
This work presents a detailed kinetic study that shows the coupling between the E2→E1 transition and Rb(+) deocclusion stimulated by Na(+) in pig-kidney purified Na,K-ATPase. Using rapid mixing techniques, we measured in parallel experiments the decrease in concentration of occluded Rb(+) and the increase in eosin fluorescence (the formation of E1) as a function of time. The E2→E1 transition and Rb(+) deocclusion are described by the sum of two exponential functions with equal amplitudes, whose rate coefficients decreased with increasing [Rb(+)]. The rate coefficient values of the E2→E1 transition were very similar to those of Rb(+)-deocclusion, indicating that both processes are simultaneous. Our results suggest that, when ATP is absent, the mechanism of Na(+)-stimulated Rb(+) deocclusion would require the release of at least one Rb(+) ion through the extracellular access prior to the E2→E1 transition. Using vanadate to stabilize E2, we measured occluded Rb(+) in equilibrium conditions. Results show that, while Mg(2+) decreases the affinity for Rb(+), addition of vanadate offsets this effect, increasing the affinity for Rb(+). In transient experiments, we investigated the exchange of Rb(+) between the E2-vanadate complex and the medium. Results show that, in the absence of ATP, vanadate prevents the E2→E1 transition caused by Na(+) without significantly affecting the rate of Rb(+) deocclusion. On the other hand, we found the first evidence of a very low rate of Rb(+) occlusion in the enzyme-vanadate complex, suggesting that this complex would require a change to an open conformation in order to bind and occlude Rb(+).


Modern approach to resistant acromegaly.
Targets of acromegaly treatment are normalization of biochemical values, removal/reduction/stabilization of the pituitary mass, control of clinical activity and mortality with a multimodal/multidisciplinary approach. Despite significant technological and pharmacological progress, still several patients with acromegaly bear a resistant somatotroph adenoma and active disease may persist for many years with resultant poor clinical outcomes. To review briefly definition and pathophysiology of resistance to acromegaly treatment and the options of medical treatment in this context, exploring the role of novel clinical and molecular biomarkers in the personalization of therapy and proposing updates to the currently available guidelines for the treatment of resistant GH-secreting adenomas. In the last few years, in parallel with the increased number of medical options available for the therapy of acromegaly, relevant advances occurred in the understanding of the role of novel molecular and clinical biomarkers in predicting the responsiveness to second-line medical treatments, such as Pegvisomant and Pasireotide LAR, and helping clinicians in the personalization of the follow-up and treatment of resistant somatotroph adenomas. The integration of these findings into the existing guidelines may represent a possibly important step forward in the management of "difficult" acromegaly patients.


Isolation of rice dwarf mutants with ectopic deposition of phenolic components including lignin in parenchyma cell walls of internodes.
Rice internodes must have the proper shape to support high-yielding panicles. The shape of internodes is controlled by various factors involved in their formation, such as developmental patterns, cell division, cell elongation, and cell wall biosynthesis. To understand the regulation of internode development, we screened dwarf mutants to identify those with a phenotype of ectopic deposits of phenolic components in parenchyma cell walls of internodes. We named these mutants ectopic deposition of phenolic components1 (edp1). Two alleles were identified, edp1-1 and edp1-2. Furthermore, these mutants showed disordered cell files in internode parenchyma. These abnormal phenotypes were very similar to that of a previously reported dwarf50 (d50) mutant. Genetic analyses of edp1 mutants revealed that the edp1 loci are distinct from d50. Our results indicate that analyses of edp1 mutants as well as the d50 mutant will be useful for understanding the molecular mechanisms behind ectopic deposition of cell wall phenolic components in internode parenchyma cells and the regulation of internode development.


Augmentation of natural killer cell activity by anti-host delayed-type hypersensitivity during the graft-versus-host reaction in mice.
During a graft-versus-host (GVH) reaction in unirradiated F1 hybrid mice there is a generalized activation of natural killer (NK) cells. We have examined whether the enhanced NK activity is due to an F1 resistance mechanism directed at the parental cells used to induce the GVH reaction. Spleen cells of C57BL/10 origin induce much more NK cell activation in B10F1 hybrids than the opposite parental type, despite a similar intensity of systemic GVH reactions. However, this does not correlate with in vivo resistance of mice with GVH reaction to a local challenge dose of B10 cells. NK cell activation in (CBA X BALB/c)F1 mice with GVH reaction involves both host and donor cells and is preceded by an anti-host delayed-type hypersensitivity (DTH) response. B10 cells have a greater ability to induce DTH in B10F1 mice than cells from the opposite parent. We propose that NK cells are one group of non-specific effector cells recruited by DTH in a GVH reaction and may contribute to the tissue pathology.


Antioxidant and prooxidant effects of polyphenol compounds on copper-mediated DNA damage.
Inhibition of copper-mediated DNA damage has been determined for several polyphenol compounds. The 50% inhibition concentration values (IC(50)) for most of the tested polyphenols are between 8 and 480 μM for copper-mediated DNA damage prevention. Although most tested polyphenols were antioxidants under these conditions, they generally inhibited Cu(I)-mediated DNA damage less effectively than Fe(II)-mediated damage, and some polyphenols also displayed prooxidant activity. Because semiquinone radicals and hydroxyl radical adducts were detected by EPR spectroscopy in solutions of polyphenols, Cu(I), and H(2)O(2), it is likely that weak polyphenol-Cu(I) interactions permit a redox-cycling mechanism, whereby the necessary reactants to cause DNA damage (Cu(I), H(2)O(2), and reducing agents) are regenerated. The polyphenol compounds that prevent copper-mediated DNA damage likely follow a radical scavenging pathway as determined by EPR spectroscopy.


Adjusting the number of spermatozoa in mini-straws by determination of the operative volume of bovine semen.
The importance of the number of sperm per insemination on fertility has been well demonstrated in cattle. This number is usually calculated from the concentration in the extended semen and a theoretical value for the operative volume of semen delivered during insemination. The objective of this experiment was to investigate the usefulness of the measurement of the delivered volume of semen when estimating sperm numbers from frozen-thawed mini-straws, by comparing the results obtained with an analytical balance to the theoretical volume. The density of semen extended with Biociphos Plus and Triladyl was determined to be 1.033 g/ml using the gamma sphere method. This value was used to convert semen weight into operative volume. The effect of semen temperature at the time of weighing (37 degrees C versus 20 degrees C) was investigated on six semen batches, two technicians measuring the operative volume of 50 straws for each combination of temperature and semen batch (a total of 1200 weighings). The temperature effect was found to be insignificant, which allowed warm semen to be weighed before motility was assessed during routine quality control. The operative volume was then measured in straws routinely produced at 17 bovine Al centers (12-105 semen batches per center, mostly three straws from each batch, a total of 1912 measurements). The observed volumes were normally distributed around 198.7 microl, 98% measuring between 180 and 210 microl. The operative volume was significantly different among centers (from 192 to 205 microl, P < 0.0001) and among batches within centers (P < 0.0001). The S.D. among straws within batches was 3.4 microl. Some centers showed high variability in straw volume whereas others were more consistent. Determination of the operative volume of frozen-thawed mini-straws by weighing the delivered contents is an accurate method for estimation of the number of sperm per dose.


Protection against paraquat-induced injury by exogenous GSH in pulmonary alveolar type II cells.
Exogenous GSH provided rat alveolar type II cells with significant protection against injury induced by paraquat. This protection was also observed in cells treated with acivicin to inhibit GSH degradation and buthionine sulfoximine to inhibit GSH synthesis. Exogenous GSH was transported into cells by a Na+-dependent system. Addition of inhibitors of this transport system, gamma-glutamyl-glutamate and probenecid, prevented the protection against injury afforded by GSH. Thus, the results indicate that alveolar type II cells can supplement endogenous synthesis of GSH with uptake of exogenous GSH to protect against paraquat-induced injury.


A novel mouse PKCδ splice variant, PKCδIX, inhibits etoposide-induced apoptosis.
Protein kinase C (PKC) δ plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKCδ generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKCδ isoform named PKCδIX (Genebank Accession No. HQ840432). PKCδIX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKCδ. PKCδIX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKCδIX provided a possibility that this PKCδ isozyme functions as a novel dominant-negative form for PKCδ due to its lack of the ATP-binding domain that is required for the kinase activity of PKCδ. Indeed, overexpression of PKCδIX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKCδIX protein could competitively inhibit the kinase activity of PKCδ. We conclude that PKCδIX can function as a natural dominant-negative inhibitor of PKCδin vivo.


Endoscopic submucosal dissection for large colorectal neoplasms.
Endoscopic submucosal dissection (ESD) for colorectal neoplasms (CRN) of >50 mm is considered technically difficult. The ITknife nano™ was developed specifically for ESD of CRN and esophageal superficial neoplasms; however, only limited data are available regarding its use in this procedure. Here we assessed the safety and efficacy of ESD using the ITknife nano™ for large CRN (>50 mm). We carried out a retrospective study, including consecutive patients with CRN larger than 50 mm that were treated by ESD between September 2002 and August 2016 at our institution. To clarify features of the ITknife nano™ and to assess its safety and efficacy, we compared en bloc/curative resection rates, complications, and resection speed between ESD done using the Dual knife™ with and without the ITknife nano™. We analyzed a total of 177 ESD-treated large CRN (median tumor size, 61 mm). Among the 133 CRN treated by ESD using the ITknife nano™, en bloc and curative resection rates were 96.2% and 80.5%, respectively. Perforation occurred in eight cases (6.0%) and delayed bleeding in four cases (3.0%). All complications were endoscopically managed. Resection speed was significantly faster for ESD using the ITknife nano™ (25.3 mm2 /min) compared to using the Dual knife™ only (19.9 mm2 /min; P = 0.02). Use of the ITknife nano™ for ESD treatment of large CRN (>50 mm) is feasible and may contribute to reduced procedure times. Further controlled studies are needed to confirm these findings.


Topographic anatomy and intraoperative USG-guided foreign bodies extraction of neglected Molotov cocktail victim: A rare case report.
Foreign body implantation resulting from explosive devices is an extraordinary occurrence that often leads to substantial morbidity among the affected individuals. Explosions caused by such devices generate a rapidly propagating blast wave emanating from the point of detonation. This study aims to present a case involving a patient who experienced multiple foreign body implantations as a consequence of a bomb explosion. A 41-year-old male presented with a history of multiple foreign bodies retained within his body for the past 22 years, originating from a homemade explosive device. At present, he reports weakness in his lower extremities, numbness extending from the umbilical region down to the lower extremities, and fecal incontinence. The patient underwent a surgical procedure for the removal of these foreign bodies, guided by ultrasonography (USG), which lasted for a duration of 12 h. The presence of foreign bodies within the human body incites an inflammatory response. In preparation for surgery, topographic anatomy is delineated through the use of pre-operative CT scans to ascertain the precise locations of these foreign bodies. Subsequently, the removal of these foreign bodies is executed under the guidance of ultrasound. The extraction of multiple foreign bodies from a patient's body is an infrequent surgical procedure. Meticulous surgical planning, aided by the utilization of X-rays and CT scans for topographic anatomical mapping, is imperative. Employing real-time ultrasound guidance during the procedure serves to minimize blood loss and mitigate potential damage to adjacent structures, thereby enhancing patient safety and reducing the likelihood of surgical complications.


Myopia prediction for children and adolescents via time-aware deep learning.
This is a retrospective analysis. Quantitative prediction of the children's and adolescents' spherical equivalent based on their variable-length historical vision records. From October 2019 to March 2022, we examined uncorrected visual acuity, sphere, astigmatism, axis, corneal curvature and axial length of 75,172 eyes from 37,586 children and adolescents aged 6-20 years in Chengdu, China. 80% samples consist of the training set, the 10% form the validation set and the remaining 10% form the testing set. Time-Aware Long Short-Term Memory was used to quantitatively predict the children's and adolescents' spherical equivalent within two and a half years. The mean absolute prediction error on the testing set was 0.103 ± 0.140 (D) for spherical equivalent, ranging from 0.040 ± 0.050 (D) to 0.187 ± 0.168 (D) if we consider different lengths of historical records and different prediction durations. Time-Aware Long Short-Term Memory was applied to captured the temporal features in irregularly sampled time series, which is more in line with the characteristics of real data and thus has higher applicability, and helps to identify the progression of myopia earlier. The overall error 0.103 (D) is much smaller than the criterion for clinically acceptable prediction, say 0.75 (D).


The course of facial corticobulbar tract fibers in the dorsolateral medulla oblongata.
The course of the corticobulbar tract (CBT) to the facial nucleus has been investigated by some previous studies. However, there are some unclear points of the course of the CBT to the facial nucleus. This study aimed to elucidate the detailed course of the CBT to the facial nucleus through the analysis of lateral medullary infarction (LMI) cases. The neurological characteristics and magnetic resonance imaging findings of 33 consecutive patients with LMI were evaluated. The location of the lesions was classified rostro-caudally (upper, middle, or lower) and horizontally. Further, we compared the neurological characteristics between the groups with and without central facial paresis (FP). Eight (24%) patients with central FP ipsilateral to the lesion were identified. Dysphagia and hiccups were more frequently observed in the group with central FP than in the group without central FP. In patients with central FP, middle medullary lesions and those including the ventral part of the dorsolateral medulla were more frequently observed. Contrastingly, patients with lesions restricted to the lateral and dorsal regions of the dorsolateral medulla did not present with central FP. The results of this study indicate that the CBT to the facial nucleus descends with the corticospinal tract at least to the middle portion of the medulla, and then ascends to the facial nucleus through the medial and ventral areas of the dorsolateral medulla after decussation.


Dissipation and energy propagation across scales in an active cytoskeletal material.
Living systems are intrinsically nonequilibrium: They use metabolically derived chemical energy to power their emergent dynamics and self-organization. A crucial driver of these dynamics is the cellular cytoskeleton, a defining example of an active material where the energy injected by molecular motors cascades across length scales, allowing the material to break the constraints of thermodynamic equilibrium and display emergent nonequilibrium dynamics only possible due to the constant influx of energy. Notwithstanding recent experimental advances in the use of local probes to quantify entropy production and the breaking of detailed balance, little is known about the energetics of active materials or how energy propagates from the molecular to emergent length scales. Here, we use a recently developed picowatt calorimeter to experimentally measure the energetics of an active microtubule gel that displays emergent large-scale flows. We find that only approximately one-billionth of the system's total energy consumption contributes to these emergent flows. We develop a chemical kinetics model that quantitatively captures how the system's total thermal dissipation varies with ATP and microtubule concentrations but that breaks down at high motor concentration, signaling an interference between motors. Finally, we estimate how energy losses accumulate across scales. Taken together, these results highlight energetic efficiency as a key consideration for the engineering of active materials and are a powerful step toward developing a nonequilibrium thermodynamics of living systems.


Cross-sectional review of US websites providing lung cancer screening recommendations following the 2021 US Preventive Services Task Force updates.
Lung cancer remains the leading cause of cancer death worldwide and an urgent public health priority. Early detection by low-dose CT (LDCT) screening and treatment of lung cancer has been shown to reduce mortality but uptake remains dismal, particularly among historically underserved groups. Following the US Preventive Services Task Force (USPSTF) expansion of its eligibility criteria to address inequities in utilization, efforts are needed to ensure dissemination of updated health information through digital means such as websites. The objective of this study was to investigate whether online websites have been updated to reflect the recent USPSTF guidelines that expanded the recommended age and smoking pack-years for lung cancer screening. In this cross-sectional study, we identified websites that provide information on lung cancer screening guidelines on May 24, 2022, approximately one year after the emergence of the updated USPSTF guidelines. The websites were assessed for recommended age to begin lung cancer screening and smoking pack-year quantity. Our study found that a lag in dissemination of updated lung cancer screening information exists. Approximately 1 year after the USPSTF guidelines were updated, 17-32% of websites providing information on lung cancer screening guidelines had not been updated. Routine monitoring of websites that provide information on lung cancer screening can help reduce misinformation, improve uptake of lung cancer screening, and prevent delays in diagnostic evaluation which disproportionally affects traditionally underserved populations.


Evaluation of biomass pretreatment to optimize process factors for different organic acids via Box-Behnken RSM method.
Biomass, as renewable energy source, is of importance to investigate to extend the conversion yield by microorganism. Because of lignocellulosic structure, biomass must be pretreated with a process, frequently inorganic acid has to be used with a problem of hazardous byproducts. Organic acid pretreatment is an efficient alternative to be investigated. Sugar beet pulp, as an agro-industrial residue of microorganism, can be utilized by pretreatment, which is usually a costly process. Pretreatment with organic acids creates a great opportunity to convert the process into more economic and effective. Moreover, pressure conditions significantly increase the yield of biodegradable sugar content. In this study, different organic acids of maleic, fumaric, oxalic, and acetic acid pretreatment was investigated to pretreatment of sugar beet pulp, which came vast amount from factories, under pressure and non-pressure conditions via Box-Behnken method to estimate optimum point of acid ratio (1, 3, 5%), time (10, 27.5, 45 min), and solid ratio factors (3, 6.5, 10%) for highest degradation. Results were also evaluated economically. As a result of the experiments, it was observed that acetic acid gave the best result with 409.16 g/L total sugar concentration than the other organic acids. The highest TS concentration of maleic, oxalic, and fumaric acid were 97.26, 97.85, and 91.37 g/L, respectively, under pressure. According to economical evaluation, owing to lower market price and highest TS formation yield, pretreatment cost of acetic acid pretreatment was found averagely 1.51 $/gTS under pressure conditions. The online version contains supplementary material available at 10.1007/s10163-021-01276-7.


PRODeepSyn: predicting anticancer synergistic drug combinations by embedding cell lines with protein-protein interaction network.
Although drug combinations in cancer treatment appear to be a promising therapeutic strategy with respect to monotherapy, it is arduous to discover new synergistic drug combinations due to the combinatorial explosion. Deep learning technology holds immense promise for better prediction of in vitro synergistic drug combinations for certain cell lines. In methods applying such technology, omics data are widely adopted to construct cell line features. However, biological network data are rarely considered yet, which is worthy of in-depth study. In this study, we propose a novel deep learning method, termed PRODeepSyn, for predicting anticancer synergistic drug combinations. By leveraging the Graph Convolutional Network, PRODeepSyn integrates the protein-protein interaction (PPI) network with omics data to construct low-dimensional dense embeddings for cell lines. PRODeepSyn then builds a deep neural network with the Batch Normalization mechanism to predict synergy scores using the cell line embeddings and drug features. PRODeepSyn achieves the lowest root mean square error of 15.08 and the highest Pearson correlation coefficient of 0.75, outperforming two deep learning methods and four machine learning methods. On the classification task, PRODeepSyn achieves an area under the receiver operator characteristics curve of 0.90, an area under the precision-recall curve of 0.63 and a Cohen's Kappa of 0.53. In the ablation study, we find that using the multi-omics data and the integrated PPI network's information both can improve the prediction results. Additionally, the case study demonstrates the consistency between PRODeepSyn and previous studies.


The Effect of COVID-19 Pandemic Restrictions on Lead Screening in a Primary Care Clinic.
Coronavirus disease 2019 (COVID-19) has disrupted outpatient pediatrics, postponing well-child care to address immediate patient safety concerns. Screening for lead toxicity is a critical component of this care. Children may be at increased risk for lead exposure at home because of social restrictions. We present data on how COVID-19 restrictions have impacted lead screening in a primary care practice. Lead testing data on 658 children in a primary care practice were analyzed to determine the effect of COVID-19 restrictions on lead screening rates, levels, and deficiencies. Lead screening significantly decreased during peak restrictions, leading to increased screening deficiencies. Despite this decrease, screening lead levels increased during peak restrictions. These data show how COVID-19 restrictions have disrupted routine care and highlight the importance of continued lead screening in at-risk populations. The electronic medical record can be leveraged to identify deficiencies to be targeted by quality improvement initiatives.


BARBEKO'ing in the lab: Versatile CRISPR screens with barcoded base editors.
Xu et al. (2021) describe a novel two-pronged CRISPR screen, termed BARBEKO, by coupling cytosine base editors and internally barcoded sgRNAs to eliminate double-stranded break-induced toxicity, enable high multiplicities of infection, and ensure experimental reproducibility.


Natural products in the treatment of pulmonary emphysema: Therapeutic effects and mechanisms of action.
Chronic obstructive pulmonary disease (COPD) is a class of lung diseases including chronic bronchitis, asthma, and emphysema. Long-time smoking is considered the main reason for developing emphysema. Emphysema can be defined as damage to the walls of the air sacs (alveoli) of the lung. It has been demonstrated that natural compounds with antioxidant and anti-inflammatory effects can effectively improve or protect the lung against this disease. This paper is dedicated to systematically review the effective natural compounds in the treatment of pulmonary emphysema. This is the first systematic and comprehensive review on the role of plant-derived secondary metabolites in managing and/or treating pulmonary emphysema STUDY DESIGN AND METHODS: A systematic and comprehensive review was done based on Scopus, PubMed, and Cochrane Library databases were searched using the "emphysema", "plant", "herb", and "phytochemical" keywords. Non-English, review, and repetitive articles were excluded from the study. Search results were included in the Prisma diagram. From a total of 1285 results, finally, 22 articles were included in the present study. The results show that some herbs such as Scutellaria baicalensis Georgi and Monascus adlay and some phytochemicals such as gallic acid and quercetin and blackboard tree indole alkaloids affect more factors in improving the lung emphysema. Also, some natural compounds such as marijuana smoke and humic acid also play an aggravating role in this disease. It also seems that some of the medicinal plants such as PM014 herbal formula, pomegranate juice and açaí berry sometimes have side effects that are inconsistent with their therapeutic effects. We concluded that natural compounds can effectively improve pulmonary emphysema due to their antioxidant, anti-inflammatory, and anti-apoptotic properties. However, additional studies are suggested to prove efficacy and side effects.


Mapping bare ground in New Zealand hill-country agriculture and forestry for soil erosion risk assessment: An automated satellite remote-sensing method.
Removing vegetation cover from hill-slope land increases risk for soil erosion and delivery of sediment to waterways. In New Zealand's productive landscapes, clear-fell harvesting of forestry blocks and winter forage grazing by agricultural livestock are two significant causes of vegetation removal. Bare ground exposed by these activities varies annually and seasonally in location and spatial extent. Modelling soil erosion therefore requires temporally and spatially explicit mapping of this bare ground. We have developed an automated mapping method using time-series satellite imagery, thereby enabling wide-area coverage and ease of updating. The temporal analysis identifies land use along with the period of vegetation removal. It produces results per land parcel (in vector format) for use in a Geographic Information System. We present a description of our method, national maps and statistics of bare ground extent in New Zealand's hill-country forestry and winter forage grazing land in 2018, and an assessment of accuracy. The attributes of the mapped land parcels are designed for input into a soil erosion estimation model such as the New Zealand Universal Soil Loss Equation.


Serum vascular endothelial growth factor in dogs with haemangiosarcoma and haematoma.
Splenic haemangiosarcomas are frequently seen in dogs. Because of their bad prognosis differentiation from other benign splenic lesions are of prognostic importance. However, because haemangiosarcoma is a tumour of the vascular system, it was hypothesised that vascular endothelial growth factor (VEGF) might play a major role in tumour growth and might thus be increased in the blood of affected dogs. The aim of this study was to investigate the clinical relevance of differences in serum VEGF concentrations between dogs with splenic haemangiosarcomas and those with non-malignant splenic lesions (haematomas) and healthy subjects using a canine ELISA. Serum VEGF levels were significantly higher in dogs with splenic masses compared with healthy dogs, but did not differ significantly between dogs with haemangiosarcomas and haematomas. VEGF has a potential clinical utility as a diagnostic marker for dogs with splenic lesions but may not be useful to differentiate among the various splenic lesions.


CD63 acts as a functional marker in maintaining hematopoietic stem cell quiescence through supporting TGFβ signaling in mice.
Hematopoietic stem cell (HSC) fate is tightly controlled by various regulators, whereas the underlying mechanism has not been fully uncovered due to the high heterogeneity of these populations. In this study, we identify tetraspanin CD63 as a novel functional marker of HSCs in mice. We show that CD63 is unevenly expressed on the cell surface in HSC populations. Importantly, HSCs with high CD63 expression (CD63hi) are more quiescent and have more robust self-renewal and myeloid differentiation abilities than those with negative/low CD63 expression (CD63-/lo). On the other hand, using CD63 knockout mice, we find that loss of CD63 leads to reduced HSC numbers in the bone marrow. In addition, CD63-deficient HSCs exhibit impaired quiescence and long-term repopulating capacity, accompanied by increased sensitivity to irradiation and 5-fluorouracil treatment. Further investigations demonstrate that CD63 is required to sustain TGFβ signaling activity through its interaction with TGFβ receptors I and II, thereby playing an important role in regulating the quiescence of HSCs. Collectively, our data not only reveal a previously unrecognized role of CD63 but also provide us with new insights into HSC heterogeneity.


Anatomical bases of percutaneous surgery for calculi in horseshoe kidney.
Horseshoe kidney is a renal fusion which combines three anatomic abnormalities: ectopia, malrotation and vascular changes. These anomalies can be recognised separately to varying degrees in unfused kidneys. Necessary modifications of the standard technique for percutaneous nephrolithotomy (PNL) are directly deducible from analysis of the anatomic data of the imaging of horseshoe kidneys. We report our experience with 5 patients (7 kidneys) who underwent PNL for calculi in horseshoe kidneys. The percutaneous approach was performed under ultrasound and fluoroscopic monitoring. In situ disintegration by ultrasonic lithotripsy and nephrostomy drainage were necessary in all cases. Modifications of the standard PNL procedure are related to the anatomic changes. The lower abdominal position of a horseshoe kidney necessitates upper or middle calyceal puncture, while the malrotation necessitates a more posterior puncture. Monitoring of the puncture needle by fluoroscopy as it is advanced postero-anteriorly is more difficult and the risk of the surgeon's hand entering the radiation path is increased. The renal pelvis is deep and a long endoscope may be required. Aberrant segmental vessels may create potential hazards. The majority of problems in location can be avoided by use of an ultrasonically guided needle. Percutaneous nephrolithotomy is the treatment of choice for calculi in horseshoe kidneys for the following reasons: the high incidence of recurrent lithiasis in horseshoe kidney and the complexity of repeated surgical approaches diminish the acceptable results of open surgery; difficulties in focussing on the calculi and drainage problems militate against the success of extracorporeal shock wave lithotripsy (ESWL); PNL has a good success rate and the least morbidity.


Global distribution of polymorphisms associated with delayed Plasmodium falciparum parasite clearance following artemisinin treatment: genotyping of archive blood samples.
The recent emergence and spread of artemisinin-resistant Plasmodium falciparum isolates is a growing concern for global malaria-control efforts. A recent genome-wide analysis study identified two SNPs at genomic positions MAL10-688956 and MAL13-1718319, which are linked to delayed clearance of parasites following artemisinin combination therapy (ACT). It is expected that continuous artemisinin pressure will affect the distribution of these SNPs. Here, we investigate the worldwide distribution of these SNPs using a large number of archived samples in order to generate baseline data from the period before the emergence of ACT resistance. The presence of SNPs in MAL10-688956 and MAL13-1718319 was assessed by nested PCR RFLP and direct DNA sequencing using 653 global P. falciparum samples obtained before the reported emergence of ACT resistance. SNPs at MAL10-688956 and MAL13-1718319 associated with delayed parasite clearance following ACT administration were observed in 8% and 3% of parasites, respectively, mostly in Cambodia and Thailand. Parasites harbouring both SNPs were found in only eight (1%) isolates, all of which were from Cambodia and Thailand. Linkage disequilibrium was detected between MAL10-688956 and MAL13-1718319, suggesting that this SNP combination may have been selected by ACT drug pressure. Neither of the SNPs associated with delayed parasite clearance were observed in samples from Africa or South America. Baseline information of the geographical difference of MAL10-688956 and MAL13-1718319 SNPs provides a solid basis for assessing whether these SNPs are selected by artemisinin-based combination therapies.


Screening for active COVID-19 infection and immunization status prior to biologic therapy in IBD patients at the time of the pandemic outbreak.
Coronavirus disease 2019 has been recently classified as pandemic infection by the World Health Organization. Patients with inflammatory bowel disease (IBD) are invited to follow the national recommendations as any other person. It is unclear whether a more aggressive clinical course might develop in asymptomatic COVID-19 infected subjects during biological therapy and current evidence does not support treatment suspension. However, during pandemic, the start of treatment with immunosuppressive drugs and biologics should be postponed whenever possible and based on an individual risk assessment. When clinical conditions and the disease activity do not allow a treatment delay, before starting a biological therapy, screening of IBD patients for COVID-19 active infection by RT-PCR should be advisable, even in absence of clinical suspicion. Serum antibody testing, when available, could provide evidence of infection as well as identify patients already immune to the disease.


Long-run consequences of parental paid work hours for child overweight status in Canada.
This paper explores the connection between the labour market and child overweight status in Canada. The labour market is a social institution which plays a critical role in determining how families live their day-to-day lives, for example, how much time and which parts of the day are available for cooking, eating and exercise. Using longitudinal data from the Statistics Canada National Longitudinal Survey of Children and Youth, we find that a history of higher hours of paid work by mothers (but not fathers) is associated with a higher probability of being 'at risk of overweight'/overweight for children aged 6-11. The policy implication we draw from this work is that additional support to better enable parents to engage in paid work without penalty to their own health or that of their children is clearly warranted.


Do postal reminders increase postpartum screening of diabetes mellitus in women with gestational diabetes mellitus? A randomized controlled trial.
Women with previous gestational diabetes mellitus rarely receive the recommended 2-hour oral glucose tolerance test (OGTT) after delivery. We sought to determine whether postal reminders to be sent after delivery to a patient, her physician, or both would increase screening rates. Patients were assigned randomly to 4 groups: reminders sent to both physician and patient, to physician but not patient, or to patient but not physician or no reminders were sent. The primary outcome was the proportion of patients who underwent an OGTT within 1 year after delivery. The secondary outcome was the performance of other postpartum screening tests. OGTT rates were significantly increased in the physician/patient reminder group (49/81 women; 60.5%), in the patient-only reminder group (42/76 women; 55.3%), and in the physician-only reminder group (16/31 women; 51.6%) compared with the no reminder group (5/35 women; 14.3%; P < .05). Postpartum reminders greatly increased screening rates for women with gestational diabetes mellitus.


[Glucose, fructose and xylitol as energy carriers in postoperative parenteral nutrition (comparative studies) (author's transl)].
The effects of fructose, glucose and xylitol, as well as their mixture in a proportion of 2:1:1 were measured and compared in the postoperative phase in a uniform group of patients receiving these substances during a 6-hour infusion. Carbohydrate balance, carbohydrate blood levels, changes in acid-base equilibrium and rises of lactate and uric acid were used as criteria for assessing the various substrates and their mixtures. Using these criteria, a carbohydrate mixture consisting of fructose, glucose and xylitol (2: 1: 1) proved to be better than the various substrates by themselves in equivalent amounts.


Developmental changes in succinate dehydrogenase activity in muscle fibers from normal and dystrophic mice.
The question of whether or not the development of dystrophic muscles is similar to that of normal muscles, prior to the manifestations of the symptoms of the disease, is investigated here. The developmental change in the activity of succinate dehydrogenase was therefore measured in individual fibers of prospectively dystrophic muscles from 10- to 28-day-old mice (strain C57Bl/6J dy2j) and compared with that of muscles from normal mice of the same age. It was found that up to 10 days of age, muscle fibers from normal and prospective dystrophic animals had low succinate dehydrogenase activities, and were all more or less uniform. Thereafter in the normal muscle the overall activity of the enzyme increased and the fibers became more heterogeneous with age. By 21 days the extensor digitorum longus muscle resembled that of the adult. At that time, fibers from prospectively dystrophic muscles had lower succinate dehydrogenase activities and were more homogeneous. Thus fibers from prospectively dystrophic muscles fail to achieve their adult characteristics by 21 days. On the basis of these results, it is suggested that muscle maturation is retarded in dystrophic animals.


Effect of retinoids and growth factor on in vitro bovine embryos produced under chemically defined conditions.
Experiments were conducted to investigate the beneficial effects of adding retinol (RT) and retinoic acid (RA) to bovine oocyte maturation media and insulin-like growth factor-I (IGF-I) to embryo culture under chemically-defined conditions. In Experiment 1.1, in vitro maturation (IVM) was performed in basic maturation media (bMM) and supplemented with 0.3microM RT or 0.5microM RA. For embryo development presumptive zygotes and embryos were placed in droplets of potassium simplex optimized medium (KSOM). Addition of RT and RA to bMM improved (p<0.05) blastocyst formation as compared with control treatments. In Experiment 1.2, using embryos originating from oocytes previously treated with RT and RA, the presumptive zygotes were placed in droplets of KSOM and embryos (2-4 cells) in droplets of fresh KSOM supplemented or not with IGF-I. The number of 2-4-cell stage embryos developing to the blastocyst and expanded blastocyst stages were greater (p<0.05) when embryo culture media was supplemented with IGF-I. In Experiment 2.1, IVM was conducted with bMM+FSH containing 0.3microM RT or 0.5microM RA. For embryo development, presumptive zygotes were placed in droplets of KSOM. Addition of RT or RA to IVM medium also enhanced (p<0.05) blastocyst formation. The supplementation of embryo culture media with IGF-I resulted in a greater number (p<0.05) of 2-4-cell stage embryos developing into blastocysts, expanded blastocysts and hatched blastocysts. In Experiment 2.2, using embryos originating from oocytes previously treated with RT and RA, presumptive zygotes were also placed in droplets of KSOM and embryos (2-4 cells) in droplets of fresh KSOM supplemented or not with IGF-I. The supplementation of embryo culture media with IGF-I resulted in a greater (p<0.05) number of 2-4-cell stage embryos developing to the blastocyst, expanded blastocyst and hatched blastocyst stages.


A comparative study of the modified Sauvé-Kapandji procedure for rheumatoid wrist with and without stabilization of the proximal ulnar stump.
We compared the clinical and radiological results of the modified Sauvé-Kapandji procedure for 41 of 86 operated rheumatoid wrists with (n=22) and without (n=19) stabilization of the proximal ulnar stump with a slip of half the extensor carpi ulnaris tendon. Gender, age, and follow-up period were similar in the two groups. We found no difference clinically or on radiographs between the two groups other than better early postoperative pain relief in those stabilized. Stabilization of the proximal ulnar stump may not be necessary in the modified Sauvé-Kapandji procedure for rheumatoid wrists.


Segmented surface coil resonator for in vivo EPR applications at 1.1GHz.
A four-loop segmented surface coil resonator (SSCR) with electronic frequency and coupling adjustments was constructed with 18mm aperture and loading capability suitable for in vivo Electron Paramagnetic Resonance (EPR) spectroscopy and imaging applications at L-band. Increased sample volume and loading capability were achieved by employing a multi-loop three-dimensional surface coil structure. Symmetrical design of the resonator with coupling to each loop resulted in high homogeneity of RF magnetic field. Parallel loops were coupled to the feeder cable via balancing circuitry containing varactor diodes for electronic coupling and tuning over a wide range of loading conditions. Manually adjusted high Q trimmer capacitors were used for initial tuning with subsequent tuning electronically controlled using varactor diodes. This design provides transparency and homogeneity of magnetic field modulation in the sample volume, while matching components are shielded to minimize interference with modulation and ambient RF fields. It can accommodate lossy samples up to 90% of its aperture with high homogeneity of RF and modulation magnetic fields and can function as a surface loop or a slice volume resonator. Along with an outer coaxial NMR surface coil, the SSCR enabled EPR/NMR co-imaging of paramagnetic probes in living rats to a depth of 20mm.


Mechanism of Qizhen decoction-mediated maturation of DC cells to activate the IL-12/JAK2/STAT4 pathway to sensitise PD-1 inhibitors in the treatment of colorectal cancer.
Traditional Chinese medicine has been utilized to treat colorectal cancer (CRC). Qizhen decoction (QZD), a potential compound prescription of traditional Chinese medicine, possesses multiple biological activities. It has been used to treat CRC in clinical practice and has been proven to be effective. To investigate the impact of QZD supported by intestinal flora in combination with PD-1 inhibitor on colorectal cancer, and to elucidate the mechanism by which QZD enhances the sensitivity of PD-1 inhibitor against colorectal cancer. Observation of Intestinal Flora Mediating the Effect of QZD Combined with PD-1 Inhibitor in the Treatment of Colorectal Cancer. We used Flow cytometry and qPCR to detect the effect of QZD combined with PD-1 inhibitor on the activation of effector T cells in a wild mouse model of colorectal cancer. In wild and germ-free mouse models, the differences in inflammatory factors, pathological change, body mass, colorectal length, and tumour load were observed. In the study of the mechanism of QZD combined with PD-1 inhibitor in the treatment of colorectal cancer, the study evaluated the abundance of Akkermansia, the phenotypes of effector T cells and DC cells, as well as inflammatory factors in each group of mice to determine whether Akkermansia played a role in activating DC cells. Based on the JAK2/TYK2/STAT4 pathway, the mechanism of PD-1 inhibitor sensitisation by QZD in colorectal cancer was further investigated. We found that QZD combined with PD-1 inhibitor could improve the therapeutic effect on colorectal cancer by inducing more critical immune functions. QZD promotes increased Akkermansia abundance in the gut. Akkermansia promotes maturation of DC cells, and mature DC cells activate the IL-12/JAK2/STAT4 pathway, which significantly activates effector T cells. Akkermansia is key to QZD combined with PD-1 inhibitor-mediated immunity exerting a therapeutic effect on colorectal cancer. The mechanism of action of the QZD sensitizing PD-1 inhibitor is to promote the maturation of DC cells to release IL-12 and activate the JAK2/STAT4 pathway to induce effector T cell activation by increasing the abundance of Akkermansia.


Prevalence and phenomenology of violent ideation and behavior among 200 young people at clinical high-risk for psychosis: an emerging model of violence and psychotic illness.
In a previously reported longitudinal study of violent ideation (VI) and violent behavior (VB) among 200 youths at clinical high-risk (CHR) for psychosis, we found that VI, hitherto underinvestigated, strongly predicted transition to first-episode psychosis (FEP) and VB, in close temporal proximity. Here, we present participants' baseline characteristics, examining clinical and demographic correlates of VI and VB. These participants, aged 13-30, were examined at Columbia University Medical Center's Center of Prevention and Evaluation, using clinical interviews and the structured interview for psychosis-risk syndromes (SIPS). At the onset of our longitudinal study, we gathered demographics, signs and symptoms, and descriptions of VI and VB. One-third of participants reported VI (n = 65, 32.5%) at baseline, experienced as intrusive and ego-dystonic, and associated with higher suspiciousness and overall positive symptoms. Less than one-tenth reported VB within 6 months of baseline (n = 17, 8.5%), which was unrelated to SIPS-positive symptoms, any DSM diagnosis or other clinical characteristic. The period from conversion through post-FEP stabilization may be characterized by heightened risk of behavioral disinhibition and violence. We provide a preliminary model of how violence risk may peak at various points in the course of psychotic illness.


Marked increases in DT diaphorase activity in malignantly transformed Syrian hamster fibroblastic cells.
NAD(P)H quinone oxidoreductase (DT diaphorase; EC 126.96.36.199) activity in cultured Syrian hamster fibroblastic cells was measured. The cells examined were classified into three categories: (1) four primary embryonic fibroblasts, (2) three non-malignant immortal cells and (3) four malignantly transformed cells. The results showed that cytosolic DT diaphorase activity in malignant cells was markedly higher than the corresponding activity in non-malignant cells (enzyme activity: (3) much greater than (1) greater than or equal to (2)). The enzyme activity was not influenced very much by the particular phase of cell growth. Thus, the increase in DT diaphorase activity seems to be a good marker for malignant transformation, at least in Syrian hamster fibroblastic cells.


Evaluating the Risk of Digitalis Intoxication Associated With Concomitant Use of Dronedarone and Digoxin Using Real-World Data.
Dronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein. Using real-world data, we evaluated the risk of digitalis intoxication in concomitant users of dronedarone and digoxin compared digoxin-alone users. We used the Clinformatics DataMart, a US claims database, to identify adult patients with atrial fibrillation (AF) or atrial flutter (AFL) who concomitantly used dronedarone and digoxin and those who used digoxin alone between July 2009 and March 2016. Digitalis intoxication during follow-up until March 2016 was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Adjusted hazard ratios (HR) for digitalis intoxication in concomitant users versus users of digoxin alone were estimated, controlling for age, sex, cohort entry year, number of medical encounters for AF or AFL, history of congestive heart failure, diabetes, hypertension, stroke, myocardial infarction, renal failure, use of drugs interacting with digoxin, and digoxin dose. Overall, 524 concomitant users and 32,459 users of digoxin alone were identified, among which 3 and 301 events of digitalis intoxication occurred during follow-up, respectively. Incidence rates were 17.25 and 9.17 cases per 1000 person-years, respectively. The adjusted HR for digitalis intoxication in concomitant users versus users of digoxin alone was 1.56 (95% CI, 0.50-4.88; P = 0.45). When digitalis intoxication was defined by ICD-9-CM and ICD-10-CM codes accompanied by laboratory testing for digoxin/digitoxin or hospitalization within 30 days, no events occurred in the concomitant users and 40 events occurred in the users of digoxin alone (incidence rate of 1.22 cases per 1000 person-years). Concomitant use of dronedarone and digoxin was uncommon in this study, and no significant increase in the risk of digitalis intoxication with concomitant use was found.


[Computer visual syndrome and occupational ophthalmopathy in PC operators].
Information technologies development resulted in occupational ophthalmopathy in PC users. The article covers criteria to define the risk group for prevention and rehabilitation measures.


Expression and localization of aromatase P450AROM, estrogen receptor-α, and estrogen receptor-β in the developing fetal bovine frontal cortex.
The enzyme aromatase (P450(AROM)) converts testosterone (T) into 17-β estradiol (E(2)) and is crucial for the control of development of the central nervous system during ontogenesis. The effects of E(2) in various brain areas are mediated by the estrogen receptor alpha (ER-α) and the estrogen receptor beta (ER-β). During fetal development, steroids are responsible for the sexual differentiation of the hypothalamus. Estrogens are also able to exert effects in other brain areas of the fetus including the frontal cortex, where they act through estrogen receptors (ERs) modulating cognitive function and affective behaviors. In this study we have determined the expression profiles of P450(AROM) and ERs in the fetal bovine frontal cortex by quantitative Real-Time PCR (qRT-PCR) throughout the prenatal development. The data show that the patterns of expression of both ERs are strongly correlated during pregnancy and increase in the last stage of gestation. On the contrary, the expression of P450(AROM) has no correlation with ERs expression and is not developmentally regulated. Moreover, we performed immunochemical studies showing that fetal neurons express P450(AROM) and the ERs. P450(AROM) is localized in the cytoplasm and only seldom present in the fine extensions of the cells; ER-α is detected predominantly in the soma whereas ER-β is only present in the nucleus of a few cells. This study provides new data on the development of the frontal cortex in a long gestation mammal with a large convoluted brain.


Antinociceptive effect of the hydroalcoholic extract of Bauhinia splendens stems in mice.
The analgesic effect of the hydroalcoholic extract of the stems of Bauhinia splendens (Leguminosae) has been investigated in chemical and thermal models of nociception in mice. The hydroalcoholic extract of B. splendens, 3-60 mg kg-1 intraperitoneally or 50-400 mg kg-1 orally, caused dose-related, and long-lasting (up to 3 h) inhibition of acetic acid-induced abdominal constriction in mice, with ID50 values of 3.2 and 177.6 mg kg-1 and maximum inhibition of 95 +/- 2 and 61 +/- 6%, respectively. In the formalin test, the extract given intraperitoneally (1-60 mg kg-1) or orally (50-400 mg kg-1) caused graded inhibition of both phases of formalin-induced pain, being about 5- to 6-fold more potent in attenuating the second phase of pain. The calculated mean ID50 values for the first and the second phases were 11.5 and 2.5 mg kg-1, respectively, for intraperitoneal administration and > 200 and 70 mg kg-1, respectively, for oral administration; the percentages of maximum inhibition for the first and the second phases were 68 +/- 6 and 99 +/- 1, respectively, for intraperitoneal administration and 37 +/- 6 and 69 +/- 9, respectively, for oral administration. However, at the same doses the extract did not significantly affect the oedematogenic response induced by formalin. The treatment of animals with naloxone (5 mg kg-1, i.p.) completely reversed the analgesic effect caused by morphine (5 mg kg-1, s.c.), but had no effect against the antinociceptive effect of the hydroalcoholic extract of B. splendens (60 mg kg-1, i.p.) when assessed against acetic acid-induced abdominal constrictions. Furthermore, the extract, in contrast with morphine, had no analgesic effect in the hot-plate test. These data show that the hydroalcoholic extract of B. splendens has significant analgesic action when assessed against several models of pain. The mechanism underlying its analgesic effect still remains unknown, but seems to be unrelated to interaction with opioid systems.


Effect of thalidomide on endostatin levels in retinal ischemia/reperfusion injury.
To evaluate the effects of thalidomide treatment on endostatin production in ischemia/reperfusion-injured guinea pigs retinas. Control, ischemia, thalidomide/ischemia groups including 7 animals in each were formed from pigmented male guinea pigs. Retinal ischemia was induced by cannulating anterior chambers and lifting the bottle to a height of 205 cm for 90 min in the ischemia and thalidomide/ischemia groups. The thalidomide/ischemia group received thalidomide (300 mg/kg/day) via nasogastric tube 24 h before ischemia and during 7 days of reperfusion. Guinea pigs were sacrified for biochemical analysis of retinal endostatin level by ELISA. The mean retinal endostatin levels of the control, ischemia and thalidomide/ischemia groups were 11.79 +/- 7.36, 14.70 +/- 4.88, 30.94 +/- 15.59 ng/ml, respectively. The mean retinal endostatin level of the thalidomide/ischemia group was significantly higher than that of the control group (p = 0.011). The mean retinal endostatin level of the thalidomide/ischemia group was higher than that of the ischemia group, but there was no statistically significant difference (p = 0.073). No statistically significant difference in the mean retinal endostatin level was found between the control and ischemia groups (p = 0.165). Thalidomide treatment increased retinal endostatin level in ischemia/reperfusion-injured guinea pig retinas.