Testing the paradigm that the denaturing effect of urea on protein stability is offset by methylamines at the physiological concentration ratio of 2:1 (urea:methylamines).
The intra- and extracellular urea concentration in many organisms is sufficiently high to destabilize (inhibit) many proteins, yet organisms survive and function. The generally accepted explanation is the counteracting hypothesis, which holds that methylamines stabilize proteins and oppose the deleterious effect of urea. The two osmolytes are typically found at 2:1 concentration ratio (urea:methylamine) under physiological conditions. Does this mean that this ratio holds for all proteins in a cell? The present study tests the counteracting hypothesis by determining the effects of urea and methylamines (trimethylamine N-oxide and sarcosine), singly and in combination at a concentration ratio of 2:1 (urea:methylamine) on the thermal denaturation equilibrium, native state<-->denatured state of three different proteins (alpha-lactalbumin, lysozyme and Ribonuclease-A). We show here that the molar concentration of a methylamine required to offset the denaturing effect of urea at a given concentration is different for different proteins.


Effects of percutaneous needle liver biopsy on dairy cow behaviour.
In cattle, percutaneous needle liver biopsy is used for scientific examination of liver metabolism. The impact of the biopsy procedure is, however, poorly investigated. Our aim was to examine the behaviour of dairy cows during and after liver biopsy. Data were collected from 18 dry cows. Percutaneous needle liver biopsies (after administration of local anaesthesia (2% Procaine)) and blood samples were taken during restraining. During the control treatment, animals were restrained and blood sampled. During the biopsy procedure, cows showed increased restlessness (P=0.008), frequency of head shaking (P=0.016), and decreased rumination (P=0.064). After biopsies, tail pressing (P=0.016) and time spent perching (P=0.058) increased. Time spent upright (P=0.10) and number of leg movements (P=0.033) increased during the night as compared to controls. Thus, liver biopsy induced behavioural changes for up to 19 h--and particularly for behaviour previously associated with pain. Even though the exact welfare impact of percutaneous needle liver biopsies in cows is not known, and the magnitude of the behavioural changes was limited, pain always has negative effects on animal welfare. Therefore, if the present biopsy procedure--involving several biopsy passes--is to be used, improvement of the anaesthetic protocol as well as the inclusion of analgesics should be considered.


Atlantic cod (Gadus morhua) embryos are highly sensitive to short-term 3,4-dichloroaniline exposure.
3,4-dichloroaniline (3,4-DCA) is one of the most widely produced anilines world-wide, used in plastic packaging, fabrics, pharmaceuticals, pesticides, dyes and paints as well as being a degradation product of several pesticides. 3,4-DCA has been detected in freshwater, brackish and marine environments. Although freshwater toxicity thresholds exist, very little toxicological information is available on marine and cold-water species. In this study, we exposed Atlantic cod (Gadus morhua) embryos (3-7 days post fertilization) to 3,4-DCA concentrations ranging from 8-747 μg/L for 4 days followed by a recovery period in clean sea water until 14 days post fertilization (dpf). The cod embryos were significantly more sensitive to acute 3,4-DCA exposure compared to other species tested and reported in the literature. At the highest concentration (747 μg/L), no embryos survived until hatch, and even at the lowest concentration (8 μg/L), a small, but significant increase in mortality was observed at 14 dpf. Delayed and concentration-dependent effects on surviving yolk-sac larvae, manifested as cardiac, developmental and morphometric alterations, more than a week after exposure suggest potential long-term effects of transient embryonic exposure to low concentrations of 3,4-DCA.


Prognostic factors for recurrence and survival in axillary node-negative breast cancer.
The question of which node-negative breast cancer patients should be treated with adjuvant systemic therapy is a debatable topic. Our approach in San Antonio is to examine the risk profile for an individual patient and attempt to classify the patient into a good risk group or a high risk group in terms of disease recurrence. Features such as small tumor size (less than 2 cm), diploid tumors with low proliferative rate, and nuclear grade I, all indicate a good prognosis with a disease-free survival of approx. 90% at 5 yr. Examination of the cost vs benefits in this category of patients suggest that routine treatment with systemic adjuvant therapy is not appropriate.


Effect of Lipid-Encapsulated Acacia Tannin Extract on Feed Intake, Nutrient Digestibility and Methane Emission in Sheep.
Tannins have become important phytochemicals in ruminant production, due to their wide range of biological activities. The use of a crude extract often comes with limitations, such as reduced feed intake and fibre digestibility, which could be overcome by the use of encapsulated tannin extract. In this study, four rumen-cannulated Merino wethers were used in a 4 × 4 Latin square design to determine the effect of encapsulating Acacia mearnsii tannin extract on intake, nutrient digestibility, and methane emission. The animals were placed on one of the following diets: control diet only, diet + silvafeed (Silvafeed ByPro, 10 g/kg feed), diet + Acacia tannin extract (ATE), 40 g/kg feed), and, diet + lipid-encapsulated-ATE (palm oil encapsulated ATE, 50 g/kg feed) in 4 cycles. Wethers were offered an Eragrotis and Lucerne hay-based total mixed ration diet above maintenance requirement with forage: concentrate ratio 50:50. Silvafeed, a commercial tannin additive, was used as a positive control. Nutrient intake was not different across the treatments, but nutrient digestibility was affected by dietary additives (p < 0.05). Compared to the control, and unlike the crude extract, encapsulated-ATE and silvafeed did not reduce dry matter, organic matter, and neutral detergent fibre digestibility. While the overall N-retention and total N-excretion (g/d) were not affected by dietary additives, ATE and encapsulated-ATE diets reduced urine-N excretion (g/d) and only a slight reduction was observed in silvafeed diet. The faecal-N proportion was highest in the ATE diet (388 g/kg N-intake), followed by encapsulated-ATE (317 g/kg), and silvafeed (267 g/kg), with the control diet having the lowest proportion (230 g/kg). The acetate:propionate (A:P) ratio reduced as a result of the inclusion of dietary additives with crude ATE and silvafeed having lower A:P ratio compared to the control diet. Methane production expressed in g/kg dry matter (DM) intake was reduced by 12%, 30% and 19% in the silvafeed, crude ATE and encapsulated-ATE diets, respectively (p < 0.05). The reduced methane production with higher neutral detergent fibre (NDF) digestibility in the encapsulated-ATE, compared to the crude-ATE, confirms that encapsulated-tannin can be used as an additive in ruminant diets.


The identification and treatment of intestinal malrotation in older children.
Intestinal malrotation is often diagnosed in infancy. The true incidence of malrotation outside of this age is unknown. These patients can present atypically or be asymptomatic and diagnosed incidentally. We evaluate the incidence, clinical presentation, ideal imaging, and intra-operative findings of patients with malrotation over 1 year of age. Retrospective review was conducted in patients older than 1 year, treated for malrotation at a single pediatric tertiary care center from 2000 to 2015. Data analyzed included demographics, presentation, imaging, intraoperative findings, and follow-up. Patients predisposed to malrotation were excluded. 246 patients were diagnosed with malrotation, of which 77 patients were older than 1 year of age. The most common presenting symptoms were vomiting (68%) and abdominal pain (57%). The most common method of diagnosis was UGI (61%). In 88%, the UGI revealed malrotation. 73 of 75 were confirmed to have malrotation at surgery. Intra-operatively, 60% were found to have a malrotated intestinal orientation and 33% with a non-rotated orientation. Obstruction was present in 22% with 12% having volvulus. Of those with follow-up, 58% reported alleviation of symptoms. Despite age malrotation should be on the differential given a variable clinical presentation. UGI should be conducted to allow for prompt diagnosis and surgical intervention.


KIF2A deficiency causes early-onset neurodegeneration.
KIF2A is an atypical kinesin that has the capacity to depolymerize microtubules. Patients carrying mutations in KIF2A suffer from progressive microcephaly and mental disabilities. While the role of this protein is well documented in neuronal migration, the relationship between its dysfunction and the pathobiology of brain disorders is unclear. Here, we report that KIF2A is dispensable for embryogenic neurogenesis but critical in postnatal stages for maturation, connectivity, and maintenance of neurons. We used a conditional approach to inactivate KIF2A in cortical progenitors, nascent postmitotic neurons, and mature neurons in mice. We show that the lack of KIF2A alters microtubule dynamics and disrupts several microtubule-dependent processes, including neuronal polarity, neuritogenesis, synaptogenesis, and axonal transport. KIF2A-deficient neurons exhibit aberrant electrophysiological characteristics, neuronal connectivity, and function, leading to their loss. The role of KIF2A is not limited to development, as fully mature neurons require KIF2A for survival. Our results emphasize an additional function of KIF2A and help explain how its mutations lead to brain disorders.


Sacral neuromodulation in the management of non-obstructive urinary retention: Test phase and predictive factors.
The aim of this study is to evaluate the success of the test phase of sacral neuromodulation in management of chronic non-obstructive urinary retention and the factors predictive of good response. This is a retrospective study carried out on a cohort of patients followed up in a tertiary University Hospital in France. Fifty-two patients with chronic non-obstructive urinary retention were included in this study. These patients were seen over the past 20 years, from the year 2000 to 2020. The initial evaluation of patients included a summary of medical and surgical history, age, BMI, history of pelvic floor disorders, initial voiding pattern, physical examination, voiding diary, initial uroflowmetry and a urodynamic study. Postoperative follow-up and analysis of complications were also carried out. A total of 52 patients were included in this study, 13 males and 39 females. Out of these patients, 17 patients (32.7%) with a median age of 47.3 years±18.1 benefited from definitive implantation of the sacral neuromodulation. The univariate analysis showed that age was the only significant variable in this study and the optimal age threshold was<58.5 years. SNM is a therapy with significant clinical benefits and low morbidity for patients with chronic non-obstructive urinary retention. The results obtained need to be confirmed with a prospective study with a larger number of patients.


Designing affinity chromatographic processes for the capture of antibodies. Part I: A simplified approach.
Protein A affinity chromatography is a standard technique for the purification of therapeutic antibodies. Recently, multi-column chromatographic processes have emerged to turn classical capture processes into more efficient and continuous systems. The design of such chromatographic processes, be they single-column or multi-column systems, is described in this work. A rational method to conceive, scale-up and compare processes is proposed and illustrated with different examples. All along this article, the results of the equilibrium theory, i.e. obtained with an infinitely efficient column, are used to normalize the system and propose a frame for a rigorous comparison between the different configurations considered in this work. Then, the impact of the fluid velocity, the column length, the refresh time, the sequence organization and the number of columns on the yield, productivity and fluid requirement is investigated. It is found that the optimal process, in terms of number of columns and residence time, depends in the targeted protein recovery. For instance, when considering a titer of 1g/L, 2 columns connected in series in the loading zone are necessary to reach 90% recovery, 3 columns to reach 95% and 4 columns to obtain 99% recovery.


Detection of systemic immunosuppressants in autologous serum eye drops (ASED) in patients with severe chronic ocular graft versus host disease.
Chronic graft versus host disease is a major consequence after allogeneic stem cell transplantation (allo-SCT) and has great impact on patients' morbidity and mortality. Besides the skin, liver, and intestines, the eyes are most commonly affected, manifesting as severe ocular surface disease. Treatment protocols include topical steroids, cyclosporine, tacrolimus, and ASED. Since these patients often receive systemic immunosuppressant therapy from their oncologists, a topical re-administration of these drugs via ASED with potentially beneficial or harmful effects is possible. The purpose of the study was to determine whether and to which extent systemic immunosuppressants are detectable in ASED. A total of 34 samples of ASED from 16 patients with hemato-oncological malignancies after allo-SCT were collected during the manufacturing process and screened for levels of cyclosporine, mycophenolic acid, everolimus, and tacrolimus via liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The study followed the tenets of the Declaration of Helsinki and informed consent was obtained from the subjects after explanation of the nature and possible consequences of the study. Cyclosporine was found in 18 ASED samples in concentrations ranging from 6.5-105.0 ng/ml (32.0 ± 22.8 ng/ml, mean ± SD). The concentration range of mycophenolic acid in 19 samples was 0.04-25.0 mg/l (4.0 ± 5.4 mg/l, mean ± SD). Everolimus and tacrolimus concentrations were well below the respective limits of quantification (< 0.6 and < 0.5 ng/ml) of the established LC-MS/MS method in all samples. Our study suggests that orally administered cyclosporine and mycophenolic acid for the treatment of systemic GvHD, but not everolimus and tacrolimus, are distinctly detectable in ASED in relevant concentrations. It is highly likely that these agents affect topical therapy of ocular GvHD. However, the extent of this effect needs to be evaluated in further studies.


Quality benchmark for trans-tibial prostheses in low-income countries.
Based on four series of patients (N=141) participating in clinical field testing of prosthetic feet and all provided with trans-tibial prostheses in accordance with the polypropylene component and assembly system developed by the International Committee of the Red Cross (ICRC) a series of quality benchmarks was developed and tested against historical data. The patient compliance demands were set for walking >1 km at 90 +/- 10%, non-users at 5 +/- 5%, discomfort at 10 +/- 10%, pain at 10 +/- 10%, and patient satisfaction at 90 +/- 10%. The technical performance demands were set for good socket fit at 60 +/- 10%, misalignment at 15 +/- 10%, insufficient craftsmanship at 10 +/- 10%, and requirements for socket change at 10 +/- 10%.


Vaccination practices in veterinary medicine: standardization versus tailored to needs?
Significant achievements have been made during the nineteenth century to improve animal health and welfare through vaccination. Vaccination standards and practices will change significantly in the next century. Vaccination programs need to be tailored to each livestock operation or individual animal in accordance with manufacturers' instructions, government regulations, scientific standards, professional organization guidelines, and veterinarian recommendations. Vaccination should always be considered in a population context. A better use of vaccine will require a different approach and a significant investment in research. Finally, all the partners involved in animal health should consider a close collaboration to meet future animal and public health challenges.


The effect of milk supplementation on bone mineral density in postmenopausal Chinese women in Malaysia.
Dietary studies often report low calcium intake amongst post-menopausal Malaysian women and calcium deficiency has been implicated as part of the etiology of age-related bone loss leading to osteoporosis. Therefore, the objective of this study was to examine the effectiveness of high calcium skimmed milk (Anlene Gold, New Zealand Milk, Wellington, New Zealand) to reduce bone loss in Chinese postmenopausal women. Two hundred subjects aged 55-65 years and who were more than 5 years postmenopausal were randomized to a milk group and control group. The milk group consumed 50 g of high calcium skimmed milk powder daily, which contained 1200 mg calcium (taken as two glasses of milk a day). The control group continued with their usual diet. Using repeated measures ANCOVA, the milk supplement was found to significantly reduce the percentage of bone loss at the total body compared to the control group at 24 months (control -1.04%, milk -0.13%; P<0.001). At the lumbar spine, the percentage of bone loss in the control group was significantly higher (-0.90%) when compared to the milk (-0.13%) supplemented group at 24 months (P<0.05). Similarly, milk supplementation reduced the percentage of bone loss at the femoral neck (control -1.21%, milk 0.51%) (P<0.01) and total hip (control -2.17%, milk -0.50%) (P<0.01). The supplemented group did not experience any significant weight gain over the 24 months. The serum 25-hydroxy vitamin D level improved significantly (P<0.01) from 69.1 +/- 16.1 nmol/l at baseline to 86.4 +/- 22.0 nmol/l at 24 months in the milk group. In conclusion, ingestion of high calcium skimmed milk was effective in reducing the rate of bone loss at clinically important lumbar spine and hip sites in postmenopausal Chinese women in Malaysia. Supplementing with milk had additional benefits of improving the serum 25-hydroxy vitamin D status of the subjects.


Generalized linear regression analysis of association of universal helmet laws with motorcyclist fatality rates.
This study evaluates the association of universal helmet laws with U.S. motorcyclist fatality rates from 1993 through 2002 using climate measures as statistical controls for motorcycling activity via quasi-maximum likelihood generalized linear regression analyses. Results revealed that motorcyclist fatalities and injuries are strongly associated with normalized heating degree days and precipitation inches, and that universal helmet laws are associated with lower motorcyclist fatality rates when these climate measures, and their interaction, are statistically controlled. This study shows that climate measures have considerable promise as indirect measures (proxies) of motorcycling activity in generalized linear regression studies.


Spirometric prediction equations and the relationship between metabolic syndrome and spirometric parameters from an island in Fujian, China.
We investigated risk factors for decreased lung function among Chinese island residents (≥30 years) to determine the relationship between metabolic syndrome (MS) and decreased lung function. From October 17, 2011 to November 1, 2011, 2607 residents aged ≥30 years who lived on the Huangqi Peninsula of Fujian were enlisted by random cluster sampling. They completed a questionnaire designed according to the Burden of Obstructive Lung Disease (BOLD) questionnaire, and underwent physical examination, blood test, and lung function evaluation. We constructed spirometric prediction equations for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), determined the lower limits of normal for FVC, FEV1 and FEV1/FVC, and examined the relationship between lung function and MS. Prediction equations for normal island residents were as follows: FVC (L) = -0.023 × age (years) + 0.042 × height (cm) + 0.641 × weight (kg) - 3.607 (males); FVC (L) = -0.017 × age (years) + 0.030 × height (cm) + 0.009 × weight (kg) - 1.741 (females); FEV1 (L) = -0.023 × age (years) + 0.040 × height (cm) + 0.010 × weight (kg) - 2.999 (males); FEV1 (L) = -0.017 × age (years) + 0.026 × height (cm) + 0.007 × weight (kg) -1.135 (females). The odds ratio for MS for increased risk of decreased FVC was 4.623 (95%CI =3.626-5.894, P<0.001), and for increased risk of decreased FEV1 was 3.043 (95%CI =2.447-3.785, P<0.001). MS is a risk factor for decreased lung function in island residents ≥30 years old.


Detection and molecular characterisation of Giardia duodenalis, Cryptosporidium spp. and Entamoeba spp. among patients with gastrointestinal symptoms in Gambo Hospital, Oromia Region, southern Ethiopia.
To assess the prevalence and genetic diversity of the enteric protozoa species G. duodenalis, Cryptosporidium spp. and Entamoeba histolytica in individuals with gastrointestinal symptoms compatible with infections by these pathogens seeking medical attention in a rural area in southern Ethiopia. A total of 92 stool samples were initially screened by direct microscopy and immunochromatography and further confirmed by molecular methods. G. duodenalis-positive samples were molecularly characterised by multilocus genotyping of the glutamate dehydrogenase and β-giardin genes of the parasite. PCR and DNA sequence analysis of the gene encoding the 60-kDa glycoprotein was used for the subtyping of Cryptosporidium isolates. Detection and differential diagnosis of E. histolytica/dispar were conducted by real-time PCR. PCR-based prevalences were 10.9% for G. duodenalis, 1.1% for Cryptosporidium spp. and 3.3% for Entamoeba spp. Seven (four novel and three known) subtypes of G. duodenalis assemblage B were identified at the GDH locus and 5 (one novel and four known) at the BG locus. A novel variant of C. hominis subtype IbA9G3 was also identified. Two Entamoeba isolates were assigned to E. dispar and an additional one to E. histolytica. Although preliminary, our results strongly suggest that giardiasis, cryptosporidiosis and amoebiasis represent a significant burden in Ethiopian rural population.


Enhanced expression of nitric oxide synthase in the early stage after increased pulmonary blood flow in rats.
Evidence that vasodilator nitric oxide mediates normal pulmonary vascular tone has led to the hypothesis that endothelial injury induced by congenital heart disease with increased pulmonary blood flow disrupts these regulatory mechanisms and its associated altered vascular reactivity. Therefore, we hypothesized that increased pulmonary blood flow results in altered expression of endothelial nitric oxide synthase (eNOS). We created an arteriovenous shunt in female Wistar (5-week-old) and measured the change of pulmonary blood flow and pressure immediately after and 1 month after the shunt operation. The protein levels of eNOS in the lung tissues of rats were assessed. The shunt immediately resulted in a significant increase in pulmonary blood flow (16.5 +/- 11.8% , pulmonary artery pressure (2.3 +/- 0.7 mm Hg), and blood O(2) saturation (16.1 +/- 11.8%) in the pulmonary artery. After 4 weeks, there was a significant increase in pulmonary blood flow (30.7 +/- 1.6%), pulmonary artery pressures (4.3 +/- 1.1 mm Hg), and blood O(2) content (43.3 +/- 17.5%). Western blot analysis demonstrated that eNOS protein was increased in the shunt lung 72 h after surgery and recovered to the control level 1 week later. This simple shunt model can induce early upregulation of eNOS expression with increased pulmonary blood flow and pulmonary artery pressure in rats.


TNFalpha in patients with end-stage heart failure on medical therapy or supported by a left ventricular assist device.
In the heart elevated levels of TNFalpha can cause lethal heart failure, like Dilated Cardiomyopathy (DCM). The level of TNFalpha production is in part determined by promoter gene polymorphisms. We investigated whether the TNFalpha promoter gene polymorphism is in this way involved in the outcome of end-stage heart failure and predicts whether patients require left ventricular assist device (LVAD) support or can be kept on medical therapy (MT)while awaiting heart transplantation (HTx). As most patients in this study received a heart transplant, the role of the TNFalpha polymorphisms in transplant rejection was studied as well. In twenty nine patients with DCM, 35 patients with Ischemic Heart Disease (IHD; both on MT), 26 patients on LVAD support and 61 cardiac transplant donors TNFalpha plasma level was detected by EASIA. In both patients groups high levels of TNFalpha plasma levels was observed however, in patients supported by LVAD this increase was much higher compared to patients on MT. Furthermore, this increase seems to be associated with the TNF 1 allele ('G' at position -308) instead of the TNF2 allele (A at position -308). The promoter polymorphisms at positions -238, -244 and -308 were observed by polymerase chain reaction and sequencing. Polymorphism at positions -238, -244 and -308 did not show any relevant differences between the groups. However, at position -308, a trend of a higher incidence of the TNF2 allele (an "A" at position -308) in DCM patients compared to donors was shown. The distribution of the TNF1 and TNF2 alleles was not different in patients on medical therapy compared to the patients supported by a LVAD. No association was found between patients' TNFalpha promoter gene polymorphism and rejection. However, patients that received a donor heart with the TNF2 allele developed more rejection episodes, compared to patients that received a donor heart with the TNF1 allele. TNFalpha levels are high in patients with end-stage heart failure on MT, but even higher in patients on LVAD support. These high TNFalpha plasma levels however, are not correlated with the TNF2 allele but seems to be associated with the TNF1 allele. Furthermore, in HTx the donor TNFalpha gene seem to play a more important role in severity of acute rejection than that of the patient.


Kawasaki Disease: An Autopsy Case Series and Review of the Literature.
Kawasaki disease (KD) is a major cause of acquired heart disease in children, and there is limited information on postmortem findings in the pediatric population in Canada. For a 15-year time span (January 2000-March 2015), we had 2 cases of KD presented to the Department of Forensic Pathology at Hamilton General Hospital. There were common cardiac findings including presence of giant coronary artery aneurysms and microscopic changes occurring within the coronary arteries and the myocardium. Evidence of old infarction was present in both heart specimens, but acute infarction was noted in one of the specimens. This case series documents postmortem findings that outline cardiac complications of KD including aneurysms, thrombotic events, and infarcts. In addition to addressing the medical complications of KD, it is also important to address the psychosocial effect due to its impact on quality of life.


A geometric morphometric analysis of acetabular shape of the primate hip joint in relation to locomotor behaviour.
The description of acetabular shape variation among primates is essential for our understanding of the locomotor behaviour and ecology of both extant and fossil species. In this study, we use two-dimensional geometric morphometrics to examine variation in acetabular shape in human and non-human primates and to determine the degree to which it co-varies with locomotor behaviour, while taking both intra and inter-specific variation into account. To these ends, we examined the acetabulum of 303 left hip bones of 27 extant genera of primates (including humans) with different locomotor behaviours. After accounting for shape variation due to sex, size, and phylogeny, the results confirm that acetabular shape varies significantly across locomotor groups. The two most differentiated locomotor groups are leapers and slow-climbing quadrupeds, which exhibit a unique acetabular shape. Furthermore, the acetabulum of humans differed significantly from all other groups, while no significant differences existed between chimpanzees and gorillas. The most noticeable differences are detected in both cranial and dorsal areas and around the acetabular horns. This variation in acetabular morphology may have biomechanical implications at the level of the hip joint, potentially determining joint range motion and load distribution during locomotion. Given the increasing number of published studies on fossil pelves, our results are widely applicable to fossil analyses, with critical implications for paleoanthropological analyses about the complex locomotor behaviour of fossil specimens and their classification into locomotor groups, which may enhance our understanding of their ecological habits.


Slowing of the time course of the excitation of squid giant axons in viscous solutions.
The time course of excitation of intracellularly perfused squid giant axons was slowed as the solution viscosity was raised by adding neutral molecules, i.e., glucose and glycerol. By twofold increase of the solution viscosity, the duration of action potential was prolonged to 2.7-fold and the maximum rate of rise decreased to one-half. At the same time, the membrane resistance at resting state increased by 60%. These effects were reversible. The time course of inward and outward currents was slowed also. When the solution viscosity increased to twofold, the time to peak inward current increased by 80%, and the amplitudes of peak inward and steady outward currents decreased by 60% and by 70%, respectively. These effects were not specific for the sodium or the potassium channel. Effects of solution viscosity occurred in both hypotonic and hypertonic solutions. Q10 values of temperature dependence of the time course of the action potential were equal in any viscous solutions. These effects in viscous solutions were explained by the change in solution viscosity but not by the change in solution osmolarities, ionic activities, or solution resistivity.


2,4,5,7-Tetranitrofluorescein in solutions: novel type of tautomerism in hydroxyxanthene series as detected by various spectral methods.
Stepwise dissociation and tautomerism of 2,4,5,7-tetranitrofluorescein (TNF) were studied by using vis-spectroscopy in dimethylsulfoxide (DMSO), in aqueous acetone, and in cetyl-trimethylammonium chloride (CTAC) micellar solutions at ionic strength of the bulk phase 4.00M KCl. The pK(a) values in DMSO and 90 mass% (CH3)2CO as well as the 'apparent'pK(a)(a) values of the substance in micellar media were determined spectrophotometrically. The neutral (molecular) form H2R is found to be completely converted into the colorless lactone. Moreover, the lactonic structure, yellow due to 'nitrophenolate' absorption band, predominates also in the case of TNF dianion R2-. Contrary to the unsubstituted fluorescein, and like 2,4,5,7-tetrabromofluorescein (eosin), the monoanion HR- of TNF with lambda(max) 522-525 nm and E(max) approximately (60-62)x10(3) dm(3)mol(-1)cm(-1) exists mainly as a deeply and intensively colored structure with non-ionized carboxylic and ionized hydroxylic group; its fluorescence spectra in various media are registered. In 90% acetone, the Stokes shift is 1.17x10(3)cm(-1), fluorescence lifetime equals 2.3 ns. An extremely expressed trend to dianion-lactone formation of R2- ion of TNF is confirmed in the systems studied. For TNF in DMSO, in aqueous acetone, in surfactant micelles, and in trichloromethane extracts of ionic associatiates with N(n-Bu)4+ and N(n-Hept)4+, the deeply colored 'quinon-phenolate' dianion, typical for all hydroxyxanthenes, is not registered at all. The sequence of dissociation of functional groups in solution is confirmed using IR spectroscopy in DMSO.


Theoretical simulation of ionic transport through a transmembrane channel.
The two-site model of Urry for the ionic conduction through a gramicidin A channel has been confirmed by theoretical calculations, using a method developed at this laboratory, which yields the potential energy profile of the ion along the channel. Preliminary results show that the pore closure could start with the spatial rearrangement of the--HN--CH3 terminal chain under the influence of the ion already in the channel.


Microanalysis of beta-lactam antibiotics and vancomycin in plasma for pharmacokinetic studies in neonates.
Rational dosing of antibiotics in neonates should be based on pharmacokinetic (PK) parameters assessed in specific populations. PK studies of neonates are hampered by the limited total plasma volume, which restricts the sample volume and sampling frequency. Available drug assay methods require large sample volumes and are labor-intensive or time-consuming. The objective of this study was to develop a rapid ultra-performance liquid chromatographic method with tandem mass spectrometry detection for simultaneous quantification of amoxicillin, meropenem, cefazolin, cefotaxime, deacetylcefotaxime, ceftriaxone, and vancomycin in 50 microl of plasma. Cleanup consisted of protein precipitation with cold acetonitrile (1:4) and solvent evaporation before reversed-phase chromatographic separation and detection using electrospray ionization tandem mass spectrometry. Standard curves were prepared over a large dynamic range with adequate limits of quantitation. Intra- and interrun accuracy and precision were within 100% +/- 15% and 15%, respectively, with acceptable matrix effects. Coefficients of variation for matrix effects and recovery were <10% over six batches of plasma. Stability in plasma and aqueous stocks was generally sufficient, but stability of meropenem and ceftriaxone in extracts could limit autosampler capacity. The instrument run time was approximately 3.50 min per sample. Method applicability was demonstrated with plasma samples from an extracorporeal membrane oxygenation-treated neonate. Different beta-lactam antibiotics can be added to this method with additional ion transitions. Using ultra-performance liquid chromatography mass spectrometry, this method allows simple and reliable quantification of multiple antibiotics in 50 microl of plasma for PK studies of neonates.


Predicting the quality of surgical exposure using spatial and procedural features from laparoscopic videos.
PURPOSE : Evaluating the quality of surgical procedures is a major concern in minimally invasive surgeries. We propose a bottom-up approach based on the study of Sleeve Gastrectomy procedures, for which we analyze what we assume to be an important indicator of the surgical expertise: the exposure of the surgical scene. We first aim at predicting this indicator with features extracted from the laparoscopic video feed, and second to analyze how the extracted features describing the surgical practice influence this indicator. METHOD : Twenty-nine patients underwent Sleeve Gastrectomy performed by two confirmed surgeons in a monocentric study. Features were extracted from spatial and procedural annotations of the videos, and an expert surgeon evaluated the quality of the surgical exposure at specific instants. The features were used as input of a classifier (linear discriminant analysis followed by a support vector machine) to predict the expertise indicator. Features selected in different configurations of the algorithm were compared to understand their relationships with the surgical exposure and the surgeon's practice. RESULTS : The optimized algorithm giving the best performance used spatial features as input ([Formula: see text]). It also predicted equally the two classes of the indicator, despite their strong imbalance. Analyzing the selection of input features in the algorithm allowed a comparison of different configurations of the algorithm and showed a link between the surgical exposure and the surgeon's practice. CONCLUSION : This preliminary study validates that a prediction of the surgical exposure from spatial features is possible. The analysis of the clusters of feature selected by the algorithm also shows encouraging results and potential clinical interpretations.


Acupuncture alters pro-inflammatory cytokines in the plasma of maternally separated rat pups.
To investigate the potential alleviating effects of acupuncture on maternal separation (MS)-induced changes in plasma pro-inflammatory cytokine levels of rat pups. On postnatal day 15, rat pups were randomly assigned to 4 groups (n=6 per group) using a random number table: normal, MS, MS with acupuncture stimulation at Shenmen (HT 7) acupoint (MS+HT 7), and MS with acupuncture stimulation at Chengshan (BL 57) acupoint (MS+BL 57) groups. Rat pups in the normal group were housed with their mothers under standard conditions; those in the MS, MS+HT 7 and MS+BL 57 groups were maternally separated and individually maintained. Acupuncture stimulation was performed at HT 7 or BL 57 acupoints once a day for 7 consecutive days. A tail suspension test was performed to measure immobility time of rats and the plasma was collected on postnatal day 21, then levels of corticosterone (CORT), interleukin (IL)-1β, IL-6 and glial cell-derived neurotrophic factor (GDNF) in plasma were measured. Compared with the normal group, the immobility time and the plasma levels of CORT, IL-1β, IL-6 and GDNF in the MS group were significantly increased (P<0.05 or P<0.01). Compared with the MS group, the immobility time and the plasma levels of CORT, IL-1β, IL-6 and GDNF were significantly reduced in the MS+HT 7 group (P<0.05 or P<0.01). Moreover, the immobility time and plasma levels of IL-1β and IL-6 in the MS+HT 7 group were significantly lower than those in the MS+BL 57 group (P<0.05). Acupuncture stimulation at HT 7 can alleviate the behavioral impairment and changes of the cytokines by MS, indicating that acupuncture can help to relieve MS-induced depression.


Predictive value of mechanomyography and accelerometry for pulmonary function in partially paralyzed volunteers.
Accelerometry (ACM) of adductor pollicis muscle has been used for monitoring of neuromuscular blockade but its validity compared with the gold standard, mechanomyography (MMG), has been questioned. During neuromuscular blockade we compared these methods and we assessed pulmonary function. In awake partially paralyzed volunteers we spirometrically assessed pulmonary function every 5 min until recovery. Rocuronium (0.01 mg kg(-1) + 2-10 microg kg(-1) min(-1)) was administered to maintain train-of-four (TOF)-ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The TOF-ratio associated with 'acceptable' pulmonary recovery [forced vital capacity (FVC) and forced inspiratory volume in 1 s (FIV1) of > or =90% of baseline] was calculated using a linear regression model. During 5-min periods of repetitive nerve stimulation we compared the squared residuals of the FVC and FIV1 estimates from TOFACM vs. TOFMMG, and compared variance of values derived from ACM and MMG using Wilcoxon's test. Limits of agreement of TOF-ratio derived from ACM and MMG were wide [0.15+/-0.016 (SD)], and variability of TOFACM exceeded that of TOFMMG[variance: 77+/-105 vs. 51+/-55% (P<0.01)]. Calculated TOF(ACM) and TOFMMG ratios of 0.56 (0.22-0.71) [mean (95%CI) and 0.6 (0.28-0.74)], respectively, predict 'acceptable' (90%) recovery of FVC while FIV1 remains impaired until TOF-ratios of 0.91 (0.82-1.07) and 0.95 (0.82-1.18), respectively. In turn, TOFMMG (TOFACM) of unity predicted 'acceptable' recovery of FVC and FIV1 in 94 (93) % and 68 (73) % of measurements, respectively. Accelerometry predicts effects of relaxation on pulmonary function as valid as the gold standard mechanomyography. We recommend that recovery of TOF ratio to 0.9-1.0 should be used as an indication of sufficient neuromuscular recovery in daily practice.


Calorie restriction can reverse, as well as prevent, aging cardiomyopathy.
Calorie restriction (CR) is the most widely studied intervention protecting from the adverse effects of aging. Almost all prior studies have examined the effects of CR initiated in young animals. Studies examining the effects of CR on development of aging cardiomyopathy found only partial prevention. The major goal of this study was to determine whether CR initiated after aging cardiomyopathy developed could reverse the cardiomyopathy. Aging cardiomyopathy in 2-year-old mice was characterized by reduced left ventricular (LV) function, cardiac hypertrophy, and increased cardiac apoptosis and fibrosis. When short-term (2 months) CR was initiated after aging cardiomyopathy developed in 20-month-old mice, the decrease in cardiac function, and increases in LV weight, myocardial fibrosis and apoptosis were reversed, such that the aging hearts in these mice were indistinguishable from those of young mice or mice where CR was initiated in young mice. If apoptosis was the mechanism for protecting against aging cardiomyopathy, then total myocyte numbers should have reverted to normal with CR, but did not. However, the alterations in cytoskeletal proteins, which contribute to aging cardiomyopathy, were no longer observed with CR. This is the first study to demonstrate complete prevention of aging cardiomyopathy by CR and, more importantly, that instituting this intervention even later in life can rapidly correct aging cardiomyopathy, which could have important therapeutic implications.


Types of adrenocorticoids and their effect on organophosphorus-induced delayed neuropathy in chickens.
The present study examined the effects of a glucocorticoid and a mineralocorticoid on organophosphorus-induced delayed neuropathy (OPIDN) as previous investigations have indicated that an endogenous steroid with both properties could alter this syndrome in chickens. The glucocorticoid triamcinolone and the mineralocorticoid deoxycorticosterone were provided in the diet beginning 1 day before and continuing 10 days after triortho-tolyl phosphate (TOTP, 360 mg/kg po), phenyl saligenin phosphate (PSP, 2.5 mg/kg im), and diisopropyl phosphorofluoridate (DFP, 1 mg/kg sc). In a manner similar to that seen with corticosterone, a low concentration (0.1 ppm) of triamcinolone reduced and a high concentration (10 ppm) exacerbated clinical signs. Concentrations of deoxycorticosterone under 80 ppm also partially delayed or ameliorated ataxia induced by TOTP, PSP, and DFP, but a combination of 0.1 ppm triamcinolone and 80 ppm deoxycorticosterone was not more effective than triamcinolone alone. Peripheral nerve damage was noted in all chickens given organophosphorus compounds, whether or not they had been given corticoids. Both steroids induced hydroxylase activity, but effects on most other enzyme systems examined were unremarkable. High concentrations of triamcinolone (10 ppm) could, however, also reduce liver cytochrome P450 levels and liver cholinesterase activity. Exacerbation of OPIDN was most notable in chickens under highest stress, as indicated by elevated heterophil-to-lymphocyte ratios. The clinical, pathological, biochemical, and hematological indices of exposure to adrenocorticoids and agents inducing OPIDN in chickens were, therefore, similar for both a synthetic glucocorticoid and the endogenous steroid corticosterone.


Six Susceptible-Infected-Susceptible Models on Scale-free Networks.
Spreading phenomena are ubiquitous in nature and society. For example, disease and information spread over underlying social and information networks. It is well known that there is no threshold for spreading models on scale-free networks; this suggests that spread can occur on such networks, regardless of how low the contact rate may be. In this paper, I consider six models with different contact and propagation mechanisms, which include models studied so far, but are apt to be confused. To compare these six models, I analyze them by degree-based mean-field theory. I find that the result depends on the details of contact and propagation mechanism.


Polarization Selective Color Filter Based on Plasmonic Nanograting Embedded Etalon Structures.
In this paper, we propose a polarization-selective color filter that can generate two different color informations simultaneously depending on the polarization direction. The proposed color filter is mainly composed of the etalon structure to generate the color by the structural resonance properties while the upper layer of the etalon is made of plasmonic nanogratings to promote polarization-dependent color properties. When the duty ratio of the silver nanogratings is fixed, the proposed color filter can maintain identical optical properties for orthogonal polarization, while the etalon structure of the proposed color filter can manipulate different color information depending on the cavity height for the horizontal polarization. Finally, we experimentally confirm that polarization-dependent security images can be generated using the proposed color filters with a fixed duty ratio of various nanograting arrays.


Auxiliary Ca(2+) channel subunits: lessons learned from muscle.
Voltage-gated Ca(2+) channels are multi-subunit complexes involved in many key functions of excitable cells. A multitude of studies in heterologous cells demonstrated that coexpression of the pore-forming alpha(1) subunits with auxiliary alpha(2)delta and beta subunits promotes membrane expression and modulates the biophysical channel properties. New null-mutant animal models and shRNA based knockdown experiments in skeletal muscle cells for the first time demonstrated the physiological roles and possible pathological effects of the alpha(2)delta-1 and beta(1a) subunits in a differentiated excitable cell. The alpha(2)delta-1 subunit is the determinant of the typical current properties of skeletal and cardiac muscle Ca(2+) channels. The beta(1a) subunit links the skeletal muscle Ca(2+) channel to the Ca(2+) release channel in the sarcoplasmic reticulum. Whether these specific functions in muscle indicate similar roles of alpha(2)delta and beta subunits as functional modulator and structural organizer, respectively, in neurons is being discussed.


Tailoring the Acidity of Liquid Media with Ionizing Radiation: Rethinking the Acid-Base Correlation beyond pH.
Advanced in situ techniques based on electrons and X-rays are increasingly used to gain insights into fundamental processes in liquids. However, probing liquid samples with ionizing radiation changes the solution chemistry under observation. In this work, we show that a radiation-induced decrease in pH does not necessarily correlate to an increase in acidity of aqueous solutions. Thus, pH does not capture the acidity under irradiation. Using kinetic modeling of radiation chemistry, we introduce alternative measures of acidity (radiolytic acidity π* and radiolytic ion product KW*), that account for radiation-induced alterations of both H+ and OH- concentration. Moreover, we demonstrate that adding pH-neutral solutes such as LiCl, LiBr, or LiNO3 can trigger a significant change in π*. This provides a huge parameter space to tailor the acidity for in situ experiments involving ionizing radiation, as present in synchrotron facilities or during liquid-phase electron microscopy.


How Trainees Come to Trust Supervisors in Workplace-Based Assessment: A Grounded Theory Study.
In competency-based medical education, workplace-based assessment provides trainees with an opportunity for guidance and supervisors the opportunity to judge the trainees' clinical practice. Learning from assessment is enhanced when trainees reveal their thinking and are open to critique, which requires trust in the assessor. If supervisors knew more about how trainees come to trust them in workplace-based assessment, they could better engender trainee trust and improve trainees' learning experience. From August 2018 to September 2019, semistructured interviews were conducted with 17 postgraduate anesthesia trainees across Australia and New Zealand. The transcripts were analyzed using constructivist grounded theory methods sensitized by a sociocultural view of learning informed by Wenger's communities of practice theory. Participants described a continuum from a necessary initial trust to an experience-informed dynamic trust. Trainees assumed initial trust in supervisors based on accreditation, reputation, and a perceived obligation of trustworthiness inherent in the supervisor's role. With experience and time, trainees' trust evolved based on supervisor actions. Deeper levels of trainee trust arose in response to perceived supervisor investment and allowed trainees to devote more emotional and cognitive resources to patient care and learning rather than impression management. Across the continuum from initial trust to experience-informed trust, trainees made rapid trust judgments that were not preceded by conscious deliberation; instead, they represented a learned "feel for the game." While other factors are involved, our results indicate that the trainee behavior observed in workplace-based assessment is a product of supervisor invitation. Supervisor trustworthiness and investment in trainee development invite trainees to work and present in authentic ways in workplace-based assessment. This authentic engagement, where learners "show themselves" to supervisors and take risks, creates assessment for learning.


Optimized technical considerations for acquiring high-quality FDG studies with a dual-headed gamma camera.
This retrospective analysis was designed to optimize the parameters and techniques required to successfully perform high-quality coincidence imaging in a general nuclear medicine department using a dual-headed gamma camera. Coincidence imaging was performed on 33 patients after an intravenous injection of 3.0-5.0 mCi fluoro-2-deoxyglucose (18F-FDG). Data for all subjects were evaluated to determine which technical considerations contributed to an overall improvement in image quality. After reviewing the data for the 33 subjects, several modified techniques were implemented and parameters were adjusted that enhanced the overall quality of the images. The extremely short half-life of 18F restricts the opportunity to repeat studies that were delayed, interrupted or technically substandard. The review of the data indicated that strict adherence to protocol is necessary to achieve optimal results while attempting to incorporate this new imaging modality into a typical nuclear medicine department.


Poststroke arm and hand paresis: should we target the cervical spinal cord?
Despite advances in understanding of corticospinal motor control and stroke pathophysiology, current rehabilitation therapies for poststroke upper limb paresis have limited efficacy at the level of impairment. To address this problem, we make the conceptual case for a new treatment approach. We first summarize current understanding of motor control deficits in the arm and hand after stroke and their shared physiological mechanisms with spinal cord injury (SCI). We then review studies of spinal cord stimulation (SCS) for recovery of locomotion after SCI, which provide convincing evidence for enhancement of residual corticospinal function. By extrapolation, we argue for using cervical SCS to restore upper limb motor control after stroke.


Prevalence of psychiatric symptoms and associated factors in the adult population from the area affected by the tailings dam rupture - Brumadinho Health Project.
To examine the prevalence of psychiatric symptoms and associated factors in the adult population of Brumadinho (MG), after the dam collapse. We included 2,740 participants with information about symptoms of post-traumatic stress disorder (PTSD), depression, anxiety, thoughts of death/self-harm, and poor sleep quality collected in 2021. Prevalence values of all conditions were estimated to compare the prevalence of psychiatric symptoms with the participants' sociodemographic characteristics and place of residence. Pearson's c2 test was used, with Rao Scott's correction. Crude and adjusted logistic regressions estimated odds ratios and 95% confidence intervals to assess the association between psychiatric symptoms and participants' characteristics. The most common condition was depressive symptoms (29.3%), followed by post-traumatic stress symptoms (22.9%) and anxious symptoms (18.9%). Regarding the association between participants' characteristics in the adjusted analysis, being a female and living in a mining area was positively associated with symptoms of PTSD, depression, anxiety, thoughts of death/self-harm, and poor sleep quality. A positive association was also found between high school education and post-traumatic stress symptoms. In contrast a negative association was found between being aged ≥60 years and symptoms of PTSD, depression, and anxiety. High prevalence values were found for all psychiatric symptoms after the dam failure in Brumadinho. Being a female, living in the mining area, being ≥60 years old, and having an educational level were all associated with the psychiatric symptoms investigated.


How perceived overqualification affects radical creativity: the moderating role of supervisor-subordinate guanxi.
This study aims to investigate the effect of perceived overqualification on radical creativity. Drawing on the conservation of resources (COR) theory, this study examined the mediating role of job crafting and the moderating role of supervisor-subordinate guanxi. Through the two-wave pre-test of 312 employees, we found that the scale reliability and validity of all variables in this study were good. According to the pre-test results, we modified the expressions of some items to obtain a more concise and effective questionnaire for the formal survey, so as to ensure the conclusions more reliable. And using two-wave survey data from 1007 employees among Chinese local organizations in the formal test to examine the hypotheses. The results indicated that perceived overqualification negatively affects radical creativity, and job crafting mediates the relationship. In addition, supervisor-subordinate guanxi reduces the effect of perceived overqualification on job crafting and the indirect effect of perceived overqualification on radical creativity via job crafting. Theoretical and practical implications are discussed.


Development and evaluation of a teaching and learning approach in cross-cultural care and antidiscrimination in university nursing students.
Cross-cultural care and antidiscrimination are vital to ethical effective health systems. Nurses require quality educational preparation in cross-cultural care and antidiscrimination. Limited evidence-based research is available to guide teachers. To develop, implement and evaluate an evidence-based teaching and learning approach in cross-cultural care and antidiscrimination for undergraduate nursing students. A quantitative design using pre- and post-survey measures was used to evaluate the teaching and learning approach. The Bachelor of Nursing program in an Australian university. Academics and second year undergraduate nursing students. A literature review and consultation with academics informed the development of the teaching and learning approach. Thirty-three students completed a survey at pre-measures and following participation in the teaching and learning approach at post-measures about their confidence to practice cross-cultural nursing (Transcultural Self-efficacy Tool) and about their discriminatory attitudes (Quick Discrimination Index). The literature review found that educational approaches that solely focus on culture might not be sufficient in addressing discrimination and racism. During consultation, academics emphasised the importance of situating cross-cultural nursing and antidiscrimination as social determinants of health. Therefore, cross-cultural nursing was contextualised within primary health care and emphasised care for culturally diverse communities. Survey findings supported the effectiveness of this strategy in promoting students' confidence regarding knowledge about cross-cultural nursing. There was no reported change in discriminatory attitudes. The teaching and learning approach was modified to include stronger experiential learning and role playing. Nursing education should emphasise cross-cultural nursing and antidiscrimination. The study describes an evaluated teaching and learning approach and demonstrates how evaluation research can be used to develop cross-cultural nursing education interventions.


The role of executive functions and theory of mind in children's prosocial lie-telling.
Children's prosocial lying was examined in relation to executive functioning skills and theory of mind development. Prosocial lying was observed using a disappointing gift paradigm. Of the 79 children (ages 6-12 years) who completed the disappointing gift paradigm, 47 (59.5%) told a prosocial lie to a research assistant about liking their prize. In addition, of those children who told prosocial lies, 25 (53.2%) maintained semantic leakage control during follow-up questioning, thereby demonstrating advanced lie-telling skills. When executive functioning was examined, children who told prosocial lies were found to have significantly higher performance on measures of working memory and inhibitory control. In addition, children who lied and maintained semantic leakage control also displayed more advanced theory of mind understanding. Although children's age was not a predictor of lie-telling behavior (i.e., truthful vs. lie-teller), age was a significant predictor of semantic leakage control, with older children being more likely to maintain their lies during follow-up questioning.


Effect of two synthetic disulfide bond variants of a 13-mer toxin from Conus californicus on the transcription of pro-inflammatory cytokines induced by LPS.
This study presents the effects of two synthetic disulfide bond variants of cal16b, a 13-mer Ca²⁺ channel blocker conotoxin, on pro- and anti-inflammatory cytokine gene transcription in the murine macrophage-like cell line J774A.1 stimulated with LPS. The globular form (cal16b_1) acted as an anti-inflammatory agent; in contrast, the ribbon disulfide variant (cal16b_2) had a pro-inflammatory effect. Our results suggest that the pro- and anti-inflammatory effects are mediated by the three-dimensional structure.


Comprehensive analysis of the differential expression profile of microRNAs in missed abortion.
To screen the key circulating microRNAs (miRNAs) involved in missed abortion (MA) and explore their role in MA process. We examined the miRNA profile from the serum of three MA patients and three early pregnancy induced abortion patients (controls) by next-generation sequencing. We analyzed the target genes of the differentially expressed (DE) miRNAs to analyze the function and pathway enrichment using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, respectively. We validated five candidate miRNAs by real time-qPCR. Integrated miRNA-mRNA-pathway network analysis was performed to show the interaction network of the candidate miRNAs and their target genes of interest with the involved pathways. It was observed that 227 miRNAs were differently expressed between the MA group and the early pregnancy control group, with 58 miRNAs downregulated and 169 miRNAs upregulated in the MA group. Real-time qPCR results revealed that expression of the five candidate miRNAs, namely hsa-miR-22-3p, hsa-miR-145-3p, hsa-miR-107, hsa-miR-361-3p, and hsa-miR-378c, was consistent with the miRNA data obtained by sequencing. Integrated miRNA-mRNA-pathway network analysis illustrated that target genes of the candidate miRNAs were mainly involved in the PI3K-Akt signaling pathway, HIF-1 signaling pathway, and VEGF signaling pathway, which would have potential significance in pregnancy and MA. We are the first to reveal the DE miRNAs involved in MA and illustrate their functional interaction network. These results might provide potential circulating biomarkers and new therapeutic targets for MA.


[Comparative study of the brain of developed and underdeveloped neonatal rodents of the Muridae family].
Morphological studies have been made of the neocortical and archicortical structures in the spiny mouse Acomys cahirinus, the only maturely born species from the family Muridae. The data obtained reveal highly developed hippocampus as compared to the neocortex in this mouse, in contrast to relationships found in other mice and rats.


A canine model of gastroesophageal reflux disease (GERD).
Although a variety of antireflux procedures and medications are used to treat gastroesophageal reflux disease (GERD), reliable large-animal models of GERD that can be used to objectively compare the efficacy of these treatments are lacking. Esophageal manometry and 24-h gastroesophageal pH monitoring with event data were performed in 18 mongrel dogs with a cervical esophagopexy. We then calculated a modified DeMeester score: The Duke Canine reflux score (DCR). Thereafter, the animals underwent a 4-cm anterior distal esophageal myotomy, incision of the left diaphragmatic crus, and intrathoracic gastric cardiopexy. Postoperative 24-h pH and manometry were obtained 2 weeks later. The postoperative 24-h pH results showed a significant increase in the mean DCR score (5.9 +/- 4.5 vs 84.9 +/- 56.1, p < 0.0002), and manometry indicated a significant decrease in mean lower esophageal sphincter (LES) pressure (7.1 +/- 2.9 vs 3.2 +/- 2.5 mmHg, p < 0.0001). This technique reliably creates a canine model of GERD.


Genomic DNA sequencing by SPEL-6 primer walking using hexamer ligation.
DNA sequencing by SPEL-6 (Sequential Primer Elongation by Ligation of 6-mers) primer walking is based on the rapid assembly of true primers by ligation of several (three to 10) contiguous hexamers complementary to a DNA template saturated with Escherichia coli single-stranded DNA-binding protein. To prove the usefulness and to check the reliability of this method, a 3-kb DNA fragment carrying the genes encoding the EcoVIII restriction-modification (RM) system was sequenced with low redundancy (2.8). The use of both single-stranded (ss) and double-stranded (ds) DNA templates was compared. For this project, 27 primers were assembled by hexamer ligation to form 18-30-nt strings of three to five hexamers. Each primer was designed based on nucleotide sequence determined in a previous run, and was produced in a matter of minutes. The overall length of the easily readable sequencing ladders was about 300-450nt. We found that strong secondary structures in the ss DNA tend to interfere with its template function for the primer assembly by hexamer ligation, especially when they overlap the 3'-end of such a primer. This was easily overcome either by avoiding such hairpin regions or by using longer strings of hexamers, since we show that their ligation is highly cooperative, and ligation efficiency increases with the length of the string (). Some general rules for successful primer assembly and prospects for using the SPEL-6 method for large-scale, fully automated fluorescent sequencing of large genomes are discussed.


Effect of splenectomy on gram-negative bacterial clearance in the presence and absence of sepsis.
Severe sepsis leads to depression of the reticulo-endothelial system (RES) with delayed bloodstream clearance of particulate matter and bacteria. Splenectomy results in increased susceptibility to infection with encapsulated organisms but its effect on the resistance to postoperative Gram-negative infection has been little studied. We have investigated the effect of splenectomy on RES function by measurement of plasma fibronectin concentrations and bacterial clearance in the presence and absence of sepsis. In experiment 1, rabbits underwent splenectomy (n = 8) or laparotomy only (n = 8) 4 weeks before a second laparotomy. In experiment 2, animals had either splenectomy (n = 8) or laparotomy only (n = 8) followed 4 weeks later by devascularization of the appendix (sepsis). Plasma fibronectin concentrations and the blood clearance and organ distribution of an intravenous injection of 75Se-labelled viable Escherichia coli (2-3 X 10(8) colony forming units (c.f.u.] were measured 24 h after the second operation. Splenectomy resulted in: (1) a persistent reduction in plasma fibronectin concentration in the presence and absence of sepsis, and (2) a delay in the bloodstream clearance with reduced hepatic (Kupffer cell) uptake of E. coli which was exaggerated in the septic splenectomized animal. It is concluded that the spleen may be important for Gram-negative bacterial clearance, possibly related to its influence on plasma fibronectin concentration and Kupffer cell function.


[Shifts in systemic hemodynamics, local blood flow and brain temperature during stimulation of its structures in a chronic experiment].
Electric stimulation of the midbrain reticular formation, of the anterior and posterior hypothalamus of unrestrained cats entailed local raise of cerebral temperature, increase in the local blood flow, and various changes of the central arterial and venous pressure. The stimulation parameters were lower than thresholds for motor responses. The threshold and suprathreshold stimulation of the stem structures led in 60% of cases to diminishing of the local cerebral blood flow together with the pressor shifts in arterial pressure and the raise of local cerebral temperature. The diminishing of the cerebral blood flow contrdictory to increasing demands of the brain tissue for energy supply, could be accounted for by the generalized excitation of the sympatho-adrenal system and indicated inadequacy of the electric brain stimulation when studying hemodynamic components of the emotional-behavioral responses.


A Systematic Review of Team Training in Health Care: Ten Questions.
As a result of the recent proliferation of health care team training (HTT), there was a need to update previous systematic reviews examining the underlying structure driving team training initiatives. This investigation was guided by 10 research questions. A literature search identified 197 empirical samples detailing the evaluation of team training programs within the health care context; 1,764 measures of HTT effectiveness were identified within these samples. Trained coders extracted information related to study design and training development, implementation, and evaluation to calculate percentages detailing the prevalence of certain training features. HTT was rarely informed by a training needs analysis (k = 47, 23.9%) and most commonly addressed communication strategies (k = 167, 84.8%). HTT programs that incorporated practice (k = 163, 82.7%) often employed high-fidelity patient simulators (k = 38, 25.2%) and provided participants with feedback opportunities (k = 107, 65.6%). Participants were typically practicing clinicians (k = 154, 78.2%) with a lower prevalence of health care students (k = 35, 17.8). Evaluations primarily relied on repeated measures designs (k = 123, 62.4%) and self-reported data (k = 1,257, 71.3%). Additional trends were identified and are discussed. Many trends in HTT practice and evaluation were identified. The results of this review suggested that, in the literature, HTT programs are more frequently following recommendations for training design and implementation (for example, providing feedback) in comparison to findings from previous reviews. However, there were still many areas in which improvement could be achieved to improve patient care.


The clinical performance of primary HPV screening, primary HPV screening plus cytology cotesting, and cytology alone at a tertiary care hospital.
Algorithms for primary human papillomavirus (HPV) screening, primary HPV screening plus cytology cotesting, and cytology alone were evaluated previously in large cohort trials for cervical cancer detection, although the quality of cytology in those studies was controversial. To investigate whether these 3 algorithms would be applicable in routine practice at a tertiary care hospital, the authors compared their clinical performance. In addition, the prevalence of HPV genotypes was determined. Cervical cytology samples (n = 1000) were tested using liquid-based cytology (LBC), a nucleic acid hybridization assay, real-time polymerase chain reaction analysis, and direct HPV DNA sequencing. The clinical performance of the 3 algorithms was compared among women in different age groups (age range, 17-86 years; median age, 44.7 years). For cervical intraepithelial neoplasia grade 2 or worse (CIN 2+), the sensitivity of primary HPV screening alone, cotesting, and LBC alone was 71.7%, 72.5%, and 63.8%, respectively; whereas the specificity was 87.5%, 96.5%, and 97.4%, respectively. Cotesting and LBC alone had slightly higher positive predictive values for CIN 2 + (97.8% and 98.9%, respectively) than primary HPV screening alone (91%), whereas primary HPV screening alone and cotesting demonstrated higher negative predictive values (63.6% and 62.5%, respectively) than LBC alone (43.2%). High-risk HPV types were detected in 24.3% of individuals. The most common type was HPV type 16 (HPV-16) followed by multiple HPV infections and HPV-58, HPV-52, HPV-31, HPV-35, HPV-51, HPV-39, HPV-56, HPV-33, HPV-18, HPV-59, and HPV-45. Primary HPV screening alone in a tertiary care hospital demonstrated a performance that was equivalent to that of cotesting for CIN 2+, irrespective of patient age. With regard to the distribution of HPV genotypes, the nonavalent HPV vaccine would prevent approximately 60% of high-risk HPV.


Predictive scoring systems for molecular responses in persons with chronic phase chronic myeloid leukemia receiving initial imatinib therapy.
It is vital for physicians and persons with chronic myeloid leukemia (CML) to accurately predict the likelihood of achieving a major molecular response (MMR) and a deep molecular response (DMR; at least MR4) at the start of imatinib-therapy, which could help in decision making of treatment goals and strategies. To answer this question, we interrogated data from 1369 consecutive subjects with chronic phase CML receiving initial imatinib-therapy to identify predictive co-variates. Subjects were randomly-assigned to training (n = 913) and validation (n = 456) datasets. Male sex, higher WBC concentration, lower haemoglobin concentration, higher percentage blood blasts and larger spleen size were significantly-associated with lower cumulative incidences of MMR and MR4 in training dataset. Using Fine-Gray model, we developed the predictive scoring systems for MMR and MR4 which classified subjects into the low-, intermediate- and high-risk cohorts with significantly-different cumulative incidences of MMR and MR4 with good predictive discrimination and accuracy in training and validation cohorts with high area under the receiver-operator characteristic curve (AUROC) values. These data may help physicians decide appropriateness of initial imatinib therapy.


Lipoprotein uptake in primary cell cultures of rabbit atherosclerotic lesions. A fluorescence microscopic and flow cytometric study.
To characterize the lipoprotein metabolism of lipid-filled cells of atherosclerotic lesions, uptake of 3,3'-dioctadecylindocarbocyanine (DiI)-labelled low density lipoprotein (LDL), acetylated LDL (Ac-LDL) and beta-very low density lipoprotein (beta-VLDL) was studied by fluorescence microscopy and flow cytometry in primary cultures of enzymatically dispersed aortic cells from cholesterol-fed rabbits. Most of the foam cells were identified as macrophages on the basis of Fc-receptors and high activities of nonspecific esterase and acid lipase, although cholesteryl ester (CE) inclusions were found by filipin staining also in smooth muscle cells (SMCs). During the culture only SMCs proliferated and were confluent in about 1 week. After incubation with DiI-Ac-LDL most macrophage foam cells were brightly fluorescent, but also many SMCs accumulated fluorescence. In SMCs, an excess of LDL inhibited the uptake of DiI-beta-VLDL and DiI-LDL, indicating that these lipoproteins were taken up by the apoB,E receptor; the activity of this receptor was low 2 days after cell isolation but increased considerably during SMC proliferation. DiI-beta-VLDL was not taken up by the macrophage foam cells until after 7 days' culture, when their CE content had decreased, reflecting a feed-back regulation of these receptors as well. Our results indicate that, in primary cultures of enzyme-dispersed cells from rabbit atherosclerotic lesions, most of the foam cells have lipoprotein receptors resembling those described in macrophages and that also many SMCs accumulate Ac-LDL.


A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion.
The identification of subtype-specific translocations has revolutionized the diagnostics of sarcoma and has provided new insight into oncogenesis. We used RNA-seq to investigate samples from individuals diagnosed with small round cell tumors of bone, possibly Ewing sarcoma, but which lacked the canonical EWSR1-ETS translocation. A new fusion was observed between BCOR (encoding the BCL6 co-repressor) and CCNB3 (encoding the testis-specific cyclin B3) on the X chromosome. RNA-seq results were confirmed by RT-PCR and through cloning of the tumor-specific genomic translocation breakpoints. In total, 24 BCOR-CCNB3-positive tumors were identified among a series of 594 sarcoma cases. Gene profiling experiments indicated that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas, particularly Ewing sarcoma. Finally, we show that CCNB3 immunohistochemistry is a powerful diagnostic marker for this subgroup of sarcoma and that overexpression of BCOR-CCNB3 or of truncated CCNB3 activates S phase in NIH3T3 cells. Thus, the intrachromosomal X-chromosome fusion described here represents a new subtype of bone sarcoma caused by a newly identified gene fusion mechanism.


Methylmercury bioaccumulation in an urban estuary: Delaware River USA.
Spatial variation in mercury (Hg) and methylmercury (MeHg) bioaccumulation in urban coastal watersheds reflects complex interactions between Hg sources, land use, and environmental gradients. We examined MeHg concentrations in fauna from the Delaware River estuary, and related these measurements to environmental parameters and human impacts on the waterway. The sampling sites followed a north to south gradient of increasing salinity, decreasing urban influence, and increasing marsh cover. Although mean total Hg in surface sediments (top 4cm) peaked in the urban estuarine turbidity maximum and generally decreased downstream, surface sediment MeHg concentrations showed no spatial patterns consistent with the examined environmental gradients, indicating urban influence on Hg loading to the sediment but not subsequent methylation. Surface water particulate MeHg concentration showed a positive correlation with marsh cover whereas dissolved MeHg concentrations were slightly elevated in the estuarine turbidity maximum region. Spatial patterns of MeHg bioaccumulation in resident fauna varied across taxa. Small fish showed increased MeHg concentrations in the more urban/industrial sites upstream, with concentrations generally decreasing farther downstream. Invertebrates either showed no clear spatial patterns in MeHg concentrations (blue crabs, fiddler crabs) or increasing concentrations further downstream (grass shrimp). Best-supported linear mixed models relating tissue concentration to environmental variables reflected these complex patterns, with species specific model results dominated by random site effects with a combination of particulate MeHg and landscape variables influencing bioaccumulation in some species. The data strengthen accumulating evidence that bioaccumulation in estuaries can be decoupled from sediment MeHg concentration, and that drivers of MeHg production and fate may vary within a small region.


Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics.
Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is an emerging drug discovery platform. PROTAC molecules, which typically contain a target protein ligand linked to an E3 ligase ligand, recruit a target protein to the E3 ligase to induce its ubiquitination and degradation. Here, we applied PROTAC approaches to develop broad-spectrum antivirals targeting key host factors for many viruses and virus-specific antivirals targeting unique viral proteins. For host-directed antivirals, we identified a small-molecule degrader, FM-74-103, that elicits selective degradation of human GSPT1, a translation termination factor. FM-74-103-mediated GSPT1 degradation inhibits both RNA and DNA viruses. Among virus-specific antivirals, we developed viral RNA oligonucleotide-based bifunctional molecules (Destroyers). As a proof of principle, RNA mimics of viral promoter sequences were used as heterobifunctional molecules to recruit and target influenza viral polymerase for degradation. This work highlights the broad utility of TPD to rationally design and develop next-generation antivirals.


Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6.
The number of old people is rising worldwide, and advancing age is a major risk factor for atherosclerotic cardiovascular disease. However, the mechanisms underlying this phenomenon remain unclear. In this Review, we discuss vascular intrinsic and extrinsic mechanisms of how ageing influences the pathology of atherosclerosis. First, we focus on factors that are extrinsic to the vasculature. We discuss how ageing affects the development of myeloid cells leading to the expansion of certain myeloid cell clones and induces changes in myeloid cell functions that promote atherosclerosis via inflammation, including a potential role for IL-6. Next, we describe vascular intrinsic factors by which ageing promotes atherogenesis - in particular, the effects on mitochondrial function. Studies in mice and humans have shown that ageing leads to a decline in vascular mitochondrial function and impaired mitophagy. In mice, ageing is associated with an elevation in the levels of the inflammatory cytokine IL-6 in the aorta, which participates in a positive feedback loop with the impaired vascular mitochondrial function to accelerate atherogenesis. We speculate that vascular and myeloid cell ageing synergize, via IL-6 signalling, to accelerate atherosclerosis. Finally, we propose future avenues of clinical investigation and potential therapeutic approaches to reduce the burden of atherosclerosis in old people.


Physicians' perceptions on the impact of COVID-19 in coronary artery disease diagnostic imaging and treatment: A Latin America survey. For the Society of Cardiovascular Imaging of the Inter-American Society of Cardiology.
Services during the pandemic were severely restricted, public reluctance to seek medical assistance rose, with a reduction of diagnostic and therapeutic modalities use in coronary artery disease (CAD). However, information about perceived barriers of care among cardiologists is limited. We aim to explore these barriers diagnostic and treatment modalities of CAD in Latin America during the pandemic. An anonymous Google form 12 closed-questions survey was conducted between November 2020 to January 2021. Latin American cardiologists members of the Imaging Society (SISIAC) of the Inter-American Society of Cardiology (SIAC) were reached by email and social media. Differences were found in relation to patients' perceived reluctance to undergo testing, particularly in South America and inpatient care (p < 0.05). Respondents' perceived barriers in the use of CV tests were higher in South America (p < 0.05) and related to public practice (p < 0.01). Barriers to the treatment of myocardial infarction were present in all regions (p < 0.05), and follow-up was influenced by COVID-19 in both public and private practices (p = 0.01). Regardless of treatment and diagnostic approach (invasive or non-invasive) followed, according to physicians' perception, the pandemic significantly impacted the clinical management of CAD in the Latin American population, similar to the global situation.


dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis.
Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood-brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood-brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS.


AAVrh10 vector corrects pathology in animal models of GM1 gangliosidosis and achieves widespread distribution in the CNS of nonhuman primates.
GM1 gangliosidosis is a rare, inherited neurodegenerative disorder caused by mutations in the GLB1 gene, which encodes the lysosomal hydrolase acid β-galactosidase (β-gal). β-gal deficiency leads to toxic accumulation of GM1 ganglioside, predominantly in the central nervous system (CNS), resulting in progressive neurodegeneration. LYS-GM101 is an AAVrh.10-based gene therapy vector carrying the human GLB1 cDNA. The efficacy of intra-cerebrospinal fluid injection of LYS-GM101 analogs was demonstrated in GM1 mouse and cat models with widespread diffusion of β-gal and correction of GM1 ganglioside accumulation in the CNS without observable adverse effects. Clinical dose selection was performed, based on a good-laboratory-practice study, in nonhuman primates (NHPs) using the clinical LYS-GM101 vector. A broadly distributed increase of β-gal activity was observed in NHP brain 3 months after intra-cisterna magna injection of LYS-GM101 at 1.0 × 1012 vg/mL CSF and 4.0 × 1012 vg/mL CSF, with 20% and 60% increases compared with vehicle-treated animals, respectively. Histopathologic examination revealed asymptomatic adverse changes in the sensory pathways of the spinal cord and dorsal root ganglia in both sexes and at both doses. Taken as a whole, these pre-clinical data support the initiation of a clinical study with LYS-GM101 for the treatment of GM1 gangliosidosis.


Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants.
Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.


DNA Origami: Recent Progress and Applications.
This chapter explores the basic concept of DNA origami and its various types. By showing the progress made in structural DNA nanotechnology during the last 15 years, the chapter draws attention to the capability of DNA origami to construct complex structures in both 2D and 3D level. As well as looking at a few examples of dynamic DNA nanostructures, the chapter also explores the possible applications of DNA origami in different fields, such as biological computing, nanorobotics, and DNA walkers.


Application of lime peel oil composite nanoemulsion to prevent toxigenic fungi in nuts.
Food byproduct oils may have antimicrobial impacts when used in coating and preservation. Nuts are known to suffer from toxigenic fungi and their related mycotoxins. The present study utilized lime oil emulsion to minimize fungal infection and reduce aflatoxin B1 (AFB1). Besides, it evaluated lime oil's impact on nuts' protection against oxidation and deterioration during storage. Lime oil was extracted using hydrodistillation, and gas chromatography (GC-MS) evaluated volatile constituents. Oil was loaded into a composite emulsion of whey protein, Arabic gum, gelatin, and carboxymethyl cellulose. The antimicrobial and antifungal properties of the nut-coating emulsion were evaluated. A simulated Aspergillus flavus infection experiment evaluated composite resistance for fungal infection and AFB1 production. Oxidation and acidity changes in nuts oil composition were evaluated by proximate analysis, fatty acid composition, and induction period. The oil majority was recorded for terpenes and monoterpenes, including limonene (44.69 ± 2.11%). The emulsion was characterized by zeta potential (-21.16 ± 1.28 mV), stability (99.61 ± 0.02%), and polydispersity index (0.41 ± 0.05). Antimicrobial properties recorded a high antibacterial inhibition zone (up to 28.37 ± 0.11 mm) and anti-mycotoxigenic fungi (up to 37.61 ± 0.24 mm). For the simulated experiment, fungal growth reduction ranged between 78.02% for filmed-peanut and 84.5% for filmed-almond, while AFB1 was not detected in filmed hazelnut and almond. During the one-year storage of samples, there was a slight change in nut oil composition and oxidation progress in filmed nuts, while there was a significant change in non-filmed nuts. The result recommended lime-composite as an edible nut coating that prevents aflatoxigenic contamination, oxidation changes, and improved shelf life.


When the social discourse on violation behaviours is challenged by the perception of everyday life experiences: Effects of non-accident experiences on offending attitudes and habits.
The aim of this article is to introduce the concept of the Non-Accident Experience (NAE) with regard to violations of traffic safety regulations. An NAE refers to the fact of not having been involved in an accident following the adoption of a behaviour socially recognised as promoting its occurrence. We hypothesise that this type of experiences has a strong effect on attitudes (valence and strength) and habits with regard to traffic offences such as speeding and drink-drive. An empirical study was conducted to test the relevance of this set of hypotheses. 543 French drivers participated to a survey designed to measure all these theoretical constructs. As expected, the results showed that the more frequently NAEs were experienced the more individuals had a favourable and weak (less certain, less important, more ambivalent) attitude towards violations, as well as strong habits. In addition, the more numerous NAEs experienced by others were perceived to be, the more ambivalent was the attitude. The discussion firstly concerns the methodological limitations of this study (e.g. use of cross-sectional design) as well as the integration of this concept into current research, especially in relation to the attitude strength concept and the theory of planned behaviour. Then, we discuss its practical implications (use of the experience based analysis technique, with consideration of both accident and non-accident experiences).


Reducing agricultural nitrous oxide emissions in China: the role of food production, forest cover, income, trade openness, and rural population.
In the light of China's carbon-neutral goal, this study examines how food production, forest cover, trade openness, and rural population contribute to the quest of addressing China's agricultural nitrous oxide emissions. Time series data ranging from 1971 to 2018 was used for analysis in this study. The autoregressive distributed lag (ARDL) technique was employed to evaluate potential cointegration as well as to ascertain the long and short-run effects of food production, forest cover, income, trade openness, and rural population on agricultural nitrous oxide emission. The Toda-Yamomoto causality analysis was also used to identify the causal relations between covariates (food production, forest cover, income, trade openness, and rural population) and the outcome variable (agricultural nitrous oxide emission). The long-run evidence is that rural population in itself tends to increase agricultural nitrous oxide emissions likewise food production. There is also validation of the existence of environmental Kuznets curve for agricultural nitrous oxide emissions. Moreover, income interacts with rural population to reduce agricultural nitrous oxide emissions in the long-run. Causality analysis indicated rural population affects the level of forest cover; forest cover is found to cause agricultural nitrous oxide emissions but the converse is not established, and income as well as the interaction between income and rural population determines agricultural nitrous oxide emissions. The short-run dynamics results establish an oscillatory equilibrium convergence for agricultural nitrous oxide emissions in event of structural disturbances. From the findings, the EKC hypothesis is relevant by offering avenue to reduce emission. Thus, income growth remains helpful in addressing nitrous oxide emission from the agricultural sector. However, research is needed to unravel why nitrous oxide tends to increase in many forest areas. Since food production cannot be halted, policy makers need to enhance the uptake of efficient food production technologies including developing and using more renewable energy for food production. It is important for authorities to attend to rural development in order to mitigate agricultural nitrous oxide emissions in China.


A facile synthesis of beta-(S-benzylmercapto)-beta, beta-cyclopentamethylene-propionic acid.
The title compound is a key intermediate for the preparation of oxytocin and vasopressin antagonists. Using sodium benzylmercaptide instead of boron trifluoride etherate as catalyst gives a better than four fold overall improvement in yield of the title compound from ethyl cyclohexylideneacetate and benzylmercaptan. The preparation of the corresponding acid labile S-p-methylbenzylmercapto and S-p-methoxybenzylmercapto analogs is also described.


Witnessing Each Other: An Intersubjective Stance for Exhibitions Relating to Substance Use and Abuse.
Most exhibitions are conceived to convey information the experts making the exhibition believe other people need or want. But the notion that the intended exhibition public will cooperate with the exhibition organizers. intent disregards the reasons people come to exhibitions and the way they use them. While the author contends that an exhibition cannot use facts to convince someone to abstain from substances they crave, exhibitions can nonetheless make a difference in lives complicated by substance use by providing representation for voices that are rarely heard and building empathy between witness and witnessed. The purpose of such an endeavor is not to change attitudes or behaviors toward a pre-determined outcome, but to facilitate a witnessing of others. The uniquely intersubjective medium of exhibition can thus succeed in this field by opening the potential of mutual, humanizing recognition among people with varied life experience of substance use and abuse.


Risk factors and their effects on the dynamic process of smoking relapse among veteran smokers.
Smoking cessation programs can help smokers make a successful attempt at quitting, but many initial quitters relapse over time. This study aims to identify risk factors for smoking relapse and examine the influence of these factors on the dynamic relapse process in an outpatient smoking cessation program for veterans. Baseline information included socio-demographic description, medical and psychiatric comorbidities, smoking history and behavior, nicotine dependence, smoking motives, and confidence in the ability to quit. The intervention involved a 4-session group therapy consisting of cognitive and pharmacological treatments. The 189 initial quitters by program completion were followed via a telephone interview 6 months later. We identified six risk factors associated with relapse within the first 6 months post quit. Furthermore, we described characteristics of the dynamic process of smoking relapse and studied the influence of the identified risk factors on the relapse curve. The effects of these risk factors can be categorized into two patterns. Annual income and age at smoking initiation showed a delayed action that influenced the relapse curve after several weeks post quit, whereas age, number of smoking coworkers, history of schizophrenia, and number of sessions attended modified the relapse process soon after quitting. The information will be useful in targeting veteran smokers who are at high risk for relapse, choosing the optimal time for post-cessation services, and developing strategies accordingly.


Oblique scaling: an algorithm to correct for a non-perpendicular camera view in tendon strain measurements.
Image distortion due to a non-perpendicular camera view introduces serious errors in tendon and ligament strain measurements when data are recorded using a single camera. These errors can be corrected with the oblique scaling algorithm using two pairs of scaling markers attached to the tendon surface. Computer simulations show that application of this algorithm reduces errors over 100 times to less than 0.06%. The method is relatively insensitive to measurement errors in the scaling marker distance but sensitive to the accuracy of alignment of the scaling markers. It can be concluded that the oblique scaling algorithm eliminates the influences of a non-perpendicular camera view in single-camera tendon and ligament strain measurements.


Condylar fractures: is open or closed reduction best?
Medline was searched and further references were identified from selected papers. Studies were included if they simultaneously compared open and closed techniques with at least one of the following outcome measures: maximum postoperative mouth opening, amount of lateral excursion and protrusion, mandibular deviation on mouth opening, facial symmetry, and joint or muscle pain. They were also required to have had at least 6 months follow-up and have been published in English. Meta-analysis was carried out using the weighted average method for fixed effects and the weighted average method for random effects. Thirteen studies were included, only one of which was a randomised controlled trial (RCT). Numerous problems were found with the information presented in the various articles. These included lack of patient randomisation, failure to classify the type of condylar fracture, variability within the surgical protocols, and inconsistencies in choice of variables and how they were reported. Because of the great variation in how the various study parameters were reported, it was not possible to perform a reliable meta-analysis. There is a need for better standardisation of data collection in future studies as well as randomisation of the patients treated so that the two approaches can be accurately compared.


Radial glia: multi-purpose cells for vertebrate brain development.
Radial glia are specialized cells in the developing nervous system of all vertebrates, and are characterized by long radial processes. These processes facilitate the best known function of radial glia: guiding the radial migration of newborn neurons from the ventricular zone to the mantle regions. Recent data indicate further important roles for these cells as ubiquitous precursors that generate neurons and glia, and as key elements in patterning and region-specific differentiation of the CNS. Thus, from being regarded mainly as support cells, radial glia have emerged as multi-purpose cells involved in most aspects of brain development.


Terminology, stereotypes and aggressive dynamics in the accident and emergency department.
There is a perception that violence against staff practising in accident and emergency (A&E) departments is increasing [Fernandes, C.M.B., Bouthillette, F., Raboud, J.M., Bullock, L., Moore, C.F., Christenson, J.M., Grafstein, E., Rae, S., Ouellet, L., Gillrie, C., Way, M., 1999. Violence in the emergency department: a survey of health care workers, Canadian Medical Association Journal 11, 1-6; Jenkins, M.G., Rocke, L.G., McNicholl, B.P., Hughes, D.M., 1998. Violence and verbal abuse against staff in the A and E departments: a survey of consultants in the United Kingdom and Republic of Ireland, Journal of Accident and Emergency Medicine 15, 262-265; . A survey of violence towards nursing staff in one large Irish Accident and Emergency department, Journal of Emergency Nursing 23(3), 214-219]. This paper discusses traditional stereotypes of the violent A&E client by critiquing the current literature. The paper then goes on to question whether some health care professionals themselves are contributing to a climate of fear and the development of conflict.