The impact of a comprehensive coronavirus disease 2019 (COVID-19) infection prevention bundle on non-COVID-19 hospital-acquired respiratory viral infection (HA-RVI) rates.
After implementing a coronavirus disease 2019 (COVID-19) infection prevention bundle, the incidence rate ratio (IRR) of non-severe acute respiratory coronavirus virus 2 (non-SARS-CoV-2) hospital-acquired respiratory viral infection (HA-RVI) was significantly lower than the IRR from the pre-COVID-19 period (IRR, 0.322; 95% CI, 0.266-0.393; P < .01). However, HA-RVIs incidence rates mirrored community RVI trends, suggesting that hospital interventions alone did not significantly affect HA-RVI incidence.


The significance of genetic erosion in the process of extinction : II. Morphological variation and fitness components in populations of varying size of Salvia pratensis L. and Scabiosa columbaria L.
The amount of genetic variation within a population is, among other things, related to population size. In small populations loss of genetic variation due to high levels of genetic drift and inbreeding may result in decline of individual fitness and increase the chance of population extinction. This chain of processes is known as genetic erosion. In this study we tested the genetic erosion hypothesis by investigating the relation between morphological variation and population size in two perennial, outbreeding plant species, Salvia pratensis and Scabiosa columbaria. To relate phenotypic variation to genetic variation the experiments were performed under common environmental conditions. For both species a positive correlation was observed between the amount of phenotypic variation and population size (Salvia r=0.915; Scabiosa r=0.703). Part of this variation is likely to have a genetic base, although maternal effects were present in the seedling and juvenile life stages. Differences between populations could in both species be attributed to parameters related to fitness, i.e. growth rate in Salvia and reproductive effort in Scabiosa. Discriminant functions reflecting these parameters did not however discriminate between large and small populations.Results are discussed in relation to the common environment approach and to electrophoretic results obtained earlier (Van Treuren et al. 1991).


Inhibition of implantation by intraluminal administration of concanavalin A in mice.
Important characteristics of endometrial implantation sites are the changes of polarity and molecular composition of the cellular surface. For this reason the masking of surface carbohydrates could lead to an inhibition of the recognition by the blastocyst of the endometrial implantation site. Considering the impact of lectins on carbohydrates, we decided to utilize the intraluminal administration (5 microliter) of different concentrations of concanavalin A (15-60 microgram) in pregnant female mice in the preimplantation phase. An inhibition of 100% of implantation wqs obtained with concentrations of 30 and 60 microgram of the lectin administered on days 3 and 4 of the pregnancy (P less than 0.001). Less important effects were observed on administering 15 or 20 microgram of the lectin (73 and 87% of inhibition) and on utilizing the different doses on days 1 and 2 of the pregnancy. Thus, we conclude that the egg must recognize certain molecules of the endometrial surface (alpha-D-mannopyranose and alpha-D-glucopyranose) in order to implant and that the making of these sites potentially constitutes a new contraceptive approach.


Exploration of m6A methylation regulators as epigenetic targets for immunotherapy in advanced sepsis.
This study aims to deeply explore the relationship between m6A methylation modification and peripheral immune cells in patients with advanced sepsis and mine potential epigenetic therapeutic targets by analyzing the differential expression patterns of m6A-related genes in healthy subjects and advanced sepsis patients. A single cell expression dataset of peripheral immune cells containing blood samples from 4 patients with advanced sepsis and 5 healthy subjects was obtained from the gene expression comprehensive database (GSE175453). Differential expression analysis and cluster analysis were performed on 21 m6A-related genes. The characteristic gene was identified based on random forest algorithm, and the correlation between the characteristic gene METTL16 and 23 immune cells in patients with advanced sepsis was evaluated using single-sample gene set enrichment analysis. IGFBP1, IGFBP2, IGF2BP1, and WTAP were highly expressed in patients with advanced sepsis and m6A cluster B. IGFBP1, IGFBP2, and IGF2BP1 were positively correlated with Th17 helper T cells. The characteristic gene METTL16 exhibited a significant positive correlation with the proportion of various immune cells. IGFBP1, IGFBP2, IGF2BP1, WTAP, and METTL16 may accelerate the development of advanced sepsis by regulating m6A methylation modification and promoting immune cell infiltration. The discovery of these characteristic genes related to advanced sepsis provides potential therapeutic targets for the diagnosis and treatment of sepsis.


C-peptide response to glucagon in type 2 diabetes mellitus: a comparison with oral glucose tolerance test.
C-peptide immunoreactivity (CPR) response during glucagon test (intravenous injection of 1 mg glucagon) was compared with CPR response during 75 g oral glucose tolerance test (oGTT) in 58 patients with newly-diagnosed, untreated type 2 (non-insulin-dependent) diabetes mellitus. Both tests were also repeated after blood glucose was well controlled with sulfonylurea or insulin in 17 patients. CPR secretory response was estimated by delta CPR, i.e. the difference between maximal and basal levels of CPR during each test. In the 58 untreated patients, the mean fasting plasma glucose (FPG) level was 12.8 +/- 0.6 mmol/L (M +/- SE), and there was no significant correlation between delta CPR during glucagon test and delta CPR during oGTT. The therapy for diabetes mellitus in 17 patients resulted in a fall in FPG (from 15.1 +/- 0.5 to 6.7 +/- 0.3 mmol/L) and a marked increase in delta CPR during oGTT (from 0.28 +/- 0.06 to 1.18 +/- 0.17 nmol/L, P < 0.01), but did not influence delta CPR during glucagon test (from 0.39 +/- 0.06 to 0.42 +/- 0.06 nmol/L, N.S.). In these patients, delta CPR during glucagon test before therapy correlated significantly with delta CPR during oGTT after therapy. Of the 13 patients who showed impaired CPR response during oGTT (delta CPR < 0.5 nmol/L) but substantial response during glucagon test (delta CPR > or = 0.5 nmol/L), 12 were successfully controlled without insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


The net parenchymal thickness predicts pancreatic fistula after pancreaticoduodenectomy: a retrospective cohort study of objective data.
The clinically relevant postoperative pancreatic fistula (CR-POPF) is still a challenging complication of pancreaticoduodenectomy (PD). This study aims to explore the predictors of CR-POPF after PD, including net parenchymal thickness (NPT) of pancreatic neck. The consecutive patients who underwent PD at a tertiary hospital were retrospectively reviewed. Univariate and multivariate analyses were conducted on the perioperative data, which was mainly extracted from the objective data, containing the results from the laboratory tests and the imaging examination. NPT refers to the total thickness of pancreatic gland excluding main pancreatic duct (MPD) at the CT film. Univariate analyses showed that total serum bilirubin (TBiL) and albumin (ALB) levels, MPD size and NPT were significantly different between the patients with and without CR-POPF. The white blood cell count, the rate of intra-abdominal infection (IAI) and the postoperative length of hospital stay (LOS) were associated with the incidence of CR-POPF. The proportion of patients with pancreatic adenocarcinoma or chronic pancreatitis was significantly lower in the CR-POPF group than in the non-CR-POPF group. Multivariate analyses manifested that ALB ≤35 g/L and NPT >10 mm were two of the independent risk factors for CR-POPF. Preoperative ALB ≤35 g/L and NPT > 10 mm were both the independent predictors of CR-POPF. CR-POPF was associated with the higher IAI rate and the extended LOS.


Occludin expression decreases with the progression of human endometrial carcinoma.
The tight junctions of the glandular epithelium are crucial for the maintenance of cell polarity, separating the plasma membrane into apical and basolateral domains. Thus abnormalities of the tight junctions may result in the structural disturbances of glandular epithelial neoplasia. In this study we introduced an anti-occludin monoclonal antibody for semiquantitative assay of the occludin expression in tissue sections of human normal and neoplastic endometrial epithelia using the Adobe Photoshop and NIH Image programs. Normal endometrial glands and samples of endometrial hyperplasia and endometrioid carcinoma grade 1 fully expressed occludin at the apical cell border. In endometrioid carcinomas grades 2 and 3, however, occludin disappeared in solid areas of the carcinomatous tissues. Occludin was also found at the apical borders of the cancer cells that formed glandular structures. Occludin expression decreased progressively in parallel with the increase in carcinoma grade, and the decreased occludin expression correlated with myometrial invasion and lymph node metastasis. These results suggest that the loss of tight junctions has a close relationship with structural atypia in the progression of human endometrial carcinomas and their malignant potential.


Phase Transformation Behavior of the Aluminosilicate Phase During High-Pressure Hydrothermal Reduction of High-Iron Red Mud.
One-step separation and recovery of sodium, aluminum and iron in high-iron red mud in a high-calcium alkaline hydrothermal system is realized by a high-pressure hydrothermal reduction process. The transformation behavior of the aluminasilica phase in high-iron red mud is mainly investigated. The results show that under the optimized conditions, a temperature of 290℃, a Na2O concentration of 240 g/L, a calcium to silicon ratio of 3.5, and a liquid-solid ratio of 5, the Na2O content in the transition slag is reduced to 0.12%, the dealkalization rate can reach 98%, and the alumina dissolution rate is 73%. When the starch-free reductant is added, the transition slag mainly consists of hematite and hydroandradite, and when the starch reductant is added (the addition amount is 1/4 that of ω(Fe2O3) in the red mud), all Fe2O3 in the transition slag is completely reduced to Fe3O4, and the main phases are magnetite and hydrogrossular.


Comparison of expression profiling of circular RNAs in vitreous humour between diabetic retinopathy and non-diabetes mellitus patients.
To compare circular (circRNA) expression levels in the vitreous humour between PDR (proliferative diabetic retinopathy) and the control groups. The present study collected vitreous humour samples of both the PDR group and the control group (composed of rhegmatogenous retinal detachment, idiopathic macular hole and idiopathic macular epiretinal membrane). All the samples were subjected to circRNA and mRNA sequencing as well as bioinformatic analysis. The vitreous humour of the PDR and control groups was collected during PPV surgery. Compared to the control group, 122 upregulated and 9 downregulated circRNAs, and 818 upregulated mRNAs and 864 downregulated mRNAs were identified. We further selected 12 circRNAs to validate the RNA expression level by qPCR; results showed that with the exception of 2 downregulated circRNAs the remaining were significantly upregulated in the PDR group, which was consistent with RNA sequencing results. Bioinformatic analysis was conducted to predict possible miRNAs absorbed by circRNAs. Each circRNA could interact with at least five miRNAs. We randomly chose three miRNAs to test the expression level in the vitreous humour by qPCR and found these miRNAs were significantly downregulated in the PDR group. The changed profiling of circRNAs in the vitreous humour was reliable and may become a promising biomarker of DR and the circRNA-miRNA-mRNA network. It may also play an important role in the progression of DR.


Insulin autoimmune syndrome with insulin-resistant diabetes at the incipient stage prior to hypoglycemic attacks.
Insulin autoimmune syndrome is characterized by spontaneous hypoglycemia, glucose intolerance, hyperinsulinemia and insulin-binding antibodies in serum without previous immunization. A 31-year-old man with Graves' disease developed insulin autoantibodies after therapy with methimazole. The patient was unique in that persistent hyperglycemia with polyuria and polydipsia had continued for several days before frequent hypoglycemic attacks appeared. We were able to extract a huge amount of immunoreactive insulin (116,000 microU/ml) with acid-ethanol from his serum obtained in the diabetic stage, and serum C-peptide immunoreactivity was as high as 268 ng/ml. The insulin-binding activity of his serum was quite potent, and when 1:5,000 diluted serum was incubated with 125I-porcine insulin, 71.2% of the label could be precipitated by polyethylene glycol. The insulin-binding protein was identified as mainly IgG with kappa light chains. Insulin-binding activity was not detected in serum obtained before methimazole therapy, suggesting that the drug was responsible for the induction of antibodies in this patient. The antibodies recognized porcine, sheep, bovine and horse insulins as well as human insulin. The mechanisms by which the antibodies produced hyper- and hypoglycemia have also been discussed.


Global and regional burden of ischemic stroke associated with atrial fibrillation, 2009-2019.
The extent of the preventable burden of ischaemic stroke associated with atrial fibrillation (AF) remains uncertain to date. To address this knowledge gap, we utilised the comparative risk assessment methodology to estimate the burden of ischaemic stroke associated with AF at both global and regional levels. The population attributable fraction for ischaemic stroke and AF was obtained from published literature, while data on the prevalence, incidence, deaths, and disability-adjusted life years (DALY) associated with ischaemic stroke were sourced from the Global Burden of Disease study database. Our analysis revealed that in 2019, globally, there were an estimated 0.7 (95% uncertainty interval [UI] of 0.55 to 0.83) million incident cases, 6.9 (5.81 to 8.12) million prevalence cases, 0.3 0.25 to 0.34) million deaths and 5.7 (4.91 to 6.57) million DALY resulting from ischaemic stroke associated with AF. The age-standardised death and DALY rates declined between 2009 and 2019 in all regions to varying degrees. Conversely, the age-standardised incidence and prevalence rates reduced only in high-income countries, Central Europe, Eastern Europe and Central Asia and Latin America and Caribbean regions. It is likely that our findings under-estimated the true burden of ischaemic stroke associated with AF due to limitations such as the use of a fixed population attributable fraction and poor quality of data. Nevertheless, we believe that our estimates provide valuable insights and highlight the urgent need for optimised management of AF through the implementation of efficacious interventions. Such efforts can help reduce the occurrence of preventable ischaemic strokes.


Effects of intravenous ethanol and of 4-methylpyrazole on alcohol drinking in alcohol-preferring rats.
Studies were undertaken to determine if elevated blood alcohol concentrations (BAC), produced by intravenous (IV) infusion of ethanol or by intraperitoneal (IP) administration of 4-methylpyrazole (4-MP), could reduce the free-choice oral alcohol consumption of adult male alcohol-preferring rats (P-rats). The IV infusion of ethanol either on a 24 or 12 (dark) hourly dose schedule reduced the amount of ethanol voluntarily ingested. There was a significant (p less than 0.05) inverse correlation between the amount of ethanol consumed orally and the amount of ethanol infused. Daily fluid and caloric intakes were not compromised. When the amount of ethanol infused was 85% or more of the control oral intake, there was a significant correlation between ethanol intake and tail-blood alcohol levels, taken at 5 min (r = 0.98; p less than 0.05) and 55 min (r = 0.93, p less than 0.05) after the last dark cycle infusion. Below the preinfusion level of 85%, the BAC were variable and did not correlate well with total ethanol intake. After a single IP injection of 4-MP, 90 mg/kg body wt, BAC increased from 10 mg% to 50-65 mg% for 2-3 days. Concomitant with the rise in BAC, these animals decreased their drinking of 10% ethanol and proportionately increased their water intake. The present studies suggest that pharmacological factors, distinct from orosensory cues, are important in regulating voluntary ethanol drinking behavior in the P-rats.


Dose-response of inhaled diltiazem on airway reactivity to methacholine and exercise in subjects with mild asthma.
Methacholine challenges were performed by 10 asthmatic subjects, 2 hours before and 15 minutes after placebo (diluent alone) and 5, 10, 15, 30, and 60 mg inhaled diltiazem given in a single-blind crossover manner. There was no significant change from placebo in the dose of methacholine required to produce a 20% decrease in forced expiratory volume in the first second (FEV1) (PD20); the fold increase in PD20 from baseline was 1.1 +/- 0.1 after placebo, 1.4 +/- 0.2 after 5 mg, 1.8 +/- 0.3 after 10 mg, 1.4 +/- 0.2 after 15 mg, 1.6 +/- 0.2 after 30 mg, and 1.2 +/- 0.1 after 60 mg. There was a 1% chance that we missed a twofold difference between placebo and the 10 mg dose because of inadequate sample size. Fifteen minutes before a standardized exercise challenge, 10 subjects received placebo, 10 mg, and the highest dose tolerated during the methacholine study (20 to 45 mg) in a randomized double-blind crossover design. The mean +/- SE maximum postexercise decrease in FEV1 was 28.8% +/- 5.7% after placebo, 23.4% +/- 4.6% after 10 mg, and 20.8% +/- 3.0% after high-dose diltiazem (P greater than 0.05). There was a 12% chance that we missed a 15% difference between placebo and the high-dose regimen because of inadequate sample size. We conclude that diltiazem does not attenuate airway reactivity to methacholine or exercise even when high concentrations are delivered to the lungs.


The Neurocognitive Basis of Spatial Reorientation.
The ability to recover one's bearings when lost is a skill that is fundamental for spatial navigation. We review the cognitive and neural mechanisms that underlie this ability, with the aim of linking together previously disparate findings from animal behavior, human psychology, electrophysiology, and cognitive neuroscience. Behavioral work suggests that reorientation involves two key abilities: first, the recovery of a spatial reference frame (a cognitive map) that is appropriate to the current environment; and second, the determination of one's heading and location relative to that reference frame. Electrophysiological recording studies, primarily in rodents, have revealed potential correlates of these operations in place, grid, border/boundary, and head-direction cells in the hippocampal formation. Cognitive neuroscience studies, primarily in humans, suggest that the perceptual inputs necessary for these operations are processed by neocortical regions such as the retrosplenial complex, occipital place area and parahippocampal place area, with the retrosplenial complex mediating spatial transformations between the local environment and the recovered spatial reference frame, the occipital place area supporting perception of local boundaries, and the parahippocampal place area processing visual information that is essential for identification of the local spatial context. By combining results across these various literatures, we converge on a unified account of reorientation that bridges the cognitive and neural domains.


Effective treatment of emulsified oil wastewater by the coagulation-flotation process.
Ship emulsified oil wastewater was used as the research object in this study. The highly efficient coagulant demulsification degreasing mechanism and microbubble flotation technology were combined and the effects of coagulant type and dosage amount on the demulsification of emulsified oil wastewater were evaluated. The influence of the mixed coagulation effect of pH values, temperature, and hydraulic condition parameters were determined and water intake, air intake, and oil content were regulated. The coagulant for the demulsification of emulsified oil wastewater was screened; the dosage was 500 mg L-1, and the removal capacity of the coagulant was in the following order: polyaluminum ferric chloride (PAFC) > polyaluminum chloride (PAC) > polysilicate aluminum ferric sulfate (PSAFS) > alum > Al2(SO4)3 > polyferric sulfate > FeCl3. Polyacrylamide (PAM) with added water was used to further reduce the oil content. The PAFC, PAC, and PSAFS were selected as coagulation-air flotation dynamic test alternative agents. The investment quantities of PAFC, PSAFS and PAM were 300 mg L-1, 300 mg L-1 and 30 mg L-1, respectively. The stirring time was 5 min, the pH value was 6.5-6.9, the flow rate was 0.25 m3 h-1, the oil content of the emulsified oil wastewater was 3000-5000 mg L-1 and the effluent oil was stable below 15 ppm. The microbubble generation device using air flotation effluent was used in the two air flotation treatments to enhance the device efficiency. The air flotation device adopted the structural design of the upper part of the water inlet and the lower part of the micro-air bubble, which can increase the collision probability of the microbubble and improve the efficiency of oil removal.


Exchange pattern of gaseous elemental mercury in an active urban landfill facility.
The environmental behavior of gaseous elemental mercury (Hg) in the ambient air was investigated from the center of a municipal landfill site (area approximately 0.6km(2)) located in Dae Gu, Korea in the winter of 2004. In order to provide insight on the Hg exchange processes in strong source areas, we continuously analyzed Hg concentration gradients developed across two heights between 1m and 5m over soil surfaces at hourly intervals. The results displayed Hg concentrations in the lower and upper levels in the range of 1.46-13.1ngm(-3) (3.33+/-1.29ngm(-3): N=139) and 1.20-13.7ngm(-3) (3.27+/-1.23ngm(-3): N=139), respectively. The results of our analysis, when divided separately into emission and dry deposition, showed that emission of Hg was fairly dominant in frequency (up to 58%) over dry deposition. By multiplying our Hg gradient data with the K-values predicted indirectly from the results of previous studies, the emission and deposition fluxes of Hg were estimated as 39.0+/-43.3ngm(-2)h(-1) (N=80) and -60.0+/-80.2ngm(-2)h(-1) (N=59), respectively. Although the magnitudes of exchange were moderately lower than previously investigated anthropogenic sources, the overall results of this study suggest that an active landfill site can act as an important source of Hg in an urban environment along with other man-made activities.


Survey of antenatal women's knowledge of maternal and fetal risks of tobacco smoking and acceptability of nicotine replacement products in pregnancy.
A survey was carried out of 145 pregnant women in the third trimester in pregnancy to assess motivators to stop tobacco smoking and assess women's knowledge of fetal and maternal risk of smoking. In addition, the survey was to assess the acceptability of nicotine replacement products use in pregnancy. The findings of this survey show that pregnant women tend to know about the maternal risks of smoking but their knowledge is deficient about fetal risks. The knowledge of the association of cot death risk and tobacco smoking appears to be the greatest motivator to stop smoking. Overall, 74% wished to stop smoking in pregnancy and 68% would accept a nicotine replacement product.


Clean Western blot signals from immunoprecipitated samples.
We present a strategy that overcomes the high background arising during Western blotting (WB) detection of proteins obtained through immunoprecipitation (IP). Traditional HRP-conjugated secondary antibodies, which detect the denatured heavy and light antibody chains, produce high background that often mask the signals of interest on WBs. Here, we show that HRP-conjugated Protein A and Protein G, which detect almost exclusively intact antibody molecules, can be effectively used to obtain clean and specific WB signals of target proteins.


Secondary surgery techniques to optimise functional and aesthetic outcomes in orofacial clefting.
Although the goal of primary surgery is to avoid the need for secondary surgery, in a proportion of patients this is not always possible. Secondary, or revisional, surgery is frequently undertaken in patients with orofacial clefts and may present a complex and challenging problem for the multidisciplinary team. There are a broad range of functional and aesthetic issues that secondary surgery might aim to address. These include palatal fistulae (that may be symptomatic for air, fluid or food), velopharyngeal insufficiency (typically manifesting with decreased intelligibility or nasal regurgitation), suboptimal cleft lip scars (that can significantly impact upon the psychosocial wellbeing of the patient), and nasal asymmetry (that is frequently accompanied by nasal airway concerns). Unilateral and bilateral clefts are each associated with a characteristic nasal deformity that requires a tailored surgical approach. Suboptimal maxillary growth in repaired orofacial clefts may impact negatively on both appearance and function; surgical correction through orthognathic surgery can be transformational for the patient. The general dental practitioner, cleft orthodontist and restorative dentist all play a critical role in this process.


The effects of age on reward magnitude processing in the monetary incentive delay task.
Previous studies have suggested age-related differences in reward-directed behavior and cerebral processes in support of the age effects. However, it remains unclear how age may influence the processing of reward magnitude. Here, with 54 volunteers (22-74 years of age) participating in the Monetary Incentive Delay Task (MIDT) with explicit cues ($1, ¢1, or nil) and timed response to win, we characterized brain activations during anticipation and feedback and the effects of age on these regional activations. Behaviorally, age was associated with less reaction time (RT) difference between dollar and cent trials, as a result of slower response to the dollar trials; i.e., age was positively correlated with RT dollar - RT cent, with RT nil as a covariate. Both age and the RT difference ($1 - ¢1) were correlated with diminished activation of the right caudate head, right anterior insula, supplementary motor area (SMA)/pre-SMA, visual cortex, parahippocampal gyrus, right superior/middle frontal gyri, and left primary motor cortex during anticipation of $1 vs. ¢1 reward. Further, these regional activities mediated the age effects on RT differences. In responses to outcomes, age was associated with decreases in regional activations to dollar vs. cent loss but only because of higher age-related responses to cent losses. Together, these findings suggest age-related differences in sensitivity to the magnitude of reward. With lower cerebral responses during anticipation to win large rewards and higher responses to outcomes of small loss, aging incurs a constricted sensitivity to the magnitude of reward.


[Optical coherence tomography in optic pit and associated maculopathy].
Of patients with an optic pit 30% develop an associated maculopathy of unknown origin. We report on 8 patients with an optic pit and associated maculopathy evaluated by optical coherence tomography (OCT) for detection of structural retinal changes and indications for the pathogenesis. A total of 8 patients (mean age 25 years) suffering from an optic pit and associated maculopathy were evaluated by biomicroscopy, fluorescein angiography (FLA) and OCT and the results were compared. Visual acuity was on average 0.5 (0.05-0.8). Funduscopy revealed a macular elevation. In clinically suspected 'pseudo' macular hole, OCT revealed foveal schisis. OCT demonstrated a retinal detachment with a typical convex schisis of the outer retinal layer (n=6), and three patients showed a neurosensory detachment with (n=2) and without (n=1) intraretinal cystoid formation. The typical macular schisis pattern in OCT in optic pit with serous maculopathy helps to differentiate this condition from other macular elevations.


Repulsive torques alone trigger crystallization of constant speed active particles.
We investigate the possibility for self-propelled particles to crystallize without reducing their intrinsic speed. We illuminate how, in the absence of any force, the competition between self-propulsion and repulsive torques determines the macroscopic phases of constant-speed active particles. This minimal model expands upon existing approaches for an improved understanding of crystallization of active matter.


Safety factor for precordial pacing: minimum current thresholds for pacing and for ventricular fibrillation by vulnerable-period stimulation.
Temporary cardiac pacing by means of rapidly applied, precordial electrodes can be of great value in selected patients suffering cardiac arrest or profound bradycardia, post-defibrillation atrioventricular block, or digitalis intoxication. This study provides data pertaining to the safety of precordial pacing measured as the ratio of the minimum current required to induce ventricular fibrillation (VF) to the minimum current required to pace the ventricular myocardium. Single rectangular pulse stimuli having durations of 1-50 ms were evaluated. In 6 anesthetized dogs, a cutaneous electrode was centered over the shaved apex beat area of the left chest and paired with a larger electrode sutured to the right chest wall. Using a specially fabricated, synchronized, high-energy pulse generator, the "most vulnerable" time in the cardiac cycle at which the least current was required to induce VF with a single shock was identified. This current was compared to the much lower current required to pace the heart in the diastolic interval. While the current required to produce either fibrillation or pacing decreased as pulse duration increased, the safety factor (i.e., the ratio of fibrillation current to pacing current) remained nearly constant, averaging 12.6 for all pulse durations examined. That is, on the average, a stimulus of any given duration between 1 and 50 ms required at least 12 times the current required for pacing to produce ventricular fibrillation. We conclude that in normal canine hearts, the risk of inducing VF during precordial pacing is small.


The RNA N6 -methyladenosine modulator HNRNPA2B1 is involved in the development of non-small cell lung cancer.
The key N6 methyladenosine (m6 A) RNA methylation regulator is associated with multiple tumour progression. However, the m6 A-associated regulators that influence non-small cell lung cancer (NSCLC) development have not been fully clarified. The m6 A regulator expression pattern of NSCLC patients from The Cancer Genome Atlas (TCGA) dataset was identified. Aberrations of m6A modulators are related to NSCLC development via cBioPortal database. Furthermore, we found that IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO are significantly correlated with advanced stage disease or clinical outcomes in NSCLC by UALCAN and Kaplan-Meier plot. Bioinformatics analysis showed that m6 A modulators (IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO) are associated with immunomodulator and immune infiltration expression in NSCLC via the Tumor Immune Estimation Resource (TIMER) database. The co-expression between these m6A-associated modulators was analysed by protein-protein interaction networks. Finally, we found that HNRNPA2B1 promotes NSCLC development in vitro by regulating cell proliferation and metastasis functions via Cell Counting Kit 8 (CCK8) and transwell assay. Our study showed that HNRNPA2B1 is a promising target and biomarker for cancer therapy in NSCLC.


Different training patterns at recovery stage improve cognitive function in ischemic stroke rats through regulation of the axonal growth inhibitor pathway.
Running wheel exercise training (RWE) and skilled reaching training (SRT) are physical training approaches with positive effects on cognitive function. However, few studies have compared the different effects of these exercises on long-term memory, and their mechanism remains unknown. This study investigated the effects of SRT and RWE, at the recovery stage, on the cognitive function of transient middle cerebral artery occlusion (tMCAO) rats and explored their association with NgR1/Rho-A/ROCK/LOTUS/LGI1 signaling. Adult Sprague-Dawley rats (n = 55) were divided into four groups after pretraining: SRT, RWE, tMCAO, and Sham. Rats were subjected to modified neurological severity score (mNSS) measurements and forelimb grip strength and the Morris water maze tests. Using immunofluorescence and western blotting, we evaluated axonal growth inhibitor expression in the peri-infarct cortex on days 28 and 56 after tMCAO. Results showed the mNSS reduced, whereas the grip strengths improved in RWE and SRT groups. The escape latency in the Morris water maze test was shorter, whereas the number of times of crossing the platform was higher in both the SRT and RWE groups than in the tMCAO group on day 56; furthermore, the parameters in the SRT group improved compared to those in the RWE group. Physical exercise training could improve cognitive functions by reducing the expression of the NgR1/RhoA/ROCK axon growth inhibitors and increasing the expression of the endogenous antagonists LOTUS/LGI1. Exercise training beginning at the recovery stage could improve the cognitive function in tMCAO rats through a mechanism probably associated with the axonal growth inhibitor pathway.


Quality of Diabetic Foot Ulcer Care: Evaluation of an Interdisciplinary Wound Care Clinic Using an Extended Donabedian Model Based on a Retrospective Cohort Study.
Diabetic foot ulcer (DFU), a serious complication of diabetes, is associated with increased morbidity and mortality and presents a substantial socioeconomic burden. However, DFU quality of care has been insufficiently studied. Therefore, the aim of this study was to evaluate the quality of DFU care at an interdisciplinary wound care clinic in Canada, based on an extended Donabedian model: structure, process and outcome quality indicators combined with patient characteristics. This was a retrospective cohort study of 140 adult patients with diabetes who were treated between 2012 and 2018 at a wound care clinic in a university-affiliated hospital in the Québec City area of Canada. Twenty-two internationally recognized quality-of-care indicators were identified from the literature. Data were collected from medical files, and the results were used to document the selected quality-of-care indicators. The principal indicators regarding structure and process were met, and outcome indicators were influenced by study population characteristics, particularly peripheral artery disease and critical limb ischemia. Moreover, this study highlights that quality-of-care indicators are essential when evaluating DFU outcomes, as structure and process indicators can also affect wound healing outcomes. This study suggests that DFU care at a Canadian wound care clinic, with an interdisciplinary approach, meets most quality-of-care indicators. The socioeconomic burden of DFUs for patients, health-care organizations and policymakers, and the paucity of quality and performance evaluations, call for more studies evaluating DFU care.


Intravenous ketamine for benzodiazepine deprescription and withdrawal management in treatment-resistant depression: a preliminary report.
We present the first evidence that sub-anesthetic ketamine infusions for treatment resistant depression (TRD) may facilitate deprescription of long-term benzodiazepine/z-drugs (BZDRs). Long-term BZDR prescriptions are potentially harmful yet common, partly because of challenging withdrawal symptoms. Few pharmacological interventions have evidence for facilitating BZDR discontinuation, and none in patients actively suffering from TRD. In this ambi-directional cohort study, discontinuation of long-term (>6 month) BZDRs was attempted in 22 patients with severe unipolar or bipolar TRD receiving a course of six subanesthetic ketamine infusions over four weeks. We investigated the rates of successful BZDRs deprescription, trajectories of acute psychological withdrawal symptoms, and subsequent BZDRs abstinence during a mean follow-up of 1 year (primary outcome). Clinically significant deteriorations in depression, anxiety, sleep, and/or suicidality during the acute BZDR discontinuation phase were measured by repeated standardized scales and analyzed by latent growth curve models and percent correct classification analysis. Of the 22 eligible patients, all enrolled in this study and 91% (20/22) successfully discontinued all BZDRs by the end of the 4-week intervention, confirmed by urinary analyses. Less than 25% of discontinuers experienced any significant worsening of anxiety, depression, sleep difficulties, or suicidality during treatment. During follow-up (mean [range] duration, 12 [3-24] months), 64% (14/22) of patients remained abstinent from any BZDRs. These preliminary results suggest that ketamine infusions for TRD may facilitate the deprescription of BZDRs, even in patients with active depressive symptoms and significant comorbidity. Further investigation is warranted into this potential novel application of ketamine.


Congenital pericardial defect associated with ruptured type A aortic dissection.
Congenital pericardial defect is a rare and little-known anomaly. Here we describe the unique clinical presentation of a 64-year-old man with partial defect of the left pericardium associated with ruptured acute type A aortic dissection manifesting massive left hemothorax. In this patient, the pericardial defect played the role of a pericardial draining window, which incidentally prevented the heart from cardiac tamponade. Emergent surgery was successfully performed with a prosthetic graft replacement.


Spectrum-effect relationship between UPLC-Q-TOF-MS fingerprint and anti-AUB effect of Clinopodium chinense (Benth.) O. Kuntze.
Clinopodium chinense (Benth.) O. Kuntze (C. chinense), a traditional Chinese medicine with significant astringent and hemostatic properties, is mainly used to treat abnormal uterine bleeding (AUB) with remarkable curative effect, but the active ingredients of which remain unclear. This study aimed to screen and identify the main anti-AUB components of C. chinense via spectrum-effect relationship analysis and experiment validation. Firstly, total extract of C. chinense (TEC) of 12 batches samples was prepared by Chinese Pharmacopoeia. The fingerprint chromatogram of TEC was established by UPLC-Q-TOF-MS. The AUB model was established by intragastric administration of mifepristone and misoprostol to pregnant rats, followed by the treatment with TEC. After drug administration lasting 7 days, metrorrhagia volume was measured, pathological changes in uterine tissue were evaluated by HE staining, the levels of TXB-2, TNF-α, and IL-6 were measured by ELISA. The spectrum-effect relationship was investigated by grey relational analysis (GRA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, the potential active ingredients of TEC screened by spectrum-effect relationship analysis were subsequently verified both in vitro and in vivo. A total of 25 common peaks were obtained from the fingerprint chromatogram of the 12 bathes TEC samples, 12 peaks were identified according to the reference substances. Comparing with the model group, TEC significantly reduced the uterine bleeding volume, alleviated endometrial injury, increased plasma TXB2 level, and decreased plasma IL-6 and TNF-α levels. Furthermore, seven components including kaempferol, quercetin, buddlejasaponin Ⅳb, hesperidin, naringenin, apigenin, and saikosaponin a were identified via spectrum-effect relationship analysis. In vitro and in vivo verification indicated that buddlejasaponin Ⅳb, hesperidin, naringenin, apigenin, and saikosaponin a were responsible for the anti-AUB activity of TEC. In conclusion, the present study established a spectrum-effect relationship for C. chinense and identified the main anti-AUB compounds in TEC, which provides insight for the exploration of bioactive components and quality control of C. chinense.


The long-term efficacy of the intrahepatic portosystemic shunt (TIPS) for the treatment of bleeding anorectal varices in cirrhosis. A case report and review of the literature.
In patients with portal hypertension and variceal hemorrhage, the transjugular intrahepatic portosystemic shunt (TIPS) is indicated when drug therapy or endoscopic treatment fails to control bleeding. Ruptured esophageal or gastric varices are the most frequent causes of portal hypertension-related hemorrhage, but anorectal varices may also bleed. Although several case reports have proposed TIPS in this situation, the long-term results of this procedure have not been described. We report here the case of a 68-year-old patient with decompensated cirrhosis who presented with recurrent hematochezia due to anorectal varices. A successful control of bleeding could be obtained after placement of TIPS. After 3 years of follow-up, rectal bleeding did not recur, the shunt remained primarily patent, and the patient did not present overt hepatic encephalopathy. TIPS procedure should be considered as an effective treatment of recurrent bleeding from anorectal varices in patients with decompensated cirrhosis.


Origin of the supernumerary X chromosome in a patient with fragile X and Klinefelter syndrome.
We report on a 10-year-old patient with the fragile X [fra(X)] syndrome and a 47,XXY karyotype. He had Martin-Bell syndrome, including typical craniofacial findings and mental retardation. The fra(X) was detected on both X chromosomes of the patient in 8% of the metaphases examined. DNA analysis using X-chromosome sequences from the pericentromeric region and from distal Xq suggests that the patient is homozygous at the fra(X) locus due to maternal nondisjunction during meiosis II.


The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20.
The WD repeat protein Cdc20 is essential for progression through mitosis because it is required to activate ubiquitin ligation by the anaphase-promoting complex (APC/C). Here we show in yeast that Cdc20 binds to the CCT chaperonin, which is known as a folding machine for actin and tubulin. The CCT is required for Cdc20's ability to bind and activate the APC/C. In vivo, CCT is essential for Cdc20-dependent cell cycle events such as sister chromatid separation and exit from mitosis. The chaperonin is also required for the function of the Cdc20-related protein Cdh1, which activates the APC/C during G1. We propose that folding of the Cdc20 family of APC/C activators is an essential and evolutionary conserved function of the CCT chaperonin.


Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study.
In the global KEYNOTE-042 study (Clinicaltrials.gov, NCT02220894), pembrolizumab significantly improved overall survival (OS) vs chemotherapy in patients with previously untreated programmed death ligand 1 (PD-L1)-positive locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. We present results from patients in KEYNOTE-042 enrolled from China in the global or extension study (NCT03850444; protocol identical to global study). Patients were randomized 1:1 (stratified by ECOG performance status 0 vs 1, squamous vs nonsquamous histology and PD-L1 tumor proportion score [TPS] ≥50% vs 1%-49%) to 35 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) or investigator's choice of 4 to 6 cycles of carboplatin plus paclitaxel or pemetrexed Q3W with optional pemetrexed maintenance for nonsquamous tumors. Primary endpoints were OS in patients with PD-L1 TPS ≥50%, ≥20% or ≥1%. Two hundred sixty-two patients (pembrolizumab, n = 128; chemotherapy, n = 134) were enrolled from China. At data cutoff (February 21, 2020; median follow-up, 33.0 [range, 25.6-41.9] months), pembrolizumab was shown to improve OS vs chemotherapy in patients with PD-L1 TPS ≥50% (hazard ratio [95% CI], 0.63 [0.43-0.94]), TPS ≥20% (0.66 [0.47-0.92]) and TPS ≥1% (0.67 [0.50-0.89]). Grade 3 to 5 treatment-related adverse events occurred less frequently with pembrolizumab vs chemotherapy (19.5% vs 68.8%). In 22 patients who completed 35 cycles of pembrolizumab, objective response rate was 77.3% and median duration of response was 27.6 months. Consistent with the global KEYNOTE-042 study, pembrolizumab improved OS vs chemotherapy in this study of Chinese patients with locally advanced/metastatic NSCLC and PD-L1 TPS ≥1%, supporting first-line pembrolizumab monotherapy for PD-L1-positive advanced/metastatic NSCLC in China.


The influence of mechanical forces and flow mechanisms on vessel occlusion.
The exact mechanism of irradiation-induced occlusion of normal or abnormal retinal vessels is still to a large extent obscure. Blood flow acts as a powerful heat dissipation mechanism. Therefore, a procedure which reduces flow velocity as rapidly as possible after the beginning of irradiation may work with higher efficiency. A theory based on a simplified assumption states that vessel narrowing techniques, which involve only a short length of the vessel to be occluded by a small focus diameter irradiation beam, are less efficient in bringing blood velocity down than a procedure which narrows the vessel over a greater length by a larger focus diameter irradiation beam. The thrombus building up over a greater length of the affected part of the vessel may also better resist the pressure head building up after thrombogenesis is complete because friction between thrombus and vessel wall is larger, and occlusion may, therefore, be more durable. One has to assess, therefore, whether a small-spot technique, which is presumed to be less efficient and may need repetitions, is in fact less innocuous for the surrounding retina--as is generally assumed--than a technique using a larger beam diameter, which, because it is more efficient, may need fewer or even no repetitions.


A sensitive enzymatic method for determination of free and esterified tissue cholesterol.
An enzymatic assay currently in use in clinical laboratories for quantitating total serum cholesterol has been modified for the determination of microgram quantities of tissue cholesterol. Two types of assays were developed. In the first, more generally useful method, lipids extracted with chloroform/methanol were solubilized by the addition of detergent and assayed for free and total cholesterol using laboratory prepared mixtures of reagents. Although different detergents were effective, it appears that Triton X-100 may be most universally applicable. In the second type of assay, commercially available reagent mixtures were employed for the determination of total cholesterol only. Results of both types of assays compare favorably with determination using the colorimetric assay on 3beta-hydroxysterols recovered from digitonides.


Fertility concerns in men with genitourinary malignancies: Treatment dilemmas, fertility options, and medicolegal considerations.
With increasing genitourinary cancer survivorship in patients of reproductive age, fertility preservation has become a greater focus in the management of these patients. We performed a review of articles pertaining to male infertility, fertility preservation, and genitourinary cancers. The aim was to review causes of infertility in patients with cancer, current options for fertility preservation, research that may expand preservation options, and ethical as well as medicolegal considerations. There are multiple causes of infertility in male patients with cancer, including the malignancy itself, and the treatments required to achieve a potential cure. Surgery can affect the normal pathways for erection, emission, and ejaculation. Chemotherapy can have a profound negative effect on spermatogenesis by causing chromosomal aberrations, maturation arrest, mutagenesis, and impaired spermatozoa motility. Radiation can cause cellular apoptosis with resultant reduction in spermatogonial stem cells. There are numerous methods to secure fertility before cancer treatment with the aid of cryopreservation ranging from simple patient-provided semen samples to complex sperm retrieval techniques. Research in the field of spermatogenic stem cells may lead to improved treatment options such as autotransplant of stem cells for repopulation of the testes after cancer treatment. Early discussion of possible fertility effects in patients undergoing genitourinary cancer treatment is critical in this era of increasing survivorship. Although current cancer treatments can cause infertility, there are well-established options for fertility preservation and current research will likely lead to improved treatment options.


Thermosensation involving thermo-TRPs.
The transient receptor potential (TRP) channels constitute a superfamily of large ion channels that are activated by a wide range of chemical, mechanical and thermal stimuli. TRP channels with temperature sensitivity are called thermo-TRPs. They are involved in diverse physiological functions through their detection of external environmental temperature and internal body temperature. Each thermo-TRP has its own characteristic temperature threshold for activation. As a group, they cover temperatures ranging from cold to nociceptive high temperatures. Recently, many studies have identified the functions of thermo-TRPs residing in deep organs where they are exposed to body temperature. Importantly, temperature thresholds of thermo-TRPs can be regulated by physiological factors enabling their function at relatively constant body temperature. Moreover, several thermo-TRPs are reportedly engaged in body temperature regulation. This review will summarize the current understanding of thermo-TRPs, including their roles in thermosensation and functional regulation of physiological responses at body temperature and the regulation of body temperature.


Correlation of plasma hormone levels and peripheral circulating lymphocyte subpopulations during human pregnancy.
Using monoclonal antibodies (OKT3, OKT4, OKT8) peripheral blood lymphocyte subsets were determined in 40 normal primiparous pregnant women and compared with those of 31 nonpregnant controls. In pregnant women plasma concentrations of estradiol, progesterone, human placental lactogen (HPL), beta subunit of human chorionic gonadotropin (beta HCG), and alpha-fetoprotein were measured by means of radioimmunoassay. We studied if correlations between peripheral lymphocyte subsets and plasma hormone levels might exist. We observed in pregnant women from 10 to 40 wk of amenorrhea a decrease in the percentage of OKT3 and OKT8 cells, and during the course of pregnancy an increase in the percentage of OKT4 cells. This increase inversely correlated with plasma beta HCG levels and directly correlated with plasma HPL levels.


Two-port robotic sleeve lobectomy using Stratafix sutures for central lung tumors.
To explore the feasibility of two-port robotic sleeve lobectomy using Stratafix sutures for central lung tumors, and to summarize the surgical techniques and clinical outcomes. We retrospectively evaluated 15 consecutive patients who underwent robotic bronchial sleeve lobectomy, performed by a single surgeon between March 2021 and September 2021. A half-continuous suture technique with two Stratafix sutures was used for bronchial anastomosis. The operative techniques and outcomes were analyzed. Complete resection was achieved in all patients undergoing different types of robotic bronchial sleeve lobectomy. There were no conversions to thoracotomy. The mean duration of surgery was 102.35 ± 46.31 min, mean time for bronchial anastomosis was 25.8 ± 15.2 min, mean blood loss was 64.71 ± 38.59 ml, and mean postoperative hospital stay was 4.76 ± 2.54 days. There was no death on follow-up within 90 days after surgery. Two-port robotic bronchial sleeve lobectomy and the novel anastomotic technique are both feasible and safe for selected patients.


Physical activity, sedentary time and sleep in cystic fibrosis youth: A bidirectional relationship?
Physical activity (PA) and sleep are highly important for those with cystic fibrosis (CF), yet, despite this and suggestions of a bidirectional relationship between these factors in healthy children, their relationship is yet to be investigated. PA, sedentary time (SED), and sleep were objectively derived over seven days in 58 youth (11.9 ± 2.7 years; 29 CF). Generalized linear latent and mixed models with a random intercept and slope at child-level were adjusted for age, sex, wear-time, type of day, group and mean PA/SED and sleep. Every additional 10 min sedentary was associated with 5.6 and 5.0 min less sleep and 10.6 and 12.0 min less wake after sleep onset (WASO) that night, in CF and healthy children, respectively. PA, regardless of intensity, was not associated with total sleep time but every additional 10 min of light PA (LPA) was associated with 3.0 min less WASO in healthy participants. Ten mins more sleep was associated with 3.1 and 1.7 min less SED in CF and healthy children, respectively. In CF, greater sleep time led to less LPA (3.6 min) the following day, whereas, in healthy children, poor sleep quality (greater WASO) was associated with more LPA (1.4 min) and moderate-to-vigorous PA (5.2 min) the following day. A bidirectional relationship between SED and subsequent total sleep time was evident, irrespective of group, whereas the relationship between sleep and PA was group dependent. These findings have important implications regarding the reciprocal effects of promoting PA or sleep quantity or quality.


Ultrasound-positive axillary lymph nodes in early breast cancer: can a patient subgroup avoid axillary lymph node dissection? A simple algorithm is suggested.
National UK guidelines suggest that axillary lymph node dissection (ALND) is no longer mandatory for selected early node-positive breast cancer patients. Our study aimed to identify patients with early breast cancer and ultrasound (USS)-positive axillary metastasis who possess low burden of axillary disease and can avoid ALND. We conducted a 5-year study of prospectively collected data of patients with clinically T1-2, N0 breast cancer and a positive USS-guided axillary biopsy. Primary outcome was involvement of 1-2 lymph nodes (low disease burden) or ≥3 lymph nodes (higher axillary disease) on final ALND histology. Tumour type, size, grade, multifocality, receptor status, number of abnormal imaged nodes and presence of lympho-vascular invasion (LVI) were recorded. Data were analysed using chi-squared and Student's t-test. One hundred and sixty-six patients underwent ALND for pT1-2 breast cancer. Seventy patients had no clinically palpable lymphadenopathy but a positive USS-guided biopsy. Of 70 patients, 32 women (46%) had low disease burden, whereas 38 women (54%) had higher axillary disease in final histology. LVI and >1 abnormal lymph node on USS were both significantly associated with higher disease burden (p = 0.050 and 0.009, respectively). Our study confirms the presence of an important patient cohort, who are clinically node-negative with a positive USS-guided biopsy and a low volume of axillary disease. No imaging modality currently has the accuracy required to identify patients with this low disease burden preoperatively but we propose a simple algorithm for axillary management in this subgroup.


Conserved and divergent mechanisms of inner kinetochore assembly onto centromeric chromatin.
Kinetochores are large protein complexes built on centromeric chromatin that mediate chromosome segregation. The inner kinetochore, or constitutive centromere-associated network (CCAN), assembles onto centromeres defined by centromere protein A (CENP-A) nucleosomes (CENP-ANuc), and acts as a platform for the regulated assembly of the microtubule-binding outer kinetochore. Recent cryo-EM work revealed structural conservation of CCAN, from the repeating human regional centromeres to the point centromere of budding yeast. Centromere recognition is determined mainly through engagement of duplex DNA proximal to the CENP-A nucleosome by a DNA-binding CENP-LN channel located at the core of CCAN. Additional DNA interactions formed by other CCAN modules create an enclosed DNA-binding chamber. This configuration explains how kinetochores maintain their tight grip on centromeric DNA to withstand the forces of chromosome segregation. Defining the higher-order architecture of complete kinetochore assemblies with implications for understanding the 3D organisation of regional centromeres and mechanisms of kinetochore dynamics, including how kinetochores sense and respond to tension, are important future directions.


Prey choice by marten during a decline in prey abundance.
We examined variation in diet choice by marten (Martes americana) among seasons and between sexes and ages from 1980-1985. During this period prey populations crashed simultaneously, except for ruffed grouse (Bonasa umbellus) which was common at the beginning and end of the study, and masked shrews (Sorex cinereus) which were abundant in 1983. Marten were catholic in selection of prey and made use of most available mammalian prey, ruffed grouse, passerine birds, berries, and insects. Diet niche was widest during the latter three years when prey was scare, particularly in late winter. Diet niche breadth was negatively correlated with abundance of all common prey species. Proportion of small prey species in the diet was correlated with absolute abundance of those species, but proportion of some large prey was related to their relative abundance. Diet choice varied among years and among seasons. Berries and insects were common in summer diets while large prey, particularly varying hare (Lepus americanus), were more frequent in winter diet than in summer diet. We found little evidence that any small mammal species was a preferred prey. Sexual size dimorphism between the sexes did not affect prey choice, nor did age. Reduced foraging effort in winter resulted in a wider diet niche only when prey was scarce. The only prediction of optimal foraging models fully supported by our data was a wider diet niche with reduced prey abundance. However, among the three most profitable prey species choice was dependent on the absolute abundance of the most profitable type (varying hare). We suggest that marten primarily forage for large prey but employ a strategy which results in encounters with small prey as well. These small prey are eaten as they provide energy at minimal cost, between captures of large prey.


The effect of tolmetin on the chronic pain and decreased functional capacity associated with degenerative joint disease.
Degenerative joint disease (DJD) is a common disorder characterized by chronic pain and limitation of activity, for which treatment with a nonsteroidal anti-inflammatory drug (NSAID) is often useful. The anti-inflammatory activity of the NSAID tolmetin sodium has been well described, being comparable in efficacy to indomethacin and effective for the relief of the acute and chronic symptoms that accompany DJD. To examine specifically the effect of tolmetin in controlling the pain and functional limitation in DJD of the spine, tolmetin was tested against placebo in a double-blind, two-segment, crossover study. Twenty-six patients (mean age, 62.5 years; range, 42-79 years) received three weeks of tolmetin 1,200 mg/d and three weeks of placebo. The results showed that tolmetin provided significantly greater relief of symptoms than placebo in virtually all measurements of joint pain and stiffness: tenderness, pain at rest, pain on motion, intensity of joint pain (P less than 0.001), and duration of morning stiffness (P = 0.002). Statistically significant improvement was noted in two of the three measures of cervical range of motion (P less than or equal to 0.01) and in all assessments of daily living activities (P = 0.001 in four parameters; P = 0.02 in a fifth parameter). Global evaluations of response to treatment by both patients and investigator also demonstrated significant effects (P less than or equal to 0.002). Significantly more placebo patients (13 of 26) than tolmetin patients (two of 26) found the medication ineffective and discontinued treatment prematurely (P = 0.01). No serious or limiting adverse reactions were seen during placebo or tolmetin therapy. The most frequently reported side effects on both therapies were gastrointestinal.(ABSTRACT TRUNCATED AT 250 WORDS)


Recurrence of hepatitis B in children with serologic evidence of past hepatitis B virus infection undergoing antileukemic chemotherapy.
Two patients showed an unusual serologic response to hepatitis B virus infection during intensive chemotherapy for acute lymphoblastic leukemia. Before treatment, one patient was anti-HBs- and anti-HBc-positive. During intensive chemotherapy these antibodies disappeared and HBsAg and HBeAg became detectable. Twenty months later, still on maintenance chemotherapy, active viral replication with high DNA polymerase levels was present. The second patient developed anti-HBc during the first course of intensive chemotherapy for acute lymphoblastic leukemia. She had anti-HBc and anti-HBe when a bone marrow relapse of the leukemia was diagnosed 3 years later and became HBsAg-positive together with high DNA polymerase levels in the serum while receiving intensive chemotherapy. Clinically no signs of active hepatitis were noted in these patients.


Bovine beta 1----4-galactosyltransferase: two sets of mRNA transcripts encode two forms of the protein with different amino-terminal domains. In vitro translation experiments demonstrate that both the short and the long forms of the enzyme are type II membrane-bound glycoproteins.
We have used S1 and primer extension analysis to demonstrate that the gene for bovine beta 1----4-galactosyltransferase specifies two sets of mRNA transcripts of different lengths. The longer mRNA transcripts initiate upstream of two in-frame ATG codons and encode a protein of 402 amino acids (long form). The shorter mRNA transcripts initiate between the two in-frame ATG codons and encode a protein of 389 amino acids (short form). These two related forms of beta 1----4-galactosyltransferase have an identical large (358 amino acids), potentially glycosylated, COOH-terminal catalytic domain, and an identical single transmembrane domain. The only difference in primary structure between the two forms is that the long form contains an NH2-terminal extension of 13 amino acids. Thus, bovine beta 1----4-galactosyltransferase fits the pattern established for murine beta 1----4-galactosyltransferase (Shaper, N. L., Hollis, G. L., Douglas, J. G., Kirsch, I. R., and Shaper, J. H. (1988) J. Biol. Chem. 263, 10420-10428). Inspection of the NH2-terminal domain suggests that the long form of the bovine enzyme, like its murine counterpart, has a functional cleavable signal sequence which would dictate that the two forms of the membrane-bound enzyme are oriented in opposite directions. We have tested this hypothesis by in vitro translation in the absence or presence of dog pancreas microsomes. In vitro translation of RNA transcripts for the long and short form of beta 1----4-galactosyltransferase in the absence of microsomes results in the synthesis of polypeptides with apparent Mr of 44,500 and 43,000, respectively. In vitro translation of each transcript in the presence of microsomes results in the synthesis of two glycosylated, endoglycosidase H-sensitive proteins with apparent Mr of 47,500 and 46,000. These experiments and additional protease protection experiments demonstrate that the COOH-terminal domain of both the short and the long form of bovine beta 1----4-galactosyltransferase are translocated into the microsomal lumen. By extrapolation, both forms of the enzyme are oriented in vivo as Type II membrane-bound glycoproteins.


Immunomodulatory effect of peripheral benzodiazepine receptor ligands on human mononuclear cells.
Immunomodulatory effect of ligands active at the peripheral benzodiazepine receptor (PBR) was examined in human peripheral blood mononuclear cells (PBMC). Ro5-4864, PK11195 and diazepam suppressed phytohemagglutinin (PHA) and concanavalin A (ConA) induced proliferation of PBMC. All three ligands inhibited interleukin-3-like activity (IL-3-LA) secretion, while the production of interleukin-2 (IL-2) was inhibited by Ro5-4864 and diazepam only. The selective central benzodiazepine ligand clonazepam did not affect the cellular immune functions examined. Our results indicate an in-vitro immuno-suppressive activity of peripheral and mixed, but not central type benzodiazepine ligands.


Vestiges of lost introns in the thermal stability map of DNA.
The absence of introns in prokaryotic genes has been explained by intron loss on various bases. Here we report another piece of evidence on intron loss, which was found in the thermal stability map of DNA. We calculated the local melting temperature of cDNA sequences and found that (i) gaps in thermal stability tend to occur near intron positions with a statistical significance, and (ii) one-third of the gaps far from intron positions can be assigned to lost introns. From these results we conclude that the gaps of thermal stability in protein coding regions are the vestiges of lost introns.


Are mouse telomeres going to pot?
Pot1 is a conserved single-stranded DNA binding protein with crucial functions in the protection of telomeres and maintenance of their length. In this issue of Cell, two papers (Hockemeyer et al., 2006; Wu et al., 2006) examine the roles of murine Pot1 homologs and describe intriguing new insights into how cells protect their chromosome ends from DNA-repair activities.


The intraocular penetration of acyclovir after subconjunctival administration.
Five patients received a subconjunctival injection (25 mg) of acyclovir before undergoing scheduled enucleation. Seven hours after injection, the observed aqueous and vitreous levels of acyclovir were above the minimum inhibitory concentrations for many herpes simplex viruses types 1 and 2. Systemic absorption measured at two and seven hours after injection was negligible.


Comparison of Isolated Sciatic Nerve and Sacral Nerve Root Endometriosis: A Review of the Literature.
This review aimed to compare isolated sciatic and sacral nerve root endometriosis in terms of anatomic distribution, patients' symptoms and history, diagnostics, treatments, and outcomes. We searched PubMed, MEDLINE, Web of Science, and Embase from inception to October 2021 using a combination of keywords including "sciatic nerve endometriosis," "sacral nerve root endometriosis," and associated Medical Subject Headings. Relevant publications and references were also checked for further articles. Two independent researchers performed the study selection. We included all original research articles, case reports, and case series in English that reported on the isolated sciatic nerve and sacral nerve root endometriosis. The initial search identified 92 articles, and 40 articles, mostly case reports and case series, were included. The review included 362 patients: with 256 and 106 patients in the sacral and the sciatic groups, respectively. In both groups, most patients had right-sided endometriosis. In the sciatic group, most of the patients presented with foot drop, leg motor weakness, and sciatic dermatome hypoesthesia. The frequencies of all these symptoms were significantly higher in the sciatic group (all p <.001). By contrast, in the sacral group, most of patients presented with pudendal neuralgia (p <.001). Intraoperative, early, late, and 1-year postoperative complications did not differ significantly between the 2 groups. This study indicated that isolated sciatic and sacral nerve root endometrioses were more common on the right side. Laparoscopic surgery was more commonly performed over traditional open or transgluteal surgery techniques. Sacral nerve root endometriosis is often accompanied by deep infiltrating endometriosis. Magnetic resonance imaging and myelography may be useful diagnostic tools in the preoperative workup. There was usually no significant improvement after surgery in cases of isolated sciatic nerve endometriosis presenting with foot drop.


Testing for mutagens in an aluminium plant. The results of Salmonella typhimurium tests on urine from exposed workers.
Urine concentrates from workers in a Söderberg potroom and an anode paste plant were tested for mutagenicity by the Salmonella reversion assay. The study is aimed at group exposure as an indicator of the effect of the work atmosphere. Urine from exposed smokers showed mutagenic activity, whereas urine from exposed non-smokers did not. The mutagenicity of exposed smokers' urine was not significantly different from the urine from non-exposed smokers. Significant mutagenicity of smokers' urine was evident only in the presence of a rat-liver metabolic system. Since an earlier expectorate analysis has shown that mutagens from the work atmosphere are deposited in the workers' respiration system and the urine analysis does not show any effect of occupational exposure, it is likely that the mutagens are eliminated from the body via other routes than renal excretion.


How carotenoids function in photosynthetic bacteria.
Carotenoids are essential for the survival of photosynthetic organisms. They function as light-harvesting molecules and provide photoprotection. In this review, the molecular features which determine the efficiencies of the various photophysical and photochemical processes of carotenoids are discussed. The behavior of carotenoids in photosynthetic bacterial reaction centers and light-harvesting complexes is correlated with data from experiments carried out on carotenoids and model systems in vitro. The status of the carotenoid structural determinations in vivo is reviewed.


Halofuginone upregulates the expression of heparanase in thioacetamide-induced liver fibrosis in rats.
Advanced hepatic fibrosis is characterized by excessive extracellular matrix deposition, where collagen and proteoglycans are the main constituents of scar tissue. In previous studies, we showed that heparanase, a heparan sulfate-degrading enzyme, and vascular endothelial growth factor (VEGF) play an important role during liver development and remodeling. In this communication, we investigated the relationship between heparanase and VEGF in thioacetamide-induced liver fibrosis in rats. Our study shows that heparanase mRNA expression levels correlate with those of VEGF during the induction and recovery stages of liver fibrosis. We further demonstrated that treating fibrotic rat livers with halofuginone (HF), a multipotent antifibrogenic drug, and subsequently subjecting them to hydrodynamics-based transfection with human VEGF-165 resulted in elevated expression of heparanase mRNA. Moreover, these rats demonstrated an improved capacity to regenerate following 70% partial hepatectomy. In vitro, HF stimulated heparanase and VEGF mRNA expression in hepatic stellate cells. Taken together, our results suggest that in addition to the known multiple functions of HF, it also enhances heparanase and VEGF expression and promotes liver regeneration. Accordingly, HF seems to possess ideal properties required to become an excellent antifibrogenic agent in humans.


Distribution of antibiotic, heavy metals and antibiotic resistance genes in livestock and poultry feces from different scale of farms in Ningxia, China.
With the rapid development of livestock and poultry breeding industries, pollution problems caused by the discharge of animal feces have become increasingly severe. Nevertheless, there are limited investigations about nutrients and pollutants in animal feces from different scale of farms, especially in Northwest China. Here we investigated nutrients content, 19 antibiotics, 7 heavy metals, 329 antibiotic resistance genes (ARGs) and 35 mobile genetic elements (MGEs) in six main livestock and poultry feces collected from 5 coastal regions of Ningxia. Pig and chicken feces exhibited higher levels of nutrients content, but antibiotics, heavy metals, ARGs and MGEs were also more abundant than those in cattle and sheep feces. Chlortetracycline hydrochloride and doxycycline hyclate were the most commonly used antibiotic, which detected with the highest rate and concentrations, especially in broiler, layer and pig feces. Strong positive correlations were found among different ARGs or between ARGs and MGEs, indicated the risk of horizontal gene transfer of ARGs. Residual antibiotic and heavy metals significantly affect the abundance of ARGs. Feeding mode and the scales of the animal farms served little effect on the distribution of the pollutants (including residual antibiotics, heavy metals, MGEs and ARGs), which were significantly different among animal types. Use of antibiotics and heavy metals should be strictly regulated, especially in chicken and pig farms, in order to control contaminants and reduce potential risks to the environment.


Guidelines for venous thromboembolism and clinical practice in Italy: a nationwide survey.
Venous thromboembolism (VTE) is a common health problem for today's society, and considering the role that it plays in surgical patients (general surgery, gynecology, and orthopedics), new advances in our understanding of the procedures and trauma characteristics are relevant and necessary. The most important and recently published guidelines concerning this problem have been taken into consideration, leading to articulate investigations and data evaluation. This project has proposed a data-survey framework available as a questionnaire in order to investigate application of the guidelines for VTE throughout the national territory. Of the total 714 Italian centers, a random sample of 214 were contacted and asked to take part in this study; of these, 146 replied (20.4% of total and 68.2% of the sample): 48 departments of general surgery, 46 departments of gynecology, and 52 departments of orthopedics. About 70% of the centers has appropriate information about surgery as a risk factor for VTE. The answers have provided evidence of an adequate knowledge of the instrumental and laboratory diagnostic pathways, useful to confirm the diagnosis of TE (80%). Data waiting compared with morbidity and mortality rates related to deep vein thrombosis and pulmonary embolism showed an increase of mortality associated with the diagnostic data timing of supply, with an exponential trend linked to the data acquisition delay. Both risk stratification and adequate application of prophylaxis together with treatment devices represent a real tool to control morbidity and mortality for VTE. Moreover, diagnostic data waiting significantly influences adequate prophylaxis. In Italy, only 40% of the centers are ready to provide diagnostic data within 12 hr.


Composition of IgA immune complexes precipitated with polyethylene glycol. A model for isolation and analysis of immune complexes.
Covalently cross-linked large and intermediate-sized IgA oligomers, prepared with IgA anti-dinitrophenyl (DNP) and bis-DNP-pimelic acid ester, were used to examine the ability of different concentrations (3.5%, 5% and 7%, w/v) of polyethylene glycol (PEG) to precipitate IgA immune complexes (IgA-IC). The size of the IgA-IC precipitated with PEG was determined by gradient polyacrylamide gel electrophoresis and quantitative autoradiography. The standard concentration of 3.5% PEG precipitated only a minor fraction (20%) of the IgA-IC. In contrast, 5% and 7% PEG precipitated 45% and 79% of the complexes, respectively. To test the influence of the antigen on the PEG assay. IgA-IC prepared with IgA anti-DNP and DNP conjugates of either bovine serum albumin or Ficoll were also used. Approximately 38% of these IgA-IC were precipitated with 3.5%, PEG. By comparison, the concentration of 5% and 7% PEG precipitated 60% and 76% of the IgA-IC, respectively. Distilled water rather than the standard borate-buffered saline was shown to be the optimal solvent for resolubilization of the PEG precipitates. Serum samples from 22 IgA nephropathy patients and 12 normal donors were tested with 3.5%, 5% and 7% PEG. Only the 7% PEG assay showed a significant difference between patients and controls (P less than 0.001) in the IgA levels of precipitates. Thus, the use of 7% PEG is recommended for the detection, isolation and analysis of large- and intermediate-sized IgA-IC.


The effects of opiates on calcium accumulation on rat peritoneal mast cells.
Opiate agonists, morphine, levorphanol and beta-endorphin increased calcium accumulation in rat peritoneal mast cells. This effect was dose dependent and beta-endorphin was 10 times more potent than morphine. The stimulation was stereospecific and inhibited by naloxone. The site of the opiate action appears to be on the outer surface of the plasma membrane since lysis of the mast cell did not alter the response to morphine. Tolerance to the opiate effect was not seen after chronic morphine administration. Morphine did not stimulate histamine release even at relatively high doses in vivo or high concentrations in vitro. It is reasoned that the enhancing effects on external calcium accumulation may reduce the critical cytosol calcium level for effecting histamine release.


Zika Virus Infection and Development of a Murine Model.
In view of the recent outbreak of Zika virus (ZIKV), there is an urgent need to investigate the pathogenesis of the symptoms associated with ZIKV infection. Since the first identification of the virus in 1947, the pathologies associated with ZIKV infection were thought to be limited with mild illness that presented fever, rashes, muscle aches, and weakness. However, ZIKV infection has been shown to cause Guillain-Barré Syndrome, and numerous cases of congenital microcephaly in children have been reported when pregnant females were exposed to the virus. The severity and the rate of spread of ZIKV in the last year has drawn alarming interest among researchers to investigate murine models to study viral pathogenesis and develop candidate vaccines. A recent study by Lazear and colleagues, in the May 2016 issue of cell host and microbe, is an effort to study the pathogenesis of contemporary and historical virus strains in various mouse models.


Combined linkage and linkage disequilibrium QTL mapping in multiple families of maize (Zea mays L.) line crosses highlights complementarities between models based on parental haplotype and single locus polymorphism.
Advancements in genotyping are rapidly decreasing marker costs and increasing marker density. This opens new possibilities for mapping quantitative trait loci (QTL), in particular by combining linkage disequilibrium information and linkage analysis (LDLA). In this study, we compared different approaches to detect QTL for four traits of agronomical importance in two large multi-parental datasets of maize (Zea mays L.) of 895 and 928 testcross progenies composed of 7 and 21 biparental families, respectively, and genotyped with 491 markers. We compared to traditional linkage-based methods two LDLA models relying on the dense genotyping of parental lines with 17,728 SNP: one based on a clustering approach of parental line segments into ancestral alleles and one based on single marker information. The two LDLA models generally identified more QTL (60 and 52 QTL in total) than classical linkage models (49 and 44 QTL in total). However, they performed inconsistently over datasets and traits suggesting that a compromise must be found between the reduction of allele number for increasing statistical power and the adequacy of the model to potentially complex allelic variation. For some QTL, the model exclusively based on linkage analysis, which assumed that each parental line carried a different QTL allele, was able to capture remaining variation not explained by LDLA models. These complementarities between models clearly suggest that the different QTL mapping approaches must be considered to capture the different levels of allelic variation at QTL involved in complex traits.


Enzymatically-synthesized xylo-oligosaccharides laurate esters as surfactants of interest.
Lipase-catalyzed synthesis of xylo-oligosaccharides esters from pure xylobiose, xylotriose and xylotetraose in the presence of vinyl laurate was investigated. The influence of different experimental parameters such as the loading of lipase, the reaction duration or the use of a co-solvent was studied and the reaction conditions were optimized with xylobiose. Under the best conditions, a regioselective esterification occurred to yield a monoester with the acyl chain at the OH-4 of the xylose unit at the non-reducing end. Surface-active properties of these pure xylo-oligosaccharides fatty esters have been evaluated. They display interesting surfactant activities that differ according to the degree of polymerization (DP) of the glycone moiety.


In vitro and in vivo embryo toxicity of antilaminin antibodies in the rat.
Rats mated after laminin immunization had higher frequencies of resorptions (57%) than those immunized with bovine serum albumin (20%) and had sera that were toxic to cultured rat embryos. In addition, sera from rats immunized with laminin A chains but not B chains were toxic to cultured embryos. The toxicity of sera to embryos was related to the reactivity of sera to specific laminin fragments rather than to sera IgG levels against intact laminin. In addition, resorptions in pregnant rats immunized with laminin were not related to the sera antilaminin IgG levels. However, levels of uterine antilaminin IgA, the predominant uterine isotype, increased considerably during the first 3.5 days of pregnancy, while sera antilaminin IgG remained constant. (Am J Reprod Immunol.


Necrotising fasciitis of the breast: A rare but deadly disease.
Necrotising fasciitis is a rare but deadly bacterial infection causing soft tissue and fascial necrosis. It is associated with a mortality rate of 25%. It is characterised by; erythematous skin, which turns dusky blue before haemorrhagic bullae develop; localised pain; and inflammation. It is most commonly found in the extremities, the abdomen or the perineum but is rarely seen in the breast. We describe a 54-year-old lady who presented with breast erythema and raised inflammatory markers. Initially treated as cellulitis, however when her symptoms did not improve and despite IV antibiotics her bloods worsened, a CT scan was performed which showed a large volume of interstitial soft tissue gas with diffuse fat stranding, consistent with necrotising fasciitis. Debridement of her breast alongside the use of sensitive antibiotics and ITU support led to a satisfactory outcome. We discuss how an early diagnosis can be made by the recognition of a triad of symptoms common in necrotising fasciitis, and how optimal management can be achieved with the incorporation of imaging to successfully identify the condition and allow targeted debridement of the areas of necrotising fasciitis. A high index of suspicion should be held if pain is disproportionate to the signs or sepsis is present. To aid an early diagnosis, imaging of the breast should be performed early to avoid delay in treatment.


Comparison of treatment indices associated with the correction and lengthening of deformities along various lower limb frontal plane directions.
The Taylor spatial frame (TSF) provides higher precision in the dimensional correction of some lower limb deformities. However, no study to date has compared the osteogenesis outcome of correction and lengthening among various directions in the frontal plane. We examined the relationship between the external fixation index (EFI) and the direction of correction in the frontal plane. We classified 25 patients undergoing correction with the TSF into three groups: Group A (8 patients, varus deformity), Group B (6 patients, valgus deformity), and Group C (9 patients, non-correction in the frontal plane). We excluded patients who underwent chemotherapy, were converted to internal fixation, had infection or pseudarthrosis, and in whom the corrected gain was <2.4 cm. No significant differences in age, sex, etiology of deformity, complication due to deformity in another plane, osteotomy distribution, TSF use duration, and correction distance were found. The average EFI was 83.4, 60.5, and 51.2 days/cm in Groups A, B, and C, respectively, with the EFI being significantly higher in Group A than in Group C (P < 0.05). Osteogenesis of varus deformities was more prolonged than that of non-correction in the frontal plane. These results provide useful insights that can aid in minimizing complications due to external fixation and improving our understanding of the mechanism of osteogenesis in the tibia.


Recruitment of non-patient volunteers with schizophrenia spectrum personality symptoms.
Authors aimed to evaluate the yield and effectiveness of recruiting community schizophrenia spectrum personality (SSP) subjects via targeted newspaper advertisements listing SSP traits. Eight newspaper advertisements listing SSP traits were placed in regional newspapers over a 3-year period. Respondents (n = 209) were screened thoroughly via telephone, and eligible subjects were invited for face-to-face clinical interviews. One hundred and one subjects (48% of the respondents) were screened out over the phone and another 30% were no-shows or refused. Of the 46 subjects who were interviewed, a majority (24 subjects; 52%) met this study's criteria for SSP. These subjects experienced significant psychotic-like symptoms, as ascertained by a self-rating scale, and showed a downward drift in their socio-economic status. One can successfully recruit SSP subjects, with high yield, using targeted telephone advertisements combined with thorough telephone screening.


The Aryne Phosphate Reaction.
Condensed phosphates are a critically important class of molecules in biochemistry. Non-natural analogues are important for various applications, such as single-molecule real-time DNA sequencing. Often, such analogues contain more than three phosphate units in their oligophosphate chain. Consequently, investigations into phosphate reactivity enabling new ways of phosphate functionalization and oligophosphorylation are essential. Here, we scrutinize the potential of phosphates to act as arynophiles, paving the way for follow-up oligophosphorylation reactions. The aryne phosphate reaction is a powerful tool to-depending on the perspective-(oligo)phosphorylate arenes or arylate (oligo-cyclo)phosphates. Based on Kobayashi-type o-silylaryltriflates, the aryne phosphate reaction enables rapid entry into a broad spectrum of arylated products, like monophosphates, diphosphates, phosphodiesters and polyphosphates. The synthetic potential of these new transformations is demonstrated by efficient syntheses of nucleotide analogues and an unprecedented one-flask octaphosphorylation.


Assessment of Biostimulation Methods Based on Chemical Communication in Female Doe Reproduction.
Biostimulation is an animal management practice that helps improve reproductive parameters by modulating animal sensory systems. Chemical signals, mostly known as pheromones, have a great potential in this regard. This study was conducted to determine the influence of short-term female rabbit exposure to different conditions, mainly pheromone-mediated, on reproductive parameters of inseminated does. Groups of 60 females/each were exposed to (1) female urine, (2) male urine, (3) seminal plasma and (4) female-female (F-F) separated, just before artificial insemination, and compared to a 'golden method' female-female interaction. The following reproductive parameters were analyzed for each group: receptivity (vulvar color), fertility (kindling rate), prolificacy and number of born alive and dead kits/litter. Our results showed that the biostimulation methods employed in this experiment did not significantly improve any of the analyzed parameters. However, female doe exposure to urine, especially to male urine, showed no significant higher fertility values (95.4%) when compared to the rest of the experimental conditions (on average 92.4%). Female-female interaction before artificial insemination, which is a common practice in rabbit farms, showed similar results as not establishing social interaction (F-F separated), which suggests that F-F interaction could be replaced by F-F separated, therefore avoiding unnecessary animal management and time cost. On the other hand, fertility ranges were lower for animals with a pale vulvar color whereas no differences were noticed among the other three colors which measure receptivity (pink, red, purple), thus suggesting that these three colors could be grouped together. Future studies should aim at determining potential chemical cues/pheromones released through bodily secretions that influence reproduction in rabbits, therefore contributing to animal welfare and to a natural image of animal production.


Impact of left ventricular ejection fraction on the effect of renin-angiotensin system blockers after an episode of acute heart failure: From the KCHF Registry.
This observational study aimed to examine the prognostic association of angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARB) in different left ventricular ejection fraction (LVEF) categories. In 3717 patients enrolled in the KCHF Registry, a multicentre registry including consecutive patients hospitalized for acute heart failure (HF), we assessed patient characteristics and association between ACE-I/ARB and clinical outcomes according to LVEF. In the three LVEF categories (reduced LVEF [HFrEF], mid-range LVEF [HFmrEF] and preserved LVEF [HFpEF]), we compared the patients with ACE-I/ARB as discharge medication and those without, and assessed their 1-year clinical outcomes. We defined the primary outcome measure as a composite of all-cause death and HF hospitalization. The 1-year cumulative incidences of the primary outcome measure were 36.3% in HFrEF, 30.1% in HFmrEF and 33.8% in HFpEF (log-rank P = 0.07). The adjusted risks of the ACE-I/ARB group relative to the no ACE-I/ARB group for the primary outcome measure were significantly lower in HFrEF and HFmrEF (HR 0.66 [95%CI 0.54-0.79], P<0.001, and HR 0.61 [0.45-0.82], P = 0.001, respectively), but not in HFpEF (HR 0.95 [0.80-1.14], P = 0.61). There was a significant interaction between the LVEF category and the ACE-I/ARB use on the primary outcome measure (Pinteraction = 0.01). ACE-I/ARB for patients who were hospitalized for acute HF was associated with significantly lower risk for a composite of all-cause death and HF hospitalization in HFrEF and HFmrEF, but not in HFpEF. ACE-I/ARB might be a potential treatment option in HFmrEF as in HFrEF.


Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function.
Despite recent efforts to increase diversity in genome-wide association studies (GWASs), most loci currently associated with kidney function are still limited to European ancestry due to the underlying sample selection bias in available GWASs. We set out to identify susceptibility loci associated with estimated glomerular filtration rate (eGFRcrea) in 80027 individuals of African-ancestry from the UK Biobank (UKBB), Million Veteran Program (MVP), and Chronic Kidney Disease genetics (CKDGen) consortia.We identified 8 lead SNPs, 7 of which were previously associated with eGFR in other populations. We identified one novel variant, rs77408001 which is an intronic variant mapped to the ELN gene. We validated three previously reported loci at GATM-SPATA5L1, SLC15A5 and AGPAT3. Fine-mapping analysis identified variants rs77121243 and rs201602445 as having a 99.9% posterior probability of being causal. Our results warrant designing bigger studies within individuals of African ancestry to gain new insights into the pathogenesis of Chronic Kidney Disease (CKD), and identify genomic variants unique to this ancestry that may influence renal function and disease.


A segmental polynomial model of ventricular electrograms as a simple and efficient morphology discriminator for implantable devices.
The goal of this study is to construct a polynomial model of the ventricular electrogram (EGM) that faithfully reproduces the EGM and can be implemented in current, low computational power implantable devices. Such a model of ventricular EGMs is still lacking. New Zealand White rabbits underwent chronic implantation of pacemakers through a left thoracotomy approach. Unipolar ventricular EGMs sampled at a frequency of 1 kHz were stored digitally in 1-minute segments before and after intravenous injection of isoproterenol or procainamide. Each cardiac cycle was divided into a QR and an RQ segment which were modeled separately using a 6th order polynomial equation. The 14 coefficients of each cardiac cycle were reproducible throughout the baseline recordings (r > or = 0.94, P < 0.002). Isoproterenol caused no changes in the coefficients of the QR segment but significantly altered all but one of the seven coefficients of the RQ segment (p(6)= 0.0039, p(5)= 0.017, p(4)= 0.00007, p(3)= 0.112, p(2)= 0.00016, p(1)= 0.0086, p(a)= 0.00003). Procainamide caused statistically significant changes in both QR segment (p(6)= 0.018, p(5)= 0.287, p(4)= 0.019, p(3)= 0.176, p(2)= 0.016, p(1)= 0.362, p(a)= 0.000044) and RQ segment (p(6)= 0.0028, p(5)= 0.036, p(4)= 0.002, p(3)= 0.058, p(2)= 0.022, p(1)= 0.718, p(a)= 0.0018) coefficients. Our data demonstrate the feasibility of a segmental polynomial equation that reproduces the phases of depolarization and repolarization of the rabbit EGM. This model is reproducible and demonstrates the expected changes with antiarrhythmic drug administration. If reproduced in humans, these findings can have wide applications in patients with implantable devices, ranging from morphologic discrimination of arrhythmias to early detection of metabolic derangements or drug effects.


How nanotechnology can enhance docetaxel therapy.
Docetaxel has been recognized as one of the most efficient anticancer drugs over the past decade; however, its poor water solubility and systemic toxicity have greatly limited its clinical application. In recent decades, the emergence of nanotechnology has provided new drug delivery systems for docetaxel, which can improve its water solubility, minimize the side effects and increase the tumor-targeting distribution by passive or active targeting. This review focuses on the research progress in nanoformulations related to docetaxel delivery - such as polymer-based, lipid-based, and lipid-polymer hybrid nanocarriers, as well as inorganic nanoparticles - addressing their structures, characteristics, preparation, physicochemical properties, methods by which drugs are loaded into them, and their in vitro and in vivo efficacies. Further, the targeted ligands used in the docetaxel nanoformulations, such as monoclonal antibodies, peptides, folic acid, transferrin, aptamers and hyaluronic acid, are described. The issues to overcome before docetaxel nanoformulations can be used in clinical and commercial applications are also discussed.


Alternative reagents for chemical noise reduction in liquid chromatography-mass spectrometry using selective ion-molecule reactions.
Reduction of ionic chemical background noise based on selective gas-phase reactions with chosen neutral reagents has been proven to be a very promising approach in liquid chromatography-mass spectrometry (LC-MS). In this study further investigations on alternative reagents including the disulfides (dimethyl disulfide, diethyl disulfide, methyl propyl disulfide), dimethyl trisulfide, ethylene oxide, and butadiene monoxide, for example, have been carried out. Tandem mass spectrometric studies of ion/molecule reactions indicate that-besides dimethyl disulfide-ethylene oxide and butadiene monoxide also exhibit very efficient reactions with background ions. Furthermore, it is confirmed that the reactions are very selective according to the test with some analyte ions. In contrast to its rapid reactions with background ions, ethylene oxide does not react, or reacts much less, with these analytes. Therefore, it can be used as an alternative reagent for noise reduction. Although reactions of the other tested neutral reagents with background ions are evaluated, they are generally not suitable as reagents for this purpose because of lack of reactivity or dramatic ion losses during reactions.


Construction of a novel chitosan-based macromolecular nanoprobe for specific fluorescent detection of H2S in live animals.
H2S is one of the signal molecules in live organisms and a poisonous gas, which is closely related to our life. The traditional synthetic small molecular organic probes often have the disadvantages of low biocompatibility. In this paper, a fluorescent nanoprobe for detecting H2S in live organisms was constructed based on chitosan. The structure of CH-CN was characterized by infrared spectroscopy, nuclear magnetic resonance, x-ray photoelectron spectroscopy (XPS), XRD and scanning electron microscope (SEM). In the presence of Na2S, the fluorescence intensity at 560 nm was significantly enhanced, and showed high selectivity and sensitivity toward H2S. Based on the good fluorescence response of CH-CN, the probe was also successfully applied to H2S imaging in HepG2 cells and zebrafish. These experimental results indicate that the probe has lower cytotoxicity and excellent stability. The present research shows a typical example of construction of chitosan-based macromolecular fluorescent materials and their bio-imaging application.