Investigation and visualization of internal flow through particle aggregates and microbial flocs using particle image velocimetry.
An advanced particle-tracking and flow-visualization technology, particle image velocimetry (PIV), was utilized to investigate the hydrodynamic properties of large aggregates in water. The laser-based PIV system was used together with a settling column to capture the streamlines around two types of aggregates: latex particle aggregates and activated sludge (AS) flocs. Both types of the aggregates were highly porous and fractal with fractal dimensions of 2.13±0.31 for the latex particle aggregates (1210-2144 μm) and 1.78±0.24 for the AS flocs (1265-3737 μm). The results show that PIV is a powerful flow visualization technique capable of determining flow field details at the micrometer scale around and through settling aggregates and flocs. The PIV streamlines provided direct experimental proof of internal flow through the aggregate interiors. According to the PIV images, fluid collection efficiency ranged from 0.052 to 0.174 for the latex particle aggregates and from 0.008 to 0.126 for AS flocs. AS flocs are apparently less permeable than the particle aggregates, probably due to the extracellular polymeric substances (EPSs) produced by bacteria clogging the pores within the flocs. The internal permeation of fractal aggregates and bio-flocs would enhance flocculation between particles and material transport into the aggregates.


Cimetidine inhibits renal procainamide clearance.
Procainamide and cimetidine are eliminated in large part by the kidneys. Both are secreted by an active transport mechanism in the proximal tubule and each inhibits secretion of the other in the isolated, perfused rabbit tubule. In this study in man, cimetidine inhibited renal clearance of oral procainamide by 36%. This was associated with a 28% decrease in the ratio of systemic clearance of procainamide to bioavailability, an 18% decrease in the elimination rate constant, and a 24% prolongation of elimination t1/2. These results suggest that cimetidine increases plasma t1/2 and decreases systemic clearance of procainamide in part by inhibiting its active secretion by the kidneys.


Are patients with isolated chronic aortic regurgitation operated in time? Analysis of survival data over a decade.
Patients suffering from chronic isolated aortic regurgitation have a less favorable outcome than patients with aortic stenosis. According to international recommendations, these patients should undergo surgery as soon as left ventricular function begins to deteriorate, that is, surgery is not to be postponed until clinical symptoms become relevant. The study was undertaken to evaluate how satisfactory our timing of surgery was, as reflected by survival data. Survival was studied retrospectively in a consecutive series of patients undergoing surgery for chronic isolated aortic regurgitation during a 10-year period in our institution. Results were compared with data from the literature. By excluding patients with aortic aneurysms and acute endocarditis, we formed a homogeneous patient group of 88 subjects. Thirty-day mortality was 1% and late mortality after a mean follow-up period of 6 years was 11%. Compared with survival data from an earlier study in which the patient population was similar and resided in the same geographic area, the results in our patient group seem to be better. It is noteworthy that despite a strong effort to recommend surgery at an earlier stage of the disease than previously, 35% of the patients had moderate or severe left ventricular dysfunction preoperatively because of late referrals. This stresses the importance of early detection and careful preoperative follow-up with noninvasive methods in patients with aortic regurgitation.


Herbal products as skincare therapeutic agents against ultraviolet radiation-induced skin disorders.
This paper aims to highlight the pharmacological aspects of listed herbal skincare products used for the treatment of various disorders caused due to ultraviolet radiation. The pharmacological aspects include safety and efficacy validation as per regulatory guidelines following internationally accepted scientific principles for their development of skincare products. Herbal products have always been used traditionally for the treatment of various skin ailments and have become more prevalent because of their safety and high efficacy benefits. The incorporation of synthetic molecules and chemical substances in the different medicinal and pharmaceutical formulations is the leading cause of the dermal toxicity. Therefore, the developments of herbal skincare products containing scientifically validated herbal ingredients have better acceptance, respect, and belief in the society. The listed herbal products in this review can help take forward the commercial development of skincare products for therapeutic as well as beauty care purposes from such plants.


Skin ageing: a comparison between Chinese and European populations. A pilot study.
Although limited data are available, it is commonly considered that Europeans and Asians have different skin ageing features. The present studies have been carried out to evaluate the influence of age and sun-exposure on the main clinical signs of Asian skin ageing. One hundred and sixty Chinese and 160 French age-matched women (age range: 20-60 years old) were clinically examined and scored by the same dermatologist. Facial wrinkles (crow's-feet, glabella and perioral wrinkles) and pigmented spots (on face and hands) were assessed in situ and standardized photographs of the face were taken. Lifelong sun-exposure was estimated from answers to a questionnaire. Comparisons were made between 10-year age groups. Results show that, for each facial skin area, wrinkle onset is delayed by about 10 years in Chinese women as compared to French women. Facial wrinkling rate over the years is linear in French women and not linear in Chinese women who appear to experience a fast ageing process between age 40 and 50. Pigmented spot intensity is a much more important ageing sign in Chinese women (severe for 30% of women over 40) than in French women (severe for less than 8% of women, irrespective of age). These first results underline that main skin ageing features (wrinkles, spots) progress differently in the Chinese and French women we have studied. They require to be confirmed on broad multicentre studies involving larger cohorts.


Hormones and Flower Development in Arabidopsis.
Sexual reproduction requires the participation of two gametes, female and male. In angiosperms, gametes develop in specialized organs, pollen (containing the male gametes) develops in the stamens, and the ovule (containing the female gamete) develops in the gynoecium. In Arabidopsis thaliana, the female and male sexual organs are found within the same structure called flower, surrounded by the perianth, which is composed of petals and sepals. During flower development, different organs emerge in an established order and throughout their development distinct tissues within each organ are differentiated. All this requires the coordination and synchronization of several biological processes. To achieve this, hormones and genes work together. These components can interact at different levels generating hormonal interplay and both positive and negative feedback loops, which in turn, gives robustness, stability, and flexibility to flower development. Here, we summarize the progress made on elucidating the role of different hormonal pathways during flower development in Arabidopsis thaliana.


[Follow-up of subjects occupationally exposed to asbestos: MRI and PET scans].
MRI and PET scans are not normally used for screening and follow-up of patients following occupational exposure to asbestos. These examinations usually complement the investigation of a parenchymal mass, an effusion or pleural thickening. PET and MRI have an excellent ability to define a parenchymal lesion as malignant (cancer versus rounded atelectasis) or a pleural lesion (mesothelioma versus plaque). MRI distinguishes perfectly the involvement of sub-pleural fat by bronchial carcinoma or mesothelioma. MRI, taking account of its lack of irradiation, could be regarded as suitable for potentially repeated examinations following initial screeing by CT scan. A comparative study of multidetector scanner versus MRI, including diffusion MRI could be, nevertheless, interesting. PET cannot be proposed for the follow up or for screening on account of the irradiation induced and the difficulty of access. Pleural plaques do not take up FDG. There is no specific study of asbestos related fibrosis and there is discordance between studies of other types of pulmonary fibrosis.


Epidemiology of HIV/AIDS among non-Hispanic black women in the United States.
HIV/AIDS has emerged as a persistent health threat to black women in the United States. For the past decade, HIV disease has been among the top 10 leading causes of death for this population. We analyzed national HIV surveillance data from 29 states with confidential name-based HIV infection reporting that have conducted integrated HIV/AIDS surveillance since at least 1998. We also analyzed AIDS surveillance data from all 50 states and the District of Columbia. In 2002, black women represented 14% of all women in the 29 states whose HIV data were analyzed but 72.3% of annual HIV infection diagnoses among women. In that same year, black women were diagnosed with HIV infection at a rate of 68.7 per 100,000, approximately 23 times the rate for white women (three per 100,000) and four times that for Hispanic women (17.2 per 100,000). Likewise, in 2002, black women represented 13% of all women in the 50 states and the District of Columbia but an estimated 67.8% of new AIDS diagnoses among women. In that same year, black women were diagnosed with AIDS at a rate of 48 per 100,000, approximately 23 times the rate for white women (2.1 per 100,000) and more than four times that for Hispanic women (10.6 per 100,000), Because black women are disproportionately affected by HIV/AIDS, effective strategies are needed to prevent new HIV infections, to detect HIV infections early and to assure adequate treatment for black women who are infected with HIV.


Analysis and prediction of traffic fatalities resulting from angle collisions including the effect of vehicles' configuration and compatibility.
Although the rapid growth in light truck vehicle (LTV) sales, including minivans, sports utility vehicles (SUVs), and light-duty trucks, has not been associated with an overall increase in collisions or traffic deaths in the US, there is a need for a research program to determine whether particular types of collisions have become more frequent or injurious because of the increase in the percent of LTVs in traffic. This paper presents an analysis of the effect of the increasing number of LTV registrations on fatal angle collision trends in the US. The analysis investigates the number of annual fatalities that result from angle collisions as well as collision configuration (car-car, car-LTV, LTV-car, and LTV-LTV). The analysis uses the Fatality Analysis Reporting System (FARS) crash databases covering the period 1975-2000. Results showed that death rates differ based on the collision configuration. Time series modeling results showed that fatalities in angle collisions will increase in the next 10 years, and that they are affected by the expected increase in the percentage of LTVs in traffic. Forecast showed that the total number of annual deaths is expected to reach 6300 deaths by the year 2010 (an increase of 12% over 2000). Analysis into the configuration of the collision indicated the seriousness of angle collisions involving an LTV striking a common passenger car (LTV-car). A time series model illustrated the significance of time lag and percent of LTVs in traffic on the increase of this type of fatal collisions. Forecasts from the time series model indicated a 32% increase in deaths due to this type of collisions in the next 10 years.


Repair of the supradiaphragmatic inferior vena cava lacerated during redo open-heart surgery.
Laceration of the inferior vena cava is among the more lethal of the vascular traumas. True mortality is higher if the lacerated segment is located in the upper part of the inferior vena cava, especially in the supradiaphragmatic portion. Knowledge of injuries of the inferior vena cava is mostly limited to those related to external trauma. The inferior vena cava may be lacerated during reoperation because of inappropriate dissection or uncontrolled traction. The authors used a diaphragmatic pericardial flap to repair the lacerated anterior wall of the supradiaphragmatic inferior vena cava and obtained good results in two cases requiring repeat open-heart surgery.


Description of a new species of Eucinetidae (Coleoptera, Scirtoidea) from Cretaceous Burmese amber.
Eucinetus parvus sp. nov. is described from late Cretaceous Burmese amber, representing the second record of Eucinetidae from the Burmese amber and the first species of the family with simple, not piercing, mouthparts. A comparison between Mesocinetidae and Eucinetidae is provided.


Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity.
The aim of this study was to identify the best sedation/analgesia protocol for laser photocoagulation (PC) of retinopathy of prematurity (ROP). This multicenter observational study included five hospitals, each using a specific sedation/analgesia protocol: local anesthesia with oxybuprocaine hydrochloride (Group L); intravenous pentazocine (Group P); intravenous fentanyl (Group F); air, oxygen and sevoflurane (AOS) inhalation (Group I). The groups were compared for pain responses, vital signs and adverse events. Heart rates and systemic blood pressures were elevated by PC in Groups L and P and Groups L, P and F, respectively. Moreover, poor analgesic efficacy was recognized in Groups L, P and F. In contrast, Group I experienced hypothermia, enteral feeding intolerance and apnea more frequently. From the viewpoint of sedation/pain relief, AOS anesthesia should be the best protocol. However, considering all the various factors together, the most reasonable one can be varied based on the patient's condition and hospital.


Genomic insight into the distribution and genetic environment of blaIMP-4 in clinical carbapenem-resistant Klebsiella pneumoniae strains in China.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a major threat to public health due to its resistance to almost all antibiotics. It is associated with substantial morbidity and mortality and poses a significant challenge to healthcare systems around the globe. Based on our previous nationwide survey of carbapenem-resistant Enterobacteriaceae (CRE) in China, seven blaIMP-4-carrying CRKP isolates were identified, all exhibiting MDR and epidemiologically linked to four different regions in China. WGS analysis revealed that the seven blaIMP-4 genes were all located on plasmids, of which five blaIMP-4 genes were located on the IncHI5 plasmids and the other two belonged to the IncN and IncFIIK plasmids, respectively. Except for the IncHI5 plasmid, conjugation assays revealed that the IncN and IncFIIK plasmids could be transferred to the recipient strain Escherichia coli J53. This study revealed significant genetic variation and identified numerous resistance factors among blaIMP-4-carrying CRKP strains in China, suggesting that blaIMP-4-carrying CRKP strains evolved via multiple phylogenetic routes and highlighting a need for expanded surveillance and establishment of control measures to prevent dissemination of CRKP strains, and facilitate development of more effective antibiotic stewardship policies and infection control programs.


Studies of antigenic components in acid extracts of group C streptococci with special reference to Streptococcus equi.
For the determination of a species-specific antigen of Streptococcus (S.) equi, acid extracts of group C streptococcal strains from horses (S. equi, S. zooepidemicus, S. equisimilis) were investigated using polyacrylamide gel electrophoresis and the immunoblotting technique. Using sera of horses suffering from strangles as well as sera from horses with respiratory infection of unknown etiology, Western blotting yielded more or less multiple banding reactions with bands in the 70, 54, 42, 40, and 31-28 kd molecular weight ranges against extracts of all of the 3 different bacterial species. However, an antigen found in this study at 18-16 kd which was highly sensitive to trypsin, proved to react specifically and regularly only with the serum of horses exposed to S. equi. The specificity of the reaction was assured by antisera of rabbits and horses vaccinated against S. equi, S. zooepidemicus or S. equisimilis, respectively, and by cross absorption of a serum originating from a mare recovered from strangles with Lancefield group C and group G streptococci as well as a strain of S. pyogenes. According to Western blot results on 180 serum pairs from horses with clinical signs of respiratory infection, 15.6% of which gave positive reactions, the 18-16 kd antigen appears as a marker suitable for qualitative testing of horse sera for antibodies to S. equi.


Effect of commonly used lavage solutions on the polymerization of bone cement.
Little is known about the impact irrigation solutions have on the material properties of cement used in hip and knee arthroplasty. We sought to compare the effect of three commonly used lavage solutions on cement polymerization. Ten groups were used for cure and mechanical testing: two cement controls, and eight cement groups mixed with test solutions. Test solutions included a commercially available benzalkonium chloride/citric acid solution (BCS), chlorhexidine gluconate (0.05%) (CHG), povidone-iodine 0.35%, and normal saline added at cement mixing onset. Cement dough-time, set-time, and compression testing were performed following The American Society for Testing and Materials guidelines. Povidone-iodine had shorter dough-time (1min 34sec, sd 1min 5sec) versus controls (1min 56sec, sd 1min 35sec), p=0.0419. Cement exposed to all lavage samples had significantly reduced set-time. Compressive strength was reduced for all surgical lavages (p<0.001). Pairwise testing revealed that all lavage treatments reduced offset strength versus controls (p<0.001). Bone cement exposed to lavage solutions during the cement mixing-phase showed accelerated set-times and decreased compressive strength. If bone is not dry, and cement has not finished mixing at the time of application, cement curing time may be shortened. Additionally, bone cement should reach dough phase prior to pre-closure surgical lavage. III; case control study.


[Secondary chondrosarcoma].
A retrospective evaluation of 101 cases of secondary chondrosarcoma was performed. The results of the analysis of X-ray data showed chondrosarcoma to develop from osteocartilaginous exostosis or chondroma (53 and 47 cases, respectively). (One case lacked roentgenologic data). The former pattern of tumor development prevailed in patients under 40 years of age, while the latter one was more frequently observed in the older age group (68% of cases in each age bracket). Secondary chondrosarcoma was most frequently localized to long tubular and flat bones (48 and 34 patients, 47.53 and 33.66%, respectively). Roentgenologic diagnosis of early stage secondary chondrosarcoma was extremely difficult. Histologic examination showed degree I cell anaplasia in most cases. Surgery is the main procedure of treatment of secondary chondrosarcoma. Relapses were observed only in patients who had undergone sparing operations. The smaller the extent of surgery, the higher relapse rate was registered. Fifteen patients (14.87%) died of tumor progression. Sparing procedures were performed in 14 of them (93.3%).


QTL mapping with different genetic systems for nine non-essential amino acids of cottonseeds.
Amino acid is an important nutrient resource for both human and animals. Using a set of 188 RILs population derived from an elite hybrid cross of upland cotton cultivars 'HS46' × 'MARCABUCAG8US-1-88' and their immortal F2 (IF2) with reciprocal backcrosses BC1F1 and BC2F1 (BC) populations in two environments, the QTLs located on the embryo genome and maternal plant genome for nine amino acids of cottonseed were studied across environments. The QTL Network-CL-2.0-seed software was used to analyze the QTLs and their genetic effects for nine amino acids. A total of 56 QTLs for nine amino acids were detected in both populations, with many having over 5% of phenotypic variation. Ten of the total QTLs could be simultaneously found in the IF2 and BC populations. For most QTLs, the genetic effects from embryo genome were more important than those from maternal plant genome for the performance of nine amino acids. Significant embryo additive main effects and maternal additive main effect with their environment interaction effects from many QTLs were also found in present experiment. Some QTLs with larger phenotypic variation were important for improving the amino-acid contents in cottonseeds.


Neurotoxicity of antibodies in cancer therapy: A review.
The objective of this manuscript is to identify the neurological side effect profile associated with different classes of antibodies used in cancer pharmacotherapy and to estimate the frequency in which these neurotoxicity occurs. A systematic review of the literature was conducted using OVID MEDLINE and EMBASE databases for articles written between January of 2010 till August of 2018. The spectrum of neurotoxicity was searched using expanded terminology, medical subject headings, truncation, spelling variations and database specific controlled vocabulary. 2134 citations were retrieved that were narrowed down to 151 when SORT 1 or SORT 2 critical appraisal tool was applied to articles with human subjects. Meta-analysis using random effect model was done to estimate the prevalence of neurological symptoms per class of antibody described in SORT1 and SORT2 articles. It was found that the most common neurotoxicity per antibody class are as follows; Bi-specific T-cell engagers was headache 38% [35-40%; I2 0%]; anti-CD20, neuropathy, 16% [7-24%, I2 65%]; anti-CD30, neuropathy 57% [46-68%, I2 72%]; anti-CD52, neuropathy 5-15%; anti-CTL4, headache 12% [7-16%, I2 49%]; anti-EGFR, headache 25% [11-38%, I2 92%]; anti-Her2, neuropathy 33% [18-49%, I2 98%]; anti-PD1 and PDL1, headache 3% [2-5%, I2 85%]; and anti-VEGF, headache 25% [16-35%, I2 73%]. Therefore, all classes of antibodies used in cancer pharmacotherapy have associated neurotoxicity with a wide spectrum of effects afflicting the nervous system as a whole. The specific side effects and the frequency at which they occur differ per class of antibody. Broader and more severe symptoms were noted to effect patients with preexisting brain lesions.


Age-related hormonal adaptations, muscle circumference and strength development with 8 weeks moderate intensity resistance training.
To examine the response of the endocrine system, strength development and muscle circumference to moderate-resistance training in younger and middle-aged men. Two groups of men of similar activity background, but differing in age (Y: 21.2±2.2years and M: 49.7±2.1years) participated in an 8-week moderate-resistance training program. Blood sampling was obtained at rest before and after training for analysis of serum testosterone, growth hormone, cortisol and ACTH concentrations. One repetition maximum for the bench press (1RM(BP)) and squat (1RM(S)); thigh (TC) and arm circumference (AC) were also measured. Both groups underwent a 1-h standardized moderate-resistance training session (three series of 8 to 15RM; nine exercises with 1-3min rest between sets) three times a week for 8weeks. Both the Y and M groups gained significant improvements in 1RM(BP), 1RM(S), TC and AC (P<0.05). Growth hormone and testosterone concentration increased for both groups, while Y men increased greater than M men in resting posttraining testosterone concentration. With training the Y and M men demonstrated significant decreases in ACTH and cortisol concentrations. These data indicate moderate-resistance training would lead to gains in maximal strength, muscle circumference and increases anabolic hormone secretion for M men and consequently promoting of health, improve daily life and delay negative effects with aging.


Biosensor and molecular-based methods for the detection of human coronaviruses: A review.
The ongoing crisis due to the global pandemic caused by a highly contagious coronavirus (Coronavirus disease - 2019; COVID-19) and the lack of either proven effective therapy or a vaccine has made diagnostic a valuable tool in disease tracking and prevention. The complex nature of this newly emerging virus calls for scientists' attention to find the most reliable, highly sensitive, and selective detection techniques for better control or spread of the disease. Reverse transcriptase-polymerase chain reaction (RT-PCR) and serology-based tests are currently being used. However, the speed and accuracy of these tests may not meet the current demand; thus, alternative technology platforms are being developed. Nano biosensor technology platforms have been established as a promising diagnostic tool for rapid and accurate detection of viruses as well as other life-threatening diseases even in resource-limited settings. This review aims to provide a short overview of recent advancements in molecular and biosensor-based diagnosis of viruses, including the human coronaviruses, and highlight the challenges and future perspectives of these detection technologies.


Temporal brow lift vs internal browpexy in females undergoing upper blepharoplasty: Effects on lateral brow lifting.
Lateral brow-lifting surgical procedures in conjunction with upper blepharoplasty may prevent secondary descent following upper blepharoplasty. To compare the results of internal browpexy (IBP) and temporal brow lift (TBL) in patients with dermatochalasis undergoing simultaneous upper blepharoplasty. This study was a single-center, parallel-group randomized controlled trial conducted on 32 female patients suitable for upper blepharoplasty. Patients were divided into two groups: the IBP group and the TBL group. The brow lift was measured using change in the distance between the ala nasi and lateral tail of the eyebrow as nasal ala to lateral brow (NALB) in millimeter (mm), and the vertical line between the lateral tail of eyebrow and horizontal line extending the lateral cantus as lateral brow plump line (LBPL) in mm before and after the surgery. The follow-up time was 6 months. The mean ± SD age of patients was 55.93 ± 7.1 years and 53.94 ± 7.7 years in the TBL and IBP groups, respectively (P > .05). No significant change in mean LBPL at 6 months compared to baseline was observed in the TBL group (baseline: 15.7 ± 1.6 mm vs 6 month: 15.8 ± 1.3 mm; P = .602). In the IBP group, a significant increase in mean LBPL at 6 months compared to baseline was observed (baseline: 15.09 ± 2.13 mm vs 6 months: 17. 43 ± 2.68 mm; P < .001). Internal browpexy combined with blepharoplasty could be considered the better procedure in patients with upper eyelid dermatochalasis in terms of long-lasting stability and lateral brow elevation.


NADPH-cytochrome P-450 reductase in the plasma membrane modulates the activation of hypoxia-inducible factor 1.
Hypoxia induces a group of physiologically important genes that include erythropoietin (EPO) and vascular endothelial growth factor (VEGF). Hypoxia-inducible factor 1 (HIF-1) was identified as a hypoxia-activated transcription factor; however, the molecular mechanisms that underlie hypoxia signal transduction in mammalian cells remain undefined. In this study, we found that a flavoprotein, NADPH-P450 reductase (NPR), could regulate the induction of EPO mRNA under hypoxic conditions. Hypoxic EPO mRNA induction in Hep3B cells was inhibited by diphenyleneiodonium chloride, which is an inhibitor of NADPH-dependent enzymes. NPR antisense cDNA was transfected into Hep3B cells, and NPR-deficient hepatocyte cells (NPR(-) cells) were established. NPR(-) cells lacked EPO induction under hypoxia, and HIF-1alpha in NPR(-) cells did not respond to either transcriptional activation or translocation to the nucleus based on electrophoretic mobility shift assays and reporter gene assay including hypoxia response element. In contrast, NPR overexpression in Hep3B cells enhanced the DNA binding activity of HIF-1alpha by luciferase reporter gene assay. A study with HeLa S3 cells produced the same results. Furthermore, anti-NPR IgG inhibited EPO induction. EPO induction inhibited by diphenyleneiodonium chloride was recovered by bovine serum albumin-NADPH (a covalent binding complex of bovine serum albumin and NADPH) as well as NADPH. These results suggested that NPR located at the plasma membrane regulates EPO expression in hypoxia, including HIF-1 activation and translocation. We further studied the expression of NPR and VEGF mRNAs in human tumor tissues and found that the NPR mRNA levels were correlated with the VEGF mRNA levels, suggesting that NPR might be an important factor in the hypoxic induction of genes such as VEGF in vivo.


Prostanoid-mediated inotropic responses are attenuated in failing human and rat ventricular myocardium.
Prostanoid-modulatory approaches in heart failure patients have displayed effects which may seem to be mutually incompatible. Both treatment with prostanoids and inhibition of prostanoid synthesis have resulted in increased mortality in heart failure patients. Currently, it is unknown if prostanoids mediate contractile effects in failing human heart and if this can explain some of the clinical effects seen after prostanoid modulatory treatments. Therefore, the objectives of this study were to determine if prostanoids could elicit direct inotropic responses in human ventricle, and if so to determine if they are modified in failing ventricle. Contractile force was measured in left ventricular strips from non-failing or failing human and rat hearts. The ratio of phosphorylated to non-phosphorylated myosin light chain 2 (MLC-2) was measured by Western blotting in myocardial strips, and the levels of prostanoid FP receptor mRNA and protein were measured in rat by real-time RT-PCR and receptor binding assays. In non-failing human hearts, prostanoids evoked a positive inotropic effect and an increase of MLC-2 phosphorylation which was absent in failing human hearts. In failing rat heart, the prostanoid FP receptor-mediated inotropic response and prostanoid FP receptor-density was reduced by ~40-50% compared to non-failing rat heart. Prostanoids mediate a sustained positive inotropic response in non-failing heart, which appears to be down regulated in failing heart. The pathophysiological significance of changes in prostanoid-mediated inotropic support in the failing heart remains to be determined.


Therapeutic potential of NADPH oxidase 1/4 inhibitors.
The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation, tissue and subcellular localization and ROS products. The most studied are NOX1, 2 and 4. Genetic deletion of NOX1 and 4, in contrast to NOX2, has revealed no significant spontaneous pathologies and a pathogenic relevance of both NOX1 and 4 across multiple organs in a wide range of diseases and in particular inflammatory and fibrotic diseases. This has stimulated interest in NOX inhibitors for therapeutic application. GKT136901 and GKT137831 are two structurally related compounds demonstrating a preferential inhibition of NOX1 and 4 that have suitable properties for in vivo studies and have consequently been evaluated across a range of disease models and compared with gene deletion. In contrast to gene deletion, these inhibitors do not completely suppress ROS production, maintaining some basal level of ROS. Despite this and consistent with most gene deletion studies, these inhibitors are well tolerated and slow or prevent disease progression in a range of models of chronic inflammatory and fibrotic diseases by modulating common signal transduction pathways. Clinical trials in patients with GKT137831 have demonstrated excellent tolerability and reduction of various markers of chronic inflammation. NOX1/4 inhibition may provide a safe and effective therapeutic strategy for a range of inflammatory and fibrotic diseases. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.


Glutathione reductase inhibitors as potential antimalarial drugs. Effects of nitrosoureas on Plasmodium falciparum in vitro.
Malarial parasites are believed to be more susceptible to oxidative stress than their hosts. BCNU(1,3-bis(2-chloroethyl)-1-nitrosourea) and HeCNU(1-(2-chloroethyl)-3-(2-hydroxythyl)-1-nitrosourea), inhibitors of the antioxidant enzyme glutathione reductase, were found to prevent the growth of Plasmodium falciparum in all intraerythrocytic stages. When exposing infected red blood cells to 38 microM BCNU or 62 microM HeCNU for one life cycle of synchronously growing parasites, the parasitemia decreased by 90%. During the formation of new ring forms, the parasites are even more susceptible to these drugs. The treatment with BCNU or HeCNU produced a rapid depletion of GSH in the parasites and their host cells; in addition, protection against lipid peroxidation was impaired in these cells. Possible mechanisms for the antimalarial action of the inhibitors are discussed. Our results suggest that erythrocyte glutathione reductase, an enzyme of known structure, might be considered as a target for the design of antimalarial drugs.


Bannwarth's syndrome: serum and CSF IgG antibodies against Borrelia burgdorferi examined by ELISA.
A newly identified spirochete, Borrelia burgdorferi, has recently been established as the causal agent of chronic meningoradiculitis (Bannwarth's syndrome, BS). An etiological diagnosis can be obtained by specific antibody determination. To detect intrathecally produced Borrelia antibodies, we examined paired serum and CSF samples from 10 BS patients and 41 controls. CSF/serum IgG specific antibody indices were calculated by relating the CSF/serum ratio of specific antibody activity to the CSF/serum ratio of total IgG and of albumin; 8/10 BS patients compared to 4/39 controls had elevated index values. In only one of the 4 positive controls could spirochetal infection be excluded. We conclude that determination of specific antibody indices is a reliable and sensitive diagnostic test for nervous system B. burgdorferi infection.


Re-Assemblable, Recyclable, and Self-Healing Epoxy Resin Adhesive Based on Dynamic Boronic Esters.
Thermosetting adhesives are commonly utilized in various applications. However, covalent cross-linked networks prevent thermosetting adhesives from being re-assembled, which necessitates higher machining precision. Additionally, the primary raw materials used in adhesive preparation are derived from non-renewable petroleum resources, which further constrain adhesive development. In this study, a recyclable adhesive was developed by incorporating dynamic boronic esters into epoxy resin derived from soybean oil. The successful synthesis of epoxidized soybean oil and boronic esters was confirmed through the analysis of proton nuclear magnetic resonance spectra and differential scanning calorimetry results. Swelling tests and tensile curves demonstrated the presence of covalently cross-linked networks. Self-healing and reprocessing experiments indicated that the cross-linked network topology could be re-assembled under mild conditions.


Is the Recommendation of a Pelvic Lymphadenectomy in Conjunction with Radical Prostatectomy in Prostate Cancer Patients Justified? Report from a Multidisciplinary Expert Panel Meeting.
Pelvic lymphadenectomy (pLA) in prostate cancer (PCa) is one of the most common uro-oncologic surgical procedures. An increased complication rate is accompanied by unproven oncologic benefit. Extent of pLA and mechanisms of metastasis are discussed controversially. We aimed to explore evidence and knowledge gaps in pLA and mechanisms of metastasis in PCa and to develop further steps to clarify oncologic benefits through an expert panel. A multidisciplinary expert meeting was initiated, compiling available facts on pLA and mechanisms of metastasis in PCa. Questions and hypotheses were formulated. The resulting protocol was modeled on priority and consistency in four anonymized voting rounds using the Delphi method (March 2018-June 2018). The oncologic benefit of pLA in PCa is still unclear. Results of randomized trials (RCTs) are pending. Extent and techniques of pLA are differently applied and inconsistently recommended by the guidelines as well as the indication for pLA. Different growth rates for the primaries and metastases and different survival curves for lymph node and organ metastasis at diagnosis argue against metastasis originating from positive nodes. However, results from clinical and basic research support this opportunity in PCa. The RCTs required to clarify the estimated low oncologic benefit of pLA prove to be difficult because of the great effort (e.g., high case number). Establishing a network of treatment centers for implementation of high-quality cohort studies could be an alternative approach. Future studies with larger panels and international participants based on the presented feasibility should be launched to set this process in motion. Until valid data are available, benefits and harms of pLA should be weighted under consideration of low-invasive techniques (e.g., sentinel pLA).


The Optimal Tumor Mutational Burden Cutoff Value as a Novel Marker for Predicting the Efficacy of Programmed Cell Death-1 Checkpoint Inhibitors in Advanced Gastric Cancer.
The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292-39.281) than in the TMB-L (3.31 months; 95% CI, 1.604-5.019; P=0.049). The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb. When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.


Stimulation of TH1 response by Helicobacter pylori neutrophil activating protein decreases the protective role of IgE and eosinophils in experimental trichinellosis.
Th2 responses seem to play an important role in defence against Trichinella spiralis (Ts). The neutrophil Activating protein of Helicobacter pylori (HP-NAP), that induces IL-12, and IL-23 expression and shifts to Th1 allergen-specific Th2 cells in vitro was used as an anti-Th2 agent in BALB/c mice infected with T. spiralis. The muscle larvae (ML) burden was lower (p < 0.02) in untreated infected animals than those infected treated with HP-NAP. In both groups there was an inverse relationship between ML burden of each animal and total IgE level (controls: r -0.617, p = 0.0013 and HP-NAP-treated: r -0.678, p = 0.0001) or eosinophil count, evaluated in the same mouse on day 42 (r -0.390, p = 0.0592 and r -0.803, p = 0.0001, respectively). Inflammatory response around the nurse cell-parasite complex was significantly higher in HP-NAP-treated infected animals than in those untreated infected, on the contrary the number of eosinophils, counted around each complex was significantly lower in the first animal group. This study provides evidence of a powerful anti-Th2 activity in vivo by HP-NAP and for the partial protective effect of Th2 responses in T. spiralis infection.


Lack of physiological improvement in performance of Callosamia promethea larvae on local host plant favorites.
As a species, the promethea silkmoth, Callosamia promethea (Saturniidae: Lepidoptera) exhibits a wide host range on 6-10 families of plants, although specific populations are known to have local foodplant favorites. We tested the hypothesis that larvae from a particular host plant lineage would show physiological adaptations to this host compared with larvae from other host plant lineages. We found no evidence that larval survival and growth was any better for larvae fed the natural plant of the parental population than for larvae from other host lineages. These natural host lineages include: black cherry (Prunus serotina Ehrh.), tuliptree (Liriodendron tulipifera L.), sassafras (Sassafras albidum (Nutt.) Nees) and spicebush (Lindera benzoin (L.) Blume). The only apparent manifestation of physiological specialization was the inability of tuliptree lineages of C. promethea to survive on paper birch (Betula papyrifera Marsh), although this may reflect the geographical pattern of adaptation to birch, rather than a negative correlation with adaptation to tuliptree. These results suggest that for C. promethea larvae, growth performance and survival is primarily influenced by plant nutritional quality, rather than physiological adaptations to the locally preferred host plant.


Most of the interleukin 1 receptor antagonist, cathepsin S, macrophage migration inhibitory factor, nerve growth factor, and interleukin 18 release by explants of human adipose tissue is by the non-fat cells, not by the adipocytes.
The present studies were designed to compare the relative release of interleukin 1 receptor antagonist (IL-1Ra), cathepsin S, macrophage migration inhibitory factor (MIF), nerve growth factor (NGF), and interleukin 18 (IL-18) by adipocytes as compared with the non-fat cells present in subcutaneous and omental adipose tissue from morbidly obese gastric bypass patients as compared with obese abdominoplasty patients. The release of IL-1Ra, cathepsin S, and MIF by explants of human adipose tissue incubated for 48 hours averaged 6, 9, and 19 pmol/g, respectively, and was far greater than the release of NGF (0.05 pmol/g) or IL-18 (0.006 pmol/g). The release by human adipocytes of IL-1Ra, cathepsin S, and MIF was 0.13, 0.32, and 2.6 pmol/g, respectively, over 48 hours, whereas NGF release was 0.003 and IL-18 0.001 pmol/g. Only the total release of MIF by human adipose tissue explants was enhanced, whereas that of IL-18 was significantly reduced in explants from morbidly obese women. Most of (55%-73%) the release of IL-1Ra, cathepsin S, MIF, NGF, and IL-18 was by the adipose tissue matrix, whereas release by stromal-vascular (SV) cells was 3% to 28% of total release over 48 hours by the adipose tissue matrix, SV cells and adipocytes. The release of NGF by adipocytes was 42%, that of MIF was 27%, and for the other factors 15% or less of release over 48 hours by the adipose tissue matrix, SV cells, and adipocytes. Our results suggest that the non-fat cells in human adipose tissue contribute to most of the release of NGF, IL-18, IL-1Ra, cathepsin S, and MIF seen during primary culture of adipose tissue explants from obese women.


What is optimum neck dissection for T3/4 buccal-gingival cancers?
Buccal-gingival (BG) cancers are an integral part of oral cancers but are biologically distinct, particularly with regard to the propensity and pattern of neck metastases. This study was undertaken to examine the adequacy of limited neck dissection in the management of these tumors. Between 1980 and 1989, 527 T3/4 BG cancers were treated surgically at Tata Memorial Hospital, Bombay. These cases were reviewed retrospectively. Among these, 178 underwent radical neck dissection (RND), 166 supradigastric dissection (SD) and 183 supraomohyoid dissection (SOHD) after confirming the negativity of levels II and III for nodal disease on frozen section. The overall incidence of histological node positivity was 42.5% (224/527). Level I was the most frequent site of metastases, with a skip rate of only 9%. The incidence of pure regional failure (primary controlled) was 3% with RND (67/178), 12% with SD (11/95) and 5% with SOHD (7/141) in patients with N0 necks. In the N+ category the regional failure was 18% with RND (20/111), 34% with SD (24/71) and 19% with SOHD (8/42). These findings show that a limited (SD) dissection is grossly inadequate in the management of T3/4 BG cancers, whereas an SOHD when neck levels II and III are confirmed negative on frozen section yields results comparable to RND for both N0 and N+ necks.


Soil-foraging animals alter the composition and co-occurrence of microbial communities in a desert shrubland.
Animals that modify their physical environment by foraging in the soil can have dramatic effects on ecosystem functions and processes. We compared bacterial and fungal communities in the foraging pits created by bilbies and burrowing bettongs with undisturbed surface soils dominated by biocrusts. Bacterial communities were characterized by Actinobacteria and Alphaproteobacteria, and fungal communities by Lecanoromycetes and Archaeosporomycetes. The composition of bacterial or fungal communities was not observed to vary between loamy or sandy soils. There were no differences in richness of either bacterial or fungal operational taxonomic units (OTUs) in the soil of young or old foraging pits, or undisturbed soils. Although the bacterial assemblage did not vary among the three microsites, the composition of fungi in undisturbed soils was significantly different from that in old or young foraging pits. Network analysis indicated that a greater number of correlations between bacterial OTUs occurred in undisturbed soils and old pits, whereas a greater number of correlations between fungal OTUs occurred in undisturbed soils. Our study suggests that digging by soil-disturbing animals is likely to create successional shifts in soil microbial and fungal communities, leading to functional shifts associated with the decomposition of organic matter and the fixation of nitrogen. Given the primacy of organic matter decomposition in arid and semi-arid environments, the loss of native soil-foraging animals is likely to impair the ability of these systems to maintain key ecosystem processes such as the mineralization of nitrogen and the breakdown of organic matter, and to recover from disturbance.


Understanding workplace violence against medical staff in China: a retrospective review of publicly available reports.
Workplace violence against medical staff in China is a widespread problem that has negative impacts on medical service delivery. The study aimed to contribute to the prevention of workplace violence against medical staff in China by identifying patterns of workplace violence, key risk factors, and the interplay of risk factors that result in workplace violence. Ninety-seven publicly reported Chinese healthcare violent incidents from late 2013 to 2017 were retrospectively collected from the internet and analysed using content analysis. A modified socio-ecological model guided analysis of the violent incidents focusing on risk. Physical violence, yinao, or a combination of physical and verbal violence were the typical forms of violence reported. The findings identified risk at all levels. Individual level risk factors included service users' unreasonable expectations, limited health literacy, mistrust towards medical staff, and inadequacy of medical staff's communication during the medical encounter. Organisational level risk factors under the purview of hospital management included problems with job design and service provision system, inadequacies with environmental design, security measures, and violence response mechanisms within hospitals. Societal level risk factors included lack of established medical dispute-handling mechanisms, problems in legislation, lack of trust and basic health literacy among service users. Situational level risks were contingent on risk factors on the other levels: individual, organisational, and societal. Interventions at individual, situational, organisational, and societal levels are needed to systematically address workplace violence against medical staff in China. Specifically, improving health literacy can empower patients, increase trust in medical staff and lead to more positive user experiences. Organizational-level interventions include improving human resource management and service delivery systems, as well as providing training on de-escalation and violence response for medical staff. Addressing risks at the societal level through legislative changes and health reforms is also necessary to ensure medical staff safety and improve medical care in China.


Carbon reduction behavior of waste power battery recycling enterprises considering learning effects.
The carbon reduction behavior of waste power battery recycling (WPBR) enterprises is essential for promoting resource conservation and environmental protection. Introducing the learning effects of carbon reduction research and development (R&D) investment, this study constructs an evolutionary game model between local governments and WPBR enterprises to study the behavior choice of carbon reduction. The paper explores the evolutionary process and factors affecting carbon reduction behavior choices of WPBR enterprises from internal R&D motivation and external regulation perspectives. The critical results reveal that the existence of learning effects significantly reduces the probability of environmental regulation by local governments while effectively increasing the probability of WPBR enterprises implementing carbon reduction. The learning rate index positively correlates with the likelihood of enterprises implementing carbon emissions reduction. In addition, carbon reduction subsidies considerably maintain considerably negative relation with the probability of enterprise carbon reduction behavior. The following conclusions are drawn: (1) The learning effect of carbon reduction R&D investment is the intrinsic driving force for WPBR enterprises' carbon reduction behavior, which can promote enterprises to proactively implement carbon reduction under fewer constraints of government environmental regulation; (2) Pollution fines and carbon trade prices in environmental regulation can promote enterprises carbon reduction, while carbon reduction subsidies inhibit their reduction behavior; (3) There exists an evolutionarily stable strategy between government-enterprise game only under the dynamic mechanism. The research provides insights for decision-making on enterprises' carbon reduction R&D investment and local government environmental regulation policy under carbon reduction targets.


X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy study.
Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). In this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)-which is also capable of simultaneously acquiring a conventional thorax radiograph (7 s, 0·035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=-0·27, p=0·089 and visual emphysema ρ=-0·45, p=0·0028), the dark-field signal (ρ=0·62, p<0·0001) yields a stronger correlation with lung diffusion capacity in the evaluated cohort. Emphysema assessment based on dark-field chest x-ray features yields consistent conclusions with findings from visual CT image interpretation and shows improved diagnostic performance than conventional clinical tests characterising emphysema. Pair-wise comparison of corresponding test parameters between adjacent visual emphysema severity groups (CT-based, reference standard) showed higher effect sizes. The mean effect size over the group comparisons (absent-trace, trace-mild, mild-moderate, and moderate-confluent or advanced destructive visual emphysema grades) for the COPD assessment test score is 0·21, for forced expiratory volume in 1 s (FEV1)/functional vital capacity is 0·25, for FEV1% of predicted is 0·23, for residual volume % of predicted is 0·24, for CT emphysema index is 0·35, for dark-field signal homogeneity within lungs is 0·38, for dark-field signal texture within lungs is 0·38, and for dark-field-based emphysema severity is 0·42. X-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema in patients with COPD because this technique provides relevant information representing the structural condition of lung parenchyma. This technique might offer a low radiation dose alternative to CT in COPD and potentially other lung disorders. European Research Council, Deutsche Forschungsgemeinschaft, Royal Philips, and Karlsruhe Nano Micro Facility.


[Diagnosis of tumor or metastasis in the liver by means of laparoscopy and gammagraphy].
Fifty-four patients with proven malignancy of the gastrointestinal tract or suspicion of primary or metastatic hepatic carcinoma were studied to evaluate the effectiveness of different diagnostic methods. Gammagraphic and laparoscopic evaluations were emphasized. The results indicated that laparoscopy was the most effective method for diagnosing primary or metastatic neoplastic liver disease.


[Aneurysm of the ampulla of Galen. Anesthetic problems].
Anesthetic management of patients with arterio-venous malformations of the vein of Galen needs to be adapted to the physiopathology of the affection. Massive blood less before clipping and congestive heart failure after clipping may be avoided by using adequate transfusion and light arterial vasodilators preserving diastolic perfusion of the heart.


Ultrasonic Perfluorohexane-Loaded Monocyte Imaging: Toward a Minimally Invasive Technique for Selective Detection of Liver Inflammation in Fatty Liver Disease.
To investigate the utility of ultrasonic (US) perfluorohexane (PFH)-loaded monocyte imaging for detection of liver inflammation in fatty liver disease. C57Bl6 mice were injected intraperitoneally with tumor necrosis factor α and assessed by US PFH-loaded monocyte imaging 3 hours later. Echogenic monocytes were injected intravenously, leading to a transient increase in liver tissue intensity on a US perfusion scan. The contrast wash-out time constant was hypothesized to reflect the degree of inflammation. Next, we evaluated US PFH-loaded monocyte imaging in Ldlr-/- mice fed a 1-week high-fat/high-cholesterol diet as model for early developing nonalcoholic steatohepatitis. Adjunct analyses included tissue markers of liver inflammation. Tumor necrosis factor α-injected mice showed a reduced wash-out time constant (mean ± SEM, 0.013 ± 0.003; n = 8) compared to controls (0.054 ± 0.009; n = 7; P = .0006), indicative of increased inflammatory adhesion molecule expression on the endothelium. The Ldlr-/- mice fed the high-fat/high-cholesterol diet showed liver inflammation, as reflected by increased (3- to 4-fold) infiltration of inflammatory cells and increased (3- to 4-fold) gene expression of tumor necrosis factor α, integrin αM, intracellular adhesion molecule, and vascular cell adhesion molecule. However, in these mice, no difference was detected in the wash-out time constant as assessed by US PFH-loaded monocyte imaging (high-fat/high-cholesterol, 0.050 ± 0.017; n = 5; chow, 0.048 ± 0.006; n = 6; P = .91). Our results indicate that US PFH-loaded monocyte imaging is able to detect vascularly expressed inflammatory adhesion molecules in the mouse liver on direct endothelial stimulation. However, in our mouse model of early developing nonalcoholic steatohepatitis, we did not detect inflammation by this method, which may suggest that the time-dependent relationship between parenchymal and endothelial inflammation remains a fundamental issue to be addressed.


Comparative surface examinations on corund blasted titanium implants and explants in total hip arthroplasty.
Blasting techniques using corundum to create rough surfaces are used in many different processes for the surface treatment of hip implants. Recent evidence points an association between residual particles and early loosenings in the sense of third-body wear. The surfaces of five unused, original-packaged CLS stems and ARR-Titan supporting rings, respectively, were compared with five explanted CLS stems and ARR-Titan supporting rings. The surface of the ARR-Titan supporting rings was adhered to Al2O3 particles at 23.2+/-2.5% on the implants and 12.3+/-3.0% on the explants (P < 0.0001). For the CLS stem, the surface to which Al2O3 particles adhered was 16.4+/-2.2 % on the implants, whereas the surface to which Al2O3 particles adhered was 12.4+/-3.3% on the explants (P = 0.0275). The results of this study show that corundum particles can be found to cover a high percentage on rough-blasted titanium surfaces of ready-to-use devices. In contrast, this contamination is significantly less on the explants treated in an identical fashion prior to implantation.


Automotive restraint systems for premature infants.
Automotive restraint systems suitable for use with low birth weight infants were crash tested using a small infant dummy developed for the study. Conventional semiupright rear-facing child restraints were tested, as well as a new car bed restraint that may be advantageous for infants who are medically fragile and who must remain in a prone or supine position. This car bed can be adapted to accommodate a very small infant effectively.


Transcriptome Profiling in the Marine Red Alga Neopyropia yezoensis Under Light/Dark Cycle.
Many organisms are subjected to a daily cycle of light and darkness, which significantly influences metabolic and physiological processes. In the present study, Neopyropia yezoensis, one of the major cultivated seaweeds used in "nori," was harvested in the morning and evening during light/dark treatments to investigate daily changes in gene expression using RNA-sequencing. A high abundance of transcripts in the morning includes the genes associated with carbon-nitrogen assimilations, polyunsaturated fatty acid, and starch synthesis. In contrast, the upregulation of a subset of the genes associated with the pentose phosphate pathway, cell cycle, and DNA replication at evening is necessary for the tight control of light-sensitive processes, such as DNA replication. Additionally, a high abundance of transcripts at dusk encoding asparaginase and glutamate dehydrogenase imply that regulation of asparagine catabolism and tricarboxylic acid cycle possibly contributes to supply nitrogen and carbon, respectively, for growth during the dark. In addition, genes encoding cryptochrome/photolyase family and histone modification proteins were identified as potential key players for regulating diurnal rhythmic genes.


[Peculiarities of medico-demographic processes in Russian Federation in the first half of the 21st century].
The authors analyze the modem dynamics in Russian population reproduction and its problems. Special attention is paid to the structure of mortality and regional variations in it. The mechanisms of changes beginning to take place nowadays, and their future development are discussed.


Nitric oxide and reactive oxygen species regulate the accumulation of heat shock proteins in tomato leaves in response to heat shock and pathogen infection.
Heat shock proteins (HSP) are produced in response to various stress stimuli to prevent cell damage. We evaluated the involvement of nitric oxide (NO) and reactive oxygen species (ROS) in the accumulation of Hsp70 proteins in tomato leaves induced by abiotic and biotic stress stimuli. A model system of leaf discs was used with two tomato genotypes, Solanum lycopersicum cv. Amateur and Solanum chmielewskii, differing in their resistance to fungal pathogen Oidium neolycopersici. Leaf discs were exposed to stress factors as heat shock and pathogen infection alone or in a combination, and treated with substances modulating endogenous NO and ROS levels. Two proteins of Hsp70 family were detected in stressed tomato leaf discs: a heat-inducible 72 kDa protein and a constitutive 75 kDa protein. The pathogenesis and mechanical stress influenced Hsp75 accumulation, whereas heat stress induced mainly Hsp72 production. Treatment with NO donor and NO scavenger significantly modulated the level of Hsp70 in variable manner related to the genotype resistance. Hsp70 accumulation correlated with endogenous NO level in S. lycopersicum and ROS levels in S. chmielewskii. We conclude NO and ROS are involved in the regulation of Hsp70 production and accumulation under abiotic and biotic stresses in dependence on plant ability to trigger its defence mechanisms.


Separation of structurally related estrogens using isocratic elution pressurized capillary electrochromatography.
In this paper, the pressurized capillary electrochromatography (pCEC) with UV detection was utilized for the separation and determination of three structurally related estrogens, such as diethylstilbestrol (DES), hexestrol (HEX) and dienestrol (DE), which were difficult to be separated by capillary electrophoresis (CE) and HPLC due to their similarity in the structure and charge-to-mass ratios. Experiments were carried out in a commercially available pCEC instrument using a capillary column packed with 3 microm octadecyl silica (ODS). Surfactant sodium dodecyl sulfate (SDS) was introduced in the mobile phase to enhance the speed of analysis. The effective factors on the retention time and separation resolution, such as the applied voltage, supplementary pressure, the pH and the concentration of the buffer solution, the concentration of SDS, and the content of acetonitrile in the mobile phase, were evaluated. Based on the investigation, 31% (v/v) acetonitrile and 69% (v/v) of 10 mmol/L phosphate buffer (pH 6.5) containing 1.0 mmol/L SDS at an applied voltage of -12 kV and a supplementary pressure of 1000 psi were found to be the optimal conditions for pCEC to separate the three estrogens. The method also had been applied to the analysis of fish muscle samples spiked with estrogens.


Sympathetic Nerve Stimulation on the perfused rat heart. Affinities of N-methylatropine and pirenzepine at pre- and postsynaptic muscarine receptors.
Rat isolated hearts with the sympathetic nerves attached were perfused with (-)-3H-noradrenaline in order to label the storage vesicles of the adrenergic nerves. Release was induced either by electrical stimulation of the nerves (3 Hz, 1 min) or by perfusion with high K+ solution (54 mM). The overflow of 3H-noradrenaline and its metabolites was determined by liquid scintillation counting after separation of the compounds by column chromatography. The experimental conditions ensured a minor contribution of 3H-metabolites to the evoked total tritium overflow. The release of 3H-noradrenaline evoked by nerve stimulation or high K+ solution was decreased in the presence of the muscarinic agonist, methacholine, N-methylatropine reversed the inhibition completely. Thus, the rat heart contains inhibitory muscarine receptors modulating noradrenaline release from adrenergic nerve fibres. In order to compare the presynaptic muscarine receptors with postsynaptic muscarine receptors in one and the same organ, the pA2 values of N-methylatropine and pirenzepine at both of these sites were measured. The antagonism of methacholine-induced inhibition of 3H-noradrenaline overflow was determined as the presynaptic parameter. pA2 values of 9.61 for N-methylatropine and 6.63 for pirenzepine were found. The methacholine-induced inhibition of the atrial tension development of isolated left rat atria paced at 2Hz was measured as a postsynaptic parameter. pA2 values of 9.90 for N-methylatropine and 6.69 for pirenzepine were found. The postsynaptic pA2 values did not differ from the presynaptic affinity constants indicating that neither substance revealed differences in structure between neuronal and myocardial muscarine receptors in the rat heart.


Linear and non-linear relationships between bioconcentration and hydrophobicity: theoretical consideration.
A non-linear relationship (e.g. Gaussian-type) between measured bioconcentration factor (BCF) and octanol/water partition coefficient (K(OW)) was noted many years ago. Many studies have focused on the cause of the breakdown in the log BCF/log K(OW) curve for highly hydrophobic chemicals with log K(OW)>6. However, there has been little investigation on the theoretical background of this feature for highly hydrophilic chemicals. In this paper, the cause of linear and non-linear relationships between log BCF and log K(OW) has been investigated on the basis of the partitioning-based mechanism for classified non-ionic and ionisable compounds. For highly hydrophilic compounds, lipid tissue in fish is not the major storage site of chemicals. Uptake from other tissues/organs plays a much more important role than the lipid content, leading to a variation of measured log BCF around 0.5. For hydrophobic chemicals with 0.5<log K(OW)<6, hydrophobicity is the principal driving force of bioconcentration and log BCF increases with increasing log K(OW). The log BCF/log K(OW) curve breaks down for highly hydrophobic chemicals with log K(OW)>6. The main reason for this is attributed to the reduced bioavailability of chemicals in water. A linear solvation energy relationship shows that the bioconcentration increases with increasing molecular size by increasing the dispersion interactions between the chemical and lipid content. Bioconcentration decreases with increasing the basicity of hydrophobic compounds by increasing the H-bonding of chemicals with water. Principal component analysis shows that the octanol/water system is the closest system, but not an ideal surrogate, to describe the bioconcentration for hydrophobic compounds as compared with other solvent/water partition systems.


Heart glucose transport and transporters in rat heart: regulation by insulin, workload and glucose.
Aspects of the regulation of the glucose transport by perfused hearts of normal rats have been studied by measuring glucose transport (via the efflux of labelled 3-O-methyl-D-glucose) and glucose transporters (via the labelled cytochalasin B binding assay). Similarly to what is observed with insulin, increasing workload (by raising perfusion pressure from 50 to 100 mm Hg) stimulated glucose transport 7 to 8-fold. Glucose (via its analog 3-O-methylglucose, used at 15 mmol/l) stimulated its own transport 4-fold. The three stimuli favored the translocation of glucose transporters from an intracellular pool (microsomes) to the plasma membrane. Insulin increased the apparent affinity (decreased dissociation constant values) of plasma membrane transporters for cytochalasin, as well as the Hill coefficient, indicating the occurrence of a positive cooperativity amongst plasma membrane transporters. Workload increased only the Hill coefficient, glucose only the apparent affinity for cytochalasin of plasma membrane transporters. This study shows that insulin, workload and glucose itself stimulate glucose transport by favouring the translocation process of glucose transporter as well as by changing, albeit by a different mechanism, the functional properties of the transporters once translocated to the plasma membrane.


Measuring blood pressure in the elderly: does atrial fibrillation increase observer variability?
To compare the interobserver and intraobserver variability of blood pressure measurements in geriatric patients in atrial fibrillation and in sinus rhythm. Prospective assessment of blood pressure measurements carried out in random order in two groups of elderly patients by five doctors unaware of the aims of the study. Acute assessment wards for geriatric medicine, Cardiff Royal Infirmary. 50 Elderly patients in sinus rhythm and 50 in atrial fibrillation. Interobserver and intraobserver variability of blood pressure measurements in the two groups expressed as the coefficient of variability and compared by the Mann-Whitney U test. Interobserver variability was significantly greater in the patients with atrial fibrillation for both systolic and diastolic pressures. Intraobserver variability was significantly greater in the atrial fibrillation group for diastolic pressures but the difference was not significant for systolic pressures. These differences were not related to pulse rate, age, or level of blood pressure. The findings suggest that in the presence of atrial fibrillation physicians' interpretations of Korotkoff sounds are less uniform, which may have important clinical implications. Possibly a standardised methodology may overcome this problem.


Emergence of chromosomally located blaCTX-M-14b and qnrS1 in Salmonella enterica serotype Kentucky ST198 in China.
Highly fluoroquinolone-resistant Salmonella enterica serotype Kentucky has become widespread in recent years, largely associated with the spread of sequence type 198 (ST198), which often leads to multidrug resistance. Research on the genomic epidemiology of Salmonella Kentucky in China is currently uncommon. In this study, we analysed the genomic epidemiology and antimicrobial resistance characteristics of Salmonella Kentucky ST198 collected from foodborne disease surveillance in Shenzhen, China, during 2010-2021, using whole-genome sequencing and antibiotic susceptibility testing. In addition, 158 global Salmonella Kentucky ST198 genomes were included for comparison. Among 8559 Salmonella isolates, 43 Salmonella Kentucky ST198 isolates were detected during 2010-2021. The global Salmonella Kentucky ST198 evolutionary tree was divided into five clades, with Shenzhen isolates distributed in clades 198.1, 198.2-1 and 198.2-2, mainly clustered with Chinese strains. Strains in clade 198.2 dominated in Shenzhen and all of them showed multidrug resistance. Nine strains showed high resistance to ceftriaxone, which was associated with blaCTX-M-14b in clade 198.2-1, which was demonstrated to be located on the chromosome. Fifteen strains showed high resistance to ciprofloxacin, which was associated with carriage of qnrS1 in clade 198.2-2. qnrS1 was first located on an IncHI2 plasmid and then transferred into the chromosome. Here we report the genomic and antimicrobial resistance characterisation of Salmonella Kentucky ST198 in Shenzhen. Of particular concern, we identified for the first time a clade 198.2-1 isolate carrying blaCTX-M-14b as well as chromosomally located qnrS1 in clade 198.2-2 of Salmonella Kentucky ST198 in China, highlighting the necessity of surveillance of clade 198.2.


Potential of methacrylated acemannan for exerting antioxidant-, cell proliferation-, and cell migration-inducing activities in vitro.
Acemannan is an acetylated polysaccharide of Aloe vera extract with antimicrobial, antitumor, antiviral, and antioxidant activities. This study aims to optimize the synthesis of acemannan from methacrylate powder using a simple method and characterize it for potential use as a wound-healing agent. Acemannan was purified from methacrylated acemannan and characterized using high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), and 1H-nuclear magnetic resonance (NMR). 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays were performed to investigate the antioxidant activity of acemannan and its effects on cell proliferation and oxidative stress damage, respectively. Further, a migration assay was conducted to determine the wound healing properties of acemannan. We successfully optimized the synthesis of acemannan from methacrylate powder using a simple method. Our results demonstrated that methacrylated acemannan was identified as a polysaccharide with an acetylation degree similar to that in A. vera, with the FTIR revealing peaks at 1739.94 cm-1 (C = O stretching vibration), 1370 cm-1 (deformation of the H-C-OH bonds), and 1370 cm-1 (C-O-C asymmetric stretching vibration); 1H NMR showed an acetylation degree of 1.202. The DPPH results showed the highest antioxidant activity of acemannan with a 45% radical clearance rate, compared to malvidin, CoQ10, and water. Moreover, 2000 µg/mL acemannan showed the most optimal concentration for inducing cell proliferation, while 5 µg/mL acemannan induced the highest cell migration after 3 h. In addition, MTT assay findings showed that after 24 h, acemannan treatment successfully recovered cell damage due to H2O2 pre-treatment. Our study provides a suitable technique for effective acemannan production and presents acemannan as a potential agent for use in accelerating wound healing through its antioxidant properties, as well as cell proliferation- and migration-inducing activities.


Interspersed poly(A) RNAs of amphibian oocytes are not translatable.
The poly(A) RNA of the Xenopus oocytes has been shown to include both single copy and interspersed transcripts. Interspersed maternal poly(A) RNAs contain repetitive sequence elements distributed within regions transcribed from single copy sequences. When renatured these RNAs form partially double-stranded RNA networks, and as shown earlier this can be utilized for preparative separation of interspersed maternal transcripts from maternal transcripts that remain single-stranded after renaturation (Anderson et al., 1982). The translational activity of these RNA fractions was tested in vitro, in wheat germ and reticulocyte systems. While the single-stranded fractions supported protein synthesis, the interspersed oocyte RNAs displayed little translational activity. Translational activity was measured in vivo by injection into the Xenopus oocyte. Oocytes previously injected with globin mRNA were injected with increasing amounts of single-stranded, double-stranded, or denatured double-stranded RNA fractions, and the amount of globin synthesis was determined. It was found that single-stranded RNA competes with globin mRNA for the limited translational apparatus of the oocyte, as manifested by a quantitative reduction of globin synthesis. However, globin synthesis was not affected when double-stranded RNA, either in renatured or denatured form, was injected. We conclude that the interspersed RNAs are not translated within the oocyte. The amount of single and double-stranded RNAs loaded onto polysomes in the injected oocytes was also determined. Sixty seven per cent of radio-iodinated single-stranded RNA pelleted with polysomes in injected oocytes, whereas less than 20% of similarly labeled double-stranded RNA pelleted with polysomes. This value is similar to that obtained when partially hydrolyzed RNA is injected, suggesting again that essentially none of the interspersed RNA is translated in vivo. The significance of these findings in relation to translational regulation during oogenesis and early development is discussed.


Development of the conditionally immortalized testicular Sertoli cell line TTE3 expressing Sertoli cell specific genes from mice transgenic for temperature sensitive simian virus 40 large T antigen gene.
We developed and characterized a conditionally immortalized testicular Sertoli cell line from transgenic mice bearing the temperature sensitive simian virus 40 large T antigen gene pSVtsA58. Established cells from 8-week-old male transgenic mice were cultured at a permissive (33C) or nonpermissive (39C) temperature on a collagen type I pre-coated culture vessel. The expression of Sertoli cell specific proteins was analyzed by reverse transcriptase-polymerase chain reaction, immunocytochemical testing and Western blot analysis. The Sertoli cell line TTE3 grew at 33C but not at 39C. Large T antigen was expressed only in the nuclei at 33C, indicating that the temperature sensitive growth phenotype of the cells arose as a result of the function of temperature sensitive simian virus 40 large T antigen. The cells did not show any colony forming activity in soft agar or form tumors in subcutaneous tissue in nude mice, showing that TTE3 cells were not transformed. The cells expressed messenger RNAs encoding steel factor, inhibin-alpha, transferrin, follicle-stimulating hormone receptor and sulfated glycoprotein-2. Moreover, expression of vimentin and zonula occludens-1 was observed in the cytoplasm and on the boundaries of the cells, respectively. Interestingly expression levels of transferrin and zonula occludens-1 were significantly elevated at 39C. TTE3 cells with these unique characteristics should serve as a useful model to study the regulation of Sertoli cell function.


[Histological changes observed in the treatment of endometrial glandular epithelioma with lynestrenol].
Lynestrenol, which is a progestogen with weak oestrogenic features, has numerous theorretical advantages in the hormonal treatment of endometrial carcinoma of the body of the uterus when associated with combined radiotherapy and surgery. Iinitial clinical impressions were confirmed by a study of the histological modifications brought about by lynestrenol in this kind of tumour in which are included some poorly differentiated or undifferentiated cases.


Gastroduodenal mucosal damage with salsalate versus aspirin: results of experimental models and endoscopic studies in humans.
Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.


The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation.
Staphylococcus aureus (S. aureus) infection is difficult to fight, previous experimental reports have demonstrated thioridazine (TZ) and tetracycline (TC) is an inhibitor of S. aureus efflux pump NorA and autolysin Atl, respectively, here, by means of molecular docking and molecular dynamics simulation, we observed that thioridazine (TZ) and tetracycline (TC) blocked the binding of substrates to NorA and Atl, respectively, and reduced their activities, and our antibacterial susceptibility test and three-dimensional checkerboard method showed that the three-drug combination of antibiotic cloxacillin (CXN), TZ and TC had a synergistic anti-Staphylococcal activity in vitro, and α-Hemolysin tests and scanning electron microscopy showed that the three-drug combination and the subinhibitory concentration of the combination significantly inhibited the secretion of α-hemolysin relative to the number of membrane-derived vesicles produced by S. aureus. Whereas Western blot and pharmacological inhibition assays showed that the three-drug combination significantly inhibited the expression of MAPK/NF-κB/NLRP3 proteins in macrophages induced with S. aureus α-hemolysin. In vivo, the drug combination significantly reduced bacterial colony-forming unit counts in the viscera of a mouse peritonitis model of S. aureus infection, therapy reduced the primary inflammatory pathology and the bacteria-stimulated release of cytokines such as IL-1β and TNF-α, and inhibited the expression of MAPK/NF-κB/NLRP3 proteins in peritoneal macrophages. Thus, the combination of efflux pump inhibitor, autolysis inhibitor and antibiotic, is a novel anti-Staphylococcal and anti-inflammatory strategy who owning good antibacterial activity and significant inhibiting staphylococcal α-hemolysin and inflammation.


Neprilysin levels in plasma and synovial fluid of juvenile idiopathic arthritis patients.
Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid. Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence. Circulating NEP levels were lower in JIA patients than in controls (42.0+/-16.6 vs 76.5+/-24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4+/-86.2 vs 40+/-15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6+/-5.2% vs 41.4+/-13%, P<0.001 and 18.1+/-7.5 vs 31.2+/-5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2+/-14.6% vs 9.1+/-2.4%, P<0.001 and 66.4+/-5.4 vs 22.8+/-14.7, P<0.001, respectively). The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzyme's role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation.


The Chain-Mediation Pathway of Social Avoidance to Depression in College Students Is Regulated by Self-Esteem.
Here, we investigated the relationship between social avoidance and depression in college students, explored the mediating roles of loneliness and trust, and the regulatory role of self-esteem, to provide a theoretical intervention approach based on internal mechanisms. Using a simple random overall sampling method, 1,021 college students were investigated using self-rating depression, social avoidance and distress, loneliness, interpersonal trust and self-esteem scales. There was a significant positive correlation between social avoidance and depression. Loneliness and interpersonal trust played chain-mediating roles between social avoidance and depression. The influence of social avoidance on interpersonal trust was regulated by self-esteem. Specifically, the social avoidance level of the low self-esteem group was more likely to be affected by interpersonal trust issues. Social avoidance not only directly affects college students' depression, it also has indirect effects through interpersonal trust and loneliness. Thus, interpersonal trust and loneliness have chain-mediating effects between social avoidance and depression in college students, and self-esteem regulates the mediation process.


Use of AlloDerm in type I tympanoplasty: a comparison with native tissue grafts.
AlloDerm, an acellular human dermis allograft, has been shown to be an effective option as a tympanic membrane (TM) graft in animals and humans and has several potential advantages, including eliminating donor site morbidity, reducing operative time, and preserving native tissues for later use. We compared AlloDerm and native tissue grafts in type I tympanoplasty with regard to operative time, graft success rate, and audiologic outcome. A retrospective chart review of tympanoplasties performed at a major tertiary referral hospital over a 31 month period, starting with the first use of AlloDerm for TM grafting at this institution. The medical charts of all patients undergoing tympanoplasty were reviewed. Only those patients undergoing type I tympanoplasty without mastoidectomy or ossicular chain reconstruction were included. These 114 patients (25 AlloDerm, 56 fascia reconstruction, and 33 fascia plus cartilage reconstruction) were compared for operative time, success rate of the graft, and change in audiologic outcome. There was a statistically significant reduction in operative time in the AlloDerm group when controlled for surgeon and choice of approach. All groups showed no statistically significant difference in the success rate of the graft and closure of audiologic air-bone gap, regardless of graft material used. AlloDerm is an effective TM graft when used in type I tympanoplasty. It is as effective as native tissues in closing the air-bone gap on audiogram as well as in graft success rate. AlloDerm may also significantly reduce operative time, depending on the surgeon's technique.


Identification of seven novel virulence genes from Xanthomonas citri subsp. citri by Tn5-based random mutagenesis.
To identify novel virulence genes, a mutant library of Xanthomonas citri subsp. citri 29-1 was produced using EZ-Tn5 transposon and the mutants were inoculated into susceptible grapefruit. Forty mutants with altered virulence phenotypes were identified. Nine of the mutants showed a complete loss of citrus canker induction, and the other 31 mutants resulted in attenuated canker symptoms. Southern blot analysis revealed that each of the mutants carried a single copy of Tn5. The flanking sequence was identified by plasmid rescue and 18 different ORFs were identified in the genome sequence. Of these 18 ORFs, seven had not been previously associated with the virulence of X. citri subsp. citri and were therefore confirmed by complementation analysis. Real-time PCR analysis showed that the seven genes were upregulated when the bacteria were grown in citrus plants, suggesting that the expression of these genes was essential for canker development.


Performance-based connectivity analysis: a path to convergence with clinical studies.
Connectivity analyses have become increasingly important in functional imaging. When used to describe the functional anatomy of a specific behavior, these analyses are generally applied to a subset of the data that demonstrate significant differences when experimental conditions are contrasted. Such data reduction is sub-optimal for a systems approach as it assumes that all data that survive the statistical contrast filter are related to the behavior and that none of the filtered data has a significant function. When such data filtering is applied to speech and language tasks, the resulting functional anatomy rarely reflects the brain lateralization established in over a century and a half of clinical studies. A two-step performance-based connectivity analysis is described in which the first step uses multiple linear regression to establish a direct relationship between regional brain activity and a measure of performance. The second step uses partial correlations to examine the functional relationships between the predictor regions and other brain regions. When applied to regional cerebral blood flow data obtained with positron emission tomography during a speech production task, the results demonstrate left lateralization of motor control areas, thalamic involvement in repetition rate, and auditory cortical suppression, all consistent with clinical observations. The integration of performance measures into the earliest stages of image analysis without reliance on data filtering based on decomposition may provide a path toward convergence with traditional descriptions of functional anatomy based on clinical studies.


An effective device to enable consistent scratches for in vitro scratch assays.
The in-vitro scratch assay is a useful method in wound healing research to assess cell migration. In this assay, a scratch is created in a confluent cell layer by mechanically removing cells through manual scraping with a sharp-edged tool. This step is traditionally done with pipette tips and is unsuitable for high-throughput assays, as the created scratches are highly variable in width and position. Commercially available solutions are often expensive, and require specific cultureware which might not be suitable for all studies. In this study, we have developed a flexible cell scratch device comprising a single wounding tool, a guide and an imaging template for consistent and reproducible scratch assays in 96-well plates. Our results showed that the device produced a more consistent scratch profile compared to the conventional method of using pipette tips. The imaging template also allowed operators to easily locate and image the same region of interest at different time points, which potentially could be used for other assays. Our flexible yet effective scratch device thus enables robust scratch assays that can be applied to different experimental needs, providing researchers with an easy and reliable tool for their studies.


The pitfalls of potassium replacement in thyrotoxic periodic paralysis: a case report and review of the literature.
Thyrotoxic Periodic Paralysis is an uncommon disorder seen primarily in Asian males and caused by excessive thyroid hormones. This is an endocrine emergency that can lead to respiratory failure, dysrhythmia, and death. The mainstay of therapy has been potassium replacement, however, recent evidence suggests propranolol is a more effective therapy. We present a severe case of TPP in a 22-year-old Latino male with rapidly progressive ascending paralysis and hypokalemia severe enough to lead to cardiac arrest.


Intraocular Pressure Telemetry for Managing Glaucoma during the COVID-19 Pandemic.
To evaluate in glaucoma patients the feasibility and use of remote monitoring of intraocular pressure (IOP) with an implanted telemetry sensor during the coronavirus disease 2019 (COVID-19) lockdown. Cross-sectional study. Patients previously implanted with a telemetric IOP sensor (Eyemate; Implandata GmbH) were included. Intraocular pressure measurements acquired by the patients during the lockdown were collected by physicians who were located remotely. A questionnaire was sent to 10 participating study centers to evaluate the clinical impact of remote monitoring of IOP via the IOP sensor system. Number of patients who obtained home IOP measurements. Data were available from all centers and from 37 eyes of 37 patients (16 patients with a sulcus-based sensor and 21 patients with a suprachoroidal sensor). Thirty-four patients obtained IOP measurements during the lockdown. Mean age of the patients was 69.3 ± 9.6 years, and 48.6% were women. A total of 8415 IOP measurements from 370 measurement days were obtained. Based on remote IOP measurements, treatment was changed in 5 patients. In another 5 patients, treatment change was considered when physicians received the IOP measurements after the lockdown. Nine of the 10 study centers judged remote IOP measurements to have a clinical impact. These results show the feasibility of patient-acquired measurement of IOP in conjunction with remote IOP monitoring by physicians with an implantable sensor. The data obtained impacted clinical decision making, including adjustment of ocular hypotensive therapy and avoiding unnecessary office visits during the COVID-19 pandemic.


Risk Factors for Readmission After Knee Arthroplasty Based on Predictive Models: A Systematic Review.
An increase in the aging yet active US population will continue to make total knee arthroplasty (TKA) procedures routine in the coming decades. For such joint procedures, the Centers for Medicare and Medicaid Services introduced programs such as the Comprehensive Care for Joint Replacement to emphasize accountable and efficient transitions of care. Accordingly, many studies have proposed models using risk factors for predicting readmissions after the procedure. We performed a systematic review of TKA literature to identify such models and risk factors therein using a reliable appraisal tool for their quality assessment. Five databases were searched to identify studies that examined correlations between post-TKA readmission and risk factors using multivariate models. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and Transparent Reporting of a multivariate prediction model for Individual Prognosis Or Diagnosis criteria established for quality assessment of prognostic studies. Of 29 models in the final selection, 6 models reported performance using a C-statistic, ranging from 0.51 to 0.76, and 2 studies used a validation cohort for assessment. The average 30-day and 90-day readmission rates across the studies were 5.33% and 7.12%, respectively. Three new significant risk factors were discovered. Current models for TKA readmissions lack in performance measurement and reporting when assessed with established criteria. In addition to using new techniques for better performance, work is needed to build models that follow the systematic process of calibration, external validation, and reporting for pursuing their deployment in clinical settings.


Risk Factors for Periprosthetic Femur Fracture and Influence of Femoral Fixation Using the Mini-Anterolateral Approach in Primary Total Hip Arthroplasty.
The mini-anterolateral (AL) approach for total hip arthroplasty (THA) has gained popularity. In contrast to other approaches, risk factors for periprosthetic femur fractures have not been well established for the AL approach. Six hundred eighty-four primary THAs performed using the AL approach were retrospectively reviewed for risk factors associated with perioperative periprosthetic femur fractures within 3 months of surgery. Risk factors evaluated were gender, age, body mass index, laterality, and Dorr ratio of the proximal femur. Cemented stems and collared uncemented stems were compared to uncemented tapered-wedge and meta-diaphyseal stems. A Student's t-test was used for continuous variables, and a chi-squared test was used for categorical variables. Of 684 primary THAs performed, 57 (8.3%) resulted in fracture. Twenty-eight (4.1%) occurred intraoperatively and 29 (4.2%) occurred postoperatively within 90 days. All intraoperative fractures were fixed at the time of surgery and healed uneventfully. Of the postoperative fractures, 15 (2.2%) were amenable to nonoperative management and healed. Fourteen (2.0%) required revision arthroplasty. There was a significantly lower rate of fracture in patients receiving cemented or collared stems (0%, n = 101) than in those receiving tapered-wedge or meta-diaphyseal fitting stems (9.8%, n = 583; P = .0009). Odds of fracture increased with female gender (P = .0063) and increasing Dorr ratio (P = .0003). Analysis showed a trend toward increased risk with older age, but did not achieve statistical significance. Body mass index and laterality showed no statistically significant effect. Performing primary THA via the AL approach, 2.0% of patients had a postoperative fracture requiring revision within the first 3 months. With cemented and collared stems, the fracture rate was significantly lower. Surgeons should consider using cemented or collared stems in high-risk patients.