Hereditary renal disease in a mutant strain of rats.
Disease of the kidney developed in breeding stock of Gunn rats. The renal lesion is the result of a new mutation. The genetic defect is inherited as an autosomal dominant trait and is apparently lethal in the homozygous condition. The abnormality manifests itself as a congenital hydronephrosis with related cystic changes in the kidney.


'Nothing can be done until everything is done': the use of complexity arguments by food, beverage, alcohol and gambling industries.
Corporations use a range of strategies to dispute their role in causing public health harms and to limit the scope of effective public health interventions. This is well documented in relation to the activities of the tobacco industry, but research on other industries is less well developed. We therefore analysed public statements and documents from four unhealthy commodity industries to investigate whether and how they used arguments about complexity in this way. We analysed alcohol, food, soda and gambling industry documents and websites and minutes of reports of relevant health select committees, using standard document analysis methods. Two main framings were identified: (i) these industries argue that aetiology is complex, so individual products cannot be blamed; and (ii) they argue that population health measures are 'too simple' to address complex public health problems. However, in this second framing, there are inherent contradictions in how industry used 'complexity', as their alternative solutions are generally not, in themselves, complex. The concept of complexity, as commonly used in public health, is also widely employed by unhealthy commodity industries to influence how the public and policymakers understand health issues. It is frequently used in response to policy announcements and in response to new scientific evidence (particularly evidence on obesity and alcohol harms). The arguments and language may reflect the existence of a cross-industry 'playbook', whose use results in the undermining of effective public health policies - in particular the undermining of effective regulation of profitable industry activities that are harmful to the public's health.


Short-term KRP203 and posttransplant cyclophosphamide for graft-versus-host disease prophylaxis.
Posttransplant high-dose cyclophosphamide (PTCY) has been increasingly used as graft-versus-host disease (GVHD) prophylaxis after HLA-haploidentical or matched hematopoietic stem cell transplantation (SCT). However, PTCY alone is insufficient and requires additional immunosuppressants such as calcineurin inhibitors. In the current study, we evaluated effects of a novel GVHD prophylaxis with PTCY in combination with short-term KRP203, a selective agonist of sphingosine-1-phosphate receptor 1 that regulates egress of lymphocytes from the secondary lymphoid organs (SLOs) in mice. Short-term oral administration of KRP203 alone induced apoptosis of donor T cells in the SLOs and ameliorated GVHD. Administration of KRP203 significantly preserved graft-versus-leukemia effects compared to cyclosporin. A combination of KRP203 on days 0 to +4 and PTCY on day +3 synergistically suppressed donor T-cell migration into the intestine and skin, and ameliorated GVHD more potently than PTCY alone. A combination of short-term KRP203 and PTCY is a promising novel calcineurin-free GVHD prophylaxis in HLA-haploidentical SCT.


The impact of metallic allergy on stent implantation: metal allergy and recurrence of in-stent restenosis.
Relation between metallic allergy and in-stent restenosis (ISR) has been inconclusive. We hypothesized that mechanism of restenosis is different between initial stent implantation and dilatation for ISR. Thus, we studied metallic allergy and restenosis in these two different situations separately. We performed follow-up angiography and patch test for metallic allergy in a total of 174 stented consecutive patients, 109 patients (63%) for restudy of initial stent implantation and 65 patients (37%) for restudy of treatment following ISR. The positive rate of patch test in initial stent implantation was not significantly different between with or without restenosis (10% vs. 9%; p=ns). Whereas, following dilatation of ISR, the incidence of positive patch test was significantly higher in patients with recurrence of restenosis than those without the recurrence (39% vs. 12%; p=0.02). Multivariate analysis revealed that the positive patch test (Odd Ratio 4.39, p=0.02) and diffuse typed ISR (Odd Ratio 3.68, p=0.03) were significant predictors of recurrent restenosis. Metal allergy does not have any correlation with the restenosis after initial stent implantation. However, metal allergy is frequently observed in patients with recurrence of ISR. Metal allergy may contribute to a mechanism in the repeat recurrence of ISR, but not to restenosis after initial stent implantation.


Dermoid perforation of the colon.
A case report of an ovarian dermoid tumor perforation the sigmoid colon in a pregnant woman is presentd. Various complications of dermoid perforation are discussed.


Variability of High-Risk Human Papillomavirus and Associated Factors among Women in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.
Sub-Saharan Africa (SSA) carries the highest burden of high-risk human papillomavirus (HR-HPV) in the world, driven by, and together with, HIV infection. This systematic review aimed to identify HR-HPV genotypes and their associated factors among women in SSA. A systematic review and meta-analysis of studies conducted in SSA on HR-HPV was conducted. Standard electronic databases were searched. R software version 3.6.0 was used for meta-analysis, with p < 0.05 considered statistically significant. We included 28 articles with a total of 22,652 participants. The overall pooled prevalence of HR-HPV genotypes was 55.13%, albeit high heterogeneity between studies. The overall pooled prevalence of HR-HPV genotypes in HIV-positive individuals was 75.51%, compared to 52.97% in HIV-negatives (OR = 4.68 (0.71-30.76)). HPV 16 (18%), 35 (10.12%), 52 (9.98%), 18 (9.7%) and 45 (6.82%) genotypes were the most prevalent. Twelve studies identified the most frequently reported risk factors associated with HR-HPV, with HIV infection (66.66%), multiple sexual partners (41.66%) and young age (41.66%) being the most reported risk factors. The combined prevalence of HR-HPV genotypes among women in general and HIV-infected women in particular remains high in SSA. The presence of several genotypes not covered by the vaccine is remarkable and suggests the need for revision of current vaccination policies to prevent HR-HPV infections.


Population pharmacokinetics of aprepitant and dexamethasone in the prevention of chemotherapy-induced nausea and vomiting.
To develop a population pharmacokinetic model of aprepitant and dexamethasone in Japanese patients with cancer, explore the factors that affect the pharmacokinetics of aprepitant, and evaluate the effect of aprepitant on the clearance of intravenous dexamethasone. A total of 897 aprepitant concentration measurements were obtained from 290 cancer patients and 25 healthy volunteers. For dexamethasone, a total of 847 measurements were obtained from 440 patients who were co-administered aprepitant (40, 125 mg, or placebo). Plasma concentration of aprepitant and dexamethasone were determined by liquid chromatography connected with a tandem mass spectrometer and analyzed by a population approach using NONMEM software. The plasma concentration time course of aprepitant was described using a one-compartment model with first-order absorption and lag time. Oral clearance (CL/F) of aprepitant was changed by aprepitant dose at doses of 40 or 125 mg. Body weight was the most influential intrinsic factor to CL/F of aprepitant. Age, ALT, and BUN also had mild effects on the CL/F. Typical population estimates of CL/F, apparent distribution volume (V(d)/F), absorption constant (K(a)) and absorption lag time were 1.54 L/h, 72.1 L, 0.893/h and 0.295 h, respectively. Inter-individual variability in CL/F, V(d)/F and K(a) were 53.9, 21.0, and 141%, respectively; intra-individual variability was 27.7%. The plasma concentration time course of intravenous dexamethasone was also described using a one-compartment model. Clearance of dexamethasone was decreased 24.7 and 47.5% by co-administration of aprepitant 40 and 125 mg. All final model estimates of aprepitant and dexamethasone fell within 10% of the bootstrapped mean. A pharmacokinetic model for aprepitant has been developed that incorporates body weight, age, ALT, BUN and aprepitant dose to predict the CL/F. The results of population pharmacokinetic analysis of dexamethasone support dose adjustment of dexamethasone in the case of co-administration with aprepitant.


Psychometric Evaluation of the Korean Version of the Student Evidence-Based Practice Questionnaire (S-EBPQ).
Evidence-based practice (EBP) is a key competency that undergraduate nursing students need to learn, as EBP competence is essential for the effective implementation of EBP. However, few studies have comprehensively assessed the aspects of EBP competence using a reliable and valid measure specific to Korean nursing students. This study aimed to translate the Student Evidence-Based Practice Questionnaire (S-EBPQ) into Korean and evaluate its psychometric properties. The original S-EBPQ was translated into Korean. After a pilot test, a convenience sample of 249 college students with more than four weeks of clinical training experience was selected from three universities in September 2017. Reliability and construct validity were evaluated using exploratory and confirmatory factor analyses. Concurrent validity was evaluated by correlating the measure with informatics competency. The exploratory factor analysis revealed four factors that explained 66.3 of the variance. The confirmatory factor analysis yielded a 4-factor structure (χ2/df = 1.52, p < .001, standardized root-mean-square residual = .07, root-mean-square error of approximation = .07, goodness of fit index = .84, comparative fit index = .91). The Cronbach's α was .81 for the total scale. The scale's correlation with informatics competency was r = .55. The Korean S-EBPQ is a reliable and valid tool that has utility for assessing EBP competence in Korean nursing students and for making comparisons of the EBP competence of nursing students from other countries.


Subcutaneous sacrococcygeal ependymoma with inguinal lymph node metastasis. Case report.
A patient with a subcutaneous sacrococcygeal ependymoma and metastasis to the inguinal lymph nodes is presented and his treatment is described. Previous reports on sacrococcygeal ependymoma are reviewed.


Neglected subtalar dislocation with unstable foot; to walk away or step our foot in?
Chronic neglected subtalar dislocation associated with a non-union talar neck fracture is rare and never documented before. The lack of information from the literature on the optimal management prompted us to describe our experience in the management of this condition. We reported a case of a 57-year-old women presented with this injury. A satisfactory outcome was obtained using a tibio-talo-calcaneal arthrodesis through a plantar approach.


Effect of sotagliflozin on ventricular arrhythmias in mice with myocardial infraction.
Ventricular arrhythmias (VAs) after myocardial infarction (MI) are an important cause of death in patients. Inhibition of sodium-glucose ligand transporter type 2 (SGLT-2) has been shown to reduce cardiovascular mortality in myocardial infarction independent of glycemic sham and prevent ventricular arrhythmias, and it is unclear whether these effects can be further enhanced by additional SGLT-1 inhibition. We investigated the effects of chronic treatment with the dual SGLT-1 and 2 inhibitor sotagliflozin (Sto) on VAs and their underlying mechanisms after MI. MI was induced by ligation of the left anterior coronary artery in 6-8 weeks-old male mice, which were fed Sto at a dose of 30 mg/kg/day for 4 weeks after surgery. The effects were assessed by echocardiography, histopathology, Langendorff Heart Perfusion System, ambulatory electrocardiography, and Western blot. In vitro experiments were performed to assess the effect of Sto on cardiomyocytes subjected to hypoxic. Compared to the MI group, Sto treatment significantly improved cardiac function and reduced infarct size and fibrosis levels. Sto also decreased action potential duration (APD) and APD alternation thresholds. Ambulatory ECG and BURST stimulation showed that Sto reduced the incidence of VAs. In addition, Sto significantly improved the expression levels of ion channels and CX43 and ameliorated the abnormal expression of Ca2+ handling proteins after MI. Mechanistically, in vivo and in vitro experiments confirmed that TLR4/CaMKII activation was enhanced after MI, while Sto significantly inhibited the activation of the TLR4/CaMKII signaling pathway. Sto improved LV remodeling and reduced the incidence of VAs after MI, which was regulated by modulating the TLR4/CaMKII signaling pathway.


Analog black holes and energy extraction by super-radiance from Bose Einstein condensates (BEC) with constant density.
This paper investigates the acoustic superradiance of the density and phase fluctuations from the single vortex state of a Bose-Einstein condensate, by employing full time-domain and asymptotic frequency domain numerical calculations. The draining bathtub model of an incompressible barotropic fluid is adopted to describe the vortex. The propagation of the axisymmetric density and phase fluctuations in the condensate are governed by the massless scalar Klein-Gordon wave equation, which establishes the rotating black-hole analogy. Hence, the amplified scattering of these fluctuations from the vortex comprise the superradiance effect. A particular coordinate transformation is applied to reveal the event horizon and the ergosphere termwise in the metric and the respective asymptotic spectral solutions. A comparative analysis of the time domain and asymptotic frequency domain results are given for a range of rotational speed of the vortex and the frequency of the impinging fluctuations. The agreement at low rotational speeds of the vortex is shown to be very good, which starts to deteriorate at higher rotational speeds due to increasing constraint violations of the time-domain calculations. We further demonstrate an asymptotic upper bound for the superradiance as a function of vortex rotational speed, provided that the vortex remains stable.


The chromosome 21 transcription factor ETS2 transactivates the beta-APP promoter: implications for Down syndrome.
The gene that codes for beta-amyloid precursor protein (beta-APP), a protein centrally involved in senile plaque formation in Down syndrome (DS) and Alzheimer's disease (AD), is located on chromosome 21. In DS beta-APP expression is three- to fourfold higher than what is expected from the 1.5-fold increased gene load, suggesting that other genes on chromosome 21 directly or indirectly can further up-regulate beta-APP. Here we show that the chromosome 21 transcription factor ETS2 transactivates the beta-APP gene via specific Ets binding sites in the beta-APP promoter and, in this respect, cooperates with the transcription factor complex AP1. We further show that brains and primary neuronal cultures from Ets2 transgenic mice, as well as 3T3 fibroblasts that overexpress ETS2, display molecular abnormalities also seen in DS, such as elevated expression of beta-APP protein, an increase in presenilin-1 and increased beta-amyloid production. We conclude that ETS2 is a transcriptional regulator of beta-APP and that overexpression of ETS2 in DS may play a role in the pathogenesis of the brain abnormalities in DS and possibly AD.


Serum gastrin in health and disease.
Recent developments have led to a further appreciation of the various species of circulating gastrin and to provocative tests for the presence of the Zollinger-Ellison syndrome. Studies of serum gastrin levels, together with other studies of physiologic response, have suggested some possible roles of gastrin in the complex gastric acid hypersecretory state that frequently accompanies duodenal ulcer. Finally, investigations of exogenous and endogenous serum gastrin have provided a mechanism to examine the possible physiologic effects of this hormone.


Ciliary activity and pollution.
The mucociliary clearance is an important part of the nonspecific defense mechanism of the human airways. Coordinated beats of cilia in the nose, trachea, and bronchi propel the mucous layer toward the pharynx, and with it inhaled microorganisms and other particles captured in the mucus. Normal function of this system depends on the efficacy of the ciliary beating and the properties of mucus. Primary ciliary dyskinesia--a congenital respiratory disease characterized by ultrastructural defects and motility disturbances of cilia--has provided us with valuable information about the role the mucociliary function plays in the protection against harmful agents in the inhaled air. Secondary ciliary dyskinesia is described in inflammatory disorders of the respiratory tract, but also some components in air pollution results in malfunction of cilia, damage of ciliated epithelium, or alteration in the mucus. This review will focus on investigations found in the literature concerning the influence of pollutants on ciliary activity. The methods applied will be evaluated.


Metabolomic plasticity in GM and non-GM potato leaves in response to aphid herbivory and virus infection.
An important aspect of ecological safety of genetically modified (GM) plants is the evaluation of unintended effects on plant-insect interactions. These interactions are to a large extent influenced by the chemical composition of plants. This study uses NMR-based metabolomics to establish a baseline of chemical variation to which differences between a GM potato line and its parent cultivar are compared. The effects of leaf age, virus infection, and aphid herbivory on plant metabolomes were studied. The metabolome of the GM line differed from its parent only in young leaves of noninfected plants. This effect was small when compared to the baseline. Consistently, aphid performance on excised leaves was influenced by leaf age, while no difference in performance was found between GM and non-GM plants. The metabolomic baseline approach is concluded to be a useful tool in ecological safety assessment.


Serial Serum Immunoglobulin G (IgG) Trough Levels in Patients with X-linked Agammaglobulinemia on Replacement Therapy with Intravenous Immunoglobulin: Its Correlation with Infections in Indian Children.
Patients with primary antibody deficiency (PAD) are being increasingly diagnosed in the developing world. However, care of these children continues to remain suboptimal due to financial and social constraints. Immunoglobulin (Ig) trough level is an important predicting factor for infections in children on replacement immunoglobulin therapy. There are no data on this aspect from the developing world. Therefore, we studied serial immunoglobulin G (IgG) trough levels in 14 children with X-linked agammaglobulinemia (XLA) receiving replacement intravenous immunoglobulin (IVIG). Infections during the course of enrolment were documented prospectively. Mean age at the time of diagnosis was 5.1 years (range 2-11 years). Mean time from onset of symptoms and initiation of therapy was 3.3 years. Two children had established chronic lung disease prior to enrolment. Total numbers of major and minor infections were 7 and 40, respectively. At a mean dose of 414 mg/kg/month of IVIG, mean trough IgG level was 435 mg/dl. Median IgG trough levels during the episodes of major and minor infections were 244 and 335 mg/dl, respectively. An escalation in IVIG dose of 100 mg/kg produced an increase in serum IgG levels by 53.6 mg/dl. Median trough IgG level of 354 mg/dl was found to be protective with 64% sensitivity and 75% specificity. A median dose of 397 mg/kg was required to keep children free of infections. Despite financial constraints and several challenges in the context of a developing country, children with XLA have good outcome on replacement immunoglobulin therapy. Furthermore, mean biological trough IgG levels are much lower than reported in for Western patients; however, studies involving larger number of subjects are required in future to draw firm conclusions.


Pkd1-inactivation in vascular smooth muscle cells and adaptation to hypertension.
Autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder characterized by renal, hepatic and pancreatic cyst formation and cardiovascular complications. The condition is caused by mutations in the PKD1 or PKD2 gene. In mice with reduced expression of Pkd1, dissecting aneurysms with prominent media thickening have been seen. To study the effect of selective disruption of Pkd1 in vascular smooth muscle cells (SMCs), we have generated mice in which a floxed part of the Pkd1 gene was deleted by Cre under the control of the SM22 promotor (SM22-Pkd1(del/del) mice). Cre activity was confirmed by X-gal staining using lacZ expressing Cre reporter mice (R26R), and quantitative PCR indicated that in the aorta Pkd1 gene expression was strongly reduced, whereas Pkd2 levels remained unaltered. Histopathological analysis revealed cyst formation in pancreas, liver and kidneys as the result of extravascular Cre activity in pancreatic ducts, bile ducts and in the glomerular Bowman's capsule. Remarkably, we did not find any spontaneous gross structural blood vessel abnormalities in mice with somatic Pkd1 gene disruption in SMCs or simultaneous disruption of Pkd1 in SMCs and endothelial cells (ECs). Extensive isometric myographic analysis of the aorta did not reveal differences in response to KCl, acetylcholine, phenylephrin or serotonin, except for a significant increase in contractility induced by phenylephrin on arteries from 40 weeks old Pkd1(del/+) germ-line mice. However, SM22-Pkd1(del/del) mice showed significantly reduced decrease in heart rate on angiotensin II-induced hypertension. The present findings further demonstrate in vivo, that adaptation to hypertension is altered in SM22-Pkd1(del/del) mice.


Duodenum-stomach anastomosis: a new technique for exocrine drainage in pancreas transplantation.
Poor vascular access due to previous surgery can be a major obstacle in pancreas transplantation for which new exocrine and vascular outflow techniques might be useful. A 34-year-old female with early onset type 1 diabetes who underwent living donor kidney transplantation 20 years ago and a failed pancreas transplantation 2 years ago presented for pancreas retransplantation. The inferior vena cava was used in the previous deceased donor pancreas transplantation and both iliac arteries had intense perivascular fibrosis, making arterial anastomosis impossible. The only remaining option for the implant was the infrarenal aorta, with venous drainage to the superior mesenteric vein and exocrine drainage to the gastric antrum. The patient had an uneventful recovery and graft function appeared normal. This report shows that when the recipient's abdominal cavity does not provide clear access for the usual surgical techniques regarding exocrine drainage, the stomach drainage procedure is an option. Duodenum-stomach anastomosis might be an alternative to portal enteric drainage because there is easy access for graft biopsies and even for procedures involving the papilla major.


Synthesis and antibacterial activity of egonol derivatives.
Synthesis of egonol derivatives, 5-(3''-chloropropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 1, 5-(3''-bromopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 2, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propanal 3, 5-(3''-iodopropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 4, 5-[3-(3''-bromopropyloxy) propyl]-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 5, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylmethanoate 6, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propyloleate 7, 5-[3''-hydroxypropyl]-6-bromo-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran 8, 4-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]butanenitrile 9, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1-benzofuran-5-yl]propylbenzoate 10, 5-[3''-hydroxypropyl]-7-methoxy-3-nitro-2-(3',4'-methylenedioxyphenyl)benzofuran 11 and their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli are reported. The starting material egonol 5-[3''-(hydroxy)propyl]-7-methoxy-2-(3', 4'methylenedioxyphenyl)benzofuran was isolated from seeds of Styrax officinalis L. The structural elucidication of these compounds (1-11) was established using 1D ((1)H, (13)C), 2D NMR (HMBC, HMQC, COSY) and LCMS spectroscopic data. While egonol and some synthesised new compounds show similar antibacterial activity and MIC values against S. aureus, B. subtilis, C. albicans and E. coli, other new derivatives show different activity against S. aureus, B. subtilis, C. albicans and E. coli.


Isolation and characterization of a larval lipoprotein from the hemolymph of Manduca sexta.
1. The larval high density lipoprotein (HDL) from the hemolymph of Manduca sexta, isolated by density gradient centrifugation, contains 61% protein, 37% lipid and 2% carbohydrate. 2. The molecular weight of HDL is 6 x 10(5), with two apoproteins of 2.85 x 10(5) and 8.1 x 10(4) daltons. 3. The large apoprotein is destroyed by trypsin treatment of the particle, while the small one is not. 4. Calculations based upon size and composition show that this particle is very different in structure from mammalian lipoproteins. It is proposed that a portion of the apoprotein occupies the central core region.


Association of apolipoprotein M and sphingosine-1-phosphate with brown adipose tissue after cold exposure in humans.
The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via 18F-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (- 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (- 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (β: 0.44, 95% CI [0.06-0.81], P = 0.024) after adjusting for study design but not BAT volume (β: 0.39, 95% CI [- 0.01-0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.


Improving liquid chromatography-mass spectrometry sensitivity for characterization of lignin oligomers and phenolic compounds using acetic acid as a mobile phase additive.
Characterization of complex lignin degradation products by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) requires a high sensitivity, which can be improved by use of optimized mobile phase additive. In this study, chromatographic separation and ionization efficiency for LC-MS analysis of lignin oligomers and lignin-derived phenolic compounds were compared among six different mobile phase additives. We found that acetic acid exhibits analytical performance superior to the other mobile phase additives for characterization of lignin degradation products by LC-(-)-ESI-MS/MS. The retention of phenolic compounds (PCs) containing carboxylic group was improved by using acidic additives instead of their ammonium salts. The use of acetic acid as an LC mobile phase additive enhanced the ionization efficiency of PCs in (-)-ESI-MS about 2 to 4 times higher than the other additives. The improved MS sensitivity with acetic acid yielded a higher coverage of fragment ions in LC-MS/MS analysis, leading to identification of four additional synthetic G-type lignin oligomers (LOs) than ammonium acetate. A similar degree of sensitivity enhancement was also demonstrated for degradation products from rice straw lignin using acetic acid additive over the others. The increased chromatographic retention and enhanced sensitivity of PCs and LOs provided by the use of acetic acid as an LC-(-)-ESI-MS mobile phase additive will facilitate structural analysis of lignin degradation products without relying on additional instrumentation.


Effects of L-arginine on blood pressure and metabolic changes in fructose-hypertensive rats.
In the present study, we examined the effects of chronic L-arginine treatment on plasma insulin levels and systolic blood pressure (SBP) in fructose-fed (F) rats. Fructose feeding resulted in hyperinsulinemia and elevated blood pressure when compared with that in controls (plasma insulin, 311.3+/-11.4 v control 164.4+/-11.8 pmol/L, P < .05; SBP, 135.4+/-4.2 v control 105.5+/-1.3 mm Hg, P < .05). L-arginine treatment of fructose-hypertensive rats prevented the development of hyperinsulinemia and hypertension (plasma insulin, 200.1+/-7.5 pmol/L; P < .05 compared with that in F rats; SBP, 108.0+/-0.9 mm Hg; P < .05 compared with F rats). However, treatment with L-arginine did not influence any of these parameters in control rats. Statistical analysis of the data of plasma insulin level and SBP, revealed a significant correlation between these two variables. On the other hand, L-arginine treatment of F rats prevented the increased glucose and insulin concentrations in response to oral glucose challenge. L-arginine treatment also prevented the decrease in insulin sensitivity of F rats. These results indicate that L-arginine treatment is able to prevent fructose-induced hypertension and hyperinsulinemia. Our data also suggest a strong relationship between hyperinsulinemia and hypertension in this hypertensive rat model. Therefore, the antihypertensive effect of L-arginine could be, at least in part, the result of the restoration of plasma insulin levels by its vasodilator ability to increase blood flow to insulin sensitive tissues.


Ruthenium-catalyzed tandem ring-opening/ring-closing/cross-metathesis of 1,6-cyclopropene-ynes and olefins for the construction of the 3-pyrroline skeleton.
Catalyzed by the first-generation Grubbs' ruthenium complex, tandem intramolecular/intermolecular metathesis of 1,6-enynes bearing a cyclopropene ring took place smoothly to produce 3-pyrroline derivatives in satisfactory yields via ring-opening/ring-closing/cross-metathesis processes.


[Intra-diverticular neoplasms of the bladder. Apropos of a squamous carcinoma].
We present a case of a cirrhotic patient suffering an intradiverticular squamous carcinoma with perforation to the peritoneal cavity, diagnosed after performance of an emergency laparotomy due to acute abdomen with infaust evolution. The rarity of the entity and the differential diagnosis imposed are the reasons for our presenting it. A series of diagnostic, prognostic and preventive aspects are considered.


Short-term testing--are we looking at wrong endpoints?
Short-term testing has been performed and interpreted on the basis of correlation between these tests and animal carcinogenicity. This empirical approach has been the only feasible one, due to a lack of knowledge of the actual genetic endpoints of relevance in carcinogenicity. However, the rapidly growing information on genetic alterations actually involved in carcinogenicity and in particular activation of oncogenes, provides facts of basic importance for the strategy of short-term testing. The presently used sets of short-term tests focus on standard genetic endpoints, mainly point mutations and chromosomal aberrations. Little attention has been paid in that connection to other endpoints, which have been shown or suspected to play an important role in carcinogenicity. These endpoints include gene amplification, transpositions, hypomethylation, polygene mutations and recombinogenic effects. Furthermore, indirect effects, for instance via radical generation and an imbalance of the nucleotide pool, may be of great significance for the carcinogenic and cocarcinogenic effects of many chemicals. Modern genetic and molecular technology has opened entirely new prospects for identifying genetic alterations in tumours and in its turn these prospects should be taken advantage of in order to build up more sophisticated batteries of assays, adapted to the genetic endpoints actually demonstrated to be involved in cancer induction. Development of new assay systems in accordance with the elucidation of genetic alterations in carcinogenicity will probably constitute one of the most important areas in genetic toxicology in the future. From a regulatory point of view the prerequisite for a development in this direction will be a flexibility of the handling of questions concerning short-term testing also at a bureaucratic level.


Kaposi's sarcoma of the foot. A review and report of 156 cases.
The authors identify the incidence of Kaposi's sarcoma in the foot, and discuss the increasing incidence of AIDS-related cases, and the increasing chance of mortality when this lesion is seen in patients under the age of 50.


The role of public policy in debt level choices among small-scale manufacturing enterprises in Ethiopia: conditional mixed process approach.
This paper explores the determinants of debt financing choices among small-scale manufacturing enterprises in Ethiopia-with special focus on the role of government policies. The study exploits survey data gathered from 1321 enterprises in the Amhara region of Ethiopia and employs conditional mixed process (CMP) system estimation technique to test the effect of public policy on firm debt levels. The relevant econometric findings confirm that policy activism through the provision of training and related intervention schemes boosts debt utilization in startup finance mix while it lowers the probability of firms' falling into higher debt levels over time. The results also show that enterprises that had some debt mix in their startup capital are more likely to be in higher debt categories than those enterprises that kick start exclusively with their own internal resources. In addition, the findings also reveal that self-reported profitability, firm age, and ownership structure have strong effects on the degree of firms' indebtedness. One major bottleneck to the survival and growth of SMEs is their relatively large default rates. One strand of the existing literature shows that firm default rates are strongly correlated with debt levels. As default rates driven by high debt levels have devastating implications for creditors, debtors, and regulators, it is very important to understand the determinants of debt levels. This study is the first to apply conditional mixed process system estimation on firm level data from Ethiopia to test the effects of government policies on debt level choices.


Status, source, human health risk assessment of potential toxic elements (PTEs), and Pb isotope characteristics in urban surface soil, case study: Arak city, Iran.
The current study was conducted to assess the level of potentially toxic elements (PTEs) contamination (Cu, Pb, Zn, Cr, As, Cd, and Ni) in surface soils from Arak city. Arak, which is an industrial city, is a prominent center of chemicals, metal/electric, manufacturing factories, and other industries. Forty-three surface soil samples were collected from 0-20 cm after removing the visible surface contamination in the dry season in June 2017. Metal concentrations were found highly variable, ranging from 174-3950 mg/kg for Cu, 181-3740 mg/kg for Pb, 48-186 mg/kg for Zn, 105-1721 mg/kg for Ni, 0.8-0.9 mg/kg for As, 114-1624 mg/kg for Cr, and 3.45-12.36 mg/kg for Cd. The results of geochemical fraction indicated that the main components of Pb, Cr, and Zn at most of the sampling sites are Fe-Mn bound/reducible. Meanwhile, the residual fraction is the dominant fraction of sequence extraction for Ni, Cu, and Cd. Higher values of reducible bound for Pb, Cr, and Zn, as well as a considerable percentage of Ni, Cu, and Cd, imply that the main source of the studied PTEs (except As) in the study area is both anthropogenic and geogenic inputs. The results of principal component analysis (PCA), correlation analysis, enrichment factor (EF), enrichment index (EI), and top enrichment factor (TEF) confirm that Pb, Ni, Cu, Cr, Cd, and Zn had a similar anthropogenic source which is confirmed by geochemical fractionation analysis. Carcinogenic risks (CR) of studied PTEs were estimated to be higher than the target limit of 1.0E-06, for adults and children except for Cr with values of 5.91E-04, and 3.81E-04 for children and adults, respectively. Higher CR values of Cr compared to other PTEs in Arak surface soil demonstrate that living target populations, including children and adults, particularly children, are more at risk of carcinogenic risks of PTEs. 206Pb/207Pb ratios of the collected samples indicated that Pb in Arak surface sample was derived from industrial inputs and deposition, as well as re-suspension vehicle exhaust emission from previously leaded gasoline. The findings concerning the applied end-member contribution of geogenic and industrial and vehicle emission represented that the contribution could vary from 68.0% to 15% (mean: 39.3) for industrial emission, 65% to 19% for vehicle exhaust (mean: 39), and 46% to 10% (mean: 21.6) for geogenic sources.


The Location of Magnetic Reconnection at Earth's Magnetopause.
One of the major questions about magnetic reconnection is how specific solar wind and interplanetary magnetic field conditions influence where reconnection occurs at the Earth's magnetopause. There are two reconnection scenarios discussed in the literature: a) anti-parallel reconnection and b) component reconnection. Early spacecraft observations were limited to the detection of accelerated ion beams in the magnetopause boundary layer to determine the general direction of the reconnection X-line location with respect to the spacecraft. An improved view of the reconnection location at the magnetopause evolved from ionospheric emissions observed by polar-orbiting imagers. These observations and the observations of accelerated ion beams revealed that both scenarios occur at the magnetopause. Improved methodology using the time-of-flight effect of precipitating ions in the cusp regions and the cutoff velocity of the precipitating and mirroring ion populations was used to pinpoint magnetopause reconnection locations for a wide range of solar wind conditions. The results from these methodologies have been used to construct an empirical reconnection X-line model known as the Maximum Magnetic Shear model. Since this model's inception, several tests have confirmed its validity and have resulted in modifications to the model for certain solar wind conditions. This review article summarizes the observational evidence for the location of magnetic reconnection at the Earth's magnetopause, emphasizing the properties and efficacy of the Maximum Magnetic Shear Model.


The New Zealand Major Trauma Registry: the foundation for a data-driven approach in a contemporary trauma system.
To describe the development of the New Zealand Major Trauma Registry (NZ-MTR) and the initial experiences of its use. The background to the development of the NZ-MTR was reviewed and the processes undertaken to implement a single-instance of a web-based national registry described. A national minimum dataset was defined and utilised. Key structures to support the Registry such as a data governance group were established. The NZ-MTR was successfully implemented and is the foundation for a new, data-driven model of quality improvement. In its first year of operation over 1,300 patients were entered into the Registry although coverage is not yet universal. Overall incidence is 40.8 major trauma cases/100,000 population. The incidence in the Māori population was 69/100,000 compared with 31/100,000 in the non-Māori population. Case fatality rate was 9%. Three age peaks were observed at 20-24 years, 50-59 years and above 85 years. Road traffic crashes accounted for 50% of all caseload. A significant proportion of major trauma patients (21%) were transferred to one or more hospitals before reaching a definitive care facility. Despite the challenges working across multiple jurisdictions, initiation of a single-instance web-based registry has been achieved. The NZ-MTR enables New Zealand to have a national view of trauma treatment and outcomes for the first time. It will inform quality improvement and injury prevention initiatives and potentially decrease the burden of injury on all New Zealanders.


Broca's aphemia: an illustrated account of its clinico-anatomic validity.
To present the case of a 54-year-old man with loss of speech, but with preservation of voluntary facio-lingual motility, language and other cognitive abilities (Broca's aphemia). Observation of patient oral communicative abilities and general behavior, neuropsychological assessment and cranial computed tomography. Computed tomography showed a hyperdense lesion in the subcortex of the left precentral gyrus corresponding to Brodmann's area 6 and 44. Neuropsychological assessment confirmed that the major cognitive domains were intact. Our patient reiterates the validity of Broca's aphemia as a clinico-anatomic entity allowing us to portray it for the first time in pictures. From a neurobehavioral perspective, aphemia is related to apraxia rather than to aphasia, a fact that may have hampered the full grasp of its far-reaching implications for neurology and aphasiology.


Pharmaceutical nanotechnology: which products are been designed against COVID-19?
The current pandemic COVID-19, caused by the SARS-CoV-2 virus, has been affecting thousands of people worldwide, promoting high numbers of deaths. With this, the world population is going through a process of changing habits, with social distance, improvement of hygiene techniques, to reduce the spread of the SARS-CoV-2 virus and, consequently, reduce the number of hospitalized people in serious condition, as well as the mortality rate. This scenario has been promoting a continuous search for researchers, in the most varied areas, for possible methods of prevention or cure. Specifically, in the field of pharmaceutical nanotechnology, a variety of products are being developed against SARS-CoV-2. Under these circumstances, we propose here an exposition of some of the nanotechnological products (nanoscale between 1 to 1000 nm) currently designed for the detection of the virus, for the prevention and treatment of COVID-19, in addition to equipment for personal protection. We believe that pharmaceutical nanotechnology will be a valuable tool in the disease from the development of products that guarantee our protection against the SARS-CoV-2 virus.


Persistent inter-observer variability of breast density assessment using BI-RADS® 5th edition guidelines.
Due to most states' legislation, mammographic density categorization has potentially far-reaching implications, but remains subjective based on BIRADS® guidelines. We aimed to determine 1) effect of BI-RADS® 5th edition (5th-ed) vs 4th-edition (4th-ed) guidelines on reader agreement regarding density assessment; 2) 5th-ed vs 4th-ed density distribution, and visual vs quantitative assessment agreement; 3) agreement between experienced vs less experienced readers. In a retrospective review, six breast imaging radiologists (BIR) (23-30 years' experience) visually assessed density of 200 screening mammograms performed September 2012-January 2013 using 5th-ed guidelines. Results were compared to 2016 data of the same readers evaluating the same mammograms using 4th-ed guidelines after a training module. 5th-ed density categorization by seven junior BIR (1-5 years' experience) was compared to eight experienced BIR. Nelson et al.'s kappas (κm, κw), Fleiss' κF, and Cohen's κ were calculated. Quantitative density using Volpara was compared with reader assessments. Inter-reader weighted agreement using 5th-ed is moderately strong, 0.73 (κw, s.e. = 0.01), similar to 4th-ed, 0.71 (κw, s.e. = 0.03). Intra-reader Cohen's κ is 0.23-0.34, similar to 4th-ed. Binary not-dense vs dense categorization, using 5th-ed results in higher dense categorization vs 4th-ed (p < 0.001). 5th-ed density distribution results in higher numbers in categories B/C vs 4th-ed (p < 0.001). Distribution for 5th-ed does not differ based on reader experience (p = 0.09). Reader vs quantitative weighted agreement is similar (5th-ed, Cohen's κ = 0.76-0.85; 4th-ed, Cohen's κ = 0.68-0.83). There is persistent subjectivity of visually assessed mammographic density using 5th-ed guidelines; experience does not correlate with better inter-reader agreement.


Cytogenetics and cell surface marker analysis in CML--1. Prediction of phenotype of acute phase transformation.
Thirty-nine patients with Philadelphia chromosome-positive (Ph1) chronic myelocytic leukemia (CML) were monitored using cytofluorometry and cytogenetics. During chronic phase, abnormal populations could be detected using commercially available monoclonal antibodies. Most of these abnormal populations had either an HLA.DR+ or an OKM1+ HLA.DR- phenotype. Thirteen patients progressed to acute phase disease. Five patients with HLA-DR+ abnormal cells during chronic phase showed no clonal evolution detectable using standard cytogenetic techniques and underwent lymphoid transformation. Seven patients with OKM1+-HLA.DR- abnormal cells exhibited chromosomal abnormalities in addition to the Ph1 and progressed to a myeloblastic acute phase. One patient with HLA.DR+ OKM1+ 63D3+ abnormal cells in chronic phase showed clonal evolution and progressed to a myelomonocytic acute phase. These results suggest that cell surface markers on chronic phase cells can be used in conjunction with cytogenetic monitoring to predict the phenotype of cells involved in the acute transformation of CML. B cells (6, 13), but not T cells (18), bearing the Ph1 have been isolated from chronic phase CML patients. Thus cells other than those of myeloid lineage may be involved. Periodic cytogenetic monitoring has been shown to detect clonal evolution (i.e. genetic changes in addition to the PH1) in as many as 75% of patients prior to the acute phase (14, 37). However, neither cytogenetic changes nor morphologic analysis appear to predict the lymphoblastic type of transformation (14). Since fluorescence analysis of cell surface markers has shown reduced numbers of normal cells (28), the identity of the 'abnormal' cells was probed with antibodies recognizing a variety of markers on immature and mature lymphoid and myeloid cells. Not only were significant numbers of abnormal cells detected in the peripheral blood of chronic phase patients, but the phenotype of the abnormal population, in combination with cytogenetic analyses, predicted the type of blasts involved in acute phase disease.


Coffee, tea, and mortality.
Except for conflicting evidence about coffee and risk of coronary disease, coffee and tea are not linked to major causes of death. Because of widespread use of both beverages and limitations of prior studies, concern persists. Using Cox models (ten covariates) we studied relations in 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. If coffee increases coronary risk, this is balanced by an unexplained lower risk of other conditions, notably cirrhosis and suicide.


Biological monitoring for exposure assessment of volatile organic compounds by Korean firefighters at the fire site.
The VOCs and metabolites in urine for exposed VOCs were evaluated for firefighters who participated in the actual fire fighting to determine whether firefighters were exposed to hazardous chemicals, which is the basic data on cancer risk of firefighters. When the fire extinguishing time is long, the concentration of benzene, PHEMA, and toluene among VOCs and metabolites in the case of fire suppression, rescue, and fire investigation work, which is estimated that the exposure of hazardous substances generated from the fire site at the time of fire suppression was large, significantly increased. In the case where the number of urination is 2 or less, the concentration of TZCA, toluene, and benzene among VOCs and metabolites was significantly increased compared to the number of urinating more than 2 times. In the concentration of VOCs and metabolites in urine corrected with creatinine, the concentrations of toluene and PHEMA in urine were significantly higher. The concentration of PHEMA in urine was higher in the group who participated in the fire suppression for more than 11 hours (long time) than the group who participated in the fire suppression for a short time.


Odor identification in mild cognitive impairment subtypes.
The current study examined odor identification using the Brief Smell Identification Test (BSIT) in mild cognitive impairment (MCI) subtypes (17 "amnestic MCI", 46 "amnestic-plus MCI", and 25 "MCI other"). Performance in participants with MCI was compared to that of participants with Alzheimer's disease (AD, n=44) and healthy elderly (n=21). MCI participants performed worse than controls, but better than those with AD. MCI subtypes did not differ. The magnitude of difference between MCI participants and controls was modest, raising some question of the clinical utility of the BSIT in early detection of MCI and early differential diagnosis.


Radiogrammetry of the soft tissue at the index finger in acromegaly.
Measurements of the soft-tissue width and phalanx width at the index finger were made in 30 acromegalic patients and compared with values obtained in a large control population. The width of the phalanx, total finger width and soft-tissue thickness are significantly larger than expected and the soft-tissue index values are significantly lower than expected. An important overlap between normal and acromegalic values is found for the soft-tissue index and width of the proximal phalanx. The measurement which best discriminates acromegalics from normal is the total finger width. The soft-tissue thickness parameter is also very sensitive for the detection of acromegalic changes and has the advantage of not being sex and age dependent.


[Biocompatibility of JJ magnetic retainer metal materials].
The purpose of this study was to evaluate the biocompatibility of new JJ-magnetic retainer metal materials. Preliminary biocompatible tests of the metal materials were performed depending on ISO 10.993-12 standard. They were cytotoxicity test, hemolysis test, acute systemic toxicity test, sensitization test and Ames test. The cytotoxicity of the metal material was grade I. The hemolysis rate was 0.45%. There was no abnormal sensitization and irritation actions in the experimental group. The metal had no action of mutagenesis and carcinogenesis. The JJ-magnetic retainer metal material showed excellent biocompatibility on the preliminary tests. It would be a good material in the way of biological safety.


[Spironolactone reduces blood pressure and albuminuria of obese hypertensive patients with metabolic syndrome].
In recent years, a role for aldosterone in pathophysiology of metabolic syndrome and hypertension in this syndrome has been suggested. However, the treatment with antagonists of mineralocorticoid receptor in these individuals has not properly addressed. To evaluate the effects of mineralocorticoid receptor blockade on blood pressure, inflammatory, metabolic and renal parameters in non-diabetic hypertensive individuals with the metabolic syndrome. Twenty nine patients with metabolic syndrome were enrolled in a prospective protocol that consisted of 2 periods: baseline (2 weeks) in which demographic data were obtained and antihypertensive medicines were withdrawn, and treatment period when the individuals were treated with spironolactone 25-50 mg once-a-day, for 16 weeks. In both periods, inflammatory, metabolic and renal parameters were assessed and the 24-hour ambulatory blood pressure monitorization was performed. After spironolactone treatment, 24 hour systolic and diastolic blood pressure decreased from 143.5 ± 15.17 mmHg to 133.2 ± 17.34 mmHg (p = 0.025) and from 85.2 ± 11.10 mmHg to 79.3 ± 11.78 mmHg (p = 0.026), respectively. HDL-cholesterol increased from 44.0 ± 8.67 mg/dl to 49.0 ± 6.75mg/dl (p = 0.000) and C-reactive protein decreased significantly from 6.3 ± 7.54 mg/l to 4.6 ± 6.3 mg/l (p = 0.009). Fasting plasma glucose, insulin, HOMA-IR and triglycerides did not change significantly after mineralocorticoid receptor blockade. Estimated glomerular filtration rate did not change whereas the logarithm of albuminuria decreased significantly from 2.5 ± 0.92 to 2.0 ± 0.9 (p = 0.028). In hypertensive subjects with MS the administration of spironolactone in monotherapy was effective for hypertension control, decreased urinary albumin excretion and increased HDL-cholester ol plasma.


Parasitic diseases in the abdomen: imaging findings.
Parasitic diseases of the liver and biliary tract include echinococcosis, schistosomiasis, toxocariasis, clonorchiasis, and opisthorchiasis, affecting millions people in some endemic areas. Amebiasis and ascariasis are believed to be the most common bowel lumen indwelling parasitic diseases, affecting billions people worldwide, but sometimes these parasites migrate inadvertently to the liver and biliary tract, resulting in liver abscess or obstructive jaundice. Imaging findings of these parasitic diseases are fairly characteristic and easy to recognize if radiologists are aware of the findings, especially in endemic areas. Because of increased immigration and frequent travelling, some patients with "exotic" parasitic diseases may be encountered in non-endemic areas, and the diagnosis may be delayed or difficult, and it is often made only after operation. This feature section was designed to provide the detailed imaging features of common parasitic diseases affecting the abdominal organs and peritoneal cavity, based on pathology-image correlation.


Effects of sustained swimming on the red and white muscle transcriptome of rainbow trout (Oncorhynchus mykiss) fed a carbohydrate-rich diet.
Training at sustainable swimming speeds can produce changes in fish skeletal muscle that are important for aquaculture due to their growth-potentiating effects. Such changes may be even more relevant when fish are fed diets containing an increasing proportion of carbohydrates as an energy source. We evaluated the effects of moderate-intensity sustained swimming on the transcriptomic response of red and white muscle in rainbow trout fed a carbohydrate-rich diet using microarray and qPCR. Analysis of the red and white muscle transcriptome in resting or swimming (1.3 body lengths/s) fish for 30days revealed significant changes in the expression of a large number of genes (395 and 597, respectively), with a total of 218 differentially expressed genes (DEGs) common for both muscles. A large number of the genes involved in glucose use and energy generation, contraction, development, synthesis and catabolism of proteins were up-regulated in red and white muscle. Additionally, DEGs in both muscles were involved in processes of defense response and apoptosis. Skeletal muscle contraction activates a transcriptional program required for the successful adaptation of both muscles to the changing demands imposed by swimming conditions. Future studies should further clarify the mechanisms involved in the adaptation of both tissues to exercise and assess possible benefits of such conditions for cultured fish.


Rapid microevolution of biofilm cells in response to antibiotics.
Infections caused by Acinetobacter baumannii are increasingly antibiotic resistant, generating a significant public health problem. Like many bacteria, A. baumannii adopts a biofilm lifestyle that enhances its antibiotic resistance and environmental resilience. Biofilms represent the predominant mode of microbial life, but research into antibiotic resistance has mainly focused on planktonic cells. We investigated the dynamics of A. baumannii biofilms in the presence of antibiotics. A 3-day exposure of A. baumannii biofilms to sub-inhibitory concentrations of antibiotics had a profound effect, increasing biofilm formation and antibiotic resistance in the majority of biofilm dispersal isolates. Cells dispersing from biofilms were genome sequenced to identify mutations accumulating in their genomes, and network analysis linked these mutations to their phenotypes. Transcriptomics of biofilms confirmed the network analysis results, revealing novel gene functions of relevance to both resistance and biofilm formation. This approach is a rapid and objective tool for investigating resistance dynamics of biofilms.


Direct autoradiographic evidence that rebamipide interacts with neutrophils in dextran sulfate sodium induced colitis in rats.
To determine the effects of rebamipide during the early stages of colitits development, colitis was induced in rats by oral administration of dextran sulfate sodium for 3 or 7 days. The target sites of (3)H-rebamipide were examined by intra-aortic infusion of the radiolabeled compound followed by autoradiography. (3)H-rebamipide was localized in goblet cells in the colon of the control rat, whereas it accumulated in the cytoplasm of mesenchymal cells in dextran sulfate sodium treated rats, localized predominantly to polymorphonuclear leucocytes.


[Effect of VEGF165 and the VEGF aptamer pegaptanib (Macugen) on the protein composition of tight junctions in microvascular endothelial cells of the retina].
VEGF signalling is deregulated in diabetic retinopathy. Therefore, VEGF inhibitors like the modified RNA-oligonucleotide pegaptanib (VEGF aptamer, Macugen) which inhibits the interaction of VEGF(165) with its receptors, are currently being discussed as therapeutic options in the treatment of diabetic retinopathy. VEGF(165) does not only stimulate the proliferation and migration of endothelial cells but also induces delocalization of occludin which is part of the so-called tight junctions of endothelial cells likely associated with the breakdown of the blood-retina barrier. To further investigate the mechanisms of action of VEGF and its inhibitor, we studied the influence of VEGF(165) and/or pegaptanib on the protein composition of tight junctions in immortalised endothelial cells of the bovine retina (iBREC) by immunofluorescence staining. The tight junction proteins ZO-1, occludin and claudin-5 are strongly expressed at the plasma membrane in confluent iBREC, but are located in the cytoplasm in non-confluent cells. In the presence of 50 ng/ml VEGF(165), occludin was found in the cytoplasm after 1 to 2 days, whereas claudin-5 was not and ZO-1 was only weakly influenced. However, after addition of 33 microg/ml pegaptanib for 24 h to VEGF(165)-treated iBREC, all tight junction proteins tested were again strongly expressed in the plasma membrane. These results confirm an important role of tight junction proteins in the mechanisms of action of VEGF and pegaptanib on endothelial cells.


Universal process-inert encoding architecture for polymer microparticles.
Polymer microparticles with unique, decodable identities are versatile information carriers with a small footprint. Widespread incorporation into industrial processes, however, is limited by a trade-off between encoding density, scalability and decoding robustness in diverse physicochemical environments. Here, we report an encoding strategy that combines spatial patterning with rare-earth upconversion nanocrystals, single-wavelength near-infrared excitation and portable CCD (charge-coupled device)-based decoding to distinguish particles synthesized by means of flow lithography. This architecture exhibits large, exponentially scalable encoding capacities (>10(6) particles), an ultralow decoding false-alarm rate (<10(-9)), the ability to manipulate particles by applying magnetic fields, and pronounced insensitivity to both particle chemistry and harsh processing conditions. We demonstrate quantitative agreement between observed and predicted decoding for a range of practical applications with orthogonal requirements, including covert multiparticle barcoding of pharmaceutical packaging (refractive-index matching), multiplexed microRNA detection (biocompatibility) and embedded labelling of high-temperature-cast objects (temperature resistance).


Uptake of Tc-99m diphosphonate in a massively calcified mitral annulus: case report.
In a patient with no recent myocardial insult, uptake of technetium-99m diphosphonate was noted in a region corresponding to massive calcification of the mitral annulus. The similarity of this finding to pathologic myocardial uptake is a potential source of error in the interpretation of myocardial scintigrams.


Complex regional pain syndrome post mastectomy.
Complex regional pain syndrome includes the previously termed condition reflex sympathetic dystrophy. It is a chronic pain disorder diagnosed on the basis of symptoms and skin changes and is known to have a psychological element. It is a rare complication after surgery, especially mastectomy. We present two females who developed this syndrome after undergoing mastectomy for chronic mastalgia. These cases demonstrate that amputation of an organ for chronic pain can result in reflex sympathetic dystrophy developing in a nearby limb.


Benign teratoma of the fallopian tube: a case report.
A benign teratoma of the fallopian tube in a 33-year-old woman with primary subfertility is reported. This is the first case reported in Singapore. The features of benign teratoma of the fallopian tube is discussed.


Onset Time of Ischemic Events and Antiplatelet Therapy after Intracranial Stent-assisted Coil Embolization.
Stent-assisted coil embolization is effective for intracranial aneurysms, especially wide-necked aneurysms; however, the optimal antiplatelet regimens for ischemic events that develop after coil embolization have not yet been established. We aimed to determine the onset time of such postoperative ischemic events and the relationship between these events and antiplatelet therapy. We performed coil embolization using a vascular reconstruction stent for 43 cases of intracranial aneurysms and evaluated the incidence of postoperative ischemic events in these cases. Nine patients showed postoperative ischemic events during the follow-up period (13 ± 7 months). Two patients developed cerebral infarction within 24 hours. Five patients developed transient ischemic attack within 40 days while they were receiving dual antiplatelet therapy. In addition, 1 patient showed cerebral infarction 143 days postoperatively during single antiplatelet therapy, and a case of transient visual disturbance was reported 191 days postoperatively (49 days after antiplatelet therapy had been discontinued). We increased the number of antiplatelet agents in 4 of these patients. The other 5 patients were under strict observation with dual antiplatelet therapy. All these patients were shifted to single antiplatelet therapy 3-13 months postoperatively. No recurrence of ischemic events was noted. Postoperative ischemic events are most likely to occur within 40 days postoperatively. For patients with postoperative ischemic events, additional ischemic events can be prevented by increasing the number of antiplatelet agents; subsequently, they can be shifted to single antiplatelet therapy after the risk of recurrence has decreased.


An ecotoxicological study of a population of the white footed mouse (Peromyscus leucopus) inhabiting a polychlorinated biphenyls-contaminated area.
White footed mice (Peromyscus leucopus) inhabiting an area surrounding a pond (Tyler) contaminated with polychlorinated biphenyls (PCBs) and metals (Cadmium, Zinc, Copper) had whole body burdens of 0.42-4.17 ppm PCBs (mean 2.3 ppm) and animals from a comparison nonpolluted site (WCC) had no detectable PCBs. Males and females caught at the polluted site in the winter months were not significantly different in body weight or length when compared to WCC animals, but Tyler animals had significantly increased relative liver, kidney, spleen and adrenal weights. In the summer months, mostly males were caught at both Tyler and WCC sites. Tyler males were significantly lighter than WCC males, and had a significantly increased relative liver weight when compared to the males from the WCC site. In addition, the adult Tyler males had significantly lower relative testis weights. At Tyler there was a significantly smaller proportion of juveniles and subadults in the population than at WCC. Polychlorinated biphenyls levels in the adult Tyler males were significantly positively correlated with relative liver weight, but there were no significant correlations with any of the other structures measured. These results suggest that at the polluted site there is inhibition of reproduction and changes in liver, spleen, adrenal, and testis function.


Subtilisin-like protease-1 secreted through type IV secretion system contributes to high virulence of Streptococcus suis 2.
Streptococcus suis serotype 2 is an emerging zoonotic pathogen that triggered two outbreaks of streptococcal toxic shock syndrome (STSS) in China. Our previous research demonstrated that a type IV secretion system (T4SS) harbored in the 89K pathogenicity island contributes to the pathogenicity of S. suis 2. In the present study, a shotgun proteomics approach was employed to identify the effectors secreted by T4SS in S. suis 2, and surface-associated subtilisin-like protease-1 (SspA-1) was identified as a potential virulence effector. Western blot analysis and pull-down assay revealed that SspA-1 secretion depends on T4SS. Knockout mutations affecting sspA-1 attenuated S. suis 2 and impaired the pathogen's ability to trigger inflammatory response in mice. And purified SspA-1 induced the secretion of IL-6, TNF-α, and IL-12p70 in THP-1 cells directly. SspA-1 is the first T4SS virulence effector reported in Gram-positive bacteria. Overall, these findings allow us to gain further insights into the pathogenesis of T4SS and STSS.


Expression analysis of rice VQ genes in response to biotic and abiotic stresses.
WRKY transcription factors are encoded by a large gene superfamily with a broad range of roles in plants. Proteins containing a short VQ (FxxxVQxLTG) motif have been recently shown to interact with WRKY transcription factors, implying that AtVQ proteins are important in the plant defense responses in Arabidopsis, either as positive or negative cofactors of WRKY transcription factors. Thirty-nine Oryza sativa genes containing the VQ motif (OsVQs) were identified and the genome structures of OsVQ proteins were characterized through genome-wide analysis in rice. Also, phylogenetic tree analysis was performed with the VQ domain of Arabidopsis and rice. The expression patterns of these OsVQ genes in plants under several stress treatments were assessed, specifically, following infection with the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), treatment with abscisic acid (ABA), or exposure to drought. The cellular localization of a few OsVQ proteins was examined using rice protoplast system. Based on our results, we suggest that OsVQ proteins function as important co-regulators during the plant defense response to biotic and abiotic stresses.


Application of a pressure area risk calculator in an intensive care unit.
This study describes the use of a pressure area risk calculator designed specifically for intensive care (ICU) patients; the calculator used was that developed by Cubbin & Jackson (1991) (Table 1). This scale is a modified Norton scale with lower scores indicative of increased risk of pressure sore formation. The unit on which this study was undertaken is a six-bedded general adult ICU. A highly significant difference in lowest recorded scores was found between the group of patients who developed pressure sores compared with the group that did not (Mann-Whitney test, p < 0.01). The differences in scores between the two groups suggest that the calculator was measuring something useful, but it should be stressed that 40% (n = 100) of patients had scores below the threshold value and did not develop scores. Risk calculations were decisive in increasing the profile of pressure area care within the ICU and for this reason alone their use can be justified. There was a pressure sore incidence of 13% with 7% of patients having sores prior to admission to the ICU. Of the sores that were noted the commonest sites to be affected within intensive care were heels. The sacrum was the commonest site for sores that had occurred prior to admission. Pressure sore incidence can prove a useful audit tool in the management of pressure area care in intensive care, but variations in incidence over time must be examined with caution.


Purification of the phytase enzyme from Lactobacillus plantarum: The effect on pansy growth and macro-micro element content.
In the present study, the phytase enzyme was purified from Lactobacillus plantarum with a 3.08% recovery, 9.57-purification fold, and with a specific activity of 278.82 EU/mg protein. Then, the effects of the 5 EU and 10 EU purified phytase was determined on the plant growth, quality, the macro-micro nutrient content of pansy (Viola × wittrockiana), which is of great importance in ornamental plants industry. The research was established under greenhouse conditions with natural light in 2017. The pansy seeds were coated with phytase enzyme solution, sown in a peat environment, and transferred to pots at the seedling period. In general, the 5 EU and 10 EU applications increase plant height, the number of leaves per plant, the number of side branches per plant, and flower height parameters compared to control. Also, micro- and macronutrient values in soil and plant samples were examined. According to the results, the phytase application on pansy cultivation positively affected the properties and yielded high quality of plants.


Unusual Presentation of Recurrent Pyogenic Bilateral Psoas Abscess Causing Bilateral Pulmonary Embolism by Iliac Vein Compression.
Psoas abscesses are a known cause of back pain, but they have not been reported as a cause of acute lower extremity thromboses and bilateral pulmonary emboli. We report a patient with bilateral psoas abscesses causing extensive pulmonary emboli through compression of the iliac vein. A 47-year-old man presented with bilateral leg swelling over 4 weeks. Physical examination revealed a thin male with bilateral leg swelling, extending to the thigh on his left side. He had hemoglobin of 10.5 g/dl, leukocytosis of 16 000/ml, and an elevated D-dimer. A computed tomography (CT) angiogram of his chest showed extensive bilateral pulmonary emboli and infarcts. He remained febrile with vague flank pain, prompting a CT of his abdomen and pelvis that showed large, multiloculated, septated, bilateral psoas abscesses with compression of the left femoral vein by the left psoas abscess and a thrombus distal to the occlusion. Two liters of pus was drained from the left psoas abscess by CT-guidance, and although the Gram staining showed Gram-positive cocci in clusters, cultures from the abscess and blood were negative. A repeat CT showed resolution of the abscesses, and the drain was removed. He was discharged to a nursing home to complete a course of intravenous antibiotics and anticoagulation. Although the infectious complications of psoas abscesses have been described in the literature, the mechanical complications of bilateral psoas abscesses are lacking. It is important to assess for complete resolution of psoas abscesses through follow-up imaging to prevent venous thromboembolic events.


Modic change is associated with increased BMI but not autoimmune diseases in TwinsUK.
Low back pain (LBP) is one of the largest causes of morbidity worldwide. The aetiology of LBP is complex, and many factors contribute to the onset. Bone marrow lesions within the vertebra adjacent to an intervertebral degenerate disc named Modic change (MC) have been suggested as a diagnostic subgroup of LBP. Autoimmune response has been proposed to be one of the causes that promote the development of MC. The aim of the current investigation is to assess prevalence and severity of MC and LBP in participants with an autoimmune disease diagnosis in a well-documented cohort of adult twin volunteers. Multivariate generalized mixed linear models (GLMM) were implemented in order to calculate the association between having an autoimmune disorder and MC prevalence, width and severe and disabling LBP. The model was corrected for family structure as well as for covariates such as age, BMI and smoking. No association was found between diagnosis of autoimmune disorder and MC. Interestingly, BMI was independently associated with MC width but not to MC prevalence. These results help to shed light on the relationship between MC and autoimmunity as well as the role of BMI in the development of the lesions. This study is the first to examine autoimmune disorders and MC prevalence in a large, population-based female cohort. The study was well powered to detect a small effect. No association was found between having a diagnosis of one or more autoimmune conditions and MC prevalence, width or LBP.


Temperature control after adult cardiac arrest: An updated systematic review and meta-analysis.
To perform an updated systematic review and meta-analysis on temperature control in adult patients with cardiac arrest. The review is an update of a previous systematic review published in 2021. An updated search including PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed on May 31, 2023. Controlled trials in humans were included. The population included adult patients with cardiac arrest. The review included all aspects of temperature control including timing, temperature, duration, method of induction and maintenance, and rewarming. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Certainty of evidence was evaluated using GRADE. The updated systematic search identified six new trials. Risk of bias in the trials was assessed as intermediate for most of the outcomes. For temperature control with a target of 32-34 °C vs. normothermia or 36 °C, two new trials were identified, with seven trials included in an updated meta-analysis. Temperature control with a target of 32-34 °C did not result in an improvement in survival (risk ratio: 1.06 [95%CI: 0.91, 1.23]) or favorable neurological outcome (risk ratio: 1.27 [95%CI: 0.89, 1.81]) at 90-180 days after the cardiac arrest (low certainty evidence). Subgroup analysis according to location of cardiac arrest (in-hospital vs. out-of-hospital) found similar results. A sensitivity analysis of nine trials comparing temperature control at 32-34 °C to normothermia or 36 °C for favorable neurological outcome at any time point also did not show an improvement in outcomes (risk ratio: 1.14 [95%CI 0.98, 1.34]). New individual trials comparing a target of 31-34 °C, temperature control for 12-24 hours to 36 hours, a rewarming rate of 0.25-0.5 °C/hour, and the effect of temperature control with fever prevention found no differences in outcomes. This updated systematic review showed no benefit of temperature control at 32-34 °C compared to normothermia or 36 °C, although the 95% confidence intervals cannot rule out a potential beneficial effect. Important knowledge gaps exist for topics such as hypothermic temperature targets, rewarming rate, and fever control.


Phased Genome Assemblies.
The ultimate goal of de novo assembly of reads sequenced from a diploid individual is the separate reconstruction of the sequences corresponding to the two copies of each chromosome. Unfortunately, the allele linkage information needed to perform phased genome assemblies has been difficult to generate. Hence, most current genome assemblies are a haploid mixture of the two underlying chromosome copies present in the sequenced individual. Sequencing technologies providing long (20 kb) and accurate reads are the basis to generate phased genome assemblies. This chapter provides a brief overview of the main milestones in traditional genome assembly, focusing on the bioinformatic techniques developed to generate haplotype information from different specialized protocols. Using these techniques as a knowledge background, the chapter reviews the current algorithms to generate phased assemblies from long reads with low error rates. Current techniques perform haplotype-aware error correction steps to increase the quality of the raw reads. In addition, variations on the traditional overlap-layout-consensus (OLC) graph have been developed in an effort to eliminate edges between reads sequenced from different chromosome copies. This allows for large presence-absence variants between the chromosome copies to be taken into account. The development of these algorithms, along with the improved sequencing technologies has been crucial to finish chromosome-level assemblies of complex genomes.


Intimal angiosarcoma of the thoracic aorta diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration: a case report.
Primary malignant tumors of the aorta are extremely rare. They are frequently located in the abdominal aorta, followed by the thoracic aorta. Sarcomas are the most common histological type. These tumors originate from the middle or intimal layer, the latter being the most common. Symptoms and radiological findings are generally nonspecific. Since their growth is endovascular, embolic phenomena can occur leading to occlusive signs and symptoms. We describe the case of a 75-year-old Hispanic man, a former tobacco smoker, with a history of pain and epigastric tenderness, dysphagia, and weight loss of approximately 6 kg. A thorax computed tomography scan showed a mass within the posterior mediastinum with poorly defined borders and heterogeneous density, located between thoracic vertebra 5-8, with a size of 78 × 53 × 76 mm, with left main bronchus compression. Endobronchial ultrasound-guided transbronchial needle aspiration was performed; it found an extrinsic posterior compression of the left main bronchus with no endobronchial injury. An intimal angiosarcoma of the thoracic aorta was diagnosed. Tumors of the aorta are rare and difficult to diagnose; they are a challenge during the diagnosis, since they usually require open surgical procedures. Endobronchial ultrasound-guided transbronchial needle aspiration associated with rapid on-site examination offered, in this case, the possibility of a successful diagnosis, avoiding major procedures. This is the first case reported in the literature of an intimal angiosarcoma of the thoracic aorta diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration.


Pearls and perils of an implantable defibrillator trial using a common control: implications for the design of future studies.
Implantable defibrillators are considered life-saving therapy in heart failure (CHF) patients. Surprisingly, the recent Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) reached an opposing conclusion from that of numerous other trials about their survival benefit in patients with advanced CHF. A critical analysis of common control trial design may explain this paradoxical finding, with important implications for future studies. Common control trials compare several intervention groups to a single rather than separate control groups. Though potentially requiring fewer patients than trials using separate controls, variation in the common control group will influence all comparisons and creates correlations between findings. During subgroup analyses, this dependency of outcomes may increase belief in the presence of a real subgroup effect when, in fact, it should increase skepticism. For example, a high (r = 0.92), statistically unlikely (p = 0.052) correlation between comparisons was observed across the subgroups reported in SCD-HeFT. Such concordance between amiodarone and a defibrillator across subgroups was unexpected, given how much the effects of these treatments significantly differed from one another in the main study. This suggests the study's subgroup findings (specifically the absence of benefit from defibrillators in advanced CHF) were not necessarily a consequence of treatment; more likely, they resulted from variation in what the treatments were compared against, the common control. Common control trials can be more efficient than other designs, but induce dependence between treatment comparisons and require cautious interpretation.


The Burkholderia pseudomallei RpoE (AlgU) operon is involved in environmental stress tolerance and biofilm formation.
Burkholderia pseudomallei, the causative agent of melioidosis, can be isolated from soil and water. To persist, adapt and survive within and outside their human host, bacteria rely on regulatory mechanisms that allow them to respond rapidly to stressful situations. We have examined the possible role of B. pseudomallei alternative sigma factor sigma(E) (RpoE) in the stress response and found that rpoE and its putative regulators (bprE-rseB-mucD) are transcribed in a single transcriptional unit. Inactivation of the rpoE operon changed the B. pseudomallei phenotype. Changes included increased susceptibility to killing by menadione and H(2)O(2), susceptibility to high osmolarity, reduced ability to form biofilms, and reduced survival in macrophage J774A.1. Therefore, we conclude that rpoE controls gene expression that contributes, at least in part, to B. pseudomallei adaptation to adverse environmental conditions.


Myelin-associated glycoprotein: electron microscopic immunocytochemical localization in compact developing and adult central nervous system myelin.
Light microscopic immunocytochemical studies have shown that myelin-associated glycoprotein (MAG) is localized in myelin of the developing CNS; but in the adult, MAG appears to be restricted to periaxonal regions of myelinated fibers. To extend these observations, we embedded optic nerves of 15-day-old rats, adult rats, and an adult human in epon after aldehyde and osmium tetroxide fixation. After 5% H2O2 pretreatment, thin sections were immunostained with 1:250-1:5,000 rabbit antiserum to rat CNS MAG according to the avidin-biotin-peroxidase complex (ABC) method. Dense deposits of reaction product covered compact myelin in both developing and adult optic nerves. When we used 1:500, 1:1,000, and 1:2,000 anti-MAG, less intense immunostaining of myelin was found. We also obtained the same localization in compact myelin with the peroxidase-antiperoxidase (PAP) method. With 1:250 anti-MAG, dense deposits of reaction product were not observed on axolemmal membranes or on oligodendroglial membranes located periaxonally and paranodally. In thin sections of adult human optic nerve, anti-MAG also stained compact myelin intensely. When thin sections of rat and human optic nerves were treated with preimmune or absorbed serum, no immunostaining was observed. Immunoblot tests showed that our MAG antisera did not react with any non-MAG myelin proteins. In contrast with earlier light microscopic data, this study shows that MAG localization does not change during CNS development; both developing and adult compact myelin sheaths contain MAG. As many biochemical studies also show that MAG is present in compact myelin, we suggest that this 100,000 dalton glycoprotein now be called myelin glycoprotein (MGP) instead of MAG.


First report of Burkholderia pseudomallei ST412 and ST734 clones harbouring blaOXA-57 but susceptible to imipenem in India.
Melioidosis caused by Burkholderia pseudomallei has become an important clinical threat, especially in Northern Australia and Southeast Asia. However, the genome information on this pathogen is limited. B. pseudomallei isolates identified from bloodstream infections from inpatients were subjected to whole-genome sequencing by IonTorrent PGM and MinION Oxford Nanopore sequencing technologies. Highly accurate complete genomes of two strains, VB3253 and VB2514, were obtained by a hybrid genome assembly method using both short and long DNA reads. Both isolates carried blaPenI and carbapenemase-encoding blaOXA-57 genes, although the isolates were susceptible to imipenem by E-test method with MIC 1 μg/mL. Multiple IS family transposases specific for all non-fermenting Gram-negative bacteria (NFGNBs)-especially IS3 and IS5, which facilitate mobilization of extended-spectrum β-lactamase (ESBL) and carbapenemase genes-were carried in these genomes. This further adds to the complexity of gene transmission. These IS families were identified only upon hybrid genome assembly and would otherwise be missed.


Localization of the locus causing Spider Lamb Syndrome to the distal end of ovine Chromosome 6.
Spider Lamb Syndrome (SLS) is a semi-lethal congenital disorder, causing severe skeletal abnormalities in sheep. The syndrome has now been disseminated into several sheep breeds in the United States, Canada, and Australia. The mode of inheritance for SLS is autosomal recessive, making the identification and culling of carrier animals difficult due to their normal phenotype. Two large pedigrees segregating for the SLS mutation were established, and a genome scan with genetic markers from previously published genome maps of cattle and sheep was used to map the locus causing SLS. Genetic linkage between SLS and several microsatellite markers, OarJMP8, McM214, OarJMP12, and BL1038, was detected, thereby mapping the SLS locus to the telomeric end of ovine Chromosome (Chr) 6. Alignment of ovine Chr 6 with its evolutionary ortholog, human Chr 4, revealed a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3).


Effect of source and level of forage in the diet on in vitro ammonia emission from manure of Holstein and Jersey dairy cows.
Reducing overall reactive N losses from dairy production systems depends substantially on reducing the atmospheric emission of manure ammonia (NH3). The objective of this study was to determine potential NH3-N emission of reconstituted manure using an in vitro protocol. Feces and urine were collected from a companion study designed as a Latin square in which 4 Holstein and 4 Jersey cows were fed diets containing 2 levels of forage neutral detergent fiber (NDF) [low-forage NDF (19%) vs. high-forage NDF (24%; dry matter basis)] from either alfalfa silage or corn silage (70:30 vs. 30:70 ratio of alfalfa silage NDF:corn silage NDF) arranged as a 2 × 2 factorial. All diets contained similar levels of crude protein (17%) and starch (23%), and had forage-to-concentrate ratios of 55:45 and 68:32 for low- and high-forage NDF diets, respectively. Measurements of NH3-N emission were conducted in a laboratory-scale chamber with 16 g of reconstituted manure (urine plus feces) incubated for 48 h at 15°C with sampling at 1, 3, 6, 12, 24, 36, and 48 h. Hourly NH3-N emissions data were analyzed using a repeated-measures mixed model in R (https://www.r-project.org/). The fixed effects were breed, forage NDF level, forage NDF source, time of sampling, and all possible interactions; cow was included as a random term. The cumulative 48-h NH3-N emissions and the scaled-up emissions accounting for daily output of manure from each cow were analyzed using the same model but without time of sampling. Level and source of forage in the diet tended to influence the pattern in hourly rate and 48-h cumulative emission, respectively. Accounting for daily manure volume differences, low-forage NDF diets led to lower estimates of daily NH3-N emissions than high-forage NDF diets (20% on a cow basis, 15% on a raw manure basis, and 18% on a manure-N basis). Compared with Holsteins, Jerseys emitted 17% lower estimated NH3-N on a cow basis, mainly due to lower manure excretion but tended to emit 15% more NH3-N expressed on a manure-N basis. Findings of this study suggested that cow breed and dietary forage NDF level should be considered in the prediction of NH3-N emission from the dairy industry.


Investigation of putative androgen-like activity of alpha 2u-globulin in castrated and estrogen-treated male rats.
alpha 2u-Globulin, a male sex-dependent protein of the rat, was tested for its ability to produce androgenic or anabolic responses. Castrated rats were injected with alpha 2u-globulin isolated from urine or kidney and the effects on urinary nitrogen excretion, body weight, and weight of ventral prostate, seminal vesicles, and levator ani muscle were studied. alpha 2u-Globulin had no effect but testosterone propionate gave the expected stimulation of nitrogen retention, body growth, and growth of androgen-responsive tissues. alpha 2u-Globulin injected into estrogen-treated male rats (animals with suppressed serum levels of alpha 2u-globulin, gonadotropins, and testosterone) was also found to be without effect on body weight and on the weight of ventral prostate, seminal vesicles, levator ani muscle, and testes. We conclude that the alpha 2u-globulin molecule, by itself, is incapable of producing, directly or indirectly, androgenlike responses.


Epigastric heteropagus twins: 3 case reports with review of literature.
Conjoined twins are rare, heteropagus conjoined twins are rarer, and epigastric heteropagus conjoined twins are rarer still. It refers to unequal and asymmetrical twinning in which the dependant component (parasite) is smaller and attached to the epigastrium of the dominant component (autosite). We report 3 cases of epigastric heteropagus conjoined twinning. A review of literature is presented along with a discussion of possible etiopathogenesis.


Theaflavin-3-gallate, a natural antagonist for Hsp90: In-silico and in-vitro approach.
Poor prognosis and metastasis have been recognized as the major cause of breast cancer related deaths worldwide. Recent experimental evidence has shown that Hsp90, the prime chaperone, is overexpressed in many cancers and is responsible if reducing the 5-year survival rate of cancer patients. Therefore, targeted inhibition of Hsp90 may be a new and effective way to target cancer as well as enhancing therapeutic outcomes. In the present study, screening and simulation of potential natural compounds result in the identification of theaflavin-3-gallate as a promising inhibitory compound of Hsp90. Further in-vitro validation of the cytotoxic effect of theaflavin-3-gallate in human breast carcinoma cell line MCF7 and normal cell line MCF10A revealed that theaflavin-3-gallate significantly inhibited the cell proliferation of MCF7 cells whereas no cytotoxic effect was observed on MCF10A cells. We also found that theaflavin-3-gallate significantly induced programmed cell death by arresting cells in the G2/M phase of the cell cycle. A significant decrease in cell migration and colony formation by theaflavin-3-gallate treatment was also observed in MCF7 cells. Furthermore, theaflavin-3-gallate significantly downregulated the mRNA expression patterns of the HSP90, MMP9, VEGFA, and SPP1 genes. Collectively, our results demonstrated theaflavin-3-gallate as a potential natural Hsp90 inhibitor that can be used to enhance the therapeutic efficacy of existing breast cancer therapies and improve overall survival of breast cancer patients.


Negative-pressure wound therapy (NPWT) for the treatment of pacemaker pocket infection in patients unable or unwilling to undergo CIED extraction.
The occurrence of cardiac pacemaker pocket infection has markedly increased and has become a new problem facing cardiovascular internists. The aim of our study was to investigate the effectiveness and safety of treating cardiac pacemaker pocket infection using negative-pressure wound therapy (NPWT) in patients who are unwilling or unable to have their cardiac implantable electronic devices (CIEDs) removed. From March 2013 to April 2019, NPWT was applied to 26 patients with cardiac pacemaker pocket infection who were unwilling or unable to have their CIEDs removed. In the first stage, a negative-pressure drainage system was placed in the pacemaker pocket after debridement. Then, NPWT was used to seal the wound, and the negative pressure (300-400 mmHg) was sustained for 5-7 days. In the second stage, the pacemaker was relocated to the subpectoral layer, and the wound was closed. In all but three of our 26 patients, the wound healed completely without complications and without evidence of residual infection. The average follow-up period was 26.92 ± 9.46 months. Only 3 diabetic patients whose tissue bacterial cultures revealed that methicillin-resistant Staphylococcus epidermidis developed uncontrolled infections. Eventually, the entire original pacemaker systems were removed, and new pacemakers were implanted in the contralateral chest wall. When warranted by strictly selected indications, the method of NPWT without CIED extraction can be considered as a new and effective treatment for patients with pacemaker pocket infection who are unwilling or unable to have the device removed.


[Sports purpura].
Recreational or regular physical and sport activities may be responsible for a wide range of cutaneous complications. Among them, "sports purpura" is a peculiar symptom that can occur during a large number of sports. "Effort purpura" defines any purpura occurring within the context of physical exercise irrespective of its cause. Therefore this clinical diagnosis includes various aetiologies. Diagnosis of traumatic purpura is often easy if the sport is mentioned in the anamnesis; cutaneous exercise - induced vasculitis must be also noted. Purpura can reveal systemic diseases or internal haemorrhage, such as spleen rupture, thrombopathies or systemic vasculitis, and other effort purpuras must be taken into account, including those related to the environment (cold, sun exposure...). Knowledge of a physical activity before the occurrence of purpura should be known by practitioner to avoid unnecessary and costly explorations in most of the cases.


Screening and identification of acetylcholinesterase inhibitors from Terminalia chebula fruits by immobilized enzyme on cellulose filter paper coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and molecular docking.
With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-β-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC50 values of 0.43 ± 0.03, 0.46 ± 0.02, 0.50 ± 0.03 and 0.51 ± 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs.