Experimental design of a liposomal lipid system: A potential strategy for paclitaxel-based breast cancer treatment.
Paclitaxel (PTX) is widely used as a first-line treatment for patients with metastatic breast cancer; however, its poor water solubility represents a major challenge for parenteral administration. The encapsulation of the PTX in drug-delivery systems with high affinity for tumor sites could improve the uptake and increase its therapeutic efficacy. In this work, long-circulating and pH-sensitive PEG-coated (SpHL-PTX) and PEG-folate-coated liposomes containing PTX (SpHL-FT-PTX) were prepared, and the physicochemical properties and in vitro cytotoxic activity were evaluated. Both formulations presented adequate physicochemical properties, including a mean diameter smaller than 200 nm, zeta potential values near the neutral range, and an encapsulation percentage higher than 93%. Moreover, SpHL-FT-PTX showed a good stability after storage for 100 days at 4 °C. The viability studies on breast cancer cell lines (MDA-MB-231 and MCF-7) demonstrated cytotoxic activity more pronounced for SpHL-FT-PTX than for SpHL-PTX or free drug for both tumor cell lines. This activity was reduced to a rate comparable to SpHL-PTX when the cells were previously treated with folic acid in order to saturate the receptors. In contrast, in the normal cell line (L929), cell viability was decreased only by free or liposomal PTX in the highest concentrations. A significantly higher selectivity index was obtained after SpHL-FT-PTX treatment compared to SpHL-PTX and free PTX. Therefore, the results of the present work suggest that SpHL-FT-PTX can be a promising formulation for the treatment of metastatic breast cancer.


Cu-MOFs based photocatalyst triggered antibacterial platform for wound healing: 2D/2D Schottky junction and DFT calculation.
Herein, we developed a multimodal antibacterial nanoplatform via synergism effect including knife-effect, photothermal, photocatalytic induced reactive oxygen species (ROS), and Cu2+ inherent attribute. Typically, 0.8-TC/Cu-NS possesses higher photothermal property with the higher photothermal conversion efficiency of 24% and the moderate temperature up to 97 °C. Meanwhile, 0.8-TC/Cu-NS exhibits the more active ROS, 1O2 and ·O2-. Hence, 0.8-TC/Cu-NS possesses best antibacterial properties against S. aureus and E. coli in vitro with efficiency of 99.94%/99.97% under near-infrared (NIR) light, respectively. In the therapeutic practical use for wound healing of Kunming mice, this system exhibits outstanding curing capacity and good biocompatibility. Based on the electron configuration measurement and density functional theory (DFT) simulation, it is confirmed that the electrons on CB of Cu-TCPP flow fleetingly to MXene trough the interface, with redistribution of charge and band upward bending over Cu-TCPP. As a result, the self-assembled 2D/2D interfacial Schottky junction have made great favor to accelerate photogenerated charges mobility, hamper charge recombination, and increases the photothermal/photocatalytic activity. This work gives us a hint to mostly design the multimodal synergistic nanoplatform under NIR light in biological applications without drug resistance.


Gallstone abscess: a delayed complication of spilled gallstone after laparoscopic cholecystectomy.
Laparoscopic cholecystectomy has become the preferred method of treatment of cholelithiasis since its inception in 1987. Although overall complication rate is less than that of traditional approach, two operative complications of laparoscopic cholecystectomy have been frequently described in the literature. One is the bile duct injury or leak and the other one spillage of stones resulting in delayed abscess formation (Horton and Florence, Am J Surg 175:375-379, 1998; Frola et al., BJR 72:201-203, 1999). The incidence of abscess is very rare (approximately 0.3%). The location of the subsequent abscess and the inflammatory masses containing stones or stone fragments is generally in the abdominal wall, subhepatic space, or the retroperitoneum below the subhepatic space but can occur anywhere in the abdomen, right thorax, at trocar site, and at incisional hernia (Zehetner et al., Am J Surg 193:73-78, 2007; Offiah et al., BJR 75:393-394, 2002; Morrin et al., AJR 174:1441-1445, 2000). We report here a case of abscess formation due to spilled stone occurring 6 months post-laparoscopic-cholecystectomy. The diagnosis was suggested by ultrasound examination and was further confirmed by computed tomography scan of the abdomen.


A novel approach for venous occlusion after endocavitary leads. The balloon-assisted tracking technique.
The balloon-assisted tracking technique can be useful in short venous occlusions that conventional venoplasty fails. This technique could be feasible and with an expected low complication rate.


Left ventricle and mitral valve reverse remodeling in response to cardiac resynchronization therapy in nonischemic cardiomyopathy.
Cardiac resynchronization therapy (CRT) improves left heart geometry and function in nonischemic cardiomyopathy (NICMP). We aimed to detail the effects of CRT on left ventricular (LV) and mitral valve (MV) remodeling using 2-dimensional transthoracic echocardiography. Forty-five consecutive patients with NICMP who underwent CRT implantation between 2009 and 2012, and had pre-CRT and follow-up echocardiograms available, were included. Paired t test, linear and logistic regression, and Kaplan-Meier survival analyses were used for statistical assessment. The mean age and QRS duration were 60 years and 157 ms, respectively, and 13 (28.9%) were female. At a mean follow-up of 3 years, there were 22 (48.9%) "CRT responders" (≥15% reduction in LV end-systolic volume index [LVESVi]). Significant improvements were observed in LV ejection fraction (26.3% vs 34.3%) and LVESVi (87.7 vs 71.1 mL/m2 ), as well as mitral regurgitation vena contracta width, MV tenting height and area, and end-systolic interpapillary muscle distance. Five-year actuarial survival was 87.5%. Multivariate regression analyses revealed the pre-CRT LVESVi (β = 0.52), and MV coaptation length (β = -0.34) and septolateral annular diameter (β = 0.25) as good correlates of follow-up LVESVi. Variables associated with CRT response were pre-CRT MV coaptation length (OR 1.75, 95% CI 1.0-3.1) and posterior leaflet tethering angle (OR 1.07, 95% CI 1.0-1.14), irrespective of baseline QRS morphology and duration (all P < .05). Cardiac resynchronization therapy improves LV and MV geometry and function in half of patients with NICMP, which is paralleled by decreased mitral regurgitation severity. The extent of pre-CRT LV remodeling and MV tethering are associated with CRT response.


MicroRNA-425-5p promotes breast cancer cell growth by inducing PI3K/AKT signaling.
MicroRNA-425-5p (miR-425-5p) has been reported to be involved in the tumorigenesis of several tumors, but its function in breast cancer is still unknown. In this study, miR-425-5p was found significantly upregulated in breast cancer cells, and predicted a poor prognosis for breast cancer patients. Overexpression of miR-425-5p could significantly promote breast cancer cell growth. Further studies showed that overexpression of miR-425-5p upregulated the protein levels of Cyclin D1, Cyclin D3, CDK4, and CDK6. However, inhibiting miR-425-5p downregulated their expression and induced cell cycle arrest at G0/G1 phase. In mechanism, overexpression of miR-425-5p increased the phosphorylation of PI3K p85 and AKT, but inhibiting miR-425-5p displayed opposite effects. Moreover, miR-425-5p bound to the 3'UTR of PTEN mRNA, and downregulated the expression levels of PTEN in both mRNA and protein levels in breast cancer cells. Collectively, the results above demonstrated that miR-425-5p was involved in the tumorigenesis of breast cancer by inducing PI3K/AKT signaling and indicated that miR-425-5p could be as a potential target for breast cancer therapy in the future.


Measurement of flying and diving metabolic rate in wild animals: Review and recommendations.
Animals' abilities to fly long distances and dive to profound depths fascinate earthbound researchers. Due to the difficulty of making direct measurements during flying and diving, many researchers resort to modeling so as to estimate metabolic rate during each of those activities in the wild, but those models can be inaccurate. Fortunately, the miniaturization, customization and commercialization of biologgers has allowed researchers to increasingly follow animals on their journeys, unravel some of their mysteries and test the accuracy of biomechanical models. I provide a review of the measurement of flying and diving metabolic rate in the wild, paying particular attention to mass loss, doubly-labelled water, heart rate and accelerometry. Biologgers can impact animal behavior and influence the very measurements they are designed to make, and I provide seven guidelines for the ethical use of biologgers. If biologgers are properly applied, quantification of metabolic rate across a range of species could produce robust allometric relationships that could then be generally applied. As measuring flying and diving metabolic rate in captivity is difficult, and often not directly translatable to field conditions, I suggest that applying multiple techniques in the field to reinforce one another may be a viable alternative. The coupling of multi-sensor biologgers with biomechanical modeling promises to improve precision in the measurement of flying and diving metabolic rate in wild animals.


Traumatic thumb carpometacarpal joint dislocations.
Isolated traumatic dislocation of the thumb carpometacarpal joint, also called the trapeziometacarpal joint, is a rare injury. Controversy still exists concerning which ligaments are the true key stabilizers for the joint and therefore need to be damaged to result in dislocation, and optimal treatment strategies for thumb carpometacarpal joint dislocations are the subject of continuing debate. We give a review of the literature concerning traumatic dislocations of the carpometacarpal joint of the thumb and propose a treatment algorithm.


Magnetization transfer ratio: a quantitative imaging biomarker for 5q spinal muscular atrophy.
We quantified peripheral nerve lesions in adults with 5q-linked spinal muscular atrophy (SMA) type 3 by analysing the magnetization transfer ratio (MTR) of the sciatic nerve, and tested its potential as a novel biomarker for macromolecular changes. Eighteen adults with SMA 3 (50% SMA 3a, 50% SMA 3b) and 18 age-/sex-matched healthy controls prospectively underwent magnetization transfer contrast imaging in a 3-Tesla magnetic resonance scanner. Two axial three-dimensional gradient echo sequences, with and without an off-resonance saturation rapid frequency pulse, were performed at the right distal thigh. Sciatic nerve regions of interest were manually traced on 10 consecutive axial slices in the images generated without off-resonance saturation, and then transferred to corresponding slices generated by the sequence with the off-resonance saturation pulse. Subsequently, MTR and cross-sectional areas (CSAs) of the sciatic nerve were analysed. In addition, detailed neurologic, physiotherapeutic and electrophysiologic examinations were conducted in all patients. Sciatic nerve MTR and CSA reliably differentiated between healthy controls and SMA 3, 3a or 3b. MTR was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0020) than in respective controls. In patients with SMA 3, MTR correlated with all clinical scores, and arm nerve compound motor action potentials (CMAPs). CSA was lower in the SMA 3 (P < 0.0001), SMA 3a (P < 0.0001) and SMA 3b groups (P = 0.0006) than in controls, but did not correlate with clinical scores or electrophysiologic results. Magnetization transfer ratio is a novel imaging marker that quantifies macromolecular nerve changes in SMA 3, and positively correlates with clinical scores and CMAPs.


Human fetal lung changes associated with maternal smoking during pregnancy.
Pulmonary impairment in the offspring of smoking mothers is well documented by epidemiologic studies. The morphologic bases for the functional impairment are largely unexplored. We studied 17 infant lungs obtained at autopsy, ten from smoking (group 1) and seven from nonsmoking (group 2) mothers, by light (LM), transmission (TEM), and scanning electron microscopy (SEM). By LM, the alveolar mean linear intercept was similar in both groups; the total lung volume and alveolar surface area increased with the increase in gestational age in all lungs studied. By SEM, the sizes of the neuroepithelial bodies (NEB) were larger in group 1 than in group 2. By SEM and TEM, ciliated cells were increased, but the amount of dense core granules was decreased, in the NEB of the smoking group. Maternal smoking during pregnancy appears to alter the size and cellular composition of fetal NEB. The detailed mechanisms of the alteration in NEB and their implications are unclear from this study and needed further clarification.


Brønsted Acid-Catalyzed Tandem Pinacol-Type Rearrangement for the Synthesis of α-(3-Indolyl) Ketones by Using α-Hydroxy Aldehydes.
A Brønsted acid-catalyzed pinacol-type rearrangement pathway is reported here to synthesize various substituted α-(3-indolyl) ketones by employing unprotected indoles and α-hydroxy aldehydes as coupling partners. Utilization of economic and readily available Brønsted acid catalyst and use of simple starting precursors exemplify the economic viability of this method. Under this developed protocol, selective migration of aryl over alkyl or a second aryl group is observed depending upon the migratory aptitude of the substituents. Applicability of this method was further demonstrated by synthesizing highly substituted carbazoles through a simple extension of this method to one-pot cascade annulation strategy.


Cavitary lung opacity of unusual cause during Behçet disease.
Pulmonary artery aneurysm must be evoked in front of any hemoptysis in a patient with Behçet disease as it requires urgent immunosuppressive therapy and often surgery.


Interactive Interventions Can Improve Hand Hygiene and Aseptic Techniques During Perioperative Care-Experience From the "Safe Hands" Project.
This paper evaluates a theory-driven, interactive hand hygiene (HH) intervention, the Safe Hands project, based on theories of organizational learning and culture including leadership support, dialogue and co-creation. This prospective quasi-experimental study used unobtrusive overt observations to evaluate adherence to HH recommendations after implementing an infection-prevention intervention. The primary outcome was differences in HH practices "Before aseptic/clean procedure" (WHO moment 2), "After body fluid exposure risk" (WHO moment 3) and performance of aseptic techniques. One operating room (OR) department served as the study hospital and the other as the control hospital, both at Swedish university hospitals. Adherence to HH guidelines was measured 4 times during 2015 to 2017. The intervention site displayed a significant improvement in adherence to HH guidelines and aseptic techniques. WHO 2; from 23.8% to 36.2%, (P = .014), WHO 3; from 22.2% to 42.3%, (P = .002), and aseptic techniques; from 17.5% to 31.6%, (P = .003). No changes in adherence were identified at the control site. The use of contaminated gloves decreased post intervention at the study operating department. This study shows that implementing tailored interventions that are underpinned by theories from organizational learning and culture can improve adherence to hand hygiene in a complex setting as the OR up to 6 months post-intervention. The interprofessional co-creation of standards operating procedures addressing specific care procedures and emphasizing the importance of aseptic techniques can be an acceptable and feasible way to reduce the risks of contaminating medical devices and patients during perioperative care.


AUF1/hnRNP D represses expression of VEGF in macrophages.
Vascular endothelial growth factor (VEGF) is a regulator of vascularization in development and is a key growth factor in tissue repair. In disease, VEGF contributes to vascularization of solid tumors and arthritic joints. This study examines the role of the mRNA-binding protein AUF1/heterogeneous nuclear ribonucleoprotein D (AUF1) in VEGF gene expression. We show that overexpression of AUF1 in mouse macrophage-like RAW-264.7 cells suppresses endogenous VEGF protein levels. To study 3' untranslated region (UTR)-mediated regulation, we introduced the 3' UTR of VEGF mRNA into a luciferase reporter gene. Coexpression of AUF1 represses VEGF-3' UTR reporter expression in RAW-264.7 cells and in mouse bone marrow-derived macrophages. The C-terminus of AUF1 contains arginine-glycine-glycine (RGG) repeat motifs that are dimethylated. Deletion of the RGG domain of AUF1 eliminated the repressive effects of AUF1. Surprisingly, expression of an AUF1-RGG peptide reduced endogenous VEGF protein levels and repressed VEGF-3' UTR reporter activity in RAW-264.7 cells. These findings demonstrate that AUF1 regulates VEGF expression, and this study identifies an RGG peptide that suppresses VEGF gene expression.


A fatal case of sclerosing mesenteritis.
A 22-year-old patient was admitted because of abdominal pain and vomiting. Computed tomography diagnosed small intestinal malignancy. Ileal resection was performed, and the histological findings were consistent with sclerosing mesenteritis. The patient was treated with enteral nutrition, corticosteroids, azathioprine and methotrexate, but died 2 years later.


Neutrophil C5a receptor and the outcome in a rat model of sepsis.
Complement fragment 5a (C5a)-C5a receptor (C5aR) signaling plays an essential role in neutrophil innate immunity. Blockade of either the ligand or the receptor improves survival rates in experimental sepsis. In the current study, sepsis was induced in rats by cecal ligation/puncture. Early in sepsis C5aR content on neutrophils significantly dropped, reached the nadir at 24 h after onset of sepsis, and progressively elevated thereafter. Western-blot, RT-PCR, and confocal microscopy analyses revealed that the loss and re-expression of C5aR during sepsis might be due, at least in part, to the receptor internalization and reconstitution. The reduction and reconstitution of C5aR correlate with the loss and restoration of innate immune functions of blood neutrophils (chemotaxis and reactive oxygen species production), respectively. Quantitative measurements of C5aR on blood neutrophils are highly predictive of survival or death during sepsis. These data suggest that neutrophil C5aR content represents an essential component of an efficient defense system in sepsis and may serve as a prognostic marker for the outcome.


Cloning and expression of the inorganic pyrophosphatase gene from the amino acid producer Brevibacterium lactofermentum ATCC 13869.
A 20-kDa Brevibacterium lactofermentum protein was detected when purifying the His-tagged FtsZBL. The protein was identified by matrix-assisted laser desorption/ionisation time of flight as the inorganic pyrophosphatase encoded by the ppa gene, which is present as a single copy in the genome of Corynebacterium glutamicum. The ppa gene was cloned from B. lactofermentum chromosomal DNA by polymerase chain reaction; it seemed to be an essential gene and it might represent an attractive target for drug discovery. The cloned ppa gene complemented a ppa- Escherichia coli mutant and a ppa-gfp gene fusion revealed that the gene product mainly accumulated at the cell poles in both E. coli and B. lactofermentum.


A Multispecies Cluster of GES-5 Carbapenemase-Producing Enterobacterales Linked by a Geographically Disseminated Plasmid.
Early and accurate treatment of infections due to carbapenem-resistant organisms is facilitated by rapid diagnostics, but rare resistance mechanisms can compromise detection. One year after a Guiana Extended-Spectrum (GES)-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole-genome sequencing (WGS; later found to be part of a cluster of 3 cases), a cluster of 11 patients with GES-5-positive K. oxytoca was identified over 18 weeks in the same hospital. Bacteria were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry, antimicrobial susceptibility testing followed European Committee on Antimicrobial Susceptibility Testing guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using polymerase chain reaction (PCR) detection of GES, pulsed-field gel electrophoresis (PFGE), and WGS for the second cluster. The identification of the first GES-5 K. oxytoca isolate was delayed, being identified by WGS. Implementation of a GES-gene PCR informed the occurrence of the second cluster in real time. In contrast to PFGE, WGS phylogenetic analysis refuted an epidemiological link between the 2 clusters; it also suggested a cascade of patient-to-patient transmission in the later cluster. A novel GES-5-encoding plasmid was present in K. oxytoca, Escherichia coli, and Enterobacter cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from 3 hospitals elsewhere in the United Kingdom. Genomic sequencing revolutionized the epidemiological understanding of the clusters; it also underlined the risk of covert plasmid propagation in healthcare settings and revealed the national distribution of the resistance-encoding plasmid. Sequencing results also informed and led to the ongoing use of enhanced diagnostic tests for detecting carbapenemases locally and nationally.


Rhythmic variations of different hemopoietic cell lines and maturation stages in aging mice.
Non-proliferative and proliferative myeloid, and lymphoid and erythroid bone marrow cells were studied in aging female C3H mice. A chronobiological approach was used and mice aged 16, 21 and 26 months were examined vs. 3 month-old mice every 3 h during the 24-h period in three different experiments. Significant circadian fluctuations were observed in most of the cell populations, even in the oldest mice. The rhythmicity patterns might be different at different times of the year, and in young mice seasonal fluctuations in the 24-h mean values were observed. The absolute numbers of the 24-h means seemed to be highest at 21 months of age in all cell lines and maturation stages. Sinus function fitting indicated a decline of the amplitudes in aging mice. Minor age-related phase-differences were indicated in some populations. However, the fitting of original data to single sinus functions was variable and often obscured important features in the cell number variations. The present investigation illustrates the importance of performing time-sequence studies in hematology.


Clinical-cytogenetic correlations in myelodysplasia (preleukemia).
Cytogenetic studies detected abnormalities in 107 (43%) of the 247 patients in this series. Some degree of overt clinical progression occurred in 55 patients (22%), this being 29% of those patients with cytogenetic abnormalities and 17% of those with normal chromosomes. The presence and complexity of a clonal cytogenetic abnormality correlated with shorter survival. In each clone category of a complexity classification (simple, complex, very complex), patients with some normal cells appeared to have better survival than those with none. In multiple regression analyses, the prognostic value of chromosomes was independent of (and second in importance to) the FAB type of myelodysplastic syndrome (MDS) whichever chromosome classification was used. Patients with refractory anemia (RA) had the lowest incidence of chromosome abnormalities and no cases were found to have only abnormal cells (AA). A greater proportion of patients with refractory anemia with an excess of blasts (RAEB) and RAEB in transformation (RAEB-t) had clonal abnormalities. Morphology alone is not at present able to distinguish between RA or refractory anemia with ringed sideroblasts and similar disorders that may not be MDS in the strict sense. Demonstration of a clonal cytogenetic abnormality remains a positive indication of the presence of the neoplastic nature of the disease.


Quantitative Analysis of Extracellular Vesicle Release Using Artificial MicroRNAs.
Despite the widely used concept of extracellular vesicle (EV)-mediated intercellular communication, we are still far from understanding what is the exact role of such nanosized vesicles in human physiology and disease. Thus, development of new methods and tools that enable the study of fundamental EV biology is valuable for advancing the field. Typically, EV production and release are monitored using approaches that rely on either antibody-based FACS assays or genetically encoded fluorescent proteins. We previously devised artificially barcoded exosomal microRNAs (bEXOmiRs) that were used as high-throughput reporters of EV release. In the first part of this protocol, basic steps and considerations for the design and cloning of bEXOmiRs are explained in detail. Next, analysis of bEXOmiR expression and abundance in cells and isolated EVs is described.


Age differences in emotion recognition: the task matters.
This study examined the impact of context information on emotion recognition from a life-span developmental perspective. The main prediction was that age-related deficits in emotion recognition will only be evident in context-poor tasks. A sample of 48 younger (M(age) = 23 years) and 35 older women (M(age) = 70 years) watched 48 film clips, each depicting a female target who talked about an emotional biographical episode and expressed one of three target emotions (i.e., happiness, sadness, or anger). Half of the films were presented without sound (context-poor condition) and the other half was presented with sound (context-rich condition). Independent of the condition, younger women were better at recognizing sadness and anger than older women. However, the condition had an effect on age differences in happiness recognition: Age-related deficits were only evident in the context-poor condition. In addition, we found that logical reasoning predicted individual differences and age-related differences in sadness and anger recognition but not in happiness recognition. The present findings suggest that age differences in emotion recognition are context and emotion specific. Together, the evidence speaks for substantial plasticity in emotion recognition (i.e., within-person variability) well into old age.


Adjustment of ultrasound exposure duration to microbubble sonodestruction kinetics for optimal cell sonoporation in vitro.
Cell sonoporation enables the delivery of various exogenous molecules into the cells. To maximize the percentage of reversibly sonoporated cells and to increase cell viability we propose a model for implicit dosimetry for adjustment of ultrasound (US) exposure duration. The Chinese hamster ovary cell suspension was supplemented with microbubbles (MB) and exposed to US, operating at the frequency of 880kHz, with a 100% duty cycle and with an output peak negative pressure (PNP) of 500kPa for durations ranging from 0.5 to 30s. Using diagnostic B-scan imaging we showed that the majority of the MB at 500kPa US peak negative pressure undergo sonodestruction in less than a second. During this time maximal number of reversibly sonoporated cells was achieved. Increase of US exposure duration did not increase sonoporated cell number, however it induced additional cell viability decrease. Therefore aiming to achieve the highest level of reversibly sonoporated cells and also to preserve the highest level of cell viability, the duration of US exposure should not exceed the duration needed for complete MB sonodestruction.


A constant cathodic potential device for faradic stimulation of osteogenesis.
The purpose of this study was to design, develop, and test a device that continuously maintains a constant potential at a cathode with respect to a reference electrode by automatically varying the potential between the cathode and an anode. The ability of the device to maintain a constant cathodic potential with respect to a silver/silver chloride reference electrode is demonstrated in acute testing with a variety of electrodes as well as in chronic testing conducted until battery failure. This constant cathodic potential device permits delivery of current at an optimal cathodic potential for faradic stimulation of osteogenesis which involves a net transfer of charge through biological tissue between, typically, an implanted cathode, the negative electrode where osteogenesis occurs, and either an implanted or a topical anode, the positive electrode required only to complete the electrical circuit. Unlike present devices that maintain a constant direct current between a cathode and an anode but permit potential between said electrodes to vary, this device presents the possible detrimental effects of an undesired electrochemical reaction due to an excessive cathodic potential.


Isolation and characterization of plant growth promoting endophytic bacteria from the rhizome of Zingiber officinale.
Endophytes, by residing within the specific chemical environment of host plants, form unique group of microorganisms. Microbially unexplored medicinal plants can have diverse and potential microbial association. The rhizome of ginger is very remarkable because of its metabolite richness, but the physiological processes in these tissues and the functional role of associated microorganisms remain totally unexplored. Through the current study, the presence of four different endophytic bacterial strains were identified from ginger rhizome. Among the various isolates, ZoB2 which is identified as Pseudomonas sp. was found to have the ability to produce IAA, ACC deaminase and siderophore. By considering these plant growth promoting properties, ZoB5 can expect to have considerable effect on the growth of ginger.


Glucocorticoids, Cyclosporine, Azathioprine, Chlorambucil, and Mycophenolate in Dogs and Cats: Clinical Uses, Pharmacology, and Side Effects.
The treatment of immune-mediated disease in dogs and cats continues to evolve as new therapies are adapted from human medicine. Glucocorticoids remain the first-line treatment followed by second-line therapies including cyclosporine, azathioprine (dogs), chlorambucil, or mycophenolate. Second-line therapies are introduced due to the patient's lack of response or intolerable effects to glucocorticoids or may be introduced early in the disease treatment due to the patient's severe life-threatening clinical presentation. The goals of immunosuppressive treatment are to achieve disease remission while minimizing drug side effects. Ultimately, gradual drug tapering to the lowest dose to maintain disease remission or successful drug withdrawal.


Targeting of antiviral drugs by coupling with protein carriers.
Side effects of antiviral drugs might be circumvented by their selective delivery into infected cells. This targeting can be obtained by conjugation of the drugs to macromolecules which are taken up specifically by the infected cells. The experiments reviewed, on this approach to antiviral chemotherapy, are mainly directed at improving the chemotherapeutic index of adenine arabinoside (ara-A) in the treatment of chronic hepatitis B by its coupling to galactosyl terminating glycoproteins.


A percutaneous coronary intervention-thrombolytic predictive instrument to assist choosing between immediate thrombolytic therapy versus delayed primary percutaneous coronary intervention for acute myocardial infarction.
Based on the thrombolytic predictive instrument (TPI), we sought to create electrocardiographically based, real-time decision support to immediate identification of patients with ST-segment elevation myocardial infarction (STEMI) likely to benefit from primary percutaneous coronary intervention (PCI) compared with thrombolysis. Using data from the Atlantic Cardiovascular Patient Outcomes Research Team (C-PORT) Trial, we tested a mathematical model predicting mortality in patients with STEMI if treated with PCI and if treated with thrombolytic therapy. We adapted the model for incorporation into computerized electrocardiograms as a PCI-TPI. For patients with STEMI in the C-PORT Trial, the model yielded unbiased mortality predictions: for those receiving thrombolysis, it predicted 6.3% mortality and actual mortality was 6.0% (95% confidence interval 3.0 to 10.6); for those receiving PCI, it predicted 4.5% mortality and actual mortality was 3.9% (95% confidence interval 1.4 to 8.2). Excellent discrimination was reflected by its receiver operating characteristic curve area of 0.86. According to the model, and validated by actual trial outcomes, 1/3 of subjects accounted for all the mortality benefit from PCI. In conclusion, for STEMI, the PCI-TPI accurately predicts mortality for treatment with PCI and with thrombolytic therapy. Incorporated into electrocardiogram, it may assist targeting PCI to those who benefit most and identifying patients before hospitalization for whom a receiving hospital should prepare for PCI.


A self-assembled, ROS-responsive Janus-prodrug for targeted therapy of inflammatory bowel disease.
A self-assembled and oxidation-degradable Janus-prodrug, termed as Bud-ATK-Tem (B-ATK-T), was fabricated by ROS-responsive aromatized thioketal (ATK) linked anti-inflammatory drug budesonide (Bud) and antioxidant tempol (Tem). Benefiting from the hydrophobic interactions and π-π stacking interactions of ATK, prodrug B-ATK-T could self-assemble into nanoparticles (NP) in water containing lecithin and DSPE-PEG2K. The morphology of B-ATK-T NP (approximate 100-120nm) was confirmed to be regular spherical by transmission electron microscope. B-ATK-T NP was endowed high drug loading content with 41.23% for Bud and 15.55% for Tem. The rapid drug release from B-ATK-T NP proceeded in an extensive reactive oxygen species (ROS)-dependent manner. More than 98% of Bud and Tem in B-ATK-T NP could release in the mimic inflammation microenvironment or phorbol-12-myristate-13-acetate (PMA)-stimulated macrophages within short time. The release of drugs in a simultaneous and proportional manner ensures that B-ATK-T NP can increase the combined efficacy of anti-inflammation and anti-oxidation. It is worth noting that B-ATK-T NP could be passively accumulated and dramatically increasing the maximum drugs concentration in the inflamed colon of mice with inflammatory bowel disease (IBD) by oral route, and avoiding potential systemic side effects. B-ATK-T NP could not only relieve colitis via inhibiting the expression of oxidative and proinflammatory mediators more than combination of free drugs, but also significantly reduce colitis-caused death. Taken together, the self-assembled, Janus-prodrug B-ATK-T NP is a promising candidate therapies for IBD, even for other inflammatory diseases.


Heritability of respiratory infection with Pseudomonas aeruginosa in cystic fibrosis.
To quantify the relative contribution of factors other than cystic fibrosis transmembrane conductance regulator genotype and environment on the acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis. Lung infection with Pa and mucoid Pa was assessed using a co-twin study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two definitions were used to establish infection: first positive culture and persistent positive culture. Genetic contribution to infection (ie, heritability) was estimated based on concordance analysis, logistic regression, and age at onset of infection through comparison of intraclass correlation coefficients. Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30 pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76. Logistic regression adjusted for age corroborated genetic control of persistent Pa infection. The correlation for age at persistent Pa infection was higher in MZ twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, -0.352 to 0.607), generating a heritability of 0.85. Genetic modifiers play a significant role in the establishment and timing of persistent Pa infection in individuals with cystic fibrosis.


Transforming engagement in learning through innovative technologies: using an audience response system in nursing orientation.
This column discusses using an audience response system in nursing orientation to enhance participant engagement while increasing educator efficiency.


Chromatin remodeling and alternative splicing: pre- and post-transcriptional regulation of the Arabidopsis circadian clock.
Circadian clocks are endogenous mechanisms that translate environmental cues into temporal information to generate the 24-h rhythms in metabolism and physiology. The circadian function relies on the precise regulation of rhythmic gene expression at the core of the oscillator, which temporally modulates the genome transcriptional activity in virtually all multicellular organisms examined to date. Emerging evidence in plants suggests a highly sophisticated interplay between the circadian patterns of gene expression and the rhythmic changes in chromatin remodeling and histone modifications. Alternative precursor messenger RNA (pre-mRNA) splicing has also been recently defined as a fundamental pillar within the circadian system, providing the required plasticity and specificity for fine-tuning the circadian clock. This review highlights the relationship between the plant circadian clock with both chromatin remodeling and alternative splicing and compares the similarities and divergences with analogous studies in animal circadian systems.


Subchorionic hematoma associated with heterotopic pregnancy following in vitro fertilization: a case report.
After treatment for infertility using in vitro fertilization (IVF)-embryo transfer, a high index of suspicion must be maintained for early diagnosis and treatment of concurrent ectopic pregnancy; however, the likelihood of a positive outcome for the intrauterine pregnancy remains uncertain. A subchorionic hematoma threatening an intrauterine gestation noted concurrently with ultrasound diagnosis of a heterotopic IVF pregnancy resolved following laparoscopic salpingectomy. Although symptomatic subchorionic hematoma may be associated with an increase in the rate of spontaneous miscarriage for a singleton pregnancy, it may not present a similar risk in the presence of a concurrent heterotopic gestation.


Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect.
We analysed the incidence of graft failure, graft-versus-host disease (GVHD) and relapse of leukaemia in 208 patients undergoing allogeneic bone marrow transplantation (BMT) for chronic myeloid leukaemia in chronic phase in eight transplant centres in Europe and the United States. 106 patients received unmanipulated donor bone marrow (Group 1) and 102 patients received marrow depleted of T-cells by incubation with the monoclonal antibodies Campath-1 or CT-2 and complement (Group 2). The incidence of graft failure was higher and of GVHD was lower in Group 2 than in Group 1. Relapse of leukaemia occurred more frequently in patients in Group 2 than in Group 1 (17 v. 2, P less than 0.001). Multivariate analysis showed that the following factors were associated with an increased risk of relapse: the use of T-cell depletion, the absence of GVHD and a high platelet count at the time of admission for transplant. The findings support the concept that a graft-versus-leukaemia effect mediated by T-lymphocytes is important for cure of leukaemia after BMT.


Dysregulation of matrix metalloproteinases and their tissue inhibitors is related to abnormality of left ventricular geometry and function in streptozotocin-induced diabetic minipigs.
This study aimed to characterize matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in relation to changes in left ventricle (LV) geometry and function in a porcine model with streptozotocin (STZ)-induced diabetes. In 15 Chinese Guizhou minipigs with STZ-induced diabetes (diabetic group) and 15 age-matched normal controls (control group), Doppler tissue imaging was performed at 6 months of diabetes. Serum MMP-2, -9, TIMP-1, -4 and B-type natriuretic peptide (BNP) were determined. Expression of MMPs, TIMPs, urokinase type-plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in aortic intima and LV myocardium was evaluated, with gelatinolytic activities of tissue MMP-2, -9 accessed by zymography. Left ventricle end-diastolic septum thickness (P < 0.05) and mass (P < 0.05) were increased, whereas peak systolic mitral annulus velocity (Sm, P < 0.001), LV systolic (P = 0.01) and diastolic strain (P < 0.001) were significantly decreased in diabetic group than in controls. Diabetic group showed higher expression of TIMP-1, -4 in aortic intima and LV myocardium (P < 0.01 or P < 0.05), with increased collagen content and elevated serum BNP level (P = 0.004) and lower gelatinolytic activities of tissue MMP-2, -9 (all P < 0.05). Semi-quantitative RT-PCR of those diabetic tissues revealed elevated mRNA levels of major TIMPs, uPA, uPAR and PAI-1. Reduction of serum MMP-2 and -9 levels was observed in diabetic group vs. control group (both P < 0.05). This study features elevated levels of TIMP-1, -4, uPA, uPAR and PAI-1, and decreased activities of MMP-2, -9 in aorta and myocardium in STZ-induced diabetic minipigs, indicating that MMP-TIMP dysregulation is associated with LV hypertrophy, cardiac dysfunction and increased cardiovascular fibrosis in diabetes.


Ion chromatographic determination of hydrolysis products of hexafluorophosphate salts in aqueous solution.
In this work, hydrolysis of three different hexafluorophosphate salts in purified water was investigated. Aqueous samples of lithium hexafluorophosphate (LiPF(6)), sodium hexafluorophosphate (NaPF(6)) and potassium hexafluorophosphate (KPF(6)) were prepared and stored for different times. Ion chromatography (IC) with UV as well as non-suppressed and suppressed conductivity detection was used for the analysis of the reaction products. For the detection and identification of the formed decomposition products, an IC method using IonPac AS14A 250 mm × 4.0 mm i.d. column and 2.5 mM KHCO(3)-2.5 mM K(2)CO(3) eluent was established. Besides hexafluorophosphate, four other anionic species were detected in fresh and matured aqueous solutions. The hydrolysis products fluoride (F(-)), monofluorophosphate (HPO(3)F(-)), phosphate (HPO(4)(2-)) and difluorophosphate (PO(2)F(2)(-)) were found and were unambiguously identified by means of standards or electrospray ionization mass spectrometry (ESI-MS). It was shown that stability of hexafluorophosphate solutions depends on the nature of the counter ion and decreases in the order potassium>sodium>lithium.


Effects of twins: maternal, fetal, and labor.
During pregnancy, many physical changes, physiological alterations, and biochemical values have been well established. Twins bring differences to many of these normal pregnancy observations. The mother has exaggerations of normal pregnancy changes. The twin fetuses often respond differently from singletons, and labor in twins presents its own unique problems. This article examines many of the adaptations in a twin pregnancy, assuming knowledge of the normal pregnancy.


Chemical constituents and gastro-protective potential of Pachira glabra leaves against ethanol-induced gastric ulcer in experimental rat model.
Gastric ulcer is a very common illness that adversely affects a significant number of people all over the globe. Phytochemical investigation of P. glabra leaf alcohol extract (PGLE) resulted in the isolation and Characterization of a new nature compound, quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)-β -D-galactoside (4), in addition to seven known compounds. They are ferulic acid (1), p- coumaric acid (2), quercetin 3-O-α-L-rhamnoside-3'-O-β-D-glucoside (3), quercetin-3- O-α -L-rhamnosyl-(1'''-6'')-(4''- O -acetyl)- β -Dgalactoside (4), quercetin-3- O-β -D-galactoside (5), 7-hydroxy maltol-3-O-β-D-glucoside (6), maltol-3- O-β -D-glucoside (7), and methyl coumarate (8) that were first to be isolated from the genus Pachira. PGLE demonstrated in vitro anti-Helicobacter pylori activity. Moreover, the in vivo gastroprotective assessment of PGLE at different dosses, 100, 200, and 400 mg/kg against ethanol induced ulceration revealed a dose-dependent gastroprotection comparable to omeprazole. PGLE attenuated gastric lesions and histopathological changes triggered by ethanol. Interestingly, PGLE exhibited an anti-inflammatory effect through down-regulating the expression of nuclear factor-ĸB and pro-inflammatory enzyme cyclooxygenase-2 in the ulcer group. It also hindered apoptosis through decreasing Bax and increasing Bcl-2 expression hence decreasing Bax/Bcl2 ratio with a subsequent reduction in caspase 3 expression. Collectively, P. glabra is a rich reservoir of various phytochemicals reflecting a promising potential for alleviation of gastric ulcer through the mediation of inflammatory and apoptotic cascades.


Social psychological theories of disordered eating in college women: review and integration.
Because peer interaction, weight/shape, and self-concept formation are particularly salient to college women, the implications of social psychological theories may be especially far-reaching during the college years. College women may be particularly vulnerable to the effects of social comparison, objectification, and uses and gratifications theories, which describe social-cognitive mechanisms that provide an individual with information regarding her own view of her body and how she perceives that others perceive her body. The current paper will review and integrate findings related to these three theories of disordered eating in college women in an effort to present a more comprehensive understanding of the social psychological mechanisms that play a role in the development and maintenance of such pathology for this group of young women. Limitations of and future directions for research on these theories will be discussed, as will their potential integration with other factors that contribute to disordered eating and implications for treatment and prevention.


Posterior Oropharyngeal Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on the healthcare system worldwide. Diagnostic testing remained one of the limiting factors for early identification and isolation of infected patients. This study aimed to evaluate posterior oropharyngeal saliva (POPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection among patients with confirmed or suspected COVID-19. The laboratory information system was searched retrospectively for all respiratory specimens and POPS requested for SARS-CoV-2 RNA detection between 1 February 2020 and 15 April 2020. The agreement and diagnostic performance of POPS against NPsp were evaluated. A total of 13772 specimens were identified during the study period, including 2130 POPS and 8438 nasopharyngeal specimens (NPsp). Two hundred and twenty-nine same-day POPS-NPsp paired were identified with POPS and NPsp positivity of 61.5% (95% confidence interval [CI] 55.1-67.6%) and 53.3% (95% CI 46.8-59.6%). The overall, negative and positive percent agreement were 76.0% (95% CI 70.2-80.9%), 65.4% (95% CI 55.5-74.2%), 85.2% (95% CI 77.4-90.8%). Better positive percent agreement was observed in POPS-NPsp obtained within 7 days (96.6%, 95% CI 87.3-99.4%) compared with after 7 days of symptom onset (75.0%, 95% CI 61.4-85.2%). Among the 104 positive pairs, the mean difference in Cp value was 0.26 (range: 12.63 to -14.74), with an overall higher Cp value in NPsp (Pearson coefficient 0.579). No significant temporal variation was noted between the 2 specimen types. POPS is an acceptable alternative specimen to nasopharyngeal specimen for the detection of SARS-CoV-2.


Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes.
Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533). Recipient T2D PRS was associated with pre-transplant T2D and the development of PTDM. T2D PRS in liver donors, but not in kidney donors, was an independent risk factor for PTDM development. The inclusion of a combined liver donor and recipient T2D PRS significantly improved PTDM prediction compared with a model that included only clinical characteristics: the area under the curve (AUC) was 67.6% (95% confidence interval (CI) 64.1-71.1%) for the combined T2D PRS versus 62.3% (95% CI 58.8-65.8%) for the clinical characteristics model (P = 0.0001). Liver recipients in the highest quintile of combined donor and recipient T2D PRS had the greatest risk of PTDM, with an odds ratio of 3.22 (95% CI 2.07-5.00) (P = 1.92 × 10-7) compared with those in the lowest quintile. In conclusion, T2D PRS identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted.


Cost impact of introducing a treatment escalation/limitation plan during patients' last hospital admission before death.
A recent study found that the use of a treatment escalation/limitation plan (TELP) was associated with a significant reduction in non-beneficial interventions (NBIs) and harms in patients admitted acutely who subsequently died. We quantify the economic benefit of the use of a TELP. NBIs were micro-costed. Mean costs for patients with a TELP were compared to patients without a TELP using generalized linear model regression, and results were extrapolated to the Scottish population. Medical, surgical and intensive care units of district general hospital in Scotland, UK. Two hundred and eighty-seven consecutive patients who died over 3 months in 2017. Of these, death was 'expected' in 245 (85.4%) using Gold Standards Framework criteria. Treatment escalation/limitation plan. Between-group difference in estimated mean cost of NBIs. The group with a TELP (n = 152) had a mean reduction in hospital costs due to NBIs of GB £220.29 (US $;281.97) compared to those without a TELP (n = 132) (95% confidence intervals GB £323.31 (US $413.84) to GB £117.27 (US $150.11), P = <0.001). Assuming that a TELP could be put in place for all expected deaths in Scottish hospitals, the potential annual saving would be GB £2.4 million (US $3.1 million) from having a TELP in place for all 'expected' deaths in hospital. The use of a TELP in an acute hospital setting may result in a reduction in costs attributable to NBIs.


Ureteral obstruction after aorto-femoral bypass surgery.
A case of ureteral obstruction from bypass surgery is presented with review of the literature. A pathogenesis for the obstruction has been suggested and specific treatment recommended. More importantly, however, a plea is made to place the ureter anterior to the graft and to study the patient both pre- and postoperatively to prevent obstruction of the ureter in these patients.


Antifungal properties of halofumarate esters.
Alkyl esters (C1--C4) of the four halofumaric acids were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes at pH 5.6 and 7.0 in the absence and presence of 10% beef serum in Sabouraud dextrose agar. The most toxic compound to each organism was: C. albicans, ethyl iodofumarate (0.054 mmole/liter); A. niger, methyl bromofumarate (0.090 mmole/liter); M. mucedo, methyl fluorofumarate (0.037 mmole/liter); and T. mentagrophytes, ethyl iodofumarate (0.020 mmole/liter). The order of overall activity of the six most toxic compounds was: ethyl iodofumarate greater than ethyl chlorofumarate greater than methyl iodofumarate = methyl bromofumarate greater than methyl chlorofumarate greater than bromofumarate.


Different levels of arsenic exposure through cooked rice and its associated benefit-risk assessment from rural and urban populations of West Bengal, India: a probabilistic approach with sensitivity analysis.
Rice arsenic (As) contamination and its consumption poses a significant health threat to humans. The present study focuses on the contribution of arsenic, micronutrients, and associated benefit-risk assessment through cooked rice from rural (exposed and control) and urban (apparently control) populations. The mean decreased percentages of As from uncooked to cooked rice for exposed (Gaighata), apparently control (Kolkata), and control (Pingla) areas are 73.8, 78.5, and 61.3%, respectively. The margin of exposure through cooked rice (MoEcooked rice) < 1 signifies the existence of health risk for all the studied exposed and control age groups. The respective contributions of iAs (inorganic arsenic) in uncooked and cooked rice are nearly 96.6, 94.7, and 100% and 92.2, 90.2, and 94.2% from exposed, apparently control, and control areas. LCR analysis for the exposed, apparently control, and control populations (adult male: 2.1 × 10-3, 2.8 × 10-4, 4.7 × 10-4; adult female: 1.9 × 10-3, 2.1 × 10-4, 4.4 × 10-4; and children: 5.8 × 10-4, 4.9 × 10-5, 1.1 × 10-4) through cooked rice is higher than the recommended value, i.e., 1 × 10-6, respectively, whereas HQ > 1 has been observed for all age groups from the exposed area and adult male group from the control area. Adults and children from rural area showed that ingestion rate (IR) and concentration are the respective influencing factors towards cooked rice As, whereas IR is solely responsible for all age groups from urban area. A vital suggestion is to reduce the IR of cooked rice for control population to avoid the As-induced health risks. The average intake (μg/day) of micronutrients is in the order of Zn > Se for all the studied populations and Se intake is lower for the exposed population (53.9) compared to the apparently control (140) and control (208) populations. Benefit-risk assessment supported that the Se-rich values in cooked rice are effective in avoiding the toxic effect and potential risk from the associated metal (As).


Antisera to synthetic peptide recognize high molecular weight enkephalin-containing proteins.
Antisera to a synthetic peptide corresponding to the 95-117 sequence of proenkephalin were used to develop a sensitive radioimmunoassay. Gel-filtration of acid extracts of bovine adrenal medulla and purified chromaffin granules revealed that the antisera recognized high molecular weight material (Mr approximately 5,000-30,000). The material in peak I ( Mr 20 ,000-30,000) and peak II (Mr 10,000-20,000) was further purified by immunoaffinity chromatography. Sequential digestion of each of these fractions with trypsin and carboxypeptidase B generated immunoreactive Met-enkephalin. This study demonstrates that antisera against a synthetic peptide cross-react with high molecular weight enkephalin-containing precursors, validating the use of these antisera in studies of enkephalin biosynthesis.


Outcomes of Autologous Stem Cell Transplantation as a Consolidative Strategy for the Treatment of Primary and Isolated Secondary Central Nervous System Diffuse Large B Cell Lymphomas.
Standard consolidation for primary diffuse large B cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is not established. This single center, retrospective observational study aims to define the outcomes of consolidative high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in patients with PCNSL and isolated secondary CNS DLBCL (SCNSL) and evaluate the prognostic factors. All consecutive patients performed an HDC/ASCT for PCNSL or isolated SCNSLs between October 2012 and February 2022 were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Among 35 patients included, 28 had PCNSL and 7 had isolated SCNSL. Median age was 51 (16-78). Males constituted 48.6%. Median follow-up after HDC/ASCT was 42.0 months. MATRIX (51.4%) and TEAM (80.0%) were the most frequent regimens of induction and conditioning, respectively. OS and PFS 1- and 2-year after HDC/ASCT were 68.0%, 57.0%, 58.0%, 48.0%, respectively. Increasing age, poor performance and comorbidities were associated with lower OS and PFS and higher non-relapse mortality (NRM). Complete response (CR) 1 at HDC/ACST was independently associated with higher OS and PFS [hazard ratio (HR): 4.67 and 6.99, respectively]. In patients < 60 years consolidative HDC/ASCT yields promising OS and PFS. Patients ≥ 60 years may less likely benefit from consolidative HDC/ASCT and should be studied further in trials of novel agents, lower doses of consolidative radiotherapy and dose-adjusted conditioning regimens. Not only age, but also comorbidities, clinical performance and response to induction correlate with outcomes. Patients with isolated SCNSL may achieve similar outcomes.


Subcellular targets of the soluble SiO2-liberated macrophage factors in experimental granulation tissue.
The supernatant from SiO2-treated macrophages increased the incorporated radioactivity of collagen in the incubated experimental granulation tissue slices, especially in the rough endoplasmic reticulum fraction, markedly over that in the respective control preparation. The effect was observed after a 20 min incubation and increases linearly at least up to 3 h. The amount of RNA and phospholipids in the rough endoplasmic reticulum, calculated per protein, increased simultaneously in the incubated slices. The incorporation of the radioactive precursors into DNA in the slices and in the nuclei from proliferating granulation tissue was enhanced significantly by the soluble fraction from SiO2-treated macrophages. This effect could be seen after a 40 min incubation in the slices and after 5 min in the nuclei, when the incorporated radioactivity in DNA began to decrease in the control experiments.


Effects of sodium nitrite on DRL performance in the rat.
Ffteen Sprague-Dawley rats were administered sodium nitrite 0.13% or 0.15% solutions in their drinking water from the age of 45 days to the end of the study. Six control rats received only tap water. At 80 days of age, rats were trained to bar press for food pellets on a CRF schedule. After reaching criterion performance the rats were switched to a DRL-20 for a period of 6 days to test for response inhibition, which was measured as a ratio of responses to reinforcements. Results indicated no significant differences between groups for response inhibition. All groups showed significant increases in learning as reflected by a decrease in ratios and an increase in total reinforcements over days. However, sodium nitrite rats compared to controls obtained significantly fewer reinforcements over sessions and a greater number of no responding periods (time-outs). One interpretation discussed was the possibility that sodium nitrite produced an increase in responding to distractible (non-task related) cues.


Invasion of poorly differentiated adenocarcinoma to the deep muscularis mucosae may be an indicator of lymph node metastasis in Barrett's esophageal cancer.
A 48-year-old man underwent endoscopic submucosal dissection (ESD) for a protruding lesion with a preoperative diagnosis of superficial Barrett's esophageal adenocarcinoma. Histopathological examination of the resected specimen showed invasion of poorly differentiated adenocarcinoma to the deep muscularis mucosa, although the predominant histology was differentiated-type and there was no lymphovascular infiltration. Additional esophagectomy with nodal dissection was conducted for possible remnant tumor cells after informed consent was given, and uncovered the presence of a metastatic lymph node. Caution is advised in the treatment of Barrett's esophageal adenocarcinoma with invasion of poorly differentiated tumor cells into the deep muscularis mucosae.


A Study on Neck Nodes in Oral Cancers, with Special Reference to Skip Metastasis.
To analyse the distribution of Neck metastases (NM) and to study frequency of skip metastases in oral squamous cell carcinoma (SCC) of oral cavity. From September 2012 to April 2013, 30 previously untreated patients with SCC of oral cavity underwent primary surgical treatment in our institution. From pathological report of Neck dissection specimen prevalence and distribution of NM were ascertained. All patients were classified according to American Joint Committee on Cancer 2005 TNM classification. Overall frequency of NM was 36.7%. Frequency of occult metastases was 33.3%. N+ metastases found in 37% cases. The overall frequency of NM in level IV and V was 9.5%. Isolated level III involvement was found in 3.3%. No isolated level IV and V involvement was found. Skip metastases to level III LN was 6.7%. We did not find any skip metastases to level IV in our study. Neck nodes at greater risk for metastases were level I and II (50 and 28.6%). Level III (11.9%), IV (7.14%), V (2.38%). The risk of skip metastases to level IV was nil in our study.


Natural product chemistry in action: the synthesis of melatonin metabolites K₁ and K₂.
Natural product chemistry often yields new compounds with great potential for economic and/or health benefits. However, most natural compounds must be artificially synthesized on an industrial scale to generate enough active ingredients to be commercially viable. Thus chemical synthesis is an essential tool of natural product chemistry. Chemical synthesis may be defined as the purposeful execution of a series of chemical reactions in order to obtain a product(s) of interest or to demonstrate important methodologies. Organic synthesis is (unsurprisingly) specifically concerned with the construction of organic compounds, which are often of an exceedingly high level of structural complexity. Each step of any form of chemical synthesis involves a chemical reaction, and the reagents and conditions for each of these need to be designed to give a good yield and a pure product. Here we illustrate this methodology using a simple protocol for the synthesis of the metabolites of the natural product melatonin, the kynurenamines N1-acetyl-N2-formyl-5-methoxykynurenine (K1) and N-acetyl-5-methoxykynurenamine (K2). The four key synthetic transformations involve (a) conversion of 4-methoxy aniline into the tert-butyl (4-methoxyphenyl)carbamate, (b) ortho-lithiation-iodination with tert-butyllithium-1,2-iodoethane, (c) use of the Sonogashira reaction with N-acetyl propargylamine, and (d) sequential alkyne hydration/formylation to give (K1) or alkyne to give (K2).


Role of Iron Accumulation in Osteoporosis and the Underlying Mechanisms.
Osteoporosis is prevalent in postmenopausal women. The underlying reason is mainly estrogen deficiency, but recent studies have indicated that osteoporosis is also associated with iron accumulation after menopause. It has been confirmed that some methods of decreasing iron accumulation can improve the abnormal bone metabolism associated with postmenopausal osteoporosis. However, the mechanism of iron accumulation-induced osteoporosis is still unclear. Iron accumulation may inhibit the canonical Wnt/β-catenin pathway via oxidative stress, leading to osteoporosis by decreasing bone formation and increasing bone resorption via the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa-B ligand (RANKL)/receptor activator of nuclear factor kappa-B (RANK) system. In addition to oxidative stress, iron accumulation also has been reported to inhibit either osteoblastogenesis or osteoblastic function as well as to stimulate either osteoclastogenesis or osteoclastic function directly. Furthermore, serum ferritin has been widely used for the prediction of bone status, and nontraumatic measurement of iron content by magnetic resonance imaging may be a promising early indicator of postmenopausal osteoporosis.


Cerebral structure in borderline personality disorder.
Computed tomographic (CT) scans of brains of patients with borderline personality disorder and normal volunteers were analyzed for ventricle-brain ratios, third ventricular size, and evidence of frontal lobe atrophy. There were no significant differences between the two groups on any of these measures except for a narrower third ventricle in borderline patients, which could be accounted for by the narrower third ventricle observed in female subjects overall. While borderline patients may show signs of subtle neurological dysfunction, they do not show evidence of structural brain pathology.


Inflammation and epilepsy: the foundations for a new therapeutic approach in epilepsy?
Emerging data from experimental epilepsy models and resected human brain tissue support the proposed involvement of innate immune system activation and consequent inflammation in epilepsy. Key mediators of this process include interleukin-1β, high-mobility group box protein 1 (HMGB1), and Toll-like receptor (TLR) signaling. These recent findings constitute the basis for a novel avenue of drug development in epilepsy, one that is not only distinct from previous approaches but uniquely based on sound neurobiological evidence.


Clinical value of ultrasonography in the detection and removal of radiolucent foreign bodies.
A series of 39 consecutive patients with a suspected retained foreign body in the hand and in whom standard soft issue radiographs were negative were examined by real-time, high-resolution ultrasound scan. At operation 20 patients had radiolucent foreign bodies (18 wood, 2 thorns) removed. Ultrasound scan correctly localized 19 of the foreign bodies before surgery and failed to detect one. No foreign body was found in 19 patients. Ultrasound scan falsely predicted the presence of a foreign body in two of these cases. High-resolution ultrasound scanning is a sensitive, accurate technique for diagnosing foreign bodies which are otherwise difficult to demonstrate by conventional radiographic techniques, and provides accurate three-dimensional localization of the object which is of value to the surgeon at operation.


Peer champions responses to nudge-based strategies designed to reduce prolonged sitting behaviour: Lessons learnt and implications from lived experiences of non-compliant participants.
Occupational sedentariness is problematic for office-based workers because of their prolonged sitting periods and the advent of technology which reduces work-based movement. A common workplace strategy to deal with this preventable health risk is to have workers engage in brief movement breaks throughout the workday. To date, the use of interventions underpinned by individual self-regulation has had less than optimal impact on changing workers sedentary work behaviours. An alternative design for workplace interventions is the use of nudge theory. Nudge theory incorporates strategies that are delivered at the point of choice designed to influence individual decision making regarding alternative behaviour options. In this study, desk-based workers were exposed to two nudge strategies which suggested alternative behaviours of regular standing and taking movement breaks during work periods to the default behaviours of prolonged sitting and sedentary work behaviour. A small group of women managers who served as peer champions (n = 6), withdrew early from the study, and then took part in an exit interview to gain an understanding of their experiences of being exposed to the two nudge strategies. Verbatim transcripts were analysed using inductive, reflexive thematic analysis. Two major themes with seven second order themes central to their experiences were extracted: facilitative behaviour and feelings (advocacy, acceptance & facilitative burden) and dysfunctional behaviours and feelings (dysfunctional behaviour & feelings, control, reactance & presenteeism). Participants initially perceived a positive exchange associated with exposure to nudge strategies. Yet, participants' emotional connection to their work roles and behaviour were perceived as a negative exchange. Participants cited numerous maladaptive feelings because of a perception of incongruency with the established work normative behaviour. These findings reveal that nudge strategies of reduced choice and social norms are viable, but perceptions of monitoring can moderate adherence.


Treatment of chronic hepatitis B with recombinant leukocyte interferon and cyanidanol.
Twelve male patients with chronic hepatitis B were treated by the combination of recombinant human alpha-interferon and cyanidanol. They received 3 million units of interferon twice a week and 2,250 mg of cyanidanol daily for 24 weeks. Four patients had sustained clinical improvement in which hepatitis B e antigen and DNA polymerase disappeared from sera and aminotransferase activities fell to normal levels. Elevated pretreatment aminotransferases were associated with the response to therapy. Also, decreased number of OKT4-positive cells prior to treatment were observed among responders. Side effects were minimal and all patients tolerated treatment on an outpatient basis. Twice weekly administration of recombinant leukocyte interferon with cyanidanol may be effective in treating chronic hepatitis when patients are appropriately selected.


Prognostic significance of IDH mutation in adult low-grade gliomas: a meta-analysis.
Mutations in the gene encoding isocitrate dehydrogenase (IDH) have been identified in approximately 65-90 % of low-grade gliomas (LGGs). Various studies examining the relationship between IDH mutation with the clinical outcome in patients with LGGs have yielded inconclusive results. The purpose of the present meta-analysis of literature is to determine this effect. We conducted a meta-analysis of 10 studies (937 patients) that evaluated the correlation between IDH mutation and overall survival (OS). For the quantitative aggregation of the survival results, the IDH mutation effect was measured by hazard ratio (HR). Overall, the pooled HR was 0.585 (95 % CI, 0.376-0.911, p = 0.025, random effect model) for patients with IDH mutation vs patients without IDH mutation. IDH mutation was associated with better overall survival of LGGs. At least this trend was observed in our analysis.


New insights into HcPTR2A and HcPTR2B, two high-affinity peptide transporters from the ectomycorrhizal model fungus Hebeloma cylindrosporum.
While plants mainly rely on the use of inorganic nitrogen sources like ammonium and nitrate, soil-borne microorganisms like the ectomycorrhizal fungus Hebeloma cylindrosporum can also take up soil organic N in the form of amino acids and peptides that they use as nitrogen and carbon sources. Following the previous identification and functional expression in yeast of two PTR-like peptide transporters, the present study details the functions and substrates of HcPTR2A and HcPTR2B by analysing their transport kinetics in Xenopus laevis oocytes. While both transporters mediated high-affinity di- and tripeptide transport, HcPTR2A also showed low-affinity transport of several amino acids-mostly hydrophobic ones with large side chains.


Gastric emptying in children with gastroesophageal reflux. I. An estimate of effective gastric emptying.
The association of gastroesophageal reflux (GER) and gastric emptying has been observed, but its importance is poorly understood. We compared 18- to 24-hour esophageal pH recordings with gastric emptying of radionuclide in apple juice in 109 children (2 weeks to 16 years old) referred for an evaluation of GER. A pH score and the pattern of GER (type I, II, and III) were obtained by esophageal pH monitoring. Gastric emptying was measured at 30 minutes (%GE30) and at 60 minutes (%GE60). The measured gastric emptying of apple juice was similar for the normal child and for those with GER regardless of pattern type. An inverse linear correlation between postcibal reflex and measured gastric emptying was demonstrated only by the eight asymptomatic children with a normal pH score (%GE30, r = -.9603, P less than .001; and %GE60, r = -.8263, P less than .05). If the contribution of postcibal reflux on gastric emptying was eliminated, then the effective gastric emptying was increased in many children with the type I (44%, P less than .05), type II (46%, P less than .05), or type III (60%, P less than .05) pattern of GER as compared with children with a normal reflux pattern (7%). In conclusion, measured gastric emptying of clear liquids is not necessarily decreased in most children with GER. Furthermore, many children with GER demonstrate an increased effective gastric emptying even though measured gastric emptying may not appear increased.


Association of miR-146a rs57095329 with Behçet's disease and its complications.
Behçet's disease is a chronic relapsing and remitting autoimmune multisystem inflammatory disease characterised by oral aphthae, genital ulcers, skin lesions, gastrointestinal involvement, arthritis, vascular lesions and neurological manifestations. We hypothesised a link between rs57095329 of miR-146a and Behçet's disease, with further links with common clinical features. We tested our hypothesis in 130 Behçet's disease patients and 131 age and sex-matched healthy controls. Behcet's disease current activity index (BDCAI) was used to assess patients' disease activity status. MiR-146a (rs57095329) was genotyped in all participants using RT-PCR and results in patients analysed according to clinical features. The frequency of the GG and AG genotypes in rs57095329 were strongly associated with Behçet's disease (adjusted OR 8.05, 95% CI 3.63-17.82; P < 0.001 and OR 2.26, 95% CI 1.27-4.04; P = 0.006, respectively), and in dominant (GG+AG > AA) and recessive (GG > AA+AG) models (both P < 0.001). Additionally, G allele distribution was significantly greater in Behçet's disease compared with controls (OR 2.85, 95% CI 1.98-4.11, P < 0.001). The AA genotype and A allele were linked to oral ulcers, the GG genotype and G allele to neurological disease, and the GG genotype and G allele to ocular disease (all P < 0.01). There were no links with genital ulceration, skin lesions, vascular disease or the result of the pathergy test. The miR-146a (rs57095329) is associated with Behçet's disease and certain genotypes and alleles with oral ulcers, and with ocular and neurological manifestations.


Improving forensic perpetrator identification with Super-Recognizers.
About a decade ago, Super-Recognizers (SRs) were first described as individuals with exceptional face identity processing abilities. Since then, various tests have been developed or adapted to assess individuals' abilities and identify SRs. The extant literature suggests that SRs may be beneficial in police tasks requiring individual identification. However, in reality, the performance of SRs has never been examined using authentic forensic material. This not only limits the external validity of test procedures used to identify SRs, but also claims concerning their deployment in policing. Here, we report the first-ever investigation of SRs' ability to identify perpetrators using authentic case material. We report the data of 73 SRs and 45 control participants. These include (a) performance on three challenging tests of face identity processing recommended by Ramon (2021) for SR identification; (b) performance for perpetrator identification using four CCTV sequences depicting five perpetrators and police line-ups created for criminal investigation purposes. Our findings demonstrate that the face identity processing tests used here are valid in measuring such abilities and identifying SRs. Moreover, SRs excel at perpetrator identification relative to control participants, with more correct perpetrator identifications, the better their performance across lab tests. These results provide external validity for the recently proposed diagnostic framework and its tests used for SR identification (Ramon, 2021). This study provides the first empirical evidence that SRs identified using these measures can be beneficial for forensic perpetrator identification. We discuss theoretical and practical implications for law enforcement, whose procedures can be improved via a human-centric approach centered around individuals with superior abilities.


Characterising and treating osteogenesis imperfecta.
Osteogenesis imperfecta is characterised by bone fragility leading to fracture and bone deformity, chronic bone pain and reduced mobility. Presentation in infancy may be anticipated through shortened or bowed femurs on antenatal ultrasound scanning, or because of family history. Other conditions can present in the neonatal period with osteoporosis and fractures, but clinical features should allow differentiation. Management is multidisciplinary, with the mainstay of medical intervention being the use of bisphosphonates. Intervention with these medications, in association with specialised nursing, physio- and occupational therapy input, has reduced fracture frequency by up to 50% in published series, and has shown significant effects on vertebral morphometry when started early (around 6 weeks age). Outcomes in older children are encouraging with a reduction in fracture frequency of up to 50%; however, the longer term effects of early intervention remain to be determined. In particular the effects on life-limiting structural outcomes such as scoliosis and basilar invagination remain unclear.


Detailed glomerular ultrastructure in Japanese type 2 diabetic patients by the quick-freezing and deep-etching method.
Mesangial expansion and glomerular basement membrane (GBM) thickening did not correlate with urinary albumin excretion (UAE) in type 2 diabetic patients in our previous studies; therefore, it was necessary to elucidate more detailed ultrastructural changes in the early stages of diabetic nephropathy (DN) in type 2 diabetic patients. The quick-freezing and deep-etching (QF-DE) method allows us to examine three-dimensional ultrastructures of human renal glomeruli in vivo at high resolution. The QF-DE method was applied to six type 2 diabetic patients without definable renal diseases other than DN. Four patients were normoalbuminuric (NA) and the other two were microalbuminuria (MA). Three control specimens were the normal parts from nephrectomies due to renal cell carcinomas. Electron microscopic morphometric analyses provided quantitative glomerular structural changes. Replica membranes were prepared by the QF-DE method, and diameters of mesh structures at the GBM and mesangial matrix (MM) were measured on electron micrographs as previously described. By the QF-DE method, both the GBM middle layer and MM were composed of polygonal meshwork structures. The mesh pores of the GBM and MM were more enlarged and irregular in shape in NA diabetic patients than those of the controls, and these ultrastructural changes became more obvious in MA patients. The mesh diameters of the GBM and MM in the diabetic patients were also larger than those of the controls. Such a mesh diameter of the GBM was well correlated with the amount of UAE, while the mesh diameter of MM showed a slight correlation with UAE. Although there were small number of subjects in the present study, the detailed ultrastructural changes in NA and MA type 2 diabetic patients, which had not been disclosed by conventional electron microscopy, were revealed by the QF-DE method. Increased mesh diameters of GBM might be related with the increase of UAE.


Synergistic effects in Mn-Co mixed oxide supported on cordierite honeycomb for catalytic deep oxidation of VOCs.
A series of Co-Mn mixed oxide catalyst supported on a cordierite monolith was facilely synthesized by ultrasonic impregnation. Its catalytic performance was evaluated in the combustion of toluene, ethyl acetate and its mixture. It was observed that with incorporating Mn into Co3O4, the formation of solid solution with spinel structure could significantly improve the catalytic activity of pure phase Co3O4. And the monolithic Co0.67Mn0.33Ox catalyst showed the best catalytic performance in the catalytic oxidation of toluene and ethyl acetate which could be completely oxidized at 220 and 180°C respectively under the reaction velocity (WHSV) about 45,000 mL/(g•hr) and pollutant concentration of 500 ppmV. The total conversion temperature of the VOCs mixture was at 230°C (500 ppmV toluene and 500 ppmV ethyl acetate) and determined by the temperature at which the most difficult molecule was oxidized. The excellent catalytic performance of monolithic Co0.67Mn0.33Ox was attributed to the higher content of Mn3+, Co3+, surface adsorbed oxygen and better redox ability. The prepared catalyst showed the good mechanical stability, reaction stability, and good adaptability to different reaction conditions.


Tailored immunosuppression after kidney transplantation - a single center real-life experience.
Kidney allograft survival continuously improved with introduction of novel immunosuppressants. However, also immunologically challenging transplants (blood group incompatibility and sensitized recipients) increase. Between 2006 and 2008, a new tailored immunosuppression scheme for kidney transplantation was implemented at the University Hospital in Zurich, together with an ABO-incompatible transplant program and systematic pre- and posttransplant anti-human leukocyte antigen (HLA) antibody screening by Luminex technology. This study retrospectively evaluated the results of this tailored immunosuppression approach with a particular focus on immunologically higher risk transplants. A total of 204 consecutive kidney transplantations were analyzed, of whom 14 were ABO-incompatible and 35 recipients were donor-specific anti-HLA antibodies (DSA) positive, but complement-dependent cytotoxicity crossmatch (CDC-XM) negative. We analyzed patient and graft survival, acute rejection rates and infectious complications in ABO-compatible versus -incompatible and in DSA positive versus negative patients and compared those with a historical control group. Overall patient, death-censored allograft survival and non-death-censored allograft survival at 4 years were 92, 91 and 87%, respectively. We found that (1) there were no differences between ABO-compatible and -incompatible and between DSA positive and DSA negative patients concerning acute rejection rate and graft survival; (2) compared with the historical control group there was a significant decrease of acute rejection rates in sensitized patients who received an induction with thymoglobulin; (3) there was no increased rate of infection among the patients who received induction with thymoglobulin compared to no induction therapy. We observed excellent overall mid-term patient and graft survival rates with our tailored immunosuppression approach. Induction with thymoglobulin was efficient and safe in keeping rejection rates low in DSA positive patients with a negative CDC-XM.


How (not what) to prescribe: nonpharmacologic aspects of psychopharmacology.
Despite advances in psychopharmacology over the past several decades, treatment outcomes for depression have not substantially improved. Depression is not being eradicated. If anything, the evidence suggests that the problem of depression and treatment-resistant depression is growing, not shrinking. As biologically reductionistic approaches dominate psychiatric practice, patient care has steered away from considering the potent effects of meaning and relationships in the psychopharmacologic treatment of our patients. By construing patients as passive recipients of concrete, specific, and straightforward medical interventions, the field has succumbed to a delusion of precision, and unwittingly moved into an era of treatment resistance in which some of our most potent tools are wasted. In such a model we have settled for treating a disorder rather than a whole person. This article is intended as a step toward remedy. Meaning effects, therapeutic alliance, ambivalence, and patient autonomy, among others, have a powerful and measurable impact on the use of medication that should be considered if we are to treat the whole person. Bringing these elements together into a coherent model of treatment, however, is only a starting point. More research is needed if we are to understand the effects these elements have when used together in an integrated model that is simultaneously personalized and evidence-based.


A case of anticoagulation-related suburothelial hemorrhage.
We report a case of a 38-year-old man with bilateral suburothelial hemorrhage secondary to anticoagulation therapy. The condition is best diagnosed with the combination of nonenhanced and excretory phase computer tomography. It represents a rare, but easily overlooked, complication of coagulopathy.


The role of immunosuppression in the efficacy of cancer gene therapy using adenovirus transfer of the herpes simplex thymidine kinase gene.
To determine whether the immune system limits or improves the therapeutic efficacy of an adenovirus vector expressing the herpes simplex thymidine kinase (HSVtk) gene in a subcutaneous tumor model. Enhanced immune reactions against tumors may be therapeutically useful. However, recent studies with adenoviral vectors show that immune responses limit the efficacy and persistence of gene expression. The effect of the immune response on cancer gene therapy with HSVtk gene delivery by an adenovirus vector followed by treatment with ganciclovir is unclear. After adenoviral transduction of a Fischer rat syngeneic mesothelioma cell line with the HSVtk gene in vitro, subcutaneous flank tumors were established. The ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Fischer rats, immunodeficient nude rats, and Fischer rats immunosuppressed with cyclosporin. HSVtk/ganciclovir therapy was more effective in nude rats and immunosuppressed Fischer rats than in immunocompetent Fischer rats. These results indicate that the immune response against adenovirally transduced cells limits the efficacy of the HSVtk/ganciclovir system and that immunosuppression appears to be a useful adjunct. These findings have important implications for clinical trials using currently available adenovirus vectors as well as for future vector design.


Questionnaire survey on female urinary frequency and incontinence.
Urinary incontinence is a well-known bothersome symptom in women, which may cause physical and psychological problems. We conducted a questionnaire survey on female urinary incontinence to investigate the disease's impact on the quality of life (QoL), the reasons women don't seek medical attention and the information they wished to obtain. From March to October 2002, a member of the Professional Women's Coalition for Sexuality and Health distributed a questionnaire about urinary frequency and urinary incontinence to women who were attending the lectures hosted by the group. We analysed 262 questionnaires: 158 people belonged to the Stress Urinary Incontinence (SUI) Group, 36 to the Overactive Bladder (OAB) Group, 22 to the Urinary Frequency (UF) Group and 18 to the Normal Group. 'Going out' was most influenced in all three groups with symptoms in their daily life. Compared with the Normal or SUI Group, the QoL in those belonging to the OAB and UF Groups was more deteriorated. The medical institution check-up rate in the SUI Group was the lowest at 7.1%, bringing down the overall consultation rate to 13.5%. More than 70% of respondents who didn't have a check-up said that they did not think it was a problem serious enough to require consultation. Urinary incontinence and frequency impairs women's QoL. It is important to provide information on these diseases and to provide medical treatments that cater to the needs of individual patients.


Gastroprotective effect of Senecio candicans DC on experimental ulcer models.
Senecio candicans DC (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris district, Tamil Nadu for which no scientific evidence exists. The present study was performed to evaluate the gastroprotective effects and acute oral toxicity of aqueous leaf extract of Senecio candicans (AESC) in experimental models. The antiulcerogenic activity of AESC was performed in two different ulcer models viz., pylorus-ligated model and ethanol-induced model using Wistar albino rats. Acute toxicity study was also performed to get information on the admissible dose for treatment of ulcer. Preliminary phytochemical screening of AESC was performed to find the active principles present, which are thus responsible for the antiulcerogenic activity. DPPH assay was performed to confirm the antioxidant activity of AESC. The acute toxicity study did not show any mortality up to 2500mg/kg b.w. of AESC. Both the ulcer models showed gastroprotective effect comparable to that of the standard Omeprazole. The results of antioxidant enzymes, histopathology sections, ATPase and mucus content of gastric secretion showed that several mechanisms are involved in the gastroprotective effect. The preliminary phytochemical screening revealed the presence of alkaloids, flavonoids and steroids in AESC. The DPPH assay confirmed the antioxidant activity of AESC. The traditional consumption of AESC for the treatment of gastric ulcer is thus true, the antioxidant constituents present in the extract plays a major role in the gastroprotective activity, but since Senecio species are known for the presence of pyrrolizidine alkaloids, a detailed study in future is required to describe the safe dose for a prolonged period.


Human activated protein C variants in a rat model of arterial thrombosis.
Activated protein C (APC) inhibits coagulation by degrading activated factor V (FVa) and factor VIII (FVIIIa), protein S (PS) functioning as a cofactor to APC. By mutagenesis of the vitamin K-dependent Gla domain of APC, we have recently created an APC variant having enhanced anticoagulant activity due to increased affinity for negatively charged phospholipid membranes. In the present study, the potential antithrombotic effects of this APC variant, and of a variant APC that is additionally mutated in the serine protease domain, have been evaluated in a blind randomized study in a rat model of arterial thrombosis. In this model, we have previously found the combination of bovine APC and PS to be highly antithrombotic. Four treatment groups each containing 10 rats were, in a blind random fashion, given intravenous bolus injections of wild-type or mutant variants of APC (0.8 mg/kg) together with human PS (0.6 mg/kg) or human PS (0.6 mg/kg) alone. A control group with 20 animals where given vehicle only. A trend to increased patency rates was noted in a group receiving one of the APC variants, but it did not reach statistical significance. In conclusion, administration of human APC variants having enhanced anticoagulant efficacy together with human PS in a rat model of arterial thrombosis did not give an efficient antithrombotic effect. The lack of effect may be due to species-specific differences between the human protein C system and the rat hemostatic system.


Socio-Demographic and Clinical Correlates of Exclusive Breastfeeding practices up to Six Months of Age.
According to the recommendations from The World Health Organization, exclusive breast feeding (EBF) should be given to infants for the first six months for healthy growth and development. However, developing countries have a wide range of variation in the practice of EBF. From this study, we aim to estimate the duration of EBF and find the impact of socio-demographic characteristics on EBF. This study was conducted at PSG Institute of Medical Sciences and Research, Coimbatore in the month of July 2018. Mothers with children aged below 4 years attending the paediatric outpatient department were included in the study. Kaplan-Meier curve analysis and logistic regression analysis were employed. Our analysis indicates that the prevalence of EBF was 58.4% among infants up to 6 months of age with mean duration of EBF 4.52 months. It was observed that mothers of a younger age (15-24 years) and with lower socio-economic status were negatively associated with the practice of providing EBF to infants up to six months of age. The findings clearly indicate that the interventions related to EBF up to six months of age should be targeted at women in the lower socio-economic status and at younger ages.


Viral haemorrhagic fevers in healthcare settings.
Viral haemorrhagic fevers (VHFs) typically manifest as rapidly progressing acute febrile syndromes with profound haemorrhagic manifestations and very high fatality rates. VHFs that have the potential for human-to-human transmission and onset of large nosocomial outbreaks include Crimean-Congo haemorrhagic fever, Ebola haemorrhagic fever, Marburg haemorrhagic fever and Lassa fever. Nosocomial outbreaks of VHFs are increasingly reported nowadays, which likely reflects the dynamics of emergence of VHFs. Such outbreaks are associated with an enormous impact in terms of human lives and costs for the management of cases, contact tracing and containment. Surveillance, diagnostic capacity, infection control and the overall preparedness level for management of a hospital-based VHF event are very limited in most endemic countries. Diagnostic capacities for VHFs should increase in the field and become affordable. Availability of appropriate protective equipment and education of healthcare workers about safe clinical practices and infection control is the mainstay for the prevention of nosocomial spread of VHFs.


Focal cerebral ischemia in the TNFalpha-transgenic rat.
To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia. Transgenic (TNFalpha-Tg) rats overexpressing the murine TNFalpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNFalpha mRNA and protein were measured and compared between TNFalpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. Post-ischemic cell death was assessed by immunohistochemistry and regional measurement of caspase-3 activity or DNA fragmentation. Unpaired t tests or analysis of variance with post hoc tests were used for comparison of group means. In TNFalpha-Tg rat brain, the aggregate mouse and rat TNFalpha mRNA level was fourfold higher than in non-Tg littermates and the corresponding TNFalpha protein level was increased fivefold (p <or= 0.01). Infarct volume was greater in TNFalpha-Tg rats than in non-Tg controls at 24 hours (p <or= 0.05) and 7 days (p <or= 0.01). Within the first 10 minutes of MCAO, cortical perfusion measured by LDF was reduced in TNFalpha-Tg rats (p <or= 0.05). However, regional vascular density was equivalent between TNFalpha-Tg and non-Tg animals (p = NS). Neural cellular apoptosis was increased in transgenic animals as shown by elevated caspase-3 activity (p <or= 0.05) and DNA fragmentation (p <or= 0.001) at 24 hours. Chronic elevation of TNFalpha protein in brain increases susceptibility to ischemic injury but has no effect on vascular density. TNFalpha-Tg animals are more susceptible to apoptotic cell death after MCAO than are non-Tg animals. We conclude that the TNFalpha-Tg rat is a valuable new tool for the study of cytokine-mediated ischemic brain injury.


Multiwalled Carbon Nanotubules Induce Pathological Changes in the Digestive Organs of Mice.
We studied the effects of regular long-term exposure to industrial nanomaterial based on multiwalled carbon nanotubules on the digestive system of mice. Nanomaterial in a concentration of 30 mg/kg was administered with drinking water over 30 days. Tissue specimens from the small intestine and liver were studied by light and electron microscopy. Multiwalled carbon nanotubules caused multiple necrotic foci in the small intestine and mixed parenchymatous degeneration in the liver. These findings suggested that multiwalled carbon nanotubules entering the digestive tract damaged intestinal villi, presumably via mechanical damage to enterocytes. It seems that multiwalled carbon nanotubules could cause degeneration indirectly, by triggering inflammatory reactions and ROS generation.


Pharmacokinetics and pharmacodynamics of oral P2Y12 inhibitors during the acute phase of a myocardial infarction: A systematic review.
The immediate administration of oral antiplatelet therapy in the form of aspirin plus a P2Y12 inhibitor is the universally recognised standard of care for patients who present with acute myocardial infarction. Despite strong recommendations for their use, there are a paucity of data describing their onset of action and clinical efficacy during the short time frames from confirmation of diagnosis to reperfusion with primary percutaneous coronary intervention. To complete a systematic review evaluating the currently available evidence regarding the pharmacokinetic and pharmacodynamic activity of orally administered clopidogrel, prasugrel and ticagrelor during the acute phase of a myocardial infarction in relation to mechanical reperfusion with primary percutaneous coronary angioplasty. We searched PubMed and EMBASE databases up to January 2016 using the terms outlined in our search strategy. Twelve papers were included in our final analysis; seven relating to pharmacodynamic studies, one to a pharmacokinetic study and four to pharmacokinetic/pharmacodynamic studies. Our results indicate that despite the administration of oral P2Y12 inhibitors including newer more potent agents that should allow for greater and more consistent levels of platelet inhibition, the physiological state of ST segment elevation MI (STEMI) and the co-administration of opioid based analgesia are associated with a reduction in the degree of platelet inhibition achieved following their administration.