Apoptosis of rabbit retinal cell after eyeball rupture.
To establish rabbit eyeball rupture model by air gun in order to observe and analyze the early injury condition and reasons of retinal cell after eyeball rupture. Forty eight healthy rabbits were randomly divided into control group and 1, 3, 6, 12 and 24 h after injury groups. After anesthesia, the rabbit eyeball rupture model was established by air gun. Then the early pathological changes of rabbit retina were observed, and apoptotic index (AI), oncosis index (OI), the relationship between the expression amounts of apoptosis-related genes and AI were analyzed. Obvious pathological lesion appeared in retina 6 h after injury. Irreversible damage occurred 12-24 h after injury. The results of AI and OI indicated that the OI peak appeared 6 h after injury and then gradually declined, while the AI increased with the prolongation of time, and the AI was higher than OI in 12 h after injury. Immunohistochemical results indicated that there was no obvious bcl-2 protein expression change. Compared with the control group and the 3, 6, 12 and 24 h after the injury groups, the expressions of p53 and Caspase-3 were significantly improved and peaked at 12 h (P<0.01). Positive correlation existed among p53, Caspase-3 expression amount and cell apoptosis amount. Apoptosis and oncosis of visual cells are the main reasons of retinal cell injury. p53 and Caspase-3 are the important factors in promoting the retinal cell apoptosis after eyeball rupture.


Bioprosthetic valve durability after stentless aortic valve replacement: the effect of implantation technique.
The Freestyle stentless bioprosthesis (FSB) (Medtronic Inc, Minneapolis, MN) is implanted using 2 techniques-subcoronary or aortic root replacement. Our objective was to determine whether the implantation technique had an impact on late reoperation for structural valve deterioration (SVD). Between 1993 and 2013, 531 patients underwent aortic valve replacement (AVR) or aortic root reconstruction with an FSB. The implantation technique was subcoronary in 430 patients (group S) and root replacement in 101 patients (group R). Median follow-up was 10.8 years for group S patients and 10.1 years for group R patients. The follow-up was complete in all patients. Mean age was 68.2 years in group S and 65.2 in group R (p = 0.001). In-hospital mortality was 3.5% and 5.0% in group S and group R, respectively (p = 0.56). Late reoperation was required in 60 (14.5%) hospital survivors in group S and 8 (8.3%) hospital survivors in group R. There were 36 reoperations in group S and 3 in group R for SVD. Freedom from reoperation for SVD was 94.6% and 76.7% at 10 and 15 years, respectively, in group S, and 98.9% and 88.1% at 10 and 15 years, respectively, for group R (p = 0.04). The subcoronary technique was an independent risk factor for late reoperation for SVD (p = 0.002). Implantation technique was not independently associated with in-hospital and long-term mortality. The Freestyle bioprosthesis implanted as a root replacement was associated with less reoperation for SVD over the long term compared with the subcoronary technique. However, the method of implantation has no influence on early and long-term survival.


Case Report: Migralepsy: The Two-Faced Janus of Neurology.
We report three cases of pediatric patients suffering from migraine aura triggered seizures. This entity, also called migralepsy, still does not have a unique definition today. Migraine and epilepsy are both episodic neurological disorders with periods of interictal well-being; this is indicative of similar pathophysiological mechanisms, such as increased neuronal excitation and ion channel dysfunction. The purpose of this paper is to discuss the clinical and instrumental features of migralepsy through the description of three clinical cases in which the symptoms of the usual migraine aura developed into a generalized tonic-clonic or focal seizure.


[Clinical signs, echocardiography and angiocardiography in mitral valve prolapse].
In a review, clinical, phonocardiographic and cardioangiographic findings in mitral valve prolaps syndrome are discussed. Echocardiography is recommended as a noninvasive screening method for the diagnosis of this syndrome.


Dual Synergistic Tumor-Specific Polymeric Nanoparticles for Efficient Chemo-Immunotherapy.
Chemo-immunotherapy has made significant progress in cancer treatment. However, the cancer cell self-defense mechanisms, including cell cycle checkpoint and programmed cell death-ligand 1 (PD-L1) upregulation, have greatly hindered the therapeutic efficacy. Herein, norcantharidin (NCTD)-platinum (Pt) codelivery nanoparticles (NC-NP) with tumor-sensitive release profiles are designed to overcome the self-defense mechanisms via synergistic chemo-immunotherapy. NC-NP remains stable under normal physiological conditions but quickly releases 1,2-diaminocyclohexane-platinum(II) (DACHPt, a parent drug of oxaliplatin) and NCTD in response to the tumor acidity. NCTD inhibits protein phosphatase 2A (PP2A) activity to relieve cell cycle arrest and downregulates the tumor PD-L1 expression to disrupt the programmed cell death-1 (PD-1)/PD-L1 interaction, synergistically enhancing Pt-based chemotherapy and immunogenic cell death-induced immunotherapy. As a result, NC-NP exhibits potent synergistic cytotoxicity and promotes T cell recruitment to generate robust antitumor immune responses. The dual synergism exhibits potent antitumor activity against orthotopic 4T1 tumors, providing a promising chemo-immunotherapy paradigm for cancer treatment.


Estimation of measurement uncertainty arising from manual sampling of fuels.
Sampling is an important part of any measurement process and is therefore recognized as an important contributor to the measurement uncertainty. A reliable estimation of the uncertainty arising from sampling of fuels leads to a better control of risks associated with decisions concerning whether product specifications are met or not. The present work describes and compares the results of three empirical statistical methodologies (classical ANOVA, robust ANOVA and range statistics) using data from a balanced experimental design, which includes duplicate samples analyzed in duplicate from 104 sampling targets (petroleum retail stations). These methodologies are used for the estimation of the uncertainty arising from the manual sampling of fuel (automotive diesel) and the subsequent sulfur mass content determination. The results of the three methodologies statistically differ, with the expanded uncertainty of sampling being in the range of 0.34-0.40 mg kg(-1), while the relative expanded uncertainty lying in the range of 4.8-5.1%, depending on the methodology used. The estimation of robust ANOVA (sampling expanded uncertainty of 0.34 mg kg(-1) or 4.8% in relative terms) is considered more reliable, because of the presence of outliers within the 104 datasets used for the calculations. Robust ANOVA, in contrast to classical ANOVA and range statistics, accommodates outlying values, lessening their effects on the produced estimates. The results of this work also show that, in the case of manual sampling of fuels, the main contributor to the whole measurement uncertainty is the analytical measurement uncertainty, with the sampling uncertainty accounting only for the 29% of the total measurement uncertainty.


Chromium and vanadate combination increases insulin-induced glucose uptake by 3T3-L1 adipocytes.
Insulin activates signaling pathways in target tissues through the insulin receptor and Tyr phosphorylation of intracellular proteins. Vanadate mimics insulin and enhances its actions through inhibition of protein Tyr phosphatases. Chromium is a micronutrient that enhances insulin action to normalize blood glucose, but the mechanism is not understood. Here we show that either vanadate or chromium stimulates Tyr phosphorylation of insulin receptor in mouse 3T3-L1 adipocytes compared to insulin alone, but a combination of vanadate and chromium is not additive. Phosphorylation of MAPK or 4E-BP1 as markers for insulin signaling is stimulated by vanadate plus insulin, and chromium does not enhance the effects. Vanadate robustly activates glucose uptake by 3T3-L1 adipocytes even without added insulin and increases insulin-stimulated glucose uptake. Chromium pretreatment of adipocytes slightly enhances glucose uptake in response to insulin, but significantly increases glucose uptake above that induced by insulin plus vanadate. These data show that chromium enhances glucose uptake even when Tyr phosphorylation levels are elevated by vanadate plus insulin, suggesting separate mechanisms of action for vanadate and chromium.


Cervical spinal stenosis with cord neurapraxia and transient quadriplegia.
Cervical spinal cord neurapraxia with transient quadriplegia is defined as a distinct clinical entity. The authors identify diminution of the anteroposterior diameter of the spinal canal as the factor that explains the described neurologic picture of the injury. Based on the result of a study of 39,377 athletes, the authors conclude that the prevalence of the injury is high and warrants attention. Given that of the patients interviewed, none recalled prodromal experience of transient motor paresis and none sustained further injury, this injury does not predispose individuals to permanent neurologic injury. No definite recurrence patterns have been established that would warrant the restriction of individuals from further activity. Activity restrictions are called for in the case of individuals with stability or chronic degenerative changes. Individuals with developmental spinal stenosis or spinal stenosis should be treated on an individual basis.


Prognostic value of K-RAS mutations in patients with non-small cell lung cancer: a systematic review with meta-analysis.
K-RAS gene mutations have been found in 20-30% of non-small cell lung cancer and occur most commonly in adenocarcinoma, however, there was no definitive conclusion about the prognostic role of K-RAS mutations in NSCLC. Herein we performed a systematic review of the literatures with meta-analysis to assess K-RAS mutations' prognostic value in NSCLC. After a methodological assessment, survival data from published studies were aggregated. Combined hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated in terms of overall survival. 41 trials (6939 patients) were included in the analysis, the overall HR was 1.45 (95% CI: 1.29-1.62), showing that K-RAS mutations have an unfavorable impact on survival of patients with NSCLC. Then a subgroup analysis was performed about ethnicity, the combined HR was 1.97 (95% CI: 1.58-2.44) for Asians, and 1.37 (95% CI: 1.25-1.5) for non-Asians. In subgroup analysis of histology, the HR was 1.39 (95% CI: 1.24-1.55) for adenocarcinoma, suggesting that K-RAS mutations were correlated with shortened survival for adenocarcinoma. When the subgroup analysis was conducted according to disease stage, K-RAS mutations were poor prognostic factors in early stages: stage I (1.81; 95% CI: 1.36-2.39) and stage I-IIIa (1.68; 95% CI: 1.11-2.55), but not in advanced stage (IIIb-IV) (1.3; 95% CI: 0.99-1.71). At last, in subgroup analysis about test methods, all of the four methods: PCR-MSOP (1.73; 95% CI: 1.35-2.2), PCR-DGGE (1.27; 95% CI: 1.01-1.62), PCR-RFLP (1.88; 95% CI: 1.42-2.49) and PCR-seq (1.34; 95% CI: 1.14-1.58) showed statistically significant impact on survival of NSCLC patients. In conclusion, this meta-analysis suggests that K-RAS mutations are associated with a worse overall survival in patients with NSCLC, especially in patients with adenocarcinoma and early stage.


Free graft foreskin anoplasty.
Reconstruction of a stenotic anal canal and repair of a stenotic perineal colostomy using a free graft foreskin. The use of free graft foreskin anoplasty was described by Freeman for the treatment of mucosal prolapse in pediatric patients. The original surgical technique was modified and employed in two adult patients for the reconstruction of the anal region. The graft, in both cases, took well with a satisfactory functional and morphological recovery of the anal canal. Free graft foreskin anoplasty, has proved to be an effective solution to stenosis in the anal canal following major local surgery.


Nemo like kinase negatively regulates NF-κB activation and coelomocytes apoptosis in Apostichopus japonicus.
Nuclear factor kappa B (NF-κB) transcription factors are related to several physiological processes, including innate and acquired immunity. In this study, a novel negative regulator of the Nemo-like kinase (NLK) gene was identified from Apostichopus japonicus through PCR (denoted as AjNLK). The complete AjNLK cDNA was of 2335 bp, with a 5'-UTR of 315 bp, a 3'-UTR of 718 bp, and a putative ORF of 1302 bp, and encoded a polypeptide of 433 amino acid residues with a typical serine/threonine protein kinase domain. Blast analysis revealed that AjNLK shared a high degree of structural conservation with its counterparts from other invertebrates and vertebrates. Spatial expression analysis indicated that the expression of AjNLK mRNA transcripts was higher in the tentacles than that in coelomocytes. The expression of AjNLK mRNA in coelomocytes was suppressed after Vibrio splendidus challenge by 0.51-fold and 0.41-fold at 72 and 96 h, respectively, compared with that in the control group. Similarly, AjNLK expression was down-regulated in primary coelomocytes exposed to 1 μg mL(-1) lipopolysaccharide (LPS). Functional investigation further revealed that the NF-κB factor p105 was induced at both mRNA and protein levels after AjNLK silencing in vitro. Meanwhile, the apoptosis of LPS-induced coelomocytes was significantly inhibited in AjNLK siRNA-transfected coelomocytes. These results supported that AjNLK negatively regulated NF-κB activation and cell apoptosis in sea cucumber.


Transsynaptic coordination of synaptic growth, function, and stability by the L1-type CAM Neuroglian.
The precise control of synaptic connectivity is essential for the development and function of neuronal circuits. While there have been significant advances in our understanding how cell adhesion molecules mediate axon guidance and synapse formation, the mechanisms controlling synapse maintenance or plasticity in vivo remain largely uncharacterized. In an unbiased RNAi screen we identified the Drosophila L1-type CAM Neuroglian (Nrg) as a central coordinator of synapse growth, function, and stability. We demonstrate that the extracellular Ig-domains and the intracellular Ankyrin-interaction motif are essential for synapse development and stability. Nrg binds to Ankyrin2 in vivo and mutations reducing the binding affinities to Ankyrin2 cause an increase in Nrg mobility in motoneurons. We then demonstrate that the Nrg-Ank2 interaction controls the balance of synapse growth and stability at the neuromuscular junction. In contrast, at a central synapse, transsynaptic interactions of pre- and postsynaptic Nrg require a dynamic, temporal and spatial, regulation of the intracellular Ankyrin-binding motif to coordinate pre- and postsynaptic development. Our study at two complementary model synapses identifies the regulation of the interaction between the L1-type CAM and Ankyrin as an important novel module enabling local control of synaptic connectivity and function while maintaining general neuronal circuit architecture.


Differential interactions of 5-(4-piperidyl)-3-isoxazolol analogues with insect γ-aminobutyric acid receptors leading to functional selectivity.
γ-Aminobutyric acid (GABA) receptors (GABARs) mediate fast inhibitory synaptic transmission and are also targets for drugs and insecticides. To better understand the molecular interactions of ligands with the orthosteric sites of GABARs, we examined 4-aryl/arylalkyl-5-(4-piperidyl)-3-isoxazolol, 4-aryl-5-(4-piperidyl)-3-isothiazolol, and 5-aryl-4-(4-piperidyl)-1-hydroxypyrazole for their antagonism with regard to three insect GABARs. The 3-isoxazolol was preferable to the 3-isothiazolol and 1-hydroxypyrazole in antagonism to common cutworm and housefly GABARs. Of the tested analogues, 4-(3-biphenylyl)-5-(4-piperidyl)-3-isoxazolol (2a) displayed the greatest antagonism for common cutworm and housefly GABARs, with IC50 values of 3.4 and 10.2 μM, respectively. In contrast to the antagonism of the two GABARs, 2a showed partial agonism for the case of small brown planthopper GABARs, with an EC50 value of 31.3 μM. Homology models and docking simulations revealed that a cation-π interaction between an analogue and an Arg residue in loop C or E of the orthosteric site is a key component of antagonism. This specific phenomenon was lacking in the interactions between 2a and the orthosteric site of small brown planthopper GABARs. These findings provide important insights into designing and developing novel drugs and insecticides.


Dietary t10,c12-CLA but not c9,t11 CLA reduces adipocyte size in the absence of changes in the adipose renin-angiotensin system in fa/fa Zucker rats.
In obesity, increased activity of the local renin-angiotensin system (RAS) and enlarged adipocytes with altered adipokine production are linked to the development of obesity-related health problems and cardiovascular disease. Mixtures of conjugated linoleic acid (CLA) isomers have been shown to reduce adipocyte size and alter the production of adipokines. The objective of this study was to investigate the effects of feeding individual CLA isomers on adipocyte size and adipokines associated with the local adipose RAS. Male fa/fa Zucker rats received either (a) control, (b) cis(c)9,trans(t)11-CLA, or (c) t10,c12-CLA diet for 8 weeks. The t10,c12-CLA isomer reduced adipocyte size and increased cell number in epididymal adipose tissue. RT-PCR and Western blot analysis revealed that neither CLA isomer altered mRNA or protein levels of angiotensinogen or AngII receptors in adipose tissue. Likewise, levels of the pro-inflammatory cytokines TNF-α and IL-6 or the anti-inflammatory cytokine IL-10 were unchanged in adipose tissue. Similarly, neither CLA isomer had any effect on phosphorylation nor DNA binding of NF-κB. Our results suggest that although the t10,c12-CLA isomer had beneficial effects on reducing adipocyte size in obese rats, this did not translate into changes in the local adipose RAS or associated adipokines.


In silico analyses of betulin: DFT studies, corrosion inhibition properties, ADMET prediction, and molecular docking with a series of SARS-CoV-2 and monkeypox proteins.
We report detailed computational studies of betulin - a pentacyclic naturally occuring triterpene, which is a precursor for a broad family of biologically active derivatives. The structure, electronic, and optical properties of betulin were studied by the density functional theory (DFT) calculations in gas phase. The reactivity and the reactive centers of betulin were revealed through its global reactivity descriptors and molecular electrostatic potential (MEP). The DFT calculations were also applied to probe betulin as a potential corrosion inhibitor for some important metals used in implants. Electron charge transfer from the molecule of betulin to the surface of all the examined metals (Ti, Fe, Zr, Co, Cu, Cr, Ni, Mn, Mo, Zn, Al, W, Ag, Au) was revealed, of which the best results were obtained for Ni, Au and Co. Bioavailability, druggability as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of betulin were evaluated using the SwissADME, BOILED-Egg and ProTox-II tools. Molecular docking was applied to examine the influence of the title compound on a series of the SARS-CoV-2 proteins as well as one of the monkeypox proteins. It was established that betulin is active against all the applied proteins with the best binding affinity with papain-like protease (PLpro) and spike protein (native) of SARS-CoV-2. The title compound is also active against the studied monkeypox protein. Interaction of betulin with papain-like protease (PLpro) was studied using molecular dynamics simulations.


From Extraction to Renewal: A Global Campaign for Healthy Energy.
A global movement is emerging in the health sector to engage in discourse and advocacy on the health impacts and health costs of energy choices--specifically the health harms of extractive, climate-disrupting energy sources such as coal and gas. Individuals and organizations in the health sector have begun to address climate and energy issues at multiple levels of engagement, including with others in the health sector, with pollution-affected communities, with policy makers, and with the media. We present recent examples of health sector advocacy and leadership on the health impacts of energy choices and opportunities for broadening and deepening the movement.


Orchio-Septopexy: A new technique to cover and fix detorsed testis undergoing fasciotomy of tunica albuginea.
Compartment Syndrome (CS) has been recognized as a potential factor that worsens testicular viability after detorsion, especially in borderline cases of prolonged ischemia. Fasciotomy of the testicular tunica albuginea to relieve the pressure associated with CS has been proposed to accommodate edema after detorsion, embracing the raw fasciotomy area with tunica vaginalis flap (TVF) or graft. Fashioning the TVF can be tedious in cases of severe scrotal edema. Herein we present a technique that facilitates and expedites the procedure, maintaining the fasciotomy area decompressed. In testicular torsion, where the testis remains with dark coloration and questionable viability after detorsion a longitudinal releasing incision is made in the tunica albuginea (fasciotomy) to decrease compartmental pressure. If signs of parenchymal recovery (bleeding points, better color) are seen an orchio-septopexy is performed, suturing the incised albuginea's edges to the septum with a running suture, avoiding CS as well as re-torsion. Orchio-septopexy was performed in 11 cases with a mean age of 11.9 years (3-17). All cases had clinic follow-up and testicular Doppler US with a mean of 9.5 months (6-24). 6/11 cases (54%) were salvaged, with good vascularity in the Doppler US and maintained more than 50% testicular volume compared to the contralateral side. Orchio-septopexy after testicular fasciotomy is a simple and fast technique that can be utilized in cases of prolonged testicular ischemia and questionable viability. More than half of the testes recovered, encouraging us to propose its utilization as well as its validation by other surgeons.


Associations of job type, income, and education with postpartum depressive symptoms: The Kyushu Okinawa Maternal and Child Health Study.
Epidemiological evidence on the role of socioeconomic status on postpartum depressive symptoms has been inconsistent. The present prospective study investigated the relationship between employment, job type, income, and education and postpartum depressive symptoms. Subjects were 1316 Japanese women. The subjects were asked to complete an Edinburgh Postnatal Depression Scale (EPDS) between three and four months postpartum. Postpartum depressive symptoms were defined as EPDS score ≥ 9. The prevalence of postpartum depressive symptoms was 8.2%. Compared with unemployment, holding a sales job was independently related to a reduced risk of postpartum depressive symptoms: the adjusted odds ratio (OR) was 0.13 (95% CI: 0.01-0.66). Compared with a household income under four million yen per year, a household income of six million yen or more per year was independently inversely associated with postpartum depressive symptoms: the adjusted OR was 0.33 (95% CI: 0.16-0.63). Compared with less than 13 years of education, both 13 or 14 years and 15 years or more were independently inversely related to postpartum depressive symptoms: the adjusted ORs were 0.40 (95% CI: 0.23-0.69) and 0.48 (95% CI: 0.28-0.82), respectively. Holding a sales job, higher household income and higher educational levels may be inversely associated with postpartum depressive symptoms.


Probabilistic analysis and simulation of crack propagation in concrete pavements and surfaces.
The surface of concrete pavement is susceptible to cracking. The propagation of a crack in a concrete structure may take the form of a one-dimensional line crack, a two-dimensional surface crack, or a three-dimensional volume crack. Predicting crack propagation in a concrete pavement surface is a complicated task. The whole process of formation, propagation, and orientation of cracks can be considered a stochastic process that necessitates a probabilistic investigation approach. In the present study, crack propagation in concrete pavements is studied from a probabilistic point of view using the concepts of multinomial Markov Chains using Random Walks. The study is based on actual probabilities of propagation and orientation of cracks obtained by tracing crack paths from a large dataset of images using custom-built software. Two random walker models are developed using the trinomial and multinomial Markov Chains. The master equation is developed assuming the trinomial Markov Chain, which has been brought for further theoretical and numerical developments. Examples of inferences and numerical simulations are presented to showcase the potential uses and applications of the proposed probabilistic approach for the design and scheduling of inspection visits and maintenance/rehabilitation strategies of concrete pavements and surfaces.


Reproducibility of mean transit time for maximal myocardial flow assessment by videodensitometry.
In the assessment of myocardial perfusion by ECG-triggered digital radiography, time parameters are calculated from the time density curve (TDC) and related to blood flow. Recently we developed a method which uses mean transit time (Tmn) as time parameter, and which is in accordance with the original principles of indicator dilution theory. In this approach, variability in vascular volume is excluded and Tmn-1, determined at maximal hyperemia, showed an excellent correlation with maximal flow in animal validation studies. For calculation of Tmn, however, a large part of the descending limb of the TDC has to be known for reliable extrapolation, and especially this part of the curve is subject to variability in image quality in man. Therefore we tested reproducibility of Tmn in 30 arteries in 20 patients. Tmn was derived from the TDCs, obtained from paired studies under identical circumstances with an interval of 10 minutes. Satisfactory images could be obtained in all but one patient. Image processing was performed in an identical way in the paired studies. Reproducibility proved to be excellent for all three coronary arteries. The absolute value of the relative differences between the first and second determination was 7 +/- 7% for the LAD, 6 +/- 3% for LCx and 4 +/- 2% for the RCA (mean +/- SD). Correlation coefficients between both measurements were 0.97, 0.95 and 0.95 for the respective arteries. Therefore, it is concluded that, using this approach, Tmn at maximal hyperemia can be determined reproducibly in man and used for maximal myocardial flow assessment.


Associate role in motion, despite concern over 'nursing on the cheap'.
Progress towards creating 1,000 nursing associates by 2017 has gathered pace.


Intratumoral microvessel density and expression of ED-A/ED-B sequences of fibronectin in breast carcinoma.
The aim of this study was to examine the correlation between intratumoral microvessel density (iMVD) and the presence of cellular fibronectin isoforms, ED-A and ED-B, in order to identify those tumours with a prominent angiogenic phenotype. 91 cases of invasive ductal breast carcinoma were evaluated for TNM, histological grading, percentage of Ki-67+ cells and receptor hormonal status. iMVD was determined as a single microvessel count in a 200 x microscope field from the region of the tumour that appeared to be most densely vascular. When the mean values of iMVD of the various groups were compared, no significant difference was noted (Mann-Whitney test). When tumours were classified as high or low iMVD, based on a cut-off value (99 vessels/0.74 mm2), cases with high iMVD were significantly more numerous in poorly differentiated G3 tumours (P = 0.01, Chi-square test), and in tumours with lymph node metastasis (N0 versus N1 + N2; P = 0.002). The possibility that high iMVD was the expression of prominent vascular neoformation was explored using ED-A and ED-B isoforms of fibronectin as markers of neoformed vessels. ED-A + and/or ED-B + blood vessels were < 10% of total vessels, were detected in approximately 50% of cases independently of iMVD values, and were not more numerous in tumour areas with hot spot vascularisation. Our findings indicate that iMVD and expression of ED-A/ED-B reflect different aspects of tumour-associated angiogenesis.


Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300.
Ski-interacting protein (SKIP), a vitamin D receptor (VDR) coactivator, also functions as a repressor in Notch signalling in association with the corepressor SMRT. Here we show that SKIP bifunctionally modulates (activates or represses) Retinoid-X receptor (RXR)- and VDR-dependent gene transcription in a cell line-specific manner, with activation in CV-1 and repression in P19 cells. The coactivator function of SKIP in these cells appeared to correlate with the relative level and ratio of expression of N-CoR and p300, with greater SKIP activation in higher p300-expressing and lower N-CoR-expressing cell-lines. C-terminal deletion of SKIP (delta334-536 aa) was associated with strong activation in both CV-1 and P19 cells. The corepressors N-CoR and SMRT and the coregulator p300 interacted with SKIP through the same N-terminal region (1-200 aa). Overall these results suggest that transcriptional action of SKIP may depend on distinct functional domains and cell line-specific interactions with both corepressors and coactivators.


Evolution and Predictive Role of Plasma Alzheimer's Disease-related Pathological Biomarkers in Parkinson's Disease.
Plasma Alzheimer's disease-related pathological biomarkers' role in Parkinson's disease (PD) remains unknown. We aimed to determine whether plasma Alzheimer's disease-related biomarkers can predict PD progression. A total of 184 PD patients and 86 healthy controls were included and followed up for 5 years. Plasma phosphorylated tau181 (p-tau181), Aβ40, and Aβ42 were measured at baseline and the 1- and 2-year follow-ups using the Quanterix-single-molecule array. Global cognitive function and motor symptoms were assessed using the Montreal Cognitive Assessment and Unified Parkinson's Disease Rating Scale part III. Genetic analyses were conducted to identify APOE and MAPT genotypes. Plasma p-tau181 levels were higher in PD than healthy controls. APOE-ε4 carriers had lower plasma Aβ42 levels and Aβ42/Aβ40 ratio. The linear mixed-effects models showed that Montreal Cognitive Assessment scores were associated with plasma p-tau181/Aβ42 ratio (β -1.719 [-3.398 to -0.040], p = .045). Higher baseline plasma p-tau181 correlated with faster cognitive decline and motor symptoms deterioration in total patients (β -0.170 [-0.322 to -0.018], p = .029; β 0.329 [0.032 to 0.626], p = .030) and APOE-ε4 carriers (β -0.318 [-0.602 to -0.034], p = .030; β 0.632 [0.017 to 1.246], p = .046), but not in the noncarriers. Higher baseline plasma Aβ40 correlated with faster cognitive decline in total patients (β -0.007 [-0.015 to -0.0001], p = .047) and faster motor symptoms deterioration in total patients (β 0.026 [0.010 to 0.041], p = .001) and APOE-ε4 carriers (β 0.044 [-0.026 to 0.049], p = .020), but not in the noncarriers. The plasma p-tau181/Aβ2 ratio monitors the cognitive status of PD. Higher baseline plasma p-tau181 and Aβ40 predict faster cognitive decline and motor symptoms deterioration in PD, especially in APOE-ε4 carriers.


Computed tomography in acute fatty liver of pregnancy.
A case of the diagnosis of acute fatty liver of pregnancy proved by biopsy is described. In this case computed tomography showed decreased attenuation over the liver, and this attenuation is compatible with fatty infiltration. Computed tomography may be useful in the differential diagnosis of jaundice in pregnancy.


The association of suprascapular neuropathy with massive rotator cuff tears: a preliminary report.
We studied a prospective, consecutive series of 8 patients presenting with massive rotator cuff tears (>5 cm. in maximum dimension), all associated with severe retraction and fatty infiltration of the supraspinatus muscle on magnetic resonance imaging studies. All 8 patients had suprascapular neuropathy shown by electromyography (EMG) findings of denervation in the supraspinatus and/or infraspinatus muscles. Clinically, all patients had severe limitation of active motion, with no patient able to elevate their affected arm actively >40 degrees . Four patients elected débridement and partial surgical repair using margin convergence principles via a mini-open approach. Follow-up of these patients averaged 24 months. All 4 patients regained the ability to elevate their affected arm to >90 degrees , and to place their hand actively behind their head without assistance. Two of the 4 surgical patients consented to follow-up EMG studies that demonstrated, in both cases, that the suprascapular nerve had significant renervation potentials, with almost complete recovery of the nerve in 1 case. We conclude that suprascapular neuropathy may be associated with massive rotator cuff tears, and that partial rotator cuff repair may allow recovery of the nerve and improvement of function.


Increased visual information gain improves bimanual force coordination.
Bimanual force control requiring asymmetrical forces between limbs is more challenging than bimanual force control when the limbs produce symmetrical forces. Previous studies investigated visual information gains between 8 and 80 pixels/N to facilitate asymmetrical force control. Given that previous studies limited visual information gain to 80 pixels/N, the current experiment expanded the range by increasing visual information gains (8, 80, 256, and 512 pixels/N). A second manipulation involved three task constraint coefficients imposed on bimanual force control: (a) left-biased, (b) right-biased, and (c) equal-biased. Analyses of 15 right-handed adult volunteers revealed a decrease in bimanual force variability and more negative correlation coefficient with increased visual information gain in the equal biased condition. Significant reductions in bimanual force variability were found between 8 and 80 pixels/N. In contrast, significant improvements in coordination patterns between hands continued up to 256 pixels/N. These novel findings demonstrate that bimanual force coordination was more sensitive to an increase in visual information gains (>80 pixels/N) than bimanual force variability.


The Biblical Job Against Zeno the Stoic: Living Purposively Versus Dying for Meaning.
Zeno the Stoic and the biblical Job react very differently to stressors in their lives. While Zeno succumbs to a relatively minor accident and takes his life, Job withstands cataclysmic losses, survives, and ultimately is restored. While Zeno's search for meaning ends in his suicide, Job's sense of purpose enables him to survive and ultimately thrive. The essential difference is that while Zeno greatly catastrophizes a relatively minor stressor in a desperate search for meaning, Job lives a life of purpose which gives his life intrinsic meaning. This distinction may be most relevant in today's chaotic world, with so many young people striving to "find themselves" in often the most destructive ways. While Job is resilient, Zeno is not. Job's biblical faith provides the grounding for his self-knowledge. Zeno the Stoic does not seem to have this foundational self-knowledge and is searching for signs that he is not adrift in an indifferent world. For some people, at least, biblical religion seems to provide a healthy foundational view which gives life essential purpose.


The enzyme interactome concept in filamentous fungi linked to biomass valorization.
Biomass represents an abundant and inexpensive source of sugars and aromatic compounds that can be used as raw materials for conversion into value-added bioproducts. Filamentous fungi are sources of plant cell wall degrading enzymes in nature. Understanding the interactions between enzymes is crucial for optimizing biomass degradation processes. Herein, the concept of the interactome is presented as a holistic approach that depicts the interactions among enzymes, substrates, metabolites, and inhibitors. The interactome encompasses several stages of biomass degradation, starting with the sensing of the substrate and the subsequent synthesis of hydrolytic and oxidative enzymes (fungus-substrate interaction). Enzyme-enzyme interactions are exemplified in the complex processes of lignocellulosic biomass degradation. The enzyme-substrate-metabolite-inhibitor interaction also provides a better understanding of biomass conversion, allowing bioproduct production from recalcitrant agro-industrial residues, thus bringing greater value to residual biomass. Finally, technological applications are presented for optimizing the interactome at various levels.


Comparison of centering pregnancy to traditional care in Hispanic mothers.
To compare maternal and infant outcomes in Hispanic women participating in the Centering Pregnancy Model (CPM) to those receiving prenatal care via the traditional model and determine acceptability of the CPM. Forty-nine women (n = 24 CPM; n = 25 traditional) participated in this quasi-experimental prospective comparative design. Participants self selected the model of care delivery. Data were collected via questionnaires at the initial visit, 34-36 weeks gestation, and postpartum. Outcome measures included: satisfaction with care delivery model, health behaviors, prenatal/postnatal care knowledge, self-esteem and depression. Breastfeeding initiation and continuation, infant birth weight, gestational age at delivery, mode of delivery and infant length of stay were also collected. Traditional participants had a history of more pregnancies, more living children, and higher levels of postpartum self-esteem compared to centering participants. Knowledge deficits and health behaviors were similar between groups. No differences were found for infant outcomes. This study provides information regarding Hispanic mothers' responses to an alternative care delivery model. Preliminary evidence suggests CPM compares with traditional care and yields a high degree of patient satisfaction. Specific pregnancy-related knowledge deficits were identified in both groups that could focus prenatal education. In light of similar outcomes in both groups; patient and provider satisfaction and economics would therefore be a factor when choosing a model of prenatal care delivery.


Antibacterial activity of phenyllactic acid against Listeria monocytogenes and Escherichia coli by dual mechanisms.
Phenyllactic acid (PLA), a phenolic acid phytochemical, is considered to be a promising candidate for use as a chemical preservative due to its broad antimicrobial activity. The antibacterial target of PLA has rarely been reported, thus investigations were performed to elucidate the antibacterial mechanism of PLA against Listeria monocytogenes and Escherichia coli. Flow cytometry analysis stained with propidium iodide (PI) demonstrated that PLA could damage the membrane integrity of L. monocytogenes, while it could not disrupt that of E. coli. The uptake of 1-N-phenylnaphthylamine (NPN) indicated that PLA interrupted the outer membrane permeability of E. coli. Scanning electron microscopy (SEM) observation visualized the damage caused by PLA as morphological changes in L. monocytogenes and E. coli. Fluorescence assays demonstrated that PLA could interact with bacterial genomic DNA in the manner of intercalation. This finding suggested dual antibacterial targets of PLA, namely membrane and genomic DNA.


Mis-segmentation in voxel-based morphometry due to a signal intensity change in the putamen.
The aims of this study were to demonstrate an association between changes in the signal intensity of the putamen on three-dimensional T1-weighted magnetic resonance images (3D-T1WI) and mis-segmentation, using the voxel-based morphometry (VBM) 8 toolbox. The sagittal 3D-T1WIs of 22 healthy volunteers were obtained for VBM analysis using the 1.5-T MR scanner. We prepared five levels of 3D-T1WI signal intensity (baseline, same level, background level, low level, and high level) in regions of interest containing the putamen. Groups of smoothed, spatially normalized tissue images were compared to the baseline group using a paired t test. The baseline was compared to the other four levels. In all comparisons, significant volume changes were observed around and outside the area that included the signal intensity change. The present study demonstrated an association between a change in the signal intensity of the putamen on 3D-T1WI and changed volume in segmented tissue images.


Noncontraceptive benefits of two combined oral contraceptives with antiandrogenic properties among adolescents.
The aim of this study was to assess the noncontraceptive benefits of two combined oral contraceptives, containing progestins with well-known antiandrogenic properties, in adolescent girls. In this prospective observational study, the effects of two formulations containing 30 mcg of ethinyl estradiol combined with 2 mg chlormadinone acetate or 3 mg drospirenone were compared. Six-month data were obtained from 156 sexually active adolescents requiring contraception. We investigated the advantages of these regimens on intermenstrual bleeding, dysmenorrhea, acne and hair and skin disorders. Furthermore, their effects on sexual interest, intercourse frequency and sexual satisfaction were evaluated. Both preparations provided effective contraception, good cycle control and beneficial effects on preexisting hair and skin disorders without effects on body weight. However, the best results were obtained with the formulation containing chlormadinone acetate, with the difference being statistically significant. Furthermore, the contraceptive adherence to teenager expectations and the counseling effectiveness enhancing compliance contribute to a high rate of continuation.


Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value.
Previous studies have reported a close relationship between type V collagen (Col V) and tumor invasion and motility in both breast cancer (BC) and lung cancer (LC). The present work aims to determine whether the extracellular-matrix (ECM)-defined microenvironment influences patient clinical outcome and investigate to which extent histological patterns of Col V expression in malignant cells have a prognostic effect in patients. To that end, we examined the expression of Col V in the tissues of 174 primary tumors (MM, N = 82; LC, N = 41; and BC, N = 46) by immunohistochemistry. We found: (1) diffuse strong green birefringence in membrane and cytoplasm individualizing malignant cells in MM; (2) a focal and weak birefringence mainly in cytoplasmic membrane involving groups of malignant cells in LC and BC; (3) higher average H-score of Col V in MM than in LC and BC samples; (4) a direct correlation between Col V histologic pattern and TNM stage IV, status and median overall survival; (5) patients with LC in TNM stage I, and Col V ≤ 41.7 IOD/mm2 had a low risk of death and a median survival time more than 20 months; (6) patients with MM in TNM stage IV and Col V > 41.7 IOD/mm2 presented a high risk of death and a median survival time of just 20 months. These findings suggest that high levels of Col V individualizing malignant cells, as observed in MM, and low levels grouping malignant cells, as observed in LC and BC, confers different immune-privileged tissue microenvironment for tumor invasion with impact on prognosis of the patients.


Atherosclerosis: the importance of HDL cholesterol and prostacyclin: a role for niacin therapy.
Niacin reduces the incidence of non-fatal myocardial way infarction, confers a significant long-term survival benefit after recovery from myocardial infarction, and has had many years of study and usage by the medical community. Recent evidence suggests that via mechanisms which elevate HDL cholesterol and also release endogenous prostacyclin, niacin should be a potent agent in the long-term treatment of atherosclerosis.


Interleukin 2 production in lymphocyte cultures: a rapid test for cancer-associated immunodeficiency in malignant cervical neoplasia.
Peripheral blood lymphocytes of patients with malignant cervical neoplasia were studied for their capacity to produce interleukin-2 (IL-2) upon in vitro mitogen stimulation. Patients with early disease (Stage I/IIA) showed levels comparable to normal controls but those with advanced disease showed reduced levels, the reduction increasing with tumour load. These findings excellently correlated with our previous observations on a depressed cellular immunity in these patients. On follow up of the patients it was noticed that those who developed recurrent disease showed sustained lower levels of IL-2 production compared to those who remained disease free. These results stress the importance of a deranged immune system in these patients and also shows the clinical and prognostic value of such an assay.


COVID-19 community assessment hubs in Ireland: A study of staff and patient perceptions of their value.
Critical care bed capacity per capita in Ireland is among the lowest in Europe. The COVID-19 pandemic has put additional strain on an over-stretched healthcare system. COVID-19 community assessment hubs (CAHs) were established to prevent unnecessary admission to acute hospitals and to reduce infection spread. The aim of this study was to assess the effectiveness and acceptability of CAHs and identify how the service might be improved or adapted for possible future use. This was a mixed methods study, incorporating co-design with clinical stakeholders. Data collection was via an online survey and semistructured telephone interviews with staff and patients conducted between January and May 2021. Thirty-one patients completed the survey and nine were interviewed. Twenty interviews were conducted with staff. The findings suggest that the CAH model was successful in providing a dedicated pathway for assessing patients with COVID-19 symptoms, whilst mitigating the risk of infection. Patients were particularly positive about the timely, comprehensive and holistic care they received, as well as the accessibility of the clinics and the friendly attitudes of the staff. Staff welcomed the training and clinical protocols which contributed to their feelings of safety and competency in delivering care to this cohort of patients. They also highlighted the benefits of working in a multidisciplinary environment. Both staff and patients felt that the hubs could be repurposed for alternative use, including the treatment of chronic diseases. This study describes staff and patients' experiences of these hubs. An unexpected outcome of this study is its demonstration of the true value of effective multidisciplinary working, not only for the staff who were deployed to this service but also for the patients in receipt of care in these hubs. This multidisciplinary patient-centred service may provide a useful model for the delivery of other services currently delivered in hospital settings. An earlier phase of this study involved interviews with COVID-19-positive patients on a remote monitoring programme. The data informed this phase. Several of the authors had worked in the CAHs and provided valuable input into the design of the staff and patient interviews.


Acute interstitial nephritis associated with moxifloxacin use.
Moxifloxacin is a fluoroquinolone antimicrobial agent with proven efficacy against community-acquired respiratory pathogens. Common adverse effects associated with its use include gastro-intestinal symptoms, but nephrotoxicity has not yet been reported to the manufacturer or in the literature (based on a MEDLINE search [key words: fluoroquinolone, moxifloxacin, kidney, interstitial, and nephritis; years: 1970-2005]). The purpose of this article was to describe a case of nephrotoxicity associated with moxifloxacin use. A 68-year-old woman weighing 65 kg was referred to our nephrology clinic by her general practitioner because of an acute increase in serum creatinine concentration (SCC). In this patient, biopsyproven acute tubulointerstitial nephritis (ATIN) developed approximately 10 days after the end of moxifloxacin therapy for a nonspecific bronchial infection. The patient initially presented with nonspecific clinical symptoms, foaming of her urine, elevated erythrocyte sedimentation rate, and the acute increase in SCC. Urinalysis revealed signs of tubulointerstitial damage, including leukocyturia and proteinuria with a high concentration of alpha(1)-microglobulin. Oral corticosteroid therapy with prednisolone was started approximately 14 days after symptom development, beginning at 1 mg/kg body weight QD. After the initiation of therapy, renal function was gradually restored over 6 months, but mild proteinuria persisted. Although the exact pathogenesis of drug-induced ATIN remains unclear, an immune-mediated hypersensitivity reaction is the assumed mechanism. Fluoroquinolones might have a nephrotoxic effect. In this patient, ATIN was likely associated with moxifloxacin use. Because the course of ATIN is unpredictable and might lead to long-term dialysis, considering ATIN as a possible diagnosis in the scenario of systemic symptoms after moxifloxacin treatment is essential.


Assessment of interleukin-12, gamma interferon, and tumor necrosis factor alpha secretion in sera from mice fed with dietary lipids during different stages of Listeria monocytogenes infection.
Recent experimental observations have determined that long-chain n-3 polyunsaturated fatty acids suppress immune functions and are involved in the reduction of infectious disease resistance. BALB/c mice were fed for 4 weeks with one of four diets containing either olive oil (OO), fish oil (FO), hydrogenated coconut oil, or a low fat level. Interleukin-12p70 (IL-12p70), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) production in the sera of mice fed these diets and challenged with Listeria monocytogenes were determined by enzyme-linked immunosorbent assay. In addition, bacterial counts from spleens of mice were carried out at 24, 72, or 96 h of infection. Here, we quantified an initial diminution of production of both IL-12p70 and IFN-gamma, which appear to play an important role in the reduction of host resistance to L. monocytogenes infection. In addition, an efficient elimination of L. monocytogenes was observed in spleens of mice fed a diet containing OO at 96 h of infection, despite reductions in IL-12p70 and TNF-alpha production, suggesting an improvement of immune resistance. Overall, our results indicate that the initial reduction of both IL-12 and IFN-gamma production before L. monocytogenes infection represents the most relevant event that corroborates the impairment of immune resistance by n-3 polyunsaturated fatty acids during the different stages of infection. However, we speculate that the modulation of other cytokines must be also involved in this response, because the alteration of cytokine production in mice fed an FO diet in a late phase of L. monocytogenes infection was similar to that in mice fed OO, whereas the ability to eliminate this bacterium from the spleen was improved in the latter group.


Rare earth elements (REEs): effects on germination and growth of selected crop and native plant species.
The phytotoxicity of rare earth elements (REEs) is still poorly understood. The exposure-response relationships of three native Canadian plant species (common milkweed, Asclepias syriaca L., showy ticktrefoil, Desmodium canadense (L.) DC. and switchgrass, Panicum virgatum L.) and two commonly used crop species (radish, Raphanus sativus L., and tomato, Solanum lycopersicum L.) to the REEs lanthanum (La), yttrium (Y) and cerium (Ce) were tested. In separate experiments, seven to eight doses of each element were added to the soil prior to sowing seeds. Effects of REE dose on germination were established through measures of total percent germination and speed of germination; effects on growth were established through determination of above ground biomass. Ce was also tested at two pH levels and plant tissue analysis was conducted on pooled samples. Effects on germination were mostly observed with Ce at low pH. However, effects on growth were more pronounced, with detectable inhibition concentrations causing 10% and 25% reductions in biomass for the two native forb species (A. syriaca and D. canadense) with all REEs and on all species tested with Ce in both soil pH treatments. Concentration of Ce in aboveground biomass was lower than root Ce content, and followed the dose-response trend. From values measured in natural soils around the world, our results continue to support the notion that REEs are of limited toxicity and not considered extremely hazardous to the environment. However, in areas where REE contamination is likely, the slow accumulation of these elements in the environment could become problematic.


Examining the concurrent and longitudinal relationship between diurnal cortisol rhythms and conduct problems during childhood.
Previous literature indicates that both hypoactivity and hyperactivity of the HPA axis may be related to conduct disorder and externalizing behaviors in young children. Using a longitudinal sample of 283 typically-developing children, the current study examined both the concurrent and the longitudinal association between HPA functioning and externalizing behavior problems, such as conduct problems. Diurnal cortisol rhythms and externalizing problems were assessed at ages 6 and 9. Results suggest that concurrent HPA functioning is not significantly related to externalizing behavior at ages 6 or 9. However, more blunted cortisol rhythms at age 6 (less change across the day from morning to evening) predicted a greater increase in externalizing behavior between age 6 and age 9 than did steeper cortisol rhythms. Further analyses revealed that this association was driven by conduct problems and aggressive behavior, rather than attention problems. The relationship between HPA functioning and subsequent externalizing behavior in children adds to the limited longitudinal work on this topic, suggesting that the association changes over time. These results may serve to clarify the inconsistencies in the cross-sectional literature, particularly with respect to young school-age children.


Cyclodextrins as growth controlling agents for enhancing the catalytic activity of PVP-stabilized Ru(0) nanoparticles.
Cyclodextrins act as growth controllers in the synthesis of PVP-stabilized Ru(0) nanoparticles, leading to enhancement of the catalytic activity in the hydrogenation of furfural.


Carpentier's flexible ring versus De Vega's annuloplasty. A prospective randomized study.
To compare the efficacy of Carpentier's tricuspid annuloplasty with De Vega's, we prospectively randomized 159 patients, operated upon between January, 1977, and January, 1980, to one of the two techniques: 76 patients were assigned to the Carpentier group and 83 to the De Vega group. The criterion for inclusion in the study was the presence of moderate to severe tricuspid regurgitation. There were no significant differences in mean age, male proportion, type of mitral lesion, incidence of aortic valvulopathy, and other preoperative and perioperative characteristics between the two groups. However, organic tricuspid damage on macroscopic intraoperative examination was more common in the Carpentier group. At the end of follow-up (average 64 months) in patients with satisfactory left heart hemodynamics, there was a significant difference in the incidence of moderate or severe tricuspid insufficiency between the two groups (De Vega, 14/41; Carpentier, 4/40; p less than 0.01). In 76 patients (40 with Carpentier's annuloplasty and 36 with De Vega's technique), contrast right ventriculography was performed postoperatively and the degree of tricuspid regurgitation assessed semiquantitatively. In both groups, control of tricuspid regurgitation was poor in patients with either high total pulmonary resistances or organic tricuspid damage. If patients with these characteristics are excluded, then significant tricuspid regurgitation was encountered in only one patient in the Carpentier group but in nine of 19 in the De Vega group (p less than 0.01). In conclusion, in the treatment of tricuspid regurgitation, better results are obtained with Carpentier's than with De Vega's annuloplasty, especially if there is no organic tricuspid damage and pulmonary resistances decrease postoperatively.


Hairy cell leukemia: Uncommon clinical features, unusual sites of involvement and some rare associations.
Unusual clinical manifestations and associations with auto-immunity or other systemic disorders are uncommon clinical features of hairy cell leukemia (HCL). The exact prevalence of these rare associations is difficult to determine as they are mostly published as anecdotal case reports and generally not included in larger published series. This chapter deals with uncommon clinical manifestations and rare sites of involvement in HCL. It also summarizes the association with systemic hemato-oncological disorders as well as second malignancies, based on review of the relevant literature and from personal experience.


Actinomycetes of the genus Streptomyces in soil from Syria.
Species identification and antagonistic properties of 55 actinomycete strains isolated from Syrian soil were studied. The actinomycete strains belonged to 22 species, of which most abundantly represented were Streptomyces antimycoticus, S. rubiginosohelvolus, S. macrosporeus and S. coerulescens. Actinomycetes belonging to 16 species exhibited antagonism in relation to Gram-positive and Gram-negative bacteria, fungi and neoplastic cells.


Mitigated cytotoxicity and tremendously enhanced gene transfection efficiency of PEI through facile one-step carbamate modification.
Extremely efficacious gene transfection vector: The rapid and facile modification of PEI with commercially available TMC produces an extremely efficacious gene delivery vector with minimal cytotoxicity. Functionalization of PEI is easily controlled by PEI:cyclic carbonate feed ratios and allows for the addition of functionality. Modified PEIs hold great potential as gene delivery systems due to easy synthesis, scalability, low cost, low toxicity, and outstanding transfection capacity.


Flat leaf formation realized by cell-division control and mutual recessive gene regulation.
Most of the land plants generally have dorsoventrally flat leaves, maximizing the surface area of both upper (adaxial) side and lower (abaxial) side. The former is specialized for light capturing for photosynthesis and the latter is specialized for gas exchange. From findings of molecular genetics, it has been considered that the coupled dynamics between tissue morphogenesis and gene regulation for cell identity is responsible for making flat leaves. The hypothesis claims that a flat leaf is generated under two assumptions, (i) two mutually recessive groups of genes specify adaxial and abaxial sides of a leaf, (ii) cell divisions are induced at the limited region in the leaf margin where both of two groups are expressed. We examined the plausibility and possibility of this hypothesis from the dynamical point of view. We studied a mathematical model where two processes are coupled, tissue morphogenesis induced by cell division and deformation, and dynamics of gene regulations. From the analysis of the model we found that the classically believed hypothesis is not sufficient to generate flat leaves with high probability. We examined several different modifications and revision of the model. Then we found that a simple additional rule of polarized cell division facilitates flat leaf formation. The result of our analysis gives prediction of possible mechanism, which can be easily verified in experiments.


A national and sub-national metaregression of the trend of insufficient physical activity among Iranian adults between 2001 and 2016.
Insufficient physical activity (IPA) caused approximately 5% of mortalities in 2017 in Iran, almost double its global average. Despite the relatively considerable burden, a knowledge gap exists regarding the trend of IPA in recent years. We described the trend of IPA prevalence utilizing the data from six rounds of STEPwise approach to risk factor Surveillance (STEPS) in Iran. We estimated the physical activity status of Iranian adults from 2006 to 2016 after adjusting for years of schooling, urbanization percentage, and wealth index. We used the spatiotemporal model to interpolate and extrapolate the IPA prevalence for the years in-between the series and from 2001 to 2006, respectively. We used the data of 177,910 participants from six STEPS surveys and found that the national prevalence of IPA had steadily increased over the course of 16 years and had almost doubled in this time period (23.1% in 2001 to 55.4% in 2016). The increase was persistent across all age and gender strata and in every province. Moreover, IPA was more prevalent among women than their male peers regardless of their age category or province of residence. The prevalence of IPA in Khuzestan (highest prevalence) was almost double compared to that in Lorestan (lowest prevalence) in 2016. The IPA prevalence increased considerably and almost doubled in 16 years among Iranian adults, particularly women. Policies need to target IPA as a high priority contributing to the burden of Non-communicable diseases.


Post-boosting of classification boundary for imbalanced data using geometric mean.
In this paper, a novel imbalance learning method for binary classes is proposed, named as Post-Boosting of classification boundary for Imbalanced data (PBI), which can significantly improve the performance of any trained neural networks (NN) classification boundary. The procedure of PBI simply consists of two steps: an (imbalanced) NN learning method is first applied to produce a classification boundary, which is then adjusted by PBI under the geometric mean (G-mean). For data imbalance, the geometric mean of the accuracies of both minority and majority classes is considered, that is statistically more suitable than the common metric accuracy. PBI also has the following advantages over traditional imbalance methods: (i) PBI can significantly improve the classification accuracy on minority class while improving or keeping that on majority class as well; (ii) PBI is suitable for large data even with high imbalance ratio (up to 0.001). For evaluation of (i), a new metric called Majority loss/Minority advance ratio (MMR) is proposed that evaluates the loss ratio of majority class to minority class. Experiments have been conducted for PBI and several imbalance learning methods over benchmark datasets of different sizes, different imbalance ratios, and different dimensionalities. By analyzing the experimental results, PBI is shown to outperform other imbalance learning methods on almost all datasets.


Presynaptic glutamic acid decarboxylase is required for induction of the postsynaptic receptor field at a glutamatergic synapse.
We have systematically screened EMS-mutagenized Drosophila for embryonic lethal strains with defects in glutamatergic synaptic transmission. Surprisingly, this screen led to the identification of several alleles with missense mutations in highly conserved regions of Dgad1. Analysis of these gad mutants reveals that they are paralyzed owing to defects in glutamatergic transmission at the neuromuscular junction. Further electrophysiological and immunohistochemical examination reveals that these mutants have greatly reduced numbers of postsynaptic glutamate receptors in an otherwise morphologically normal synapse. By overexpressing wild-type Dgad1 in selected neurons, we show that GAD is specifically required in the presynaptic neuron to induce a postsynaptic glutamate receptor field, and that the level of postsynaptic receptors is closely dependent on presynaptic GAD function. These data demonstrate that GAD plays an unexpected role in glutamatergic synaptogenesis.


Small ubiquitin-like modifier (SUMO) recognition of a SUMO binding motif: a reversal of the bound orientation.
Sumoylation has recently been identified as an important mechanism that regulates protein interactions and localization in essential cellular functions, such as gene transcription, subnuclear structure formation, viral infection, and cell cycle progression. A SUMO binding amino acid sequence motif (SBM), which recognizes the SUMO moiety of modified proteins in sumoylation-dependent cellular functions, has been consistently identified by several recent studies. To understand the mechanism of SUMO recognition by the SBM, we have solved the solution structure of SUMO-1 in complex with a peptide containing the SBM derived from the protein PIASX (KVDVIDLTIESSSDEEEDPPAKR). Surprisingly, the structure reveals that the bound orientation of the SBM can reverse depending on the sequence context. The structure also reveals a novel mechanism of recognizing target sequences by a ubiquitin-like module. Unlike ubiquitin binding motifs, which all form helices and bind to the main beta-sheet of ubiquitin, the SBM forms an extended structure that binds between the alpha-helix and a beta-strand of SUMO-1. This study provides a clear mechanism of the SBM sequence variations and its recognition of the SUMO moiety in sumoylated proteins.


Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing.
Pancreatic ductal adenocarcinoma (PDA) is an inherently immune cell deprived tumor, characterized by desmoplastic stroma and suppressive immune cells. Here we systematically dissect PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening, and identify Vps4b and Rnf31 as essential factors required for escaping CD8+ T cell killing. For Vps4b we find that inactivation impairs autophagy, resulting in increased accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis. For Rnf31 we demonstrate that it protects tumor cells from TNF-mediated caspase 8 cleavage and subsequent apoptosis induction, a mechanism that is conserved in human PDA organoids. Orthotopic transplantation of Vps4b- or Rnf31 deficient pancreatic tumors into immune competent mice, moreover, reveals increased CD8+ T cell infiltration and effector function, and markedly reduced tumor growth. Our work uncovers vulnerabilities in PDA that might be exploited to render these tumors more susceptible to the immune system.


Usefulness of cardiac biomarkers to predict cardiac recovery in patients on extracorporeal membrane oxygenation support for refractory cardiogenic shock.
No prognostic markers of myocardial recovery in patients with refractory cardiogenic shock requiring circulatory support are known, but early identification of patients who will not recover might provide an opportunity to change the treatment strategy to improve outcome. Because N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin are prognostic markers in patients with cardiac failure, we hypothesized that, among patients with refractory cardiogenic shock of potentially reversible cause supported with extracorporeal membrane oxygenation (ECMO), the kinetics of these markers might help identify patients who would recover. This was a prospective, observational, single-center study in a medical-surgical intensive care unit. Among 41 consecutive patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, 18 recovered and were successfully weaned off the machine. Blood N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin concentrations were determined on days 1, 3, and 7 post-ECMO. Neither the absolute values of those biomarkers at days 1, 3, or 7 nor their kinetics during the first week differed between patients weaned or not. Areas under the receiver operating characteristic curves (95% confidence interval) of the day 1-to-day 3 biomarker changes for predicting cardiac recovery were 0.54 (0.36-0.71), 0.61 (0.43-0.78), 0.61 (0.42-0.77), 0.56 (0.38-0.73), and 0.61 (0.43-0.78), respectively. In patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, early measurements of cardiac biomarkers are not useful for identifying those who would recover.


Prediction of essential genes in prokaryote based on artificial neural network.
Rapid identification of new essential genes is necessary to understand biological mechanisms and identify potential targets for antimicrobial drugs. Many computational methods have been proposed. To construct an essential genes classifier which satisfies more different organisms, and to study the redundancy of features used in the prediction of essential genes. We designed a 57-12-1 artificial neural network model to predict the essential genes of 31 prokaryotic genomes. Four methods including self-predictions of each organism, the leave-one-genome-out method, predicting all by one organism, and self-predictions of all organisms were applied to assess the predictive performance. Additionally, the 57 features used in the artificial neural network model were analyzed by weighted principal component analysis to screen the key features strongly related to the essentiality of genes. Our results compared with previous researches indicate that our models had better generalizability. Furthermore, this method reduced the features to 29 while maintaining stable prediction performance overall, suggesting that some features are redundant for gene essentiality, and the screened features contained more important biological information for gene essentiality. This study showed the effectiveness and generalizability of our artificial neural network model. In addition, the screened features could be used as key features in computational analysis and biological experiments.


2/8 translocation in a Japanese Burkitt's lymphoma.
A new translocation between chromosomes 2 and 8, t(2p-; 8q+), was found in fresh lymphoma cells from a Japanese patient with Epstein-Barr virus-carrying Burkitt's lymphoma, and in a lymphoma cell line derived from this patient. There was no 14q+ translocation, as has been previously described in African and North American Burkitt's lymphomas.


CA-UNet Segmentation Makes a Good Ischemic Stroke Risk Prediction.
Stroke is still the World's second major factor of death, as well as the third major factor of death and disability. Ischemic stroke is a type of stroke, in which early detection and treatment are the keys to preventing ischemic strokes. However, due to the limitation of privacy protection and labeling difficulties, there are only a few studies on the intelligent automatic diagnosis of stroke or ischemic stroke, and the results are unsatisfactory. Therefore, we collect some data and propose a 3D carotid Computed Tomography Angiography (CTA) image segmentation model called CA-UNet for fully automated extraction of carotid arteries. We explore the number of down-sampling times applicable to carotid segmentation and design a multi-scale loss function to resolve the loss of detailed features during the process of down-sampling. Moreover, based on CA-Unet, we propose an ischemic stroke risk prediction model to predict the risk in patients using their 3D CTA images, electronic medical records, and medical history. We have validated the efficacy of our segmentation model and prediction model through comparison tests. Our method can provide reliable diagnoses and results that benefit patients and medical professionals.


What do "interpersonally sensitive" supervisors do and how do supervisees experience a relational approach to supervision?
In two investigations, we identified explicitly relational supervision strategies and examined whether use of these strategies was associated with perceptions of the supervisory alliance and evaluations of the supervisor. First, ratings by nine supervision researchers identified five clearly relational in-session strategies (focus on countertransference, exploration of feelings, attend to parallel process, focus on the therapeutic process, focus on the supervisory alliance) in the Critical Events model of supervision. Based on these expert ratings, we created and assessed the Relational Behavior Scale (RBS). Analyses with two samples of supervisees at all levels of training supported the measure's reliability and factorial validity. The RBS's validity was further indicated by its unique association with the "interpersonally sensitive" style of supervision. In both studies, supervisees perceived more frequent use of relational behavior on the part of psychoanalytic/psychodynamic/humanistic supervisors than cognitive-behavioral supervisors. Moreover, as hypothesized, supervisors' use of relational behavior in a specific session mediated the association between trainees' alliance perceptions and evaluations of their supervisors in that session. The identification of specific in-session supervision behaviors that explain one way in which a strong alliance contributes to trainees' positive experiences of their supervisors has implications for supervision theory, research, and practice.


Headache.
Headache can be a symptom of vast pathologies, and common secondary headache including head or neck trauma, cranial or cervical vascular disorder, non-vascular intracranial disorders headache related to a substance or its withdrawals, infection, disorders of homeostasis, disorders of cranium or facial mouth or cranial disorders, and headache attributable to psychiatric. Stroke-related headache has been reported between 7 and 65% and headache is also the most frequent symptom of cerebral venous thrombosis, which is present in nearly 90% of patients.


[Effects and mechanism of genistein on the proliferation and apoptosis in human nasopharyngeal carcinoma cell lines CNE].
To investigate the effects and mechanism of genistein on proliferation inhibition and onset of apoptosis in nasopharyngeal carcinoma cell line CNE. Antiproliferative effect of genistein against CNE was tested by MTT method. Apoptotic phenotype of CNE was observed by electron microscope. Cell apoptosis percentage and cell cycle phase distribution of CNE were measured by flow cytometric assay. A time dependent and dose dependent proliferation inhibition was demonstrated in CNE, the high potency has the obvious suppression on tumor growth function; Genistein induces nasopharyngeal cancer cell early apoptosis rate but to strengthen along with the density increase, 200 micromol/L group is highest, is 49.9%; and genistein induced a G2/ M cell cycle arrest. The characteristic morphological changes of apoptosis in CNE cells was observed after treated by genistein. The time dependent and dose dependent proliferation inhibitory effect of genistein on nasopharyngeal cancer cells. Genistein's mechanism on suppressing effect is probably associated with inducing the cell apoptosis and intervening the cell circle of carcinoma cell. The results provide evidence for the potential usefulness of genistein in the prevention and treatment of human nasopharyngeal carcinoma.


Can Continuity of Care Reduce Hospitalization Among Community-dwelling Older Adult Veterans Living With Dementia?
Hospitalization is a difficult experience, especially for patients with dementia. Understanding whether better continuity of care (COC) reduces hospitalizations can indicate interventions that might help curb hospitalizations. To estimate the causal impact of COC on hospitalizations and different reasons for hospitalization among community-dwelling older veterans with dementia. Population-based observational study using nationwide Veterans Health Administration data linked to Medicare claims in Fiscal Years (FYs) 2014-2015. To account for unobserved confounders we used an instrumental variable for COC-whether veteran changed residence by more than 10 miles. Community-dwelling veterans with dementia aged 66 and older, enrolled in Traditional Medicare (n=105,528). Bice-Boxerman Continuity of Care (BBC) index (0-worst to 1-best COC); binary indicators of any hospitalization for all causes, for ambulatory care sensitive conditions (ACSCs) and for reasons grouped by major diagnostic category. The mean BBC in FY 2014 was 0.32 (SD, 0.23). In FY 2015 43.3% of the cohort veterans were hospitalized. A 0.1 higher BBC resulted in 2.4% (95% confidence interval, 0.5%-4.4%) lower probability of hospitalization for all causes. BBC was not associated with hospitalization for ACSCs. Grouped by major diagnostic category, a 0.1 higher BBC resulted in 3.8% (95% confidence interval, 2.1%-5.4%) lower probability of hospitalization for neuropsychiatric diseases/disorders, with no impact on hospitalizations for circulatory, respiratory, infectious, kidney and urinary, digestive, musculoskeletal, and endocrine-metabolic diseases/disorders. Among community-dwelling older veterans with dementia, better COC resulted in less hospitalizations, and this effect was primarily due to less hospitalization for neuropsychiatric diseases/disorders but not hospitalization for ACSCs, or other hospitalization reasons.


Mapping endocrine surgery: Workforce analysis from the last six decades.
We analyzed the demographics of high-volume surgeons (HVS) for endocrine operations. We characterized HVS by region, specialty, gender, teaching-affiliation, American Association of Endocrine Surgeons (AAES) membership, and decade they entered practice. Providers were general surgeons (GS) and otolaryngologists (ENT); fellowship trained (FT) or not FT (NFT). We identified 395 HVS in 47 states entering practice between 1958 and 2011. Sixty-eight percent were GS, 35% were FT, and 35% were AAES members. GS, FT surgeons, and endocrine surgery FT surgeons (ES) performed more operations per surgeon. More FT surgeons were in Northeast, West (W), and Midwest than Southeast (SE) and Southwest (SW; P < .0001). More teaching surgeons and AAES members were in the Northeast and Midwest than SE, W, and SW (P < .0001). FT-GS increased over decades (P < .0001) but not FT-ENT (P = .3). Representation of ES, AAES members, and females increased over decades (P < .0001). The workforce for endocrine operations displayed increased representation of GS, FT surgeons, and women, correlating with the profile of recent AAES fellowship graduates. More insight is needed to understand why most HVS were not AAES members. Regional disparities can guide the placement of endocrine surgeons into both academic and community practices, increasing trainee exposure and patient access to specialty care.


Vertical stratification of sand fly diversity in relation to natural infections of Leishmania sp. and blood-meal sources in Jamari National Forest, Rondônia State, Brazil.
Almost 1000 cases of American cutaneous leishmaniasis have been registered yearly in Rondônia State, Brazil. Little is known about the Leishmania transmission cycle (vectors and reservoirs) in the state. This study aimed to evaluate sand fly fauna from two vertical stratification layers in order to identify potential vectors and their blood-meal sources. The study was conducted in Jamari National Forest. Sand flies were collected in the canopy (15 m) and at ground level (1 m) using HP light traps during four months, February, April, August and October, 2018. Insects were identified to the species level, and females were subjected to DNA extraction and PCR targeting minicircle kDNA and hsp70 (for Leishmania detection and species identification), and cytb (to identify blood-meal sources). Exploratory data analysis was used to determine mean of abundance and species richness between stratifications. The hsp70 and cytb sequences were analyzed and compared with sequences from GenBank. Overall, 68 species were identified from 15,457 individuals. On the Potosi trail, 7531 individuals of 49 species were collected; canopy captures totaled 6463 individuals of 46 species, while ground captures totaled 1068 individuals of 38 species. On the Santa Maria trail, 7926 individuals of 61 species were collected; canopy captures totaled 6136 individuals of 51 species, while ground captures totaled 1790 individuals of 53 species. A total of 23 pools were positive for kDNA (canopy n = 21, ground n = 2). Only two samples were sequenced for hsp70 (both in canopy); one sequence exhibited similarity with Leishmania braziliensis (Lutzomyia davisi pool) and another with L. naiffi (Lu. antunesi pool). The cytb fragment was amplified in 11 of 86 samples. Sample sequencing identified cytb DNA from 5 blood-meal sources: Micrastur gilvicollis, Psophia viridis, Tamandua tetradactyla, Homo sapiens and Choloepus didactylus. Sand fly fauna is more diverse in the canopy than at ground level. Factors such as blood-meal sources, resting sites, and abiotic components probably contribute to high abundance in the canopy. Our results reinforce the possibility that Lu. antunesi and Lu. davisi participate in Leishmania transmission in forest environments and may play an important role in transmission from sylvatic to human hosts.


Predictive value of oxidative stress biomarkers in drug-free patients with bipolar disorder.
Oxidative stress is one of the primary etiological mechanisms of bipolar disorder (BD). The present study was conducted over a period of 24 months on Tunisian on 34 drug‑free male patients with BD (mean age: 34.5 years) and 101 age and gender matched controls (mean age: 34.20 years) were enrolled in the study. Plasma reduced glutathione (GSH) and total thiols levels were significantly decreased in patients compared to controls (respectively p < .001; p = .009). In addition, malondialdehyde (MDA), advanced oxidation protein products (AOPP), protein carbonyls (PC) and homocysteine (Hcys) concentrations and glutathione peroxidase (GSH-Px) activity were significantly increased in patients compared to controls (p = .002; p < .001; p = .001; p < .001 and p = .016, respectively). The binary logistic regression analysis revealed that MDA, AOPP and Hcys could be considered as independent risk factors for BD. When using CombiROC analysis, a remarkable increase in the area under the curve (AUC) with higher sensitivity (Se) and specificity (Sp) for MDA, AOPP, PC, GSH-Px and Hcys combined markers was observed. Overall, the identification of the predictive value of these five selected biomarkers related to oxidative stress in drug free patients should lead to a better identification of the etiological mechanism of BD.


The stimulatory action of phosphodiesterase inhibitors on the flexor reflex of the hind limb in the spinal rat.
We studied the action of the following phosphodiesterase inhibitors (PDEIs): rolipram (4-[3-cyclopentoxy-5-methoxyphenyl]-2-pyrrolidione), Ro 20-1724 (4-[3-butoxy-4-methoxybenzyl]-2-imidazolidione), 1-methyl-3-isobutylxanthine (IMBX) and theophylline on flexor reflex activity of the hind limb in the spinal rat. Potentiation of this reflex is thought to be due to enhancement of either 5-hydroxytryptaminergic or alpha-adrenergic transmission in the spinal cord. All the inhibitors potentiated flexor reflex activity in a dose-dependent manner in the following order of potency: rolipram greater than Ro 20-1724 greater than IBMX greater than theophylline. Their stimulatory action in this model paralleled their known potency in inhibiting phosphodiesterase (PDE). Neither the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine nor the alpha-adrenoceptor blocker phenoxybenzamine prevented potentiation of flexor reflex activity by PDEIs. It is suggested that (1) the PDEIs potentiate flexor reflex activity through a novel spinal mechanism which does not involve alpha-adrenoceptors of 5-HT receptors in the spinal cord but rather is related to the inhibition of PDE localized postsynaptically; (2) flexor reflex activity in the spinal rat can be a useful experimental preparation to estimate the in vivo effects of known PDEIs.


Dental anxiety, cardiovascular changes and patient preconceptions toward implants and root canal treatments: An observational study.
There is little information about dental anxiety and the patient's vital signs during dental procedures. This study evaluates and compare patient anxiety levels and cardiovascular changes before and during root canal treatment (RCT) and single-tooth implant procedures. Preoperative data and pre-treatment considerations were recorded. HR and SpO2 were monitored during treatment procedures at five points. Data were analyzed accordingly using Mann Whitney or X2 tests. 80 patients met the inclusion criteria. Anxiety and fear scores were strongly correlated (p< 0.001). Both treatments resulted in low levels of dental anxiety and fear. Patients with a prior dental bad experience presented higher anxiety scores in the implant treatment group (p< 0.05). Implant treatment was considered a more time-consuming and more painful procedure than root canal treatment (p< 0.05). No significant relation was found between the level of anxiety with HR and SpO2. No significant relation was found between the level of dental anxiety with HR and SpO2. Single-implant treatment was pre-considered to be a more time-consuming and more painful procedure when compared with a RCT. HR was higher at the initial stages and decreased as both procedures finished. Key words:Dental anxiety, endodontics, dental implants, oximetry, heart rate.


Perspectives of Canadian Stakeholders on Criteria for Appropriateness for Total Joint Arthroplasty in Patients With Hip and Knee Osteoarthritis.
As rates of total joint arthroplasty (TJA) for osteoarthritis (OA) rise, there is a need to ensure appropriate use. We undertook this study to develop criteria for appropriate use of TJA. In prior work, we used qualitative methods to separately assess OA patients' and arthroplasty surgeons' perceptions regarding appropriateness of patient candidates for TJA. The current study reviewed the appropriateness themes that emerged from each group, and a series of statements were developed to reflect each unique theme or criterion. A group of arthroplasty surgeons then indicated their level of agreement with each statement using electronic voting. Where ≤70% agreed or disagreed, the criterion was discussed and revised, and revoting occurred. In standardized telephone interviews, OA patient focus group participants indicated their level of agreement with each revised criterion. Qualitative research in 58 OA patients and 14 arthroplasty surgeons identified 11 appropriateness criteria. Member-checking in 15 surgeons (including 5 who had participated in the qualitative study) resulted in agreement on 6 revised criteria. These included evidence of arthritis on joint examination, patient-reported symptoms negatively impacting quality of life, an adequate trial of appropriate nonsurgical treatment, realistic patient expectations of surgery, mental and physical readiness of patient for surgery, and patient-surgeon agreement that potential benefits exceed risks. Thirty-six of the original 58 OA patient focus group participants (62.1%) participated in the member-check interviews and endorsed all 6 criteria. Patients and surgeons jointly endorsed 6 criteria for assessment of TJA appropriateness in OA patients. Prospective validation of these criteria (assessed preoperatively) as predictive of postoperative patient-reported outcomes is under way and will inform development of a surgeon-patient decision-support tool for assessment of TJA appropriateness.


Polychromatic microdiffraction characterization of defect gradients in severely deformed materials.
This paper analyzes local lattice rotations introduced in severely deformed polycrystalline titanium by friction stir welding. Nondestructive three-dimensional (3D) spatially resolved polychromatic X-ray microdiffraction, is used to resolve the local crystal structure of the restructured surface from neighboring local structures in the sample material. The measurements reveal strong gradients of strain and geometrically necessary dislocations near the surface and illustrate the potential of polychromatic microdiffraction for the study of deformation in complex materials systems.


Six new lignans from the leaves and stems of Schisandra sphenanthera.
Six new lignans, schisphenlignans F-K (1-6), together with ten known ones, were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR, MS and CD spectra. In addition, some compounds were tested for their acute activity on insulin sensitivity in 3T3-L1 differentiated adipocytes and anti-HIV-1 activity.


Single-dose palifermin prevents severe oral mucositis during multicycle chemotherapy in patients with cancer: a randomized trial.
Mucositis can be a serious complication of cancer treatment. Palifermin reduces mucositis when given in multiple doses to patients undergoing hematopoietic stem-cell transplantation. To evaluate the efficacy of palifermin given as a single dose before each cycle in patients receiving multicycle chemotherapy. Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00267046) The University of Texas M.D. Anderson Cancer Center, Houston, Texas. 48 patients with sarcoma were randomly assigned in a 2:1 ratio to receive palifermin or placebo. All patients received doxorubicin-based chemotherapy (90 mg per m(2) of body surface area over 3 days, by infusion). Palifermin (180 µg per kg of body weight) or placebo was administered intravenously as a single dose 3 days before each chemotherapy cycle (maximum, 6 cycles). Patients who had severe mucositis received open-label palifermin in subsequent cycles. Oral assessment of mucositis by using World Health Organization (WHO) oral toxicity scale (grades 0 to 4), with moderate to severe mucositis (grades 2 to 4) as the main outcomes; patient-reported outcome questionnaire; and daily symptom record diary. A median of 6 blinded cycles (range, 1 to 6) were completed by the palifermin group and 2 (range, 1 to 6) by the placebo group. Compared with placebo, palifermin reduced the cumulative incidence of moderate to severe (grade 2 or higher) mucositis (44% vs. 88%; P < 0.001; difference, -44 percentage points [95% CI, -71 to -16 percentage points) and severe (grade 3 or 4) mucositis (13% vs. 51%; P = 0.002; difference, -38 percentage points [CI, -67 to -9 percentage points]). The main adverse effects were thickening of oral mucosa (72% in the palifermin group vs. 31% in the placebo group; P = 0.007) and altered taste. Seven of the 8 patients who had severe mucositis in the placebo group received open-label palifermin. None of these patients had severe mucositis in the subsequent cycles (a total of 17) with open-label palifermin. Study limitations include smaller sample size for the control group, inclusion of only patients with sarcoma, and perceived unblinding of the treatment because of notable differences between the biologic effects of palifermin and placebo. A single dose of palifermin before each cycle reduced the incidence and severity of mucositis. The drug was generally well tolerated, but most patients experienced thickening of oral mucosa. Further investigation is needed to determine whether palifermin use will facilitate greater adherence to chemotherapy regimens by reducing mucositis.


Metabolic Features of Activated Memory CD4+ T-Cells Derived from HIV-Infected Immunological Non-responders to Highly Active Antiretroviral Therapy.
Immunological non-responders (INR) are HIV-infected subjects that fail to restore CD4+ T-cell counts despite undetectable HIV viral load, which is controlled by highly active antiretroviral therapy (HAART). In INR, impaired immune restoration is linked to low-productive proliferation of memory CD4+ T-lymphocytes. Taking into account that T-cell ability to divide depends on the activity of metabolic pathways, we aimed to determine rates of mitochondrial respiration and glycolysis in memory CD4+ T-cells of INR. Two groups of HIV-infected HAART-treated patients were studied: immunological non-responders and subjects with an adequate immunological response to therapy (immunological responders - IR). Control (C) group comprised uninfected volunteers. In both groups of HIV-infected patients glycolytic activity of memory CD4+ T-cells was lower than that in C. Mitochondrial respiration rate in memory CD4+ T-cells derived from IR was comparable to that of C at basal state, however, after stimulation IR failed to reach the values of uninfected subjects. INR had the lowest mitochondrial respiration rate both at basal state and after stimulation. Taken together, the data presented herein demonstrate that low regenerative potential of memory CD4+ T-cells derived from INR might be linked to diminished lymphocytes' metabolic activity.


Regulating function of coenzymization and decoenzymization of the lactate dehydrogenase isozymes in the mouse tissues during hypoxia.
To study the characteristics of changes of LDH enzyme patterns of mice under slight hypoxia. Mice treated with artificial hypoxia, various tissues were made for the test of LDH enzymatic activity by the specific staining technique. LDH (1-5) relative percentage enzymatic activity (RPEA) were measured with CS-910 dual-wavelength thin layer chromatography scanner. The RPEA of LDH isozymes of various tissues after slight hypoxia shifted to the isozymes LDH1 and LDH2, whose principal subunits are H subunits, and the RPEA of LDH1 (H4), LDH2 (H3M) increased, while RPEA of LDH5 (M4) in various tissues decreased prominently except the cardiac muscle, and that of LDH4 (HM3) decreased as well. After polyacrylamide gel electrophoresis (PAGE) of the hypoxia treated cardiac muscle specimen was made, activity subbands originated regularly in the isoyme patterns of LDH, with the regularity of LDH1 (0 subband), LDH2 (0-1 subbands), LDH3 (0-2 subbands), LDH4 (1-3 subbands), LDH5 (2-4 subbands). After adding appropriate amount of NAD+ to the hypoxia treated cardiac muscle specimen, PAGE showed the subbands of four isoymes (LDH2-LDH5) reduced or even totally disappeared in the isozyme patterns. The negative feedback regulation of coenzymization and decoenzymization of LDH isozymes is one of the mouse stress responses to slight hypoxia.


Liquid Chromatography/Mass Spectrometry based serum metabolomics study on recurrent abortion women with antiphospholipid syndrome.
The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. The pathogenic mechanisms that damage the fetal-maternal unit and cause abnormal placental development are incompletely understood in APS patients. Liquid Chromatography/Mass Spectrometry (LC/MS) based metabolomics are applied for the mechanism of disease and further supporting the research of diagnosis and management in recent years. The aim of this research was to investigate the difference of serum metabolic profiles in recurrent abortion women with APS and healthy women to explore the mechanism of this disease. Serum samples of 25 recurrent abortion women with APS and 25 healthy women were collected and analyzed by LC/MS in this study. Potential biomarkers were discovered by multivariate statistical analysis and then identified based on analysis results. Totally, we identified five biomarkers that involved in different metabolic pathway such as purine metabolism, amino acid metabolism and tyrosine metabolism. These biomarkers showed different roles in disease development. Metabolomics was proved as a powerful tool in understanding the mechanism of recurrent abortion caused by APS.


The Efficacy of Aged Garlic Extract on Gingivitis - A Randomized Clinical Trial.
To assess gingivitis and gingival bleeding following the consumption of Aged Garlic Extract versus placebo for a period of four months. A randomized, controlled, examiner-blind, two-treatment parallel group study was conducted. Participants were stratified and randomly assigned equally to a regimen group using Aged Garlic Extract (AGE) or a control group, based on gender, age, baseline number of bleeding sites, and gingival health status. Assessment was performed at baseline and at one, two, three, and four months. Clinical assessment was conducted by three experienced calibrated examiners. One hundred and fifty-one participants followed the inclusion criteria; 50.3% males, with an average age of 32.7 ± 8.2 years. Only 134 subjects completed the four-month study (11.3% attrition rate). A statistically significant decrease of the Modified Gingival Index and Gingival Bleeding Index scores was shown for the AGE compared to the placebo group, both between and within groups (p < 0.001). This research demonstrated that daily consumption of AGE benefits oral health by reducing gingival inflammation and gingival bleeding, as compared to a placebo control.


Paracentrotus lividus eggs contain different RNAs at the animal and vegetal poles.
Paracentrotus lividus eggs were divided by centrifugation into nucleated and anucleated halves. Fertilization and development of the two halves permitted us to establish that nucleated and anucleated fragments correspond, respectively, to the animal and vegetal parts. RNA was extracted from both egg halves and submitted to differential display. Northern blot analysis confirmed their maternal origin and showed that each transcript has a different expression pattern during development. By Northern blot and in situ hybridization experiments we ascertained that Bep2 and PlAn1 are localized in the animal part, whereas 16S rRNA, Plveg1, and L27 in the vegetal part, and that Plun1 is uniformly distributed. Moreover, by treating P. lividus eggs with detergent, in presence or not of drugs such as colchicine and cytochalasin B, we demonstrated the involvement of the cytoskeleton only in localization of Bep2, PlAn1, and Plun1, suggesting that different mechanisms are utilized for animal and vegetal distribution.