Extended lymphadenectomy in esophageal cancer is crucial.
Surgery with lymphadenectomy remains the mainstay of treatment for esophageal cancer. The optimal extent of nodal dissection is controversial. Evidence is accumulating, however, that could demonstrate the benefits of extended lymphadenectomy, which include more accurate disease staging, better locoregional disease control, and improved survival. Except in very early disease where nodal metastases are rare, extended lymphadenectomy is indicated. Data from a randomized controlled trial comparing transhiatal and transthoracic resection have shown better survival in patients with limited nodal burden. Other investigations on en bloc resection, three-field lymphadenectomy, and large-scale international collaborative studies have all provided evidence for the more extensive approach to enhance cure for esophageal cancer. The more extended surgery does lead to potentially higher morbidity rates, and thus surgeons should be versatile in applying such techniques in carefully selected patients, so that postoperative survival and quality of life of patients are not compromised. The challenge in the future is how to tailor surgical strategies for individual patients in order to achieve the best outcome.


Feasibility of a label-free X-ray method to estimate brain amyloid load in small animals.
Amyloid plaque in the brain is associated with a wide range of neurodegenerative diseases such as Alzheimer's and Parkinson's and defined as aggregates of amyloid fibrils rich in β-sheet structures. We report a label-free method based on small-angle X-ray scattering (SAXS) to estimate amyloid load in an intact mouse head with skull. The method is based on recording and analyzing the X rays elastically scattered from the β-sheets of amyloid plaques in a mouse head at angles smaller than 10° and energies between 30 and 45 keV. The method is demonstrated by acquiring the spectral SAXS data of an amyloid model and an excised head from a wild-type mouse for 600 s. We captured the distinct scattering peaks of the amyloid plaques at momentum transfer (q) of 6 and 13 nm-1 associated with β-sheet structure. We first show linear correlation between the mass fraction of the amyloid target and the area under the peak (AUP) of the scattering curve. We report results for estimating amyloid load in a fixed mouse head by recovering the characteristic scattering signal from the amyloid target situated at various locations. The coefficient of variation in the amyloid load estimate is found to be less than 10%. There are no previously described label-free X-ray methods for the estimation of amyloid load in an intact head. We demonstrated the feasibility of a label-free method based on SAXS to potentially estimate brain amyloid in small animals.


Dynamical Quantum Phase Transition and Quasi Particle Excitation.
Dynamical phase transitions (DPTs) are signaled by the non-analytical time evolution of the dynamical free energy after quenching some global parameters in quantum systems. The dynamical free energy is calculated from the overlap between the initial and the time evolved states (Loschmidt amplitude). In a recent study it was suggested that DPTs are related to the equilibrium phase transitions (EPTs) (Heyl, M. et al. Phys. Rev. Lett. 110, 135704 (2013)). We here study an exactly solvable model, the extended XY model, the Loschmidt amplitude of which provides a counterexample. We show analytically that the connection between the DPTs and the EPTs does not hold generally. Analysing also the general compass model as a second example, assists us to propound the physical condition under which the DPT occurs without crossing the equilibrium critical point, and also no DPT by crossing the equilibrium critical point.


Depression in later life: an overview with treatment recommendations.
We have already entered a new, more exciting, and hopeful era in the treatment of late-life depression. The increasing numbers of older adults who are surviving to more advanced ages and the greater recognition of late-life depression's prevalence and impact on quality of life emphasize how important it is to detect and treat this disorder. Our increasing repertoire of evidence-based psychotherapeutic, pharmacologic, and neurotherapeutic treatment interventions offers many treatment alternatives, allowing substantial individualization of treatment approach. Demonstration of the effectiveness of depression treatment in primary care suggests the feasibility of increasing our patients' access to care. Growing appreciation of the pathophysiology of depression and its interrelationships with cognitive impairment may increase our ability to limit or delay certain aspects of cognitive impairment through more aggressive treatment of depression. Improved recognition and treatment of late-life depression holds great potential for improving physical and mental health in later life, reducing disability in later years, and improving quality of life.


Two defence systems eliminate plasmids from seventh pandemic Vibrio cholerae.
Horizontal gene transfer can trigger rapid shifts in bacterial evolution. Driven by a variety of mobile genetic elements-in particular bacteriophages and plasmids-the ability to share genes within and across species underpins the exceptional adaptability of bacteria. Nevertheless, invasive mobile genetic elements can also present grave risks to the host; bacteria have therefore evolved a vast array of defences against these elements1. Here we identify two plasmid defence systems conserved in the Vibrio cholerae El Tor strains responsible for the ongoing seventh cholera pandemic2-4. These systems, termed DdmABC and DdmDE, are encoded on two major pathogenicity islands that are a hallmark of current pandemic strains. We show that the modules cooperate to rapidly eliminate small multicopy plasmids by degradation. Moreover, the DdmABC system is widespread and can defend against bacteriophage infection by triggering cell suicide (abortive infection, or Abi). Notably, we go on to show that, through an Abi-like mechanism, DdmABC increases the burden of large low-copy-number conjugative plasmids, including a broad-host IncC multidrug resistance plasmid, which creates a fitness disadvantage that counterselects against plasmid-carrying cells. Our results answer the long-standing question of why plasmids, although abundant in environmental strains, are rare in pandemic strains; have implications for understanding the dissemination of antibiotic resistance plasmids; and provide insights into how the interplay between two defence systems has shaped the evolution of the most successful lineage of pandemic V. cholerae.


The effect of temporal environmental heterogeneity on community structure: a replicated experimental study.
Periodicity, predictability and stochasticity of environmental perturbations are shown to influence the community structure that develops in microcosms. Sets of replicate, microalgal communities were subjected to different temporal patterns of rarefaction and resource resupply and their species-abundance patterns after 120 days of such manipulations were determined. Perturbations having, 1, 7, and 28 day periodicities differentially effected community structure. The predictability of these perturbations had a less profound influence on the communities which developed than the average perturbation periodicity.


Cervical cancer in Ethiopia - predictors of advanced stage and prolonged time to diagnosis.
In Ethiopia, most cervical cancer patients present at advanced cancer stages, long time after they experience first symptoms. We investigated possible predictors of long time spans between symptom onset and pathologic diagnosis (patient intervals). We also aimed to seek out predictors for advanced cancer stage diagnosis. We conducted a retrospective cohort study among 1575 cervical cancer patients who were registered at Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia between September 2008 and September 2012. Cox proportional hazards regression was used to find predictors of long patient intervals. Cumulative odds ordinal logistic regression was used to identify predictors of cancer stage at diagnosis. Median patient interval was 30 weeks, with the interval substantially longer in patients residing in rural than urban areas. Longer patient intervals were associated with more advanced cancer stages at pathologic diagnosis. HIV-positive women had an almost 1.5 times increased risk of diagnosis at a more advanced stage. Cervical cancer patients are diagnosed after long time periods leading to advanced stages at diagnosis. Measures to raise awareness about cervical cancer, to increase screening and to shorten the time interval from recognition of symptoms to diagnosis are urgently needed.


Identification of unknown experimental parameters from noisy apertureless scanning near-field optical microscope data with an evolutionary procedure.
We determine a set of experimental parameters through the application of an evolutionary inversion procedure. The input to the algorithm is experimental apertureless scanning near-field optical microscope data. The performance of our inversion procedure is assessed by means of a comparison with a nonevolutionary technique.


Characterisation of de novo MAPK10/JNK3 truncation mutations associated with cognitive disorders in two unrelated patients.
The c-Jun N-terminal kinases (JNKs) are stress-activated serine-threonine kinases that have recently been linked to various neurological disorders. We previously described a patient with intellectual disability (ID) and seizures (Patient 1), carrying a de novo chromosome translocation affecting the CNS-expressed MAPK10/JNK3 gene. Here, we describe a second ID patient (Patient 2) with a similar translocation that likewise truncates MAPK10/JNK3, highlighting a role for JNK3 in human brain development. We have pinpointed the breakpoint in Patient 2, which is just distal to that in Patient 1. In both patients, the rearrangement resulted in a predicted protein interrupted towards the C-terminal end of the kinase domain. We demonstrate that these truncated proteins, although capable of weak interaction with various known JNK scaffolds, are not capable of phosphorylating the classical JNK target c-Jun in vitro, which suggests that the patient phenotype potentially arises from partial loss of JNK3 function. We next investigated JNK3-binding partners to further explore potential disease mechanisms. We identified PSD-95, SAP102 and SHANK3 as novel interaction partners for JNK3, and we demonstrate that JNK3 and PSD-95 exhibit partially overlapping expression at synaptic sites in cultured hippocampal neurons. Moreover, JNK3, like JNK1, is capable of phosphorylating PSD-95 in vitro, whereas disease-associated mutant JNK3 proteins do not. We conclude that reduced JNK3 activity has potentially deleterious effects on neuronal function via altered regulation of a set of post-synaptic proteins.


Determination of nanoparticle heteroaggregation attachment efficiencies and rates in presence of natural organic matter monomers. Monte Carlo modelling.
Understanding the transformation and transport of manufactured nanoparticles (NPs) in aquatic systems remains an important issue due to their potential hazard. Once released in aquatic systems, NPs will interact with natural compounds such as suspended inorganic particles and/or natural organic matter (NOM) and heteroaggregation will control their ultimate fate. Unfortunately, systematic experimental methods to study heteroaggregation are not straightforward and still scarce. In addition, the description of heteroaggregation rate constants and attachment efficiencies is still a matter of debate since no clear definition exists. In this work, an original cluster-cluster Monte Carlo model is developed to get an insight into heteroaggregation process descriptions. A two-component system composed of NPs and NOM fulvic acid monomers is investigated by considering several water models to cover a range of (relevant) conditions from fresh to marine waters. For that purpose, homo- and hetero- individual attachment efficiencies between NPs and NOM units are adjusted (NP-NP, NOM-NOM and NP-NOM). The influence of NP/NOM ratio, NOM-NOM homoaggregation versus heteroaggregation, and surface coating effects is studied systematically. From a quantitative point of view, aggregation rate constants as well as attachment efficiencies are calculated as a function of physical time so as to characterize the individual influence of each parameter and to allow future comparison with experimental data. Heteroaggregation processes and global attachment efficiencies corresponding to several mechanisms and depending on the evolution of heteroaggregate structures all along the simulations are defined. The calculation of attachment efficiency values is found dependent on NP/NOM concentration ratios via coating effects, by the initial set of elementary attachment efficiencies and influence of homoaggregation. Marine water represents a specific case of aggregation where all particle contacts are effective. On the other hand, in "ultrapure" and "fresh waters", a competition between homo- and heteroaggregation occurs depending on the initial attachment efficiencies therefore indicating that a subtle change in the NP surface properties as well as in the water chemistry have a significant impact on heteroaggregation processes.


3D echocardiography allows rapid and accurate surgical planning in complex aortic root abscess cases.
Despite 3D echocardiography (3DE) acquiring significantly greater data than standard 2D echocardiography (2DE), it is underutilized in assessing cardiac anatomy and physiology. A key advantage is the ability of a single 3DE acquisition to be post-processed to generate volume rendered 3D models and an unlimited number of multiplanar reconstruction (MPR) images. We describe the case of a highly anxious patient with life-threatening complex aortic valve endocarditis and aortic root abscess, refusing transesophageal echocardiography (TOE) under general anaesthesia with tachycardia, breathlessness and acute kidney injury precluding accurate or safe gated (computed tomography) CT, who was comprehensively assessed with a rapid 3DE-TOE under sedation. This led to timely surgery and an excellent outcome for the patient.


FOXD1 is required for 3D patterning of the kidney interstitial matrix.
The interstitial extracellular matrix (ECM) is comprised of proteins and glycosaminoglycans and provides structural and biochemical information during development. Our previous work revealed the presence of transient ECM-based structures in the interstitial matrix of developing kidneys. Stromal cells are the main contributors to interstitial ECM synthesis, and the transcription factor Forkhead Box D1 (Foxd1) is critical for stromal cell function. To investigate the role of Foxd1 in interstitial ECM patterning, we combined 3D imaging and proteomics to explore how the matrix changes in the murine developing kidney when Foxd1 is knocked out. We found that COL26A1, FBN2, EMILIN1, and TNC, interstitial ECM proteins that are transiently upregulated during development, had a similar distribution perinatally but then diverged in patterning in the adult. Abnormally clustered cortical vertical fibers and fused glomeruli were observed when Foxd1 was knocked out. The changes in the interstitial ECM of Foxd1 knockout kidneys corresponded to disrupted Foxd1+ cell patterning but did not precede branching dysmorphogenesis. The transient ECM networks affected by Foxd1 knockout may provide support for later-stage nephrogenic structures.


Progressive deconstruction of Arundo donax Linn. to fermentable sugars by acid catalyzed ionic liquid pretreatment.
Acid enhanced ionic liquid (IL) 1-n-butyl-3-methylimidazolium chloride ([C4 mim]Cl) pretreatment has shown great potential for boosting the yield of sugars from biomass cost-effectively and environmental-friendly. Pretreatment with shorter processing time will promote the commercial viability. In this work, pretreatment of reduced Amberlyst catalysis time of 34 min was demonstrated to be the most effective among time-varying pretreatments, evidenced by partial removal of hemicellulose and cellulose crystal transformation of Arundo donax Linn. A higher fermentable sugar concentration of 10.42 g/L (2% substrate) was obtained after 72 h of saccharification than the others. Total processing time to reach 92% glucose yield was cut down to approximately 26 h. Progressive deconstruction of crop cell wall was occurred with increased catalysis time by gradual releasing of H3O(+) of Amberlyst. However, vast lignin re-deposited polymers on fibers could hinder further enzymatic hydrolysis. These discoveries provide new insights into a more economic pretreatment for bioethanol production.


The role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins by macrophages.
We have previously shown that cultured macrophages secrete lipoprotein lipase (LPL) into the culture medium. The purpose of these experiments was to determine the role of LPL in the uptake of very low density lipoproteins (VLDL). Both J774 cells and mouse peritoneal macrophages took up and degraded normotriglyceridemic VLDL in a saturable manner. Uptake of VLDL was effectively competed for by rabbit beta-VLDL, human VLDL, but not by native LDL or acetyl LDL. LPL activity accelerated saturable uptake of VLDL but was not a prerequisite for it. This was most clearly seen in experiments with apo-C-II-deficient VLDL. Although no hydrolysis of VLDL triglyceride occurred, saturable uptake and degradation of the C-II-deficient lipoprotein occurred. However, addition of apo-C-II enhanced saturable uptake. Normal VLDL also promoted cellular accumulation of both triglycerides and cholesteryl esters. Accumulation of triglyceride occurred by uptake of intact VLDL particles, by uptake of a triglyceride-depleted particle produced by the action of LPL, and by the direct uptake of free fatty acids generated by the activity of LPL. In turn, the latter process was influenced by the amount of albumin in the medium capable of being an acceptor for free fatty acids. Finally, we have shown that when albumin is present in the medium, the macrophage is capable of mobilizing most of its stored triglyceride over 24 h, even as its cholesteryl ester content remains constant. These studies may be relevant to the ability of VLDL to promote macrophage accumulation of cholesteryl ester, even as triglyceride accumulation is minimized.


Wyatt v. Stickney: a consent decree.
On September 22, 1986, Judge Myron Thompson issued a consent decree in the Wyatt v. Stickney litigation. The settlement occurred 14 years after Judge Frank M. Johnson, Jr. rendered his landmark decision in this case. The consent decree included termination of the court's active supervision of the state's mental health system, termination of the receivership, and termination of the court monitor's powers. The state agreed to adhere to Wyatt standards, maintain Title XIX accreditation, continue deinstitutionalization efforts, and develop an internal advocacy and quality assurance program. Mechanisms are also to be put in place to apprise the plaintiffs' attorneys of progress in these efforts.


Retracted: Path Deconstruction of Agricultural Environmental Sustainable Development Policy in the Process of International Agricultural Trade Liberalization.
[This retracts the article DOI: 10.1155/2022/3101244.].


Comparing the analgesic efficacy of morphine plus ketamine versus morphine plus placebo in patients with acute renal colic: A double-blinded randomized controlled trial.
Renal colic (RC) is a common cause for emergency department visits. This study was conducted to compare the analgesic efficacy of morphine plus ketamine (MK) versus morphine plus placebo (MP) in patients with acute renal colic. Using a single center, double-blind, two-arm, parallel-group, randomized controlled trial, 200 patients were equally and randomly divided to receive 0.1 mg/kg morphine plus normal saline and 0.1 mg/kg morphine plus 0.2 mg/kg ketamine. The severity of renal colic was assessed by VAS at baseline, 20 and 40 min after drug injection. The number of adverse events also was recorded. Totally, 200 patients completed the study. Mean age of the patients was 35.60 ± 8.17 years. The patients were mostly men (68.5%). The severity of pain between the groups was not significantly different at baseline. Both groups showing a significant reduction in VAS scores across the three time points. The main effect comparing the two types of intervention was significant (F = 12.95, p = 0.000), suggesting a significant reduction in pain severity of patients in the MK group. The number of patients who suffered from vomiting was significantly higher in MP group than that of MK group (13 and 3, respectively (P = 0.009)). However, the risk of dizziness in the MK group was >2 times higher than MP group (relative risk: 2.282, 95% CI: 1.030-5.003, P = 0.039). The number of patients who needed rescue analgesia was significantly lower in the MK group (OR, 0.43 (0.22-0.83)). Adding 0.2 mg/kg ketamine to 0.1 mg/kg morphine can reduce the renal colic pain, nausea and vomiting more than morphine alone; however, it was associated with higher number of patients with dizziness.


Primary tumor characteristics and next-generation sequencing mutations as biomarkers for melanoma immunotherapy response.
Considerable advances in melanoma have been realized through immunotherapy. The principal aim was to determine whether primary tumor characteristics or next-generation sequencing (NGS) could serve as markers of immunotherapy response. The study cohort consisted of 67 patients who received immunotherapy for recurrent or metastatic melanoma and for whom primary tumor biopsies and pathology reports were available. A subset of 59 patient tumors were profiled using an NGS panel of 50 cancer-related genes. Objective response rate to immunotherapy was assessed using RECIST v1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were used as endpoints. Lymphovascular invasion (LVI) strongly correlated with an increased proportion of immunotherapy responders (p = .002). PFS interval (p = .003) and OS (p = .036) were significantly higher in patients with LVI. NRAS mutation was more strongly correlated with an increased proportion of immunotherapy responders (p =.050). PFS was significantly higher in patients with NRAS mutation (p = .042); no difference in OS (p = .111). This analysis demonstrates an association between lymphovascular invasion and immunotherapy response. Additionally, NGS mutation analysis demonstrated a potential association between NRAS mutations and immunotherapy response.


Solitary renal plasmacytoma with palisading tumor vascularity.
A solitary extramedullary plasmacytoma of the kidney associated with contralateral myeloma kidney is reported. The tumor demonstrated extensive palisading tumor vessels, heretofore thought to be characteristic of renal lymphoma. Plasmacytoma as the etiology of a renal mass should be considered when there is nonfunction of a normal-appearing contralateral kidney.


Role of dopamine D1 receptors in cocaine lethality.
One group of heterogeneously bred HS mice was assigned to test coadministration of the selective D1 antagonist SCH 23390 with a dose of cocaine (95 mg/kg) that was observed to produce 80% lethality, whereas a second group was tested by cotreatment with the newly developed full-efficacy D1 agonist dihydrexidine (DHX) and a dose of (60 mg/kg) cocaine previously shown to be nonlethal. The mice in the former group displayed decreased lethality going from 80% with coadministered vehicle to 15% after pretreatment with the highest dose (0.45 mg/kg) of SCH 23390. In the other group of mice there was no lethality seen when vehicle or 10 mg/kg DHX was coadministered with 60 mg/kg cocaine, but a dose-responsive increase in lethality with increasing DHX doses; the maximal lethality of 80% occurred when 25 mg/kg DHX was coadministered with cocaine. These results confirm the effects of D1 antagonism decreasing cocaine lethality as reported previously when rats were used, and extend the findings to D1 agonism; both observations evidence a role for the D1 receptor in the lethal effects, be they central, cardiopulmonary, or anesthetic, of cocaine.


Alanine aminotransferase course, serum hepatitis B virus DNA, and liver stiffness measurement for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B.
To evaluate the utility of the combination of alanine aminotransferase (ALT) course, hepatitis B virus (HBV) DNA level, and liver stiffness measurement (LSM) for determining significant liver disease in hepatitis B e antigen (HBeAg)-negative patients. Three hundred and ninety nine consecutive HBeAg-negative patients with HBV DNA >2000 IU/mL and documented serial measurements of ALT were enrolled to undergo LSM followed by liver biopsy. Using ALT <40 IU/L as a normal value, 142 patients had persistently normal ALT (PNALT), whereas 257 had persistently or intermittently elevated ALT (PIEALT) in the prior year. Among patients with HBV DNA of 2000-19 999, 20 000-199 999, and ≥200 000 IU/mL, significant pathological lesions defined as the presence of moderate to severe necroinflammation and/or significant fibrosis by METAVIR scoring was present in 40%, 45%, and 71% of the PIEALT group, and 15%, 31%, and 36% of the PNALT group, respectively. In PNALT patients with HBV DNA <20 000 IU/mL, liver biopsy could be avoided in 88% when LSM <7 kPa is used as an indicator of non-significant liver histology but 12% of those who indeed had significant pathological lesions would be missed. In PIEALT patients with HBV DNA ≥20 000 IU/mL, the need for liver biopsy could be reduced by 53% with a false positive rate of 14% when LSM ≥7 kPa is used as a predictor of significant pathological lesions. The combination of serial ALT, viral load, and LSM appears to be a promising non-invasive tool. A management algorithm for HBeAg-negative patients comprising these non-invasive measures is proposed with liver biopsy being pursued in selected cases.


Progress in the preparation, application, and recycling of black phosphorus.
Black phosphorus nanosheets (BPNSs) are a new member of the nanomaterial family, and they have good development potential in electrochemistry, electronics, optoelectronics, environmental protection, biomedical, and other fields because of their bandgap width, high anisotropy, broad optical absorption, high carrier mobility and many other features. Although many articles have been published about the preparation and application of BPNSs, these aspects have not been elucidated, and we aimed to fill this knowledge gap in this review. First, we used VOSviewer software to sort out articles published in the past 5 years and drew a literature map, which allowed us to sort out the relationship between various studies related to BPNSs, and reflect on the research focus in recent years. Because BPNSs must be made from black phosphorus (BP), and BPNSs are a nano form of BP, the collation of the BP preparation scheme was also helpful for the related research on BPNSs. This paper introduces the preparation of bulk BP and BPNSs, analyzes and compares the advantages and disadvantages of each method, and points out the most promising methods in the future. Then, we propose improvement directions for this method. We also introduce the characterization of BPNSs and combine it with the subsequent photocatalytic application of BPNSs. As a new material, the effect of BPNSs on the environment is still unknown; thus, an end treatment scheme for BPNSs is summarized according to existing methods. Based on the experience of nanomaterial treatment, this paper proposes a research focus for the end treatment of BPNSs in the future, providing a reference scheme for the end treatment of other nanomaterials. Finally, we summarize the full text and propose recommended methods and improvement plans.


Burkholderia vietnamiensis infection in a haematological unit: Case series and review of literature of this new emerging pathogen.
Burkholderia vietnamiensis causes opportunistic infection in immunocompromised individuals. It closely resembles other non-fermentative Gram-negative bacteria. Accuracy in diagnosis has improved with the use of new modalities. Here, we describe four patients of lymphoblastic disorder on chemotherapy, who presented with fever due to blood stream infection. Multidrug resistant B. vietnaminensis was isolated in blood culture and identified using MALDI-TOF MS. All of them responded to a switch in antibiotic therapy based on sensitivity reports. This is the first case series from North India highlighting the importance of this less known organism as an important pathogen in immunocompromised patients.


Acyclic monoterpenoid-rich essential oil of Cymbopogon distans mitigates skin inflammation: a chemico-pharmacological study.
The topical application of essential oils is considered an effective treatment for skin diseases. Cymbopogon distans (Nees ex Steud.) Wats (Poaceae) is a promising aromatic grass widespread in the Himalayan temperate zone. Therefore, using in-vitro and in-vivo bioassays, we examined the chemical and pharmacological characteristics of essential oil hydro-distilled from C. distans coded as CDA-01, specifically concerning skin inflammation. Characterization using GC-FID and GC-MS provided a chemical fingerprint for CDA-01, enabling the identification of 54 compounds; amongst them, citral (34.3%), geranyl acetate (21.2%), and geraniol (16.4%) were the most abundant. To examine the anti-inflammatory potential, CDA-01 treatment on LPS-stimulated macrophage cells in addition to 12-O-tetradecanoylphorbol-13-acetate (TPA) generated cutaneous inflammatory reaction in the mouse ear was assessed through quantification of the inflammatory markers. Consequently, CDA-01 demonstrated protection against inflammation caused by LPS by lowering the pro-inflammatory cytokines (IL-6 and TNF-α) level in HaCaT cells with negligible cytotoxicity. Consistent with the in-vitro findings, CDA-01 treatment reduced pro-inflammatory mediators (TNF-, IL-6, and NO) and lipid peroxidation in an in-vivo investigation. Subcutaneous inflammation in TPA-treated mice ears was similarly decreased, as evidenced by the histological and morphological studies. As a result of our findings, it is possible that CDA-01 could be an effective treatment for skin inflammation disorders.


Appropriate timing of coronary artery bypass grafting after acute myocardial infarction.
Optimal timing of coronary artery bypass grafting (CABG) after acute myocardial infarction (AMI) remains the subject of fierce debate. Therefore, the recommended deferral ranges from immediate intervention to surgery 4 weeks after infarction. Especially, the increasing cohorts of patients at old age or with poor left ventricular function, whose mortality rates are additionally enhanced, may profit from focused analyses. This study aims at clarifying the appropriate timing of CABG after AMI, with special regard to high-risk patients (Age >70 years, left ventricular ejection fraction (LVEF) <30%). Retrospective analysis was performed in 3475 patients who had undergone isolated CABG between 2005 and 2009. Those 1168 patients with previous AMI (<30 days) were categorized in groups, depending on deferral of surgery: <6 hours after AMI (A), 6 hours-1 day (B), 2-3 days (C), 4-10 days (D), 11-20 days (E), and 21-30 days (F). Furthermore, subgroups with an age >70 years or a LVEF <30% were examined. The mortality rates in groups A-F were 14.8, 10.2, 8.8, 4.2, 2.3, and 2.0%, whereas only the values of groups A-D were significantly increased versus the mortality rate of patients without previous AMI (1.9%). In patients over 70 years, we observed operative mortalities of 26.3, 14.3, 11.9, 6.1, 4.2, and 3.1% (groups A-F) versus 2.5% (no previous AMI), while 27.4, 15.4, 11.7, 6.0, 3.7, and 2.8% (groups A-F) versus 2.7% (no previous AMI) of patients with a LVEF <30% died during the first 30 days after surgery. In both subanalyses of high-risk patients, the enhanced mortalities of groups A-E reached significance. Multivariate analysis of operative risk factors revealed that CABG within 10 days after AMI and age over 60 years are independently associated with operative mortality. CABG early after AMI (<10 days) is accompanied by significantly increased mortality, especially in elderly patients or in patients with a severely impaired LVEF. At least the critical time period of 3 days should be avoided-whenever the hemodynamics is stable enough.


Androgen and 19-norsteroid profiles in human preovulatory follicles from stimulated cycles: an isotope dilution-mass spectrometric study.
Follicular fluid was aspirated from preovulatory follicles of women under ovarian stimulation for in vitro fertilization and analyzed by a highly specific technique based on gas chromatography-mass spectrometry associated with stable isotope dilution. 19-Nortestosterone and 19-norandrostenedione were identified and quantified for the first time in human follicular fluid. There was a strong positive correlation between 19-nortestosterone and estradiol-17 beta and between 19-norandrostenedione and estrone concentrations, thus indicating a common cellular origin. The accumulation of 19-norsteroids in follicular fluid confirms that they are weakly active intermediates in the multistep enzymatic conversion of androgen to estrogen. Testosterone concentrations were significantly lower than those obtained by radioimmunoassay; cross-reaction with substantially higher levels of 19-nortestosterone seems to be at the origin of this discrepancy. Androstenedione concentrations were similar to those reported in the literature and it was therefore confirmed that an estradiol/androstenedione concentration ratio above 20 is favourable for oocyte cleavage. Other and some newly estimated androgens are: testosterone sulfate, 5-androstene-3 beta, 17 beta-diol 3-sulfate and disulfate, dihydrotestosterone sulfate, epitestosterone, 19-hydroxyandrostenedione, 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane-3 beta, 17 beta-diol, 5 alpha-androstane-3,17-dione and androsterone. Dehydroepiandrosterone sulfate was by far the most abundant androgen in this type of follicles.


Strain and temperature dependent aggregation of Candida auris is attenuated by inhibition of surface amyloid proteins.
Candida auris is a multi-drug resistant human fungal pathogen that has become a global threat to human health due to its drug resistant phenotype, persistence in the hospital environment and propensity for patient to patient spread. Isolates display variable aggregation that may affect the relative virulence of strains. Therefore, dissection of this phenotype has gained substantial interest in recent years. We studied eight clinical isolates from four different clades (I-IV); four of which had a strongly aggregating phenotype and four of which did not. Genome analysis identified polymorphisms associated with loss of cell surface proteins were enriched in weakly-aggregating strains. Additionally, we identified down-regulation of chitin synthase genes involved in the synthesis of the chitinous septum. Characterisation of the cells revealed no ultrastructural defects in cytokinesis or cell separation in aggregating isolates. Strongly and weakly aggregating strains did not differ in net surface charge or in cell surface hydrophobicity. The capacity for aggregation and for adhesion to polystyrene microspheres were also not correlated. However, aggregation and extracellular matrix formation were all increased at higher growth temperatures, and treatment with the amyloid protein inhibitor Thioflavin-T markedly attenuated aggregation. Genome analysis further indicated strain specific differences in the genome content of GPI-anchored proteins including those encoding genes with the potential to form amyloid proteins. Collectively our data suggests that aggregation is a complex strain and temperature dependent phenomenon that may be linked in part to the ability to form extracellular matrix and cell surface amyloids.


Carpels as leaves: meeting the carbon cost of reproduction in an alpine buttercup.
We investigated the role of photosynthesis by reproductive organs in meeting the carbon costs of sexual reproduction in the snow-buttercup, Ranunculus adoneus. The exposed green carpels of snow-buttercup flowers have 1-2 stomata each. Net carbon assimilation rates of flowers are negative during bud expansion, but rise to zero at maturity, and become positive during early fruit growth. Experimental removal of separate whorls of flower parts demonstrated that the showy, nectary-housing petals account for most of the respiration cost of flower presentation. Conversely, photosynthesis by female organs contributes to a flower's carbon balance. Dipteran pollinators of R. adoneus are most active in sunny mid-morning to mid-afternoon intervals. At this time of day, rates of carpel photosynthesis (Amax) meet respiratory costs of pollinator attraction in fully expanded flowers. Achenes remain photosynthetically active until dispersal, and positive net carbon assimilation rates characterize infructescences throughout fruit maturation. Photosynthetic rates of achenes are positively correlated with infructescence growth rates. We tested the causal basis of this relationship by experimentally shading developing infructescences. Mature achenes from shaded infructescences were 16-18% smaller than those from unshaded controls. Leaf photosynthetic rates did not differ between plants bearing shaded and unshaded seed heads. Since female reproductive organs are only 8% more costly in terms of caloric investment than male ones and contribute to their own carbon balance, it is plausible that the energy cost of male function equals or exceeds that of female function in this hermaphroditic species.


Impact of gender and sex work on sexual and injecting risk behaviors and their association with HIV positivity among injecting drug users in an HIV epidemic in Togliatti City, Russian Federation.
Togliatti City is witness to a large epidemic of human immunodeficiency virus (HIV) associated with injecting drug use (IDU). This study sought to examine whether risk behaviors and risk factors associated with HIV differed across a sample IDUs by gender and sex work. A sample of IDU (n = 423) comprising female sex workers (SWs) (n = 66), non-sex workers (nonSWs) (n = 89) and men (n = 268) were recruited by field workers in community settings. Behavioral and HIV prevalence data were collected. HIV prevalence did not differ across the groups ( approximately 56%), but gender adversely affected some risk factors. A comparison of risk behaviors indicated that SWs were more likely to engage in risky injecting behaviors than either men or nonSWs. They were also more likely to report a history of sexually transmitted infections. IDUs involved in sex work and IDU nonSWs require specific and targeted interventions to facilitate safer injecting and sexual behaviors.


Unusual chromosome 9 polymorphism and reproductive failure.
Partial inversion of an unusually large 9qh variant is reported in a 28-year-old normal female with reproductive failure (karyotype: 46,XX,9[qh +,inv(p11;q12)]mat).


How I manage Evans Syndrome and AIHA cases in children.
The management of Evans Syndrome in children is challenging due to the lack of evidence-based data on treatment. Steroids, the first-choice therapy, are successful in about 80% of cases. For children who are resistant, relapse or become steroid-dependent, rituximab is considered a valid second-line treatment, with the exception of those with an underlying diagnosis of autoimmune lymphoproliferative syndrome who may benefit from other options such as mycophenolate mofetil and sirolimus. Better knowledge of the immunological mechanisms underlying cytopenias and the availability of new immunosuppressive drugs can be helpful in the choice of more targeted therapies that would enable the reduction of the use of long-term steroid administration or other more aggressive options, such as splenectomy or stem cell transplantation. This manuscript provides an overview of the pathogenic background of the disease, and suggests a clinical approach to diagnosis and treatment with a particular focus on the management of relapsing/resistant disease.


Cannabinoids inhibit testosterone secretion by mouse testes in vitro.
Addition of delta-9-tetrahydrocannabinol or cannabinol to an incubation medium containing decapsulated mouse testes caused a significant reduction in the accumulation of testosterone in the medium. This result suggests that the reported effects of cannabis on male sexual and reproductive function may result from direct inhibition of testicular steroidogenesis by both psychoactive and nonpsychoactive constituents of marihuana.


Effect of Dietary Forage: Concentrate Ratio on Pre-Caecal and Total Digestive Tract Digestibility of Diverse Feedstuffs in Donkeys as Measured by the Mobile Nylon Bag Technique.
The domestic donkey is a unique equid species with specific nutritional requirements, however, limited laboratory evidences are available to address the digestibility contribution of the prececum in relation to the total digestive tract. In the present study, six caecum-fistulated adult female Xinjiang donkeys served as the experimental animals in a 3 × 3 Latin square design, and mobile nylon bag technique was applied to determine the effect of dietary F:C ratio on pre-caececum and total digestive tract digestibility of rice straw, alfalfa hay, corn meal, and soybean meal. The dietary treatments included: (1) HF, a high-fiber ration (F:C = 80:20), (2) MF, a medium-fiber ration (F:C = 55:45), and (3), LF, a low-fiber ration (F:C = 35:65). The experiment consisted of three consecutive Latin square periods, and each period lasted 25 days. In each period, the animals were administrated naso-gastrically nylon bags (38 μm pore size) containing aforementioned feeds. After 1.5 h intubation, the bags were checked once an hour and collected at the ileo-caecal junction (small intestine bag, D1) and in the feces (fecal bag, D2). Regardless whatever feeds were introduced, the percentage of bag collected (BC) was quadratically (HF) or linearly (MF and LF) increased against different fixed bag collection time. The highest BC occurred in MF (73.8%), but no significant difference was observed between HF (62.3%) and LF (50.8%). The lowest mean bag retention time was observed in HF (2.7 h), and no significant difference occurred between MF (4.6 h) and LF (5.0 h) diets. For each feed, D1 and D2 digestibility for DM, CP, NDF, and ADF did not differ among three dietary treatments (p > 0.05). Regardless of whatever diets were fed to the donkeys, D2 digestibility for DM and CP among the feeds ranked as: soybean meal > corn meal > alfalfa hay > rice straw (p < 0.01). D1 digestibility for DM among the feeds ranked as: corn meal > soybean meal > alfalfa hay > rice straw (p < 0.01). D1 digestibility for CP among the feeds ranked as: soybean meal > corn meal > alfalfa hay > rice straw (p < 0.01). In summary, dietary forage: concentrate ratio did not affect pre-caecal or total tract nutrient digestibility. The fiber level in feeds was the main limiting factor to affect the digestibility contribution of the pre-caecum in relation to the total digestive tract.


Fabrication of a three-dimensional nanostructured biomaterial for tissue engineering of bone.
A plasma process for the surface modification of HA powders has been developed. Acrylic acid and acrylic acid/octadiene plasma deposited films onto HA particles have demonstrated to interact with SBF allowing the calcium dissolution-precipitation mechanism. Therefore, a nanostructured composite between HA and a self-assembling peptide scaffold (RAD16-I) has been developed. The differentiation of mESC in this scaffold has been studied, in order to test the osteogenic capacity of the new composite material. We have observed that the mESC can be induced to produce Ca salts (mineralization) in a 3D-microenvironment and moreover, this activity can be enhanced by the presence of HA particles into the nanofiber scaffold.


The activation of human factor IX.
The activation of factor IX purified from human plasma has been studied. Factor XIa and kallikrein separately activated factor IX to factor IXa. In both cases factor IXa had an apparent molecular wight of about 42-45000 in sodium dodecyl sulphate-polyacrylamide disc gel electrophoresis compared with a molecular weight of about 70000 for the native factor IX. The activation by XIa required Ca2+-ions, wherease Ca2+-in and factor VII or Russell's-viper venom alone did not activate factor IX. Trypsin activated and plasmin inactivated factor IX.


High throughput screening data for a case study of CHO cell culture process development.
In this article, we present four sets of data from high-throughput screening (HTS) studies of different chemically defined media using an industrially relevant Chinese hamster ovary (CHO) cell line. While complex hydrolysate media was used in the early phase process development and manufacturing of a monoclonal antibody (mAb), here we seek to determine an appropriate chemically defined media for late phase process development. Over 150 combinations of chemically defined basal media, feed media, and basal and feed media supplements, such as polyphenolic flavonoid antioxidants (including rosmarinic acid (RA)), were evaluated in four HTS studies to replace the complex hydrolysate media. Specifically, these four screening studies incorporated custom design of experiment (DOE), one-factor-at-a-time (OFAT), and definitive screening design methodologies for titer improvement. Titer was improved two fold compared to the early phase process using the addition of RA to chemically defined media. This dataset exemplifies how HTS can be used as an effective approach to systematically and statistically determine media composition and supplementation to increase mAb titer. These data were presented in connection with a published paper [1].


Mechanisms of rabies virus neutralization by glycoprotein-specific monoclonal antibodies.
Incubation of radiolabeled rabies virus with neutralizing monoclonal antibodies (MAbs) resulted in complete neutralization of the virus but only partial inhibition of virus binding to, and internalization by, BHK cells. Several of the neutralizing MAbs were capable of preventing infection after virus adsorption to cells; up to 30% of the bound virus was released when cells containing adsorbed virus were incubated with these MAbs at 4 degrees, indicating that the release of bound virus accounts only in part for the neutralization of adsorbed virus. To study the mechanism of neutralization of cell-bound virus, temperature shift experiments were carried out to follow the fate of neutralized cell-adsorbed virus at 37 degrees. Treatment of infected cells with each of the tested neutralizing MAbs had no effect on virus uptake at 37 degrees and the MAbs were endocytosed together with the virus; however, the ability of some of the MAbs to neutralize cell-adsorbed rabies virus correlated with the fusion inhibition activity of these MAbs. We hypothesize from these data that these MAbs neutralize rabies virus by inhibiting the intraendosomal acid-catalyzed fusion step that leads to virus uncoating.


The fork head transcription factor Fkh5/Mf3 is a developmental marker gene for superior colliculus layers and derivatives of the hindbrain somatic afferent zone.
Fork head-5 (Fkh5; also known as Mf3 and TWH) is a transcription factor of the winged helix family. As part of an extended project to understand the function of this protein in the developing mouse brain, in the present work we have used Fkh5/Mf3 expression as a marker to study the development of the midbrain and hindbrain. In the midbrain, Fkh5/Mf3 is expressed in the superior colliculus, in the ventricular layer of the inferior colliculus and in the isthmus. In the superior colliculus, Fkh5/Mf3 is expressed by cells of layers 4a and 4c since early in development. In the hindbrain, Fkh5/Mf3 is a longitudinal marker (as opposed to a transverse or rhombomeric one), since it labels nuclei belonging to the somatic afferent zone (ventral cochlear nucleus, cuneate and external cuneate nuclei, principal and spinal nuclei of the trigeminal). In addition, Fkh5/Mf3 is expressed by the developing endopiriform nucleus and by the olivary pretectal nucleus. The results suggest that Fkh5/Mf3 has an early role in the lamination of the tectum and in the longitudinal differentiation of the hindbrain.


Pyridine-containing m-phenylene ethynylene oligomers having tunable basicities.
Incorporation of a pyridine monomer into the backbone of a m-phenylene ethynylene oligomer allows functionalization of the interior binding cavity of the folded oligomer. The basicity of the inwardly directed pyridine moiety was modulated by changing the substituents on the pyridine ring and through oligomer folding, granting access to a pK(a) range of 5-14 in acetonitrile. [reaction: see text]


Familial eruptive lentiginosis.
Eruptive lentiginosis is a rare condition characterized by the abrupt spreading of asymptomatic pigmented macules over the entire body without systemic associations. We report mother and daughter, both of whom developed abrupt dissemination of numerous pigmented skin lesions.


Effect of mixing ratio and total solids content on temperature-phased anaerobic codigestion of rice straw and pig manure: Biohythane production and microbial structure.
Long-term semi-continuous experiments were carried out under three feedstock conditions to study the effects of mixing ratio and total solids (TS) content on temperature-phased anaerobic codigestion of rice straw (RS) and pig manure (PM). The results showed that biohythane only produced from the mixture with 6% TS content and its average content were 12.83 ± 1.19% (hydrogen) and 23.68 ± 1.12% (methane). Increasing mixture TS content and decreasing its RS ratio increased biohythane production and organic matter removal by creating a suitable process pH and increasing the anaerobic reaction rates. The highest biohythane production of the mixture reached 73.09 ± 3.03 ml/g VS (hydrogen) and 235.81 ± 9.30 ml/g VS (methane) at a mixing ratio of 5:1 and TS content of 6%. A variety of hydrogen-producing bacteria were found in the thermophilic reactor and Clostridium_sensu_stricto_1 played an important role. Butyric acid fermentation is the main hydrogen-producing pathway. Methanobacterium and Methanosaeta were dominant archaea in the mesophilic reactor.


Soluble urokinase plasminogen activator receptor measurements: influence of sample handling.
The influence of sample handling on soluble urokinase plasminogen activator receptor (suPAR) concentrations in serum and EDTA plasma was studied in 16 healthy premenopausal women. Blood was collected in dry tubes and tubes containing EDTA and kept at 4 degrees C or 20 degrees C for 1, 3, 8, 24 or 72 hours before processing into serum or EDTA plasma. In addition, serum and EDTA plasma were frozen and thawed 1-8 times. All suPAR measurements were performed by ELISA. No significant differences were found between serum or EDTA plasma suPAR concentrations when whole blood samples were kept for 1, 3, 8 or 24 hours. Significantly higher suPAR levels were found in samples kept for 72 hours at 20 degrees C compared to samples processed into serum or EDTA plasma after short-term storage for no more than 24 hours after collection. No significant differences were observed when whole blood was kept at 4 degrees C for up to 72 hours. Repeated freezing and thawing had no significant effect on the serum and EDTA plasma suPAR levels. suPAR values in blood samples are dependent on the handling procedures of the samples. All samples of whole blood must be processed into EDTA plasma or serum within 24 hours if kept at 20 degrees C and within 72 hours if kept at 4 degrees C. However, repeated freezing/thawing cycles had no influence on suPAR values in the samples.


Derivation and characterization of gut-like structures from embryonic stem cells.
Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages of all three embryonic germ layers in vitro. The hanging drop culture of ES cell suspension in the absence of leukemia inhibitory factor induces aggregation and differentiation of the cells into simple or cystic embryoid bodies (EBs). After 6 d of hanging drop culture, the resulting EBs are plated onto plastic dishes for the outgrowth culture. At d 21 after outgrowth culture, cell populations of EBs can give rise to three-dimensional gut-like structures that exhibit spontaneous contraction and highly coordinated peristalsis. The gut-like structures have large lumens surrounded by three layers: epithelium, lamina propria, and muscularis. Ganglia are scattered along the periphery, and interstitial cells of Cajal are distributed among the smooth muscle cells. The fundamental process of formation of the in vitro organized gut-like structures is similar to embryonic gastrointestinal development in vivo. The EBs at the 6-d egg-cylinder stage may have the potential to regulate developmental programs associated with cell lineage commitment and provide an appropriate microenvironment to differentiate ES cells into enteric derivatives of all three embryonic germ layers and reproduce the gut organization process in vitro.


Effects of fillers combined with biosorbents on nutrient and heavy metal removal from biogas slurry in constructed wetlands.
The performance of fillers (biochar and zeolite) and their combinations with biosorbents (compound microbial agent and chlorella) in nutrients and heavy metals removal from biogas slurry in constructed wetlands (CWs) planted water spinach (Ipomoea aquatica) and plant uptake of heavy metals was investigated. The results demonstrated that the removal rate of nutrients in CWs was all above 60%. COD removal efficiencies were not significantly affected by fillers and biosorbents, all above 80%. The removal rates of TN and NH4+-N were the highest when the two fillers and two biosorbents were added, and the combination of biochar and chlorella presented the optimal removal effect on TP. The efficiency of removing heavy metals from biogas slurry in CWs was As > Zn > Cu, and their removal rates were 35.38%-83.89%, 8.15%-23.69% and 0.32%-0.88%, respectively. The removal efficiency of As by the combination of biochar and composite microbial agent was high. The combination of the two fillers and two biosorbents had the best effect on reducing Cu and Zn enrichment in the aboveground part of water spinach in each treatment, while biochar alone had the best effect on reducing As enrichment in the aboveground and underground parts of water spinach. This study can provide a basis for the application of fillers and biosorbents in the treatment of biogas slurry in livestock and poultry farms in wetlands.


Plasticity of IL-2 and IL-2 receptor chains in rat lymphoid tissues in situ after stimulation with staphylococcal enterotoxin A.
Although the effects of mitogens on the synthesis of interleukin-2 (IL-2) and IL-2 receptor (IL-2r) have been described, a detailed in situ analysis of the spatio-temporal changes of the expression of the IL-2 gene and the three IL-2r components in lymphoid tissues is still missing. Therefore, we analyzed the IL-2 and IL-2r expression after a staphylococcal enterotoxin A (SEA)-induced T cell activation on a cellular and anatomical basis in the Wistar rat. SEA caused a rapid induction of IL-2 mRNA in T cells of spleen, lymph node, and thymus, followed by the appearance of high systemic IL-2 serum levels (5 ng/ml), and a significant increase of CD25 on CD4+ and CD8+ lymphocytes. The histotopographic analysis of the IL-2r chains revealed a strong upregulation of IL-2r alpha (alpha) and IL-2r beta (beta) mRNAs in similar T cell specific compartments of spleen, lymph node, and thymus as seen for IL-2 mRNA. The abundant constitutive expression of IL-2r gamma (gamma) mRNA was unaffected by SEA. The parallel upregulation of IL-2, IL-2ralpha, and beta chains in conjunction with the continuous presence of the IL-2rgamma chain predominantly in T cell regions of immune organs suggests that the biological effects of IL-2 are essentially limited to T cells, at least after superantigen stimulation.


Gene therapy for RAB28: What can we learn from zebrafish?
The eye is particularly suited to gene therapy due to its accessibility, immunoprivileged state and compartmentalised structure. Indeed, many clinical trials are underway for therapeutic gene strategies for inherited retinal degenerations (IRDs). However, as there are currently 281 genes associated with IRD, there is still a large unmet need for effective therapies for the majority of IRD-causing genes. In humans, RAB28 null and hypomorphic alleles cause autosomal recessive cone-rod dystrophy (arCORD). Previous work demonstrated that restoring wild type zebrafish Rab28 via germline transgenesis, specifically in cone photoreceptors, is sufficient to rescue the defects in outer segment phagocytosis (OSP) observed in zebrafish rab28-/- knockouts (KO). This rescue suggests that gene therapy for RAB28-associated CORD may be successful by RAB28 gene restoration to cones. It also inspired us to critically consider the scenarios in which zebrafish can provide informative preclinical data for development of gene therapies. Thus, this review focuses on RAB28 biology and disease, and delves into both the opportunities and limitations of using zebrafish as a model for both gene therapy development and as a diagnostic tool for patient variants of unknown significance (VUS).


Scanning Ultrafast Spectral Dynamics of Triphenylamine-Modified Vinylbenzothiazole Derivative: Role of Solvent Polarity and Temperature.
The photophysical properties of a donor-acceptor compound based on triphenylamine-modified vinylbenzothiazole derivative (BTTM) are investigated by multispectral techniques. Based on the pump-probe and pump-dump/push-probe technique, it is found that the hybridized localized excited (LE) and charge transfer (CT) state (HLCT) participates in the relaxation process of excited BTTM. The excited state is the LE-dominated HLCT state in cyclohexane; then it evolves to the CT-dominated HLCT state in a high polarity solvent. Meanwhile, a new intermediate state named the HLCT' state also exists in a high polar solvent. When the temperature of BTTM film drops, the increasing photoluminescence (PL) lifetime and PL quantum yield are assigned to the nonradiative recombination inactivation. The pump-probe data show that exciton-exciton annihilation originating from exciton collision gradually increases owing to the weakening of phonon-exciton scattering at low temperature. Our results provide comprehensive insight into the optoelectronic properties of organic molecules.


Excitatory amino acids have different effects on horizontal cells in eyecup and isolated retina.
Horizontal cells in the mudpuppy eyecup responded to continuous superfusion with L-glutamate, L-aspartate, kainate and quisqualate with a transient depolarization and reduction of the light evoked responses. However, in isolated retina preparations, in which these substances were applied to the photoreceptor side of the retina, the effects were sustained as long as the agonists were present. These results suggest that the transient action of these agonists in eyecup preparations was due to the rapid development of an intraretinal diffusion barrier, and are consistent with the hypothesis that photoreceptors release an excitatory amino acid transmitter.


Treatment of neovascular age-related macular degeneration with intravitreal bevacizumab: efficacy of three consecutive monthly injections.
To report the efficacy of treatment of neovascular age-related macular degeneration (AMD) with intravitreal bevacizumab (Avastin; Genentech, Inc, South San Francisco, California, USA) when administered in a series of three monthly injections followed by a period of observation. Retrospective case series. Retrospective review of consecutive eyes with all choroidal neovascular lesion subtypes resulting from neovascular AMD treated with intravitreal bevacizumab. Treatment consisted of a pars plana injection of 1.25 mg Avastin (0.05 ml bevacizumab at a concentration of 25 mg/ml). Evaluation consisted of a complete ophthalmologic examination, including best-corrected visual acuity (VA) measurement, ophthalmoscopy, and optical coherence tomography. Eyes received a series of three monthly injections followed by a three-month period of observation. A total of 36 patients (37 eyes) received a series of three consecutive monthly intravitreal injections of bevacizumab. Twenty (54%) of 37 eyes had no previous treatments for neovascular AMD in the eye that received bevacizumab. Seventeen (46%) of 37 eyes had received some previous treatment before initiation of bevacizumab therapy. Intravitreal Avastin therapy produced an improvement in foveal thickness over time in eyes with neovascular AMD. This improvement was sustained during the series of three monthly injections. All eyes experienced worsening after three months without treatment. No statistically significant effect on VA was demonstrated in this series. Intravitreal bevacizumab therapy produced an improvement in foveal thickness over time in eyes with neovascular AMD when one injection was given each month for three consecutive months. All eyes experienced increased foveal thickening during the subsequent three months without treatment.


New dimensions: the dietitian in private practice.
Private practice is coming to the fore in the profession of dietetics. It can serve as a much needed arm of the health care delivery system in the area of nutrition. Institutions need to re-evaluate and expand their opportunities to sue private practioners, thus releasing more employee time for short-term remedial counseling and education. Referral processes need to be designed and implemented to open new opportunities for consumers to choose and obtain continuing services. Private practice must be included in funding methods, such as third-party payment. Educationl institutions must design programs to prepare persons for private practice. The profession must solve the problem of obtaining community recognition of properly qualified professional authority. The profession must also support the concept of a lifetime career in direct private practice and plan career tracks to keep the most able practioners available to consumers.


Axonal transport of muscarinic receptors in vesicles containing noradrenaline and dopamine-beta-hydroxylase.
Presynaptic muscarinic receptors labeled with [3H]dexetimide and noradrenaline in dog splenic nerves accumulated proximally to a ligature at the same rate of axonal transport. After fractionation by differential centrifugation, specific [3H]quinuclidinyl benzilate or [3H]dexetimide binding revealed a distribution profile similar to that of dopamine-beta-hydroxylase and noradrenaline. Subfractionation by density gradient centrifugation showed two peaks of muscarinic receptors; the peak of density 1.17 contained noradrenaline and dopamine-beta-hydroxylase whereas that of density 1.14 was devoid of noradrenaline. Therefore the foregoing experiments provide evidence that presynaptic muscarinic receptors are transported in sympathetic nerves in synaptic vesicles which are similar to those containing noradrenaline and dopamine-beta-hydroxylase. This suggests a possible coexistence of receptor and neurotransmitter in the same vesicle.


Reproducibility of breath hydrogen concentration measurements in dogs after change of diet.
To assess reproducibility of breath hydrogen (H2) concentration measurements in dogs on 3 consecutive days after introduction of a new diet. 10 healthy colony-source dogs. Procedure Dogs were fed a commercial pet food for a minimum of 10 days before introduction of a high-carbohydrate commercial diet. Expired breath samples were collected at baseline and every 90 minutes for 18 hours on the first 3 days after introduction of the new diet. The area under the curve (AUC) for breath H2 concentration versus time on days 1, 2, and 3 were compared by use of repeated-measures ANOVA. The (AUC) did not differ significantly among test days 1, 2, and 3. Expired breath H2 concentration in dogs indicated good reproducibility during the first 3 days after introduction of a new diet. It is not necessary to provide a period for adaptation to a test diet prior to performing breath H2 tests in dogs.


A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis.
One hundred fifty-one patients with primary biliary cirrhosis (PBC) grouped into four strata based on entry serum bilirubin ( < 2 mg/dL vs. 2 md/dL or greater) and liver histology (stages I, II vs. stages III, IV-Ludwig criteria) were randomized within each stratum to ursodiol or placebo given in a single dose of 10 to 12 mg/kg at bedtime for 2 years. Placebo- (n = 74) and ursodiol- treated (n = 77) patients were well matched at baseline for demographic and prognostic factors. Ursodiol induced major improvements in biochemical tests of the liver in strata 1 and 2 (entry bilirubin < 2), but had less effect on laboratory tests in patients with entry serum bilirubin of > or +2 (strata 3 and 4). Histology was favorably affected by ursodiol in patients in strata 1 and 2 but not in strata 3 and 4. Ursodiol enrichment in fasting bile obtained at the conclusion of the trail was approximately 40% and comparable in all strata. Thus, differences in ursodiol enrichment of the bile acid pool do not explain better responses of laboratory tests and histology found in patients with less advanced PBC. Patients treated will ursodiol tended to develop a treatment failure less frequently that those who received placebo, particularly in strata 1 and 2 (ursodiol 42%, placebo 60%, P = .078). Development of severe symptoms (fatigue/pruritus) and doubling of serum bilirubin were reduced significantly in ursodiol-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)


About canonical, non-canonical and immunogenic cell death: Basic mechanisms and translational applications: A meeting report of the International Cell Death Society.
International Cell Death Society held its 25th meeting, entitled "About canonical, non-canonical, and immunogenic cell death: basic mechanisms and translational applications" in Seoul, South Korea, May 31-June 2, 2018, addressed the most current issues in the field. Now that many types and pathways of cell death are recognized, attention has turned to how the threshold to death is maintained or surpassed, and how and what intracellular signals control the process. Most of the speakers addressed these topics, focusing on mitochondria and on new high-resolution techniques that promise to answer current questions.


Identification of cell-surface markers for detecting breast cancer cells in ovarian tissue.
The safety of ovarian tissue autotransplantation in oncology patients cannot be ensured, as current tumor-detection methods compromise the ovarian tissue viability. Although non-destructive methods (for instance near-infrared fluorescence imaging) can discriminate malignant from healthy tissues while leaving the examined tissues unaffected, they require specific cell-surface tumor markers. We determined which tumor markers are suitable targets for tumor-specific imaging to exclude the presence of breast cancer cells in ovarian tissue. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded specimens of ten ovaries from premenopausal patients. Additionally, we screened a tissue microarray containing tumor tissue cores from 24 breast cancer patients being eligible for ovarian tissue cryopreservation. The following cell-surface tumor markers were tested: E-cadherin, EMA (epithelial membrane antigen), Her2/neu (human epidermal growth factor receptor type 2), αvβ6 integrin, EpCAM (epithelial cell adhesion molecule), CEA (carcinoembryonic antigen), FR-α (folate receptor-alpha), and uPAR (urokinase-type plasminogen activator receptor). For each tumor, the percentage of positive breast tumor cells was measured. None of the ten ovaries were positive for any of the markers tested. However, all markers (except CEA and uPAR) were present on epithelial cells of inclusion cysts. E-cadherin was present in the majority of breast tumors: ≥90 % of tumor cells were positive for E-cadherin in 17 out of 24 tumors, and 100 % of tumor cells were positive in 5 out of 24 tumors. Of the markers tested, E-cadherin is the most suitable marker for a tumor-specific probe in ovarian tissue. Methods are required to distinguish inclusion cysts from breast tumor cells.


The use of Light Green and Orange II as quantitative protein stains, and their combination with the Feulgen method for the simultaneous determination of protein and DNA.
The protein dyes Light Green and Orange II were studied separately and in combination with the Feulgen-Pararosanilin(SO2) and -Thionin(SO2) method for the simultaneous determination of DNA and protein. - With polyacrylamide modelfilms the pH dependency, specificity and stoichiometry of Light Green and Orange II have been investigated. The results of both staining methods with different biological objects have been compared. - In addition, the Feulgen-Thionin(SO2) method was studied with model films with respect to its specificity and stoichiometry. In biological objects it has been compared with the Feulgen-Pararosanilin(SO2) method. - When combining the Light Green staining with the Feulgen-Pararosanilin(SO2) procedure and the Orange II staining with Feulgen-Thionin(SO2), both Feulgen-DNA stainings, which were first applied, proved to be unaffected by the following protein staining procedure. When the Feulgen procedure was carried out without the dye, followed by Light Green staining, the latter became reduced when a sulfite water rinse was included but was unaffected when a running tap water rinse was used. In the case of the Orange II staining a serious reduction in dye binding capacity was found in both situations. - When the Feulgen-Pararosanilin(SO2) Light Green procedure was carried out on isolated nuclei with all dyes present, a decrease of protein dye binding was observed, similar to that found with the well-known Feulgen-Pararosanilin(SO2) Naphthol Yellow S combination. It is concluded that in spite of this reduction the latter two combinations can be used for the cytophotometric analysis of DNA and protein in the same object.


Dentatorubropallidoluysian degeneration: clinical, neuro-ophthalmologic, biochemical, and pathologic studies on autosomal dominant form.
Four cases in two generations of a Japanese family are described as affected by an autosomal dominant-inherited cerebellar ataxia, pyramidal and extrapyramidal signs, and abnormal ocular movements, resembling Machado-Joseph disease. The neuro-ophthalmologic examination suggests the involvement of multiple motor control systems. The neuropathologic examination of one case showed neuronal loss in the subthalamic nuclei, pallidum, dentate nuclei of cerebellum, and red nuclei, which is distinct from Machado-Joseph disease.


Outcomes Impacting Quality of Life in Advanced Parkinson's Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel.
It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson's disease (PD), and that improvements in these metrics are correlated. Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms. This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms. A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC = 0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p < 0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC = 0.42), sleep (0.54), and daytime sleepiness (0.40; all p < 0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC = 0.23; p = 0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time.


Comparative effects of arginine and other amino acid deprivation on in vitro expression of lymphocyte activation markers.
Enteral or parenteral arginine supplementation enhances lymphocyte activation after mitogenic stimulation, in rats and humans. Arginine deprivation in culture media is associated with a reduction of lymphocyte activation; this effect, however, has not yet been proven to be specific for arginine. This study was designed to evaluate the specificity of arginine deprivation from culture media on the reduction of in vitro lymphocyte activation. Peripheral blood mononuclear cells, obtained from 11 healthy volunteers, were cultured in RPMI 1640, selectively deprived of single amino acids (i.e. arginine, phenylalanine, leucine, methionine, and threonine) and supplemented with phytohemagglutinin (PHA). The expression of interleukin-2 receptor and transferrin receptor was evaluated by cytometric analysis; the levels of soluble IL-2 receptor were determined by immuno-enzymatic assay. Results were compared with those obtained by culturing cells in non-deprived, RPMI 1640 medium. The expression of transferrin and IL-2 receptor, as well as the levels of IL-2 soluble receptor, were significantly reduced in all deprived media irrespective of the lacking amino acid. These results suggest that the reduction of in vitro lymphocyte activation is not an arginine specific effect. Therefore, the known enhancement of immune response, following arginine supplementation in vivo, is likely to involve a more complex series of events.


The effects of subtotal pancreatectomy on renal growth in streptozotocin diabetic rats.
Increases in kidney size and function are characteristic features of the early stages of Type I diabetes mellitus, and may contribute to the pathogenesis of diabetic nephropathy. Other studies have shown that the relative circulating concentrations of insulin and glucagon may be regulatory to renal growth and function. In order to elucidate the role of pancreatic glucagon in diabetic renal growth, subtotal pancreatectomy was performed prior to administration of streptozotocin to rats. Glycosuria and kidney weight were significantly reduced by subtotal pancreatectomy, although creatinine clearance and blood glucose levels were not different from diabetic controls. These data suggest that hyperglucagonemia may be an important mediator of renal growth in insulinopenic diabetes mellitus.


The introduction of fox rabies into Italy (2008-2011) was due to two viral genetic groups with distinct phylogeographic patterns.
Fox rabies re-emerged in north-eastern Italy at the end of 2008 and circulated until early 2011. As with previous rabies epidemics, the Italian cases were linked to the epidemiological situation in adjacent regions. To obtain a comprehensive picture of the dynamics of the recent Italian epidemic, we performed a detailed evolutionary analysis of RABVs circulating in north-eastern Italy. Sequences were obtained for the hyper-variable region of the nucleoprotein gene, the complete glycoprotein gene, and the intergenic region G-L from 113 selected fox rabies cases. We identified two viral genetic groups, here referred to as Italy-1 and Italy-2. Phylogenetic and phylogeographic analyses revealed that both groups had been circulating in the Western Balkans and Slovenia in previous years and were only later introduced into Italy (into the Friuli Venezia Giulia region-FVG), occupying different areas of the Italian territories. Notably, viruses belonging to the Italy-1 group remained confined to the region of introduction and their spread was minimised by the implementation of oral fox vaccination campaigns. In contrast, Italy-2 viruses spread westward over a territory of 100 km from their first identification in FVG, likely crossing the northern territories where surveillance was inadequate. A genetic sub-group (Italy-2A), characterised by a unique amino acid mutation (D106A) in the N gene, was also observed to occupy a distinct geographic cluster. This molecular epidemiological analysis of the 2008-2011 fox rabies epidemic will contribute to future control programmes both at national and regional levels. In particular, our findings highlight the weaknesses of the national surveillance strategy in the period preceding rabies re-emergence, and of control plans implemented immediately after rabies notification, and underline the need of a coordinated approach at the regional level for both the surveillance and control of wildlife rabies.


Gene polymorphisms that can predict response to anti-TNF therapy in patients with psoriasis and related autoimmune diseases.
Psoriasis (Ps) is a chronic inflammatory disease with an important genetic component. It shares pathophysiological mechanisms with other autoimmune diseases such as psoriatic arthritis (PsA), rheumatoid arthritis (RA) and Crohn's disease (CD). These conditions can be treated using biological drugs such as infliximab, adalimumab and etanercept, which selectively block the proinflammatory cytokine tumor necrosis factor (TNF)-α. Although these agents have greatly improved the prognosis of Ps, PsA, RA and CD, they do not cure the disease and are expensive; in addition, significant proportions of patients do not respond or develop serious adverse effects. Therefore, it is important to investigate biomarkers, such as gene polymorphisms, that can predict which patients will respond best to a specific drug. Some polymorphisms in genes TNF, TNF receptor superfamily 1B (TNFR1B) and TNFα-induced protein 3 gene (TNFAIP3) have been associated with response to anti-TNF therapy in patients with Ps. The present article reviews other polymorphisms that could also play a role in prediction of response to these treatments.


Rat hippocampal slice culture models for the evaluation of neuroprotective agents.
Organotypic slices cultured for weeks in vitro represent an extremely valuable strategy for the investigation of the long-term properties of neuronal circuits under physiological and pathological conditions. Here, we describe how to prepare rat organotypic hippocampal slice cultures and how to expose them for appropriate periods of time to excitotoxic agents or to oxygen and glucose deprivation conditions, in order to mimic the pattern of pyramidal cell damage which is observed in vivo and in other in vitro models. This preparation is very useful not only to study synaptic plasticity or the pathways and mechanisms of neurodegeneration but also to evaluate the effects of neuroprotective agents.


MicroRNA-326-5p enhances therapeutic potential of endothelial progenitor cells for myocardial infarction.
Our study sought to investigate the therapeutic effects and mechanisms of miR-326-5p-overexpressing endothelial progenitor cells (EPCs) on acute myocardial infarction (AMI). Mouse EPCs were isolated, purified, and identified by flow cytometry and uptake of DiI-ac-LDL. The target gene of miR-326-5p was predicted using target prediction algorithms and verified by dual-luciferase reporter assay, RT-qPCR, and Western blot. After EPCs were transfected with the agomir or antagomir of miR-326-5p, tube formation assay and Matrigel plug angiogenesis assay were conducted in four groups (NC, miR-326-5p agomir, miR-326-5p antagomir, and miR-326-5p agomir+Wnt1 agonist). In addition, a mouse model of MI was established and treated with the injection of miR-326-5p-EPCs, miR-326-5p-EPCs+ Wnt1 agonist, EPCs-NC, or PBS/control into the peri-infarcted myocardium. Subsequently, cardiac function was monitored by echocardiography at 7 and 28 days postoperatively. Finally, the infarcted hearts were collected at 28 days, and the size of myocardial infarction was measured by Masson's trichrome staining and the neovascularization in the peri-infarcted area was examined through immunofluorescence staining. Luciferase reporter assay indicated that Wnt1 was a direct target of miR-326-5p. Using RT-qPCR and Western blot analysis, we further demonstrated that the expression level of Wnt1 was negatively correlated with miR-326-5p expression in EPCs. Both in vitro study of tube formation assay and in vivo investigation of subcutaneous Matrigel plug assay revealed that the miR-326-5p agomir could significantly enhance the angiogenic capacity of EPCs, and this effect was partially inhibited by Wnt1 agonist. Meanwhile, miR-326-5p antagomir could obviously reduce the the angiogenic capacity of EPCs in vivo compared with that in the NC group. Moreover, the transplantation of miR-326-5p-overexpressing EPCs in the ischemic hearts of mice significantly enhanced the angiogenesis in the peri-infarcted zone and improved the cardiac function. However, the enhanced capacity of angiogenesis of miR-326-5p-overexpressing EPCs was remarkably neutralized by Wnt1 agonist, accompanied by the decreased improvement in cardiac function. miR-326-5p significantly enhanced the angiogenic capacity of EPCs. Transplantation of miR-326-5p-overexpressing EPCs improved cardiac function for AMI therapy, which can be a novel strategy for enhancing therapeutic angiogenesis in ischemic heart diseases.


Various autogenous fresh demineralized tooth forms for alveolar socket preservation in anterior tooth extraction sites: a series of 4 cases.
The aim of this study was to evaluate the clinical relevance of autogenous fresh demineralized tooth (Auto-FDT) prepared at chairside immediately after extraction for socket preservation. Teeth were processed to graft materials in block, chip, or powder types immediately after extraction. Extraction sockets were filled with these materials and dental implants were installed immediately or after a delay. A panoramic radiograph and a conebeam CT were taken. In two cases, tissue samples were taken for histologic examination. Vertical and horizontal maintenance of alveolar sockets showed some variance depending on the Auto-FDT and barrier membrane types used. Radiographs showed good bony healing. Histologic sections showed that it guided good new bone formation and resorption pattern of the Auto-FDT. This case series shows that Auto-FDT prepared at chairside could be a good material for the preservation of extraction sockets. This study will suggest the possibility of recycling autogenous tooth after immediate extraction.


Somatotype and size of elite female basketball players.
The aim of this study was to compare the somatotype and size of elite female basketball players in terms of playing position and team performance. Anthropometry and somatotype data were collected on 168 players from 14 countries before the Women's World Basketball Championship, Australia, 1994. There were 64 guards (mean +/- s: age 25.4 +/- 3.3 years, height 1.72 +/- 0.06 m, mass 66.1 +/- 6.2 kg, somatotype = 2.9-3.9-2.6), 57 forwards (age 25.2 +/- 3.8 years, height 1.81 +/- 0.06 m, mass 73.3 +/- 5.9 kg, somatotype = 2.8-3.5-3.2) and 47 centres (age 24.1 +/- 3.1 years, height 1.90 +/- 0.06 m, mass 82.6 +/- 8.2 kg, somatotype = 3.2-3.1-3.4). Mean somatotypes by position were significantly different (F = 7.73, P < 0.01). Guards had greater mesomorphy than centres and less ectomorphy than forwards and centres. When discriminant function analysis was applied to endomorphy, mesomorphy, ectomorphy, age, height and mass, only height, mass and ectomorphy entered (Wilks' lambda = 0.351, F = 31.40, P < 0.000), 70% of the variance was accounted for, and 72% of players were correctly classified. In the four top versus four bottom teams, guards were taller and more ectomorphic, forwards were taller, with lower mesomorphy and higher ectomorphy, and centres did not differ. Thus there are some differences in somatotypes by position and team placing, but the combination of height, mass and ectomorphy provide the best differentiation by position.


Separation and characterization of products resulting from the reaction of cis-diamminedichloroplatinum (II) with deoxyribonucleosides.
The cancer chemotherapeutic drug cis-diamminedichloroplatinum (II) (cis-DDP) was reacted with deoxyribonucleosides, and the products were separated by high-pressure liquid chromatography and characterized by 1H nuclear magnetic resonance. Monofunctional platination occurred at N(3) of cytidine, N(7) of guanosine, N(1) of adenosine, and N(7) of adenosine. Bifunctional platination occurred with guanosine N(7) to N(7), adenosine N(7) to N(7), and adenosine N(1) to N(7). In addition, mixed bifunctional products N(7) of guanosine-N(1) of adenosine and N(7) of guanosine-N(7) of adenosine were obtained. No bifunctional adducts were obtained that contained cytidine, presumably due to steric hindrance as trans-DDP did cross-link two cytidine residues. Similarly, no adenosine N(1) to N(1) was detected with cis-DDP. The only other products detected were obtained at high levels of cis-DDP and probably represented polymeric forms in which platinum chelates to itself.


Experience of adult patients and professionals with a program for the prevention of alcohol withdrawal delirium in the acute care setting-A case study.
To investigate the experiences of adult patients and professionals with the prevention of alcohol withdrawal delirium program DESIGN AND METHODS: A simple, descriptive case study with several units of analysis was chosen as the study design. Six patients, 15 nurses, one family member, and two physicians METHODS: Semi-structured interviews and observation sessions. The Braun and Clarke thematic analysis method was used for the data analysis. Three main themes were identified: "Talking about alcohol," "Monitoring withdrawal symptoms," and "Collaboration with the Advanced Practice Nurse for delirium management." The program is highly beneficial in this field of practice and is widely accepted by all those involved. The Advanced Practice Nurse played an important role to facilitate the processes.


Complex cytogenetic aberrations in a well-differentiated chondrosarcoma.
The cytogenetic analysis of a well-differentiated (grade I) chondrosarcoma is presented. Despite a low-grade histopathology, metaphase preparations of tumor cells were characterized by numerous structural chromosome aberrations and a striking degree of genetic instability; the t(9;22)(q31;q12) that has been described recently in extraskeletal myxoid chondrosarcoma was not observed. This report suggests that chondrosarcomas may be heterogeneous cytogenetically. In chondrosarcoma, it appears that "high-grade" cytogenetic abnormalities do not necessarily engender a high-grade histology. These findings offer a possible explanation for the clinical aggressiveness of certain low-grade chondrosarcomas.


Identification and management of patients with hypertension in the polyclinic system of the Russian Federation.
Cardiovascular diseases, including hypertension and type 2 diabetes mellitus, are the major determinants of poor health in the Russian Federation. This study assessed the feasibility of establishing a program to identify and manage hypertension and associated cardiovascular risk factors in an outpatient clinic within the Russian polyclinic system. In urban polyclinic in Kazan, Tatarstan, which is responsible for 77,000 covered lives, we enrolled 192 patients with hypertension of whom 68 had type 2 diabetes mellitus screened from various clinics within the polyclinic. After collection of baseline data, patients were treated for hypertension and those risk factors amenable to pharmaceutic intervention and counseled on those that required behavior modification. Baseline blood pressure was 173.9+/-20.7/104.2+/-15.3 mm Hg in those with hypertension only (n=124) and 172.9+/-26.0/97.9+/-16.4 mm Hg in those with both hypertension and type 2 diabetes mellitus. More than 80% of the entire group had a body mass index >25 kg/m2 and left ventricular hypertrophy. Nearly 70% had total cholesterol >5.2 mmol/L. Of the diabetics, more than 50% had glycosylated hemoglobin (HbA1c)>or=8%. Less than 10% of this self-selected population smoked. Blood pressure decreased modestly, but significantly, in both groups of patients. There were no significant changes in obesity, cholesterol, smoking, or HbA1c in the diabetics. Identification, recruitment, management, and follow-up of patients with chronic disorders is feasible within the Russian polyclinic system. However, to have a more profound effect on risk factor profiles, a wider effort is needed than one restricted to the clinic itself.


[HPLC Specific Fingerprint of Alcohol Extract of Andrographis paniculata].
To establish the specific fingerprint of alcohol extract of Andrographis paniculata by HPLC. The analysis was performed on Cosmosil 5C18 -MS-II (250 mm x 4. 6 mm, 5 µm) column, with gradient phase consisting of acetonitrile and water at the flow rate of 1. 0 mL/min. The UV detection wavelength was set at 225 nm, and column temperature was 30 °C. The specific fingerprint chromatogram was established and seven common peaks were identified by comparison with the reference standards and LC-MS. The relative retention times were 1. 00 (No. 1, andrographolide), 1. 04 (No. 2, deoxyandrographoside), 1. 07 (No. 3, isoandrographolide), 1. 10 (No. 4, 14-deoxy-11, 12-didehydroandrographoside), 1. 50 (No. 5, neoandrographolide), 1. 75 ( No. 6, deoxyandrographolide) and 1. 79 (No. 7, dehydroandrographolide). The method is simple and reproducible with high precision, which can provide the basis for the quality control and evaluation of alcohol extract of Andrographis paniculata and its preparations.


The accumulation of elements in plants growing spontaneously on small heaps left by the historical Zn-Pb ore mining.
The study evaluated the levels of nine metals, namely Ca, Cd, Fe, K, Mg, Mn, Pb, Tl, and Zn, in soils and tissues of ten plant species growing spontaneously on heaps left by historical mining for Zn-Pb ores. The concentrations of Cd, Pb, Tl, and Zn in heap soils were much higher than in control soils. Plants growing on heaps accumulated excessive amounts of these elements in tissues, on average 1.3-52 mg Cd kg(-1), 9.4-254 mg Pb kg(-1), 0.06-23 mg Tl kg(-1) and 134-1479 mg Zn kg(-1) in comparison to 0.5-1.1 mg Cd kg(-1), 2.1-11 mg Pb kg(-1), 0.02-0.06 mg Tl kg(-1), and 23-124 mg Zn kg(-1) in control plants. The highest concentrations of Cd, Pb, and Zn were found in the roots of Euphorbia cyparissias, Fragaria vesca, and Potentilla arenaria, and Tl in Plantago lanceolata. Many species growing on heaps were enriched in K and Mg, and depleted in Ca, Fe, and Mn. The concentrations of all elements in plant tissues were dependent on species, organ (root vs. shoot), and species-organ interactions. Average concentrations of Ca, K, and Mg were generally higher in shoots than in roots or similar in the two organs, whereas Cd, Fe, Pb, Tl, and Zn were accumulated predominantly in the roots. Our results imply that heaps left by historical mining for Zn-Pb ores may pose a potential threat to the environment and human health.


Nannochloropsis sp. biomass recovery by Electro-Coagulation for biodiesel and pigment production.
Biofuel production from microalgal biomass could be an alternative solution to conventional biofuels typically dependent on food and high land/water demanding crops. However, the economic and energetic viability of microalgal biofuels is limited by their harvesting processes. The finding of innovative, low cost and efficient harvesting method(s) is imperative. In this study, the Electro-Coagulation (EC) was studied as a process to harvest the marine Nannochloropsis sp. microalga. Several EC operational conditions were studied and the best EC recovery efficiency (>97%) was achieved using a current density of 8.3 mA cm(-2) for 10 min. The quality of the recovered microalgal biomass was evaluated in terms of total lipids, fatty acid and pigment profile where no significant differences were observed after EC treatment. The energy requirements of the harvesting process were estimated and the combination of EC and centrifugation processes proved to decrease significantly the energy demand when compared with the individual process.


Normoxic accumulation of HIF1α is associated with glutaminolysis.
The stabilization of the transcription factor and prognostic tumor marker hypoxia-inducible factor 1α (HIF1α) is considered to be crucial for cellular metabolic adaptations to hypoxia. However, HIF1α has also been shown to accumulate under normoxic conditions, although this phenomenon is poorly understood. We investigated the conditions for normoxic HIF1α stabilization in different tumor cell lines (e.g., two mammary carcinoma cell lines and three oral squamous cell carcinoma cell lines) via Western blot analysis or immunohistochemical staining. The transcriptional activity of HIF1 was demonstrated by analyzing the messenger RNA (mRNA) expression of the HIF1 target carbonic anhydrase 9 (CA9) via PCR. Our data demonstrate that the combined incubation of tumor cells with glutamine and growth factors (e.g., EGF, insulin, and serum) mediates the normoxic accumulation of HIF1α in vitro. Consequently, the inhibition of glutaminolysis by a glutaminase inhibitor blocked the normoxic accumulation of HIF1α. Additionally, the normoxic HIF1α protein displayed nuclear translocation and transcriptional activity, which was confirmed by the induction of CA9 mRNA expression. Furthermore, the normoxic accumulation of HIF1α was associated with impaired proliferation of tumor cells. Finally, ammonia, the toxic waste product of glutaminolysis, induced a normoxic accumulation of HIF1α to the same extent as glutamine. Our study suggests that HIF1α is involved in the regulation of glutamine metabolism and the cellular levels of the toxic metabolic waste product ammonia under normoxia. Hence, our results, together with data presented in the literature, support the hypothesis that HIF1α and its target genes play a crucial role in metabolic pathways, such as glutaminolysis and glycolysis, under both hypoxic and normoxic conditions. Therefore, the inhibition of HIF1α (and/or HIF1α target genes) could emerge as a promising therapeutic approach that would result in the accumulation of toxic metabolic waste products in tumor cells as well as the reduction of their nutrition and energy supply.


Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents.
Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4+/- mice (hyperglycemic and hyperinsulinemic mice). Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4+/- mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions. In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D.