Determination of absorption and scattering coefficients for nonhomogeneous media. 2: experiment.
Separation of the scattering contribution from the total optical attenuation is necessary to determine the absorption portion of nonhomogeneous media such as naturally occurring minerals. In order to investigate experimentally the applicability of a previously developed two-flux radiative transfer model that takes into account surface reflections and collimated incidence, we have measured pulverized and sintered scattering standards prepared from a glass of known absorption coefficient variation. The new model produces an accuracy improvement up to a factor of 2.5 over the Kubelka-Munk theory. Off-axis scattering measurements were made with improved instrumentation between 0.33 microm and 2.7 microm. The model was then applied to the mineral rhodochrosite in this range to obtain accurate values of scattering and absorption.


Mortality after hip resurfacing versus total hip arthroplasty in young patients: a single surgeon experience.
The aims of this study were to investigate the following questions: (I) what are the mortality rates in patients age 55 years and younger who underwent a hip resurfacing arthroplasty (HRA) versus a standard total hip arthroplasty (THA)? (II) is the type of operation independently associated with mortality? The database of a single high-volume surgeon was reviewed for patient's age 55 years and younger who underwent a hip arthroplasty between 2002 and 2010. This yielded 505 HRA patients and 124 THA patients. Chi-square analysis was performed to identify a 5-year mortality rate difference between the two cohorts. Multivariable Cox-Regression analyses were used to determine whether the type of operation was independently associated with mortality. There were 8 mortalities (1.6%) in the HRA cohort and 11 (8.9%) in the THA cohort, a statistically significant difference (P<0.001) on univariate analysis. Low mortality rates produced underpowered multivariate models. We have demonstrated that patients age 55 and younger who undergo HRA have a significantly lower mortality rate than those undergoing THA. This is consistent with multiple previously published large database studies.


Synchronous papillary thyroid carcinoma and breast ductal carcinoma.
A 48-year-old woman was admitted to our hospital with a lump in her left breast. She was diagnosed with synchronous papillary thyroid carcinoma and breast ductal carcinoma. The patient underwent four cycles of neoadjuvant chemotherapy with epirubicin and cyclophosphamide, and one cycle of docetaxel. She then underwent left breast mastectomy and radical resection of thyroid cancer (total thyroidectomy and bilateral central group [levels VI and VII] lymph node dissection) at the same time. She was administered three cycles of chemotherapy with docetaxel and radiotherapy. The patient had no metastasis in the follow-up period. A literature search was performed to characterize the epidemiology, etiology, management, and prognosis of this condition. We speculate that hormone treatment could be a probable pathogenesis of synchronous breast and thyroid cancers.


[How safe is laparoscopic cholecystectomy?].
Laparoscopic cholecystectomy (LCE) is the standard treatment for symptomatic non-complicated cholecystolithiasis. However, there is still an ongoing debate about the appropriate surgical approach in cases with complicated cholecystolithiasis. As a result, an initial decision whether to use the open or laparoscopic approach must be primarily based on patient safety. Additional indications favouring the use of LCE must not lead to an increase in the rate of serious complications. All patients who underwent operations for cholecystolithiasis performed in a single surgical centre, from 1 / 1 / 1994 to 12 / 31 / 2007, were considered in this analysis. Parameters for the characterisation of the results were intervention-associated hospital mortality and iatrogenic transsection of the common bile duct. 5 084 cholecystectomies were performed during the study period, 84 % (n = 4 272) intended as laparoscopic and 16 % (n = 812) as open procedures. The LCE operations were done by 36 surgeons. The conversion rate to open surgery was 6.2 % (n = 265), in cases of acute cholecystitis, however, it was 26.3 % (n = 86). One LCE procedure involved an iatrogenic bile duct transsection (0.02 %). The in-hospital mortality rate for LCE was 0.05 % (n = 2). In the hands of experienced surgeons LCE is a safe procedure for the treatment of symptomatic, non-complicated cholecystolithiasis. Associated with complicated cholecystolithiasis however are an increase in conversion rate and thus the risk of severe complications.


Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation.
In chronic lymphocytic leukemia (CLL), clonal rearrangement of the immunoglobulin heavy chain locus (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. At the time of initial presentation, DNA from patients with CLL was polymerase chain reaction (PCR)-amplified using consensus Variable (VH) and Joining (JH) region primers using complementarity determining region III consensus region primers or a panel of VH family-specific framework region 1 (FR1) primers. The clonal product was directly sequenced and patient-specific probes constructed using N region nucleotide sequences. We amplified and sequenced the CDRIII region and designed patient specific oligonucleotide probes for the detection of MRD in 55 of 66 patients (84%, 90% Confidence Intervals (CI): 74% to 90%) with poor prognosis CLL referred for autologous and allogeneic bone marrow transplantation (BMT). To determine the clinical utility of this technique, PCR amplification was performed on patient samples at the time of and following autologous (21 patients) and allogeneic (10 patients) BMT in whom serial bone marrow samples obtained after BMT were available for analysis. We show that the persistence of MRD after BMT is associated with increased probability of relapse. In all cases that have relapsed to date, the IgH CDRII region was identical at the time of initial presentation and at relapse suggesting that clonal evolution of the IgH locus is unusual in this disease. The finding that a significant number of patients remain disease free and with no evidence of PCR-detectable MRD after BMT suggests that high-dose therapy may contribute to improved outcome in selected patients with CLL.


Involvement of protein synthesis and degradation in long-term potentiation of Schaffer collateral CA1 synapses.
Expression of synaptic plasticity involves the translation of mRNA into protein and, probably, active protein degradation via the proteasome pathway. Here, we report on the rapid activation of synthesis and degradation of a probe protein with the induction of long-term potentiation (LTP) in the hippocampal Schaffer collateral CA1 pathway. The proteasome inhibitor MG132 significantly reduced the field EPSP slope potentiation and LTP maintenance without acutely affecting basal synaptic transmission. To visualize protein dynamics, CA1 pyramidal cells of hippocampal slices were transfected with Semliki Forest virus particles expressing a recombinant RNA. This RNA contained the coding sequence for a degradable green fluorescence protein with a nuclear localization signal (NLS-d1EGFP) followed by a 3'- untranslated region dendritic targeting sequence. NLS-d1EGFP fluorescence remained stable in the low-frequency test stimulation but increased with LTP induction in the cell body and in most dendritic compartments of CA1 neurons. Applying anisomycin, a protein synthesis inhibitor, caused NLS-d1EGFP levels to decline; a proteasome inhibitor MG132 reversed this effect. In the presence of anisomycin, LTP induction accelerated the degradation of NLS-d1EGFP. When both inhibitors were present, NLS-d1EGFP levels remained unaffected by LTP induction. Moreover, LTP-induced acceleration of NLS-d1EGFP synthesis was blocked by rapamycin, which is consistent with the involvement of dendritic mammalian target of rapamycin in LTP-triggered translational activity. Our results clearly demonstrate that LTP induction not only leads to a rapid increase in the rate of protein synthesis but also accelerates protein degradation via the proteasome system.


Contributions of unstirred-layer effects to apparent electrokinetic phenomena in the gall-bladder.
Passage of electric current across rabbit gall-bladder, which is preferentially permeable to cations, causes water flow towards the negative electrode, as expected for electroosmosis in a cation-selective membrane. Current passage also causes development of a "polarization potential difference", i.e. a transepithelial potential difference (p.d.) which transiently remains after cessation of current flow and decays back to zero with a half-time of 22 to 90 sec. The polarization p.d. is due to current-induced local changes of salt concentration in unstirred layers, mainly at the serosal face of the epithelium. These changes originate through the so-called transport-number effect. Calculation shows that much of the observed current-induced water flow represents an osmotic flow due to these local concentration changes, rather than representing true electroosmosis. By implication, a large component of streaming potentials in the gall-bladder is a boundary diffusion potential, owing to water flow producing local changes of salt concentration in unstirred layers.


Scintigraphic assessment of cardiac adrenergic innervation in patients with essential hypertension.
To assess the regional cardiac adrenergic innervation in patients with essential hypertension (EHT), simultaneous iodine-123 metaiodobenzylguanidine ([123I]MIBG) and thallium-201 (201Tl) myocardial imagings were performed in five patients with EHT, seven patients with hypertrophic cardiomyopathy (HCM), and seven normal subjects. Short axial images at rest were divided into five segments: anterior, septal, posterior, lateral, and apical segments. Percent regional uptake (%RU) of 201Tl except the septal segment in patients with EHT showed no significant difference. However, the %RU of [123I]MIBG at posterior, lateral, and apical segments was significantly lower than that at anterior and septal segments in EHT. This intraimage heterogeneity of [123I]MIBG was also observed in HCM. These results suggest that there is a difference in regional adrenergic innervation of the left ventricle with myocardial hypertrophy.


Stent graft treatment for abdominal aortic aneurysm repair: recent developments in therapy.
Minimally invasive endovascular techniques for the treatment of abdominal aortic aneurysms have significantly reduced the morbidity of these procedures compared with standard surgical repair. In addition, patients with extensive comorbid medical illnesses in whom standard operative repair is contraindicated may be successfully treated using endovascular means. Recently, several important developments have significantly advanced this area of treatment. The Food and Drug Administration has approved four endovascular stent grafts for the treatment of abdominal aortic aneurysms: the Medtronic AneuRx, the W.L. Gore Excluder, the Cook Zenith, and the Guidant Ancure. The Zenith received approval for marketing in 2003 and has gained relatively wide use, in part because of its ability to treat aneurysms with relatively large-diameter implantations zones. Also in 2003, Guidant Corporation withdrew the Ancure graft from marketing and distribution. The withdrawal was influenced by difficulties encountered using the graft's delivery system and improper reporting to the Food and Drug Administration. Enrollment has also been recently completed for the phase II Food and Drug Administration trials of the Medtronic Talent graft and the Cordis Fortron graft. These devices have been approved for use in the European Union and are awaiting Food and Drug Administration panel meeting in the United States. Several significant advances have also occurred recently in stent graft research and development. Of particular significance has been the initiation of the phase I trial of the Trivascular Enovus graft. Deployment of the Trivascular graft may be accomplished through a delivery system that is considerably reduced in profile. The potential for percutaneous application of the graft may be available in the future. In selecting the specific stent graft to be used for endovascular abdominal aortic aneurysm repair, the specific graft characteristics must be considered, particularly with regard to the individual patient's anatomic and physiologic characteristics. Comparative analysis of the several of the various stent grafts has been performed. Results have varied with regard to the need for secondary interventions, aneurysm sac size reduction, and the occurrence of continued perfusion of the aneurysm sac. In addition, the indications for use of endovascular grafts compared with standard open surgery have not yet been fully defined. This article describes the general principles of use for endovascular devices for the repair of abdominal aortic aneurysms. It details the features and results for the devices in current use, and highlights the recent developments in stent graft treatment of abdominal aortic aneurysms.


Glucocorticoids attenuate T cell receptor signaling.
Glucocorticoids (GCs) affect peripheral immune responses by inhibiting T cell immunity at several stages of the activation cascade, causing impaired cytokine production and effector function. The recent demonstration that the thymic epithelium and possibly thymocytes themselves produce steroids suggests that endogenous GCs also play a role in the control of T cell development. As both peripheral responsiveness and thymic differentiation appear to be regulated by the quantity and quality of intracellular signals issued by antigen-major histocompatibility complex-engaged T cell receptor (TCR) complexes, we investigated the effects of GCs on the signaling properties of T cells stimulated by anti-CD3 monoclonal antibodies or agonist peptides. We demonstrate in this work that dexamethasone, a synthetic GC, inhibits the early signaling events initiated upon TCR ligation, such as tyrosine phosphorylation of several TCR-associated substrates including the zeta chain, the ZAP70 kinase, and the transmembrane adapter molecule linker for activation of T cells. Hypophosphorylation was not a consequence of reduced kinase activity of src protein tyrosine kinases, but was correlated with an altered- membrane compartmentalization of these molecules. These observations indicate that in addition to their well-described ability to interfere with the transcription of molecules involved in peripheral responses, GCs inhibit T cell activation by affecting the early phosphorylating events induced after TCR ligation.


Luteolin suppresses cancer cell proliferation by targeting vaccinia-related kinase 1.
Uncontrolled proliferation, a major feature of cancer cells, is often triggered by the malfunction of cell cycle regulators such as protein kinases. Recently, cell cycle-related protein kinases have become attractive targets for anti-cancer therapy, because they play fundamental roles in cellular proliferation. However, the protein kinase-targeted drugs that have been developed so far do not show impressive clinical results and also display severe side effects; therefore, there is undoubtedly a need to investigate new drugs targeting other protein kinases that are critical in cell cycle progression. Vaccinia-related kinase 1 (VRK1) is a mitotic kinase that functions in cell cycle regulation by phosphorylating cell cycle-related substrates such as barrier-to-autointegration factor (BAF), histone H3, and the cAMP response element (CRE)-binding protein (CREB). In our study, we identified luteolin as the inhibitor of VRK1 by screening a small-molecule natural compound library. Here, we evaluated the efficacy of luteolin as a VRK1-targeted inhibitor for developing an effective anti-cancer strategy. We confirmed that luteolin significantly reduces VRK1-mediated phosphorylation of the cell cycle-related substrates BAF and histone H3, and directly interacts with the catalytic domain of VRK1. In addition, luteolin regulates cell cycle progression by modulating VRK1 activity, leading to the suppression of cancer cell proliferation and the induction of apoptosis. Therefore, our study suggests that luteolin-induced VRK1 inhibition may contribute to establish a novel cell cycle-targeted strategy for anti-cancer therapy.


A strategy for fabricating nanoporous gold films through chemical dealloying of electrochemically deposited Au-Sn alloys.
We report a novel strategy for the fabrication of nanoporous gold (NPG) films. The fabrication process involves the electrodeposition of a gold-tin alloy, followed by subsequent chemical dealloying of tin. Scanning electron microscopy (SEM) images show a bicontinuous nanoporous structure formed on the substrates after chemical dealloying. Energy dispersive x-ray (EDX) analysis indicates that there are no impurities in the Au-Sn alloy film with an average composition of 58 at. % Au and 42 at. % Sn. After dealloying, only gold remains in the NPG film indicating the effectiveness of this technique. X-ray diffraction (XRD) results reveal that the as-prepared Au-Sn alloy film is composed of two phases (Au5Sn and AuSn), while the NPG film is composed of a single phase (Au). We demonstrate that this approach enables the fabrication of NPG films, either freestanding or supported on various conductive substrates such as copper foil, stainless steel sheet and nickel foam. The resulting NPG electrode exhibits enhanced electrocatalytic activity toward both H2O2 reduction and methanol oxidation compared to the polished Au disc electrode. Our strategy provides a general method to fabricate high quality NPG films on conductive substrates, which will broaden the application potential of NPG or NPG-based materials in various fields such as catalysis, optics and sensor technology.


Lin28 and Imp are Required for Stability of Bowl Transcripts in Hub Cells of the Drosophila Testis.
Hub cells comprise a niche for germline stem cells and cyst stem cells in the Drosophila testis. Hub cells arise from common somatic gonadal precursors in embryos, but the mechanism of their specification is still poorly understood. Here we find that RNA binding proteins Lin28 and Imp mediate transcript stability of Bowl, a known hub specification factor; Bowl transcripts were reduced in the testis of Lin28 and Imp mutants, and also when RNA-mediated interference against Lin28 or Imp was expressed in hub cells. In tissue culture Luciferase assays involving the Bowl 3'UTR, stability of Luc reporter transcripts depended on the Bowl 3'UTR and required Lin28 and Imp. Our findings suggest that proper Bowl function during hub cell specification requires Lin28 and Imp in the testis hub cells.


Tumor necrosis factor-related apoptosis-inducing ligand induces cytotoxicity specific to osteosarcoma by microRNA response elements.
As the most common primary bone neoplasm, osteosarcoma is highly aggressive and represents a high risk to human health. Biological agents, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), are considered promising therapeutic strategies for osteosarcoma. The current issue limiting the application of TRAIL gene therapy is that normal cells are also affected due to the lack of tumor selectivity. The present study aimed to employ the miRNA response elements (MREs) of microRNA (miR)-34 and miR-122, which are tumor suppressors, to enable the selective expression of TRAIL by adenoviral vectors in osteosarcoma cells. The results revealed that miR-34 and miR-122 were underexpressed in osteosarcoma tissues, compared with normal tissues. The MREs of miR-34 and miR-122 ensured that the luciferase gene was expressed selectively in osteosarcoma cells. Adenovirus (Ad)-TRAIL-34-122, which expressed TRAIL in an miR-34 and miR-122-regulated manner, selectively expressed TRAIL in the osteosarcoma cells assessed, which was detected using reverse transcription quantitative polymerase chain reaction, immunoblotting and ELISA. Apoptosis and cytotoxicity were also detected in the osteosarcoma cells, compared with the normal cells. Animal experiments further indicated that Ad-TRAIL-34-122 was able to reduce the growth of osteosarcoma xenografts without toxicity to the liver. In conclusion, the present study identified a novel miRNA-regulated biological cancer therapy against osteosarcoma, which is tumor selective and may be promising for future clinical treatment.


Current perspectives on the perioperative management of the latex-allergic patient.
The increasing incidence of latex allergy necessitates thorough preanesthetic screening for risk factors, which will be delineated in this article, that are associated with latex allergy. The pathophysiology, epidemiology, and testing procedures for latex allergy will be reviewed. This case report will illustrate the management of a patient who was found to be latex-sensitive during surgery and the management of intraoperative anaphylaxis is provided. Safe perioperative care can be provided for latex-sensitive patients if latex avoidance techniques are used consistently.


Reproducibility of method and hormonal influences in induction of breast cancer in rats by gastric instillation of methylcholanthrene [abstract].
We have reported a high incidence and sex linkage of breast cancer in Wistar rats following gastric instillation of methylcholanthrene (J. Nat. Cancer Inst., 10:255, 1949, and 13:307, 1952). For this report, reproducibility of method and effects of estradiol and testosterone are evaluated in 103 male and 169 female rats which received methylcholanthrene 6 times a week throughout the experiments. The 169 female rats represent a pool of groups of 10 or more animals used as controls for experiments run during the past several years. Tumor incidence ranged from 73-100%, with a combined average of incidence 82%. The high incidence of pituitary tumors in both sexes treated with estradiol; the decrease in breast cancers in methylcholanthrene-treated females receiving testosterone or estradiol; and the incidence of breast cancers in both sexes receiving only estradiol permit speculation regarding the role of the pituitary gland in induction of breast cancer by methylcholanthrene in our experiments. The sharp drop in incidence of breast tumor in animals receiving methylcholanthrene and estradiol suggests involvement of a pituitary factor or factors in induction of breast tumors by methylcholanthrene; with the development of pituitary tumors in animals receiving estradiol, these factors may no longer be available. Estradiol-induced breast cancer in the rat may utilize a mechanism independent of the pituitary.


OPC-21268 antagonizes arginine vasopressin-induced vasoconstrictor response in the spinally-anesthetized dog.
We studied the antagonistic actions of OPC-21268 (1-(1-[4-(3-acetylaminopropoxy)-benzoyl]-4-piperidyl)-3,4-dihydro- 2(1H)-quinolinone) on the arginine vasopressin (AVP)-induced vasoconstrictor response in the spinally-anesthetized dog. OPC-21268 at doses of 0.3, 1.0 and 3.0 mg/kg, i.v. produced a rightward parallel shift of the dose-response curves for AVP in a dose-dependent manner. The doses of OPC-21268 were similar to those that inhibited the AVP-induced vasoconstrictor response in the rat. This observation suggests that OPC-21268 acts as a V1-AVP-receptor antagonist in peripheral resistance vessels in dogs as well as in rats.


Redox state and carbonic anhydrase isozyme IX expression in human renal cell carcinoma: biochemical and morphological investigations.
Clear renal cell carcinomas (RCC) frequently express carbonic anydrase IX (CA IX) because of non-functional mutation of von Hippel Lindau (VHL) tumor suppressor gene. CA IX is a tumor-associated transmembrane antigen, which catalyzes the extracellular, reversible hydration of carbon dioxide to bicarbonate and proton and thereby contributes to acidification of extracellular milieu. Extracellular acidic pH facilitates tumor growth and progression. CA IX expression is upregulated by Hypoxia Inducible Factor-1 (HIF-1), which is negatively controlled by oxygen via wild type VHL protein and is also regulated by the cell redox state. We investigated the immunohistochemical pattern of distribution of CA IX in a small series (14 cases) of RCCs. CA IX expression was matched with the redox state of RCC, stratifying our series in relation to clinical and histopathological parameters, such as Fuhrman grade, staging, proliferation markers expression, and particularly, the presence of necrosis. Our results show for the first time the existence of a perivascular pattern of CA IX distribution in RCC. We also found a significant relationship between CA IX expression and the presence of necrosis. Tumors with higher CA IX expression exhibited higher degree of necrosis (p < 0.05). Notably, an almost significant relationship between the redox state and CA IX expression was detected in RCC patients with 5 years disease-free survival, most of them showing organ-confined disease. Tumors with lower redox state showed an algebraically higher degree of CA IX expression. On the contrary, tumors with higher redox state exhibited an algebraically lower CA IX expression (p = 0.057). The observed relationship of CA IX expression and necrosis suggests a role for CA IX in RCC. Further investigations are necessary to further establish the role of the redox state in regulation of CA IX expression in RCC.


KNOWLEDGE ABOUT RISK AND PROTECTIVE MEASURES RELATED TO DIAGNOSTIC RADIATION AMONG MEDICAL STAFF IN TEACHING HOSPITALS (WASIT PROVINCE).
The aim: The goal of this research is to find out how much medical staff is acknowledged about radiation protection. Materials and methods: In Teaching Hospitals, Wasit Province, a questionnaire study in 165 medical personnel was conducted. Part 1 of the questionnaire included sociodemographic information such as age, gender, and employment, whereas part 2 included 16 knowledge-related questions, divided into two sections: health risk (8 questions) and preventative strategies (8 questions). The descriptive analysis was carried out according to the data types: qualitative data were described using frequency and percentages, while quantitative data was described using the mean and standard deviation. The Chi-square test or Fisher's Exact Test were employed to analyze the relationship between the variables. Participants were given a score of 1 for all accurate answers, and a score of 0 for wrong and "don't know" responses. There were 165 participants general, among them 93 males and 72 females; with a mean age of 35.489.570. Results: Only 27 people (16.36%) had a good knowledge score, while more than half (61.21%) earned an average knowledge score. 30% of radiology technicians had a good level of knowledge, and 26.5 % of those working in radiology units had a good level of expertise as well. Increasing the frequency of radiation exposure showed to have a strong relationship with participant knowledge score, with those with repeated exposure during the day having the greatest proportion (21.4%) of good knowledge. Conclusions: This study had shown that there is a need to increase awareness about risks of radiation exposures among those who works in this field. Considering the above, the study recommends making training about the risks and methods of radiation protection compulsory, especially for workers in radiography units. In addition, the curricula of medical institutes must be updated and the latest research findings on ways to prevent radiation should be added. Finally, the issue of exposure to radiation is very important and dangerous, therefore, all sectors of society must join for the best awareness of its risks.


Society for Pediatric Radiology John Caffey Award. MR appearance of blood and blood products: an in vitro study.
There are conflicting reports on the appearance of blood and blood clot as seen in the human body by MRI. This study was designed to show the in vitro MR signal intensity of human blood products in the fresh state and to evaluate the serial MRI changes that occur over time (2 weeks). T1 relaxation times were also measured. Anticoagulated whole blood, plasma, serum, white blood cell concentrates, platelet concentrates, lysed red cells, red cell concentrates, and blood clot were studied. The results show that plasma and serum have similar T1 values, as do lysed and intact erythrocytes. T1 of serum and plasma rose initially and then fell with the aging of the samples. T1 of red blood cells, clot, and packed red blood cells decreased for the first 48 hr and then remained constant for 7 days before increasing to the initial values by 2 weeks. Platelets and white blood cells had little influence on the MR image. However, temperature had a significant effect on T1 and signal intensity. In vivo clots are complex mixtures of whole clot, lysing clot, serum, and plasma influenced in various ways by the adjacent normal or diseased tissues. The chemical and physical properties of the mixture change constantly. Because of the clot's complex nature, determining the age of a hematoma from the appearance of clots on the MR image may not be possible.


Marchiafava-Bignami disease: a case report.
Marchiafava-Bignami Disease (MBD) is a rare, severe and usually fatal neurological disorder associated with chronic alcoholism. Previously, the definite diagnosis was confirmed at the autopsy. After the era of modern imaging technology, diagnosis was based on clinical profiles, history of alcoholism and specific location of pathology in corpus the callosum demonstrated by MRI. The authors reported a case of MBD in a 41 year-old alcoholic Thai male who presented with acute confusion and ataxia. MRI of the brain demonstrated demyelination, edema and necrosis of the corpus callosum with extensive symmetrical subcortical white matter lesions. He had a dramatic recovery after treatment with intravenous thiamine. Follow-up MRI revealed atrophic and cystic changes of the corpus callosum and almost complete resolution of the subcortical lesions. Recently, 15 cases of MBD with specific corpus callosal lesion, demonstrated by MRI, were published in the English literature. All had a favorable outcome after treatment with thiamine. Only one case had extensive extracallosal lesions and this case also had a good recovery after treatment. Now, MBD is not a fatal disease and early diagnosis and treatment are crucial.


Sorting signals in the measles virus wild-type glycoproteins differently influence virus spread in polarized epithelia and lymphocytes.
The spread of virus infection within an organism is partially dictated by the receptor usage of the virus and can be influenced by sorting signals present in the viral glycoproteins expressed in infected cells. In previous studies, we have shown that the haemagglutinin (H) and fusion protein (F) of the measles virus (MV) vaccine strain MV(Edm) harbour tyrosine-dependent sorting signals which influence virus spread in both lymphocytes and epithelial cells to a similar degree. In contrast with the vaccine strain, MV wild-type virus does not use CD46 but CD150/SLAM and a not clearly identified molecule on epithelial cells as receptors. To determine differences in viral spread between vaccine and wild-type virus, we generated recombinant MV expressing glycoproteins of both the wild-type strain WTFb and the corresponding tyrosine mutants. In contrast with observations based on vaccine virus glycoproteins, mutations in wild-type virus H and F differently influenced cell-to-cell fusion and replication in polarized epithelia and lymphocytes. For wild-type H, our data suggest a key role of the cytoplasmic tyrosine signal for virus dissemination in vivo. It seems to be important for efficient virus spread between lymphocytes, while the tyrosine signal in the F protein gains importance in epithelial cells as both signals have to be intact to allow efficient spread of infection within epithelia.


Ciclesonide ( Byk Gulden).
Ciclesonide, a non-halogenated inhaled corticosteroid with anti-inflammatory activity, is under development by Byk Gulden, Aventis and Teijin as a potential treatment for asthma [213439]. It was also being developed by Byk Gulden for chronic obstructive pulmonary disease (COPD), but no development had been reported for this indication since 1999; however, Teijin was carrying out clinical trials in this indication at the end of 2000. During 2000, Byk Gulden was carrying out phase III trials in the US and Europe and in March 2001, results were expected in the third quarter of 2001 [312399], [383726], [423659]. Two inhalant formulations (multidose powder and propellant filled) and a nasal formulation of ciclesonide are being developed by Byk Gulden for the treatment of asthma and seasonal allergic rhinitis, respectively [337147]. The compound is formulated for once-daily dosing and demonstrated good efficacy without corticosteroid-associated systemic side effects [409257]. In January 2001, Byk Gulden expected launch of a CFC-free multidose inhaler formulation in 2003 [395596]; in March 1999, launch of a nasal formulation was expected in 2004 and a multidose powder inhaler in 2005 [337147]. By September 2001, the compound was in phase III trials in the US for asthma, with a potential US launch anticipated by Aventis in 2004 [423465]. In November 2001, Aventis expected to submit an NDA to the FDA in 2003 [428057]. Teijin, which has a development and licensing agreement with Byk Gulden for the treatment of asthma and COPD in Japan, commenced phase I trials of ciclesonide in Japan in spring 1999, had completed these during 2000, and began phase II trials by September of that year [383726]. An NDA is expected to befiled in Japan in 2003. In October 2000 and April 2001, Merrill Lynch predicted peak sales of Euro400 million in 2007, with sales of Euro5 million in 2002, rising to Euro150 million in 2004 [395562], [420574]. Deutsche Bank predicted in August 2001, that sales of the product would reach Euro70 million in 2004, rising to Euro150 million in 2005 [420814].


N-terminal residues of the chemotaxis inhibitory protein of Staphylococcus aureus are essential for blocking formylated peptide receptor but not C5a receptor.
Staphylococcus aureus excretes a factor that specifically and simultaneously acts on the C5aR and the formylated peptide receptor (FPR). This chemotaxis inhibitory protein of S. aureus (CHIPS) blocks C5a- and fMLP-induced phagocyte activation and chemotaxis. Monoclonal anti-CHIPS Abs inhibit CHIPS activity against one receptor completely without affecting the other receptor, indicating that two distinct sites are responsible for both actions. A CHIPS-derived N-terminal 6 aa peptide is capable of mimicking the anti-FPR properties of CHIPS but has no effect on the C5aR. Synthetic peptides in which the first 6 aa are substituted individually for all other naturally occurring amino acids show that the first and third residue play an important role in blocking the FPR. Using an Escherichia coli expression system, we created mutant CHIPS proteins in which these amino acids are substituted. These mutant proteins have impaired or absent FPR- but still an intact C5aR-blocking activity, indicating that the loss of the FPR-blocking activity is not caused by any structural impairment. This identifies the first and third amino acid, both a phenylalanine, to be essential for CHIPS blocking the fMLP-induced activation of phagocytes. The unique properties of CHIPS to specifically inhibit the FPR with high affinity (kd=35.4 +/- 7.7 nM) could be an important new tool to further stimulate the fundamental research on the mechanisms underlying the FPR and its role in disease processes.


Improved vascular organization enhances functional integration of engineered skeletal muscle grafts.
Severe traumatic events such as burns, and cancer therapy, often involve a significant loss of tissue, requiring surgical reconstruction by means of autologous muscle flaps. The scant availability of quality vascularized flaps and donor site morbidity often limit their use. Engineered vascularized grafts provide an alternative for this need. This work describes a first-time analysis, of the degree of in vitro vascularization and tissue organization, required to enhance the pace and efficacy of vascularized muscle graft integration in vivo. While one-day in vitro was sufficient for graft integration, a three-week culturing period, yielding semiorganized vessel structures and muscle fibers, significantly improved grafting efficacy. Implanted vessel networks were gradually replaced by host vessels, coupled with enhanced perfusion and capillary density. Upregulation of key graft angiogenic factors suggest its active role in promoting the angiogenic response. Transition from satellite cells to mature fibers was indicated by increased gene expression, increased capillary to fiber ratio, and similar morphology to normal muscle. We suggest a "relay" approach in which extended in vitro incubation, enabling the formation of a more structured vascular bed, allows for graft-host angiogenic collaboration that promotes anastomosis and vascular integration. The enhanced angiogenic response supports enhanced muscle regeneration, maturation, and integration.


Wear and hardness of different core build-up materials.
Before crown preparation, teeth with extensive coronal destructions are built up with core materials. Sometimes, these build ups are exposed to the oral environment without the protection of crowns. Therefore, this in vitro investigation was aimed at evaluating the wear, surface roughness, Vickers hardness, and surface structure of 10 core composites, two glass ionomer cements (GICs), and four posterior restoration composites. The three-body wear was tested after water storage and 2,00,000 cycles. We measured both surface roughness and Vickers hardness (DIN 50133) and evaluated the surface structures by scanning electron microscopy. Results were statistically analyzed by use of the Mann-Whitney U test (alpha = 0.05). Lowest wear was found for the restorative composites (20 microm Grandio; others about 40 microm). A comparison of the composites Build-It, Chroma Core, Rebilda LC, and Rebilda DC to Quixfil showed similar wear values for each material (43-50 microm). Wear values of GICs and all others core composites ranged between 58 and 75 microm. Only Ti-Core showed significantly higher wear than all other materials (p < 0.05). All core materials except Ti-Core (35 HV) showed Vickers hardness values between 42 and 61 HV. Most core composites, particularly Build-It, Multicore Flow, Rebilda LC, Ecusit, and Tetric Evo Ceram, showed more homogenous surface structures compared to GICs and restorative composites. Therefore, wear values of core build-up materials not only differed widely but were higher than those of conventional restorative materials; yet, core build-up materials showed advantageous surface structures.


CARE-compliant stereotactic radiotherapy of urothelial nodal metastases: A case report.
The aim of the present study was to report the case of a 58-year-old male patient with ureteral carcinoma who underwent ureteroileostomy treatment. At 2 years following surgery, six lymph node metastases (LNMs) were detected in the patient's para-aortic and pelvic regions using 18F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT. All LNMs were treated using stereotactic body radiotherapy (SBRT; 35-40 Gy/5 fractions). At 3 months after radiotherapy, 18F-FDG-PET/CT examination revealed a complete radiological and metabolic response of all targeted treatment sites in the patient. In the 2 years following radiotherapy, another three same-dose SBRT treatments were performed on single or multiple LNMs, which were all detected in the abdomen and pelvis of the patient. Overall, a total of 11 LNMs were targeted in the patient and all exhibited complete radiological and metabolic response following treatment. The only treatment side effect reported by the patient was a slight and temporary loss of appetite. In patients with lymph node oligometastases there are two options for radiotherapy: i) Irradiation focusing on LNMs alone; and ii) prophylactic irradiation of the entire lymph node area combined with a boost on macroscopic lesions. In the patient discussed in the present study, the choice of irradiation focusing on LNMs alone made it possible to postpone systemic therapies and instead use an optimally tolerated treatment. The treatment outcome in this patient indicated that there was no radioresistance of urothelial LNMs.


Low-Dose Pesticide Mixture Induces Accelerated Mesenchymal Stem Cell Aging In Vitro.
The general population is chronically exposed to multiple environmental contaminants such as pesticides. We have previously demonstrated that human mesenchymal stem cells (MSCs) exposed in vitro to low doses of a mixture of seven common pesticides showed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation toward adipogenesis. Thus, we hypothesized that common combination of pesticides may induce a premature cellular aging of adult MSCs. Our goal was to evaluate if the prolonged exposure to pesticide mixture could accelerate aging-related markers and in particular deteriorate the immunosuppressive properties of MSCs. MSCs exposed to pesticide mixture, under long-term culture and obtained from aging donor, were compared by bulk RNA sequencing analysis. Aging, senescence, and immunomodulatory markers were compared. The protein expression of cellular aging-associated metabolic markers and immune function of MSCs were analyzed. Functional analysis of the secretome impacts on immunomodulatory properties of MSCs was realized after 21 days' exposure to pesticide mixture. The RNA sequencing analysis of MSCs exposed to pesticide showed some similarities with cells from prolonged culture, but also with the MSCs of an aged donor. Changes in the metabolic markers MDH1, GOT and SIRT3, as well as an alteration in the modulation of active T cells and modifications in cytokine production are all associated with cellular aging. A modified functional profile was found with similarities to aging process. Stem Cells 2019;37:1083-1094.


Safe time limits of aortic cross-clamping and cardiopulmonary bypass in adult cardiac surgery.
We evaluated the impact of aortic cross-clamping time (XCT) and cardiopulmonary bypass time (CPBT) on the immediate and late outcome after adult cardiac surgery and attempted to identify their safe time limits. This study includes 3280 patients who underwent adult cardiac surgery of various complexities. Myocardial protection was achieved with tepid continuous antegrade/retrograde blood cardioplegia. Receiver operating characteristics (ROC) curve analysis showed that XCT (area under the curve, AUC: 0.66), CPBT (AUC: 0.73) and CPBT with unclamped aorta (AUC: 0.77) were significantly associated with 30-day postoperative mortality. XCT of increasing 30-minute intervals (Odds Ratio (OR) 1.21, 95%C.I. 1.01-1.52) and CPBT of increasing 30-minute intervals (OR 1.47, 95%C.I. 1.27-1.71) were independent predictors of 30-day mortality. The best cutoff value for XCT was 150 min (30-day death: 1.8% vs. 12.2%, adjusted OR 3.07, 95%C.I. 1.48-6.39, accuracy 91.5%) and for CPBT 240 min (30-day death: 1.9% vs. 31.5%, adjusted OR 8.78, 95%C.I. 4.64-16.61, accuracy 96.0%). These parameters were significantly associated also with postoperative morbidity, particularly with postoperative stroke. XCT and CPBT are predictors of immediate postoperative morbidity and mortality. In our experience, cardiac procedures with CPBT<240 min and XCT<150 min were associated with a rather low risk of immediate postoperative adverse events independently of the complexity of surgery patient's operative risk.


Enhancement of GABAA receptor-mediated conductances induced by nerve injury in a subclass of sensory neurons.
1. The effects of axotomy on the electrophysiologic properties of adult rat dorsal root ganglion (DRG) neurons were studied to understand the changes in excitability induced by traumatic nerve injury. Nerve injury was induced in vivo by sciatic nerve ligation with distal nerve transection. Two to four weeks after nerve ligation, a time when a neuroma forms, lumbar (L4 and L5) DRG neurons were removed and placed in short-term tissue culture. Whole cell patch-clamp recordings were made 5-24 h after plating. 2. DRG neurons were grouped into large (43-65 microns)-, medium (34-42 microns)-, and small (20-32 microns)- sized classes. Large neurons had short duration action potentials with approximately 60% having inflections on the falling phase of their action potentials. In contrast, action potentials of medium and small neurons were longer in duration and approximately 68% had inflections. 3. Pressure microejection of gamma-aminobutyric acid (GABA, 100 microM) or muscimol (100 microM) onto voltage-clamped DRG neurons elicited a rapidly desensitizing inward current that was blocked by 200 microM bicuculline. To measure the peak conductance induced by GABA or muscimol, neurons were voltage-clamped at a holding potential of -60 mV, and pulses to -80 mV and -100 mV were applied at a rate of 2.5 or 5 Hz during drug application. Slope conductances were calculated from plots of whole cell current measured at each of these potentials. 4. GABA-induced currents and conductances of control DRG neurons increased progressively with cell diameter. The mean GABA conductance was 36 +/- 10 nS (mean +/- SE) in small neurons, 124 +/- 21 nS in medium neurons, and 527 +/- 65 nS in large neurons. 5. After axotomy, medium neurons had significantly larger GABA-induced conductances compared with medium control neurons (390 +/- 50 vs. 124 +/- 21; P < 0.001). The increase in GABA conductance of medium neurons was associated with a decrease in duration of action potentials. In contrast, small neurons had no change in GABA conductance or action potential duration after ligation. The GABA conductance of large control neurons was highly variable, and ligation resulted in an increase that was significant only for neurons > 50 microns. The mean action potential duration in large neurons was not significantly changed, but neurons with inflections on the falling phase of the action potential were less common after ligation. There was no difference in resting potential or input resistance between control and ligated groups, except that the resting potential was less negative in small cells after axotomy.(ABSTRACT TRUNCATED AT 400 WORDS)


Only minor stem cell mobilization in head and neck irradiated patients treated with hyperbaric oxygen.
Hyperbaric oxygen, (HBO) is used to treat several conditions including late radiation tissue injury. Previous studies have suggested that HBO mobilizes bone marrow derived stem/progenitor cells (SPC) to the peripheral blood, however possible cumulative effects were highly variable. We have investigated a possible HBO-induced mobilization of SPCs by determining CD34+CD45dim cell numbers, as well as SPCs in general. The latter were characterized by high aldehyde dehydrogenase (ALDH) activity by use of the Aldefluor® assay. We included ten patients admitted for HBO treatment of radiation tissue injury. Six patients completed the 29-30 HBO treatment exposures. We also investigated possible HBO-induced effects on platelet activation as measured by flow cytometry and functional analyses. We found a weak and insignificant tendency toward mobilization of CD34+CD45dim cells after a single HBO exposure versus before. Additionally, we found an additive effect of 15 HBO exposures on the increase in CD34+CD45dim cells relative to the pre-1st-HBO values. These changes were significantly more than zero but less than a doubling. We could not demonstrate a significant effect of HBO on the content of Aldefluor® positive SPCs in peripheral blood. There was no significant effect on platelet activation overall. However, in patients with increased expression of activation markers at baseline, we found a decrease after one exposure although this was not reflected in functional tests. We found a minor statistically significant mobilizing effect of HBO treatment on the bone marrow derived stem/progenitor cell content in peripheral blood after 15 treatments (n = 10 patients), but no effect after 30 treatments (n = 6 patients). However, because of the low number of patients we cannot confidentially prove or disprove the null hypothesis. The possibility that HBO treatment reduces the number of activated platelets could not be demonstrated nor excluded.


Short- and long-term repopulation of lethally irradiated mice by bone marrow stem cells enriched on the basis of light scatter and Hoechst 33342 fluorescence.
Murine bone marrow subpopulations enriched in hemopoietic stem cells were transfused into lethally irradiated hosts to determine the contribution of host cells and two types of donor cells to marrow repopulation. Donor cell suspensions were a mixture of marrows from two congenic lines of mice containing electrophoretically distinguishable alloenzymes of phosphoglycerate kinase (PGK-A and PGK-B). The donor cells were sorted by high forward light scatter, low-to-intermediate perpendicular light scatter, and low Hoechst 33342 fluorescence intensity. The congenic hosts contained a third distinct marker, glucose phosphate isomerase (GPI-A). The two markers in the donor cells allowed determination of the clones generated by the seeded cells over a 36-week period of observation. The clone number declined rapidly during the first 12 weeks following transplantation and reached stable levels at 20 weeks, indicating the number of long-term repopulating cells (LTRC). The sorted subpopulation was enriched 170-fold for day-13 spleen colony-forming units (CFU-S), 235-fold for cells providing a 30-day survival, and 136- to 160-fold for LTRC. Survival for the 36-week observation period was 40%-100% for groups of hosts receiving 100-3000 sorted cells and 80% for controls receiving 2 x 10(5) unsorted cells. In all groups, similar distribution of phenotypes among peripheral blood erythrocytes, platelets, and lymphocytes at 36 weeks suggested that the repopulating donor stem cells were pluripotential. Transfusion of 3000 sorted cells, containing about 5 LTRC and 60 CFU-S, assured continuous repopulation with 95%-100% donor cells 4 to 36 weeks after transplantation, whereas significant numbers of host cells re-emerged temporarily or permanently when lower numbers of LTRC and CFU-S were transfused. The data indicate that both the quality and quantity of pluripotential stem cells in sorted bone marrow are important for complete long-term marrow reconstitution.


New heterocyclic derivatives of benzimidazole with germicidal activity--IX--HPLC detection of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2) in biological samples.
The HPLC technique for the isolation and quantitation of 5-fluoro-2-(5'-nitro-2'-furyl)benzimidazole (F-O-NO2), previously described by the same Authors, in biological samples from mice is reported. Evidence is given that the highest biological concentration and the time needed for reaching it depend both on the dose and on the administration route. In fact, almost the same maximal biological concentration of F-O-NO2 (about 0.18 micrograms/mouse) is reached after 60 min from either 40 mg/Kg IP or 200 mg/Kg os drug administration, whereas the maximal biological concentration of F-O-NO2 (5.75 micrograms/mouse) is reached after 30 min from 120 mg/Kg IP drug administration.


Impact of early life stress on the reinforcing and behavioral-stimulant effects of psychostimulants in rhesus monkeys.
Early life stress has effects on behavior and stress reactivity, which are linked to enhanced sensitivity to stimulants in rodents. This study investigated whether rhesus monkeys that experienced early life stress would show altered sensitivity to the reinforcing effects of stimulants as compared with controls. Control (n=5) and maternally separated (n=4) monkeys were trained to self-administer cocaine (0.1 mg/kg/injection) under a second-order schedule of intravenous drug delivery. The rate of acquisition and subsequent dose-effect determinations for cocaine (0.01-1.0 mg/kg/injection) and amphetamine (0.003-0.3 mg/kg/injection) provided complementary measures of reinforcing effectiveness. In addition, stimulant-induced increases in home cage activity and dopamine D2 receptor binding potential were quantified with positron emission tomography neuroimaging. Compared with controls, maternally separated monkeys showed lower responding during the acquisition of self-administration and in the dose-response curves for both stimulants, and significantly lower response rates during maintenance of cocaine self-administration. Maternally separated monkeys also failed to exhibit stimulant-induced increases in motor activity. Groups did not differ in dopamine D2 receptor binding potential in the caudate nucleus or the putamen. Taken together, the results of this study do not provide support for early life stress leading to enhanced vulnerability to stimulant use in the nonhuman primate model employed.


The clinical and endocrine assessment of three different antiandrogen regimens combined with a very long-acting gonadotrophin-releasing hormone analogue.
Tumor flare is reported in up to 40% of patients treated with gonadotrophin-releasing hormone analogues for prostate cancer. In order to investigate the optimal way to eliminate tumor flare, we have treated patients with one of three different antiandrogen regimens used in combination with gonadotrophin-releasing hormone (GnRH) agonist. The early results of this study are presented here. Thirty patients with advanced symptomatic disease were randomized to receive either cyproterone acetate 50 or 100 mg three times daily or flutamide 250 mg three times daily given for 1 week before and during the first month of GnRH agonist treatment. The endocrine profiles of these patients were compared with those of historic controls treated with depot agonist alone. Three patients treated with low-dose cyproterone acetate and one with flutamide developed a transient exacerbation of their disease. No patients treated with the higher-dose cyproterone acetate regimen developed tumor flare. No patients treated with cyproterone acetate had an increase in serum testosterone above baseline following depot GnRH agonist implantation. All patients treated with flutamide had increases in serum testosterone, but this did not significantly increase further with implantation. This study suggests that all patients receiving GnRH agonist treatment should be pretreated with cyproterone acetate 100 mg three times daily for 1 week before implantation and for the first treatment month.


Involvement of BcStr2 in methionine biosynthesis, vegetative differentiation, multiple stress tolerance and virulence in Botrytis cinerea.
The Str2 gene encodes a cystathionine γ-synthase that is a key enzyme in methionine (Met) biosynthesis in Saccharomyces cerevisiae. Met plays a critical role in protein synthesis and diverse cellular processes in both eukaryotes and prokaryotes. In this study, we characterized the Str2 orthologue gene BcStr2 in Botrytis cinerea. The BcStr2 mutant was unable to grow on minimal medium (MM). In addition, conidia of the mutant were unable to germinate in water-agar medium within 15 h of incubation. Supplementation with 1 mm Met or 0.5 mg/mL homocysteine, but not 1 mm cysteine or 0.5 mg/mL glutathione, rescued the defect in mycelial growth of the BcStr2 deletion mutant. These results indicate that the enzyme encoded by BcStr2 is involved in the conversion of cysteine into homocysteine. The mutant exhibited decreased conidiation and impaired sclerotium development. In addition, the BcStr2 mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents and thermal stress. The mutant demonstrated dramatically decreased virulence on host plant tissues. All of the defects were restored by genetic complementation of the mutant with wild-type BcStr2. Taken together, the results of this study indicate that BcStr2 plays a critical role in the regulation of various cellular processes in B. cinerea.


Spatial Engineering Direct Cooperativity between Binding Sites for Uranium Sequestration.
Preorganization is a basic design principle used by nature that allows for synergistic pathways to be expressed. Herein, a full account of the conceptual and experimental development from randomly distributed functionalities to a convergent arrangement that facilitates cooperative binding is given, thus conferring exceptional affinity toward the analyte of interest. The resulting material with chelating groups populated adjacently in a spatially locked manner displays up to two orders of magnitude improvement compared to a random and isolated manner using uranium sequestration as a model application. This adsorbent shows exceptional extraction efficiencies, capable of reducing the uranium concentration from 5 ppm to less than 1 ppb within 10 min, even though the system is permeated with high concentrations of competing ions. The efficiency is further supported by its ability to extract uranium from seawater with an uptake capability of 5.01 mg g-1, placing it among the highest-capacity seawater uranium extraction materials described to date. The concept presented here uncovers a new paradigm in the design of efficient sorbent materials by manipulating the spatial distribution to amplify the cooperation of functions.


Ischiectomy With Limb Preservation for a Dog With Ischial Chondrosarcoma: Case Report and Surgical Technique.
To describe the surgical technique for ischiectomy in the dog and to report the procedure in a case. Case report. An 11-year-old spayed female mixed breed dog with chondrosarcoma of the ischium. The dog presented for hindlimb lameness and evaluation after a radiographic finding of a lytic lesion confined to the left ischium. Following staging and confirmation of stage 1 disease, an ischiectomy with preservation of the hindlimb was performed. The dog recovered from surgery and was initially moderately lame on the hindlimb. Over time, the dog regained satisfactory hindlimb use and was alive >500 days postoperative with no evidence of local recurrence or metastatic disease. Ischiectomy with hindlimb preservation is a technically straight-forward procedure and in this case, resulted in good hindlimb function postoperatively. The procedure should be considered for the treatment of dogs with bone tumors confined to the ischium.


Species-specific mutation rates for ampC derepression in Enterobacterales with chromosomally encoded inducible AmpC β-lactamase.
AmpC β-lactamases are encoded on the chromosomes of certain Enterobacterales and lead to clinical resistance to various β-lactams in case of high-level expression. In WT bacteria with inducible AmpC, the expression is low, but selection of stably ampC-derepressed mutants may occur during β-lactam therapy. Thus, for Enterobacter spp., Citrobacter freundii complex, Serratia spp. and Morganella morganii that test susceptible in vitro to oxyimino-cephalosporins, the EUCAST expert rules recommend suppressing susceptibility testing results for these agents or noting that their use in monotherapy should be discouraged, owing to the risk of selecting resistance. However, clinical observations suggest that emergence of resistance is not equally common in all species with inducible AmpC. To determine species-specific mutation rates, which are more accurate and reproducible than previously described mutant frequencies, for ampC derepression in Enterobacterales with inducible AmpC. Mutation rates were determined using a protocol based on Luria-Delbrück fluctuation analyses. Overall, 237 isolates were analysed. Mutation rates were high in Enterobacter cloacae complex, Enterobacter aerogenes, C. freundii complex and Hafnia alvei isolates, with a mean mutation rate of 3 × 10-8. In contrast, mean mutation rates were considerably lower in Providencia spp., Serratia spp. and especially M. morganii isolates. Furthermore, we observed species-specific variations in the resistance patterns of ampC-derepressed mutants. Our data might help to predict the risk of treatment failure with oxyimino-cephalosporins in infections by different Enterobacterales with inducible AmpC. Moreover, we make a proposal for optimization of the current EUCAST expert rule.


Celebrating eighty years of radionuclide therapy and the work of Saul Hertz.
March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics.


Cardioprotection with white wine.
The cardioprotective effects of red wine have been attributed to several polyphenolic antioxidants including resveratrol and proanthocyanidins. The goal of the present study was to determine whether white wines could also provide cardioprotection. Three different white wines (white wine #1, #2 and #3) were chosen for this study. Ethanol-free extracts of the wines were prepared by vacuum evaporation. Rats weighing approximately 200 g were given either 50 mg/kg or 100 mg/kg of each wine extract for 3 weeks. The rats were anesthetized and sacrificed and their hearts were excised for the preparation of isolated working rat heart. All hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function including heart rate, left ventricular developed pressure (LVDP), maximum first derivative of developed pressure (LVdp/dtmax), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEP), aortic flow (AF) and coronary flow (CF) were continuously monitored and myocardial infarct size was measured at the end of the experiments. The results of our study demonstrated that among the three different white wines, only white wine #2 conferred cardioprotection as evidenced by improved postischemic ventricular recovery compared with controls. The same white wine at a dose of 50 mg/kg also showed improvement in postischemic contractile recovery but the differences compared with controls were not significant. The amount of malondialdehyde production from these hearts was lower than that found in control hearts, indicating reduced formation of reactive oxygen species in white wine #2-treated rats. In vitro studies using a chemiluminescence technique revealed that white wine #2 scavenged both superoxide anions and hydroxyl radicals. The results of our study demonstrate that white wine #2 provided cardioprotection and the cardioprotective effect of the wine can be attributed, at least in part, to its ability to function as an in vivo antioxidant.


Lens and retina regeneration: transdifferentiation, stem cells and clinical applications.
In this review we present a synthesis on the potential of vertebrate eye tissue regeneration, such as lens and retina. Particular emphasis is given to two different strategies used for regeneration, transdifferentiation and stem cells. Similarities and differences between these two strategies are outlined and it is proposed that both strategies might follow common pathways. Furthermore, we elaborate on specific clinical applications as the outcome of regeneration-based research.


Decay-accelerating factor in guinea pig stomachs following ischemia reperfusion stress.
A complement regulatory protein, decay-accelerating factor (DAF, CD55), is known to protect host tissues from autologous complement activation. DAF is present on the apical side of human gastric epithelial cells, and its expression increases during gastritis. To develop an animal model for analysis of DAF expression on gastric cells, a mAb to guinea pig DAF was successfully used. Although DAF expression in the mucosal epithelium of the stomach is weak, as judged by immunohistochemical staining with the mAb, it was temporarily up-regulated at 12 and 24 h, and at 3 days after ischemia reperfusion (I/R) (p < 0.05). The DAF mRNA level in gastric tissues was determined by Northern blot analysis and found to be highest at 6 h after I/R, returning to the baseline at 24 h. Strong DAF mRNA expression was observed in the cytoplasm of cells beneath the eroded tissues 6 h after I/R. In guinea pigs, alternative splicing of DAF mRNA generates both GPI-anchored types and transmembrane types of DAF. RT-PCR analysis revealed that mRNAs of the transmembrane types had become significantly dominant by 6 h after I/R, whereas levels for the GPI-anchored types remained unchanged. In guinea pigs depleted of complement by cobra venom factor treatment, the area of erosion and the up-regulation of DAF expression in gastric epithelial cells after I/R were significantly limited compared with the normocomplementemic group, indicating that DAF may be up-regulated by an inflammatory stress.


Toward a deeper understanding of the harms caused by partner stalking.
This study examined stalking prevalence, patterns, and harm among 210 women with civil protective orders (PO) against violent male partners or ex-partners. Results suggest that stalking is associated with PO violations and almost every other type of partner violence. Also, women who have been stalked by violent partners report significantly more distress and harm than even women who experience PO violations but not stalking. Results of key informant perceptions suggest many victim service (n=116) and criminal justice professionals (n=72) do not seem to understand the extent or gravity of the harms caused by partner stalking especially when contrasted with victim reports of harm. Furthermore, key informant reports of their advice to women being stalked by an ex-partner were not consistent with recommendations for stalking victims in general.


Myelinated, but not unmyelinated axons, reversibly down-regulate N-CAM in Schwann cells.
There is evidence from chicks and mice that N-CAM expression in Schwann cells is subject to significant regulation during development and following injury. In the present work, rat sciatic nerve and immunohistochemical methods have been used to study developmental and injury-related modulation of N-CAM in Schwann cells, using cell type specific markers to identify different Schwann cell populations, and cell counting to quantify their size. The study has sought to determine unambiguously whether immature Schwann cells in developing nerves and denervated Schwann cells in injured adult nerves express surface N-CAM, and has investigated the temporal relationship between the gradual loss of surface N-CAM and the differentiation of myelin-forming Schwann cells, monitored by the sequential appearance of the glycolipid galactocerebroside and the myelin-specific protein P0. Further points examined are whether this down-regulation of N-CAM is rapidly reversible following loss of axonal contact, and whether N-CAM reappearance in Schwann cells depends on protein synthesis. In nerves from 17- to 18-day embryos, 90% of the Schwann cells, identified with Ran-1 antibodies, expressed surface N-CAM. In nerves from newborn rats many cells are in the early stage of myelin synthesis and therefore express galactocerebroside, although they have not yet acquired P0. Suspension staining of dissociated cells from this nerve showed that 92% of the galactocerebroside-positive cells were also N-CAM positive. In suspension staining of nerves from 5-day, 10-day and adult rats, P0-positive cells were essentially N-CAM negative.(ABSTRACT TRUNCATED AT 250 WORDS)


Modified bronchial anastomosis in video-assisted thoracoscopic sleeve lobectomy: a report of 32 cases.
Bronchial anastomosis is a key technical challenge in sleeve lobectomy, especially when using the video-assisted thoracoscopic surgery (VATS) approach. A retrospective study was conducted to evaluate the feasibility and safety of a modified bronchial anastomosis technique developed by the authors at Fujian Union Hospital. From October 2010 to October 2015, we performed 32 cases of VATS sleeve lobectomy through a three-port or single-port approach. All bronchial anastomoses were performed using modified bronchial anastomosis technique: the bronchial anastomosis was begun with an initial stitch on the posterior wall, and the bilateral quarters of the circumference were continuously sutured. The other two bilateral quarters were then similarly sutured, and the last knot was made outside the bronchial lumen. All cases were completed uneventfully. No perioperative deaths or serious complications occurred. The mean operative time, bronchial anastomosis time, and blood loss volume were 271.8±67.5, 37.6±12.0 min, and 177.5±102.9 mL, respectively. The mean follow-up time was 21.0±11.7 months, and the follow-up rate was 96.9% (31/32). An electronic bronchoscope scan was performed 6 months after surgery, and a fine healing stoma was detected in all cases. No anastomotic fistula, anastomotic stenosis, or other serious postoperative anastomotic complications occurred until the end of follow-up. Modified bronchial anastomosis technique applied in bronchial anastomosis was safe and feasible in three-port and single-port VATS sleeve lobectomy with good short-term and long-term therapeutic results. Adequate management of the operative process and implementation of a skilled bronchial anastomosis technique could help to reduce the difficulty of VATS sleeve lobectomy.


Agreement and consistency of five different clinical gait analysis systems in the assessment of spatiotemporal gait parameters.
Measuring gait function has become an essential tool in the assessment of mobility in aging populations for both, clinicians and researchers. A variety of systems exist that assess gait parameters such as gait cycle time, gait speed or duration of relative gait phases. Due to different measurement principles such as inertial or pressure sensors, accurate detection of spatiotemporal events may vary between systems. To compare the absolute agreement and consistency in spatiotemporal gait parameters among five different clinical gait analysis systems using different sensor technologies. We compared two devices using inertial sensors (GaitUp & Mobility Lab), two devices using pressure sensor systems (GAITRite & Zebris) as well as one optical system (OptoGait). Twelve older adults walked at self-selected speed through a walkway integrating all of the above systems. Basic spatiotemporal parameters (gait cycle time, cadence, gait speed and stride length) as well as measures of relative phase (stance phase, swing phase, double stance phase, single limb support) were extracted from all systems. We used Intraclass Correlation Coefficients as measures of agreement and consistency. High agreement and consistency between all systems was found for basic spatiotemporal parameters, whereas parameters of relative phase showed poorer agreement and consistency. Overground measurement (GAITRite & OptoGait) showed generally higher agreement with each other as compared to inertial sensor-based systems. Our results indicate that accurate detection of both, the heel-strike and toe-off event are crucial for reliable results. Systematic errors in the detection of one or both events may only have a small impact on basic spatiotemporal outcomes as errors remain consistent from step to step. Relative phase parameters on the other hand may be affected to a much larger extent as these differences lead to a systematic increase or reduction of relative phase durations.


Nanonization of Magnoflorine-Encapsulated Novel Chitosan-Collagen Nanocapsules for Neurodegenerative Diseases: In Vitro Evaluation.
Neurodegeneration is one of the most common diseases in the aged population, characterized by the loss in the function of neuronal cells and their ultimate death. One of the common features in the progression of this type of diseases is the oxidative stress. Drugs which are currently being used have been found to show lateral side effects, which is partly due to their inefficiency to cross blood-brain barrier. Nanoencapsulation of bioactive compounds is a profound approach in this direction and has become a method of choice nowadays. This study involved the evaluation of the anti-oxidative properties of magnoflorine (MF), which is an aporphine quaternary alkaloid, and synthesis of MF-loaded chitosan-collagen nanocapsules (MF-CCNc) for its better efficacy as a potent anti-oxidant. Physiochemical characterization of the synthesized nanocapsules was done by using dynamic light scattering and transmission electron microscopy. It revealed that the synthesized nanocapsules are of small size range, as small as 12 ± 2 nm, and are more or less of spherical shape. Sustained release was shown by MF in the in vitro drug release studies. Both MF and MF-CCNc were found to have good anti-oxidant potential with IC50 < 25 μg/mL. No major cytotoxicity was shown by the synthesized nanocapsules on SH-SY5Y cells. In silico anti-acetylcholinesterase (AChE) studies were also done, and they revealed that MF can be a potent inhibitor of AChE.


Conformation of single block copolymer chain in two-dimensional microphase-separated structure studied by scanning near-field optical microscopy.
The localization and orientation of the symmetric diblock copolymer chain in a quasi-two-dimensional microphase-separated structure were studied by scanning near-field optical microscopy (SNOM). In the monolayer of poly(isobutyl methacrylate)-block-poly(octadecyl methacrylate) (PiBMA-b-PODMA), the individual PiBMA subchains were directly observed by SNOM, and the center of mass (CM) and orientational angle relative to the phase interface were examined at the single chain level. It was found that the position of the CM and the orientation of the PiBMA subchain in the lamellar structure were dependent on the curvature of the PiBMA/PODMA interface. As the interface was bent toward the objective chain, the block chain preferred the CM position closer to the domain center, and the conformation was strongly oriented perpendicularly to the domain interface. With increase of the curvature, the steric hindrance among the block chain increases, resulting in the stretched conformation.


Identifying interdisciplinary research priorities to prevent and treat pediatric obesity in New York City.
It is well recognized that an interdisciplinary approach is essential in the development and implementation of solutions to address the current pediatric obesity epidemic. In two half-day meetings that included workshops and focus groups, faculty from diverse fields identified critically important research challenges, and gaps to childhood obesity prevention. The purpose of this white paper is to describe the iterative, interdisciplinary process that unfolded in an academic health center setting with a specific focus on underrepresented minority groups of Black and Hispanic communities, and to summarize the research challenges and gaps related to pediatric obesity that were identified in the process. Although the research challenges and gaps were developed in the context of an urban setting including high-risk populations (the northern Manhattan communities of Washington Heights, Inwood, and Harlem), many of the issues raised are broadly applicable. The processes by which the group identified research gaps and methodological challenges that impede a better understanding of how to prevent and treat obesity in children has resulted in an increase in research and community outreach collaborations and interdisciplinary pursuit of funding opportunities across units within the academic health center and overall university.


Administration of a herbal formulation enhanced blastocyst implantation via IκB activation in mouse endometrium.
BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model. In vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues. BCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group. These results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.


Isolation of three testis-specific genes (TSA303, TSA806, TSA903) by a differential mRNA display method.
We isolated three human testis-specific genes by a differential mRNA display method. The cDNAs contained open reading frames of 1620, 453, and 333 nucleotides, encoding 540, 151, and 111 amino acids, respectively. The first of these genes, designated TSA303, encodes a novel protein homologous to TCP20, one of the subunits of the human TRiC chaperonin complex that can bind newly synthesized or unstable folding intermediates of polypeptides and assist substrate proteins in folding, assembly, and transport. The second, TSA806, encodes a novel protein containing 3.3 contiguous repeats of the cdc10/swi6 (ankyrin) motif that was originally found in products of cell cycle control genes of yeast and cell fate determination genes in Drosophila and Caenorhabditis elegans. The third gene, TSA903, encodes a protein homologous to the C-terminal region of murine uridine monophosphate kinase. Northern blot analysis confirmed that in 16 human adult tissues examined, each of these genes was expressed specifically in the testis. From the results of cDNA screening of nearly 1 million plaques, the abundance of each transcript in a preparation of total mRNA was estimated as 0.0004% (TSA303), 0.0006% (TSA806), and 0.0002% (TSA903). Our results imply that the differential display method is a powerful tool for isolation of tissue-specific genes even if they are expressed at a level as low as 1 in several hundred thousand to a million molecules of total mRNA.


Gastroenteritis outbreak in British troops, Iraq.
Gastroenteritis affected many British military personnel during the war in Iraq. In the first month, 1,340 cases were seen; 73% of patients required hospital admission and 36% were hospital staff. In a survey of 500 hospital staff, 76% reported gastroenteritis, which was more likely in clinical workers. Investigations showed only caliciviruses.


A Supramolecular Ice Growth Inhibitor.
Safranine O, a synthetic dye, was found to inhibit growth of ice at millimolar concentrations with an activity comparable to that of highly evolved antifreeze glycoproteins. Safranine inhibits growth of ice crystals along the crystallographic a-axis, resulting in bipyramidal needles extended along the <0001> directions as well as and plane-specific thermal hysteresis (TH) activity. The interaction of safranine with ice is reversible, distinct from the previously reported behavior of antifreeze proteins. Spectroscopy and molecular dynamics indicate that safranine forms aggregates in aqueous solution at micromolar concentrations. Metadynamics simulations and aggregation theory suggested that as many as 30 safranine molecules were preorganized in stacks at the concentrations where ice growth inhibition was observed. The simulations and single-crystal X-ray structure of safranine revealed regularly spaced amino and methyl substituents in the aggregates, akin to the ice-binding site of antifreeze proteins. Collectively, these observations suggest an unusual link between supramolecular assemblies of small molecules and functional proteins.


A phase II trial of docetaxel with bevacizumab as first-line therapy for HER2-negative metastatic breast cancer (TORI B01).
Addition of the antiangiogenic agent bevacizumab to paclitaxel significantly improves response rates and progression-free survival for metastatic breast cancer (MBC). To assess the activity of docetaxel plus bevacizumab, a multicenter phase II trial was conducted. Patients with measurable first-line HER2/neu-negative MBC were eligible. This trial began as a 2-arm study with a docetaxel-alone arm. When bevacizumab became widely available, it was converted to a 1-arm open-label trial of docetaxel/bevacizumab. Patients enrolled in the docetaxel-alone arm were permitted to cross over to docetaxel/bevacizumab. Patients received bevacizumab 15 mg/kg and docetaxel 75 mg/m2 intravenously (I.V.) every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. From March 2005 to September 2006, 76 patients were enrolled. Of the 7 patients who were randomized to docetaxel alone, 6 crossed over to docetaxel/bevacizumab (included in the safety analysis only). Two patients were found to be ineligible before receiving drug. Efficacy data are based on the 67 patients who were originally enrolled in the docetaxel/bevacizumab arm and received at least 1 dose of study medication. The confirmed objective response rate is 51% (34 of 67) with 9% complete responses (6 of 67) and 42% partial responses (28 of 67). Nine additional patients (13%) had stable disease lasting >or= 6 months. With a median follow-up of 21.7 months, the median time to progression is 9.3 months, and median overall survival is 26.3 months. Common grade 3/4 adverse events included neutropenia (33%), leukopenia/lymphopenia (25%), fatigue (22%), infection (17%), pain (16%), and hypertension (9%). Docetaxel/bevacizumab was generally well tolerated with manageable toxicity and promising efficacy results.


Presenting qualitative data through the co-construction of a model.
Research skills are developed in pre-registration midwifery curricula to enhance student midwives' appreciation and appropriate application of evidence within their midwifery practice. A spontaneous, innovative session was facilitated based on student experiences of non-midwifery placements, which helped demonstrate how qualitative data are analysed and can then be presented. By listening to each other's varied experiences, the students were able to relate their research knowledge to date with their collective 'empirical data' to enhance their understanding of presenting qualitative research. The paper reports on the learning process. It is an evaluation of the session, with student permission for publication gained; it is not research.


The creation of a database of odorous compounds focused on molecular rigidity and analysis of the molecular features of the compounds in the database.
It is important to select odorous molecules for experiments on olfaction and for the development of an electronic nose. Odorous molecules having a small number of conformers, namely structurally rigid molecules, are assumed to interact with a small number of types of olfactory receptor proteins or to interact with the proteins in a simpler manner than that of fairly flexible molecules. Focusing on the rigidity of molecular structures, we collected 287 odorous molecules from data sources, which included 1205 chemicals in total and a database of the 287 odorous molecules (DB_odMOL) was created using CS ChemFinder Pro (version 5.0). The logarithmic value of the octanol/water partition coefficient (log P) and melting point, boiling point and vapour pressure of the molecules were estimated using CS Chem3D Pro. The database DB_odMOL accumulates these estimated data in addition to literature values for odour quality, odour detection thresholds and the safety of molecules. The rigidity of the 287 molecules was further analysed by conformational analysis performed by molecular mechanics using Conformer in CS Chem3D Pro (version 5) and 72 rigid odorous molecules were selected. The 287 molecules were also analysed based on atomic composition, substructure and molecular size. Sixty-two odorous molecules among the 72 rigid odorous molecules were further selected based on their atomic composition. The 62 rigid molecules with simple atomic composition that were finally selected should be useful for researchers in choosing odorous molecules for the study of olfaction, including the fields of molecular biology, physiology, structure-odour relationships and other fields of the study concerning odour.


Assembly of colloidal molecules, polymers, and crystals in acoustic and magnetic fields.
A dynamically adjustable colloidal assembly technique is presented, which combines magnetic and acoustic fields to produce a wide range of colloidal structures, ranging from discrete colloidal molecules, to polymer networks and crystals. The structures can be stabilized and dried, making them suitable for the fabrication of advanced materials.


Proteomic analysis of membrane proteins from a radioresistant and moderate thermophilic bacterium Deinococcus geothermalis.
Deinococcus geothermalis is a radioresistant and moderate thermophilic bacterium. Little was known about the membrane or membrane associated proteins of this bacterium. This study established the membrane subproteome profile of D. geothermalis, using 1-D PAGE and LC-MS/MS analysis following Triton X-114 detergent extraction. A total of 552 proteins from the membrane preparations were identified from two independent trials. In the total identified proteins, 117 were membrane subproteomic proteins, and 89 of them were described for the first time in D. geothermalis including fimbrial pilin (Dgeo_2038), cytochrome bd ubiquinol oxidase (Dgeo_2705) and multi-sensor (Dgeo_2096). The major membrane subproteomic proteins were distributed into 18 functional groups including nutrient transport and metabolism, energy production and conversion, cell wall/membrane biogenesis and a poorly characterized subclass. The identifications of Deinococcus-specific proteins, such as cell surface receptor IPT/TIG (Dgeo_1119) and four hypothetical proteins, demonstrated the special protein composition and functions in the cell membrane of Deinococcus. The results provide a basis for quantitative proteomic analysis, which will facilitate the understanding of the adaptation of this organism to different environmental stresses and the development of strategies for bioremediation of environmental waste.


Processing of vibrotactile inputs from hairy skin by neurons of the dorsal column nuclei in the cat.
The capacity of single neurons of the dorsal column nuclei (DCN) for coding vibrotactile information from the hairy skin has been investigated in anesthetized cats to permit quantitative comparison first with the capacities of DCN neurons responding to glabrous skin vibrotactile inputs and second with those of spinocervical tract neurons responding to vibrotactile inputs from hairy skin. Dynamically sensitive tactile neurons of the DCN the input of which came from hairy skin could be divided into two classes, one associated with hair follicle afferent (HFA) input, the other with Pacinian corpuscle (PC) input. The HFA-related class was most sensitive to low-frequency (<50 Hz) vibration and had a graded response output as a function of vibrotactile intensity changes. PC-related neurons had a broader vibrotactile sensitivity, extending to > or =300 Hz and appeared to derive their input from the margins of hairy skin, near the footpads, or from deeper PC sources such as the interosseous membranes or joints. HFA-related neurons had phaselocked responses to vibration frequencies up to approximately 75 Hz, whereas PC neurons retained this capacity up to frequencies of approximately 300 Hz with tightest phaselocking between 50 and 200 Hz. Quantitative measures of phaselocking revealed that the HFA-related neurons provide the better signal of vibrotactile frequency up to approximately 50 Hz with a switch-over to the PC-related neurons above that value. In conclusion, the functional capacities of these two classes of cuneate neuron appear to account for behavioral vibrotactile frequency discriminative performance in hairy skin, in contrast to the limited capacities of vibrotactile-sensitive neurons within the spinocervical tract system.


Vasoactive intestinal polypeptide and neuropeptide Y act indirectly to increase neurite outgrowth of dissociated dorsal root ganglion cells.
Recent studies suggest that rearrangement of synaptic circuitry of primary afferent neurons in the spinal cord may contribute, in part, to hyperalgesia that is often associated with peripheral nerve injury. This study of cultured adult rat dorsal root ganglion cells examined whether vasoactive intestinal polypeptide and neuropeptide Y, which are up-regulated in sensory neurons following nerve transection, possibly contribute to the morphological alterations induced by nerve injury. Neurite outgrowth of dissociated dorsal root ganglion cells was examined two weeks following either sciatic nerve transection or intrathecal administration of test agents via osmotic pumps. Dissociated cells taken from rats with transected sciatic nerve or following intrathecal administration of either vasoactive intestinal polypeptide or neuropeptide Y had a significant increase in the percentage of cells with neurites as compared to dorsal root ganglion cells taken from normal animals. Intrathecal administration, into rats with nerve lesion, of the vasoactive intestinal polypeptide and neuropeptide Y antagonists, vasoactive intestinal polypeptide(10-28) and alpha-trinositol, respectively, significantly attenuated the nerve injury-induced increase in neurite outgrowth. Vasoactive intestinal polypeptide and neuropeptide Y had no influence on neurite outgrowth when applied to normal dissociated dorsal root ganglion cells, however, when added to cells co-cultured with spinal cord explants, both peptides significantly increased the percentage of cells with neurites. K252a, a protein kinase inhibitor, attenuated the trophic action of neuropeptide Y, but not that of vasoactive intestinal polypeptide. The action of vasoactive intestinal polypeptide on neurite outgrowth was attenuated by the protein kinase A inhibitor, the Rp-isomer of adenosine-3',5'-cyclic monophosphorothioate. The results suggest that the peptides may contribute, indirectly, to the nerve injury-induced increase in neurite outgrowth of sensory neurons via separate spinally-derived neurotrophic factors and the study provides further insight into the possible mechanisms underlying hyperalgesia associated with nerve injury.


Water-Induced Breaking of the Coulombic Ordering in a Room-Temperature Ionic Liquid Metal Complex.
Control of ion arrangements in ionic liquids represents a major challenge owing to the presence of the predominant coulombic interactions between cationic and anionic ion species that forms the coulombic ordering. Here, water-induced ion rearrangement in a room-temperature ionic liquid (RT-IL) metal complex, (1-ethyl-3-methylimidazolium)2 [MnN(CN)4 ], is demonstrated through coordinative interactions between anions. Solidification occurred, which was associated with the formation of a "separated" structure consisting of cation columns and anionic cyanide-bridged one-dimensional coordination polymers. The energy diagram is in accord with the resultant RT-IL incorporating mononuclear [MnN(CN)4 ]2- molecules being a kinetic phase stabilized by inter-ion repulsions of the anionic divalent metal complex moieties. Water acts to decrease the coulombic interactions, including repulsion, giving rise to breaking of the coulombic ordering arising from coordination bond formation in the IL phase.


Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension.
Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers (ACEIs/ARBs) had no harmful effects on coronavirus disease 2019 (COVID-19) patients complicated with hypertension. To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs. All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study. Some patients switched from ACEIs/ARBs to calcium channel blocker (CCBs) after admission, while others continued using non-ACEIs/ARBs. We compared characteristics and clinical outcomes between these two groups of patients. A total of 53 patients were enrolled, 27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs. After controlling potential confounding factors using the Cox proportional hazards model, hospital stay was longer in patients who discontinued ACEIs/ARBs, with a hazard ratio of 0.424 (95% confidence interval: 0.187-0.962; P = 0.040), upon discharge than patients using other anti-hypertensive drugs. A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases [hazard ratio = 0.224 (95% confidence interval: 0.005-0.998; P = 0.0497)]. Patients in the discontinued ACEIs/ARBs group had longer hospital stays. Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.


[Mechanism of ascorbic acid transport in the aqueous humor].
The concentration of ascorbic acid in the aqueous humor in many species (including humans and oxen) is several times higher than the plasma concentration. The role of ascorbic acid as a protective mechanism in the intraocular tissues against light-induced damage is discussed. We have performed uptake studies using 14C-labeled ascorbic acid in cultured bovine pigmented ciliary epithelial cells in order to study the mechanisms for ascorbic acid transport from the ciliary body to the aqueous humor. We found that intracellular accumulation of ascorbic acid was Na(+)-dependent. Data from kinetic experiments suggest the presence of a co-transport system for 2 Na+ and 1 ascorbate. The oxidized form of the vitamin (dehydro-ascorbic acid, DHA) was taken up in the cell by a Na(+)-independent mechanism. Using thin-layer chromatographic assay, we found intracellularly only ascorbic acid after incubation with extracellular DHA, indicating the presence of DHA reductase activity in ciliary body epithelial cells. Thus, these cells possess two mechanisms for intracellular accumulation of ascorbic acid: (1) co-transport for 2 Na+ and 1 ascorbate and (2) a Na(+)-independent DHA transport in cooperation with intracellular DHA reductase. These mechanisms could be involved in the transport of ascorbic acid from the stroma to the aqueous humor.


Application of Ice for Postoperative Total Knee Incisions - Does this Make Sense? A Pilot Evaluation of Blood Flow Using Fluorescence Angiography.
Introduction Total knee arthroplasty (TKA) is a common procedure with significant advances over the past several years, many pertaining to improved perioperative pain control. Cryotherapy is one method thought to decrease swelling and pain postoperatively. To our knowledge no study has directly visualized the effect cryotherapy has on skin blood flow following TKA. The primary aim was to determine if cryotherapy (icing) affects peri-incisional skin blood flow and if this is lessened with an alternate placement of the ice. We hypothesized that blood flow would decrease following cryotherapy, and this decrease would be greater with ice placed directly over the incision as compared to placement along the posterior knee. Methods This study included 10 patients who underwent TKA. During the postoperative hospitalization, they were given an injection of indocyanine green dye. A baseline image was recorded of the skin blood flow. Images were then collected following a five-minute interval placement of ice over the incision. The experiment was then repeated with the ice placed along the posterior knee. Results There was an approximate 40% decrease in skin blood flow following placement of the ice compared to baseline. We observed a greater decrease in blood flow when ice was placed over the incision as compared to when ice was placed posterior to the knee (p ≤ 0.020). Conclusion We found a significant decrease in peri-incisional blood flow with icing of the knee. Physicians should be cognizant of this when recommending cryotherapy to patients after surgery, especially in at-risk wounds.