Origins of gliogenic stem cell populations within adult skin and bone marrow.
The generation of Schwann cells from precursors within adult skin and bone marrow is of significant clinical interest because of the opportunities for disease modelling and strategies for remyelination. Recent evidence has suggested that glial cells can be generated from (i) mesenchymal stem cells (MSCs) within adult bone marrow and (ii) skin-derived precursor cells (SKPs) within adult skin. However, there is a need to clarify the developmental mechanism whereby such multipotent adult stem cell populations generate glia. We used Wnt1-Cre/Rosa26R(LacZ) and Wnt1-Cre/Rosa26R(YFP) neural crest reporter mice to test the hypothesis that (i) MSCs and (ii) SKPs represent adult gliogenic precursor cells of neural crest origin. We demonstrate that, although labeled cells can be identified within long bone preparation, such cells are rarely found in marrow plugs. Moreover, we did not find evidence of a neural crest origin of bone marrow-derived MSCs and were not able to provide a developmental rationale for the derivation of glial cells from MSCs using this approach. In contrast, we provide robust evidence for the neural crest origin of SKPs derived from adult skin. These precursor cells reliably generate cells with a Schwann cell phenotype, expressing appropriate transcription factors and Schwann cell markers. We demonstrate multiple anatomical origins of gliogenic SKPs within adult skin. We conclude that SKPs, rather than bone marrow-derived MSCs, represent a more defined and developmentally rational source for the study and generation of Schwann cells from readily accessible adult tissues.


Evolution of Cu single atom catalysts to nanoclusters during CO2 reduction to CO.
We synthesized Cu single atoms embedded in a N-doped porous carbon catalyst with a high Faradaic efficiency of 93.5% at -0.50 V (vs. RHE) for CO2 reduction to CO. The evolution of Cu single-atom sites to nanoclusters of about 1 nm was observed after CO2 reduction at a potential lower than -0.30 V (vs. RHE). The DFT calculation indicates that Cu nanoclusters improve the CO2 activation and the adsorption of intermediate *COOH, thus exhibiting higher catalytic activity than CuNx sites. The structural instability observed in this study helps in understanding the actual active sites of Cu single atom catalysts for CO2 reduction.


Aggressive plasmablastic multiple myeloma in a 42-year-old: is inflammatory bowel disease or infliximab treatment to be blamed?
A man in his early 40s with a history of ulcerative colitis, treated with infliximab, was diagnosed with plasmablastic multiple myeloma. He was treated with chemotherapy and stem cell transplant but developed recurrence and ultimately died from metastatic disease. Could inflammatory bowel disease or infliximab therapy have any role in development of myeloma in this young patient? The role of inflammatory bowel disease and infliximab therapy in the development of multiple myeloma is controversial but interesting and worth considering.


Use of the blood substitute HBOC-201 in critically ill patients during sickle crisis: a three-case series.
Red blood cell (RBC) transfusion is an important treatment modality during severe sickle cell crisis (SCC). SCC patients who refuse, or cannot accept, RBCs present a unique challenge. Acellular hemoglobin (Hb)-based oxygen carriers (HBOCs) might be an alternative for critically ill patients in SCC with multiorgan failure due to life-threatening anemia. HBOC-201 (HbO2 Therapeutics) has been administered to more than 800 anemic patients in 22 clinical trials, but use of any HBOCs in critically ill sickle cell patients with organ failure is exceedingly rare. In the United States, HBOC-201 is currently only available for expanded access. We report three cases of HBOC-201 administered to critically ill sickle cell disease patients in SCC with multiorgan failure, either who refused RBCs (Jehovah's Witnesses) or for whom compatible RBCs were not available. Two patients received more than 20 units of HBOC-201, while the other received 6. The 27 units used in the third case equals the largest volume a patient has successfully received to date. All three patients survived to hospital discharge. These reports suggest that blood substitutes such as HBOC-201 can provide an oxygen bridge in SCC with multiorgan failure, until corpuscular Hb levels recover to meet metabolic demand, and highlight the compelling biochemical properties that warrant further investigation.


Parent-based interventions for preventing or reducing adolescent substance use - A systematic literature review.
Despite the increasing relevance of peers, parents remain important socializing agents for their adolescent children and are therefore promising agents for inclusion in prevention or intervention programs. This systematic review provides an overview of the effectiveness of parent-based programs in preventing, curbing or reducing substance use (i.e. alcohol, tobacco and cannabis) among 10 to 18-year-olds. The databases PubMed, PsychInfo, Eric and Google Scholar were used to identify randomized trials published within the past 12years evaluating effects on adolescent substance use. Of the 653 identified in the first screening, 39 publications dealing with 13 programs were included. Results reveal desirable effects of parenting measures such as rule-setting, monitoring and parent-child communication. There was also some evidence in terms of preventing, curbing or reducing adolescent substance use. However, this appears to depend particularly on the age group of the adolescents in question, the kind of parents included and the intensity of the program. To conclude, the results of this systematic review underline the importance of including parents in programs aiming to impede initiation of substance use or curb or reduce already existing substance use in adolescence.


Effect of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia: A randomized, 1-year study.
Antipsychotic drugs are limited in their ability to improve the overall outcome of schizophrenia. Adding psychosocial treatment may produce greater improvement in functional outcome than does medication treatment alone. To evaluate the effectiveness of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia. Randomized controlled trial. Ten clinical sites in China. Clinical sample of 1268 patients with early-stage schizophrenia treated from January 1, 2005, through October 31, 2007. Intervention Patients were randomly assigned to receive antipsychotic medication treatment only or antipsychotic medication plus 12 months of psychosocial intervention consisting of psychoeducation, family intervention, skills training, and cognitive behavior therapy administered during 48 group sessions. The rate of treatment discontinuation or change due to any cause, relapse or remission, and assessments of insight, treatment adherence, quality of life, and social functioning. The rates of treatment discontinuation or change due to any cause were 32.8% in the combined treatment group and 46.8% in the medication-alone group. Comparisons with medication treatment alone showed lower risk of any-cause discontinuation with combined treatment (hazard ratio, 0.62; 95% confidence interval, 0.52-0.74; P < .001) and lower risk of relapse with combined treatment (0.57; 0.44-0.74; P < .001). The combined treatment group exhibited greater improvement in insight (P < .001), social functioning (P = .002), activities of daily living (P < .001), and 4 domains of quality of life as measured by the Medical Outcomes Study 36-Item Short Form Health Survey (all P < or = .02). Furthermore, a significantly higher proportion of patients receiving combined treatment obtained employment or accessed education (P = .001). Compared with those receiving medication only, patients with early-stage schizophrenia receiving medication and psychosocial intervention have a lower rate of treatment discontinuation or change, a lower risk of relapse, and improved insight, quality of life, and social functioning. clinicaltrials.gov Identifier: NCT00654576.


Polymer-supported O-alkylisoureas: useful reagents for the O-alkylation of carboxylic acids.
Polymer-supported O-alkylisoureas were prepared by reaction of an alcohol with a polymer-supported carbodiimide under copper(II) catalysis. These reagents were used to transform carboxylic acids into the corresponding methyl, benzyl, allyl, and p-nitrobenzyl esters in a highly chemoselective manner in high yields and in very high purity after simple resin filtration and solvent evaporation. The reactions could be carried out using both conventional or microwave heating, with reaction times as short as 3-5 min in the latter case, without compromising yield, purity, or chemoselectivity. Unfortunately, the corresponding solid-supported tert-butyl isoureas could not be prepared.


Accuracy of AccessBio Immunoglobulin M and Total Antibody Rapid Immunochromatographic Assays for the Diagnosis of Acute Scrub Typhus Infection.
Using archived samples, we assessed the diagnostic capacity of a rapid immunochromatographic test (ICT) for the detection of Orientia tsutsugamushi IgM and total antibodies to aid with the diagnosis of acute scrub typhus infection in febrile patients in Laos. The sensitivity and the specificity of the ICT for the detection of IgM were 96.8% (121/125 samples; 95% confidence interval [CI], 92.1 to 99.1%) and 93.3% (98/105 samples; 95% CI, 86.7 to 97.3%), respectively. For the detection of total antibodies, the sensitivity was 97.6% (122/125 samples; 95% CI, 93.1 to 99.5%), but the specificity was much lower, at 71.4% (75/105 samples; 95% CI, 61.8 to 79.8%).


Kidney transplantation in patients with HIV infection.
HIV infection is a common cause of ESRD, particularly among blacks. Advances in antiretroviral therapy have greatly improved the survival of HIV patients, including those with renal disease. Despite concerns about the risk of immunosuppressive medications for HIV patients, emerging studies have now reported acceptable short-term outcomes for eligible HIV recipients undergoing renal transplantation, and an ongoing multicenter clinical trial reported 1-year patient and graft survival similar to that of HIV-uninfected kidney recipients. In these studies, the interactions between calcineurin inhibitors and HIV medications that are also metabolized by the cytochrome P450 system required substantial dosing modifications and careful monitoring of calcineurin inhibitor trough levels. These studies also revealed an elevated risk of acute rejection of the kidney allograft but few reports of opportunistic infections or viremia that could not be controlled. Long-term follow-up studies will be important to examine these outcomes and the development of malignancy to fully evaluate the risk and benefits of kidney transplantation among HIV-positive recipients.


An analysis of the educational levels of migrants.
"The educational level has significant bearings on the migration of population. As one of the factors that can brook no underestimation in the developing commodity economy, it determines, to a certain extent, the size, direction, and occupation or profession of population migration. The Institute of Population at the Academy of Social Sciences of China conducted a sampling survey of the migration of population in 74 cities of 16 provinces, municipalities and autonomous regions in 1986, and this paper presents a summary analysis of the dynamics of different educational levels of the migrating population surveyed."


An Evaluation of the Reliability, Construct Validity, and Factor Structure of the Static-2002R.
The fundamental psychometric properties of the subscales found in the Static-2002R, an actuarial measure of sexual recidivism risk, were evaluated in the current study. Namely, the reliability, concurrent and construct validity, and factor structure of the Static-2002R subscales were examined with a sample of 372 adult male sex offenders. In addition to using validated measures of sexual violence risk to examine concurrent validity, construct-related measures taken from extant risk measures and psychometric tests were correlated with three of the subscales to assess overall construct validity. Moderate support was found for the reliability of the Static-2002R. The concurrent and construct validity of the General Criminality, Persistence of Sexual Offending, and Deviant Sexual Interest subscales were supported. Generally, these findings further support the Static-2002R as a valid sex offender risk appraisal instrument that encompasses multiple distinct, clinically relevant, risk domains.


An empirical analysis of rock climbers' response to hazard warnings.
This paper reports the results of a field test of the hazard warning system used in rock climbing. The system is succinct; it differentiates between magnitudes of hazard; and it establishes a "warnings vocabulary." The empirical hazard response models include an "individuating factor," which influences the likelihood of injury, and the severity of injury as independent variables. The models indicate that climbers do assess a "personal" probability of injury and incorporate the hazard warning message when choosing climbing routes. Climbers of greater technical ability are more likely to climb hazardous routes, but they mitigate the likelihood of the hazardous outcome by reducing the technical difficulty of the hazardous route chosen. The response increases with the degree of hazard involved.


Te-based glass fiber for far-infrared biochemical sensing up to 16 μm.
Chalcogenide glass fibers are very suitable to carry out mid-infrared spectroscopy by Fiber Evanescent Wave Spectroscopy (FEWS). Nowadays, selenide glasses are used for FEWS, but the reachable domain is limited in the infrared to typically 12 µm. Te-rich glasses, due to their heavy atomic weight, are better for far-infrared sensing but they crystallize easily and until now that was difficult to prepare operational optical fibers from such glasses. In this work, Te-Ge-AgI highly purified glasses have been prepared and successfully drawn into optical fiber. The minimum of attenuation is 3 dB/m around 10 μm, which is up to now the lowest value ever measured for Te-based fiber. Overall, such fibers open the sensing window up to 16 μm against 12 µm so far. Then, for the first time, tapered telluride fibers with different diameters at the sensing zone were obtained during the fiber drawing process. Chloroform and butter were used to test the fiber infrared sensing ability, and the sensitivity has been greatly enhanced as the sensing zone fiber diameter decreases. Finally, the new protocol of telluride glass preparation allows shaping them into efficient functional fibers, opening further in the mid-infrared which is essential for chemical spectroscopy.


Purification and Interconversion of Homoserine Dehydrogenase from Daucus carota Cell Suspension Cultures.
Homoserine dehydrogenase from cell suspension cultures of carrot (Daucus carota L.) has been purified to apparent homogeneity by a combination of selective heat denaturation, ion exchange and gel filtration chromatographies, and preparative gel electrophoresis. Carrot homoserine dehydrogenase is composed of subunits of equal molecular weight (85,000 +/- 5,000). During purification, the enzyme exists predominantly in two molecular weight forms, 180,000 and 240,000. The enzyme can be reversibly converted from one form to the other, and each has different regulatory properties. When the enzyme is dialyzed in the presence of 5 millimolar threonine, the purified enzyme is converted into its trimeric form (240,000), which is completely inhibited by 5 millimolar threonine and is stimulated 2.6-fold by K(+). When the enzyme is dialyzed in the presence of K(+) and absence of threonine, the purified enzyme is converted into a dimer (180,000), which is not inhibited by threonine and is only stimulated 1.5-fold by K(+). The enzyme also can polymerize under certain conditions to form higher molecular weight aggregates ranging in size up to 720,000, which also are catalytically active. This interconversion of homoserine dehydrogenase conformations may reflect the daily stream of events occurring in vivo. When light stimulates protein synthesis, the threonine pool decreases in the chloroplast, while K(+) concentrations increase. The change in threonine and K(+) concentrations shift the homoserine dehydrogenase from the threonine-sensitive to the threonine-insensitive conformation resulting in increased production of threonine, which would meet the demands of protein synthesis. The reverse process would occur in the dark.


Investigating the effect of dietary calcium levels on ileal endogenous amino acid losses and standardized ileal amino acid digestibility in broilers and laying hens.
Two studies were conducted to evaluate the effect of dietary Ca levels (low, 1% and high, 3%) on ileal endogenous amino acid losses (IEAAL) and standardized ileal amino acid digestibility (SIAAD) in broilers (BR) and laying hens (LH) fed nitrogen-free diets (NFD) and distiller's dried grain with solubles (DDGS)-based diets. A total of 384 male Cobb 500 BR and 288 LH were used in a completely randomized design (CRD) with 16 (BR) or 12 (LH) replicate cages with 6 birds/replicate. IEAAL and apparent ileal digestibility (AID) of AA were analyzed using the GLM procedure of SAS appropriate for a CRD while SIAAD values were analyzed using the GLM procedure of SAS appropriate for a 2 × 2 factorial arrangement of treatments. For BR, IEAAL and N losses (mg/kg of dry matter intake, DMI) were higher (P < 0.05) when NFD with high Ca level was fed (total AA was 39%, N was 35% higher). For most of the AA, AID was higher (P < 0.05) in BR fed DDGS-based diet with high Ca level. High dietary Ca resulted in higher (P < 0.05) SIAAD for all the AA except for Arg, Lys, Met, Cys, and Tyr. For LH, AID of AA was higher (P < 0.05) for the DDGS diet with high Ca level in 13 of the 18 AA evaluated. There was interaction (P < 0.05) between diet Ca level and correction method on LH SIAAD values for Thr, Asp, Gly, and Ser. The SIAAD values for 8 AA were higher (P < 0.05) in birds on high Ca DDGS diet. Correction with low Ca NFD resulted in higher (P < 0.05) SIAAD values for all the AA. Result from this study showed that high Ca increased total IEAAL in BR by 39% but decreased same by 27% in LH. Finally, SIAAD values were increased in BR fed high Ca DDGS-based diet while SIAAD value in LH was lower when correction was done using values from high Ca-NFD fed birds.


Noninvasive Blood and Tissue Analysis: Raman Spectroscopy, One Perspective for Monitoring of Glucose and Beyond.
Noninvasive in vivo blood and tissue analysis remains a challenge to medical technology epitomized by the ongoing quest to replace fingerstick self-monitoring of blood glucose. Recent developments warrant comment on near-term prospects for using Raman spectroscopy to meet that challenge. These developments combined with 20 years of experimentation with noninvasive blood and tissue analysis suggest that it may be possible and practical to perform noninvasive in vivo glucose analysis with improvements in (1) the enabling technologies for making Raman measurements and (2) an underlying anatomical-physiological model of how in vivo spectroscopic measurements are made and interpreted. We review the substantial progress made toward meeting the challenge and the personal, public health, and economic implications of these ongoing efforts.


An Interesting Case of Intramuscular Myxoma with Scapular Bone Lysis.
Introduction. Intramuscular myxoma is a rare benign primitive tumor of the mesenchyme founded at the skeletal muscle level; it presents itself like an unpainful, slow-growing mass. Myxomas with bone lysis are even more rare; only 7 cases have been reported in the English literature, but never at the shoulder level. Case Presentation. We describe an 83-year-old patient with a growing mass in the deltoid muscle with unique scapular lysis, without any symptom. Magnetic resonance imaging (MRI) and a biopsy were performed and the diagnosis of intramuscular myxoma has been retained. In front of this diagnosis of nonmalignant lesion, the decision of a simple follow-up was taken. One year after this decision, the patient was still asymptomatic. Conclusion. In the presence of an intramuscular growing mass with associated bone lysis, intramuscular myxoma as well as malignant tumor should be evoked. MRI has to be part of the initial radiologic appraisal but biopsy is essential to confirm the diagnosis. By consensus, the standard treatment is surgical excision but conservative treatment with simple follow-up can be an option.


Osmolytes ameliorate the effects of stress in the absence of the heat shock protein Hsp104 in Saccharomyces cerevisiae.
Aggregation of the prion protein has strong implications in the human prion disease. Sup35p is a yeast prion, and has been used as a model protein to study the disease mechanism. We have studied the pattern of Sup35p aggregation inside live yeast cells under stress, by using confocal microscopy, fluorescence activated cell sorting and western blotting. Heat shock proteins are a family of proteins that are produced by yeast cells in response to exposure to stressful conditions. Many of the proteins behave as chaperones to combat stress-induced protein misfolding and aggregation. In spite of this, yeast also produce small molecules called osmolytes during stress. In our work, we tried to find the reason as to why yeast produce osmolytes and showed that the osmolytes are paramount to ameliorate the long-term effects of lethal stress in Saccharomyces cerevisiae, either in the presence or absence of Hsp104p.


Vascular procedures in the critically ill obese patient.
The increasing societal prevalence of obesity is consequential to the increasing number of critically ill obese patients. Vascular procedures are an essential aspect of care in these patients. This article reviews the general, anatomic, and physiologic considerations pertaining to vascular procedures in critically ill obese patients. In addition, the use of ultrasonography for these procedures is discussed.


Extraordinarily high conductivity of flexible adhesive films by hybrids of silver nanoparticle-nanowires.
Highly conductive flexible adhesive (CFA) film was developed using micro-sized silver flakes (primary fillers), hybrids of silver nanoparticle-nanowires (secondary fillers) and nitrile butadiene rubber. The hybrids of silver nanoparticle-nanowires were synthesized by decorating silver nanowires with silver nanoparticle clusters using bifunctional cysteamine as a linker. The dispersion in ethanol was excellent for several months. Silver nanowires constructed electrical networks between the micro-scale silver flakes. The low-temperature surface sintering of silver nanoparticles enabled effective joining of silver nanowires to silver flakes. The hybrids of silver nanoparticle-nanowires provided a greater maximum conductivity (54 390 S cm(-1)) than pure silver nanowires, pure multiwalled carbon nanotubes, and multiwalled carbon nanotubes decorated with silver nanoparticles in nitrile butadiene rubber matrix. The resistance change was smallest upon bending when the hybrids of silver nanoparticle-nanowires were employed. The adhesion of the film on polyethylene terephthalate substrate was excellent. Light emitting diodes were successfully wired to the CFA circuit patterned by the screen printing method for application demonstration.


CD44+/CD24- Cancer Stem Cells Are Associated With Higher Grade of Canine Mammary Carcinomas.
The CD44+/CD24- phenotype identifies cancer stem cell (CSC) properties in canine mammary carcinoma (MC); however, the histopathological features associated with this phenotype remain to be elucidated. Here, we determined whether the CD44+/CD24- phenotype was associated with hormonal receptor (HR; estrogen receptor [ER] and/or progesterone receptor [PR]) status and/or triple (ER, PR, and human epithelial growth factor receptor 2)-negative (TN) subtype; conventional histological evaluation was also performed. We found that, as single markers, both CD44+ and CD24+ were associated with less aggressive histological types, low grade, and a non-TN subtype; both markers were associated with HR positivity. On the other hand, a CD44+/CD24- phenotype was associated with higher grade of carcinoma. Therefore, our results suggest that immunohistochemical phenotyping for CD44/CD24 is useful for the evaluation of tumor behavior as well as CSC-like properties in canine MCs.


Three-dimensional motion analysis of facial movement during verbal and nonverbal expressions in healthy subjects.
Functional impairments of facial expressions alter the quality of life and their quantitative analysis is key to describing and grading facial function and dysfunction. The aim of this investigation was to quantify 3D lip movements in a group of healthy young subjects. Lip movements during five repetitions of common and random sequences of vowels and nonverbal expressions were recorded using an optoelectronic 3D motion analyzer. The mean maximum displacement of facial landmarks was used to compute 3D unilateral mobility and the symmetry indices (SI) separately for each sex. Facial mobility was significantly greater during open-mouth than closed-mouth smiles. Facial movement among the subjects was largest during articulation of the vowel /a/ and smallest for /i/. Lips were pursed with a SI very close to 95%, while smiles were slightly more asymmetric. The vowel /a/ was articulated with significantly greater symmetry than /e/, /i/ and /u/. The outcomes suggest that the proposed method characterized normal facial animations satisfactorily, so it could be a useful tool for assessing patients with facial lesions and dentofacial deformities. Patient assessment would profit from this quantitative approach, which would reduce discrepancies among several clinical examinations. Clin. Anat. 29:991-997, 2016. © 2016 Wiley Periodicals, Inc.


Update: changes in notifiable disease surveillance data--United States, 1992-1993.
Since April 1990, CDC has graphically presented changes in reported cases of 14 notifiable infectious diseases reported through the National Notifiable Diseases Surveillance System (NNDSS). Figure I of each issue of MMWR displays on a log scale the ratio of the number of cases reported in the most recently ended 4-week period to that of the mean of the number of cases reported in 15 historical 4-week periods. During 1992-1993, Figure I has indicated a decline in incidence in selected reportable diseases (e.g., measles, mumps, and rubella). Declines in the incidence of these diseases could represent either true declines or changes in notifiable disease surveillance (e.g., a lower percentage of all cases was reported than previously). During June-August, 1993, CDC evaluated the surveillance system to determine the reasons for the declines. This report summarizes the results of the evaluation.


A highly sensitive and efficient UPLC-MS/MS assay for rapid analysis of tedizolid (a novel oxazolidinone antibiotic) in plasma sample.
Tedizolid (TDZ) is a novel oxazolidinone class antibiotic, indicated for the treatment of acute bacterial skin and skin structure infections in adults. In this study a highly sensitive UPLC-MS/MS assay was developed and validated for the determination of TDZ in rat plasma using rivaroxaban as an internal standard (IS). Both TDZ and IS were separated on an Acquity UPLC BEH™ C18 column using an isocratic mobile phase comprising of acetonitrile-20 mm ammonium acetate (85:15, v/v), eluted at 0.3 mL/min flow rate. The plasma sample was processed by liquid liquid extraction technique using ethyl acetate as an extracting agent. The analyte and IS were detected in positive mode using electrospray ionization source. The precursor to product ion transitions at m/z 371.09 > 343.10 for TDZ and m/z 435.97 > 144.94 for IS were used for the quantification in multiple reaction monitoring mode. The calibration curve was linear in the concentration range of 0.74-1500 ng/mL and the lower limit of quantification was 0.74 ng/mL only. The developed assay was validated following standard guidelines for bioanalytical method validation (US Food and Drug Administration) and all the validation results were within the acceptable limits. The developed assay was successfully applied into a pharmacokinetic study in rats. Copyright © 2016 John Wiley & Sons, Ltd.


Radiation dose and leukemia risk in patients treated for cancer of the cervix.
To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.


Islet versus pancreas transplantation in Brazil: Defining criteria for pancreas allocation decision.
Many studies have evaluated whether there are characteristics related to pancreas donors and the islet isolation process that can influence pancreatic islet yield. However, this analysis has not yet been performed in Brazil, one of the world leaders in whole pancreas organ transplantation (WOPT), where pancreas allocation for pancreatic islet transplantation (PIT) has no officially defined criteria. Definition of parameters that would predict the outcome of islet isolation from local pancreas donors would be useful for defining allocation priority in Brazil. To analyze the relationship between multiple donor-related and islet isolation variables with the total number of isolated pancreatic islet equivalents (IEQ) in a brazilian sample of pancreas donors. Several variables were analyzed in 74 pancreata relative to the outcome of total IEQs obtained at the end of the process. In univariate analysis, body mass index (BMI) (p = 0.003), the presence of fatty infiltrates in the pancreas as observed during harvesting (p = 0.042) and pancreas digestion time (p = 0.046) were identified as variables related to a greater IEQ yield. In a multivariate analysis a statistically significant contribution to the variability of islet yield was found only for the BMI (p = 0.017). A ROC curve defined a BMI = 30 as a cut-off point, with pancreata from donors with BMI > 30 yielding more islets than donors with BMI < 30 (p< 0.001). These data reinforce the importance of the donor BMI as a defining parameter for successful islet isolation and establishes this variable as a potential pancreas allocation criterion in Brazil, where there is unequal competition for good quality organs between WOPT and PIT.


Descriptions of two new species of Rhopalovalva Kuznetzov, 1964 (Lepidoptera: Tortricidae) from China.
Two new species of Rhopalovalva Kuznetzov are described from China: R. macrocuculla Zhang and Li, sp. nov., and R. connata Zhang and Li, sp. nov. Photographs of the adults and genitalia are provided. We report the first occurrence of the absence of an uncus in the male genitalia of a Rhopalovalva species. A key to the Chinese species is provided based on the characters of the male genitalia. We also comment on the generic characters of Rhopalovalva.


Performance of cardiovascular risk scores in mortality prediction ten years after Acute Coronary Syndromes.
The objective of this study was to evaluate the performance of the Framingham risk score (FRS) and risk score by the American College of Cardiology/American Heart Association (SR ACC/AHA) in predicting mortality of patients ten years after acute coronary syndrome (ACS). This is a retrospective cohort study that included patients aged ≥ 18 years with ACS who were hospitalized at the Coronary Intensive Care Unit (ICU) of the Botucatu Medical School Hospital from January 2005 to December of 2006. A total of 447 patients were evaluated. Of these, 118 were excluded because the mortality in 10 years was not obtained. Thus, 329 patients aged 62.9 ± 13.0 years were studied. Among them, 58.4% were men, and 44.4% died within ten years of hospitalization. The median FRS was 16 (14-18) %, and the ACC/AHA RS was 18.5 (9.1-31.6). Patients who died had higher values of both scores. However, when we classified patients at high cardiovascular risk, only the ACC/AHA RS was associated with mortality (p <0.001). In the logistic regression analysis, both scores were associated with mortality at ten years (p <0.001). Both FRS and SR ACC/AHA were associated with mortality. However, for patients classified as high risk, only the ACC/AHA RS was associated with mortality within ten years.


The human placental bed: histology, immunohistochemistry and pathology.
There has been much interest recently on local intra-uterine materno-fetal interactions particularly in the placental bed where cellular relationships between mother and fetus are at their most intimate. While few histopathologists are expected to interpret formal placental bed biopsy specimens, confrontation with tissue from this site is common following abortion, post-partum haemorrhage or molar gestation. This review gives an account of recent advances in our knowledge of the histology, immunohistochemistry and pathology of the placental bed. It focuses particularly on extravillous trophoblast populations and their relationship to maternal cells and emphasizes the importance of vascular changes.


Recognition for home care's role in disaster preparedness: our time has come...but are we ready for it?
Those of us in the home care and hospice industry know we have a major role in disaster preparedness. Our history is rich with examples of that. We have participated in events such as the Great Influenza Pandemic of 1918 and other pandemics, mass immunizations programs, communicable disease outbreaks, and of course, after natural disasters such as Hurricane Katrina.


Structure of hydronium (H3O+)/chloride (Cl-) contact ion pairs in aqueous hydrochloric acid solution: a Zundel-like local configuration.
A comprehensive analysis of the H(3)O(+) and H(2)O structure in the first solvation shell about Cl(-) in aqueous HCl solutions is reported from X-ray absorption fine structure (XAFS) measurements. Results show increasing degree of contact ion pairing between Cl(-) and H(3)O(+) as the HCl concentration increases from 6.0 m, 10.0 m, and finally 16.1 m HCl (acid concentrations are expressed as molality or mole HCl/1000 g water). At the highest acid concentration there are on average, approximately 1.6 H(3)O(+) ions and 4.2 H(2)O's in the first shell about Cl(-). The structure of the Cl(-)/H(3)O(+) contact ion pair is distinctly different from that of the H(2)O structure about Cl(-). The Cl-O bond length (2.98 A) for Cl(-)/H(3)O(+) is approximately 0.16 A shorter than the Cl(-)/H(2)O bond. The bridging proton resides at an intermediate position between Cl and O at 1.60 A from the Cl(-) and approximately 1.37 A from the O of the H(3)O(+). The bridging-proton structure of this contact ion pair, (Cl-H-OH(2)), is similar to the structure of the water Zundel ion, (H(2)O-H-OH(2)(+)). In both cases there is a shortened Cl-O or O-O bond, and the intervening proton bond distances are substantially longer than for the covalent bonds of either HCl or H(2)O. A detailed structural analysis of the aqueous chloride species, Cl(-)/(H(2)O)(n), was also completed as part of this study in order to understand the relative importance of various XAFS photoelectron scattering paths. For aqueous Cl(-) the measured Cl-O and Cl-H distances of 3.14 A and 2.23 A, respectively, are in excellent agreement with earlier neutron and X-ray diffraction results. Overall, these results significantly improve our understanding of the interaction of H(3)O(+) with Cl(-). The results are of interest to fundamental physical chemistry and they have important consequences in biochemical, geochemical, and atmospheric processes.


Methylation-Induced Silencing of ALDH2 Facilitates Lung Adenocarcinoma Bone Metastasis by Activating the MAPK Pathway.
Bone metastasis (BM) dramatically reduces the quality of life and life expectancy in lung adenocarcinoma (LUAD) patients. There is an urgent need to identify potential biomarkers for application in the treatment of this deadly disease. We compared patient BM, LUAD, and para-LUAD tissues using proteomic analysis and identified aldehyde dehydrogenase 2 (ALDH2), which can detoxify acetaldehyde to acetic acid, as one of the key regulators in lung tumor metastasis. Both the mRNA and protein levels of ALDH2 were significantly lower in tumor tissues than in normal tissues and were lowest in BM tissues with increased migratory capacity. Also, ALDH2 was upregulated following treatment with 5-azacitidine, a DNA methyltransferase inhibitor, in H1299, H460, and HCC827 cells. Further, we identified a potential methylated CpG island 3, with the longest methylated CpG island area in ALDH2, and performed bisulfite genomic sequencing of these sites. An average of 78.18% of the sites may be methylated in CpG island 3. Knockdown of DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and methylated CpG binding protein 4 (MBD4) upregulated ALDH2 expression. ALDH2 functions as a mitogen-activated protein kinase (MAPK) upstream to inhibit cell proliferation and migration, promote cell apoptosis, and alter the epithelial-mesenchymal transition (EMT) by elevating E-cadherin and attenuating vimentin. Cell proliferation and migration were inhibited after the addition of the JNK inhibitor SP600125. In the multivariate analysis, M stage (p = 0.003), ALDH2 (p = 0.008), and phospho-c-Jun N-terminal kinase (p-JNK) (p = 0.027) expression were independent prognostic factors for overall survival in patients with BM. In vivo experiments also showed that ALDH2 expression could suppress tumor formation. In summary, we found that ALDH2 expression is a prognostic factor for BM in LUAD and that DNMT3A and MBD4 repression of ALDH2 via a MAPK-dependent pathway alters the EMT process, indicating that these proteins could act as potential biomarkers or therapeutic targets for LUAD metastasis.


Peroxynitrite induces airway hyperresponsiveness in guinea pigs in vitro and in vivo.
Peroxynitrite (ONOO-) is a cytotoxic product of the rapid reaction between nitric oxide and superoxide that may initiate inflammation. Isolated perfused tracheas from guinea pigs were incubated from the mucosal side for 15 min with peroxynitrite (1 to 100 muM). Thereafter, concentration-response curves to histamine and methacholine were constructed on the preparations. Peroxynitrite (10 muM) caused a significant hyperresponsiveness; the maximal contractions in response to histamine and methacholine were enhanced by 30% and 40%, respectively. In the peroxynitrite-treated group, clear epithelial damage as well as eosinophil destruction were detected. Moreover, 3, 5, and 10 days after intratracheal instillation of peroxynitrite (100 nmol), a significant rise in pulmonary resistance to histamine of anesthetized animals was observed. It is suggested that the generation of peroxynitrite from nitric oxide superoxide radicals during inflammatory processes induces epithelial damage, mediator release, and hence airway hyperresponsiveness. These findings may have clinical implications, because airway inflammation, epithelial damage, and hyperresponsiveness are characteristic features in patients suffering from asthma.


New Insights into Osteointegration and Delamination from a Multidisciplinary Investigation of a Failed Hydroxyapatite-Coated Hip Joint Replacement.
Hydroxyapatite (HA) coatings have become very popular in uncemented total hip arthroplasty (THA). Analysis of retrievals and tissue samples from an HA-coated femoral stem, which failed within 14 months after THA, provides exceptional insights into the failure mechanism, as well as the process of osteointegration of such an implant. Retrievals were photo-documented. Samples were examined by micro-computed tomography, X-ray diffraction (XRD) and embedded in polymethylmethacrylate for histology. The coating had partially delaminated. The sandblasted surface of the stem was partially polished by the delaminated HA coating, indicating failure before revision. In the tissue samples, the HA coating was well integrated by newly formed bone trabeculae. No adverse biological reaction was observed. XRD analysis showed that residues of the HA coating were still present and could clearly be differentiated from the surrounding bone. Preferential orientation of the HA crystallites could be identified within the newly formed bone, representing a potential mechanical weakness induced either by physiologic strain or by the coating. current HA coatings, relatively thick and made of high crystallinity HA, may be prone to delamination, as also seen in our study. Recent efforts have aimed towards thinner (<1 μm) coatings with nanocrystalline HA structures that possibly relate to lower delamination risks. However, the question arises if HA coatings are beneficial since sandblasted non-coated stems offer similar results without the risk of delamination. XRD not only permits differentiation between the HA from the coating and the HA of the ongrown bone, it also provides new insights into the microstructure of this newly formed bone.


A proviral role for CpG in cytomegalovirus infection.
TLR9-dependent signaling in plasmacytoid dendritic cells is a key contributor to innate immune defense to mouse CMV infection. We aimed to study the expression and potential contribution of TLR9 signaling in human CMV (HCMV) infection of primary fibroblasts. HCMV infection strongly induced TLR9 expression in two of three fibroblast types tested. Furthermore, the TLR9 ligand CpG-B induced a strong proviral effect when added shortly after HCMV infection, enhancing virus production and cell viability. However, not all CpG classes displayed proviral activity, and this correlated with their IFN-beta-inducing ability. The proviral effect of CpG-B correlated completely with concurrent viral up-regulation of TLR9 in fibroblasts. Importantly, the timing of CpG addition was a critical parameter; in striking contrast to the proviral effect, CpG addition at the time of infection blocked viral uptake and nearly abolished HCMV production. The contrasting and time-dependent effects of CpG on HCMV infectivity reveal a complex interplay between CpG, TLR9, and HCMV infection. Additionally, the data suggest a potentially harmful role for CpG in the promotion of HCMV infection.


Experimental Aujeszky's disease in blue foxes (Alopex lagopus).
Blue foxes were inoculated orally with Aujeszky's disease virus. Several foxes were killed at the onset of clinical signs and other animals spontaneously died. The incubation period ranged from 3 to 6 days and was followed by a short illness characterized by anorexia, depression and coma. At autopsy, no specific gross findings were observed. Microscopically, lesions included a non-suppurative meningoencephalitis with neuronal necrosis, gliosis, neuronophagia and mononuclear cell cuffing. Viral antigen was detected by immunoperoxidase technique.


Trends in Comorbid Conditions Among Medicaid Enrollees With HIV.
As antiretroviral therapy has become more effective, persons with HIV live longer and develop conditions that are characteristic of older populations. Understanding changes in comorbid conditions has important implications for the complexity and cost of care, particularly for Medicaid programs and their enrollees, which comprise about 40% of all persons with HIV. Thus, our objective was to examine trends in comorbid conditions for Medicaid enrollees with HIV. Using 2001-2012 administrative claims data from the 14 states (NY, CA, FL, TX, MD, NJ, PA, IL, GA, NC, VA, LA, OH, MA) with the highest HIV prevalence, we identified 494 322 unique Medicaid enrollees with HIV, representing 5.8 million person-quarters after exclusions. We estimated changes over time in enrollee characteristics, proportions of enrollees with the 10 most common comorbid conditions, and number of comorbid conditions per enrollee. Over time, the average age for HIV Medicaid enrollees increased, and the proportion enrolled in a managed care plan also increased. In 2012, the highest proportion of enrollees exhibited evidence of hypertension (31%), psychiatric disease (26%), any liver disease (25%), and pulmonary disorder (23%). Nine of the 10 comorbid conditions increased over time, whereas HIV-related conditions declined. The largest adjusted relative increases in 2012 vs 2003 were observed for renal insufficiency (adjusted odds ratio [aOR], 2.20; P < .001), hyperlipidemia (aOR, 1.80; P < .001), and psychiatric disease (aOR, 1.45; P < .001). Despite improvements in antiretroviral therapy and better control of patients' HIV, we found substantial increases in rates of comorbid conditions over time. These findings have important implications for the complexity and costs of clinical care and for state Medicaid programs.


A human-centered design of a dental discharge summary (DDS) for patients.
Patients are often provided with sub-optimal information regarding their clinic visits. Patients sometimes forget post-discharge instructions provided verbally, and infrequently follow preventative advice to improve health. In this research we propose to develop and evaluate a dental discharge summary (DDS) for patients through a human-centered design process. Our long term goals are to automatically generate a personalized discharge summary after each clinic encounter to educate and motivate patients to maintain excellent oral health.


Multipoint Pacing with Fusion-optimized Cardiac Resynchronization Therapy: Using It All to Narrow QRS Duration.
Adaptive atrioventricular (AV)-shortening algorithms have achieved QRS duration (QRSd) narrowing in traditional cardiac resynchronization therapy (CRT) patients. Multipoint pacing (MPP) has also demonstrated benefit in this population. An additional site of activation via intrinsic conduction of the septum may further contribute to CRT; however, the incorporation of all strategies together has yet to be explored. We therefore developed and tested a method combining MPP-CRT and controlled septal contribution to create a multifuse pacing (MFP) technique, establishing four ventricular activation sites for CRT patients using measurements from intracardiac electrograms (EGMs) and incorporating an AV-delay shortening algorithm (SyncAV™; Abbott Laboratories, Chicago, IL, USA) to narrow the QRSd. Patients in sinus rhythm with an AV conduction time of less than 350 ms were included in this analysis and were further stratified by strictly defined left bundle branch block (sLBBB) or nonspecific intraventricular conduction delay (IVCD). EGM-based measurements to determine the QRS septal onset to right ventricular (RV) time (SRAT) and the left ventricular (LV) to RV pacing conduction time were collected and applied to a formula to facilitate MFP. QRSd was compared between before and after programming. A total of 22 patients (19 men and three women) with similar baseline characteristics were compared (all values in mean ± standard deviation). The overall baseline QRSd of 153.31 ± 24.60 ms was decreased to 115.31 ± 16.31 ms after MFP programming (p < 0.0001). The measured SRAT was 59.40 ± 28.49 ms, resulting in a negative AV offset of -20.0 ± 24.97 ms. Patients in the sLBBB group (n = 7) were aged 67.8 ± 13.3 years and had a QRSd of 168.85 ± 27.29 ms that decreased to 113 ± 16.69 ms for a reduction of 55.42 ± 19.3 ms or 32.1% (p = 0.0003). In the IVCD group (n = 15), the baseline QRSd of 146.06 ± 20.29 ms was decreased to 116 ± 16.66 ms for a reduction of 30.07 ± 16.41 ms or 20.62% (p = 0.0001). When comparing the sLBBB and IVCD groups, the sLBBB group was favored by a reduction of 25.35 ms (p = 0.00046). Ultimately, MFP achieved statistically significant reductions in QRSd in all patients tested in this analysis. The benefit was also significantly better in the sLBBB group as compared with in the IVCD group.


Integrin β1 subunit signaling is involved in the directed migration of human retinal pigment epithelial cells following electric field stimulation.
Direct current electric fields (EFs) can induce directed cell migration in a wide variety of cells, and this has been proven to be of importance in wound healing. Here we observed the effects of EFs on cultured human retinal pigment epithelial (RPE) cells and explored the possible involvement of integrin β1 subunit signaling in the process. Cultured human RPE cells were exposed to an EF at 5 V/cm for 3 h. The rate and directionality of cell migration were quantified. The distribution of integrin β1 subunit was measured by immunohistochemistry and the expression of integrin β1 subunit and phosphorylated focal adhesion kinase (FAK) was determined by PCR and Western blotting. Experiments were performed in the presence or absence of anti-integrin β1 subunit antibody. During exposure to an EF at 5 V/cm for 3 h, the separated human RPE cells and wounded RPE monolayer demonstrated a cathodal-directed migration. The distribution of integrin β1 subunit in the cells was also polarized to the cathode, and the expression in mRNA and its protein level were obviously increased. Furthermore, exposure to EFs of 5 V/cm triggered the phosphorylation of FAK in human RPE cells. In contrast, blocking of integrin β1 subunit suppressed the directed migration of RPE cells and reduced the activation of FAK in EFs. These findings indicate that EF exposure results in directed migration of the separated RPE cells and RPE monolayer. These effects may partially act through the activation of integrin β1 subunit signaling.


Design of New Procedures for Diagnosing Prevalent Diseases Using a Low-Cost Telemicroscopy System.
Currently, the diagnosis of prevalent diseases such as malaria, tuberculosis, or diarrheal diseases in rural areas of developing countries requires the displacement of the patient from their community health post to their reference health center or to ship a sample. This delays diagnosis and the treatment of disease. Conduct research to develop a new method for rapid low-cost diagnosis of prevalent diseases in rural areas of developing countries (malaria, tuberculosis, parasitic infections, vaginal infections, and cervical cancer). The study was divided into three phases. The first related to the drafting and validating of new protocols for the preparation of samples that should be adapted to be carried out in areas without power and with little trained personnel. The second phase consisted of developing a telemicroscopy system looking for low cost, software compatibility, and technical quality. Finally, the third phase evaluated the system as a diagnostic tool using direct observation with a conventional microscope as the gold standard. The validation of the new protocols showed that 100% of the vaginal swabs were processed correctly when using direct smear, while they were only 86.3% correct when using Gram stain; 68.3% of fecal samples were correctly processed using Kinyoun stain; 61.7% of blood samples when using thin film; and 83.8% when using thick film. Phase 2 permitted the development of a low-cost (<$250) and low-power (<15 W) telemicroscopy system that allows real-time consultation between health technicians and specialists. Finally, phase 3 proved that there was no difference between the diagnostics obtained by direct observation in a microscope and those ones obtained through the new telemicroscopy system. This study has verified the effectiveness of the telemicroscopy system as a diagnostic tool, given the complete agreement between the diagnoses made with it and those made with the gold standard.


Investigating the effect of couple-centered counseling by Gottman method on the intimacy of infertile couples referring to the infertility Ward of Fatemieh hospital, Hamadan, Iran in 2020: a quasi-experimental study.
Infertility is among the most unpleasant experiences for couples struggling with it. Therefore, coping with its associated psychological burden has become a concern in many societies due to its negative impacts on couples' lives and intimacy levels. Lack of marital intimacy leads to unfortunate consequences such as dissatisfaction with marital relationships between spouses. Therefore, these people should be encouraged to find an effective solution to cope with infertility. Regarding the importance of the emotional relationship between infertile couples and the success rate of infertility treatment, this study aims to determine the effect of couple-centered counseling by the Gottman method on marital intimacy of infertile couples referred to the infertility ward of Fatemieh Hospital in Hamadan. The sample of this quasi-experimental study included 60 infertile couples in the evaluation phase of treatment with primary infertility. We collected data in a referral infertility center in Hamadan (Iran) between December 2020 and May 2021. Marital intimacy was measured using Thompson & Walker's Marital Intimacy Questionnaire. At the beginning of the study, the intervention and control groups completed this questionnaire. The intervention group received Gottman couple-centered counseling based on GATHER principles in 8 sessions. The groups completed the questionnaires 4 weeks after the last intervention session again. If the distribution was normal, the ANCOVA test was used to evaluate the differences between the two groups. Intra-group comparisons were performed using paired t-test, and intergroup comparisons were performed using an independent t-test. The mean score of female intimacy increased significantly after the intervention (P = 0.009). There was no significant difference in socio-demographic characteristics between groups (P < 0.05), both of which were adjusted in ANCOVA. After the intervention, the mean marital intimacy scores were significantly higher in women participating in the intervention group (from 75.6 (±10.63) to 78.86 (±7.87)). In addition, after the ANCOVA test, the difference was statistically significant (P = 0.009; MD: 3.74, CI: 0.95 and 6.52). The mean score of male marital intimacy increased after the intervention (from 78.93 (±10.21) to 78.9 (±9.79)), although the difference was not statistically significant (P = 0.54; MD: -0.58, CI: - 2.51 and 1.34). The findings support the effective role of Gottman's couple-centered counseling in increasing marital intimacy by raising couples' awareness about the principles of proper relationships between them. This outcome suggests that counseling with couples, especially in critical life situations, can improve their relationship in the infertility treatment process and prevent emotional divorce and other negative impacts on their lives. IRCT Registration Number IR.UMSHA.REC.1399.535, registered on 21/09/2020.


Genome-wide analyses in bacteria show small-RNA enrichment for long and conserved intergenic regions.
Interest in finding small RNAs (sRNAs) in bacteria has significantly increased in recent years due to their regulatory functions. Development of high-throughput methods and more sophisticated computational algorithms has allowed rapid identification of sRNA candidates in different species. However, given their various sizes (50 to 500 nucleotides [nt]) and their potential genomic locations in the 5' and 3' untranslated regions as well as in intergenic regions, identification and validation of true sRNAs have been challenging. In addition, the evolution of bacterial sRNAs across different species continues to be puzzling, given that they can exert similar functions with various sequences and structures. In this study, we analyzed the enrichment patterns of sRNAs in 13 well-annotated bacterial species using existing transcriptome and experimental data. All intergenic regions were analyzed by WU-BLAST to examine conservation levels relative to species within or outside their genus. In total, more than 900 validated bacterial sRNAs and 23,000 intergenic regions were analyzed. The results indicate that sRNAs are enriched in intergenic regions, which are longer and more conserved than the average intergenic regions in the corresponding bacterial genome. We also found that sRNA-coding regions have different conservation levels relative to their flanking regions. This work provides a way to analyze how noncoding RNAs are distributed in bacterial genomes and also shows conserved features of intergenic regions that encode sRNAs. These results also provide insight into the functions of regions surrounding sRNAs and into optimization of RNA search algorithms.


Endogenous opioid peptides and regulation of drinking and feeding.
Considerable work across the last 10 yr has implicated the endogenous opioid peptides in the regulation of ingestion. The opioid antagonists, such as naloxone and naltrexone, reduce intake of water, flavored water, and food. Naloxone's effects are pharmacologically specific, ie, its effects are dose-related and stereoselective. Further, a variety of antagonists produce similar effects. A primary site of action of naloxone, with respect to intake, is in the central nervous system. Naloxone's effects are also behaviorally specific, ie, its effects seem particularly related to palatability functions. The effects of opioid agonists, in small doses, enhance intake of some nutrients, but these effects are not opposite those of the antagonists. Benzodiazepines enhance drinking and eating and apparently interact with opioid systems. These observations combine with those directly measuring features of the endogenous opioid peptides to support a conclusion that opioid peptides are part of a system for regulating ingestion.


State Transitions and Crystalline Structures of a Single Polyethylene Chain: MD Simulations.
The structures of a single polyethylene chain were investigated using all-atom molecular dynamics simulations with a series of cutoff distances. We found that a long single chain with a short cutoff distance undergoes coil, globule, and crystal states during a continuous cooling process. The globule state vanishes for short chains less than a certain length where there is large conformational fluctuation. A tight-folding model was applied to analyze the folded structures, and the re-entry modes show that a shorter chain prefers the nearest folding while a longer one prefers the second or third nearest folding. Our results show that a single polyethylene chain can exhibit condensed phenomena of state transitions, which could be heuristic for single-chain physics and polymer crystallization.


Simplest method for creating micropatterned nanostructures on PDMS with UV light.
The fabrication of micropatterned structures on PDMS is a critical step in soft lithography, microfluidics, and many other PDMS-based applications. To substitute traditional mold-casting methods, we develop a simple method to create micropatterned nanostructures on PDMS in one step. After exposing a flat PDMS surface to a UV pen lamp through a photomask (such as a TEM grid), micropatterned nanostructures can be formed readily on the PDMS surface. We also demonstrate that fabricated PDMS can be used for the microcontact printing of protein immunoglobulin (IgG) on solid surfaces. This method is probably the simplest method of creating micropatterned nanostructures on PDMS reported so far because it does not need casting, surface coating, or chemical reagents. Only a UV pen lamp and a photomask are required, and this method can be performed under ambient conditions without vacuum. We expect that this method will greatly benefit researchers who use PDMS regularly in various applications such as soft lithography and microfluidics.


Continuous vs. intermittent vancomycin therapy for Gram-positive infections not caused by methicillin-resistant Staphylococcus aureus.
The aim of this study was to evaluate the effects of vancomycin pharmacokinetics (PKs) on effectiveness and safety in the treatment of Gram-positive infections due to pathogens other than methicillin-resistant Staphylococcus aureus (MRSA). Prospective study including septic patients received either continuous (N.=21) or intermittent (N.=21) infusions of vancomycin; the target drug concentration was 15-20 mg/L and target area under the curve of vancomycin concentrations over the minimum inhibitory concentration of the pathogen on day 1 (AUC24/MIC) >400. Clinical and microbiological responses, the development of acute kidney injury (AKI) and therapy costs were recorded. The median AUC24/MIC was 195(133-343) vs. 189(136-328) mg/L*h in the continuous and intermittent infusion groups. Target drug concentrations were achieved in 15/21 vs. 9/21 (P=0.12) patients and AUC24/MIC>400 in only 5/21 vs. 3/21 (P=0.35) patients of continuous and intermittent groups, respectively. High clinical cure (17/21 for continuous vs. 17/21 for intermittent, P=1.00) and microbiological eradication (17/21 vs. 15/21, P=0.47) were observed in both groups and not associated with drug concentrations or with AUC24/MIC. AKI was diagnosed during therapy in 5/21 patients in the continuous group and 8/21 in the intermittent group (P=0.32). The median total therapy costs were lower in the continuous than in the intermittent group (377 [304-485] vs. 552 [371-644] €, P=0.04). Vancomycin resulted in high clinical response during non-MRSA Gram-positive infections treatment even at drug concentrations lower than those for MRSA. A continuous infusion of vancomycin was associated with a significant reduction in therapy costs compared to intermittent infusions.


Bronchial associated lymphoid tissue (BALT) lymphoma presenting as chronic lung sepsis.
A 58-year-old woman was referred from her general practitioner to the respiratory clinic with a 2 year history of recurrent pulmonary infections, mucus hypersecretion and right lobe consolidation following a severe pneumonic illness in 2006. She had no significant risk factors for respiratory disease. Chest computed tomography showed an air bronchogram and right lower lobe consolidation. On initial routine investigation IgA and IgG were normal; however, a discrete IgM paraprotein band in the mid gamma region was seen on serum electrophoresis. She was referred for haematological investigations. Bone marrow biopsy was positive for monoclonal lymphoplasmocytoid B cells and the patient was diagnosed with Waldenström's macroglobulinaemia. Due to recurrent infections and an unclear diagnosis of the lung process, a right lower lobectomy and wedge resection of the middle lobe was performed. This showed bronchial associated lymphoid tissue lymphoma arising in the marginal zone. She has been well since surgery with no further respiratory infections.


Cardiovascular surgery patients' respiratory responses to morphine before extubation.
Analgesia is commonly withheld from cardiovascular surgery patients who are soon to be withdrawn from mechanical ventilation to prevent respiratory depression that can postpone extubation. The effects of analgesia on respiration have not been studied adequately. In this study, weaning parameter measurements were obtained to determine the respiratory impact of a low dose of intravenous morphine administered to cardiovascular surgery patients who were ready to be weaned from the ventilator. A pretest-posttest, quasi-experimental, repeated measures design was used. Eleven alert patients who experienced postoperative pain and met two of five weaning parameter criteria received 1 mg to 5 mg of morphine. Weaning parameters were measured before the intervention and at 15 and 30 minutes afterward. As hypothesized, the administration of low-dose morphine did not have a negative effect on weaning parameters. Mean weaning parameter values either increased or remained the same after the administration of morphine. Despite the small sample size, the results of dependent t tests revealed statistically significant improvements, using an alpha level of 0.05, in the mean tidal volume and negative inspiratory force values at the 30-minute measurement, and in the vital capacity value at the 15-minute measurement. The findings from this study help to refute the notion that a low dose of intravenous morphine will cause respiratory depression, and further suggest that the administration of morphine may enhance patients' respiratory function. If additional research supports this study's findings, both the goals of weaning postoperative patients from the ventilator and controlling pain may be achieved simultaneously.


Visualization of anatomical structures of epigastric organs by use of automatically segmented 3-D ultrasound image volumes--first results.
The detection and the staging of tumors and their metastases in parenchymatous organs of the epigastric organs today is improved by the enormous increase of imaging system's efficiency. For an increasing number of findings, which shall be dissected in intention to cure, the feasibility of diagnostics and therapy-planning based on sonograms was investigated. In 3-D US image volumes of approx. 20 patients, characteristic anatomical structures (e.g., vessels, abscesses, tumors) were detected by specifically adapted automatic computer-based segmentation and visualized. The detection of pathological findings, their quantification and their spatial assignment to anatomical main structures was essentially simplified by 3-D image acquisition and 2-D and 3-D visualization of segmented images.


Imaging with second-harmonic radiation probes in living tissue.
We demonstrate that second-harmonic radiation imaging probes are efficient biomarkers for imaging in living tissue. We show that 100 nm and 300 nm BaTiO(3) nanoparticles used as contrast markers could be detected through 50 μm and 120 μm of mouse tail tissue in vitro or in vivo. Experimental results and Monte-Carlo simulations are in good agreement.


Selected optical properties of mixtures of cholesteric liquid crystals.
The reflection, transmission, optical activity, and extinction ratio of a series of mixtures of cholesteryl oleyl carbonate, cholesteryl nonanoate, and cholesteryl chloride of different proportions were measured. The wavelength of minimum transmission (lambda(o)), maximum rate of change of optical activity, and minimum extinction ratio were found nearly to coincide. The bandwidth of these phenomena is of the order of 500 A. The optical rotation asymptotically approaches plus and minus infinity at lambda(o). The variation of lambda(o) with temperature is linear between 20 degrees C and 35 degrees C with a slope of 50 A degrees C(-1). By varying the composition, lambda(o) could be varied from 5000 A to 11000 A.


Senescence marker protein-30 (SMP30) deficiency impairs myocardium-induced dilation of coronary arterioles associated with reactive oxygen species.
Senescence marker protein-30 (SMP30) decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30's effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary arterioles in wild-type (WT) mice exposed to supernatant collected from isolated paced cardiac myocytes from SMP30 KO or WT mice. Pacing increased hydrogen peroxide in myocytes, and hydrogen peroxide was greater in SMP30 KO myocytes compared to WT myocytes. Antimycin enhanced and FCCP (oxidative phosphorylation uncoupler in mitochondria) decreased superoxide production in both groups. Addition of supernatant from stimulated myocytes, either SMP30 KO or WT, caused vasodilation. The degree of the vasodilation response to supernatant was smaller in SMP30 KO mice compared to WT mice. Administration of catalase to arterioles eliminated vasodilation in myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in myocyte supernatant of SMP30 KO mice. This vasoconstriction was eliminated by olmesartan, an angiotensin II receptor antagonist. Thus, SMP30 deficiency combined with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocytes. SMP30 plays an important role in the regulation of coronary vascular tone by myocardium.


Neural correlates of blood flow measured by ultrasound.
Functional ultrasound imaging (fUSI) is an appealing method for measuring blood flow and thus infer brain activity, but it relies on the physiology of neurovascular coupling and requires extensive signal processing. To establish to what degree fUSI trial-by-trial signals reflect neural activity, we performed simultaneous fUSI and neural recordings with Neuropixels probes in awake mice. fUSI signals strongly correlated with the slow (<0.3 Hz) fluctuations in the local firing rate and were closely predicted by the smoothed firing rate of local neurons, particularly putative inhibitory neurons. The optimal smoothing filter had a width of ∼3 s, matched the hemodynamic response function of awake mice, was invariant across mice and stimulus conditions, and was similar in the cortex and hippocampus. fUSI signals also matched neural firing spatially: firing rates were as highly correlated across hemispheres as fUSI signals. Thus, blood flow measured by ultrasound bears a simple and accurate relationship to neuronal firing.


Significance of dopamine metabolites in the evaluation of drugs acting on dopaminergic neurons.
The effect of various drugs was studied on 3-methoxytyramine (3-MT) concentrations in rat striatum. The drugs were chosen for their ability to interfere with the dopaminergic system at different levels. Dopamine (DA) acidic metabolites, i.e. homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), were also measured. Changes of 3-MT, unlike those of DOPAC and HVA, seem to reflect the functional activity of dopaminergic neurons. In fact drugs believed to increase or decrease DA content in the synaptic cleft produce predictable changes of striatal 3-MT. Thus cocaine, nomifensine and d-amphetamine increase 3-MT concentrations while gamma-butyrolactone, alpha-methyltyrosine and apomorphine decrease it.


Improvements in gene therapy: averting the immune response to adenoviral vectors.
Gene therapy is an interesting approach for the correction of defective genes, the treatment of cancer and the introduction of immunomodulatory genes. Various techniques for gene transfer into cells or tissues have been developed within the last decade; these can be divided generally into viral and nonviral gene transfer systems. Nonviral techniques include the liposome- or gene gun-mediated introduction of therapeutic genes; however, the efficiency of gene transfer by these applications is still very low. In contrast, viruses have optimised their strategies for efficient infection of virtually any cell type in a mammalian organism. The genetic modification of genomes from different virus families (Adenoviridae, Retroviridae, Herpesviridae) led to the development of gene therapy vectors with a similar capacity to infect cells or tissues as that of wild type viruses. In contrast to wild type viruses, gene therapy vectors are engineered to transfer therapeutic genes into the target cells or tissues. In addition, they have lost their capacity for replication in target cells, because of the removal of essential genes, which allows replication only in specialised packaging cell lines engineered for the production of recombinant viruses. Despite considerable progress over the past decade in the generation of gene transfer systems with reduced immunogenic properties, the remaining immunogenicity of many gene therapy vectors is still the major hurdle, preventing their frequent application in clinical trials. Recombinant adenoviruses have been shown to be promising vectors for gene therapy, since they are able to transduce both quiescent and proliferating cells very efficiently. However, a major disadvantage of adenoviral vectors lies in the activation of both the innate and adaptive parts of the recipient's immune system when applied in vivo. The inflammatory responses induced by adenovirus particles can be very strong and can be fatal in patients treated with these adenoviral constructs. Therefore, many experiments have been performed in the effort to prevent these inflammatory responses mediated by adenoviral particles. The depletion of cell populations responsible for these inflammatory responses as well as the application of immunosuppressive drugs have been investigated. Moreover, the generation of less immunogenic adenoviral vectors by further genetic modification within the adenoviral genome has led to vectors with reduced immunogenic properties. Both strategies to reduce inflammatory responses against adenoviral particles are discussed in this review.


Structural and Functional Plasticity in the Maternal Brain Circuitry.
Parenting recruits a distributed network of brain structures (and neuromodulators) that coordinates caregiving responses attuned to the young's affect, needs, and developmental stage. Many of these structures and connections undergo significant structural and functional plasticity, mediated by the interplay between maternal hormones and social experience while the reciprocal relationship between the mother and her infant forms and develops. These alterations account for the remarkable behavioral plasticity of mothers. This review will examine the molecular and neurobiological modulation and plasticity through which parenting develops and adjusts in new mothers, primarily discussing recent findings in nonhuman animals. A better understanding of how parenting impacts the brain at the molecular, cellular, systems/network, and behavioral levels is likely to significantly contribute to novel strategies for treating postpartum neuropsychiatric disorders in new mothers, and critical for both the mother's physiological and mental health and the development and well-being of her young.


Early Target Attainment With Continuous Infusion Meropenem and Piperacillin/Tazobactam and Utilization of Therapeutic Drug Monitoring in Critically Ill Patients: A Retrospective Cohort Study From 2017 to 2020.
We analyzed the attainment of early pharmacological targets of continuous infusion meropenem and piperacillin/tazobactam and the use and effect of a real-time therapeutic drug monitoring (TDM) program on subsequent dosing and target attainment in patients who are critically ill. This was a single-center, retrospective study among patients hospitalized in the intensive care unit in a Swiss tertiary care hospital from 2017 to 2020. The primary outcome was target attainment [100% tT ≥ 4xECOFF (Pseudomonas aeruginosa)] of continuous infusion meropenem and piperacillin/tazobactam within 72 hours after initiation of treatment. A total of 234 patients were included. Median first meropenem (n = 186 of 234) and piperacillin (n = 48 of 234) concentration was 21 mg/L (interquartile range [IQR], 15.6-28.6) and 100.7 mg/L (IQR, 64.0-160.2), respectively. Pharmacological target was attained in 95.7% (95% confidence interval [CI], 91.7-98.1) of patients receiving meropenem and 77.0% (95% CI, 62.7-87.9) treated with piperacillin/tazobactam. In the univariable and multivariable logistic regression, body weight and estimated glomerular filtration rate were negatively associated with target attainment. Subsequently, meropenem dosage was decreased or stopped in 35 of 186 (18.8%) and 89 of 186 (47.9%) patients, respectively, and increased in 2 of 186 (1.1%) patients. Continuous infusion meropenem and piperacillin/tazobactam yielded excellent and moderate early pharmacological target attainment in critically ill patients, respectively. The TDM was mainly used to decrease meropenem dosage.


Urinary stone formation: Dent's disease moves understanding forward.
Renal stones form in the late collecting duct in a complex milieu involving salts and protein components of the urine together with direct interactions at the epithelial cells lining the duct. The operation of newly discovered physiological controls that limit crystal formation by feedback mechanisms which sense the luminal environment are discussed. Adhesion at the epithelial surface and intracellular processing of crystals comprise a previously unrecognised mechanism for limiting crystal growth, which may be disrupted resulting in disease. Dent's disease is discussed as a paradigm of a complex renal tubular disease resulting in renal stone formation. Defects in endosomal acidification, due to ablation of the CLC-5 voltage-gated Cl- channel, result in defects in both proximal and collecting duct endosomal traffic leading to stone formation.


Salinity Effects on Photosynthesis and Growth in Alternanthera philoxeroides (Mart.) Griseb.
Alternanthera philoxeroides, alligator weed, was grown at five different NaCl concentrations to determine the effect of salinity on factors related to the net rate of CO(2) uptake (P(n)). Over the range of 0 to 400 millimolar NaCl, P(n) declined 51%. Stomatal conductance declined in parallel with P(n) and as a result there was no reduction in intercellular CO(2) concentration and therefore no reduction in the amount of CO(2) available for photosynthesis. The CO(2) compensation point did not change with salt stress. Increases in leaf thickness tended to compensate slightly for the negative effects of salinity on leaf cell metabolism, at least in relation to P(n). On a mesophyll cell area basis, soluble protein was relatively constant in leaves developed at 100 to 400 millimolar NaCl while total chlorophyll decreased at all salinities. Dry weight production and P(n) were closely correlated in alligator weed grown at different salinities. Plants produced less leaf area per unit dry weight as salinity increased, which may aid in water conservation.


A fetal Wolff-Parkinson-White syndrome diagnosed prenatally by magnetocardiography.
We report a case of fetal Wolff-Parkinson-White (WPW) syndrome diagnosed prenatally by magnetocardiography (MCG). At 32 weeks' gestation, the fetus was diagnosed to have a paroxysmal supraventricular tachycardia by ultrasonography and direct fetal electrocardiogram (ECG). Transplacental fetal therapy by maternal oral administration of propranolol resolved the fetal tachyarrhythmia. Although the wave forms of the fetal MCG at 32 weeks' gestation were normal, the fetal MCG at 35 weeks' gestation showed a short PR interval and a long QRS complex duration with a delta wave, indicating WPW syndrome. The findings of the fetal MCG were confirmed by the postnatal ECG. MCG made the prenatal diagnosis of WPW syndrome possible.


Introduction to endoscopy in the cat: where to start? What to buy?
For many years, endoscopy and minimally invasive surgery have been considered 'standard' in human healthcare. With the expansion of the used medical equipment market, and the falling cost of new equipment, veterinary practitioners are now starting to appreciate first-hand the benefits of performing endoscopic procedures: for example, vastly improved visualisation of the surgical site, reduced tissue trauma, minimal postoperative pain and faster recovery times, especially in feline patients. In addition, clients almost always choose a less invasive procedure if the capabilities are present, and will often consent to these procedures sooner than they would to conventional surgery. This article aims to guide the general feline practitioner towards a basic understanding of endoscopic and ancillary equipment, and in the direction of appropriate training required to perform routine endoscopic procedures. The authors draw on information provided in a combination of published texts, articles, reviews and their own clinical experience to provide a practical information guide for the clinician interested in feline endoscopy.


High-density synthetic peptide microarrays: emerging tools for functional genomics and proteomics.
New approaches for manufacturing and application of peptide arrays on planar surfaces are emerging, thereby opening advanced opportunities to probe the expression and function of the proteome. In complementing DNA and protein array analyses, peptide fragment screening directly addresses functional protein interaction sites, leading to a detailed insight into the discovered molecular recognition events, placing them in the context of the whole genome, and even allowing rapid determination of the chemical nature of these interactions. This information can then be transferred into powerful small peptide tools that interfere with these interactions in vivo and help to link targets with phenotypes. With the spreading of new peptide array tools, peptide screening will extend its impact on modern genome-driven molecular biology. This will advance the systematic discovery and validation of new pharmaceutical targets as well as the development of potent molecular diagnostics for medical and ecological monitoring.


Beam-shaping technique for improving the beam quality of a high-power laser-diode stack.
We report a beam-shaping technique that reconfigures the beams to improve the beam quality and enhance the power density for a ten-array high-power laser-diode stack by using two optical rectangular cubes and two stripe-mirror plates. The reshaped beam has threefold improvement in beam quality, and its power density is effectively enhanced. On the basis of this technique, we focus the beam of the high-power laser-diode stack to effectively end pump a high-power fiber laser.


H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy.
Double-strand breaks (DSBs) are the most deleterious DNA lesions, which, if left unrepaired, may have severe consequences for cell survival, as they lead to chromosome aberrations, genomic instability, or cell death. Various physical, chemical, and biological factors are involved in DSB induction. Cells respond to DNA damage by activating the so-called DNA damage response (DDR), a complex molecular mechanism developed to detect and repair DNA damage. The formation of DSBs triggers activation of many factors, including phosphorylation of the histone variant H2AX, producing gammaH2AX. Phosphorylation of H2AX plays a key role in DDR and is required for the assembly of DNA repair proteins at the sites containing damaged chromatin as well as for activation of checkpoints proteins which arrest the cell cycle progression. In general, analysis of gammaH2AX expression can be used to detect the genotoxic effect of different toxic substances. When applied to clinical samples from cancer patients, evaluation of gammaH2AX levels may allow not only to monitor the efficiency of anticancer treatment but also to predict of tumor cell sensitivity to DNA damaging anticancer agents and toxicity of anticancer treatment toward normal cells.


A data-driven framework for identifying nonlinear dynamic models of genetic parts.
A key challenge in synthetic biology is the development of effective methodologies for characterization of component genetic parts in a form suitable for dynamic analysis and design. In this investigation we propose the use of a nonlinear dynamic modeling framework that is popular in the field of control engineering but is novel to the field of synthetic biology: Nonlinear AutoRegressive Moving Average model with eXogenous inputs (NARMAX). The framework is applied to the identification of a genetic part BBa_T9002 as a case study. A concise model is developed that exhibits accurate representation of the system dynamics and a structure that is compact and consistent across cell populations. A comparison is made with a biochemical model, derived from a simple enzymatic reaction scheme. The NARMAX model is shown to be comparably simple but exhibits much greater prediction accuracy on the experimental data. These results indicate that the data-driven NARMAX framework is an attractive technique for dynamic modeling of genetic parts.


Photooxidation of bisphenol A (BPA) in water in the presence of ferric and carboxylate salts.
In this work, the photooxidation of bisphenol A (BPA), a suspected endocrine disruptor (ED), in water in the presence of ferric and oxalate ions was investigated in a concentric reactor under a 125 W high-pressure mercury lamp (lambda> or = 365 nm). The photooxidation efficiencies were dependent on the pH values and ferric/oxalate concentration ratios (Fe(III)/Ox) in the water, with higher efficiency at pH 3.50+/-0.05 and Fe(III)/Ox 10.0/120.0 micromol l(-1). The initial rate of photooxidation increases with increasing the initial concentration of BPA from 2.0 to 5.0 mg l(-1) while do not change at 5.0 and 10.0 mg l(-1). However, higher removal efficiency of BPA is archived at lower BPA initial concentration over range of 2.0 to 10.0 mg l(-1). For 2.0 mg l(-1) BPA, the initial rate of photooxidation is 0.06 mg l(-1)min(-1). By using UV-Vis spectrum and LC-MS techniques, the predominant photooxidation product BPA-o-catechol was identified and the mechanisms for the oxidative degradation were proposed. When BPA reacted with OH radicals, C atoms in 3-position were added with OH radicals followed by O2 peroxidation and HO2 radical escape. Then catechol derivatives were produced. After that, the two H atoms on the hydroxy group were extracted in two individual steps to form intermediates semiquinone radical and o-quinone. The intermediates underwent further oxidation, benzene ring cleavage and decarboxylation, up to mineralization ultimately.


Role of speed vs. grade in relation to muscle pump function at locomotion onset.
We sought to clarify the roles of contraction frequency (speed) and contraction force (grade) in the rise in muscle blood flow at the onset of locomotion. Shoemaker et al. (Can J Physiol Pharmacol 76: 418-427, 1998) explored this relationship in human handgrip exercise and found that the time course of the rise in muscle vascular conductance was similar when a light weight was lifted in a fast cadence and a heavy weight was lifted in a slow cadence (total work constant). This indicates that muscle pumping (contraction frequency) was of limited importance in governing the time course. Rather, vasodilator substances released in proportion to the total work performed appeared to determine the pattern and extent of the rise in conductance. We hypothesized that conductance would rise faster during locomotion at a high speed (frequency) and low grade (force) than at a low speed and high grade, despite similar total increases in conductance, owing to more effective muscle pumping at faster contraction rates. Seven male rats performed nine 1-min bouts of treadmill locomotion across a combination of three speeds (5, 10, and 20 m/min) and three grades (-10, 0, and +15 degrees ) in random order. Locomotion at 10 m/min and 0 degrees grade and 20 m/min and -10 degrees grade led to an equal rise in terminal aortic vascular conductance. However, the equal rise was achieved more quickly at the higher running speed, suggestive of more effective muscle pumping. Across the nine combinations of exercise, speed began to exert a statistically significant influence on conductance by the 3rd s of locomotion. Grade did not begin to exert an influence until the 12th s of locomotion (similar to the delays reported for arteriolar dilation to muscle contraction). Additional experiments in dogs provided similar results. Thus the muscle pump appears to initiate the increase in blood flow in proportion to contraction frequency at locomotion onset.


Effect of diethylstilbestrol on ion fluxes in oat roots.
Effects of diethylstilbestrol (DES) on ion fluxes in oat roots (Avena sativa L.) were investigated by measuring K(+) and Cl(-) absorption and K(+) efflux. DES rapidly decreased the absorption of K(+) ((86)Rb) and (36)Cl(-) by excised roots; 10(-4) molar DES inhibited Cl(-) absorption in 1 minute and K(+) absorption in 1 to 2 minutes. With a 10-minute incubation period, K(+) and Cl(-) absorption were inhibited 50% by 1.1x10(-5) molar and 8.4x10(-6) molar DES, respectively. Treatment for 3 minutes with 10(-4) molar DES caused irreversible inhibition of K(+) absorption. Increasing concentrations of KCl in the absorption media decreased the DES inhibition. Experiments with the DES analogs, DES dipropionate, dienestrol and hexestrol, showed that the steric configuration and the hydroxyl group of the DES molecule are important in determining the inhibitory capacity of the compound.DES increased the efflux of (86)Rb from excised roots only after a 10-minute lag period. In 10(-4) molar DES, roots lost 82% of their radionuclide content in 1 hour. Comparison of efflux curves for roots loaded for 20 hours and those loaded for 15 minutes suggested that DES increased the permeability of the plasma membrane after about 10 minutes and the permeability of the tonoplast after 10 to 20 minutes. Oligomycin and dinitrophenol also increased the loss of (86)Rb, but the lag period was about 4 hours.The rapid effect of DES on ion absorption and the slower effect on ion efflux suggest that DES initially inhibits ion uptake by affecting the transport mechanism at the plasma membrane in some manner other than alteration of membrane permeability.


[Treatment of distant iodine-negative metastases of thyroid cancer with 32P].
The results of radiphosphotherapy in 20 patients with iodine-negative metastases of thyroid cancer in the lung and bones have been analyzed. The treatment was carried out in two stages: radical surgery and 32P therapy of metastases. A dose of 100-185 MBq of the radionuclide was administrated weekly (total dose-300-700 MBq). As a result, improvement in treating stage IV thyroid tumor was registered.


Parvovirus Infection in a Child Presenting with Erythema Multiforme and Vasculitis after a Yellow Jacket Bee Sting.
Parvovirus B19 has a wide spectrum of clinical manifestations. Erythema multiforme and vasculitis are rarely reported with parvovirus B19 infections. Reactions to insect stings can range from local swelling to life-threatening systemic reactions. There have been rare reports of unusual reactions, such as vasculitis, occurring in a temporal relationship with insect stings. We report an 8-year-old patient having Parvovirus B-19-related erythema multiforme and vasculitis after a yellow jacket bee sting.


Promoter methylation of IGFBP-3 and p53 expression in ovarian endometrioid carcinoma.
Insulin-like growth factor binding protein (IGFBP-3) is an antiproliferative, pro-apoptotic and invasion suppressor protein which is transcriptionally regulated by p53. Promoter methylation has been linked to gene silencing and cancer progression. We studied the correlation between IGFBP-3 and p53 expression as well as IGFBP-3 promoter methylation in ovarian endometrioid carcinoma (OEC) by immunohistochemical staining and quantitative methylation-specific PCR (qMSP). Additionally, we assessed the molecular regulatory mechanism of wild type (wt) p53 on IGFBP-3 expression using two subclones of OEC, the OVTW59-P0 (low invasive) and P4 (high invasive) sublines. In 60 cases of OEC, 40.0% showed lower IGFBP-3 expression which was significantly correlated with higher IGFBP-3 promoter methylation. p53 overexpression was detected in 35.0% of OEC and was unrelated to clinical outcomes and IGFBP-3. By Kaplan-Meier analysis, patients with lower IGFBP-3, higher IGFBP-3 promoter methylation, and normal p53 were associated most significantly with lower survival rates. In OEC cell line, IGFBP-3 expression was correlated with IGFBP-3 promoter methylation. IGFBP-3 expression was restored after treatment with a DNA methy-transferase inhibitors (5-aza-deoxycytidine) and suppressed by a p53 inhibitor (pifithrin-alpha). The putative p53 regulatory sites on the promoter of IGFBP-3 were identified at -210, -206, -183 and -179 bases upstream of the transcription start site. Directed mutagenesis at these sites quantitatively reduced the transcription activity of IGFBP-3. Our data suggests that IGFBP-3 silencing through IGFBP-3 promoter methylation in the absence of p53 overexpression is associated with cancer progression. These results support a potential role of IGFBP-3 methylation in the carcinogenesis of OEC.


Differences in carbapenem resistance genes among Acinetobacterbaumannii, Acinetobacter genospecies 3 and Acinetobacter genospecies 13TU in Taiwan.
A total of 81 clinical isolates of the three clinically important Acinetobacter spp., namely Acinetobacterbaumannii, Acinetobacter genospecies 3 and Acinetobacter genospecies 13TU, were analysed for differences in carbapenem resistance genes. Of the 81 isolates, 40 (49%) were resistant to carbapenems. Most A. baumannii isolates (47/53, 88.7%) contained the ISAba1-bla(OXA-51)-like gene and exhibited a higher minimum inhibitory concentration to imipenem than A. baumannii without the ISAba1 element. All four carbapenem-resistant A. genospecies 3 isolates contained bla(IMP-1) and an ISAba3-bla(OXA-58)-like gene. Three A. genospecies 13TU isolates contained an ISAba3-bla(OXA-58)-like and either a bla(IMP-1) or a bla(VIM-11) gene. The five bla(IMP-1)-containing strains were resistant to imipenem and were positive for metallo-beta-lactamase (MBL) activity by the Etest, and the two bla(VIM-11)-containing strains were susceptible to imipenem and were MBL-negative by Etest. Imipenem hydrolysis tests showed that the bla(IMP-1)-containing strains exhibited much higher imipenem-hydrolysing activity than the two bla(VIM-11)-containing strains. No transcripts of bla(VIM-11) or bla(OXA-58)-like genes were detected. Analysis of outer membrane proteins showed that OprD was absent in the only bla(IMP-1)-containing A. genospecies 13TU strain owing to the presence of a premature stop codon in the oprD gene. In summary, several differences were detected between the carbapenem resistance genes of clinical Acinetobacter spp. in Taiwan, and loss of OprD may be associated with imipenem resistance in A. genospecies 13TU.


One-year mortality in coagulase-negative Staphylococcus and Staphylococcus aureus infective endocarditis.
The aim of this study was to investigate in-hospital mortality and 12-month mortality in patients with coagulase-negative Staphylococcus (CoNS) compared to Staphylococcus aureus (S. aureus) infective endocarditis (IE). We used a prospective cohort study of 66 consecutive CoNS and 170 S. aureus IE patients, collected at 2 tertiary university hospitals in Copenhagen (Denmark) and at 1 tertiary university hospital in Gothenburg (Sweden). Median (range) C-reactive protein at admission was higher in patients with S. aureus IE (150 mg/l (1-521) vs 94 mg/l (6-303); p<0.001), which may suggest a more serous infection. CoNS was associated with prosthetic valve IE (49% vs 24%; p<0.001) and median diagnostic delay was longer in CoNS IE patients (20 d (0-232) vs 9 d (0-132); p<0.001). In-hospital mortality was equally high in both groups but 25% of the CoNS IE patients had died after 1 y compared to 39% of patients with S. aureus IE (p =0.05). In conclusion, CoNS IE was associated with a long diagnostic delay and high in-hospital mortality, whereas post-discharge prognosis was better in this group of patients compared to patients with IE due to S. aureus.


Social differences in late fetal death and infant mortality in Sweden 1985-86.
Social differences in late fetal death and infant mortality were examined in a population-based prospective study. All singletons born to Nordic citizens in Sweden 1985-86 were included, 185,156 births in all. The overall rates of late fetal death and infant mortality were 3.5 and 5.3 per 1000 respectively. Socio-economic status of the household (SES) and mothers' education were used as social indicators. Logistic regression analyses showed significant odds ratios between 1.3 and 1.8 for late fetal death for blue-collar workers and women with less than 12 years education. The analyses of neonatal mortality showed a U-shaped relationship: both unskilled blue-collar workers and high level white-collar workers had significant odds ratios (OR) as compared with intermediate level white-collar workers (OR = 1.5). Similar results were obtained when using the mothers' education as indicator of social status: 9 years education or less or 15 years or more were associated with significant higher mortality rates than 12 years education (OR = 1.6). An inverse relationship between social status and post-neonatal mortality was seen in the crude analysis. Mothers' education revealed more social differences than SES (crude OR = 2.0 and 1.5 respectively in the least privileged group). However, when adjusting for the effects of maternal age, parity and smoking, no significant odds ratios for the social variables were obtained.