Incidence and Impact of COVID-19 in MS: A Survey From a Barcelona MS Unit.
To investigate the incidence of coronavirus disease 2019 (COVID-19) in a single-center cohort of patients with MS and to explore the contribution of their comorbidities and therapies to the outcome. A cross-sectional mixed-method study was conducted involving an email-based, self-administered questionnaire sent on May 21, 2020, to 586 patients with MS followed at the MS Unit of Hospital Clinic, University of Barcelona, along with telephone interview, and review of electronic medical records until June 18, 2020. The cumulative incidence of confirmed COVID-19 (positive PCR or antibody test) and all COVID-19 cases (confirmed and suspected) from the start of the pandemic was compared with the population estimates for Barcelona. A total of 407 patients (69.5%) completed the survey. Most of the responders (67%) were female. The responders had a median age of 48 years (range 19-86), relapsing-remitting disease (84%), at least 1 comorbidity (45%), and were on disease-modifying therapy (DMT; 74.7%). COVID-19 was confirmed in 5 patients (1.2%) and suspected in 46 (11.3%). The cumulative incidence of confirmed COVID-19 cases was similar to that of the general population but was almost 2-fold higher when all cases were considered (p < 0.001). Six patients (11.7%) were hospitalized, of which 5 had good recovery and 1 died. Hospitalized patients were more frequently male, had diabetes and had progressive forms of MS (p < 0.05). DMT was not associated with the risk of infection or the outcome. In the studied MS cohort, the incidence of COVID-19 was higher than that of the general population; however, most patients did not require hospitalization and had a good outcome despite the frequent presence of comorbidities and treatment with DMT.


Initial experience with an electron FLASH research extension (FLEX) for the Clinac system.
Radiotherapy delivered at ultra-high-dose-rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. A linear accelerator (Clinac 23EX) was modified to include a non-clinical FLASH research extension (the Clinac-FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane-parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre-existing vault was deemed sufficient. The Clinac-FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached a maximum dose rate >3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes >10 × 10 cm2 . The output stability of the FLASH system exhibited a dose deviation of <1%. Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non-FLASH dose rate (18 Gy/s), which induced large-size cells. Our studies characterized the non-clinical Clinac-FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra-high-dose-rate capabilities for scientists.


MGMT gene silencing and benefit from temozolomide in glioblastoma.
Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents. We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. The MGMT promoter was methylated in 45 percent of 206 assessable cases. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P<0.001 by the log-rank test; hazard ratio, 0.45; 95 percent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy; their median survival was 21.7 months (95 percent confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radiotherapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in survival between the treatment groups. Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.


The putative RNA-processing protein, THO2, is a microtubule-associated protein in tobacco.
THO2 is a component of the THO-TREX (transcription and export factor) complex that participates in mRNA metabolism and export from the nucleus in yeast and animal cells. Here we report that tobacco putative THO2-related protein (NtTHO2) is a microtubule-associated protein, which directly binds to microtubules in vitro and co-localizes with cortical microtubules in vivo. We purified endogenous NtTHO2 by cycles of microtubule polymerization-depolymerization from crude extracts of tobacco BY-2 miniprotoplasts. Purified NtTHO2 sedimented with microtubules in vitro. Immunofluorescence revealed that NtTHO2 was present in both the nucleus and cytoplasm. In interphase, cytoplasmic NtTHO2 was localized along cortical microtubules. In the mitotic phase, NtTHO2 was localized to the mitotic spindle but not to either the preprophase band or the phragmoplast. In mature cells of seedling roots, and in BY-2 cells in which proliferation was stopped by removing 2,4-D, NtTHO2 staining was confined mainly to the nucleolus. These results suggest that NtTHO2 is a multifunctional protein that participates in mRNA metabolism, and also functions within the cortical microtubules and mitotic spindle.


Evaluation of Clinical Gait Analysis parameters in patients affected by Multiple Sclerosis: Analysis of kinematics.
Clinical Gait Analysis is commonly used to evaluate specific gait characteristics of patients affected by Multiple Sclerosis. The aim of this report is to present a retrospective cross-sectional analysis of the changes in Clinical Gait Analysis parameters in patients affected by Multiple Sclerosis. In this study a sample of 51 patients with different levels of disability (Expanded Disability Status Scale 2-6.5) was analyzed. We extracted a set of 52 parameters from the Clinical Gait Analysis of each patient and used statistical analysis and linear regression to assess differences among several groups of subjects stratified according to the Expanded Disability Status Scale and 6-Minutes Walking Test. The impact of assistive devices (e.g. canes and crutches) on the kinematics was also assessed in a subsample of patients. Subjects showed decreased range of motion at hip, knee and ankle that translated in increased pelvic tilt and hiking. Comparison between the two stratifications showed that gait speed during 6-Minutes Walking Test is better at discriminating patients' kinematics with respect to Expanded Disability Status Scale. Assistive devices were shown not to significantly impact gait kinematics and the Clinical Gait Analysis parameters analyzed. We were able to characterize disability-related trends in gait kinematics. The results presented in this report provide a small atlas of the changes in gait characteristics associated with different disability levels in the Multiple Sclerosis population. This information could be used to effectively track the progression of MS and the effect of different therapies.


β-endorphin-induced inhibition of vitellogenic follicular growth in the fish Oreochromis mossambicus: evidence for opioidergic mediation of ovarian stress response.
The opioid peptide β-endorphin (β-EP) is known to play modulatory role in vertebrate reproduction. The objective of the present study was to determine the influence of β-EP and the opioid receptor antagonist naltrexone (NALT) on follicular development in normal, and stressed female tilapia Oreochromis mossambicus. Administration of 4 µg β-EP, but not 0.5 or 1.5 µg β-EP daily for 22 days caused a significant reduction in the mean GSI, HSI, and number of Stage IV (vitellogenic) follicles compared to experimental controls during the prespawning phase of the ovarian cycle. Furthermore, the Stage V (vitellogenic) follicles were completely absent during the prespawning phase concomitant with the significantly lower serum levels of estradiol and cortisol in 4 µg β-EP treated fish compared to experimental controls. On the other hand, exposure of the fish to mild acute stressors for 22 days caused changes in the ovary similar to that of high dose of β-EP, whereas administration of NALT attenuated these effects. The results reveal that β-EP exerts inhibitory effect on the vitellogenic follicular growth through the suppression of ovarian steroidogenesis. The study provides evidence for the opioidergic mediation of the ovarian stress response for the first time in fish.


General Anesthetic Management of a Patient With Hypertrophic Cardiomyopathy for Oral Surgery: Did Digitalis Contribute to Bradycardia?
Stabilization of circulatory dynamics is a critical issue in the anesthetic management of patients with hypertrophic cardiomyopathy (HCM). In this report, we managed general anesthesia for a 74-year-old male patient with nonobstructive HCM who developed circulatory instability intraoperatively. Severe bradycardia measuring 35 beats/min and hypotension measuring 78 mm Hg systolic were observed during surgery. Using stroke volume variation and stroke volume from the FloTrac as indices, successful circulatory management was performed with dopamine. The hypotension and bradycardia were thought to be the result of methyldigoxin and possibly associated with our perioperative management. Cardiology consult should have been obtained. We demonstrated that the FloTrac can be beneficial in diagnosing and managing cardiovascular instability and administration of dopamine in the anesthetic management of nonobstructive HCM patients.


Arterial pressure above the upper cerebral autoregulation limit during cardiopulmonary bypass is associated with postoperative delirium.
Mean arterial pressure (MAP) below the lower limit of cerebral autoregulation during cardiopulmonary bypass (CPB) is associated with complications after cardiac surgery. However, simply raising empiric MAP targets during CPB might result in MAP above the upper limit of autoregulation (ULA), causing cerebral hyperperfusion in some patients and predisposing them to cerebral dysfunction after surgery. We hypothesized that MAP above an ULA during CPB is associated with postoperative delirium. Autoregulation during CPB was monitored continuously in 491 patients with the cerebral oximetry index (COx) in this prospective observational study. COx represents Pearson's correlation coefficient between low-frequency changes in regional cerebral oxygen saturation (measured with near-infrared spectroscopy) and MAP. Delirium was defined throughout the postoperative hospitalization based on clinical detection with prospectively defined methods. Delirium was observed in 45 (9.2%) patients. Mechanical ventilation for >48 h [odds ratio (OR), 3.94; 95% confidence interval (CI), 1.72-9.03], preoperative antidepressant use (OR, 3.0; 95% CI, 1.29-6.96), prior stroke (OR, 2.79; 95% CI, 1.12-6.96), congestive heart failure (OR, 2.68; 95% CI, 1.28-5.62), the product of the magnitude and duration of MAP above an ULA (mm Hg h; OR, 1.09; 95% CI, 1.03-1.15), and age (per year of age; OR, 1.01; 95% CI, 1.01-1.07) were independently associated with postoperative delirium. Excursions of MAP above the upper limit of cerebral autoregulation during CPB are associated with risk for delirium. Optimizing MAP during CPB to remain within the cerebral autoregulation range might reduce risk of delirium. clinicaltrials.gov NCT00769691 and NCT00981474.


Host-guest antenna materials.
The focus of this review is on host-guest composites with photonic antenna properties. The material generally consists of cylindrical zeolite L crystals the channels of which are filled with dye molecules. The synthesis is based on the fact that molecules can diffuse into individual channels. This means that, under the appropriate conditions, they can also leave the zeolite by the same way. In some cases, however, it is desirable to block their way out by adding a closure molecule. Functionalization of the closure molecules allows tuning of, for example, wettability, refractive index, and chemical reactivity. The supramolecular organization of the dyes inside the channels is a first stage of organization. It allows light harvesting within a certain volume of a dye-loaded nanocrystalline zeolite and radiationless transport to both ends of the cylinder or from the ends to the center. The second stage of organization is the coupling to an external acceptor or donor stopcock fluorophore at the ends of the channels, which can trap or inject electronic excitation energy. The third stage of organization is the coupling to an external device through a stopcock molecule. The wide-ranging tunability of these highly organized materials offers fascinating new possibilities for exploring excitation-energy-transfer phenomena, and challenges for developing new photonic devices.


Impact of Hurricane Maria on mold levels in the homes of Piñones, Puerto Rico.
Hurricane Maria struck Puerto Rico on September 20, 2017, severely impacting the island. In order to quantify the impact of the hurricane on the indoor air quality, we evaluated the fungal levels in households (n = 20) of the Piñones community for the period of 2018 and 2019. For each dust sample collected, the 36 Environmental Relative Moldiness Index (ERMI) molds were quantified using qPCR assays, and then Shannon Diversity Index (SDI) values for the fungal populations were calculated. Homes were in five separate regions, regarding their proximity in the studied area. We found that for regions with reported least water damage, the SDI values were similar for both sampled years, but for regions that reported mid-to-high level of damage region, the SDI values were significantly higher. Households that reported remediation actions between the two sampled years showed similar values for the second year as those that did not report any major impact. Our preliminary data provides insights into the significant impacts of hurricanes into indoor fungal environment.


Multiple Sources of Prescription Payment and Risky Opioid Therapy Among Veterans.
Opioid overdose and other related harms are a major source of morbidity and mortality among US Veterans, in part due to high-risk opioid prescribing. We sought to determine whether having multiple sources of payment for opioids-as a marker for out-of-system access-is associated with risky opioid therapy among veterans. Cross-sectional study examining the association between multiple sources of payment and risky opioid therapy among all individuals with Veterans Health Administration (VHA) payment for opioid analgesic prescriptions in Kentucky during fiscal year 2014-2015. Source of payment categories: (1) VHA only source of payment (sole source); (2) sources of payment were VHA and at least 1 cash payment [VHA+cash payment(s)] whether or not there was a third source of payment; and (3) at least one other noncash source: Medicare, Medicaid, or private insurance [VHA+noncash source(s)]. Our outcomes were 2 risky opioid therapies: combination opioid/benzodiazepine therapy and high-dose opioid therapy, defined as morphine equivalent daily dose ≥90 mg. Of the 14,795 individuals in the analytic sample, there were 81.9% in the sole source category, 6.6% in the VHA+cash payment(s) category, and 11.5% in the VHA+noncash source(s) category. In logistic regression, controlling for age and sex, persons with multiple payment sources had significantly higher odds of each risky opioid therapy, with those in the VHA+cash having significantly higher odds than those in the VHA+noncash source(s) group. Prescribers should examine the prescription monitoring program as multiple payment sources increase the odds of risky opioid therapy.


Duodenal expression of a putative stimulator of Fe transport and transferrin receptor in anemia and hemochromatosis.
Stimulator of Fe Transport (SFT) and transferrin receptor (TfR) are proteins involved in iron transport. This study evaluated iron metabolism protein expression in duodenal biopsy specimens from controls and patients with abnormal iron metabolism. Twelve controls, 8 patients with iron deficiency anemia, 7 with HFE-related hemochromatosis, and 6 with non-HFE-related iron overload were studied. Immunohistochemistry was performed on duodenal biopsy specimens with anti-TfR and anti-SFT antibodies which recognize a putative stimulator of Fe transport of ~80 kilodaltons. In controls, the putative stimulator of Fe transport was expressed in the middle and distal part of the villi in the subapical cytoplasmatic region. Its expression increased in anemics and, to a lesser degree, in HFE-related hemochromatotics, whereas it was reduced in patients with non-HFE-related iron overload. TfR expression showed a crypt-to-tip gradient in controls, but not in anemics, in whom it was uniformly overexpressed. TfR expression was intermediate in HFE-related hemochromatotics and similar to controls in non-HFE-related iron overload. Expression of the putative stimulator of Fe transport and TfR increases in iron deficiency. Increased expression of both proteins is present only in HFE-related hemochromatotics suggesting that other factors may be involved in determining non-HFE-related iron overload phenotype.


Lithotripsy of Calcified Aortic Valve Leaflets by a Novel Ultrasound Transcatheter-Based Device.
The increasing incidence of calcific aortic valve disease necessitates the elaboration of new strategies to retard the progression of the pathology with an innovative solution. While the increasing diffusion of the transcatheter aortic valve replacements (TAVRs) allows a mini-invasive approach to aortic valve substitution as an alternative to conventional surgical replacement (SAVR) in an always larger patient population, TAVR implantation still has contraindications for young patients. In addition, it is liable to undergo calcification with the consequent necessity of re-intervention with conventional valve surgery or repeated implantation in the so-called TAVR-in-TAVR procedure. Inspired by applications for non-cardiac pathologies or for vascular decalcification before stenting (i.e., coronary lithotripsy), in the present study, we show the feasibility of human valve treatment with a mini-invasive device tailored to deliver shockwaves to the calcific leaflets. We provide evidence of efficient calcium deposit ruptures in human calcified leaflets treated ex vivo and the safety of the treatment in pigs. The use of this device could be helpful to perform shockwaves valvuloplasty as an option to retard TAVR/SAVR, or as a pretreatment to facilitate prosthesis implantation and minimize the occurrence of paravalvular leak.


[Preclinical evaluation of the safety of biotechnology products: specific aspects].
Biotechnology-derived products represent a class of increasingly numerous drugs. One of their major characteristics is extreme diversity, which requires specific approaches for the preclinical evaluation of their safety. The selection of relevant animal species is not easy, as most of these products are human-specific. Thus, only one species will often be used, i.e. primates. As most of these products are large molecules, they can be directly immunogenic. When they are human-specific, no animal model is available to predict the risk. Many biotechnology-derived products have an expected influence on the immune system. This must be taken into account in the preclinical strategy of immunotoxicity evaluation that is now required for every new drug. As conventional toxicity testing is generally limited, safety pharmacology studies should include more than the core battery of assays required by current guidelines in order to complement missing data as much as possible. Because of these particularities, a comprehensive investigation of metabolism and pharmacokinetics is not usually needed. Some products can cross-react with cellular components not intended as therapeutic targets. It is, therefore, essential to rule out the risk of possible cross-reactions that can result in adverse effects. Finally, viral safety is a crucial component of the preclinical safety evaluation of these products. Overall, biotechnology-derived products raise specific issues because of their innovative and original characteristics, and it is difficult to address all these issues if not by using a case-by-case approach.


Louis Pasteur and the birth of microbiology in Denmark.
Høiby N. Louis Pasteur and the birth of microbiology in Denmark. APMIS 2022. Louis Pasteur's work initiated the birth of microbiology in Denmark. Carl Julius Salomonsen was the pioneer who inspired and taught Christian Gram, Thorvald Madsen and Bernhard Bang bacteriological techniques in his annual bacteriological course which he started in 1883 at the University of Copenhagen. These pioneers developed Danish human and veterinary microbiology and became world famous. Emil Chr. Hansen developed Danish technical/industrial microbiology in the Carlsberg Laboratory and purified yeast and designed equipment for the propagation of pure yeast which was used worldwide in beer brewing. He also became world famous. The fascinating birth and development of Danish microbiology is summarized in this article, which is dedicated to the 200th birthday of Louis Pasteur, December 27, and 100th birthday of the Danish Pasteur Society, October 25, 2022.


Unraveling the redox properties of the global regulator FurA from Anabaena sp. PCC 7120: disulfide reductase activity based on its CXXC motifs.
Cyanobacterial FurA works as a global regulator linking iron homeostasis to photosynthetic metabolism and the responses to different environmental stresses. Additionally, FurA modulates several genes involved in redox homeostasis and fulfills the characteristics of a heme-sensor protein whose interaction with this cofactor negatively affects its DNA binding ability. FurA from Anabaena PCC 7120 contains five cysteine residues, four of them arranged in two redox CXXC motifs. Our goals were to analyze in depth the putative contribution of these CXXC motifs in the redox properties of FurA and to identify potential interacting partners of this regulator. Insulin reduction assays unravel that FurA exhibits disulfide reductase activity. Simultaneous presence of both CXXC signatures greatly enhances the reduction rate, although the redox motif containing Cys(101) and Cys(104) seems a major contributor to this activity. Disulfide reductase activity was not detected in other ferric uptake regulator (Fur) proteins isolated from heterotrophic bacteria. In vivo, FurA presents different redox states involving intramolecular disulfide bonds when is partially oxidized. Redox potential values for CXXC motifs, -235 and -238 mV, are consistent with those reported for other proteins displaying disulfide reductase activity. Pull-down and two-hybrid assays unveil potential FurA interacting partners, namely phosphoribulokinase Alr4123, the hypothetical amidase-containing domain All1140 and the DNA-binding protein HU. A novel biochemical activity of cyanobacterial FurA based on its cysteine arrangements and the identification of novel interacting partners are reported. The present study discloses a putative connection of FurA with the cyanobacterial redox-signaling pathway.


Angle- and energy-resolved plasmon coupling in gold nanorod dimers.
The plasmon coupling in the dimers of Au nanorods linked together at their ends with dithiol molecules has been studied. The plasmon coupling in the dimers composed of similarly sized nanorods gives antibonding and bonding plasmon modes. The plasmon wavelengths of the two modes have been found to remain approximately unchanged, with the scattering intensity ratio between the antibonding and bonding modes decaying rapidly as the angle between the nanorods is increased. This plasmon coupling behavior agrees with that obtained from both electrodynamic calculations and modeling on the basis of the dipole-dipole interaction. The electric field in the gap region is largely enhanced for the bonding mode, while that for the antibonding mode is even smaller than the far field, highlighting the importance of selecting appropriate plasmon modes for plasmon-enhanced spectroscopies. An anti-crossing-like behavior in the plasmon coupling energy diagram has further been revealed for linearly end-to-end assembled dimers composed of differently sized nanorods. This result will be useful for plasmonic applications where the plasmon wavelength is required to be controllable but without sacrificing the electric field enhancement.


Effects of efforts to optimise morbidity and mortality rounds to serve contemporary quality improvement and educational goals: a systematic review.
The quality and safety movement has reinvigorated interest in optimising morbidity and mortality (M&M) rounds. We performed a systematic review to identify effective means of updating M&M rounds to (1) identify and address quality and safety issues, and (2) address contemporary educational goals. Relevant databases (Medline, Embase, PubMed, Education Resource Information Centre, Cumulative Index to Nursing and Allied Health Literature, Healthstar, and Global Health) were searched to identify primary sources. Studies were included if they (1) investigated an intervention applied to M&M rounds, (2) reported outcomes relevant to the identification of quality and safety issues, or educational outcomes relevant to quality improvement (QI), patient safety or general medical education and (3) included a control group. Study quality was assessed using the Medical Education Research Study Quality Instrument and Newcastle-Ottawa Scale-Education instruments. Given the heterogeneity of interventions and outcome measures, results were analysed thematically. The final analysis included 19 studies. We identified multiple effective strategies (updating objectives, standardising elements of rounds and attaching rounds to a formal quality committee) to optimise M&M rounds for a QI/safety purpose. These efforts were associated with successful integration of quality and safety content into rounds, and increased implementation of QI interventions. Consistent effects on educational outcomes were difficult to identify, likely due to the use of methodologies ill-fitted for educational research. These results are encouraging for those seeking to optimise the quality and safety mission of M&M rounds. However, the inability to identify consistent educational effects suggests the investigation of M&M rounds could benefit from additional methodologies (qualitative, mixed methods) in order to understand the complex mechanisms driving learning at M&M rounds.


[The Cairo Conference and the assertion of sexual and reproductive rights as a basis for sexual and reproductive health].
The article focuses on the International Conference on Population and Development held in El Cairo, Egypt, in 1994. The Conference addressed issues related to sexual and reproductive rights, actions to be adopted to improve the situation of young girls, the status of women, the situation of adolescents and gender equality as basic components to improve the sexual and reproductive health of the population. The concluding recommendations in this conference constitute the action program. This document also addresses some issues that generated long discussions to reach consensus during the conference. It summarizes the follow up performed on the action program in the following years and ends with the report of the Peruvian government and the civil society twenty years after the conference.


5-year survival after bone marrow transplantation for aplastic anemia.
The International Bone Marrow Transplant Registry reported experience from 179 transplant teams worldwide on patients treated with bone marrow transplantation for severe aplastic anemia. The cohort consisted of 470 patients (283 male, 187 female), mean age 20 years, who received an HLA-identical sibling bone marrow transplant for aplastic anemia between 1988 and 1992. The etiology of aplastic anemia was usually idiopathic, with a small number of cases caused by hepatitis or toxin exposure. Congenital aplastic anemia was not considered. Expected mortality was based on the United States 1992 Total Population Mortality Table. Additional data were obtained from the author.


Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer.
A phase 2 trial of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer led to an objective response in approximately 30% of patients and a median survival of 14 months. In the current study, the authors report further efficacy data of a larger cohort of such patients treated with the GemCap regimen. Patients aged >18 years and who had a diagnosis of locally advanced biliary cancer received first-line treatment with capecitabine at a dose of 650 mg/m(2) twice daily for 14 days and gemcitabine at a dose of 1,000 mg/m(2) on Day 1 and Day 8, every 3 weeks until disease progression. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Between July 2001 and January 2005, 75 patients were enrolled in the study. At a median follow-up of 9.5 months, the overall response rate was 29% (95% confidence interval [95% CI], 19.4-41%), with a median duration of 9.7 months (range, 3-36 months). Three patients achieved complete responses, with a median duration of 17 months (range, 9-27 months). The median progression-free survival and overall survivals were 6.2 months (95% CI, 4.4-8.3 months) and 12.7 months (95% CI, 9.5-31 months), respectively. The GemCap regimen is active in patients with biliary cancer. Randomized trials are warranted to define the impact of such a regimen on patient survival and quality of life.


Dependency on de novo protein synthesis and proteomic changes during metamorphosis of the marine bryozoan Bugula neritina.
Metamorphosis in the bryozoan Bugula neritina (Linne) includes an initial phase of rapid morphological rearrangement followed by a gradual phase of morphogenesis. We hypothesized that the first phase may be independent of de novo synthesis of proteins and, instead, involves post-translational modifications of existing proteins, providing a simple mechanism to quickly initiate metamorphosis. To test our hypothesis, we challenged B. neritina larvae with transcription and translation inhibitors. Furthermore, we employed 2D gel electrophoresis to characterize changes in the phosphoproteome and proteome during early metamorphosis. Differentially expressed proteins were identified by liquid chromatography tandem mass spectrometry and their gene expression patterns were profiled using semi-quantitative real time PCR. When larvae were incubated with transcription and translation inhibitors, metamorphosis initiated through the first phase but did not complete. We found a significant down-regulation of 60 protein spots and the percentage of phosphoprotein spots decreased from 15% in the larval stage to12% during early metamorphosis. Two proteins--the mitochondrial processing peptidase beta subunit and severin--were abundantly expressed and phosphorylated in the larval stage, but down-regulated during metamorphosis. MPPbeta and severin were also down-regulated on the gene expression level. The initial morphogenetic changes that led to attachment of B. neritina did not depend on de novo protein synthesis, but the subsequent gradual morphogenesis did. This is the first time that the mitochondrial processing peptidase beta subunit or severin have been shown to be down-regulated on both gene and protein expression levels during the metamorphosis of B. neritina. Future studies employing immunohistochemistry to reveal the expression locality of these two proteins during metamorphosis should provide further evidence of the involvement of these two proteins in the morphogenetic rearrangement of B. neritina.


Molecular evolution of Zika virus during its emergence in the 20(th) century.
Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda in 1947. Although entomological and virologic surveillance have reported ZIKV enzootic activity in diverse countries of Africa and Asia, few human cases were reported until 2007, when a Zika fever epidemic took place in Micronesia. In the context of West Africa, the WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever at Institut Pasteur of Dakar (http://www.pasteur.fr/recherche/banques/CRORA/) reports the periodic circulation of ZIKV since 1968. Despite several reports on ZIKV, the genetic relationships among viral strains from West Africa remain poorly understood. To evaluate the viral spread and its molecular epidemiology, we investigated 37 ZIKV isolates collected from 1968 to 2002 in six localities in Senegal and Côte d'Ivoire. In addition, we included strains from six other countries. Our results suggested that these two countries in West Africa experienced at least two independent introductions of ZIKV during the 20(th) century, and that apparently these viral lineages were not restricted by mosquito vector species. Moreover, we present evidence that ZIKV has possibly undergone recombination in nature and that a loss of the N154 glycosylation site in the envelope protein was a possible adaptive response to the Aedes dalzieli vector.


Phylogenomic resolution of scorpions reveals multilevel discordance with morphological phylogenetic signal.
Scorpions represent an iconic lineage of arthropods, historically renowned for their unique bauplan, ancient fossil record and venom potency. Yet, higher level relationships of scorpions, based exclusively on morphology, remain virtually untested, and no multilocus molecular phylogeny has been deployed heretofore towards assessing the basal tree topology. We applied a phylogenomic assessment to resolve scorpion phylogeny, for the first time, to our knowledge, sampling extensive molecular sequence data from all superfamilies and examining basal relationships with up to 5025 genes. Analyses of supermatrices as well as species tree approaches converged upon a robust basal topology of scorpions that is entirely at odds with traditional systematics and controverts previous understanding of scorpion evolutionary history. All analyses unanimously support a single origin of katoikogenic development, a form of parental investment wherein embryos are nurtured by direct connections to the parent's digestive system. Based on the phylogeny obtained herein, we propose the following systematic emendations: Caraboctonidae is transferred to Chactoidea new superfamilial assignment: ; superfamily Bothriuroidea revalidated: is resurrected and Bothriuridae transferred therein; and Chaerilida and Pseudochactida are synonymized with Buthida new parvordinal synonymies: .


Age and Sex Disparities in Discharge Statin Prescribing in the Stroke Belt: Evidence From the Reasons for Geographic and Racial Differences in Stroke Study.
Stroke is a costly and debilitating disease that disproportionately affects blacks. Despite the efficacy of statins, evidence suggests racial disparities may exist in statin prescribing. We analyzed discharge medications for participants hospitalized for an ischemic stroke during follow-up of the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study. Medications on admission and discharge were abstracted from medical records. Among the 666 eligible incident strokes (2003-2013), analyses were restricted to 323 participants who were not statin users at the time of admission and had no history of atrial fibrillation. Overall, 48.7% were prescribed a statin on discharge. In the Stroke Belt, participants aged 65 years and older were 47% less likely to be discharged on a statin compared with those younger than 65 years (relative risk [RR], 0.53; 95% CI, 0.38-0.74). This association was not observed in non-Stroke Belt residents. Outside the Stroke Belt, blacks were more likely than whites to be discharged on a statin (RR, 1.42; 95% CI, 1.04-1.94), while no black:white association was present among Stroke Belt residents (RR, 0.93; 95% CI, 0.69-1.26; P for interaction=0.228). Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin (RR, 0.69; 95% CI, 0.50-0.94) while men outside the Stroke Belt were more likely to be discharged on a statin (RR, 1.38; 95% CI, 0.99-1.92; P for interaction=0.004). Statin discharge prescribing may differ among Stroke Belt and non-Stroke Belt residents, particularly in older Americans and men.


Myophosphorylase (PYGM) mutations determined by next generation sequencing in a cohort from Turkey with McArdle disease.
This study aimed to identify PYGM mutations in patients with McArdle disease from Turkey by next generation sequencing (NGS). Genomic DNA was extracted from the blood of the McArdle patients (n = 67) and unrelated healthy volunteers (n = 53). The PYGM gene was sequenced with NGS and the observed mutations were validated by direct Sanger sequencing. A diagnostic algorithm was developed for patients with suspected McArdle disease. A total of 16 deleterious PYGM mutations were identified, of which 5 were novel, including 1 splice-site donor, 1 frame-shift, and 3 non-synonymous variants. The p.Met1Val (27-patients/11-families) was the most common PYGM mutation, followed by p.Arg576* (6/4), c.1827+7A>G (5/4), c.772+2_3delTG (5/3), p.Phe710del (4/2), p.Lys754Asnfs (2/1), and p.Arg50* (1/1). A molecular diagnostic flowchart is proposed for the McArdle patients in Turkey, covering the 6 most common PYGM mutations found in Turkey as well as the most common mutation in Europe. The diagnostic algorithm may alleviate the need for muscle biopsies in 77.6% of future patients. A prevalence of any of the mutations to a geographical region in Turkey was not identified. Furthermore, the NGS approach to sequence the entire PYGM gene was successful in detecting a common missense mutation and discovering novel mutations in this population study.


Efficacy of percutaneous radiofrequency ablation may vary with clear cell renal cell cancer histologic subtype.
The purpose of the study is to determine if clear cell renal cell cancer (RCC) subtype predicts efficacy in percutaneous radiofrequency (RF) ablation of RCC. Patients who underwent percutaneous RF ablation for histologically proven RCC subtypes were retrospectively reviewed. Group comparisons were done using univariate and multivariate logistic regression analysis to determine factors impacting primary, secondary, and total technique effectiveness. A p value less than 0.05 was considered significant. One hundred pathologically proven RCC lesions in 84 patients were analyzed. The median (mean) follow-up was 24 (27) months (range 1-106 months). Overall RF ablation primary, secondary and total technique effectiveness was 86%, 9%, and 95%, respectively. Clear cell subtype demonstrated worse treatment efficacy with primary, secondary, and total technique effectiveness of 42/55 (76.4%), 8/55 (14.5%), and 50/55 (90.9%), respectively. Non-clear cell subtypes had primary, secondary, and total technique effectiveness of 44/45(97.8%), 1/45 (2.2%), 45/45 (100%), respectively. The difference in primary (p = 0.002), secondary (p = 0.032), and total (p = 0.038) technique effectiveness between the two groups was statistically significant. Clear cell RCC was a novel predictor of primary, secondary, and total technique efficacy in the percutaneous RF ablation of clear cell RCC.


Effects of paracentesis on the blood-aqueous barrier: a light and electron microscopic study on cynomolgus monkey.
The effects of paracentesis on the blood-aqueous barrier of cynomolgus monekeys were studied by light and electron microscopy. The following regions of the eye were examined: ciliary body, iris, Schlemm's canal, juxtacanalicular connective tissue, and trabecular meshwork. Prominent structural alterations were seen in the ciliary epithelium at the anterior portion of the pars plicata, but the epithelium at the posterior portion of the pars plicata and at the pars plana appeared less disrupted. Plasma proteins which crossed the capillary endothelium accumulated in the stroma, and appeared in the posterior chamber through the enlarged extracellular spaces of the ciliary epithelium. The plasma proteins in the ciliary stroma of the anterior portion of the pars plicata moved to the stroma of the iris root; whereas in the iris the capillary endothelium provide an impermeable barrier to proteins. Following paracentesis, the lumen of Schlemm's canal was invaded by blood, and through newly formed gaps in the endothelial lining of the inner wall of the canal, the plasma proteins and red blood cells rapidly diffused into the juxtacanalicular connective tissue, trabecular meshwork, and anterior chamber. On the basis of the present experiments, the protein of the aqueous humor can be considered as originating from both the anterior portion of the pars plicata and the inner wall of Schlemm's canal.


St. Louis area Medicaid HMOs discuss managed care plus (MC+).
The medicaid Managed Care program (MC+) will be implemented in stages across the state of Missouri. In the St. Louis area the enrollment process began June 1, 1995. HMOs will be paid on a capitated basis by the State of Missouri Division of Medical Services (Medicaid). HMOs may pay physicians on a capitated or fee-for service basis. Individuals have 30 days to change HMOs after enrollment. There will be an annual open enrollment period for those who choose to switch HMOs. MC+ will begin operations in St. Louis on September 1. The auto-assignment process will begin August 15. The remaining unenrolled population will be parcelled out according to the following percentages: [table: see text]


CpG Site-Specific Regulation of Metallothionein-1 Gene Expression.
Metal-binding inducible proteins called metallothioneins (MTs) protect cells from heavy-metal toxicity. Their transcription is regulated by metal response element (MRE)-binding transcription factor-1 (MTF1), which is strongly recruited to MREs in the MT promoters, in response to Zn and Cd. Mouse Mt1 gene promoter contains 5 MREs (a-e), and MTF1 has the highest affinity to MREd. Epigenetic changes like DNA methylation might affect transcription and, therefore, the cytoprotective function of MT genes. To reveal the CpG site(s) critical for Mt1 transcription, we analyzed the methylation status of CpG dinucleotides in the Mt1 gene promoter through bisulfite sequencing in P1798 mouse lymphosarcoma cells, with high or low MT expression. We found demethylated CpG sites near MREd and MREe, in cells with high expression. Next, we compared Mt1 gene-promoter-driven Lucia luciferase gene expression in unmethylated and methylated reporter vectors. To clarify the effect of complete and partial CpG methylation, we used M.SssI (CG→5mCG) and HhaI (GCGC→G5mCGC)-methylated reporter vectors. Point mutation analysis revealed that methylation of a CpG site near MREd and MREe strongly inhibited Mt1 gene expression. Our results suggest that the methylation status of this site is important for the regulation of Mt1 gene expression.


Role of Zebrafish fhl1A in Satellite Cell and Skeletal Muscle Development.
Four-and-a-half LIM domains protein 1 (FHL1) mutations are associated with human myopathies. However, the function of this protein in skeletal development remains unclear. Whole-mount in situ hybridization and embryo immunostaining were performed. Zebrafish Fhl1A is the homologue of human FHL1. We showed that fhl1A knockdown causes defective skeletal muscle development, while injection with fhl1A mRNA largely recovered the muscle development in these fhl1A morphants. We also demonstrated that fhl1A knockdown decreases the number of satellite cells. This decrease in satellite cells and the emergence of skeletal muscle abnormalities were associated with alterations in the gene expression of myoD, pax7, mef2ca and skMLCK. We also demonstrated that fhl1A expression and retinoic acid (RA) signalling caused similar skeletal muscle development phenotypes. Moreover, when treated with exogenous RA, endogenous fhl1A expression in skeletal muscles was robust. When treated with DEAB, an RA signalling inhibitor which inhibits the activity of retinaldehyde dehydrogenase, fhl1A was downregulated. fhl1A functions as an activator in regulating the number of satellite cells and in skeletal muscle development. The role of fhl1A in skeletal myogenesis is regulated by RA signaling.


Solution equilibrium behind the room-temperature synthesis of nanocrystalline titanium dioxide.
Formation of nanocrystalline and monodisperse TiO2 from a water soluble and stable precursor, ammonium oxo-lactato-titanate, (NH4)8Ti4O4(Lactate)8·4H2O, often referred to as TiBALDH or TALH, is demonstrated to be due to a coordination equilibrium. This compound, individual in the solid state, exists in solution in equilibrium with ammonium tris-lactato-titanate, (NH4)2Ti(Lactate)3 and uniform crystalline TiO2 nanoparticles (anatase) stabilized by surface-capping with lactate ligands. This equilibrium can be shifted towards nano-TiO2via application of a less polar solvent like methanol or ethanol, dilution of the solution, introduction of salts or raising the temperature, and reverted on addition of polar and strongly solvating media such as dimethyl sulfoxide, according to NMR. Aggregation and precipitation of the particles were followed by DLS and could be achieved by a decrease in their surface charge by adsorption of strongly hydrogen-bonding cations, e.g. in solutions of ammonia, ethanolamine or amino acid arginine or by addition of ethanol. The observed equilibrium may be involved in formation of nano-titania on the surface of plant roots exerting chelating organic carboxylate ligands and thus potentially influencing plant interactions.


Comparison of serum cystatin C and creatinine levels in determining glomerular filtration rate in children with stage I to III chronic renal disease.
Pediatric studies are relatively scarce on the superiority of cystatin C over creatinine in estimation of glomerular filtration rate (GFR). This study measured cystatin C and serum creatinine levels, and compared GFR estimated from these two parameters in patients with chronic renal disease. This prospective, observational, controlled study included 166 patients aged 1-18 years diagnosed with stage I to III chronic renal disease, and 29 age- and sex-matched control subjects. In all patients, GFR was estimated via creatinine clearance, Schwartz formula, Zappitelli 1 and Zappitelli 2 formula and the results were compared using Bland-Altman analysis. Patients and controls did not differ with regard to height, body weight, BMI, serum creatinine and serum cystatin levels, and Schwartz formula-based GFR (p > 0.05). There was a significant relationship between creatinine and cystatin C levels. However, although creatinine levels showed a significant association with age, height, and BMI, cystatin C levels showed no such association. ROC analysis showed that cystatin C performed better than creatinine in detecting low GFR. Cystatin C is a more sensitive and feasible indicator than creatinine for the diagnosis of stage I to III chronic renal disease.


Fish intake and risks of total and cause-specific mortality in 2 population-based cohort studies of 134,296 men and women.
Despite a proposed protective effect of fish intake on the risk of cardiovascular disease, epidemiologic evidence on fish intake and mortality is inconsistent. We investigated associations of fish intake, assessed through a validated food frequency questionnaire, with risks of total and cause-specific mortality in 2 prospective cohort studies of 134,296 Chinese men and women (1997-2009). Vital status and date and cause of death were ascertained through annual linkage to the Shanghai Vital Statistics Registry database and biennial home visits. Cox regression was used to calculate hazard ratios and corresponding 95% confidence intervals. After excluding the first year of observation, the analysis included 3,666 deaths among women and 2,170 deaths among men. Fish intake was inversely associated with risks of total, ischemic stroke, and diabetes mortality; the corresponding hazard ratios for the highest quintiles of intake compared with the lowest were 0.84 (95% confidence interval (CI): 0.76, 0.92), 0.63 (95% CI: 0.41, 0.94), and 0.61 (95% CI: 0.39, 0.95), respectively. No associations with cancer or ischemic heart disease mortality were observed. Further analyses suggested that the inverse associations with total, ischemic stroke, and diabetes mortality were primarily related to consumption of saltwater fish and intake of long-chain n-3 fatty acids. Overall, our findings support the postulated health benefits of fish consumption.


Sensory properties of ginseng solutions modified by masking agents.
Ginseng is one of the most popular functional ingredients found in energy drink formulations. Although ginseng is known for its health benefits, ginseng is also notorious for imparting a bitter taste. Incorporating ginseng into beverages without the bitterness, while still maintaining its health benefits, is necessary for developing an acceptable product. Thus, the objectives of this study were to (1) identify effective treatments for minimizing the bitterness of ginseng in water base and model energy drink base solutions and (2) determine the sensory effects of incorporating different treatment levels to minimize the bitterness of ginseng. A series of pilot studies investigating bitterness reducing treatments were conducted, which included: congruent flavor addition, bitterness blocking agent incorporation, enzymatic modification, ingredient interaction, and complexation. Based on the results of a series of pilot studies, γ-cyclodextrin (γ-CD) and β-cyclodextrin (β-CD) complexation agents were identified as having the most potential. Effectiveness of the γ-CDs, β-CDs, and combinations of γ- and β-CDs were tested in 100 mL water and in 100 mL model energy drink base solutions containing 0.052 g 80% ginsenosides panax ginseng, using descriptive sensory analysis. Twelve trained panelists evaluated 42 solution treatments (3 treatments × 7 levels × 2 bases) for bitter attributes with and without nose clips. Overall, the most effective treatments were 0.09 g γ-CDs in 100 mL of solution and 1 g β-CDs in 100 mL solution, which both reduced the bitterness intensity of the solutions by half. Incorporation of these levels of CDs in water and model energy drink base solutions containing ginseng will aid in the development of functional beverages that are more acceptable to a wider range of consumers.


Electromagnetic Field Could Protect SH-SY5Y Cells Against Cisplatin Cytotoxicity, But Not MCF-7 Cells.
Cisplatin [cis-dichlorodiammine platinum (II), CDDP], morphine (Mor), and electromagnetic field (EMF) induced oxidative stress. In this study, we tried to increase the cytotoxicity of CDDP in combination with Mor and/or EMF in MCF-7 and SH-SY5Y cells. Furthermore, we evaluate the expression levels of 11 antioxidant genes in both cell lines. We designed four treatments: CDDP alone, "CDDP+Mor," "CDDP+EMF," and "CDDP+Mor+EMF." Serial dilutions of CDDP, Mor (5.0 μM), and EMF (50 Hz, 0.50 mT, "15 min field-on/15 min field-off") were used for estimation of relative IC50 values. The mRNA expression levels of antioxidant genes were determined by real-time PCR. The IC50 value of CDDP in "CDDP+Mor+EMF" treatment was significantly higher than CDDP alone and "CDDP+Mor" treatments in both cell lines. Whereas the expression levels of antioxidant genes in the four treatments showed similar patterns in MCF-7 cells, in SH-SY5Y cells, most of the antioxidant genes showed an upregulation with "CDDP+EMF" and "CDDP+Mor+EMF" treatments. Moreover, significant differences in the number of upregulated genes were observed between different treatments in SH-SY5Y cells. The molecular mechanism of CDDP-reduced cytotoxicity in our designed combinations is probably different in MCF-7 and SH-SY5Y cells. CDDP in combination with EMF could protect SH-SY5Y cells from the cytotoxicity, whereas it has no significant change in MCF-7 cells.


Long-term application of some catecholamines elevates levels of other catecholamines in rats.
Male Sprague-Dawley rats were treated during 20 h with subcutaneously implanted tablets (controlled release systems) containing either adrenaline (A), noradrenaline (NA), isoprenaline (ISO) or just placebos. Levels of the exogenously administered catecholamines (CA) in plasma and liver homogenate were significantly higher than in controls throughout the test time. During NA application endogeneous A and dopamine (DA) plasma values rose considerably, while ISO application enhanced endogenous NA and A levels. Adrenaline application increased NA and DA plasma levels. Several possibilities for this phenomenon are discussed, and it is concluded that previous papers dealing with observations of long term action of CA's should be reevaluated unless the influence of the artificially given CA on the elevation of endogenous CA's has been already taken into consideration.


The Chronic Overlapping Pain Condition Screener.
Ten Chronic Overlapping Pain Conditions (COPCs) are currently recognized by the National Institutes of Health Pain Consortium (eg, irritable bowel syndrome, chronic migraine headache, and chronic low back pain). These conditions affect millions of Americans; however, assessing these conditions, their co-occurrence, and their relationship to treatment has proven challenging due to time constraints and a lack of standardized measures. We present a Chronic Overlapping Pain Condition-Screener (COPC-S) that is logic-driven, efficient, and freely available in electronic format to nonprofit entities. Thirty experts were convened to identify and modify self-report criteria for each COPC as well as criteria that trigger the administration of the diagnostic criteria from a body map and a brief series of questions. Their recommendations were then programmed into the Research Electronic Data Capture platform and refined for comprehensibility and ease of use by patient focus groups. The electronic screener and physician-administered criteria were both administered to patients with known COPCs in a counter-balanced fashion to determine the level of agreement between methods. The expert panel identified screening items/body map regions and diagnostic criteria for all 10 COPCs. Patients found the content comprehensible and the platform easy to use. Cohen's Kappa statistics suggested good agreement between the electronic COPC-S and criteria administered by a physician (κ = .813). The COPC-S is an efficient tool for screening multiple COPCs and has applicability to research studies, clinical trials, and clinical practice. PERSPECTIVE: Assessing COPCs remains a challenge for researchers and clinicians. The COPC-S is an efficient and logic-driven electronic tool that allows for the rapid screening assessment of 10 COPCs. The instrument may have utility in research and clinical settings.


Gene transfer of integration defective anti-HSV-1 meganuclease to human corneas ex vivo.
Corneal graft rejection is a major problem in chronic herpetic keratitis (HK) patients with latent infection. A new class of antiviral agents targeting latent and active forms of herpes simplex virus type 1 (HSV-1) is importantly required. Meganucleases are sequence-specific homing endonucleases capable of inducing DNA double-strand breaks. A proof-of-concept experiment has shown that tailor-made meganucleases are efficient against HSV-1 in vitro. To take this work a step forward, we hypothesized that the pre-treatment of human corneas in eye banks using meganuclease-encoding vectors will allow HK patients to receive a medicated cornea to resist the recurrence of the infection and the common graft rejection problem. However, this strategy requires efficient gene delivery to human corneal endothelium. Using recombinant adeno-associated virus, serotype 2/1 (rAAV2/1), efficient gene delivery of a reporter gene was demonstrated in human corneas ex vivo. The optimum viral dose was 3.7 × 10(11) VG with an exposure time of 1 day, followed by 6 days incubation in de-swelling medium. In addition, 12 days incubation can result in transgene expression in excess of 70%. Using similar transduction conditions, meganuclease transgene expression was detected in 39.4% of the endothelial cells after 2 weeks in culture. Reduction of the total viral load in the media and the endothelial cells of corneas infected with HSV-1 was shown. Collectively, this work provides information about the optimum conditions to deliver genetic material to the cornea, and demonstrates for the first time the expression of meganuclease in human corneas ex vivo and its antiviral activity. In conclusion, we demonstrate that the treatment of human corneas in eye banks before transplantation is a new approach to address the unmet clinical needs in corneal diseases.


[Discrepancy between imaging and neurophysiology in deep brain stimulation of medial pallidum and subthalamic nucleus in Parkinson's disease].
The objective of this work is to assess the discrepancy in distance between the target chosen by magnetic resonance imaging (MRI) and the final electrode placement after intraoperative microrecording in patients submitted to deep brain stimulation (DBS) for alleviating the Parkinson's disease (PD). Thirty patients with PD and motor complications were operated with stereotactic surgery by MRI and microrecording. In 19 patients, the target chosen was the subthalamic nucleus (STN) and in 11 others the target was globus pallidus internus (GPi). In this work it is considered that the electrode has a current field below usual parameters of 1.5 mm radius. Consequently, when the distance error between the final physiological target and the MRI target, is between 1.5 and 3 mm was considered as partial discrepancy and distances of 3 mm or more were considered as total discrepancy. Partial discrepancy for STN and GPi were in 25 and 33% of the cases respectively and total discrepancy was 57 and 42% for each nucleus. The average distance error between both targets, final and image, for X stereotactic coordinate (mediolateral distance) was 1.54 mm for STN and 0.8 mm for GPi. The average distance for Y coordinate (anteroposterior distance) was 2.3 mm for STN and 2.2 mm for GPi. There is a significant discrepancy between the final physiological target after microrecording and the target chosen by MRI during surgery for alleviating PD that may induce variations or absence of clinical efficacy in parkinsonian patients submitted to the DBS surgery. Authors suggest the necessity of the microelectrode recording in order to reach the surgical target with the best clinical condition.


Spontaneous germ cell death by apoptosis in epididymis of the adult bat Artibeus lituratus.
Many factors can lead cells to apoptosis during the various stages of cell life. This study was undertaken to characterize germ cell death in the epididymis of the adult Artibeus lituratus by histochemical and immunohistochemical techniques using light microscopy and transmission electron microscopy. The results showed that cells with a nuclear phenotype and ultrastructural characteristics of chromatin compaction were common in apoptosis. The Apoptag test confirmed that the suspected cells were apoptotic. It is suggested that immature germ cells, when released from the germinative epithelium, may be directed towards the epididymis instead of being disposed of in the testicle. Furthermore, intact immature cells can leave the testicle in the initial phases of apoptosis and complete this phenomenon in the epididymis.


EphrinB1 expression is dysregulated and promotes oncogenic signaling in medulloblastoma.
Eph receptors and ephrin ligands are master regulators of oncogenic signaling required for proliferation, migration, and metastasis. Yet, Eph/ephrin expression and activity in medulloblastoma (MB), the most common malignant brain tumor of childhood, remains poorly defined. We hypothesized that Eph/ephrins are differentially expressed by sonic hedgehog (SHH) and non-SHH MB and that specific members contribute to the aggressive phenotype. Affymetrix gene expression profiling of 29 childhood MB, separated into SHH (N = 11) and non-SHH (N = 18), was performed followed by protein validation of selected Eph/ephrins in another 60 MB and two MB cell lines (DAOY, D556). Functional assays were performed using MB cells overexpressing or deleted for selected ephrins. We found EPHB4 and EFNA4 almost exclusively expressed by SHH MB, whereas EPHA2, EPHA8, EFNA1 and EFNA3 are predominantly expressed by non-SHH MB. The remaining family members, except EFNB1, are ubiquitously expressed by over 70-90 % MB, irrespective of subgroup. EFNB1 is the only member differentially expressed by 28 % of SHH and non-SHH MB. Corresponding protein expression for EphB/ephrinB1 and B2 was validated in MB. Only ephrinB2 was also detected in fetal cerebellum, indicating that EphB/ephrinB1 expression is MB-specific. EphrinB1 immunopositivity localizes to tumor cells within MB with the highest proliferative index. EphrinB1 overexpression promotes EphB activation, alters F-actin distribution and morphology, decreases adhesion, and significantly promotes proliferation. Either silencing or overexpression of ephrinB1 impairs migration. These results indicate that EphrinB1 is uniquely dysregulated in MB and promotes oncogenic responses in MB cells, implicating ephrinB1 as a potential target.


Improving Primary Care Medication Processes by Using Shared Electronic Medication Plans in Switzerland: Lessons Learned From a Participatory Action Research Study.
Several countries have launched health information technology (HIT) systems for shared electronic medication plans. These systems enable patients and health care professionals to use and manage a common list of current medications across sectors and settings. Shared electronic medication plans have great potential to improve medication management and patient safety, but their integration into complex medication-related processes has proven difficult, and there is little scientific evidence to guide their implementation. The objective of this paper is to summarize lessons learned from primary care professionals involved in a pioneering pilot project in Switzerland for the systemwide implementation of shared electronic medication plans. We collected experiences, assessed the influences of the local context, and analyzed underlying mechanisms influencing the implementation. In this formative action research study, we followed 5 clusters of health care professionals during 6 months. The clusters represented rural and urban primary care settings. A total of 18 health care professionals (primary care physicians, pharmacists, and nurses) used the pilot version of a shared electronic medication plan on a secure web platform, the precursor of Switzerland's electronic patient record infrastructure. We undertook 3 group interviews with each of the 5 clusters, analyzed the content longitudinally and across clusters, and summarized it into lessons learned. Participants considered medication plan management, digitalized or not, a core element of good clinical practice. Requirements for the successful implementation of a shared electronic medication plan were the integration into and simplification of clinical routines. Participants underlined the importance of an enabling setting with designated reference professionals and regular high-quality interactions with patients. Such a setting should foster trusting relationships and nurture a culture of safety and data privacy. For participants, the HIT was a necessary but insufficient building block toward better interprofessional communication, especially in transitions. Despite oral and written information, the availability of shared electronic medication plans did not generate spontaneous demand from patients or foster more engagement in their medication management. The variable settings illustrated the diversity of medication management and the need for local adaptations. The results of our study present a unique and comprehensive description of the sociotechnical challenges of implementing shared electronic medication plans in primary care. The shared ownership among multiple stakeholders is a core challenge for implementers. No single stakeholder can build and maintain a safe, usable HIT system with up-to-date medication information. Buy-in from all involved health care professionals is necessary for consistent medication reconciliation along the entire care pathway. Implementers must balance the need to change clinical processes to achieve improvements with the need to integrate the shared electronic medication plan into existing routines to facilitate adoption. The lack of patient involvement warrants further study.


sst2 somatostatin receptor expression reverses tumorigenicity of human pancreatic cancer cells.
Among the five cloned somatostatin receptor subtypes (sst1 to sst5), sst2 mediates the antiproliferative effect of somatostatin analogues in vitro. Somatostatin analogues have been shown to inhibit cell growth in vitro and in vivo in pancreatic cancer models that expressed sst2. We recently demonstrated the loss of sst2 gene expression in human pancreatic adenocarcinomas and most of the derived pancreatic cancer cell lines. In the present study, we corrected the sst2 defect in human pancreatic cancer BxPC-3 and Capan-1 cells by stable transfection with human sst2 cDNA. In the absence of exogenous ligand, both BxPC-3 and Capan-1 cells expressing sst2 showed a significant reduction in cell growth. This inhibitory effect was blocked by treatment with antiserum to somatostatin. sst2-expressing cells produced somatostatin-like immunoreactivity that mainly corresponded to somatostatin 14, indicating the induction of a negative autocrine loop. In other respects, sst2 expression in Capan-1 cells induced a significant reduction of clonogenicity in soft agar. Moreover, a significantly reduced (Capan-1 cells) or suppressed (BxPC-3 cells) tumor growth in athymic nude mice was observed. The reversal of tumorigenicity induced by the restoration of sst2 expression suggests that the loss of sst2 contributes to the malignancy of human pancreatic cancers.


The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease.
The P2X7 receptor is a trimeric ATP-gated cation channel found predominantly, but not exclusively, on immune cells. P2X7 activation results in a number of downstream events, including the release of proinflammatory mediators and cell death and proliferation. As such, P2X7 plays important roles in various inflammatory, immune, neurologic and musculoskeletal disorders. This review focuses on the use of P2X7 antagonists in rodent models of neurologic disease and injury, inflammation, and musculoskeletal and other disorders. The cloning and characterization of human, rat, mouse, guinea pig, dog, and Rhesus macaque P2X7, as well as recent observations regarding the gating and permeability of P2X7, are discussed. Furthermore, this review discusses polymorphic and splice variants of P2X7, as well as the generation and use of P2X7 knockout mice. Recent evidence for emerging signaling pathways downstream of P2X7 activation and the growing list of negative and positive modulators of P2X7 activation and expression are also described. In addition, the use of P2X7 antagonists in numerous rodent models of disease is extensively summarized. Finally, the use of P2X7 antagonists in clinical trials in humans and future directions exploring P2X7 as a therapeutic target are described.


High-dose ketoconazole for treatment of fungal infections of the central nervous system.
Mortality and complication rates remain unacceptably high with conventional intravenous and intrathecal therapy for patients with coccidioidal meningitis and intracerebral fungal lesions. We studied the ventricular and lumbar cerebrospinal fluid penetration of ketoconazole and the responses to therapy in two patients receiving ketoconazole orally, 800 mg daily, and amphotericin B intraventricularly for meningeal and extrameningeal coccidioidomycosis. Five patients received only 1200 mg of ketoconazole: one had uncomplicated coccidioidal meningitis, three had obstructive hydrocephalus due to coccidioidal meningitis, and one had a histoplasmal brain abscess. Ketoconazole concentrations in ventricular and lumbar fluid ranged from 0.05 to 1.65 micrograms/mL 4 and 8 hours after the dose. The mean penetration of ketoconazole (+/- SD) was 1.9% +/- 0.8% for ventricular fluid and 5.4% +/- 2.6% for lumbar fluid. Ketoconazole concentrations in cerebrospinal fluid varied directly with those in serum and with cerebrospinal fluid protein content. The encouraging clinical responses, convenience, safety, and the consistent penetration of ketoconazole into obstructed and nonobstructed cerebrospinal fluid support the use of these regimens as alternatives to conventional therapy.


New monoclonal antibody, 1C5, reactive with human cervical adenocarcinoma of the uterus, with immunodiagnostic potential.
A murine monoclonal antibody, 1C5, was produced by fusion of spleen cells obtained from mice immunized with CAC-1, a human cell line of adenocarcinoma derived from uterine cervix, and NS/1 myeloma cells. 1C5 can be used for the staining of routine formalin-fixed and paraffin-embedded tissue sections. 1C5-defined antigen was found to have a molecular weight of 26,000. The 1C5-defined antigen was resistant to neuraminidase and trypsin treatment, but sensitive to periodate treatment, indicating that an epitope of the 1C5-defined antigen is a carbohydrate moiety. Immunohistochemical study using immunoperoxidase staining demonstrated that 1C5 reacted with 87% of adenocarcinomas of the uterine cervix, 39% of endometrial carcinomas of the uterus, 100% of ovarian mucinous cystadenocarcinomas, 43% of ovarian serous cystadenocarcinomas, 45% of adenocarcinomas of the colon, and 40% of gastric adenocarcinomas, thus showing the broad reactivity to adenocarcinoma cells of various origins. However, 1C5 did not show any reactivity to ectocervix epithelium, cervical intraepithelial neoplasia, or squamous cell carcinoma of the uterine cervix. In addition, adenocarcinoma of the uterine cervix exhibited strong cytoplasmic reactivity with 1C5, whereas endometrial carcinoma of the uterus showed the luminal reactivity. 1C5 also reacts with 95% ethanol-fixed malignant cells in cervical smears.


[Risk factors associated with the acquisition of multiresistant bacteria in a pediatric nursery]
OBJECTIVE: To identify the risk factors in patients who had a multiresistant bacteria during their staying in a Pediatric Intensive Care Unit and in a pediatric nursery of a tertiary teaching hospital.METHODS: Chart review of the patients who stayed in the units from January, 1995 to July, 1997 and had a multiresistant microorganism isolated (both infection and colonization). A case-control study was done using McNemar test for group comparison and using stepwise logistic regression to select independent risk factors. The following risk factors were tested: prior hospital staying, underlying disease, intensive care unit admission, surgical procedure, urinary catheter, central venous line, ventilator, prior antibiotic therapy and skin lesion.RESULTS: Among 52 patients, 66 multiresistant bacteria were identified (among them, 33 were gram-negative bacilli and 33 were methicillin-resistant S. aureus). The logistic regression analysis of the case-control study identified 2 risk factors: prior antibiotic therapy and skin lesion. A single risk factor was indicated for patients with gram-negative bacilli. Nevertheless, for patients with methicillin-resistant S. aureus, central venous lines and skin lesion were significant.CONCLUSION: Prior antibiotic therapy and skin lesion were the factors associated with the acquisition of multiresistant bacteria. Besides skin lesion, for oxacilin-resistant S. aureus colonized patients, central venous catheter use was a risk factor. The strategies employed to limit the spread of those bacteria in the hospital should consider these three factors.


[Nutrition management based on urine collection in patients under home care].
We calculate the salt intake, the protein intake and the % creatinine generation rate, the index for the muscle volume/exercise, based on the sodium, urea and creatinine level in the urine in patients under home care and retain the data in the database. To date, 45 patients under home care have been enrolled. The mean age is 70.9 years (+/-13.8, SD). The underlying disease treated under home care include malignant tumor in 23 patients (51.1%), cerebrovascular disorders in 11 patients (24.4%), neurological/muscular disorders in 6 patients (13.3%) and other diseases in 5 patients (11.1%). The analysis of the data obtained from the collected urine has revealed that the % creatinine generation rate was significantly low in the patients with neurological/muscular disorders and that the % creatinine generation rate, the protein intake and the salt intake were high in the patients under the central venous nutrition. The analysis has also revealed that the % creatinine generation rate and the protein intake were lower in the patients who are less independent in daily lives. These findings substantiate that the 24-hour urine collection is useful for the assessment of nutritional condition in patients under home care.


Mammary tumor induction loci in GR and DBAf mice contain one provirus of the mouse mammary tumor virus.
The mammary tumor induction genes Mtv-1 in mouse strain DBAf and Mtv-2 in strain GR control the complete expression of the endogenous mouse mammary tumor virus (MMTV). We have used a combination of genetic, biochemical and molecular biological methods to identify and correlate specific copies of the endogenous MMTV proviral genes with the biological properties of the tumor induction genes Mtv-1 and Mtv-2. These Mtv induction genes contain specific MMTV proviral information, as was concluded from restriction enzyme analysis and molecular hybridization of DNAs of congenic mouse strains and of progenitors of backcross populations. The congenic strains differed from the parental strains GR and 020 only in the Mtv-2 gene, one lacking the Mtv-2 gene (GR/Mtv-2-) and one having obtained this gene (020/Mtv-2+). The gain or loss coincided with two Eco RI cellular DNA fragments containing MMTV DNA information. Since Eco RI cuts the exogenous proviral variant of MMTV DNA once, we assume that these two cellular DNA fragments contain one MMTV provirus. The same cellular DNA fragments containing MMTV DNA information segregated together with MMTV expression in the offspring population of the backcross. In a similar backcross analysis of the induction gene Mtv-1 it was also demonstrated that the Mtv-1 gene comprises one MMTV provirus. These data indicate that Mtv induction genes contain specific but different MMTV proviral genes and that nly a limited number of the MMTV proviruses present in the cellular DNA is associated with the control of proviral expression.


Integrating community-based verbal autopsy into civil registration and vital statistics (CRVS): system-level considerations.
Reliable and representative cause of death (COD) statistics are essential to inform public health policy, respond to emerging health needs, and document progress towards Sustainable Development Goals. However, less than one-third of deaths worldwide are assigned a cause. Civil registration and vital statistics (CRVS) systems in low- and lower-middle-income countries are failing to provide timely, complete and accurate vital statistics, and it will still be some time before they can provide physician-certified COD for every death. Proposals: Verbal autopsy (VA) is a method to ascertain the probable COD and, although imperfect, it is the best alternative in the absence of medical certification. There is extensive experience with VA in research settings but only a few examples of its use on a large scale. Data collection using electronic questionnaires on mobile devices and computer algorithms to analyse responses and estimate probable COD have increased the potential for VA to be routinely applied in CRVS systems. However, a number of CRVS and health system integration issues should be considered in planning, piloting and implementing a system-wide intervention such as VA. These include addressing the multiplicity of stakeholders and sub-systems involved, integration with existing CRVS work processes and information flows, linking VA results to civil registration records, information technology requirements and data quality assurance. Integrating VA within CRVS systems is not simply a technical undertaking. It will have profound system-wide effects that should be carefully considered when planning for an effective implementation. This paper identifies and discusses the major system-level issues and emerging practices, provides a planning checklist of system-level considerations and proposes an overview for how VA can be integrated into routine CRVS systems.


American Academy of Pediatrics. Committee on Nutrition. Calcium requirements in infancy and childhood.
Various aspects of calcium metabolism and methods for estimating total body calcium content in man were reviewed. From the data available, it is possible to make an estimate of the retention of calcium that is needed to sustain normal growth in body composition. However, the dietary requirements for different periods of growth cannot be defined precisely. Dietary calcium needs are most critical during those periods of life when requirements are known to be high. The low-birth-weight infant, the lactating woman, and the adolescent boy all have requirements. Individuals whose milk intake must be restricted should receive advice on nonmilk foods that are high in calcium.


Preparation and analgesic activity of Eudragit RS100 microparticles containing diflunisal.
Two different techniques, the quasi-emulsion solvent diffusion method and spray drying that provide polar and nonpolar preparation environments, were used to prepare microspheres from Eudragit RS100 (RS) (acrylic/methacrylic copolymer) incorporating the nonsteroidal anti-inflammatory drug diflunisal. The effects of pH on the preparation medium and drug/polymer ratio on production yield and drug incorporation, as well as on the in vitro drug release at pH 1.2 and 6.8 from tabletted microparticles, were evaluated. The drug-polymer interactions and the effect of diflunisal incorporation in the polymer matrix on drug crystallinity have been evaluated by using differential scanning calorimetry, IR and ultraviolet spectroscopy, x-ray diffraction, and microscopy analysis. A preliminary biological assay confirmed that diflunisal maintains its analgesic activity after intraperitoneal administration to rats.


Nodules on the Anterior Neck Following Poly-L-lactic Acid Injection.
Poly-L-lactic acid (PLLA) is a synthetic biologic polymer that is suspended in solution and can be injected for soft-tissue augmentation. The most common adverse events generally are transient in nature, such as swelling, tenderness, pain, bruising, and bleeding. Persistent adverse events of PLLA primarily are papule and nodule formation. Injecting PLLA into the anterior neck is an off-label procedure and may cause a higher incidence of nodule formation.


Molecular markers reveal narrow genetic base and culturing-associated genetic drift in Teretrius nigrescens Lewis populations released for the biological control of the larger grain borer in Africa.
In biological control, successful establishment of a natural enemy species depends on its adaptability in the introduced range including its ability to re-establish desired ecological interactions with the pest. These are affected by genetic parameters hitherto largely unresolved in biological control. The larger grain borer (LGB), Prostephanus truncatus, an invasive species from meso-America, is the most important post-harvest pest of maize in Africa. We studied the genetic structure of Teretrius nigrescens, a predatory beetle previously released for the control of the pest in Africa, to test the hypothesis that establishment patterns were a result of ecotype-environment mismatch and to follow up on our earlier reports of distinct lineages of the predator. We studied 13 populations of T. nigrescens, using 16 polymorphic microsatellite markers. Five genetic populations with a hierarchical structure and significant isolation by distance were detected. The most diverse population was found in southern Mexico, consistent with earlier lineage coexistence observations. Populations introduced to Africa maintained genetic similarity to local geographic populations of their area of origin. The more successful Benin releases were also more genetically diverse. Loss of rare alleles and a higher frequency of existing private alleles in some populations indicated population expansions following bottleneck events. Sustainable biological control should accommodate pest and natural enemy species, and monitor genetic changes associated with introduction and release.


[Percutaneous lumbar facet denervation. Indications and significance in chronic backache].
The lumber facet joints have been established as a source of low back pain which may radiate to the leg. Because there are no reliable clinical signs which confirm the diagnosis injections of an anaesthetic agent into the joints are necessary. Therapeutically a percutaneous radiofrequency destruction of the medial branches of lumbar dorsal rami may relieve such pain. Success rate, however, is depending on a careful selection of patients.


Socio-ecological predictors of mental health outcomes among healthcare workers during the COVID-19 pandemic in the United States.
Healthcare workers are at increased risk of adverse mental health outcomes during the COVID-19 pandemic. Studies are warranted that examine socio-ecological factors associated with these outcomes to inform interventions that support healthcare workers during future disease outbreaks. We conducted an online cross-sectional study of healthcare workers during May 2020 to assess the socio-ecological predictors of mental health outcomes during the COVID-19 pandemic. We assessed factors at four socio-ecological levels: individual (e.g., gender), interpersonal (e.g., social support), institutional (e.g., personal protective equipment availability), and community (e.g., healthcare worker stigma). The Personal Health Questionnaire-9, Generalized Anxiety Disorder-7, Primary Care Post-Traumatic Stress Disorder, and Alcohol Use Disorders Identification Test-Concise scales assessed probable major depression (MD), generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD), respectively. Multivariable logistic regression models were used to assess unadjusted and adjusted associations between socio-ecological factors and mental health outcomes. Of the 1,092 participants, 72.0% were female, 51.9% were frontline workers, and the mean age was 40.4 years (standard deviation = 11.5). Based on cut-off scores, 13.9%, 15.6%, 22.8%, and 42.8% had probable MD, GAD, PTSD, and AUD, respectively. In the multivariable adjusted models, needing more social support was associated with significantly higher odds of probable MD, GAD, PTSD, and AUD. The significance of other factors varied across the outcomes. For example, at the individual level, female gender was associated with probable PTSD. At the institutional level, lower team cohesion was associated with probable PTSD, and difficulty following hospital policies with probable MD. At the community level, higher healthcare worker stigma was associated with probable PTSD and AUD, decreased satisfaction with the national government response with probable GAD, and higher media exposure with probable GAD and PTSD. These findings can inform targeted interventions that promote healthcare workers' psychological resilience during disease outbreaks.


Comparison of immunocytologic localization of insulin-like growth factor binding protein-4 in normal and polycystic ovary syndrome human ovaries.
The cytologic localization and cellular levels of insulin-like growth factor binding protein-4 (IGFBP-4) in follicular and stromal compartments of normal and polycystic ovary syndrome (PCOS) ovaries during follicular growth and regression were investigated by the avidin/biotin immunoperoxidase method with a polyclonal antibody to human IGFBP-4, and a comparative assessment of IGFBP-4 expression in normal and PCOS ovaries was provided. In normal human ovaries, IGFBP-4 was immunolocalized to the oocyte throughout follicular growth, while the surrounding granulosa and theca cells were negligible for IGFBP-4 immunostaining in primordial, preantral and antral follicles. IGFBP-4 immunostaining became apparent, however, in the lutein cells of corpora lutea and the granulosa and theca cells of atretic follicles. In PCOS ovaries, prominent immunostaining for IGFBP-4 was apparent not only in the oocyte, but also in the surrounding granulosa cells in preantral follicles. In antral follicles from PCOS women without hyperinsulinemia, IGFBP-4 immunostaining was more prominent in the granulosa cells than the theca cells, whereas in antral follicles from PCOS women with hyperinsulinemia IGFBP-4 immunostaining was more prominent in the theca cells than the granulosa cells. Furthermore, in atretic follicles within PCOS ovaries IGFBP-4 immunostaining was prominent in the theca cells, regardless of the association of hyperinsulinemia. These results demonstrate for the first time that there is a great difference in cellular expression of IGFBP-4 between normal and PCOS human ovaries. In light of the high affinity of IGFBP-4 for IGF-1, the abundant expression of IGFBP-4 in granulosa and theca cells of preantral and antral follicles of PCOS ovaries may lead to decreases in the bioavailability of IGF-I in those follicles. The decrease in IGF-I-mediated stimulation of gonadotropin actions on granulosa and theca cells in preantral and antral follicles may impair the induction of aromatase activity, causing an androgenic microenvironment which is characteristic of atretic follicles and PCOS follicles.


[Prophylaxis of laryngeal nerve injuries in thyroid surgery].
The problem of injury of recurrent laryngeal nerve (RLN) is topical despite large usage and detailed development of surgical treatment of thyroid gland (TG). The results of 3603 operations on TG were analyzed. The 1st group consisted of 560 patients operated in 1981-1988 by O.V. Nikolaev's method without dissection of RLN, the 2nd group--3043 patients operated in 1989-1998 with intraoperative imaging of RLN on the one or two sides. In the 1st group the injury of RLN was revealed in 39 (7.0%) patients, in 4 of them--bilateral. In 2nd group it was revealed in 10 (0.3%) patients. Present data lead to a conclusion that intraoperative imaging of RLN in operation on the thyroid gland is necessary.


Spatiotemporal changes in the genetic diversity in French bloom-forming populations of the toxic cyanobacterium, Microcystis aeruginosa.
Microcystis aeruginosa is a toxic cyanobacterium, which is able to bloom in a wide range of freshwater ecosystems. By sequencing the Internal Transcribed Spacer (ITS) of the ribosomal operon, we compared the genetic composition of several French bloom-forming M. aeruginosa populations from two reservoirs located on the Loire River, at two sampling points located between these reservoirs, and finally in two ponds closely linked to this river. No significant difference was found in the genetic diversity of the six Microcystis populations but we evidenced a strong genetic differentiation between most of these populations. Indeed, the Microcystis population in the Grangent reservoir was genetically differentiated from the other three populations sampled further downstream, implying that no massive transfer of population occurs from this reservoir to downstream segments. We also found genetic differentiation between the populations from the two ponds, and between these populations and those from the Loire River. On the other hand, the same dominant genotype was found in the populations sampled both in the river and in the Villerest reservoir, suggesting the selection of a distinct genotype adapted to river conditions and also an accumulation of this genotype in the downstream reservoir. Finally, by comparing our ITS sequences with those available in the GenBank, no biogeographical differentiation could be detected at a global scale, suggesting that most of the Microcystis genotypes seem to be ubiquitous.


Diffuse Dermal Angiomatosis of the Breast With an Apparent Etiology of Underlying Calcified Thrombosed Artery With Adjacent Fat Necrosis.
In this report, the authors present a case of diffuse dermal angiomatosis (DDA) with an underlying mass lesion of the breast, which proved to be a large calcified, thrombosed artery with adjacent fat necrosis. Histologically, DDA consists of hyperplastic vessels, which diffusely infiltrate the papillary and reticular dermis forming small vascular lumina. The condition is associated with various underlying conditions, many of which result in local tissue ischemia. In the past, DDA was most commonly reported on the lower extremities; however, it seems that this entity is more common on the breast than previously recognized. Various treatments have proven beneficial, including revascularization, oral corticosteroids, smoking cessation, and isotretinoin. In this case, our patient benefited from primary excision of the affected area.


Luminescent Solar Concentrators Based on Renewable Polyester Matrices.
This study reports for the first time the use of bio-based alternatives for PMMA as host matrix for luminescent solar concentrators (LSCs). Notably, two types of renewable polyesters were synthesized in varying molar ratios via a two-step melt-polycondensation reaction with dibutyl tin oxide as catalyst. The first is a homopolymer of diethyl 2,3:4,5-di-O-methylene galactarate (GxMe) and isosorbide (IGPn), and the second is a random copolymer of GxMe with 1,3-propanediol and dimethyl terephthalate (GTPn). The two polyesters were found to be optically transparent, totally amorphous with a Tg higher than 45 °C and temperature resistance comparable to PMMA. Lumogen Red (LR) and an aggregation-induced emission (AIE) fluorophore, TPETPAFN, were utilized as fluorophores and the derived thin polymer films (25 μm) were found highly homogeneous, especially for those prepared from GTPn, possibly due to the presence of compatibilizing terephthalate units in the matrix composition and the higher molecular weight. The spectroscopic characterization and the optical efficiency determination (ηopt ) evidenced LSCs performances similar or superior to those collected from LR/PMMA thin films. Noteworthy, ηopt of 7.7 % and 7.1 % were recorded for the GTPn-based matrix containing LR and TPETPAFN, respectively, thus definitely supporting the bio-based polyesters as renewable and highly fluorophore-compatible matrices for high-performance LSCs.


Association of dietary habits with levels of physical activity and screen time among adolescents living in Saudi Arabia.
Understanding the inter-relationships between lifestyle factors in youth is important with respect to the development of effective promotional programmes for healthy eating and active living. The present study aimed to explore the associations of dietary habits (DH) with physical activity (PA) and screen time (ST) among Saudi adolescents aged between 15 and 19 years of age relative to gender. Data were obtained from the Arab Teens Lifestyle Study, a school-based multicentre lifestyle study conducted in 2009/2010 in three major cities in Saudi Arabia. A multistage stratified cluster random sampling technique was used. The number of participants with complete data for DH and PA was 2886 and the respective number for DH and ST was 2822. Assessment included weight, height, body mass index, total daily ST (television viewing, video/computer games and Internet use), PA and DH using self-reported questionnaires. Females were significantly more sedentary and less active than males (P < 0.001). Two-way analysis of covariance, controlling for age, showed significant (P < 0.05) gender by PA and gender by ST interactions for several DH. Logistic regression analyses revealed significant associations of higher PA with a higher consumption of fruit, vegetables, milk, French fries/potato chips and energy drinks, whereas higher ST was significantly associated with a higher consumption of sugar-sweetened drinks, fast foods, cake/doughnuts and energy drinks. Healthful dietary habits were associated mostly with PA, whereas sedentary behaviours, independent of PA, negatively impacted upon eating behaviours. The low PA levels and high sedentary levels of Saudi females represent a great concern. The results reported in the present study have important implications for both youth public health policies and intervention programmes.


Characterizing Different Modes of Interplay Between Rap1 and H3 Using Inducible H3-depletion Yeast.
Histones and transcription factors (TFs) are two important DNA-binding proteins that interact, compete, and together regulate transcriptional processes in response to diverse internal and external stimuli. Condition-specific depletion of histones in Saccharomyces cerevisiae using a galactose-inducible H3 promoter provides a suitable framework for examining transcriptional alteration resulting from reduced nucleosome content. However, the effect on DNA binding activities of TFs is yet to be fully explored. In this work, we combine ChIP-seq of H3 with RNA-seq to elucidate the genome-scale relationships between H3 occupancy patterns and transcriptional dynamics before and after global H3 depletion. ChIP-seq of Rap1 is also conducted in the H3-depletion and control treatments, to investigate the interplay between this master regulator TF and nucleosomal H3, and to explore the impact on diverse transcriptional responses of different groups of target genes and functions. Ultimately, we propose a working model and testable hypotheses regarding the impact of global and local H3 depletion on transcriptional changes. We also demonstrate different potential modes of interaction between Rap1 and H3, which sheds light on the potential multifunctional regulatory capabilities of Rap1 and potentially other pioneer factors.


Catecholamine content of cerebral tissue after occlusion or manipulation of middle cerebral artery in cats.
The authors determined by fluorimetry the norepinephrine-epinephrine content (NE-E) of cerebral tissue from 38 cats, to ascertain whether constriction of hypersensitive arterial vessels by vasoactive agents in ischemic cerebral tissue could cause extension of cerebral infarcts and worsening of neurological deficits. Twenty-three cats had the left middle cerebral artery (MCA) occluded transorbitally, and 10 cats had sham operations. Five cats had only the surgical procedures necessary for obtaining tissue; mean NE-E content was 0.30 mug/gm (SD=0.041). For the other 33 cats, including those with sham operations, values were variable, ranging from 0.07 to 0.60 mug/gm. Low values usually were obtained for ischemic hemispheres 24 hours and 7 days after MCA occlusion, but at other times values could be high or low on either side. Many factors unrelated to tissue damage, including arterial manipulation, influence the catecholamine content of cerebral tissue.


GENDERED CHALLENGE, GENDERED RESPONSE: Confronting the Ideal Worker Norm in a White-Collar Organization.
This article integrates research on gendered organizations and the work-family interface to investigate an innovative workplace initiative, the Results-Only Work Environment (ROWE), implemented in the corporate headquarters of Best Buy, Inc. While flexible work policies common in other organizations "accommodate" individuals, this initiative attempts a broader and deeper critique of the organizational culture. We address two research questions: How does this initiative attempt to change the masculinized ideal worker norm? And what do women's and men's responses reveal about the persistent ways that gender structures work and family life? Data demonstrate the ideal worker norm is pervasive and powerful, even as employees begin critically examining expectations regarding work time that have historically privileged men. Employees' responses to ROWE are also gendered. Women (especially mothers) are more enthusiastic, while men are more cautious. Ambivalence about and resistance to change is expressed in different ways depending on gender and occupational status.


Prescriptions for dietary sodium in patients with chronic kidney disease: how will this shake out?
Patients with chronic kidney disease (CKD) are at risk of exhibiting expanded extracellular volume, and low-sodium diets are often prescribed to limit clinical complications from this condition. Fan et al. performed a post hoc study from the database of the Modification of Diet in Renal Disease Study. Their article, as well as other recent observations, suggests that a low-sodium diet may not be as beneficial as previously thought in all CKD patients.