Red light-transmittance bagging promotes carotenoid accumulation of grapefruit during ripening.
Light, a crucial environmental signal, is involved in the regulation of secondary metabolites. To understand the mechanism by which light influences carotenoid metabolism, grapefruits were bagged with four types of light-transmitting bags that altered the transmission of solar light. We show that light-transmitting bagging induced changes in carotenoid metabolism during fruit ripening. Compared with natural light, red light (RL)-transmittance treatment significantly increases the total carotenoid content by 62%. Based on weighted gene co-expression network analysis (WGCNA), 'blue' and 'turquoise' modules are remarkably associated with carotenoid metabolism under different light treatment (p < 0.05). Transcriptome analysis identifies transcription factors (TFs) bHLH128, NAC2-like/21/72, MYB-like, AGL11/AGL61, ERF023/062, WRKY20, SBPlike-7/13 as being involved in the regulation of carotenoid metabolism in response to RL. Under RL treatment, these TFs regulate the accumulation of carotenoids by directly modulating the expression of carotenogenic genes, including GGPPS2, PDS, Z-ISO, ZDS2/7, CRTISO3, CYP97A, CHYB, ZEP2, CCD1-2. Based on these results, a network of the regulation of carotenoid metabolism by light in citrus fruits is preliminarily proposed. These results show that RL treatments have great potential to improve coloration and nutritional quality of citrus fruits.


Cost analysis of transmural home care for terminal cancer patients.
The economic implications of home care service programmes for oncology patients remain unclear. This quasi-experimental study investigated the costs of a transmural home care programme for terminal cancer patients and compared them to those of the standard care available. The programme intended to optimize communication, cooperation and coordination between the intra- and extra- mural health care organizations (transmural care). Complete sets of data could be retrieved for 57 of the 79 patients in the intervention group, and for 29 of the 37 patients in the control group. Comparison of the intervention and control group revealed significantly lower pharmaceutical and rehospitalization costs in the intervention group, whilst community nursing and home help costs were significantly higher. However, no significant difference could be found for total health care costs between the groups. In view of this, and that the programme has proved to have significantly positive effects on both the patient's and direct caregiver's quality of life, the installation of such programmes in every hospital with a multidisciplinary oncology unit is recommended.


Preserved thrombin-inducible platelet activation in thienopyridine-treated patients.
Abundant thrombin generation may be a major reason for subsequent thromboembolic events in patients with cardiovascular disease receiving dual antiplatelet therapy. We therefore investigated the susceptibility of thienopyridine responders and nonresponders to thrombin receptor-activating peptide (TRAP)-6- and adenosine diphosphate (ADP)-inducible platelet activation. Response to clopidogrel or prasugrel was determined by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and multiple electrode aggregometry (MEA) in 317 patients undergoing angioplasty and stenting for cardiovascular disease. Baseline, TRAP-6-, and ADP-inducible P-selectin expression, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and monocyte-platelet aggregate (MPA) formation were measured as sensitive parameters of platelet activation. In patients with high on-treatment residual ADP-inducible platelet reactivity (HRPR), baseline P-selectin expression, GPIIb/IIIa and MPA formation were similar to those in patients without HRPR (all P > 0.05). After platelet activation with TRAP-6 or ADP, patients with HRPR by both assays exhibited significantly higher levels of P-selectin expression, GPIIb/IIIa and MPA formation than patients with an adequate thienopyridine-mediated platelet inhibition (all P ≤ 0.02). However, high levels of TRAP-6-inducible P-selectin, GPIIb/IIIa and MPA formation also occurred in 20.4%, 19.1% and 20.1% of the good responders by the VASP assay, and in 19.6%, 16.6% and 20.6% of the good responders by MEA, respectively. Thienopyridine nonresponders are more susceptible to thrombin- and ADP-inducible platelet activation than patients with good platelet inhibition. However, even patients with adequate thienopyridine-mediated platelet inhibition often show a preserved responsiveness to thrombin. These patients may benefit from additional thrombin receptor blockage or inhibition of thrombin generation.


Studies on the release of drugs from O/W emulsion ointments using the mathematical interpretations. Part 3: Kinetic approach.
Kinetic models describing the drug release process from oil-in-water (O/W) emulsions through artificial membranes have been proposed. It has been shown that the kinetic approach appears to be useful in analysis of this problem.


Role of extracellular matrix in the regeneration of a pacinian corpuscle.
The pacinian corpuscle is composed of an inner and an outer core or bulb. The former is formed by tightly packed and multi-layered thin cellular processes (lamellae) of lamellar cells which surround a centrally located axon terminal, and the latter, also called the capsule, is made up of very loosely piled layers of thin cells which encircle the inner core. Lamellar cells of the inner core are considered to be specialized Schwann cells, and the outer core cells are modified perineurial cells. In the present study, the matrix filling the extracellular spaces of the inner core consisted of basal lamina-like amorphous materials, sparce fine collagen fibrils, and the ground substance embedding these structural components. No definite basal laminae were found on the inner core lamellae except on the peripherally located ones which had distinct basal laminae. Outer-core cells were invested along the entire contour by distinct basal laminae. The interspace between the inner and outer cores was a continuation of the nerve endoneurium. The purpose of this investigation was to determine whether the extracellular matrix of the pacinian corpuscle, especially that of the inner core, has the ability to cause corpuscle regeneration, i.e. to make the regenerating axons and Schwann cells differentiate into corpuscular axon terminals and inner core cells, respectively. Pacinian corpuscles in the periosteum at the distal end of the fibula of mice were repeatedly frozen (3-5 times) in situ with forceps cooled with liquid nitrogen. Within 2-3 days, all the cellular constituents of the corpuscle had degraded, while the extracellular matrices of the inner and outer cores apparently remained undamaged. After 5-7 days, regenerating axons and accompanying immature Schwann cells entered these extracellular matrices of the inner cores. A remarkable finding was that these immature Schwann cells were detached from the axon, and sent thin cellular processes around the axon in a characteristic fashion, basically forming the same pattern as lamellae in a normal corpuscle. The regeneration of the inner core was completed by about 40 days after the freezing treatment. In the outer core, perineurial cells proliferated and extended through the basal lamina tubes of the old cells, becoming new outer core cells. These findings indicate that the extracellular matrix of the pacinian corpuscle has a specific property to cause the regeneration of the corpuscle.


2-[3-(4-Chloro-phen-yl)-5-(4-fluoro-phen-yl)-4,5-di-hydro-1H-pyrazol-1-yl]-5-[(4-fluoro-phen-yl)diazen-yl]-4-methyl-thia-zole.
The mol-ecule of the title compound, C25H18ClF2N5S, comprises almost co-planar fluoro-phenyl, methyl-thia-zolyl, pyrazolyl and chloro-phenyl rings with the second fluoro-phenyl ring almost perpendicular to this plane. One fluoro-phenyl group is disordered over two components of occupancy ratio 0.767 (10):0.233 (10) related by a 24.2 (8)° twist. In the crystal, two mol-ecules related by inversion symmetry are linked by a pair of C-H⋯F contacts in an R(8)2 2 geometry.


Spontaneous and X-ray-induced deletion mutations in a LacZ plasmid-based transgenic mouse model.
Transgenic mouse mutation models carrying bacterial marker genes in bacteriophage lambda shuttle vectors have been applied to study spontaneous or induced mutations in vivo. However, due to the nature of the shuttle vector these models are insensitive to large deletions. Clastogenic agents, which predominantly induce large deletions, were therefore found to yield very low responses in these assays. Here we report the use of LacZ plasmid-based transgenic mice, allowing the detection of a broad spectrum of mutations. Treatment of mice with X-rays (5 x 50 rads) resulted in induction of up to about 5-fold higher mutation frequencies in lung, spleen and liver. Analysis of spontaneous and induced mutant LacZ genes indicated that at least 40-50% of all mutations were caused by deletions. The possibility of detecting a broad spectrum of mutations with this system suggests that the LacZ plasmid-based transgenic mouse may be the mammalian model of choice for studying spontaneous and induced mutations in vivo.


High expression of protein phosphatase 4 is associated with the aggressive malignant behavior of colorectal carcinoma.
Recent evidence suggests an important role of protein phosphatase 4 (PP4C) in the progression of several cancers, including breast cancer, lung cancer and pancreatic ductal adenocarcinoma. However, the contribution of PP4C to colorectal carcinoma (CRC) remains elusive. The expression of PP4C in CRC tissues compared with matched non-tumor tissues and CRC cells was detected using quantitative RT-PCR, immunohistochemistry and western blotting assays. Through univariate and Kaplan-Meier analysis, we correlated the PP4C expression with clinicopathological features and patient survival. A series of experiments, including cell proliferation, lentiviral infection, cell invasion and MMP gelatinase activity assays, were performed to investigate the underlying mechanisms. Through further experiments, tumor growth and metastasis were evaluated in vivo using a xenogenous subcutaneously implant model and a tail vein metastasis model. In the present study, we found that PP4C expression is frequently increased in human CRC and that the upregulation of PP4C correlates with a more invasive tumor phenotype and poor prognosis. The ectopic expression of PP4C promoted CRC cell proliferation, migration and invasion in vitro and tumor growth and lung metastasis in vivo. Silencing the expression of PP4C resulted in the inhibition of cell proliferation and invasion. Further investigations showed that phosphorylated Akt (p-AKT) is required for the PP4C-mediated upregulation of MMP-2 and MMP-9, which promotes cell invasion. Our data suggested a potential role of PP4C in tumor progression and provided novel insights into the mechanism of how this factor positively regulated cell proliferation and invasion in CRC cells.


Fuel utilization following injury: relationship to hormonal environment.
To investigate the relationship between fuel metabolism, insulin resistance, and hormonal environment, insulin clamp studies and indirect calorimetry were performed in nine normal volunteers after they had received a continuous infusion of the three "stress" hormones, cortisol, glucagon, and epinephrine, for 3 days. Studies after a 3-day infusion of saline served as control. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild to moderate injury. In this altered environment, insulin failed to suppress endogenous glucose production and resulted in reduced glucose disposal. The glucose that was taken up was oxidized, not stored. Furthermore, insulin failed to suppress fat oxidation. The altered hormonal environment achieved by triple hormonal infusion, simulated many of the features of post-traumatic fuel metabolism.


Soluble epoxide hydrolase inhibitors with carboranes as non-natural 3-D pharmacophores.
In the present article we describe the creation of a small carboranylcarboxamide compound library followed by a screening campaign at the soluble epoxide hydrolase (sEH). We identified meta-carboranyl alkylamides, -anilides, and -benzylamides as potent sEH inhibitors. Furthermore, we optimized the scaffolds and we derived structure-activity relationships. The most potent benzylamide 33 (MS1) was similar to a previously reported adamantane derivative and gave an IC50 value of 0.07 μM for meta- and 0.08 μM for para-carborane at isolated sEH. The ortho-derivative suffered deboronation. The results underline the potential of carboranes as non-natural 3-D pharmacophores to extend the chemical space in drug discovery.


Increased Efficacy of Zinc Complexes With Picolinic and Aspartic Acids Against Herpes Simplex Virus (HSV) Infection When Combined With the Pavine Alkaloid (-)-Thalimonine.
Complexes of zinc with picolinic and aspartic acids inhibit key steps of HSV-1 replication affecting different virus-specific targets. As was recently demonstrated by us, the pavine alkaloid (-)-thalimonine irreversibly inhibits HSV-1 infection in cultured cells. The aim of the present study was the evaluation of the combined effect of zinc complexes and (-)-thalimonine on uninfected and HSV-1 infected cells. The data obtained have shown that zinc complexes and the alkaloid exert decreased cytotoxicity (antagonistic effect) and significantly increased anti-HSV-1 activity (synergistic effect) when applied in dual chess-board combinations as compared to the individual effects of compounds tested. These combinations are also effective against the infection caused by a resistant to acyclovir (ACV) HSV-1 mutant and the effect has been recognised as synergistic.


A patient with severe congenital neutropenia harbors a missense ELANE mutation due to paternal germline mosaicism.
Clinical and genetic characteristics of ELANE mutation of a 3-year-old male who had a severe congenital neutropenia (SCN) were examined. We then investigated whether CRISPR/Cas9-mediated gene editing could correct the mutation. The proband underwent extensive clinical assessments, such as exome sequencing and bioinformatics analysis, so that pathogenic genes could be identified. Sanger sequencing was also utilized for confirmation. The cell line, 293-ELANE, harboring ELANE mutation was generated, and the mutation was then corrected by CRISPR/Cas9-mediated homology-directed repair (HDR). The ELANE gene test in the proband unveiled a heterozygous de novo missense mutation: c. 248T > A (p.V83D), which was not detected in his asymptomatic parents who had provided peripheral blood samples. We found that 46.01% of his father's sperm cells had the same mutation. These results demonstrate that the proband inherited the ELANE mutation from his father, who had an average neutrophil count but had a germline mosaicism. The highest repair efficiency of CRISPR/Cas9-mediated HDR for 293-ELANE is 4.43%. We identified a missense mutation (p.V83D) in ELANE that causes SCN. This is the first report on paternal semen mosaicism of an ELANE mutation. Our study paves the way for preimplantation genetic diagnosis (PGD) based on ELANE mutation prevention and clinical treatment of congenital disabilities.


Basic Amino Acids Within the Juxtamembrane Domain of the Epidermal Growth Factor Receptor Regulate Receptor Dimerization and Auto-phosphorylation.
Epidermal growth factor receptor (EGFR) dysregulation is observed in many human cancers and is both a cause of oncogenesis and a target for chemotherapy. We previously showed that partial charge neutralization of the juxtamembrane (JX) region of EGFR via the EGFR R1-6 mutant construct induces constitutive receptor activation and transformation of NIH 3T3 cells, both from the plasma membrane and from the ER when combined with the ER-retaining L417H mutation (Bryant et al. in J Biol Chem 288:34930-34942, 2013). Here, we use chemical crosslinking and immunoblotting to show that these mutant constructs form constitutive, phosphorylated dimers in both the plasma membrane and the ER. Furthermore, we combine this electrostatic perturbation with conformationally-restricted receptor mutants to provide evidence that activation of EGFR R1-6 dimers requires functional coupling both between the EGFR extracellular dimerization arms and between intracellular tyrosine kinase domains. These findings provide evidence that the electrostatic charge of the JX region normally serves as a negative regulator of functional dimerization of EGFR.


Prophylactic oophorectomy in colorectal carcinoma.
It is a well established fact that women with recurrent colorectal carcinoma have a high frequency of ovarian metastases. This study was undertaken to see if microscopic metastases could be found in serial sections of ovaries removed at the time of primary operation. Of 58 patients, 4 had microscopic metastases and an additional 2 patients had macroscopic metastases. This finding, plus the risk of the development of a primary ovarian carcinoma, favors prophylactic oophorectomy in women with colorectal carcinoma.


Advances in autophagy modulation of natural products in cervical cancer.
Natural products play a critical role in drug development and is emerging as a potential source of biologically active metabolites for therapeutic intervention, especially in cancer therapy. In recent years, there is increasing evidence that many natural products may modulate autophagy through various signaling pathways in cervical cancer. Understanding the mechanisms of these natural products helps to develop medications for cervical cancer treatments. In recent years, there is increasing evidence that many natural products may modulate autophagy through various signaling pathways in cervical cancer. In this review, we briefly introduce autophagy and systematically describe several classes of natural products implicated in autophagy modulation in cervical cancer, hoping to provide valuable information for the development of cervical cancer treatments based on autophagy. We searched for studies on natural products and autophagy in cervical cancer on the online database and summarized the relationship between natural products and autophagy modulation in cervical cancer. Autophagy is a lysosome-mediated catabolic process in eukaryotic cells that plays an important role in a variety of physiological and pathological processes, including cervical cancer. Abnormal expression of cellular autophagy and autophagy-related proteins has been implicated in cervical carcinogenesis, and human papillomavirus infection can affect autophagic activity. Flavonoids, alkaloids, polyphenols, terpenoids, quinones, and other compounds are important sources of natural products that act as anticancer agents. In cervical cancer, natural products exert the anticancer function mainly through the induction of protective autophagy. The regulation of cervical cancer autophagy by natural products has significant advantages in inducing apoptosis, inhibiting proliferation, and reducing drug resistance in cervical cancer.


An algorithm to identify pregnancies in BIFAP Primary Care database in Spain: Results from a cohort of 155 419 pregnancies.
There has been a notable progress on the development of methods for identification of pregnancies using primary care databases. We aimed to evaluate the prescription of medications during pregnancy applying a novel algorithm. We identified pregnancies in women aged 15 to 49 years registered in the Database for Pharmacoepidemiological Research in Primary Care (BIFAP) between 2002 and 2015. The algorithm applied sequential cycles that searched in hierarchical order for indicators of conception, delivery or pregnancy loss, and other codes suggestive of pregnancy. Length of pregnancy was assessed by searching for last menstrual period (LMP) date, gestational age, and outcomes of pregnancy. Prescription of specific drugs during the pre-pregnancy period and first trimester and time trends during pregnancy were evaluated. We identified a total of 155 419 pregnancies during the study period (77.5% completed pregnancies, 21.5% pregnancies losses, 0.8% ectopic pregnancies, and 0.2% stillbirths). Excluding vitamins and supplements, 43.8% of women received at least one prescription during the pre-pregnancy period and 68.4% during the first trimester. During the first trimester, the most commonly drugs prescribed were analgesics (16.3%) followed by antibiotics (11.8%). From 2002/2003 to 2014/2015, there was an increase of prescriptions for thyroid hormones (1.0% vs 4.7%), H2 blockers (1.0% vs 2.2%), and PPIs (1.4% vs 2.2%). While antidepressants (2.0% vs 1.5%) and benzodiazepines (3.1% vs 2.4%) decreased in the last period. Having in mind the challenges of identifying pregnancies in health care databases, this study demonstrates the usefulness of BIFAP database for studies on drug utilization during pregnancy.


Non-HFE hepatic iron overload.
Numerous clinical entities have now been identified to cause pathologic iron accumulation in the liver. Some are well described and have a verified hereditary basis; in others the genetic basis is still speculative, while in several cases nongenetic iron-loading factors are apparent. The non- HFE hemochromatosis syndromes identifies a subgroup of hereditary iron loading disorders that share with classic HFE-hemochromatosis, the autosomal recessive trait, the pathogenic basis (i.e., lack of hepcidin synthesis or activity), and key clinical features. Yet, they are caused by pathogenic mutations in other genes, such as transferrin receptor 2 ( TFR2), hepcidin ( HAMP), hemojuvelin ( HJV) , and ferroportin ( FPN), and, unlike HFE-hemochromatosis, are not restricted to Caucasians. Ferroportin disease, the most common non- HFE hereditary iron-loading disorder, is caused by a loss of iron export function of FPN resulting in early and preferential iron accumulation in Kupffer cells and macrophages with high ferritin levels and low-to-normal transferrin saturation. This autosomal dominant disorder has milder expressivity than hemochromatosis. Other much rarer genetic disorders are associated with hepatic iron load, but the clinical picture is usually dominated by symptoms and signs due to failure of other organs (e.g., anemia in atransferrinemia or neurologic defects in aceruloplasminemia). Finally, in the context of various necro-inflammatory or disease processes (i.e., chronic viral or metabolic liver diseases), regional or local iron accumulation may occur that aggravates the clinical course of the underlying disease or limits efficacy of therapy.


Cutting balloon: review on principles and background of use in peripheral arteries.
This review describes peripheral use of cutting balloon (CB) angioplasty (CBA), its characteristics, and its distinction from conventional BA and describes the experimental and clinical background of its current use in peripheral arteries.


An iterative approach to class II predictions.
An iterative approach to resolving protein-peptide binding motifs is appropriate when the length of the binding protein is variable and a variety of amino acid residues may successfully occupy multiple positions. This chapter describes an iterative algorithm that first aligns binding peptides of variable lengths and then extracts a quantitative motif from the resulting alignment. Numerous examples are presented to illustrate the utility of the iterative process.


Quantitative prediction of fetal plasma concentration of fluvoxamine during dosage-tapering to the mother.
Although selective serotonin reuptake inhibitors have been used during pregnancy for the treatment of depression and anxiety disorders, the fetal plasma concentration profiles of them remained unclear. Therefore, the aim of this study was to develop a pharmacokinetic model to estimate fetal plasma concentration profiles of fluvoxamine, and to clarify the differences with those of paroxetine. Perfusion studies using human placentae obtained from full-term pregnant women were conducted to estimate transplacental pharmacokinetic parameters for fluvoxamine. The characteristics of placental permeability were compared with those of paroxetine in our previous report. Using a developed model and these parameters, fetal plasma concentration profiles of fluvoxamine administered to mothers were simulated. The results of perfusion studies and transplacental transfer kinetic parameters indicated that fluvoxamine is less efficiently distributed to placental tissue than paroxetine. The model predicted a maternal-fetal plasma concentration ratio of 0.376 after repeated maternal administration of fluvoxamine, similar to the ratio for paroxetine. However, if the mother ceased taking drug, the model predicted a half-life of fluvoxamine in fetal plasma of 35 h, which is longer than that of paroxetine (10 h). We used the model to evaluate a proposed taper regimen for full-term pregnant women taking fluvoxamine that would minimize the risk of neonatal withdrawal syndrome. The obtained parameters and developed model enabled us to predict the fetal plasma concentration profiles of fluvoxamine. The risk of neonatal withdrawal syndrome due to abrupt discontinuation may be less with fluvoxamine than with paroxetine.


Development of highly inhomogeneous temperature profile within electrically heated alkali silicate glasses.
According to Joule's well-known first law, application of electric field across a homogeneous solid should produce heat uniformly in proportion to the square of electrical current. Here we report strong departure from this expectation for common, homogeneous ionic solids such as alkali silicate glasses when subjected even to moderate fields (~100 V/cm). Unlike electronically conducting metals and semiconductors, with time the heating of ionically conducting glass becomes extremely inhomogeneous with the formation of a nanoscale alkali-depletion region, such that the glass melts near the anode, even evaporates, while remaining solid elsewhere. In situ infrared imaging shows and finite element analysis confirms localized temperatures more than thousand degrees above the remaining sample depending on whether the field is DC or AC. These observations unravel the origin of recently discovered electric field induced softening of glass. The observed highly inhomogeneous temperature profile point to the challenges for the application of Joule's law to the electrical performance of glassy thin films, nanoscale devices, and similarly-scaled phenomena.


[A chest tube can be inserted safely utilizing standard technique. Minithoracotomy should not be performed routinely].
The National Swedish Board of Health and Welfare has concluded that a minithoracotomy should be used for the insertion of a chest tube. Our opinion is that a less than 2 cm skin incision followed by blunt dissection through the chest wall is equally safe provided that the anatomical landmarks of the safe triangle are identified and the lung is not adherent to the chest wall. A prerequisite for safe treatment is an examination of the chest x-ray, supervision of chest tube function and the patient. Chest tube malfunction or complications should be managed urgently.


Thrombin is a regulator of astrocytic endothelin-1.
Endothelin-1, a potent vasoconstrictor of cerebral vessels, is produced by rat primary astrocytes and is subject to autostimulatory regulation in these cells. In this study we examined the effect of thrombin on astrocytic endothelins and report that endothelin-1 is released into the culture fluid in response to thrombin treatment. However, increased production of endothelin-1 is not accompanied by a concomitant increase in steady-state levels of endothelin-1 mRNA as assessed by reverse transcriptase-polymerase chain reaction, even though thrombin stimulation leads to increased inositolphospholipid turnover and activation of the nuclear factor AP1. Thus, astrocytic production of endothelin-1 may be mainly post-transcriptionally regulated in response to thrombin stimulation. In addition, two endothelin receptor genes (ET(A) and ETB) were found to be transcribed simultaneously in primary astrocyte cultures, and both thrombin and endothelin-1 stimulation result in a distinct temporary decrease in ET(A) mRNA. These studies suggest a role for thrombin in the regulation of brain perfusion through astrocytic endothelin-1 expression.


Management objective importance in fisheries: an evaluation using the analytic hierarchy process (AHP).
In determining the importance of criteria in the management of fisheries, two key issues stand out-the definition of a succinct set of criteria and the determination of which interest groups play a defining role in the management development process. This is indeed the case for all natural resource management problems, and many other environmental problems as well. The analytic hierarchy process (AHP) provides an effective framework for such an analysis. The AHP is generally used to evaluate importance amongst criteria based on the concept of paired comparison. This paper considers the development of a representative criteria hierarchy, and uses data obtained from a pairwise comparison survey based on the UK fisheries of the English Channel to investigate priorities that exist among different interest groups in the fisheries. The implementation of the AHP in this application provides a useful tool for analysis of criteria amongst groups involved in the management process with diverse interests.


Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats.
Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and alleviate opioid tolerance and dependence. Our present studies in male Sprague-Dawley rats assessed the abuse potential of oxycodone+ultra-low-dose naltrexone (NTX) versus oxycodone alone. The lowest NTX dose (1 pg/kg/infusion), but not slightly higher doses (10 and 100 pg/kg/infusion), enhanced oxycodone (0.1 mg/kg/infusion) intravenous self-administration, suggesting a reduced rewarding potency per infusion. During tests of reinstatement performed in extinction conditions, co-self-administration of any of these three NTX doses significantly reduced drug-seeking precipitated by priming injections of oxycodone (0.25 mg/kg, s.c.), a drug-conditioned cue, or foot-shock stress. During self-administration on a progressive-ratio schedule, animals self-administering oxycodone (0.1 mg/kg/infusion)+NTX (1 pg/kg/infusion) reached a "break-point" sooner and showed a trend toward less responding compared to rats self-administering oxycodone alone (0.1 mg/kg/infusion). In the final experiment, the addition of ultra-low-dose NTX (10 pg/kg, s.c.) enhanced the acute stimulatory effect of oxycodone (1 mg/kg, s.c.), as well as locomotor sensitization produced by repeated oxycodone administration (7 x 1 mg/kg, s.c.). In summary, this work shows that ultra-low-dose NTX co-treatment augments the locomotor effects of oxycodone as it enhances opioid analgesia, but reduces oxycodone's rewarding potency and subsequent vulnerability to relapse.


Chromosome segregation: playing polo in prophase.
During mitosis, in most eukaryotes, cohesin is removed from chromosomes in two steps. A paper in the March issue of Molecular Cell identifies Polo-like kinase as a key regulator for the first step that releases much of cohesin during prophase.


Aporphines. 25-trimethylislyl derivatives of N-methyl and N-propyl aporphines: gas chromatographic and mass spectrometric properties.
A series of synthetic, semisynthetic and naturally occurring aporphine alkaloids were converted to the O-trimethylsilyl derivatives, and analyzed by gas chromatography mass spectrometry. A discussion of structurally informative fragment ions along with gas chromatographic data is presented. Their applicability to the analysis of biological metabolites of apomorphine, a CNS active structural analog of dopamine, is discussed.


Plant transpiration at high elevations: Theory, field measurements, and comparisons with desert plants.
The influence of elevational changes on plant transpiration was evaluated using leaf energy balance equations and well-known elevational changes in the physical parameters that influence water vapor diffusion. Simulated transpirational fluxes for large leaves with low and high stomatal resistances to water vapor diffusion were compared to small leaves with identical stomatal resistances at elevations ranging from sea level to 4 km. The specific influence of various air temperature lapse rates was also tested. Validation of the simulated results was accomplished by comparing actual field measurements taken at a low elevation (300 m) desert site with similar measurements for a high elevation (2,560 m) mountain research site. Close agreement was observed between predicted and measured values of transpiration for the environmental and leaf parameters tested.Substantial increases in solar irradiation and the diffusion coefficient for water vapor in air (D wv) occurred with increasing elevation, while air and leaf temperatures, the water vapor concentration difference between the leaf and air, longwave irradiation, and the thermal conductivity coefficient for heat in air decreased with increasing elevation. These changes resulted in temperatures for sunlit leaves that were further above air temperature at higher elevations, especially for large leaves. For large leaves with low stomatal resistances, transpirational fluxes for low-elevation desert plants were close to those predicted for high-elevation plants even though the sunlit leaf temperatures of these mountain plants were over 10°C cooler. Simulating conditions with a low air temperature lapse rate (0.003° C m-1 and 0.004° C m-1) resulted in predicted transpirational fluxes that were greater than those calculated for the desert site. Transpiration for smaller leaves decreased with elevation for all lapse rates tested (0.003° C m-1 to 0.010° C m-1). However, transpirational fluxes at higher elevations were considerably greater than expected for all leaves, especially larger leaves, due to the strong influence of increased solar heating and a greater D wv. These results are discussed in terms of similarities in leaf structure and plant habit observed among low-elevation desert plants and high-elevation alpine and subalpine plants.


"Cervicomastoid Versus Retromandibular Extension of Pre-Auricular Incision in Transmasseteric Anteroparotid Approach for Condylar Fracture Management-a Prospective Study".
Treating mandibular condylar fractures has always been a matter of debate and controversy. However, there are various approaches, but it is of utmost importance that the surgical procedure must guarantee maximum safety for the facial nerve with best cosmetic outcome and minimizing complications. This prospective study was designed to compare cervicomastoid and retromandibular extension of pre-auricular incision in transmasseteric anteroparotid approach for condylar fractures management. The study was conducted in the Department of Oral and Maxillofacial Surgery, Bapuji Dental College and Hospital, Davangere from November 2015 to May 2017, and a total of 16 condylar fractures were surgically accessed for the management and were divided into two groups, cervicomastoid (Group A) and retromandibular extension (Group B) for evaluating parameters such as to assess the access to condylar region, post-operative edema, cosmetic outcome, time taken to access and facial nerve injury. Clinically the time taken was significantly less in the cervicomastoid group even though, there was no statistically significant difference regarding access to the fracture site, post-operative edema, facial nerve injury and cosmetic outcome between two groups. In our opinion the anteroparotid transmasseteric approach is appropriate for surgical management of mandibular condylar fractures as it provides adequate access, ensures safety of the facial nerve and is relatively easy to master. We realize that rather both incisions are good, but cervicomastoid variant is better choice in many aspects one being time taken for the surgery because of better tissue laxity of neck skin when seen in comparison.


Overcoming Obstacles in Professional Development During COVID-19.
The unexpected challenges of COVID-19 forced our nation to "rework" normal practices and routines. Kathy Chappell states that nurse professional development practitioners must be problem focused and solution oriented. Led by a nurse professional development specialist, planners employed innovation and creativity to address the problems found in one professional development program. This article assures readers that remote day-long conferences are well accepted and useful in today's fast-paced learning environment.


Endoscopic septoplasty: Tips and pearls.
This article is designed to provide a step-by-step description of our endoscopic septoplasty technique and discuss its difficulties and technical tips. Endoscopic septoplasty comprises 10 steps: diagnostic endoscopy, subperichondral infiltration, left mucosal incision, dissection of the left subperichondral flap, cartilage incision (0.5 centimetre posterior to the mucosal incision), dissection of the right subperichondral flap, anterior cartilage resection, perpendicular plate dissection, dissection and resection of the maxillary crest, endoscopic revision, mucosal suture and Silastic stents. A satisfactory postoperative result was observed at 3 months in 97% of cases in this series. The main contraindication to endoscopic septoplasty is anterior columellar deviation of the nasal septum requiring a conventional procedure.


Nocturnal eating disturbs phosphorus excretion in young subjects: a randomized crossover trial.
Nocturnal eating have recently increased. Serum phosphorus levels and regulators of phosphorus have circadian variations, so it is suggested that the timing of eating may be important in controlling serum phosphorus levels. However, there have been no reports on the effects of nocturnal eating on phosphorus metabolism. The objective was to evaluate the effects of nocturnal eating on phosphorus metabolism. Fourteen healthy men participated in two experimental protocols with differing dinner times. The design of this study was a crossover study. The subjects were served test meals three times (breakfast; 07:30 h, lunch; 12:30 h, dinner; 17:30 or 22:30 h) a day. Blood and urine samples were collected to assess diurnal variation until the following morning. The following morning, fasting serum phosphorus levels in the late dinner group were markedly higher than those in the early dinner group (p < 0.001), although serum calcium levels were maintained at approximately constant levels throughout the day in both groups. Fluctuations in urinary calcium excretion were synchronized with the timing of dinner eating, however, fluctuations in urinary phosphorus excretion were not synchronized. Urinary phosphorus excretions at night were inhibited in the late dinner group. In the late dinner group, intact parathyroid hormone levels didn't decrease, and they were significantly higher in this group compared with the early dinner group at 20:00 h (p = 0.004). The following morning, fasting serum fibroblast growth factor 23 levels in the late dinner group had not changed, but those in the early dinner group were significantly increased (p = 0.003). Serum free fatty acid levels before dinner were significantly higher in the late dinner group compared with the early dinner group. Our results indicate that nocturnal eating inhibits phosphorus excretion. It is suggested that nocturnal eating should be abstained from to manage serum phosphorus levels to within an adequate range.


The road less traveled: activating an oncogenic kinase.
Elevated phosphoinositide 3-kinase (PI3K) activity in human tumors has prompted widespread efforts to develop chemical PI3K inhibitors for oncology indications. In an innovative new study, Gong et al. report the discovery of a highly selective activator of the PI3Kα isoform, with promising activity in assays of nerve regrowth and cardioprotection from ischemia-reperfusion injury (IRI).


Role of protein, amino acids, and enzyme activity on odor production from anaerobically digested and dewatered biosolids.
The main objective of this research was to test the hypothesis that bioavailable protein and, more specifically, the sulfur-containing amino acids within the protein, can be degraded by proteolytic enzymes to produce odor-causing compounds--mainly volatile sulfur compounds (VSCs)--during biosolids storage. To achieve these objectives, samples of digester effluent and cake solids were collected at 11 different wastewater treatment plants in North America, and the samples were analyzed for protein and amino acid content and general protein-degrading enzyme activity. At the same time, cake samples were stored using headspace bottles, the concentration of VSCs were measured using gas chromatography, and olfactometry measurements were made by a trained odor panel. The results showed that the bound cake protein content and methionine content was well-correlated with VSC production and the detection threshold measured by the odor panel.


Anthracycline-formaldehyde conjugates and their targeted prodrugs.
The sequence of research leading to a proposal for anthracycline cross-linking of DNA is presented.The clinical anthracycline antitumor drugs are anthraquinones, and as such are redox active. Their redoxchemistry leads to induction of oxidative stress and drug metabolites. An intermediate in reductive glycosidiccleavage is a quinone methide, once proposed as an alkylating agent of DNA. Subsequent research nowimplicates formaldehyde as a mediator of anthracycline-DNA cross-linking. The cross-link at 5'-GC-3'sites consists of a covalent linkage from the amino group of the anthracycline to the 2-amino groupof the G-base through a methylene from formaldehyde, hydrogen bonding from the 9-OH to the G-base onthe opposing strand, and hydrophobic interactions through intercalation of the anthraquinone. The combinationof these interactions has been described as a virtual cross-linkof DNA. The origin of the formaldehyde in vivo remains a mystery. In vitro, doxorubicin reacts withformaldehyde to give firstly a monomeric oxazolidine, doxazolidine, and secondly a dimeric oxazolidine,doxoform. Doxorubicin reacts with formaldehyde in the presence of salicylamide to give the N-Mannich baseconjugate, doxsaliform. Doxsaliform is several fold more active in tumor cell growth inhibition than doxorubicin,but doxazolidine and doxoform are orders of magnitude more active than doxorubicin. Exploratory researchon the potential for doxsaliform and doxazolidine as targeted cytotoxins is presented. A promisinglead design is pentyl PABC-Doxaz, targeted to a carboxylesterase enzyme overexpressed in liver cancercells and/or colon cancer cells.


[Specificity of the interaction of carcinogenic and cytostatic agents with the elements of the genome at different levels of its organization].
The analysis of the literature permits drawing a conclusion that according to DNA binding site-specificity carcinogens and antitumour drugs can be divided into GC- and AT-binding compounds. When interacting with eucaryotic DNA such specificity leads to an increased binding of carcinogens and antitumour drugs to the repeat-rich DNA (satellite DNA, alpha-DNA, flanking regions of genes). It is supposed that specificity of the binding of chemical compounds on higher levels of genome organization (active and inactive chromatin, nuclear matrix-bound DNA) is also defined by the affinity of compounds to GC- or AT-rich repeats.


Uterine arteriovenous malformation: a rare cause of uterine bleeding. Diagnosis and treatment.
A case of uterine arteriovenous malformation following a dilatation and curettage is presented. Initial diagnosis with colour and pulsed Doppler ultrasound and treatment with transcatheter arterial embolization are described.


Shape and size optimization of truss structures by Chaos game optimization considering frequency constraints.
An engineering system consists of properly established activities and put together to achieve a predefined goal. These activities include analysis, design, construction, research, and development. Designing and constructing structural systems, including buildings, bridges, highways, and other complex systems, have been developed over the centuries. However, the evolution of these systems has been prolonged because the overall process is very costly and time-consuming, requiring primary human and material resources to be utilized. One of the options for overcoming these shortcomings is the utilization of metaheuristic algorithms as recently developed intelligent techniques. These algorithms can be utilized as upper-level search techniques for optimization procedures to achieve better results. Shape and size optimization of truss structures are considered in this paper utilizing the Chaos Game Optimization (CGO) as one of the recently developed metaheuristic algorithms. The principles of chaos theory and fractal configuration are considered inspirational concepts. For the numerical purpose, the 10-bar, 37-bar, 52-bar, 72-bar, and 120-bar truss structures as four of the benchmark problems in this field are considered as design examples in which the frequency constraints are considered as limits that have to be dealt with during the optimization procedure. Multiple optimization runs are also conducted for having a comprehensive statistical analysis, while a comparative investigation is also conducted with other algorithms in the literature. Based on the results of the CGO and other approaches from the literature, the CGO can provide better and competitive results in dealing with the considered truss design problems. In summary, the CGO can provide better solutions in dealing with the considered real-size structural design problems with higher levels of complexity.


Does tight control of systemic factors help in the management of diabetic retinopathy?
Diabetic retinopathy (DR), one of the leading causes of preventable blindness, is associated with many systemic factors that contribute to the development and progression of this microvascular complication of diabetes. While the duration of diabetes is the major risk factor for the development of DR, the main modifiable systemic risk factors for development and progression of DR are hyperglycemia, hypertension, and dyslipidemia. This review article looks at the evidence that control of these systemic factors has significant benefits in delaying the onset and progression of DR.


Assessment of edema volume in skin upon injury in a mouse ear model with optical coherence tomography.
Accurate measurement of edema volume is essential for the investigation of tissue response and recovery following a traumatic injury. The measurements must be noninvasive and repetitive over time so as to monitor tissue response throughout the healing process. Such techniques are particularly necessary for the evaluation of therapeutics that are currently in development to suppress or prevent edema formation. In this study, we propose to use optical coherence tomography (OCT) technique to image and quantify edema in a mouse ear model where the injury is induced by a superficial-thickness burn. Extraction of edema volume is achieved by an attenuation compensation algorithm performed on the three-dimensional OCT images, followed by two segmentation procedures. In addition to edema volume, the segmentation method also enables accurate thickness mapping of edematous tissue, which is an important characteristic of the external symptoms of edema. To the best of our knowledge, this is the first method for noninvasively measuring absolute edema volume.


[Effect of euphylline and no-shpa on cerebrovascular resistance and the survivability of animals after cerebral ischemia].
In acute experiments on anesthetized cats with total ischemia of the brain (15-minute arrest of blood autoperfusion of the cerebral vessels by a stable blood volume) it was shown that euphylline and no-shpa administered before ischemia or in the early period after ischemia inhibit or prevent the development of the postischemic phenomenon of non-recovery of the cerebral blood flow. The two drugs contributed to survival of albino rats following the brain ischemia produced by ligation of both carotid arteries.


Prospective Single-Center Observational Study of the Allergenic Potential of Mercromina Film and Other Common Antiseptics in Patients With Contact Dermatitis.
Although Mercromina Film and other topical antiseptics are widely used, they are not included in the standard series recommended by the Spanish Contact Dermatitis and Skin Allergy Research Group for testing suspected allergic contact dermatitis (ACD). Furthermore, no recent studies have investigated the allergenic potential of merbromin. To determine the allergenic potential of merbromin and compare it with that of other topical antiseptics widely used in clinical practice, including povidone-iodine, chlorhexidine, and eosin. Prospective single-center observational safety study of 105 patients with suspected ACD seen at the dermatology department of our hospital. Of the 105 patients studied, 1.9% had a positive patch test to merbromin and 12.4% were sensitized to povidone-iodine. The differences in the proportion of patients with ACD to Betadine Solución Dérmica (povidone-iodine) compared with the rest of the antiseptics was statistically significant (McNemar test, P<.05). No adverse reactions were observed in any of the patients. Based on the patch tests conducted, Mercromina Film has very low allergenic potential. The highest allergenic potential was observed for povidone-iodine.


A pairwise meta-analytic comparison of aortic valve area determined by planimetric versus hemodynamic methods in aortic stenosis.
Aortic valve area (AVA) is commonly determined from 2-dimensional transthoracic echocardiography (2D TTE) by the continuity equation; however, this method relies on geometric assumptions of the left ventricular outflow tract which may not hold true. This study compared mean differences and correlations for AVA by planimetric (2-dimensional transesophageal echocardiography [2D TEE], 3-dimensional transesophageal echocardiography [3D TEE], 3-dimensional transthoracic echocardiography [3D TTE], multi-detector computed tomography [MDCT], and magnetic resonance imaging [MRI]) with hemodynamic methods (2D TTE and catheterization) using pairwise meta-analysis. Ovid MEDLINE®, Ovid EMBASE, and The Cochrane Library (Wiley) were queried for studies comparing AVA measurements assessed by planimetric and hemodynamic techniques. Pairwise meta-analysis for mean differences (using random effect model) and for correlation coefficients (r) were performed. Forty-five studies (3014 patients) were included. Mean differences between planimetric and hemodynamic techniques were 0.12 cm2 (95%CI 0.10-0.15) for AVA (pooled r = 0.84; 95%CI 0.76-0.90); 1.36cm2 (95%CI 1.03-1.69) for left ventricular outflow tract area; and 0.13 cm (95%CI 0.07-0.20) for annular diameter (pooled r = 0.76; 95% CI 0.64-0.94); 0.67 cm2 (95%CI 0.59-0.76) for annular area (pooled r = 0.74; 95%CI 0.55-0.86). Planimetric techniques slightly, but significantly, overestimate AVA when compared to hemodynamic techniques.


Cytokeratin and CD56 aberrant co-expression in diffuse large B-cell lymphoma, NOS misinterpreted as metastatic neuroendocrine carcinoma by FNAC.
Aberrant expression of epithelial and neuroendocrine markers is rare in diffuse large B-cell lymphoma (DLBCL) and can lead to erroneous diagnosis with inappropriate treatment. This case report describes a case of DLBCL with a co-expression of cytokeratins and CD56 that was misdiagnosed as metastatic neuroendocrine carcinoma.


Congenital Pelizaeus-Merzbacher disease (Seitelberger type), malformation and cystic degeneration of the central nervous system.
The present paper reports on the case of a neonate child with multiple malformations affecting osteogenesis and the central nervous system (microcephaly, pachygyria). Morphologically, myelin staining supplied evidence of the total lack of myelin sheaths (myelin aplasia). The cerebellar cortex was malformed and altered by cystic degeneration. Electron microscopy confirmed the aplasia of the myelin sheaths and revealed the presence of concentric multilamellar formations in the glial cells (myelination glia), and in areas of cystic degeneration. The morphologic aspects clearly showed the relationship of this congenital aplasia of the myelin sheaths with the congenital Pelizaeus-Merzbacher disease (Seitelberger type). The cystic degeneration differs from the spongy degeneration of the brain (van Bogaert-Bertrand disease) and should be considered a result of maldeveloped nervous tissue.


Early regression of paraurethral cyst in a neonate.
Paraurethral cyst is a rare cause of interlabial mass formation in female neonates. Paraurethral cysts are generally asymptomatic, and spontaneous regression is expected. However, the management of paraurethral cysts is a controversial topic. Here, we report the case of a female neonate with a paraurethral cyst that regressed spontaneously on day 3 after birth. Urgent surgical treatment of these cysts is not recommended during the early neonatal period.


Influence of the adrenal gland on the pressor effect and antagonistic potency of angiotensin II analogs.
In ganglion blocked vagotomized rats, several 1,8-substituted angiotensin II analogs (250 ng/kg/min, i.v.) antagonized the pressor effect of angiotensin II. Dose ratios measured at the ED20 levels were: [Sar1,Ile8]-28; [Gac1,Ile8]- 19;[MeAla1,Ile8i1- 16;[MeIle1,Ile8]- 10;[sar1,Ala8]- 9;[me2Gly1,Ile8]- 4. Elimination of aspajtic acid in position 1 of [Ile8]-angiotensin II significantly reduced the antagonistic potency of the analog. No antagonistic effect was observed with [Phe4,Ile8] and [Ala4,Ile8]-angiotensin II even when infused at 6 mug/kg/min. During infusion, a partial rise in blood pressure was observed with all the above 1,8-substituted angiotensin II analogs. Phentolamine (100 mug/rat) injected 30 min after the start of the analog infusion reduced and sometimes abolished the pressor effect. However, phenoxybenzamine )Pbz, 2 mg/kg) injected 30 min prior to the analog infusion diminished but did not completely abolish the initial pressor effect. In adrenalectomized rats, the pressor effect was reduced by approximately 50 percent and disappeared completely 15-30 min after start of the infusion. Under these conditions, dose ratios of [Sar1,Ile8]-,[MeAla1,Ile8]- and [Gac1,Ile8]-angiotensin II were significantly reduced. Noradrenaline, 83 ng/kg/min. increased the ED20 value of angiotensin II(ratio 1.79) in normal rats but did not do so in adrenalectomized rats. In these rats no regular correlation was found between the angiotensin II ED20 values and initial blood pressure. These data indicate that under the present experimental conditions, the low pressor effect observed with these angiotensin II antagonists appears to be due to both adrenal catecholamine release and a direct vasoconstrictor effect. Variations in antagonistic activity of angiotensin II analogs, apart from changes introduced in the molecule, may be the manifestation of a complex interaction between angiotensin II, its antagonists, and the sympathoadrenal system.


Wave propagation in a model of the arterial circulation.
The propagation of the arterial pulse wave in the large systemic arteries has been calculated using a linearised method of characteristics analysis to follow the waves generated by the heart. The model includes anatomical and physiological data for the 55 largest arteries adjusted so that the bifurcating tree of arteries is well matched for forward travelling waves. The peripheral arteries in the model are terminated by resistance elements which are adjusted to produce a physiologically reasonable distribution of mean blood flow. In the model, the pressure and velocity wave generated by the contraction of the left ventricle propagates to the periphery where it is reflected. These reflected waves are re-reflected by each of the bifurcations that they encounter and a very complex pattern of waves is generated. The results of the calculations exhibit many of the features of the systemic arteries, including the increase of the pulse pressure with distance away from the heart as well as the initial decrease and then the large increase in the magnitude of back flow during late systole going from the ascending aorta to the abdominal aorta to the arteries of the leg. The model is then used to study the effects of the reflection or absorption of waves by the heart and the mechanisms leading to the incisura are investigated. Calculations are carried out with the total occlusion of different arterial segments in order to model experiments in which the effects of the occlusion of different arteries on pressure and flow in the ascending aorta were measured. Finally, the effects of changes in peripheral resistance on pressure and velocity waveforms are also studied. We conclude from these calculations that the complex pattern of wave propagation in the large arteries may be the most important determinant of arterial haemodynamics.


Conditional mouse mutants highlight mechanisms of corticotropin-releasing hormone effects on stress-coping behavior.
Hypersecretion of central corticotropin-releasing hormone (CRH) has been implicated in the pathophysiology of affective disorders. Both, basic and clinical studies suggested that disrupting CRH signaling through CRH type 1 receptors (CRH-R1) can ameliorate stress-related clinical conditions. To study the effects of CRH-R1 blockade upon CRH-elicited behavioral and neurochemical changes we created different mouse lines overexpressing CRH in distinct spatially restricted patterns. CRH overexpression in the entire central nervous system, but not when overexpressed in specific forebrain regions, resulted in stress-induced hypersecretion of stress hormones and increased active stress-coping behavior reflected by reduced immobility in the forced swim test and tail suspension test. These changes were related to acute effects of overexpressed CRH as they were normalized by CRH-R1 antagonist treatment and recapitulated the effect of stress-induced activation of the endogenous CRH system. Moreover, we identified enhanced noradrenergic activity as potential molecular mechanism underlying increased active stress-coping behavior observed in these animals. Thus, these transgenic mouse lines may serve as animal models for stress-elicited pathologies and treatments that target the central CRH system.


Gut glucagon, enteroglucagon, gut glucagonlike immunoreactivity, glicentin--current status.
Glucagonlike substances in extracts of intestinal mucosa were already described in 1948 by Sutherland and deDuve (1), who used a bioassay technique for the identification. After the development of the first glucagon radioimmunoassays, Unger and co-workers (2,3) confirmed that intestinal extracts contained peptides that "crossreacted" in the glucagon radioimmunoassay [hence gut "glucagonlike immunoreactivity" (GLI)]. In 1968, the same group discovered that the gut GLIs consisted of at least two peptides, GLI I and II (4), both of which differed immunochemically from pancreatic glucagon and, therefore, necessarily had different chemical structures (4,5). Developments during the last decade in the field of peptide chemistry, particularly improved purification and sequencing techniques, have greatly advanced our knowledge of gut peptides, including the enteroglucagons, and the chemical structure of several of the members of this heterogenous group of peptides is now known. Furthermore, progress in the field of nucleotide and gene technology has also spread to this area of research, and although many problems remain unresolved, the progress made has sufficiently important implications to justify a review of the most recent advances.


PS II model-based simulations of single turnover flash-induced transients of fluorescence yield monitored within the time domain of 100 ns-10 s on dark-adapted Chlorella pyrenoidosa cells.
The set up described in Steffen et al. (Biochemistry 40:173-180, 2001) was used to monitor in the time domain from 100 ns to 10 s single turnover flash-induced transients of the normalized fluorescence yield (SFITFY) on dark-adapted cells of the thermophilic algae Chlorella pyrenoidosa Chick. Perfect data fit was achieved within the framework of a previously proposed model for the PS II reaction pattern (Lebedeva et al., Biophysics 47:968-980, 2002; Belyaeva et al., Biophysics 51:860-872, 2006) after its modification by taking into account nonradiative decay processes including nonphotochemical quenching due to time-dependent populations of P680(+*) and (3)Car. On the basis of data reported in the literature, a consistent set of rate constants was obtained for electron transfer at the donor and acceptor sides of PS II, pH in lumen and stroma, the initial redox state of plastoquinone pool and the rate of plastoquinone oxidation. The evaluation of the rate constant values of dissipative processes due to quenching by carotenoid triplets in antennae and P680(+*)Q(A)(-*) recombination as well as the initial state populations after excitation with a single laser flash are close to that outlined in (Steffen et al., Biochemistry 44:3123-3133, 2005a). The simulations based on the model of the PS II reaction pattern provide information on the time courses of population probabilities of different PS II states. We analyzed the maximum (F(m)(STF)) and minimum (F(0)) of the normalized FL yield dependence on the rate of the recombination processes (radiative and dissipative nonradiative) and of P680(+*) reduction. The developed PS II model provides a basis for theoretical comparative analyses of time-dependent fluorescence signals, observed at different photosynthetic samples under various conditions (e.g. presence of herbicides, other stress conditions, excitation with actinic pulses of different intensity, and duration).


An Efficient and Recyclable Nanoparticle-Supported Cobalt Catalyst for Quinoxaline Synthesis.
The syntheses of quinoxalines derived from 1,2-diamine and 1,2-dicarbonyl compounds under mild reaction conditions was carried out using a nanoparticle-supported cobalt catalyst. The supported nanocatalyst exhibited excellent activity and stability and it could be reused for at least ten times without any loss of activity. No cobalt contamination could be detected in the products by AAS measurements, pointing to the excellent activity and stability of the Co nanomaterial.


Differences in Adolescent Emotion Regulation and Impulsivity: A Group Comparison Study of School-Based Recovery Students.
Recovery high schools (RHS) vary in organization and operating philosophy, but are designed to support the unique needs of students struggling with substance use disorders (SUD). Previous research on youth risk taking behaviors suggests emotion regulation is a key predictor of outcomes. Specifically, the ability to respond in adaptive rather than maladaptive ways is often associated with challenges of impulsivity, poor distress tolerance, and adolescent substance use. The current study considers data from RHS students in order to answer research questions concerning impulsivity and emotion regulation of youth working to change their risk trajectories in comparison to group of typically developing youth. Participants (n = 114) in the study were composed of students enrolled in 3 RHS programs and a comparison group of similar aged youth (15-20 years) without an identified SUD. Data collection occurred through an anonymous online survey set of four measures of reactivity and impulsivity, emotion regulation, and parent and peer influence, as well as an online version of the Stroop Inhibitory Control Task. Participants in the three RHS groups reported decreased emotion regulation abilities, increased impulsivity and increased peer influence when compared to the comparison group; differential effects within RHS are presented. Conclusions/Importance: Results are consistent with the extant literature that difficulty regulating emotions is associated with an increased risk for substance abuse and suggests these difficulties persist in early recovery. Results also suggest the need to better understand how different operating philosophies of programs influence student outcomes and the recovery process.


Preliminary investigations using Recover Latent Fingerprint Technology on unfired ammunition and fired cartridge cases.
Previous studies have identified the potential benefit of the disulfur dinitride (S₂N₂) process to operationally relevant substrates. However, the majority of this work was conducted on prototype equipment that had substantial differences to the commercialised system (Recover Latent Fingerprint Technology (LFT)) in terms of design and chemical delivery. This paper evaluates the performance of Recover LFT on a problematic exhibit encountered within a fingerprint enhancement laboratory: unfired and fired ammunition. Three pseudo-operational experiments involving non-groomed, naturally handled fingermarks were conducted on the most commonly encountered types of ammunition used in crime in the United Kingdom (UK). In addition, Recover LFT was compared against Superglue Fuming followed by Basic Yellow 40 (BY40) Fluorescent Dye Staining (a commonly used alternative) to ascertain if the process provides added benefit to fingermark recovery rates. The results show that fingermark visualisation on small calibre cartridge cases remains difficult with few marks achieving enough ridge detail for comparison. However, this paper also shows that the novel Recover LFT process, which is still in its infancy and requiring optimisation, is no worse than currently implemented visualisation processes and is therefore worth further investigation.


The efficacy of trovafloxacin versus ceftriaxone in the treatment of experimental brain abscess/cerebritis in the rat.
Current estimates of the mortality associated with brain abscesses range from 0-24%, with neurological sequellae in 30-55% of survivors. Although the incidence of brain abscess appears to be increasing, likely due to an increase in the population of immunosuppressed patients, the condition is still sufficiently uncommon to make human clinical trials of therapy problematic. An animal model to study the efficacy of new treatment regimens, specifically, new antimicrobial agents is therefore necessary. This study uses a well-defined experimental paradigm as an inexpensive method of inducing and studying the efficacy of antibiotics in brain abscess. The rat model of brain abscess/cerebritis developed at this institution was used to determine the relative efficacy of trovafloxacin as compared to ceftriaxone in animals infected with Staphylococcus aureus. S. aureus ( approximately 10(5) CFU in 1 microliter) was injected with a Hamilton syringe, very slowly, over the course of 70 minutes after a two mm burr hole was created with a spherical carbide drill just posterior to the coronal suture and four mm lateral to the midline. Eighteen hours later treatment was begun; every 8 hours the rats were dosed with subcutaneous ceftriaxone (n = 10), trovafloxacin (n = 11) or 0.9% sterile pyogen-free saline (n = 10). After four days of treatment the brains were removed and sectioned with a scalpel. The entire injected hemisphere was homogenized and quantitative cultures performed. The mean +/- SEM log(10) colony forming units/ml S. aureus recovered from homogenized brain were as follows: controls 6.10 +/- 0.28; ceftriaxone 3.43 +/- 0.33; trovafloxacin 3.65 +/- 0.3. There was no significant difference in bacterial clearance between ceftriaxone versus trovafloxacin (p = 0.39). Trovafloxacin or other quinolones may provide a viable alternative to intravenous antibiotics in patients with brain abscess/cerebritis.


Ramipril versus placebo in kidney transplant patients with proteinuria: a multicentre, double-blind, randomised controlled trial.
Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of end-stage renal disease and death in non-transplant patients with proteinuria. We examined whether ramipril would have a similar beneficial effect on important clinical outcomes in kidney transplant recipients with proteinuria. In this double-blind, placebo-controlled, randomised trial, conducted at 14 centres in Canada and New Zealand, we enrolled adult renal transplant recipients at least 3-months post-transplant with an estimated glomerular filtration rate (GFR) of 20 mL/min/1·73m(2) or greater and proteinuria 0·2 g per day or greater and randomly assigned them to receive either ramipril (5 mg orally twice daily) or placebo for up to 4 years. Patients completing the final 4-year study visit were invited to participate in a trial extension phase. Treatment was assigned by centrally generated randomisation with permuted variable blocks of 2 and 4, stratified by centre and estimated GFR (above or below 40 mL/min/1·73 m(2)). The primary outcome was a composite consisting of doubling of serum creatinine, end-stage renal disease, or death in the intention-to-treat population. The principal secondary outcome was the change in measured GFR. We ascertained whether any component of the primary outcome had occurred at each study visit (1 month and 6 months post-randomisation, then every 6 months thereafter). This trial is registered with ISRCTN, number 78129473. Between Aug 23, 2006, and March 28, 2012, 213 patients were randomised. 109 were allocated to placebo and 104 were allocated to ramipril, of whom 109 patients in the placebo group and 103 patients in the ramipril group were analysed and the trial is now complete. The intention to treat population (placebo n=109, ramipril n=103) was used for the primary analysis and the trial extension phase analysis. The primary outcome occurred in 19 (17%) of 109 patients in the placebo group and 14 (14%) of 103 patients in the ramipril group (hazard ratio [HR] 0·76 [95% CI 0·38-1·51]; absolute risk difference -3·8% [95% CI -13·6 to 6·1]). With extended follow-up (mean 48 months), the primary outcome occurred in 27 patients (25%) in the placebo group and 25 (24%) patients in the ramipril group (HR 0·96 [95% CI 0·55-1·65]); absolute risk difference: -0·5% (95% CI -12·0 to 11·1). There was no significant difference in the rate of measured GFR decline between the two groups (mean difference per 6-month interval: -0·16 mL/min/1·73m(2) (SE 0·24); p=0·49). 14 (14%) of patients died in the ramipril group and 11 (10%) in the placebo group, but the difference between groups was not statistically significant (HR 1·45 [95% CI 0·66 to 3·21]). Adverse events were more common in the ramipril group (39 [38%]) than in the placebo group (24 [22%]; p=0·02). Treatment with ramipril compared with placebo did not lead to a significant reduction in doubling of serum creatinine, end-stage renal disease, or death in kidney transplant recipients with proteinuria. These results do not support the use of angiotensin-converting enzyme inhibitors with the goal of improving clinical outcomes in this population. Canadian Institutes of Health Research.


Hematuria in the burned child.
Hematuria is a frequent complication in burn patients, but its clinical significance has not been reported. The incidence, etiologies, treatment, and outcome of hematuria in 1,785 burn patients treated from 1964 to 1983, have been reviewed. Ninety-one patients had hematuria (greater than 15 RBC/HPF with unspun urine). There were five main causes: urinary infections (UTI), 50 cases; renal calculi (RC), 14 cases, including 3% and 5% total body surface area burn patients; catheter trauma, 7 cases; renal vein thrombosis (RVT), 5 cases; and acute renal failure (ATN), 4 cases. Ten patients died in the UTI group, five with Candida as the infecting organism. No RC patients died, but two required surgical extraction of their stones. This incidence of RC may be due to large intake of dairy products and antacids and to prolonged immobilization. The catheter trauma group had no deaths and was the youngest group. One RVT patient was diagnosed clinically and successfully treated surgically. The other three were diagnosed at necropsy. The ATN patients all developed renal failure late as part of multiple organ system failure and all died. We conclude hematuria is a serious finding in burn patients and prompt diagnosis of its etiology and treatment are essential for maintaining renal function and patient survival.


Plyometric Exercises: Optimizing the Transfer of Training Gains to Sport Performance.
Rapid force production and its transmission to the skeleton are important factors in movements that involve the stretch-shortening cycle. Plyometric exercises are known to augment this cycle and thereby improve the neuromechanical function of the muscle. However, the training exercises that maximize translation of these gains to sports performance are not well defined. We discuss ways to improve this transfer.


Use of high-performance polyethylene fibres as a reinforcing phase in poly(methylmethacrylate) bone cement.
First results are presented concerning the elastic and ultimate mechanical behaviour of p(MMA) bone cement reinforced with as-received and surface-modified Spectra 900 polyethylene fibres. Even though the surface chemistry and reactivity of the fibres was modified, the surface oxidation and surface grafting treatments of the polyethylene fibres apparently did not significantly affect the mechanical properties of the polyethylene-reinforced p(MMA) bone cement or improve the interfacial bonding. This may be attributed to the rather unfavourable area-to-volume ratio of PE fibres for such treatments, as well as to the necessarily low content of PE fibres in the bone cement which does not allow a clear differentiation between the various samples.


Effect of Fluid Resuscitation Strategies for Obese Patients with Sepsis and Septic Shock: A Systematic Review.
As the Surviving Sepsis Campaign (2021) recommended, patients with sepsis should be given a liquid infusion of 30 ml/kg (ideal body weight). However, the strategy may result in insufficient resuscitation for obese patients with sepsis. Therefore, we conducted a systematic evaluation of the effectiveness of the initial resuscitation strategy in obese sepsis patients. A computer search of PubMed, Embase, Cochrane library, and other databases collected cohort studies from the beginning of the survey to December 2021 to include articles evaluating initial resuscitation strategies for sepsis-obese patients. Of the six studies included, five used ideal body weight infusion strategies, and three used actual body weight infusion strategies. Differences in fluid volume were observed between the two strategies, but no significant difference was observed in the mortality of obese sepsis patients. In addition, there may be an infusion strategy other than the above two infusion methods, and the safety and efficacy of the new infusion strategy are unclear. The obesity paradox has been observed in most infusion strategies. The association between obesity and infusion strategy has rarely been investigated in patients with sepsis and septic shock, and the existing results are conflicting. The risk of bias in all included studies was moderate or high. Before providing broad recommendations on the optimal first resuscitation approach to lower the chance of mortality, further clinical trials, and prospective research need to be done.


Surgical Providers' Perceptions of the Patient Portal: Before and After the 21st Century Cures Act.
In April 2021, the Information Blocking Rule (IBR) of the 21st Century Cures Act went into effect giving patients immediate access to notes, radiology reports, lab results, and surgical pathology. We aimed to examine changes in surgical providers' perceptions of patient portal usage before and after its implementation. We administered a 37-question survey prior to the implementation of the IBR and a 39-question follow-up survey 3 mo later. The survey was sent to all surgeons, advanced practice providers, and clinic nurses in our surgical department. The response rate to pre surveys and post surveys was 33.7% and 30.7%, respectively. Providers' preference for communication via the patient portal (compared to phone or in person) regarding lab, radiology, or pathology results remained similar. While there was an increase in messages received from patients, there was no difference in the self-reported time spent on the electronic health record (EHR). Prior to the implementation of the blocking rule, 75.8% of providers believed that the portal increased workload which decreased to 57.4% on our follow-up survey. About one-third of providers screened positive for burnout before (32%) which decreased slightly (27.4%). Although 43.9% of providers reported the Cures Act had changed their practice, there was no difference in self-reported EHR usage, preferred method of interaction with patients, overall workload, or burnout. Initial concerns regarding the IBR's effect on job satisfaction, patient anxiety, and quality of care had lessened. Further exploration into how patients having immediate access to their EHRs has changed surgical practice is needed.


Organizational factors associated with the use of contingency management in publicly funded substance abuse treatment centers.
A promising area within technology transfer studies is the identification of organizational factors that influence the adoption of treatment innovations. Although studies have identified organizational factors associated with the adoption of pharmacological innovations, few studies have examined organizational factors in the adoption of psychosocial innovations, among which contingency management (CM) is a significant practice. Using data from a sample (N = 318) drawn from the population of publicly funded treatment centers in the United States, this study modeled organizational factors falling in the domains of structural characteristics, workforce variables, values and norms, and patient characteristics associated with the use of CM. Organizations were more likely to use CM if they embrace a supportive therapeutic approach, are research friendly, offer only outpatient levels of care, or serve drug-court patients. Implications for studying the diffusion and implementation of evidence-based psychosocial interventions are discussed.


Patients with repaired tetralogy of Fallot and the HIF1A1744C/T variant have increased imaging markers of diffuse myocardial fibrosis.
Right ventricular fibrotic remodeling has been identified pre- and postoperatively in patients with tetralogy of Fallot (ToF) and linked to adverse outcomes. Polymorphisms of hypoxia inducible factor-1-alpha (HIF1A) have been associated with the fibrotic burden by cardiac magnetic resonance (CMR) late gadolinium enhancement imaging. Their association with diffuse fibrotic myocardial remodeling is unknown. We sought to determine whether polymorphisms in HIF1A are related to CMR markers of diffuse myocardial fibrosis. Patients with repaired ToF who had undergone CMR with T1 mapping as well as whole genome sequencing were included. Myocardial native T1 was quantified using a modified Look-Locker inversion recovery sequence and measured in the left ventricular free wall, the interventricular septum, and the right ventricular free wall. Patients who had at least one functioning allele of HIF1A were compared to those who did not using the Mann Whitney U test for continuous variables and chi-square or the Fischer test for discrete variables. 46 patients had both CMR and whole genome sequencing. Only one HIF1A variant was identified in the cohort and present in 13 patients. There were no significant differences in demographics, surgical variables, right or left ventricular volumes or function between patients with and without the variant. Despite a trend towards a lower age at the time of CMR (11.3 vs 13.7 years; p = 0.07), patients with HIF1A variants had higher native T1 values (1094 vs. 1050; p = 0.027) in the right ventricular outflow tract myocardium, reflecting increased diffuse interstitial ventricular fibrosis in them. Hypoxia-inducible factor is associated with imaging markers of increased diffuse right ventricular fibrosis late after repair of tetralogy of Fallot.


Which genotype of Helicobacter pylori-cagA or cagE-Is better associated with gastric Cancer risk? Lessons from an extremely high-risk area in Iran.
The association of the H. pylori cagA- /cagE-positive genotypes with the risk of gastric cancer (GC) in Ardabil-a high-risk area in North-West Iran-was assessed. Genotyping was performed in DNA from fresh gastric biopsies (N = 218). Occurrence of H. pylori infection was 85.32% (186/218). The total frequency of the cagA+vs. cagA-, cagE+vs. cagE-, cagA+/cagE-vs. AGCs (all genotype combinations), cagA-/cagE+vs. AGCs, cagA-/cagE-vs. AGCs, cagA+/cagE+vs. AGCs, cagA+/cagE-vs. cagA-/cagE+, and cagA+/cagE+vs. cagA-/cagE- genotypes was 102/186 (54.8%), 89/186 (47.8%), 38/186 (20.4%), 25/186 (13.4), 59/186 (31.7%), 64/186 (34.4%), 38/63 (38.63%), and 64/123 (52.0%), respectively. The cagE+vs. cagE- (59.6% (65/109) in GC vs. 31.2% (24/77) in non-atrophic gastritis, NAG) and the cagA+/cagE+vs. cagA-/cagE- genotypes (66.7% (40/60) in GC vs. 38.1% (24/63) in NAG) showed an increased association with the risk of GC in Ardabil (odds ratio [OR] = 3.262, 95% confidence interval [CI]: 1.763-6.038, p = .0001 and OR = 3.250; 95% CI: 1.552-6.808, p = .002, respectively). We propose that the H. pylori cagE+ but not cagA+ genotype significantly increased the risk of GC in this extremely high-risk population. Therefore, it may play a significant role in determining H. pylori-related clinical outcome.


Serum anti-Mullerian hormone levels correlate with ovarian response in idiopathic hypogonadotropic hypogonadism.
The role of serum AMH levels in prediction of ovarian response in idiopathic hypogonadotropic hypogonadism (IHH) was evaluated. MATERIAL METHOD(S): Twelve patients with IHH underwent controlled ovarian hyperstimulation (COH) for IVF were enrolled in this prospective study. Serum AMH levels were studied on the 2nd or 3rd day of an induced menstrual cycle by a preceding low-dose oral contraceptive pill treatment. A fixed dose (150-300 IU/day) of hMG was given in all COH cycles. Correlations between serum AMH levels, COH outcomes and embryological data were investigated. Mean serum AMH levels was 3.47 ± 2.15 ng/mL and mean serum peak estradiol was 2196 ± 1705 pg/mL. Mean number of follicles >14 mm, >17 mm on hCG day and MII oocytes were 4.14 ± 3.2, 4 ± 2.5 and 7.28 ± 3.5, respectively. Mean number of grade A embryos and transferred embryos were 3.28 ± 2.4 and 2.5 ± 0.7, respectively. The clinical pregnancy rate per patient was 41.6 % (5/12). Positive correlations were observed between serum AMH levels and MII oocytes (r = 0.84), grade A embryos (r = 0.85), serum peak estradiol levels (r = 0.87), and number of follicles >14 mm (r = 0.83) and >17 mm (r = 0.81) on hCG day, respectively. AMH appears as a promising marker of ovarian response in patients with IHH undergoing IVF.


Simultaneous gastroesophageal pH monitoring and the diagnosis of alkaline reflux.
The diagnosis of alkaline gastroesophageal reflux (AGER) by esophageal pH-monitoring is elusive because several other causes may raise esophageal pH above 7. This study approaches the issue by simultaneously recording esophageal and gastric pH with a 2.1 mm assembly of two antimony electrodes in refluxing (n = 69) and nonrefluxing (n = 40) children. On the basis of the information gathered, patients were divided into four groups: acid refluxers (GER, n = 40 or 57%), alkaline refluxers (AGER, n = 8 or 11%), alkalacid refluxers (AAGER, n = 15 or 22%), and silent refluxers or false negatives (SGER, n = 6 or 9%). Children with AGER could not be differentiated from other refluxers nor from controls by esophageal pH information alone. Prolonged gastric buffering or alkalinization could be documented in both AGER and AAGER children, indicating extended duodenogastric reflux (DGR) in them. The incidence of esophagitis was not significantly different between the groups of refluxers: 75% for AGER and AAGER, 73% for GER, and 67% for SGER. AGER, a disorder involving both pyloric and gastroesophageal barriers, is as significant a problem in children as in adults and may lead to severe complications even in the absence of excessive acid exposure. Monitoring esophageal pH alone is insufficient for making the diagnosis of AGER. The diagnosis can be made with little more expense and similar patient discomfort using the two-probe test. We suggest the need for a critical reassessment of the current antacid and prokinetic GER treatments and of antireflux operations which leave DGR intact while correcting GER.


Nail as a foreign body in a neonate, an unusual presentation at an unusual age.
Children are prone to ingest substances due to their exploratory nature and tendency to put everything in the mouth. Commonly ingested foreign bodies are coins, batteries and buttons. Foreign body ingestion in neonates is a very rare presentation and always needs important consideration as it can be a part of child abuse and can lead to serious life threatening consequences.


Analysis for urinary catecholamines by liquid chromatography with amperometric detection: methodology and clinical interpretation of results.
A method is presented for the quantitative analysis of urinary unconjugated norepinephrine, epinephrine, and dopamine as discrete entities. The procedure requires initial purification of the specimen on aluminum oxide and a boric acid-gel. We used "high-performance" reversed-phase paired-ion chromatography, with a flow-through amperometric cell as the detector. The CV was 6% for determination of norepinephrine, 11% for epinephrine, and 6% for dopamine monitored at physiologic concentrations of these compounds in urine. In a population study, urine specimens from 117 normal pediatric and adult subjects, 85 hypertensive patients, and 22 patients with surgically proved pheochromocytoma were analyzed. The specificity of the method for detection of pheochromocytoma was 100%, with a sensitivity of 97%.


La Sota vaccination may not protect against virus shedding and the lesions of velogenic Newcastle disease in commercial turkeys.
The aim of this project is to study the clinical signs and lesion of velogenic Newcastle disease (vND) in commercial turkeys, and also to find out if La Sota vaccination offered protection against these signs and lesions. The cockerels were included as positive controls. One hundred and twenty turkey poults and cockerels were divided into eight groups as follows: unvaccinated unchallenged turkeys (UUT), unvaccinated challenged turkeys (UCT), vaccinated unchallenged turkeys (VUT), vaccinated challenged turkeys (VCT), and along the same lines, the cockerel groups were UUC, UCC, VUC and vaccinated challenged cockerels (VCC). Vaccination was at 3 weeks of age while challenge was at 6 weeks of age. The unvaccinated turkeys and cockerels (UCT and UCC) showed different degrees of depression, diarrhoea and later paralysis at challenge. Total mortality was 100% in cockerels within 6 days, but 60% in turkeys. Similar but milder clinical signs were found in the VCC with a total mortality of 13.3%. The VCT showed mild drop in feed and water consumption, and no mortality. All the challenged groups had significant (p < 0.05) loss of weight when compared with their controls. Necropsy showed that while the UCC had severe proventricular haemorrhages, intestinal and caecal tonsil ulcers, the UCT had no digestive tract lesion. There was severe atrophy of the lymphoid organs in all the challenged groups. Histopathological sections of the bursa, spleen and thymus in all the challenged groups with special emphasis on the vaccinated and unvaccinated turkeys with mortalities of 0 and 60%, respectively, had very severe necrosis and depletion of the lymphoid tissue. Virus was isolated from the cloacal swabs. The haemagglutination inhibition antibodies were significantly higher (p < 0.05) in the challenged groups than the unchallenged. The above observations in the intestinal tracts of UCT are of diagnostic significance while the gross and microscopic lesions in the UCT and VCT show that La Sota vaccination may not protect turkeys against the destruction of the lymphoid organs by vND as earlier reported in chickens. This may lead to immunosuppression and production problems in areas where vND is enzootic.


[Routes of spread of the current rabies epizoonosis in Europe].
The present report describes the spreading paths of the rabic epidemic that is rapidly reaching Italy from Central Europe. The epidemiologic situation of neighbouring countries is examined and the sanitary measures undertaken in Europe against epidemic are compared.


Nationwide analysis of plastic and reconstructive procedural volume in the United States during the COVID-19 pandemic.
This study aims to define the impact of the novel Coronavirus Disease 2019 (COVID-19) pandemic on the volume of common plastic and reconstructive procedures in the United States. TrinetX is a national, federated database that was utilized in surveying plastic and reconstructive procedural volumes among 53 Healthcare organizations (HCO) between March 2018 and May 2021. This timeframe was divided into pre-pandemic (March 2018 to February 2020) and pandemic periods (March 2020 to May 2021). Each period was then sub-divided into four seasons of the year and the mean monthly procedural volume per HCO was compared. A student's t-tests comparing pre-pandemic and pandemic seasonal mean procedural volumes were used for statistical analysis. A total of 366,032 patient encounters among 53 HCO were included. The average seasonal volume per HCO of all procedures reduced from 872.11 procedures during pre-pandemic seasons to 827.36 during pandemic seasons. Spring 2020 vol declined for most procedures as 15 of 24 (63%) assessed procedure categories experienced statistically significant decreases. Spring 2021 experienced rebounds with 15 of 24 (63%) assessed procedures showing statistically significant increases. During the pandemic period, the average procedural volume per HCO of 14 procedure categories was significantly less than the pre-pandemic average procedural volume. Overall, an inverse relationship was observed between novel COVID-19 cases and plastic and reconstructive surgery procedure volumes in the United States.


Genetic variability of the stolbur phytoplasma vmp1 gene in grapevines, bindweeds and vegetables.
Evaluation of the genetic variability of stolbur phytoplasma infecting grapevines, bindweeds and vegetables, collected in different central and southern Italian regions. Phytoplasma isolates belonging to stolbur subgroup 16SrXII-A were subjected to molecular characterization by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP), to investigate two different nonribosomal genes: tuf and vmp1. In grapevines, 32% of samples were infected by tuf-a type and 68% by tuf-b type, with different relative incidences in the regions surveyed. All herbaceous samples (bindweeds, tomato, tobacco, pepper, celery) were infected by tuf-b. The gene vmp1 showed higher polymorphism in grapevines (nine profiles) than herbaceous plants (six) by RFLP analysis, in agreement with nucleotide sequences' analysis and virtual digestions. The phylogenetic analysis of vmp1 gene sequences supports the RFLP data and demonstrates the accuracy of RFLP for preliminary assessments of genetic diversity of stolbur phytoplasmas and for screening different vmp types. Stolbur represents a serious phytosanitary problem in the areas under investigation, owing to heavy economic losses in infected grapevines and vegetables. Molecular information about the complex genotyping of the vmp1 gene provides useful data towards a better understanding of stolbur epidemiology. Moreover, this study clarifies some different vmp1 genotype classifications of stolbur, providing molecular data in comparison with previous investigations.


Bone strength is reduced in a neonatal androgenized rat model.
Whether polycystic ovary syndrome (PCOS) affects bone health during a woman's lifespan remains controversial. An androgenized rodent model replicated many metabolic and reproductive features of women with PCOS, and we aimed to use it to investigate the impact of androgens on microarchitecture (by micro-CT), bone mechanical strength, bone formation and resorption markers in rats with intact ovaries (SHAM) who underwent oophorectomy. Wistar rats (Rattus norvegicus albinus) were employed for the experiments in this study. The protocol of androgenization consisted of the application of 1.25 mg s.c. testosterone propionate beteween days 2-5 of life, while the controls received the same amount of corn oil s.c. as previously established. Androgenized SHAM rats exhibited chronic anovulation identified by vaginal cytology and a reduction in the proportion of corpus luteum in the ovary in comparison to control SHAM rats. The realization of the ovariectomy or SHAM procedure occurred on Day 100 of life. All groups (n = 8) were followed-up for 180 days to address the study endpoints. Micro-CT from androgenized female rats (SHAM) showed a divergence between the trabecular and cortical bone profiles. Compared to SHAM controls, these rats had an increase in trabecular bone mass with a diminution in bone resorption C-terminal telopeptide of type 1 collagen (CTX) (p < 0.05), a concomitant decrease in cortical area and thickness in the femur, and a reduction in the strength of the femur on the mechanical test (p < 0.01). Our results suggest that a reduction in the cortical thickness and cortical area observed in PCOS model rats was associated with a reduced strength of the femur, despite increased trabecular formation. Ovariectomy in the androgenized OVX group limited the progression rate of cortical bone loss, resulting in bone resistance and cortical thickness comparable to those observed in the control OVX group.


Interstitial 6q deletion: clinical and array CGH characterisation of a new patient.
We report on a patient with an interstitial 6q deletion presenting with moderate mental retardation, persisting hypotonia, facial dysmorphism, but no internal malformations. Standard cytogenetic analysis identified a de novo interstitial 6q deletion. Molecular karyotyping using a 1 Mb array estimated the size of the deletion at approximately 14 Mb encompassing band q16 of chromosome 6. This case report illustrates how the molecular delineation enables improved genotype-phenotype correlations of chromosomal abnormalities to be made and may improve medical care and genetic counselling in individuals with chromosomal imbalances.


First records of Ungla Navás (Neuroptera: Chrysopidae) from Venezuela, with descriptions of seven new species.
Ungla Navás is a small and relatively unstudied genus of Neotropical Chrysopini (Neuroptera: Chrysopidae: Chrysopinae) from Central and South America. Here, the genus is reported from Venezuela for the first time, and seven new species are described: Ungla demarmelsi sp. nov.; Ungla diazi sp. nov.; Ungla curimaguensis sp. nov.; Ungla martinsi sp. nov.; Ungla nigromaculifrons sp. nov.; Ungla rubricosa sp. nov.; and Ungla yutajensis sp. nov.


Distributions of 137Cs and 90Sr activity concentrations in trunk of Scots pine (Pinus sylvestris L.) in the Chernobyl zone.
Possibility of the economical utilization of forests in the radioactive contaminated areas depends on compliance of the radionuclide activity concentrations in wood with the hygiene norms or national standards that are established by the governments or regulators. Since such regulations consider wood as a whole, development of the sampling methods for assessment of compliance of wood to the norms or standards requires the adequate addressing the issues related to heterogeneity of the radionuclide distributions within the tree trunks. In this paper we present spatial distributions of the 90Sr and 137Cs activity concentrations in the trunk wood of mature Scots pine (Pinus sylvestris L.) trees in the Chernobyl exclusion zone in the late stage (30 years) after the deposition. Four 52-53 year old model trees were sampled in the forest stand located in approximately 5 km from the accidental nuclear reactor. The radionuclide concentrations were measured in 156 wood samples collected from the wood disks cut off the tree trunks at the set of heights. To address variability of the tree sizes and radionuclide concentrations between the individual trees, we applied the corresponding relative indices enabling identification of the general patterns of the spatial distributions of 90Sr and 137Cs. We demonstrated significant differences in bioavailability and distribution trends between the studied radionuclides. 137Cs is translocated to the younger parts of the tree trunk, while the 90Sr concentrations are higher in heartwood and in senescing tissues, which is explained by the different chemical properties of Cs and Sr and by different physiological roles played in plant development by their chemical analogs and major plant nutrition elements, Ca and K respectively. In this reason, the principal distribution patterns of the studied radionuclides in the trunk wood do not significantly change with time, and the results of our study generally are in good agreement with those obtained in the earlier stage after the deposition. The above trends are clearly expressed in both radial and longitudinal directions and result in systematic deviation of the concentrations estimated based on core sampling from the average concentrations in the whole tree trunk.