Nicardipine and adenosine "flush cocktail" to prevent no-reflow during rotational atherectomy.
Rotational atherectomy (RA) has a unique mechanism of action-it utilizes plaque abrasion with microparticle embolization in order to achieve luminal enlargement. This microscopic atheroembolic debris can lead to platelet activation, with vasoconstriction and/or mechanical obstruction of distal coronary resistance vessels, leading to no-reflow and myocardial necrosis. We developed a prospective registry to evaluate the efficacy of the prophylactic administration of intracoronary nicardipine and adenosine within the RA "flush cocktail" as a method of preventing no-reflow and non-Q-wave myocardial infarction (MI) in patients treated with RA in their native coronary arteries. One hundred seventy-six consecutive patients (204 lesions; mean age, 66+/-12 years) were treated with a flush cocktail containing nicardipine (10 microg/ml), adenosine (5 microg/ml), nitroglycerin (10 microg/ml), and unfractionated heparin (1 IU/ml) during RA. The primary study end points were postprocedural Thrombolysis in Myocardial Infarction (TIMI) flow score and non-Q-wave MI, as determined by creatine phosphokinase (CPK) and creatine phosphokinase-MB (CPK-MB) levels. Secondary end points included baseline and acute final minimum lumen diameters, and percent diameter stenosis. TIMI flow scores were analyzable in 155 of 176 patients (88%), and in 181 of 204 treated vessels/lesions (88.7%). As compared to baseline, the final TIMI score worsened in 4 patients (2%), was unchanged in 121 patients (78%), and improved in 30 patients (19%). One hundred fifty of 155 patients (96.7%), and 175 of 181 treated vessels (96.6%) had TIMI 3 flow at the completion of the procedure. Excluding those patients with elevated baseline CPK values of >190 IU/l (n=7), only 5 of 176 (2.8%) patients had CPK-MB values more than three times the upper limit of normal at 12-18 h postprocedure. There were no in-hospital Q-wave MIs or deaths. An intracoronary flush cocktail containing a combination of two potent arteriolar vasodilators, nicardipine and adenosine, appears to be a safe and effective regimen for minimizing no-reflow events and periprocedural myonecrosis during RA.


ZIF67@MFC-Derived Co/N-C@CNFs Interconnected Frameworks with Graphitic Carbon-Encapsulated Co Nanoparticles as Highly Stable and Efficient Electrocatalysts for Oxygen Reduction Reactions.
Development of nonprecious metal catalysts for oxygen reduction reaction (ORR) to reduce or eliminate Pt-based electrocatalysts is of great importance for fuel cells. Herein, Co/N-codoped carbon with carbon nanofiber (CNF) interconnected three-dimensional (3D) frameworks and graphitic carbon-encapsulated Co nanoparticles were designed and successfully prepared via the in situ growth of zeolitic imidazolate framework-67 (ZIF67) with biomass nano-microfibrillar cellulose (MFC) and then pyrolysis. The catalyst (Co/N-C@CNFs) exhibited outstanding long-term catalytic durability with 92.7% current retention after 70 000 s, which was much higher than that of commercial Pt/C in alkaline media. The support and connection of CNFs to Co/N-C frameworks and the protection of Co nanoparticles by graphite layers contribute to their impressive long-term catalytic stability. Meanwhile, Co/C-N@CNFs displayed excellent ORR catalytic performance (E0 = 0.952 V vs RHE, E1/2 = 0.852 V vs RHE, and n: 4.2) in alkaline media. This strategy provides new insights into developing advanced nonprecious metal carbon-based catalysts for ORR.


Enhancing saccharification of wheat straw by mixing enzymes from genetically-modified Trichoderma reesei and Aspergillus niger.
To increase the efficiency of enzymatic hydrolysis for plant biomass conversion into renewable biofuel and chemicals. By overexpressing the point mutation A824 V transcriptional activator Xyr1 in Trichoderma reesei, carboxymethyl cellulase, cellobiosidase and β-D-glucosidase activities of the best mutant were increased from 1.8 IU/ml, 0.1 IU/ml and 0.05 IU/ml to 4.8 IU/ml, 0.4 IU/ml and 0.3 IU/ml, respectively. The sugar yield of wheat straw saccharification by combining enzymes from this mutant and the Aspergillus niger genetically modified strain ΔcreA/xlnR c/araR c was improved up to 7.5 mg/ml, a 229 % increase compared to the combination of wild type strains. Mixing enzymes from T. reesei and A. niger combined with the genetic modification of transcription factors is a promising strategy to increase saccharification efficiency.


Expression in E. coli of the catalytic domain of rat poly(ADP-ribose)polymerase.
A 2 kilobase pair cDNA coding for the entire C-terminal catalytic domain of rat poly(ADP-ribose)polymerase has been expressed in E. coli. The overproduced 55 kDa polypeptide is active in synthesizing poly(ADP-ribose) and the 4 kDa N-terminal region of this domain is recognized by the monoclonal antibody C I,2 directed against the calf enzyme. Also, the minor alpha-chymotrypsin cleavage site found in the human catalytic domain is not present in the rat enzyme as revealed by the absence of the 40 kDa specific degradation product in the E. coli cells expressing the rat domain. The expression of this partial rat cDNA should thus permit the rapid purification and subsequent crystallization of the catalytic domain of the enzyme.


Indian Academy of Pediatrics Guidelines on Screen Time and Digital Wellness in Infants, Children and Adolescents.
Screen-based media have become an important part of human lifestyle. In view of their easy availability and increasing use in Indian children, and their excessive use being linked to physical, developmental and emotional problems, there is a need to develop guidelines related to ensure digital wellness and regulate screen time in infants, children, and adolescents. To review the evidence related to effects of screen-based media and excessive screen time on children's health; and to formulate recommendations for limiting screen time and ensuring digital wellness in Indian infants, children and adolescents. An Expert Committee constituted by the Indian Academy of Pediatrics (IAP), consisting of various stakeholders in private and public sector, reviewed the literature and existing guidelines. A detailed review document was circulated to the members, and the National consultative meet was held online on 26th March 2021 for a day-long deliberation on framing the guidelines. The consensus review and recommendations formulated by the Group were circulated to the participants and the guidelines were finalized. Very early exposure to screen-based media and excessive screen time (>1-2h/d) seems to be widely prevalent in Indian children. The Group recommends that children below 2 years age should not be exposed to any type of screen, whereas exposure should be limited to a maximum of one hour of supervised screen time per day for children 24-59 months age, and less than two hours per day for children 5-10 years age. Screen time must not replace other activities such as outdoor physical activities, sleep, family and peer interaction, studies and skill development, which are necessary for overall health and development of the children and adolescents. Families should ensure a warm, nurturing, supportive, fun filled and secure environment at home, and monitor their children's screen use to ensure that the content being watched is educational, age-appropriate and non-violent. Families, schools and pediatricians should be educated regarding the importance of recording screen exposure and digital wellness as a part of routine child health assessment, and detect any signs of cyberbullying or media addiction; and tackle it timely with expert consultation if needed.


[Problems of the cutaneous malignant melanoma near the eye (author's transl)].
A description is given of a cutaneous malignant melanoma in the region of the lid angle with involvement of the upper and lower lid and the tarsal and bulbal conjunctiva.


miR-502-5p affects gastric cancer progression by targeting PD-L1.
Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer. Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot. The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels. These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.


Concepts in ectopic hormone production.
Non-endocrine tumours are capable of production of ectopic hormones, precursor molecules subunits and hormone-related fragments. The measurement of these may provide biochemical markers of malignancy, allowing presymptomatic diagnosis which may lead ultimately to an improved prognosis for the patient. The study of ectopic humoral syndromes may yield new insights into the nature of cellular differentation and the fundamental process of malignant change.


Gynecologic Ultrasound Evaluation of the Nongravid Woman with Pelvic Pain.
Pelvic pain is a common condition. Many underlying gynecologic and nongynecologic conditions can contribute to this symptom. Pelvic ultrasound using comprehensive 2-dimensional interactive imaging techniques as well as color Doppler and 3-dimensional imaging optimizes the detection of inciting etiologies.


[Changes of coagulation parameters during stimulation in the IVF programme and in ovarian hyperstimulation syndrome].
Evaluation of changes in hemostasis system during the ovarian stimulation in IVF programme and in patients with severe form of ovarian hyperstimulation syndrome. Review article. Unica, Institute for Reproductive Medicine, Brno. Survey and discussion based on literature review. Activation of coagulation system during the ovarian stimulation and in the development of ovarian hyperstimulation syndrome is mentioned. The risk of thrombosis is increased if the patient is carrier of thrombophilic status.


Erythropoietic effects of space flight.
Various factors which are important in the regulation of erythropoiesis have been studied in dehydrated mice in the belief that some information would be gained relevant to the erythropoietic effects of space flight. Dehydration reduced the plasma volume and, because changes in red cell volume were minimal, the hematocrit was elevated. Thus a state of relative erythrocytosis was produced. Our understanding of the mechanism whereby these changes decreased red cell production is uncertain and appears to differ somewhat from the erythroid suppression seen following elevation of the hematocrit in animals with an absolute erythrocytosis. It is suggested that factors outside of the normal erythropoietic control pathway (such as energy balance) may play an important role in the decrease in red cell volume seen in man following space flight.


GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells.
Hippocampal activity influences neurogenesis in the adult dentate gyrus; however, little is known about the involvement of the hippocampal circuitry in this process. In the subgranular zone of the adult dentate gyrus, neurogenesis involves a series of differentiation steps from radial glia-like stem/progenitor (type-1) cells, to transiently amplifying neuronal progenitor (type-2) cells, to postmitotic neurons. In this study, we conducted GFP-targeted recordings of progenitor cells in fresh hippocampal slices from nestin-GFP mice and found that neuronal progenitor (type-2) cells receive active direct neural inputs from the hippocampal circuitry. This input was GABAergic but not glutamatergic. The GABAergic inputs depolarized type-2 cells because of their elevated [Cl(-)](i). This excitation initiated an increase of [Ca(2+)](i) and the expression of NeuroD. A BrdU-pulse labeling study with GABA(A)-R agonists demonstrated the promotion of neuronal differentiation via this GABAergic excitation. Thus, it appears that GABAergic inputs to hippocampal progenitor cells promote activity-dependent neuronal differentiation.


Prevention and early treatment of opportunistic viral infections in patients with leukemia and allogeneic stem cell transplantation recipients.
A leading complication of leukemia therapy and stem cell transplantation is opportunistic viral infections. Infections caused by cytomegalovirus, herpes simplex, varicella-zoster, Epstein-Barr, and the community respiratory viruses are associated with significant morbidity and mortality in this highly immunosuppressed population. Fortunately, a growing armamentarium is allowing more effective prophylaxis of these pathogens. This article reviews the epidemiology and prophylactic strategies available for these common opportunistic viral pathogens.


Dysfunctional temporal stages of eye-gaze perception in adults with ADHD: A high-density EEG study.
ADHD has been associated with social cognitive impairments across the lifespan, but no studies have specifically addressed the presence of abnormalities in eye-gaze processing in the adult brain. This study investigated the neural basis of eye-gaze perception in adults with ADHD using event-related potentials (ERP). Twenty-three ADHD and 23 controls performed a delayed face-matching task with neutral faces that had either direct or averted gaze. ERPs were classified using microstate analyses. ADHD and controls displayed similar P100 and N170 microstates. ADHD was associated with cluster abnormalities in the attention-sensitive P200 to direct gaze, and in the N250 related to facial recognition. For direct gaze, source localization revealed reduced activity in ADHD for the P200 in the left/midline cerebellum, as well as in a cingulate-occipital network at the N250. These results suggest brain impairments involving eye-gaze decoding in adults with ADHD, suggestive of neural signatures associated with this disorder in adulthood.


End of life care for the most common women cancers in Taiwan.
Women with terminal cancer are assumed to choose hospice care over aggressive treatment at the end of life. With new chemotherapy and target therapy options, it becomes more difficult to decide between hospice care and aggressive management. It is also crucial to consider the cost increases leading to severe financial burdens on healthcare systems. To better understand treatment options at the individual level, this study set out to describe trends in end-of-life care for the four leading cancers in women in Taiwan. This was a population-based retrospective cohort study. The data source was obtained between January 1, 2000, and December 31, 2013, from Taiwan's National Health Insurance Research Database. We identified 98,575 women with a diagnosis of breast (18,596), colorectal (23,734), liver and biliary (28,795) or lung (27,450) cancer who had died during the study period. Hospital data for services provided in the last 6 months of life, including hospice services and aggressive managements (chemotherapy, frequent hospitalisation, emergency room [ER] visits, intensive care unit [ICU] admission and endotracheal intubation), were collected. Hospice utilisation increased over the study period, with 25.85%, 25.34%, 21.23% and 26.55% of female patients with breast, colorectal, liver and biliary, and lung cancer receiving hospice care, respectively. However, the number of women undergoing aggressive treatments in the last 6 months of life remained high, with the breast cancer group having the highest chemotherapy rate, the colorectal cancer group having frequent hospitalisation and the liver and biliary cancer group having frequent ER visits and ICU admissions. Increasing hospice utilisation among women with the four most common cancers in Taiwan indicates that hospice services have gradually become well accepted over the past 13 years; however, the real focus is on the ineffective treatment preceding hospice care, and late referral was also a notable problem.


Macrophage-stimulating protein polymorphism rs3197999 is associated with a gain of function: implications for inflammatory bowel disease.
Crohn's disease and ulcerative colitis, the two main types of inflammatory bowel disease (IBD), were reported to be associated with a variety of genetic polymorphisms. A subset of these polymorphisms was identified in both diseases and only three of them were found in primary sclerosing cholangitis (PSC). rs3197999 (Arg689Cys) located in the MST1 gene is one of the most convincingly replicated IBD/PSC-associated polymorphisms but its functional consequences have not been investigated, yet. We expressed both MST1 gene variants (Arg(689) (MSP(wt)) and Cys(689) (MSP(mut)) in a eukaryotic cell system and compared their stimulatory effects on macrophage-like THP-1 cells. Except for the rate of apoptosis that remained unchanged, MSP(mut) significantly increased the stimulatory effect of MSP (macrophage-stimulating protein) on chemotaxis and proliferation by THP-1 cells, indicating a gain of function associated with the Arg689Cys exchange. A broad set of evidence reported previously suggests that pro-inflammatory changes in macrophage function have a major role in the initiation of the inflammatory process in IBD and PSC. Therefore, the gain of function observed with rs3197999 in MST1 might provide a cellular mechanism for the consistent association of this polymorphism with an increased risk for IBD and PSC.


ABSDELL Model: Development and Internal Validation of a Risk Prediction Model of LVEF Decline in Breast Cancer Patients Treated With Trastuzumab.
This study aims to establish an integrated model for predicting trastuzumab-associated decline of Left ventricular ejection fraction (LVEF) during drug administration. A retrospective study of 212 women who diagnosed with HER2-positive breast cancer and treated with chemotherapy and trastuzumab was conducted. Medical records were collected from 6 months before staring trastuzumab to 3 years afterwards. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to select variables, time-dependent receiver operating characteristic (ROC) curve and calibration plots were used to evaluate the model. The adjusted C-index and Brier scores were calculated using a bootstrap internal validation procedure. The median age of participants is 53.2 years old. The median length of follow-up was 336 days. There were 72 patients (33.96%) whose LVEF declined ≥ 10% (10 absolute percent points). Seven factors, namely age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), mitral peak E-wave velocity (E-wave), left ventricular end-systolic diameter (LVESD) and LVEF, were selected. The name of the ABSDELL model was formed by the initials of each predictor. The area under the curve (AUC) of the model was 0.802 in 1 year and 0.881 in 3 years. Calibration plots indicate the predicted and actual probabilities were highly consistent. In the internal validation, 1-year and 3-year adjusted C-index was 0.801 and 0.881, and adjusted Brier score was 0.118 and 0.091, separately. The ABSDELL model can effectively predicts the probability of LVEF decline in breast cancer patients treated with trastuzumab.


Effective Prognostic Model for Therapy Response Prediction in Acute Myeloid Leukemia Patients.
Acute myeloid leukemia (AML) is a hematopoietic disorder characterized by the malignant transformation of bone marrow-derived myeloid progenitor cells with extremely short survival. To select the optimal treatment options and predict the response to therapy, the stratification of AML patients into risk groups based on genetic factors along with clinical characteristics is carried out. Despite this thorough approach, the therapy response and disease outcome for a particular patient with AML depends on several patient- and tumor-associated factors. Among these, tumor cell resistance to chemotherapeutic agents represents one of the main obstacles for improving survival outcomes in AML patients. In our study, a new prognostic scale for the risk stratification of AML patients based on the detection of the sensitivity or resistance of tumor cells to chemotherapeutic drugs in vitro as well as MDR1 mRNA/P-glycoprotein expression, tumor origin (primary or secondary), cytogenetic abnormalities, and aberrant immunophenotype was developed. This study included 53 patients diagnosed with AML. Patients who received intensive or non-intensive induction therapy were analyzed separately. Using correlation, ROC, and Cox regression analyses, we show that the risk stratification of AML patients in accordance with the developed prognostic scale correlates well with the response to therapy and represents an independent predictive factor for the overall survival of patients with newly diagnosed AML.


Effect of exogenous thymidine on sister-chromatid exchange frequency in Chinese hamster ovary cells with bromodeoxyuridine- and chlorodeoxyuridine-substituted chromosomes.
There are conflicting reports on the effect of exogenous thymidine (dThd) on the frequency of sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells. Thymidine has been reported either to increase or to have no effect on SCE frequency under similar experimental conditions. To resolve this controversy, we have carried out a series of experiments to examine the effect of dThd on CHO cells cultured with 5-bromodeoxyuridine (BrdUrd). In addition, we have examined the effect of dThd on CHO cells cultured with 5-chlorodeoxyuridine (CldUrd), a much more potent inducer of SCEs than BrdUrd. The addition of 100 microM dThd to the culture medium caused a consistent decrease in the yield of SCEs in cells grown in BrdUrd for two cell cycles. The decrease was even greater when cells were grown in dThd and CldUrd. Analysis of twin and single SCEs indicated that dThd must be present during the first cell cycle to reduce the frequency of SCEs. Because excess dThd is thought to have an effect when DNA replicates on a template substituted with a halogenated nucleoside, dThd at concentrations from 100 microM to 9 mM was added to cultures for the second cell cycle after a first cell cycle in BrdUrd. In this experiment, the presence of dThd increased SCE frequency in a dose-dependent manner. The results suggest that if dThd competes with halogenated nucleosides and thus decreases their incorporation into DNA, SCEs are suppressed in the subsequent cell cycle, whereas if excess dThd creates a dNTP pool imbalance, SCEs can be increased.


Plasma-initiated polymerization of chitosan-based CS-g-P(AM-DMDAAC) flocculant for the enhanced flocculation of low-algal-turbidity water.
In this work, a highly efficient and environmentally friendly chitosan-based graft flocculant, namely, acrylamide- and dimethyl diallyl ammonium chloride-grafted chitosan [CS-g-P(AM-DMDAAC)], was prepared successfully through plasma initiation. FTIR results confirmed the successful polymerization of CS-g-P(AM-DMDAAC) and P(AM-DMDAAC). P(AM-DMDAAC) was the copolymer of acrylamide- and dimethyl diallyl ammonium chloride. SEM results revealed that a densely cross-linked network structure formed on the surface. XRD results verified that the ordered crystal structure of chitosan in CS-g-P(AM-DMDAAC) was changed into an amorphous structure after plasma-induced polymerization. The flocculation results of low-algal-turbidity water further showed the optimal flocculation efficiency of turbidity removal rate, COD removal rate, and Chl-a removal rate were 99.02%, 96.11%, and 92.20%, respectively. The flocculation efficiency of CS-g-P(AM-DMDAAC) were significantly higher than those obtained by cationic polyacrylamide (CPAM) and Polymeric aluminum and iron (PAFC). This work provided a valuable basis for the design of eco-friendly naturally modified polymeric flocculants to enhance the flocculation of low-algal-turbidity water.


Load displacement behavior of the human lumbo-sacral joint.
The three-dimensional load displacement behavior of nine fresh adult L5-S1 spine motion segments was studied. Static test forces up to 160 N in anterior, posterior, and lateral shear, test forces up to 320 N in compression, and test moments up to 15.7 Nm in flexion, extension, lateral bending, and torsion were used. The six displacements of the center of the inferior L5 endplate were measured 15 and 60 s after the load was applied. Specimens were then retested after posterior element excision. The results show that at the maximum test force, intact specimen mean (SD) displacements ranged from 1.65 mm (0.63 mm) in lateral shear to 2.21 mm (0.87 mm) in posterior shear. Posterior element excision resulted in an average 1.66-fold increase in shear translations. At the maximum moment, rotations ranged from 3.38 degrees (1.03 degrees) in torsion to 7.19 degrees (1.77 degrees) in flexion. Posterior element excision resulted in an average 2.09-fold increase in bending rotations and a 2.74-fold increase in the average torsional rotation. In general, these L5-S1 joints were stiffer than more cranial lumbar segments in flexion, extension, and lateral bending and were less stiff in torsion tests.


Genome-association analysis of Korean Holstein milk traits using genomic estimated breeding value.
Holsteins are known as the world's highest-milk producing dairy cattle. The purpose of this study was to identify genetic regions strongly associated with milk traits (milk production, fat, and protein) using Korean Holstein data. This study was performed using single nucleotide polymorphism (SNP) chip data (Illumina BovineSNP50 Beadchip) of 911 Korean Holstein individuals. We inferred each genomic estimated breeding values based on best linear unbiased prediction (BLUP) and ridge regression using BLUPF90 and R. We then performed a genome-wide association study and identified genetic regions related to milk traits. We identified 9, 6, and 17 significant genetic regions related to milk production, fat and protein, respectively. These genes are newly reported in the genetic association with milk traits of Holstein. This study complements a recent Holstein genome-wide association studies that identified other SNPs and genes as the most significant variants. These results will help to expand the knowledge of the polygenic nature of milk production in Holsteins.


Cellular and Subcellular Level Localization of Maize Lipids and Metabolites Using High-Spatial Resolution MALDI Mass Spectrometry Imaging.
Recent technological advances have pushed the achievable spatial resolution for mass spectrometry imaging (MSI) to cellular and subcellular levels. Direct visualization of maize tissues by this tool has provided key insights into the localization of metabolites and lipids. This chapter outlines methodology for sample preparation, data acquisition, and data analysis of maize tissue sections using high-spatial resolution matrix-assisted laser desorption ionization (MALDI)-MSI, as well as the incorporation of a multi-resolution optical system, which allows for simple inter-conversion between different resolution setups (5, 10, and 50 μm imaging).


Evaluation of congenital left ventricular aneurysm in the fetus by velocity vector imaging.
We report a case of left ventricular aneurysm evaluated using the velocity vector imaging (VVI) technique, an angle-independent method used to calculate the tissue velocity strain and strain rate on routine gray scale two-dimensional images and display the velocities of endocardial points as vectors overlaid on B-mode images. It uses a combination of speckle tracking and complex geometric analysis, allowing tracing of myocardial activity throughout the cardiac cycle. In this case, evaluation of the myocardial dynamics in the fetus by VVI was started at 27 weeks of gestation, and both the systolic and diastolic velocities and the ejection fraction in the aneurysmal segment were less than in the other segments. VVI imaging at 35 weeks of gestation showed this difference even more clearly. Postnatal VVI examination showed no significant difference between results for the systolic and diastolic velocities or ejection fraction and those obtained at the prenatal VVI examination. VVI seemed to be as useful at this time, especially for assessing ventricular systolic function, as it was for postnatal examination.


Oxycodone vs. fentanyl in the treatment of early post-operative pain after laparoscopic cholecystectomy: a randomised double-blind study.
It has been suggested that oxycodone is superior to other opioids in the treatment of visceral pain. We therefore compared the effect of intravenous (i.v.) oxycodone and i.v. fentanyl on post-operative abdominal (visceral) pain after outpatient laparoscopic cholecystectomy. Seventy-eight patients were randomised to intra- and post-operative pain treatment with either oxycodone (n=39) or fentanyl (n=39). The patients received 10 mg oxycodone/100 microg fentanyl at the end of anaesthesia. In the post-anaesthetic care unit (PACU), 5 mg oxycodone/50 microg fentanyl was administered to patients with moderate pain [3-5 on a numeric rating scale (NRS)], and 10 mg oxycodone/100 microg fentanyl was administered to patients with severe pain (>5 on an NRS). The following measures were recorded: intensity of pain at arrival, after 30, 60 and 90 min and at discharge from the PACU; total consumption of oxycodone/fentanyl; nausea; vomiting; sedation and pressure tolerance thresholds. The median intra- and post-operative consumption of oxycodone was 15 mg (range: 10-40 mg) and the consumption of fentanyl was 200 microg (range: 100-500 microg). The intensity of abdominal pain was significantly lower in the oxycodone group at arrival (P<0.05), after 30, 60 and 90 min, and at discharge from the PACU (P<0.01). There was a strong tendency towards more side effects with oxycodone. Oxycodone provided better analgesia but also more side effects, suggesting that the doses used in the present study may not be equipotent.


Skin B/N-doped anatase TiO2 {001} nanoflakes for visible-light photocatalytic water oxidation.
The limited visible-light-responsive photoactivities of most doped wide-bandgap photocatalysts with widened absorption range have long been the obstacles for the efficient conversion of solar energy to chemical energy by photocatalysis. The weak transport ability of visible-light-induced low-energy charge carriers, and numerous recombination centers arising from the energy-band modifiers along the transport path are two major factors responsible for such a mismatch. A potential solution is to shorten the transport path of photo-induced charges in well-modulated light absorbers with low-dimensional structure and the spatially concentrated dopants underneath their surfaces. As a proof of concept, skin B/N-doped red anatase TiO2 {001} nanoflakes with the absorption edge up to 675 nm were synthesized in this study. Experimental results revealed that boron dopants in the TiO2 nanoflakes from the hydrolysis of nanosized TiB2 played a crucial role in controlling nitrogen doping in the surface layer of the nanoflakes. As visible light excitation occurs at the surface layer, the photons can be sufficiently absorbed by the formed energy levels at the surface layers, and the photogenerated charge carriers can effectively migrate to the surface, thus leading to efficient visible-light-responsive photocatalytic oxygen evolution activity from water oxidation.


L-tryptophan transport through a hydrophobic liquid membrane using AOT micelles: dynamics of the process as revealed by small angle X-ray scattering.
Hydrophobic liquid membranes have a high technological potential in many fields of separation science. The dynamics of these systems is very complex and still not fully understood. In this work we studied the effect of the incorporation of cationic and anionic L-tryptophan at pH 1.8 and 10.0, respectively, in Aerosol-OT reverse micelles performing small angle X-ray scattering experiments. The use of a synchrotron radiation source allowed efficient in situ data acquisition. Several insights on L-tryptophan transport dynamics through hydrophobic membranes containing AOT could be obtained from these SAXS experiments, such as amino acid site localization and changes in the reverse micelle sizes.


Unraveling the effects of low protein-phenol binding affinity on the structural properties of beta-lactoglobulin.
Non-covalent interactions of phenolics with proteins cannot always be readily identified, often leading to contradictory results described in the literature. This results in uncertainties as to what extent phenolics can be added to protein solutions (for example for bioactivity studies) without affecting the protein structure. Here, we clarify which tea phenolics (epigallocatechin gallate (EGCG), epicatechin and gallic acid) interact with the whey protein β-lactoglobulin by combining various state-of-the-art-methods. STD-NMR revealed that all rings of EGCG can interact with native β-lactoglobulin, indicating multidentate binding, as confirmed by the small angle X-ray scattering experiments. For epicatechin, unspecific interactions were found only at higher protein:epicatechin molar ratios and only with 1H NMR shift perturbation and FTIR. For gallic acid, none of the methods found evidence for an interaction with β-lactoglobulin. Thus, gallic acid and epicatechin can be added to native BLG, for example as antioxidants without causing modification within wide concentration ranges.


A diffuse T lymphocytic gastrointestinal mucosal infiltration associated with Sjögren's syndrome resulting in a watery diarrhea syndrome and responsive to immunosuppressive therapy.
We report the case of a 45-yr-old white man, investigated for chronic diarrhea, malabsorption and weight loss associated with sicca syndrome. Endoscopic and x-ray examinations showed normal macroscopic mucosa in gastrointestinal tract (GIT). Immunohistochemistry showed diffuse polyclonal T cell lymphocytes infiltrating either epithelium and lamina propria in GIT. There was no villous atrophy in the jejunum and ileum. Corticosteroids, azathioprine, and cyclosporine failed to improve symptoms. Monthly intravenous cyclophosphamide administered over 1 yr, stopped the diarrhea and weight loss. The patient is free of symptoms up to a 5-yr follow-up.


Management of diastolic heart failure--a practical review of pathophysiology and treatment trial data.
The lack of large randomised controlled trials to guide therapy in diastolic heart failure causes some difficulties for evidence-based medicine practising clinicians. Traditionally, treatments for systolic heart failure have been highjacked for diastolic heart failure without much proof of benefit. However, recent studies have began to provide some evidence base for our practice. Betablockers and angiotensin receptor antagonists have recently been shown to reduce hospitalisation in large randomised controlled trials. Diuretic based antihypertensive regimes have been shown to reduce heart failure by 50%. Left ventricular hypertrophy regression is likely to be a good surrogate endpoint for diastolic heart failure, although definitive proof for this is not yet available. Angiotensin receptor antagonists, ACEI, calcium channel blockers, diuretics and aldosterone blockers have all been shown to cause left ventricular hypertrophy regression. We recommend these drugs to achieve strict blood pressure control together with dietary and lifestyle modification for the treatment of diastolic heart failure. We emphasise the importance of rate control, as diastolic heart-failure patients tolerate tachycardia poorly. We further argue that the pathophysiology of diastolic heart failure is part of systolic heart failure and the two should not be thought of as separate entities. Therefore, our traditional practice of using systolic heart failure treatments for diastolic heart failure is theoretically sound and should not cause us undue anxiety.


Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury.
Although dialysis has been used in the care of patients with acute kidney injury (AKI) for over 50 years, very little is known about the potential benefits of uremic control on systemic complications of AKI. Since the mortality of AKI requiring renal replacement therapy (RRT) is greater than half in the intensive care unit, a better understanding of the potential of RRT to improve outcomes is urgently needed. Therefore, we sought to develop a technically feasible and reproducible model of RRT in a mouse model of AKI. Models of low- and high-dose peritoneal dialysis (PD) were developed and their effect on AKI, systemic inflammation, and lung injury after ischemic AKI was examined. High-dose PD had no effect on AKI, but effectively cleared serum IL-6, and dramatically reduced lung inflammation, while low-dose PD had no effect on any of these three outcomes. Both models of RRT using PD in AKI in mice reliably lowered urea in a dose-dependent fashion. Thus, use of these models of PD in mice with AKI has great potential to unravel the mechanisms by which RRT may improve the systemic complications that have led to increased mortality in AKI. In light of recent data demonstrating reduced serum IL-6 and improved outcomes with prophylactic PD in children, we believe that our results are highly clinically relevant.


Morningness and eveningness: when do patients take their antiepileptic drugs?
Almost one-third of epilepsy patients continue to have seizures despite adequate drug treatment. Chronotherapy (based on dynamic changes in drug pharmacology and disease-related processes) could be a promising treatment option. We aimed to explore whether different circadian types adjust administration times of anti-epileptic drugs (AEDs) as a step in exploring chronotherapeutic possibilities. We performed a questionnaire-based study to compare behavior of different circadian types in relation to times of taking drugs. Circadian type was determined by the Morningness-Eveningness Questionnaire. Results clearly show that morning types are taking their AEDs significantly earlier than do evening types on free days. Times of taking AEDs in the morning on work days also differ significantly between morning and evening types. Regardless of circadian type, drugs on free days are taken later than on working days. In conclusion, our study shows that patients adapt times of taking medication to their circadian type.


Alcian blue pyridine variant interaction with DNA and RNA polynucleotides and G-quadruplexes: changes in the binding features for different biosubstrates.
This work concerns an analysis of the binding mechanism of a copper phthalocyanine (Alcian Blue-tetrakis(methylpyridinium) chloride, ABTP) to natural calf thymus DNA, G-quadruplexes (G4) and synthetic RNA polynucleotides in the form of double polyriboadenylic·polyribouridylic acid (poly(A)·poly(U)) or triple strands polyriboadenylic·2polyribouridylic acid (poly(A)·2poly(U)). ABTP is a well know dye that might undergo novel applications, but its interaction with DNA is scarcely studied and we lack information on possible RNA or G4 binding. This might be related to system complexity due to the presence of supramolecular dye-dye aggregates. Despite this, we show here that apparent parameters can be calculated, which provide information on the binding mechanism. Absorbance titrations in the presence of biosubstrate excess, melting and circular dichroism experiments show that ABTP binds to both RNAs and DNA. External/groove binding is the main feature for RNAs, whereas partial intercalation is the major binging mode for DNA. ABTP externally binds to both hybrid, parallel and anti-parallel G4s but seem to show a slightly different binding mode and a preference for anti-parallel structures. The thermodynamic features of the different systems are also discussed in the frame of the enthalpy-entropy compensation phenomenon.


Adult mental health provision in England: a national survey of acute day units.
Acute Day Units (ADUs) exist in some English NHS Trusts as an alternative to psychiatric inpatient admission. However, there is a lack of information about the number, configuration, and functioning of such units, and about the extent to which additional units might reduce admissions. This cross-sectional survey and cluster analysis of ADUs aimed to identify, categorise, and describe Acute Day Units (ADUs) in England. English NHS Mental Health Trusts with ADUs were identified in a mapping exercise, and a questionnaire was distributed to ADU managers. Cluster analysis was used to identify distinct models of service, and descriptive statistics are given to summarise the results of the survey questions. Two types of service were identified by the cluster analysis: NHS (n = 27; and voluntary sector services (n = 18). Under a third of NHS Trusts have access to ADUs. NHS services typically have multi-disciplinary staff teams, operate during office hours, offer a range of interventions (medication, physical checks, psychological interventions, group sessions, peer support), and had a median treatment period of 30 days. Voluntary sector services had mostly non-clinically qualified staff, and typically offered supportive listening on a one-off, drop-in basis. Nearly all services aim to prevent or reduce inpatient admissions. Voluntary sector services had more involvement by service users and carers in management and running of the service than NHS services. The majority of NHS Trusts do not provide ADUs, despite their potential to reduce inpatient admissions. Further research of ADUs is required to establish their effectiveness and acceptability to service users, carers, and staff.


The effect of L-carnitine supplementation on insulin resistance, sex hormone-binding globulin and lipid profile in overweight/obese women with polycystic ovary syndrome: a randomized clinical trial.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. Insulin resistance and dyslipidemia are linked to PCOS. L-Carnitine supplementation as a management strategy for women with PCOS has been proposed. The effect of L-carnitine supplementation on insulin resistance, sex hormone-binding globulin (SHBG) and lipid profile in overweight/obese women with PCOS was investigated. This randomized, double-blind, controlled clinical trial, was conducted on 62overweight/obese women with PCOS. Participants were randomly assigned into two groups to receive 1000 mg/day L-carnitine or placebo (1000 mg starch) for 12 weeks. L-Carnitine supplementation compared to the placebo showed a significant improvement in insulin [- 0.7 (- 7.3 to 4.0) vs. 0.7 (- 3.0 to 5.2); P = 0.001], homeostatic model assessment for insulin resistance [- 0.4 (- 1.7 to 1.1) vs. 0.0 (- 0.7 to 1.3); P = 0.002], quantitative insulin sensitivity check index (+ 0.01 ± 0.02 vs. - 0.01 ± 0.01; P = 0.02) and a non-significant change toward improvement in SHBG (+ 11.5 ± 40.2 vs. - 3.2 ± 40.2; P = 0.2). However, there was no significant differences between the two groups in serum levels of fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein-cholesterol and high density lipoprotein cholesterol (P > 0.05). 12-week L-carnitine supplementation in overweight or obese women with PCOS ameliorate insulin resistance, but has no effect on SHBG and lipid profile. Studies with higher dosages and duration of L-carnitine intake are required. The trial was registered on 30 December 2019 at Iranian Registry of Clinical Trials IRCT20191016045131N1. Registered on 30th December 2019 at Iranian Registry of Clinical Trials (IRCT20191016045131N1).


On-chip cytometry using plasmonic nanoparticle enhanced lensfree holography.
Computational microscopy tools, in particular lensfree on-chip imaging, provide a large field-of-view along with a long depth-of-field, which makes it feasible to rapidly analyze large volumes of specimen using a compact and light-weight on-chip imaging architecture. To bring molecular specificity to this high-throughput platform, here we demonstrate the use of plasmon-resonant metallic nanoparticles to automatically recognize different cell types based on their plasmon-enhanced lensfree holograms, detected and reconstructed over a large field-of-view of e.g., ~24 mm².


Smith-Robinson Procedure with an Autologous Iliac Crest Graft and Caspar Plating: Report of 65 Patients with an Average Follow-up of 22 Years.
Anterior cervical discectomy and fusion with plate stabilization (ACDF+PS) is an accepted surgical procedure. We sought to evaluate the long-term clinical results of ACDF+PS with a special focus on pain, functional outcome, and adjacent segment disease. Retrospectively, 139 patients who underwent ACDF+PS were reviewed with a standardized questionnaire including the current neurologic status, Neck Disability Index, EuroQuol-5 Dimension, Patient Satisfaction Index, Hospital Anxiety and Depression Scale, the Odom criteria, complications at the iliac crest donor side, and limitations in quality of life. Mean follow-up time was 22 years (range: 17-34 years). Sixty five (46.8%) patients were evaluated by completed questionnaires, and 74 (53.2%) did not participate. Forty-six patients attended a physical examination. ACDF+PS were performed at 1 level in 28 patients, at 2 levels in 29 patients, and at 3 levels in 8 patients. Fifty (83.3%) of the patients with preoperative pain remained free of pain and did not require another procedure as the result of degenerative cervical disease. The mean NDI was 14%; according to the Odom criteria 86.2% of patients reported good-to-excellent functional recovery. A total of 100% of patients were satisfied or very satisfied with their outcome and would decide to undergo ACDF+PS again. Two developed adjacent segment disease and needed a second procedure. ACDF+PS resulted in a significant increase in function, pain relief, and to a high degree of patient satisfaction. The rate for symptomatic adjacent segment disease was 4.5% after 20 years' follow-up.


The Celestial Frame and the Weighting of the Celestial Pole Offsets in the Computation of VLBI-Based Corrections for the Main Lunisolar Nutation Terms.
Very long baseline interferometry (VLBI) is the only technique in space geodesy that can determine directly the celestial pole offsets (CPO). In this paper, we make use of the CPO derived from global VLBI solutions to estimate empirical corrections to the main lunisolar nutation terms included in the IAU 2006/2000A precession-nutation model. In particular, we pay attention to two factors that affect the estimation of such corrections: the celestial reference frame used in the production of the global VLBI solutions and the stochastic model employed in the least-squares adjustment of the corrections. In both cases, we have found that the choice of these aspects has an effect of a few μas in the estimated corrections.


[Orthodontic movement and root resorption].
Frequent sequela following orthodontic treatment is some degree of root resorption. Much controversy exists concerning its cause and predisposing factors. The purpose of this study was a review of the literature.


Polydopamine-mediated graphene oxide and nanohydroxyapatite-incorporated conductive scaffold with an immunomodulatory ability accelerates periodontal bone regeneration in diabetes.
Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge. Here, a polydopamine-mediated graphene oxide (PGO) and hydroxyapatite nanoparticle (PHA)-incorporated conductive alginate/gelatin (AG) scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment. PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold. The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca2+ channels. Moreover, the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species (ROS)-scavenging ability and anti-inflammatory activity. It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages. The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive, ROS-scavenging, anti-inflammatory, and immunomodulatory abilities. This study provides fundamental insights into the synergistical effects of conductivity, osteoinductivity, and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.


Venous thromboembolic disease: comparison of the diagnostic process in men and women.
There has been concern that women may be limited to fewer major diagnostic tests than men. Whether this applies to patients with pulmonary embolism (PE) or deep venous thrombosis (DVT) has not been determined. To assess whether there is a sex disparity in the application of diagnostic tests for PE or DVT, in reaching a diagnosis, or in using medical facilities. A study of cross-sectional samples of hospitalizations from 21 separate years using data from the National Hospital Discharge Survey. Noninstitutional hospitals in the 50 states and the District of Columbia from 1979 through 1999. The National Hospital Discharge Survey abstracts demographic and medical information from the medical records of inpatients. For 1979 through 1999, the number of patients sampled ranged from 181000 to 307000.Measurements The number of sampled patients with DVT and with PE and the number of diagnostic tests performed were determined from the International Classification of Diseases, Ninth Revision, Clinical Modification codes at discharge. A multistage estimation procedure gave an estimation of values for the entire United States. Age-adjusted rates of the diagnosis of PE per 100000 population and of DVT per 100000 population were not lower in women. Rates of the use of ventilation-perfusion lung scans, venous ultrasonography of the lower extremities, and contrast venography were not lower in women. Durations of hospitalization for PE or DVT were comparable in men and women. Data from the National Hospital Discharge Survey do not support a sex bias in the diagnosis of PE or DVT, the use of diagnostic tests, or the duration of hospitalization for PE or DVT.


Initial validation of a numeric zero to ten scale to measure children's state anxiety.
Although children experience physical and behavioral consequences from anxiety in many health care settings, anxiety assessment and subsequent management is not often performed because of the lack of clinically useful subjective scales. Current state anxiety scales are either observational or multidimensional self-report measures requiring significant clinician and patient time. Because anxiety is subjective, in this pilot study, we evaluated the validity of a self-report numeric 0-10 anxiety scale that is easy to administer to children in the clinical setting. A descriptive correlation research design was used to determine the concurrent validity for a numeric 0-10 anxiety scale with the state portion of the State-Trait Anxiety Inventory for Children (STAIC). During clinic preoperative visits, 60 children, 7-13 yr, provided anxiety scores for the 0-10 scale and the STAIC pre- and posteducation. Simple linear regression and Pearson correlation were performed to determine the strength of the relationship. STAIC was associated with the anxiety scale both preeducation (beta = 1.20, SE[beta] = 0.34, F[1,58] = 12.74, P = 0.0007) and posteducation (beta = 1.97, SE[beta]) = 0.31, F[1,58] = 40.11, P < 0.0001). Correlations were moderate for pre-education (r = 0.424) and posteducation (r = 0.639). This initial study supports the validity of the numeric 0-10 anxiety self-report scale to assess state anxiety in children as young as 7 yr.


Damien de Veuster (1840-1889): A life devoted to lepers.
Father Damien de Veuster, or Saint Damien of Molokai (1840-1889), was one of the pioneers of the holistic approach to care provision for leprosy patients and contributed to the overcoming of the patients' social stigmatization. He devoted his life to the lepers living in America's only leper colony, on the Hawaiian island of Molokai, where people with leprosy were required to live under government-sanctioned medical quarantine. Father Damien gained practical skills in caring for the sick, eagerly learning wound cleansing, bandaging techniques, and drug administration from a nurse. Mahatma Gandhi said that Father Damien's work had inspired his own social campaigns in India.


Impact of Serum Human Chorionic Gonadotropin and Luteinizing Hormone Receptor Expression to Oocyte Maturation Rate: A Study of Controlled Ovarian Stimulation.
Few studies have assessed the impact of serum human chorionic gonadotropin (hCG) levels before oocyte retrieval and luteinizing hormone receptor (LHR) mRNA expression. The objective was to assess the correlations between serum hCG levels at 12-h posttrigger granulosa cell LHR mRNA expression during the in vitro fertilization (IVF) cycle with oocyte maturation rate and to determine the cutoff level of serum hCG at 12-h posttrigger. A cross-sectional was conducted for this study at the IVF center of Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. Recombinant follicle-stimulating hormone was used on day 2 of the menstrual cycle with multiple doses of a gonadotropin-releasing hormone antagonist. Recombinant hCG was used to trigger ovulation. At 12-h posttrigger, hCG serum levels were measured using an enzyme-linked immunosorbent assay. Pearson's correlation coefficient was used to evaluate the correlation between oocyte maturation rates, serum hCG levels, and LHR mRNA levels. Cutoff values were determined using a receiver operating characteristic (ROC) curve. Serum hCG levels were positively correlated (r = 0.467;P < 0.01), and LHR mRNA expression was weakly correlated (r = 0.073; P = 0.701) with oocyte maturation. The cutoff of serum hCG for a high maturation rate was 77 mIU/mL, with an area under the ROC curve of 0.765 (95% confidence interval: 0.598-0.939) andP < 0.001. Oocyte maturation is correlated with serum hCG levels with 77 mIU/mL as the cutoff point for oocyte retrieval.


Kidney disease progression and collider bias in GWAS.
New genome-wide meta-analysis for longitudinal kidney function decline identified several genetic loci related to kidney disease progression. The study illustrated the complexity of modeling longitudinal traits in genome-wide association studies and highlighted the issue of a collider bias that can be introduced when a kidney disease progression phenotype is adjusted for baseline kidney function. Herein, we briefly outline the key findings of this study, their limitations, and implications for future studies.


Hormone-sensitive adenylate cyclase along the nephron of genetically hypophosphatemic mice.
The response of the adenylate cyclase (AC) activity to PTH and calcitonin was measured along the nephron of normal (N) and mutant hypophosphatemic (Hyp) mice of the C 57 BL/6J strain, using in vitro single tubule AC microassay. In each experiment, a Hyp mouse was paired to a N mouse from the same litter. In the presence of PTH (10 U/ml), AC activities (femtomoles cAMP per millimeter of tubule per 30-min incubation) were reduced in the proximal convoluted tubule of Hyp mice as compared to N mice in all experiments (448 +/- (SEM) 46 vs. 831 +/- 79, N = 4, P less than 0.01). Some decrease in AC response to PTH also was noted in the cortical portion of the thick ascending limb of the loop of Henle (476 +/- 70 in Hyp mice vs. 719 +/- 83 in N mice, N = 4, P = NS). The Hyp and N AC responses to PTH were similar in the "bright" and "granular" portions of the distal convoluted tubule (1524 +/- 177 in Hyp mice and 1538 +/- 228 in N mice, N = 4). The other segments tested were not responsive to PTH (except the pars recta of the proximal tubule). In the presence of salmon calcitonin (10 ng/ml), a striking 5- to 12-fold increase in AC activity of the "bright" and "granular" portions of the distal convoluted tubule was observed in each Hyp mouse as compared to its paired N control (2434 +/- 618 vs. 399 +/- 56, N = 6, P less than 0.01). The AC response to calcitonin was also increased, though to a lesser extnet (Hyp/N = 1.8) in the "light" portion of the distal tubule (590 +/- 60 in Hyp and 352 +/- 36 in N mice, P less than 0.01). Other segments of the mouse nephron were also observed to contain calcitonin-sensitive AC, but the responses were of limited magnitude only and were not statistically different in Hyp and N mice. Dose-response curves showed that the decrease of the response to PTH in the proximal tubule as well as the increase of the response to calcitonin in the distal tubule were present in Hyp mice for the whole range of hormone concentrations tested. In both structures, the apparent Km for the cyclase activation by the hormone was similar in the Hyp and its paired N mouse.


TLR2 and TLR4 gene expression in peripheral monocytes in nondiabetic hypertensive patients: the effect of intensive blood pressure-lowering.
The activation of innate immune receptors, such as Toll-like receptors (TLRs), participates in the pathogenesis of cardiovascular diseases. The authors evaluated TLR2 and TLR4 gene expression in the peripheral monocytes of nondiabetic hypertensive patients compared with normotensive individuals and investigated the effect of intensive systolic blood pressure (SBP)-lowering. Included were 43 nondiabetic hypertensive patients with essential hypertension who were randomly assigned to an intensive treatment arm, with an SBP target of <130 mm Hg, or a standard arm, with an SBP target of <140 mm Hg. TLR2 and TLR4 messenger RNA (mRNA) levels in monocytes were estimated before and 12 weeks after therapy initiation. Sixteen healthy individuals were included for comparison. Hypertensives revealed significantly higher TLR4 mRNA levels compared with normotensives (985 ± 885 vs 554 ± 234, P=.005). In contrast, no statistically significant difference was found in TLR2. Compared with standard treatment, intensive treatment significantly downregulated TLR2 and TLR4 mRNAs, expressed as fold induction (0.66 ± 0.49 vs 1.38 ± 1.65 and 0.62 ± 0.3 vs 1.9 ± 1.2, respectively; P<.001 for both). In conclusion, TLR4 mRNA levels in peripheral monocytes are significantly elevated in nondiabetic hypertensive patients. Intensive control of SBP results in attenuation of TLR2 and TLR4 gene expression in those patients. Our findings suggest that a strict SBP target in nondiabetic hypertensive patients may offer additional benefits.


Functional properties of in vitro excitatory cortical neurons derived from human pluripotent stem cells.
The in vitro derivation of regionally defined human neuron types from patient-derived stem cells is now established as a resource to investigate human development and disease. Characterization of such neurons initially focused on the expression of developmentally regulated transcription factors and neural markers, in conjunction with the development of protocols to direct and chart the fate of differentiated neurons. However, crucial to the understanding and exploitation of this technology is to determine the degree to which neurons recapitulate the key functional features exhibited by their native counterparts, essential for determining their usefulness in modelling human physiology and disease in vitro. Here, we review the emerging data concerning functional properties of human pluripotent stem cell-derived excitatory cortical neurons, in the context of both maturation and regional specificity.


Presynaptic GABA autoreceptors on GABAergic nerve endings of the rat substantia nigra.
The release of 3H-GABA evoked by exposure to 30 mM potassium during 1 min was found to calcium independent in the rat occipital cortex and calcium dependent in the substantia nigra. Exposure to either muscimol 1 microM or GABA 1 microM inhibited the potassium-evoked release of 3H-GABA from the substantia nigra but not from the occipital cortex. The inhibitory effect of muscimol 1 microM on the potassium-evoked release of 3H-GABA from the substantia nigra was significantly antagonized by picrotoxin 10 microM. Exposure to either 10 or 100 microM pricrotoxin alone did not affect the potassium-evoked release of 3H-GABA. These results are compatible with the presence of a negative feedback mechanism in bagaergic nerve terminals of the rat substantia nigra which is mediated by presynaptic GABA autoreceptors. In addition, these results emphasize the importance of the calcium-dependent nature of the release of the neurotransmitter for demonstrating the modulation of transmitter release through presynaptic receptors.


Stable, position-related responses to retinoic acid by chick limb-bud mesenchymal cells in serum-free cultures.
Retinoic acid (RA) has dramatic effects on limb-skeletal patterning in vivo and may well play a pivotal role in normal limb morphogenesis. RA's effects on the expression of pattern-related genes in the developing limb are probably mediated by cytoplasmic RA-binding proteins and nuclear RA-receptors. Little is known, however, about how RA modifies specific cellular behaviors required for skeletal morphogenesis. Earlier studies supported a role for regional differences in RA concentration in generating the region-specific cell behaviors that lead to pattern formation. The present study explores the possibility that position-related, cell-autonomous differences in the way limb mesenchymal cells respond to RA might have a role in generating pattern-related cell behavior. Mesenchymal cells from different proximodistal regions of stage 21-22 and 23-24 chick wing-buds were grown in chemically defined medium and exposed to 5 or 50 ng/ml of RA for 4 days in high-density microtiter cultures. The effects of RA on chondrogenesis in these cultures clearly differed depending on the limb region from which the cells were isolated. Regional differences in RA's effects on growth over 4 days in these cultures were less striking. The region-dependent responses of these cells to RA proved relatively stable in culture despite ongoing cytodifferentiation. This serum-free culture model will be useful in exploring the mechanisms underlying the region-dependent responsiveness of these cells to RA.


Skewed sex ratios at birth: A review of global trends.
Several cultures in the world traditionally favor the birth of sons over that of daughters. This preference drives various forms of discrimination against female births ultimately reflected in demographic imbalances. Over the last decades, modern reproductive technology has made prenatal diagnosis widely accessible to parents. In certain Asian and Eastern European countries, this has led to skewed sex ratio at birth (SRB) as a result of sex-selective abortions. After reviewing motivations and circumstances associated to prenatal sex selection, our paper analyzes global trends in sex imbalances at birth as well as their parity, regional and socio-economic differentials. We focus our attention on the experience of Azerbaijan, India, and South Korea as instances of three distinct SRB trajectories. Finally, we discuss scenarios concerning the future of these sex imbalances and the implications of a consistent number of "missing women" for affected societies.


Assessment of shoulder active range of motion in prone versus supine: a reliability and concurrent validity study.
As swimming and surfing are prone dominant sports, it would be more sport specific to assess shoulder active range of motion in this position. To determine the reliability of the inclinometer and HALO© for assessing shoulder active range of motion in supine and prone and the concurrent validity of the HALO©. Concurrent validity is based on the comparison of the HALO© and inclinometer. To determine if active range of motion (AROM) differences exists between prone and supine when assessing shoulder internal (IR) and external rotation (ER). The design included clinical measurement, reliability and validity. Thirty shoulders (mean age = 26.8 years) without pathology were evaluated. Measurements were taken in supine and prone with both an inclinometer and HALO© device. Active ER ROM in prone was significantly higher than in supine when using both devices. Intra-rater reliability (within and between session) intraclass correlation coefficient (ICC) values ranged between 0.82-0.99 for both devices in supine and prone. An ICC test revealed a significant (p < 0.01) correlation for both devices in IR and ER movements (ICC3,1 = 0.87 and ICC3,1 = 0.72), respectively. This study has shown prone assessment of active ER and IR ROM to be a reliable and appropriate method for prone dominant athletes (swimmers and surfers). In this study greater ER ROM was achieved in prone compared to supine. This finding highlights the importance of standardizing the test position for initial and follow up assessments. Furthermore the HALO


Auxin-dependent regulation of growth via rolB-induced modulation of the ROS metabolism in the long-term cultivated pRiA4-transformed Rubiacordifolia L. calli.
Gene transfer from Agrobacterium to plants is the best studied example of horizontal gene transfer (HGT) between prokaryotes and eukaryotes. The rol genes of A. rhizogenes (Rhizobium rhizogenes) provide uncontrolled root growth, or "hairy root" syndrome, the main diagnostic feature. In the present study, we investigated the stable pRiA4-transformed callus culture of Rubia cordifolia L. While untransformed callus cultures need PGRs (plant growth regulators) as an obligatory supplement, pRiA4 calli is able to achieve long-term PGR-free cultivation. For the first time, we described the pRiA4-transformed callus cultures' PGR-dependent ROS status, growth, and specialized metabolism. As we have shown, expression of the rolA and rolB but not the rolC genes is contradictory in a PGR-dependent manner. Moreover, a PGR-free pRiA4 transformed cell line is characterised as more anthraquinone (AQ) productive than an untransformed cell culture. These findings pertain to actual plant biotechnology: it could be the solution to troubles in choosing the best PGR combination for the cultivation of some rare, medicinal, and woody plants; wild-type Ri-plants and tissue cultures may become freed from legal controls on genetically modified organisms in the future. We propose possible PGR-dependent relationships between rolA and rolB as well as ROS signalling targets. The present study highlighted the high importance of the rolA gene in the regulation of combined rol gene effects and the large knowledge gap in rolA action.


Persistent posterior globe flattening after orbital cavernous haemangioma excision.
A 54-year-old man presented with left intraconal cavernous haemangioma resulting in globe compression and hyperopia. The tumour was excised completely via lateral orbitotomy approach. Complete excision of tumour did not result in resolution of globe flattening and hyperopia after 21 months. Persistent globe flattening despite removal of a longstanding orbital tumour may be caused by remodelling of the sclera from long-term compression.


Effect of a long acting glucagon selective somatostatin analogue on plasma glucose, insulin and glucagon levels in the anaesthetized rat during arginine infusion.
The effects of somatostatin and a long acting, glucagon selective somatostatin analog (des-Ala1Gly2[His4,5-D-TrP8]-somatostatin) used studied during arginine tolerance tests in normal anaesthetized rats. Arginine infusion in control animals resulted in a rapid increase in plasma insulin and glucagon, and an increase of 15 +/- 5 mg/dl in plasma glucose. Somatostatin infusion (1 mg/kg/h) resulted in suppression of basal insulin secretion and a decrease in arginine-induced insulin and glucagon release. Glucose levels increased rapidly during the combined arginine-somatostatin infusion reaching a peak of 72 +/- 10 mg/dl above basal levels. Similar results were obtained when somatostatin was injected SC (1 mg/kg) at times 0, 15, 30, and 45 minutes (arginine infused from 30-60 minutes). A single injection (1 mg/kg) of the long-acting somatostatin analogue resulted in significant inhibition of basal insulin and glucagon release; during arginine infusion glucagon levels rose only slightly, the insulin response was, however, nearly normal, and only a small arginine-induced increase in glucose levels was observed. Carbohydrate absorption was not influenced by either somatostatin or the analogue.


Noninvasive quantification of regional ventricular function in rats: assessment of serial change and spatial distribution using ultrasound strain analysis.
The optimal method for quantitative assessment of regional ventricular function in rats remains unclear. The goal of this study was to investigate the use of ultrasonic strain rate (SR) and strain analysis in evaluating the serial change and spatial distribution of regional contractile function in rats. In all, 22 anesthetized rats underwent incremental dobutamine infusion (protocol 1) for assessment of serial change or underwent coronary ligation (protocol 2) for assessment of spatial distribution. For protocol 1, the serial change of systolic SR and strain during dobutamine was measured in the posterior myocardium on the short-axis view, and the systolic strain was compared with the percent change in wall thickening. For protocol 2, the spatial distribution of strain profile was analyzed in normal, peripheral ischemic, and central ischemic regions that were identified by myocardial contrast echocardiography. In protocol 1, the incremental dobutamine infusion resulted in a gradual increase in peak systolic SR. In contrast, peak systolic strain increased with low-dose dobutamine but tended to decrease for higher doses of dobutamine. Further, the serial change of peak systolic strain corresponded to changes in percent change in wall thickening, but the strain values were always lower than percent change in wall thickening. In protocol 2, the strain profile indicated postsystolic thickening in the peripheral ischemic region and indicated systolic wall thinning in the central ischemic region. Ultrasonic determination of SR and strain is an accurate and noninvasive method of quantitation of the serial change and spatial distribution of regional contractile function in rats.


Treatment of early chronic lymphocytic leukemia: intermittent chlorambucil versus observation.
The effect of early therapy on the course of chronic lymphocytic leukemia (CLL) has not been established. Fifty-nine patients with indolent Rai stage I and II CLL were randomized to receive intermittent chlorambucil once a month or to receive no treatment. The two groups were comparable in entry characteristics. At 5 years from randomization there was no significant difference in survival between the two groups although the proportion of patients exhibiting active disease 5 years after randomization is 70 per cent in the untreated group and 55 per cent in the treated group. In this study, early treatment of CLL with intermittent chlorambucil did not result in a survival advantage for patients with indolent stage I and II CLL.


Multisystem Inflammatory Syndrome in Children: An International Survey.
To describe presentation, hospital course, and predictors of bad outcome in multisystem inflammatory syndrome in children (MIS-C). Retrospective data review of a case series of children meeting the published definition for MIS-C who were discharged or died between March 1, 2020, and June 15, 2020, from 33 participating European, Asian, and American hospitals. Data were collected through a Web-based survey and included clinical, laboratory, electrocardiographic, and echocardiographic findings and treatment management. We included 183 patients with MIS-C: male sex, 109 (59.6%); mean age 7.0 ± 4.7 years; Black race, 56 (30.6%); obesity, 48 (26.2%). Overall, 114 of 183 (62.3%) had evidence of severe acute respiratory syndrome coronavirus 2 infection. All presented with fever, 117 of 183 (63.9%) with gastrointestinal symptoms, and 79 of 183 (43.2%) with shock, which was associated with Black race, higher inflammation, and imaging abnormalities. Twenty-seven patients (14.7%) fulfilled criteria for Kawasaki disease. These patients were younger and had no shock and fewer gastrointestinal, cardiorespiratory, and neurologic symptoms. The remaining 77 patients (49.3%) had mainly fever and inflammation. Inotropic support, mechanical ventilation, and extracorporeal membrane oxygenation were indicated in 72 (39.3%), 43 (23.5%), and 4 (2.2%) patients, respectively. A shorter duration of symptoms before admission was found to be associated with poor patient outcome and for extracorporeal membrane oxygenation and/or death, with 72.3% (95% confidence interval: 0.56-0.90; P = .006) increased risk per day reduction and 63.3% (95% confidence interval: 0.47-0.82; P < .0001) increased risk per day reduction respectively. In this case series, children with MIS-C presented with a wide clinical spectrum, including Kawasaki disease-like, life-threatening shock and milder forms with mainly fever and inflammation. A shorter duration of symptoms before admission was associated with a worse outcome.


C1q/TNF-related protein-9 attenuates atherosclerosis through AMPK-NLRP3 inflammasome singling pathway.
C1q tumor necrosis factor-related protein 9 (CTRP9) has been suggested to exert an atheroprotective effect by modulating the inflammation, foam cell formation, endothelia and smooth muscle cell function via Adenosine Monophosphate Activated Protein Kinase (AMPK) pathway. On the other hand, the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome plays an critical role in the atherosclerosis development, which is regulated by the AMPK. However, whether the CTRP9 affects the activity of NLRP3 inflammasome during the atherosclerosis development remains unclear, which would be elucidated in the current study. The macrophage cells were stimulated with the oxidized low-density lipoprotein (ox-LDL) and also treated with the recombinant CTRP9 in the meantime. The activation of NLRP3 inflammasome was determined by measuring the releasing of IL-1β and caspase-1 p10 via ELISA and western blot, respectively. Then the AMPK was inhibited in macrophages by Dorsomorphin. Finally, the CTRP9-AMPK-NLRP3 inflammasome pathway was validated in the mouse model of atherosclerosis. The CTRP9 could down-regulate the expression of NLRP3 protein and also the activity of NLRP3 inflammasome in the ox-LDL activated macrophages. Inhibiting the AMPK significantly restored the activities of NLRP3 inflammasome. In the apolipoprotein E-deficient mice, lentiviral expression of CTRP9 could suppress the atherosclerosis development, which could be abolished by AMPK inhibition. Our data here indicated that the CTRP9 showed atheroprotective function via CTRP9-AMPK- NLRP3 inflammasome pathway.


Visible-light promoted photoredox catalysis in flow: addition of biologically important α‑amino radicals to michael acceptors.
Visible light promoted photoredox catalyzed formation of α-amino radicals from cyclic tertiary amine compounds and their subsequent addition to Michael acceptors performed in flow conditions allowed access to a wide range of functionalized N-aryl-substituted tetrahydroisoquinolines (THIQs) and N-aryl-substituted tetrahydro-β-carbolines (THBCs). Visible light in conjunction with Ru(bpy)3Cl2 photocatalyst allowed the formation and high reactivities of α-amino radicals in flow conditions at room temperature. These reactions gave valuable products with high efficiencies; some previously unavailable reaction pathways photo or thermal reaction conditions; i.e. direct synthesis of 1-substituted (THBCs) via α-amino radical path were successfully realized in flow. The use of custom-made FEP tube microreactor proved to be the key to succesfull α-amino-radical formation and overall reaction performance in flow. Three types of light transparent custom-made microfluidic devices were tested, among them glass/silicon and FEP type reactor showed very good results in the conversion of tested compounds. Plausible reaction mechanism is proposed in accordance with known principles of photo activation of tertiary amines. Visible light promoted C(sp3)-H functionalization of N-aryl-protected tetrahydroisoquinolines and N-aryl-protected tetrahydro-β-carbolines in microflow conditions via a-amino radical pathway with various coupling partners in excellent yields and efficiencies.


Essential role of ferrous iron in cyanide-resistant respiration in Hansenula anomala.
Antimycin A-dependent induction of cyanide-resistant respiration in Hansenula anomala was completely blocked by o-phenanthroline, alpha,alpha'-dipyridyl, or 8-hydroxyquinoline. Pulse-labeling of the cells with [35S]methionine in the presence of both antimycin A and o-phenanthroline indicated that the 36-kDa protein previously reported to be involved in cyanide-resistant respiration [(1989) J. Biochem. 105, 864-866] was formed in mitochondria even under these conditions. The addition of Fe2+, but not Fe3+, ions to these cells in the presence of cycloheximide resulted in the rapid expression of cyanide-resistant respiration activity. These results suggest that in the presence of both antimycin A and o-phenanthroline an inactive form of the 36-kDa protein was formed and Fe2+ ions converted it to the active form. It is also likely that Fe2+ ions are involved in the reaction mechanism of cyanide-resistant respiration.


Late cardiac tamponade following open-heart surgery: detection by echocardiography.
Late cardiac tamponade following open-heart operation is a potentially lethal complication that is often difficult to diagnose. A case of cardiac tamponade occurring two weeks after left ventricular aneurysmectomy and coronary bypass surgery is reported. Despite opening of the anterior pericardium during operation, echocardiography revealed characteristic findings, which permitted prompt recognition of this disorder.


Mechanism of oxidation of 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+).
Oxidase electrode measurements have shown that the neurotoxin metabolite 1-methyl-4-phenyl-2,3-dihydropyridinium autoxidizes to hydrogen peroxide and 1-methyl-4-phenylpyridinium in a reaction promoted by iron chelates. The mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity is discussed in the light of these findings.


Examining Protective Factors Against Violence among High-risk Youth: Findings from the Seattle Social Development Project.
This paper examined proximal and distal effects of protective factors specified in the social development model (SDM) on youth violence among high-risk youth. Data come from the Seattle Social Development Project, a longitudinal study of development from childhood into adulthood. A community sample of 808 participants from the Seattle Public School District was surveyed from the 5th grade through adulthood. This paper uses data from participants' adolescent years, ages 10-18. Higher levels of protective factors in early and middle adolescence reduced the odds of violence during late adolescence in the full sample and in two different risk groups (high cumulative risk and low SES). Although risk exposure increased the odds of violence, protective factors in middle adolescence predicted lower odds of violence during late adolescence. Importantly, protective factors had a greater effect in reducing violence among youth exposed to high levels of cumulative risk than among youth exposed to lower levels of cumulative risk. This difference was not observed between youth from higher and lower SES families. Protective factors specified in the SDM appear to reduce violence in late adolescence even among youth from low SES families and youth exposed to high levels of cumulative risk.


Label-free detection of leukemic myeloblasts in hyaluronic acid.
Chronic myeloid leukemia is generally required bone marrow biopsy for diagnosis. Although examining peripheral blood is less invasive, it has not been fully validated as a routine diagnostic test due to suboptimal sensitivity. To overcome this limitation, a number of methodologies based on microfluidics have been developed for sorting circulating tumor cells from peripheral blood of patients with leukemia.In order to develop a more convenient method, we designed an analysis protocol using motion microscopy that amplifies cellular micro motions in a captured video by re-rendering pixels to generate extreme magnified visuals. Intriguingly, no fluctuations around leukemic myeloblasts were observed with a motion microscope at any wavelength of 0-10 Hz. However, use of 0.05% hyaluronic acid, one type of non-newtonian fluid, demonstrated fluctuations around leukemic myeloblasts under conditions of 25 μm/s and 0.5-1.5 Hz with a motion microscope.Thus, the non-invasive detection of leukemic myeloblasts can offer a valuable supplementary diagnostic tool for assessment of drug efficacy for monitoring patients with chronic myeloid leukemia.


Behavioral responses of a leaf beetle to injury-related changes in its salicaceous host.
Adults of the leaf beetle Plagiodera versicolora Laich, avoided previously injured shoots of Salix alba 'Tristis' in favor of nearby uninjured ones. The response was rapid and persisted for five days of study. During brief periods of observation, the vast majority of beetles engaged in behaviors other than locomotion such as feeding and resting. Furthermore, the proportions of beetles walking were similar on injured and uninjured shoots. It appears that under these experimental conditions previous injury did not greatly increase searching behavior of the beetles. Leaves on previously injured shoots received less subsequent herbivory than uninjured ones. Findings of these experiments are consistent with patterns of herbivory observed in the field and known reproductive responses of beetles to diets of injured leaves. These results provide new information toward understanding relatively low levels of herbivory on individual willow leaves associated with the feeding of P. versicolora.


Benign endometrial adenofibroma and polyp in patients receiving tamoxifen: findings on transvaginal ultrasonography and magnetic resonance imaging.
Tamoxifen, a selective estrogen receptor modulator, is widely used to treat breast cancer, but an association has been reported between tamoxifen and the development of endometrial lesions, including endometrial carcinoma, endometrial polyps, and endometrial hyperplasia. There have also recently been a few reports on the relation between tamoxifen and adenofibroma. We present two case reports, one of a patient with a uterine adenofibroma and one of a patient with an endometrial polyp, both of whom received tamoxifen. Cases 1 and 2 are 75- and 65-year-old postmenopausal women, respectively, undergoing tamoxifen therapy. In both cases, endometrial thickening and many small cysts in the uterine cavity were revealed by transvaginal ultrasonography or magnetic resonance imaging. Postoperative microscopic examination confirmed the mass as an adenofibroma in case 1 and as an endometrial polyp in case 2.


The prevalence of female-to-male intimate partner violence in an urban emergency department.
Female-to-male intimate partner violence (IPV) recently has become a recognized health care issue. We screened a heterosexual male Emergency Department population for IPV using the HITS scale, a four-question survey. Two hundred eighty-two men were enrolled in the study. Basic demographics, along with the answers to the HITS scale, were analyzed. Of the men screened, 29.3% had a positive history of IPV. Men who were positive for IPV were more likely to score higher on questions regarding the frequency of verbal aggression than actual or threatened physical violence. This study reinforces the need to screen both genders for IPV in the Emergency Department.


The impact of the surgeon's experience on the results of laparoscopic hernia repair.
The aim of this study was to evaluate our experience with the totally extraperitoneal (TEP) laparoscopic approach to hernia repair. We performed a prospective study of 1227 hernia repairs using the TEP technique over a 7-year period. The main outcome measurements were postoperative complications, conversion rate, learning curve effect, surgery time, hospital stay, return to work, and recurrence rate. The mean operating time was > 60 min during the first 50 cases, but it fall to 32 min for the last 200 cases (p < 0.05). The conversion rate was 5.7% (56 patients); declining from 17% in the first 100 cases to 2.2% for the final 500 cases (p < 0.01). There were 79 complications (6.4%) and 23 recurrences (2.3%); 42% of the complications and 61% of the recurrences appeared in the first 100 cases (p < 0.05). This study shows that postoperative complications, conversion rate, operating time, and recurrences are all substantially reduced as the surgeon's experience increases. Thus, once the learning curve is surpassed, TEP repair represents a good alternative to open techniques.


The neonicotinoid insecticide thiamethoxam enhances expression of stress-response genes in Zea mays in an environmentally specific pattern.
Recent studies indicate that thiamethoxam (TMX), a neonicotinoid insecticide, can affect plant responses to environmental stressors, such as neighboring weeds. The molecular mechanisms behind both stable and environmentally specific responses to TMX likely involve genes related to defense and stress responses. We investigated the effect of a TMX seed treatment on global gene expression in maize coleoptiles both under normal conditions and under low ratio red to far-red (R:FR) light stress induced by the presence of neighboring plants. The neighboring plant treatment upregulated genes involved in biotic and abiotic stress responses and affected specific photosynthesis and cell-growth related genes. Low R:FR light may enhance maize resistance to herbivores and pathogens. TMX appears to compromise resistance. The TMX treatment stably repressed many genes that encode proteins involved in biotic stress responses, as well as cell-growth genes. Notably, TMX effects on many genes' expression were conditional on the environment. In response to low R:FR, plants treated with TMX engage genes in the JA pathway, as well as other stress-related response pathways. Neighboring weeds may condition TMX-treated plants to become more stress tolerant.


Effects of peripheral and local administration of picrotoxin on the release of newly synthesized 3H-dopamine in the caudate nucleus of the cat.
The release of 3H-DA was estimated in superfusates of a superfusion cannula introduced into the caudate nucleus of "encéphale isolé" cats. 3H-DA was continuously formed from L-3,5-3H-tyrosine introduced into the superfusion medium. Injected at the periphery, picrotoxin (2.5 mg/kg, i.p.) markedly enhanced the release of 3H-DA, the effect being particularly pronounced 90 min after the drug injection. The effects of the local introduction of picrotoxin into the substantia nigra and into the caudate nucleus on 3H-DA release were also examined to ensure the specificity of the result. Picrotoxin (10(5) M) added into the superfusing medium of a second superfusion cannula introduced in to the substantia nigra enhanced by 2 to 5 times the release of 3H-DA during the drug application. No effect could be seen when the tip of the superfusion cannula was not exactly localized into the substantia nigra. Although less pronounced, a stimulation of 3H-DA release was also seen when picrotoxin(10(6) M) was added directly into the superfusion medium of the cannula introduced into the caudate nucleus. These results suggest that some gabaergic neurons are involved in the control of DA release by acting on dopaminergic cell bodies or dendrites into the substantia nigra. Other gabaergic neurons may directly or indirectly act on dopaminergic terminals within the caudate nucleus.


Urinary excretion of thiamine in pre-school children in Northeast Thailand.
Urine samples of 85 Thai pre-school children ages below 5 years were taken for thiamine determination related to creatinine. The thiamine status of these children investigated was found to be normal. No difference in the urinary thiamine levels was observed between male and female subjects.


Experimental Test of the Educational Impact of the Newly Proposed FDA Graphic Cigarette Warnings Among U.S. Adults.
In August 2019, the U.S. Food and Drug Administration proposed a set of 13 new graphic warnings for cigarette packaging and advertisements. We evaluated these warnings relative to text-only equivalents for their ability to educate the public regarding harms of smoking and influence outcomes associated with quitting. In an experimental within-subjects design, U.S. adult nonsmokers, smokers, and dual smoker/electronic cigarette (e-cigarette) users (N = 412) recruited from an online internet platform evaluated the newly proposed graphic warnings and corresponding text-only warnings on understandability, perceived new knowledge, worry elicited about the content of the warning, discouragement from smoking, and encouragement to use e-cigarettes. Graphic warnings were generally rated as providing better understanding, more new knowledge, eliciting more worry about harms of smoking, and providing more discouragement from smoking relative to text-only warnings. The newly proposed graphic warnings could influence important responses to warnings associated with motivation to reduce smoking.


Studies of the haemopoietic microenvironment. II. Content of glycosaminoglycans in murine bone marrow and spleen under anaemic and polycythaemic conditions.
Different glycosaminoglycans are described to be involved in processes of cell proliferation and differentiation. To investigate a possible direct involvement of glycosaminoglycans within the haemopoietic organs in erythropoiesis, biochemical separation and quantification of splenic and bone marrow glycosaminoglycans in anaemic and polycythaemic mice were performed. Hyaluronic acid, chondroitin sulphate A, B and C were present in both organs under both conditions. Both in spleen and bone marrow of polycythaemic mice very low amounts of chondroitin sulphate A, B and C, and a higher amount of hyaluronic acid were found in comparison to normal mice. In anaemic mice only the amount of splenic chondroitin sulphate C was found to be lower than in normal mice. It is demonstrated that considerable changes in sulphated and unsulphated glycosaminoglycans occur during erythropoietic stimulation and suppression. The present findings do not indicate a causal relationship between sulphated glycosaminoglycan levels in the haemopoietic organs and the extend of erythropoietic maturation.


Specific interaction of IP6 with human Ku70/80, the DNA-binding subunit of DNA-PK.
In eukaryotic cells, DNA double-strand breaks can be repaired by non-homologous end-joining, a process dependent upon Ku70/80, XRCC4 and DNA ligase IV. In mammals, this process also requires DNA-PK(cs), the catalytic subunit of the DNA-dependent protein kinase DNA-PK. Previously, inositol hexakisphosphate (IP6) was shown to be bound by DNA-PK and to stimulate DNA-PK-dependent end-joining in vitro. Here, we localize IP6 binding to the Ku70/80 subunits of DNA- PK, and show that DNA-PK(cs) alone exhibits no detectable affinity for IP6. Moreover, proteolysis mapping of Ku70/80 in the presence and absence of IP6 indicates that binding alters the conformation of the Ku70/80 heterodimer. The yeast homologue of Ku70/80, yKu70/80, fails to bind IP6, indicating that the function of IP6 in non-homologous end-joining, like that of DNA-PK(cs), is unique to the mammalian end-joining process.


Phosphate alleviates arsenate toxicity by altering expression of phosphate transporters in the tolerant barley genotypes.
The contribution of the phosphate transporters (PHTs) in uptake of arsenate (As5+) and phosphate (P) is a widely recognized mechanism. Here we investigated how P regulates the uptake of As5+ and the subsequent effects on growth and relative expression of PHTs. The study was conducted on 3 barley genotypes differing in As tolerance (ZDB160, As-tolerant; ZDB115, moderately tolerant; ZDB475, As-sensitive) using a hydroponic experiment. There were 3 As5+ (0, 10 and 100µM) and 3P (0, 50 and 500µM) levels. The results showed that the negative effect of As stress on plant growth, photosynthesis and cell ultra-structure is As dose and barley genotype dependent, confirming the distinctly genotypic difference in As tolerance. As uptake and accumulation in plant tissues are closely associated with inhibited extent of growth and photosynthesis, with the tolerant genotype ZDB160 having lower As content than other two genotypes. The toxic effect caused by As stress could be alleviated by P addition, mainly due to reduced As uptake. Moreover, the tolerant genotype showed relatively lower expression PHTs than sensitive ones upon exposure to both As stress and P addition, suggesting regulation of PHTs expression is a major mechanism for relative uptake of As and P, in subsequence affecting As tolerance. Moreover, among 6 PHTs examined in this study, the expressions of PHT1.3, PHT1.4 and PHT1.6 showed the marked difference among the three barley genotypes in responses to As stress and P addition, indicating further research on the contribution of phosphate transporters to As and P uptake should be focused on these PHTs.


Family interaction and communication deviance in disturbed and normal families. Questions of strategy: rejoinder to Jacob and Grounds.
Perhaps the best way to respond to Jacob and Grounds' critique is to focus on the more important issues they raise and to clarify some of the apparent confusion. It seems there are several general classes of criticism that Jacob and Grounds have offered: arbitrariness in selection of studies, inconsistency in reporting findings, inaccuracies in the data reported, and an overly favorable conclusion with respect to the communication deviance literature. Each of these issues will be dealt with here, using as many specific illustrations and examples as space permits.


A liquid chromatographic-tandem mass spectrometric method for the determination of two selective thymidylate synthase inhibitors, BGC945 and BGC638, in mouse plasma.
A LC-tandem mass spectrometry method to quantify the quinazoline-based thymidylate synthase inhibitors BGC945 and BGC638 in mouse plasma was developed. BGC945 and BGC638 were extracted from mouse plasma using protein precipitation with acetonitrile. Chromatography was performed on a Fluophase RP 5 microm, 100 mmx2.0mm i.d. column using a gradient of ammonium acetate and acetonitrile as a mobile phase with a flow rate of 0.2 mLmin(-1). The injection volume for each sample was 20 microL with a total run time of 7.5 min. This method was validated in the range 25-4000 nM (r2=0.99). The analytical assay performance showed that the method was accurate (mean intra- and inter-day assay R.E. were below 12% and 11%, respectively), reproducible (mean intra- and inter-day R.S.D. were less than 13% and 5% for all quality control levels, respectively) and sensitive (lower limit of quantification was 25 nM) in the range studied. This validated method has been used to define the first pharmacokinetic report of BGC945 and BGC638 in mice.


Cerebellopontine angle meningiomas: clinical manifestations and diagnosis.
Cerebellopontine angle (CPA) meningiomas constitute about 1% of intracranial meningiomas. The clinical aspects of a series of 32 patients with surgically confirmed CPA meningiomas are analyzed. The most common symptoms at the time of the initial evaluation were from the eighth cranial nerve (unilateral hearing loss--24 patients, vertigo or imbalance--19 patients, tinnitus--11 patients), and the fifth cranial nerve (altered sensation--9 patients, facial pain--5 patients). On examination, the most common findings were absent caloric response (19 patients), nystagmus (16 patients), diminished facial sensation (14 patients), ataxia (13 patients), reduced hearing (9 patients), and facial weakness (9 patients). There was often a long interval from the onset of symptoms to the correct diagnosis of a tumor. Brain stem auditory evoked potentials, blink reflex testing, posterior fossa myelography, computerized tomographic scanning, and angiography were abnormal in all patients in whom the test was done, but all tests were not performed on all patients. Computerized tomographic scanning and angiography are important for definitive diagnosis and for planning surgical treatment. The histopathology of the temporal bone was studied in three patients with meningiomas in the region of the internal auditory meatus.