Sleep patterns and insomnia among adolescents: a population-based study.
The aim of the current study was to examine sleep patterns and rates of insomnia in a population-based study of adolescents aged 16-19 years. Gender differences in sleep patterns and insomnia, as well as a comparison of insomnia rates according to DSM-IV, DSM-V and quantitative criteria for insomnia (Behav. Res. Ther., 41, 2003, 427), were explored. We used a large population-based study in Hordaland county in Norway, conducted in 2012. The sample included 10,220 adolescents aged 16-18 years (54% girls). Self-reported sleep measurements included bedtime, rise time, time in bed, sleep duration, sleep efficiency, sleep onset latency, wake after sleep onset, rate and frequency and duration of difficulties initiating and maintaining sleep and rate and frequency of tiredness and sleepiness. The adolescents reported short sleep duration on weekdays (mean 6:25 hours), resulting in a sleep deficiency of about 2 h. A majority of the adolescents (65%) reported sleep onset latency exceeding 30 min. Girls reported longer sleep onset latency and a higher rate of insomnia than boys, while boys reported later bedtimes and a larger weekday-weekend discrepancy on several sleep parameters. Insomnia prevalence rates ranged from a total prevalence of 23.8 (DSM-IV criteria), 18.5 (DSM-V criteria) and 13.6% (quantitative criteria for insomnia). We conclude that short sleep duration, long sleep onset latency and insomnia were prevalent in adolescents. This warrants attention as a public health concern in this age group.


Epilepsy Following Neonatal Seizures Symptomatic Of Stroke.
Investigators from Child Neurology and Clinical Neurophysiology, Pediatric University Hospital, Padua, Italy studied the long term risk of developing epilepsy in patients with EEG confirmed neonatal seizures and arterial ischemic stroke.


Does Transcranial Alternating Current Stimulation Induce Cerebellum Plasticity? Feasibility, Safety and Efficacy of a Novel Electrophysiological Approach.
Cerebellum-brain functional connectivity can be shaped through different non-invasive neurostimulation approaches. In this study, we propose a novel approach to perturb the cerebellum-brain functional connectivity by means of transcranial alternating current stimulation (tACS). Twenty-five healthy individuals underwent a cerebellar tACS protocol employing different frequencies (10, 50, and 300 Hz) and a sham-tACS over the right cerebellar hemisphere. We measured their after-effects on the motor evoked potential (MEP) amplitude, the cerebellum-brain inhibition (CBI), the long-latency intracortical inhibition (LICI), from the primary motor cortex of both the hemispheres. In addition, we assessed the functional adaptation to a right hand sequential tapping motor task. None of the participants had any side-effect. Following 50 Hz-tACS, we observed a clear contralateral CBI weakening, paralleled by a MEP increase with a better adaptation to frequency variations during the sequential tapping. The 300 Hz-tACS induced a contralateral CBI strengthening, without significant MEP and kinematic after-effects. The 10 Hz-tACS conditioning was instead ineffective. We may argue that tACS protocols could have interfered with the activity of CBI-sustaining Purkinje cell, affecting motor adaptation. Our safe approach seems promising in studying the cerebellum-brain functional connectivity, with possible implications in neurorehabilitative settings.


Differential roles of miR-199a-5p in radiation-induced autophagy in breast cancer cells.
Autophagy is a self-degrading process that is triggered by diverse stimuli including ionizing radiation. In this study we show novel phenomena in which transfection of miR-199a-5p mimic significantly suppresses IR-induced autophagy in MCF7 cells, and up-regulates basal and IR-induced autophagy in MDA-MB-231 breast cancer cells. We also identify DRAM1 and Beclin1 as novel target genes for miR-199a-5p. Overexpression of miR-199a-5p inhibits DRAM1 and Beclin1 expression in MCF7 cells, while it enhances expression of these genes in MDA-MB-231 cells. Furthermore, we show that miR-199a-5p sensitizes MDA-MB-231 cells to irradiation. Therefore, our data identify miR-199a-5p as a novel and unique regulator of autophagy, which plays an important role in cancer biology and cancer therapy.


Characterization and targeting of malignant stem cells in patients with advanced myelodysplastic syndromes.
Myelodysplastic syndrome (MDS) is a chronic hematologic disorder that frequently evolves to more aggressive stages and in some cases leads to acute myeloid leukemia (AML). MDS arises from mutations in hematopoietic stem cells (HSCs). Thus, to define optimal therapies, it is essential to understand molecular events driving HSC pathogenesis. In this study, we report that during evolution of MDS, malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. Specifically, metabolic analyses of the MDS stem cell compartment show a profound activation of protein synthesis machinery and increased oxidative phosphorylation. Pharmacological targeting of protein synthesis and oxidative phosphorylation demonstrated potent and selective eradication of MDS stem cells in primary human patient specimens. Taken together, our findings indicate that MDS stem cells are reliant on specific metabolic events and that such properties can be targeted prior to the onset of clinically significant AML, during antecedent MDS.


Glomerular filtration rate in transplantation patients: estimation of renal function using Tc-99m DTPA.
The clinical assessment of a transplanted kidney is often difficult, especially in the immediate postoperative period. The biochemical parameters used to monitor renal function change slowly and can take several days to reflect the actual renal status. We have modified a technique for determining the glomerular filtration rate (GFR) from a Tc-99m DTPA renal scan and have found that it correlates with the actual GFR throughout the postoperative course. In addition, we describe a method for changing dose calibrator measurements into administered counts. This technique for determining the GFR provides a quick and accurate assessment of renal function and is useful to guide therapeutic decisions.


Deficiency in the ability of serum from pigs on an atherogenic diet to stimulate the migration of 3T3 cells in culture.
The serum of pigs developing atherosclerosis is deficient in the ability to stimulate the migration of Balb/c-3T3-A31 cells in culture. This deficiency appears to be due to the presence of an inhibitor located in lipoprotein-free serum. The migration assay was used to follow the changing migration activity of the serum of pigs on a changing diet.


Contact behaviour of children and parental employment behaviour during school closures against the pandemic influenza A (H1N1-2009) in Japan.
To identify epidemiological determinants of the contact behaviour of children and their impact on parental employment, during school closures that took place over the course of the 2009 pandemic influenza (H1N1-2009) in Japan. A retrospective survey was conducted in Japanese households between October 2009 and May 2010 by administration of a standardized questionnaire. Demographic and behavioural variables were explored, in association with the frequency with which children left the home and the risk of parents being absent from work during school closures. Data from 882 eligible households were analysed. A total of 181/882 (20.5%) of households reported that children left the home for nonessential reasons during school closures. No impact on parental working hours was reported by 742/882 (84.1%) of households. Univariate analyses showed that the frequency with which children left the home was dependent on age, extent of school closure and requirement for special childcare arrangements. A greater understanding of age-dependent behaviours, during school closures as a consequence of a pandemic, is required. Consideration of a public policy to permit a paid leave of absence from work for parents during school closures may be beneficial; the cost-effectiveness of such a measure should be assessed in future.


Factors influencing tooth loss in European populations.
This study aimed to identify the factors influencing the changes in the number of teeth present and the number of healthy or filled surfaces between two time points. Repeated cross-sectional data from population-based studies, namely the German Oral Health Studies (DMS-III vs. DMS-V), the Studies of Health in Pomerania (SHIP-START-0 vs. SHIP-TREND-0), and the Jönköping study (2003 vs. 2013), were analysed. Oaxaca decomposition models were constructed for the outcomes (number of teeth, number of healthy surfaces, and number of filled surfaces). The number of teeth increased between examinations (DMS: +2.26 [adults], +4.92 [seniors], SHIP: +1.67, Jönköping: +0.96). Improvements in education and dental awareness brought a positive change in all outcomes. An increase in powered toothbrushing and inter-dental cleaning had a great impact in DMS (adults: +0.25 tooth, +0.78 healthy surface, +0.38 filled surface; seniors: +1.19 teeth, 5.79 healthy surfaces, +0.48 filled surface). Inter-dental cleaning decreased by 4% between SHIP-START-0 and SHIP-TREND-0, which negatively affected the outcomes. From this study, it can be concluded that education may be the most important factor having a direct and indirect effect on the outcomes. However, for better oral health, powered toothbrushing and inter-dental cleaning should not be neglected.


Robotic Ureteral Reconstruction.
Robotically assisted laparoscopic techniques may be used for proximal and distal ureteral strictures. Distal strictures may be approached with ureteroneocystotomy, psoas hitch, and Boari flap. Ureteroureterostomy, buccal mucosa graft ureteroplasty, and appendiceal flap ureteroplasty are viable techniques for strictures anywhere along the ureter. Ileal ureteral substitution is reserved for more extensive disease, and autotransplantation is reserved for salvage situations.


Spatial interpolation methods to predict airborne pesticide drift deposits on soils using knapsack sprayers.
Spatial predictions of drift deposits on soil surface were conducted using eight different spatial interpolation methods i.e. classical approaches like the Thiessen method and kriging, and some advanced methods like spatial vine copulas, Karhunen-Loève expansion and INLA. In order to investigate the impact of the number of locations on the prediction, all spatial predictions were conducted using a set of 39 and 47 locations respectively. The analysis revealed that taking more locations into account increases the accuracy of the prediction and the extreme behavior of the data is better modeled. Leave-one-out cross-validation was used to assess the accuracy of the prediction. The Thiessen method has the highest prediction errors among all tested methods. Linear interpolation methods were able to better reproduce the extreme behavior at the first meters from the sprayed border and exhibited lower prediction errors as the number of data points increased. Especially the spatial copula method exhibited an obvious increase in prediction accuracy. The Karhunen-Loève expansion provided similar results as universal kriging and IDW, although showing a stronger change in the prediction as the number of locations increased. INLA predicted the pesticide dispersion to be smooth over the whole study area. Using Delaunay triangulation of the study area, the total pesticide concentration was estimated to be between 2.06% and 2.97% of the total Uranine applied. This work is a first attempt to completely understand and model the uncertainties of the mass balance, therefore providing a basis for future studies.


Activation of cholinergic anti-inflammatory pathway contributes to the protective effects of 100% oxygen inhalation on zymosan-induced generalized inflammation in mice.
The 100% oxygen inhalation has been demonstrated to have a protective effect on mice with zymosan-induced generalized inflammation. However, the underlying mechanism is largely unknown. The present study was designed to explore the role of the cholinergic anti-inflammatory pathway in this animal model. Oxygen inhalation was given to mice at 4 and 12 h after zymosan injection. One group of mice underwent vagotomy 7 d before zymosan injection. The other two groups of mice either received nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine, or α7 nicotinic acetylcholine receptor (α7nAChR) antagonist methyllycaconitine 30 min before oxygen was given. The 100% oxygen treatment significantly decreased the serum level of TNF-α and increased the serum level of IL-10. The pathologic changes of the heart, lung, liver, and kidney were attenuated, as well as the dysfunction of liver and kidney. The 7-d survival rate of zymosan-challenged mice was also improved. Conversely, all these protective effects caused by pure oxygen treatment were abolished in those animals that received anti-cholinergic treatments. The cholinergic anti-inflammatory pathway may be involved in the 100% oxygen protective mechanism against zymosan-induced generalized inflammation in mice.


Inhibitory innervation of the guinea-pig urethra; roles of CO, NO and VIP.
The inhibitory innervation of guinea-pig urethral smooth muscle was investigated histochemically and functionally. The distribution of immunoreactivities to haem oxygenases (HO), neuronal NO synthase (nNOS), and vasoactive intestinal polypeptide (VIP) was studied, and the functional effects of the corresponding putative transmitters, CO, NO, and VIP, were assessed. HO-2 immunoreactivity was found in all nerve cell bodies of intramural ganglia, localized between smooth muscle bundles in the detrusor, bladder base and proximal urethra. About 70% of the ganglionic cell bodies were also NOS-immunoreactive (IR), whereas a minor part was VIP-IR. Some ganglion cells exhibiting tyrosine hydroxylase (TH) activity were demonstrated. Rich numbers of NOS-IR varicose nerve terminals could be found innervating the smooth muscle of the urethra, whereas VIP-IR terminals were less numerous. A rich number of TH-IR terminals were observed. The bladder showed a similar distribution of nerves, although only a few number of TH-IR nerves could be found. In bladder preparations exposed to sodium nitroprusside, cGMP-IR cells could be seen, forming an interconnecting network with long spindle-shaped processes. The cGMP-IR cells were especially abundant in the outer smooth muscle layers of the bladder, but less numerous in the urethra. In urethral strip preparations, electrical field stimulation evoked long-lasting frequency-dependent relaxations. The relaxations were not inhibited by the NO-synthesis inhibitor, L-NOARG, or enhanced by the NO-precursor, L-arginine. The haem precursor, 5-aminolevulinic acid (5-ALA), or the inhibitor of guanylate cyclase, ODQ, did not affect the urethral relaxations. Exogenously applied NO, SIN-1, and VIP relaxed the preparations by approximately 50%, whereas the relaxation evoked by exogenous CO was minor. These results suggest that CO probably is not involved in non-adrenergic, non-cholinergic inhibitory control of the guinea-pig urethra, where a non-NO/cGMP mediated relaxation seems to be predominant.


Estimation of the radioactive source dispersion from Fukushima nuclear power plant accident.
Following the Fukushima nuclear power plant accident detections of (133)Xe have been made in various locations. Using results of these remote measurements the Fukushima (133)Xe source term has been reconstructed and compared with previously reconstructed (137)Cs and (131)I source terms. The reconstruction is accomplished by applying atmospheric transport modeling and an adapted least square error method. The obtained results are in agreement with previous estimations of the Fukushima radionuclide source, and also serve as a proof of principle for source term reconstruction based on atmospheric transport modeling.


Lateral neck radiography for prediction of difficult orotracheal intubation.
Failed endotracheal intubation is a principal cause of morbidity and mortality in anesthetized patients. The aim of this study was to investigate the efficiency of lateral neck radiography in predicting difficult intubation. In a prospective triple-blind study, 100 patients (aged 18-89 yr), scheduled for elective surgery were randomly selected. Lateral neck X-ray was obtained from each of the patients before operation. Several angles and parameters on the X-ray were proposed to illustrate a relationship with easy or difficult intubation. A radiologist recorded these angles before the operation. An anaesthesiologist also determined the Mallampati score preoperation. At the time of intubation, two other anesthesiologists performed a laryngoscopy and, according to established criteria, identified the patients as easy or difficult intubation. The results were then compared with each other. Fifteen patients were identified as having difficult intubation (laryngoscopy Grades III and IV). Sensitivity and specificity of the Mallampati Class test were 26% and 100%, respectively. The sensitivity and specificity of the lateral neck X-ray for three measured angles were 100%. The positive and negative predictive values (NPVs) for those angles were 100% and for Mallampati classification were 100% and 80%, respectively. Compared to the Mallampati Class test, our method of analyzing the lateral X-ray, although not as easy and universally applicable as Mallampati Class test, proved to be a suitable method for predicting difficult intubation.


Clozapine repackaged into dose administration aids: a common practice in Australian hospitals.
Clozapine is an atypical antipsychotic used in the treatment of schizophrenia. Due to the patient profile there is a high rate of repackaging of clozapine into dose administration aids (DAAs). Because of reports from hospital pharmacists about discoloration of returned clozapine tablets that have been repackaged into DAAs, the aim of this study was to evaluate the chemical, physical and photostability of these tablets repackaged into a DAA. Clozapine tablets were repackaged into DAAs and evaluated for physicochemical stability over a 6-week period at a controlled room temperature (25±1°C; 60±1.5% relative humidity (RH)) and accelerated conditions (40±1°C; 75±1.5% RH). In addition, photostability studies were performed according to the International Committee on Harmonisation (ICH) guidelines. Chemical stability was confirmed for all storage conditions, including for those photostability (ICH conditions), with the clozapine content occurring within the British Pharmacopoeial (BP) range of 90-110%. Although the physical stability was confirmed for all tests at room temperature (weight uniformity, hardness, friability, disintegration and dissolution), under accelerated conditions the disintegration test did not meet BP requirements. However, the subsequent dissolution test was successful with 85% of clozapine dissolving in 45min. This study illustrates that clozapine, when correctly repackaged, maintains its physical and chemical stability for 6 weeks. As no discoloration of the tablets was observed, it is assumed that the reports received were as a result of improper handling by patients. Based on these findings, it is recommended that patients be advised on the correct handling and storage of their DAAs.


Recent Progress in Metal Halide Perovskite-Based Tandem Solar Cells.
Metal halide perovskite (MHP)-based tandem solar cells are a promising candidate for use in cost-effective and high-performance solar cells that can compete with fossil fuels. To understand the research trends for MHP-based tandem solar cells, a general introduction to single-junction and multiple-junction MHP solar cells and the configuration of tandem devices is provided, along with an overview of the recent progress regarding various MHP-based tandem cells, including MHP/crystalline silicon, MHP/CuInGaS, MHP/organic photovoltaic, MHP/quantum dot, and all-perovskite tandem cell. Future research directions for MHP-based tandem solar cells are also discussed.


After going through chemotherapy I can't see another needle.
Needle anxiety not only impacts on a patient's quality of life but can delay or prevent future medical care. Our survey of women with breast cancer indicated that 78/208 women (37.5%) reported feeling anxious about injections. Patients who reported needle anxiety were significantly younger (t(206)=3.72; P<0.01), with a lower body mass index (BMI) (t(182)=2.16; P<0.05), experience of chemotherapy (chi(2)(1)=8.29; P<0.01), a lower internal health locus of control (t(187)=2.28; P<0.05) and higher levels of state (t(197)=-3.58; P<0.01) and trait anxiety (t(197)=-2.30; P<0.05). Patients repeatedly highlighted the experience of chemotherapy as having caused their needle anxiety. Patient discourse suggests that chemotherapy related needle anxiety is a result of physical (e.g. finding a suitable vein) and environmental (e.g. the chemotherapy room) factors. Patients with cancer require psychosocial support during all stages of care, this should include the application of techniques to prevent or ameliorate the development of anxiety caused by certain aspects of cancer treatments, such as the development of chemotherapy-related needle anxiety.


Accuracy Evaluation of 14 Maxillary Full Arch Implant Treatments Performed with Da Vinci Bridge: A Case Series.
The use of pterygoid implants can be an attractive alternative to sinus bone grafting in the treatment of posterior atrophic maxilla. This technique has not been widely used because of the difficulty of the surgical access, the presence of vital structures, and the prosthetic challenges. The use of dynamic computer aided implantology (DCAI) allows the clinician to utilize navigation dental implant surgery, which allows the surgeon to follow the osteotomy site and implant positioning in real time. A total of 14 patients (28 pterygoid implants and 56 intersinusal implants) were enrolled in the study for a full arch implant prosthetic rehabilitation (4 frontal implants and 2 pterygoids implants), using a dynamic navigation system. The reported accuracy of pterygoid implants inserted using DCAI was 0.72 mm at coronal point, 1.25 mm at apical 3D, 0.66 mm at apical depth, and 2.86° as angular deviation. The use of pterygoid implants in lieu of bone grafting represents a valid treatment opportunity to carry out a safe, accurate, and minimally invasive surgery, while reducing treatment time and avoiding cantilevers for a full implant prosthetic rehabilitation of the upper arch.


Fine structure of Sarcocystis singaporensis merogony stages preceding sarcocyst formation in the rat.
The fine structure of merogony stages of Sarcocystis singaporensis (Zaman and Colley, 1975) is described from experimentally infected laboratory rats, 10 days after being fed sporocysts obtained from naturally infected Python reticulatus from Singapore. Infection was shown to consist exclusively of S. singaporensis. Parasites developed in the endothelial cells of the lungs, brain, kidney and heart. Infection comprised meronts prior to division, dividing and divided meronts, and dispersed merozoites. Undivided meronts developed deep pellicular invaginations and extensions of the nucleus toward the cell boundary, seemingly to sustain metabolic exchange. The course of merogonous development was the same in all organs. Hypertrophy of the endothelium induced by invading merozoites appeared to lead to obstruction of the capillary lumen.


Molecular functions of Mrhl lncRNA in mouse spermatogenesis.
Mrhl lncRNA regulates the Wnt signaling pathway in mouse spermatogonial cells, resulting in the commitment of B-type spermatogonia to meiotic entry through Mrhl lncRNA-mediated regulation of Sox8. Mrhl lncRNA regulates chromatin dynamics of the Sox8 promoter/enhancer interaction through chromatin looping. Proliferation and meiotic division of spermatogonial stem cells are highly regulated biological processes that occur during spermatogenesis. In addition to protein-coding genes, the mammalian genome encodes thousands of lncRNAs which are spatio-temporally expressed and play key role(s) in cellular differentiation and development. Mrhl lncRNA is one such mono-exonic polyadenylated non-coding RNA encoded within the 15th intron of the mouse Phkb gene. Mrhl lncRNA is expressed in mouse testis amongst other tissues. The RNA is nuclear localized and predominantly bound to chromatin in GC-1 spg cells (derived from B-type spermatogonia). It regulates multiple genes belonging to different biological processes including Wnt signaling. Wnt activation of GC-1 spg cells downregulates Mrhl lncRNA expression, in turn activating the expression of meiotic marker genes and downregulating stem cell markers. We have mapped the genomic loci bound by Mrhl lncRNA and identified 37 genes to be regulated by its physical association. Sox8 gene, one among these, is regulated through its interaction at its promoter through RNA:DNA:DNA triplex structure and chromatin looping mediated by the architectural proteins CTCF and YY1. Here, we summarize our major findings on this novel lncRNA starting from its discovery to biological function(s), particularly during meiotic commitment/initiation in mouse spermatogenesis.


Health and productivity burden of coronary heart disease in the working Indonesian population using life-table modelling.
The impact of coronary heart disease (CHD) and its effect on work productivity at a population level remains unknown in Indonesia. This study estimates the health and productivity lost to CHD in terms of years of life, quality-adjusted life years (QALYs) and productivity-adjusted life years (PALYs). A life-table model was constructed to simulate the experiences of Indonesians currently aged 15-54 years (working age) with CHD, followed-up to 55 years (retirement age). The life-table analysis was then repeated assuming that the cohort did not have CHD. Differences in the results reflected the impact of CHD. Demographical, prevalence and mortality data were based on the 2017 Global Burden of Disease study and 2018 Indonesian National Health Survey. Costs, productivity indices and utilities were derived from published sources. The cost of each PALY was assumed to be equivalent to gross domestic product per equivalent full-time worker (US$11 765). Future costs and outcomes were discounted by 3% annually. Differences in total deaths, years of life and PALYs represented the impact of CHD. At present, 1 954 543 (1.45%) Indonesians of working-age have CHD. By retirement age, it was estimated that CHD resulted in 32 492 (36.6%) excess deaths, 128 132 (0.5%) years of life lost, 2 331 495 (10.5%) QALYs lost and 1 589 490 (6.9%) PALYs lost. The economic impact of lost productivity amounted to US$33.3 billion, and healthcare costs to US$139 billion. The health and economic burden of CHD in Indonesia looms large. This highlights the importance of its prevention and control, strategies for which, if effective, will deliver financial return.


Physical activity in different periods of life, sedentary behavior, and the risk of ovarian cancer in the NIH-AARP diet and health study.
Physical activity and sedentary behavior may influence ovarian cancer risk, but clear evidence is lacking. We prospectively investigated the relations of self-reported physical activity and sedentary behavior to ovarian cancer incidence in a cohort of 148,892 U.S. women ages 50-71 years at baseline (1995-1996), who were followed through 2006. Multivariate Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI). We also conducted analysis by hormone use, body mass index (BMI), and cancer subtype. We identified 753 incident epithelial ovarian cancers. Overall, neither physical activity nor sedentary behavior at baseline was associated with ovarian cancer risk. Compared with women who never or rarely engaged in vigorous physical activity in the past year, women who reported more than 5 times/week of vigorous physical activity had an RR of 1.05 (95% CI, 0.84-1.32). Women who sat 7+ hours/day had an RR of 1.05 (95% CI, 0.80-1.37) compared with those reporting <3 hours of sitting. The associations were not modified by hormone use or BMI and were similar for both serous and non-serous subtypes. Physical activity and sedentary behavior in middle and older ages were not associated with ovarian cancer risk. We found no clear support for a role of physical activity and sedentary behavior in ovarian cancer risk.


Coagulation abnormalities in adults with cryptogenic stroke and patent foramen ovale.
A patent foramen ovale (PFO) is found by transesophageal echocardiography in one half of patients with cryptogenic stroke (CS). Coagulation abnormalities may promote paradoxical emboli in these patients. Seventeen patients were identified with PFO and CS. Thirty-one percent of patients had hematologic risk factors for venous thrombosis. These included abnormal activated protein C resistance and increased anticardiolipin antibodies. Patients with coagulation abnormalities and a PFO were three times as likely to be treated with warfarin compared to aspirin (P<0.05). Prothrombotic states are common in patients with PFO and CS and identifying these conditions may impact the choice of antithrombotic therapy.


Formation of halogenated by-products of parabens in chlorinated water.
Chemical transformations of four alkyl esters of p-hydroxybenzoic acid, parabens, in chlorinated water samples are investigated. Quantification of the parent species and identification of their reaction by-products were performed using gas chromatography in combination with mass spectrometry. Experiments were accomplished considering free chlorine and paraben concentrations at the mg L(-1) and microg L(-1) level, respectively. Concentration of water samples, using solid-phase extraction, and silylation of the target species were carried out in order to improve the detectability of parent species and their possible transformation products, achieving quantification limits at the low ng L(-1) level. Under employed experimental conditions, the decrease in the concentrations of parabens followed pseudo-first-order kinetics. Half-lives values obtained for model ultrapure water solutions were in good agreement with those observed in tap water samples. For the first type of sample, only two by-products were detected for each paraben. They corresponded to chlorination of the aromatic ring in one or two carbons situated in ortho-positions to the hydroxyl group. Both species were also generated after the addition of parabens to chlorinated tap water. Moreover, three new transformation products were noticed for each parent compound. They were identified as bromo- and bromochloro-parabens, formed due to the existence of traces of bromide in tap water sources. Experiments carried out by mixing paraben-containing personal care products with tap water, containing free chlorine, confirmed the formation of all above described halogenated by-products. In addition, the presence of the di-chlorinated forms of methyl and propyl paraben has been detected for first time in raw sewage water samples.


Dietary Intake and Nutritional Status in Diabetic and Nondiabetic Patients With Chronic Kidney Disease Stage 4-5 (NutriDiab Study).
The aim of the present study was to assess the dietary intake and nutritional status of patients with chronic kidney disease (CKD) stage 4-5 according to the presence of diabetes. This observational and cross-sectional study included adult patients with CKD stage 4-5 referred to a nephrology unit, between October 2018 and March 2019. Daily dietary intake was evaluated by 24-hour dietary inquiry and urine excretion. Nutritional status was assessed by measuring body composition using bioimpedance analysis and muscle function using handgrip strength. Undernutrition was considered using the protein energy wasting score. A total of 75 CKD patients were included, 36 (48%) of whom had diabetes; median age (interquartile range) was 71 (60-80) years. The median weight-adjusted dietary energy intake (DEI) was 22.6 (19.1-28.2) kcal/kg/day and the mean weight-adjusted dietary protein intake (DPI) was 0.86 ± 0.19 g/kg/day. There was no significant difference in DEI and DPI between patients with diabetes and those without, except for weight-adjusted DPI which was significantly lower in diabetic patients (P = .022). In univariate analysis, diabetes was associated with weight-adjusted DPI (coefficient [95% confidence interval] -0.237 [-0.446; -0.004] kcal/kg/day; P = .040), but this association did not remain significant in multivariate analysis. Nutritional status did not differ significantly between diabetic and nondiabetic patients except for lean tissue mass, which was lower in diabetic patients (P = .046). The proportion of patients with protein energy wasting was not significantly different between diabetic and nondiabetic patients (13.9% vs. 10.2%, respectively). In the present cohort, DPI and DEI were not significantly different between diabetic and nondiabetic CKD patients. Diabetes was not found to be associated with dietary intakes in CKD stage 4-5 patients.


Proof of evidence of changes in global terrestrial biomes using historic and recent NDVI time series.
Climate change affects plant dynamics and functioning of terrestrial ecosystems. This study aims to investigate temporal changes in global vegetation coverage and biomes during the past three decades. We compared historic annual NDVI time series (1982, 1983, 1984 and 1985) with recent ones (2015, 2016, 2017 and 2018), captured from NOAA-AVHRR satellite observations. To correct the NDVI time series for missing data and outliers, we applied the Harmonic Analysis of Time Series (HANTS) algorithm. The NDVI time series were decomposed in their significant amplitude and phase given their periodic fluctuation, except for ever green vegetation. Our findings show that the average NDVI values in most biomes have increased significantly (F-value<0.01) by 0.05 ndvi units over during the past three decades, except in tundra, and deserts and xeric shrublands. The highest rates of change in the harmonic components were observed in the northern hemisphere, mainly above 30° latitude. Worldwide, the mean annual phase reduced by 9° corresponding to a 9 days shift in the beginning of the growing season. Annual phases in the recent time series reduced significantly as compared to the historic time series in the five major global biomes: by 14.1, 14.8, 10.6, 9.5, and 22.8 days in boreal forests/taiga; Mediterranean forests, woodlands, and scrubs; temperate conifer forests; temperate grasslands, savannas, and shrublands; and deserts, and xeric shrublands, respectively. In tropical and subtropical biomes, however, changes in the annual phase of vegetation coverage were not statistically significant. The decrease in the level of phases and acceleration of growth and changes in plant phenology indicate the increase in temperature and climate changes of the planet.


Epileptic focus induced by intrahippocampal cholera toxin in rat: time course and properties in vivo and in vitro.
A small dose (0.5-1.0 micrograms) of cholera toxin injected into rat hippocampus induced an epileptic focus which discharged intermittently for 7-10 days. Epileptic discharges lasting from 70 ms to 2 min were recorded in vivo through implanted electrodes. The longer bursts could generalize to the neocortex, and occasionally caused motor seizures. The epileptic bursts reached a maximum 3-4 days after injection, and then declined to occasional brief interictal discharges by 9 days. Postmortem histology revealed no evidence of gross pathology or neuronal loss. Hippocampal slices prepared from rats < 8 days after injection of cholera toxin, and maintained in vitro, generated brief spontaneous and evoked epileptic bursts, usually lasting < 1 s. Spontaneous bursts always started in subregion CA3c, and propagated through the pyramidal layer at a mean of 0.18 m/s. Intracellular recordings from CA3 pyramidal layer cells always revealed simultaneous paroxysmal depolarization shifts during epileptic bursts. Epileptic activity, both in vivo and in vitro, required the whole toxin molecule. Injections of either the B subunit or the vehicle solution were not epileptogenic. Therefore binding of the toxin to neuronal membranes, which is mediated by the B subunit, was not sufficient for the epileptogenic effects of cholera toxin. This suggested that the activation of Gs which requires the whole molecule, was necessary. Gs activation is known to stimulate cyclic AMP production, but forskolin, which directly stimulates adenyl cyclase, failed to produce epileptic activity, even though it depressed action potential accommodation and afterhyperpolarizations (AHPs). While further work is required to resolve the basic mechanisms of cholera toxin induced epileptic foci, we propose that they require the activation of Gs, which can enhance Ca2+ currents and modify excitatory synaptic transmission directly. Cyclic AMP induced changes in these properties cannot be excluded. However, cyclic AMP induced reductions in action potential accommodation and AHPs, which are found in cholera toxin foci, may contribute to, but are not sufficient for, epileptogenesis. Cholera toxin differs from the commonly used epileptic agents in that its main action is on G proteins and second messenger systems, rather than on synaptic transmission directly. Furthermore it has a prolonged time course, and does not cause gross pathology. These features combine to make it a distinctive model for epilepsy and neuronal synchronization.


Chronic neonatal blockade of NMDA receptor does not affect developmental polyamine metabolism but results in altered response to the excitotoxic induction of ornithine decarboxylase.
Neonatal rats were subjected to chronic blockade of the N-methyl-D-aspartate (NMDA) receptor through daily systemic administration of increasing doses of the competitive antagonist CGP 39551 from postnatal days 1-22. Treatment did not result in any significant alteration of the levels of putrescine, spermidine and spermine or in the constitutively expressed activity of the key enzyme for polyamine biosynthesis, ornithine decarboxylase (ODC), as evaluated at 10 and 20 days of age. However, in 30-day-old rats significant differences were observed in the process of excitotoxic ODC induction in the olfactory cortex and the hippocampus of chronically-treated rats: the increase of ODC activity caused by systemic administration of kainic acid took place more rapidly but it was shorter and apparently reached a smaller peak in treated animals as compared to controls. This result, in conjunction with previous data on neurochemistry and locomotor activity of similarly treated rats, strengthens the suggestion that functional alterations of some brain circuits may be the consequence of the blockade of NMDA receptor during the critical neonatal period of brain maturation.


Conservation of a DNA-binding site in the largest subunit of eukaryotic RNA polymerase II.
Using a monoclonal antibody to a DNA-binding site of calf RNA polymerase II, we found that this site occurs on the largest subunit and is structurally similar in RNA polymerase II of widely divergent eukaryotes. In immuno-blotting of electrophoretically separated subunits, the monoclonal antibody recognized a determinant on the largest polypeptide of all RNA eukaryotic polymerase II forms tested, with a preference for the IIA enzyme subunit of 215 X 10(3) Mr over the partially proteolyzed 180 X 10(3) Mr form. This site is conserved on human, chicken, Drosophila, wheat germ and yeast RNA polymerase II, all of which reacted strongly with the monoclonal antibody. These results contrasted with those obtained with polyclonal antibodies to non-functional determinants of the calf enzyme. The reactivity of the polyclonal antibody with eukaryotic RNA polymerase II steadily decreased with increasing evolutionary distance from the original antigen; the yeast enzyme showed no cross-reactivity. These results suggest that a basic functional feature of eukaryotic RNA polymerase II has been strongly conserved and support the view that divergence of RNA polymerase II has taken place mainly in other, perhaps regulatory, sites of the enzyme.


Display of prolonged EEG recordings.
An interactive minicomputer system for displaying, storing and providing hard copy output of prolonged EEG recordings has been described. Perhaps the most significant feature of the system is the versatility gained by using a minicomputer. The routines developed initially solely for the display and storage of the EEG have recently been readily modified to control a different playback unit. They also form an integral part of a software package being written to set up a data base for prolonged EEG recordings and also for the study of artefacts in ambulatory recordings.


Second-line and subsequent therapy for ovarian carcinoma.
Ovarian carcinoma continues to be the leading cause of death among gynecologic malignancies. Paclitaxel and platinum chemotherapy is still the treatment of choice after primary debulking surgery. Salvage chemotherapy with several single agents has only modest activity and does not prolong survival of patients with relapsed ovarian carcinoma. An intense search has been made for novel approaches to treatment of ovarian cancer, and several new treatments, such as immunotherapy and gene therapy, show promise. Newer combination chemotherapy regimens and molecularly targeted therapy need to be developed. High-dose chemotherapy with autologous stem-cell transplantation appears to benefit selected groups of patients and is still investigational. Whole abdominal radiotherapy for relapsed microscopic disease should be studied in prospective randomized trials. Women with advanced ovarian carcinoma should continue to be encouraged to participate in well-designed clinical trials.


The association between prolyl hydroxylase metabolism and cell growth in cultured L-929 fibroblasts.
Prolyl 4-hydroxylase (EC 184.108.40.206) is a key enzyme in collagen biosynthesis, its active form is a tetramer (alpha 2 beta 2). In L-929 fibroblasts in the log phase of culture there is a low level of active enzyme. When the cell culture reaches confluency, prolyl hydroxylase activity in cells increases by a process that requires de novo RNA and protein synthesis. The same result may be achieved by crowding the cells (replating log phase cells at the density of stationary phase cells). In the work reported here we further examined induction of the enzyme. RNA synthesis necessary for enzyme induction is complete 6 h after "crowding" while protein synthesis requires 12 h. Thymidine (0.2-0.5 mM) added to log phase cells will also cause enzyme induction to the level found in "crowded" or resting cells. We also looked at the decay of the enzyme activity after subculture. This occurs rapidly (enzyme half-life is 1-2 h) and is concurrent with the re-entry of resting cells into cell cycle; however, thymidine added at the time of subculture to block DNA synthesis does not prevent the loss of prolyl hydroxylase activity. These results suggest that when cells are not engaged in propagation, they begin to synthesize luxury proteins such as prolyl hydroxylase. However, the loss of prolyl hydroxylase during subculture is probably not a direct consequence of DNA synthesis.


A crystallin gene network in the mouse retina.
The present study was designed to examine the regulation of crystallin genes and protein in the mouse retina using the BXD recombinant inbred (RI) strains. Illumina Sentrix BeadChip Arrays (MouseWG-6v2) were used to analyze mRNA levels in 75 BXD RI strains along with the parental strains (C57Bl/6J and DBA/2J), and the reciprocal crosses in the Hamilton Eye Institute (HEI) Retina Dataset (www.genenetwork.org). Protein levels were investigated using immunoblots to quantify levels of proteins and indirect immunohistochemistry to define the distribution of protein. Algorithms in the Genomatix program were used to identify transcription factor binding sites common to the regulatory sequences in the 5' regions of co-regulated set of crystallin and other genes as compared to a set of control genes. As subset of genes, including many encoding lens crystallins is part of a tightly co-regulated network that is active in the retina. Expression of this crystallin network appears to be binary in nature, being expressed either at relatively low levels or being highly upregulated. Relative to a control set of genes, the 5' regulatory sequences of the crystallin network genes show an increased frequency of a set of common transcription factor-binding sites, the most common being those of the Maf family. Chromatin immunoprecipitation of human lens epithelial cells (HLEC) and rat retinal ganglion cells (RGC) confirmed the functionality of these sites, showing that MafA binds the predicted sites of CRYGA and CRYGD in HLE and CRYAB, CRYGA, CRYBA1, and CRYBB3 in RGC cells. In the retina there is a highly correlated group of genes containing many members of the α- β- and γ-crystallin families. These genes can be dramatically upregulated in the retina. One transcription factor that appears to be involved in this coordinated expression is the MAF family transcription of factors associated with both lens and extralenticular expression of crystallin genes.


Bioavailability and toxicity of microplastics to fish species: A review.
The prevalence of microplastics in aquatic environments has raised concerns about their availability and risks to aquatic biota. Since fish is an important source of animal protein for human beings, the occurrence and potential impacts of microplastics in fishes deserve special attention. Although there have been an increasing number of studies concerning microplastics ingestion and effects in fish, review papers specifically focusing on this issue are few. This review summarized the current knowledge about the bioavailability and toxicity of microplastics to fish species. By collating literatures, it can be concluded that microplastics contamination could occur in almost all types of aquatic habitats around the globe. Both field and laboratory studies suggest that fishes are very susceptible to microplastics ingestion. Compared with marine species, freshwater fishes have been less studied. Microplastics alone or in combination with other contaminants could cause various health problems to fish after exposure. There still exist some debates over the environmental relevance of the laboratory-based effect studies and the relative contribution of microplastics in increasing the exposure of fish to hazardous chemicals. Hopefully, this review could extend the current knowledge on the ecotoxicological impacts of microplastics contamination to fish and provide guidance for future research.


Trends in advanced oral drug delivery system for curcumin: A systematic review.
Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome these limitations, nanocarrier-based drug delivery systems (NDS) are one of the most effective approaches being extensively explored over the last few decades to improve curcumin's physicochemical and pharmacological effects. Various NDS could provide productive platforms for addressing the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Among the 48 included studies, 3 studies were randomized controlled clinical trials, while 45 studies were animal models. To date, only five curcumin NDS have been studied in healthy volunteers: γ-cyclodextrin, phytosome, liposome, microemulsion and solid dispersion, while most curcumin NDS have been studied in animal models. Most included studies found that NDS could increase oral bioavailability of curcumin as compared to free curcumin. In conclusion, this systematic review showed evidence of the positive effect of NDS for enhancement of oral bioavailability of curcumin. EXECUTIVE SUMMARY: Curcumin is globally recognized for its health benefits, but its clinical application has been limited by its poor aqueous solubility and stability, which causes poor absorption in the gastrointestinal tract (GI tract) via oral administration. Nanocarrier-based drug delivery systems (NDS) are considered as a productive platform to solve the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Overall, most studies found that all studied NDS could increase the absorption of curcumin as compared to free curcumin. Curcumin was rapidly absorbed and exhibited a long residence time after oral administration of curcumin NDS. In summary, this systematic review showed positive impacts of NDS for enhancement of oral absorption of curcumin.


The effect of copper on osmoregulation in the freshwater amphipod Gammarus pulex.
The influence of copper on osmoregulation in the freshwater amphipod Gammarus pulex was determined from the analysis of water permeability, haemolymph sodium concentration, sodium influx and gill Na(+)/K(+) ATPase and Mg(2+) ATPase activity. Exposure to nominal copper concentrations of 100 microg l(-1) or greater caused a significant reduction in both haemolymph sodium concentration and sodium influx within 4 h. Measurements of water permeability, expressed as the half-time of exchange of body water (t(1/2)), excluded structural gill damage as the cause of this fall in haemolymph sodium. Copper at 10 microg l(-1) or above in the assay solution significantly reduced gill Na(+)/K(+) ATPase activity. In contrast gill Mg(2+) ATPase activity was markedly less affected by copper. These differences in enzyme sensitivity were considered with respect to the potential mechanisms of copper toxicity.


Role of mRNA expression of transcription factors in glucocorticoid sensitivity of peripheral blood mononuclear cells and disease state in rheumatoid arthritis.
To investigate the mechanisms underlying glucocorticoid (GC) resistance in rheumatoid arthritis (RA), we evaluated the suppressive effects of prednisolone (PSL) or methylprednisolone (MPSL) on the blastogenesis of peripheral blood mononuclear cells (PBMC). We also measured the expression of mRNA for transcription factors [GC receptor-alpha (GRalpha) and activator protein-1] known to be involved in the exertion of GC effects. Twenty-six patients with RA and 17 healthy subjects were studied. IC50 of PSL and MPSL on the blastogenesis of PBMC stimulated with concanavalin A in vitro was estimated. Transcripts for GRalpha, c-fos, c-jun, and GAPDH genes in PBMC were quantitatively determined by real-time RT-PCR procedures. The amount of c-fos transcript in PBMC from RA patients was significantly high compared to the healthy subjects (p = 0.001). However, no difference was found in the amounts of mRNA of other transcription factors between the patients and healthy subjects. When PSL or MPSL IC50 in patients were directly correlated with patients' characteristics in RA, the duration of disease showed a significant positive correlation with PSL IC50 (p = 0.035). However, no significant association of PSL or MPSL IC50 with GRalpha, c-fos, or c-jun mRNA expression determined by RT-PCR was observed. Additionally, there were significant correlations between the amount of GRalpha mRNA and inflammatory indices such as erythrocyte sedimentation rate (p < 0.001) and C-reactive protein (p < 0.05) in the RA patients. Chronic exposure to inflammation in RA suggests a decrease in the GC sensitivity of peripheral lymphocytes. Although c-fos and GRalpha transcripts in PBMC have been implicated in the pathology of RA, the amount of expression of these factors may not be critical for the development of GC insensitivity in the PBMC in RA.


Exploring Social Justice in Mixed/Divided Cities: From Local to Global Learning.
University of Haifa and the University of Maryland, Baltimore faculty developed a parallel binational, interprofessional American-Israeli course which explores social justice in the context of increasing urban, local, and global inequities. This article describes the course's innovative approach to critically examine how social justice is framed in mixed/divided cities from different professional perspectives (social work, health, law). Participatory methods such as photo-voice, experiential learning, and theatre of the oppressed provide students with a shared language and multiple media to express and problematize their own and others' understanding of social (in)justice and to imagine social change. Much learning about "self" takes place in an immersion experience with "others." Crucial conversations about "the other" and social justice can occur more easily within the intercultural context. In these conversations, students and faculty experience culture as diverse, complex, and personal. Students and faculty alike found the course personally and professionally transformative. Examination of social justice in Haifa and Baltimore strengthened our appreciation for the importance of context and the value of global learning to provide insights on local challenges and opportunities.


Whole brain methionine-enkephalin of ethanol-avoiding and ethanol-preferring c57BL mice.
These experiments systematically investigated ethanol preference in both the C57Bl/6N and C57Bl/6J mice utilizing three-choice 2-bottle preference test. In addition, these sublines were evaluated for whole brain methionine-enkephalin levels, which were significantly lower in C57Bl/6J mice (alcohol preferring) compared to C57Bl/6N mice (alcohol non-preferring). This finding supports the involvement of the peptidyl opiates in ethanol seeking behavior.


5-Ene-4-thiazolidinones - An efficient tool in medicinal chemistry.
The presented review is an attempt to summarize a huge volume of data on 5-ene-4-thiazolidinones being a widely studied class of small molecules used in modern organic and medicinal chemistry. The manuscript covers approaches to the synthesis of 5-ene-4-thiazolidinone derivatives: modification of the C5 position of the basic core; synthesis of the target compounds in the one-pot or multistage reactions or transformation of other related heterocycles. The most prominent pharmacological profiles of 5-ene derivatives of different 4-thiazolidinone subtypes belonging to hit-, lead-compounds, drug-candidates and drugs as well as the most studied targets have been discussed. Currently target compounds (especially 5-en-rhodanines) are assigned as frequent hitters or pan-assay interference compounds (PAINS) within high-throughput screening campaigns. Nevertheless, the crucial impact of the presence/nature of C5 substituent (namely 5-ene) on the pharmacological effects of 5-ene-4-thiazolidinones was confirmed by the numerous listed findings from the original articles. The main directions for active 5-ene-4-thiazolidinones optimization have been shown: i) complication of the fragment in the C5 position; ii) introduction of the substituents in the N3 position (especially fragments with carboxylic group or its derivatives); iii) annealing in complex heterocyclic systems; iv) combination with other pharmacologically attractive fragments within hybrid pharmacophore approach. Moreover, the utilization of 5-ene-4-thiazolidinones in the synthesis of complex compounds with potent pharmacological application is described. The chemical transformations cover mainly the reactions which involve the exocyclic double bond in C5 position of the main core and correspond to the abovementioned direction of the 5-ene-4-thiazolidinone modification.


Management of septic shock.
Septic shock due to bacterial and other infections remains an increasing cause of hospital mortality and morbidity. Early recognition and prompt management with diagnostic evaluation, antimicrobial therapy, surgery when indicated and advanced life support undoubtedly saves many lives. Once treatment has been instituted, careful and frequent monitoring is required to optimise therapy and detect complications at an early stage. However, once shock and organ failure have become established the mortality remains high and has changed little in the last few years despite improvements in intensive management. A variety of other approaches to treatment are under investigation but as yet there are insufficient data to recommend their use.


Factors affecting clearance of hepatitis B e antigen in hepatitis B surface antigen carrier children.
To understand the natural history of chronic hepatitis B virus infection in children, we studied factors affecting the clearance of hepatitis B e antigen (HBeAg). One hundred sixty-nine apparently healthy children whose sera were positive for HBeAg and hepatitis B surface antigen (HBsAg) and who were recruited by screening were followed prospectively to delineate the HBeAg clearance rate. Another 59 carrier children visiting the outpatient clinic because of symptoms or abnormal liver function were studied for comparison. The annual HBeAg clearance rate was low (less than 2%) during the first 3 years of life but increased with age. The HBeAg clearance rate in children older than 6 years of age was lower in those whose mothers had HBsAg positivity (14.3%) than in those whose mothers had no detectable HBsAg (35.3%). Children who were brought for medical care had higher HBeAg clearance rates (42.4%) than those who were recruited by screening (14.6%) because immune clearance of hepatitis B virus and hence HBeAg often led to hepatocellular damage manifested by abnormal liver function profiles or by symptoms that had caused the parents to seek medical care for their children. We conclude that age, source of subject recruitment, and maternal HBsAg status are important factors affecting HBeAg clearance rate in HBsAg carriers.


In-vivo transfection of the proopiomelanocortin gene, precursor of endogenous endorphin, by use of radial shock waves alleviates neuropathic pain.
Neuropathic pain is difficult to control and patient response to current treatment is often inadequate. Opioids have been widely used to treat a variety of pain states, but have several side effects. Endogenous opioids are clinically safe, but are not used for treatment because of rapid metabolism. However, in-vivo transfection of endogenous opioid genes could have a powerful and safe analgesic effect. The purpose of this study was to investigate the efficacy of proopiomelanocortin (POMC, a precursor of the endogenous opioid peptide β-endorphin) gene transfer by use of radial shock waves (RSWs) in a rat neuropathic pain model. As a neuropathic pain model, we used the Bennett chronic constriction injury (CCI) method. Immediately after CCI induction, POMC plasmid was injected into the rats' gastrocnemius muscle followed by exposure to RSW. Mechanical allodynia was measured for 4 weeks and dorsal root ganglion (DRG) neurons were sectioned and immunostained. β-Endorphin blood levels and the number of β-endorphin-immunoreactive (IR) muscle fibers increased over 28 days. β-Endorphin overexpression caused a decrease in the number of calcitonin gene-related peptide (CGRP)-IR DRG neurons and suppressed neuropathic pain induced by CCI without causing adverse side effects. The size-distribution pattern of CGRP-IR DRG neurons shifted from small to large cells in the CCI group; however, the number of both small and large CGRP-IR cells decreased in the POMC group. POMC gene transfection alleviated allodynia and reduced CGRP expression in DRG neurons without adverse effects. CGRP is not produced in large neurons under physiologic conditions; however, in this study CGRP expression was shifted to large neurons after nerve injury. This change in cell-size distribution suggests that CGRP expression in large neurons is related to neuropathic pain. These findings suggest that POMC gene transfection using RSWs is a safe and effective treatment for neuropathic pain.


Ultracytochemical study of Ca++-ATPase and K+-NPPase activities in retinal photoreceptors of the guinea pig.
Ca++-ATPase activity was demonstrated histochemically at light- and electron-microscopic levels in inner and outer segments of retinal photoreceptor cells of the guinea pig with the use of a newly developed one-step lead-citrate method (Ando et al. 1981). The localization of ouabain-sensitive, K+-dependent p-nitrophenylphosphatase (K+-NPPase) activity, which represents the second dephosphorylative step of the Na+-K+-ATPase system, was studied by use of the one-step method newly adapted for ultracytochemistry (Mayahara et al. 1980). In retinal photoreceptor cells fixed for 15 min in 2% paraformaldehyde the electron-dense Ca++-ATPase reaction product accumulated significantly on the inner membranes of the mitochondria but not on the plasmalemma or other cytoplasmic elements of the inner segments. The membranes of the outer segments remained unstained except the membrane arrays in close apposition to the retinal pigment epithelium. The cytochemical reaction was Ca++- and substrate-dependent and showed sensitivity to oligomycin. When Mg++-ions were used instead of Ca++-ions, a distinct reaction was also found on mitochondrial inner membranes. In contrast to the localization of the Ca++-ATPase activity, the K+-NPPase activity was demonstrated only on the plasmalemma of the inner segments, but not on the mitochondria, other cytoplasmic elements or the outer segment membranes. This reaction was almost completely abolished by ouabain or by elimination of K+ from the incubation medium.


Does socioeconomic status predict course and outcome in patients with psychosis?
We examined the relationship between socioeconomic status (SES) and course and outcome of patients with psychosis. Two hypotheses were examined: a) patients with higher best-ever SES will have better course and outcome than those with lower best-ever SES, and b) patients with greater downward drift in SES will have poorer course and outcome than those with less downward drift. Data were drawn from the baseline and 2-year follow-up assessments of the UK700 Case Management Trial of 708 patients with severe psychosis. The indicators of SES used were occupational status and educational achievement. Drift in SES was defined as change from best-ever occupation to occupation at baseline. For the baseline data highly significant differences were found between best-ever groups and negative symptoms (non-manual vs. unemployed--coef -10.5, p=0.000, 95% CIs 5.1-15.8), functioning (non-manual vs. unemployed--coef -0.6, p=0.000, 95% CIs 0.3 to -0.8) and unmet needs (manual vs. unemployed - coef 0.5, p=0.004, 95% CIs 0.2-0.9). No significant differences between best-ever groups were found for days in hospital, symptoms, perceived quality of life and dissatisfaction with services. Significant differences for clinical and social variables were found between drift and non-drift SES groups. There were no significant findings between educational groups and clinical and social variables. Best-ever occupation, but not educational qualifications, appeared to predict prognosis in patients with severe psychosis. Downward drift in occupational status did not result in poorer illness course and outcome.


Influence of shoes and heel strike on the loading of the hip joint.
The forces and moments acting at the hip joint influence the long-term stability of the fixation of endoprostheses and the course of coxarthrosis. These loads may depend on the kind of footwear and the walking or running style. These factors were investigated in a patient with instrumented hip implants. He wore different sports shoes, normal leather shoes, hiking boots and clogs and walked barefoot with soft, normal and hard heel strikes. The loads were lowest while walking and jogging without shoes. All shoes increased the joint force and the bending moment at the implant slightly but the torsional moment rose by up to 50%. No relation was found between the different type of shoes and the load increase, only shoes with very hard soles were clearly disadvantageous. Soft heels, soles or insoles did not offer advantages. Gait stability seems to play the most important role in increasing the joint loading and should be the criterion for the choice of footwear. Smooth gait patterns with soft heel strikes are the only means to reduce joint loading during slow jogging.


Putative termination sites for rDNA transcription in rice.
A clone bearing a 9.8 kb insert DNA containing the rDNA unit was identified by screening an EcoR1 library of rice DNA in lambda Charon 4 phage with [32P]-rRNAs. The S1 nuclease mapping of the rDNA-precursor rRNA hybrids showed the presence of two transcription termini on the rDNA. They were mapped at positions 616 and 620 nucleotides downstream to the end of the 25S rRNA gene. The 18 nucleotide sequence, where the transcription terminates on the rDNA in rice and mice are homologous albeit in the reverse orientation.


Additional dydrogesterone for the treatment of chronic endometritis treated with antibiotic in premenopausal women with endometrial polyps: a retrospective cohort study.
To assess the efficacy of dysdrogesterone in the treatment of chronic endometritis (CE) treated with antibiotic in premenopausal women with endometrial polyps (EPs). Routine detection of endometrium was simultaneously conducted to determine whether there was CE by syndecan-1 (CD138), while women underwent hysteroscopic polypectomy in our hospital. Antibiotic was given for the treatment of CE. A total of 235 premenopausal women with CE who underwent hysteroscopic polypectomy were enrolled in the retrospective observational study. In the control group, single antibiotic was given for the treatment of CE form January 2016 to December 2018, and in the treatment group additional dydrogesterone was used from January 2019 to November 2020. Comparison of cure rates of CE with different treatment regimens was performed. The cure rates of CE in dydrogesterone and antibiotic combination group and the single antibiotic group were 85.2% and 74.3%, respectively, with overall cure rate of 80.0% (188/235). The combination group showed better effects regarding the cure rate of CE (P < .05). Multivariate analysis confirmed that the cure rate of CE was not affected by age, body mass index, number of EPs, the status of estrogen receptor and the status of progesterone receptor. Conversely, dydrogesterone and endometrial scratching were beneficial factors for cure rate increase with antibiotic treatment. Combination of dydrogesterone and antibiotic was more effective for cure rate of CE than antibiotic alone in premenopausal women after hysteroscopic polypectomy. Endometrial scratching also contributed to the cure rate increase with antibiotic treatment.


Hippocampal dysfunction in cured Cushing's syndrome patients, detected by (1) H-MR-spectroscopy.
Proton magnetic resonance spectroscopy ((1) H-MRS) is a sensitive, noninvasive imaging technique capable of measuring brain metabolites in vivo. Chronic exposure to endogenous hypercortisolism in Cushing's syndrome (CS) is associated with negative effects on memory and hippocampal volumes, even after biochemical cure. To investigate metabolites in the hippocampi of CS patients and controls, using (1) H-MRS. Eighteen right-handed cured CS patients (age 44·8 ± 12·5 years, 12·6 ± 3·8 years of education) and 18 right-handed healthy controls, matched for age (40·0 ± 11·9) and years of education (14·4 ± 3·8), underwent 3-Tesla magnetic resonance imaging (3T MRI) and (1) H-MRS including the head of each hippocampus. Concentrations of Glu (Glutamate), Glx (Glutamate + Glutamine), NAA (N-Acetyl-aspartate), total NAA (N-Acetyl-aspartate + N-Acetyl-aspartyl-Glutamate), Cho (Glycerophosphocholine and Phosphocholine compounds), Cr (Creatine) and MI (mionositol) were measured (mmol/l). Hippocampal volumes (mm(3) ) were additionally calculated using an automated procedure (FreeSurfer). CS patients had lower NAA than controls in the left and right hippocampus (5·2 ± 1·0 vs 6·1 ± 0·7, P < 0·05; 4·9 ± 0·8 vs 6·1 ± 0·6, P < 0·001, respectively), and lower total NAA on the right side (5·7 ± 0·9 vs 6·3 ± 0·9, P < 0·05), suggesting neuronal dysfunction/loss. CS patients had higher Glx than controls in both hippocampi (10·4 ± 1·9 vs 8·6 ± 1·4, P < 0·01; 9·9 ± 1·6 vs 8·9 ± 1·3, P < 0·05, respectively), suggesting glial proliferation, as a repair mechanism after neuronal dysfunction. No differences were found in the other brain metabolites, and there were no differences in left (3815·78 ± 502·96) and right (3980·75 ± 369·44) total hippocampal volumes between CS patients and controls (3945·08 ± 408·90 and 4108·39 ± 365·11, respectively). Persistently abnormal metabolites are evidenced in the hippocampi of CS patients despite endocrine cure. These functional alterations could be early markers of glucocorticoid neurotoxicity, preceding hippocampal volume reduction.


Virtual and Augmented Simulations in Mental Health.
This examines significant trends and developments in the utilization of virtual reality (VR) and augmented reality (AR) simulations in the field of mental health and education. The objective is to gain insights into the emerging applications of VR/AR in mental health interventions and their potential impact on patient outcomes. The review also includes personal observations on the effectiveness and challenges associated with VR/AR simulations and the rise of exciting, disruptive artificial intelligence large language models. The findings of this review contribute to the understanding of the current state of VR/AR technology in mental health and highlight potential future directions in this rapidly evolving field. Recent studies have shown that VR/AR simulation is an effective and promising approach for treating various anxiety disorders, including specific phobias, social anxiety disorder, and post-traumatic stress disorder (PTSD). Simulated environments can be tailored to induce provoking situations, allowing individuals to learn from and gradually confront and grow in controlled and safe environments. Recent findings in the field of virtual reality simulations in mental health indicate that VR/AR exposure therapy is effective for treating anxiety disorders, while interventions show promise in improving social skills in individuals working with patients. In a broader sense, the use of VR/AR as an educational tool shows enormous potential now that functional generative artificial intelligence (AI) is recently available.


Determinants of bumetanide response in the dog: effect of probenecid.
The pharmacokinetics and pharmacodynamics of intravenous bumetanide (0.250 mg/kg), alone (treatment I) and after probenecid pretreatment (treatment II), were studied in four mongrel dogs. Lactated Ringer's solution was administered by vein throughout both treatments at a flow rate of 2 ml/min to avoid fluid and electrolyte depletion. Bumetanide and probenecid concentrations were analyzed by HPLC, sodium by flame photometry, and creatinine by colorimetry. Although the probenecid markedly reduced the plasma and renal clearances of bumetanide, as well as the fraction excreted unchanged in the urine, there was no significant difference between treatments I and II in the 4-hr natriuretic and diuretic responses. However, analysis of the dose-response curves between treatments I and II showed that sodium excretion was better correlated with bumetanide urinary excretion rate than with plasma concentration. The reasons for a poor correlation between treatments during the early time periods are discussed.


Association of potential salivary biomarkers with diabetic retinopathy and its severity in type-2 diabetes mellitus: a proteomic analysis by mass spectrometry.
The aim of our study was to characterize the human salivary proteome and determine the changes in protein expression in two different stages of diabetic retinopathy with type-2 diabetes mellitus: (1) with non-proliferative diabetic retinopathy (NPDR) and (2) with proliferative diabetic retinopathy (PDR). Type-2 diabetes mellitus without diabetic retinopathy (XDR) was designated as control. In this study, 45 saliva samples were collected (15 samples from XDR control group, 15 samples from NPDR disease group and 15 samples from PDR disease group). Salivary proteins were extracted, reduced, alkylated, trypsin digested and labeled with an isobaric tag for relative and absolute quantitation (iTRAQ) before being analyzed by an Orbitrap fusion tribrid mass spectrometer. Protein annotation, fold change calculation and statistical analysis were interrogated by Proteome Discoverer. Biological pathway analysis was performed by Ingenuity Pathway Analysis. Data are available via ProteomeXchange with identifiers PXD003723-PX003725. A total of 315 proteins were identified from the salivary proteome and 119 proteins were found to be differentially expressed. The differentially expressed proteins from the NPDR disease group and the PDR disease group were assigned to respective canonical pathways indicating increased Liver X receptor/Retinoid X receptor (LXR/RXR) activation, Farnesoid X receptor/Retinoid X receptor (FXR/RXR) activation, acute phase response signaling, sucrose degradation V and regulation of actin-based motility by Rho in the PDR disease group compared to the NPDR disease group. Progression from non-proliferative to proliferative retinopathy in type-2 diabetic patients is a complex multi-mechanism and systemic process. Furthermore, saliva was shown to be a feasible alternative sample source for diabetic retinopathy biomarkers.


Source-specific ecological risk assessment and quantitative source apportionment of heavy metals in surface sediments of Pearl River Estuary, China.
In this study, surface sediments of the Pearl River Estuary were collected from 29 stations and investigated the spatial distribution, pollution level, quantitative source apportionment, and source-specific ecological risk of 10 heavy metals. The mean concentrations followed the order of Mn > Zn > Cr > Cu > Ni > Pb > As > Co > Cd > Hg. In terms of spatial distribution, it showed that the heavy metals were enriched in the inner Pearl River Estuary with 'extremely high' level of Hg, whereas, Cd and Zn posed 'moderate to high' contamination potential. We apportioned four main sources using positive matrix factorization model, in which natural geogenic and industrial manufacturing sources accounted for 36.84% and 27.11% of the total, respectively. However, the source-specific risk assessment suggested that mixed anthropogenic sources were the main contributors, and ecological risks were strongly affected by anthropogenic imports from the surrounding cities.


Perioperative dexamethasone reduces post-surgical sequelae of wisdom tooth removal. A split-mouth randomized double-masked clinical trial.
The effect of endo-alveolar and sub-mucosal administration of dexamethasone sodium phosphate to prevent inflammatory sequelae after surgical removal of lower third molars was studied. Forty-three patients underwent bilateral extractions of lower third molars and were randomly assigned to receive either dexamethasone 4 mg (group A) or 10 mg (group B) as endo-alveolar powder or 10 mg as sub-mucosal injection (group C) unilaterally. The controlateral site served as control and did not receive any steroid administration. Facial edema, trismus and pain perception were evaluated at the 2nd and 7th postoperative day. A multivariate analysis revealed that treatment and ostectomy time were both significantly positively associated with the degree of postoperative trismus and edema. Other baseline classification variables (e.g., molar classification) were also predictive of the degree of change in all clinical parameters. Test sites treated (any steroid application) showed greater reductions in all clinical parameters recorded compared to control. No statistically significant differences were observed between the three test groups. Both sub-mucosal and endo-alveolar administration of dexamethasone are effective in reducing postoperative sequelae of surgical removal of lower wisdom teeth.


Harnessing metabolism of hepatic macrophages to aid liver regeneration.
Liver regeneration is a dynamic and regulated process that involves inflammation, granulation, and tissue remodeling. Hepatic macrophages, abundantly distributed in the liver, are essential components that actively participate in each step to orchestrate liver regeneration. In the homeostatic liver, resident macrophages (Kupffer cells) acquire a tolerogenic phenotype and contribute to immunological tolerance. Following toxicity-induced damage or physical resection, Kupffer cells as well as monocyte-derived macrophages can be activated and promote an inflammatory process that supports the survival and activation of hepatic myofibroblasts and thus promotes scar tissue formation. Subsequently, these macrophages, in turn, exhibit the anti-inflammatory effects critical to extracellular matrix remodeling during the resolution stage. However, continuous damage-induced chronic inflammation generally leads to hepatic macrophage dysfunction, which exacerbates hepatocellular injury and triggers further liver fibrosis and even cirrhosis. Emerging macrophage-targeting strategies have shown efficacy in both preclinical and clinical studies. Increasing evidence indicates that metabolic rewiring provides substrates for epigenetic modification, which endows monocytes/macrophages with prolonged "innate immune memory". Therefore, it is reasonable to conceive novel therapeutic strategies for metabolically reprogramming macrophages and thus mediate a homeostatic or reparative process for hepatic inflammation management and liver regeneration.


Oil contamination of sediments by freeze-drying versus air-drying for organic geochemical analysis.
Freeze-drying is widely used in geochemical laboratories for preparing wet solid environmental samples such as sediments and soils before being analyzed for their contents and states of various metal elements and labile organic components that may be temperature- and/or redox-sensitive. Screening bulk geochemical analysis of two Artic lake sediment samples prepared by freeze-drying displayed unexpectedly high contents of labile organic matter (OM) represented by the Rock-Eval S1 peaks (e.g., 8.12 and 4.84 mg HC/g sediment). The amount of labile OM was reduced greatly for the freeze-dried sediment samples after a thorough cleaning of the freeze-drier sample chamber (e.g., 2.75 and 1.46 mg HC/g sediment), but was still significantly higher than that of the equivalent air-dried samples (e.g., 0.76 and 0.23 mg HC/g sediment). Compositional analysis of the labile OM fractions by gas chromatography (GC) of both freeze-dried and air-dried aliquots of the same sediments indicates the presence of unresolved complex mixture (UCM) humps of C10-C23 hydrocarbons in the freeze-dried samples. In contrast, air-dried samples, either real sediments or blank laboratory materials represented by clean sand and thermally spent shale, do not show the C10-C23 hydrocarbon UCM humps on their GC traces. The hydrocarbon UCM humps persist in the freeze-dried samples even they further went through air-drying at ambient conditions. Both bulk and compositional analytical results in this work appear to indicate the potential risk of introduction of external hydrocarbons to the prepared materials during freeze-drying process, especially if an aged freeze-drier was used without being thoroughly cleaned and if pump oil and cooling fluids were components of the device.


A curiosity in the history of sciences: the words "megrim" and "migraine".
Vertigo has been described by medical doctors since Antiquity, but the condition is not limited to human medicine. It is also interesting to note that vertigo-related disorders were long only mentioned in the descriptions of migraine: however, in the Corpus Hippocraticum, a pain with vertigo (odunê kai skotodiniê) was not considered as hemicrania; in Aretaeus medical text, scotoma was clearly another disease than heterocraniê; although there could be metastases between them (pain could be followed by vertigo, as Boerhaave translated from Greek to Latin); Caelius Aurelianus, Ibn Zuhr of Seville, Īsmā'īl Jurjānī considered vertigo as a separate entity from "migraine" as well. One had to wait until 1831 for "ophthalmic migraine" (Piorry) to take systematically this disorder into account (to more or less causally relate it to migraine), and 1988 for the International Headache Society to acknowledge vertigo as a symptom of aura in "basilar migraine," which was given the better name of basilar-type migraine in 2004. From this point of view, veterinary medicine presents a particular interest because, for centuries, diseases mainly affecting horses - called in French "migraine," "mal de tête" (headache), "douleur de tête" (head pain), or in English "megrim(s)," "head-ach," "pain," and for which it is not self-evident that they are in any way related with the conditions that bear these names in humans - have been connected with vestibular impairments. Whatever is the relationship between the human and animal pathologies and, although it is impossible to interpret animal signs (abnormal behavior) with human symptoms (complaints), some impressive descriptions, written by Anglo-Saxon authors for the most part, seem to have played a significant role in the history of migraine. The purpose is to examine how a word in its English veterinary medical sense could have influenced French medical descriptions.


Pathogenicity of anti-ganglioside antibodies in the Guillain-Barré syndrome.
Guillain-Barré syndrome (GBS) is a postinfectious inflammatory polyradiculo-neuropathy characterized by flaccid paralysis. Antibodies directed against glycolipid structures (gangliosides), which are highly expressed in the peripheral nervous system, are frequently detected in sera from GBS patients. These antibodies interfere with nerve conduction and have been shown to activate phagocytes via IgG receptors (FcgammaR). These findings support an important role of glycolipid-specific antibodies in the pathogenesis of GBS.


Association of TNFAIP3 interacting protein 1, TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study.
TNFAIP3 interacting protein 1, TNIP1 (ABIN-1) is involved in inhibition of nuclear factor-κB (NF-κB) activation by interacting with TNF alpha-induced protein 3, A20 (TNFAIP3), an established susceptibility gene to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recent genome-wide association studies revealed association of TNIP1 with SLE in the Caucasian and Chinese populations. In this study, we investigated whether the association of TNIP1 with SLE was replicated in a Japanese population. In addition, association of TNIP1 with RA was also examined. A case-control association study was conducted on the TNIP1 single nucleotide polymorphism (SNP) rs7708392 in 364 Japanese SLE patients, 553 RA patients and 513 healthy controls. Association of TNIP1 rs7708392C was replicated in Japanese SLE (allele frequency in SLE: 76.5%, control: 69.9%, P = 0.0022, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.13-1.74). Notably, the risk allele frequency in the healthy controls was considerably greater in Japanese (69.9%) than in Caucasians (24.3%). A tendency of stronger association was observed in the SLE patients with renal disorder (P = 0.00065, OR 1.60 [95%CI 1.22-2.10]) than in all SLE patients (P = 0.0022, OR 1.40 [95%CI 1.13-1.74]). Significant association with RA was not observed, regardless of the carriage of human leukocyte antigen DR β1 (HLA-DRB1) shared epitope. Significant gene-gene interaction between TNIP1 and TNFAIP3 was detected neither in SLE nor RA. Association of TNIP1 with SLE was confirmed in a Japanese population. TNIP1 is a shared SLE susceptibility gene in the Caucasian and Asian populations, but the genetic contribution appeared to be greater in the Japanese and Chinese populations because of the higher risk allele frequency. Taken together with the association of TNFAIP3, these observations underscore the crucial role of NF-κB regulation in the pathogenesis of SLE.


Grammatical morphology in aphasia: evidence from three languages.
Aspects of grammatical morphology in Broca's and Wernicke's aphasia were elicited under controlled conditions in three language groups: English, Italian and German. Results suggest that the agrammatism/paragrammatism distinction does not work well for richly-inflected languages. Language-specific ratios of closed class morphology were preserved even among non-fluent patients, with significantly more morphology produced by German and Italian patients. German and Italian patients were also much more likely to furnish the article before nouns--despite or perhaps because of the fact that articles are more complex and informative in those languages. Although patients assigned the correct article most of the time, there were a significant number of article errors (i.e. paragrammatic substitution). Error analyses showed that substitutions are not random, reflecting difficulty in access rather than loss. Substitutions were more common in German, where the complex case and gender markings on the article increase the probability of error. Within each language, error patterns were quite similar for Broca's and Wernicke's aphasics. However, at a detailed level patient group differences in error production were detected. German Broca's aphasics tend to avoid difficult case forms by substituting a simpler, less-marked morphosyntactic frame. Wernicke's aphasics try instead to produce the more marked, oblique constructions, resulting in a less conservative error pattern.


Translocation of protein kinase C in porcine thyroid cells following exposure to thyrotropin.
We have previously shown that protein kinase C activators modulate differentiated thyroid function in vitro; however, how protein kinase C may be activated physiologically is unknown. The present studies were undertaken in order to determine whether TSH could activate protein kinase C in vitro. Following exposure of porcine thyroid cells to TSH, translocation of protein kinase C from the cytosol to its membrane-bound form was observed. Maximal translocation occurred at the lowest TSH concentration able to trigger this response (10 mU/ml) but persisted at higher concentrations (20-100 mU/ml). Time-course studies revealed that translocation of protein kinase C was seen only after 40 min. TSH could also produce a similar translocation in human neutrophils (known to have TSH receptors). In thyroid cells pre-treated with TSH, modulation of phorbol-mediated protein kinase C translocation was noted. These results indicate that TSH causes the translocation of protein kinase C in porcine thyroid cells (and possibly other TSH receptor-containing cells) and therefore may regulate the action of protein kinase C on differentiated thyroid function.


7T HR FID-MRSI Compared to Amino Acid PET: Glutamine and Glycine as Promising Biomarkers in Brain Tumors.
(1) Background: Recent developments in 7T magnetic resonance spectroscopic imaging (MRSI) made the acquisition of high-resolution metabolic images in clinically feasible measurement times possible. The amino acids glutamine (Gln) and glycine (Gly) were identified as potential neuro-oncological markers of importance. For the first time, we compared 7T MRSI to amino acid PET in a cohort of glioma patients. (2) Methods: In 24 patients, we co-registered 7T MRSI and routine PET and compared hotspot volumes of interest (VOI). We evaluated dice similarity coefficients (DSC), volume, center of intensity distance (CoI), median and threshold values for VOIs of PET and ratios of total choline (tCho), Gln, Gly, myo-inositol (Ins) to total N-acetylaspartate (tNAA) or total creatine (tCr). (3) Results: We found that Gln and Gly ratios generally resulted in a higher correspondence to PET than tCho. Using cutoffs of 1.6-times median values of a control region, DSCs to PET were 0.53 ± 0.36 for tCho/tNAA, 0.66 ± 0.40 for Gln/tNAA, 0.57 ± 0.36 for Gly/tNAA, and 0.38 ± 0.31 for Ins/tNAA. (4) Conclusions: Our 7T MRSI data corresponded better to PET than previous studies at lower fields. Our results for Gln and Gly highlight the importance of future research (e.g., using Gln PET tracers) into the role of both amino acids.


Synthesis of 6-arylthio analogs of 2',3'-dideoxy-3'-fluoroguanosine and their effect against hepatitis B virus replication.
A key compound, 2-amino-6-chlor-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)puine, was prepared from 2-amino-6-chloropurine riboside in 5 steps, then subjected to the nucleophilic displacement with benzenethiols to afford 6-arylthio congeners. These compounds showed a similar anti-HBV effect to that of 2',3' dideoxy-3'-fluoroguanosine.


Enantioselective synthesis of allenic esters via an ylide route.
Pseudo-C2-symmetric chiral phosphorus ylides have been designed and synthesized for the enantioselective preparation of allenic esters, and up to 92% ee has been achieved.


Contingency management interventions for abstinence from cigarette smoking in pregnancy and postpartum: A systematic review and meta-analysis.
Contingency management is one of the most effective treatments for substance use disorders in not-pregnant people. The most recent quantitative review of its efficacy among pregnant and postpartum women who smoke cigarettes concluded with moderate certainty that those receiving contingent financial incentives were twice as likely to be abstinent compared with controls. We aimed to update and extend previous reviews. Five databases were systematically searched for randomized controlled trials (RCTs) published before December 2022 that assessed the effectiveness of incentives for abstinence from substance use. Data from trials of smoking abstinence were pooled using a random-effects meta-analysis model (restricted maximum likelihood). Results are reported as risk-ratios (RRs) with 95% confidence intervals (CIs). This study is registered with PROSPERO, CRD42022372291. Twelve RCTs (3136) pregnant women) were included. There was high certainty evidence that women receiving incentives were more likely to be abstinent than controls at the last antepartum assessment (12 RCTs; RR = 2.43, 95% CI 2.04-2.91, n = 2941, I2 = 0.0%) and moderate certainty evidence at the longest postpartum assessment while incentives were still available (five RCTs; RR = 2.72, 1.47-5.02, n = 659, I2 = 44.5%), and at the longest postpartum follow-up after incentives were discontinued (six RCTs; RR = 1.93, 1.08-3.46, n = 1753, I2 = 51.8%). Pregnant women receiving incentives are twice as likely to achieve smoking abstinence during pregnancy suggesting this intervention should be standard care for pregnant women who smoke. The results also demonstrate that abstinence continues into the postpartum period, including after incentives are discontinued, but more trials measuring outcomes in the postpartum period are needed to strengthen this conclusion.


Studying semi-dynamic digestion kinetics of food: Establishing a computer-controlled multireactor approach.
In this work, a multireactor system to study digestion (MuReDi) kinetics is introduced. For this, a custom-made automated system with four independent syringe pumps (BioXplorer 100, H.E.L Group) was acquired. This system consists of multiple, small-scale reactors allowing to study digestion as a function of time and thus to determine digestion kinetics. The different digestion conditions used in the oral, gastric, and small intestinal phase were based on the digestion protocols published by the INFOGEST consortium. We showed that the minimum working volume of a reactor is 30 mL. Besides, repeatability of the digestion kinetics was shown for two food systems: a liquid Ensure® Plus Vanilla drink, and a solid, cooked lentil sample. When comparing static digestion kinetics with semi-dynamic ones, a significantly different digestion pattern was observed. In the static case, a relatively fast hydrolysis rate was observed until a clear plateau was reached. Oppositely, for the semi-dynamic case, a delayed start of the hydrolysis process was noticed. In the gastric phase, this was explained by the decreasing pH and the large pH dependency of pepsin activity. In the small intestine, the lag phase was relatively shorter, yet clearly present. Here we related it to the gradual enzyme (and bile salt) secretion that had to diffuse towards the substrate before hydrolysis could start. Generally, this work showed that the MuReDi system could be used to perform a semi-dynamic digestion approach which largely impacted the overall digestion kinetics. This is important to consider in future in vitro food digestion simulation work to come closer to physiologically relevant digestion kinetics.


α-L-rhamnosidase: production, properties, and applications.
α-L-rhamnosidase [EC 22.214.171.124] belongs to glycoside hydrolase (GH) families (GH13, GH78, and GH106 families) in the carbohydrate-active enzymes (CAZy) database, which specifically hydrolyzes the non-reducing end of α-L-rhamnose. Αccording to the sites of catalytic hydrolysis, α-L-rhamnosidase can be divided into α-1, 2-rhamnosidase, α-1, 3-rhamnosidase, α-1, 4-rhamnosidase and α-1, 6-rhamnosidase. α-L-rhamnosidase is an important enzyme for various biotechnological applications, especially in food, beverage, and pharmaceutical industries. α-L-rhamnosidase has a wide range of sources and is commonly found in animals, plants, and microorganisms, and its microbial source includes a variety of bacteria, molds and yeasts (such as Lactobacillus sp., Aspergillus sp., Pichia angusta and Saccharomyces cerevisiae). In recent years, a series of advances have been achieved in various aspects of α-validates the above-described-rhamnosidase research. A number of α-L-rhamnosidases have been successfully recombinant expressed in prokaryotic systems as well as eukaryotic systems which involve Pichia pastoris, Saccharomyces cerevisiae and Aspergillus niger, and the catalytic properties of the recombinant enzymes have been improved by enzyme modification techniques. In this review, the sources and production methods, general and catalytic properties and biotechnological applications of α-L-rhamnosidase in different fields are summarized and discussed, concluding with the directions for further in-depth research on α-L-rhamnosidase.


Visual prognosis of disciform degeneration in myopia.
A retrospective study was done on a consecutive series of patients presenting to the Moorfields Eye Hospital with visual reduction secondary to angiographically proven subretinal neovascularization associated with myopia (Förster-Fuchs' spot), with a short history of visual loss, and free of other ocular disease. The visual acuity at follow-up was compared to that at presentation, and related to size and location of the neovascular complex, as well as patient age, and duration of follow-up. The results show a generally poor prognosis in that 43% of the patients lost two or more lines of vision, while 60% were less than or equal to 6/60 at last follow-up. As expected there was a direct relationship between visual acuity and the distance of the neovascular tissue from the fovea, and an inverse relationship between acuity and the size of the lesion. There seems to be a short neovascular growth phase, with early visual loss.


The effect of perindopril on postural instability in older people with a history of falls-a randomised controlled trial.
double-blind, parallel group, placebo-controlled randomised trial. we recruited people aged >65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors. we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24). perindopril did not improve postural sway in older people at risk of falls. ISRCTN58995463.


Induction of differentiation of the human histocytic lymphoma cell line U-937 by hypericin.
Hypericin, a photosensitizing plant pigment, was found to be a potent inducer of differentiation of human myeloid leukemia U-937 cells. At a concentration of 0.2 microM, hypericin exhibited 50% growth inhibition. An effect on cell differentiation by hypericin was assessed by its ability to induce phagocytosis of latex particles, and to reduce nitroblue tetrazolium (NBT). Approximately 51% of 0.2 microM hypericin-treated cells were stained with NBT and 63% showed phagocytic activity. In order to establish whether hypericin induces differentiation of U-937 cells to macrophage or granulocyte, esterase activities and cell sizes were measured. When U-937 cells were treated with 0.2 microM and 0.15 microM of hypericin, the alpha-naphthyl acetate esterase activity was increased by 38.4% and 48.1%, respectively, but naphthol AS-D chloroacetate esterase activity was not influenced. The size of hypericin-treated cells in terms of cell mass was larger than that observed in untreated cells as determined by flow cytometry. Protein kinase C (PKC) inhibitor, NA-382, decreased the NBT reducing activity of hypericin, whereas a cAMP-dependent protein kinase A (PKA) inhibitor, H-89, did not show any influence on the differentiation. These results indicate that hypericin triggers differentiation toward monocyte/macrophage lineage by PKC stimulation.