Pharmacodynamic properties of felodipine.
This overview presents the pharmacodynamic properties of felodipine as studied in animal experiments with emphasis on results from our laboratory. Felodipine is 100-fold more potent in causing inhibition of spontaneously active vascular smooth muscle than myocardium in vitro. This vascular selectivity is significantly greater than that of nifedipine (potency ratio 15). Verapamil, D-600, La3+ and reduction of [Ca2+]o lack selectivity. The cellular mechanisms underlying this variable selectivity are not clear at present. In conscious spontaneously hypertensive rats (SHR), the plasma concentration required for 20% reduction of mean arterial pressure is approximately 10 nmol. Mean arterial pressure is lowered dose-dependently as a result of reduced peripheral vascular resistance accompanied by increased cardiac output due to transient tachycardia and increased stroke volume. There was rapid resetting of the baroreflex set point but unaltered sensitivity after felodipine and hydralazine in SHR. Therefore, the reflexogenic increase in heart rate and plasma renin activity subsided within 3 to 5 hours of continuous felodipine administration in SHR. In addition, there was a uniform dilatation of the peripheral vascular beds after felodipine administration. During long term treatment of SHR with felodipine, progression of left ventricular and vascular wall hypertrophy was prevented. Within the 'therapeutic dose range', the only primary effect observed in addition to arterial vasodilation is diuresis/natriuresis caused by a renal tubular action.


Nitrogen, silicon co-doped carbon dots as the fluorescence nanoprobe for trace p-nitrophenol detection based on inner filter effect.
P-nitrophenol (PNP) has been widely applied to industry processing for many purposes, but the persistence and toxicity of residuum may pose risks to human health. To analyze PNP in industrial and agricultural wastewater, a versatile fluorescent probe sensing platform was proposed. In this work, we devised a fluorescence approach that utilized nitrogen, silicon co-doped carbon dots (N,Si-CDs) to monitor PNP originating from the inner filter effect (IFE). The N,Si-CDs were generated in a one-step hydrothermal synthesis, and which possessed outstanding fluorescence signal and water-dispersity. Emission at 441 nm was monitored with excitation at 360 nm using a common spectrofluorometer. The method achieved an exceptionally low limit of detection (LOD) of 0.011 μM. Furthermore, this method not only eliminates the interference from metal ions and acid ions, but also provides a potential application prospect for N,Si-CDs in the field of water monitoring. Analysis of tap and lake water led to 93.30-106.30% recoveries and <1% relative standard deviation at 2.5-25 μM PNP concentrations.


Burden of depression and predictors among Ethiopian stroke survivors: Cross-sectional study.
stroke is a common cause of mortality and morbidity in low- and middle-income countries. It is a very sudden episode in the patients' lives and can lead to multiple psychosocial, social, and economic consequences, and psychiatric problems. poststroke depression is the most common and major neuropsychiatric consequence of stroke that affects one-third of stroke survivors. The aim of this study to assess the burden of depression and its predictors among stroke survivors with local version validated Patient Health Questionnaire. An institutional-based cross-sectional study was conducted among stroke patients at selected tertiary level hospitals. Data were collected by interview method using structured questionnaires, and patient medical record reviews and data were recruited by using consecutive sampling method. Bivariate and multivariable binary logistic regression model analysis was used with SPSS version 23 to identify factors associated with depression. A total of one hundred eighty stroke patients participated in the study with a response rate of 88.2%. The overall prevalence of depression is 49.6% (95% CI: 42.8, 56.7). Occupation, marital status, level of education of stroke patients was significantly associated with post stroke depression with P < 0.05. The study findings presented that nearly half of the stroke patients suffered from post stroke depression. Post-stroke depression was strongly associated with patient occupation, marital status, and level of education There is urgent need for integration of screening for and management of post-stroke depression among stroke survivors.


The Effect of IL-6 174G > C Gene Polymorphism on Gastrointestinal Cancer: a Systematic Review and Meta-analysis.
IL-6 gene polymorphisms can play a role in the development or control of cancer by affecting cytokines. Gastrointestinal cancer is one of the most common types of cancer worldwide. The aim of this study was to investigate the effect of polymorphism of the IL-6 174G > C gene on gastrointestinal cancers based on a systematic review and meta-analysis, including gastric, colorectal, and esophageal cancer. In this study, a systematic and meta-analytical review of the study data on the effect of polymorphism of IL-6 174G > C gene on gastrointestinal cancer (gastric, colorectal, and esophageal cancer) in Scopus, EMBASE, Web of Science, PubMed, and Science Direct Databases was extracted without any time limit until April 2020. In order to perform the analysis of eligible studies, the model of random effects was used and the heterogeneity of studies was investigated with I2 index. Data analysis was performed with Comprehensive Meta-Analysis software (Version 2). The total number of surveyed studies in patients with colorectal cancer was 22 studies. Based on the results of meta-analysis, the odds ratio of GG genotype in patients with colorectal cancer was 0.88. The odds ratio of GC genotype obtained in patients with colorectal cancer was 0.88 and the odds ratio of CC genotype in patients with colorectal cancer was 0.92. The total number of surveyed studies in patients with gastric cancer was 12. Based on the meta-analysis results, the odds ratio of GG genotype in patients with gastric cancer was 0.74, the odds ratio of GC genotype in patients with gastric cancer was 1.27, and the odds ratio of CC genotype in patients with gastric cancer was 0.78. The total number of surveyed studies in esophageal cancer patients was 3 studies. Based on the results of meta-analysis, the odds ratio of GG genotype in patients with esophageal cancer was 0.57, the odds ratio of GC genotype in patients with esophageal cancer was 0.44, and the odds ratio of chance of CC genotype in patients with esophageal cancer was 0.99. In general, different genotypes of polymorphism of the IL-6 174G > C gene reduce the risk of gastric, colorectal, and esophageal cancer. However, the GC genotype of this gene was associated with a 27% increased risk of gastric cancer.


Recording single- and multi-unit neuronal action potentials from the surface of the dorsal root ganglion.
The dorsal root ganglia (DRG) contain cell bodies of primary afferent neurons, which are frequently studied by recording extracellularly with penetrating microelectrodes inserted into the DRG. We aimed to isolate single- and multi-unit activity from primary afferents in the lumbar DRG using non-penetrating electrode arrays and to characterize the relationship of that activity with limb position and movement. The left sixth and seventh lumbar DRG (L6-L7) were instrumented with penetrating and non-penetrating electrode arrays to record neural activity during passive hindlimb movement in 7 anesthetized cats. We found that the non-penetrating arrays could record both multi-unit and well-isolated single-unit activity from the surface of the DRG, although with smaller signal to noise ratios (SNRs) compared to penetrating electrodes. Across all recorded units, the median SNR was 1.1 for non-penetrating electrodes and 1.6 for penetrating electrodes. Although the non-penetrating arrays were not anchored to the DRG or surrounding tissues, the spike amplitudes did not change (<1% change from baseline spike amplitude) when the limb was moved passively over a limited range of motion (~20 degrees at the hip). Units of various sensory fiber types were recorded, with 20% of units identified as primary muscle spindles, 37% as secondary muscle spindles, and 24% as cutaneous afferents. Our study suggests that non-penetrating electrode arrays can record modulated single- and multi-unit neural activity of various sensory fiber types from the DRG surface.


Genome-wide association study of the level of blood components in Pekin ducks.
Blood components are considered to reflect nutrient metabolism and immune activity in both humans and animals. In this study, we measured 12 blood components in Pekin ducks and performed genome-wide association analysis to identify the QTLs (quantitative trait locus) using a genotyping-by-sequencing strategy. A total of 54 QTLs were identified for blood components. One genome-wide significant QTL for alkaline phosphatase was identified within the intron-region of the OTOG gene (P = 1.31E-07). Moreover, 21 genome-wide significant SNPs for the level of serum cholinesterase were identified on six different scaffolds. In addition, for serum calcium, one genome-wide significant QTL was identified in the upstream region of gene RAB11B. These results provide new markers for functional studies in Pekin ducks, and several candidate genes were identified, which may provide additional insights into specific mechanisms for blood metabolism in ducks and their potential application for duck breeding programs.


Discrimination of ginseng cultivation regions using light stable isotope analysis.
Korean ginseng is considered to be a precious health food in Asia. Today, thieves frequently compromise ginseng farms by pervasive theft. Thus, studies regarding the characteristics of ginseng according to growth region are required in order to deter ginseng thieves and prevent theft. In this study, 6 regions were selected on the basis of Korea regional criteria (si, gun, gu), and two ginseng-farms were randomly selected from each of the 6 regions. Then 4-6 samples of ginseng were acquired from each ginseng farm. The stable isotopic compositions of H, O, C, and N of the collected ginseng samples were analyzed. As a result, differences in the hydrogen isotope ratios could be used to distinguish regional differences, and differences in the nitrogen isotope ratios yielded characteristic information regarding the farms from which the samples were obtained. Thus, stable isotope values could be used to differentiate samples according to regional differences. Therefore, stable isotope analysis serves as a powerful tool to discriminate the regional origin of Korean ginseng samples from across Korea.


Vasoconstrictor and dilator responses to neurokinin A in isolated guinea pig heart.
Effects of neurokinin A (NKA) and substance P (SP) on coronary resistance vessels were studied in isolated guinea pig hearts perfused with isotonic buffer containing 20 mM KCl. Injections of NKA and SP caused dose-dependent reductions in perfusion pressure with ED50 values of 14.0 and 0.326 pmol, respectively. Blockade of nitric oxide synthesis or removal of the endothelium inhibited vasodilator responses to neurokinins. Infusions of NKA or SP caused tachyphylaxis and cross-desensitization to the other neurokinin but not to acetylcholine. Injections of 2.5 nmol NKA increased perfusion pressure by 31 +/- 8% when given after tachyphylaxis developed to infused SP (2.5 nmol/100 microliters/min). It was concluded that 1) neurokinins cause an endothelium-dependent relaxation of coronary resistance vessels by stimulating NK-1 receptors on endothelial cells, and 2) desensitization of the receptor mediating vasodilation unmasks a vasoconstrictor response to NKA.


Abnormal hemoglobin H band in myelodysplastic syndromes (MDS): A case report.
Myelodysplastic syndrome (MDS) is a group of heterogeneous diseases derived from hematopoietic stem cells characterized by hemolytic anemia and high risk of conversion to acute leukemia. MDS is an age-related disease in which approximately 80% of patients are over 60years of age, male and female. Anemia is the most common clinical condition, and many patients are also associated with infection and bleeding. When the amount of α globin synthesis is insufficient, the remaining β chain forms tetramer β4, i.e. HbH. The latter forms a precipitate in red blood cells, leading to hemolytic anemia, called HbH disease, the majority of which is congenital, a small number of patients with myelodysplastic syndrome and acute myeloid leukemia may appear HbH (called acquired HbH disease). We reported a 71years old male patient diagnosed as myelodysplastic syndromes (MDS) in our hospital. The patient has a negative α-thalassemia gene test. The H band is detected by hemoglobin electrophoresis. This article analyzed and discussed this case with MDS, as well reviewed MDS.


Vegetarians: Past, Present, and Future Regarding Their Diet Quality and Nutritional Status.
The term "vegetarian" usually refers to individuals who exclude meat, fish, poultry and/or their derived products from their diet [...].


Hippocampus-specific deletion of tissue plasminogen activator "tPA" in adult mice impairs depression- and anxiety-like behaviors.
Anxiety and depression are multifactorial disorders that have become prominent health problems all over the world. Neurotrophic factors have emerged underlying pathogenesis of these diseases. Although a number of studies indicate that the hippocampus-brain-derived neurotrophic factor (BDNF) may be involved in these psychiatric illnesses, little is known about the molecular mediators of these disorders. In this study we further investigate the role of tissue plasminogen activator (tPA), a serine protease involved in pro-BDNF cleavage to BDNF, in depression and anxiety-like behaviors in adult mice. To address this issue, we investigated the effect of hippocampus tPA manipulation, using viral vectors, on anxiety- and depression-like behaviors, including the marble burying test (MBT), elevated plus maze (EPM), tail suspension test (TST), novelty suppressed feeding (NSF) and forced swim test (FST). Our results showed that tPA knock-down - using lentiviral vectors expressing specific short hairpin RNAs (LV-shRNA) - increased the number of buried marbles together with the digging time in the MBT and decreased the time spent in open the arms of an EPM. In addition, tPA-knock down in the hippocampus increased immobility in the FST and TST, and increased time to feed in the NSF test. These effects were reversed when tPA-over-expressing vectors (LV-tPA) were injected in the hippocampus. We also found that BDNF protein levels were elevated in the hippocampus of mice receiving tPA-expressing vectors. Together, our results imply that tPA manipulation may provide an effective therapeutic intervention for depression and anxiety disorders.


Use of imaging techniques for non-invasive assessment in the diagnosis and staging of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and represent a common finding in highly prevalent metabolic disorders (i.e. type 2 diabetes, metabolic syndrome, obesity). Non-alcoholic steatohepatitis (NASH) requires liver biopsy for grading and staging the liver damage by the assessment of steatosis, inflammation and fibrosis. In parallel with the development of numerous 'liquid' biomarkers and algorithms that combine anthropometric and laboratory parameters, innovative hepatic imaging techniques have increasingly been developed to attempt to overcome the need for biopsy, both in diagnosis and staging of NAFLD, and in possible use in the follow-up of the disease. In this review, we focused on the different imaging techniques trying to highlight the strengths and disadvantages of different approaches, particularly for ultrasound techniques, in stratifying liver injury and fibrosis in patients with NAFLD / NASH.


Cross-sectional geometrical properties and bone mineral contents of the human radius and ulna.
The mechanical strength of the human radius and ulna depends on their geometrical and material properties. This study quantifies the cortical bone cross-sectional properties of the adult radius and ulna (cross-sectional area, thickness, centroids, area moments of inertia and section moduli) using computerized tomographic (CT) scanning coupled with image processing along the lengths of eight human cadaveric forearms. Bone mineral mass and apparent ash density were also quantified at serial locations. Sites of significant variation of selected geometric and mineral properties along the length of each forearm bone were determined. Our results show that interpolation of CT measurements made at 10 and 30% of the radial length in the radius and 30 and 90% of the radial length in the ulna can provide approximate geometric values over the 10-90% region. This information can be used to develop a protocol using the fewest sites to clinically assess changes in forearm bone geometry. Regression analyses did not show significant linear relationships between geometric properties and apparent cortical ash density. Thus, CT derived geometric properties are not helpful in estimating the extent of changes in bone density. Area moment of inertia results suggest that the junction of the middle and distal third of the radius, and the ulnar shaft region may have increased vulnerability to fractures. The former is likely due to the change in moment of inertia values, whereas the latter is due to the relatively small magnitude of cross-sectional moments along the ulnar shaft as compared to the proximal or distal ends. This is consistent with fracture patterns observed clinically when a single forearm bone is fractured: Galeazzi fracture of the radius and nightstick fracture of the ulna.


Adapting Equity-Focused Approaches to Address Workflow Challenges During COVID-19: Lessons for the Health Care Workforce.
The COVID-19 pandemic has severely impacted certain racial and ethnic groups due to systemic racism and poor governmental emergency responses. Health organizations and leaders worked strategically to pivot their workflows to meet the emerging needs of their patient population. In this perspective, three examples are shared of successful interventions that made workflow improvements to be efficient while ensuring excellent patient care during the pandemic and beyond. Lessons from the initiatives are ones that health professionals can advocate for and easily adopt to ensure that medical mistreatment and disparities for some patient populations do not continue to flourish.


The effect of tissue expansion on peripheral nerves.
The effect of tissue expansion on peripheral nerves was studied in 214 rats. Slow expansion (over 15 days) is better tolerated than rapid expansion (over 3 days). The resulting increase in length of the nerve is proportional to the degree of expansion. All the nerves which underwent expansion showed a decrease in conduction velocity and this reduction was greater for nerves which were elongated by 50% or more.


CHARGE syndrome. Part II. Hearing loss.
CHARGE is a mnemonic for a syndrome with multiple congenital anomalies that occurs with normal chromosomes. The unique external ear anomalies have been described in CHARGE Syndrome Part I in this journal. This report describes the distinctive middle ear and sensorineural losses that occur in the syndrome, both of which can be progressive and, in most cases, are moderate to severe. There is evidence to indicate that these losses are due to congenital ossicular anomalies, eustachian tube dysfunction from craniofacial malformation, and cochlear involvement that is greatest for high frequencies.


Identifying children at high somatic risk: possible long-term effects on parental conceptualizations of the children's personality and behavior.
The identification of alpha 1 antitrypsin deficiency (ATD) in neonates was hypothesized to have negative long-term consequences on the parents' views of the children's personality characteristics. This hypothesis was tested by comparing 5-7-year-old children's personality and behavioral characteristics, as reported by parents of 61 children with ATD versus parents of 61 control children without ATD. Data were collected by both interviews in the home and temperament questionnaires. No evidence was found of the hypothesized negative effect on parental views.


Identification of Plasmodium falciparum reticulocyte binding protein RBP-2 homologue a and b (PfRBP-2-Ha and -Hb) sequences that specifically bind to erythrocytes.
Plasmodium falciparum reticulocyte binding protein RBP-2 homologues a and b (PfRBP-2-Ha and -Hb) have been described as being high molecular weight proteins, expressed at the P. falciparum merozoite apical extreme, belonging to a family of proteins found in other Plasmodium involved in the search for erythrocyte populations before being invaded by merozoites. 185, 20-mer-long non-overlapping peptides, spanning the entire PfRBP-2-Ha and -Hb sequences, were synthesised, radiolabelled and tested in erythrocyte binding assays. Fifteen PfRBP-2-Ha and -Hb high binding activity peptides (HBAPs) specifically binding to erythrocytes with high affinity were identified. Dissociation constants were between 70 and 300 nM and Hill coefficients were 1 approximately. HBAPs residues critical for binding to erythrocytes were determined. Cross-linking was performed allowing possible receptors for PfRBP-2-Ha and -Hb to be identified on the surface of the erythrocytes. Some of the HABPs showed merozoite invasion inhibition greater than 90% in in vitro assays.


Hypercaloric lipid and glucose infusion reduces the mitochondrial respiratory activity in the regenerating rat liver.
In order to evaluate the liver mitochondrial response to an increased energy load, eight groups of rats were studied: a control group (no surgery), a sham-operated group, and 6 groups that had undergone partial hepatectomy (PH). The PH rats either had no infusion following surgery, saline, isocaloric lipid, hypercaloric lipid, isocaloric glucose or hypercaloric glucose infusion. After isolation of liver mitochondria 6, 12, 18 and 24 h after surgery states 3 and 4 of respiration were measured in vitro in the presence of succinate. State 3 and 4 mitochondrial respiration was higher in the sham-operated rats 6 h after surgery than in the control animals, and a gradual decrease towards control values occurred in the 12-24 h period following surgery. Results in mitochondria from PH rats showed variable results, in most cases both State 3 and 4 respiration was higher after PH, while the respiratory control index in general was lower. State 3 respiration was significantly increased in the PH isocaloric lipid and glucose infused groups 6, 12 and 18 h, but not 24 h after partial hepatectomy. The PH hypercaloric glucose and hypercaloric lipid infused rats showed decreases in the liver mitochondrial oxygen consumption after 6, 12 and 18 h of liver regeneration, this was more pronounced after hypercaloric lipid infusion. These results suggest that, in vitro, the surgery tends to increase Status 3 and Status 4 mitochondrial respiration. The hypercaloric parenteral nutrition, both lipid and glucose based, significantly decreased liver mitochondrial oxygen consumption in partially hepatectomized rats, particularly in the first hours of liver regeneration, with restoration 24 h after surgery.


Identification of Cytotoxic Flavor Chemicals in Top-Selling Electronic Cigarette Refill Fluids.
We identified the most popular electronic cigarette (EC) refill fluids using an Internet survey and local and online sales information, quantified their flavor chemicals, and evaluated cytotoxicities of the fluids and flavor chemicals. "Berries/Fruits/Citrus" was the most popular EC refill fluid flavor category. Twenty popular EC refill fluids were purchased from local shops, and the ingredient flavor chemicals were identified and quantified by gas chromatography-mass spectrometry. Total flavor chemical concentrations ranged from 0.6 to 27.9 mg/ml, and in 95% of the fluids, total flavor concentration was greater than nicotine concentration. The 20 most popular refill fluids contained 99 quantifiable flavor chemicals; each refill fluid contained 22 to 47 flavor chemicals, most being esters. Some chemicals were found frequently, and several were present in most products. At a 1% concentration, 80% of the refill fluids were cytotoxic in the MTT assay. Six pure standards of the flavor chemicals found at the highest concentrations in the two most cytotoxic refill fluids were effective in the MTT assay, and ethyl maltol, which was in over 50% of the products, was the most cytotoxic. These data show that the cytotoxicity of some popular refill fluids can be attributed to their high concentrations of flavor chemicals.


Active APPL1 sequestration by Plasmodium favors liver-stage development.
Intracellular pathogens manipulate host cells to survive and thrive. Cellular sensing and signaling pathways are among the key host machineries deregulated to favor infection. In this study, we show that liver-stage Plasmodium parasites compete with the host to sequester a host endosomal-adaptor protein (APPL1) known to regulate signaling in response to endocytosis. The enrichment of APPL1 at the parasitophorous vacuole membrane (PVM) involves an atypical Plasmodium Rab5 isoform (Rab5b). Depletion of host APPL1 alters neither the infection nor parasite development; however, upon overexpression of a GTPase-deficient host Rab5 mutant (hRab5_Q79L), the parasites are smaller and their PVM is stripped of APPL1. Infection with the GTPase-deficient Plasmodium berghei Rab5b mutant (PbRab5b_Q91L) in this case rescues the PVM APPL1 signal and parasite size. In summary, we observe a robust correlation between the level of APPL1 retention at the PVM and parasite size during exoerythrocytic development.


Ultrastructural and physicochemical characterization of pH receptive chlorhexidine-loaded poly-L-glycolic acid-modified orthodontic adhesive.
This study aims to evaluate the feasibility of chlorhexidine (CHX)-loaded poly-L-glycolic acid (PLGA) nanoparticles as a modifier of a commercial orthodontic adhesive via the assessment of physicochemical, biological, and mechanical properties at tooth-bracket interface. CHX-loaded PLGA nanoparticles were synthesized using double emulsion-solvent evaporation method and characterized using transmission electron microscopy and Raman analysis. CHX-loaded PLGA nanoparticles in Transbond XT orthodontic adhesive were prepared using two different concentrations of the CHX (25 and 50%) and characterized for degree of conversion (DC), antimicrobial, and cytotoxicity testing. Bonded specimens were tested for shear bond strength (SBS) and adhesive remnant index (ARI) at tooth-bracket interface. The synthesized PLGA nanoparticles averaged between 60 and 80 nm in size. After loading CHX inside PLGA nanoparticles, the morphology of the PLGA nanoparticles was considerably changed. Orthodontic bracket bonded with 25% CHX-loaded PLGA-modified adhesive demonstrated DC scores similar to control group. Both 25 and 50% CHX-loaded PLGA-modified adhesive specimens showed higher antibacterial activity against S. mutans compared to control group. The least mean SBS values were exhibited by 50% CHX-loaded PLGA-modified adhesive samples, while a statistically significant difference was observed in the mean ARI values among all study groups at all-time points (p = .018). This study indicates that the addition of CHX-loaded PLGA nanoparticles in Transbond XT achieved stable bonds with enhanced antimicrobial and mechanical properties.


Imaging of nonspecific (nonherpetic) acute viral infections.
Encephalitis is an acute infection of brain parenchyma characterized clinically by fever, headache, and an altered level of consciousness. In the twenty-first century several outbreaks of encephalitis have been reported. Urbanization and encroachment on natural environments, the ease of world travel, and global trade have led to the spread of vectors and viruses.


Lowering the onset potential of Zr-doped hematite nanocoral photoanodes by Al co-doping and surface modification with electrodeposited Co-Pi.
Herein, in situ zirconium-doped hematite nanocoral (Zr-Fe2O3 (I) NC) photoanode was prepared via a specially designed diluted hydrothermal approach and modified with Al3+ co-doping and electrodeposited cobalt-phosphate ("Co-Pi") cocatalyst. Firstly, an unintentional in situ Zr-Fe2O3 (I)) NC photoanode was synthesized, which achieved an optimum photocurrent density of 0.27 mA/cm2 at 1.0 V vs. RHE but possessed a more positively shifted onset potential than conventionally prepared hematite nanorod photoelectrodes. An optimized amount of aluminum co-doping suppresses the bulk as well as surface defects, which causes a negative shift in the onset potential from 0.85 V to 0.8 V vs. RHE and enhances the photocurrent density of Zr-Fe2O3(I) NC from 0.27 mA/cm2 to 0.7 mA/cm2 at 1.0 V vs. RHE. The electrodeposited Co-Pi modification further reduce the onset potential of Al co-doped Zr-Fe2O3(I) NC to 0.58 V vs. RHE and yield a maximum photocurrent of 1.1 mA/cm2 at 1.0 V vs. RHE (1.8 mA/cm2 at 1.23 V vs RHE). The improved photocurrent at low onset potential can be attributed to synergistic effect of Al co-doping and Co-Pi surface modification. Further, during photoelectrochemical water-splitting, a 137 and 67 μmol of hydrogen (H2) and oxygen (O2) evolution was achieved over the optimum Co-Pi-modified Al-co-doped Zr-Fe2O3(I) NC photoanode within 6 h. The proposed charge transfer mechanism in optimum Co-Pi-modified Alco-doped Zr-Fe2O3(I) NC photoanodes during the photoelectrochemical water splitting was also studied.


A gene expression control technology for cell-free systems and synthetic cells via targeted gene silencing and transfection.
Synthetic cells, expressing proteins using cell-free transcription-translation (TXTL), is a technology utilized for a variety of applications, such as investigating natural gene pathways, metabolic engineering, drug development or bioinformatics. For all these purposes, the ability to precisely control gene expression is essential. Various strategies to control gene expression in TXTL have been developed; however, further advancements on gene-specific and straightforward regulation methods are still needed. Here, we present a method of control of gene expression in TXTL using a "silencing oligo": a short oligonucleotide, designed with a particular secondary structure, that binds to the target messenger RNA. We demonstrated that silencing oligo inhibits protein expression in TXTL in a sequence-dependent manner. We showed that silencing oligo activity is associated with RNase H activity in bacterial TXTL. To complete the gene expression control toolbox for synthetic cells, we also engineered a first transfection system. We demonstrated the transfection of various payloads, enabling the introduction of RNA and DNA of different lengths to synthetic cell liposomes. Finally, we combined the silencing oligo and the transfection technologies, demonstrating control of gene expression by transfecting silencing oligo into synthetic minimal cells.


ChiS histidine kinase negatively regulates the production of chitinase ChiC in Streptomyces peucetius.
Computational analysis of sequence homology of the chiSRC gene cluster, encoding a chitinase in Streptomyces peucetius, showed that the gene cluster could be a two-component regulon comprising a sensor kinase (chiS) and a response regulator (chiR). To prove that the ChiSRC is an authentic two-component system, the chiS gene was cloned and expressed in E.coli and the purified protein was used for biochemical analysis. In this report, we provide biochemical evidence to show that the sensor kinase encoded by chiS gene indeed is a histidine kinase capable of autophosphorylation and the histidine 144 residue of the ChiS protein is the phosphate acceptor. An insertion mutation at the chiS locus led to overproduction chitinase protein in S. peucetius implying that the chiC gene is negatively regulated by the two-component system.


Effect of modified high-flow oxygen therapy on positive end-expiratory pressure and end-expiratory lung volume based on simulated lung platform.
The aim of this study was to assess the effect of modified high-flow oxygen therapy on end-expiratory lung volume (EELV) and positive end-expiratory pressure (PEEP) in tracheotomized patients with normal pulmonary, acute hypoxic respiratory failure (AHRF) or chronic obstructive pulmonary disease (COPD). A ventilator and an artificial lung model were used to simulate the normal or strong inspiratory effort state of normal lung, AHRF and COPD patients. The traditional high-flow respiratory humidification therapy device connected with a standard interface (group A), and the modified therapy device added two types of resistance valves (group B, inner diameter 7.7 mm, length 24.0 mm; group C, inner diameter 7.7 mm, length 34.0 mm) to the exhalation end of the standard interface. The changes of end-expiratory lung volume (ΔEELV) and PEEP with the increase of flow rate (10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min) in the three groups was recorded. Under simulated conditions of normal lung, AHRF and COPD, as the flow rate increased by using the modified therapy device, the PEEP values in all groups showed an exponential increasing trend, and the ΔEELV also increased accordingly. In addition, under the same flow rate level, the PEEP values of the two modified high-flow oxygen therapies (Group B and Group C) were significantly higher than those of the standard high-flow oxygen therapy (Group A) (p < 0.05). In the normal lung model with normal or strong inspiratory effort, and in the AHRF or COPD model with strong inspiratory effort, when the flow rate was higher than 30 L/min, the PEEP levels of Group B were significantly lower than those of Group C (p < 0.05). In the AHRF model with normal inspiratory effort, when the flow rate was between 10 L/min and 60 L/min, the PEEP levels of Group B were significantly lower than those of Group C (p < 0.05). Moreover, in the COPD model with normal inspiratory effort, the PEEP levels of Group B were significantly lower than that of Group C only when the flow rate was 60 L/min (p < 0.05). The addition of different types of resistance valves to the high-flow exhalation end may be a feasible solution to improve the clinical efficacy of tracheotomized high-flow oxygen therapy.


The ecology of nutrient sensation and perception in insects.
Insects are equipped with neurological, physiological, and behavioral tools to locate potential food sources and assess their nutritional quality based on volatile and chemotactile cues. We summarize current knowledge on insect taste perception and the different modalities of reception and perception. We suggest that the neurophysiological mechanisms of reception and perception are closely linked to the species-specific ecology of different insects. Understanding these links consequently requires a multidisciplinary approach. We also highlight existing knowledge gaps, especially in terms of the exact ligands of receptors, and provide evidence for a perceptional hierarchy suggesting that insects have adapted their reception and perception to preferentially perceive nutrient stimuli that are important for their fitness.


A model of an intraprostatic vas deferens in the rat.
The study of the effect of hormones in seminal fluid upon prostate tissue is hampered by the lack of a suitable model. Such a model is described in this paper, and its possible usefulness is discussed. The vas deferens of the rat is moved from its normal position into a surgical incision into the ventral prostate. Squamous metaplasia of epithelium in prostatic acini at early stages is replaced by cuboidal epithelium. At later stages, normal-appearing glandular epithelium is seen as close as 50 micrometers to the vas deferens. The structure of the vas deferens is not affected.


Data from molecular dynamics simulations in support of the role of human CES1 in the hydrolysis of Amplex Red.
This data article contains the results of molecular dynamics (MD) simulations performed to assess the stability of the previously computed complex between the hCES1 structure and the Amplex Red (AR) substrate (Miwa et al., 2015) [1] and to compare the dynamic behavior of this complex with that of the corresponding hCES1-deacetylAR product. The study involves both standard molecular dynamics (MD) and steered (SMD) simulations to offer a quantitative comparison of the stability for the two complexes. With regard the standard MD runs, the data article graphically reports the r.m.s.d. profile of the ligand׳s atoms as well as the dynamic behavior of key contacts involving the catalytic Ser221 residue. The SMD simulations provide a comparison of the pull forces required to undock the two ligands and reveal that Van der Waals and hydrophobic interactions play a key role in complex stabilization.


Hip disarticulation in peripheral vascular disease.
The authors had to perform hip disarticulation on vascular patients in an increasing number - in spite of the general amputation principles. In the majority of the cases hip disarticulation followed other, more distal amputations of the same lower limb. Results of wound-healing, prosthetic fitting and mortality are poor, nevertheless this operation may lengthen life, relieve pain and lead to a tolerable life, usually bound to wheel-chair.


Beyond a Simple Effect: Variable and Changing Responses to Anthropogenic Noise.
A growing number of experimental studies have demonstrated that exposure to anthropogenic noise can affect the behavior and physiology of a variety of aquatic organisms. However, work in other fields suggests that responses are likely to differ between species, individuals, and situations and across time. We suggest that issues such as interspecific and intrapopulation variation, context dependency, repeated exposure and prior experience, and recovery and compensation need to be considered if we are to gain a full understanding of the impacts of this global pollutant.


Immunohistochemical assessment of Ki67 and p53 expression assists the diagnosis and grading of ulcerative colitis-related dysplasia.
To assess whether Ki67 and p53 immunostaining may assist the diagnosis and grading of ulcerative colitis-related dysplasia. Location of Ki67 staining and location and intensity of p53 staining were assessed in ulcerative colitis (UC) cases showing the features of high-grade dysplasia (HGD, n = 14), low-grade dysplasia (LGD, n = 22), 'indefinite for dysplasia' (n = 12), or regenerative atypia (RA, n = 22). Good intra- and inter-observer reproducibilities were demonstrated in the performance of these assessments. All the dysplasia cases showed extension of Ki67 staining above the basal third of the crypt. Moderate intensity p53 staining was seen in 10/22 RA cases, but strong intensity p53 staining was seen only in cases of dysplasia. All the cases of HGD showed extension of Ki67 and p53 staining above the basal two thirds of the crypt. Restriction of Ki67 staining to the basal third of the crypt appears to exclude a diagnosis of dysplasia whereas strong intensity p53 staining suggests a diagnosis of dysplasia. Restriction of Ki67 or p53 staining to the basal two-thirds of the crypt appears to exclude a diagnosis of HGD.


Advances in diagnosis and treatment of spinal hemangioblastomas.
Spinal hemangioblastoma usually leads to large intramedullary cysts. Until recently clinical and conventional radiological examination was often not able to detect single or multiple tumor niduses at the wall of a secondary syringomyelia cyst. Thus during surgical exploration the tumor not infrequently was missed, leading to misinterpretation of the pathological entity as syringomyelia, spinal gliosis or low grade spinal astrocytoma. This often resulted in explorative biopsy or decompressive laminectomy. Clinical deterioration postoperatively was not uncommon due to the remaining tumor and increasing spinal cord enlargement. Now magnetic resonance imaging allows the exact preoperative localization of the medullary lesion apart from the accompanying cysts and facilitates differential diagnosis of primary syringomyelia or other spinal cord neoplasms. Microsurgical techniques and laser-assisted resection have improved the outcome. We report on eight patients with spinal hemangioblastoma treated in our clinic since the installation of magnetic resonance imaging and laser-assisted microneurosurgery.


Solvothermal synthesis of well-dispersed NaMgF3 nanocrystals and their optical properties.
Complex metal fluoride NaMgF(3) nanocrystals were successfully synthesized via a solvothermal method at a relatively low temperature with the presence of oleic acid, and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectra, photoluminescence (PL) excitation and emission spectra, respectively. In the synthetic process, oleic acid as a surfactant played a crucial role in confining the growth and solubility of the NaMgF(3) nanocrystals. The as-prepared NaMgF(3) nanocrystals have quasi-spherical shape with a narrow distribution. A possible formation mechanism of the nanocrystals was proposed based on the effect of oleic acid. The as-prepared NaMgF(3) nanocrystals are highly crystalline and well-dispersed in cyclohexane to form stable and clear colloidal solutions, which demonstrate a strong emission band centered at 400 nm in photoluminescence (PL) spectra compared with the cyclohexane solvent. The PL properties of the colloidal solutions of the as-prepared nanocrystals can be ascribed to the trap states of surface defects.


Influence of climatic conditions and soil type on 99TcO4- uptake by rye grass.
Climatic changes over the long term will modify significantly the biosphere, with glaciation events probably taking place in the next 100 000 years. This is important to safety assessments of nuclear waste disposal facilities that contain high-level and long-lived waste. The soils will evolve toward new situations, and their properties will be consequently modified (e.g. an increase of soil organic matter may be expected in a cooler climate). These changes in soil properties would affect the mobility and the soil-to-plant transfer of radionuclides such as (99)Tc. This study aimed at simulating the cooling of climatic conditions for soils representative of a Jurassic limestone plateau, and the effect on transfer parameters of (99)TcO(4)(-) in the soil-plant systems was investigated. The cooler conditions were simulated by increasing elevation, a surrogate for climate change. Soils were sampled in similar geological background and topography at different elevations in the north east of France (Lorraine and Jura). Soil/solution distribution coefficients (K(d)) of (99)TcO(4)(-) were measured on soil samples in short-term batch experiments with 1:10 soil:solution ratio. Rye grass was grown on the soils spiked with (99)TcO(4)(-) at temperature regimes adapted to each soil. Also, two different temperature regimes (cold and temperate) were applied to one soil to test the effect of plant physiology and evapotranspiration on (99)TcO(4)(-) uptake. K(d) values did not show significant differences among soils in aerobic conditions, and were not significantly different from 0. During plant culture, reduction of (99)Tc was never totally achieved in soils, including in a peaty OM soil. Concentration ratios (CR) were calculated on a dry weight basis and ranged from 20 to 370. CR were always higher in high temperature regimes than in cold temperatures. They were also inversely correlated with soil organic matter (OM) content. A decrease of CR values from 5 to 10-fold was observed with increasing soil OM. Results suggested that the water holding capacity, in which (99)Tc is diluted, the nitrification potential of the soils and the evapotranspiration of plants (efficiency of uptake of soluble (99)TcO(4)(-)) were strongly involved in these differences.


The natural history of vertebral artery origin stenosis.
We sought to determine the long-term survival and natural history of vertebral artery origin stenosis (VAOS) as it relates to stroke. We retrospectively reviewed clinical data on patients admitted at a single institution for possible stroke between 2004 and 2007 and selected subjects who underwent angiography of the neck. We classified VAOS subjects as having "moderate" to "severe" (≥50%) occlusion. Age-, sex-, and race-matched control subjects with no evidence of VAOS on angiography were selected from our study population. Long-term follow-up data were collected and death certificates were searched for comparison among cases and controls. A Kaplan-Meier curve was plotted based on time to event (stroke or death). Fifty-eight of the 358 subjects were found to have VAOS (16.2%). Four subjects were excluded because of stenting; therefore, 54 cases and 54 matched controls were included for long-term follow-up analysis. In our study population, we calculated that the relative risk of having a stroke or dying in patients with VAOS was 6 times that of patients without VAOS (P < .02). The observed 5-year survival rate for patients with VAOS was 67% (36/54) compared to 89% (48/54) in control subjects (P < .01). Patients with VAOS are at a significantly higher risk of having a stroke or dying. Subsequent prospective, multicenter studies are needed to validate our results.


Acitretin-induced enthesitis in a patient with psoriatic arthritis.
A patient with psoriatic arthritis and cutaneous psoriasis took acitretin for 10 years to treat his skin lesions. Radiographs disclosed exuberant ossifications in several entheses. Their features were not typical for psoriatic arthritis but were consistent with acitretin-induced hyperostosis. Retinoids are known to induce hyperostosis, most notably when they are used in high dosages and over long periods. The concomitant presence of two conditions affecting the entheses may explain the exuberant nature of the ossifications in our patient.


Polymerization efficiency of chemically cured and visible light-cured orthodontic adhesives: degree of cure.
The use of light-cured orthodontic adhesives in combination with the new generation of ceramic brackets has become popular from an esthetic standpoint. The purpose of this article was to evaluate the degree of cure (DC) of selected light-cured and chemically cured adhesives bonded to ceramic and stainless steel brackets. The optical properties of eight types of brackets (single-crystal alumina, polycrystalline alumina, polycrystalline allumina with polycarbonate base, and stainless steel) were evaluated by diffuse visible light transmittance spectroscopic analysis. The degree of cure (DC) of a visible light-cured orthodontic adhesive bonded to these brackets under direct (20 seconds through the bracket) and indirect (2 x 10 seconds from the incisal and cervical edges of the bracket) irradiation was measured by micro-MIR FTIR spectroscopy. Brackets bonded to a chemically cured, two-paste orthodontic adhesive were used as a control group. According to the results the single-crystal alumina brackets showed the highest diffuse transmittance values at 468 nm followed by polycrystalline alumina and polycarbonate-base alumina types. Direct irradiation resulted in low DC values that were strongly correlated to the diffuse transmittance measurements at 468 nm (r = 0.73, p < 0.05). Indirect irradiation manifested significantly higher DC values than direct irradiation in the stainless steel bracket group, which yielded values comparable to those found in some indirectly irradiated polycrystalline bracket groups.


Long-acting reversible contraceptives use among adolescent girls and young women in high fertility countries in sub-Saharan Africa.
Given the instrumental role long-acting reversible contraceptives (LARCs) play in reducing unintended pregnancies, there is a need to understand the factors that predict their use among adolescent girls and young women in high fertility countries. Our study examined the prevalence and predictors of LARCs use among adolescent girls and young women in high fertility countries in sub-Saharan Africa. We pooled data from the women's files of the most recent Demographic and Health Surveys (DHS) from 2010 to 2020 of the top ten high fertility countries in sub-Saharan Africa, which are part of the DHS programme. The total sample was 5854 sexually active adolescent girls and young women aged 15-24 who were using modern contraceptives at the time of the survey. Descriptive and multilevel logistic regression models were used in the analyses. The results were presented using percentages and adjusted odds ratio (AOR) with their respective 95% confidence intervals (CIs). At the descriptive level, the overall prevalence of LARCs utilisation was 17.6% in the ten countries, with the lowest of 1.7% in Angola and the highest of 55.8% in Mali. Adolescent girls and young women who were married had a lower likelihood of LARCs utilisation than those who were never married [AOR = 0.63, 95% CI = 0.45, 0.88]. Adolescent girls and young women who wanted no more children had higher odds of LARCs use compared to those who wanted more children [AOR = 1.56, 95% CI = 1.09, 2.26]. Adolescent girls and young women with one to three births [AOR = 6.42, 95% CI = 4.27, 9.67], and those with four or more births [AOR = 7.02, 95% CI = 3.88, 12.67] were more likely to use LARCs compared to those who had no children. Countries in sub-Saharan Africa with lower probability of utilizing LARCs were Angola, Niger and Mozambique, whereas adolescent girls and young women in Mali had higher probability of utilizing LARCs. Our findings suggest that LARCs utilisation among adolescent girls and young women is low in high fertility countries in sub-Saharan Africa. To reduce the rates of unplanned pregnancies and induced abortions, it is imperative that adolescent girls and young women in sub-Saharan Africa are educated on the advantages of utilising LARCs. Additionally, governments, policymakers, and stakeholders in sub-Saharan Africa should raise awareness by executing health promotion measures to enhance the demand for LARCs among adolescent girls and young women. Achieving these would not only prevent unplanned pregnancies and induced abortions, but also help meet the United Nation's health and well being for all as enshrined in Sustainable Development Goals 3 and 5.


Association between periodontal disease and stroke.
Periodontitis is a very common human infection. There is evidence that periodontitis is associated with cerebrovascular disease (CVD) and stroke. The aim of this study is to examine the relationship between periodontal disease and CVD in observational studies. An electronic search of the English literature using PubMed was conducted. A meta-analysis of the studies reporting on the risk of stroke in patients with periodontitis was performed. Six prospective and seven retrospective studies met the inclusion criteria. Patients with both hemorrhagic and ischemic cerebrovascular events, fatal and nonfatal, were included. Definition of periodontitis was taken directly from included studies. Most studies have been adjusted for common cardiovascular risk factors. Separate statistical analysis was performed for prospective and retrospective studies. Overall adjusted risk of stroke in subjects with periodontitis was 1.47 times higher than in subjects without (95% confidence interval, 1.13-1.92;P = .0035) in prospective and 2.63 times (95% confidence interval, 1.59-4.33;P = .0002) in retrospective studies. The application of the trim and fill algorithm does not change the initial significant inference. There is evidence that periodontitis is associated with increased risk of stroke. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity of the studies as well as the differences in periodontitis definition.


Anaerobic selenite-reducing bacteria and their metabolic potentials in Se-rich sediment revealed by the combination of DNA-stable isotope probing, metagenomic binning, and metatranscriptomics.
Microorganisms play a critical role in the biogeochemical cycling of selenium (Se) in aquatic environments, particularly in reducing the toxicity and bioavailability of selenite (Se(IV)). This study aimed to identify putative Se(IV)-reducing bacteria (SeIVRB) and investigate the genetic mechanisms underlying Se(IV) reduction in anoxic Se-rich sediment. Initial microcosm incubation confirmed that Se(IV) reduction was driven by heterotrophic microorganisms. DNA stable-isotope probing (DNA-SIP) analysis identified Pseudomonas, Geobacter, Comamonas, and Anaeromyxobacter as putative SeIVRB. High-quality metagenome-assembled genomes (MAGs) affiliated with these four putative SeIVRB were retrieved. Annotation of functional gene indicated that these MAGs contained putative Se(IV)-reducing genes such as DMSO reductase family, fumarate and sulfite reductases. Metatranscriptomic analysis of active Se(IV)-reducing cultures revealed significantly higher transcriptional levels of genes associated with DMSO reductase (serA/PHGDH), fumarate reductase (sdhCD/frdCD), and sulfite reductase (cysDIH) compared to those in cultures not amended with Se(IV), suggesting that these genes played important roles in Se(IV) reduction. The current study expands our knowledge of the genetic mechanisms involved in less-understood anaerobic Se(IV) bio-reduction. Additinally, the complementary abilities of DNA-SIP, metagenomics, and metatranscriptomics analyses are demonstrated in elucidating the microbial mechanisms of biogeochemical processes in anoxic sediment.


Effects of six weeks of detraining on retention of functional fitness of old people after nine weeks of multicomponent training.
To examine the effects of age on functional fitness after six weeks of detraining. Elderly subjects, aged 60-86 years, completed a nine week multicomponent exercise training programme. They performed the senior fitness test every two weeks during the six week detraining period, and the responses of 12 young-old subjects (YO, aged 60-73 years) and nine older subjects (O, aged 74-86 years) were compared. Functional fitness improved during the exercise training period. Performances in the chair stand and six minute walk for the O group had significantly declined compared with post-training values after two weeks of detraining (p<0.01), whereas there were no significant changes in the YO group. Scores on the functional fitness tests declined further between two and four weeks of detraining in both of the groups (p<0.01). In the YO group, there were significant losses in performance on the chair stand, chair sit and reach, and six minute walk tests, and in the O group on the chair stand and up and go tests after six weeks of detraining compared with after four weeks of detraining (p<0.01). The components of functional fitness most affected by detraining were lower extremity flexibility after two and four weeks of detraining, and agility/dynamic balance after six weeks of detraining. Changes in lower extremity flexibility, up and go, and six minute walk performances in response to six weeks of detraining are affected by age in elderly adults.


Non-small cell lung cancer coexisting with pulmonary aspergilloma.
A 77-year-old male with a long-standing history of smoking and working in mines was referred to our department for the evaluation of an enlarging subpleural mass in the right upper lobe. Both transbronchial and computed tomography-guided biopsies of the mass were non-diagnostic. A partial resection of the right S2 mass under video-assisted thoracic surgery (VATS) confirmed the diagnosis of primary non-small cell lung cancer. VATS right upper lobectomy (ND2a) was then performed for complete resection. Histological examination revealed that the mass composed of adenocarcinoma and the dilated bronchioles contained Aspergillus, the fungal component. Here we report a rare case of non-small cell lung cancer coexisting with pulmonary aspergillosis. The morphologic coexistence pattern of the two pathologies was believed to be the colonization of saprophytic Aspergillus in the bullous air spaces, obstructed by or contained within the tumor, according to the progression of the lung cancer.


Tumors of the body and tail of the pancreas.
THE ABSTRACT IS AVAILABLE AT THE CLINICAL PANCREATIC DISORDER I: Acute pancreatitis. North Am J Med Sci 2011; 3: 316-319. doi: 10.4297/najms.2011.3316.


Apelin-13-induced proliferation and migration induced of rat vascular smooth muscle cells is mediated by the upregulation of Egr-1.
Apelin-13 plays an important role in the migration and proliferation of vascular smooth muscle cells (VSMCs); however, the underlying mechanisms are still unclear. Egr-1 is a nuclear transcription factor, which is considered to be the critical initiating factor of the processes of VSMC proliferation and migration. Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker of the phenotypic modulation that is a necessary condition of VSMC proliferation and migration. We hypothesized that the role of Apelin-13 is mediated via upregulation of Egr-1. To test this hypothesis, we analyzed the effects of Apelin-13 treatment on Egr-1 mRNA and protein expression in A10 rat aortic VSMCs by RT-PCR and Western blotting, respectively. Results showed that, Apelin-13 upregulated the expression of Egr-1. Furthermore, treatment with the extracellular-regulated protein kinase (ERK) inhibitor, PD98059, inhibited the upregulation of Egr-1 by Apelin-13. In addition, this upregulation was inhibited by treatment of VSMCs with the Egr-1 specific deoxyribozyme ED5 (DNAenzyme/10-23 DRz). Furthermore, ED5 treatment was found to significantly inhibit Apelin-13-induced migration and proliferation of VSMCs using transwell and MTT assays, respectively. The evaluation of OPN mRNA and protein expression levels by RT-PCR and Western blot analyses revealed that ED5 treatment also inhibited Apelin-13-induced OPN upregulation. The results of this study indicated that Apelin-13 upregulates Egr-1 via ERK. Furthermore, Apelin-13 induced the proliferation and migration of VSMCs as well as the upregulation of OPN via the upregulation of Egr-1. These results will provide an important theoretical and experimental basis for the control of inappropriate remodeling of vessel walls, and will hopefully lead to the prevention and treatment of vascular remodeling diseases.


Population pharmacokinetic modeling and dosing simulation of avalglucosidase alfa for selecting alternative dosing regimen in pediatric patients with late-onset pompe disease.
Avalglucosidase alfa (AVAL) was approved in the United States (2021) for patients with late-onset Pompe disease (LOPD), aged ≥ 1 year. In the present study, pharmacokinetic (PK) simulations were conducted to propose alternative dosing regimens for pediatric LOPD patients based on a bodyweight cut-off. Population PK (PopPK) analysis was performed using nonlinear mixed effect modeling approach on pooled data from three clinical trials with LOPD patients, and a phase 2 study (NCT03019406) with infantile-onset Pompe disease (IOPD: 1-12 years) patients. A total of 2257 concentration-time points from 91 patients (LOPD, n = 75; IOPD, n = 16) were included in the analysis. The model was bodyweight dependent allometric scaling with time varying bodyweight included on clearance and distribution volume. Simulations were performed for two dosing regimens (20 mg/kg or 40 mg/kg) with different bodyweight cut-off (25, 30, 35 and 40 kg) by generating virtual pediatric (1-17 years) and adult patients. Corresponding simulated individual exposures (maximal concentration, Cmax and area under the curve in the 2-week dosing interval, AUC2W), and distributions were calculated. It was found that dosing of 40 mg/kg and 20 mg/kg in pediatric patients < 30 kg and ≥ 30 kg, respectively, achieved similar AVAL exposure (based on AUC2W) to adult patients receiving 20 mg/kg. PK simulations conducted on the basis of this model provided supporting data for the currently approved US labelling for dosing adapted bodyweight in LOPD patients ≥ 1 year by USFDA.


"It was then that I thought 'whaat? This is not my Dad": The implications of the 'still the same person' narrative for children and young people who have a parent with dementia.
This research used auto/biographical interviews to explore the experiences of 19, 8 to 31 year olds who had a parent with dementia. Thematic analysis revealed challenges occasioned by the master narrative that people with dementia are 'still' the same person they were prior to the onset of their condition. While this notion is - rightly - at the heart of person-centered care in dementia services, the 'still' discourse conflicts with the experiences of young people. Their accounts suggest that the construction of their parent as the same person is not helpful and that, furthermore, expectations that they will behave and feel towards that parent as they did before are a source of distress in what is already a challenging situation. This paper highlights the need to equip young people with support that acknowledges that their parent may well be drastically different to the Mum or Dad they previously 'knew'.


Leveraging interpretable machine learning algorithms to predict postoperative patient outcomes on mobile devices.
Setting patient and family expectations for postoperative outcomes is an important aspect of care, a cornerstone of which is accurate, personalized, and explainable risk estimation. Modern machine learning offers a plethora of models that can effectively capture the complex, nonlinear contributions of preoperative risk factors to the surgical patient's overall risk. However, most of these models produce risk estimates that are not interpretable, which compromises trust in these systems, renders them unaccountable, and limits their widespread adoption. Recent developments in machine learning have been successful at creating risk calculators that address this gap, producing explainable risk estimates without compromising accuracy. In this work, we describe how the state of the art in postoperative risk estimation addresses the shortcomings of older methods, and how they have been applied in a clinical setting. We conclude with a discussion of the potential of machine learning models to be systematically integrated in health care more broadly and future prospects beyond passive risk prediction.


Further studies on the localization of angiotensin-II-like immunoreactivity in the anterior pituitary gland of the male rat, comparing various antisera to pituitary hormones and their specificity.
Using immunocytochemistry with the sensitive avidin-biotin complex method and an antibody to the beta subunit of rat luteinizing hormone (rat LH beta) provided by the National Hormone and Pituitary Program, NIADDK, to identify gonadotrops, the presence of angiotensin II-like immunoreactivity in the gonadotrops of the anterior pituitary gland of male rats was confirmed. However, using an antibody to rat prolactin, no angiotensin II-like immunoreactivity could be found in lactotrops. This finding is at variance with a previous report from this laboratory, in which the lactotrops were identified with an NIADDK antibody to human prolactin. The possibility that the antibodies to human prolactin cross-reacted with rat LH was therefore investigated by a noncompetitive radioimmunological binding assay. At the same dilution used in immunocytochemistry, two different NIADDK antihuman prolactin antisera displayed 49% and 24% binding of labeled rat LH beta. Similar cross reactions were demonstrated immunocytochemically. There was no cross reactivity between rat LH beta and the antibody to rat prolactin. Consequently, the staining reported to be in lactotrops in the previous study was probably in gonadotrops.


Differentiation of Pituitary Adenoma from Rathke Cleft Cyst: Combining MR Image Features with Texture Features.
To differentiate pituitary adenoma from Rathke cleft cyst in magnetic resonance (MR) scan by combing MR image features with texture features. A total number of 133 patients were included in this study, 83 with pituitary adenoma and 50 with Rathke cleft cyst. Qualitative MR image features and quantitative texture features were evaluated by using the chi-square tests or Mann-Whitney U test. Binary logistic regression analysis was conducted to investigate their ability as independent predictors. ROC analysis was conducted subsequently on the independent predictors to assess their practical value in discrimination and was used to investigate the association between two types of features. Signal intensity on the contrast-enhanced image was found to be the only significantly different MR image feature between the two lesions. Two texture features from the contrast-enhanced images (Histo-Skewness and GLCM-Correlation) were found to be the independent predictors in discrimination, of which AUC values were 0.80 and 0.75, respectively. Besides, the above two texture features (Histo-Skewness and GLCM-Contrast) were suggested to be associated with signal intensity on the contrast-enhanced image. Signal intensity on the contrast-enhanced image was the most significant MR image feature in differentiation between pituitary adenoma and Rathke cleft cyst, and texture features also showed promising and practical ability in discrimination. Moreover, two types of features could be coordinated with each other.


Opsonic effect of rainbow trout (Salmo gairdneri) antibody on phagocytosis of Yersinia ruckeri by trout leukocytes.
Partly purified peripheral blood leukocytes from normal rainbow trout (Salmo gairdneri) were used to study the influence of specific antibody on phagocytic uptake and intracellular killing of Yersinia ruckeri, a bacterial pathogen of trout. Specific antibody exerted a significant opsonic effect on the rate of phagocytic ingestion of the bacteria but did not affect the rate of intracellular killing. The results are discussed with reference to the current understanding of fish antibody function and phagocytosis by fish leukocytes.


Repetitive DNAs in the slug Milax nigricans: association of ribosomal (18S-28S and 5S rDNA) and (TTAGGG)n telomeric sequences in the slug M. nigricans (Mollusca: Gastropoda: Pulmonata).
Spermatocyte chromosomes of the slug Milax nigricans (Mollusca: Gastropoda: Pulmonata) were studied using silver staining (Ag-NOR) and fluorescent in situ hybridization (FISH) with four repetitive DNA probes [18S rDNA, 5S rDNA, (TTAGGG)n and (GATA)n]. Silver impregnation was inadequate to localize the chromosome sites of nucleolus organizer regions (NORs) since no silver dots occurred on the chromosomes at spermatogonial metaphase and a diffuse silver stainability could be observed on the bivalents at metaphase-I. Unlike silver staining, single-colour rDNA FISH consistently mapped major ribosomal sites (18S-28S rDNA) on two small-sized chromosomes in spermatogonial cells and on the correspondent metaphase-I bivalent in spermatocytes. While telomeric (TTAGGG)n sequence hybridized to all chromosomes, (GATA)n probe localized abundant hybridization sites, dispersed throughout the genome. Simultaneous double-colour FISH demonstrated a close chromosomal association of 18S-28S rDNA, 5S rDNA and (TTAGGG)n.


cDNA clones coding for the structural subunit of a chicken brain nicotinic acetylcholine receptor.
Nicotinic acetylcholine receptors (AChRs) immunoaffinity-purified from brains are composed of only two kinds of subunits rather than the four kinds present in muscle-type AChRs. Here we report the N-terminal protein sequences of the structural subunits of AChRs from rat and chicken brains and the cloning of full-length cDNAs for the chicken brain AChR structural subunit. Previously, the N-terminal amino acid sequence of the ACh-binding subunit of AChR immunoaffinity-purified from rat brain was shown to correspond to the cDNA alpha 4. Thus, cDNA sequences are now known for both of the subunits that form one AChR subtype in vivo.


Evaluation of hospital management of paediatric out-of-hospital cardiac arrest.
Pediatric out of hospital cardiac arrest (POHCA) is rare, with high mortality and neurological morbidity. Adherence to Pediatric Advanced Life Support guidelines standardizes in-hospital care and improves outcomes. We hypothesized that in-hospital care of POHCA patients was variable and deviations from guidelines were associated with higher mortality. POHCA patients in the London-Middlesex region between January 2012 and June 2020 were included. The care of children with ongoing arrest (intra-arrest) and post-arrest outcomes were reviewed using the Children's Hospital, London Health Sciences Centre (LHSC) patient database and the Adverse Event Management System. 50 POHCA patients arrived to hospital, with 15 (30%) patients admitted and 2 (4.0%) surviving to discharge, both with poor neurological outcomes and no improvement at 90 days. Deviations occurred at every event with intra-arrest care deviations occurring mostly in medication delivery and defibrillation (98%). Post-arrest deviations occurred mostly in temperature monitoring (60%). Data missingness was 15.9% in the intra-arrest and 1.7% in the post-arrest group. Deviations commonly occurred in both in-hospital arrest and post-arrest care. The study was under-powered to identify associations between DEVs and outcomes. Future work includes addressing specific deviations in intra-arrest and post-arrest care of POHCA patients and standardizing electronic documentation.


Neuroimaging of social motivation during winning and losing: Associations with social anhedonia across the psychosis spectrum.
Individuals with psychosis spectrum disorders (PSD) have difficulty developing social relationships. This difficulty may reflect reduced response to social feedback involving functional alterations in brain regions that support the social motivation system: ventral striatum, orbital frontal cortex, insula, dorsal anterior cingulate cortex, and amygdala. Whether these alterations span PSD is unknown. 71 individuals with PSD, 27 unaffected siblings, and 37 control participants completed a team-based fMRI task. After each trial, participants received performance feedback paired with the expressive face of a teammate or opponent. A 2 × 2 (win versus loss outcome x teammate versus opponent) repeated measures ANOVA by group was performed on activation in the five key regions of interest during receipt of feedback. Across groups, three social motivation regions, ventral striatum, orbital frontal cortex, and amygdala, showed sensitivity to feedback (significant main effect of outcome), with greater activation during win versus loss trials, regardless of whether the feedback was from a teammate or opponent. In PSD, ventral striatum and orbital frontal cortex activation to win feedback was negatively correlated with social anhedonia scores. Patterns of neural activation during social feedback were similar in PSD, their unaffected siblings, and healthy controls. Across the psychosis spectrum, activity in key social motivation regions during social feedback was associated with individual differences in social anhedonia.


High-mobility group box 1 protein promotes dengue virus replication by interacting with untranslated regions of viral genome.
Dengue virus (DENV) is most prevalent arthropod-borne human pathogen belongs to Flaviviridae family causes thousands of deaths annually. HMGB1 is highly conserved, ubiquitously expressed, non-histone nuclear protein which plays important role in diseases like metabolic disorders, cancer, and viral infections. However, the importance of HMGB1 in DENV infection is understudied. In this study, we observed that DENV-2 induces cytoplasmic translocation and secretion of HMGB1. Interestingly, inhibition of HMGB1 secretion by ethyl pyruvate (EP) enhanced viral propagation while silencing of HMGB1 resulted in abrogated viral replication in DENV-2 infected A549 cells. RNA-Electrophoretic mobility shift assay and immunoprecipitation showed that HMGB1 interacts with 5'-3' UTRs of DENV-2 genome. This interaction further stimulates production of proinflammatory cytokines like TNF-α, IL-6 and IL-1β which have been implicated in pathogenesis of severe DENV disease. Together, our finding suggests that DENV-2 modulates HMGB1 translocation and HMGB1-DENV-2 UTRs RNA interaction further induces proinflammatory cytokines production in A549 cells. This study discloses HMGB1 as an important host factor contributing to disease pathogenesis and hence can be targeted as an alternative approach for antiviral development against DENV virus infection.


Posttraumatic autoimmune reaction in peripheral nerve: effect of two successive injuries at different locations.
We studied the influence of previous nerve damage on the evolution of recovery that follows a second nerve injury. Recovery from nerve injury was assessed by analyzing rats' foot prints during a 74-day period. In addition, at the end of this period, the surgically treated sciatic nerves were immunohistochemically stained for the presence of immunoglobulins, an indicator of an autoimmune reaction. We found there was a moderately adverse effect of previous nerve damage on the sciatic functional recovery, a fact that suggests some systemic response to the distantly placed initial damage. Immunohistochemical staining showed various degrees of immunoglobulin deposition depending on the type of the two injuries. An interpretation of our results is proposed.


OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy in diffuse large B-cell lymphoma.
OX40 enhances the T-cell activation via costimulatory signaling. However, its molecular characteristics and value in predicting response to immunochemotherapy in DLBCL remain largely unexplored. Here, we performed an integrative analysis of sequencing and multiplex immunofluorescence staining, and discovered abnormally higher expression of OX40 in DLBCL patients. Elevated OX40 could activate T cells leading to a higher immune score for tumor immune microenvironment (TiME). OX40 upregulation simultaneously happened with immune-related genes including PD-1, CTLA4 and TIGIT et,al. Patients with high OX40 expression exhibited a lower Ann Arbor stage and IPI score and more easily achieved a complete response/partial response. The analysis of infiltrated T-cell subset revealed that patients with a greater number of CD4+/OX40+ or CD8+/OX40+ T cells had a longer OS. Our findings indicated that OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy, providing insights for the application of OX40 agonist in DLBCL patients.


Disparities in the use of colorectal cancer screening in a universally insured population during the COVID-19 pandemic.
Despite the known efficacy of colorectal cancer (CRC) screening, the rates of individuals undergoing such testing have remained lower than target thresholds, even prior to the healthcare disruptions associated with the COVID-19 pandemic. We evaluated the impact of the COVID-19 pandemic on CRC screening within a nationally representative US population and assessed disparities in screening across racial/ethnic groups and socioeconomic (SES) strata. We performed a retrospective cross-sectional study using all eligible TRICARE beneficiaries aged 45-64 years between FY 2018 and 2021. High-risk individuals, those with a previous or current CRC diagnosis, and/or a personal/family history of colonic polyps, were excluded. The pre-COVID-19 period (September 1, 2018-March 31, 2020) was compared to the COVID-19 period (April 1, 2020-September 30, 2021). Secondary analyses were performed, evaluating the interaction between the COVID-19 time period, race, and our proxy for socioeconomic status. During the study period, we identified 1,749,688 eligible individuals. Following the onset of the COVID-19 pandemic, CRC screening overall decreased from 34% in the pre-pandemic period to 30% following the onset of the pandemic (p < 0.001). This finding persisted even after adjusting for confounders in multivariable analysis (odds ratio [OR] for the pandemic timeframe: 0.79; 95% CI: 0.27, 0.31; p < 0.001). In the setting of SES, in the pandemic period, the odds of individuals from both Senior Enlisted (OR: 0.55; 95% CI: 0.54, 0.56) and Junior Enlisted sponsor ranks (OR: 0.27; 95% CI: 0.25, 0.30) were diminished as compared to Senior Officers. We found a 21% reduction in the odds of CRC screening in the context of the COVID-19 pandemic. Reductions in colonoscopies and other types of screening tests were not offset by changes in the use of at-home tests such as Cologuard.


Comparison between the L-DOPA histofluorescence procedure and the indirect immunofluorescence with anti-T6 and -HLA-DR monoclonal antibodies in visualizing Langerhans cells of human epidermis.
In order to assess the reliability of the L-DOPA histofluorescence (HF) procedure in visualizing the Langerhans cells (LC) of human epidermis, serial sections of human normal skin samples have been incubated with L-DOPA and alternatively processed for the L-DOPA HF and the indirect IF with anti-T6 and anti-HLA-DR monoclonal antibodies. Results demonstrated a good correlation of LC labelling; comparison between the number of L-DOPA positive (T6 positive and L-DOPA positive) HLA-DR positive dendritic cells did not show statistically significant differences. Therefore, the L-DOPA HF represents a valuable method for detecting LC in the human normal epidermis.


Removal of an intraperitoneal foreign body using a single port laparoscopic procedure.
To remove a foreign body from the peritoneal cavity in laparoscopic surgery, 2 or 3 ports are usually used. We have recently performed such a removal using a single 10-mm transumbilical port, a 0-degree laparoscope, a Farabeuf retractor, and a laparoscopic grasping forceps. Two patients with ventriculoperitoneal shunt catheter (V-P shunt) were admitted to our unit during the last year. They previously had a shunt catheter implanted for hydrocephalus of unknown cause. The complete migration of the ventriculoperitoneal shunt catheter into the peritoneal cavity was observed in these patients 12 and 7 years after the implantation. The laparoscopic removal of the migrated catheter was decided on. Its presence and location were confirmed by the use of a 0-degree laparoscope, through a 10-mm trocar port. The catheter was held and pulled out using a grasping forceps that was pushed in just beside the trocar port. The laparoscopic approach enables safe removal of a foreign body in the peritoneal cavity. The procedure can be performed using a single port.


An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial.
To evaluate the efficacy and safety of a nano-emulsion artificial tear (OM3) containing carboxymethylcellulose (CMC) and glycerin, flaxseed oil and castor oil, and three osmoprotectants (levocarnitine, erythritol, and trehalose) compared with an artificial tear (Refresh Optive Advanced [ROA]) containing the same ingredients with the exception of trehalose and flaxseed oil. In this multicenter, double-masked, randomized, two-arm, parallel-group, 6-visit study (screening, baseline, and days 7, 30, 60, and 90), subjects with dry eye disease underwent an open-label, 7-day run-in with CMC 0.5% (Refresh Plus), before 1:1 randomization to OM3 or ROA for 90 days (both instilled ≥2 daily). Ocular Surface Disease Index (OSDI; primary endpoint change from baseline at day 90), tear film breakup time (TBUT), and ocular staining (combined/corneal/conjunctival) were assessed; change from baseline in these parameters was calculated at each timepoint. Treatment-related adverse events (AEs) were assessed at each visit. Overall, 242 subjects were randomized (OM3, n = 120; ROA, n = 122). At day 90, significant improvements in OSDI, ocular staining and TBUT were evident in both treatment groups. Significant (P < 0.05) between-group differences in favor of OM3 were observed for combined ocular staining (all timepoints), corneal staining (day 90), and conjunctival staining (day 30). Treatment-related AEs were higher in the ROA (9.8%) versus OM3 (6.7%) group; blurred vision was among the most commonly reported AE (OM3 0% vs ROA 4.1%). These findings support the application of OM3, a novel preservative-free, nano-emulsion tear formulation with trehalose and flaxseed oil, for the treatment of dry eye disease.


Community engagement with genetics: public perceptions and expectations about genetics research.
Knowledge of molecular biology and genomics continues to expand rapidly, promising numerous opportunities for improving health. However, a key aspect of the success of genomic medicine is related to public understanding and acceptance. Using community consultations and an online survey, we explored public attitudes and expectations about genomics research. Thirty-three members of the general public in Newfoundland, Canada, took part in the community sessions, while 1024 Atlantic Canadians completed the online survey. Overall, many participants noted they lacked knowledge about genetics and associated research and took the opportunity to ask numerous questions throughout sessions. Participants were largely hopeful about genomics research in its capacity to improve health, not only for current residents, but also for future generations. However, they did not accept such research uncritically, and a variety of complex issues and questions arose during the community consultations and were reflected in survey responses. With the proliferation of biobanks and the rapid pace of discoveries in genomics research, public support will be crucial to realize health improvements. If researchers can engage the public in regular, transparent dialogue, this two-way communication could allow greater understanding of the research process and the design of efficient and effective genetic health services, informed by the public that will use them.


How to choose healthier urban biking routes: CO as a proxy of traffic pollution.
According to the World Health Organization (WHO) air pollution in urban areas, mainly associated with inhalation of gaseous pollutants and particulate matter emitted from motor vehicles, is responsible for one million deaths per year. Carbon monoxide (CO) from the incomplete combustion of fuel is known to bind with hemoglobin, decreasing the blood oxygen-delivery and inducing tissues hypoxia; being more pronounced under conditions of stress like physical activity. The present study demonstrates the usefulness of a compact CO sensor (Alphasense CO-B4) mounted on a bicycle to evaluate atmospheric levels of CO associated with urban microenvironments within a growing Australian city (Brisbane). Urban bike pathways show pronounced and significant variations in air quality according to the surrounding microenvironment and the time of day. The inhaled dose in real time and the CO total dose over each trip were valuable for estimating the air quality of the route, and identifed how the health benefits of riding a bicycle could be partially offset by poor air quality depending on where and when a cycle route is taken in the inner-city. Finally, environmental conditions, such as wind speed, were found to significantly affected atmospheric CO concentrations, at least during the study period. The present work provides information regarding commuters' exposure to atmospheric pollutants, necessary for modifying the population's (including cyclists) perception of pollution in the urban environment, providing people with the opportunity to choose a healthier route.


Effect of Costus pictus per se and in combination with Metformin and Enalapril in streptozotocin induced diabetic nephropathy in rats.
The present study was designed to investigate the effect of methanolic extract of Costus pictus (MECP) per se and in combination with drugs (Metformin and Enalapril) used in clinical practice in streptozotocin (STZ) induced diabetic nephropathy (DN) in rats. Diabetes was induced in male Wistar rats by a single injection of STZ (50 mg/kg i.p.). After 28 days diabetic rats were divided into six groups. Two groups were treated with MECP (200 mg/kg p.o.), MECP (400 mg/kg p.o.) respectively; one group was treated with metformin (225 mg/kg), enalapril (3.2 mg/kg) combination; and two groups were treated with a combination of metformin, enalapril and MECP (200 mg/kg) and combination of metformin, enalapril and MECP (400 mg/kg) respectively. One group was kept as diabetic control. At the end of the study, body weight, kidney weight, and kidney hypertrophy index were evaluated. Biochemical and antioxidant parameters were evaluated. TGF-β levels in serum were estimated. Histopathology of the kidney was also studied. The combination therapy showed a significant increase in the body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in STZ induced diabetic nephropathy in rats. It also normalized the altered levels of serum and urine parameters. Histopathological evaluation revealed that combination therapy reduced the vacuolar degeneration of tubules. The results indicate that combination therapy of metformin, enalapril, and MECP has beneficial effects in management of diabetic nephropathy.


An investigation into the role of ascorbic acid in renal calculogenesis in albino rats.
Neither stone nor calcium oxalate crystal deposition was observed in the kidneys of rats after oral ingestion of 60 mg. L-ascorbic acid daily for three months, although urinary excretion of stone inhibitors (magnesium and citrate) was decreased and oxalate increased. The highly acidic pH of urine and reduced calcium excretion might have prevented their deposition.


Phosphate uptake by immobilized Acinetobacter calcoaceticus cells in a full scale activated sludge plant.
An in situ study of the P-uptake ability of Acinetobacter calcoaceticus was carried out using the alginate immobilization technique. Immobilized A. calcoaceticus cells displayed a high P-uptake ability (> 97% P-accumulating cells) when immersed in the aerobic zone of an activated sludge system for 30-240 min. The overall P-accumulation pattern of the anaerobic zone depicted a typical P-release mechanism. However, limited P-accumulation was also observed at this stage. Growth and anaerobiosis were not prerequisites for P-uptake. The immobilized cell retention time in the anaerobic zone did not affect remarkably the inherent P-uptake ability of immobilized A. calcoaceticus when exposed to the aerobic stage. P-uptake and release were reversible and depended on the environmental conditions to which immobilized cells were exposed. Immobilization of A. calcoaceticus using alginate can be regarded as a reliable method of studying pure cultures in the activated sludge process.


Impact of waist circumference on cardiac phenotype in hypertensives according to gender.
Our aim was to assess the differential effect of waist circumference on left-ventricular (LV) structural and functional alterations, in hypertensive males and females. One thousand seven hundred and eighty nine consecutive, nondiabetic, essential hypertensives (aged 55.8 +/- 13.5 years, 966 females), included in the 3H Study, an ongoing registry of hypertension-related-target-organ damage, were classified to obese and nonobese groups according to Adult Treatment Panel III criteria. All participants underwent complete echocardiographic study including LV diastolic function evaluation by means of conventional and tissue Doppler imaging (TDI) methods, averaging early and late diastolic mitral annular peak velocities (Em, Am, Em/Am) from four separate sites of measurement. Hypertensive obese women compared with nonobese exhibited significantly greater LV mass index and prevalence of LV hypertrophy (by 5.5 g/m(2), P = 0.003, and 8.8%, P = 0.005, respectively), while such differences were not present among men. Obese women compared to nonobese ones were accompanied by lower transmitral E/A (by 0.08, P < 0.001), TDI-derived Em/Am (by 0.12, P < 0.001), and higher E/Em ratio (by 0.8, P = 0.016). In contrast, hypertensive obese men compared to nonobese ones exhibited lower E and Em (by 0.04 m/s and 0.6 cm/s, both P < 0.05). A significant interaction between sex and abdominal obesity was observed only regarding TDI-derived Am and Em/Am. Furthermore, waist circumference was a predictor of E/A (beta = -0.097, P = 0.002) and Em/Am (beta = -0.116, P = 0.001), independently of body size, in females but not in males. The adverse effect of abdominal obesity on LV alterations is more pronounced among female hypertensives, suggesting that routine measurement of waist circumference provides additional information on cardiac phenotype especially in women.


Contracting opportunities: interpreting post-asylum geographies of mental health care in Auckland, New Zealand.
In New Zealand, the process of deinstitutionalization is continuing to unfold as a specific manifestation of welfare state restructuring rather than as a discrete process within the health care sector. In this paper we consider the geography of mental health care in Auckland, New Zealand's only metropolitan city. Here, a highly fluid and competitive housing market has profoundly (re)shaped the opportunities for community care. We report on findings from a survey of representatives of the key agencies providing mental health care in central Auckland. We argue that the re-placing of mental health care into the community has often involved the separation of residential and treatment issues, to the detriment of the communities, institutions and (especially) individuals involved. We trace this fragmentation back to the primacy of the ideology of restructuring over the philosophy of deinstitutionalization. We build our argument around a discussion of the Mental Health (Compulsory Assessment and Treatment) Act 1992 and the apparent subordination of the Act to the emerging of a 'contract state' and broader legislation, such as the Resource Management Act 1991, the Privacy Act 1992 and the Commerce Act 1986, which underpins the re-regulation of New Zealand society.


The turnover number for band 3-mediated sulfate transport in phosphatidylcholine bilayers.
The anion transport system of the human erythrocyte membrane was reconstituted in unilamellar phosphatidylcholine vesicles, and a vesicle subpopulation of a narrow size distribution was isolated from the sample by gel filtration. In this subpopulation, the turnover number of the transport protein (the band 3 protein) for sulfate transport was determined. It was found that, in the reconstituted system, the protein transports sulfate 5-10 times faster than in the human erythrocyte membrane.


Corrigendum: Emerging work environments in the pandemic era: a gendered approach to work-life balance programs.
[This corrects the article DOI: 10.3389/fsoc.2023.1120288.].


What Remains up to 7 Months after Severe and Moderate Pneumonia in Non-Vaccinated Patients with Long COVID? Results of a CT Study.
There is a growing evidence of long-lasting lung changes after COVID-19. Our aim was to assess the degree of lung injury and evaluate the recovery process of 4-7-month-non-vaccinated convalescent patients discharged from hospital after moderate and severe COVID-19 pneumonia, who presented with symptoms of long-COVID. On control lung CT after mean 5-month recovery period, we classified and determined the prevalence of residual radiological abnormalities in 39 symptomatic patients. To assess the advancement of the persisting changes we used the total severity score (TSS) and the chest CT score and then correlated the results with clinical data. On follow-up CT images, 94.9% of patients showed persistent radiological abnormalities. The most frequent changes were ground-glass opacities (74.4%), reticular pattern (64.1%), fibrotic changes (53.8%), nodules (33.3%), bronchiectasis (15.4%), vascular enlargement (10.3%), and cavitation (5.1%). The median TSS score was 4.1 points (interquartile range 3), whereas the median of the chest CT score 5.4 points (interquartile range of 4.5). No significant differences were observed between sex subgroups and between the severe and moderate course groups. There were no association between both CT scores and the severity of the initial disease, indicating that, mean 5 months after the disease, pulmonary abnormalities reduced to a similar stage in both subgroups of severity.


Comparison of fluorochrome-labeled and 51Cr-labeled targets for natural killer cytotoxicity assay.
An alternative method for measuring in vitro cellular cytotoxicity has been developed utilizing the carboxyfluorescein derivative 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) as the target cell label. Target cells labeled with the fluorescent dye are incubated with effector cells, if killing of targets occurs, BCEDF is released analogous to 51Cr release. Measurement of specific lysis in this assay is based on the direct measurement of dye retained by the remaining viable target cells using the Pandex FCA. In paired experiments we have compared the fluorochrome assay to the standard 51Cr release assay in measuring porcine natural killer cytotoxicity. The target labeling time with BCECF is 30 min as opposed to 1 h with 51Cr; and there is no significant dye reincorporation after release. The optimal target number per incubation well for the BCECF assay is 5 X 10(3) cells. In both the BCECF and 51Cr release assays, maximum percent specific lysis is reached after 3-4 h incubation. By 2 h incubation, the BCECF assay reaches the maximum seen with 51Cr and in a 4 h assay the maximum NK activity measured with BCECF labeled targets is always higher than that measured with 51Cr-labeled targets. In paired experiments, we have shown the reproducibility of the BCECF assay and that the BCECF assay measures NK enhancement by NK enhancing monoclonal antibody and inhibition by NK inhibiting monoclonal antibody as good as the 51Cr release assay, if not better. In conclusion, the BCECF assay is a reliable and reproducible measure of in vitro cellular cytotoxicity, eliminates the use of radioisotopes and is cost efficient.


Synthesis and antiproliferative activity of C-homo-lactam derivatives of 7-deoxycholic acid.
Using deoxycholic acid as starting materials, a series of 12a-aza-C-homo-12-one 7-deoxycholic acid derivatives were synthesized The antiproliferative activity of the synthesized compounds against some carcinoma cell lines was investigated. The results showed that some 12-oxy-12a-aza-C-homo-7-deoxycholic acid derivatives displayed distinct cytotoxicity to HeLa (human cervical carcinoma) and Tu 686 (laryngocarcinoma) tumor cell lines. In particular, the IC50 values of the compounds 6 and 7 against Tu 686 cells are 16.7 and 19.8 μM/L respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.


Prostaglandin analogues in the anterior eye: their pressure lowering action and side effects.
Topical application of prostaglandin (PG) analogues are currently the most commonly used intraocular pressure lowering drugs in glaucoma. They have been available since the mid 1990's, and are efficacious and generally well tolerated, the compliance rates are good due to the once a day application regime. The mode of action of PGs is by increasing the aqueous humour outflow primarily via the uveoscleral route, and also (but to a lesser degree) the conventional trabecular meshwork pathway. Increased outflow is primarily accomplished by remodelling the extracellular matrix components in both of the outflow pathways. PGs are associated with very few systemic side effects. The side effects of concern are all concentrated in the eye. Conjunctival hyperaemia is a common mild but transient complication. Since the development of this class of drug the most worrying and unusual side effect is a change in the pigmentation of the melanin-containing tissues close to the application site, i.e. eyelid skin, eyelashes and iris. As the prostaglandin induced iris darkening (PIID) is irreversible on cessation of the drugs it was of particular concern. We report here the findings from many studies which strongly indicate that there are no histopathological changes occurring in the iris tissue that has developed the darkening side effect. The only definitive change that has been detected in the cases of PIID is a small enlargement of the size of the existing melanin granule population and it has been shown that this change in melanin granule size is sufficient to account for the PIID. These findings point to the conclusion that the darkening developed following PG use is of a purely cosmetic effect with little or no serious consequences.


Polymerase chain reaction amplification applied to the determination of beta-like globin gene cluster haplotypes.
We report here on the application of the polymerase chain reaction (PCR) technique for the determination of the beta-like gene cluster haplotypes. Seven fragments containing each one of the following polymorphic sites--Xmnl 5' to the G gamma gene, HindIII in the IVSII of G gamma and A gamma gene, HincII 3' and inside the gamma gene, Hinfl 5' of the beta gene, and HpaI 3' of the beta gene--are amplified using the PCR technique. Each amplified fragment is subsequently digested with the appropriate enzyme, analyzed by electrophoresis on agarose gel containing ethidium bromide, and visualized under ultraviolet light. This technique has the advantages of rapidity, safety, and cost-effectiveness.