Large-Scale QSAR in Target Prediction and Phenotypic HTS Assessment.
The advent of in silico compound target prediction offers a potential paradigm shift in how large compound collections are understood and used strategically in high-throughput screens (HTS). Specifically, phenotypic HTS hits may be annotated both with known targets and predicted targets using large-scale QSAR models, enabling a more sophisticated hit assessment. Efforts in massive bioactivity data integration and standardization is empowering such compound-target annotations. These approaches differ fundamentally from the traditional role of QSAR in lead optimization and binding affinity predictions to global, probabilistic target predictions for thousands of human proteins.


Absorption of 1-Dicysteinethioacetal-5-Hydroxymethylfurfural in Rats and Its Effect on Oxidative Stress and Gut Microbiota.
The absorption of a 5-hydroxymethylfurfural (HMF)-cysteine adduct, 1-dicysteinethioacetal-5-hydroxymethylfurfural (DCH), and its effect on antioxidant activity and gut microbiota were investigated. Results indicated that DCH is more easily absorbed in rats than HMF. Serum DCH concentrations were 15-38-fold of HMF concentrations from 30 to 180 min after intragastrical administration at the level of 100 mg/kg of body weight, and 2.7-4.5% of absorbed DCH was converted to HMF. The malondialdehyde content in the plasma, heart, liver, and kidneys significantly increased after drug (100 mg/kg of bw) administration for 1 week, suggesting that HMF and DCH were oxidative-stress-inducing agents, instead of antioxidant agents, in rats. HMF and DCH also modulated gut microbiota. HMF promoted the growth of Lactobacillus, Tyzzerella, Enterobacter, and Streptococcus. DCH increased the ratio of Firmicutes/ Bacteroidetes and promoted the growth of Akkermansia, Shigella, and Escherichia while inhibiting the growth of Lactobacillus.


Association between age at menarche and age at menopause among women of an indigenous population of North Bengal, India.
Menarche and menopause are two major components of a woman's reproductive life. Ages at menarche and menopause vary widely between and within populations and are influenced by various factors, both genetic and environmental. The present community-based cross-sectional investigation aimed to assess the association between ages at menarche and natural menopause among women belonging to the indigenous Rajbanshi population of North Bengal, India. The investigation was carried out from January 2015 to May 2015 among 510 Rajbanshi women aged between 45 and 55 years residing in the district of Darjeeling, West Bengal, India. A structured schedule was used to collect data on ages at menarche and natural menopause, marital status, parity, education, age of first and last pregnancies, duration of breastfeeding, nature of occupation, health status, smoking and monthly family income. Anthropometric measurements of height and weight were recorded and Body Mass Index (BMI) calculated. The statistical analyses, which included descriptive statistics and binary logistic regression (BLR), were done using SPSS. The women's mean age of menarche and median age of natural menopause were 12.52 years and 50 years, respectively. The BLR analysis indicated that education, age at first pregnancy had significant effects on the age at natural menopause among women who experienced menarche at <12 years of age (p<0.05). In the case of women who attained menarche at ≥12 years of age, marital status, age at last pregnancy, parity, education, duration of breastfeeding, smoking, occupation, monthly income and BMI had a greater influence on age at natural menopause. There appears to be an indirect association between age at menarche and age at natural menopause, along with different predictor variables, among the Rajbanshi women.


Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System.
There is a great need for living valve replacements for patients of all ages. Such constructs could be built by tissue engineering, with perspective of the unique structure and biology of the aortic root. The aortic valve root is composed of several different tissues, and careful structural and functional consideration has to be given to each segment and component. Previous work has shown that immersion techniques are inadequate for whole-root decellularization, with the aortic wall segment being particularly resistant to decellularization. The aim of this study was to develop a differential pressure gradient perfusion system capable of being rigorous enough to decellularize the aortic root wall while gentle enough to preserve the integrity of the cusps. Fresh porcine aortic roots have been subjected to various regimens of perfusion decellularization using detergents and enzymes and results compared to immersion decellularized roots. Success criteria for evaluation of each root segment (cusp, muscle, sinus, wall) for decellularization completeness, tissue integrity, and valve functionality were defined using complementary methods of cell analysis (histology with nuclear and matrix stains and DNA analysis), biomechanics (biaxial and bending tests), and physiologic heart valve bioreactor testing (with advanced image analysis of open-close cycles and geometric orifice area measurement). Fully acellular porcine roots treated with the optimized method exhibited preserved macroscopic structures and microscopic matrix components, which translated into conserved anisotropic mechanical properties, including bending and excellent valve functionality when tested in aortic flow and pressure conditions. This study highlighted the importance of (1) adapting decellularization methods to specific target tissues, (2) combining several methods of cell analysis compared to relying solely on histology, (3) developing relevant valve-specific mechanical tests, and (4) in vitro testing of valve functionality.


Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees.
Costimulation of neutrophils and cytokines may play an important role in organ injury in sepsis. Pentoxifylline inhibits various neutrophil functions in vitro, and attenuates endotoxin-induced production of TNF in both in vitro and in vivo models. To assess the effect of pentoxifylline on neutrophil activation in endotoxemia, nine adult chimpanzees (Pan troglodytes) were i.v. injected with saline (n = 2), Escherichia coli endotoxin (4 ng/kg; n = 4), or E. coli endotoxin (4 ng/kg) in combination with pentoxifylline (500 mg/3 h, starting 30 min before the endotoxin injection; n = 3). Serial blood samples were obtained for measurements of leukocyte counts and the granulocytic proteinases elastase complexed with alpha 1-antitrypsin and lactoferrin, and cytokines during the next 5 h. No changes were observed in the saline-treated chimpanzees. Endotoxin induced a marked leukocytosis and neutrophilia, which were slightly reduced by pentoxifylline. In contrast, pentoxifylline almost completely prevented endotoxin-induced neutrophil degranulation: peak elastase-alpha 1-antitrypsin was 164 +/- 21 ng/ml (mean +/- SE) after endotoxin alone, vs 71 +/- 7 ng/ml after endotoxin with pentoxifylline (t = 3 h; p < 0.05); peak lactoferrin was 329 +/- 15 and 182 +/- 5 ng/ml, respectively (t = 5 h; p < 0.05). Pentoxifylline also inhibited the endotoxin-induced release of TNF (271 +/- 26 vs 55 +/- 23 pg/ml at t = 1.5 h; p < 0.05) and IL-6 (225 +/- 42 vs 73 +/- 25 pg/ml at t = 2 h; p < 0.05). IL-8 release was not significantly inhibited by pentoxifylline. In none of the animals activation of the C system could be detected. We conclude that pentoxifylline attenuates neutrophil activation in endotoxemia in chimpanzees, probably in part by inhibiting the release of TNF.


[Ectopic pregnancy risk factors after assisted reproductive technology].
Ectopic pregnancies are more frequent among pregnancies resulting from assisted reproductive technology (ART) than in natural conceptions (6% to 7% vs 1%). Fivnat registry has allowed us to analyse 349 ectopics among 6049 clinical pregnancies collected from 1986 to 1990. Ectopic rate decreased with increasing women's age, and since 1986. The risk was also decreased in infertilities of non tubal origin, except for those of unknown origin in which it was at the same level than for tubal infertility. The risk was increased by 65% in stimulation regimens involving clomiphene citrate (CC). The observed decrease from 1986 to 1990 was strongly related to the decrease in use of CC.


Topotecan inhibits human immunodeficiency virus type 1 infection through a topoisomerase-independent mechanism in a cell line with altered topoisomerase I.
Topotecan (TPT), a known inhibitor of topoisomerase I, has previously been shown to inhibit the replication of several viruses. The mechanism of inhibition was proposed to be the inhibition of topoisomerase I. We report that TPT decreased replication of human immunodeficiency virus type 1 (HIV-1) in CPT-K5, a cell line with a topoisomerase I mutation. TPT inhibited production of HIV-1 RNA and p24 in CPT-K5 and wild-type cells equally effectively. The antiviral effects of TPT were observed not only in the topoisomerase-mutated CPT-K5 line but also in peripheral blood mononuclear cells (PBMC) acutely infected with clinical isolates and in OM10.1 cells latently infected with HIV and activated by tumor necrosis factor alpha. Little toxicity from TPT was noted in HIV-1-infected PBMC and in CPT-K5 and OM10.1 cells as measured by cell growth and proliferation assays. These observations suggest that TPT targets factors in virus replication other than cellular topoisomerase I and inhibits cytokine-mediated activation in latently infected cells by means other than cytotoxicity. These results suggest a potential for TPT and for other camptothecins in anti-HIV therapy alone and in combination with other antiretroviral drugs.


Mesenchymal Stem Cells Overexpressing Angiotensin-Converting Enzyme 2 Rescue Lipopolysaccharide-Induced Lung Injury.
Bone marrow-derived mesenchymal stem cells (MSCs), which have beneficial effects in acute lung injury (ALI), can serve as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2), a counterregulatory enzyme of ACE that degrades angiotensin (Ang) II into Ang 1-7, has a protective role against ALI. Because ACE2 expression is severely reduced in the injured lung, a therapy targeted to improve ACE2 expression in lung might attenuate ALI. We hypothesized that MSCs overexpressing ACE2 would have further benefits in lipopolysaccharide (LPS)-induced ALI mice, when compared with MSCs alone. MSCs were transduced with ACE2 gene (MSC-ACE2) by a lentiviral vector and then infused into wild-type (WT) and ACE2 knockout (ACE2(-/y)) mice following an LPS-induced intratracheal lung injury. The results demonstrated that the lung injury of ALI mice was alleviated at 24 and 72 h after MSC-ACE2 transplantation. MSC-ACE2 improved the lung histopathology and had additional anti-inflammatory effects when compared with MSCs alone in both WT and ACE2(-/y) ALI mice. MSC-ACE2 administration also reduced pulmonary vascular permeability, improved endothelial barrier integrity, and normalized lung eNOS expression relative to the MSC group. The beneficial effects of MSC-ACE2 could be attributed to its recruitment into the injured lung and enhanced local expression of ACE2 protein without changing the serum ACE2 levels after MSC-ACE2 transplantation. The biological activity of the increased ACE2 protein decreased the Ang II amount and increased the Ang 1-7 level in the lung when compared with the ALI and MSC-only groups, thereby inhibiting the detrimental effects of accumulating Ang II. Therefore, compared to MSCs alone, the administration of MSCs overexpressing ACE2 resulted in a further improvement in the inflammatory response and pulmonary endothelial function of LPS-induced ALI mice. These additional benefits could be due to the degradation of Ang II that accompanies the targeted overexpression of ACE2 in the lung.


Array-Based Epigenetic Aging Indices May Be Racially Biased.
Epigenetic aging (EA) indices are frequently used as predictors of mortality and other important health outcomes. However, each of the commonly used array-based indices has significant heritable components which could tag ethnicity and potentially confound comparisons across racial and ethnic groups. To determine if this was possible, we examined the relationship of DNA methylation in cord blood from 203 newborns (112 African American (AA) and 91 White) at the 513 probes from the Levine PhenoAge Epigenetic Aging index to ethnicity. Then, we examined all sites significantly associated with race in the newborn sample to determine if they were also associated with an index of ethnic genetic heritage in a cohort of 505 AA adults. After Bonferroni correction, methylation at 50 CpG sites was significantly associated with ethnicity in the newborn cohort. The five most significant sites predicted ancestry with a receiver operator characteristic area under the curve of 0.97. Examination of the top 50 sites in the AA adult cohort showed that methylation status at 11 of those sites was also associated with percentage European ancestry. We conclude that the Levine PhenoAge Index is influenced by cryptic ethnic-specific genetic influences. This influence may extend to similarly constructed EA indices and bias cross-race comparisons.


Life Course Pathways From Childhood Socioeconomic Status to Later-Life Cognition: Evidence From the Wisconsin Longitudinal Study.
A growing body of research indicates that older adults are at greater risk for poorer cognition if they experienced low socioeconomic status (SES) as children. Guided by life course epidemiology, this study aimed to advance understanding of processes through which childhood SES influences cognition decades later, with attention to the role of scholastic performance in adolescence and SES in midlife. We used data from the Wisconsin Longitudinal Study (WLS), which has followed a cohort of high school graduates since they were 18 years old in 1957. Childhood SES was measured prospectively in adolescence, and measures of memory and language/executive functioning were based on neurocognitive assessments at age 72. We used participants' scores on a statewide standardized test in high school as an indicator of scholastic performance in adolescence. The measure of SES in midlife included years of postsecondary education, income, and occupation status at age 53. Findings from structural equation models indicated that scholastic performance in adolescence and midlife status attainment together fully mediated associations between childhood SES and both memory and language/executive functioning at age 72. Adolescent scholastic performance was directly associated with later-life cognition, as well as indirectly through midlife status attainment. Findings provide support for both latency and social pathway processes when considering how SES in childhood influences later-life cognition. Results contribute to growing calls for social policies and programs to support optimal brain health at multiple phases throughout the life course, especially among individuals with lower SES as children.


[The radiation dose problem in computed tomography. Actual data and strategies for a corrected use of ionizing radiation in computed tomography].
New technologies in these years has taken to a spread and to a growth of the CT application with an increase of patients and population exposure. In clinical practice some technical devices can be used to reduce the exposure dose of multidetector CT that allows radiologist to answer the clinical question with less damage to the patient. The radiologist remains however the guarantor of the ionizing radiation exposition and he has to consider also the opportunity to use other methodics (MR, US) to answer some questions. The radiologist has the role to evaluate the clinical indication to the exam demanded from other doctor and has the responsibility for exam management and for progressive radiologic course, controls and follow-up.


Antioxidant, electrochemical, thermal, antimicrobial and alkane oxidation properties of tridentate Schiff base ligands and their metal complexes.
In this study, two Schiff base ligands (HL(1) and HL(2)) and their Cu(II), Co(II), Ni(II), Pd(II) and Ru(III) metal complexes were synthesized and characterized by the analytical and spectroscopic methods. Alkane oxidation activities of the metal complexes were studied on cyclohexane as substrate. The ligands and their metal complexes were evaluated for their antimicrobial activity against Corynebacterium xerosis, Bacillus brevis, Bacillus megaterium, Bacillus cereus, Mycobacterium smegmatis, Staphylococcus aureus, Micrococcus luteus and Enterococcus faecalis (as gram-positive bacteria) and Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Yersinia enterocolitica, Klebsiella fragilis, Saccharomyces cerevisiae, and Candida albicans (as gram-negative bacteria). The antioxidant properties of the Schiff base ligands were evaluated in a series of in vitro tests: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and reducing power activity of superoxide anion radical generated non-enzymatic systems. Electrochemical and thermal properties of the compounds were investigated.


Quality of life and gender role behavior in disorders of sexual differentiation in India.
Culture-specific tools to assess longterm psychosocial outcomes for patients with disorders of sexual differentiation are scant. We conducted a study to develop tools for evaluating gender role behavior and health related quality of life for Indian adolescent patients with intersex disorders. We also studied factors important to parents while deciding sex of rearing for their baby. A 29-item gender role behavior questionnaire and an 18-item health related quality-of-life questionnaire were administered to 82 healthy controls, 13 patients with intersex disorders and 18 patients with type 1 diabetes mellitus. Internal consistency was checked by Cronbach's alpha and test-retest reliability using intra-class correlation coefficient. Responses of 28 parents to a questionnaire on factors affecting the decision of sex of rearing were recorded on a 5-point Likert scale in order of importance. Cronbach's alpha was 0.92 and 0.75, and intra-class correlation coefficient 0.76 and 0.75, for the gender role behavior and quality-of-life questionnaires respectively, indicating a high degree of internal consistency and stability. The mean composite scores for healthy girls on the gender role behavior questionnaire (82.5 +/- 8.7) differed significantly from that for healthy boys (53.2 +/- 7.1, p <0.001). Factors important to parents while making decisions for sex of rearing were appearance of the genitalia, medical advice, ability to bear children and economic independence. We have created valid tools to study gender role behavior and quality of life in adolescent patients with intersex disorders in India. We have also identified in a quantitative way the factors of greatest importance to parents while deciding sex of rearing. These results have direct utility in the management of patients with intersex disorders in India and other similar cultures.


Potentiation of the teratogenic effects induced by coadministration of retinoic acid or phytanic acid/phytol with synthetic retinoid receptor ligands.
Previous studies in our laboratory identified retinoid-induced defects that are mediated by RAR-RXR heterodimerization using interaction of synthetic ligands selective for the retinoid receptors RAR and RXR in mice (Elmazar et al. 1997, Toxicol Appl Pharmacol 146:21-28; Elmazar et al. 2001, Toxicol Appl Pharmacol 170:2-9; Nau and Elmazar 1999, Handbook of experimental pharmacology, vol 139, Retinoids, Springer-Verlag, pp 465-487). The present study was designed to investigate whether these RAR-RXR heterodimer-mediated defects can be also induced by interactions of natural and synthetic ligands for retinoid receptors. A non-teratogenic dose of the natural RXR agonist phytanic acid (100 mg/kg orally) or its precursor phytol (500 mg/kg orally) was coadministered with a synthetic RARalpha-agonist (Am580; 5 mg/kg orally) to NMRI mice on day 8.25 of gestation (GD8.25). Furthermore, a non-teratogenic dose of the synthetic RXR agonist LGD1069 (20 mg/kg orally) was also coadministered with the natural RAR agonist, all- trans-retinoic acid (atRA, 20 mg/kg orally) or its precursor retinol (ROH, 50 mg/kg orally) to NMRI mice on GD8.25. The teratogenic outcome was scored in day-18 fetuses. The incidence of Am580-induced resorptions, spina bifida aperta, micrognathia, anotia, kidney hypoplasia, dilated bladder, undescended testis, atresia ani, short and absent tail, fused ribs and fetal weight retardation were potentiated by coadministration of phytanic acid or its precursor phytol. Am580-induced exencephaly and cleft palate, which were not potentiated by coadministration with the synthetic RXR agonists, were also not potentiated by coadministration with either phytanic acid or its precursor phytol. LGD1069 potentiated atRA- and ROH-induced resorption, exencephaly, spina bifida, aperta, ear anotia and microtia, macroglossia, kidney hypoplasia, undescended testis, atresia ani, tail defects and fetal weight retardation, but not cleft palate. These results suggest that synergistic teratogenesis can be induced by coadministration of a natural RXR ligand (phytanic acid) with a synthetic RAR agonist (Am580). Thus, certain potentially useful therapeutic agents or nutritional factors such as phytanic acid should be tested for teratogenic risk by coadministration with other retinoid receptor agonists.


Supramolecular systems-based extraction-separation techniques coupled to mass spectrometry.
The combination of supramolecular chemistry and MS has not only been fruitful in the field of gas-phase fundamental studies of host-guest complexes and supramolecular assemblies. Mass spectrometric analysis has also benefited from the ability of supramolecular systems to behave as pseudophases in which solutes partition from the bulk solvent phase. Supramolecular systems-based extraction and concentration schemes and separation techniques have been widely used in different fields of analytical chemistry and are ideally suited for coupling with MS. This review describes the present status of the application of supramolecular chemistry in mass spectrometric analysis and includes topics such as the use of coacervative liquid-liquid extraction and hemimicelle/admicelle-based SPE of organic compounds prior to chromatography and electrophoresis. It also discusses the recent advances in enantioselective analysis using CD in electrophoresis- and chromatography-MS. The potential and analytical challenges of these approaches in environmental and bioanalytical chemistry, where one can expect significant developments in the future, are outlined.


Artificial Manduca sexta forewings for flapping-wing micro aerial vehicles: how wing structure affects performance.
A novel approach to fabricating and testing artificial insect wings has been developed. Utilizing these new techniques, locally harvested hawk moth (Manduca sexta) forewings are compared to engineered forewings with varying wing structures. A number of small, flexible engineered forewings were fabricated with identical planform size and shape but with variations in camber, ribbing, thickness and composition. A series of static and dynamic assessments compares the forewings in terms of structure and performance. Data from these experiments show that the fabrication method can produce artificial forewings with similar properties to that of M. sexta. Flexural stiffness (EI) data shows a maximum percent difference of 41% between the left and right natural M. sexta forewings, whereas engineered forewings have a maximum percent difference of 18%. When deflection is induced from the ventral side of the forewing, EI values are at least 9.1% higher than when it is induced from the dorsal side. According to simulations, approximately 57% of this difference can be attributed to the camber of the forewings. Fabricated forewings produced comparable amounts of lift to natural M. sexta forewings (1.00 gF and 0.96 gF at 25 Hz flapping frequency respectively).


Congenital Lambert-Eaton myasthenic syndrome.
A 4 year old girl had been hypotonic and areflexic since birth with delayed milestones in motor development. Repetitive stimulation at high rates performed at 3 years elicited an incremental response typical of the Lambert-Eaton Syndrome.


Photoacoustic imaging of occlusal incipient caries in the visible and near-infrared range.
This study aimed to demonstrate the presence of dental caries through a photoacoustic imaging system with visible and near-infrared wavelengths, highlighting the differences between the 2 spectral regions. The depth at which carious tissue could be detected was also verified. Fifteen permanent molars were selected and classified as being sound or having incipient or advanced caries by visual inspection, radiography, and optical coherence tomography analysis prior to photoacoustic scanning. A photoacoustic imaging system operating with a nanosecond pulsed laser as the light excitation source at either 532 nm or 1064 nm and an acoustic transducer at 5 MHz was developed, characterized, and used. En-face and lateral (depth) photoacoustic signals were detected. The results confirmed the potential of the photoacoustic method to detect caries. At both wavelengths, photoacoustic imaging effectively detected incipient and advanced caries. The reconstructed photoacoustic images confirmed that a higher intensity of the photoacoustic signal could be observed in regions with lesions, while sound surfaces showed much less photoacoustic signal. Photoacoustic signals at depths up to 4 mm at both 532 nm and 1064 nm were measured. The results presented here are promising and corroborate that photoacoustic imaging can be applied as a diagnostic tool in caries research. New studies should focus on developing a clinical model of photoacoustic imaging applications in dentistry, including soft tissues. The use of inexpensive light-emitting diodes together with a miniaturized detector will make photoacoustic imaging systems more flexible, user-friendly, and technologically viable.


Iron deposition at mineralization fronts and osteoid formation following chronic cadmium exposure in ovariectomized rats.
To investigate whether chronic exposure of cadmium (Cd) chloride induces osteomalacic lesions similar to Itai-itai disease (IID), ovariectomized rats were injected intravenously with the cadmium at doses of 0.05 and 0.5 mg/kg/day, 5 days per week, for 50 weeks. In six rats in the 0.5 mg/kg group, the administration was continued for up to 70 weeks. In the 0.5 mg/kg group, the plasma concentration of calcium was similar in the treatment and control groups throughout the treatment period. The urinary excretion of calcium increased from 20 weeks and the increase became marked from 40 weeks. Histopathologically, osteoid seams in the femur, tibia, and humerus were increased from 50 weeks, and these changes became prominent at 70 weeks. Hypertrophy and hyperplasia of chief cells in the parathyroid were also observed from 50 weeks. The osteoid morphometry of the trabecular bone of the femur and sternum revealed a dose-dependent increase in osteoid/bone volumes. Roentgenographs of the antebrachial and metacarpal bones taken at 70 weeks showed so-called paper bone. The bone Cd content markedly increased until 25 weeks, but thereafter decreased linearly for up to 70 weeks. In contrast to the Cd content, the iron content decreased until 25 weeks, but thereafter increased until 70 weeks. Undecalcified section of the humerus showed the deposition of iron and formation of osteoid at mineralization fronts. Our data suggest that osteomalacic lesions were caused by chronic Cd intoxication, and that iron, as well as Cd, was involved in osteoid formation.


Cryptic diversity of the rocky crab genus Glebocarcinus Nations, 1975 (Crustacea: Decapoda: Cancridae): description of a new species from Russian coastal waters of the Sea of Japan based on morphology, DNA and distribution.
A new cancrid crab species Glebocarcinus kashini sp. nov. (Decapoda: Brachyura: Cancridae) is described from Russian coastal waters of the Sea of Japan. The new species can be clearly separated from relative and sibling, Glebocarcinus amphioetus (Rathbun, 1898), by a less prominent and granulated dorsal surface of the carapace and dorsal surface of the cheliped propodus, less prominent sculpture of the carapace front and bluntly triangular anterolateral teeth of the carapace. Comparison of COI gene sequences supports the subdivision of these two species and shows their clear genetic separation from a related species, the American pygmy rock crab, G. oregonensis (Dana, 1852). Along the mainland coast of the Sea of Japan, G. kashini and G. amphioetus possibly overlap only in Posyet Bay and adjacent areas; the new species is distributed to the north from the bay while G. amphioetus is distributed to the south. Previous and new records of G. amphioetus from the area are discussed.


Factors affecting cold acclimation and thermogenesis in man.
Three types of cold exposure are observed in man: systemic moderate cold (SM), systemic severe cold (SS), and local severe cold (LS). Contrary to rat, prolonged exposure to SM cold does not produce non-shivering thermogenesis, as it does in the rat, possibly because of lack of active brown adipose tissue. Instead there is a reduction in heat production, in shivering, and in discomfort through a process known as habituation. No adaptation was found with exposure to SS cold, since shivering and discomfort always prevail and there is indirect evidence of enhanced sympathetic response after repeated exposure to SS cold. Exposure to LS cold leads to adaptive responses in which discomfort and autonomic activity are reduced. It is suggested that LS adaptation is also related to habituation.


Polymorphisms of the factor VII gene associated with the low activities of vitamin K-dependent coagulation factors in one-month-old infants.
Despite administration of vitamin K (VK), some infants show lower activity of VK-dependent coagulation factors and they could develop intracranial hemorrhage. For preventing VK deficiency bleeding (VKDB) in infants, oral administration of VK and a screening test for VK deficiency are carried out in Japan. For the screening, the total activity of VK-dependent coagulation factors is measured using a commercial product, Normotest. This study was undertaken to clarify the importance of the following genetic and environmental factors on the coagulation status in one-month-old infants: two polymorphisms in the factor VII gene, -323P0/10 (a 10-bp insertion in the promoter region at position -323) and R353Q (the replacement of arginine [R] with glutamine [Q] at residue 353) and sex, age, gestational age, birth weight, and feeding regimen. Two hundred Japanese infants (34.6 +/- 4.0 days old) were screened for VK-dependent coagulation activity with Normotest and were genotyped for the two polymorphisms. Among the subjects screened, 18 infants (9%) carried the P10 allele and 26 (13%) carried the R353Q allele. Multiple regression analysis showed that the 10-bp inserted (P10) allele or the Q allele was associated with the lower coagulation activities. The coagulation activities for the R/Q genotype were significantly lower than those for the R/R genotype and those for the P0/P10 genotype were significantly lower than those for the P0/P0 genotype. Therefore, infants who carry the P10 allele or the Q allele show lower activity of VK-dependent coagulation factors. These infants may have a higher risk of VKDB manifestation.


Entecavir promotes CD34⁺ stem cell proliferation in the peripheral blood and liver of chronic hepatitis B and liver cirrhosis patients.
Entecavir (ETV) has been used for more than 2 decades in treating hepatitis B virus (HBV) infections. It has shown significant anti-HBV effect and has led to histological improvement in the liver of chronic hepatitis B (CHB) patients. In patients treated with ETV for over two years, reversal of cirrhosis to normal tissue has also been observed. However, the mechanisms of these tissue repairing or recovery processes are not yet clear. In order to determine the roles that bone marrow and liver stem/progenitor cells play in these processes, we evaluated the CD34⁺ and CD133⁺ stem/progenitor cells in peripheral blood from 292 patients and liver tissues from 43 patients who had received therapies with and without ETV. A significant increase in both CD34⁺ and CD133⁺ cells was found in CHB and cirrhosis patients compared to the healthy controls. In patients treated with ETV, CD34⁺ cells increased 2 and 4 fold in peripheral blood and liver tissues, respectively, while their CD4⁺ and CD8⁺ cells remained the same. On the other hand, CD133⁺ cells did not change or even slightly decreased with ETV treatment. Results from immunohistochemistry staining, real time RT-PCR, and the enzyme-linked immunosorbent assay also revealed the same level of CD34⁺ cell increase and CD133⁺ cell decrease (or no change) in ETV treated patients, compared to patients without ETV therapies. Liver functions in patients with ETV treatment improved in general, but one liver cirrhosis patient with high expression of CD133 in liver tissue developed hepatocellular carcinoma (HCC). In summary, ETV may have differential effects on various stem cell subtypes. ETV-activated stem cells in bone marrow and liver tissues may contribute to the recovery from injuries caused by HBV infection. They also contribute to the regeneration of normal tissue and the recovery of normal liver function. Meanwhile, ETV does not activate stem cells that may participate in the initiation of HCC.


Correction of gradient-induced phase errors in radial MRI.
To correct gradient-induced phase errors in radial MRI. Gradient-induced eddy currents affect the MRI data acquisition by gradient delays and phase errors that may lead to severe image artifacts for non-Cartesian imaging scenarios such as radial trajectories. While gradient delays are dealt with by respective shifts of the acquisition window during radial image acquisition, this work introduces a simple method for quantifying and correcting phase errors from the actual data prior to image reconstruction. For a given gradient system, the approach yields a specific phase error per gradient that can be used for correcting the raw data. Phantom studies at 9.4 T demonstrated marked improvements in radial image quality. It could be shown that the phase correction is not compromised by data undersampling. Moreover, the selective correction of gradient-induced phase errors retained the phase information caused by different concentrations of a paramagnetic contrast agent. The proposed method does not require additional reference measurements and separately corrects for phase errors induced by eddy currents, while retaining the residual phase of the object which may carry physiologic information.


Inhibition of in vitro and in vivo brown fat differentiation program by myostatin.
Obesity arises mainly due to the imbalance between energy storage and its expenditure. Metabolically active brown adipose tissue (BAT) has recently been detected in humans and has been proposed as a new target for anti-obesity therapy because of its unique capacity to regulate energy expenditure. Myostatin (Mst), a negative regulator of muscle mass, has been identified as a potential target to regulate overall body composition. Although the beneficial effects of Mst inhibition on muscle mass are well known, its role in the regulation of lipid metabolism, and energy expenditure is not very clear. We tested the effects of Mst inhibition on the gene regulatory networks that control BAT differentiation using both in vivo and in vitro model systems. PRDM16 and UCP1, two key regulators of brown fat differentiation were significantly up regulated in levator-ani (LA) and gastrocnemius (Gastroc) muscles as well as in epididymal (Epi) and subcutaneous (SC) fat pads isolated from Mst knock out (Mst KO) male mice compared with wild type (WT) mice. Using mouse embryonic fibroblast (MEFs) primary cultures obtained from Mst KO group compared to the WT group undergoing adipogenic differentiation, we also demonstrate a significant increase in select genes and proteins that improve lipid metabolism and energy expenditure. Treatment of Mst KO MEFs with recombinant Mst protein significantly inhibited the gene expression levels of UCP1, PRDM16, PGC1-α/β as well as BMP7. Future studies to extend these findings and explore the therapeutic potential of Mst inhibition on metabolic disorders are warranted.


Bridging from particle to macroscopic scales in uniaxial magnetic gels.
Connecting the different length scales of characterization is an important, but often very tedious task for soft matter systems. Here, we carry out such a procedure for the theoretical description of anisotropic uniaxial magnetic gels. The so-far undetermined material parameters in a symmetry-based macroscopic hydrodynamic-like description are determined starting from a simplified mesoscopic particle-resolved model. This mesoscopic approach considers chain-like aggregates of magnetic particles embedded in an elastic matrix. Our procedure provides an illustrative background to the formal symmetry-based macroscopic description. There are presently other activities to connect such mesoscopic models as ours with more microscopic polymer-resolved approaches; together with these activities, our study complements a first attempt of scale-bridging from the microscopic to the macroscopic level in the characterization of magnetic gels.


Uncoupling PR gene expression from NPR1 and bacterial resistance: characterization of the dominant Arabidopsis cpr6-1 mutant.
In Arabidopsis, NPR1 mediates the salicylic acid (SA)-induced expression of pathogenesis-related (PR) genes and systemic acquired resistance (SAR). Here, we report the identification of another component, CPR 6, that may function with NPR1 in regulating PR gene expression. The dominant CPR 6-1 mutant expresses the SA/NPR1-regulated PR genes (PR-1, BGL 2, and PR-5) and displays enhanced resistance to Pseudomonas syringae pv maculicola ES4326 and Peronospora parasitica Noco2 in the absence of SAR induction. cpr 6-1-induced PR gene expression is not suppressed in the cpr 6-1 npr1-1 double mutant but is suppressed when SA is removed by salicylate hydroxylase. Thus, constitutive PR gene expression in cpr 6-1 requires SA but not NPR1. In addition, resistance to P. s. maculicola ES4326 is suppressed in the cpr 6-1 npr1-1 double mutant, despite expression of PR-1, BGL 2, and PR-5. Resistance to P. s. maculicola ES4326 must therefore be accomplished through unidentified antibacterial gene products that are regulated through NPR1. These results show that CPR 6 is an important regulator of multiple signal transduction pathways involved in plant defense.


The Benefits of Working Memory Capacity on Attentional Control under Pressure.
The present study aimed to examine the effects of working memory capacity (WMC) and state anxiety (SA) on attentional control. WMC was manipulated by (a) dividing participants into low- and high-WMC groups (Experiment 1), and (b) using working memory training to improve WMC (Experiment 2). SA was manipulated by creating low- and high-SA conditions. Attentional control was evaluated by using antisaccade task. Results demonstrated that (a) higher WMC indicated better attentional control (Experiments 1 and 2); (b) the effects of SA on attentional control were inconsistent because SA impaired attentional control in Experiment 1, but favored attentional control in Experiment 2; and (c) the interaction of SA and WMC was not significant (Experiments 1 and 2). This study directly manipulated WMC by working memory training, which provided more reliable evidence for controlled attention view of WMC and new supportive evidence for working memory training (i.e., far transfer effect on attentional control). And the refinement of the relationship between anxiety and attentional control proposed by Attentional Control Theory was also discussed.


Prevention of parastomal hernia using mesh in patients undergoing rectum extirpation.
Developing a parastomal hernia can lead to emergency surgery and cause discomfort. Placing a pro-phylactic mesh around the ostomy may potentially prevent hernias from developing. Randomised clinical trials and reviews have reported contradictory results from this prophylactic procedure with different rates of hernias and success. This descriptive cohort study aimed to investigate the rate of parastomal hernia after applying prophylactic mesh in patients undergoing surgery for rectal cancer. In the period from 2010 to 2016, we included 133 patients who had a permanent colostomy with prophylactic mesh placement due to rectal cancer. The patients were seen in the ostomy ambulatory at least three times annually, and bulges and hernias were registered by a trained nurse. Computed tomography was used for verification of parastomal hernia. Data were registered retrospectively from patient files. After a median follow-up of 22 months, 24% of patients developed a parastomal hernia. Development of parastomal bulge without a subsequent hernia diagnosis was seen in 21%. The one-year rate of parastomal hernia was 9.7%. This cohort study supports the thesis of a low short-time rate of parastomal hernia in patients who had a prophylactic mesh placed during the ostomy formation and indicates that the rate of hernia increases over time after the first post-operative year. none. not relevant.


Sudden infant death syndrome and reported maternal smoking during pregnancy.
We investigated the effect of maternal smoking during pregnancy on the relative risk of sudden infant death syndrome (SIDS) by linking data from Georgia birth and death certificates from 1997 to 2000. We estimated the effect of misclassifying smokers as non-smokers and the effect of being misclassified on SIDS rates, and we calculated the fraction of cases caused by exposure. Of all SIDS cases, 21% were attributable to maternal smoking; among smokers, 61% of SIDS cases were attributable to maternal smoking. Maternal smoking during pregnancy is associated with a significantly increased risk of SIDS.


The Use of Blood Biomarkers in Precision Medicine for the Primary Prevention of Atherosclerotic Cardiovascular Disease: a Review.
A biomarker is a substance, structure, or process that indicates the presence of a disease, infection, or environmental exposure. Clinically useful biomarkers are measurable, improve diagnostic or prognostic performance, and ultimately aid clinicians in determining the initiation, duration, or magnitude of therapy. The purpose of this review is to explore the roles of various blood biomarkers of atherosclerotic cardiovascular disease (ASCVD) and how their use may improve the precision with which clinicians can identify, treat, and ultimately prevent ASCVD. Our review will include lipid biomarkers, markers of cardiac injury and wall stress, markers of inflammation, and a few others. Several biomarkers have recently been highlighted as "risk-enhancing factors" in the 2019 American College of Cardiology/American Heart Association Guideline for the Primary Prevention of ASCVD, which can help guide shared decision-making. These included elevated low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, or high-sensitivity C-reactive protein. However, some other biomarkers mentioned in this review are not commonly used despite showing initial promise as prognostic of ASCVD risk, as it is not clear how treatment decisions should be changed after their measurement among asymptomatic individuals. Future studies should focus on whether biomarker-directed management strategies can improve clinical outcomes.


A Stepwise Intraoperative Protocol to Minimize Complications after Volar Plating.
Background Although outcome of volar plating is generally good, care should be taken to avoid specific iatrogenic and preventable complications, with an incidence reporting averaging 15%. Flexor tendon rupture due to a prominent plate, extensor tendon rupture due to a dorsal protruding screw tips, cartilage lesions due to intra-articular screw placement, loss of reduction due to insufficient stability, and persisting ulnar pain with distal radioulnar joint instability due to unstable triangular fibrocartilaginous complex lesions or unstable ulnar styloid base fractures all have been described. Purpose We believe that a majority of these complications can be prevented by meticulous assessment of several intraoperative parameters during volar plating. Therefore, we introduce the WRIST protocol, a stepwise easy-to-remember manual that combines multiple fluoroscopic measurements to guide intraoperative decision making. Conclusion Large prospective studies of the "WRIST" protocol are needed for validation. But we believe that it may help surgeons to optimize surgical technique, functional and radiographic outcome, and prevent complications when treating distal radial fractures.


Evaluation of the shape, viability, stemness and osteogenic differentiation of cell spheroids formed from human gingiva-derived stem cells and osteoprecursor cells.
The present study was performed to create stem cell spheroids from human gingiva-derived stem cells and osteoprecursor cells and to evaluate the maintenance of the stemness, the viability and osteogenic differentiation of the cell spheroids. Gingiva-derived stem cells were isolated, and a total of 6×105 stem cells and osteoprecursor cells were seeded into concave micromolds at various ratios. Gingiva-derived stem cells and/or osteoprecursor cells formed spheroids in concave microwells. The spheroids demonstrated a smaller diameter when the number of osteoprecursor cells seeded was lower. The majority of cells in the spheroids were identified to be live cells and the cell spheroids preserved viability throughout the experimental period. The cell spheroids, which contained stem cells, were positive for stem-cell markers. Cell spheroids in concave microwells demonstrated a statistically significant increase in alkaline phosphatase activity as time progressed (P<0.05). A statistically significant difference in phosphatase activity was observed in the stem cell alone group when compared with the osteoprecursor cell group at day 5 (P<0.05). Mineralized extracellular deposits were observed in each group after Alizarin Red S staining. Within the limits of the present study, cell spheroids from gingival cells and osteoprecursor cells maintained shape, viability, stemness and osteogenic differentiation potential.


Optimising the medical management of benign prostatic hyperplasia.
The ageing population is presenting an increasing demand on future healthcare services. In males, prostatic disease is one of the commonest disorders contributing to this. Alternatives to surgical intervention have to be considered as the preferred option for individuals and whether this be a therapeutic or a financial option to be taken. Two major medical alternatives are alpha-blockers and 5-alpha reductase inhibitors. The results of such treatment can be very beneficial in selected groups of patients. Side-effects with improved drugs electivity are reducing. Overall, while surgery still holds the gold standard, medical therapy has a significant role in the treatment of benign prostatic hypertrophy. Cost analysis may be a factor in deciding which treatment to have.


Distinct effects of anterior pyriform cortex and the lateral hypothalamus lesions on protein intake in rats.
Several specific locations in brain, including pyriform cortex and hypothalamus, are associated with regulation of food intake. Although lesions of these locations significantly alter food intake, their involvement in the selection of macronutrients is not well characterized. In this study, we examined distinct effects of anterior pyriform cortex (APC) and lateral hypothalamus (LH) lesions on protein intake in rats. The APC or LH of male adult rats were lesioned by treatment with kainic acid, and the rats were then given free access to two kinds of casein diets containing high (60%) and low (5%) protein. Total energy content of these diets was kept constant by changing the carbohydrate content. Following the APC lesions, body weight and food intake decreased, but returned to control levels on day 13 and day 4, respectively. APC lesions did not change the ratio of protein intake. In contrast, LH lesions disturbed body weight gain and the selection of a high protein diet for at least two weeks, although food intake returned to control levels by day 2. Our results suggest that LH, but not APC, may play an important role in the selection of protein intake in rats.


Diagnosis of hereditary hemochromatosis in the era of genetic testing.
Homozygous C282Y mutation in HFE gene is responsible for the majority of hereditary hemochromatosis cases. Since 1996 this mutation can be identified by a simple genetic test. To determine the clinical presentations in patients with homozygous HFE C282Y mutation and the impact of genetic testing on the time needed for diagnosis. A total of 414 patients diagnosed with C282Y homozygous hereditary hemochromatosis before and after the introduction of genetic testing were evaluated regarding symptoms and clinical findings at diagnosis as well as first hemochromatosis-related clinical features in their past medical history. At the time of diagnosis, the predominant symptom was joint pain, in particular of the hands/wrists. Those patients presenting with hand/wrist arthralgia had significantly higher ferritin levels than patients without this joint involvement (p = 0.0005 for males and p < 0.0001 for females). After the introduction of the HFE genetic test an earlier diagnosis after first onset of hemochromatosis-associated clinical features was observed between 2006 and 2009 vs. 2000-2005 p = 0.01). Arthralgia, in particular of the hands/wrists, is a hallmark of hereditary hemochromatosis and its presence is associated with higher ferritin levels. Despite the availability of a genetic test, it often takes more than 6 years from the first onset of clinical features to diagnose hereditary hemochromatosis. This underlines the importance of raising the awareness of hemochromatosis and its typical clinical presentations.


Electron microscopical localization of the lead in peripheral blood neutrophils of the rat with timm sulphide silver method and X-ray probe microanalysis.
The distribution of lead ions in rat peripheral neutrophils was investigated using Timm sulphide silver method. In the neutrophils of adult male rats the Pb-precipitates were electron microscopically localized at 1.5, 3.0 and 6.0 hours after a single intraperitoneal injection of lead at dose 150 mgPb kg b. w. After increased lead ions input to cell matrix a formation of cytoplasmic metal deposits as well as an aggregation of Pb-complexes within deep invaginations of nuclear membrane was detectable. Furthermore, the neutrophils were prepared to examination by scanning electron microscope according to Domagała et al. (1979). In neither case there was a clear difference of neutrophil surface morphology between exposed and control populations. The same preparations were then used to X-ray probe microanalysis, and correlation between the presence of Timm reaction product and lead indication was obtained.


[Injuries of the liver].
In first 9 months of the war, on our Clinic we accepted 138 wounded with injury of liver, diagnosed during the operation. Injuries of liver are classified (Moor) on 5 groups. Harder injuries are treated using: deep sutturae of liver or debridman with haemostasis, with deep sutturae, resection of liver, tamponade of hepatotomia. Each surgery is analysed. The most frequent way of treating was with deep sutturae with or without debridman. Concerning the small mortality 7.2%, and rare complications 3.2%, this way of treating is accepted under condition to analyse indications for using this method.


Circadian regulation of lung repair and regeneration.
Optimal lung repair and regeneration are essential for recovery from viral infections, including influenza A virus (IAV). We have previously demonstrated that acute inflammation and mortality induced by IAV is under circadian control. However, it is not known whether the influence of the circadian clock persists beyond the acute outcomes. Here, we utilize the UK Biobank to demonstrate an association between poor circadian rhythms and morbidity from lower respiratory tract infections, including the need for hospitalization and mortality after discharge; this persists even after adjusting for common confounding factors. Furthermore, we use a combination of lung organoid assays, single-cell RNA sequencing, and IAV infection in different models of clock disruption to investigate the role of the circadian clock in lung repair and regeneration. We show that lung organoids have a functional circadian clock and the disruption of this clock impairs regenerative capacity. Finally, we find that the circadian clock acts through distinct pathways in mediating lung regeneration - in tracheal cells via the Wnt/β-catenin pathway and through IL-1β in alveolar epithelial cells. We speculate that adding a circadian dimension to the critical process of lung repair and regeneration will lead to novel therapies and improve outcomes.


The Reliability of the Divergence Angle for Evaluating Rotational Implant Positioning in Medial Unicompartmental Knee Replacement.
Background Unicompartmental knee arthroplasty (UKA) is a highly effective surgical procedure used to treat patients with osteoarthritis affecting a single knee compartment. UKA has gained significant popularity, accompanied by an expansion of its surgical indications. This increasing trend can be attributed to the consistently excellent clinical outcomes associated with UKA, which rival those achieved with total knee arthroplasty (TKA). However, despite these advancements, implant rotation malposition remains a prevalent factor contributing to early failure in UKA cases. The aim of this study is to analyze the rotational positioning of femorotibial implants in UKA and to identify an appropriate angle formed by the femoral component and the tibial component using a newly described angle. Methods This was a retrospective study of patients' data of 40 medial UKA cases of 33 patients who were operated on in our hospital between October 1998 and March 2019. The study introduces a new angle called the "divergence angle." This angle is formed between the lateral portion of the femoral component and the lateral part of the tibial component, as measured on a patellofemoral Merchant view at 30 degrees of knee flexion. The divergence angle was evaluated through radiographic assessment by two independent reviewers. Results According to statistical analysis, the divergence angle was highly reliable with both intra- and inter-observer reproducibility. Intra-observer reproducibility was excellent with an intra-class correlation coefficient (ICC) between 0.901 and 0.933 (p < 0.001). The inter-observer reproducibility was excellent with an ICC of 0.92 (p < 0.001). The Gaussian curve confirmed the normal distribution of the divergence angle values with moderate dispersion of values. The majority of the angles of divergence (85%) measured between the femoral and tibial components were less than 10 degrees (n = 34), with a mean angle of 6.3 ± 4.5°. Conclusion The divergence angle between the femoral and tibial components, measured at 30 degrees of knee flexion using the Merchant view, is an easily accessible, reliable, and reproducible method. This technique enables the assessment of the optimal rotational positioning of implants in medial UKA.


From Race to Racism: Teaching a Tool to Critically Appraise the Use of Race in Medical Research.
Despite the ubiquitous use of race within scientific literature, medical trainees are not taught how to critically appraise the use of racial categories. We developed a tool to appraise the use of race in medical literature and a workshop to teach this approach. Third-year medical students and second- and third-year residents participated in workshops between 2015 and 2018. We evaluated our UME workshop with a postworkshop survey. We evaluated our GME workshop with a pretest, immediate posttest, and 6-month posttest on self-assessed knowledge, skills, and use of the Critical Appraisal of Race in Medical Literature (CARMeL) tool in subsequent journal clubs. We delivered this workshop to 560 students and 82 residents. Of the initial 140-student cohort evaluating the workshop, 99 (71% response rate) highly rated clarity of presentation, quality of teaching, and quality of slides. Of PGY 2 and PGY 3 residents, 67 (82% response rate) rated the workshop greater than 4.5 out of 5 on quality, clarity, and appropriateness of content. Residents had significant improvements in self-assessed knowledge and skills immediately after the session and 6 months later. Of residents, 74% reported using the CARMeL tool in subsequent presentations. We designed the CARMeL tool and a workshop to teach it. Trainees rated this workshop as useful, with the majority of residents later applying the tool. Limitations included a lack of objective assessment of knowledge acquisition. We recommend that institutions invest time in faculty development and pair new faculty with those experienced in anti-oppressive facilitation.


The Association of Tacrolimus Formulation on Cerebral Blood Flow and Cognitive Function.
Calcineurin inhibitors are inherent vasoconstrictors. Cerebral vasoconstriction can reduce cerebral blood flow (CBF), and negatively impact cerebrovascular response (CVR) to exercise, and cognitive function. The once-daily extended-release (LCP) tacrolimus has fewer side effects than the immediate-release (IR) tacrolimus. The role of calcineurin inhibitors on CBF and the impact of specific formulations of tacrolimus on CBF, CVR, and cognitive function are unknown. In this pilot study, we evaluated whether changing from IR tacrolimus to LCP tacrolimus modulates CBF, CVR, or cognitive function in kidney transplant (KT) recipients. We randomized (2:1) 30 stable KT recipients on IR tacrolimus to intervention (switch to LCP tacrolimus) and control (continue IR tacrolimus) arms. We measured CBF, CVR, and cognitive function at baseline and at 12 wk. We used ANCOVA to evaluate changes in outcome variables, with baseline values and study arm as covariates. We used descriptive statistics with mean changes in outcome variables to compare the 2 groups. Participants were 51 ± 13 y old. There was no difference in plasma tacrolimus levels at baseline and at 12 wk in the 2 arms. The changes in CBF, resting middle cerebral artery velocity, CVR, and cognitive function were more favorable in the intervention arm than in the control group. Changing IR tacrolimus to LCP tacrolimus may improve CBF, cerebrovascular dynamics, and cognitive function in KT recipients. Larger studies are needed to confirm these results.


[Diagnosis of basal body temperature, serum progesterone and endometrial biopsy for luteal phase defect].
Fourteen infertile women and two women with recurrent abortions were suspected of having luteal phase defect (LPD) by BBT charts. In these patients, the midluteal phase serum progesterone (P) levels were determined together with histological examination by the late luteal endometrial biopsies during the same cycle. The diagnostic criteria for LPD was BBT of luteal phase < or = eleven days, mean P level of 3 blood samples taken on three days during midluteal phase was less than 48 nmol/L (15 ng/ml) and the histological dating of endometrium was two or more days behind. The results showed that histological abnormality and low P level were 6.3% and 31.3%, respectively. When histological abnormality combined with lowered P level at the same cycle, the diagnosis of LPD increased to 87.5%. The author suggests that both midluteal phase P level and late luteal endometrial histological examination should be assessed at the same cycle in the diagnosis of LPD. BBT should also be assessed.


Immunopeptidomics toolkit library (IPTK): a python-based modular toolbox for analyzing immunopeptidomics data.
The human leukocyte antigen (HLA) proteins play a fundamental role in the adaptive immune system as they present peptides to T cells. Mass-spectrometry-based immunopeptidomics is a promising and powerful tool for characterizing the immunopeptidomic landscape of HLA proteins, that is the peptides presented on HLA proteins. Despite the growing interest in the technology, and the recent rise of immunopeptidomics-specific identification pipelines, there is still a gap in data-analysis and software tools that are specialized in analyzing and visualizing immunopeptidomics data. We present the IPTK library which is an open-source Python-based library for analyzing, visualizing, comparing, and integrating different omics layers with the identified peptides for an in-depth characterization of the immunopeptidome. Using different datasets, we illustrate the ability of the library to enrich the result of the identified peptidomes. Also, we demonstrate the utility of the library in developing other software and tools by developing an easy-to-use dashboard that can be used for the interactive analysis of the results. IPTK provides a modular and extendable framework for analyzing and integrating immunopeptidomes with different omics layers. The library is deployed into PyPI at https://pypi.org/project/IPTKL/ and into Bioconda at https://anaconda.org/bioconda/iptkl , while the source code of the library and the dashboard, along with the online tutorials are available at https://github.com/ikmb/iptoolkit .


Shortage of chemical fuel as a cause of fatigue: studies by nuclear magnetic resonance and bicycle ergometry.
The technique of nuclear magnetic resonance (n.m.r.) is briefly described to illustrate its use for estimating metabolite levels in vivo. Our studies of fatigue in anaerobic frog muscle at 4 degree C are described in relation to (a) force development, (b) speed of relaxation and (c) the switching on and off of glycolysis. Both (a) and (b) are closely related, though in different ways, to the concentrations of key metabolites. In contrast, (c) is not related to metabolite levels as such but to the events of contraction and relaxation. A special n.m.r. technique (saturation transfer) has been used to study the creatine kinase system in vivo. The results show that this system is highly active and is in equilibrium in resting muscle. The free [ADP] is consequently only a small fraction of that found by analysis of muscle extracts. Studies of human power production as a function of duration of exercise also indicate that it is shortage of chemical fuel that brings short- and medium-term exercise (0.1-10 min) to a halt. It is proposed to extend n.m.r. methods to human subjects in the near future. A working hypothesis to account for fatigue is suggested in which both the contractile system and the activating system play a part.


The alternative splicing landscape of a coral reef fish during a marine heatwave.
Alternative splicing is a molecular mechanism that enables a single gene to encode multiple transcripts and proteins by post-transcriptional modification of pre-RNA molecules. Changes in the splicing scheme of genes can lead to modifications of the transcriptome and the proteome. This mechanism can enable organisms to respond to environmental fluctuations. In this study, we investigated patterns of alternative splicing in the liver of the coral reef fish Acanthochromis polyacanthus in response to the 2016 marine heatwave on the Great Barrier Reef. The differentially spliced (DS; n = 40) genes during the onset of the heatwave (i.e., 29.49°C or +1°C from average) were related to essential cellular functions such as the MAPK signaling system, Ca(2+) binding, and homeostasis. With the persistence of the heatwave for a period of one month (February to March), 21 DS genes were detected, suggesting that acute warming during the onset of the heatwave is more influential on alternative splicing than the continued exposure to elevated temperatures. After the heatwave, the water temperature cooled to ~24.96°C, and fish showed differential splicing of genes related to cyto-protection and post-damage recovery (n = 26). Two-thirds of the DS genes detected across the heatwave were also differentially expressed, revealing that the two molecular mechanisms act together in A. polyacanthus to cope with the acute thermal change. This study exemplifies how splicing patterns of a coral reef fish can be modified by marine heatwaves. Alternative splicing could therefore be a potential mechanism to adjust cellular physiological states under thermal stress and aid coral reef fishes in their response to more frequent acute thermal fluctuations in upcoming decades.


Effect of different concentrations of omega-3 fatty acids on stimulated THP-1 macrophages.
Inflammation plays a central role in chronic diseases occurring in the contemporary society. The health benefits of omega-3 (n-3) fatty acids (FAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been reported. However, their mechanisms of action are poorly understood. We explored dose and time effects of EPA, DHA, and a mixture of EPA + DHA on the expression of inflammatory genes in stimulated macrophages. Lipopolysaccharide was used to stimulate human THP-1 macrophages. Cells were incubated in different conditions in the presence of n-3 FAs and LPS, and mRNA levels of inflammatory genes were measured by real-time PCR. Cytokine levels in culture media were measured. The mixture of EPA + DHA had a more effective inhibitory effect than either DHA or EPA alone, DHA being more potent than EPA. For both EPA and DHA, 75 μM of FAs had a more important anti-inflammatory effect than 10 or 50 μM. For gene expression, EPA had the greater action during the post-incubation (after LPS treatment) condition while DHA and EPA + DHA were more potent during the co-incubation (n-3 FAs and LPS). Cytokine concentrations decreased more markedly in the co-incubation condition. These results suggest that in stimulated macrophages, expression levels of genes involved in inflammation are influenced by the dose, the type of n-3 FAs, and the time of incubation.


Desulfurization of gasoline.
Although gasoline blending streams exhibit widely varying sulfur concentrations, significant quantities of low-sulfur motor gasoline cannot be manufactured by reallocation of existing components without substantial sacrifices in the useful properties of the remaining fuels having normal sulfur levels. To meet the anticipated demand for low-sulfur unleaded gasoline which may be required for catalyst-equipped automobiles it will be necessary to install process equipment based on known hydrotreating technology. The effects which this construction program would exert on the activities, abilities and needs of one petroleum refiner are sketched for two degrees of sulfur removal. The impacts of installing the process facilities which would be necessary are discussed in terms of time requirements, capital needs, and added energy expenditures.


There is no functional small-fibre neuropathy in prurigo nodularis despite neuroanatomical alterations.
Prurigo nodularis (PN) is a pruritic condition with altered epidermal neuroanatomy as demonstrated previously. Here we elucidated neuroimmunological mechanisms by combining functional, morphological and gene expression experiments in twelve subjects with PN and eight healthy controls. Subjects with PN showed a reduced intra-epidermal nerve fibre density (IENFD) in lesional skin. Quantitative sensory testing indicated maintenance of somatosensory function compared to controls. None of the tested molecular markers including the neuron-distracting SEMA3A and neuron-attracting NGF were altered in lesional vs non-lesional skin in PN subjects. Accordingly, we speculate that scratching may contribute to reduced IENFD rather than an authentic endogenous neuropathy.


Rapid progression of symptomatic vertebrobasilar artery dissection on magnetic resonance imaging: a case report.
Spontaneous intracranial vertebrobasilar dissection can manifest with various clinical symptoms, including subarachnoid hemorrhage or ischemic symptoms from impaired posterior circulation. A 29-year-old woman came to our emergency department with a sudden onset of left sided mild motor weakness and headache. Initial magnetic resonance imaging (MRI) showed mild luminal irregularities in the vertebrobasilar arteries with an eccentric periluminal hematoma. Follow-up MRI obtained 3 days later showed a progression of vertebrobasilar dissection to multifocal stenoses with an increased intramural hematoma.


Do Patients with Pre-Existing Psychiatric Illness Have an Increased Risk of Infection after Injury?
Trauma remains a leading cause of death and long term-morbidity. We have shown that patients who sustain traumatic injuries are at increased risk for the development of infectious complications. Psychiatric illnesses (PIs) are also noted to occur frequently among the general population. The presence of a PI has been shown to be a risk factor for the development of infections. Despite the prevalence of both traumatic injuries and psychiatric diseases, there are little data relating the impact of PI on the outcome of patients with trauma. We hypothesize that the presence of a PI will be associated with an increased risk of an infection developing after injury. This is a five year retrospective chart review of all admitted patients with trauma age 18 years and older. Patients with and without a major psychiatric illness were compared. Demographic data, mechanism of injury and Injury Severity Score (ISS) were reviewed. Co-morbidities included diabetes mellitus, obesity, pre-injury steroid use, and International Classification of Diseases, 9th edition, based psychiatric illness. All infections were diagnosed by microbiologic criteria (urinary tract infection [UTI], ventilator-associated pneumonia) or Centers for Disease Control and Prevention criteria for clinically evident infections (surgical site infection). Of the 11,147 admitted trauma patients, 14.5% had a pre-injury PI diagnosis. The PI patients were older (61.5 ± 0.5 vs. 54.3; p < 0.001), more often female (56% vs. 39.1%; p < 0.001), and had no difference in blunt mechanism rates (88.4% vs. 89.9%; p = 0.06) or median ISS (9 vs. 9; p = 0.06). There was no difference between PI and non-PI patients in pre-injury diabetes mellitus (13.4% vs. 12.7%; p = 0.4), steroid use (2.5% vs. 1.9%; p = 0.1), but patients with PI were more likely to be obese (15.7% vs. 13.6%; p = 0.03). Patients with PI were more likely to have an infection develop (10.4% vs. 7.5%; p < 0.001). The most common infection in both groups was UTI (6.9% vs. 4.2%; p < 0.001). Compared with non-PI patients, adjusting for age, gender, ISS, diabetes mellitus, and obesity, patients with PI were more likely to have an infection develop (odds ratio 1.3, 95% confidence interval = 1.1-1.5) Conclusions: Patients with an underlying PI are at increased risk of having a UTI after traumatic injury. This study identifies a previously unknown independent risk factor for UTIs in patients with trauma. This stresses the need for increased awareness and attention to this vulnerable population.


Nontemplate synthesis of CH3NH3PbBr3 perovskite nanoparticles.
To date, there is no example in the literature of free, nanometer-sized, organolead halide CH3NH3PbBr3 perovskites. We report here the preparation of 6 nm-sized nanoparticles of this type by a simple and fast method based on the use of an ammonium bromide with a medium-sized chain that keeps the nanoparticles dispersed in a wide range of organic solvents. These nanoparticles can be maintained stable in the solid state as well as in concentrated solutions for more than three months, without requiring a mesoporous material. This makes it possible to prepare homogeneous thin films of these nanoparticles by spin-coating on a quartz substrate. Both the colloidal solution and the thin film emit light within a narrow bandwidth of the visible spectrum and with a high quantum yield (ca. 20%); this could be advantageous in the design of optoelectronic devices.


[The filterability of whole blood (the role of leukocytes and erythrocytes)].
Filterability of the blood with various red cell and leukocyte concentrations was examined in 17 patients with coronary heart disease. The blood was filtered through a filter with pore diameter of 5 microns under a pressure of 100 cm water column. Blood filterability drastically deteriorated if leukocyte concentrations in the blood increased and depended on the leukocyte filtration characteristics. The number of red cells passed through the filter was in direct proportion with the blood red cell count.


JUN is important for ocular hypertension-induced retinal ganglion cell degeneration.
Ocular hypertension, a major risk factor for glaucoma, is thought to trigger glaucomatous neurodegeneration through injury to retinal ganglion cell (RGC) axons. The molecular signaling pathway leading from ocular hypertension to RGC degeneration, however, is not well defined. JNK signaling, a component of the mitogen-activated protein kinase (MAPK) family, and its canonical target, the transcription factor JUN, have been shown to regulate neurodegeneration in many different systems. JUN is expressed after glaucoma-relevant injuries and Jun deficiency protects RGCs after mechanical injury to the optic nerve. Here, we tested the importance of JNK-JUN signaling for RGC death after ocular hypertensive axonal injury in an age-related, mouse model of ocular hypertension. Immunohistochemistry was performed to evaluate JUN expression in ocular hypertensive DBA/2J mice. JUN was expressed in a temporal and spatial pattern consistent with a role in glaucomatous injury. To determine the importance of JUN in ocular hypertension-induced RGC death, a floxed allele of Jun and a retinal expressed cre recombinase (Six3-cre) were backcrossed onto the DBA/2J background. Intraocular pressure (IOP) and gross morphology of the retina and optic nerve head were assessed to determine whether removing Jun from the developing retina altered IOP elevation or retinal development. Jun deficiency in the retina did not alter DBA/2J IOP elevation or retinal development. Optic nerves and retinas were assessed at ages known to have glaucomatous damage in DBA/2J mice. Jun deficiency protected RGC somas from ocular hypertensive injury, but did not protect RGC axons from glaucomatous neurodegeneration. Jun is a major regulator of RGC somal degeneration after glaucomatous ocular hypertensive injury. These results suggest in glaucomatous neurodegeneration, JNK-JUN signaling has a major role as a pro-death signaling pathway between axonal injury and somal degeneration.


Integrative gene regulatory network analysis reveals light-induced regional gene expression phase shift programs in the mouse suprachiasmatic nucleus.
We use the multigenic pattern of gene expression across suprachiasmatic nuclei (SCN) regions and time to understand the dynamics within the SCN in response to a circadian phase-resetting light pulse. Global gene expression studies of the SCN indicate that circadian functions like phase resetting are complex multigenic processes. While the molecular dynamics of phase resetting are not well understood, it is clear they involve a "functional gene expression program", e.g., the coordinated behavior of functionally related genes in space and time. In the present study we selected a set of 89 of these functionally related genes in order to further understand this multigenic program. By use of high-throughput qPCR we studied 52 small samples taken by anatomically precise laser capture from within the core and shell SCN regions, and taken at time points with and without phase resetting light exposure. The results show striking regional differences in light response to be present in the mouse SCN. By using network-based analyses, we are able to establish a highly specific multigenic correlation between genes expressed in response to light at night and genes normally activated during the day. The light pulse triggers a complex and highly coordinated network of gene regulation. The largest differences marking neuroanatomical location are in transmitter receptors, and the largest time-dependent differences occur in clock-related genes. Nighttime phase resetting appears to recruit transcriptional regulatory processes normally active in the day. This program, or mechanism, causes the pattern of core region gene expression to transiently shift to become more like that of the shell region.


COVID-19 Vaccine Hesitancy Among Patients Attending the General Outpatient Clinic in a Tertiary Hospital in Southern Nigeria.
Background As most of the available studies on acceptance of the coronavirus disease 2019 (COVID-19) vaccine were done prior to the development of a vaccine, this study aimed to determine the current willingness to receive the available COVID-19 vaccines in Nigeria and ascertain factors influencing its acceptance. Methodology A cross-sectional descriptive study using a paper-based questionnaire was conducted among patients aged 18 years and above, attending the General Outpatient Clinic of Federal Medical Centre, Asaba, Delta State, Nigeria (n= 366). Data were analyzed using SPSS version 26 (Armonk, NY: IBM Corp.). Univariate and bivariate analyses were conducted at an alpha level of significance set at p<0.05. Results This study comprised 366 participants, of which 56.28% were willing to take a COVID-19 vaccine if it was made available to them. Generally, it was found that participants aged <40 years (56.90%), females (56.88%), singles (57.32%), and unemployed respondents (67.44%) were more willing to receive the vaccine than others. Those who agreed that COVID-19 was not an invention by man (p=0.031; OR=1.64; 95% CI=1.05, 2.58) were more likely to receive a vaccine. Suspicion of the government's intentions about COVID-19 was a perceived barrier by participants to accepting a vaccine. Conclusion Our findings represent one of the few estimates of the acceptability of the COVID-19 vaccine in Nigeria. They can be used to guide the planning and development of future public health efforts, increasing the awareness of the COVID-19 vaccine, its acceptability, and its uptake.


Proposed diagnostic reference levels for general radiography and mammography in Japan.
Diagnostic reference levels (DRLs 2015) in Japan were first published in 2017, on the Japan Network for Research and Information on Medical Exposures network. Medical facilities in Japan are now presumably reconsidering radiation doses at their facilities and approaching protection optimisation through the application of DRLs 2015. However, since more than 3 years have elapsed since publication, radiation doses received by patients in Japan may have diverged from DRLs 2015. We therefore undertook the present study. Based on our questionnaire survey implemented in 2017, we estimated the entrance skin dose (ESD) under general radiography fields and the mean glandular dose (MGD) under mammography, to compile a report on the doses received by patients under general radiography fields and mammography, and to propose new DRLs as replacements for DRLs 2015. Radiation doses under general radiography fields and mammography were estimated from the results of the 2017 questionnaire survey and applied to determine new DRLs at 75% values of dose distributions in general radiography fields and at 95% values of dose distributions in mammography. Among all the modes for general radiography fields and mammography, median ESD and MGD were significantly smaller with flat panel detector systems than with computed radiography systems. Comparison of the results with DRLs 2015 values showed a trend toward decreases in all imaging methods of the general radiography fields and mammography ranging from 5.0% (child chest radiography) to 31.7% (skull radiography). Moreover, responses showed that DRLs 2015 were recognised and used for comparison at many facilities. We have described the doses received by patients in general radiography fields and mammography in 2017 and proposed new DRLs as replacements for DRLs 2015. The DRLs we proposed for general radiography fields and mammography were determined to be lower than DRLs 2015 for all modes.


Behavior of human dermal fibroblasts in three-dimensional fibrin clots: dependence on fibrinogen and thrombin concentration.
Fibrin sealant products are used in hemostasis and tissue sealing, and potentially as a cell delivery vehicle. In this study, fibrin sealant was evaluated as a delivery vehicle for human dermal fibroblasts. Fibroblast proliferation and migration were assessed in various dilutions of fibrin sealant by changing the fibrinogen and thrombin concentration. Fibroblasts proliferated well within three-dimensional (3-D) fibrin clots consisting of fibrinogen (5-17 mg/mL) and thrombin (1-167 U/mL). These fibroblasts also retained good morphology and growth characteristics after migrating out of the 3-D fibrin clots. Furthermore, using Western blot and fluorescence-activated cell-sorting analysis, we found that the expression of growth factors and interleukins in the entire fibroblast-fibrin construct was dependent on the fibrin sealant formulation. For example, in a formulation in which fibroblasts showed modest proliferation and migration, interleukin 8 was secreted to a lesser extent than in a formulation that supported robust proliferation and migration. To our knowledge, this is the first time that it has been shown that modifying the concentration of fibrinogen and thrombin affects fibroblast behavior within formed 3-D fibrin clots. In addition, some of these formulations present an ideal delivery vehicle for fibroblasts that could be used for the treatment of chronic wounds.


Subcutaneous phaeohyphomycosis.
This report shows images of a case of subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in a patient who has undergone renal transplantation. The paper comments briefly on the disease and emphasizes the need to take this mycosis into account in the differential diagnosis of other dermatoses, including non-infectious dermatoses.


High temperature purge and trap procedure for determining seven volatile N-nitrosamines in animal feed, using gas chromatography/thermal energy analyzer.
A rapid and sensitive procedure is described for determining 4 N-nitrosodialkylamines (dimethyl, diethyl, dipropyl, and dibutyl) and the N-nitroso analogs of piperidine, pyrrolidine, and morpholine in animal feed. The volatile N-nitrosamines were isolated by using a modified high temperature purge and trap apparatus designed for multiple sample cleanup. The feed sample was mixed with mineral oil and a nitrosation inhibitor, and the N-nitrosamines were purged onto a ThermoSorb/N cartridge, eluted with acetone-dichloromethane (1 + 1), and determined by gas chromatography, using a thermal energy analyzer. The effects of purge rate, purge time, and temperature on recovery are discussed. Feed samples spiked with 10, 50, and 200 ppb of the 7 N-nitroso compounds yielded recoveries ranging from 70 to 97%, with precision ranging from 1.3 to 5.4% and minimum detectable levels in the low parts-per-billion range.


Disseminated Bacillus Calmette-Guerin infections after intravesical therapy.
Intravesical instillation of Bacillus Calmette-Guerin (BCG) is the treatment of choice for superficial bladder carcinoma. Disseminated BCG infection presenting as granulomatous hepatitis or pneumonitis is a very rare complication of this treatment. Here we report a case series of seven patients previously treated with BCG presenting with pneumonitis. In two of the cases, identification of Mycobacterium bovis was achieved with molecular methods.


The RIB element in the goaG-pspF intergenic region of Escherichia coli.
The sequence (2,700 bp) between the aldH and pspF genes of Escherichia coli was determined. The pspF gene encodes a sigma54 transcriptional activator of the phage shock protein (psp) operon (pspA to pspE). Downstream of the pspF transcribed region are two open reading frames (ORFs), ordL and goaG, convergently oriented with respect to pspF. These two ORFs, together with the adjacent aldH gene, may constitute a novel operon (aldH-ordL-goaG). The goaG-pspF intergenic region contains a complex extragenic mosaic element, RIB. The structure of this RIB element, which belongs to the BIME-1 family, is Y(REP1) > 16 < Z1(REP2), where Y and Z1 are palindromic units and the central 16 bases contain an L motif with an ihf consensus sequence. DNA fragments containing the L motif of the psp RIB element effectively bind integration host factor (IHF), while the Y palindromic unit (REP1) of the same RIB element binds DNA gyrase weakly. Computer prediction of the pspF mRNA secondary structure suggested that the transcribed stem-loop structures formed by the 3'-flanking region of the pspF transcript containing the RIB element can stabilize and protect pspF mRNA. Analysis of pspF steady-state mRNA levels showed that transcripts with an intact RIB element are much more abundant than those truncated at the 3' end by deletion of either the entire RIB element or a single Z1 sequence (REP2). Thus, the pspF 3'-flanking region containing the RIB element has an important role in the stabilization of the pspF transcript.


Temperature Impacts on Soil Microbial Communities and Potential Implications for the Biodegradation of Turfgrass Pesticides.
Maintaining healthy turfgrass often results in the use of pesticides to manage weed, insect, and disease pests. To identify and understand potential nontarget impacts of pesticide usage while still maintaining attractive and functional turfgrass sites, it is important to improve our understanding of how pesticides degrade in various environments throughout the growing season. Temperature heavily influences microbial community composition and activity, and the microbial community often heavily influences pesticide degradation in soil ecosystems. Pesticide transformation products generated through the action of soil microbial degradation networks can vary in their toxicity, with the potential result that a pesticide applied in the spring at 10°C could produce different transformation products with different toxicological impacts than the sample pesticide applied to the same site at 22°C. The objective of this review is to examine past research surrounding soil microbial activity related to pesticide degradation and provide a foundation for how the soil microbiome interacts with pesticides and how seasonal temperature variations may influence those interactions.


Interaction of [125I] beta nerve growth factor with acidic proteins.
We have demonstrated that the beta nerve growth factor will interact with various acidic proteins apparently nonspecifically. When 125I-labeled beta nerve growth factor at a concentration of 3.8 X 10(-10) M is incubated with an acidic protein at 2 mg/ml (4.5 X 10(-6)-4.4 X 10(-5) M), a complex is formed. This complex changes the isoelectric point of the 125I-labeled beta nerve growth factor sufficiently so that the 125I-labeled beta nerve growth factor migrates anomalously in polyacrylamide gel electrophoresis. The interaction between beta nerve growth factor and bovine serum albumin, which appears to be complex, may be the cause of the previously reported activation of the beta nerve growth factor when bovine serum albumin is present in a typical bioassay.


Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9.
The primary structure of galectin-3, a approximately 30 kDa galactoside-binding protein (aka CBP-35, mL-34, hL-31, L-29, Mac-2, and epsilon BP), reveals two structural domains: an amino-terminal domain consists of a Pro-Gly-rich motif, and a globular carboxyl-terminal domain containing a carbohydrate-binding site. In this study, we report that the amino-terminal domain of galectin-3 contains a cleavage site for two members of the matrix metalloproteinase family of enzymes: the 72 kDa (gelatinase A, MMP-2) and the 92 kDa (gelatinase B, MMP-9) proteinases. The major cleavage site for the gelatinases in galectin-3 is at the Ala62-Tyr63 bond, and its hydrolysis by these enzymes was inhibited by TIMP-2. Cell-surface expression of galectin-3 was reduced following treatment of viable T47D human breast carcinoma cells with gelatinase A. These results suggest that galectin-3 may be a substrate for gelatinases and that its degradation may play a role in modulating the biological activities of galectin-3.


Socio-economic impacts of working horses in urban and peri-urban areas of the Cape Flats, South Africa.
In the Cape Flats townships, Cape Town, South Africa, there are more than 250 working cart horses. They serve the community with scrap metal and garden refuse removal, human transport and the selling of goods. A questionnaire was undertaken to understand the social and economic impacts of a horse and cart in the Cape Flats on individual owners and/or drivers, their households and the community. A mixture of classical quantitative questions combined with qualitative participatory technique questions were used. A total of 100 participants took part in the questionnaire, who cart with 163 horses between them. The majority (89%) identified the cart horse income as their primary income source. Apart from the participants, an additional 716 people were supported financially through this income, where the mean number of children supported was 2.9 (95% confidence interval [CI]: ±0.42) per interviewed participant. Scrap metal transportation was the most common work and the season (winter) had a negative impact on their ability to work. The spatial extent to which a cart horses work was determined and related back to the impact on the horse and participant of the survey. It was demonstrated that the cart horse industry had an impact not only on those who worked in the industry, but also on the surrounding residents, either through their work or through supporting others with their income. This study revealed that the concepts of 'One Health' and 'Health in Social-Ecological Systems', in action as horse and human health within the Cape Flats are closely intertwined.


Effects of arterial-portal glucose difference on gluconeogenesis from lactate in the isolated bivascular-perfused rat liver.
The effects of arterial-portal glucose difference on the gluconeogenesis from lactate were studied using the bivascular perfused liver isolated from the fasted rat. The liver was cyclically perfused at flow rates of 14 ml/min from the portal vein and of 7 ml/min from the hepatic artery with the total volume of 35 ml of perfusion medium containing 2 mM glucose, 3 mM lactate and (U-14C)-lactate for 20 min. Glucose was infused at a rate of 27.75 mumol/min into the arterial cannula (A-experiment) or the portal cannula (P-experiment), making each arterial-portal glucose gradient of +3.96 mM (arterial glucose > portal glucose) and -1.98 mM (arterial glucose < portal glucose) throughout the experiment. Perfusate lactate concentration was lower in A-experiment than in P-experiment (1.40 +/- 0.25 vs 1.93 +/- 0.23 mM at 20 min, mean +/- SD, p < 0.05). Incorporation of radioactivity from (U-14C)-lactate into glucose carbon 1 in perfusate was 5.7 +/- 0.8% of total radioactivity per 20 min in A-experiment vs 2.8 +/- 0.6%/20 min in P-experiment (p < 0.01). These results suggest that the arterial-portal glucose difference is an important factor to regulate the hepatic gluconeogenesis.


COVID-Net CT-2: Enhanced Deep Neural Networks for Detection of COVID-19 From Chest CT Images Through Bigger, More Diverse Learning.
The COVID-19 pandemic continues to rage on, with multiple waves causing substantial harm to health and economies around the world. Motivated by the use of computed tomography (CT) imaging at clinical institutes around the world as an effective complementary screening method to RT-PCR testing, we introduced COVID-Net CT, a deep neural network tailored for detection of COVID-19 cases from chest CT images, along with a large curated benchmark dataset comprising 1,489 patient cases as part of the open-source COVID-Net initiative. However, one potential limiting factor is restricted data quantity and diversity given the single nation patient cohort used in the study. To address this limitation, in this study we introduce enhanced deep neural networks for COVID-19 detection from chest CT images which are trained using a large, diverse, multinational patient cohort. We accomplish this through the introduction of two new CT benchmark datasets, the largest of which comprises a multinational cohort of 4,501 patients from at least 16 countries. To the best of our knowledge, this represents the largest, most diverse multinational cohort for COVID-19 CT images in open-access form. Additionally, we introduce a novel lightweight neural network architecture called COVID-Net CT S, which is significantly smaller and faster than the previously introduced COVID-Net CT architecture. We leverage explainability to investigate the decision-making behavior of the trained models and ensure that decisions are based on relevant indicators, with the results for select cases reviewed and reported on by two board-certified radiologists with over 10 and 30 years of experience, respectively. The best-performing deep neural network in this study achieved accuracy, COVID-19 sensitivity, positive predictive value, specificity, and negative predictive value of 99.0%/99.1%/98.0%/99.4%/99.7%, respectively. Moreover, explainability-driven performance validation shows consistency with radiologist interpretation by leveraging correct, clinically relevant critical factors. The results are promising and suggest the strong potential of deep neural networks as an effective tool for computer-aided COVID-19 assessment. While not a production-ready solution, we hope the open-source, open-access release of COVID-Net CT-2 and the associated benchmark datasets will continue to enable researchers, clinicians, and citizen data scientists alike to build upon them.


Interocular symmetry in macular choroidal thickness in children.
Objective. To report interocular differences in choroidal thickness in children using spectral domain optical coherence tomography (SD-OCT) and correlate findings with biometric data. Methods. This observational cross-sectional study included 91 (182 eyes) healthy children aged 6 to 17 years with no ocular abnormality except refractive error. After a comprehensive eye exam and axial length measurement, high definition macular scans were performed using SD-OCT. Two observers manually measured the choroidal thickness at the foveal center and at 1500 µm nasally, temporally, inferiorly, and superiorly. Interocular differences were computed; correlations with age, gender, refractive error, and axial length were performed. Results. Mean age was 10.40 ± 3.17 years; mean axial length and refractive error values were similar between fellow eyes. There was excellent correlation between the two observers' measurements. No significant interocular differences were observed at any location. There was only a trend for right eyes to have higher values in all thicknesses, except the superior thickness. Most of the choroidal thickness measurements correlated positively with spherical equivalent but not with axial length, age, or gender. Conclusion. Choroidal thickness measurements in children as performed using SD-OCT revealed a high level of interobserver agreement and consistent interocular symmetry. Values correlated positively with spherical equivalent refraction.


Spatially variant autofocus for circular synthetic aperture sonar.
Circular synthetic aperture sonar (CSAS) is a method for improving the resolution and target detection capabilities of a synthetic aperture sonar system. CSAS data are difficult to focus because of their large aperture sizes and elevation sensitivity. This difficulty has sometimes been addressed by using transponders or distributing isotropic scatterers in the field of view of the system; however, this comes at the cost of reduced practicality. As an alternative, map-drift based multipoint autofocus ("multilateration") was proposed by Cantalloube and Nahum [IEEE Trans. Geosci. Remote Sens. 49, 3730-37 (2011)] for autofocusing analogous circular synthetic aperture radar data. Multilateration also solves the problem of aberration spatial variance by providing a three-dimensional navigation correction. In circular synthetic aperture focusing problems, though, correcting aberrations is a joint navigation and elevation estimation problem, and the present work extends the multilateration approach to simultaneously solve both a navigation solution and coordinate corrections for the multilateration control patches. Additionally, methods for addressing the stability and behavior of the inverse problem are addressed, and an adaptive weighting scheme for reducing the influence of outliers is presented. The field results demonstrate near optimal point-spread functions on distributions of natural isotropic scatterers and robustness in regions with bathymetric variability.