Jet dispensing of multi-layered films for the co-delivery of three antihypertensive agents.
Three-layer thin films comprising of two polymers as substrate (ethyl cellulose and, copovidone K28) and three antihypertensive agents (hydrochlorothiazide, amiloride HCl, and carvedilol) were printed using jet dispensing technology. Two film formulations with different ethyl cellulose to copovidone K28 ratio (i.e., 90/10 and 50/50 w/w) were prepared using a three-course dispensing. The films were characterized regarding surface morphology, solid-state properties, polymer-drug interactions, drug distribution in each layer, and in vitro drug release. All the components of the films were found to be in the amorphous state apart from hydrochlorothiazide which retained its crystallinity. FT-IR spectroscopy revealed hydrogen bond interactions between carvedilol and copovidone K28. Combinations of ethyl cellulose and copovidone K28 provide suitable polymeric film substrates with the ability to modify drug release. Particularly, decreased ethyl cellulose to copovidone K28 weight ratio was found to suppress the crystallization of hydrochlorothiazide and to increase the release rate of the dispensed drugs. Jet dispensing was found to be a rapid technology for the preparation of multi-layered films that can be used as personalized formulations for the delivery of combinations of drugs.


Survival after dispatcher-assisted cardiopulmonary resuscitation in out-of-hospital cardiac arrest.
Strategies to increase provision of bystander CPR include mass education of laypersons. Additionally, programs directed at emergency dispatchers to provide CPR instructions during emergency calls to untrained bystanders have emerged. The aim of this study was to evaluate the association between dispatcher-assisted CPR (DA- CPR) and 30-day survival compared with no CPR or spontaneously initiated CPR by lay bystanders prior to emergency medical services in out of hospital cardiac arrest (OHCA). Nationwide observational cohort study including all consecutive lay bystander witnessed OHCAs reported to the Swedish Register for Cardiopulmonary Resuscitation in 2010-2017. Exposure was categorized as: no CPR (NO-CPR), DA-CPR and spontaneously initiated CPR (SP-CPR) prior to EMS arrival. Propensity-score matched cohorts were used for comparison between groups. Main Outcome was 30-day survival. A total of 15 471 patients were included and distributed as follows: NO-CPR 6440 (41.6%), DA-CPR 4793 (31.0%) and SP-CPR 4238 (27.4%). Survival rates to 30 days were 7.1%, 13.0% and 18.3%, respectively. In propensity-score matched analysis (DA-CPR as reference), NO-CPR was associated with lower survival (conditional OR 0.61, 95% CI 0.52-0.72) and SP-CPR was associated with higher survival (conditional OR 1.21 (95% CI 1.05-1.39). DA-CPR was associated with a higher survival compared with NO-CPR. However, DA-CPR was associated with a lower survival compared with SP-CPR. These results reinforce the vital role of DA-CPR, although continuous efforts to disseminate CPR training must be considered a top priority if survival after out of hospital cardiac arrest is to continue to increase.


Correction: Tissue expression of antigens of ABH blood groups in species of New World Monkeys (Aotus infulatus, Callithrix jacchus, Sapajus apella and Saimiri sciureus).
[This corrects the article DOI: 10.1371/journal.pone.0241487.].


Isolated supravalvular aortic stenosis with left ventricular diverticulum and cleft mitral valve: Surgical repair in adulthood.
Supravalvular aortic stenosis is an uncommon but well characterized congenital narrowing of the ascending aorta above the level of the coronary arteries. It can be a familial disorder, can occur sporadically, or can be associated with Williams syndrome. We are reporting a very rare presentation of supravalvular aortic stenosis with associated left ventricular diverticulum and cleft mitral valve. Repair consisted of resection of the ascending aorta, patch augmentation of the aortic root, and mitral valve repair. Follow-up echocardiography demonstrated normal mitral and aortic valve function and a postoperative three-dimensional computed tomographic scan showed a normal shape of the reconstructed ascending aorta.


Developmental expression of protein C and protein S in the rat.
In order to better understand the expression of the Protein C/Protein S anticoagulant system, we have isolated and characterized cDNAs coding for rat Protein C and Protein S. These cDNAs were used in Northern analysis to determine tissue-specificity and developmental expression patterns for mRNAs coding for Proteins C and S. In rats, Protein C mRNA is expressed almost exclusively in liver with a small amount of expression in kidney, diaphragm, stomach, intestine, uterus and placenta. Protein C mRNA was not expressed in brain, heart, lung, spleen, small intestine, large intestine, ovary, or urinary bladder. In liver, Protein C mRNA is expressed at very low levels at prenatal day 18 and these levels increased to maximal levels by postnatal day 13. The size of the mRNA coding for rat Protein C is approximately 1.9 kb. Rat Protein S mRNA was expressed in all tissues examined: brain, heart, lung, diaphragm, liver, spleen, stomach, small intestine, large intestine, kidney, adrenal ovary, uterus, placenta, and urinary bladder. Interestingly, there were 4 bands hybridizing with the rat protein S cDNA that were evident in many of the tissues examined, corresponding to mRNA sizes of approximately 3.5, 2.6, 1.8, and 0.3 kb. There was a difference in tissue-specificity of each mRNA. The 1.8 kb band is generally the most prominent autoradiographic band in any tissue. From these results, it is evident that the expression of Protein C mRNA is similar to that of other vitamin K-dependent proteins. The expression of Protein S mRNA, however, is surprisingly complex and may include alternative splicing of mRNA to generate the various sizes evident on Northern analysis.


Treating co-occurring first-episode psychosis and borderline personality: a pilot randomized controlled trial.
First-episode psychosis and borderline personality disorder are severe mental disorders that have their onset in youth. Their co-occurrence is clinically well recognized, is associated with significant risks and is complex to treat. Yet, there is no published specific intervention for this problem. This study reports a pilot randomized controlled trial comparing combined specialist first-episode treatment plus specialist early intervention for borderline personality, entitled Helping Young People Early, with specialist first-episode treatment alone. We aimed to evaluate the safety and feasibility of adding early intervention for borderline personality. The study investigated the safety of specialist first-episode treatment plus specialist early intervention for borderline personality in relation to deterioration in psychosis, aggression, self-harm and suicidality, and feasibility in relation to the completion of therapy phases. Sixteen patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria for first-episode psychosis and borderline personality (four or more DSM-IV criteria) were randomized either to specialist first-episode treatment alone or specialist first-episode treatment plus specialist early intervention for borderline personality and were followed up at the end of treatment and 6 months later. The results showed that it was feasible to recruit and assess a high risk and complex group of patients who were agreeable to study participation. Specialist first-episode treatment plus specialist early intervention for borderline personality was an acceptable and safe treatment. A larger-scale randomized controlled trial of early intervention for borderline personality for young first-episode psychosis patients with co-occurring full or subsyndromal borderline personality is warranted.


An intron-encoded protein is active in a gene conversion process that spreads an intron into a mitochondrial gene.
The intron of the mitochondrial 21S rRNA gene of Saccharomyces cerevisiae possesses a long internal reading frame (ORF) that is conserved in various yeast species. In crosses between intron-plus and intron-minus variants, this intron determines a specific gene conversion phenomenon, which results in the integration of the intron sequence within all previously intron-minus copies of the gene. We show, from a frameshift mutant within the intron ORF and from the need of mitochondrial protein synthesis, that ORF encodes a protein active in the gene conversion that spreads the intron within populations of interbreeding strains. This new intron function is reminiscent of the "transposase" encoded by mobile genetic elements and is discussed in relation to other intron functions.


A method of purifying sheep sIg+ lymphocytes as a tool for class II MHC antigen analysis.
A method is described for the purification of sheep lymphocytes carrying class II MHC antigens. After incubation of purified blood lymphocytes on anti-IgM-coated petri dishes, the adherent fraction contained 95% sIg-positive cells determined by immunofluorescence. When tested with cross-reacting anti-class II (bovine and human) monoclonal antibodies, more than 95% of these cells were positive either by immunofluorescence or cytotoxicity. This technique will permit studies of the polymorphism of sheep class II antigens.


Preparation and characterization of polyhydroxyalkanoates macroporous scaffold through enzyme-mediated modifications.
Polyhydroxyalkanoates (PHAs) are hydrophobic biodegradable thermoplastics that have received considerable attention in biomedical applications due to their biocompatibility, mechanical properties, and biodegradability. In this study, the degradation rate was regulated by optimizing the interaction of parameters that influence the enzymatic degradation of P(3HB) film using response surface methodology (RSM). The RSM model was experimentally validated yielding a maximum 21 % weight loss, which represents onefold increment in percentage weight loss in comparison with the conventional method. By using the optimized condition, the enzymatic degradation by an extracellular PHA depolymerase from Acidovorax sp. DP5 was studied at 37 °C and pH 9.0 on different types of PHA films with various monomer compositions. Surface modification of scaffold was employed using enzymatic technique to create highly porous scaffold with a large surface to volume ratio, which makes them attractive as potential tissue scaffold in biomedical field. Scanning electron microscopy revealed that the surface of salt-leached films was more porous compared with the solvent-cast films, and hence, increased the degradation rate of salt-leached films. Apparently, enzymatic degradation behaviors of PHA films were determined by several factors such as monomer composition, crystallinity, molecular weight, porosity, and roughness of the surface. The hydrophilicity and water uptake of degraded salt-leached film of P(3HB-co-70%4HB) were enhanced by incorporating chitosan or alginate. Salt-leached technique followed by partial enzymatic degradation would enhance the cell attachment and suitable for biomedical as a scaffold.


Study on the effect of heat treatment on amethyst color and the cause of coloration.
The effect of heat treatment on amethyst color was studied from a new perspective of chromaticity of gemstones and the cause of amethyst coloration was discussed based on the results of X-ray diffraction, ultraviolet-visible spectroscopy. The results show that the amethyst color has no significant relationship with cell parameters but the crystallinity index decreases as temperature rises. The absorption band at 545 nm in the UV-visible spectrum can be related to a charge-transfer transition of Fe3+ and O2-, which has a significant relationship with amethyst lightness and chroma. The color at different temperatures can be divided into three stages: The amethyst stage with temperature below 420 °C, the prasiolite stage with temperature between 420 and 440 °C where the color center is the most unstable, the citrine stage with temperature above 440 °C. The color change degree of heated amethyst is related to its initial color. When the initial color is darker, the color difference of heated amethyst is larger, and the easier it is to change the color after heat treatment. A more appropriate heating temperature to obtain citrine by heating amethyst is about 560 °C.


Structure-function analyses and molecular modeling of caffeic acid-O-methyltransferase and caffeoyl-CoA-O-methyltransferase: revisiting the basis of alternate methylation pathways during monolignol biosynthesis.
Ten protein sequences, each of caffeic acid-O-methyltransferase (COMT) and caffeoyl-coenzyme A-O-methyltransferase (CCoAOMT), catalyzing methylation of precursors of monolignol from selected dicots and monocots have been analyzed and compared on the basis of their amino acid sequence, motifs/domains, three-dimensional (3D) structure, and substrate binding. The isoelectric points of all the COMT and CCoAOMT sequences analyzed were found to vary in the pH range of 5 to 6. Molecular weight analyses suggested CCoAOMT to be smaller monomeric proteins (27-29 kDa) as compared with those of COMTs (39-40 kDa), which were dimeric. On the basis of phylogenetic analysis, COMT and CCoAOMT were clustered into two major groups, each of which could be further divided into two subgroups of monocots and dicots. Modeling and superimposition of COMT and CCoAOMT sequences of alfalfa (Medicago sativa) revealed that both were quite different at the 3D levels, although they had similarity in the core region. Molecular docking of 16 putative substrates (intermediates of monolignol biosynthesis pathway) revealed that both enzymes interact with all 16 substrates in a similar manner, with thiol esters being the most potent and binding of these putative substrates to CCoAOMT being more efficient.


Altered nucleosome spacing associated with Down syndrome.
Micrococcal nuclease digestions of human leukocytes were analyzed using gel electrophoresis. The relative size (or average number of nucleotides) of nucleosomes was determined. The mean nucleosome size of the normal 46 chromosome karyotype is 185 +/- 2 bp. There was no significant variation in nucleosome size within the normal population due to age, sex, or race. The mean nucleosome size of the Down syndrome samples is 173 +/- 3 bp. These two groups have separate normal distribution curves which do not overlap and are significantly different at P < 0.1%.


The ALT upper reference interval debate: Blame it on the alcohol.
In 2017, the American College of Gastroenterology (ACG) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition published clinical guidelines recommending the use of alanine aminotransferase (ALT) upper reference limits (URL) of 33, 25, 26, and 22 U/l for men, women, boys, and girls, respectively. This was opposed by laboratory experts who advocated for the use of higher URL of 59, 41, 33, and 24 U/l instead. We suspected that the variable inclusion of individuals who consumed alcohol to be a major contributing source of URL variability and debate. Outpatient ALT data (n = 7379) were collected from unique individuals ≥13 y with BMIs of ≥19 and ≤25. A total of 222 (3%) were excluded due to suspected liver disease. Patients were split into a pediatric group (age 13-17 y), an alcohol-restricted adult group (age 18-20 y), and adults with access to alcohol by decade (i.e., age 21-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 y). All ALT values were measured on Roche Cobas 8000 with pyridoxal phosphate and traceable to the IFCC-reference measurement procedure. We derived URL similar to CALIPER for our pediatric population, but closer to ACG-proposed URL in our alcohol-restricted adult group. The URL increased significantly in men and women for all other age groups. The discrepancy in ALT URL in clinical laboratories may be attributable in part due to the variable inclusion of individuals who recently consumed alcohol in local population derivation studies.


Parent Perceptions of Child Weight Status in Mexican-Origin Immigrant Families: An Investigation of Acculturation, Stress, and Coping Factors.
Parents often underestimate their child's weight status, particularly when the child is overweight or obese. This study examined acculturation, stress, coping, and involuntary responses to stress and their relation to estimation of child's weight status among Mexican-origin immigrant families. Eighty-six families provided data on child's height and weight, caregiver's perception of their child's weight status, and caregiver's responses to acculturation, stress, and coping scales. Parents underestimated their child's weight status, particularly when the child was overweight or obese. Although acculturation and stress were not associated with accuracy, parents' responses to stress were linked to parent perceptions. Parents who reported more frequent use of involuntary engagement (e.g., rumination, physiological arousal) were more accurate. Future research, as well as healthcare providers, should consider how parents manage and respond to stress in order to fully understand the factors that explain weight perceptions among Mexican-origin immigrant parents.


Regression of lymphosarcoma by treatment with acetylsalicylic acid in rats.
Increased synthesis of prostaglandins (PGs) may be an important promoting factor in the development of lymphosarcoma. Thus, inhibition of PG synthesis may represent a logical way of controlling the growth of lymphosarcomatous cells. In order to verify this hypothesis, two groups of rats with lymphosarcoma have been used: the test-group received acetyl salicylic acid (54 mg/animal/day) and the control-group received the same quantity of physiological saline solution. After 4 days of treatment, the lymph nodes stopped growing in the test-group. Microscopic and electron microscopic examinations of lymph node sections were carried out after 11 days of treatment. These showed for the test-group the disappearance of the characteristics of malignancy.


Associations between primary motor cortex organization, motor control and sensory tests during the clinical course of low back pain. A protocol for a cross-sectional and longitudinal case-control study.
In people with low back pain (LBP), altered motor control has been related to reorganization of the primary motor cortex (M1). Sensory impairments in LBP have also been suggested to be associated with reorganization of M1. Little is known about reorganization of M1 over time in people with LBP, and whether it relates to changes in motor control and sensory impairments and recovery. This study aims to investigate 1) differences in organization of M1 of trunk muscles between people with and without LBP, and whether the organization of M1 relates to motor control and sensory impairments (cross-sectional component) and 2) reorganization of M1 over time and its relation with changes in motor control and sensory impairments and experienced recovery (longitudinal component). A case-control study with a cross-sectional and five-week longitudinal component is conducted in participants with LBP (N = 25) and participants without LBP (N = 25). Participants with LBP received usual care physiotherapy. Various tests were administered at baseline and follow-up. Following an anatomical MRI, organization of M1 (Center of Gravity and Area of the cortical representation of trunk muscles) was determined using transcranial magnetic stimulation. Quantitative sensory testing, a spiral-tracking motor control test, graphesthesia, two-point discrimination threshold and various self-reported questionnaires were also assessed. Multivariate multilevel analysis will be used for statistical analysis. We will address the gaps in knowledge about the association between reorganization of M1 and motor control and sensory tests during the clinical course of LBP. This study is registered at DOI 10.17605/OSF.IO/5C8ZG.


Reproducibility of measurements of potential doubling time of tumour cells in the multicentre National Cancer Institute protocol T92-0045.
We compared the flow cytometric measurement and analysis of the potential doubling time (Tpot) between three centres involved in the National Cancer Institute (NCI) protocol T92-0045. The primary purpose was to understand and minimize the variation within the measurement. A total of 102 specimens were selected at random from patients entered into the trial. Samples were prepared, stained, run and analysed in each centre and a single set of data analysed by all three centres. Analysis of the disc data set revealed that the measurement of labelling index (LI) was robust and reproducible. The estimation of duration of S-phase (T(S)) was subject to errors of profile interpretation, particularly DNA ploidy status, and analysis. The LI dominated the variation in Tpot such that the level of final agreement, after removal of outliers and ploidy agreement, reached correlation coefficients of 0.9. The sample data showed poor agreement within each of the components of the measurement. There was some improvement when ploidy was in agreement, but correlation coefficients failed to exceed values of 0.5 for Tpot. The data suggest that observer-associated analysis of T(S) and tissue processing and tumour heterogeneity were the major causes of variability in the Tpot measurement. The first two aspects can be standardized and minimized, but heterogeneity will remain a problem with biopsy techniques.


Intrauterine Growth Restriction and Risk of Diverse Forms of Kidney Disease during the First 50 Years of Life.
Previous studies have shown that individuals with low birth weight (LBW) or small for gestational age (SGA) have higher risk of kidney failure. This study investigates birth-related exposures and risk of CKD and other kidney diagnoses. The Medical Birth Registry of Norway has registered extensive medical data on all births in Norway since 1967. The Norwegian Patient Registry has registered diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008. Data from these registries were linked, and risk of CKD and other groups of kidney disease were analyzed using logistic regression statistics. LBW (below the tenth percentile), SGA (birth weight below the tenth percentile for gestational age), and preterm birth (<37 weeks) were analyzed as exposures. A total of 2,663,010 individuals were included. After a mean follow-up of 26 years (maximum 50 years), 4495 had been diagnosed with CKD and 12,818 had been diagnosed with other groups of kidney disease. LBW was associated with an odds ratio (OR) for CKD of 1.72 (95% confidence interval [95% CI], 1.60 to 1.90), SGA with an OR of 1.79 (95% CI, 1.65 to 1.94), and preterm birth with an OR of 1.48 (95% CI, 1.33 to 1.66). Analyses using diagnosis of CKD at stages 3-5 as end point showed similar results. Results were similar for men and women. We analyzed adjusted ORs for other groups of kidney disease and found that LBW was associated with an adjusted OR of 1.44 (95% CI, 1.33 to 1.56) for acute kidney disease, 1.24 (95% CI, 1.14 to 1.36) for GN, 1.35 (95% CI, 1.17 to 1.56) for cystic kidney disease, and 1.15 (95% CI, 1.06 to 1.25) for kidney disease resulting from kidney or urinary tract malformations. LBW, SGA, and preterm birth are associated with higher risk of CKD in the first 50 years of life. Risk of other groups of kidney disease was less pronounced. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_17_CJN04080320.mp3.


Sacubitril/Valsartan Shows Improvement of the Cardio-Ankle Vascular Index in a Hypertensive Patient.
A 72-year-old man presented to our clinic with hypertension. Arterial stiffness evaluated by cardio ankle vascular index (CAVI) was markedly increased at 13.5. We treated him using 80 mg/day of valsartan for three months. CAVI was decreased from 13.5 to 13.0. However, his BP fluctuations were still high. We changed the treatment to angiotensin receptor-neprilysin inhibitor (ARNI) with increasing doses up to 400 mg. Independent of the change in blood pressure at the time of measurement, CAVI improved with ARNI dose. Hypertension treatment with an awareness of the cardio-vascular interaction might be a possibility prevents future heart failure development effectively.


Reactivation of hepatitis B virus in a patient with adult T-cell leukemia-lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab.
The introduction of molecularly targeted drugs has increased the risk of reactivation of hepatitis B virus (HBV), which is a potentially fatal complication following anticancer chemotherapy even in patients who have previously resolved their HBV infection. CC chemokine receptor 4 (CCR4) has been identified as a novel molecular target in antibody therapy for patients with adult T-cell leukemia-lymphoma (ATL) and peripheral T-cell lymphoma, and the humanized anti-CCR4 monoclonal antibody mogamulizumab has been developed. We reported HBV reactivation of an ATL patient with previously resolved HBV infection after mogamulizumab treatment in a dose-finding study for this antibody. Our retrospective analysis using preserved samples also revealed the detailed kinetics of HBV DNA levels before and just after HBV reactivation.


Intramolecular vinyl quinone Diels-Alder reactions: asymmetric entry to the cordiachrome core and synthesis of (-)-isoglaziovianol.
A short and asymmetric entry to the core structure of the cordiachromes has been developed, allowing access to (-)-isoglaziovianol in seven steps. Our synthesis includes a Trost asymmetric allylic alkylation and a reaction cascade triggered by a vinyl quinone Diels-Alder reaction and followed by intramolecular nucleophilic interception.


Niban gene is commonly expressed in the renal tumors: a new candidate marker for renal carcinogenesis.
Functional inactivation of tuberous sclerosis 2 gene (Tsc2) leads to renal carcinogenesis in the hereditary renal carcinoma Eker rat models. Recent studies revealed a role of tuberin, a TSC2 product, in suppressing the p70 S6 kinase (p70S6K) activity via inhibition of mammalian target of rapamycin (mTOR). Phosphorylated S6 protein, a substrate of p70S6K, was expressed in the early lesions in Eker rats, and this expression was suppressed by the treatment of rapamycin, an inhibitor of mTOR. We previously isolated the novel gene Niban expressed in renal carcinogenesis of Eker rats. In this study, we demonstrated that the expression of Niban was detected from early preneoplastic lesions in Eker rats. Interestingly, in contrast to the phosphorylated S6 protein, the expression of Niban was unchanged and early lesions still remained even after treatment with rapamycin. These results might suggest the existence of another pathway independent of mTOR-S6K pathway in Tsc2 mutant renal carcinogenesis. In addition, Niban was also expressed in other renal carcinoma models, including Tsc1 and Tsc2 knockout mice, and various types of human renal cell carcinomas. Thus, Niban was commonly expressed in renal carcinomas and might be a new marker for renal carcinogenesis.


Formation of superoxide in the reaction of photolytically altered nifedipine--a nitroso compound--with unsaturated membrane lipids.
Nifedipine, which is unstable at light, is photolytically converted to the corresponding 4-[2'-nitrosophenyl]-pyridine (NTP). We reported earlier that NTP react with unsaturated lipids in a pseudo Diels-Alder reaction, thus forming stable nitroxide radicals. In this paper we report that superoxide is being generated in the latter reaction. Superoxide formation was evidenced by SOD-inhibitable cytochrome c reduction in the reaction of NTP with egg phosphatidylcholine at molar ratio 1:1, and 1:3. In this reaction an ESR-observable nitroxide radical was formed. Maximum nitroxide formation was observed after 90 min; the addition of SOD (93 units/ml) increased the concentration of nitroxide. This effect of SOD was reversed by catalase, indicating involvement of hydrogen peroxide in this effect. The nitroxide radical formation appears to be metal-independent, since neither iron salts, nor an iron chelator, desferal, influenced the nitroxide formation. Although production of superoxide in our system was only observed at high concentrations of NTP and of unsaturated lipids, this reaction may be of potential cytotoxic significance due to redox cycling of the nitroxide/hydroxylamine couple in cellular systems.


Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors.
The phase I GATTO study (NCT03360734) explored the feasibility, tolerability and preliminary activity of combining gatipotuzumab, a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin 1 (TA-MUC1) and an anti-epidermal growth factor receptor (anti-EGFR) antibody in refractory solid tumors. Initially the study enrolled primary phase (PP) patients with EGFR-positive metastatic solid tumors, for whom no standard treatment was available. Patients received gatipotuzumab administered at 1400 mg every 2 weeks, 6 weeks after the start of the glyco-optimized anti-EGFR antibody tomuzotuximab at 1200 mg every 2 weeks. As this regimen was proven safe, enrollment continued in an expansion phase (EP) of patients with refractory metastatic colorectal cancer, non-small-cell lung cancer, head and neck cancer and breast cancer. Tomuzotuximab and gatipotuzumab were given at the same doses and gatipotuzumab treatment started 1 week after the first dose of the anti-EGFR antibody. Additionally, investigators could use a commercial anti-EGFR antibody in place of tomuzotuximab. A total of 52 patients were enrolled, 20 in the PP and 32 in the EP. The combined treatment was well tolerated and no dose-limiting toxicity was observed in the whole study, nor related serious adverse event or death. Preliminary activity of the combination was observed, with one and four RECIST partial responses in the PP and EP, all in colorectal cancer patients. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 (sTA-MUC1) in serum. In the EP, patients with baseline sTA-MUC1 levels above the median appeared to have improved progression-free survival and overall survival. Combination of a TA-MUC1-targeting antibody and an EGFR-targeting antibody is safe and feasible. Interesting antitumor activity was observed in heavily pretreated patients. Future studies should test this combination together with chemotherapy and explore the potential of sTA-MUC1 as a companion biomarker for further development of the combination.


[Cellular strategies in bone tissue engineering: a review].
The objective of bone tissue engineering is to reconstruct bone stock using matrix structures, osteoinductor factors and osteogenic cells. Different types of natural or synthetic biomaterials are available or under development. The objective of recent work is to optimize matrix materials, particularly with better cell adhesion to the surface and better osteoconduction. For osteoinductors, most research is currently focused on bone morphogenetic protein (BMP) and angiogenic factors such as vascular endothelial growth factor (VEGF). Concerning the nature of the cells to be implanted, there is a clear dissociation between fundamental and clinical studies. Many clinical studies have demonstrated the strong osteogenic potential of fresh harvested total bone marrow. There has been nevertheless little fundamental work on the use of total bone marrow as a source of cells for bone tissue engineering. Most of the fundamental work has been focused on the use of mesenchymatous stromal cells selected from bone marrow and cultivated ex vivo. This approach which was first developed more than fifteen years ago has shown that the adjunction of these cells can improve the osteoformative capacity of bone substitutes. This strategy has, however, had almost no clinical impact to date since only two studies involving four patients have been reported. The purpose of this article is to review current research concerning bone tissue engineering using total bone marrow and mesenchymatous stromal cells.


Nail Salon a Potential Source of a Rare Mycobacterium Fortuitum Infection In Proximal Tibia Megaprosthesis? A Case Report.
Mycobacterium Fortuitum (M. Fortuitum) is a type of opportunistic pathogen commonly found in water/soil and belongs to the nontuberculosis mycobacteria (NTM) family. Prosthetic joint infection due to M. Fortuitum is extremely rare. We present a case of a 21-year-old female with an infection following a radical resection of the proximal tibia due to a parosteal osteosarcoma.


Genomic imprinting of the IGF2R/AIR locus is conserved between bovines and mice.
Genomic imprinting is an epigenetic phenomenon that leads to genes monoallelically expressed in a parent-of-origin-specific manner and plays an important role in the embryonic development and postnatal growth of mammals. Imprinted genes usually occur in clusters in a chromosomal region and are regulated by a cis-acting imprinting control region that involves differential DNA methylation modification. Igf2r, Slc22a2 and Slc22a3 are three maternally expressed genes on mouse chromosome 17. The paternally expressed long noncoding RNA (lncRNA) Air and the nonimprinted gene Slc22a1 are also located in the imprinted region. Comparative characterization of imprinted clusters between species is useful for us to understand the biological significance and epigenetic regulating mechanism of genomic imprinting. The aim of this study was to analyze the allelic expression pattern of AIR and SLC22A1-3 genes in cattle and to determine the role of DNA methylation in regulating gene expression. Allelic expression analysis was performed in bovine adult tissues and term placenta using an SNP-based approach. We found that IGF2R, AIR and SLC22A3 were monoallelically expressed in all detected bovine somatic tissues, including heart, liver, spleen, lung, kidney, muscle, fat and brain. In bovine placenta, IGF2R and SLC22A3 are maternally expressed; however, the AIR gene is paternally expressed. Tissue-specific monoallelic expression of SLC22A2 is detected in bovines, with monoallelic expression in the spleen and brain but biallelic expression in kidney tissues. SLC22A1 is only detected in bovine liver and kidney tissues and is biallelicly expressed, which is consistent with the imprint expression in mice. To determine the possible role of DNA methylation in regulating the monoallelic/imprinted expression of bovine IGF2R, AIR, SLC22A2, and SLC22A3 genes, we analyzed the DNA methylation status of CpG islands in the first exon of SLC22A2, the promoter region of SLC22A3 and region 2 in the second intron of the IGF2R gene by bisulfite sequencing. Two differentially methylated regions (DMRs) were detected in the first exon of bovine SLC22A3 and the common regions of IGF2R and AIR. This suggests that DNA methylation is involved in the regulation of monoallelic/imprinted expression of IGF2R, AIR and SLC22A3 genes in cattle.


Effects of inattention and hyperactivity/impulsivity symptoms on development of nicotine dependence from mid adolescence to young adulthood.
The relationship of Attention-Deficit/Hyperactivity Disorder (ADHD) and smoking is well documented. However, it is unclear whether ADHD symptoms relate to nicotine dependence (ND) symptoms from adolescence to young adulthood. We sought to assess the relationship of ADHD Hyperactivity-Impulsivity (H/I) and Inattention (I) symptoms with ND symptoms in a community sample from adolescence to young adulthood (ages 18-21). Participants were adolescents (n = 672) smoking at least one whole cigarette in their lifetime. Participants are members of a prospective cohort study (ages 14-22) evaluating the bio-behavioral predictors of smoking. Data were analyzed with a two-piece latent growth curve model. ADHD-I symptoms were associated with ND symptoms acceleration in adolescence, but slowing acceleration in young adulthood, whereas ADHD-H/I symptoms were associated with ND symptoms acceleration in young adulthood. The results suggest the relationship of ADHD and ND symptoms may differ by symptom type, and the developmental period assessed.


Leptospira interrogans serovars Bratislava and Muenchen animal infections: Implications for epidemiology and control.
Strains of Leptospira interrogans belonging to two very closely related serovars - Bratislava and Muenchen - have been associated with disease in domestic animals, in particular pigs, but also in horses and dogs. Similar strains have also been recovered from various wildlife species. Their epidemiology is poorly understood. Two hundred and forty seven such isolates, from UK domestic animal and wildlife species, were examined by restriction endonuclease analysis in an attempt to elucidate their epidemiology. A representative sub-sample of 65 of these isolates was further examined by multiple-locus variable-number tandem repeat analysis and 22 by secY sequencing. Ten restriction pattern types were identified. The majority of isolates fell into one of three restriction endonuclease analysis pattern types designated B2a, B2b and M2a. B2a was ubiquitous and was isolated from 10 species and represented the majority of the horse and all dog isolates. B2b was very different, being isolated only from pigs, indicating that this type was maintained by pigs. The pattern M2a was reported for the majority of isolates from pigs but also was common in small rodents isolates. Five restriction pattern types were found only in wildlife suggesting that they are unlikely to pose a disease threat to domestic animals. Multiple-locus variable-number tandem repeat analysis identified six clusters. The REA types B2a and B2b were all found in one MLVA cluster while the majority of the M2a strains examined occurred in another cluster. The secY sequencing detected only one sequence type, clustered with other serovars of Leptospira interrogans.


[Results of treatment following corrective surgery of Whitehead anus].
For the corrective surgery of a Whitehead anus an uncomplicated operative treatment was developed, which up to now has been performed on 34 patients. The operative technique and the late results obtained are presented.


Primary Disease, Sex, and Racial Differences in Health-Related Quality of Life in Adolescents and Young Adults with Heart Failure.
Health-related quality of life (HRQOL) is an important clinical and research trial endpoint in adult heart failure and has been shown to predict mortality and hospitalizations in adult heart failure populations. HRQOL has not been adequately studied in the growing pediatric and young adult heart failure population. This study described HRQOL in adolescents and young adults (AYAs) with heart failure and examined primary disease, sex, race, and other correlates of HRQOL in this sample. Participants in this cross-sectional, single-center study included adolescent and young adults with heart failure and a parent/guardian. Patients and their parent/proxies completed the PedsQL, a well-established measure of HRQOL in pediatric chronic illness populations. HRQOL is impaired in AYAs with heart failure resulting from dilated, hypertrophic, or other cardiomyopathy, congenital heart disease, or post-transplant with rejection/complications. Patients identifying as white endorsed poorer total HRQOL than non-white patients (p = 0.002). Subscale analysis revealed significant correlations between female sex (p = 0.01) and white race (p = 0.01) with poorer self-reported physical functioning. Family income was unrelated to HRQOL. Functional status was strongly associated with total (p = 0.0003) and physical HRQOL (p < 0.0001). Sociodemographic and disease-specific risk and resilience factors specific to HRQOL in AYAs with heart failure include primary cardiac disease, race, sex, and functional status. Building upon extensive work in adult heart failure, utilization, and study of HRQOL as a clinical and research trial outcome is necessary in pediatric heart failure. Developing targeted interventions for those at greatest risk of impaired HRQOL is an important next step.


An Artificial Nerve Capable of UV-Perception, NIR-Vis Switchable Plasticity Modulation, and Motion State Monitoring.
The first flexible organic-heterojunction neuromorphic transistor (OHNT) that senses broadband light, including near-ultraviolet (NUV), visible (vis), and near-infrared (NIR), and processes multiplexed-neurotransmission signals is demonstrated. For UV perception, electrical energy consumption down to 536 aJ per synaptic event is demonstrated, at least one order of magnitude lower than current UV-sensitive synaptic devices. For NIR- and vis-perception, switchable plasticity by alternating light sources is yielded for recognition and memory. The device emulates multiplexed neurochemical transition of different neurotransmitters such as dopamine and noradrenaline to form short-term and long-term responses. These facilitate the first realization of human-integrated motion state monitoring and processing using a synaptic hardware, which is then used for real-time heart monitoring of human movement. Motion state analysis with the 96% accuracy is then achieved by artificial neural network. This work provides important support to future biomedical electronics and neural prostheses.


Care Coordination and Transition Management: A New Course to Prepare Prelicensure Students.
There is a need for RNs to be skilled at coordinating care and improving transitions within and across a wide variety of clinical settings and in diverse populations. A care coordination and transition management (CCTM) course was developed to address this growing need. The course was designed to promote enhanced clinical reasoning as well as synthesis and application of CCTM concepts while focusing on the patient and family perspectives. Learning activities incorporated individual writing assignments, discussion board assignments, and a group project. Students demonstrated the application of CCTM concepts in individual and group assignments and used prior and current clinical experiences to connect theory to practice. This course helped preli-censure students learn and apply CCTM concepts. Learning activities within the CCTM course could be adapted to be effective in all forms of undergraduate programs as well as graduate nursing programs. [J Nurs Educ. 2023;62(8):471-474.].


On the photoionization spectrum of propyne: a fully ab initio simulation of the low-energy spectrum including the Jahn-Teller effect and the spin-orbit interaction.
The low energy photoionization spectrum of propyne (CH3-CCH), which reveals the vibronic structure of the propyne cation, is simulated using vibronic coupling theory. The spin-orbit interaction is included using an intensity borrowing approach, enabling determination of the (X̃(2)E1/2,3/2, v = 0) splitting and the relative photoionization intensity of these closely spaced levels. The results are compared with recent experimental studies and misstatements are corrected.


Pulmonary alterations in Behcet's disease.
This study aims to demonstrate pulmonary alterations (PA) in patients with Behcet's disease by using CT. CTs of 50 patients with Behcet's disease and 20 others in a control group have been evaluated retrospectively for PA (septal, reticular, nodular, atelectatic opacities). Eight out of 50 patients (16%) with Behcet's disease showed PA. Three out of 20 (15%) in the control group showed PA. No differences were observed between Behcet's disease patients and the control group regarding pulmonary alterations (p=0.917). No differences were observed in the disease duration, ages and sex in either group in those with and without PA. Pulmonary alterations can be seen in patients with Behcet's disease, but these alterations are not significant.


Molecular cloning and characterization of seven class III peroxidases induced by overexpression of the agrobacterial rolB gene in Rubia cordifolia transgenic callus cultures.
Here, seven new class III peroxidase genes of Rubia cordifolia L., RcPrx01-RcPrx07, were isolated and characterized. Expression of the Prx genes was studied in R. cordifolia aerial organs as well as in cells transformed with the rolB and rolC genes of Agrobacterium rhizogenes and cells transformed with the wild-type A. rhizogenes A4 strain. In rolC- and rolB-transformed cells, the rol genes were expressed under the control of the 35S promoter, whereas in A. rhizogenes A4-transformed cells the rol genes were expressed under the control of their native promoters. All studied peroxidase genes were greatly upregulated in rolB-overexpressing cells. In contrast, overexpression of the rolC gene and expression of the rol genes under the control of their native promoters had little effect on the abundance of peroxidase transcripts. In accordance with this observation, peroxidase activity was substantially increased in rolB cells and was slightly affected in other transformed cells. Our results indicate that rolB strictly affects the regulation of a set of seven R. cordifolia class III peroxidases.


What makes a competent clinical teacher?
Clinical teaching competency is a professional necessity ensuring that clinicians' knowledge, skills and attitudes are effectively transmitted from experts to novices. The aim of this paper is to consider how clinical skills are transmitted from a historical and reflective perspective and to link these ideas with student and teacher perceptions of competence in clinical teaching. The reflections are informed by a Delphi process and professional development survey designed to capture students' and clinicians' ideas about the attributes of a competent clinical teacher. In addition, the survey process obtained information on the importance and 'teachability' of these characteristics. Four key characteristics of the competent teacher emerged from the Delphi process: clinically competent, efficient organizer, group communicator and person-centred. In a subsequent survey, students were found to be more optimistic about the 'teachability' of these characteristics than clinicians and scored the attribute of person-centredness higher than clinicians. Clinicians, on the other hand, ascribed higher levels of importance to clinical competency, efficient organization and group communication than students. The Delphi process created a non-threatening system for gathering student and clinician expectations of teachers and created a foundation for developing methods for evaluating clinical competency. This provided insights into differences between teachers' and students' expectations, their importance, and professional development.


Lifetime increased cancer risk in mice following exposure to clinical proton beam-generated neutrons.
To evaluate the life span and risk of cancer following whole-body exposure of mice to neutrons generated by a passively scattered clinical spread-out Bragg peak (SOBP) proton beam. Three hundred young adult female FVB/N mice, 152 test and 148 control, were entered into the experiment. Mice were placed in an annular cassette around a cylindrical phantom, which was positioned lateral to the mid-SOBP of a 165-MeV, clinical proton beam. The average distance from the edge of the mid-SOBP to the conscious active mice was 21.5 cm. The phantom was irradiated with once-daily fractions of 25 Gy, 4 days per week, for 6 weeks. The age at death and cause of death (ie, cancer and type vs noncancer causes) were assessed over the life span of the mice. Exposure of mice to a dose of 600 Gy of proton beam-generated neutrons, reduced the median life span of the mice by 4.2% (Kaplan-Meier cumulative survival, P=.053). The relative risk of death from cancer in neutron exposed versus control mice was 1.40 for cancer of all types (P=.0006) and 1.22 for solid cancers (P=.09). For a typical 60 Gy dose of clinical protons, the observed 22% increased risk of solid cancer would be expected to decrease by a factor of 10. Exposure of mice to neutrons generated by a proton dose that exceeds a typical course of radiation therapy by a factor of 10, resulted in a statistically significant increase in the background incidence of leukemia and a marginally significant increase in solid cancer. The results indicate that the risk of out-of-field second solid cancers from SOBP proton-generated neutrons and typical treatment schedules, is 6 to 10 times less than is suggested by current neutron risk estimates.


Impact of tourists on emergency department in a high-tourism alpin area: An observational study.
The exponential growth of tourism worldwide could have consequences for healthcare services in tourist locations. The impact of the tourist population on access to emergency departments (EDs) is currently unknown. To describe the characteristics of tourist access in an ED of an alpine tourist area in a period prior to the COVID-19 pandemic. All patients evaluated at the ED of the Merano Hospital from January 1, 2017, to December 31, 2019, were considered and divided into two study groups: locals and tourists. Analyses were conducted to assess the impact of tourists in terms of weighted ED admissions and differences in admission characteristics. Finally, for tourist patients only, an analysis of severity according to their type of healthcare system of provenance was performed. A total of 208,875 ED presentations were considered, of which 90.7% (189,406) were by local patients and 9.3% (19,469) were by tourists. The median ED admission rate was 1.65 admissions per 1000 overnight stays for locals versus 0.90 admissions per 1000 overnight stays for tourists. The time series analysis revealed a greater seasonal variation in accesses by tourists than by resident patients. A higher proportion of accesses with a severe code was found among tourist patients, while the local population exhibited a higher proportion of patients with a non-urgent code. In the tourist population, patients from a country with a free-market healthcare system had a higher number of ED presentations for severe conditions or that required hospitalisation than tourists from countries with Bismarck or Beveridge healthcare systems. The tourist population can have an important impact on EDs in high-impact tourist areas. The seasonality of the tourist population indicates the need for health policies that focus on educating the tourist population on the correct use of the ED.


Toward the antibody-catalyzed chemiluminescence. Design and synthesis of hapten.
Hapten 4 was synthesized to generate catalytic antibodies triggering chemiluminescence by catalyzing the decomposition of the 1,2-dioxetane 3. The hapten 4 was so designed as to elicit a negatively charged functional group in the antibody combining site to catalyze the beta-elimination of the protecting group in 3 as well as to lock the protecting group into an energetically favorable anti-periplanar conformation.


Identification of PP2A as a novel interactor and regulator of TRIP-Br1.
TRIP-Br proteins are a novel family of transcriptional coregulators involved in E2F-mediated cell cycle progression. Three of the four mammalian members of TRIP-Br family, including TRIP-Br1, are known oncogenes. We now report the identification of the Balpha regulatory subunit of serine/threonine protein phosphatase 2A (PP2A) as a novel TRIP-Br1 interactor, based on an affinity binding assay coupled with mass spectrometry. A GST-TRIP-Br1 fusion protein associates with catalytically active PP2A-ABalphaC holoenzyme in vitro. Coimmunoprecipitation confirms this association in vivo. Immunofluorescence staining with a monoclonal antibody against TRIP-Br1 reveals that endogenous TRIP-Br1 and PP2A-Balpha colocalize mainly in the cytoplasm. Consistently, immunoprecipitation followed by immunodetection with anti-phosphoserine antibody suggest that TRIP-Br1 exists in a serine-phosphorylated form. Inhibition of PP2A activity by okadaic acid or transcriptional silencing of the PP2A catalytic subunit by small interfering RNA results in downregulation of total TRIP-Br1 protein levels but upregulation of serine-phosphorylated TRIP-Br1. Overexpression of PP2A catalytic subunit increases TRIP-Br1 protein levels and TRIP-Br1 co-activated E2F1/DP1 transcription. Our data support a model in which association between PP2A-ABalphaC holoenzyme and TRIP-Br1 in vivo in mammalian cells represents a novel mechanism for regulating the level of TRIP-Br1 protooncoprotein.


Wettability and in-vitro study of titanium surface profiling prepared by electrolytic plasma processing.
Electrolytic plasma processing (EPP) was used to create hydrophilic surface profiles on titanium. The wettability, surface morphology characteristics and chemical composition of the treated samples were studied as a function of EPP processing parameters. The EPP profiled surfaces comprised of a characteristic "hills and valleys" morphology because of continuous surface melting and freezing cycles. A bimodal surface profile was produced with 2-3 μm height hills and valleys with nano-roughness (≤200 nm). The produced profile resulted in a significant contact angle decrease (from 38.7° to 5.4°). Ratios of actual surface area to projection area (r) and fraction of solid surface remaining dry (φ) were obtained from profilometry. The surface characteristics and large r values produced by EPP were able to induce hemi-wicking. Hence, EPP produced superhydrophilic surfaces on Ti. The bioactivity of EPP treated Ti was evaluated using cell free and MC3T3 cells in-vitro studies. The treated Ti surface significantly increased the bioactivity and formed stoichiometric hydroxyapatite after immersion in a bone cell culture medium for 21 days. Cells' attachment and proliferation studies indicated that EPP treated surface significantly enhances the cells' adhesion and growth after 24 and 48 h compared to the untreated surface. The results show that Ti surface profiling by EPP constitutes a promising method to potentially improve bone implant bonding.


Stimulation of prostaglandin E2 (PGE2) production by arachidonic acid, oestrogen and parathyroid hormone in MG-63 and MC3T3-E1 osteoblast-like cells.
Polyunsaturated fatty acids (PUFAs) as well as oestrogen (E2) and parathyroid hormone (PTH) affect bone cells. The aim of the study was to determine whether arachidonic acid (AA), E2, and PTH increase prostaglandin E(2) (PGE(2)) synthesis in MG-63 and MC3T3-E1 osteoblastic cells and the level of mediation by COX-1 and COX-2. PGE(2) levels were determined in the conditioned culture media of MG-63 and MC3T3-E1 osteoblasts after exposure to AA, PTH and E2. Cells were pre-incubated in some experiments with the unselective COX inhibitor indomethacin or the COX-2 specific blocker NS-398. Indirect immunofluorescence was performed on MG-63 cells to detect the presence and location of the two enzymes involved. AA increased PGE(2) secretion in both cell lines; production by MC3T3-E1 cells, however, was significantly higher than that of MG-63 cells. This could be due to autoamplification via the EP(1) subtype of PGE receptors in mouse MC3T3-E1 osteoblasts. Both COX-1 and COX-2 affected the regulation of PGE(2) synthesis in MG-63 cells. E2 had no effect on PGE(2) secretion in both cell lines, while PTH caused a slight increase in PGE(2) synthesis in the MG-63 cell line.


Usefulness of cefovecin disk-diffusion test for predicting mecA gene-containing strains of Staphylococcus pseudintermedius and clinical efficacy of cefovecin in dogs with superficial pyoderma.
Cefovecin has been widely used to treat skin infections in dogs. The relationship of the cefovecin disk-diffusion test results to the presence of the mecA gene and the clinical efficacy of cefovecin have not been fully evaluated. To determine the usefulness of an in vitro cefovecin disk-diffusion test in predicting the presence of the mecA gene in Staphylococcus pseudintermedius, as well as the in vivo efficacy of cefovecin therapy in dogs with superficial pyoderma. Twenty-six S. pseudintermedius strains isolated from 22 dogs with pyoderma were used. In vitro disk-diffusion test results of cefovecin were compared with agar-dilution test results, the presence of the mecA gene, and the improvement in clinical scores of dogs with superficial pyoderma at 14 days post treatment. There was a significant linear correlation (r = -0.83) between the diameter of the obvious zone of inhibition by disk diffusion and the minimal inhibitory concentration for cefovecin (P < 0.0001). Receiver operating characteristic analysis revealed that zone diameters between 25 and 27 mm exhibited better sensitivity (92.9%) and specificity (100.0%) for detection of strains carrying the mecA gene. The mean improvement in clinical scores in dogs carrying cefovecin-resistant strains was significantly lower than in dogs carrying cefovecin-susceptible strains (P < 0.01). The cefovecin disk-diffusion test with a cut-off value estimated in this study was valuable for predicting mecA gene carriage in S. pseudintermedius, as well as the in vivo efficacy of cefovecin therapy in dogs with superficial pyoderma caused by S. pseudintermedius.


The relationship between cesarean section rate in term singleton pregnancies, maternal weight, and weight gain during pregnancy.
Pregravid maternal weight and appropriate weight gain during pregnancy might be associated with increased cesarean section rate. We used data from the Slovenian National Perinatal Information System to select singleton pregnancies born at ≥38 weeks, during the period between 2003 and 2012. We calculated the frequencies of urgent and elective cesarean sections (UCS and ECS, respectively) in mothers who gained less than, more than, and as recommended by the Institute of Medicine (IOM) according to their pregravid body mass index (BMI). The analysis included 170,121 women who delivered singletons ≥38 weeks. A total of 24,327 (14.3%) women underwent cesarean section: 14,692 (8.6%) UCS and 9635 (5.7%) ECS. The frequency of cesareans, both UCS and ECS, increases as BMI increases irrespective of weight gain pattern. The frequency of urgent cesareans in all women increases and that of elective cesareans among obese women decreases as the level of weight gain increases from undergainers to overgainers. The combination of pregravid BMI and weight gain pattern is an important determinant of cesarean section rates at term.


Longitudinal risk of maternal hospitalization for mental illness following preterm birth.
Preterm birth may affect maternal mental health, yet most studies focus on postpartum mental disorders only. We explored the relationship between preterm delivery and the long-term risk of maternal hospitalization for mental illness after pregnancy. We performed a longitudinal cohort study of 1,381,300 women who delivered between 1989 and 2021 in Quebec, Canada, and had no prior history of mental illness. The exposure was preterm birth, including extreme (<28 weeks), very (28-31 weeks), and moderate to late (32-36 weeks). The outcome was subsequent maternal hospitalization for depression, bipolar, psychotic, stress and anxiety, personality disorders, and self-harm up to 32 years later. We used adjusted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between preterm birth and mental illness hospitalization. Compared with term, women who delivered preterm had a higher rate of mental illness hospitalization (3.81 vs. 3.01 per 1000 person-years). Preterm birth was associated with any mental illness (HR 1.38, 95% CI 1.35-1.41), including depression (HR 1.37, 95% CI 1.32-1.41), psychotic disorders (HR 1.35, 95% CI 1.25-1.44), and stress and anxiety disorders (HR 1.42, 95% CI 1.38-1.46). Delivery at any preterm gestational age was associated with the risk of mental hospitalization, but risks were greatest around 34 weeks of gestation. Preterm birth was strongly associated with mental illness hospitalization within 2 years of pregnancy, although associations persisted throughout follow-up. Women who deliver preterm may be at risk of mental disorders in the short and long term.


Blocking GARP-mediated activation of TGF-β1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice.
Transmembrane protein GARP binds latent TGF-β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immune-mediated regressions of murine tumors, indicating that Treg-derived TGF-β1 inhibits anti-tumor immunity. TGF-β1 exerts a vast array of effects on immune responses. For example, it favors differentiation of TH17 cells and B-cell switch to IgA production, two important processes for mucosal immunity. Here, we sought to determine whether treatment with anti-GARP:TGF-β1 mAbs would perturb immune responses to intestinal bacterial infection. We observed no aggravation of intestinal disease, no systemic dissemination, and no alteration of innate or adaptative immune responses upon oral gavage of C. rodentium in highly susceptible Il22r-/- mice treated with anti-GARP:TGF-β1 mAbs. To examine the effects of GARP:TGF-β1 blockade on Ig production, we compared B cell- and TH cell- responses to OVA or CTB protein immunization in mice carrying deletions of Garp in Tregs, B cells, or platelets. No alteration of adaptive immune responses to protein immunization was observed in the absence of GARP on any of these cells. Altogether, we show that antibody-mediated blockade of GARP:TGF-β1 or genetic deletion of Garp in Tregs, B cells or platelets, do not alter innate or adaptive immune responses to intestinal bacterial infection or protein immunization in mice. Anti-GARP:TGF-β1 mAbs, currently tested for cancer immunotherapy, may thus restore anti-tumor immunity without severely impairing other immune defenses. PRéCIS: Immunotherapy with GARP:TGF-β1 mAbs may restore anti-tumor immunity without impairing immune or inflammatory responses required to maintain homeostasis or host defense against infection, notably at mucosal barriers.


Interaction of amino acids with silver(I) ions.
The reactivity of silver(I) ions towards twenty amino acids has been studied in aqueous unbuffered solutions using an ion-selective electrode as a highly sensitive monitor. Contrary to general belief, silver ions are not completely specific for cysteine, but also react with lysine, arginine, methionine and, to a minor extent, cystine. Nevertheless the interaction with all of these species except cysteine is too weak to affect significantly the determination of thiol in proteins by the customary argentometric titration method. The possible origin of errors arising in such titrations is discussed.


Oral microbiota may affect osteoradionecrosis following radiotherapy for head and neck cancer.
Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer (HNC). However, its etiology and pathogenesis have not been completely elucidated. Recent studies suggest the involvement of the oral microbiota in the development of ORN. The aim of this study was to assess the correlation between oral microbiota and the extent of bone resorption in ORN patients. Thirty patients who received high-dose radiotherapy for HNC were enrolled. Tissue specimens were collected from the unaffected and affected sides. The diversity, species differences and marker species of the oral microbial community were determined by 16 S rRNA sequencing and bioinformatics analysis. The ORN group had greater microbial abundance and species diversity. The relative abundance of f_Prevotellaceaeand, f_Fusobacteriaceae, f_Porphyromonadaceae, f_Actinomycetaceae, f_Staphylococcaceae, g_Prevotella, g_Staphylococcus, s_Endodontalis and s_Intermedia were particular;y increased in ORN, suggesting a potential association between the oral microbiota and ORN. Furthermore, g_Prevotella, g_Streptococcus, s_parvula and s_mucilaginosa were identified as potential diagnostic and prognostic biomarkers of ORN. Association network analysis also suggested an overall imbalance in species diversity and ecological diversity in the oral microbiota of ORN patients. In addition, pathway analysis indicated that the dominant microbiota in ORN may disrupt bone regeneration by regulating specific metabolic pathways that increase osteoclastic activity. Radiation-induced ORN is associated with significant changes in the oral microbiota, and the latter may play a potential role in the etiopathology of post-radiation ORN. The exact mechanisms through which the oral microbiota influence osteogenesis and osteoclastogenesis remain to be elucidated.


Adaptation to hypoxic stress involves amino acid metabolism: A case in sea cucumber.
Low dissolved oxygen (LO) in seawater negatively affects aquatic animals and has received considerable attention. However, there is still much to learn about how echinoderms, which are keystone species in benthic ecosystems, respond to hypoxic stress. Here, we detected differentially expressed metabolites (DEMs) in sea cucumber (Apositchopus japonicus) between normoxic conditions (NC group) and hypoxic conditions (2 mg L-1) for 3 and 7 days (i.e., LO3 and LO7 groups). A total of 243, 298, and 178 DEMs were found in the NC versus LO3, NC vs. LO7, and LO3 vs. LO7 comparisons, respectively. Amino acids were the most abundant class of DEMs, and "biosynthesis of amino acids" was an enriched pathway in all three comparisons. Most of the enriched metabolite sets under hypoxic stress were related to metabolism. As the duration of the hypoxia treatment extended, the metabolism-related process maintained an upward trend, and signaling pathways maintained a downward trend. Thus, metabolism-related processes are affected in hypoxia-stressed sea cucumber, and amino acid metabolism is the most important process for adaption to hypoxic conditions, potentially function in osmotic regulation and energy regulation. Our results shed light on the adaptative strategies of sea cucumber to challenging environmental conditions.


Renal Dysfunction is the Strongest Prognostic Factor After Carotid Artery Stenting According to Real-World Data.
Through the progression of devices, the adaptation of carotid artery stenting (CAS) has been expanded according to the non-inferiority of CAS for carotid endarterectomy reported by several randomized control trials. To maintain favorable outcomes, identifying prognostic factors is essential for optimizing treatment indications and periprocedural management. This study focused on the prognostic factors of CAS using real-world data. This retrospective multicenter cohort study aimed to identify the prognostic factors after CAS using real-world data from the stroke registry of Yokohama (STrOke Registry of Yokohama; STORY) from January 1, 2018 to May 31, 2021. Patient characteristics, procedural factors, complications, and prognoses were collected using medical records. Data from 107 patients were enrolled in this study after excluding those with insufficient data (2 cases). The mean participant age was 74.9±8.2 years, and 66 patients (61.7%) were symptomatic. Symptomatic lesions were a significant prognostic factor in the overall analysis (p=0.003). A multivariate analysis showed that the estimated glomerular filtration rate (eGFR) (odds ratio: 1.11, p=0.003) and staged CAS (odds ratio: 38.9, p=0.04) were independent prognostic factors. The odds ratio and relative risk of mRS deterioration when eGFR was under 49 mL/min/1.73 m2 compared with when eGFR was above 49 mL/min/1.73 m2 were 5.2 and 3.74, respectively. In this real-world multicenter study, we established independent prognostic factors for CAS using high totality data. For patients with symptomatic lesions and low eGFR (≤49 mL/min/1.73 m2), indication for treatment should be considered strictly.


Surface-based haemangioma of the tibia: a case report.
We present in this paper a case of surface-based haemangioma of the tibia in a 34-year-old patient which had been misdiagnosed as periostitis. X-ray examination demonstrated a periosteal reaction, confirmed by a MRI showing a soft tissue mass adjacent to bone. We performed an incisional biopsy and made a diagnosis of haemangioma only after examining the histological results. An angiographic study was performed in order to have embolisation of the vessels, but this was not possible because of the excessive number and calibre of afferent arteries. No further symptoms arose after biopsy and therefore an en bloc or radical excision was not performed. Indications for making a correct diagnosis and performing a suitable treatment are presented below.


Annular phase-only mask for high focal depth.
We present an annularly distributed phase-only mask that generates an axial irradiance distribution identical to the point spread function of the Dowski-Cathey lens [Appl. Opt. 34, 1859 (1995)]. This apodizer has an ambiguity function with a bow-tie effect, and consequently its axial modulation transfer function varies slowly with spherical aberration.


Pest status, molecular evolution, and epigenetic factors derived from the genome assembly of Frankliniella fusca, a thysanopteran phytovirus vector.
The tobacco thrips (Frankliniella fusca Hinds; family Thripidae; order Thysanoptera) is an important pest that can transmit viruses such as the tomato spotted wilt orthotospovirus to numerous economically important agricultural row crops and vegetables. The structural and functional genomics within the order Thysanoptera has only begun to be explored. Within the > 7000 known thysanopteran species, the melon thrips (Thrips palmi Karny) and the western flower thrips (Frankliniella occidentalis Pergrande) are the only two thysanopteran species with assembled genomes. A genome of F. fusca was assembled by long-read sequencing of DNA from an inbred line. The final assembly size was 370 Mb with a single copy ortholog completeness of ~ 99% with respect to Insecta. The annotated genome of F. fusca was compared with the genome of its congener, F. occidentalis. Results revealed many instances of lineage-specific differences in gene content. Analyses of sequence divergence between the two Frankliniella species' genomes revealed substitution patterns consistent with positive selection in ~ 5% of the protein-coding genes with 1:1 orthologs. Further, gene content related to its pest status, such as xenobiotic detoxification and response to an ambisense-tripartite RNA virus (orthotospovirus) infection was compared with F. occidentalis. Several F. fusca genes related to virus infection possessed signatures of positive selection. Estimation of CpG depletion, a mutational consequence of DNA methylation, revealed that F. fusca genes that were downregulated and alternatively spliced in response to virus infection were preferentially targeted by DNA methylation. As in many other insects, DNA methylation was enriched in exons in Frankliniella, but gene copies with homology to DNA methyltransferase 3 were numerous and fragmented. This phenomenon seems to be relatively unique to thrips among other insect groups. The F. fusca genome assembly provides an important resource for comparative genomic analyses of thysanopterans. This genomic foundation allows for insights into molecular evolution, gene regulation, and loci important to agricultural pest status.


Predicting radiotherapy-induced xerostomia in head and neck cancer patients using day-to-day kinetics of radiomics features.
The images acquired during radiotherapy for image-guidance purposes could be used to monitor patient-specific response to irradiation and improve treatment personalisation. We investigated whether the kinetics of radiomics features from daily mega-voltage CT image-guidance scans (MVCT) improve prediction of moderate-to-severe xerostomia compared to dose/volume parameters in radiotherapy of head-and-neck cancer (HNC). All included HNC patients (N = 117) received 30 or more fractions of radiotherapy with daily MVCTs. Radiomics features were calculated on the contra-lateral parotid glands of daily MVCTs. Their variations over time after each complete week of treatment were used to predict moderate-to-severe xerostomia (CTCAEv4.03 grade ≥ 2) at 6, 12 and 24 months post-radiotherapy. After dimensionality reduction, backward/forward selection was used to generate combinations of predictors.Three types of logistic regression model were generated for each follow-up time: 1) a pre-treatment reference model using dose/volume parameters, 2) a combination of dose/volume and radiomics-based predictors, and 3) radiomics-based predictors. The models were internally validated by cross-validation and bootstrapping and their performance evaluated using Area Under the Curve (AUC) on separate training and testing sets. Moderate-to-severe xerostomia was reported by 46 %, 33 % and 26 % of the patients at 6, 12 and 24 months respectively. The selected models using radiomics-based features extracted at or before mid-treatment outperformed the dose-based models with an AUCtrain/AUCtest of 0.70/0.69, 0.76/0.74, 0.86/0.86 at 6, 12 and 24 months, respectively. Our results suggest that radiomics features calculated on MVCTs from the first half of the radiotherapy course improve prediction of moderate-to-severe xerostomia in HNC patients compared to a dose-based pre-treatment model.


Aminoquinolines afford resistance to cerebral malaria in susceptible mice.
Malaria treatment is impeded by increasing resistance to conventional antimalarial drugs. Here we explored the activity of ten novel benzothiophene, thiophene and benzene aminoquinolines. In vitro testing was performed by the lactate dehydrogenase assay in chloroquine (CQ)-sensitive Plasmodium falciparum strain 3D7 and CQ-resistant (CQR) P. falciparum strain Dd2. In vivo activity was evaluated by a modified Thompson test using C57BL/6 mice infected with Plasmodium berghei ANKA strain. Nine of the ten compounds had a lower 50% inhibitory concentration (IC50) than CQ against the CQR strain Dd2. Five of these compounds that were available for in vivo evaluation were shown to be non-toxic. All five compounds administered at a dose of 160mg/kg/day for 3 days prolonged the survival of treated compared with untreated mice. Untreated control mice died by Day 7 with a mean parasitaemia of 15%. Among treated mice, a dichotomous outcome was observed, with a two-third majority of treated mice dying by Day 17 with a low mean parasitaemia of 5%, whilst one-third survived longer with a mean hyperparasitaemia of 70%; specifically, five of these mice survived a mean of 25 days, whilst two even survived past Day 31. The significant antimalarial potential of this aminoquinoline series is illustrated by its excellent in vitro activity against the CQRP. falciparum strain and significant in vivo activity. Interestingly, compounds ClAQ7, ClAQ9 and ClAQ11 were able to confer resistance to cerebral malaria and afford a switch to hyperparasitaemia to mice prone to the neurological syndrome.


[Direct medical costs of breast cancer treatment at the Joliot Curie Institute of the Aristide Le Dantec Hospital in Dakar, Senegal].
in 2020, the incidence of breast cancer was 2261419 cases worldwide, 1186598 cases in Africa and 817 cases in Senegal. However, direct medical costs of cancer treatment are not known in Senegal. For a better resource allocation, it is important to estimate costs. The purpose of this study is to analyze direct medical costs of breast cancer treatment at the Joliot Curie Institute in Dakar. we conducted a retrospective study of patients diagnosed with breast cancer between January and December 2017 at the Joliot Curie Institute. A questionnaire survey and semi-structured interviews were conducted among patients and their relatives to reconstruct direct medical costs. average direct medical costs of breast cancer treatment at the Joliot Curie Institute were $33 713.45 with a minimum of $1 495.15 and a maximum of $10 662.97 over an average period of 31 months. These costs include chemotherapy (29%); diagnosis (15%) and surgery (15%). Costs of radiotherapy and prescription medicines accounted for 13% for each procedure. Medical costs were related to educational level (p=0.05) and stage of disease (p=0.03). direct medical costs of breast cancer treatment are very high in Senegal. Direct medical costs of maximum treatment is $10 662.97 and of minimum treatment is $495.15, reflecting an average cost of $3 713.45.


Synergistic Inhibition of R5 HIV-1 by the Fusion Protein (FLSC) IgG1 Fc and Maraviroc in Primary Cells: Implications for Prevention and Treatment.
Antiretroviral (ARV) drugs targeting retroviral enzymes have been extensively employed to treat HIV-1 infection. Drawbacks of this approach include cost, toxicity, and the eventual emergence of resistant strains that threaten prophylactic and/or therapeutic efficacy. Accordingly, efforts to develop next-generation ARV approaches are warranted, particularly if they can offer a higher threshold of resistance. We have previously shown that FLSC, a fusion protein containing gp120(BAL) and the D1 and D2 domains of human CD4, specifically binds CCR5, an important cellular co-receptor, and inhibits the entry of R5 HIV isolates. (FLSC) IgG1, a fusion of FLSC and the hinge-C(H)2-C(H)3 region of human IgG1, has an increased antiviral activity, likely due to the resultant bivalency. In this study, we show CCR5 reduction upon (FLSC) IgG1 treatment both by standard flow cytometry and visualized using a novel nanoparticle method. A β-lactamase virus-cell fusion assay was used to quantify (FLSC) IgG1 inhibition of HIV-1 entry into both cell lines and primary cells. Synergistic anti-viral activities of (FLSC) IgG1 and MVC in primary cells were evaluated by measuring supernatant p24 levels via ELISA and calculated using the MacSynergy™ II program. We previously reported that treatment with the CCR5 small molecule antagonist Maraviroc (MVC) increased the apparent exposure of the (FLSC) IgG1 binding sites on CCR5, leading us to wonder if the two compounds used in combination might synergize in their anti-viral activity. Here we show that this is indeed the case. We demonstrate that fusion protein (FLSC) IgG1, strongly synergizes with the CCR5 antagonist Maraviroc to successfully inhibit both MVC-sensitive and MVC-resistant R5 HIV-1. Observed synergy between (FLSC) IgG1 and MVC was high in both, cell lines and primary PBMCs. This has relevance for future in vivo studies. In addition, synergy occurred both with MVC-sensitive viruses and MVC-resistant viruses, partially restoring the inhibitory effect of MVC. These findings suggest that a combinatorial treatment based on these two compounds has potential merit and that future in vivo studies are warranted.


Advances in cell-penetrating poly(disulfide)s for intracellular delivery of therapeutics.
Efficient intracellular delivery is essential for most therapeutic agents; however, existing delivery vectors face a dilemma between efficiency and toxicity, and always encounter the challenge of endolysosomal trapping. The cell-penetrating poly(disulfide) (CPD) is an effective tool for intracellular delivery, as it is taken up through thiol-mediated cellular uptake, thus avoiding endolysosomal entrapment and ensuring efficient cytosolic availability. Upon cellular uptake, CPD undergoes reductive depolymerization by glutathione inside cells and has minimal cytotoxicity. This review summarizes CPD's chemical synthesis approaches, cellular uptake mechanism, and recent advances in the intracellular delivery of proteins, antibodies, nucleic acids, and other nanoparticles. Overall, CPD is a promising candidate carrier for efficient intracellular delivery.


Complicated jejunal diverticulosis - a rare but important diagnosis to consider in abdominal pain: a report of three cases.
Jejunal diverticulosis, a form of acquired false diverticula, is considered to be a rare clinical entity, which is mostly asymptomatic. But, in case of complications, jejunal diverticulosis can present as acute abdominal distress. Due to its rarity in clinical manifestation, jejunal diverticulosis may lead to a diagnostic and therapeutic delay. We report on 3 interdisciplinary cases of complicated jejunal diverticulosis by diverticulitis, diverticular bleeding, and perforation. We want to highlight the fact that complicated jejunal diverticulosis should be considered as a differential diagnosis in cases of unclear abdominal pain.


Chlamydia pneumoniae: inflammation and instability of the atherosclerotic plaque.
Coronary heart disease remains the most common cause of death in industrialized countries. Although atherosclerosis is generally asymptomatic in the early stages, progressive plaque development leads to arterial stenosis which is characterized by angina and may eventually lead to unstable angina, myocardial infarction and cardiac death. Evidence that the coagulation cascade is activated during acute coronary events has justified the use of antithrombotic agents such as aspirin, heparin and low molecular weight heparin (LMWH) in the standard management of acute coronary syndromes. The inflammatory process is also known to play a significant role in the pathogenesis of atherosclerosis, resulting in a cycle of continued inflammatory cell activation and ongoing cell recruitment. As the human leukocyte-associated antigen (HLA) system plays a key role in the regulation of the inflammatory process, the expression of HLA antigens in patients with symptomatic coronary heart disease has been investigated. These studies have demonstrated a relationship between the major histocompatibility complex (MHC) class II expression and the most severe pattern of angina refractory to conventional therapy, within the framework of a chronic infectious disease. A number of studies have documented an association between coronary heart disease and the presence of high titres of antibodies to Chlamydia pneumoniae, and this organism has been implicated in plaque instability. Such findings have stimulated interest in the role of C. pneumoniae in the pathogenesis of coronary heart disease, with a view to developing novel and effective treatment approaches. The ROXIS study showed a lower incidence of acute ischaemic events in patients with unstable angina treated with an antichlamydial antibiotic, roxithromycin.


Identification of canonical neural events during continuous gameplay of an 8-bit style video game.
Cognitive neuroscience suffers from a unique and pervasive problem of generalizability. Since neural findings are often interpreted in the context of a specific manipulation during a carefully controlled task, it is hard to transfer knowledge from one task to another. In this report we address problems of generalizability with two methodological advancements. First, we aimed to transcend status quo experimental procedures with a continuous, engaging task environment. To this end, we created a novel 8-bit style continuous space shooter video game that elicits a multitude of goal-oriented events, such as crashing into a wall or blowing up an enemy with a missile. Second, we aimed to objectively define the psychological significance of these events. To achieve this aim, we used pattern classification of EEG data to derive predictive weights from carefully controlled pre-game exemplar events (oddball target detection and gambling wins and losses) and transferred those weights to EEG activities during video game events. All major goal-oriented events (crashes into the wall, crashes into an enemy, missile hit on an enemy) had a significant between-task transfer bias towards oddball target weights in the time range of the canonical P3, indicating the presence of similar salience detection processes. Missile hits on an enemy were specifically identified as gambling wins, confirming the hypothesis that this goal-oriented event was appetitive. These findings suggest that it is possible to identify the contribution of canonical neural activities during otherwise ambiguous and uncontrolled task performance.


Identification of immune infiltration-related biomarkers in carotid atherosclerotic plaques.
Atherosclerosis is a chronic lipid-driven inflammatory response of the innate and adaptive immune systems, and it is responsible for several cardiovascular ischemic events. The present study aimed to determine immune infiltration-related biomarkers in carotid atherosclerotic plaques (CAPs). Gene expression profiles of CAPs were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the CAPs and control groups were screened by the "limma" package in R software. Immune cell infiltration between the CAPs and control groups was evaluated by the single sample gene set enrichment analysis. Key infiltrating immune cells in the CAPs group were screened by the Wilcoxon test and least absolute shrinkage and selection operator regression. The weighted gene co-expression network analysis was used to identify immune cell-related genes. Hub genes were identified by the protein-protein interaction (PPI) network. Receiver operating characteristic curve analysis was performed to assess the gene's ability to differentiate between the CAPs and control groups. Finally, we constructed a miRNA-gene-transcription factor network of hub genes by using the ENCODE database. Eleven different types of immune infiltration-related cells were identified between the CAPs and control groups. A total of 1,586 differentially expressed immunity-related genes were obtained through intersection between DEGs and immune-related genes. Twenty hub genes were screened through the PPI network. Eventually, 7 genes (BTK, LYN, PTPN11, CD163, CD4, ITGAL, and ITGB7) were identified as the hub genes of CAPs, and these genes may serve as the estimable drug targets for patients with CAPs.


Thermodynamic parameters for the protonation and the interaction of arsenate with Mg2+, Ca2+ and Sr2+: Application to natural waters.
Thermodynamic parameters for the protonation of AsO43- and for the interaction with Mg2+, Ca2+ and Sr2+ were reported, comprehensive also of their dependence on ionic strength, considering the 0.1 ≤ I ≤ 1 M range and using NaCl as background salt. The same speciation models were obtained for Mg2+, Ca2+ and Sr2+ systems, with the formation of three different species: ML, MLH and MLH2 (L = AsO43-). Mono- and di-protonated species were very weak, with formation constant values (log K) ranging from 1.45 to 3.23. In order to have a complete picture of thermodynamic properties of the systems under study and to fill the shortage of thermodynamic data on arsenate complex systems, the ligand protonation and metal complex enthalpies were also determined by calorimetric titrations, at t = 25 °C and in NaCl at I = 0.7 M (for H+-AsO43- species also at I = 0.1 M). On the light of the proposed speciation models, examples of As(V) distribution in some natural waters are reported.


Body mass index trajectories in childhood is predictive of cardiovascular risk: results from the 23-year longitudinal Georgia Stress and Heart study.
The childhood high body mass index (BMI) is associated with cardiovascular risk, but the association between childhood BMI trajectory patterns and cardiovascular risk remains unclear. The purposes of this study are to identify subgroups of individuals with similar trajectories in BMI during childhood, and to determine the relationship of childhood BMI trajectories with subclinical cardiovascular disease in young adulthood, indexed by intima-media thickness (IMT) and left ventricular mass index (LVMI). The participants were from the Georgia Stress and Heart (GSH) study. A total of 626 participants with BMI measured 3-12 times during childhood (5-18 years old) were included. By using latent class models, three trajectory groups in BMI were identified, including high increasing (HI), moderate increasing (MI) and normal group. We found that childhood trajectory of BMI was significantly associated with IMT and LVMI in young adulthood even after adjustment for BMI in young adulthood. Our results suggested that different BMI trajectory patterns exist during childhood. We for the first time reported the association between childhood BMI trajectory patterns and subclinical cardiovascular risk in young adulthood, indicating that monitoring trajectories of BMI from childhood may help to identify a high cardiovascular risk population in early life.


Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study.
Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. Clinical Trials.gov identifier: NCT02804100.


[Detection of autoimmune lipoprotein--antibody complex in human plasma and aortic wall].
An immune complex of lipoprotein-antibody was found in human blood plasma and in tissue liquid of aorta, impaired by atherosclerosis. In the majority of cases the antigen component of the immune complex was lipoprotein of very low density. After dissociation of the complex at acid pH, immunoglobulin G was isolated, which was identified by double immunodiffusion in agar gel; the immunoglobulin reacted in RBS both with autological and, in some cases, with isological lipoproteins.


Cross-linked surface Ig attaches to actin.
In lymphocytes and P3 myeloma cells, cross-linking of surface Ig by the capping and patching phenomenon has been used to demonstrate the induction of a specific association between surface Ig and cellular actin.


Dataset on performance of solar powered agricultural produce cooling storage system under tropical conditions.
Much of the post-harvest loss of agricultural produce in developing countries is due to lack of proper storage facilities. Agricultural produce such as peppers, tomatoes and fruits are highly perishable in nature; thus, maintaining the optimal air conditions inside the storage cabinet helps extending their shelf lives. The datasets contained in this paper are performance test carried out on agricultural produce cooling storage system under tropical conditions for various cooling pads (jute fibre) thickness and under no load and load conditions. The parameters recorded under these conditions include wet and dry bulb temperatures, relative humidity of the surroundings, relative humidity and temperature within the cooling chamber taken consecutively for 4 days with different pad thickness and for 5 days and 8days under no load and load conditions, respectively. Results obtained show that pad thickness of 80 mm has the highest cooling efficiency of 84.7% and temperature within the cooling chamber was found dropped to 25 °C and average relative humidity of cooling chamber increased to 82.4% as compared to 64.8% for ambient condition.


Regression of a prolactin-secreting pituitary tumor during long-term treatment with bromocriptine.
A nulliparous woman with 12 years of amenorrhea, galactorrhea, and hyperprolactinemia and radiologic evidence of a pituitary macroadenoma was treated with large doses of bromocriptine. During treatment the greatly increased prolactin levels normalized and ovulatory menstrual cycles were regained after 48 weeks of treatment. A transsphenoidal surgical exploration of the pituitary fossa was performed after 27 months of treatment. The findings at surgery suggested that regression of the pituitary adenoma had occurred during the prolonged treatment with bromocriptine. After discontinuation of the therapy, the patient continued to ovulate and subsequently conceived.


The use of fluvastatin in cardiovascular risk management.
Fluvastatin was the first synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) to be developed and is used in the management of dyslipidaemia in primary and secondary prevention of cardiovascular disease. This article reviews the properties of fluvastatin and experience accrued through its use in clinical practice and clinical trials. Relevant publications were identified through the PubMed database and product information held by the US Federal Drug Administration was also reviewed. In the authors' opinion, fluvastatin exhibits a favourable safety profile in comparison to other statins, with a low incidence of adverse effects and a reduced propensity for interactions with other drugs. However, fluvastatin is a less potent cholesterol-lowering agent than newer statins on the market and its future predominant use is likely to be in niche patient groups at risk of side effects or drug interactions with other agents.


Monitoring the biomechanical response of individual cells under compression: a new compression device.
Skeletal muscle cells are sensitive to sustained compression, which can lead to the development of pressure sores. Although it is known that this type of tissue breakdown depends on the magnitude and duration of the applied load, the exact relationship between cell deformation and damage remains unclear. To gain more insight into this process, a method has been developed, that incorporates the use of a new loading device and confocal microscopy. The loading device is able to compress individual cells, either statically or dynamically, while measuring the resulting forces. Experiments can be performed under ideal environmental conditions, comparable with those of a CO2 incubator. First compression experiments on C2C12 mouse myoblasts showed the shape changes that cells undergo during static compression by the loading device. Calculations using the three-dimensional confocal images showed no change in volume and an increase in the surface area of the cell as a result of compression. The device presented here provides a useful way to monitor the biomechanical response of skeletal muscle cells during long-term compression experiments. Therefore it will contribute to the knowledge about strain-induced cell damage, as seen in pressure sores and other mechanically induced clinical conditions.


Representation of female authors in the Canadian Journal of Anesthesia: a retrospective analysis of articles between 1954 and 2017.
Females remain under-represented in academic anesthesiology. Our objectives were to investigate gender differences over time in the first and last authors of published articles as well as corresponding citation rates in the Canadian Journal of Anesthesia (CJA). We conducted a cross-sectional, retrospective analysis of first and last authors' gender from editorials and original articles published in the CJA in a sample of one calendar year of each decade between 1954 to 2017. We analyzed the relationships between author gender, year of publication, article type, and number of citations. Out of 639 articles identified, 542 (85%) were original investigations and 97 (15%) were editorials. Where gender could be confidently identified, the majority (461/571, 81%) of first authors were male. Although there was an increase in the proportion of female first authors over time, this increase was outpaced by the overall increase in female anesthesiologists in Canada. Original articles received more citations and were more likely to have a female first author than editorial articles were. An original article with a female first author resulted in 0.34 (95% confidence interval, 0.28 to 0.39; P < 0.001) more citations per article than a male first author when adjusting for year of publication. Our study shows that, despite a slow increase over time, female authors are under-represented relative to male authors in the CJA and relative to the changing demographics of anesthesiologists in Canada. The reasons for this disparity are multifactorial and further research is needed to identify effective solutions.


[Impact of Brownian motion and magnetic fields of erythrocytes on spin echo signal of blood protons].
A reduction in blood So2 and ESR is shown to lead to the decay of a spin echo signal. This effect is explained by the impact of red blood cell magnetic field fluctuations caused by the Brownian motion. The authors propose to use the effect to monitor red blood cell agglutination.