Measurement and prediction of subjective gradations of images in presence of monochromatic aberrations.
The three objectives of this study were (i) to explore the effect of various levels of aberrations on subjective vision by scoring images, (ii) to compare subjective scores obtained with real optics and simulated images and (iii) to test the ability of image quality metrics to predict these scores. In a first experiment, 14 subjects evaluated the quality of images degraded by 0.05, 0.1, 0.2, 0.4 and 0.8μm of defocus, astigmatism, trefoil, coma, spherical aberration (SA4) and secondary spherical aberration (SA6) by putting a mark on a 5-items continuous grading scale. The desired aberration was introduced either by a deformable mirror or by displaying a simulated image. In the second experiment, 5 of the previous subjects evaluated the quality of through-focus images in presence of SA4, SA6 and combinations of SA4 and SA6. Both experiments were performed with an artificial pupil of 6mm diameter. The addition of increasing amounts of aberrations reduced the subjective grading of the targets, with SA6, SA4 and defocus being the most degrading aberrations. The correlation between the results obtained with the AO device and with simulated images gave a r(2) of 0.95. Combinations of 0.4μm of SA4 and 0.2μm of SA6 of opposite signs induced a bimodal through-focus image score curve. We were able to anticipate the subjective gradation of subject's vision thanks to image quality metrics (r(2)=0.92). Image quality score shows similar results as that obtained by objective image quality metrics, which provides a useful tool for optical designers and practitioners.


Exhaled Breath Analysis in Heart Failure.
Heart failure (HF) is a clinical condition that presents high morbidity and mortality and is one of the main reasons for hospital admissions all over the world. Although biochemical processes that occur in the body during heart failure are known, this syndrome is still associated to poor prognosis. Exhaled breath analysis has emerged as a promising noninvasive tool in different clinical conditions and, recently, it has been also tested in patients with HF. This review presents the main breath HF biomarkers, which reflect metabolic changes that occur in this complex syndrome. It also discusses the diagnostic and prognostic value of exhaled breath compounds for HF and makes a short description of the main technologies involved in this analysis. Some perspectives on the area are presented as well.


The Field Liaison Program of the American College of Surgeons.
The Liaison Fellow/Associate Program is a viable means of upgrading hospital cancer programs. In no way does it usurp administrative channels of hospital staffs but provides a mechanism of receiving and utilizing activities which have been successful in other hospitals. I urge all of you seriously to involve your hospitals in this program.


Ala analogues of the cyclolinopeptide A.
Analogues of cyclolinopeptide A, due to the replacement of each amino acid in the Pro1-Pro2-Phe3-Phe4 sequences with an L-Ala residue, were synthesized by classical method in solution. Mixed anhydride and N,N'-dicyclohexylcarbodiimide coupling methods have been used for the synthesis of both linear and cyclic peptides. The products were characterized by Rf values and uv spectra, as well as by fast atom bombardment spectroscopy. 1H-nmr studies on [Ala2] analogues are also reported. Preliminary data in CDCl3 solution, at low temperature, seems more promising.


Hard ticks and their bacterial endosymbionts (or would be pathogens).
The symbiotic microorganisms of arthropod vectors are highly significant from several points of view, partly due to their possible roles in the transmission of pathogenic causative agents by blood-sucking vectors. Although ticks are well studied because of their significance to human health, novel microbial associations remain to be described. This review summarises several endosymbiotic bacterial species in hard ticks from various parts of the world, including Coxiella-, Francisella-, Rickettsia- and Arsenophonus-like symbionts as well as Candidatus Midichloria mitochondrii and Wolbachia. New methodologies for the isolation and characterization of tick-associated bacteria will, in turn, encourage new strategies of tick control by studying their endosymbionts.


Oxygen-dependent distinct expression of hif-1α gene in aerobic and anaerobic tissues of the Amazon Oscar, Astronotus crassipinnis.
The aquatic habitats of the Amazon basin present dramatic variation of oxygen level, and, to survive such changes, many aquatic animals developed biochemical and physiological adaptations. The advanced teleost Astronotus crassipinnis (Perciformes) is a fish tolerant to hypoxia and known to endure such naturally variable environments. Hypoxia-Inducible factor-1α (hif-1α) is among the most important and studied genes related to hypoxia-tolerance, maintaining regular cellular function and controlling anaerobic metabolism. In the present work, we studied hif-1α expression and related it to changes in metabolic pathways of Astronotus crassipinnis exposed to 1, 3 and 5 h of hypoxia, followed by 3 h of recovery. The results show that A. crassipinnis depresses aerobic metabolic under hypoxia, with a decrease in glycolysis and oxidative enzyme activities, and increases its anaerobic metabolism with an increase in LDH activity coupled with a decrease in oxygen consumption, which indicates an increase in anaerobic capacity. In addition, the animal differentially regulates hif-1α gene in each tissue studied, with a positive relationship to its metabolic profile, suggesting that hif-1α might be one of the most important induction factors that regulate hypoxia tolerance in this species.


The role of calcium in the organization of fibrillin microfibrils.
The microfibrillar glycoprotein fibrillin has a multidomain structure which contains forty-three epidermal growth factor-like motifs with calcium-binding consensus sequences. We have utilized intact microfibrils isolated from human dermal fibroblast cultures to investigate the putative influence of bound calcium on microfibrillar organization and integrity. Incubation with EDTA or EGTA rapidly resulted in gross disruption of microfibril morphology. The treatment induced disorganization of the interbead domains although the regular beaded arrangement was always apparent. These changes were readily reversible on replacing calcium, indicating that the treatment had not compromised microfibrillar integrity. The data localize calcium binding EGF-like repeats to the interbead domains and indicate that lateral packing of fibrillin monomers is calcium-dependent. This arrangement suggests how mutations in epidermal growth factor-like domains of fibrillin might cause the disruption in microfibril organization and interactions which underlies the clinical symptoms of some Marfan syndrome patients.


Ripretinib: First Approval.
Ripretinib (QINLOCK™) is a novel type II tyrosine switch control inhibitor being developed by Deciphera Pharmaceuticals for the treatment of KIT proto-oncogene receptor tyrosine kinase (KIT)-driven and/or platelet derived growth factor receptor A (PDGFRA)-driven cancers, including gastrointestinal stromal tumour (GIST). Ripretinib inhibits KIT and PDGFRA kinase, including wild-type, primary and secondary mutations, as well as other kinases, such as PDGFRB, TIE2, VEGFR2 and BRAF. In May 2020, oral ripretinib received its first approval in the USA for the treatment of adult patients with advanced GIST who have received prior treatment with ≥ 3 kinase inhibitors, including imatinib. The US FDA, Health Canada and the Australian Therapeutic Goods Administration collaborated on the review of the ripretinib new drug application in this indication as part of Project Orbis; regulatory review in Australia and Canada is ongoing. Clinical development for GIST, solid tumours and systemic mastocytosis is underway in several countries worldwide. This article summarizes the milestones in the development of ripretinib leading to this first approval for the treatment of advanced GIST.


Effect of T-cell deficiency on the formation of periapical lesions in mice: histological comparison between periapical lesion formation in BALB/c and BALB/c nu/nu mice.
The role of T-cells in the development of periapical lesions was investigated immunohistochemically using 16 normal (BALB/c) mice and 16 nude (BALB/c nu/nu) mice (congenitally T-cell-deficient mice). The pulp chambers of maxillar first molars of all mice were opened, and the infiltrated immunocytes (anti-Thy1.2, -Lyt-1, -Lyt-2, -L3T4, -I-Ad, -IgG, and -IgM positive cells) were determined immunohistochemically at 2, 4, 6, and 8 wk after operation. Periapical lesions appeared at 2 wk in both mouse groups. Numerous anti-I-Ad positive-stained cells appeared at 2 wk, anti-I-Ad, -Thy1.2 (-Lyt-1, -L3T4), -IgG positive-stained cells appeared between 4 and 8 wk, and periapical lesions with bone resorption rapidly increased until 4 wk in normal mice. On the other hand in nude mice, only anti-I-Ad and -IgG positive cells were present from 4 to 6 wk, and the progress of periapical lesions with inflammatory cells stopped at 6 wk. Furthermore, numerous fibroblasts were found instead of inflammatory cells at 8 wk. These findings suggest that the progression of periapical lesions with bone resorption required helper T-cells and numerous immunoglobulin-producing cells.


Raft forming system-an upcoming approach of gastroretentive drug delivery system.
In recent era various technologies have been made in research and development of controlled release oral drug delivery system to overcome various physiological difficulties such as variation in gastric retention and emptying time. To overcome this drawback and to maximize the oral absorption of various drugs, novel drug delivery systems have been developed. Gastroretentive drug delivery system is facing many challenges which can be overcome by upcoming newly emerging approach i.e. raft forming system. The purpose of writing this review is to focus on recent development of stomach specific floating drug delivery system to circumvent the difficulties associated with formulation design. Various gastroretentive approaches that have been developed till now are also discussed. The present study provides valuable information & highlights advances in this raft forming system. This review attempts to discuss various factors like physiological factors, physicochemical factors and formulation factors to be considered in the development of the raft forming system. Different types of smart polymers used for their formulation have also been summarized. The review focuses on the mechanism, formulation and development of the raft forming system. This review also summarizes the studies to evaluate the performance and application of these systems. The study finally highlights advantages, disadvantages, and marketed preparation of the raft forming system.


Left ventricular failure due to a rare variant of congenital adrenal hyperplasia.
"Hypertensive" variant of congenital adrenal hyperplasia is rare. The authors describe an interesting case of a 6-y-old boy who presented with an acute respiratory illness and progressive breathlessness since 1 y. Genital hyperpigmentation was noticed since 2 y of age; the onset of pubarche and increasing penile size at 4 y. He was admitted in congestive cardiac failure with a blood pressure of 150/100 mm Hg. Facial acne; slight facial, pubic hair and penile enlargement were additionally noted. Chest radiograph revealed cardiomegaly. Basal ACTH and 17-OHP levels were high. A diagnosis of congenital adrenal hyperplasia (11β-hydroxylase deficiency) was made due to hypertension with virilized genitalia. Cardiac failure was controlled with fluid restriction and diuretics; he was started on prednisolone, spironolactone and nifedipine. This case is presented for its rarity where hypertension can cause complication of cardiac failure, if diagnosis is delayed despite early features of pseudoprecocious puberty.


Donkey genome and insight into the imprinting of fast karyotype evolution.
The donkey, like the horse, is a promising model for exploring karyotypic instability. We report the de novo whole-genome assemblies of the donkey and the Asiatic wild ass. Our results reflect the distinct characteristics of donkeys, including more effective energy metabolism and better immunity than horses. The donkey shows a steady demographic trajectory. We detected abundant satellite sequences in some inactive centromere regions but not in neocentromere regions, while ribosomal RNAs frequently emerged in neocentromere regions but not in the obsolete centromere regions. Expanded miRNA families and five newly discovered miRNA target genes involved in meiosis may be associated with fast karyotype evolution. APC/C, controlling sister chromatid segregation, cytokinesis, and the establishment of the G1 cell cycle phase were identified by analysis of miRNA targets and rapidly evolving genes.


Structural analysis of four strains of Paracoccus denitrificans.
Two out of eleven newly isolated strains of Paracoccus denitrificans were investigated by light and electron microscopic methods and compared with two strains of P. denitrificans already kept in culture collections. Samples were taken from different growth phases revealing short rods and nearly spherical cells in the exponential growth phase, and an increasing ratio of nearly spherical cells in the stationary growth phase. Cell division followed the binary fission mode; higher cell aggregates were not observed. Fine structural analysis revealed extracellular surface material stainable with Ruthenium red, a gram-negative cell wall and different storage material inclusions. Structural properties and variations within the four strains under investigation are discussed and compared with those of related bacteria.


Differential retinal growth appears to be the primary factor producing the ganglion cell density gradient in the rat.
We have studied the distribution of retinal ganglion cells (RGCs) that had been retrogradely labelled from bilateral injections of horseradish peroxidase into the retino-recipient nuclei of albino rats aged from the 22nd postconceptional day (22PCD-day of birth) to adulthood. During the period in which most (85%) of the naturally occurring RGC loss takes place (22-26 PCD) the distribution of RGCs remains almost uniform. Between the 26 and 32PCD (11th postnatal day), the peak RGC density decreases by only 20% while the RGC density at the superior retinal periphery decreases by 80%. In the same period a centro-peripheral RGC density difference of 4:1 becomes apparent. We have interpreted these changes to be due to a phase of rapid differential retinal growth (with more growth occurring at the retinal periphery). Thereafter the reduction in RGC density (and presumably retinal growth) is more uniform resulting by adulthood in a centro-peripheral RGC density ratio of 5:1.


Controversy clarified: an updated review of clinical psychology and tele-health.
One of the most controversial topics in the field of clinical psychology, online tele-health, or the integration of computers and the internet with therapeutic techniques, remains at the forefront of many debates. Despite potential interest, there are numerous factors that a psychologist must consider before integrating an online tele-health intervention into their own practice. This article outlines literature pertinent to the debate. The article begins with a brief history of the use of non-face-to-face interventions as well as the earliest recorded use of "tele-health" before discussing the modern benefits and risks associated with usage. Considerations for the psychologist as well as the client are detailed; incorporating ethical implications. The authors conclude that the utilization of tele-health interventions is an exponentially expanding field that should continue to be explored. Despite many well-conceived studies, a psychologist should educate themselves in all aspects of the new modes of intervention (e.g., ethical, legal, evidence-based treatments) before attempting to implement them into everyday practice. The article ends with a discussion on the acceptance among psychologists, as well as the outlook for the future.


Isolation characterization and idiotype of Lewis rat antibodies against peptide 68-88 of guinea pig myelin basic protein.
Antibodies against the 19 amino acid encephalitogenic peptide )residues 68-88) of guinea pig myelin basic protein (GPBP) were raised in Lewis (Le) rats. Anti-peptide antibodies were isolated from immune ascitic fluids by affinity chromatography using peptide 43-88-Sepharose 4B. The purified antibodies were characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and isoelectric focusing. Immunoglobulin class was determined by radioimmunoassay. Anti-idiotypic (anti-ID) antibodies were raised in a rabbit using purified anti-peptide antibodies from a single rat. The results of these experiments showed antibody heterogeneity both within an individual anti-peptide antiserum and between antisera from different rats. Antibody activity was found in IgG1, IgG2, and IgE immunoglobulin classes. Isoelectric focusing revealed multiple bands within a population of purified antibodies with significant pattern variation from one antiserum to another. Idiotypic characterization showed various levels of cross-reactive idiotypes present in some sera while these were absent in others.


On the solidification of a supercooled liquid droplet lying on a surface.
We model the solidification and subsequent cooling of a supercooled liquid droplet that is lying on a cold solid substrate after impact. It is assumed that solidification occurs for a given fixed droplet shape. The shapes used by the model are a sphere, truncated spheres, and an experimentally registered droplet shape. The freezing process is conduction-dominant and is modeled as a one-phase Stefan problem. This moving boundary problem is reformulated with the enthalpy method and then solved numerically with an implicit finite-difference technique. The numerical results for the simple case of a spherical droplet touching a surface are similar to those of a freely freezing spherical droplet and are well confirmed by the 1D asymptotic analytical model of Feuillebois et al. (J. Colloid Interface Sci. 169 (1995) 90). A freezing water droplet is considered as an example. The numerical results for full freezing time, subsequent cooling time, and last freezing point coordinate for the various droplets shapes are fitted by analytical functions depending on supercooling, thermal resistance of the target surface (expressed by Biot number), and spreading parameter. These functions are proposed for direct application, thus avoiding the need to solve the full freezing and cooling problem.


The distal C-terminal region of the KcsA potassium channel is a pH-dependent tetramerization domain.
The intracellular C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is a 40-residue-long segment that natively adopts a helical bundle conformation with 4-fold symmetry. A hallmark of KcsA behavior is pH-induced conformational change, which leads to the opening of the channel at acidic pH. Previous studies have reached conflicting conclusions as to the role of the CTD in this transition. Here, we investigate the involvement of this domain in pH-mediated channel opening by NMR using a soluble peptide corresponding to residues 128-160 of the CTD (CTD34). At neutral pH, CTD34 exhibits concentration-dependent spectral changes consistent with oligomer formation. We prove this slowly tumbling species to be a tetramer with a dissociation constant of (2.0±0.5)×10(-)(11) M(3) by NMR and sedimentation equilibrium experiments. Whereas monomeric CTD34 is only mildly helical, secondary chemical shifts prove that the tetrameric species adopts a tight native-like helical bundle conformation. The tetrameric species undergoes pH-dependent dissociation, and CTD34 is fully monomeric below pH 5.0. The structural basis for this phenomenon is the destabilization of the tetrameric CTD34 by protonation of residue H145 in the monomeric form of the peptide. We conclude that (i) the CTD34 peptide is independently capable of forming a tetrameric helical bundle, and (ii) this structurally significant conformational shift is modulated by the effects of solution pH on residue H145. Therefore, the involvement of this domain in the pH gating of the channel is strongly suggested.


[Theoretical analysis of the membrane transport non-homogeneous non-electrolyte solutions: influence of thermodynamic forces on thickness of concentration boundary layers for binary solutions].
The nonlinear mathematical model equations for membrane transport of binary non-electrolyte solutions was presented. This model, the influence of the volume flows caused by simultaneous action of osmotic and hydraulic forces in concentration boundary layers creation, controlled by concentration Rayleigh number is taken into account. In a basis of obtained fourth order equations, the numerical calculations of concentration boundary layers thicknesses (delta(l) and delta(h)) for five variables: concentration (C(h)), hydrostatic pressure difference (deltaP), hydraulic permeability (L(p)), reflection (sigma), solute permeability (omega) coefficients and concentration Rayleigh number (R(c)) were performed. Characteristics obtained in the study show that external forces cause nonlinear increase or decrease of the concentration boundary layers thicknesses.


Regulation of p53 under hypoxic and inflammatory conditions in periodontium.
Different studies suggest that inflammation as well as hypoxia leads to an increase of p53 protein levels. However, the implication of p53 during oral inflammatory processes is still unknown. The aim of this study was therefore to investigate the effect of hypoxia and inflammation on p53 regulation in human periodontium in vitro and in vivo. Under hypoxic and normoxic conditions, human primary periodontal ligament (PDL) fibroblasts (n = 9) were stimulated with lipopolysaccharides (LPS) from Porphyromonas gingivalis (P.g.), a periodontal pathogenic bacterium. After different time points, cell viability was tested; p53 gene expression, protein synthesis, and activation were measured using quantitative RT-PCR, immunoblotting, and immunofluorescence. Moreover, healthy and inflamed periodontal tissues were obtained from 12 donors to analyze p53 protein in oral inflammatory diseases by immunohistochemistry. LPS-P.g. and hypoxia initially induced a significant upregulation of p53 mRNA expression and p53 protein levels. Nuclear translocation of p53 after inflammatory stimulation supported these findings. Hypoxia first enhanced p53 levels, but after 24 h of incubation, protein levels decreased, which was accompanied by an improvement of PDL cell viability. Immunohistochemistry revealed an elevation of p53 immunoreactivity in accordance to the progression of periodontal inflammation. Our data indicate that p53 plays a pivotal role in PDL cell homeostasis and seems to be upregulated in oral inflammatory diseases. Upregulation of p53 may promote the destruction of periodontal integrity. A possible relationship with carcinogenesis may be discussed.


12-O-Tetradecanoylphorbol-13-acetate (TPA) is anti-tumorigenic in liver cancer cells via inhibiting YAP through AMOT.
TPA stimulates carcinogenesis in various types of cancers. However, we found that TPA inhibits transformative phenotypes in liver cancer cells via the translocation of YAP from the nucleus, where it functions as a transcriptional co-factor, to the cytoplasm. Such effects led to a separation of YAP from its dependent transcription factors. The inhibitory effects of TPA on YAP were AMOT dependent. Without AMOT, TPA was unable to alter YAP activity. Importantly, the depletion of YAP and AMOT blocked the TPA-reduced transformative phenotypes. In sum, TPA has been established as an anti-tumorigenic drug in liver cancer cells via YAP and AMOT.


The relationship between cell proliferation and differentiation and mapping of putative dental pulp stem/progenitor cells during mouse molar development by chasing BrdU-labeling.
Human dental pulp contains adult stem cells. Our recent study demonstrated the localization of putative dental pulp stem/progenitor cells in the rat developing molar by chasing 5-bromo-2'-deoxyuridine (BrdU)-labeling. However, there are no available data on the localization of putative dental pulp stem/progenitor cells in the mouse molar. This study focuses on the mapping of putative dental pulp stem/progenitor cells in addition to the relationship between cell proliferation and differentiation in the developing molar using BrdU-labeling. Numerous proliferating cells appeared in the tooth germ and the most active cell proliferation in the mesenchymal cells occurred in the prenatal stages, especially on embryonic Day 15 (E15). Cell proliferation in the pulp tissue dramatically decreased in number by postnatal Day 3 (P3) when nestin-positive odontoblasts were arranged in the cusped areas and disappeared after postnatal Week 1 (P1W). Root dental papilla included numerous proliferating cells during P5 to P2W. Three to four intraperitoneal injections of BrdU were given to pregnant ICR mice and revealed slow-cycling long-term label-retaining cells (LRCs) in the mature tissues of postnatal animals. Numerous dense LRCs postnatally decreased in number and reached a plateau after P1W when they mainly resided in the center of the dental pulp, associating with blood vessels. Furthermore, numerous dense LRCs co-expressed mesenchymal stem cell markers such as STRO-1 and CD146. Thus, dense LRCs in mature pulp tissues were believed to be dental pulp stem/progenitor cells harboring in the perivascular niche surrounding the endothelium.


Understanding barriers to vaccination against invasive meningococcal disease: a survey of the knowledge gap and potential solutions.
Invasive meningococcal disease (IMD) is a leading cause of life-threatening bacterial meningitis and septicemia. Evidence points to a knowledge gap among parents, teenagers, and healthcare providers (HCPs) regarding IMD and available vaccines, including those against the highly prevalent serogroup B. An online survey was conducted between March 27 and 12 April 2019, to gather insights into the knowledge that parents/guardians have about IMD vaccines. The children were aged 2 months to 10 years in Australia, Brazil, Germany, Greece, Italy, and Spain, 5-20 years in the UK, and 16-23 years in the USA. The findings were discussed in the context of the available literature and solutions were proposed to minimize the knowledge gap and the barriers to vaccination against IMD. The survey demonstrated that parents have a good understanding of IMD but a limited understanding of the different serogroups and vaccines. The available literature highlighted multiple barriers to IMD vaccine uptake; these may be reduced through education of HCPs, clear recommendations to parents by HCPs, the use of technology, and disease-awareness initiatives that engage parents through physical and digital channels. Further studies are warranted to assess the impact of the COVID-19 pandemic on IMD vaccination.


Paradoxical increase of ventricular fibrillation threshold in response to coronary sinus obstruction.
We determined the ventricular fibrillation threshold (VFT) changes in response to graded coronary sinus (CS) obstruction in 13 chloralose-anesthetized dogs with fixed heart rate (150 min-1, mean systemic arterial pressure (80 mm Hg), and cardiac index (100 ml/min.kg-1 body weight). VFT in milliamperes (VFTmA) increased linearily with CS pressure (CSP) increases up to 41.2 +/- 1.4 mm Hg (VFTmA = 6.5 + 0.14 CSP mm Hg, p less than 0.01). Total coronary venous effluent (CBF) did not change significantly, suggesting compensatory coronary vasodilation. Myocardial O2 consumption also remained unchanged. At higher CSP, both CBF and VFT declined precipitously (VFTmA = 20.9 - 0.27 CSP mm Hg, p less than 0.02). With simultaneous increases of systemic arterial along with CSP, VFT increased again along with the CSP-induced reduction of gradient until it reached 42.8 +/- 3.2 mm Hg. We conclude that with coronary venous obstruction, despite coronary perfusion gradient reduction to about 40 mm Hg, CBF remains constant. This constant flow vasodilation is associated with substantial (82%) VFT increase. The mechanism may involve enhanced homogeneity of CBF distribution and increased extracellular fluid.


The Science and (Lost) Art of Psoralen Plus UVA Phototherapy.
PUVA phototherapy is the therapeutic use of psoralens and UVA light to treat inflammatory skin diseases, with psoriasis the prototype disease. Naturally occurring phototoxic compounds, psoralens interact with UVA to suppress DNA synthesis and cell proliferation and induce apoptosis of inflammatory cells. Well-developed therapeutic protocols for psoriasis guide psoralen and UVA doses, treatment frequency, and safety measures, and these protocols also may be used to treat other inflammatory dermatoses.


Comparison and the lipid-lowering ability evaluation method discussion of Dendrobium officinale polysaccharides from different origins based on principal component analysis.
As typical acetylated glucomannans, Dendrobium officinale polysaccharides (DOPs) from different origins differ in their structural characteristics and some of their physicochemical properties. To rapidly select D. officinale plants, we systematically investigate the differences among DOPs from different origins and analyzed the structural characteristics, such as the degree of acetylation and monosaccharide composition; the physicochemical properties, such as solubility, water absorption and apparent viscosity; and the lipid-lowering activity of the obtained DOPs. Principal component analysis (PCA), a method for analyzing multiple variables, was used to analyze the relationship between the physicochemical and structural properties, and lipid-lowering activity. It was found that the structural and physicochemical characteristics had significant effects on lipid-lowering activity, and DOPs with a high degree of acetylation, high apparent viscosity and large D-mannose-to-d-glucose ratio were associated with greater lipid-lowering activity. Therefore, this study provides a reference for the selection and application of D. officinale.


The Revised Mental Health Inventory-5 (MHI-5) as an ultra-brief screening measure of bidimensional mental health in children and adolescents.
The Mental Health Inventory-5 (MHI-5) is a brief, valid, and reliable international instrument for assessing mental health in adults. The aim of the present study is to examine the psychometric properties of the MHI-5 in children and adolescents. A sample of 595 students (10-15 years old) completed the MHI-5 Spanish version adapted for this study, as well as another measure of anxiety and depression symptoms, and a clinical interview as a gold standard. The overall coefficient obtained indicate good internal consistency. A unique factor solution explaining a 53.70% and a two-factor structure explaining 69.20% of the total variance were obtained. The correlations with total and subscale scores of anxiety and depression were significant. A ROC analysis showed good properties as a screening test to predict anxiety and depressive diagnoses in children and adolescents. The Revised MHI-5 presents two essential changes: a simplified 4-point response format and a new factor solution including distress and well-being. These outcomes show that the Revised MHI-5 is a brief, valid, and reliable measure to bidimensionally assess mental health and screening emotional disorders in children and adolescents.


Influence of salivary pellicle formation time on enamel demineralization--an in situ pilot study.
This study assessed the protective potential of salivary pellicles formed in situ over periods ranging from 2 to 24 h. Pellicles were produced on enamel slabs mounted on the palatal aspect of removable acrylic splints and exposed to the oral environment in three subjects for 2, 6, 12 and 24 h. Enamel specimens with and without pellicles were immersed in citric acid (1%) for 60 s, and the amount of dissolved calcium was measured by atomic absorption spectroscopy. In addition, specimens were processed for transmission electron microscopy (TEM). Mean values (standard deviations) for calcium release (mg/l related to the specimen's surface area of 5 x 5 mm(2)) were: 2-h pellicle 6.94 (1.55); 6-h pellicle 6.69 (2.05); 12-h pellicle 6.57 (2.31); 24-h pellicle 5.71 (2.46); enamel without pellicle 8.95 (1.66). There were no significant differences in calcium release that were dependent on pellicle formation time, but in comparison to enamel specimens without pellicle, significantly less (p <0.05) demineralization of the enamel was observed in pellicle-covered specimens. TEM showed that the pellicle was partly, but not completely dissolved following acid exposure. It is concluded that even a 2-h in-situ-formed pellicle layer protects the enamel surface to a certain extent against demineralization.


Less is more: single dose versus extended antibiotic prophylaxis for transperineal prostate biopsy.
There is an ongoing debate as to the appropriate regimen of antibiotic prophylaxis with transperineal (TP) biopsy. The objective of this study was to report the rate of infection following TP biopsy at a high-volume institution and assess the impact of single dose antibiotics at the time of biopsy versus outpatient antibiotics in preventing postprocedural infections. Records of men undergoing TP prostate biopsy from 2012 to 2022 were reviewed. Patients were divided into two groups, those who received single dose intravenous (IV) antibiotics at the time of biopsy (n = 440) and those who received both IV antibiotics at the time of biopsy and outpatient antibiotics before/after biopsy (n = 327). Post biopsy infection was defined as at least one of the following: fever (≥ 38.3°C) with/without symptoms of urinary tract infection or positive urine culture (> 105 colony forming units) within 72 hours post biopsy. The rates of infection were compared between the two groups. A total of 767 biopsies were included in the study. Infection rate post TP biopsy was 1.83% (n = 14). The infection rate for patients with single dose prophylaxis was 2.05% (n = 9) and 1.53% (n = 5) for those that received the extended antibiotic regimen. No significant difference in infection rates between the different antibiotic regimens was found (p = 0.597). Overall rates of infection after TP prostate biopsy are very low. Our data indicate that single dose and extended regimen of antibiotic prophylaxis show similar infection rates. These findings support antibiotic stewardship and encourage further research into the appropriate regimen of prophylaxis for TP prostate biopsy.


Implants placed into alveoli with periapical lesions: an experimental study in dogs.
To histologically analyze the effect of a curettage of the granulation tissue on healing at implants installed immediately after the extraction of teeth presenting periapical lesions. In seven dogs, the dental pulp was removed from the pulp chamber and from the root canals of the right and left third and the fourth mandibular premolars and of the left second premolar. The chambers were left opened and, after 3 months, apical lesions were present, and the premolars were extracted. One alveolus each premolar was selected and, before implant installation, the apical lesions of two alveoli were curetted (curettage group) while the other three were not treated (no-treatment group). The second right premolar was also extracted (Negative control group). Six implants each dog were installed, and a fully submerged healing was allowed. Four months after, biopsies were collected, and histological analyses were performed. The proportions of new bone at the entire body of the implant was 70.2 ± 10.7% at the no-treatment group, 72.1 ± 14.8% at the curettage group, and 69.6 ± 3.7% at the negative control group. The respective new bone proportion at the apical aspect of the implants was 68.4 ± 17.5%, 61.5 ± 27.3%, and 78.1 ± 5.7%. None of the differences among the various groups were statistically significant. No inflammatory infiltrates were seen in the apical region. In this experimental study, it is concluded that the removal of the granulation tissue seems not to be necessary to obtain a proper osseointegration of implants installed immediately after the extraction of teeth presenting a periapical lesion.


Beyond induced mutants: using worms to study natural variation in genetic pathways.
Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of induced mutations can vary widely depending on the genetic background. Moreover, induced mutations in one genetic background do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation. Because other wildtype Caenorhabditis spp., including C. elegans, are now available, we review how current mapping resources and methodologies within and between species support the use of Caenorhabditis spp. for studying genetic variation, with a focus on pathways associated with human disease.


Association of congenital, diffuse electrical disease in children with normal heart: sick sinus syndrome, intraventricular conduction block, and monomorphic ventricular tachycardia.
Rhythm disturbances in children with structurally normal hearts are usually associated with abnormalities in cardiac ion channels. The phenotypic expression of these abnormalities ("channelopathies") includes: long and short QT syndromes, Brugada syndrome, congenital sick sinus syndrome, catecholaminergic polymorphic ventricular tachycardia, Lènegre-Lev disease, and/or different degrees of cardiac conduction disease. The study group consisted of three male patients with sick sinus syndrome, intraventricular conduction disease, and monomorphic sustained ventricular tachycardia. Clinical data and results of electrocardiography, Holter monitoring, electrophysiology, and echocardiography are described. In all patients, the ECG during sinus rhythm showed right bundle branch block and long QT intervals. First-degree AV block was documented in two subjects, and J point elevation in one. A pacemaker was implanted in all cases due to symptomatic bradycardia (sick sinus syndrome). Atrial tachyarryhthmias were observed in two patients. The common characteristic ventricular arrhythmia was a monomorphic sustained ventricular tachycardia, inducible with ventricular stimulation and sensitive to lidocaine. In one patient, radiofrequency catheter ablation was successfully performed. No structural abnormalities were found in echocardiography in the study group. Common clinical and ECG features suggest a common pathophysiology in this group of patients with congenital severe electrical disease.


Small ruminant lentiviruses: immunopathogenesis of visna-maedi and caprine arthritis and encephalitis virus.
The small ruminant lentiviruses include the prototype for the genus, visna-maedi virus (VMV) as well as caprine arthritis encephalitis virus (CAEV). Infection of sheep or goats with these viruses causes slow, progressive, inflammatory pathology in many tissues, but the most common clinical signs result from pathology in the lung, mammary gland, central nervous system and joints. This review examines replication, immunity to and pathogenesis of these viruses and highlights major differences from and similarities to some of the other lentiviruses.


TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure.
Elevated hydrostatic pressure induces retinal ganglion cell (RGC) apoptosis in culture. The authors investigated whether the transient receptor potential vanilloid 1 (TRPV1) channel, which contributes to pressure sensing and Ca(2+)-dependent cell death in other systems, also contributes to pressure-induced RGC death and whether this contribution involves Ca(2+). trpv1 mRNA expression in RGCs was probed with the use of PCR and TRPV1 protein localization through immunocytochemistry. Subunit-specific antagonism (iodo-resiniferatoxin) and agonism (capsaicin) were used to probe how TRPV1 activation affects the survival of isolated RGCs at ambient and elevated hydrostatic pressure (+70 mm Hg). Finally, for RGCs under pressure, the authors tested whether EGTA chelation of Ca(2+) improves survival and whether, with the Ca(2+) dye Fluo-4 AM, TRPV1 contributes to increased intracellular Ca(2+). RGCs express trpv1 mRNA, with robust TRPV1 protein localization to the cell body and axon. For isolated RGCs under pressure, TRPV1 antagonism increased cell density and reduced apoptosis to ambient levels (P <or= 0.05), whereas for RGCs at ambient pressure, TRPV1 agonism reduced density and increased apoptosis to levels for elevated pressure (P <or= 0.01). Chelation of extracellular Ca(2+) reduced RGC apoptosis at elevated pressure by nearly twofold (P <or= 0.01). Exposure to elevated hydrostatic pressure induced a fourfold increase in RGC intracellular Ca(2+) that was reduced by half with TRPV1 antagonism. Finally, in the DBA/2 mouse model of glaucoma, levels of TRPV1 in RGCs increased with elevated IOP. RGC apoptosis induced by elevated hydrostatic pressure arises substantially through TRPV1, likely through the influx of extracellular Ca(2+).


Erratum: 53-attosecond X-ray pulses reach the carbon K-edge.
Nature Communications 8:186 doi: 10.1038/s41467-017-00321-0 (2017); Article published online: 4 August 2017.


Bioavailability of two tablet preparations of carbimazole in man.
1. The bioavailability of two 5 mg tablet formulations of carbimazole (Neomercazole [A] and Carbazole [B]) have been compared in six euthyroid subjects. There was considerable inter-patient variation in absolute bioavailability although, for each subject, peak plasma concentrations of methimazole were similar with both formulations. 2. Mean peak plasma concentrations were seen on average 62 min after administration of tablet A as compared to 40 min after tablet B. This is consistent with the finding that the disintegration and dissolution times were shorter for formulation B than for formulation A. The mean area under the plasma concentration curve and the 6 h plasma concentration of methimazole tended to be greater after tablet A. These differences could be of significance in the treatment of thyrotoxicosis.


Nondirected living kidney donation. Is Australia ready?
The Renal Transplant Advisory Committee has recently approved nondirected kidney donation. If ratified at state level, it will allow volunteers to anonymously donate a kidney to any patient on the transplant waiting list. General practitioners, as well as more specialised services, may be approached by patients wishing to make such donations. This article summarises the scant literature on nondirected donation. Contrary to commonly held beliefs, this type of donor may not necessarily exhibit psychopathology, and this form of donation may raise fewer ethical concerns than are raised by living related donors.


Characteristics of hopanoid hydrocarbons in ambient PM₁₀ and motor vehicle emissions and coal ash in Taiyuan, China.
Hopanoid hydrocarbon content in ambient particulate matter (PM) of less than or equal to 10 μm aerodynamic diameter (PM10) was sampled at seven sites representative of different functional districts, and measured by gas chromatography-mass spectrometry. 17α(H),21β(H)-hopane (C30αβ) and 17α(H),21β(H)-30-norhopane (C29αβ) were dominant in all samples. Hopanes in motor vehicle emissions from various fuel-type engines (gasoline, diesel and natural gas) and coal ash were qualitatively measured, and the amount of C30αβ was about two to three times greater than that of C29αβ. Distinct seasonal variations (winter/summer differences) were observed at higher concentrations (45.54-108.29 ng/m(3)) of total hopanes in winter and lower (2.59-28.26 ng/m(3)) in summer. There were also clear spatial variations of hopanes in Taiyuan, with samples with greater hopane concentrations in downtown areas, but less in summer. The spatial distribution reversed in winter. Distributions and relative abundances of selected hopanes from PM10 and source emissions indicated that in summer, vehicle exhaust was the dominant fossil fuel combustion source (C30αβ was >C29αβ), and that the contribution of coal combustion was slightly greater at suburban sites. However, the contribution of coal combustion sources increased significantly at all sites in winter, especially in suburban areas, where C29αβ exceeded C30αβ. Hopanoid indexes revealed a classification of vehicle exhaust and coal combustion emissions in PM10. The results imply that during rapid urbanization, it is crucial to strengthen the construction of infrastructure such as central heating in new city districts and to increase the use of natural gas instead of residential coal burning.


NMR microimaging studies of water diffusivity in saturated, microporous systems.
A novel microimaging method is described for measuring the effective diffusion coefficient (D infinity) of water in saturated, microporous materials. A simple multicompartment computer simulation was used to show how the value of D infinity, when combined with measurements of water proton relaxation times and pulsed field gradient spin-echo amplitudes, allows the pore size distribution and pore connectivity to be characterized.


Large-scale comparative analysis reveals different bacterial community structures in full- and lab-scale wastewater treatment bioreactors.
The activated sludge process is widely used for biological wastewater treatment due to its low cost and high efficiency. Although numerous lab-scale bioreactor experiments have been conducted to investigate the microorganism performance and mechanisms in activated sludge, understanding the bacterial community differences between full- and lab-scale bioreactors has remained elusive. In this study, we investigated the bacterial communities in 966 activated sludge samples obtained from various bioreactors, including both full- and lab-scale ones, from 95 previous studies. Our findings reveal significant differences in the bacterial communities between full- and lab-scale bioreactors, with thousands of bacterial genera exclusive to each scale. We also identified 12 genera that are frequently abundant in full-scale bioreactors but rarely observed in lab-scale reactors. By using a machine-learning method, organic matter and temperature were determined as the primary factors affecting microbial communities in full- and lab-scale bioreactors. Additionally, transient bacterial species from other environments may also contribute to the observed bacterial community differences. Furthermore, the bacterial community differences between full- and lab-scale bioreactors were verified by comparing the results of lab-scale bioreactor experiments to full-scale bioreactor sampling. Overall, this study sheds light on the bacteria overlooked in lab-scale studies and deepens our understanding of the differences in bacterial communities between full- and lab-scale bioreactors.


Tenascin-C is a potential cancer-associated fibroblasts marker and predicts poor prognosis in prostate cancer.
Tenascin-C (TNC), as a member of the extracellular matrix (ECM), plays an important role in cancer cell proliferation and migration and tumor invasion in various types of cancer. Here, we attempted to investigate the role of TNC as a prognostic factor in prostate cancer. We studied TNC expression via immunohistochemistry in 145 prostate cancer tissue samples. The clinicopathological relevance of TNC expression was examined, as well as other cancer-associated fibroblasts (CAFs)-related factors. Our results showed that the high levels of TNC expression in prostate cancer stroma was significantly associated with lymph node metastasis (P = 0.024) and clinical stage (P = 0.032). Furthermore, TNC was positively correlated with increased micro-vessel density (MVD) (P = 0.017) and tumor associated macrophage (TAM) population (P = 0.025). In both univariate and multivariate Cox regression analyses, TNC (P < 0.001) was an independent poor prognostic factor for overall survival in prostate cancer patients. Moreover, over-expression of TNC (P < 0.001), SMA (P = 0.042) and vimentin (P = 0.010) were significantly correlated with the lower overall survival. In addition, TNC expression in prostate cancer stroma was significantly associated with FSP1 (P = 0.011), SMA (P = 0.021), and vimentin (P = 0.002). In conclusion, our study revealed that high level of TNC as a potential biomarker of CAFs was significantly correlated with the poor prognosis for prostate cancer patients.


Nonlinear absorption in biological tissue for high intensity focused ultrasound.
In recent years the propagation of the high intensity focused ultrasound (HIFU) in biological tissue is an interesting area due to its potential applications in non-invasive treatment of disease. The base principle of these applications is the heat effect generated by ultrasound absorption. In order to control therapeutic efficiency, it is important to evaluate the heat generation in biological tissue irradiated by ultrasound. In his paper, based on the Khokhlov-Zabolotkaya-Kuznetsov (KZK) equation in frequency-domain, the numerical simulations of nonlinear absorption in biological tissues for high intensity focused ultrasound are performed. We find that ultrasound thermal transfer effect will be enhanced with the increasing of initial acoustic intensity due to the high harmonic generation. The concept of extra absorption factor is introduced to describe nonlinear absorption in biological tissue for HIFU. The theoretical results show that the heat deposition induced by the nonlinear theory can be nearly two times as large as that predicated by linear theory. Then, the influence of the diffraction effect on the position of the focus in HIFU is investigated. It is shown that the sound focus moves toward the transducer compared with the geometry focus because of the diffraction of the sound wave. The position of the maximum heat deposition is shifted to the geometry focus with the increase of initial acoustic intensity because the high harmonics are less diffraction. Finally, the temperature in the porcine fat tissue changing with the time is predicated by Pennes' equation and the experimental results verify the nonlinear theoretical prediction.


Nonredundant roles of keratinocyte-derived IL-34 and neutrophil-derived CSF1 in Langerhans cell renewal in the steady state and during inflammation.
IL-34 and colony-stimulating factor 1 (CSF1) are two alternative ligands for the CSF1 receptor that play nonredundant roles in the development, survival, and function of tissue macrophages and Langerhans cells (LCs). In this study, we investigated the spatio-temporal production of IL-34 and its impact on skin LCs in the developing embryo and adult mice in the steady state and during inflammation using Il34(LacZ) reporter mice and newly generated inducible Il34-knockout mice. We found that IL-34 is produced in the developing skin epidermis of the embryo, where it promotes the final differentiation of LC precursors. In adult life, LCs required IL-34 to continually self-renew in the steady state. However, during UV-induced skin damage, LC regeneration depended on neutrophils infiltrating the skin, which produced large amounts of CSF1. We conclude that LCs require IL-34 when residing in fully differentiated and anatomically intact skin epidermis, but rely on neutrophil-derived CSF1 during inflammation. Our demonstration that neutrophils are an important source of CSF1 during skin inflammation may exemplify a mechanism through which neutrophils promote their subsequent replacement with mononuclear phagocytes.


Development and clinical implementation of tailored image analysis tools for COVID-19 in the midst of the pandemic: The synergetic effect of an open, clinically embedded software development platform and machine learning.
During the emerging COVID-19 pandemic, radiology departments faced a substantial increase in chest CT admissions coupled with the novel demand for quantification of pulmonary opacities. This article describes how our clinic implemented an automated software solution for this purpose into an established software platform in 10 days. The underlying hypothesis was that modern academic centers in radiology are capable of developing and implementing such tools by their own efforts and fast enough to meet the rapidly increasing clinical needs in the wake of a pandemic. Deep convolutional neural network algorithms for lung segmentation and opacity quantification on chest CTs were trained using semi-automatically and manually created ground-truth (Ntotal = 172). The performance of the in-house method was compared to an externally developed algorithm on a separate test subset (N = 66). The final algorithm was available at day 10 and achieved human-like performance (Dice coefficient = 0.97). For opacity quantification, a slight underestimation was seen both for the in-house (1.8 %) and for the external algorithm (0.9 %). In contrast to the external reference, the underestimation for the in-house algorithm showed no dependency on total opacity load, making it more suitable for follow-up. The combination of machine learning and a clinically embedded software development platform enabled time-efficient development, instant deployment, and rapid adoption in clinical routine. The algorithm for fully automated lung segmentation and opacity quantification that we developed in the midst of the COVID-19 pandemic was ready for clinical use within just 10 days and achieved human-level performance even in complex cases.


Chemotherapy drug shortages in paediatric oncology: A 14-year single-centre experience in Belgium.
Shortages of chemotherapy are a growing challenge for the healthcare system. We present the burden of drug shortages of chemotherapeutics in the paediatric hemato-oncology unit of a tertiary care hospital and solutions that were used to manage them. Between January 2001 and December 2014, 54 individual shortages were detected, affecting a total number of 21 different drugs. In total, 4127 shortage days were registered with a mean duration of 196.5 SD ± 144.0 days per individual drug shortage. Methotrexate, doxorubicin and carboplatin had the longest supply disruptions. Solutions to address the problems were purchase of a generic alternative, a change of individual treatment plans, cohorting of patients and import from abroad.


Hip Asymmetry: Implications in Body Contouring Surgery.
Asymmetry of the hips and its implication in body contouring procedures has not yet been reported. Hip asymmetry is common in the general population and may account for uneven abdominoplasty scar and the apparent discrepancies in volume following liposuction of the hips and flanks. The goal of this study was to determine the presence of hip asymmetry in women presenting for abdominal contouring surgery. Analysis of preoperative photographs of 100 female patients was performed by three independent plastic surgeons. They were asked to evaluate for hip asymmetry and, when present, determine which side was higher. Adobe Photoshop was also used to objectively measure hip asymmetry. Patients were women with no known history of hip abnormalities; age ranged from 17 to 64 years and the body mass index ranged from 16 to 47 kg/m(2). All three plastic surgeon reviewers found that the majority of patients had hip asymmetry, with raters 1, 2, and 3 documenting discrepancies in hip height in 88, 60, and 76 percent of patients, respectively. The interrater reliability was 0.713. Chi-square statistical analysis suggested that the raters were not statistically different from one another (p = 0.086). The objective analysis found asymmetry in 82 percent of patients. The results showed that the majority of patients who present for abdominal contouring surgery have asymmetric hips. Patients are usually unaware of the unevenness of their own hips; however, they often notice postoperative discrepancies in scar height after abdominoplasty or volume differences after liposuction.


Canonical and Non-Canonical Wnt Signaling in Immune Cells.
Cell differentiation, proliferation, and death are vital for immune homeostasis. Wnt signaling plays essential roles in processes across species. The roles of Wnt signaling proteins and Wnt ligands have been studied in the past, but the context-dependent mechanisms and functions of these pathways in immune responses remain unclear. Recent findings regarding the role of Wnt ligands and Wnt signaling in immune cells and their immunomodulatory mechanisms suggest that Wnt ligands and signaling are significant in regulating immune responses. We introduce recent key findings and future perspectives on Wnt ligands and their signaling pathways in immune cells as well as the immunological roles and functions of Wnt antagonists.


Influence of dioxin-related compounds on physical function in Yusho incident victims.
Few studies have examined the influence of dioxin-related compounds on human physical function, and existing results are inconsistent. In 1968, accidental human exposure to rice oil contaminated with dioxin-related compounds resulted in the development of Yusho oil disease in Japan. We aimed to determine whether the degree of exposure to dioxin-related compounds was associated with physical function in Yusho patients. In 2016, 65 men (average age: 65.7 years) and 77 women (average age: 64.7 years) participated in a nationwide health examination in Fukuoka prefecture. Functional reach, gait speed, hand grip strength, and toe grip strength were evaluated as part of physical function. The serum levels of polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofurans, and non-ortho polychlorinated biphenyls were measured using high-resolution gas chromatography and high-resolution mass spectrometry. We examined the association between physical function tests and serum toxic equivalency (TEQ) values. A 10-fold increase in serum TEQ levels was negatively associated with functional reach (adjusted b = -4.07, p = 0.017) and hand grip strength (adjusted b = -2.20, p = 0.0245) in men. No association was observed between serum TEQ level and physical function in women. Our findings suggest that dioxin-related compounds have a negative influence on physical function in men. However, these findings should be interpreted carefully. Future studies examining additional data on musculoskeletal disorders are warranted.


Willingness to Participate in At-Home HIV Testing Among Young Adults Who Use Opioids in Rural Appalachia.
New HIV infections associated with injection drug use are of major concern in rural US communities. This study explores acceptability of, consent for, and uptake of free at-home HIV testing among people who use drugs (PWUD) in one of the nation's epicenters for drug-related harms and HIV vulnerability: Rural Central Appalachia. Eligible participants were 18-35 years old, lived in Appalachian Kentucky, and reported using opioids to get high in the previous 30 days. A majority reported being likely (63.6%, 96/151) to take a free at-home HIV tests and 66.9% (101/151) consented to receive one. Among those who were randomly selected to receive a Home Access HIV-1 test kit (n = 37), 37.8% mailed in blood spots and 21.6% called to receive results. This study provides evidence that PWUD may be willing to take an at-home test, but other barriers may inhibit actual completion.


Lead in soil: recommended maximum permissible levels.
Lead in soil has been recognized as a public health problem, particularly among children. In recent years, attention has been directed to cumulative adverse effects of lead at low levels of intake. Lead-contaminated soil and dust have been identified as important contributors to blood lead levels. Based on available data on blood lead and lead in soil, an approach has been developed to suggest a permissible level of lead in soil, below which there will be reasonable certainty that adverse health effects will not occur. An acceptable level of 600 ppm of lead in soil suggested as a "safe" level would contribute no more than 5 micrograms/dl to total blood lead of children under 12 years of age. Maximum permissible levels of lead in soil have been recommended based on the dose-response relationship of lead in soil and blood lead in children.


The development of a six-station OSCE for evaluating the clinical competency of the student nurses before graduation: A validity and reliability analysis.
Assessing clinical competency in undergraduate nursing students is essential before they enter clinical practice. The objective structured clinical examination (OSCE) is widely used and is part of clinical competency assessment. Aim The aim of this study was to develop and validate a six-station OSCE for evaluating the clinical competency of the student nurses before graduation. One-group longitudinal observational study. An OSCE of 6 stations of 10 min each was adopted. Blueprint setting, checklist development, and standard patient and examiner training were conducted. The mean, standard deviation, item scale (item-total correlation) and comparisons of extreme groups for item analysis. The inter-coder of examiners and inter-case of students were used to test reliability. Content Validity and concurrent validity were used to evaluate validity of OSCE. One hundred nursing students participated in this study. The mean OSCE score of students who passed the registered nurses' examination was significantly higher than that of students who failed. Significant differences in OSCE score between students who remain versus left clinical job were observed at 3, 6 and 9 months after graduation. The OSCE is predictable method for assessing undergraduate students' first year clinical retention.


Pain and anxiety control: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will cover pain theories and dentin hypersensitivity, referred pain, oral pain not of dental origin, barodontalgia, local anesthetics, long-acting local anesthetics, intrapulpal anesthesia, intraligamentary anesthesia, intraosseous anesthesia, inferior alveolar nerve block anesthesia, Gow-Gates anesthesia technique, Vazirani-Akinosi anesthesia technique, second-division block anesthesia technique, endodontic postoperative pain, effect of occlusal adjustment on endodontic pain, paresthesia associated with periradicular pathosis, analgesics, sedation, and endodontic flare-ups.


Safety and feasibility of reduced-port site surgery for robotic posterior retroperitoneal adrenalectomy.
Minimally invasive surgery, such as laparoscopic adrenalectomy and robotic adrenalectomy, has become a treatment of choice for benign adrenal tumors. Efforts are ongoing to minimize the invasiveness of the procedure and to reduce the number of port sites. The primary endpoint of this study was the safety and feasibility of a reduced-port site technique for robotic posterior retroperitoneal adrenalectomy (RPRA). This study retrospectively analyzed 74 RPRAs performed by a single surgeon, including 30 conventional three-port site early-phase RPRAs, 30 three-port site late-phase RPRAs, and 14 reduced-port site RPRAs. Reduced-port site RRPA was defined as using two port sites: one for a multi-glove port and one for an additional side port. The clinicopathological features and surgical outcomes were compared in these three groups. No major complications were observed following RPRA in the three groups of patients. Operation time, pain score, and hospital stay did not differ significantly among these three groups. RPRA using a reduced-port site system was safe and feasible and may be a good alternative to conventional three-port site RPRA for benign adrenal tumors in certain situations.


Generation and evaluation of a chimeric classical swine fever virus expressing a visible marker gene.
Classical swine fever virus (CSFV) is a noncytopathogenic virus, and the incorporation of an enhanced green fluorescent protein (EGFP) tag into the viral genome provides a means of direct monitoring of viral infection without immunostaining. It is well established that the 3' untranslated region (3'-UTR) of the CSFV plays an important role in viral RNA replication. Although CSFV carrying a reporter gene and chimeric CSFV have been generated and evaluated, a chimeric CSFV with a visible marker has not yet been reported. Here, we generated and evaluated a chimeric virus containing the EGFP tag and the 3'-UTR from vaccine strain HCLV (C-strain) in the genetic background of the highly virulent CSFV Shimen strain. The chimeric marker CSFV was fluorescent and had an approximately 100-fold lower viral titer, lower replication level of viral genome, and weaker fluorescence intensity than the recombinant CSFV with only the EGFP tag or the parental virus. Furthermore, the marker chimera was avirulent and displayed no viremia in inoculated pigs, which were completely protected from lethal CSFV challenge as early as 15 days post-inoculation. The chimeric marker virus was visible in vitro and attenuated in vitro and in vivo, which suggests that CSFV can be engineered to produce attenuated variants with a visible marker to facilitate in vitro studies of CSFV infection and replication and to develop of novel vaccines against CSF.


Impact of Home Hospice Care on Patients with Advanced Lung Cancer: A Longitudinal Population-Based Study in Taiwan.
The effectiveness of home hospice care was helping patients to die at home, and reducing symptom burden. The study objective was to explore the impact of home hospice care on death at home, end-of-life (EOL) care, and health care costs among patients with advanced lung cancer in their last month of life. Using Taiwan's National Health Insurance Claims Database, we analyzed factors associated with home hospice care using logistic regression analysis. We enrolled 568 patients with advanced lung cancer under hospice care who died during 1997-2011, of which 238 (41.9%) received home hospice care. Compared with the inpatient hospice (IH) group, the home hospice (HH) group had a larger portion die at home (55.5% versus 22.1%, p < 0.001), but a smaller portion stayed in hospital more than 14 days in their last month of life (67.3% versus 40.8%, p < 0.001). The mean health care cost was less in the HH group than in the IH group (US $1,385.00 ± $1,370.00 and US $2,155.00 ± $1,739.00 [p < 0.001], respectively). Female patients' (p = 0.001) decreased hospital stay in the last month of life (p < 0.001) and longer hospice care duration (p = 0.003) were predictors of receiving home hospice care in advanced lung patients. Home hospice care enables patients with advanced lung cancer to increase the 33.4% chance of dying at home, to spend an average of eight-days less in hospital stay, and to save 35.7% health care costs in the last month of life, compared with their counterparts with only inpatient hospice care. Female patients' decreased hospital stay and longer hospice care duration were the predictors of receiving home hospice care.


Andes virus and first case report of Bermejo virus causing fatal pulmonary syndrome.
Two suspected hantavirus pulmonary syndrome (HPS) cases from Bolivia occurred in May and July 2000 and were confirmed by enzyme-linked immunosorbent assay (ELISA)-ANDES using N-Andes recombinant antigen serology. Clot RNAs from the two patients were subjected to reverse transcription-polymerase chain reaction (PCR) amplification and sequencing. We describe two characterized cases of HPS. One was caused by infection with Bermejo virus and the other with Andes Nort viral lineage, both previously obtained from Oligoryzomys species. This is the first report of molecular identification of a human hantavirus associated with Bermejo virus.


Persister cancer cells: Iron addiction and vulnerability to ferroptosis.
Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it can be used as a defense mechanism against pathogens or even harnessed by T cells to sensitize tumor cells toward effective killing. Conversely, ferroptosis is considered one of the main cell death mechanisms promoting degenerative diseases. Emerging evidence suggests that ferroptosis represents a vulnerability in certain cancers. Here, we critically review recent advances linking ferroptosis vulnerabilities of dedifferentiating and persister cancer cells to the dependency of these cells on iron, a potential Achilles heel for small-molecule intervention. We provide a perspective on the mechanisms reliant on iron that contribute to the persister cancer cell state and how this dependency may be exploited for therapeutic benefits.


Worries of childhood cancer survivors in young adulthood.
Childhood cancer survivors worry about many issues related to their cancer history. As they grow older, additional issues may emerge. This study of a sample of Korean young adults aims to understand childhood cancer survivors' worries. A purposeful sample of 28 childhood cancer survivors was recruited through survivor and parent-advocacy foundations and support groups in Korea. Qualitative in-depth interviews were conducted over the phone or in person. Participants ranged in age from 20 to 36, were diagnosed before age 19, and had completed treatment at the time of the study. Through qualitative interviews, survivors' worries were identified in the following five themes: romantic relationships and marriage, fertility and the health of future children, work and social life, family, and physical health. The study's findings support the importance of understanding the worries of childhood cancer survivors in young adulthood and the need for developing services and programs to help survivors acquire the appropriate social skills and coping strategies to mitigate their worries.


Immunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung.
The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by submucosal nerves and ganglion cells and, in the mucosal lining by solitary NE cells and neuroepithalial bodies (NEB's). The latter two components variably express pan-NE markers including NSE, chromogranin (s) and, notably, synaptophysin. The expression of serotonin, bombesin, calcitonin and leu-enkephalin has been well established; additional eutopic materials include somatostatin and calcitonin gene-related peptide. Solitary NE cells and NEB's are epithelial structures as defined by their consistent cytokeratin expression. Hyperplasia and dysplasia of NE cells may be found in association with various forms of chronic injury; they have been noted in chronic bronchiectasis and in the vicinity of neoplasms of various types. Hyperplastic and dysplastic pulmonary NE cells frequently express ectopic materials particularly ACTH. NE neoplasms of the bronchopulmonary tract comprice a spectrum that includes a) carcinoids, b) well differentiated NE carcinomas, c) intermediate cell NE carcinomas and d) small cell NE carcinomas. The precise pathologic criteria defining these entities are discussed in detail as are their clinical implications. The entire spectrum of lung NE neoplasms express NE markers demonstrable by immunocytochemistry; these include pan-NE markers, serotonin and numerous neuropeptides. The expression of multiple hormonal materials is frequent. Within any given tumor, some variation in expression may be noted in different sites and in different periods of the "normal" or therapeutically modified lifespan of the tumor. The entire spectrum of lung NE neoplasms is epithelial for they express cytokeratin polypeptides and desmoplakin; subsets of the tumors coexpress cytokeratins and neurofilament proteins. Also, subsets of these NE neoplasms may be immunostained with monoclonal antibodies to antigens related to exocrine phenotype suggesting focal amphicrine features.


Reversible surface binding of cadmium and lead by lactic acid and bifidobacteria.
Extensive cadmium and lead contamination of water has been reported to occur locally as a result of human activities. Lactic acid bacteria have been reported to remove cadmium and lead from water. The aim of this work was to clarify the mechanisms of cadmium and lead removal from water. In addition, the effect of other metals, reversibility of binding and recyclability of the biomass was assessed. Based on our earlier data, the two most promising lactic acid bacteria, Lactobacillus fermentum ME3 and Bifidobacterium longum 46, were selected for these experiments. The results showed that the presence of other cationic metals and blocking of carboxyl and phosphoryl groups reduced cadmium and lead removal. These results suggest involvement of electrostatic interactions in cadmium and lead removal, and support our earlier findings. Transmission electron micrographs showed large deposits of lead on the bacterial surface suggesting formation of metallic lead precipitates. Both cadmium and lead removal were reversible processes established by full recovery of removed metal after desorption with dilute solutions of EDTA and HNO(3). Resorption capacity of both biomasses tested was reduced after regeneration with 10 mM EDTA and 15 mM HNO(3). Taken together, the results suggest involvement of several reversible mechanisms such as ion exchange and precipitation in cadmium and lead binding by lactic acid bacteria. The results show that specific lactic acid bacteria have the potential for removal of cadmium and lead from water although reduction in resorption capacity after regeneration of the biomass may form a problem. Since the studies so far have mainly focused on removal of single metals from pure water, metal removal in conditions of natural waters should be assessed in further experiments.


Animal domesticators.
Humans have been domesticating plants, animals and microbes for centuries. But are we alone in doing so? Brooker and Feeney explain how domestication by animals of other species goes back even farther.


Rapid blotting of IgG to nitrocellulose with minimal IgM contamination.
A rapid method is described for the non-electrophoretic transfer of IgG from 0.5 mm thick agarose gels to nitrocellulose. Since the agarose gels are attached to a solid support, the blot is unidirectional. However, 90% of the IgG is transferred in 10 min with no visible loss of resolution. In this procedure, less than 2% of the IgM antibodies are transferred from the gel to the nitrocellulose membrane. Therefore, this technique can be used in IgG spectrotype analysis or antigen-specific assays without the prior removal of IgM antibodies. Approximately 5-6 h are needed to run the gels, blot, and develop the protein pattern with double-antibody immunoperoxidase staining.


[Self-contained neurosurgical cryoprobe].
A cryoprobe with an interchangeable container (vessel) holding the cryoprobe has been designed, this enabling it to dispense with the use of hoses to deliver the coolant to and remove it from the Dewar vessel and the vacuum pump. The cryogenic action provided for by a single ampoule lasts 5 minutes. The small diameter of the cryoprobe makes for a minimal traumatization of the surrounding structures, while the absence of connecting hoses makes for its easy handling.


Prostate-specific antigen-based prostate cancer screening: reduction of prostate cancer mortality after correction for nonattendance and contamination in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.
Large randomized screening trials provide an estimation of the effect of screening at a population-based level. The effect of screening for individuals, however, is diluted by nonattendance and contamination in the trial arms. To determine the prostate cancer (PCa) mortality reduction from screening after adjustment for nonattendance and contamination. A total of 34,833 men in the core age group, 55-69 yr, were randomized to a screening or control arm in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). Prostate-specific antigen (PSA) testing was offered to all men in the screening arm at 4-yr intervals. A prostate biopsy was offered to men with an elevated PSA. The primary end point was PCa-specific mortality. Nonattendance was defined as nonparticipation in the screening arm. Contamination in the control arm was defined as receiving asymptomatic PSA testing or a prostate biopsy in the absence of symptoms. Relative risks (RRs) were calculated with an intention to screen (ITS) analysis and after correction for nonattendance and contamination using a method that preserves the benefits obtained by randomization. The ITS analysis resulted in an RR of 0.68 (95% confidence interval [CI], 0.53-0.89) in favor of screening at a median follow-up of 13 yr. Correction for both nonattendance and contamination resulted in an RR of 0.49 (95% CI, 0.27-0.87) in favor of screening. PCa screening as conducted in the Rotterdam section of the ERSPC can reduce the risk of dying from PCa up to 51% for an individual man choosing to be screened repeatedly compared with a man who was not screened. This benefit of screening should be balanced against the harms of overdiagnosis and subsequent overtreatment. ISRCTN49127736.


The impact of perception of discrimination and sense of belonging on the loneliness of the children of Chinese migrant workers: a structural equation modeling analysis.
The children of migrant workers can experience several mental health problems after they enter the cities, among which, loneliness is the most prominent and the most common psychological problem. The current study aimed to examine the impact of discrimination perception on loneliness of migrant children, mainly focused on confirmation of the mediator role of sense of belonging. 357 children of Chinese migrant workers were as participants involving in this research. Data were collected by using the Perception of Discrimination Scale, Sense of Belonging Instrument, and the Social and Emotional Loneliness Scale. The results revealed that both perception of discrimination and sense of belonging were significantly correlated with loneliness of the children of migrant workers. Structural equation modeling indicated that sense of belonging partially mediated perception of discrimination to job loneliness. Sense of belonging played a significant role in the relation between perception of discrimination and loneliness of the children of migrant workers.


Impaired motor unit recovery and maintenance in a knock-in mouse model of ALS-associated Kif5a variant.
Kinesin family member 5A (KIF5A) is an essential, neuron-specific microtubule-associated motor protein responsible for the anterograde axonal transport of various cellular cargos. Loss of function variants in the N-terminal, microtubule-binding domain are associated with hereditary spastic paraplegia and hereditary motor neuropathy. These variants result in a loss of the ability of the mutant protein to process along microtubules. Contrastingly, gain of function splice-site variants in the C-terminal, cargo-binding domain of KIF5A are associated with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease involving death of upper and lower motor neurons, ultimately leading to degradation of the motor unit (MU; an alpha motor neuron and all the myofibers it innervates) and death. These ALS-associated variants result in loss of autoinhibition, increased procession of the mutant protein along microtubules, and altered cargo binding. To study the molecular and cellular consequences of ALS-associated variants in vivo, we introduced the murine homolog of an ALS-associated KIF5A variant into C57BL/6 mice using CRISPR-Cas9 gene editing which produced mutant Kif5a mRNA and protein in neuronal tissues of heterozygous (Kif5a+/c.3005+1G>A; HET) and homozygous (Kif5ac.3005+1G>A/c.3005+1G>A; HOM) mice. HET and HOM mice appeared normal in behavioral and electrophysiological (compound muscle action potential [CMAP] and MU number estimation [MUNE]) outcome measures at one year of age. When subjected to sciatic nerve injury, HET and HOM mice have delayed and incomplete recovery of the MUNE compared to wildtype (WT) mice suggesting an impairment in MU repair. Moreover, aged mutant Kif5a mice (aged two years) had reduced MUNE independent of injury, and exacerbation of the delayed and incomplete recovery after injury compared to aged WT mice. These data suggest that ALS-associated variants may result in an impairment of the MU to respond to biological challenges such as injury and aging, leading to a failure of MU repair and maintenance. In this report, we present the behavioral, electrophysiological and pathological characterization of mice harboring an ALS-associated Kif5a variant to understand the functional consequences of KIF5A C-terminal variants in vivo.


Interaction of noncompetitive inhibitors with the acetylcholine receptor. The site specificity and spectroscopic properties of ethidium binding.
The spectroscopic properties and specificity of binding of a fluorescent quaternary amine, ethidium, with acetylcholine receptor-enriched membranes from Torpedo californica have been examined. Competition binding with [3H]phencyclidine in the presence of carbamylcholine showed that ethidium binds with high affinity to a noncompetitive inhibitor site (KD = 3.6 X 10(-7) M). However, in the presence of alpha-toxin, ethidium's affinity is substantially lower (KD approximately 1 X 10(-3) M). Ethidium was also found to enhance [3H]acetylcholine binding with a KD characteristic of ethidium binding to a high-affinity noncompetitive inhibitor site. These findings indicate that ethidium binds to an allosteric site which is regulated by agonist binding and can convert the agonist sites from low to high affinity. Fluorescence titrations of ethidium in the presence of carbamylcholine yielded a similar KD (2.5 X 10(-7) M) and showed an ethidium stoichiometry of one site/acetylcholine receptor monomer. Ethidium was completely displaced by noncompetitive inhibitors such as phencyclidine, histrionicotoxin, and dibucaine. The enhanced fluorescence lifetime of the bound species showed that the increased fluorescence intensity reflects a 13-fold increase in quantum yield for the complex compared to ethidium in buffer. Fractional dissociation of ethidium with phencyclidine produced a double-exponential fluorescence decay rate with lifetime components characteristic of ethidium free in solution and bound to the receptor. These data argue that the alterations in ethidium fluorescence elicited by other ligands is due to a change in the fraction of specifically bound ethidium rather than a change in quantum yield of a pre-existing ethidium-acetylcholine receptor complex. The extent of polarization indicates that bound ethidium is strongly immobilized. The magnitude of the quantum yield enhancement and the shifts of excitation and emission maxima of bound ethidium suggest that its binding site is within a hydrophobic domain with limited accessibility to the aqueous phase.


[Inhibitive effect of umbellatus polyporus polysaccharide on cachexic manifestation induced by toxohormone-L in rats].
To investigate the effect of treatment of cachexia with Umbellatus Polyporus Polysaccharide (UPP). UPP was used to treat cachexia induced by toxohormone-L. Toxohormone-L from ascites fluid with primary hepatoma could induce lipolysis in vitro significantly, inhibit the intake behavior, decrease the level of blood zinc, increase that of blood copper (P < 0.01), upp could inhibit these effects. Toxohormone-L was closely related with neoplastic cachexia and UPP could inhibit this effect induced by toxohormone-L significantly.


Acylated iridoid glycosides with hyaluronidase inhibitory activity from the rhizomes of Picrorhiza kurroa Royle ex Benth.
Seven new acylated iridoid glycosides, picrorhizaosides A-G (1-7), were isolated from the methanol extract of the rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae), in addition to six known iridoid glycosides (8-13). The structures of these new iridoids, including their stereochemistry, were determined based on chemical and physicochemical evidence derived from NMR and MS analysis. Of the isolates, picrorhizaosides D (4, IC50 = 43.4 μM) and E (5, 35.8 μM); picrosides I (8, 60.7 μM), II (9, 22.3 μM), and IV (11, 59.2 μM); and minecoside (13, 57.2 μM), exhibited a similar or stronger hyaluronidase inhibitory activity than those of the antiallergic medicines disodium cromoglycate (64.8 μM), ketotifen fumarate (76.5 μM), and tranilast (227 μM).


Measurement of serum aldosterone in picomolar level by LC-MS/MS using charge-tagged technique.
Aldosterone is a mineralocorticoid steroid hormone, the measurement of which in the clinical laboratory is principally performed for the investigation of primary hyperaldosteronism. Primary hyperaldosteronism is a specifically treatable and potentially curable form of hypertension, which typically presents as drug-resistant hypertension and, in up to 37% of cases, hypokalemia. Accurate measurement of aldosterone concentration is essential for correct diagnosis. The serum concentrations of aldosterone are in the picomolar range and therefore sensitive aldosterone assays are required. With the advancement in instrumentation of LC-MS/MS, the picomolar range of aldosterone can be easily measured by the newer models, but for those with a less sensitive instrument, special technique for sample preparation to enhance assay sensitivity is required. This work described the use of charge-tagging for the picomolar measurement of serum aldosterone in a less sensitive LC-MS/MS instrument. The assay was linear up to 3000 pmol/L with lower limit of quantitation at 80 pmol/L. The mean relative recovery was 96.5% with a range of 89.3-101.6% for aqueous calibrators and the mean relative recovery was 94.8% with a range of 87.5-101.4% for serum calibrators. Intra-assay CVs range from 8.2% to 11.3%, and inter-assay CVs ranged from 8.5% to 13.5% at concentration range from 229 to 1720 pmol/L. The LC-MS/MS method compared well (y = 1.04x + 8.97) with the in-use radioimmunoassay method. There was no significant difference found (p = 0.7135) between results determined by LC-MS/MS and radioimmunoassay method.


Development of a targeted behavioral treatment for smoking cessation among individuals with Chronic Obstructive Pulmonary Disease.
Smoking cessation for individuals with Chronic Obstructive Pulmonary Disease (COPD) is medically critical, but smoking for coping motives is a common barrier. In this evaluation of three treatment components (Mindfulness, Practice Quitting, and Countering Emotional Behaviors), we conducted two studies guided by the ORBIT model. Study 1 was a single-case design experiment (N = 18); Study 2 was a pilot feasibility study (N = 30). In both studies, participants were randomized to receive one of the three treatment modules. Study 1 examined implementation targets, changes in smoking for coping motives, and changes in smoking rate. Study 2 examined overall feasibility and participant-rated acceptability, and changes in smoking rate. Study 1: Treatment implementation targets were met by 3/5 Mindfulness participants, 2/4 Practice Quitting participants, and 0/6 Countering Emotional Behaviors participants. The Practice Quitting condition led to 100% of participants meeting the clinically significant threshold in smoking for coping motives. Incidence of quit attempts ranged from 0-50%, and smoking rate was reduced by 50% overall. Study 2: Recruitment and retention met feasibility targets, with 97% of participants completing all four treatment sessions. Participants reported high treatment satisfaction by qualitative responses and rating scales (M = 4.8/ 5.0). Incidence of quit attempts ranged from 25-58%, and smoking rate was reduced by 56% overall. These two small-N studies provide complementary findings on internal validity and implementation of the novel intervention. While Study 1 provided initial support for plausibility of clinically significant change, Study 2 provided data on key feasibility parameters. Smoking cessation for individuals with COPD is medically critical. We conducted an early-phase evaluation of a novel behavioral treatment focused on reducing smoking for coping motives. Results provided initial support for plausibility of clinically significant change and feasibility of the intervention.


Long-term exposure to ambient ozone and cardiovascular diseases: Evidence from two national cohort studies in China.
The health effects of ambient ozone have been investigated in many previous studies. However, the effects of long-term exposure to ambient ozone on the incidence of cardiovascular disease (CVD) remain inconclusive. To estimate the associations of long-term exposure to maximum daily 8-hours average ozone (MDA8 O3) with the incidence of total CVD, heart disease, hypertension, and stroke. This was a prospective cohort study, and the data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011-2018 and the China Family Panel Studies (CFPS) implemented during 2010-2018. We applied a Cox proportional hazards regression model to evaluate the associations of MDA8 O3 with total CVD, heart disease, hypertension, and stroke risks, and the corresponding population-attributable fractions (PAF) attributable to MDA8 O3 were also calculated. All analyses were conducted by R software. The mean MDA8 O3 concertation of all included participants in the CHARLS and CFPS were 51.03 part per billion (ppb) and 51.15 ppb, respectively. In the CHARLS including 18,177 participants, each 10 ppb increment in MDA8 O3 concentration was associated with a 31% increase [hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.22-1.42] in the risk of incident heart disease, and the corresponding population-attributable fractions (PAF) was 13.79% [10.12%-17.32%]. In the CFPS including 30,226 participants, each 10 ppb increment in MDA8 O3 concentration was associated with an increase in the risk of incident total CVD (1.07 [1.02-1.13]), and hypertension (1.10 [1.03-1.18]). The PAFs of total CVD, and hypertension attributable to MDA8 O3 were 3.53% [0.82%-6.16%], and 5.11% [1.73%-8.38%], respectively. Stratified analyses showed greater associations in males, urban areas, and Southern China. Long-term exposure to MDA8 O3 may increase the incidence of CVD. Therefore, the policies that control O3 and related precursors are persistently needed.


Three consistent patterns of response to substituted acridines in a variety of bacterial tester strains used for mutagenicity testing.
91 substituted acridines were tested for mutagenicity in 1 strain of Escherichia coli (TA78) and 4 strains of Salmonella typhimurium (TA90, TA1537, TA98 and TA100). In general, compounds fall into 3 groups: (i) inactive in all strains, (ii) active in TA78, TA90 and TA1537, or (iii) active in TA98 and often one or more of the other frameshift strains. Compounds of class iii have previously been shown to differ from the others in causing excisible damage to DNA and in showing an enhanced mutagenic response when the plasmid pKM101 is present.


A comparison of hair bundle mechanoreceptors in sea anemones and vertebrate systems.
Hair bundle mechanoreceptors of the acousticolateralis system of vertebrates are similar to hair bundles found on tentacles of sea anemones, primitive marine invertebrates. In each case, hair bundles consist of actin-based stereocilia interconnected by extracellular linkages. Recently, considerable attention has been directed to one class of linkages called "tip links." Tip links interconnect the tip of one stereocilium to the adjacent, taller stereocilium. According to the currently favored hypothesis for signal transduction, tip links may be "gating springs" that gate cation channels opened during deflection of the hair bundle. To depolarize the membrane, deflections must be directed so as to induce strain on the tip links. Deflections in the opposite direction lead to hyperpolarization of the membrane. Hair cells adapt to prolonged deflection of hair bundles. Whereas in some vertebrates, adaptation is incomplete (i.e., the current fails to return to baseline), adaptation in anemones appears to be complete. Signal transduction is reversibly blocked by agents thought to interact with the transduction channel including streptomycin. In addition, signal transduction is abolished following exposure to agents thought to attack tip links including calcium-depleted buffers or elastase. Hair cells of lower vertebrates can be replaced by division and differentiation of supporting cells. In chickens, a repair system exists wherein tip links are replaced via a mechanism that does not involve protein synthesis. The repair mechanism of anemones involves synthesis of new proteins that may constitute replacement linkages and accessory proteins that attach the linkages to appropriate integral proteins.


First SARS-CoV-2 vaccine booster and influenza vaccination: risk assessment of COVID-19 hospitalisation and death.
the influenza and SARS-CoV-2 viruses share a common respiratory symptomatology and transmission mode. COVID-19 and influenza R0 overlapped in the first epidemic wave. In autumn 2021-winter 2022, the influenza epidemic had a delayed onset compared to pre-COVID-19 years and lower incidence rates than in the pre-pandemic period. The SARS-CoV-2 and influenza vaccination campaign overlapped in 2021-2022. to evaluate in the SARS-CoV-2 vaccinated cohort the effect of different timing of influenza vaccination on hospitalisations for COVID-19 and overall mortality. prospective cohort study. subjects aged 65 years or older who were administered the first booster dose of SARS-COV-2 vaccine between 01.10.2021 and 01.03.2022. Based on the date of influenza vaccination, subjects were divided into the following 4 different mutually exclusive groups: 1. two vaccinations in the same vaccination session; 2. influenza vaccination following SARS-CoV-2 vaccination; 3. influenza vaccination preceding SARS-CoV-2 vaccination; 4. no influenza vaccination. Using Cox regression models, hazard ratio (HR) and corresponding 95% confidence intervals (95% CI) of hospitalisation and death were estimated for the influenza-vaccinated subjects compared to influenza-unvaccinated subjects. ordinary hospital admissions for COVID-19 and general mortality. the cohort included 618,964 subjects: 16.3% received two vaccinations in the same vaccination session, 8.5% received the influenza vaccination after SARS-CoV-2 vaccination, 33.9% received it before and 41.1% did not receive an influenza vaccination. Those vaccinated against both SARS-CoV-2 and influenza had a combined HR of 0.73 (0.62-0.86) of hospitalisation for COVID-19 and 0.55 (0.49-0.62) of overall mortality compared to those vaccinated against SARS-CoV-2 only. influenza vaccination combined with SARS-CoV-2 vaccination increases the protective effect against hospitalisations and overall mortality compared to SARS-CoV-2 vaccination alone. Both organisational and communication actions aimed to promote and encourage vaccination are required.


Production and characterization of monoclonal antibodies specific for bovine gamma-interferon.
Nine stable hybridoma cell lines were established which secreted specific monoclonal antibodies (MAbs) to bovine gamma-interferon (BoIFN-gamma). Specific binding of each of the MAbs to recombinant BoIFN-gamma (rBoIFN-gamma) was demonstrated in an indirect ELISA, whilst none of the MAbs bound to rBoIFN-alpha or rBoIFN-beta. In a Western blot the MAbs reacted with the 16 kDa and 32 kDa polypeptides present in rBoIFN-gamma preparations. Competitive ELISA's showed that four MAbs bound to one epitope on rBoIFN-gamma, and the other five MAbs bound to a separate epitope. Two MAbs, each recognising different epitopes, were shown to neutralise the anti-viral activity of natural BoIFN-gamma.