A computer-aided measuring system for the characterization of yeast populations combining 2D-image analysis, electronic particle counter, and flow cytometry.
An integrated measuring system was developed that directly compares the shape of size distributions of Saccharomyces cerevisiae populations obtained from either microscopic measurements, electronic particle counter, or flow cytometer. Because of its asymmetric mode of growth, a yeast population consists of two different subpopulations, parents and daughters. Although electronic particle counter and flow cytometer represent fast methods to assess the growth state of the population as a whole, the determination of important cell cycle parameters like the fraction of daughters or budded cells requires microscopic observation. We therefore adapted a semiautomatic and interactive 2D-image processing program for rapid and accurate determination of volume distributions of the different sub-populations. The program combines the capacity of image processing and volume calculation by contour-rotation, with the potential of visual evaluation of the cells. High-contrast images from electron micrographs are well suited for image analysis, but the necessary air drying caused the cells to shrink to 35% of their hydrated volume. As an alternative, hydrated cells overstained with the fluorochrome calcofluor and visualized by fluorescence light microscopy were used. Cell volumes calculated from length, and diameter measurements with the assumption of an ellipsoid cell shape were underestimated as compared to volumes derived from 2D-image analysis and contour rotation, because of a deviating cell shape, especially in the older parent cells with more than one bud scar. The bimodal volume distribution obtained from microscopic measurements was identical to the protein distribution measured with the flow cytometer using cells stained with dansylchloride, but differed significantly from the size distribution measured with the electronic particle counter. Compared with the flow cytometer, 2-D image analysis can thus provide accurate distributions with important additional information on, for instance, the distributions of subpopulations like parents, daughters, or budded cells.


Catalytic Addition of Alcohols into Carbodiimides Promoted by Organoactinide Complexes.
The insertion of alcohols into carbodiimides mediated by benzimidazolin-2-iminato actinide complexes [(BimR1/R2N)AnN″3] [N″ = N(SiMe3)2] is presented herein. Analysis of single-crystal data revealed that steric hindrance, rather than electronic properties, plays an important role in determining the accessibility for this insertion process. All actinide complexes showed excellent activities under very mild conditions. Stoichiometric reactions in combination with kinetic and thermodynamic studies allow us to propose a plausible active species and a mechanism for the catalytic cycle.


Energy, Carbon and Renewable Energy: Candidate Metrics for Green-aware Routing?
There are all sort of indications that Internet usage will go only upwards, resulting in an increase in energy consumption and CO2 emissions. At the same time, a significant amount of this carbon footprint corresponds to the information and communication technologies (ICT) sector, with around one third being due to networking. In this paper we have approached the problem of green networking from the point of view of sustainability. Here, alongside energy-aware routing, we have also introduced pollution-aware routing with environmental metrics like carbon emission factor and non-renewable energy usage percentage. We have proposed an algorithm based on these three candidate-metrics. Our algorithm provides optimum data and control planes for three different metrics which regulate the usage of different routers and adapt the bandwidth of the links while giving the traffic demand requirements utmost priority. We have made a comparison between these three metrics in order to show their impact on greening routing. The results show that for a particular scenario, our pollution-aware routing algorithm can reduce 36% and 20% of CO2 emissions compared to shortest path first and energy-based solutions, respectively.


Quantitative Trait Locus Mapping and Identification of Candidate Genes for Resistance to Fusarium Wilt Race 7 Using a Resequencing-Based High Density Genetic Bin Map in a Recombinant Inbred Line Population of Gossypium barbadense.
Fusarium wilt caused by Fusarium oxysporum f. sp. vasinfectum (FOV) is one of the most destructive diseases in cotton (Gossypium spp.) production, and use of resistant cultivars is the most cost-effective method managing the disease. To understand the genetic basis of cotton resistance to FOV race 7 (FOV7), this study evaluated a recombinant inbred line (RIL) population of 110 lines of G. barbadense from a cross between susceptible Xinhai 14 and resistant 06-146 in eight tests and constructed a high-density genetic linkage map with resequencing-based 933,845 single-nucleotide polymorphism (SNP) markers covering a total genetic distance of 2483.17 cM. Nine quantitative trait loci (QTLs) for FOV7 resistance were identified, including qFOV7-D03-1 on chromosome D03 in two tests. Through a comparative analysis of gene expression and DNA sequence for predicted genes within the QTL region between the two parents and selected lines inoculated with FOV7, GB_D03G0217 encoding for a calmodulin (CaM)-like (CML) protein was identified as a candidate gene. A further analysis confirmed that the expression of GB_D03G0217 was suppressed, leading to increased disease severity in plants of the resistant parent with virus induced gene silencing (VIGS).


Atom-economical synthesis of a high silica CHA zeolite using a solvent-free route.
A high silica CHA zeolite is successfully synthesized in the presence of a small amount of N,N,N-dimethylethylcyclohexylammonium bromide under solvent-free conditions. Catalytic tests for the selective catalytic reduction of NOx with NH3 (NH3-SCR) and methanol-to-olefins (MTO) show that the sample from the solvent-free route exhibits comparable catalytic properties to that from the conventional route.


Multiple pigmented basal cell carcinomas.
Basal cell carcinoma is the most common of all skin cancers and the most prevalent one among Caucasians. Rarely, these tumors are seen in other races. We report a 77-year-old Korean woman who presented with multiple darkly pigmented enlarging nodules on her scalp, face, trunk, and extremities. The patient had first noted a 6-mm pigmented lesion on her left eyebrow 10 years previously. Since then, other lesions had appeared in many locations on her body. She had been otherwise healthy and without a history of exposure to arsenic or radiation. There was no family history of skin cancer, xeroderma pigmentosum, or basal cell nevus syndrome. On physical examination, multiple darkly pigmented dome-shaped papules and nodules were present on her scalp, face, right forearm, lower abdomen, and inguinal areas. They ranged in size from 0.5 mm to 2 cm. The larger ones showed central ulceration. Multiple biopsy specimens from different sites showed pigmented basal cell carcinomas. Clinically, there was no evidence of nevus sebaceus, xeroderma pigmentosum, basal cell nevus syndrome, or immunodeficiency. Clinical workup including chest radiography, abdominal ultrasound, bone scan, and brain computerized axial tomography scan did not demonstrate primary or secondary tumors. The results of serologic and hematologic tests were also within normal limits. This is an unusual case report of multiple pigmented basal cell carcinomas in an Asian woman without any predisposing risk factors.


Level of play and coach-rated game intelligence are related to performance on design fluency in elite soccer players.
Executive brain functions are innate mechanisms for regulating behavior. While the impact of suboptimal executive functions has been characterized in patients, their contribution to individual success has not been elucidated. We set out to understand how executive functions relate to successful human behavior by examining their relation to game intelligence in sport - the ability to read a game and quickly adapt the behavior. In elite soccer players (n = 51), those playing in national teams (national team players) significantly outperformed those only playing at premier league level (premier league players) in Design Fluency (DF), a complex visuo-spatial executive function test that includes measures of creativity and cognitive flexibility. Their result showed a moderate correlation with coach rated game intelligence, remained also when correcting for low level cognitive capacity and was most evident when considering cognitive flexibility. DF capacity also correlated with number of assists made during the season but not with number of made goals during the same period, linking the fast planning of several steps in DF to fast planning of several steps in the soccer game. Altogether, our data suggests that DF capacity relates to success in soccer both on a subjective and on an objective level.


A one-dimensional theoretical prediction of the effect of reduced end-plate permeability on the mechanics of the intervertebral disc.
The permeability of the cartilage end-plate (CEP) may play an important role in intervertebral disc (IVD) degeneration by controlling the convective and diffusive transport of metabolites into the nucleus pulposus. A one-dimensional poroelastic model was used to predict the effect of a CEP of lower permeability than the disc tissue on the convective transfer into and out of the IVD. With decreasing CEP permeability, associated with degeneration, the model predicted that the change in disc height with time became more linear; the disc could not rehydrate as quickly; and internal fluid movement was slowed. This study has shown that CEP permeability will only markedly have an effect on fluid movement, and hence convective nutrition, if the permeability of the CEP is reduced to less than that of the disc tissue.


[A Case of Germ Cell Tumor in which Necrotic Tissue Revealed hCG-Positive in Surgical Specimen of Post-Chemotherapy Retroperitoneal Lymph Node Dissection].
The patient was a 27-year-old male. In December 2020, he was diagnosed with a primary extragonadal germ cell tumor of the retroperitoneum with inferior vena caval (IVC) involvement. After 3 courses of bleomycin, etoposide and cisplatinum and 3 courses of paclitaxel, ifosfamide and cisplatin, the serum human chorionic gonadotropin (hCG) level remained abnormally low. He was referred to our department after follow-up for 2 months. Since the hCG level continued to decrease during follow-up, we decided to perform marker-positive surgery. He underwent retroperitoneal lymph node dissection. We also resected a part of the IVC wall and tumor in the IVC. The serum hCG level was normalized at 5 days after surgery. Pathological examination revealed only necrotic tissue. Immunohistochemistry showed hCG positive in the necrotic tissue.


Proton magnetic resonance spectroscopy and outcome in term neonates with chorioamnionitis.
Evaluate brain metabolites, which reflect neuroinflammation, and relate to neurodevelopmental outcomes in healthy term neonates exposed to chorioamnionitis. Thirty-one healthy term neonates with documented fetal inflammatory response after maternal chorioamnionitis underwent magnetic resonance spectroscopy (MRS), with voxels placed in basal ganglia (BG) and frontal white matter. Bayley III examinations were performed at 12 months of age. Infants with below average outcomes did not show the same increase in NAA/Cho ratios postnatally as the group with normal outcomes. Decreased NAA/Cho and increased Lac/Cr in BG correlated with lower motor and cognitive composite scores, respectively, controlling for postnatal age. In males, increased lactate/NAA in BG were associated with lower motor scores. Funisitis severity was associated with decreased NAA/Cho and increased mI/NAA in males. In healthy term newborns with chorioamnionitis, MRS ratios shortly after birth may provide evidence of occult neuroinflammation, which may be associated with worse performance on 1-year neurodevelopmental tests.


The transmission potential of Rift Valley fever virus among livestock in the Netherlands: a modelling study.
Rift Valley fever virus (RVFV) is a zoonotic vector-borne infection and causes a potentially severe disease. Many mammals are susceptible to infection including important livestock species. Although currently confined to Africa and the near-East, this disease causes concern in countries in temperate climates where both hosts and potential vectors are present, such as the Netherlands. Currently, an assessment of the probability of an outbreak occurring in this country is missing. To evaluate the transmission potential of RVFV, a mathematical model was developed and used to determine the initial growth and the Floquet ratio, which are indicators of the probability of an outbreak and of persistence in a periodic changing environment caused by seasonality. We show that several areas of the Netherlands have a high transmission potential and risk of persistence of the infection. Counter-intuitively, these are the sparsely populated livestock areas, due to the high vector-host ratios in these areas. Culex pipiens s.l. is found to be the main driver of the spread and persistence, because it is by far the most abundant mosquito. Our investigation underscores the importance to determine the vector competence of this mosquito species for RVFV and its host preference.


Exploring Zeptosecond Quantum Equilibration Dynamics: From Deep-Inelastic to Fusion-Fission Outcomes in ^{58}Ni+^{60}Ni Reactions.
Energy dissipative processes play a key role in how quantum many-body systems dynamically evolve toward equilibrium. In closed quantum systems, such processes are attributed to the transfer of energy from collective motion to single-particle degrees of freedom; however, the quantum many-body dynamics of this evolutionary process is poorly understood. To explore energy dissipative phenomena and equilibration dynamics in one such system, an experimental investigation of deep-inelastic and fusion-fission outcomes in the ^{58}Ni+^{60}Ni reaction has been carried out. Experimental outcomes have been compared to theoretical predictions using time dependent Hartree-Fock and time dependent random phase approximation approaches, which, respectively, incorporate one-body energy dissipation and fluctuations. Excellent quantitative agreement has been found between experiment and calculations, indicating that microscopic models incorporating one-body dissipation and fluctuations provide a potential tool for exploring dissipation in low-energy heavy ion collisions.


Effect of 13-norleucin motilin on water and ion transport in the human jejunum.
Passage of the interdigestive migrating myoelectric complex through the proximal small bowel is associated with elevated plasma motilin levels and an increase in transmucosal potential difference suggesting altered ion transport. The aim of the present study was to investigate whether motilin may have an effect on intestinal water and ion transport. Steady state jejunal perfusion studies were carried out in healthy volunteers while either saline (control) or synthetic motilin (256 pmol/kg X h) was infused via peripheral vein. Plasma motilin levels rose from a mean of 31 to a plateau of 832 pmol/L. Motilin infusion significantly reduced absorption of water, sodium, potassium, and chloride when a plasmalike electrolyte solution was perfused. During perfusion with a bicarbonate-free salt solution, motilin significantly enhanced secretion of water, potassium, and chloride. Chloride secretion was active inasmuch as it occurred against both an electrical and chemical gradient. Motilin infusion had no effect on transit time during perfusion of the 30-cm jejunal test segments. We conclude that motilin can act as an intestinal secretagogue in the human jejunum.


Transient regimes and crossover for epitaxial surfaces.
We apply a formalism for deriving stochastic continuum equations associated with lattice models to obtain equations governing the transient regimes of epitaxial growth for various experimental scenarios and growth conditions. The first step of our methodology is the systematic transformation of the lattice model into a regularized stochastic equation of motion that provides initial conditions for differential renormalization-group (RG) equations for the coefficients in the regularized equation. The solutions of the RG equations then yield trajectories that describe the original model from the transient regimes, which are of primary experimental interest, to the eventual crossover to the asymptotically stable fixed point. We first consider regimes defined by the relative magnitude of deposition noise and diffusion noise. If the diffusion noise dominates, then the early stages of growth are described by the Mullins-Herring (MH) equation with conservative noise. This is the classic regime of molecular-beam epitaxy. If the diffusion and deposition noise are of comparable magnitude, the transient equation is the MH equation with nonconservative noise. This behavior has been observed in a recent report on the growth of aluminum on silicone oil surfaces [Z.-N. Fang, Thin Solid Films 517, 3408 (2009)]. Finally, the regime where deposition noise dominates over diffusion noise has been observed in computer simulations, but does not appear to have any direct experimental relevance. For initial conditions that consist of a flat surface, the Villain-Lai-Das Sarma (VLDS) equation with nonconservative noise is not appropriate for any transient regime. If, however, the initial surface is corrugated, the relative magnitudes of terms can be altered to the point where the VLDS equation with conservative noise does indeed describe transient growth. This is consistent with the experimental analysis of growth on patterned surfaces [H.-C. Kan, Phys. Rev. Lett. 92, 146101 (2004); T. Tadayyon-Eslami, Phys. Rev. Lett. 97, 126101 (2006)].


RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells.
Antibody diversification by somatic hypermutation, gene conversion, and class switch recombination is completely dependent on activation-induced cytidine deaminase (AID). A recent report showing induction of DNA mutations in Escherichia coli by overexpression of AID, Apobec-1, and related members of the RNA-editing cytidine deaminase family suggested that they may directly modify deoxycytidine in DNA in mammalian cells (DNA-editing model). We therefore examined whether Apobec-1 bona fide RNA-editing enzyme could show somatic hypermutation and class switching activities in murine B lymphocytes and fibroblasts. Unlike AID, Apobec-1 was unable to induce somatic hypermutation or class switching. The results force a reevaluation of the physiological significance of the DNA deaminase activities of AID and Apobec-1 in E. coli and in vitro.


Iron toxicity: new conditions continue to emerge.
During the past half century, excessive/misplaced iron has been observed to be a risk factor for an increasing number and diversity of disease conditions. An extensive list of conditions and of the types of iron association were published in early 2008. Within the subsequent year, four additional disorders have been recognized to be enhanced by iron: aging muscle atrophy, viral replication, rosacea and pulmonary alveolar proteinosis. This paper adds new data and emphasis on these disorders as entities associated with increased iron load and toxicity.


Weighted gene co-expression network analysis revealed the key pathways and hub genes of potassium regulating cotton root adaptation to salt stress.
Soil salinization is one of the main abiotic stresses affecting cotton yield and planting area. Potassium application has been proven to be an important strategy to reduce salt damage in agricultural production. However, the mechanism of potassium regulating the salt adaptability of cotton has not been fully elucidated. In the present research, the appropriate potassium application rate for alleviating salt damage of cotton based on different K+/Na+ ratios we screened, and a gene co-expression network based on weighted gene co-expression network analysis (WGCNA) using the transcriptome data sets treated with CK (0 mM NaCl), S (150 mM NaCl), and SK8 (150 mM NaCl + 9.38 mM K2SO4) was constructed. In this study, four key modules that are highly related to potassium regulation of cotton salt tolerance were identified, and the mitogen-activated protein kinase (MAPK) signaling pathway, tricarboxylic acid (TCA) cycle and glutathione metabolism pathway were identified as the key biological processes and metabolic pathways for potassium to improve cotton root salt adaptability. In addition, 21 hub genes and 120 key candidate genes were identified in this study, suggesting that they may play an important role in the enhancement of salt adaptability of cotton by potassium. The key modules, key biological pathways and hub genes discovered in this study will provide a new understanding of the molecular mechanism of potassium enhancing salinity adaptability in cotton, and lay a theoretical foundation for the improvement and innovation of high-quality cotton germplasm.


Significance of Microvascular Function in Visual-Functional Mismatch Between Invasive Coronary Angiography and Fractional Flow Reserve.
Despite a moderate correlation between angiographical stenosis and physiological significance, the mechanism of discordance has not been fully elucidated, particularly regarding the significance of microvascular function. This study sought to clarify whether microvascular function affects visual-functional mismatch between quantitative coronary angiography (QCA) and fractional flow reserve (FFR). We assessed QCA, FFR, coronary flow reserve, and the index of microcirculatory resistance in 849 non-left-main coronary lesions with visually estimated intermediate stenoses from 532 patients. Clinical and lesion-specific characteristics and physiological parameters associated with mismatch and reverse mismatch were studied. Coronary flow reserve and index of microcirculatory resistance showed a weak, but significant, correlation with FFR (R=0.306, P<0.001 and R=0.158, P<0.001, respectively). Four hundred twenty-two lesions were visually nonsignificant (diameter stenosis assessed by QCA [QCA-DS] ≤50%) and 427 lesions were visually significant (QCA-DS >50%). Among visually nonsignificant lesions, FFR ≤0.80 (reverse mismatch) was observed in 129 lesions (30.6%). Among visually significant lesions, FFR >0.80 (mismatch) were observed in 179 lesions (41.9%). The significant predictors of reverse mismatch were male sex, nonculprit lesions of acute coronary syndrome, left anterior descending artery location, smaller QCA reference diameter, greater QCA-DS, lower coronary flow reserve, and lower index of microcirculatory resistance. Mismatch was associated with right coronary artery location, greater QCA reference diameter, smaller QCA-DS, lesion length, higher coronary flow reserve, and higher index of microcirculatory resistance. There was a high prevalence of visual-functional mismatches between QCA and FFR. The discrepancy was related to clinical characteristics, lesion-specific factors, and microvascular resistance that was undistinguishable by coronary angiography, thus suggesting the importance of physiological lesion assessment.


Transferring the Selectivity of a Natural Antibody into a Molecularly Imprinted Polymer.
Natural antibodies are widely used for their unprecedented reproducibility and the remarkable selectivity for a wide range of analytes. However, biodegradability and the need to work in biocompatible environments limit their applications. Molecularly imprinted polymers are a robust alternative. While molecularly imprinted polymers have shown remarkable selectivities for small molecules, large structures as proteins, viruses or entire cells are still problematic and flexible structures are virtually impossible to imprint. We have developed a method to form a polymeric copy of the antibodies instead. This book chapter aims to summarize the progress with this technique. To make it easier for other scientists to use this methods I critically discuss advantages and drawbacks of the method compared to alternative techniques. The discussion should help to identify for which applications this technique would be valuable. Finally, I provide a practical guide to use this new method. I highlight potential problems and give hints for possible improvements or adaptations for different applications.


[Surveillance of bacterial resistance in children aged 0-14 years from 2018 to 2022].
Objective: To understand the distribution and antimicrobial resistance of common bacteria from children aged 0-14 years from China Antimicrobial Resistance Surveillance System. Methods: Bacterial resistance data of 2 575 040 strains from children aged 0-14 years were extracted from the national bacterial resistance surveillance reports from October 2018 to September 2022 and resistance changes were further analyzed by comparing with all data in each year. Results: The total number of bacteria isolated from children in 2018-2022 ranged from 415 306-588 016 strains, accounted for 15.9% (514 193/3 234 372), 16.2% (572 107/3 528 471), 12.8% (415 306/3 249 123), 13.0% (485 418/3 743 027), and 12.2% (588 016/4 828 509), respectively. The proportions of gram-positive bacteria among children were 45.4% (233 456/514 193), 44.5% (254 869/572 107), 44.7% (185 756/415 306), 42.6% (206 903/485 418), and 41.7% (245 044/588 016), respectively. The top five isolates of gram-positive bacteria were Staphylococcus aureus (36.0%-38.8%), Streptococcus pneumoniae (27.1%-31.7%), Staphylococcus epidermidis (7.3%-9.3%), Enterococcus faecium (4.0%-4.8%), and Enterococcus faecium (2.5%-3.6%), and the top five isolates of gram-negative bacteria were Escherichia coli (21.8%-26.2%), Haemophilus influenzae (14.4%-26.4%), Klebsiella pneumoniae (10.1%-14.7%), Moraxella catarrhalis (7.3%-11.9%), and Pseudomonas aeruginosa (5.5%-6.8%). The bacteria from children aged 0-14 years commonly isolated from sputum samples (48.8%-57.0%). The prevalence of methicillin-resistant S. aureus was 28.7%-30.1%. The detection rates of vancomycin-resistant E. faecalis or E. faecium were 0.1%-0.3%. The proportions of non-cerebrospinal fluid-derived penicillin-resistant S. pneumoniae were 0.7%-1.6%. The prevalence of cefotaxime and (or) ceftriaxone-resistant E. coli and K. pneumoniae decreased were 43.7%-50.0% and 31.8%-42.7%, respectively. The resistant rates of E. coli to imipenem and meropenem were 1.2%-1.9% and 1.2%-2.0%, respectively, and the resistant rates of K. pneumoniae to imipenem and meropenem were 7.3%-10.1% and 8.2%-12.2%, respectively. About 6.6%-10.2% and 5.3%-9.6% of the P. aeruginosa isolates showed resistant to imipenem and meropenem, respectively, while 17.2%-24.0% and 19.0%-29.4% of the Acinetobacter baumannii isolates were resistant to imipenem and meropenem, respectively. Conclusions: There is no significant change in the composition of common clinical pathogens in children aged 0-14 years from 2018 to 2022. The prevalence of some resistant bacteria such as methicillin-resistant S. aureus and carbapenem-resistant Enterobacterales is decreasing. However, it is necessary to pay attention to antimicrobial resistance of bacteria from children and long-term monitoring of the prevalence of resistant bacteria should be conducted.


A Parent-child yoga intervention for reducing attention deficits in children with congenital heart disease: the Yoga for Little Hearts Feasibility Study Protocol.
Preschoolers and school-aged children with congenital heart disease (CHD) are at higher risk of attention deficit hyperactivity disorder (ADHD) compared with the general population. To this day, no randomised controlled trial (RCT) aiming to improve attention has been conducted in young children with CHD. There is emerging evidence indicating that parent-child yoga interventions improve attention and reduce ADHD symptoms in both typically developing and clinical populations. This is a single-blind, two-centre, two-arm trial during which 24 children with CHD and their parents will be randomly assigned to (1) a parent-child yoga intervention in addition to standard clinical care or (2) standard clinical care alone. All participants will undergo standardised assessments: (1) at baseline, (2) immediately post-treatment and (3) 6 months post-treatment. Descriptive statistics will be used to estimate the feasibility and neurodevelopmental outcomes. This feasibility study will evaluate: (1) recruitment capacity; (2) retention, drop-out and withdrawal rates during the yoga programme and at the 6-month follow-up; (3) adherence to the intervention; (4) acceptability of the randomisation process by families; (5) heterogeneity in the delivery of the intervention between instructors and use of home-based exercises between participants; (6) proportion of missing data in the neurodevelopmental assessments and (7) SD of primary outcomes of the full RCT in order to determine the future appropriate sample size. Ethical approval has been obtained by the Research Ethics Board of the Sainte-Justine University Hospital. The findings will be disseminated in peer-reviewed journals and conferences and presented to the Canadian paediatric grand round meetings. NCT05997680.


The diversity of electron-transport behaviors of molecular junctions: correlation with the electron-transport pathway.
We report the electron-transport behaviors of a number of molecular junctions composed of pi-conjugated molecular wires. From calculations performed by using density functional theory (DFT) combined with the non-equilibrium Green's function (NEGF) method, we found that the length-conductivity relations are diverse, depending on the particular molecular structures. The results reveal that the conductance-length dependence follows an exponential law for many conjugated molecules with a single channel, such as oligothiophene, oligopyrrole and oligophenylene. Therefore, a quantitative relation between the energy gap (E(g))(infinity) of the molecular wire and the attenuation factor beta can be defined. However, when the molecular wires have multichannels, the decay of conductance does not follow the exponential relation. For example, the conductance of porphyrin-based oligomers and fused thiophene decays almost linearly. The diversity of electron-transport behaviors of molecular junctions is directly dominated by the electron-transport pathway.


Collecting duct carcinoma of the kidney: Imaging observations of a rare tumor.
Collecting duct carcinoma (CDC) is a rare type of renal neoplasm. Early diagnosis is possibly the only factor leading to a prolonged survival for patients with CDC. The purpose of the present study was to characterize the imaging features of CDC and improve its diagnosis. Radiological data of six patients were retrospectively reviewed by three experienced radiologists, including six cases examined with non-contrast computed tomography (CT) scans, five with contrast-enhanced CT scans, one with magnetic resonance urography, one with renal dynamic imaging and two with conventional whole-body 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans. All patients were pathologically confirmed with CDC. In total, seven tumors were detected in the six cases, with a mean size of 5.3 cm. Of the tumors, two were solid and the rest were complex solid and cystic. In addition, six tumors were located in medullary areas and only one tumor was found in the cortical location. Cystic components were observed in five tumors. Weak enhancements were observed in all six tumors examined with contrast-enhanced CT, and heterogeneous enhancements were also observed in the majority of these tumors with the exception of one tumor. Infiltrative growth and expansible growth were found in five and two tumors, respectively. Metastatic lesions were detected in all six patients. On MR urography, the involved kidney exhibited similar imaging observations to the CT scan. Renal dynamic imaging revealed a decreased renal function in the involved kidney and an increased renal function in the contralateral kidney. On PET/CT imaging, a marked uptake of 18F-FDG was found in primary and metastatic lesions. The results of the present study indicated that medullary location, weak and heterogeneous enhancement, infiltrative growth, damage of renal function in the involved kidney and a marked uptake of 18F-FDG are imaging observations commonly identified in patients with CDC. When a renal tumor exhibits these imaging features, CDC may be suggested as a valuable differential diagnosis.


Magnons as pseudo-Goldstones in La-based cuprates: the effects of doping.
In the Néel phase of La-based cuprates, magnons are pseudo-Goldstones as the rotational symmetry of the spin system is explicitly broken by the small anisotropies. Respecting the approximate SO(3) symmetry we calculate the doping and temperature dependence of the magnon gaps in La2-xSrxCuO4 (LSCO) within the framework of the anisotropic linear σ-model coupled to dipoles representing holes. We show that the temperature behaviour of the reduced magnon gaps depends weakly on the hole concentration and that the relative in-plane gap reduction with doping is insensitive to anisotropies of the parent compound. The obtained magnon gaps agree with experiments on LSCO, in particular the strong in-plane gap reduction with doping is reproduced.


Resilience in 2021-Descriptive Analysis of Individuals Accessing Virtual Mental Health Services: Retrospective Observational Study.
Psychological resilience has been extensively studied by developmental researchers, and there is a growing body of literature regarding its role in psychiatry and psychopathology research and practice. This study contributes to this growing literature by providing real-world evidence on the relationship between resilience and clinical symptoms among a large sample of employed Americans. This study aimed to describe resilience levels in individuals accessing Ginger, a virtual mental health system, in addition to the association of resilience with demographic characteristics, baseline depression, and anxiety symptoms. We conducted a retrospective observational study of 9165 members who signed up for Ginger and completed a baseline survey between January 1 and August 5, 2021. We used multivariate regression models to test for associations between baseline resilience and other member characteristics. Baseline resilience scores centered on a mean of 23.84 (SD 6.56) and median of 24 (IQR 8) out of 40, with 81.0% (7424/9165) of the sample having low resilience at baseline. Despite having relatively higher resilience scores, members with no or mild depression or anxiety still had low resilience scores on average. Self-reported suicidal ideation was associated with lower resilience. Overall, members had low baseline resilience, similar to resilience levels observed in trauma survivors in prior studies. Younger members and those with higher levels of depression and anxiety at intake reported lower levels of resilience at baseline. Notably, members with no or mild depression or anxiety still had low resilience scores on average, suggesting a need for mental health support among individuals who might not typically be recommended for treatment based on traditional clinical assessments, such as the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item Generalized Anxiety Disorder scale (GAD-7). Two suggestions for topics of future research are to develop treatment recommendations based on the Connor-Davidson Resilience Scale and to understand the interaction between resilience levels and symptom-based outcome measures, such as the PHQ-9 and the GAD-7.


Repair of Lower Canalicular Laceration Using the Mini-Monoka Stent: Primary and Revisional Repairs.
We present our results of primary repair of lower canalicular injury using the Mini-Monoka stent and report our experience with revisional repair of canalicular blocks to treat epiphora following primary repair METHODS:: We performed primary repair in 169 canalicular laceration patients using Mini-Monoka. The primary repair was defined as the first operation proceeded within 48 hours after injury. Revisional repairs were performed in patients who underwent primary repair of canalicular laceration and subsequently complained of epiphora with canalicular block owing to peripheral scarring. In revisional repair, a Mini-Monoka stent was reinserted to maintain the realigned lacrimal pathway. The primary repair achieved functional success in 94.7% of patients. After primary repair, nine patients complained of epiphora. Two of 9 patients underwent CDCR and 5 underwent revisional repair of canalicular blockage. The revisional repair achieved functional success in 4 of 5 patients. After revisional repair, scar contracture and asymmetry of the medial canthus or malposition of the lower lacrimal punctum were corrected. Cosmetically, all 5 patients were satisfied with the results. Functionally, one patient complained persistent epiphora and was treated with CDCR. We were able to experience simple, safe, and successful primary repair of lower canalicular injuries using the Mini-Monoka stent. If epiphora owing to canalicular block after primary repair and asymmetry of the medial canthus owing to scar contracture or malposition of lacrimal punctum are present, scar release and realignment of the canaliculus with Mini-Monoka insertion at the time of revisional repair are recommended.


Analysis of leaf forage value and screening of different populations of Pteroceltis tatarinowii, a rare and endemic species in China.
To fully exploit the economic value of the Chinese endemic species Pteroceltis tatarinowii and provide new resources for forage production, the forage nutritional value of P. tatarinowii leaves from different populations was analyzed and evaluated. The results were as follows: 1) There were significant differences in the forage nutrient indices of leaves from different populations. The crude protein content was 10.77%-18.65%, with an average of 14.58%, and the SDJN population had the highest crude protein content. The average crude fat, crude fiber content was 7.62%; the average neutral detergent fiber content was 25.33%; and the average acid detergent fiber contents were 6.79%, 7.62%, 25.33%, and 17.52%, respectively. The average phosphorus and calcium content in the leaves was 0.785 g·kg-1 and 58.01 g·kg-1, respectively. The tannin content was much lower than the antifeedant standard, at an average of 4.97 g·kg-1. The average total amounts of hydrolyzed and free amino acids in the leaves were 108.20 mg·g-1 and 47.87 mg·g-1, respectively. Thus, P. tatarinowii leaves have high crude protein, crude fat, and calcium contents, and low fiber, tannin contents, and are protein-rich. These results provide evidence that this species can be developed into an excellent woody forage tree. 2) There were significant differences in the forage quality evaluation indices among the populations. The forage indices of NDP, ADP, DMI, DDM, and RFV of 21 populations all met the super standard of the American Grass and Grassland Association (AFGC) for hay, two crude protein indices met the grade 1 standard, and 12 crude protein indices met the grade 2 standard. Four high-protein and high-RFV forage populations (SDJN, SDZZ, SXLQ, and AHXX) were selected. 3) The results of the correlation analysis showed that there was no significant correlation between the forage characteristics of P. tatarinowii leaves and latitude and longitude, indicating no significant geographical variation. However, the forage characteristics were strongly correlated with elevation, average annual temperature, and annual precipitation. Thus, high elevation, low temperatures, and rainy weather can improve the forage value of the leaves. P. tatarinowii can be planted to provide leaf forage in cold and wet areas at a specific elevation. Moreover, the forage value of P. tatarinowii leaves can be further improved by increasing nitrogen fertilizer and reducing K and Ca fertilizers during cultivation. 4) Cluster analysis revealed obvious regionalism. Taking the Yangtze River Basin as the limit, cluster analysis divided the species into four population groups: the Yangtze River Basin and northern, southwestern, and eastern coastal populations.


Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats.
Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis, but the actual species responsible remains unclear. We studied the alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline (control) treatment, hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O(2) consumption, and cardiac efficiency were markedly depressed in LPS hearts compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats, and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca(2+)-independent NO synthase (NOS) activity, and inducible NOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS-treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.


Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen-Presenting Cells.
To determine at the phenotypic, functional, and transcriptional levels whether abatacept, a CTLA-4Ig molecule that binds with high affinity to CD80/86 on antigen-presenting cells (APCs) and is used to treat rheumatoid arthritis, induces a state of immunologic tolerance in T cells and dendritic cells in mice. We investigated the capacity of abatacept to regulate the development of antigen-specific immunologic tolerance in vivo using murine models of priming and tolerance to generate highly purified antigen-specific T cell populations and CD11c+ APCs. These were combined with detailed immunologic and full genome transcriptional analyses. We found that abatacept inhibited T cell activation, but did not render T cells anergic or lead to the generation of Treg cells. However, it induced a sustained inhibition of T cell activation due to the inability of these cells to progress through the cell cycle following T cell receptor stimulation. We also observed that this state was accompanied by an inhibition of dendritic cell activation due to their reduced licensing by T cells. This study provides detailed insight into the mode of action of abatacept, demonstrating that its effectiveness is not due to the induction of T cell tolerance, but rather to a sustained inhibition of T cell activation that results in reduced functionality of APCs, with significant implications for its clinical application.


[The role of phospholipase A2, 5-lipoxygenase, and cyclooxygenase in activation of human neutrophil "oxygen burst": the modulating effect of osmolality of the medium].
The roles of phospholipase A2, 5-lipoxygenase and cyclooxygenase in activation of "oxidative burst" in human neutrophils have been studied under isoosmotic (320 mOsM), hypoosmotic (200 mOsM) and hyperosmotic (420 mOsM) conditions. The oxidative burst induced by phorbol-12-myristate-13-acetate (PMA), calcium ionophore A23187 and opsonized zymosan was followed by luminol-dependent chemiluminescence (CL). There were no differences in the concentration dependences of CL inhibition at 320 mOsM and 200 mOsM in the presence of the phospholipase A2 inhibitor, p-bromphenacylbromide. Contrariwise, at 420 mOsM the sensitivity to inhibition was decreased by PMA and A23187 but increased by opsonized zymosan. A change in the medium osmolality in the presence of the 5-lipoxygenase inhibitor quercetin did not result in the modification of the concentration dependence of CL inhibition induced by any of the activators. In the presence of the cyclooxygenase inhibitor, meclofenamic acid, the "oxidative burst" induced by PMA and A23187 at 200 mOsM was manifested as a decrease of the sensitivity to inhibition, while at 420 mOsM this sensitivity was increased in comparison with that observed under isoosmotic conditions. The data obtained suggest that phospholipase A2 and cyclooxygenase play a role in the mechanism of the modulating effect of the medium osmolality on the "oxidative burst" in neutrophils, while 5-lipoxygenase is unimportant for this process.


Mild electrical stimulation with heat stimulation increase heat shock protein 70 in articular chondrocyte.
The objective of this study is to investigate the effects of mild electrical stimulation (MES) and heat stress (HS) on heat shock protein 70 (HSP70), that protects chondrocytes and enhances cartilage matrix metabolism, in chondrocyte and articular cartilage. Rabbit articular chondrocytes were treated with MES and/or HS. The safeness was assessed by LDH assay and morphology. HSP70 protein, ubiquitinated proteins and HSP70 mRNA were examined by Western blotting and real-time PCR. Rat knee joints were treated with MES and/or HS. HSP70 protein, ubiquitinated proteins, HSP70 mRNA and proteoglycan core protein (PG) mRNA in articular cartilage were investigated. In vitro, HS increased HSP70 mRNA and HSP70 protein. MES augmented ubiquitinated protein and HSP70 protein, but not HSP70 mRNA. MES + HS raised HSP70 mRNA and ubiquitinated protein, and significantly increased HSP70 protein. In vivo, HS and MES + HS treatment augmented HSP70 mRNA. HS modestly augmented HSP70 protein. MES + HS significantly increased HSP70 protein and ubiquitinated proteins. PG mRNA was markedly raised by MES + HS. This study demonstrated that MES, in combination with HS, increases HSP70 protein in chondrocytes and articular cartilage, and promotes cartilage matrix metabolism in articular cartilage. MES in combination with HS can be a novel physical therapy for osteoarthritis by inducing HSP70 in articular cartilage.


The fate of insulin in rat hepatocytes. Evidence for the release of an immunologically active fragment.
We have investigated the fate of 125I-insulin after binding by rat hepatocytes. Approximately 30% of the bound radioactivity dissociated from the cells as intact 125I-insulin; approximately 56% dissociated as 125I- and 125I-Tyr. The remaining radioactivity was recovered as peptides that we postulate are intermediate products of insulin metabolism. Experiments were performed in the presence of chloroquine (0.1 mM), an agent known to inhibit the intracellular processing of 125I-insulin. As expected, chloroquine increased the amount of radioactivity recovered as intact 125I-insulin (P less than 0.005) and decreased the amount of 125I- and 125I-Tyr (P less than 0.005). In addition, chloroquine decreased the amount of one of the insulin peptides (P less than 0.005), but increased the amount of the other (P less than 0.01). These data suggest the presence of two pathways of insulin metabolism in rat hepatocytes, one of which is inhibited by chloroquine. We have found a second pathway by which insulin is degraded due to the removal of several amino acids from the carboxy-terminus of the B-chain. The resulting fragment bound poorly to insulin receptors on IM-9 cultured human lymphocytes, and probably has little if any biologic activity. However, this fragment bound well to anti-insulin antibody and constituted about 20% of the immunoreactive radioactivity that dissociated from the hepatocytes.


iPSC-Derived Trabecular Meshwork Cells Stimulate Endogenous TM Cell Division Through Gap Junction in a Mouse Model of Glaucoma.
Decreased trabecular meshwork (TM) cellularity has been implicated as a major reason for TM dysfunction and aqueous humor (AH) outflow abnormalities in primary open angle glaucoma. We previously found that transplantation of induced pluripotent stem cell (iPSC)-derived TM cells can restore TM function and stimulate endogenous TM cell division. The goal of the present study is to investigate whether signaling via gap junctions is involved in this process. Differentiated iPSCs were characterized morphologically, transcriptionally, and immunohistochemically. After purification, iPSC-TM were co-cultured with mouse TM (MTM) cells to mimic the transplantation procedure. Through the pharmacological antagonists and short hairpin RNA (shRNA) technique, the gap junction function in iPSC-based therapy was determined. In the co-culture system, iPSC-TM increase MTM cell division as well as transfer of Ca2+ to MTM. This effect was blocked by treatment with the gap junction inhibitors carbenoxolone (CBX) or flufenamic acid (FFA). The shRNA mediated knock down of connexin 43 (Cx43) expression in iPSC-TM also results in decreased Ca2+ transfer and lower MTM proliferation rates. In vivo, Cx43 downregulation in transplanted iPSC-TM weakened their regenerative role in an Ad5.myocilinY437H mouse model of glaucoma. Mice receiving these cells exhibited lower TM cellularity and higher intraocular pressure (IOP) than those receiving unmodified iPSC-TM. Our findings reveal a crucial role of gap junction, especially Cx43, in iPSC-based TM regeneration, and provides insights to enhance the regenerative effect of iPSCs in glaucoma therapy.


Replacing Lectures with Small Groups: The Impact of Flipping the Residency Conference Day.
The flipped classroom, an educational alternative to the traditional lecture, has been widely adopted by educators at all levels of education and across many disciplines. In the flipped classroom, learners prepare in advance of the face-to-face meeting by learning content material on their own. Classroom time is reserved for application of the learned content to solving problems or discussing cases. Over the past year, we replaced most residency program lectures with small-group discussions using the flipped-classroom model, case-based learning, simulation and procedure labs. In the new model, residents prepared for conference by reviewing a patient case and studying suggested learning materials. Conference day was set aside for facilitated small-group discussions about the case. This is a cross-cohort study of emergency medicine residents who experienced the lecture-based curriculum to residents in the new flipped-classroom curriculum using paired comparisons (independent t-tests) on in-training exam scores while controlling for program year level. We also compared results of the evaluation of various program components. We observed no differences between cohorts on in-training examination scores. Small-group methods were rated the same across program years. Two program components in the new curriculum, an updated format of both adult and pediatric case conferences, were rated significantly higher on program quality. In preparation for didactics, residents in the new curriculum report spending more time on average with outside learning materials, including almost twice as much time reviewing textbooks. Residents found the new format of the case conferences to be of higher quality because of the inclusion of rapid-fire case discussions with targeted learning points.


Competency of Nicotiana tabacum L. stem tissues to dedifferentiate is associated with differential levels of cell cycle gene expression and endogenous cytokinins.
The expression of the mitotic cyclin Arath; CYCB1;1 and of the cyclin-dependent kinase Arath; CDC2a was located by beta-glucuronidase histochemical detection and in situ hybridization, and was quantified by 4-methylumbelliferyl beta- D-glucuronide assay in tobacco stem tissues during both in vivo differentiation and in vitro dedifferentiation. The changes in localization of endogenous cytokinins were also determined during both processes using quantitative analysis and in situ immunocytochemistry. The CDC2a promoter was expressed continuously during stem development, with particularly high expression in the shoot apical meristem and in the internal and external primary phloem. CYCB1 expression was not restricted to the dividing cells; its expression in the shoot apical meristem was particularly high in the leaf-forming peripheral cells but the gene was also expressed throughout development in the internal and external phloem in which the rate of cell division was reduced or zero. Following in vitro culture, the internal phloem cells appeared to be particularly competent to re-enter the cell cycle within a short lag phase while the pith tissue reactivated later. In culture, cells that resumed division were found to accumulate cytokinins. The high competency of primary phloem to dedifferentiate was associated with its capacity to express CDC2a and CYCB genes and the presence of high cytokinin levels, providing some insights into the determinants of competency for resuming cell division.


Effect of abomasal pectin infusion on digestion and nitrogen balance in lactating dairy cows.
Two experiments were conducted to test the hypothesis that increasing carbohydrate fermentation in the large intestine would increase intestinal conversion of blood urea N to microbial protein, thereby reducing urinary N output. In experiment 1, 3 multiparous Holstein cows were used in an incomplete 4 x 4 Latin square with 14-d periods. Cows were fed the same basal diet and treatments were the abomasal infusion of 0, 0.5, or 1 kg/d of citrus pectin, or the addition of 1 kg/d of molasses to the basal diet. Experiment 2 used 6 cows in a double reversal design with four 21-d periods. Cows were fed one basal diet and treatments were the abomasal infusion of either 0 or 1 kg/d of pectin. In experiment 1, pectin infusion linearly decreased basal ration intake from 25.0 to 23.2 kg/d. This was prevented in experiment 2 by restricted feeding, and basal ration intake was 22.2 kg/d. Abomasal pectin caused numeric decreases in total tract apparent digestibility of neutral detergent fiber and neutral detergent solubles in experiment 1 and significantly decreased starch digestibility in experiment 2, suggesting that pectin may have reduced postruminal nutrient digestibility. Pectin infusion did not affect milk yield but decreased milk fat percentage from 3.69 to 3.53% in experiment 2. Increasing abomasal pectin tended to decrease urinary N and increase fecal N in experiment 1 and these effects were significant in experiment 2. For both experiments, urinary N decreased 26 g/d, approximately 10% of daily urine N output. Abomasal pectin did not affect fecal pH or DM content; however, in experiment 2, pectin decreased fecal ammonia from 19.8 to 13.4 mmol/kg of DM and increased fecal purines from 13.8 to 15.8 mmol/kg of DM. In both experiments, excretion of fecal purines was increased from 15 g/d for 0 kg/d pectin to 18 g/d for 1 kg/d pectin, although this increase was only significant in experiment 2. These results suggest that manipulating dairy diets to increase postruminal fermentation may reduce urinary N and consequently manure ammonia losses. However, abomasal pectin tended to decrease both ruminal ammonia concentration and urinary purine derivative output in experiment 2, suggesting that postruminal pectin fermentation may have compromised rumen microbial protein production.


Metal Halide Perovskites for Solar Fuel Production and Photoreactions.
Photocatalysis is an easily configurable and cost-effective technology for the conversion of solar energy into chemical energy. Recently, increasing attention has been given to metal halide perovskite (MHP) photocatalysts because of the development of stabilization strategies for MHPs under reaction conditions. From this perspective, we first describe several substantial breakthroughs in the photocatalytic application of MHPs. Performance trends in the solar fuel production applications of MHPs, including photocatalytic H2 generation and photocatalytic CO2 reduction reactions, are then described. Recent developments to extend the use of MHPs to various photocatalytic organic transformations are also highlighted. Finally, we propose several scientific challenges for the practical implications of MHPs for solar fuel production and various photoreactions.


Mitral Valve Echodensities in a Young-Adult Female with Relapsing Polychondritis, Transiently Positive Lupus Anticoagulant, and Systemic Embolism.
Valvular strands seen on echocardiography carry a wide differential diagnosis and may not always have a clear etiology despite taking clinical context into account. The decision of whether to provide anticoagulation for these lesions can be challenging. Case Presentation. A young adult female with an extensive rheumatologic history involving relapsing polychondritis and positive lupus anticoagulant presents to the emergency department with a discolored and painful right toe, as well as right auricular pain and swelling. Initial work-up revealed a possible splenic infarct, vasculitis of the right lower extremity, and mitral valve echodensities on echocardiography, without evidence of infective endocarditis. Due to concern that nonbacterial thrombotic endocarditis may be the cause of the patient's thromboembolic event, her valvular lesions were treated with low molecular weight heparin while awaiting serial imaging. When follow-up echocardiography showed no change in the size of her mitral valve lesions, which would be most consistent with Lambl's excrescences, the care team still faced a decision about which long-term anticoagulation to prescribe. This patient of childbearing age wished to avoid the teratogenicity and long-term monitoring associated with warfarin therapy. Although warfarin was the preferred agent for the patient's rheumatologic comorbidities, she elected to receive enoxaparin therapy for long-term thromboembolism prophylaxis. Even when accounting for clinical context, valvular lesions seen on echocardiography often have uncertain etiology and may require time and serial imaging to determine which treatment to pursue. When long-term anticoagulation is provided for females of childbearing age, shared decision-making with consideration of the patient's personal priorities and comorbidities is essential.


A quantitative analysis of cell volume and resting potential determination and regulation in excitable cells.
This paper quantifies recent experimental results through a general physical description of the mechanisms that might control two fundamental cellular parameters, resting potential (Em) and cell volume (Vc), thereby clarifying the complex relationships between them. Em was determined directly from a charge difference (CD) equation involving total intracellular ionic charge and membrane capacitance (Cm). This avoided the equilibrium condition dEm/dt = 0 required in determinations of Em by previous work based on the Goldman-Hodgkin-Katz equation and its derivatives and thus permitted precise calculation of Em even under non-equilibrium conditions. It could accurately model the influence upon Em of changes in Cm or Vc and of membrane transport processes such as the Na+-K+-ATPase and ion cotransport. Given a stable and adequate membrane Na+-K+-ATPase density (N), Vc and Em both converged to unique steady-state values even from sharply divergent initial intracellular ionic concentrations. For any constant set of transmembrane ion permeabilities, this set point of Vc was then determined by the intracellular membrane-impermeant solute content (X-i) and its mean charge valency (zX), while in contrast, the set point of Em was determined solely by zX. Independent changes in membrane Na+ (PNa) or K+ permeabilities (PK) or activation of cation-chloride cotransporters could perturb Vc and Em but subsequent reversal of such changes permitted full recovery of both Vc and Em to the original set points. Proportionate changes in PNa, PK and N, or changes in Cl- permeability (PCl) instead conserved steady-state Vc and Em but altered their rates of relaxation following any discrete perturbation. PCl additionally determined the relative effect of cotransporter activity on Vc and Em, in agreement with recent experimental results. In contrast, changes in Xi- produced by introduction of a finite permeability term to X- (PX) that did not alter zX caused sustained changes in Vc that were independent of Em and that persisted when PX returned to zero. Where such fluxes also altered the effective zX they additionally altered the steady state Em. This offers a basis for the suggested roles of amino acid fluxes in long-term volume regulatory processes in a variety of excitable tissues.


[Retrospective analysis of ruthenium-106 brachytherapy for small and medium-sized malignant melanoma of the posterior choroid].
Transpupillary thermotherapy is a new and most promising treatment modality for up to medium-sized choroidal melanoma at the posterior pole. We analysed the results of conventional ruthenium-106 brachytherapy in these special tumour subgroup. Results of ruthenium-106 brachytherapy (radioactive dose to the tumour apex 150 Gy) in a series of 52 eyes with primary malignant choroidal melanoma (posterior to the equator, thickness </= 4.5 mm, base diameter </= 12 mm) were evaluated retrospectively. Mean tumour thickness was 3.2 mm. The posterior tumour margin was in 20 eyes </= 2 optic disc diameter away from the macula and in 10 eyes </= 2 optic disc diameter away from the optic disc. Follow-up was 3 - 9 years (median 5.6 years). Tumour control was achieved in 48 eyes (92 %): completely flattened scar in 71 %, residual prominence </= 2 mm in 16 %, no apparent response (but high reflectivity in ultrasonographic examination) in 5 %. 4 eyes were removed because of tumour regrowth (3 x) or secondary glaucoma (1 x). Visual outcome mainly depends on tumour location in respect of fovea and the optic nerve. Because 40 % of the eyes developed radiation maculopathy and 20 % radiation optic neuropathy 25 eyes (48 %) reached a final visual acuity </= 0.2. 40 eyes (77 %) revealed a visual loss of at least 2 lines. Two patients died of liver metastases. In posterior choroidal melanoma ruthenium-brachytherapy achieved an excellent rate of tumour control, but functional results were disappointing because of late radiation sideeffects. Transpupillary thermotherapy as an adjunct to ruthenium plaque radiotherapy may be able to reduce the radioactive dose.


Clinical research: assessing the future in a changing environment; summary report of conference sponsored by the American Medical Association Council on Scientific Affairs, Washington, DC, March 1996.
Concerns about funding of clinical research underlie all other problems identified at the Council on Scientific Affairs conference. Future National Institutes of Health (NIH) budgets are likely to be constant at best, and the general public expects cost containment to be an ongoing goal; this is exacerbated by the impending Medicare Trust Fund crisis. Meanwhile, traditional financial support of clinical research in academic medical centers (AMCs) through cross-subsidization is imperiled by competitive pressures largely caused by managed care. Although managed care organizations (MCOs) are potentially rich sources of funding and other resources, and some not-for-profit companies are conducting some research, for-profit MCOs have not demonstrated an understanding of the importance of clinical research. Young physicians are being discouraged from careers as clinical researchers and established investigators are "dropping out" because of demands for clinical productivity and competition for research grants, loss of patients/research subjects to managed care, perceived lack of status and compensation, and overall uncertainty about continued financial support. Efforts to assist current and potential clinical investigators are discussed in this report. Loss of patients, denial of reimbursement, and competition with MCOs and contract research organizations (CROs) have placed AMCs under unprecedented pressure. However, research centers located in AMCs have allowed investigators to conduct clinical research by providing a "protected environment." Furthermore, many AMCs are determined to continue conducting clinical research and are addressing related problems. Although the NIH will continue to be a major source of funding for clinical research, partnerships between various private and public entities provide important opportunities to maximize the productivity of all individuals and institutions involved. Potential partnerships include MCOs, AMCs, CROs, pharmaceutical companies and other industry, the Department of Defense, the Veterans Health Administration, practice-based physicians, and private foundations and patient support groups. "Partnerships in advocacy" for clinical research will be essential. Efforts to recruit for-profit MCOs to the clinical research endeavor identified in this report include (1) emphasizing issues of interest to them (eg, outcomes research); (2) stressing the significance of some research to the marketplace; (3) developing criteria to distinguish individual MCOs on the basis of their contribution to the public interest; (4) equating money spent on research with "R&D dollars" spent in nonmedical business enterprises; and (5) educating purchasers of health care (eg, corporate health plan directors) about clinical research. Conducting clinical research in all managed care settings requires leadership, the understanding and cooperation of physicians and support staff, wise use of limited resources (ie, funding only the best research projects), sound methodology, and above all, the perception that the research will ultimately improve patient care.


Structural Mechanism and Inhibitors Targeting EGFR Exon 20 Insertion (Ex20ins) Mutations.
Epidermal growth factor receptor (EGFR) targeted therapy is one of the most important and effective strategies to combat EGFR mutant nonsmall-cell lung cancer (NSCLC). However, a substantial number of patients bearing EGFR exon 20 insertion (Ex20ins) mutations respond poorly to common EGFR targeted therapies. This clinical need remained unmet until recently, when the EGFR Ex20ins mutation inhibitor mobocertinib was approved by the FDA. Despite this progress, the structural mechanisms of EGFR Ex20ins mutation resistance and characterization of inhibitor binding modes have not been systematically summarized. Herein, we analyze the structural mechanisms for ligand binding and resistance and summarize recent developments for the reported inhibitors of EGFR Ex20ins mutations. Furthermore, this Perspective aims to provide insights for the design of the next generation of EGFR Ex20ins inhibitors.


New evidence on learning trajectories in a low-income setting.
Using a unique longitudinal dataset collected from primary school students in Pakistan, we document four new facts about learning in low-income countries. First, children's test scores increase by 1.19 SD between Grades 3 and 6. Second, going to school is associated with greater learning. Children who dropout have the same test score gains prior to dropping out as those who do not but experience no improvements after dropping out. Third, there is significant variation in test score gains across students, but test scores converge over the primary schooling years. Students with initially low test scores gain more than those with initially high scores, even after accounting for mean reversion. Fourth, conditional on past test scores, household characteristics explain little of the variation in learning. In order to reconcile our findings with the literature, we introduce the concept of "fragile learning," where progression may be followed by stagnation or reversals. We discuss the implications of these results for several ongoing debates in the literature on education from Low- and Middle-Income Countries (LMICs).


Ketotifen in the management of infants with bronchopulmonary dysplasia.
Ketotifen, a histamine (H1) antagonist, inhibits PAF-induced eosinophil accumulation and airway hyperreactivity. Bronchopulmonary dysplasia (BPD) is a complex disorder in which bronchial hyperreactivity is usually present. An open randomized trial was carried out with this agent in infants with chronic BPD who were followed up for 6 months. The efficacy of the drug was evaluated according to respiratory symptom and medication scores, in which numerical values were assigned to various other antiasthmatic agents used to control wheezing. No adverse clinical or biochemical sequelae were noted during treatment. The mean respiratory symptom and mean medication scores were significantly higher worse in the control group in comparison with the infants treated with ketotifen.


Epimedium flavonoids protect neurons and synapses in the brain via activating NRG1/ErbB4 and BDNF/Fyn signaling pathways in a chronic cerebral hypoperfusion rat model.
Cerebral hypoperfusion is a common feature of cerebral small vascular disease (CSVD), which has been considered as one of the causes of cognitive decline in recent years. Epimedium flavonoids (EF) are the main ingredients extracted from Epimedium. The purpose of this study was to investigate the effects of EF on cognitive impairment, and the underlying mechanisms in rats with permanent occlusion of the bilateral common carotid artery (2VO). EF (50, 100, and 200 mg/kg) was intragastrically administered for 12 weeks starting 2 weeks after 2VO surgery. The results showed that EF treatment improved learning and memory impairment in 2VO rats evaluated by novel object recognition and Y-maze tests. NeuN immunohistochemical staining indicated that EF alleviated neuronal loss in the hippocampus and cerebral cortex of 2VO rats. MAP-2 immunofluorescence staining and western blotting showed that EF protected neuronal dendrites and increased the expression of cytoskeleton proteins MAP-2 and NF200 in the hippocampus of 2VO rats. Moreover, EF protected the synapse ultrastructure detected by transmission electron microscopy, and increased the expression of synaptic plasticity-related proteins, including synaptophysin, synaptotagmin-I, synapsin I, PSD-95, p-NMDA2B, and p-CaMKII-α in the hippocampus of 2VO rats. In addition, EF increased the expression of neuregulin-1 (NRG-1), p-ErbB4, brain-derived neurotrophic factor (BDNF), p-Fyn, PI3K, p-Akt, and p-CREB in the hippocampus of 2VO rats. These results suggest that EF may protect neurons and synapses by activating the NRG1/ErbB4, BDNF/Fyn, and P13 K/Akt/CREB pathways in the hippocampus and cerebral cortex, thus improving cognitive impairment induced by chronic cerebral hypoperfusion. EF may be a potential candidate drug for chronic cerebral hypoperfusion and CSVD therapy.


An improved and combined reverse transcription-polymerase chain reaction assay for reliable detection of metastatic melanoma cells in peripheral blood.
The application of reverse transcription-polymerase chain reaction (RT-PCR) for detection of metastatic melanoma cells in peripheral blood has been used by a number of different scientific groups with both encouraging and discouraging results. We describe an improved, combined RT-PCR assay for tyrosinase mRNA, which can detect a single, viable melanoma cell in 10-15 ml of peripheral blood. The assay has been found to be highly sensitive, reproducible, cost-effective and clinically applicable. Furthermore, we developed a simple but effective procedure which prevents carry-over contamination. We present evidence indicating that the chance of obtaining normal melanocyte contamination with the needle prick during blood sampling is only 2% among all skin categories. It was found that the phenomenon of illegitimate transcription does not contribute to sporadic false positives. We conclude that the assay, as described here, is of clinical relevance and is a potentially powerful tool for studying various aspects of melanoma biology.


Parallel synthesis of 1,3-dihydro-1,4-benzodiazepine-2-ones employing catch and release.
An efficient solid-phase method has been developed for the parallel synthesis of 1,3-dihydro-1,4-benzodiazepine-2-one derivatives. A key step in this procedure involves catching crude 2-aminobenzoimine products 4 on an amino acid Wang resin 10. Mild acidic conditions then promote a ring closure and in the same step cleavage from the resin to give pure benzodiazepine products 12. The 2-aminobenzoimines 4 can be synthesized from either 2-aminobenzonitriles 1 and Grignard reagents 2 or from iodoanilines 5 and nitriles 7 allowing a range of diversification. Further diversification can be introduced to the benzodiazepine products by N-alkylation promoted by a resin bound base and alkylating agents 13.


Circadian aspects of serum prolactin and TSH lowering by bromocriptine in patients with prostatic hypertrophy.
Bromocriptine mesylate lowers the serum concentration of prolactin and TSH in patients with prostatic hypertrophy as a function of drug administration time. The effect of a 2.5-mg dose in lowering these two hormones in presumably similar patients is statistically highly significant and relatively large at unusual test times (in the evening); at other, conventional test or administration times (early morning or midday), it is smaller, questionable, or not demonstrable with the dose and conditions used. Dosing without timing may lead to reduced effect or lack of effect, ambiguity and controversy, and lack of timing may account for the circumstance that an effect of bromocriptine upon TSH in human serum was not previously established. Rigorous assessment of the effect of bromocriptine mesylate upon circulating TSH and prolactin requires consideration of the entire spectrum of rhythms, ultradian and infradian as well as circannual. The circadian approach here analyzed represents a step toward that goal and indicates that the circadian frequency is a critical determinant of this response. Manipulation of TSH concentration in serum, in turn, is of interest in view of the demonstrated alteration of the circannual TSH rhythm in patients with prostatic cancer.


Group A beta-hemolytic streptococcal colitis with secondary bacteremia.
We report a case of a 5-year-old girl with invasive colitis and secondary bacteremia caused by group A beta-hemolytic streptococcus. Although group A beta-hemolytic streptococcus is occasionally isolated from stool, it is a rare cause of colitis. This is the first report of group A beta-hemolytic streptococcus pancolitis with secondary bacteremia.


Lagging-strand DNA replication origins are required for conjugal transfer of the promiscuous plasmid pMV158.
The promiscuous streptococcal plasmid pMV158 is mobilizable by auxiliary plasmids and replicates by the rolling-circle mechanism in a variety of bacterial hosts. The plasmid has two lagging-strand origins, ssoA and ssoU, involved in the conversion of single-stranded DNA intermediates into double-stranded plasmid DNA during vegetative replication. Transfer of the plasmid also would involve conversion of single-stranded DNA molecules into double-stranded plasmid forms in the recipient cells by conjugative replication. To test whether lagging-strand origins played a role in horizontal transfer, pMV158 derivatives defective in one or in both sso's were constructed and tested for their ability to colonize new hosts by means of intra- and interspecies mobilization. Whereas either sso supported transfer between strains of Streptococcus pneumoniae, only plasmids that had an intact ssoU could be efficiently mobilized from S. pneumoniae to Enterococcus faecalis. Thus, it appears that ssoU is a critical factor for pMV158 promiscuity and that the presence of a functional sso plays an essential role in plasmid transfer.


Design, manufacturing, evaluation, and performance of a 3D-printed, custom-made nozzle for laser wakefield acceleration experiments.
Laser WakeField Acceleration (LWFA) is extensively used as a high-energy electron source, with electrons achieving energies up to the GeV level. The produced electron beam characteristics depend strongly on the gas density profile. When the gaseous target is a gas jet, the gas density profile is affected by parameters, such as the nozzle geometry, the gas used, and the backing pressure applied to the gas valve. An electron source based on the LWFA mechanism has recently been developed at the Institute of Plasma Physics and Lasers. To improve controllability over the electron source, we developed a set of 3D-printed nozzles suitable for creating different gas density profiles according to the experimental necessities. Here, we present a study of the design, manufacturing, evaluation, and performance of a 3D-printed nozzle intended for LWFA experiments.


Effect of diuretics on the tubuloglomerular feedback response.
To study the influence of diuretics on the tubuloglomerular feedback mechanism, early proximal stop-flow pressure (SFP) was measured during loop exposure to different drug concentrations. SFP was recorded continuously during arrested flow and at a perfusion rate of 50 nL/min. The perfusate consisted of isotonic saline, to which varying amounts of furosemide. bumetanide, piretanide, or hydrochlorothiazide were added to obtain final concentrations between 10(-6) and 10(-4)M. The loop diuretics furosemide, bumetanide, and piretanide showed inhibition: an inverse log-linear relation between the luminal concentration and the respective feedback response. No differences between the dose-response curves of furosemide, bumetanide, or piretanide could be demonstrated. The effective concentration range was between 10(-6) and 10(-4)M, the mean effective dose (ED50) was close to 10(-5)M for each of them. In contrast, hydrochlorothiazide did not alter the feedback response. The effect of loop diuretics was rapidly and repeatedly reversible.


Hereditary spherocytosis: a study of splenectomized persons.
Sixty-one persons splenectomized for hereditary spherocytosis have been studied and compared to 36 nonsplenectomized clinically affected and to 77 nonaffected family members. Serum IgM levels were reduced by 25% and IgD levels were nearly doubled in the splenectomized group. No fatal bacterial infection was identified by history covering a total of 800 postsplenectomy years. Platelet counts remained elevated for many years after removal of the spleen, as did the number of leukocytes, lymphocytes, and monocytes. Heinz bodies were seen in 3% of red cells after splenectomy. Though within the range of "normal," reticulocyte levels and serum bilirubin levels were satistically higher in the splenectomized group than in the nonaffected persons. Hemoglobin levels were higher in splenectomized affected persons than in matched controls of the same sex and maturity.


Oligodontia, microcephaly and facial dysmorphia syndrome.
Congenital absence of third molars is common. However absence of the other permanent teeth is relatively rare. Absence of teeth may be isolated or associated to other features. We had the opportunity to examine a girl with oligodontia associated to microcephaly, to facial dysmorphia and to short stature.


Utility of near infrared fluorescent cholangiography in detecting biliary structures during challenging minimally invasive cholecystectomy.
Surgeons can minimize the risk of bile duct injury (BDI) during challenging mini-invasive cholecystectomy through technical standardization by means of a precise anatomical landmark identification (Critical View of Safety) and advanced technology for biliary visualization. Among these systems, the adoption of magnified stereoscopic 3-dimensional view provided by robotic platforms and near infrared fluorescent cholangiography (NIRF-C) is the most promising. In this prospective cohort study, we evaluated all consecutive minimally invasive cholecystectomies (laparoscopic and robotic) performed with NIRF-C between May 2022 and January 2023 at General Surgery Unit, Department of Health Sciences, University of Milan, San Paolo Hospital (Milan, Italy). Inclusions criteria were as follows: (1) acute cholecystitis (emergency group), (2) history of chronic cholecystitis or complicated cholelithiasis (deferred urgent group), (3) difficult cases (patients affected by cirrhosis, with scleroatrophic gallbladder or BMI > 35 kg/m2). For each group, the detection rate and visualization order of the main biliary structures were reported (cystic duct, CD; common hepatic duct, CHD; common bile duct, CBD; and CD-CHD junction). A total of 101 consecutive patients were enrolled, including 83 laparoscopic and 18 robotic cholecystectomies. All patients were stratified into three subgroups: (a) emergency group (n = 33, 32.7%), (b) deferred urgent group (n = 46, 45.5%), (c) difficult group (n = 22, 21.8%). Visualization of at least one biliary structure was possible in 94.1% of cases (95/101). Interestingly, all four main structures were detected in 43.6% of cases (44/101). The CD was the structure identified most frequently, being recognized in 91/101 patients (90.1%), followed by CBD (83.2%), CHD (62.4%), and CD-CHD junction (52.5%). In the subset of patients that underwent emergency surgery for AC, the CD-CHD confluence was identified in only 45.5% of cases. However, early and precise identification of CBD (75.8%) and CD (87.9%) allowed safe isolation, clipping, and transection of the cystic duct. In the deferred urgent group, the CBD and the CD were easily identified as first structure in a high percentage of cases (65.2% and 41.3% respectively), whereas the CD-CHD junction was the third structure to be identified in 67.4% of cases, the highest value among the three subgroups. In the difficult group, NIRF-C did not prove to be a useful tool for biliary visualization. The rates of failure of visualization were elevated: CBD (27.3%), CD (18.2%), CHD (54.5%), and CD-CHD (68.2%). NIRF-C is a powerful real-time diagnostic tool to detect CBD and CD during minimally invasive cholecystectomy, especially when inflammation due to acute or chronic cholecystitis subverted the anatomy of the hepatoduodenal ligament.


Cycloalkanoindoles. 2. 1-Alkyl-1,2,3,4-tetrahydrocarbazole-1-ethanamines and related compounds. Potential antidepressants.
The synthesis is described of a series of cycloalkanoindoles, comprising tetrahydrocarbazoles, a cyclopentindole, and a cycloheptindole, all bearing an ethanamine side chain at position 1. The acute toxicities of these compounds were evaluated, as well as their potential antidepressant properties, using tests based on the prevention of ptosis induced by reserpine and tetrabenazine. 9-Ethyl-N,N1-trimethyl-1,2,3,4-tetrahydrocarbazole-1-ethanamine (AY-24 614) was found to be the most potent analogue, having an ED50 of 0.12 mg/kg ip in preventing reserpine-induced ptosis in mice and an ED50 at 3.3 mg/kg ip in preventing tetrabenazine-induced ptosis in rats.


Pilot Trial of a Home-based Physical Activity Program for African American Women.
This study aimed to assess the feasibility of a Home-based, Individually-tailored Physical activity Print (HIPP) intervention for African American women in the Deep South. A pilot randomized trial of the HIPP intervention (N = 43) versus wellness contact control (N = 41) was conducted. Recruitment, retention, and adherence were examined, along with physical activity (7-d physical activity recalls, accelerometers) and related psychosocial variables at baseline and 6 months. The sample included 84 overweight/obese African American women 50-69 yr old in Birmingham, AL. Retention was high at 6 months (90%). Most participants reported being satisfied with the HIPP program and finding it helpful (91.67%). There were no significant between-group differences in physical activity (P = 0.22); however, HIPP participants reported larger increases (mean of +73.9 min·wk (SD 90.9)) in moderate-intensity or greater physical activity from baseline to 6 months compared with the control group (+41.5 min·wk (64.4)). The HIPP group also reported significantly greater improvements in physical activity goal setting (P = 0.02) and enjoyment (P = 0.04) from baseline to 6 months compared with the control group. There were no other significant between-group differences (6-min walk test, weight, physical activity planning, behavioral processes, stage of change); however, trends in the data for cognitive processes, self-efficacy, outcome expectations, and family support for physical activity indicated small improvements for HIPP participants (P > 0.05) and declines for control participants. Significant decreases in decisional balance (P = 0.01) and friend support (P = 0.03) from baseline to 6 months were observed in the control arm and not the intervention arm. The HIPP intervention has great potential as a low-cost, high-reach method for reducing physical activity-related health disparities. The lack of improvement in some domains may indicate that additional resources are needed to help this target population reach national guidelines.


Transmission across the water-air interface: resolving the impact of multiple interactions at the sea surface.
A series of Monte Carlo and HydroLight radiative transfer simulations are used to demonstrate that the traditional form of the Fresnel transmission across the water-air interface is accurate. This contradicts assertions to the contrary in a recent paper [Opt. Express25, 27086 (2017)10.1364/OE.25.027086] that suggested that the impact of multiple surface interactions had previously been ignored and that the transmission factor was dependent upon the turbidity of the water.


Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular cells at angiographic concentrations: in vitro study.
To test in vitro whether gadolinium-based contrast agents induce fewer toxic effects on renal tubular cells than does an iodinated contrast medium at concentrations used for angiography. LLC-PK1 cells were incubated with iomeprol, gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, gadodiamide, and corresponding mannitol solutions for 24 hours at 37 degrees C in two experimental settings: measurements with equally attenuating solutions and measurements with equimolar solutions. Cytotoxicity was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, trypan blue testing, and an assay to detect apoptosis and necrosis. Data were analyzed with analyses of variance and post hoc tests. Yielding the same x-ray attenuation, iomeprol-300 and iomeprol-150 at concentrations of 2.34-18.75 mg of iodine per milliliter induced significantly (P < .001) lower inhibition of MTT conversion (74%-102% of undamaged control cells) compared with 15.63-125.00 mmol/L concentrations of the gadolinium-based agents (mean percentages of undamaged control cells: 48%-80%, 50%-87%, 60%-95%, and 56%-92% with gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, and gadodiamide, respectively). At equimolar concentrations (62.5 mmol/L), iomeprol-190 induced a mean extent of inhibition of MTT conversion (69% of undamaged control cells) similar to that induced by gadoterate meglumine (71%) and gadodiamide (70%), whereas gadopentetate dimeglumine and gadobenate dimeglumine induced stronger effects (63% and 64%, respectively; P < .001). At trypan blue testing, there were more dead cells after incubation with 125 mmol/L gadopentetate dimeglumine than after incubation with iomeprol-190 (57% vs 19%, P < .001). The 125 mmol/L gadopentetate and gadobenate formulations induced more necrosis and apoptosis than did gadoterate meglumine, gadodiamide, and iomeprol (mean percentage difference between treated and untreated control cells: for necrosis, +124%, +95%, +17%, -6%, and +3%, respectively; for apoptosis, +34%, +35%, +13%, +4%, and +5%, respectively; P < .001). At angiographic concentrations, gadolinium-based contrast agents do not induce fewer cytotoxic effects on cultured renal tubular cells than does iomeprol.


The Polymorphism Analyses of Short Tandem Repeats as a Basis for Understanding the Genetic Characteristics of the Guanzhong Han Population.
The short tandem repeat (STR) loci are polymorphic markers in the combined DNA index system (CODIS) and non-CODIS STR loci. Due to the highly polymorphic characteristic of STR loci, they are popular and widely used in forensic DNA typing laboratories. In this study, 22 STR loci (1 CODIS, 21 non-CODIS STR loci) and an Amelogenin locus were genotyped and analyzed in 590 unrelated individuals of the Guanzhong Han population. None of the 22 STR loci deviated from the Hardy-Weinberg equilibrium, and all the loci were in the linkage equilibrium state. We observed 247 alleles, and the corresponding allelic frequencies ranged from 0.0008 to 0.3695 in the Guanzhong Han population. The combined power of discrimination and the cumulative exclusion probability was 0.999 999 999 999 999 999 999 999 999 346 36 and 0.999 999 999 709 74, respectively. The results including Nei's D A genetic distance, multidimensional scaling analysis, and principal component analysis showed that the Guanzhong Han population has closer genetic affinities with Northern Han, Chengdu Han, and Xinjiang Hui groups from China based on allelic frequencies of 15 overlapped STR loci from Guanzhong Han and 13 reference groups. The present results indicated that Microreader™ 23sp ID kit included highly polymorphic loci, and it could be well used for individual identification, paternity testing, and population genetics in the Guanzhong Han population.


Subclinical psychotic experiences and subsequent contact with mental health services.
Although psychotic experiences in people without diagnosed mental health problems are associated with mental health service use, few studies have assessed this prospectively or measured service use by real-world clinical data. To describe and investigate the association between psychotic experiences and later mental health service use, and to assess the role of symptoms of common mental health disorders in this association. We linked a representative survey of south-east London (SELCoH-1, n=1698) with health records from the local mental healthcare provider. Cox regression estimated the association of PEs with rate of mental health service use. After adjustments, psychotic experiences were associated with a 1.75-fold increase in the rate of subsequent mental health service use (hazard ratio (HR) 1.75, 95% CI 1.03-2.97) compared with those without PEs. Participants with PEs experienced longer care episodes compared with those without. Psychotic experiences in the general population are important predictors of public mental health need, aside from their relevance for psychoses. We found psychotic experiences to be associated with later mental health service use, after accounting for sociodemographic confounders and concurrent psychopathology. None. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) license.


Alcohol's Secondhand Harms in the United States: New Data on Prevalence and Risk Factors.
This study examined a range of indicators of alcohol's harm to others (AHTO) among U.S. adults and assessed sociodemographic and alcohol-related risk factors for AHTO. The data came from 8,750 adult men and women in two parallel 2015 U.S. national surveys conducted in English and Spanish. Both surveys used computer-assisted telephone interviews and two-stage, stratified, list-assisted, random samples of adults ages 18 and older. One in five adults experienced at least one of ten 12-month harms because of someone else's drinking. The prevalence of specific harm types and characteristics differed by gender. Women were more likely to report harm due to drinking by a spouse/partner or family member, whereas men were more likely to report harm due to a stranger's drinking. Being female also predicted family/financial harms. Younger age increased risk for all AHTO types, except physical aggression. Being of Black/other ethnicity, being separated/widowed/divorced, and having a college education without a degree each predicted physical aggression harm. The harmed individual's own heavy drinking and having a heavy drinker in the household increased risk for all AHTO types. The risk for physical aggression due to someone else's drinking was particularly elevated for heavy drinking women. Secondhand effects of alcohol in the United States are substantial and affected by sociodemographics, the harmed individual's own drinking, and the presence of a heavy drinker in the household. Broad-based and targeted public health measures that consider AHTO risk factors are needed to reduce alcohol's secondhand harms.


Determinants of Turkish households' out-of-pocket expenditures on three categories of health care services: A multivariate probit approach.
This study identifies the driving forces that contribute to the probabilities of incidence of out-of-pocket (OOP) expenditures by households in Turkey. Factors affecting the probability of OOP expenditures on medical products/devices/supplies (MP), outpatient services (OTS), and inpatient services (ITS) are examined using the Household Budget Survey data gathered by the Turkish Statistical Institute in 2018. The study applies the multivariate probit model. The incidence of OOP spending varied with 48.9% of the households reporting OOP expenditure on MP, 22.4% on OTS, and 25.4% on ITS. The largest probability changes were associated with household disposable annual income, household type and size, age category, and having private health insurance. Gender and marital status also influenced expenditures in some categories. Lifestyle choices had small and mixed effects, with smoking and alcohol consumption lowering the probability of OOP spending. From a policy standpoint, households with the lowest incomes, large households, and those where the household head was 'others' (retiree, student, housewife, not actively working, etc.) or had a condition preventing employment seemed to report OOP expenditures less frequently and may have chosen not to receive healthcare services, leading to the need for more healthcare services later.


Similar transition states mediate the Q-cycle and superoxide production by the cytochrome bc1 complex.
The cytochrome bc complexes found in mitochondria, chloroplasts and many bacteria play critical roles in their respective electron transport chains. The quinol oxidase (Q(o)) site in this complex oxidizes a hydroquinone (quinol), reducing two one-electron carriers, a low potential cytochrome b heme and the "Rieske" iron-sulfur cluster. The overall electron transfer reactions are coupled to transmembrane translocation of protons via a "Q-cycle" mechanism, which generates proton motive force for ATP synthesis. Since semiquinone intermediates of quinol oxidation are generally highly reactive, one of the key questions in this field is: how does the Q(o) site oxidize quinol without the production of deleterious side reactions including superoxide production? We attempt to test three possible general models to account for this behavior: 1) The Q(o) site semiquinone (or quinol-imidazolate complex) is unstable and thus occurs at a very low steady-state concentration, limiting O(2) reduction; 2) the Q(o) site semiquinone is highly stabilized making it unreactive toward oxygen; and 3) the Q(o) site catalyzes a quantum mechanically coupled two-electron/two-proton transfer without a semiquinone intermediate. Enthalpies of activation were found to be almost identical between the uninhibited Q-cycle and superoxide production in the presence of antimycin A in wild type. This behavior was also preserved in a series of mutants with altered driving forces for quinol oxidation. Overall, the data support models where the rate-limiting step for both Q-cycle and superoxide production is essentially identical, consistent with model 1 but requiring modifications to models 2 and 3.


Vision-related Quality of Life in Glaucoma Suspect or Early Glaucoma Patients.
To determine the association of vision-related quality of life (QoL) to demographic factors and visual function in glaucoma suspect or early glaucoma patients. We administered the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) on the same day as a comprehensive ocular examination to participants either with glaucoma or at high risk for developing glaucoma. Regression models were used to determine the association between VFQ-25 composite and subscale scores, visual field status, logMAR equivalent visual acuity (VA), age, and sex. In all analyses we used data from the eye with the best mean deviation (MD), best pattern SD, and best VA. Data from 198 participants were analyzed. The mean best MD (±SD) was 0.02±1.52 dB (range, -5.11 to 2.63 dB) and the mean best pattern SD was 1.75±1.03 dB (range, 0.91 to 8.36 dB). The mean VFQ-25 composite score was 91.6±6.7 (range, 54.5 to 100.0). Composite score and the Distance Activities, Color Vision subscale scores were associated with best MD (P≤0.05). The General Vision and Driving subscale scores were associated with best VA (P≤0.03). The composite score and the Distance Activities, Driving, and Color Vision subscale scores were associated with age (P≤0.05). Finally, the Distance Activities, Driving, and Peripheral Vision subscale scores were associated with sex (P≤0.04). Vision-related QoL is associated with visual field status even in early and suspected glaucoma. It is also associated with VA, age, and sex. Particular decreases in QoL are related to distance activities, driving, and color vision.