Acute bronchial and hematologic effects following inhalation of a single dose of PAF. Comparison between asthmatics and normal subjects.
This study compared the acute bronchial and hematologic effects of inhaled platelet activating factor (PAF) (30 micrograms as a single dose) in 19 patients with mild asthma and 19 normal subjects. Each subject underwent a methacholine bronchial challenge 1 week before PAF challenge to determine the concentration of methacholine causing a 20 percent fall in FEV1 (PC20M). On the day of PAF challenge, specific conductance (SGaw), FEV1, FEF25-75, and platelet and leukocyte counts were measured before, and 5, 10, 15, and 20 min after PAF inhalation. Changes in pulmonary and hematologic parameters were expressed as percent of control (saline solution/ethanol solution). Unlike normal subjects, subjects with asthma had bronchial hyperresponsiveness to methacholine: geometric mean (range): 0.59 mg/ml (0.07 to 9.8) vs > 32 mg/ml. Acute bronchial obstruction over the first 20 min after PAF inhalation was more pronounced in asthmatics than in normal subjects whatever the functional index considered (p < 0.01). In asthmatics (n = 19), mean (SEM) maximal fall in SGaw, FEV1, and FEF25-75 reached 50 percent (6), 11 percent (4), and 19 percent (5), respectively, while in normal subjects (n = 19) the maximal decreases were 24 percent (6), 4 percent (1), and 6 percent (1), respectively. In asthmatics, no correlation was found between log PC20M and log fall in FEV1 after PAF (r = 0.04 p > 0.05). In asthmatics and normal subjects, inhaled PAF caused a transient fall in neutrophils and monocytes by 5 min followed by a full recovery at 15 min and 20 min. These hematologic changes were not significantly different between the two groups. While not correlated with their airway responsiveness to methacholine, asthmatics, compared with normal subjects, develop an exaggerated acute airway obstruction in response to PAF. In contrast, hematologic changes induced by PAF do not differ between asthmatics and normal subjects.


Inducing the loss of conditionally dispensable chromosomes in Nectria haematococca during vegetative growth.
A procedure for inducing and detecting the loss of conditionally dispensable (CD) chromosomes in filamentous fungi during vegetative growth was developed using Nectria haematococca mating population VI as a model. CD chromosomes in two different isolates of N. haematococca were tagged via integrative transformation with a gene conferring resistance to hygromycin B. In each case the transformation vector included chromosome-specific DNA in order to direct its homologous recombination with the desired chromosome. Chromosome loss was induced by exposing tagged isolates to inhibitory concentrations of benomyl either for protracted periods of time on solid medium or for short periods of time in liquid medium. After exposure to benomyl, isolates that lost the tagged chromosome were identified by their loss of resistance to hygromycin B. Electrophoretic karyotyping was used to verify that isolates which failed to grow on hygromycin B lacked an intact CD chromosome. Ten other chemicals known to interfere with mitotic events or cell development in other organisms did not induce CD chromosome loss in N. haematococca.


Carbon nanodot aqueous binding phase-based diffusive gradients in thin films device for measurement of dissolved copper and lead species in the aquatic environment.
A reliable method for the determination of dissolved Cu2+ and Pb2+ species in water via a diffusive gradient in thin films (DGT) device using water-soluble carbon nanodots (CD) as the binding agent was developed (CD-DGT). The uptake of dissolved Cu2+ and Pb2+ species by CD-DGT increased linearly with a deployment time of over 120 h, while the uptake of Ca2+, Mg2+, Cd2+, Zn2+, Ni2+, and Co2+ by CD-DGT has no significant linear accumulation during the same deployment time. The concentrations of the dissolved Cu2+ and Pb2+ species measured using CD-DGT are in good agreement with the element concentrations spiked directly in a tested synthesis solution. The performance of CD-DGT for the determination of dissolved Cu2+ and Pb2+ species is found to be independent of ionic strength in the range of 0.001-0.05 mol L-1 and in the pH range from 5 to 8. The presence of fulvic acid and tannic acid has no significant influence on the uptake of dissolved Cu2+ and Pb2+ species by CD-DGT under the tested conditions. In different water samples, good agreement was observed between the dissolved Cu2+ and Pb2+ concentrations measured by CD-DGT, and diffusive equilibration in the thin film devices was found. Based on the results obtained, CD-DGT enables the selective and quantitative determination of dissolved Cu2+ and Pb2+ species in water.


Interferon-gamma induces class I HLA and beta 2-microglobulin expression by human amnion cells.
In contrast to other human nucleated cells, amnionic epithelial cells do not normally express class I HLA antigens. It is not known whether the failure of display of those antigens occurs because genes for HLA expression are deleted or are defective, or if gene expression is repressed. The results of the present study demonstrate that amnionic epithelial cells exposed to IFN-gamma express levels of class I HLA antigens and beta 2-microglobulin that are readily detectable in immunoperoxidase and immunofluorescence stains. The findings suggest that failure of transcription may be responsible for failure of normal expression of class I HLA antigens and beta 2-microglobulin by cells of the amnion membrane. Class II antigens, which are normally expressed by very few cell types, were not expressed by amnion cells under any test conditions.


Electronic messaging intervention for management of cardiovascular risk factors in type 2 diabetes mellitus: A randomised controlled trial.
To determine the effectiveness of an electronic messaging support service for management of cardiovascular risk factors in patients with diabetes. Microletter and short message service are widely used, but their health education benefit for people with type 2 diabetes mellitus has not been investigated. Convenience sample study with randomised group assignment. Participants completed survey questionnaires, physical and laboratory evaluations between May 2015 and May 2016 and were then randomly assigned to two groups for receipt of a microletter + short message or a phone call (control). Appointment reminders and health information were sent to the intervention patients by microletter + short message. Every three months, intervention patients and control patients were followed up by telephone. After 12 months, changes in cardiovascular risk factors in each group were evaluated and compared. There were no statistically significant changes or between-group differences in daily smoking and drinking. There were statistically significant between-group differences in glycated haemoglobin (p = .034), postprandial plasma glucose (p = .001), postprandial insulin (p = .005), total cholesterol (p = .038) and low-density lipoprotein (p < .001). Levels of glycated haemoglobin (p = .011), fasting plasma glucose (p = .007), postprandial plasma glucose (p < .001), fasting insulin (p = 0.004), postprandial insulin (p < .001), total cholesterol (p < .001) and low-density lipoprotein (p < .001) were found to be decreased significantly in intervention patients. Systolic blood pressure decreased significantly in patients only followed by telephone (p = .014). The microletter + short message intervention was an effective means of reducing cardiovascular risk in patients with type 2 diabetes mellitus. Regular smartphone communication had a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus. Regular smartphone communication has a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus.


Rheological separation of the megathrust seismogenic zone and episodic tremor and slip.
Episodic tremor and accompanying slow slip, together called ETS, is most often observed in subduction zones of young and warm subducting slabs. ETS should help us to understand the mechanics of subduction megathrusts, but its mechanism is still unclear. It is commonly assumed that ETS represents a transition from seismic to aseismic behaviour of the megathrust with increasing depth, but this assumption is in contradiction with an observed spatial separation between the seismogenic zone and the ETS zone. Here we propose a unifying model for the necessary geological condition of ETS that explains the relationship between the two zones. By developing numerical thermal models, we examine the governing role of thermo-petrologically controlled fault zone rheology (frictional versus viscous shear). High temperatures in the warm-slab environment cause the megathrust seismogenic zone to terminate before reaching the depth of the intersection of the continental Mohorovičić discontinuity (Moho) and the subduction interface, called the mantle wedge corner. High pore-fluid pressures around the mantle wedge corner give rise to an isolated friction zone responsible for ETS. Separating the two zones is a segment of semi-frictional or viscous behaviour. The new model reconciles a wide range of seemingly disparate observations and defines a conceptual framework for the study of slip behaviour and the seismogenesis of major faults.


Follow-up of post-transplant minimal residual disease and chimerism in childhood lymphoblastic leukaemia: 90 d to react.
Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days -30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre- or post-transplant MRD status ≥10(-3) . Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention.


Cardioprotection from metabolism to molecules to certainties.
Starting millions of years ago, the heart developed metabolic and molecular cardioprotective paths. The concept of metabolic protection includes the recent successful early provision of glucose-insulin-potassium (GIK) to patients with acute coronary syndromes in the ambulance to inhibit high harmful free-fatty acid levels. Molecular cardioprotective pathways also developed in primeval times. The 2 major paths are the RISK (Reperfusion Injury Salvage Kinases) path and the SAFE (Survival Activating Factor Enhancement) path, on which our group in Cape Town has focused. These paths help to lessen ischaemic-perfusion damage, and may, hypothetically, also be activated by intense exercise.


Parallel algorithm for the computation of the Hartree-Fock exchange matrix: gas phase and periodic parallel ONX.
In this paper we present an efficient parallelization of the ONX algorithm for linear computation of the Hartree-Fock exchange matrix [J. Chem. Phys. 106, 9708 (1997)]. The method used is based on the equal time (ET) partitioning recently introduced [J. Chem. Phys. 118, 9128 (2003)] and [J. Chem. Phys. 121, 6608 (2004)]. ET exploits the slow variation of the density matrix between self-consistent-field iterations to achieve load balance. The method is presented and some benchmark calculations are discussed for gas phase and periodic systems with up to 128 processors. The current parallel ONX code is able to deliver up to 77% overall efficiency for a cluster of 50 water molecules on 128 processors (2.56 processors per heavy atom) and up to 87% for a box of 64 water molecules (two processors per heavy atom) with periodic boundary conditions.


Clumped isotope measurements of small carbonate samples using a high-efficiency dual-reservoir technique.
The measurement of multiply substituted isotopologues of CO2 derived from carbonate has allowed the reconstruction of paleotemperatures from a single phase (CaCO3 ), circumventing uncertainty inherent in other isotopic paleothermometers. Traditional analytical techniques require relatively large amounts of carbonate (3-8 mg per replicate), which limits the applicability of the clumped isotope proxy to certain geological materials such as marine microfossils, commonly used for paleoclimate reconstructions. Clumped isotope ratio measurements of small samples were made on a new, high-efficiency, dual-reservoir sample-preparation inlet system attached to a Thermo-Finnigan MAT 253 mass spectrometer. Sample gas produced on the inlet is introduced from a 10 mL reservoir directly into the source via a capillary. Reference gas fills an identical 10 mL reservoir installed between the reference bellows and the capillary. The gas pressures in the two reservoirs are initially balanced, and are allowed to decrease together over the run. Carbonate samples from 1 mg to 2.6 mg produced Δ47 values equivalent to those from the traditional two-bellows method with identical single-sample precision (1 SE = 0.005-0.015‰) and external standard error (SE = 0.006-0.015‰, n = 4-6). The size of sample needed to achieve good precision is controlled by the sensitivity of the mass spectrometer and the size of the fixed reservoirs and adjacent U-trap installed on our inlet. The high-precision clumped isotope measurements of small aliquots of carbonate obtained in this method allows for the application of this proxy to a wider range of geological sample materials, such as marine microfossils, that until now have been nearly impossible to analyze given sample size limitation.


Effects of introducing an enhanced recovery after surgery programme for patients undergoing open hepatic resection.
Enhanced recovery after surgery (ERAS) protocols are coming to represent the standard of care in many surgical procedures, yet data on their use following hepatic surgery are scarce. The aim of this study was to review outcomes after the introduction of an ERAS programme for patients undergoing open hepatic resection. A retrospective review of patients undergoing open hepatic resection from March 2005 to June 2011 was carried out. The primary outcome measure was total hospital length of stay (LoS) (including readmissions). Principles associated with enhanced recovery after surgery were documented and analysed as independent predictors of hospital LoS. A total of 120 patients underwent 128 consecutive hepatic resections, 84 (65.6%) of which were performed in patients with underlying colorectal metastases and 64 (50.0%) of which comprised major hepatic resections. The median hospital LoS was reduced from 6 days to 3 days from the first to the fourth quartiles of the study population (P = 0.021). The proportion of patients suffering complications (26.6%) remained constant across the series. Readmissions increased from the first quartile (none of 32 patients) to the fourth quartile (seven of 32 patients) (P = 0.044). Following multivariate analysis, only the development of a complication (P < 0.001), total postoperative i.v. fluid (P = 0.003) and formation of an anastomosis (P = 0.006) were independent predictors of hospital LoS. An ERAS programme can be successfully applied to patients undergoing open hepatic resection with a reduction in hospital LoS, but an increase in the rate of readmissions.


Direct-to-consumer DNA testing: the fallout for individuals and their families unexpectedly learning of their donor conception origins.
Increasing numbers of donor-conceived individuals (and/or parents) are seeking individuals genetically related through donor conception. One route is through 'direct-to-consumer' (DTC) DNA testing, prompting calls for fertility services to alert donors and prospective parents to the increasing unsustainability of anonymity and secrecy. The complexity of interpreting DNA results in this context has also been discussed, including their lack of absolute certainty, as has the need for professional and peer support. This commentary highlights a different 'threat', from individuals learning of their donor-conception origins through the use of such tests by themselves or relatives for such purposes as genealogy or health checks. It illustrates the personal complexities faced by three older women and their families on learning not only of their genetic relationship to each other but also to 15 more donor-related siblings. DTC DNA services are a growing feature of modern life. This commentary raises ethical questions about their responsibilities towards those inadvertently learning of donor conception origins and the responsibilities of fertility services to inform prospective parents and donors of this new phenomenon. Considerations of how and when parents should tell their children of their donor-conception origins here instead become how and when children should inform their parents.


Effect of External Electric Field Stress on Gliadin Protein Conformation.
A molecular dynamic (MD) modeling approach was applied to evaluate the effect of external electric field on gliadin protein structure and surface properties. Static electric field strengths of 0.001 V/nm and 0.002 V/nm induced conformational changes in the protein but had no significant effect on its surface properties. The study of hydrogen bond evolution during the course of simulation revealed that the root mean square deviation, radius of gyration and secondary structure formation, all depend significantly on the number hydrogen bonds formed. This study demonstrated that it is necessary to gain insight into protein dynamics under external electric field stress, in order to develop the novel food processing techniques that can be potentially used to reduce or eradicate food allergens.


Family discord and stress predictors of depression and other disorders in adolescent children of depressed and nondepressed women.
To test the hypothesis that family stress variables are associated with the effects of maternal depression on offspring diagnoses and examined whether such factors may be differentially associated with disorders in offspring of depressed and never-depressed women. Eight hundred sixteen mothers and their 15-year-old children in an Australian community completed cross-sectional assessments of mother and youth diagnoses, interviewer-rated and self-reported quality of marital relationship/status, quality of parent-child relationship, and interviews for youth chronic and episodic stress. Women with depression histories were oversampled and included 458 never-depressed and 358 women with current or past major depressive episodes or dysthymic disorder. Significant interaction effects were found between maternal depression and family discord/stress variables such that high levels of environmental risk factors were significantly associated with youth depression in children of depressed women compared with low levels of adverse conditions and were generally less associated with depression in children of nondepressed women. Nondepressive disorders were associated with adverse family and stress factors for both groups of children. The results are consistent with a multiple risk factor model of depression transmission in high-risk families and suggest a pattern of reactivity to adverse conditions among children of depressed women. The results suggest that psychosocial factors may contribute to diagnoses in offspring of depressed women in community samples.


Direct liquid chromatography tandem mass spectrometry analysis of amino acids in human plasma.
Here we describe a new HPLC-MS/MS method using a mixed mode stationary phase and a binary gradient of elution for the rapid separation and quantification of AAs in human plasma without derivatization or ion pairing reagent addition. The sample preparation procedure consists in a single dilution step after protein precipitation with sulfosalicylic acid. The proposed method allows for the unambiguous identification and analysis of 52 AAs and related compounds including the separation of isomers and isobars in an 18 min chromatographic run including the conditioning and the equilibration times. AAs were detected by selective reaction monitoring. Internal calibration was used for the quantification of 37 AAs, including 25 using the corresponding isotopically labeled internal standards. External calibration (no internal standard) was used for five additional analytes. Qualitative detection was achieved for the remaining compounds. Validation studies evaluated accuracy, linearity, within- and between-run precision, lower limits of detection and quantification for 37 amino acids present in commonly used quality control samples. For within-run precision CVs averaged 3.8 % (n = 30) for all compounds. For between-run precision, CVs averaged 8.6 % for all compounds (n = 20). Correlation with the common standard ion-exchange chromatography with post-column derivatization method was also performed for 32 plasma samples. While the proposed method is at least 50 times more sensitive, the data showed good correlation with slopes equal or higher than 0.9 and correlation coefficients mostly higher than 0.90. The method was successfully applied for analysis of plasma samples for detection of inherited disorders of amino acid metabolism.


Tobacco use, beliefs and risk awareness in university students from 24 low, middle and emerging economy countries.
The aim of this study was to determine the prevalence of tobacco use, beliefs and risk awareness and psychosocial correlates of tobacco use among university students in 24 low, middle and emerging economy countries. Using anonymous questionnaires, data were collected from 16953 undergraduate university students (mean age 20.9, SD=2.9) from 25 universities in 24 countries across Asia, Africa and the Americas. Results indicate that overall 13.3% of the university students were current tobacco users, 22.4% for men and 6.6% for women, ranging from 3.8% in Singapore to 32.5% in Cameroon. The risk awareness of the smoking lung cancer link was 83.6%, while the risk awareness of the smoking heart disease link was 46.5%. Multivariate logistic regression found that older age, male gender, having a wealthy family background, living in a low income country, residing off campus on their own, poor beliefs in the importance not to smoke, awareness of the smoking heart disease link, hit by a sexual partner, depressive symptoms, and substance use (binge drinking and illicit drug use) were associated with current tobacco use.


Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family.
This study aimed to identify genetic mechanisms underlying severe retinal degeneration in one large family from northern Sweden, members of which presented with early-onset autosomal recessive retinitis pigmentosa and juvenile macular dystrophy. The clinical records of affected family members were analysed retrospectively and ophthalmological and electrophysiological examinations were performed in selected cases. Mutation screening was initially performed with microarrays, interrogating known mutations in the genes associated with recessive retinitis pigmentosa, Leber congenital amaurosis and Stargardt disease. Searching for homozygous regions with putative causative disease genes was done by high-density SNP-array genotyping, followed by segregation analysis of the family members. Two distinct phenotypes of retinal dystrophy, Leber congenital amaurosis and Stargardt disease were present in the family. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was carrier of the same mutation and a novel ABCA4 mutation c.4773+3A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants, which were evaluated by bioinformatics tools. In conclusion, presence of different genetic mechanisms resulting in variable phenotype within the family is not rare and can challenge molecular geneticists, ophthalmologists and genetic counsellors.


How many deaths can be prevented by newborn screening for congenital adrenal hyperplasia?
Congenital adrenal hyperplasia (CAH) is increasingly being included in newborn screening programs. Screening can prevent neonatal mortality in children with salt-wasting CAH, but the number of deaths prevented is not known. Cost-effectiveness analyses of screening require estimates of the probability of mortality in CAH. We reviewed the literature to identify cohort studies of children with CAH ascertained clinically in the absence of screening. We abstracted the numbers of infant deaths attributable to CAH. We also addressed sex ratios among children with clinically detected CAH and the contribution of ascertainment bias to unbalanced ratios. The evidence suggests a probability of infant death due to adrenal crises in salt-wasting CAH of 4% or less in contemporary advanced economies without screening for CAH. This is lower than previous estimates, although the rate of mortality could be considerably higher in populations with limited clinical awareness or access. Although screening for CAH is conducted in a number of countries, further research is still needed to provide reliable estimates on the numbers of prevented deaths, along with evidence-based assessments of the potential benefits, harms, and costs of screening.


Effect of somatosensory stimulation of two and three nerves on upper limb function in healthy individuals.
Improvement in motor function has been reported in healthy subjects following somatosensory stimulation (SS) of individual upper limb peripheral nerves. This effect could have beneficial applications in rehabilitation, but there is little knowledge of the effects of stimulating multiple upper limb nerves. This study evaluated the effects of SS of two and three nerves on hand function. A single blind within-group repeated measures design was utilized. Ten healthy subjects (27.1 ± 5.4 years [mean ± SD], three men) were recruited and, after a familiarization session, were given SS to the ipsilateral hand in a randomized order to two (ulnar and median) and three (ulnar, median and radial) nerves on two occasions separated by at least one week. The time required to complete the Jebsen-Taylor Hand Function Test (JTHFT) and handgrip strength of the ipsilateral hand were measured before and immediately after each SS session. Total JTHFT time decreased significantly by an average of 3.58 ± 2.75 s (9.9%; P = 0.003) and 4.10 ± 3.20 s (11.6%; P = 0.003) following SS to two and three nerves, respectively, but no difference between the two was found. Handgrip strength decreased significantly by 1.82 ± 1.91 kgf (P = 0.015) following SS to three nerves only. This study suggests that SS of three nerves may facilitate motor training but may also induce a reduction in muscle performance. Further studies are needed to determine the clinical implications of these findings for neurological rehabilitation.


Association patterns of Pseudomonas aeruginosa clinical isolates as revealed by virulence traits, antibiotic resistance, serotype and genotype.
The aims of this study were to assess the association patterns of 96 clinical isolates of Pseudomonas aeruginosa using hierarchical cluster analysis from data obtained from the measurement of the physicochemical cell surface properties, adhesion and initial biofilm formation abilities, to investigate any correspondence with source, serotype, beta-lactam pattern, motility and M13-PCR genogroup or clonal lineage, as well as to select clinical isolates that could act as representatives of the genotypic and phenotypic diversity of this P. aeruginosa population from a Portuguese Central Hospital. The isolates were phenotypically characterized by their ability to adhere and form biofilms on polystyrene surfaces, their affinity to hexadecane and silicone, their swimming and twitching abilities, their antibiotic susceptibility patterns and their serotypes. No particular phenotypic cluster associated with the same source, serotype, beta-lactam pattern, motility and M13-PCR genogroup and clonal lineage was found. Nevertheless, five representative strains of the P. aeruginosa population from this Hospital, selected on the basis of low genetic similarity, were also found to be dispersed among the phenotypic clusters.


[Bone marrow cells of mice immunized with different rabies vaccines].
Cytogenetic studies of bone marrow cells of mice after inoculated differently with viral vaccines (fixed rabies virus, antirabic vaccine with the remainder virulence and fully inactivated with ultraviolet light antirabic vaccine) showed that all the vaccines, except the fully inactivated one, caused temporary damages of chromosomes interfering with the process of the first mitotic divisions after the beginning of immunization. The live fixed rabies virus caused a secondary, more significant increase in the frequency of chromosome aberrations at later periods of investigation (30-60 days after starting the experiments). The fluorescent antibody technique detected the specific fixed rabies virus antigen in the bone marrow cells of immunized animals within 3-90 days.


Cross-Cultural Validation of the Rorschach Developmental Index.
The Developmental Index (DI) has recently been introduced as a composite Rorschach measure of psychological development and maturation, which can be used both with the Comprehensive System (Exner, 2003), and with the recently developed Rorschach Performance Assessment System (Meyer, Viglione, Mihura, Erard, & Erdberg, 2011). As the DI is new, and its validity has not yet been investigated with independent non-U.S. samples, we tested the correlation between DI and age using 3 relatively large samples, 2 of which were from outside the United States (total N = 902). Other Rorschach variables presumably associated with maturation, such as complexity and productivity, were also investigated. As expected, the DI significantly correlated with age, with small variations across the 3 samples. Importantly, the correlation between DI and age remained statistically significant also after controlling for productivity (i.e., the number of responses) and complexity.


Association of Prenatal and Postnatal Exposures to Warm or Cold Air Temperatures With Lung Function in Young Infants.
Little is known about long-term associations of early-life exposure to extreme temperatures with child health and lung function. To investigate the association of prenatal and postnatal heat or cold exposure with newborn lung function and identify windows of susceptibility. This population-based cohort study (SEPAGES) recruited pregnant women in France between July 8, 2014, and July 24, 2017. Data on temperature exposure, lung function, and covariates were available from 343 mother-child dyads. Data analysis was performed from January 1, 2021, to December 31, 2021. Mean, SD, minimum, and maximum temperatures at the mother-child's residence, estimated using a state-of-the-art spatiotemporally resolved model. Outcome measures were tidal breathing analysis and nitrogen multiple-breath washout test measured at 2 months of age. Adjusted associations between both long-term (35 gestational weeks and first 4 weeks after delivery) and short-term (7 days before lung function test) exposure to ambient temperature and newborn lung function were analyzed using distributed lag nonlinear models. A total of 343 mother-child pairs were included in the analyses (median [IQR] maternal age at conception, 32 [30.0-35.2] years; 183 [53%] male newborns). A total of 246 mothers and/or fathers (72%) held at least a master's degree. Among the 160 female newborns (47%), long-term heat exposure (95th vs 50th percentile of mean temperature) was associated with decreased functional residual capacity (-39.7 mL; 95% CI, -68.6 to -10.7 mL for 24 °C vs 12 °C at gestational weeks 20-35 and weeks 0-4 after delivery) and increased respiratory rate (28.0/min; 95% CI, 4.2-51.9/min for 24 °C vs 12 °C at gestational weeks 14-35 and weeks 0-1 after delivery). Long-term cold exposure (5th vs 50th percentile of mean temperature) was associated with lower functional residual capacity (-21.9 mL; 95% CI, -42.4 to -1.3 mL for 1 °C vs 12 °C at gestational weeks 15-29), lower tidal volume (-23.8 mL; 95% CI, -43.1 to -4.4 mL for 1 °C vs 12 °C at gestational weeks 14-35 and weeks 0-4 after delivery), and increased respiratory rate (45.5/min; 95% CI, 10.1-81.0/min for 1 °C vs 12 °C at gestational weeks 6-35 and weeks 0-1 after delivery) in female newborns as well. No consistent association was observed for male newborns or short-term exposure to cold or heat. In this cohort study, long-term heat and cold exposure from the second trimester until 4 weeks after birth was associated with newborn lung volumes, especially among female newborns.


Modular Uniportal Video-Assisted Thoracoscopic Lobectomy and Lymphadenectomy: A Novel Pattern of Endoscopic Lung Cancer Resection.
Since the development of the uniportal video-assisted thoracoscopic surgery (VATS) technique, the use of uniportal VATS has become increasingly popular for the surgical resection of non-small cell lung cancer (NSCLC). The objective of this study is to introduce a novel modularly designed surgical pattern for uniportal VATS for lung cancer resection and to investigate the safety, feasibility, and efficacy of this novel method. The clinical data of NSCLC patients who underwent a curative uniportal VATS lobectomy between March 2015 and April 2016, including via the modular pattern (MP) and the conventional pattern (CP), were retrospectively collected and analyzed. Perioperative and postoperative parameters, including the operation duration, estimated intraoperative blood loss, rate of conversion to thoracotomy, lymph node dissection number, and postoperative complications, were compared between the two groups. A total of 321 patients were identified, among whom 221 underwent MP uniportal VATS lobectomy and 100 were treated via CP uniportal VATS lobectomy. Patients in the MP group experienced a shorter operation duration (135.58 ± 47.16 minutes versus 148.86 ± 42.53 minutes, P = .017) and less estimated intraoperative blood loss (75.20 ± 37.99 mL versus 89.50 ± 41.11 mL, P = .003) than patients in the CP group. No significant difference was observed in the intraoperative conversion rate (2.7% versus 5.0%, P = .477), total number of lymph nodes dissected (24.67 ± 7.73 versus 25.34 ± 7.62, P = .471), postoperative drainage duration (4.86 ± 1.96 days versus 4.78 ± 2.10 days, P = .755), length of stay (9.60 ± 2.93 days versus 9.97 ± 2.80 days, P = .286), or incidence of postoperative complications between the two groups. No postoperative deaths occurred. MP uniportal VATS lobectomy combined with mediastinal lymphadenectomy appears to be a safe and feasible technique for the treatment of NSCLC. The use of this technique can reduce the operation duration and intraoperative blood loss.


Fetal diagnosis of left ventricular aneurysm of the free wall and the interventricular septum: report of two cases and review of the literature.
Two cases of aneurysmatic bulgings of the free left ventricular wall and the interventricular septum, respectively diagnosed in late third trimester pregnancies are described. The diagnosis was confirmed by meticulous echocardiographic examination of the fetuses, who were referred for dysrhythmia. Based on sonographic findings and analysis of the clinical outcome, our previous cases emphasise management options both antenatally and postnatally. We further reviewed the current literature and discussed differences between aneurysmatic lesions with respect to their specific localisation to enhance our understanding of these fetal cardiac anomalies.


Experiences of communities with Lebanon's model of care for non-communicable diseases: a cross-sectional household survey from Greater Beirut.
Assess community perceptions of the Lebanese care model for non-communicable diseases (NCDs) and trust in the health system among others, and test association between them. Cross-sectional study using multistage random sampling and targeting adult community members living with NCDs. Households in Greater Beirut-Lebanon. 941 respondents including 574 Lebanese community members and 367 Syrian refugees. Three main outcomes (barriers to care seeking, perceptions of the care model and trust in healthcare) were assessed including by multiple linear regressions. Reported NCDs were hypertension (51.3%) and diabetes (34.5%), followed by chronic respiratory conditions (21.9%) and other cardiovascular diseases (20.0%). Communities reported seeking care from different sources. While 78% of Lebanese participants had visited private clinics at least once within the 6 months preceding the survey, 56% of Syrian refugees had done so. Determinants of access to care were health coverage, gender, and employment among Lebanese, and socioeconomic status among Syrian refugees. Lebanese community members had more positive perceptions of the care model compared with Syrian refugees and determinants included sociodemographic characteristics and the type of providers. Trust in the health system was higher among Syrian compared with Lebanese participants and was significantly influenced by the care model score and barriers to care seeking. Our study generated evidence about the experience of people living with NCDs with Lebanon's care model and can inform service delivery interventions towards a more inclusive person-centred approach.


Psychosocial evaluation of living liver donors-State of current practices in the United States.
We surveyed living donor liver transplant programs in the United States to describe practices in the psychosocial evaluation of living donors focused on (1) composition of psychosocial team; (2) domains, workflow, and tools of the psychosocial assessment; (3) absolute and relative mental health-related contraindications to donation; and (4) postdonation psychosocial follow-up. We received 52 unique responses, representing 33 of 50 (66%) of active living donor liver transplant programs. Thirty-one (93.9%) provider teams included social workers, 22 (66.7%) psychiatrists, and 14 (42.4%) psychologists. Validated tools were rarely used, but domains assessed were consistent. Respondents rated active alcohol (93.8%), cocaine (96.8%), and opioid (96.8%) use disorder, as absolute contraindications to donation. Active suicidality (97%), self-injurious behavior (90.9%), eating disorders (87.9%), psychosis (84.8%), nonadherence (71.9%), and inability to cooperate with the evaluation team (78.1%) were absolute contraindications to donation. There were no statistically significant differences in absolute psychosocial contraindications to liver donation between geographical areas or between large and small programs. Programs conduct postdonation psychosocial follow-up (57.6%) or screening (39.4%), but routine follow-up of declined donors is rarely conducted (15.8%). Psychosocial evaluation of donor candidates is a multidisciplinary process. The structure of the psychosocial evaluation of donors is not uniform among programs though the domains assessed are consistent. Psychosocial contraindications to living liver donation vary among the transplant programs. Mental health follow-up of donor candidates is not standardized.


Severity of interpersonal problems in individuals with body dysmorphic disorder.
Body dysmorphic disorder (BDD) is a relatively common and often severe disorder. Although individuals with BDD have markedly poor psychosocial functioning, the nature of interpersonal problems has been only minimally investigated. This study examined the severity, domains, and correlates of interpersonal problems in 51 individuals with BDD using the Inventory of Interpersonal Problems-64 (IIP-64) and other reliable and valid measures. Compared to norms for a U.S. community sample, individuals with DSM-IV BDD reported greater severity of interpersonal problems across most IIP-64 domains. BDD subjects' scores were most elevated on the Socially Inhibited and Nonassertive subscales. More severe BDD symptoms were significantly correlated with higher scores on the Socially Inhibited, Nonassertive, and Vindictive/Self-Centered subscales and with IIP-64 total score. In a logistic regression analysis, BDD severity and a personality disorder were independently associated with severity of interpersonal problems. These findings suggest that individuals with BDD have significant problems with interpersonal relationships, particularly in the areas of social inhibition and nonassertiveness.


Biotransformation on the triterpenoid saponin of Ardisia gigantifolia by Aspergillus avenaceus AS 3.4454.
Compound 1, a triterpenoid saponin from Ardisia gigantifolia Stapf. showing potential anti-tumor activity, was transformed into three derivatives (2-4) by Aspergillus avenaceus 3.4454. Among them, compounds 2 and 3 are new compounds. Their structures were elucidated on the basis of 1D NMR, 2D NMR, HR-ESI-MS, and optical rotation data. Compounds 1-3 were evaluated for their cytotoxicity against human hepatocellular carcinoma and normal liver cells by cell counting kit 8 colorimetric assay. Compound 3 displayed better cytotoxicity against Bel-7402 and HepG2 cell lines and much weaker cytotoxicity against normal liver L02 cell than that of positive control (epirubicin hydrochloride).


Generation and characterization of an inducible transgenic model for studying mouse esophageal biology.
To facilitate the in vivo study of esophageal (stem) cell biology in homeostasis and cancer, novel mouse models are necessary to elicit expression of candidate genes in a tissue-specific and inducible fashion. To this aim, we developed and studied a mouse model to allow labeling of esophageal cells with the histone 2B-GFP (H2B-GFP) fusion protein. First, we generated a transgenic mouse model expressing the reverse tetracycline transactivator rtTA2-M2 under control of the promoter (ED-L2) of the Epstein-Barr virus (EBV) gene encoding the latent membrane protein-1 (LMP-1). The newly generated ED-L2-rtTA2-M2 (ED-L2-rtTA) mice were then bred with the previously developed tetO-HIST1H2BJ/GFP (tetO-H2B-GFP) model to assess inducibility and tissue-specificity. Expression of the H2B-GFP fusion protein was observed upon doxycycline induction but was restricted to the terminally differentiated cells above the basal cell layer. To achieve expression in the basal compartment of the esophagus, we subsequently employed a different transgenic model expressing the reverse transactivator rtTA2S-M2 under the control of the ubiquitous, methylation-free CpG island of the human hnRNPA2B1-CBX3 gene (hnRNP-rtTA). Upon doxycycline administration to the compound hnRNP-rtTA/tetO-H2B-GFP mice, near-complete labeling of all esophageal cells was achieved. Pulse-chase experiments confirmed that complete turnover of the esophageal epithelium in the adult mouse is achieved within 7-10 days. We show that the esophagus-specific promoter ED-L2 is expressed only in the differentiated cells above the basal layer. Moreover, we confirmed that esophageal turn-over in the adult mouse does not exceed 7-10 days.


Spatial and temporal MRI profile of ischemic tissue after the acute stages of a permanent mouse model of stroke.
To characterize the progression of injured tissue resulting from a permanent focal cerebral ischemia after the acute phase, Magnetic Resonance Imaging (MRI) monitoring was performed on adult male C57BL/6J mice in the subacute stages, and correlated to histological analyses. Lesions were induced by electrocoagulation of the middle cerebral artery. Serial MRI measurements and weighted-images (T2, T1, T2* and Diffusion Tensor Imaging) were performed on a 9.4T scanner. Histological data (Cresyl-Violet staining and laminin-, Iba1- and GFAP-immunostainings) were obtained 1 and 2 weeks after the stroke. Two days after stroke, tissues assumed to correspond to the infarct core, were detected as a hyperintensity signal area in T2-weighted images. One week later, low-intensity signal areas appeared. Longitudinal MRI study showed that these areas remained present over the following week, and was mainly linked to a drop of the T2 relaxation time value in the corresponding tissues. Correlation with histological data and immuno-histochemistry showed that these areas corresponded to microglial cells. The present data provide, for the first time detailed MRI parameters of microglial cells dynamics, allowing its non-invasive monitoring during the chronic stages of a stroke. This could be particularly interesting in regards to emerging anti-inflammatory stroke therapies.


Myeloblastoma (granulocytic sarcoma) of the ovary.
Myeloblastic neoplasms occur in patients with leukemia. In women, the ovary is a common site. The cells of the tumor are identical histochemically to those in the peripheral blood. The Giemsa stain, PAS stain, and Leder stain assist in the diagnosis. The tumors are responsive to radiation therapy, chemotherapy, and operative removal, but tend to be associated with decreased survival. This report describes a case of myeloblastoma of the ovary in an 18-year-old woman. The clinical and pathologic features of these tumors are described. The literature is reviewed briefly.


Nesiritide: review of clinical pharmacology and role in heart failure management.
Nesiritide mimics the actions of endogenous B-type natriuretic peptides. Clinical studies on patients who had acute decompensated heart failure demonstrated rapid-onset dose-related vasodilatory effects. Nesiritide reduces pulmonary capillary wedge pressure and improves dypsnea. These effects compared favorably to standard treatments. It decreases preload and afterload and suppresses the renin-angiotensin-aldosterone axis and the release of norepinephrine. Nesiritide also promotes diuresis and has no proarrhythmic effects. Nesiritide is a valuable therapeutic option in the treatment of patients hospitalized for decompensated heart failure. On-going studies target the examination of its long-term effects on mortality and morbidity and its pharmacoeconomic benefits to the healthcare system.


Assessment of Genetic Variability and Evolutionary Relationships of Rhizoctonia solani Inherent in Legume Crops.
Rhizoctonia solani is one of the most common soil-borne fungal pathogens of legume crops worldwide. We collected rDNA-ITS sequences from NCBI GenBank, and the aim of this study was to examine the genetic diversity and phylogenetic relationships of various R. solani anastomosis groups (AGs) that are commonly associated with grain legumes (such as soybean, common bean, pea, peanut, cowpea, and chickpea) and forage legumes (including alfalfa and clover). Soybean is recognized as a host for multiple AGs, with AG-1 and AG-2 being extensively investigated. This is evidenced by the higher representation of sequences associated with these AGs in the NCBI GenBank. Other AGs documented in soybean include AG-4, AG-7, AG-11, AG-5, AG-6, and AG-9. Moreover, AG-4 has been extensively studied concerning its occurrence in chickpea, pea, peanut, and alfalfa. Research on the common bean has been primarily focused on AG-2, AG-4, and AG-1. Similarly, AG-1 has been the subject of extensive investigation in clover and cowpea. Collectively, AG-1, AG-2, and AG-4 have consistently been identified and studied across these diverse legume crops. The phylogenetic analysis of R. solani isolates across different legumes indicates that the distinct clades or subclades formed by the isolates correspond to their specific anastomosis groups (AGs) and subgroups, rather than being determined by their host legume crop. Additionally, there is a high degree of sequence similarity among isolates within the same clade or subclade. Principal coordinate analysis (PCoA) further supports this finding, as isolates belonging to the same AGs and/or subgroups cluster together, irrespective of their host legume. Therefore, the observed clustering of R. solani AGs and subgroups without a direct association with the host legume crop provides additional support for the concept of AGs in understanding the genetic relationships and evolution of R. solani.


Spatial association between speciated fine particles and mortality.
Particulate matter (PM) has been linked to a range of serious cardiovascular and respiratory health problems, including premature mortality. The main objective of our research is to quantify uncertainties about the impacts of fine PM exposure on mortality. We develop a multivariate spatial regression model for the estimation of the risk of mortality associated with fine PM and its components across all counties in the conterminous United States. We characterize different sources of uncertainty in the data and model the spatial structure of the mortality data and the speciated fine PM. We consider a flexible Bayesian hierarchical model for a space-time series of counts (mortality) by constructing a likelihood-based version of a generalized Poisson regression model that combines methods for point-level misaligned data and change of support regression. Our results seem to suggest an increase by a factor of two in the risk of mortality due to fine particles with respect to coarse particles. Our study also shows that in the Western United States, the nitrate and crustal components of the speciated fine PM seem to have more impact on mortality than the other components. On the other hand, in the Eastern United States, sulfate and ammonium explain most of the fine PM effect.


[Source apportionment of soil heavy metals in Jiapigou goldmine based on the UNMIX model].
The paper determines 16 kinds of metal elements' concentration in soil samples which collected in Jipigou goldmine upper the Songhua River. The UNMIX Model which was recommended by US EPA to get the source apportionment results was applied in this study, Cd, Hg, Pb and Ag concentration contour maps were generated by using Kriging interpolation method to verify the results. The main conclusions of this study are: (1)the concentrations of Cd, Hg, Pb and Ag exceeded Jilin Province soil background values and enriched obviously in soil samples; (2)using the UNMIX Model resolved four pollution sources: source 1 represents human activities of transportation, ore mining and garbage, and the source 1's contribution is 39. 1% ; Source 2 represents the contribution of the weathering of rocks and biological effects, and the source 2's contribution is 13. 87% ; Source 3 is a comprehensive source of soil parent material and chemical fertilizer, and the source 3's contribution is 23. 93% ; Source 4 represents iron ore mining and transportation sources, and the source 4's contribution is 22. 89%. (3)the UNMIX Model results are in accordance with the survey of local land-use types, human activities and Cd, Hg and Pb content distributions.


Characterization of conformers of D 1 of photosystem II using site-directed antibodies.
Antibodies have been raised to synthetic peptides, corresponding to a region in the loop spanning helices 4 and 5 of D 1 protein (Ala 250-Phe 265) and to a region anticipated to be near the C terminus of mature D 1 (His 332-Ala 345). Polyclonal antibodies to the sequence His 332-Ala 345 reacted with a 32 kDa polypeptide in thylakoid preparations identified as D 1 from its resistance (pea) or susceptibility (wheat) to lysine-C degradation. A monoclonal antibody to His 332-Ala 345 reacted preferentially with a faster migrating polypeptide in SDS electrophoresis, a putative conformer of D 1. Polyclonal antibodies to the sequence Ala 250-Phe 265 also reacted with the faster running polypeptide but not with the population of molecules running at 32 kDa. The putative conformer of D 1 from wheat appears to be more resistant than the main D 1 population to lysine-C degradation. Peptide analyses by Takahashi et al. [(1988) FEBS Lett, 240, 6-8] suggest Asn 335-Ala 344 lies at the processed C terminus. The present report provides immunological confirmation that this sequence is retained in mature D 1.


Gas-liquid critical parameters of asymmetric models of ionic fluids.
The effects of size and charge asymmetry on the gas-liquid critical parameters of a primitive model (PM) of ionic fluids are studied within the framework of the statistical field theory based on the collective variables method. Recently, this approach has enabled us to obtain the correct trends of the both critical parameters of the equisize charge-asymmetric PM without assuming ionic association. In this paper, we focus on the general case of an asymmetric PM characterized by the two parameters: hard-sphere diameter, lambda=sigma+/sigma-, and charge, z=q+/|q-|, ratios of the two ionic species. We derive an explicit expression for the chemical potential conjugate to the order parameter which includes the effects of correlations up to the third order. Based on this expression we consider the three versions of PM: a monovalent size-asymmetric PM (lambda not equal 1, z=1) , an equisize charge-asymmetric PM (lambda=1, z not equal 1) and a size- and charge-asymmetric PM (lambda not equal 1, z=2) . Similar to simulations, our theory predicts that the critical temperature and the critical density decrease with the increase in size asymmetry. Regarding the effects of charge asymmetry, we obtain the correct trend of the critical temperature with z , while the trend of the critical density obtained in this approximation is inconsistent with simulations, as well as with our previous results found in the higher-order approximation. We expect that the consideration of the higher-order correlations will lead to the correct trend of the critical density with charge asymmetry.


The role of a cAMP-dependent pathway in the uterine relaxant action of relaxin in rats.
The aim of this study was to investigate the role of the adenylyl cyclase pathway, and in particular cyclic AMP-dependent protein kinase A, in the relaxant action of relaxin in the isolated uterus of the nonpregnant rat. The purportedly selective inhibitor of cAMP-dependent protein kinase A N-[2-(methylamino) ethyl]-5-isoquinolinesulfonamide hydrochloride (H-8) (at 100 mumol l-7) antagonized relaxin, salbutamol (an agonist at beta-adrenoceptors) and levcromakalim (a K+ channel opener) to a similar extent (by factors of 3.1, 1.9 and 2.8, respectively), demonstrating that it is not a selective inhibitor. Relaxin and levcromakalim were less potent and had smaller, maximal, relaxant effects in longitudinal myometrium than in intact uterus cut in the longitudinal plane. By contrast, nifedipine (a Ca2+ channel blocker) was equipotent in the two preparations and salbutamol only slightly less potent in the longitudinal myometrium. Relaxin did not alter the cyclic AMP-dependent protein kinase A activity ratio in longitudinal myometrium, but did increase the activity ratio by a factor of 2.0 +/- 0.2 in the intact uterus. Salbutamol, the positive control, increased this activity ratio in both longitudinal myometrium (by 1.9 +/- 0.3 times) and in the intact uterus (by 3.8 +/- 0.3 times), whereas the negative control levcromakalim had no effect. Relaxin seems to act as a relaxant of longitudinal myometrium by a cyclic AMP-independent mechanism but possibly interacts with the circular myometrium or endometrium to release a relaxant factor via a cyclic-AMP-dependent mechanism.


Multimodal cell with simultaneous electrochemical quartz crystal microbalance and in operando spectroscopic ellipsometry to understand thin film electrochemistry.
To inform the development of advanced electrodes for energy storage, water treatment, and catalysis, among other applications, we need to improve our understanding of how material structure evolves during electrochemical operation. Insight into the evolution of local atomic structure during electrochemical operation is accessible through a range of sophisticated in operando probes, but techniques for in operando observation of macroscale electrode phenomena (e.g., swelling, dissolution, and chemical degradation) are limited. This macroscale understanding is critical to establish a full picture of electrochemical material behavior. Here, we report a multimodal cell for simultaneous electrochemical quartz crystal microbalance (EQCM) and in operando spectroscopic ellipsometry (SE). This SE-EQCM cell allows for the measurement of mass, thickness, optical properties, and electrochemical properties together in one device. Using polyaniline (PANI) as a test case, we demonstrate the use of this SE-EQCM cell to rapidly measure known phenomena and reproduce a range of prior results during the electrodeposition, electrochemical cycling, and electrochemical degradation of PANI. In particular, the simultaneous mass and thickness measurement afforded by this cell allows us to distinguish known qualitative differences in the degradation of PANI under oxidative and reductive potentials. The SE-EQCM cell we report promises to reveal new insights into the electrochemical behavior of thin film materials for a range of applications.


Fpga based hardware synthesis for automatic segmentation of retinal blood vessels in diabetic retinopathy images.
Diabetic Retinopathy (DR) is a disorder that affects the structure of retinal blood vessels due to long-standing diabetes mellitus. Real-Time mass screening system for DR is vital for timely diagnosis and periodic screening to prevent the patient from severe visual loss. Human retinal fundus images are widely used for an automated segmentation of blood vessel and diagnosis of various blood vessel disorders. In this work, an attempt has been made to perform hardware synthesis of Kirsch template based edge detection for segmentation of blood vessels. This method is implemented using LabVIEW software and is synthesized in field programmable gate array board to yield results in real-time application. The segmentation of blood vessels using Kirsch based edge detection is compared with other edge detection methods such as Sobel, Prewitt and Canny. The texture features such as energy, entropy, contrast, mean, homogeneity and structural feature namely ratio of vessel to vessel free area are obtained from the segmented images. The performance of segmentation is analysed in terms of sensitivity, specificity and accuracy. It is observed from the results that the Kirsch based edge detection technique segmented the edges of blood vessels better than other edge detection techniques. The ratio of vessel to vessel free area classified the normal and DR affected retinal images more significantly than other texture based features. FPGA based hardware synthesis of Kirsch edge detection method is able to differentiate normal and diseased images with high specificity (93%). This automated segmentation of retinal blood vessels system could be used in computer-assisted diagnosis for diabetic retinopathy screening in real-time application.


Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia.
Autosomal dominant hypercholesterolemia (ADH) is a frequent (1/500) monogenic inherited disorder characterized by isolated elevation of LDL leading to premature cardiovascular disease. ADH is known to result from mutations at two main loci: LDLR (encoding the low density lipoprotein receptor), and APOB (encoding apolipoprotein B100), its natural ligand. We previously demonstrated that ADH is also caused by mutations of the PCSK9 (proprotein convertase subtilisin/kexin type 9) gene that encodes Narc-1 (neural apoptosis-regulated convertase 1). However, the role of this novel disease locus as a cause of hypercholesterolemia remains unclear. In the present study, we analysed the PCSK9 coding region and intronic junctions in 130 adult or pediatric patients with ADH, previously found as being non LDLR/non APOB mutation carriers. Four novel heterozygous missense variations were found: c.654A>T (p.R218S), c.1070G>A (p.R357H), c.1405C>T (p.R469W), and c.1327G>A (p.A443T). All mutations were absent in 340 normolipidemic controls. Except for the A443T, all mutations are nonconservative and modify a highly conserved residue. Segregation with hypercholesterolemia is incomplete in one pedigree. Type and severity of hyperlipidemia and of cardiovascular disease could vary among subjects from the same family. Finally, the proband carrying the R357H mutation exhibited very high plasma cholesterol during pregnancy, whereas the proband carrying the p.R469W mutation exhibited a severe phenotype of hypercholesterolemia in combination with a LDLR mutation resulting from a frameshift at residue F382 (1209delC). These observations suggest that variations in PCSK9 are a rare cause of non LDLR/non APOB ADH (approximately 2.3%) and that additional environmental or genetic factors may contribute to the phenotype caused by PCSK9 missense mutations in humans.


Spectral effects of LEDs on chlorophyll fluorescence and pigmentation in Phalaenopsis 'Vivien' and 'Purple Star'.
We examined the effect of light emitting diode (LED) lighting in greenhouse facilities on growth, chlorophyll fluorescence and pigmentation in Phalaenopsis 'Vivien' and 'Purple Star' under purpose-built LED arrays yielding c. 200 µmol m(-2) s(-1) at plant height for 14 h per day and 24/18°C day/night temperature, respectively, from January to April 2013. The light treatments were (1) 40% blue in 60% red (40% B/R), (2) 0% blue in 100% red (0% B/R) and (3) white LEDs with 32% blue in white (32% B/W, control), with background daylight under shade screens. The plants were harvested twice for leaf growth and pigmentation. There was no clear pattern in the spectral effect on growth since the order of leaf size differed between harvests in March and April. Fv /Fm was in the range of 0.52-0.72, but overall slightly higher in the control, which indicated a permanent downregulation of PSII in the colored treatments. The fluorescence quenching showed no acclimation to color in 'Purple Star', while 'Vivien' had lower ETR and higher NPQ in the 40% B/R, resembling low light acclimation. The pigmentation showed corresponding spectral response with increasing concentration of lutein while increasing the fraction of blue light, which increased the light absorption in the green/yellow part of the spectrum. The permanent downregulation of PSII moved a substantial part of the thermal dissipation from the light regulated NPQ to non-regulated energy losses estimated by ΦNPQ and ΦNO and the difference found in the balance between ΦPSII and ΦNPQ in 'Vivien' disappeared when ΦNO was included in the thermal dissipation.


Theology, religious traditions, and bioethics.
The social and medical ethos within which bioethics emerged in the late 1960s and early 1970s was constituted in part by religious questions and religious thinkers. However, this identifiably religious influence on bioethics subsequently seemed to decline. How has this diminished impact come about, and what significance, if any, does it hold for the ways we now do bioethics? What difference, finally, do religious perspectives make for bioethics? These were the overarching questions that led the Hastings Center to initiate a research project on the relation of Religion and Bioethics, culminating in this special supplement to the Hastings Center Report.


The utility of the International Classification of Functioning, Disability and Health checklist for evaluating disability in a community-dwelling geriatric population sample.
The aim of this study was to investigate disability in community-dwelling individuals aged 65 years and over using the International Classification of Functioning, Disability and Health (ICF) checklist and the World Health Organization Disability Assessment Schedule II (WHODAS-II) and to compare how these two ICF-based instruments measured disability in an attempt to show the utility of the ICF checklist in a field setting to describe disability. In this population-based, cross-sectional and descriptive study, data on the ICF checklist and the WHODAS-II were collected from 200 selected participants who lived in a small town. Both the ICF checklist and the WHODAS-II identified a considerable proportion of the elderly with a disability in life areas relevant to cognition and domestic life in a similar manner, the proportions ranging from 52.5 to 68.5%. However, the proportions of those with a disability showed a statistically significant difference in the domains of the two instruments relevant to mobility, self-care, and participation in society. Although the absolute intrarater agreement for matching items of the instruments ranged from 40.5 to 87.5%, kappa statistics showed slight to moderate agreement for the original ICF qualifier and mostly moderate agreement with reduced response options. ICF qualifiers were found to discriminate between the WHODAS-II domain scores in those with no, mild-moderate and severe-complete difficulty. The disparity between the data obtained from the ICF checklist and the WHODAS-II in some domains may have resulted from differing interpretations of the items of the ICF checklist, lower reliability of some of the items, and the current feature of the qualifiers used without any adaptations. The ICF checklist has the potential to be used in a field setting, provided that some modifications are made.


Comparative efficacy and safety of vaginal misoprostol versus dinoprostone vaginal insert in labor induction at term: a randomized trial.
To compare efficacy and safety of vaginal misoprostol (PGE(1) analog) with dinoprostone (PGE(2) analog) vaginal insert for labor induction in term pregnancies. A total of 112 women with singleton pregnancies of > or =37 weeks of gestation, and low Bishop scores underwent labor induction. The subjects were randomized to receive either 50 mug misoprostol intravaginally every 4 h to a maximum of five doses or a 10 mg dinoprostone vaginal insert for a maximum of 12 h. Time interval from induction to vaginal delivery, vaginal delivery rates within 12 and 24 h, requirement of oxytocin augmentation, incidence of tachysystole and uterine hyperstimulation, mode of delivery, rate of cesarean section due to fetal distress and neonatal outcome were outcome measures. Student's t test, Chi square test, Fischer's exact test were used for statistical analysis. Time interval from induction to vaginal delivery was found to be significantly shorter in misoprostol group when compared to dinoprostone subjects (680 +/- 329 min vs. 1070 +/- 435 min, P < 0.001). Vaginal delivery rates within 12 h were found to be significantly higher with misoprostol induction [n = 37 (66%) vs. n = 25 (44.6%); P = 0.02], whereas vaginal delivery rates in 24 h did not differ significantly between groups [n = 41 (73.2%) vs. n = 36 (64.2%); P = 0.3]. More subjects required oxytocin augmentation in dinoprostone group [n = 35 (62.5%) vs. n = 20 (35.7%), P = 0.005] and cardiotocography tracings revealed early decelerations occurring more frequently with misoprostol induction (10.7 vs. 0%, P = 0.03). Tachysystole and uterine hyperstimulation, mode of delivery, rate of cesarean sections due to fetal distress and adverse neonatal outcome were not demonstrated to be significantly different between groups (P = 1, P = 0.5, P = 0.4, P = 0.22, P = 0.5). Using vaginal misoprostol is an effective way of labor induction in term pregnant women with unfavorable cervices, since it is associated with a shorter duration of labor induction and higher rates of vaginal delivery within 12 h. Misoprostol and dinoprostone are equally safe, since misoprostol did not result in a rise in maternal and neonatal morbidity, namely, tachysystole, uterine hyperstimulation, cesarean section rates and admission to neonatal intensive care units as reported previously in literature.


Blockade of NKG2D/NKG2D ligand interaction attenuated cardiac remodelling after myocardial infarction.
Accumulating evidence demonstrates that cardiomyocyte death contributes to the onset and progression of heart failure (HF) after myocardial injury. Recent studies revealed that immune/inflammatory reactions play important roles in cardiovascular diseases. However, it remains unclear whether immunosurveillance system, which eliminates cytopathic cells, including infected or malignant cancer cells, is involved in cardiomyocyte death, though cardiomyocytes are exposed to pathological stresses during post-infarct remodelling. The aim of this study is to clarify the pathophysiological significance of Natural Killer Group 2 member D (NKG2D)/NKG2D ligand (NKG2DL)-mediated cell death in HF after myocardial infarction (MI). MI was generated by ligating left anterior descending artery in mice. The expression of NKG2D, NKG2DLs, especially Retinoic acid early induced transcript-1ɛ (Rae-1ɛ), perforin and granzyme B was concomitantly up-regulated after MI. Immunohistological analysis revealed that Rae-1 was expressed on the membranes of injured cardiomyocytes in the infarct and border area. The MI-induced increase of Rae-1 expression was suppressed in p53-/- mice and Rae-1 was induced by the overexpression of p53. We identified p53-binding sites in Rae-1ɛ gene promoter, by chromatin immunoprecipitation assay, indicating that Rae-1 expression was mediated partially through p53. Flow cytometric analysis indicated that NKG2D-expressing immune cells in the post-infarct myocardium were mainly γδT cells. The co-culture with γδT cells increased the frequency of apoptotic cells in the cultured cardiomyocytes. The blockade of NKG2D/NKG2DL interaction by intraperitoneal injection of anti-Rae-1ɛ antibody after MI reduced the frequency of apoptotic cardiomyocytes, accompanied by suppression of cardiac fibrosis, attenuating cardiac dysfunction. Finally, tamoxifen-inducible cardiomyocyte-specific Rae-1ɛ overexpressing mice exhibited the susceptibility to post-infarct remodelling with increased cardiomyocyte apoptosis and severer cardiac dysfunction. The interaction between immune cells and cardiomyocytes via NKG2D/NKG2DL induces cardiomyocyte death, exacerbating cardiac remodelling after MI. The blockade of NKG2D/NKG2DL interaction could be a promising therapeutic strategy against HF.


Music and movement to exercise older people.
While life expectancy is increasing, research suggests that there has not been a corresponding improvement in health in older age. This article considers the role of exercise in promoting healthy ageing and describes a nurse-led exercise programme for older people.


Is micronucleus assay in nasal mucosa cells an appropriate technique for detecting genotoxins by inhalation in humans? A systematic review.
This study aimed to evaluate the scientific literature on the micronucleus assay in nasal mucosa as an appropriate method for evaluating genotoxicity caused by chemical agents. According to the PRISMA guidelines, only in vivo human studies with micronucleus assays using nasal cells were considered. Reviews, case reports, editorials, letters to the editor, and articles not written in English were excluded. The following scientific databases/search engines were used: PubMed/MEDLINE, Scopus, and Web of Science. Results: This review included 13 studies. Four articles detected no statistical significance regarding the frequency of micronuclei while nine articles showed an increase in micronuclei in nasal cells. In the qualitative analysis, two articles were considered strong, eight were moderate and three were weak. The micronucleus assay using nasal mucosa cells is a sensitive and effective technique for assessing DNA damage and an appropriate method for monitoring humans continuously exposed to chemicals.


Computation of pump-leak flux balance in animal cells.
Many vital processes in animal cells depend on monovalent ion transport across the plasma membrane via specific pathways. Their operation is described by a set of nonlinear and transcendental equations that cannot be solved analytically. Previous computations had been optimized for certain cell types and included parameters whose experimental determination can be challenging. We have developed a simpler and a more universal computational approach by using fewer kinetic parameters derived from the data related to cell balanced state. A file is provided for calculating unidirectional Na(+), K(+), and Cl(-) fluxes via all major pathways (i.e. the Na/K pump, Na(+), K(+), Cl(-) channels, and NKCC, KC and NC cotransporters) under a balanced state and during transient processes. The data on the Na(+), K(+), and Cl(-) distribution and the pump flux of K(+) (Rb(+)) are obtained on U937 cells before and after inhibiting the pump with ouabain. There was a good match between the results of calculations and the experimentally measured dynamics of ion redistribution caused by blocking the pump. The presented approach can serve as an effective tool for analyzing monovalent ion transport in the whole cell, determination of the rate coefficients for ion transfer via major pathways and studying their alteration under various conditions.


Hepatic drug metabolism in older people with body composition changes.
Dosage adjustment is essential in older individuals because they are prone to experience a decline in liver function and changes in body composition. However, quantitative tests or equations for evaluating the activity of hepatic drug metabolism have not yet been clearly established. We examined hepatic drug metabolism activities in older individuals, focusing on changes in body composition parameters. Lansoprazole and nifedipine, substrates of the metabolic enzymes cytochrome P450 (CYP) 2C19 and 3A4, respectively, were selected to study hepatic drug metabolism. Residual samples from blood test for older patients were evaluated to determine drug metabolism. The body composition of relevant patients was determined by analyzing characteristic parameters of skeletal muscle mass index (SMI), handgrip strength (HGS) and hepatic steatosis index (HSI). The differences in hepatic drug metabolism were studied statistically among categories in terms of the cut-off value of these parameters. Older male patients receiving lansoprazole and nifedipine in the low SMI (<7.0 kg/m2 ) category showed an 85-90% reduction in respective CYP2C19 and CYP3A4 metabolic activities compared with the normal SMI category. For the female patients, CYP2C19 and CYP3A4 metabolic activities showed no significant correlation with SMI and HGS. Fatty liver disease (HSI ≥36) was found to reduce CYP2C19 metabolic activity particularly in older female patients. Low CYP2C19 metabolic activity was statistically correlated with low SMI in male patients and high HSI in female patients, whereas low CYP3A4 metabolic activity was statistically correlated with low HGS in male patients. Geriatr Gerontol Int 2022; 22: 449-454.


Crystal-Structure Simulation of Methylthiolated Peri-Condensed Polycyclic Aromatic Hydrocarbons for Identifying Promising Molecular Semiconductors: Discovery of 1,3,8,10-tetrakis(methylthio)peropyrene Showing Ultrahigh Mobility.
The crystal structures of molecular semiconductors critically affect their carrier-transport properties. One of the promising crystal structures that afford high carrier mobility is a brickwork structure recently reported for 1,3,6,8-tetrakis(methylthio)pyrene (MT-pyrene) showing ultrahigh mobility. However, such ultrahigh mobility is not realized in other methylchalocogenolated pyrenes, owing to subtle differences in the molecular positions in their crystal structures. This means that, for developing superior molecular semiconductors, it is desirable to simulate the crystal structure with sufficient quality before time-consuming and labor-intensive synthetic trials. To realize this, a new computational approach is developed to simulate crystal structures of all methylchalocogenolated pyrenes, which is then applied to MT-pyrene-related methylthiolated peri-condensed polycyclic aromatic hydrocarbons including perylene, peropyrene, and terrylene derivatives. Among these, 1,3,8,10-tetrakis(methylthio)peropyrene (MT-peropyrene) is expected to show high mobility based on the simulated crystal structures. Thus, MT-peropyrene is chosen as the synthetic target, and a new peropyrene synthesis method is developed. Thus synthesized MT-peropyrene has virtually the same crystal structure as the simulated one, and its single-crystal field-effect transistors show mobility as high as 30 cm2 V-1 s-1 and band-like transport behaviors. These results indicate that the present crystal-structure simulation is a powerful tool for exploring promising molecular semiconductors.


Expression of cell proliferation markers in pituitary adenomas--correlation and clinical relevance of MIB-1 and anti-topoisomerase-IIalpha.
Pituitary adenomas represent an inhomogeneous tumor entity in terms of growth rate, invasiveness and recurrence. To improve understanding of their different biological behaviour, tumor cell proliferation markers are applied. The aim of this study was to assess proliferation rates overall and in clinico-pathological subgroups using MIB-1 and the recently introduced cell proliferation marker anti-topoisomerase-IIalpha (Topo-IIalpha). Further, we correlated the two markers, and defined the clinical value of Topo-IIalpha in pituitary adenomas as compared to MIB-1. We analyzed tumor cell proliferation rates using MIB-1 and Topo-IIalpha antibodies on samples of 260 primary pituitary adenomas. We excluded recurrent cases and cases with drug pretreatment. Median patient age at the time of surgery was 47 years (range 14-86 years), the male:female ratio was 1:1. The total cohort comprised 110 non-functioning and 150 functioning cases. Subtyping was performed according to hormonal expression as defined by WHO. Tumor size and invasiveness were noted from surgical and/or radio logical reports in 95% of cases. Overall MIB-1 index was median 1.8% (range 0.2-23.6%), Topo-IIalpha index was median 1.0% (range 0-14.4%) with a strong correlation between the two markers ( R=0.837, P<0.001). As compared to MIB-1, mean Topo-IIalpha values were significantly lower by a factor 1.8. Only MIB-1 was significantly higher in invasive as compared to non-invasive adenomas, in tumors < or =3 cm in diameter, and in the age-group 21-40. Female gender had significantly higher MIB-1 and Topo-IIalpha indices than male. Silent ACTH-cell and PRL-producing adenomas had the highest, null-cell adenomas and gonadotropinomas the lowest proliferation values, respectively. Our data show a strong correlation between MIB-1 and Topo-IIalpha indices in pituitary adenomas. Only MIB-1 but not Topo-IIalpha demonstrated significantly higher values in invasive adenomas. Therefore, MIB-1 seems more useful than Topo-IIalpha for decisions regarding postoperative patient management.


The association of neuropsychiatric symptoms and environment with quality of life in assisted living residents with dementia.
We conducted this study to determine whether neuropsychiatric symptoms and environmental characteristics are associated with quality of life in assisted living residents with dementia. We used a cross-sectional study of 134 residents from 22 facilities and employed the Alzheimer's Disease-Related Quality of Life Scale and the Neuropsychiatric Inventory. A scale was developed to capture the homelike climate of each facility. Linear regression analyses were used to estimate the relationship of neuropsychiatric symptoms and homelike climate with quality of life, controlling for sociodemographics, cognition, functional dependence, and physical health. Exploratory analyses and graphical techniques were employed to test for environmental-level moderating effects. Agitation, depression, apathy, and irritability were significant predictors of quality of life, explaining 29% of the variance. Neither facility size nor homelike environment was significantly associated with quality of life in univariate analyses. Size of facility moderated the relationship between agitation and quality of life. Neuropsychiatric symptoms impair quality of life in residents with dementia. Further research should investigate the role of other environmental aspects.


Chemical assembly systems: layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients.
While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels--choice of starting material, reagent, or order of reaction modules--enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).


[Simplified scale for medication adherence related problems in anti-retroviral therapy].
The purpose is to describe an own-developed scale for medication adherence evaluation of HIV patients under antiretroviral therapy, and to compare it with other previously described methods. The six-item scale was compared with a pharmacy record about the delivery of medication. Accordance between scale and a four-item Morisky-type scale (measure 1) and a percentage of doses taken as prescribed during the past two weeks (measure 2) was computed. The own-scale showed 93% sensitivity, 70% specificity, a likelihood ratio of 3.08 and good agreement compared with the pharmacy record (k = 0.62, p < 0.001). Agreement between the scale and measure 1 and measure 2 was very weak (k = 0.12, p = 0.446 and k = 0.10, p = 0.273 respectively). 39.7% of patients was considered as adherent according with the own-scale and was observed correlation between adherence and clinical outcomes. The scale appears to be a valid instrument to check and detect adherence related problems compared with the pharmacy medication record. Easiness to use make feasible to consider as an adequate tool to detect non-adherent patients or patients with adherence related problems into the daily clinical practice.


Renal macrophage activation and Th2 polarization precedes the development of nephrotic syndrome in Buffalo/Mna rats.
At 8 weeks, Buffalo/Mna rats spontaneously develop a nephrotic syndrome associated with focal segmental glomerulosclerosis (FSGS). We have previously demonstrated that this glomerulopathy recurs after renal transplantation, thus supporting the relevance of this rat model to human idiopathic nephrotic syndrome [1]. In this study, we describe renal immune abnormalities which appear in parallel to the initiation and progression of the spontaneous Buffalo/Mna nephropathy. Buffalo/Mna rat kidney samples were harvested before (4 weeks) and after the occurrence of proteinuria (at 10, 18, and 24 weeks, and at 12, 15, 18, and 24 months). Renal immune cell populations [total lymphocytes, macrophages, T, B, and natural killer (NK) cells] and the expression kinetics of various related cytokine [transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10, IL-12, and IL-13], chemokine [regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein-l (MCP-1)] and T-cell receptor beta (TCR beta) chain transcripts were studied serially during the course of the disease. In the Buffalo/Mna kidneys, in parallel to the proteinuria, the focal and segmental glomerular lesions began to develop at 10 weeks (affecting 2.4 +/- 0.8% of glomeruli), increased in number, then in intensity (10.4 +/- 0.8% at 24 weeks, 14.6 +/- 2.3% at 12 months, and 28.9 +/- 7.4% at 18 months). Before the onset of the disease, at a nonproteinuric stage, the transcript expression analysis revealed a strong production of some macrophage-associated cytokines, particularly TNF-alpha (350-fold higher than control levels), which was corroborated by monocyte infiltration. A minor T-cell infiltrate (associated with an increase in Cbeta TCR transcripts), with a predominantly Th2 profile and the down-regulation of Th1 cytokines was also observed. These abnormal macrophage and T-cell patterns remained stable after the onset of the disease. No changes in chemokine and TGF-beta transcripts were observed during the initial stages of the disease. Our data suggest that the Buffalo/Mna rat disease may be the result of an immunologic disorder, involving macrophages and Th2 lymphocytes. We hypothesize that this modified environment could result in the production of a factor deleterious to the glomeruli. Thus, this rat strain could provide a new model for the study of human nephrotic syndrome.


Neoadjuvant pemetrexed plus cisplatin followed by pleurectomy for malignant pleural mesothelioma.
Despite becoming the preferred surgical technique for malignant pleural mesothelioma, pleurectomy/decortication has received few prospective clinical trials. Therefore, the Japan Mesothelioma Interest Group conducted a prospective multi-institutional study to evaluate the feasibility of neoadjuvant chemotherapy followed by pleurectomy/decortication. Patients with histologically confirmed, resectable malignant pleural mesothelioma underwent neoadjuvant chemotherapy comprising pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 for 3 cycles, followed by pleurectomy/decortication. The primary end point was macroscopic complete resection rate regardless of the surgical technique used. Among the 24 patients enrolled, 20 received neoadjuvant chemotherapy and 18 proceeded to surgery, all of whom achieved macroscopic complete resection. Pleurectomy/decortication was performed in 15 patients. The trial satisfied the primary end point, with a macroscopic complete resection rate of 90% (18/20, 95% confidence interval, 68.3-98.8). No treatment-related 30- and 90-day mortality occurred. The overall survival after 1 and 2 years and median overall survival after registration were 95.0% (95% confidence interval, 69.5-99.3), 70.0% (95% confidence interval, 45.1-85.3), and 3.45 years (95% confidence interval, 1.64 to not available), respectively. The cumulative incidence of progression after 1 and 2 years and median time to progression were 33.3% (95% confidence interval, 17.3-64.1), 61.1% (95% confidence interval, 42.3-88.3), and 1.71 years (95% confidence interval, 1.00-2.99), respectively. The best postoperative value for forced expiratory volume was 78.0% of preoperative values. Neoadjuvant chemotherapy followed by pleurectomy/decortication was feasible with acceptable survival and mortality/morbidity. Postoperative pulmonary function was approximately 80% of the preoperative pulmonary function.


Microfluidic Platform with Multiplexed Electronic Detection for Spatial Tracking of Particles.
Microfluidic processing of biological samples typically involves differential manipulations of suspended particles under various force fields in order to spatially fractionate the sample based on a biological property of interest. For the resultant spatial distribution to be used as the assay readout, microfluidic devices are often subjected to microscopic analysis requiring complex instrumentation with higher cost and reduced portability. To address this limitation, we have developed an integrated electronic sensing technology for multiplexed detection of particles at different locations on a microfluidic chip. Our technology, called Microfluidic CODES, combines Resistive Pulse Sensing with Code Division Multiple Access to compress 2D spatial information into a 1D electrical signal. In this paper, we present a practical demonstration of the Microfluidic CODES technology to detect and size cultured cancer cells distributed over multiple microfluidic channels. As validated by the high-speed microscopy, our technology can accurately analyze dense cell populations all electronically without the need for an external instrument. As such, the Microfluidic CODES can potentially enable low-cost integrated lab-on-a-chip devices that are well suited for the point-of-care testing of biological samples.


Evaluation of the endoscopic revision of dacryocystorhinostomy failure cases: a cohort study.
The dacryocystorhinostomy (DCR) procedure is linked to a high success rate; however, cases of tearing recurrence are not rare and should be managed efficiently. Thus, evaluating cases of DCR failure allows highlighting the factors significantly impacting the results in order to realize better controlled primary surgeries. Twenty-eight patients were operated in our Otolaryngology Department for endoscopic revision of DCR failure between January 2019 and June 2022. Their clinical presentation, postoperative evolution, and findings of the primary and revision surgeries were assessed until the actual follow-up. The first surgery was based on an external approach in 17 patients and the bicanalicular silicone tube intubation was kept for a mean of 4.25 months. The recurrence delay varied from 0.5 to 9 months. Revision surgery revealed synechia in 10 patients, a completely closed DCR ostium in 22 patients (78.57%) by mucosal scarring and granulation, and lacrimal sac fibrosis in 16 patients (57.14%). A significant correlation was found between maintenance of the silicone intubation tube greater than or equal to 3 months and lacrimal sac fibrosis (P=0.016<0.05). Thus, better controlled primary surgeries with optimal exposure, wild marsupialisation of the lacrimal sac and no longer systematic bicanalicular intubation which should be dedicated to difficult anatomies and canalicular affections should guarantee better functional results.


Prenatal phencyclidine induces heightened neurodegeneration in rats in some brain regions, especially during 2nd trimester, but possible anti-apoptotic effects in others.
Phencyclidine administered to the developing rat brain at high doses for a few hours during late foetal life induces apoptotic neurodegeneration in several brain regions. We sought to investigate whether prolonged, low level foetal exposure to phencyclidine during different gestational periods (2nd trimester versus 3rd trimester) would have different effects on several brain regions showing neurodegeneration as assessed using silver stains. Pregnant rats were treated with phencyclidine (5.45 mg/day) continuously for 5 days via minipumps, and the pups were either perfused immediately after birth and silver-stained for degeneration, or allowed to mature and then tested for behavioural deficits. In the newborn pups, there was a substantial increase in the number of agrophilic cells in entorhinal cortex and subiculum; this effect was greater when the drug was given during 2nd trimester. However, in the ventromedial nucleus of the hypothalamus, both the 2nd and 3rd trimester phencyclidine pups had significantly fewer degenerating cells than the controls. Behavioural tests of rotorod and open field performance in the pups allowed to mature indicated decreased motor coordination and hyperactivity in the 3rd trimester phencyclidine pups, but minimal alterations in the 2nd trimester pups. Thus, prenatal exposure to phencyclidine can have either neurodegenerative or antiapototic effects depending upon brain region, and there is a discrepancy between persisting behavioural deficits and amount of cell loss for time of maximal prenatal effect of the drug.


The relationship between hot flashes and fatty acid binding protein 2 in postmenopausal women.
Hot flashes, the most bothering symptom of menopause, are linked to a metabolic inflammation. Due to estrogen deficiency in menopause, dysbiosis is observed. The intestinal barrier affects the interaction of microbiota in healthy or unhealthy individuals. This study investigates the relationship between hot flashes and gut permeability in postmenopausal women. In this cross-sectional study, we divided 289 women, aged 40-65 years, into four groups based on their hot-flash severity: HF0: never experienced hot flashes; HFm: mild hot flashes; HFM: moderate hot flashes; HFS: severe hot flashes. The measured variables included the clinical parameters; hot flashes experience; fasting plasma levels of zonulin, fatty acid binding protein 2 (FABP2), endotoxin, and cytokines/chemokines. We used multiple linear regression analysis to evaluate the relationship between hot flashes and the previously mentioned gut barrier proteins. The study was performed in a hospital medical center. The hot flashes had a positive tendency toward increased levels of circulating FABP2 (P-trend = 0.001), endotoxin (P-trend = 0.031), high-sensitivity C-reactive protein (hs-CRP) (P-trend = 0.033), tumor necrosis factor alpha (TNF-α) (P-trend = 0.017), and interferon-inducible protein-10 (IP10) (P-trend = 0.021). Spearman's correlation analysis revealed significant correlations of FABP2 with endotoxin, TNF-α, monocyte chemoattractant protein-1, IP10, and hs-CRP in the 289 postmenopausal women included in this study. Linear regression analysis revealed that hot-flash severity had significant assoiciations with FABP2 (P-trend = 0.002), but not with zonulin. After adjusting for body mass index, age, and menopause duration, multivariate linear regression analysis revealed the differences between HFs (% difference (95% confidence interval), 22.36 (8.04, 38.59), P = 0.01) and HF0 groups in terms of FABP2 levels. This study shows that hot flashes are significantly associated with FABP2 levels in postmenopausal women. It suggests that severe hot flashes are linked to an increase in intestinal barrier permeability and low-grade systemic inflammation.


[Familial vesicoureteral reflux (author's transl)].
One family with all four children affected by vesicoureteral reflux is reported. The mother of children has shrinking kidneys. The possibility, that the congenital abnormality of vesicoureteral reflux is inherited, is discussed. The awareness, that reflux may be familial, led to search for the abnormality in close relatives.


Hyperphagia in dementia: 2. Food choices and their macronutrient contents in hyperphagia, dementia and ageing.
Up to one third of dementia sufferers eat an increased quantity of food compared with their premorbid intake, at some stage during the dementia. In addition, over half of people with dementia are reported, by their carers, to show a marked change in food choice, particularly an increased liking for sweet food. The macronutrient content of foods chosen and the ratio of sweet to savoury foods were investigated experimentally using a standardized mixed meal. Three subject groups were studied: 17 people with dementia who were reported by their carers to overeat and who ate excessively under experimental conditions; 14 people with dementia who ate a normal amount; and, normal, non-demented controls (18 under 50 years old and 14 over 50 years old). The results showed that the normal elderly people chose a lower proportion of high-protein food than the young. The proportion of protein eaten was lower in people with dementia than in age-matched controls and was even lower in the hyperphagic dementia group. The proportion of sweet food eaten was higher in people with dementia and even higher in people with dementia who were hyperphagic. Various mechanisms to account for the results are discussed.


Kidney disease among children in sub-Saharan Africa: systematic review.
The global burden of kidney disease is increasing, and several etiologies first begin in childhood. Risk factors for pediatric kidney disease are common in Africa, but data regarding its prevalence are lacking. We completed a systematic review of community-based studies describing the prevalence of proteinuria, hematuria, abnormal imaging, or kidney dysfunction among children in sub-Saharan Africa (SSA). Medline and Embase were searched. Five hundred twenty-three references were reviewed. Thirty-two references from nine countries in SSA were included in the qualitative synthesis. The degree of kidney damage and abnormal imaging varied widely: proteinuria 32.5% (2.2-56.0%), hematuria 31.1% (0.6-67.0%), hydronephrosis 11.3% (0.0-38.0%), hydroureter 7.5% (0.0-26.4%), and major kidney abnormalities 0.1% (0.0-0.8%). Serum creatinine was reported in four studies with insufficient detail to identify the prevalence renal dysfunction. A majority of the studies were performed in Schistosoma haematobium endemic areas. A lower prevalence of kidney disease was observed in the few studies from nonendemic areas. Published data on pediatric kidney disease in SSA are highly variable and dependent on S. haematobium prevalence. More community-based studies are needed to describe the burden of pediatric kidney disease, particularly in regions where S. haematobium infection is nonendemic.