Systematic screening for drug-resistant tuberculosis with Xpert(®) MTB/RIF in a referral hospital in Cambodia.
Limited access to drug susceptibility testing (DST) in referral hospitals contributes to delayed detection of multidrug-resistant tuberculosis (MDR-TB). To document the impact of identifying rifampicin (RMP) resistance using Xpert(®) MTB/RIF on time to diagnosis and time to treatment, and evaluate its performance under programmatic conditions. Using a prospective observational study, we screened presumptive MDR-TB cases with Xpert and solid culture/conventional DST. RMP resistance was confirmed using a line-probe assay (LPA). We recorded diagnostic and treatment delays. We performed rpoB gene sequencing post hoc to resolve discordant RMP susceptibilities. We screened 299 of 345 presumptive MDR-TB individuals, and identified 44 Xpert RMP-resistant cases: 16/165 (10%) were new and 28/136 (20%) retreated. The median time to diagnosis was 2 days (Xpert) vs. an additional 6 with LPA; the median time to treatment was 14 days. Confirmatory LPA on 39/44 revealed 27 concordant, 6 discordant and 6 invalid results. Xpert RMP resistance was confirmed in respectively 24/30 (80%) and 21/23 (91%) by phenotypic DST and rpoB sequencing. Screening presumptive MDR-TB patients with Xpert enabled rapid diagnosis and treatment of MDR-TB. Xpert performed well, provided appropriate risk assessment was done. Rapid confirmatory testing added little to clinical decision making. Our findings support the latest World Health Organization guidelines to abandon confirmatory LPA in favour of repeat Xpert when in clinical doubt, pending phenotypic DST.


Metabolic evaluation of obese and nonobese siblings.
To test the hypotheses that obese adolescents have a lower resting metabolic rate and less aerobic endurance than their nonobese siblings. Case-referent study of obese and nonobese siblings from the same kindred. Tertiary referral center. Telephone screening of community volunteers resulted in a consecutive sample of 16 kindreds. Obese and nonobese siblings were similar in age, height, and pubertal status. Significantly more female subjects were in the obese group (p less than 0.01). Body composition studies revealed that the obese siblings had higher body fat (p less than 0.001) but that fat-free mass was similar to that of the lean siblings. Resting metabolic rates determined by indirect calorimetry for the obese and nonobese pairs did not differ. Although the obese siblings appeared less fit when maximal oxygen consumption was measured in relation to total weight, maximal oxygen consumption did not differ when values were standardized for fat-free mass. The obese adolescents did not have a reduced resting metabolic rate. As in adults, the relationship between resting metabolic rate and fat-free mass was similar for obese and nonobese children and adolescents. Any decreased sport participation by the obese siblings was not due to inherent reductions in aerobic capacity.


Biocontrol of Alternaria alternata and Fusarium oxysporum by Trichoderma asperelloides and Bacillus paralicheniformis in tomato plants.
The objective of this work was to evaluate the effectiveness of the putative biocontrol agents (PBA) Bacillus paralicheniformis and Trichoderma asperelloides in vitro and in vivo to control two of the most important tomato plant diseases: vascular wilt (Fusarium oxysporum) and early blight (Alternaria alternata). The assessment of the in vitro interactions between the PBA and the phytopathogenic fungi was performed by dual confrontation assays. The biocontrol effectiveness of the individual and combined PBA treatments towards individual phytopathogen inoculations was evaluated in tomato plants. T. asperelloides was able to exert an outstanding mycoparasitic effect on both phytopathogenic fungi in the in vitro tests by hyphal strangulation and penetration. In addition, the individual PBA treatments were effective in the biocontrol of A. alternata and F. oxysporum in tomato plants reducing the plant disease severity in more than 53.8 and 66.7% for each of the pathogens, respectively. On the other hand, the combined use of the tested strains showed similar effectiveness in the biocontrol of A. alternata, but no synergism was observed. In addition, it was concluded that B. paralicheniformis protected the plants from the attack of A. alternata through the induction of the systemic resistance of the plant. This study demonstrated the effectiveness of the individual and combined use of the strains tested for the biocontrol of A. alternata and F. oxysporum in tomato plants.


Synthesis, structure-activity relationship, and biological evaluation of quinolines for development of anticancer agents.
Tetrahydro-β-carbolines (THβCs) are a kind of natural alkaloids with multiple pharmaceutical activities. Herein, a focused compound library derived from THβCs was synthesized and their anticancer activities were studied in several cancer cell lines. Among them, three compounds showed considerable anticancer activities with low micromolar to submicromolar IC50 values. The abilities to induce apoptosis and alter mitochondrial membrane potential levels, which are comparable to those of the commercial anticancer drug adriamycin, were confirmed by one representative compound (21) on the B16/F10 cell line. Our preliminary structure-activity relationship studies indicated that alkylamines with suitable lengths are very important for potency improvement.


Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.
With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity. In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18-59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 μg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 μg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual. Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 μg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 μg group, four (17%) of 24 in the 6 μg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 μg group, 12 (50%) of 24 in the 6 μg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 μg group, 19 (79%) of 24 in the 6 μg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 μg group, 42 (35%) of 120 in the 6 μg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 μg group, 23 (19%) of 120 in the 6 μg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group, and none (0%) of 59 in the placebo group. Taking safety, immunogenicity, and production capacity into account, the 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials. Chinese National Key Research and Development Program and Beijing Science and Technology Program.


Idiopathic guttate hypomelanosis.
Idiopathic guttate hypomelanosis is a common and frequently ignored dermatosis. It appears late in life and increases with aging. The studies so far reported do not support the hypothesis of a residual leukoderma following trauma, and the relation of IGH to chronic solar exposure has not yet been documented. However, the role of ultraviolet A and ultraviolet B in the pathogenesis of this dermatosis should be explored by more refined methods. Although it may be genetically modulated, a multifactorial etiology rather than a single cause is likely. An active depigmenting mechanism may underlie the melanocyte disturbance instead of a simple residual defect. Intralesional triamcinolone in very low concentrations with or without minigrafts of normally pigmented skin could be of some therapeutic value.


Sphinganine is associated with 24-h MAP in the non-sleepy with OSA.
Excessive daytime sleepiness is a debilitating symptom of obstructive sleep apnea (OSA) linked to cardiovascular disease, and metabolomic mechanisms underlying this relationship remain unknown. We examine whether metabolites from inflammatory and oxidative stress-related pathways that were identified in our prior work could be involved in connecting the two phenomena. This study included 57 sleepy (Epworth Sleepiness Scale (ESS) ≥ 10) and 37 non-sleepy (ESS < 10) participants newly diagnosed and untreated for OSA that completed an overnight in-lab or at home sleep study who were recruited from the Emory Mechanisms of Sleepiness Symptoms Study (EMOSS). Differences in fasting blood samples of metabolites were explored in participants with sleepiness versus those without and multiple linear regression models were utilized to examine the association between metabolites and mean arterial pressure (MAP). The 24-h MAP was higher in sleepy 92.8 mmHg (8.4) as compared to non-sleepy 88.8 mmHg (8.1) individuals (P = 0.03). Although targeted metabolites were not significantly associated with MAP, when we stratified by sleepiness group, we found that sphinganine is significantly associated with MAP (Estimate = 8.7, SE = 3.7, P = 0.045) in non-sleepy patients when controlling for age, BMI, smoking status, and apnea-hypopnea index (AHI). This is the first study to evaluate the relationship of inflammation and oxidative stress related metabolites in sleepy versus non-sleepy participants with newly diagnosed OSA and their association with 24-h MAP. Our study suggests that Sphinganine is associated with 24 hour MAP in the non-sleepy participants with OSA.


Update of the activity of cefditoren and comparator oral beta-lactam agents tested against community-acquired Streptococcus pneumoniae isolates (USA, 2004-2006).
Cefditoren and other orally administered cephalosporins are infrequently included in resistance surveillance studies. Here we evaluated 359 contemporary (2004-2006) strains of Streptococcus pneumoniae, including penicillin-intermediate (12.0%) and -resistant (22.8%) subsets from United States patients by reference broth microdilution methods. Cefditoren was the most potent cephalosporin tested (MIC(50), 0.015 mg/L), including against penicillin-intermediate strains (MIC(50), 0.12 mg/L), and was two-, four- and eight-fold more active than cefuroxime, cefdinir and cefprozil, respectively. Penicillin-resistant strains were largely resistant to all tested ss-lactams. We confirm the continued spectrum and potency for cefditoren against S. pneumoniae that surpasses that of other orally administered cephalosporins.


miR-215 suppresses papillary thyroid cancer proliferation, migration, and invasion through the AKT/GSK-3β/Snail signaling by targeting ARFGEF1.
The incidence of papillary thyroid cancer (PTC) has been rapidly increasing in recent years. PTC is prone to lymph node metastasization, which further increases the recurrence rate and mortality of thyroid cancer. However, the underlying mechanisms of this process remain elusive. Several reports have shown that the microRNA miR-215 plays an important role in cancer metastasis. Here, we investigated, for the first time, the potential association between miR-215 and metastasis in PTC. The results of qPCR analysis demonstrated that miR-215 was downregulated in PTC cell lines and tissues, and lower levels of miR-215 correlated with lymph node metastasis of PTC. In vitro and in vivo assays revealed that restoration of miR-215 dramatically inhibited PTC cell proliferation and metastasis. We identified ADP ribosylation factor guanine nucleotide-exchange factor 1 (ARFGEF1) as the target, which mediated the function of miR-215. The expression of ARFGEF1 was inhibited by miR-215, and the effects of miR-215 were abrogated by re-expression of ARFGEF1. Moreover, we found that miR-215 suppressed PTC metastasis by modulating the epithelial-mesenchymal transition via the AKT/GSK-3β/Snail signaling. In summary, our study proves that miR-215 inhibits PTC proliferation and metastasis by targeting ARFGEF1 and indicates miR-215 as a biomarker for PTC prognosis.


Fatal gastrointestinal haemorrhage due to coexisting primary aorto-enteric and aorto-colic fistulae. Complicating untreated atheromatous abdominal aortic aneurysm.
We report a case of aorto-enteric and aorto-colonic fistulae in a 73 year old man with no previous abdominal surgery which resulted in massive gastrointestinal haemorrhage and death and was undiagnosed despite several hospital admissions and endoscopic examinations. This case serves to highlight an extremely rare but fatal condition, which is potentially treatable, if an early diagnosis is made.


Closed-state inactivation and pore-blocker modulation mechanisms of human CaV2.2.
N-type voltage-gated calcium (CaV) channels mediate Ca2+ influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and nociceptive transmission. Here, we elucidate a cryo-electron microscopy (cryo-EM) structure of the human CaV2.2 complex in apo, ziconotide-bound, and two CaV2.2-specific pore blockers-bound states. The second voltage-sensing domain (VSD) is captured in a resting-state conformation, trapped by a phosphatidylinositol 4,5-bisphosphate (PIP2) molecule, which is distinct from the other three VSDs of CaV2.2, as well as activated VSDs observed in previous structures of CaV channels. This structure reveals the molecular basis for the unique inactivation process of CaV2.2 channels, in which the intracellular gate formed by S6 helices is closed and a W-helix from the domain II-III linker stabilizes closed-state inactivation. The structures of this inactivated, drug-bound complex lay a solid foundation for developing new state-dependent blockers for treatment of chronic pain.


Vision modulates somatosensory cortical processing.
Over 150 years ago, E.H. Weber declared that experience showed that tactile acuity was not affected by viewing the stimulated body part. However, more recent investigations suggest that cross-modal links do exist between the senses. Viewing the stimulated body site improves performance on tactile discrimination and detection tasks and enhances tactile acuity. Here, we show that vision modulates somatosensory cortex activity, as measured by somatosensory event-related potentials (ERPs). This modulation is greatest when tactile stimulation is task relevant. Visual modulation is not present in the P50 component reflecting the primary afferent input to the cortex but appears in the subsequent N80 component, which has also been localized to SI, the primary somatosensory cortex. Furthermore, we replicate previous findings that noninformative vision improves spatial acuity. These results are consistent with a hypothesis that vision modulates cortical processing of tactile stimuli via back projections from multimodal cortical areas. Several neurophysiological studies suggest that primary and secondary somatosensory cortex (SI and SII, respectively) activity can be modulated by spatial and tactile attention and by visual cues. To our knowledge, this is the first demonstration of direct modulation of somatosensory cortex activity by a noninformative view of the stimulated body site with concomitant enhancement of tactile acuity in normal subjects.


Effect of cortisone on cells at the bone-marrow interface.
A study of the association between the rate of proliferation of marrow fibroblast-like stromal cells (in vitro) and the rate of endosteal bone mineralization (EsMR) (in vivo) was undertaken in an osteopenic rat model. We report that 200 g male rats treated with cortisone acetate (5 mg/day for 7 days) exhibit decreases in marrow fibroblast colony-forming units (FCFU) and tetracycline-based measurements of EsMR at the level of the femoral midshaft. In cortisone-treated rats recovering for 1-3 weeks, the FCFU census and EsMR normalized during the first posttreatment week, remained at control levels after 2-3 weeks, and exhibited a relapse in the third week which signified only partial recovery. These changes were unrelated to patterns of body weight gain. The data indicate that the FCFU census can serve to index endosteal osteoblast vigor.


Monitoring of biogenic amines and drugs of various therapeutic groups in urine samples with use of HPLC.
A high-performance liquid chromatography method for simultaneous separation and determination of biogenic amines [dopamine, epinephrine, serotonin and its six metabolites (normetanephrine, metanephrine, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylglycol, homovanilic acid and 5-hydroxyindoloacetic acid)] with drugs from different therapeutically groups [analgesics (paracetamol, metamizol), diuretics (furosemide) and antibiotics (cefazolin, fluconazole)] was developed. A chromatographic column with pre-column with octadecylsilane phase (C18e ) and two detectors - diode array serial connected and fluorescence - was used. Gradient elution of mixture of acetate buffer (pH 4.66) and methanol as a mobile phase was applied. The limit of detection (LOD) of 8-10 ng/mL and limit of quantitation (LOQ) of 24-30 ng/mL for biogenic amines, as well as the LOD of 50-100 ng/mL and the LOQ of 150-300 ng/mL for drugs, were determined. The applied sample preparation method allowed recoveries of 93% for the biogenic amines and 92% for the drugs to be achieved. The developed procedure has been applied to simultaneous determination of the examined compounds in urine samples and could be used in clinical analysis.


Development of a proof-of-concept microfluidic portable pathogen analysis system for water quality monitoring.
Waterborne diseases cause millions of deaths worldwide, especially in developing communities. The monitoring and rapid detection of microbial pathogens in water is critical for public health protection. This study reports the development of a proof-of-concept portable pathogen analysis system (PPAS) that can detect bacteria in water with the potential application in a point-of-sample collection setting. A centrifugal microfluidic platform is adopted to integrate bacterial cell lysis in water samples, nucleic acid extraction, and reagent mixing with a droplet digital loop mediated isothermal amplification assay for bacteria quantification onto a single centrifugal disc (CD). Coupled with a portable "CD Driver" capable of automating the assay steps, the CD functions as a single step bacterial detection "lab" without the need to transfer samples from vial-to-vial as in a traditional laboratory. The prototype system can detect Enterococcus faecalis, a common fecal indicator bacterium, in water samples with a single touch of a start button within 1 h and having total hands-on-time being less than 5 min. An add-on bacterial concentration cup prefilled with absorbent polymer beads was designed to integrate with the pathogen CD to improve the downstream quantification sensitivity. All reagents and amplified products are contained within the single-use disc, reducing the opportunity of cross contamination of other samples by the amplification products. This proof-of-concept PPAS lays the foundation for field testing devices in areas needing more accessible water quality monitoring tools and are at higher risk for being exposed to contaminated waters.


Protocol to establish an oviduct epithelial cell line derived from Gallus gallus using Percoll for in vitro validation of recombinant proteins.
In vitro validation of therapeutic and recombinant proteins expressed from transgenic chickens is limited by the co-culture of fibroblasts. Here, we present a protocol for isolating pure epithelial cells derived from the magnum tubular glands of the chicken oviduct. We describe steps for preparing solutions and buffers, tissue collection, processing, dissociation, and Percoll density centrifugation to separate the epithelial cells from co-isolated fibroblasts. We then detail procedures for expressing a recombinant IgG antibody in the Percoll-derived epithelial cell line.


Differentiating novel coronavirus pneumonia from general pneumonia based on machine learning.
Chest CT screening as supplementary means is crucial in diagnosing novel coronavirus pneumonia (COVID-19) with high sensitivity and popularity. Machine learning was adept in discovering intricate structures from CT images and achieved expert-level performance in medical image analysis. An integrated machine learning framework on chest CT images for differentiating COVID-19 from general pneumonia (GP) was developed and validated. Seventy-three confirmed COVID-19 cases were consecutively enrolled together with 27 confirmed general pneumonia patients from Ruian People's Hospital, from January 2020 to March 2020. To accurately classify COVID-19, region of interest (ROI) delineation was implemented based on ground-glass opacities (GGOs) before feature extraction. Then, 34 statistical texture features of COVID-19 and GP ROI images were extracted, including 13 gray-level co-occurrence matrix (GLCM) features, 15 gray-level-gradient co-occurrence matrix (GLGCM) features and 6 histogram features. High-dimensional features impact the classification performance. Thus, ReliefF algorithm was leveraged to select features. The relevance of each feature was the average weights calculated by ReliefF in n times. Features with relevance larger than the empirically set threshold T were selected. After feature selection, the optimal feature set along with 4 other selected feature combinations for comparison were applied to the ensemble of bagged tree (EBT) and four other machine learning classifiers including support vector machine (SVM), logistic regression (LR), decision tree (DT), and K-nearest neighbor with Minkowski distance equal weight (KNN) using tenfold cross-validation. The classification accuracy (ACC), sensitivity (SEN), specificity (SPE) of our proposed method yield 94.16%, 88.62% and 100.00%, respectively. The area under the receiver operating characteristic curve (AUC) was 0.99. The experimental results indicate that the EBT algorithm with statistical textural features based on GGOs for differentiating COVID-19 from general pneumonia achieved high transferability, efficiency, specificity, sensitivity, and impressive accuracy, which is beneficial for inexperienced doctors to more accurately diagnose COVID-19 and essential for controlling the spread of the disease.


High incorporation of dietary 1-O-heptadecyl glycerol into tissue plasmalogens of young rats.
When 1-O-heptadecyl-rac-glycerol was fed (20 mg/g of food) to 19-day-old rats for 10 days, a high incorporation of the heptadecyl group into the 1-O-alk-1'-enyl group of ethanolamine plasmalogens of all tissues was observed. For example, 62% of the alkenyl groups from liver plasmalogen was of the 17:0 variety. The analogous values for other tissues were 62% in kidney, 57% in lung, 57% in heart, 50% in intestine, 43% in erythrocytes, 25% in testis and 8% in brain. The corresponding figures in the control rats (fed normal rat chow) were only 2-3% of 17:0 for all tissues. Available evidence indicates that dietary 1-O-heptadecyl-sn-glycerol is utilized to form tissue plasmalogens without the cleavage of the ether bond. The relevance of these results to the possible dietary ether lipid therapy of patients suffering from congenital ether lipid deficiency is discussed.


Use of an endorectal mucosal advancement flap to treat H-type rectovestibular fistula in patients with a normal anus.
The combination of an H-type rectovestibular fistula (RVF) and a normal anus is a rare type of anorectal malformation, resulting in abnormal communication between the normal rectum and vestibule in girls. Among the surgical methods used to treat this condition are simple fistula resection and extensive perineal dissection, but postoperative fistula recurrence is frequent. We utilized the endorectal mucosal advancement flap technique on three patients with H-type RVFs and a normal anus, all of whom had favorable outcomes.


The potentially Z-DNA-forming sequence d(GTGTACAC) crystallizes as A-DNA.
(GT)n/(CA)n sequences have stimulated much interest because of their frequent occurrence in eukaryotic DNA and their potential for forming the left-handed Z-DNA structure. We here report the X-ray crystal structure of a self-complementary octadeoxynucleotide, d(GTGTACAC), at 2.5 A resolution. The molecule adopts a right-handed double-helical conformation belonging to the A-DNA family. In this alternating purine-pyrimidine DNA minihelix the roll and twist angles show alternations qualitatively consistent with Calladine's rules. The average tilt angle of 9.3 degrees is between the values found in A-DNA (19 degrees) and B-DNA (-6 degrees) fibers. It is envisaged that such intermediate conformations may render diversity to genomic DNA. The base-pair tilt angles and the base-pair displacements from the helix axis are found to be correlated for the known A-DNA double-helical fragments.


Strongyloides papillosus: changes in transcript levels of lysozyme and aspartic protease 2 in percutaneously migrated larvae.
The infection of the host is the crucial event in the life-cycle of parasites. To understand the molecular mechanisms of this important step, different methods are used in present studies. For analysis of changes in transcript levels the most sensitive method is the quantitative real-time PCR (qPCR). For an accurate analysis the evaluation of a set of adequate reference genes is necessary. The present study aimed to analyse the transcriptional levels of two genes of interest, the putative aspartic protease Spa-asp-2 and the putative lysozyme Spa-lys, in infective, free-living larvae of Strongyloides papillosus at different ages and from long-term and short-term infections and percutaneously migrated ("parasitic") larvae. Percutaneously migrated larvae were collected using the PERL chamber system and ovine skin in vitro. Reference genes identified as most suitable for transcriptional analysis according to geNorm analysis were genes for the eukaryotic translation elongation factor 1 alpha (Spa-eft-2), actin variation 2 (Spa-act-v2) and beta tubulin (Spa-tbb-1). Transcriptional analysis of the genes in percutaneously migrated larvae showed an upregulation of Spa-asp-2, while Spa-lys was downregulated. Data from the presented study provide a first glance into the changes of transcript levels of S. papillosus induced by percutaneous migration.


How ecosystems recover from pulse perturbations: A theory of short- to long-term responses.
Quantifying stability properties of ecosystems is an important problem in ecology. A common approach is based on the recovery from pulse perturbations, and posits that the faster an ecosystem return to its pre-perturbation state, the more stable it is. Theoretical studies often collapse the recovery dynamics into a single quantity: the long-term rate of return, called asymptotic resilience. However, empirical studies typically measure the recovery dynamics at much shorter time scales. In this paper we explain why asymptotic resilience is rarely representative of the short-term recovery. First, we show that, in contrast to asymptotic resilience, short-term return rates depend on features of the perturbation, in particular on the way its intensity is distributed over species. We argue that empirically relevant predictions can be obtained by considering the median response over a set of perturbations, for which we provide explicit formulas. Next, we show that the recovery dynamics are controlled through time by different species: abundant species tend to govern the short-term recovery, while rare species often dominate the long-term recovery. This shift from abundant to rare species typically causes short-term return rates to be unrelated to asymptotic resilience. We illustrate that asymptotic resilience can be determined by rare species that have almost no effect on the observable part of the recovery dynamics. Finally, we discuss how these findings can help to better connect empirical observations and theoretical predictions.


Transcription factor GATA-3 regulates the transcriptional activity of dopamine beta-hydroxylase by interacting with Sp1 and AP4.
GATA-3 is a zinc finger transcription factor that is expressed in T cell lineages as well as in the nervous system during development. In this study, we report that forced expression of GATA-3 resulted in an increased number of dopamine beta-hydroxylase (DBH)-expressing neurons in primary neural crest stem cell (NCSC) culture, suggesting that the DBH gene may be a downstream target gene of GATA-3. GATA-3 robustly transactivates the promoter function of the noradrenaline (NA)-synthesizing DBH gene, via two specific upstream promoter domains; one at -62 to -32 bp and the other at -891 to -853 bp. Surprisingly, none of these domains contain GATA-3 binding sites but encompass binding motifs for transcription factors Sp1 and AP4, respectively. Protein-protein interaction analyses both in vitro and in vivo and chromatin immunoprecipitation (ChIP) assays showed that GATA-3 effects its transcriptional regulatory function through physical interactions with these transcription factors.


Speculating about cognitive experiments using schizophrenics.
Several models of selective attention are reviewed, emphasizing how breakdowns in various parts of each model could result in certain attentional deficits. It is concluded that some evidence suggests that the ability to mobilize attention may not be as impaired in schizophrenia as is the ability to choose which stimuli are appropriate for attention. If so, then in any cognitive experiment involving schizophrenics, any schizophrenic subject would be particularly distracted by certain extraneous stimuli, while other schizophrenic subjects would be particularly distracted by other stimuli. The importance of this possibility for cognitive research in schizophrenia is discussed.


COVID-19 Quarantine Dramatically Affected Male Sexual Behavior: Is There a Possibility to Go Back to Normality?
We performed a monocentric longitudinal study on sexually active male patients, from May 2021 to October 2021, with SARS-CoV-2 infection confirmed with a nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR). The questionnaires were delivered by email. The study period was divided into the periods before getting tested (T1), during quarantine (T2), 1 month after a negative test (T3), and 3 months after a negative test (T4). All participants were invited to complete these questionnaires: 10- and 6-item questionnaires, a sexual distress schedule (SDS), and the international index of erectile function questionnaire of 15 items (IIEF-15). The primary endpoint was to evaluate the impact of quarantine on male sexual function (SF) during and after the SARS-CoV-2 infection. A total of 22 male patients met the inclusion criteria. The differences for both SDS and IIEF-15 scores, between T1−T2 (27 (IQR 24.0−32.2) vs. 37.5 (IQR 34.2−45.5), 45 (IQR 38.0−50.2) vs. 28.5 (IQR 19.5−38.0)), T2−T3 (37.5 (IQR 34.2−45.5) vs. 28 (IQR 24.0−31.0), and 28.5 (IQR 19.5−38.0) vs. 39.5 (IQR 35.5−44.2)) were statistically significant (p < 0.001), respectively. Moreover, between T1−T4, no statistically significant difference (p > 0.05) was recorded in both SDS (27 (IQR 24.0−32.2) vs. 26.5 (IQR 24−30.2)) and IIEF-15 (45 (IQR 38.0−50.2) vs. 28.5 (IQR 19.5−38.0)). In 20 patients (90.9%), SARS-CoV-2 had a huge impact on relationship and sexual life, but no patient attended a clinic for sexual difficulties. In conclusion quarantine has negatively influenced SF in infected patients; however, 3 months after the rRT-PCR negative test, a promising return to the preinfection SF values is observed.


Protein Coating of DNA Origami.
DNA origami has emerged as a common technique to create custom two- (2D) and three-dimensional (3D) structures at the nanoscale. These DNA nanostructures have already proven useful in development of many biotechnological tools; however, there are still challenges that cast a shadow over the otherwise bright future of biomedical uses of these DNA objects. The rather obvious obstacles in harnessing DNA origami as drug-delivery vehicles and/or smart biodevices are related to their debatable stability in biologically relevant media, especially in physiological low-cation and endonuclease-rich conditions, relatively poor transfection rates, and, although biocompatible by nature, their unpredictable compatibility with the immune system. Here we demonstrate a technique for coating DNA origami with albumin proteins for enhancing their pharmacokinetic properties. To facilitate protective coating, a synthesized positively charged dendron was linked to bovine serum albumin (BSA) through a covalent maleimide-cysteine bonding, and then the purified dendron-protein conjugates were let to assemble on the negatively charged surface of DNA origami via electrostatic interaction. The resulted BSA-dendron conjugate-coated DNA origami showed improved transfection, high resistance against endonuclease digestion, and significantly enhanced immunocompatibility compared to bare DNA origami. Furthermore, our proposed coating strategy can be considered highly versatile as a maleimide-modified dendron serving as a synthetic DNA-binding domain can be linked to any protein with an available cysteine site.


Loss of positional information when tracking multiple moving dots: the role of visual memory.
Pylyshyn, Z.W. and Storm, R.W. (1988) (Tracking multiple independent targets: Evidence for a parallel tracking mechanism. Spatial Vision, 3(3), 179-197) proposed that human observers could simultaneously track up to five dots when presented with an array of dots moving in a random manner. In contrast, Tripathy, S.P., and Barrett, B.T. (2004) (Severe loss of positional information when detecting deviations in multiple trajectories. Journal of Vision, 4(12):4, 1020-1043, http://journalofvision.org/4/14/4/, doi: 10.1167/4.12.4) showed that when a threshold paradigm was employed, observers' ability to track deviations in straight-line trajectories is severely compromised when attending to two or more dots. In this study we present a series of four experiments that investigates the role of attention and visual memory while tracking deviations in multiple trajectories using a threshold paradigm. Our stimuli consisted of several linear, non-parallel, left-to-right trajectories, each moving at the same speed. At the trajectory mid-point (reached simultaneously by all dots), one of the dots (target) deviated clockwise or counter-clockwise. The observers' task was to identify the direction of deviation. The target trajectory was cued in the second half of the trial either by disappearance of distractors at the monitor's mid-line (Experiment 1) or by means of a change in colour of the target (Experiment 2); in both cases deviation thresholds rose steeply when the number of distractor trajectories was increased from 0 (typical threshold approximately 2 degrees) to 3 (typical threshold>20 degrees). When all the trajectories were presented statically in a single frame (Experiment 3), thresholds for identifying the orientation change of the target trajectory remained relatively unchanged as the number of distractor trajectories was increased. When a temporal delay of a few hundred milliseconds was introduced between the first and second halves of trajectories (Experiment 4), deviation thresholds increased steeply. These results suggest that the persistence of trajectory-traces in visual sensory memory may play an important part in determining thresholds for detecting deviations in trajectories.


Association of sociodemographic and maternal healthcare factors with birth registration in Angola.
Angola has a high burden of unregistered children and efforts to increase birth-registration coverage have not yielded the desired progress. This study aimed to examine sociodemographic and healthcare-related factors associated with birth registration in Angola. Secondary data analysis of the Maternal and Child Health (MCH) Handbook randomised controlled trial conducted in Benguela province, Angola and involving 11,006 women. For this analysis, we excluded women with missing data on birth registration (n = 1424), multiple gestation (n = 243), and those with infant death (n = 6). The final study population included 9333 women with infants under one year of age. We used multilevel mixed-effects logistic regression analysis to determine sociodemographic and healthcare-related factors associated with the registration of a child's birth. Of the 9333 live births, 25% (95% confidence interval [CI] = 13.4-41.8) were registered, while 21% (95%CI = 11.1-35.7) were registered with certificate. There were higher proportions of registered births among mothers who possessed the MCH Handbook across various demographic and healthcare indicators. Birth registration was most significantly associated with facility-based delivery (odds ratio [OR] = 2.97; 95%CI = 2.45-3.61), possession of MCH Handbook (OR = 2.04; 95%CI = 1.70-2.46), and complete scheduled vaccination visits (OR = 1.69; 95%CI = 1.44-1.97). Higher maternal age and education level, belonging to the highest wealth quintile, beginning antenatal care in the first trimester, attending at least four antenatal care visits, and using postnatal care services were positively associated with registration of birth. Maternal healthcare factors showed significant associations with birth registration and integrating birth-registration processes with certain maternal and child health services may further raise awareness and boost registration levels in Angola.


SARS-CoV-2 fusion peptide sculpting of a membrane with insertion of charged and polar groups.
The fusion peptide of SARS-CoV-2 spike is essential for infection. How this charged and hydrophobic domain occupies and affects membranes needs clarification. Its depth in zwitterionic, bilayered micelles at pH 5 (resembling late endosomes) was measured by paramagnetic NMR relaxation enhancements used to bias molecular dynamics simulations. Asp830 inserted deeply, along with Lys825 or Lys835. Protonation of Asp830 appeared to enhance agreement of simulated and NMR-measured depths. While the fusion peptide occupied a leaflet of the DMPC bilayer, the opposite leaflet invaginated with influx of water and choline head groups in around Asp830 and bilayer-inserted polar side chains. NMR-detected hydrogen exchange found corroborating hydration of the backbone of Thr827-Phe833 inserted deeply in bicelles. Pinching of the membrane at the inserted charge and the intramembrane hydration of polar groups agree with theory. Formation of corridors of hydrated, inward-turned head groups was accompanied by flip-flop of head groups. Potential roles of the defects are discussed.


Ultraviolet-emitting conjugated polymer poly(9,9'-alkyl-3,6-silafluorene) with a wide band gap of 4.0 eV.
An ultraviolet-emitting conjugated polymer, poly(9,9'-alkyl-3,6-silafluorene) with a wide band gap of 4.0 eV, has been synthesized and characterized.


Role for the double-stranded RNA-activated protein kinase PKR in Ad-TNF-alpha gene therapy in esophageal cancer.
Tumor necrosis factor alpha (TNF-alpha) is a cytokine with direct antitumor activity. Clinical trials with TNF-alpha have been limited because of the severe side effects of systemic administration. Gene therapy with an adenoviral vector allows delivery of high local doses of TNF-alpha. Activation of protein kinase R (PKR) has been implicated as a general transducer of apoptosis in response to a variety of different stimuli including TNF-alpha. We, therefore, evaluated the role of PKR in Ad-TNF-alpha-induced apoptosis in esophageal cancer cells. A tetracycline-responsive adenoviral vector was used to transfect the TNF-alpha gene (Ad-TNF-alpha) into human esophageal cancer cell lines Bic1, Seg1 and TT, as well as in transformed PKR(+/+) and PKR(-/-) early-passage mouse embryo fibroblasts. Ad-luciferase, Ad-Bak, and mock infection with phosphate buffered saline solution were used as controls. Gene expression was determined by Western blot analysis. Apoptosis was detected by propidium iodide staining and fluorescence-activated cell sorter analysis. Overexpression of TNF-alpha in the lysate was evident in all cell lines treated with Ad-TNF-alpha. Treatment with Ad-TNF-alpha was associated with PKR upregulation and induction of apoptosis. Inhibition of TNF-alpha expression by tetracycline resulted in downregulation of PKR and decreased apoptosis. Transduction of PKR(+/+) and PKR(-/-) mouse embryo fibroblasts with Ad-TNF-alpha demonstrated that Ad-TNF-alpha-induced apoptosis was mediated in part through a PKR-dependent process. These results suggest that Ad-TNF-alpha-mediated apoptosis in esophageal cancer cell lines is dependent in part on PKR upregulation. Strategies to enhance PKR upregulation may allow increased Ad-TNF-alpha antitumoral activity in the treatment of esophageal cancer.


Transcatheter Versus Surgical Closure of Acute Ruptured Sinus of Valsalva Aneurysms with Associated Ventricular Septal Defects.
Transcatheter ruptured sinus of valsalva aneurysm (RSOVA) closure is an alternative to surgery. When a restrictive ventricular septal defect (rVSD) coexists, there are doubts about support for an occluder and persistent left ventricular (LV) dilatation. We compared the outcomes of patients from a single centre with rVSD and RSOVA after surgery or transcatheter intervention in the past 8 years in this study. Location of rVSD did not alter the approach. Compliant balloon interrogation before transcatheter closure was occasionally used to assess significance of interventricular shunt or aortic regurgitation. Procedural success and LV dimensions before and after treatment were analyzed. Seventeen patients with a mean age of 36.64 ± 12.58 years were analyzed. 12/13 catheter procedures (92%) were successful, of whom eight patients had an outlet VSD. rVSD was closed with device in one patient with perimembranous rVSD, but unaddressed in others. Four patients underwent balloon interrogation. Surgery included the single patient who failed intervention. Transcatheter group had more acute symptoms and advanced functional class than surgical group, though not significant. At a median follow-up of 4.5 (1-7.5) years, the mean LV dimensions (50.3 ± 10.1 mm and 50.1 ± 3.1 mm, p = 0.46) were not different in the transcatheter and surgical groups. Mean end-diastolic volumes (110.5 ± 42. 1 ml and 98.5 ± 37.5 ml, p = 0.91) were not significantly different either. Transcatheter RSOVA closure success was not altered by rVSD despite their location underneath the aneurysms, including outlet rVSD with defect in aortoventricular junction. Persistent LV dilatation was not observed after catheter intervention even when the VSD was not closed.


First report of the genus Conostigmus Dahlbom (Hymenoptera: Ceraphronoidea: Megaspilidae) from India with description of a new species.
The genus Conostigmus Dahlbom (Hymenoptera: Ceraphronoidea: Megaspilidae) is reported for the first time from India, along with description and illustration of Conostigmusneotubifer sp. n. A comparative discussion on the morphological affinities of the new species with its putative sister Conostigmustubifer Dessart is provided. An intermixing of character states of genera Conostigmus as well as Dendrocerus Ratzeburg is observed.


Body esteem in Chinese adolescents: effect of gender, age, and weight.
This study examined the associations of body esteem with gender, age, and Body Mass Index (BMI) among 905 Hong Kong adolescents using the Body-Esteem Scale (BES). Older age, male gender and lower BMI were associated with better body esteem. Multiple regression analyses indicated significant main effects of gender, age and weight on BES-Total. Significant interaction effects of gender × BMI and gender × age × BMI were also found on BES-Weight (beta = -0.149, p = .028) and BES-Total (beta = -0.139, p = .044). Improvement of body esteem with age may be associated with age-related BMI differences.


The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia.
The pathogenesis of bronchopulmonary dysplasia (BPD), a devastating lung disease in preterm infants, includes inflammation, the mechanisms of which are not fully characterized. Here we report that the activation of the NLRP3 inflammasome is associated with the development of BPD. Hyperoxia-exposed neonatal mice have increased caspase-1 activation, IL1β and inflammation, and decreased alveolarization. Nlrp3(-/-) mice have no caspase-1 activity, no IL1β, no inflammatory response and undergo normal alveolarization. Treatment of hyperoxia-exposed mice with either IL1 receptor antagonist to block IL1β or glyburide to block the Nlrp3 inflammasome results in decreased inflammation and increased alveolarization. Ventilated preterm baboons show activation of the NLRP3 inflammasome with increased IL1β:IL1ra ratio. The IL1β:IL1ra ratio in tracheal aspirates from preterm infants with respiratory failure is predictive of the development of BPD. We conclude that early activation of the NLRP3 inflammasome is a key mechanism in the development of BPD, and represents a novel therapeutic target for BPD.


[Results from the 2012 Paediatric National Survey on Empirical Use of Antibiotics in Children in Spain (ABES Study)].
There are currently several national guidelines on the appropriate empirical use of antibiotics in Spanish children. But, do the Spanish paediatricians use these guidelines when prescribing antimicrobials? A national study from was conducted from April to June 2012 using an on-line questionnaire on the empirical selection of antibiotics in children. An e-mail was sent to paediatrician members of the Spanish Association of Paediatrics (AEP) or its Regional or Paediatric Specialties Societies. Current guidelines and consensus documents were used to determine the appropriateness of the responses. A total of 1214 responses were received. Eighty five per cent of the treatments selected by Spanish paediatricians were adjusted to guidelines. The least appropriate responses were obtained in those infectious diseases with no national consensus document at the time of the survey (73% in this case). Spanish paediatricians mainly select empirical antibiotics in accordance with current guidelines. However, there are features that could be improved in our country. The preparing and implementation of national consensus documents on the management of paediatric infectious diseases should be continued. We propose to regularly perform these kinds of surveys, including real prescription studies, and to also extend it to other paediatric specialities, in order to promote appropriateness of use of all the paediatric drugs in our country.


Increased intensity of contrast material immediately after late angioplasty of infarct-related coronary artery is associated with reduced ventricular volumes at six months.
To assess the contribution of residual muscle perfusion in the infarcted territory to prevent ventricular remodeling, 24 patients with 1-vessel disease underwent coronary angiography and angioplasty of a critical left anterior descending coronary stenosis 18+/-11 days after a first anterior myocardial infarction. The degree of stenosis was assessed using biplane quantitative angiography, whereas ventricular volumes, together with regional wall motion, were computed from single-plane ventriculography. Patients were reevaluated at 6 months after they had been subdivided according to the videointensity of the territory of the culprit vessel, as assessed from images obtained during main stem dye contrast injections before and immediately after angioplasty using a subtraction technique (group A, increased intensity [n= 15]; group B, no change [n=9]), assuming that higher peak intensities reflect greater myocardial blood volume. There was a significant time group interaction for ventricular volumes (diastolic, -13+/-12% for group A vs +20+/-24% for group B, p=0.008; systolic, -15+/-19% for group A vs +18+/-36% for group B, p=0.017), although no interaction was evident for the degree of resolution of coronary stenosis or the extent of recovery of regional dysfunction. The effects on volumes were paralleled by changes in ventricular end-diastolic pressure (-3+/-7 mm Hg in group A vs +5+/-6 mm Hg in group B, p=0.006), although baseline clinical characteristics and medical regimen over the 6-month period were quite comparable between the 2 groups. In conclusion, despite late angioplasty of the culprit vessel, ventricular remodeling is prevented mainly when the procedure guarantees improved perfusion at the muscular level. The result is not necessarily mediated by recovery of regional systolic function.


Reduction in radioactive internal contamination by 99mTc among medical personnel in nuclear medicine facilities with the use of respiratory tract protection measures.
The main objective of the present publication was to assess the reduction of internal radioactive contamination with 99mTc among medical personnel of nuclear medicine facilities using generally available respiratory tract protection systems. During the current research project, four respiratory tract protection systems were tested by estimation of 99mTc activity levels in blood samples collected from medical personnel. Medical staff were equipped with a disposable surgical mask, a half mask with gas absorbers, a half mask with aerosol absorbers and a half mask with gas absorbers with added Petryanov filter. The presented results indicate that wearing only a disposable surgical mask may significantly reduce radioactive internal contamination among medical personnel and improve their safety in the workplace. The best results of reduced 99mTc concentration in the blood were achieved by the use of a half mask with gas absorbers with added Pertryanov filters and a half mask with aerosol absorbers, where the reduction factors were estimated at 90% and 80%, respectively. Respiratory tract protection systems should become standard equipment for medical personnel performing ventilation-perfusion SPECT lung scans.


Smoking risk and the likelihood of quitting among African-American female light and heavy smokers.
While African-American females are more likely to be light smokers compared to their counterparts of other racially classified social groups (RCSGs), they are more likely to carry a heavier burden of smoking-related morbidity and mortality. Thus, it is critical that African-American female light smokers are targeted to engage in smoking cessation. Research has revealed that African-American women are less likely to have a successful quit attempt following a cessation intervention than females from other RCSGs. It has been postulated that the low smoking cessation rates among African-American female light smokers may be due to the lack of appropriate psychosocioculturally tailored cessation interventions that address issues of stress and coping that explain why they smoke and continue to smoke that may differ from their heavy smoker counterparts. The purpose of this study was to ascertain whether African-American female light smokers differed from their heavy smoker counterparts on psychosociocultural stress and coping factors. Findings revealed no differences in the sociodemographic variables of age, income, education and BMI; in the psychosociocultural measures of acculturative stress, race-related stress and coping; or in the smoking characteristics of menthol smoking status, cotinine level and CYP2A6 metabolic functioning between light and heavy smokers. However, the study found that African-American female light smokers take longer to smoke their first cigarette of the day, have a lower smoking risk, are more likely to quit, and exhibit lower carbon monoxide levels than African-American female heavy smokers. The current study suggests that other than the obvious factors of greater likelihood of quitting, lower smoking risk, longer latency to smoke and lower carbon monoxide levels, specific smoking cessation programs may not need to be differentially psychosocio-culturally tailored for African-American female light smokers compared to their heavy-smoking counterparts.


Association between unintended pregnancy and maternal antenatal care services use in Ethiopia: analysis of Ethiopian demographic and health survey 2016.
Unintended pregnancy disproportionately affects women in low and middle-income countries including Ethiopia. Previous studies identified the magnitude and negative health outcomes of unintended pregnancy. However, studies that examined the relationship between antenatal care (ANC) utilization and unintended pregnancy are scarce. This study aimed to examine the relationship between unintended pregnancy and ANC utilization in Ethiopia. This is a cross-sectional study conducted using the fourth and most recent Ethiopian Demographic Health Survey (EDHS) data. The study comprised a weighted sample of 7,271 women with last alive birth and responded to questions on unintended pregnancy and ANC use. The association between unintended pregnancy and ANC uptake was determined using multilevel logistic regression models adjusted for possible confounders. Finally p < 5% was considered significant. Unintended pregnancy accounted for nearly a quarter of all pregnancies (26.5%). After adjusting for confounders, a 33% (AOR: 0.67; 95% CI, 0.57-0.79) lower odds of at least one ANC uptake and a 17% (AOR: 0.83; 95% CI, 0.70-0.99) lower odds of early ANC booking were found among women who had unintended pregnancy compared to women with intended pregnancy. However, this study founds no association (AOR: 0.88; 95% CI, 0.74, 1.04) between unintended pregnancy and four or more ANC visits. Our study found that having unintended pregnancy was associated with a 17 and 33% reduction in early initiation and use of ANC services, respectively. Policies and programs designed to intervene against barriers to early initiation and use of ANC should consider unintended pregnancy.


Sublethal Effects of Arsenic on Oxygen Consumption, Hematological and Gill Histopathological Indices in Chanos chanos.
The current study was performed aiming to evaluate possible changes in the effect on oxygen consumption, hematology and gill histopathological parameters in fish (Chanos chanos) upon exposure to sublethal concentration of the metalloid arsenic. Bioassay tests were conducted for determining the LC50 values of arsenic for 96 h. Oxygen consumption in control and arsenic-exposed fish was estimated using Winkler's method. Red blood corpuscular (RBC) count was examined with a Neubauer counting chamber under a phase contrast microscope. Hemoglobin (Hb) was estimated following the acid hematin method. Histopathological studies were carried by processing and staining the gill tissues with hematoxylin and eosin in accordance with standard histological techniques. They were then subjected to examination under a scanning electron microscope. Chanos chanos exposed to 1/10th of LC50 (24.61%) for a period of 30 days exhibited a maximum decline in the rate of respiration, followed by a decline in RBC and Hb above 45.59% and 51.60%, respectively. Significant toxic lesions encompassing fused gill lamellae, detached gill epithelium, hyperplasia and hypertrophy of respiratory epithelium became heavy handed on the 30th day. Information synthesized from our study serves to be useful in monitoring and managing (As) contamination in the aquatic environment.


Weight loss is a major contributor to improved sexual function after bariatric surgery.
The relative contribution of anthropometric, hormonal, and metabolic changes after bariatric surgery (BS) on sexual function (SF) in severely obese subjects is not well established. Prospective observational case series study of 39 men undergoing BS. SF was assessed by means of the international index of erectile function (IIEF) before and at 1 year after surgery. At the same time points, anthropometric (body mass index, waist circumference), hormonal (testosterone, sex hormone binding globulin, estradiol, gonadotropins, inhibin B, prolactin, leptin), and metabolic parameters (insulin sensitivity, C-reactive protein, lipid profile, hemoglobin A1c, presence of hypertension or sleep apnea) were assessed. BS was associated with marked weight loss (77.18% excess weight loss), improved IIEF score (baseline: 54.85 ± 16.59, 1 year: 61.21 ± 14.10; p < 0.01), gonadal function (testosterone: baseline 256.36 ± 120.98, 1 year: 508.01 ± 161.90; p < 0.001), and improved metabolic profile. However, on multivariate regression analysis whereas changes in body mass index (beta: -0.677, p = 0.001), and baseline IIEF score (beta: -0.397, p = 0.023), were independent predictors of the changes in the IIEF score at 1 year after surgery, changes in hormonal and metabolic factors were not. Variables in the model accounted for 66% of the postsurgical variation in the IIEF score. Similar results were found when the different IIEF-sexual domains were evaluated, except for intercourse satisfaction for which no independent predictor was identified. Weight loss's beneficial effects on SF occurring after BS are beyond the parallel improvement in gonadal and metabolic profiles.


Rummeliibacillus suwonensis sp. nov., isolated from soil collected in a mountain area of South Korea.
A Gram-positive, facultatively aerobic, rod-shaped, non-motile, terminal spore-forming bacterium, designated strain G20(T), was isolated from soil collected in a mountain region of Suwon, South Korea. On the basis of 16S rRNA gene sequence similarity, this strain was shown to be related to Rummeliibacillus pycnus NBRC 101231(T) (97.4%) and Rummeliibacillus stabekisii KSC-SF6g(T) (95.7%). DNA-DNA hybridization studies showed 42% and 50% similarity of strain G20(T) with R. pycnus NBRC 101231(T) and R. stabekisii KSC-SF6g(T), respectively. The DNA G content of G20(T) was 37.8 mol%, the major cellular fatty acids were iso-C15:0 and anteiso-C15:0, and the predominant menaquinones were MK-7 and MK-8. On the basis of phylogenetic, chemotaxonomic, and phenotypic characteristics, we propose this strain to be a novel species and the third member of genus Rummeliibacillus. We suggest the name Rummeliibacillus suwonensis sp. nov. The type strain is G20(T) (KACC 17316(T) =KEMB 9005-003(T) =JCM 19065(T)).


Functional Applications of Nucleic Acid-Protein Hybrid Nanostructures.
Combining the diverse chemical functionality of proteins with the predictable structural assembly of nucleic acids has enabled the creation of hybrid nanostructures for a range of biotechnology applications. Through the attachment of proteins onto or within nucleic acid nanostructures, materials with dynamic capabilities can be created that include switchable enzyme activity, targeted drug delivery, and multienzyme cascades for biocatalysis. Investigations of difficult-to-study biological mechanisms have also been aided by using DNA-protein assemblies that mimic natural processes in a controllable manner. Furthermore, advances that enable the recombinant production and intracellular assembly of hybrid nanostructures have the potential to overcome the significant manufacturing cost that has limited the use of DNA and RNA nanotechnology.


The efficacy of PUVA and narrowband UVB phototherapy in the management of generalised granuloma annulare.
Generalised granuloma annulare (GGA) is a significant cosmetic issue for patients but evidence is lacking to guide optimum treatment. We reviewed our patients with GGA treated with PUVA and narrowband UVB (NBUVB). A telephone questionnaire obtained the patients' perspective in terms of treatment response, remission and overall satisfaction. Twenty patients, all female, were treated. Twelve patients had 15 courses of PUVA therapy (10 oral, 5 bath PUVA) and 10 had 12 courses of NB UVB (two patients had both). There was clearance or minimal residual disease (MRD) on clinical examination in eight of 12 patients after PUVA. Remission was for six months in seven patients extending to one year or more in five patients. Nine patients were contactable after PUVA therapy. They reported their satisfaction as excellent (n = 1), very good (n = 2) or good (n = 4), and two were disappointed. There was clearance or MRD in seven patients treated with NBUVB. Remission was for six months in at least three patients and greater than 1 year in at least 2 patients. Eight patients were contactable and reported satisfaction as excellent (n = 1) or good (n = 5) and two were disappointed. PUVA and NBUVB were effective in at least half of patients and they achieved satisfactory remission. Patients' perceptions of the improvement after phototherapy were lower compared with their dermatologists' assessment.


A pilot study of abuse among Vietnamese Amerasians.
This report describes a pilot study of the prevalence of physical and sexual abuse, and current levels of psychological distress correlated with a history of abuse, in a group of Vietnamese Amerasians bound for the United States. A sample of Vietnamese Amerasians, part of a larger cohort originally selected in Vietnam, was assessed in the Philippines. Subjects completed a self-administered questionnaire regarding a history of physical and/or sexual abuse and three other self-administered questionnaires: the Hopkins Symptom Checklist-25, the Vietnamese Depression Scale, and the Youth Self Report. A history of physical and/or sexual abuse was reported by 22% of male and 18% of female Amerasians. Abused male Amerasians reported significantly higher levels of psychological distress than nonabused male Amerasians, while abused and nonabused female Amerasians did not differ in their levels of psychological distress.


Tissue discrimination by bioelectrical impedance during PLL resection in anterior decompression surgery for treatment of cervical spondylotic myelopathy.
The electrical properties of biological tissues differ depending on their physical properties. This study aimed to explore if bioelectrical impedance (modulus and phase) would discriminate tissues relevant to resection of the posterior longitudinal ligament (PLL) in anterior cervical decompression surgery. PLL resection via an anterior approach was performed on the C4/5 segments in six mini-pigs. The bioelectrical impedance measurements were performed for two tissue groups (annulus fibrosus, endplate cartilage, sub-endplate cortical bone, and PLL; PLL, dura mater, spinal cord, and nerve root) using a novel probe and a precision inductance-capacitance-resistance meter. For each group, impedance was analyzed in terms of modulus and phase along a broad spectrum of frequencies (200-3000 kHz) using a nonparametric statistical analysis (Kruskal-Wallis). The analysis showed a clear difference among the tissues. The modulus and phase show the same changing trend with frequency and present lower values at higher frequencies. Among annulus fibrosus, endplate cartilage, sub-endplate cortical bone, and PLL, it was possible to discriminate each tissue at every frequency point, considering the phase (p < 0.05), while this was not always the case (i.e., annulus fibrosus vs PLL at frequency of 200 kHz, 400 kHz, and 3000 kHz, p > 0.05) for modulus. Among PLL, dura mater, spinal cord, and nerve root, for every comparison, a statistically significant difference was reported in the modulus, phase, or both (p < 0.05). The results indicated the potential of bioelectrical impedance to provide real-time tissue differentiation and enhance safe PLL resection in anterior cervical decompression surgery, particularly in robot-assisted minimally invasive surgery (RMIS).


Risk Stratification in Acute Coronary Syndrome by Comprehensive Morphofunctional Assessment With Optical Coherence Tomography.
Artificial intelligence enables simultaneous evaluation of plaque morphology and computational physiology from optical coherence tomography (OCT). This study sought to appraise the predictive value of major adverse cardiovascular events (MACE) by combined plaque morphology and computational physiology. A total of 604 patients with acute coronary syndrome who underwent OCT imaging in ≥1 nonculprit vessel during index coronary angiography were retrospectively enrolled. A novel morphologic index, named the lipid-to-cap ratio (LCR), and a functional parameter to evaluate the physiologic significance of coronary stenosis from OCT, namely, the optical flow ratio (OFR), were calculated from OCT, together with classical morphologic parameters, like thin-cap fibroatheroma (TCFA) and minimal lumen area. The 2-year cumulative incidence of a composite of nonculprit vessel-related cardiac death, cardiac arrest, acute myocardial infarction, and ischemia-driven revascularization (NCV-MACE) at 2 years was 4.3%. Both LCR (area under the curve [AUC]: 0.826; 95% CI: 0.793-0.855) and OFR (AUC: 0.838; 95% CI: 0.806-0.866) were superior to minimal lumen area (AUC: 0.618; 95% CI: 0.578-0.657) in predicting NCV-MACE at 2 years. Patients with both an LCR of >0.33 and an OFR of ≤0.84 had significantly higher risk of NCV-MACE at 2 years than patients in whom at least 1 of these 2 parameters was normal (HR: 42.73; 95% CI: 12.80-142.60; P < 0.001). The combination of thin-cap fibroatheroma and OFR also identified patients at higher risk of future events (HR: 6.58; 95% CI: 2.83-15.33; P < 0.001). The combination of LCR with OFR permits the identification of a subgroup of patients with 43-fold higher risk of recurrent cardiovascular events in the nonculprit vessels after acute coronary syndrome.


Transurethral laser surgery for benign prostate hyperplasia in octogenarians: safety and outcomes.
To evaluate the morbidity and perioperative outcome of different laser prostate techniques among octogenarians. We performed a retrospective review of our prospectively maintained laser prostate surgery database between 1998 and 2012. We identified 264 octogenarians (16.5%) who underwent laser prostate surgery. Perioperative morbidity and mortality in addition to the functional outcome of these procedures were assessed. Risk factors and predictors of the outcome were analyzed. The mean age at time of procedure was 84 ± 3.5 years. Holmium laser enucleation of the prostate was done in 171 (64.7%), holmium laser ablation of the prostate in 16 (6%), holmium laser transurethral incision of the prostate in 13 (5%) and photoselective vaporization of the prostate in 64 (24.3%). Procedures for octogenarians increased from 11% at the end of 2002 to 19% at 2012. A total of 68 perioperative complications occurred in 52 procedures (19.6%), without any perioperative deaths. There were 56 (82.3%) low-grade complications (Clavien grade I-II) and 12 (17.7%) high-grade complications (Clavien grade ≥ III). A longer operating time was an independent risk factor for perioperative morbidity on multivariate analysis. Significant improvement of symptoms score (International Prostate Symptom Score-Quality of Life) associated with objective improvement of urine flow parameters (maximum flow [Q-max] and postvoid residual) were reported at different follow-up assessments in the first year (P <.05). Persistent urge or stress incontinence, or both, were found in 4 (1.5%). Total urinary incontinence occurred in 1 patient, with neurologic deficit as the underlying cause. De novo urethral stricture was reported in 8 patients (3%). Octogenarians undergoing laser prostate surgery for treatment of benign prostate hyperplasia have limited perioperative morbidity. Laser prostate surgery can achieve good functional outcome and maintain quality of life of seniors. Furthermore, it is safe in seniors with a high morbidity index; however, longer operating time is an independent risk factor for perioperative morbidity.


Alectinib relieves ischemic strokes caused by left atrial metastasis in a NSCLC patient with a novel SLC34A2-ALK (exon 1: exon 15) fusion.
The adoption of molecular profiling in non-small cell lung cancers (NSCLC) have promoted the discoveries of novel anaplastic lymphoma kinase (ALK) mutation patterns including rare intergenic rearrangements. It is always meaningful to report the structure of these fusions and their responses to ALK-inhibitors for future reference. Reports of cerebral ischemic strokes caused by atrial metastases through lymphohematogeneous spread are scarce. A 35-year-old woman with no history of astherosclerosis presented with sudden onset of diplopia and facial palsy. Brain MRI scan discovered multiple infarcts around cortical and subcortical areas supplied by bilateral middle cerebral arteries, the occlusions of which were confirmed by angiography. Echocardiogram revealed intracavity appendages in atriums. The histology following valve debridement displayed endocardial metastases from lung cancer on mitral and trucuspid valves. PET/CT found right lower lobe primary tumor and mediastinal lymphadenopathies. The histology of primary lung tumor suggested adenocarcinoma and a DNA-based next-generation sequencing (NGS) test uncovered an intergenic (FAM49A, RAD51AP2)-ALK (intergenic: A14) rearrangement. Further RNA-based NGS uncovered a novel SLC34A2-ALK (exon 1: exon 15) fusion. Strokes recurred after valve surgery and vegetations reappeared on the mitral valve. Alectinib 600 mg bid was administered based on molecular finding and achieved remarkable tumor regression. Neurologic symptoms were largely relieved. No new infarctions or cerebral metastases has ever been found since. We report a novel SLC34A2-ALK rearrangement responding well to alectinib in a very interesting case of peripheral lung adenocarcinoma presenting with recurrent cerebral ischemic strokes due to endocardial metastases.


Can you help me?: knowledge sharing within the nursing profession.
In the business world, knowledge sharing has been credited with advantages in productivity. When applied to health care, a comprehensive knowledge-sharing program can help nurses compete in today's globalized and highly competitive health care market while improving patient outcomes.


Extracellular hydrolysis of diadenosine polyphosphates, ApnA, by bovine chromaffin cells in culture.
An ectoenzyme hydrolyzing diadenosine polyphosphates (ApnA) to AMP and Ap(n-1) has been studied in cultured chromaffin cells from bovine adrenal medulla. The KM value for extracellular Ap4A hydrolysis was 2.90 +/- 0.72 microM, the V(max) value obtained was 11.59 +/- 0.92 pmol/min x 10(6) cells (116 pmol/min.mg total protein). Ap3A, Ap5A, Ap6A, and Gp4G were competitive inhibitors of Ap4A hydrolysis with K(i) values of 3.65, 1.10, 1.20, and 2.65 microM, respectively. Phosphatidylinositol-specific phospholipase C removes the ApnA hydrolase activity from cultured chromaffin cells, suggesting an anchorage of this protein to the plasma membrane through the phosphatidylinositol. The turnover time for this enzyme calculated in the presence of cycloheximide was 38.94 +/- 1.53 hr for cultured chromaffin cells.


Development and Psychometric Validation of the Taste And Smell Tool for Evaluation (TASTE) Questionnaire.
The human senses of taste and smell are essential in everyday life. However, as clinical testing of the senses and patient-reported sensory problems are often diverging, additional validated questionnaires are essential for the evaluation of chemosensory impairments. To develop an instrument with all relevant domains concerning chemosensory dysfunction and quality of life using modern psychometrics. The study was designed as a questionnaire study for developing a new instrument. The study started in 2019 and was completed in 2022. Patients with chemosensory dysfunction were recruited from a specialized smell and taste clinic at an ear, nose, and throat department in Denmark. Healthy participants with no history of chemosensory dysfunction were recruited through social media. Eight domains were included (distorted chemosensation, emotional, food and meals, social, hygiene, danger, work, and relationship), and 35 items were generated based on review of the existing literature and interviews with patients and experts. Participants were tested with the Major Depression Inventory, 36-Item Short Form Health Survey, Taste Sprays, and Sniffin' Sticks for chemosensory function. Descriptive statistics were calculated for all items. Reliability, internal consistency, and validity were investigated, and a Rasch model was fitted. Healthy controls (n = 39) filled out the questionnaire for comparison of known-groups validity. Confirmatory factor analysis was performed. Finally, item reduction was performed, resulting in a final version with 21 items in 8 domains. The study included responses from 316 patients, 183 women (58%) and 133 men (42%), with a mean (SD) age of 57 (15.1) years. Rasch model fit was acceptable with P > .05 for all items. An 8-dimensional confirmatory factor analysis model showed a better fit than a bifactor confirmatory factor analysis model. Cronbach α ranged from 0.65 to 0.86. Criterion validity with the Sniffin' Sticks, Taste Sprays, Major Depression Inventory, and the 36-Item Short Form Health Survey was satisfactory. The test-retest reliability was good in all domains, ranging from 0.55 to 0.86. All domains were discriminative, except the social and work domains. In this survey study, the instrument was validated with 8 domains related to chemosensory dysfunction and quality of life. All items had good internal consistency, test-retest reliability, interitem correlations, item-total correlations, and Rasch model fit. The questionnaire appears suitable for use in clinical and research settings.


Epstein-Barr virus latency: current and future perspectives.
EBV drives resting B cells to continuous proliferating latently infected cells. A restricted program of viral transcription contributes to latency and cell proliferation important for growth transformation. Recent interest in latency and transformation has provided new data about the roles of the EBV encoded latent proteins and non-coding RNAs. We broadly describe the transcription, epigenetic, signaling and super-enhancer functions of the latent nuclear antigens in regulating cellular transcription; the role of LMP2 in utilization of the autophagosome to control cell death, and the association between LMP1, the linear ubiquitin chain assembly complex and TRAF1 which are important for transformation. This review explores recent discoveries with new insights into therapeutic avenues for EBV related malignancies.


Colorimetric response of dithizone product and hexadecyl trimethyl ammonium bromide modified gold nanoparticle dispersion to 10 types of heavy metal ions: understanding the involved molecules from experiment to simulation.
A new kind of analytical reagent, hexadecyl trimethyl ammonium bromide (CTAB), and dithizone product-modified gold nanoparticle dispersion, is developed for colorimetric response to 10 types of heavy metal ions (M(n+)), including Cr(VI), Cr(3+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+). The color change of the modified gold nanoparticle dispersion is instantaneous and distinct for Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+). The color change results from the multiple reasons, such as electronic transitions, cation-π interactions, formation of coordination bonds, and M(n+)-induced aggregation of gold nanoparticles (AuNPs). The different combining capacity of heavy metal ions to modifiers results in the different broadening and red-shifting of the plasmon peak of modified AuNPs. In addition, Cr(VI), Cu(2+), Co(2+), Ni(2+), and Mn(2+) cause the new UV-vis absorption peaks in the region of 360-460 nm. The interactions between the modifiers and AuNPs, and between the modifiers and M(n+), are investigated by using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The results confirm that AuNPs are modified by CTAB and dithizone products through electrostatic interactions and Au-S bonds, respectively, and the M(n+)-N bonds form between M(n+) and dithizone products. Furthermore, the experimental and density functional theory calculated IR spectra prove that dithizone reacts with NaOH to produce C6H5O(-) and [SCH2N4](2-). The validation of this method is carried out by analysis of heavy metal ions in tap water.


Liquid Chromatographic Chiral Separation of Acenocoumarol and Its Hemiketal Form.
Acenocoumarol, an anticoagulant drug, was separated successfully using polysaccharide-based chiral stationary phases columns namely Cellulose Chiralpak® IB and Chiralcel® OD, using various normal mobile phases by high-performance liquid chromatography. However, the appearance of four well separated peaks confirmed the presence of the hemiketal form of 4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one.


Severe Hypoglycemia and Incidence of QT Interval Prolongation Among Adults With Type 2 Diabetes.
There is a paucity of large-scale epidemiological studies on the link between severe hypoglycemia (SH) and corrected QT (QTc) interval prolongation in type 2 diabetes (T2DM). To evaluate the association of SH with QTc prolongation in adults with T2DM. Prospective cohort analysis of participants enrolled in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without QTc prolongation at baseline. SH was assessed over a 24-month period. Incident QTc prolongation was ascertained using follow-up electrocardiograms. Modified Poisson regression was used to generate the risk ratio (RR) and 95% CI for QTc prolongation. Among 8277 participants (mean age 62.6 years [SD 6.5], 38.7% women, 62.8% White), 324 had ≥1 SH episode (3.9%). Over a median of 5 years, 517 individuals developed QTc prolongation (6.3%). Participants with SH had a 66% higher risk of QTc prolongation (RR 1.66, 95% CI 1.16-2.38). The incidence of QTc prolongation was 10.3% (27/261) and 14.3% (9/63) for participants with 1 and ≥2 SH, respectively. Compared with no SH, RRs for patients with 1 and ≥2 SH episodes were 1.57 (95% CI 1.04-2.39) and 2.01 (95% CI 1.07-3.78), respectively. Age modified the association of SH with QTc prolongation (PInteraction = .008). The association remained significant among younger participants (<61.9 years [median age]: RR 2.63, 95% CI 1.49-4.64), but was nonsignificant among older participants (≥61.9 years: RR 1.37, 95% CI 0.87-2.17). In a large population with T2DM, SH was associated with an increased risk of QTc prolongation independently of other risk factors such as cardiac autonomic neuropathy. The association was strongest among younger participants.


On Going to a New Era of Microgel Exhibiting Volume Phase Transition.
The discovery of phenomena of volume phase transition has had a great impact not only on bulk gels but also on the world of microgels. In particular, research on poly(N-isopropylacrylamide) (PNIPAM) microgels, whose transition temperature is close to body temperature, has made remarkable progress in almost 35 years. This review presents some breakthrough findings in microgels that exhibit volume phase transitions and outlines recent works on the synthesis, structural analysis, and research direction of microgels.


Emergence of nosocomial Mycobacterium massiliense infection in Goiás, Brazil.
A cluster of surgical site infection cases after arthroscopic and laparoscopic procedures occurred between 2005 and 2007 in Goiânia, in the central region of Brazil. Nontuberculous mycobacteria (NTM) were isolated from samples (exudates from cutaneous abscesses) from 18 patients of seven private hospitals. There were no reports of post-surgical arthroscopic and laparoscopic mycobacterial infections in Goiânia apart from this period. The 18 isolates were identified as Mycobacterium massiliense by PCR-restriction digestion of the hsp65 gene, pulsed-field gel electrophoresis (PFGE) comparisons, and rpoB partial gene sequencing. All isolates were typed as a single clone, indicating that they have the same origin, which suggests a common source of infection for all patients.


Personality Influences Risk of Parasitism in Fish.
Influence of fish personality on infection rate is poorly studied. In the experiments on young-of-the-year Oncorhynchus mykiss and cercariae of the trematode Diplostomum pseudospathaceum, we tested the hypothesis that infection rate differs between more and less active ("bold" and "shy") fish. Will individual differences in infection persist upon re-infection? Fish serve as a second intermediate host for this trematode. Positive correlation was found between the results of consecutive infections. Accumulation of parasites with successive infections leads to an aggregated distribution of D. pseudospathaceum among the hosts, affecting individual fitness and polymorphism in fish populations. Persistent individual differences in parasite burden among fish and, as a result, vulnerability for predators confirms the role of parasites as an important factor of natural selection.


Terahertz structured light: nonparaxial Airy imaging using silicon diffractive optics.
Structured light - electromagnetic waves with a strong spatial inhomogeneity of amplitude, phase, and polarization - has occupied far-reaching positions in both optical research and applications. Terahertz (THz) waves, due to recent innovations in photonics and nanotechnology, became so robust that it was not only implemented in a wide variety of applications such as communications, spectroscopic analysis, and non-destructive imaging, but also served as a low-cost and easily implementable experimental platform for novel concept illustration. In this work, we show that structured nonparaxial THz light in the form of Airy, Bessel, and Gaussian beams can be generated in a compact way using exclusively silicon diffractive optics prepared by femtosecond laser ablation technology. The accelerating nature of the generated structured light is demonstrated via THz imaging of objects partially obscured by an opaque beam block. Unlike conventional paraxial approaches, when a combination of a lens and a cubic phase (or amplitude) mask creates a nondiffracting Airy beam, we demonstrate simultaneous lensless nonparaxial THz Airy beam generation and its application in imaging system. Images of single objects, imaging with a controllable placed obstacle, and imaging of stacked graphene layers are presented, revealing hence potential of the approach to inspect quality of 2D materials. Structured nonparaxial THz illumination is investigated both theoretically and experimentally with appropriate extensive benchmarks. The structured THz illumination consistently outperforms the conventional one in resolution and contrast, thus opening new frontiers of structured light applications in imaging and inverse scattering problems, as it enables sophisticated estimates of optical properties of the investigated structures.


Density compensation in allopatric populations of the pygmy shrewSorex minutus on Gotland and the outer hebrides: evidence for the effect of interspecific competition.
Pygmy shrewsSorex minutus occur allopatrically in Ireland, the Outer Hebrides and Gotland in Sweden, and sympatrically with common shrewsS. minutus on the European mainland and in England. Competition theory redicts higher population density in allopatric populations as a consequence of relaxed competition. Here this prediction is tested by comparing allopatric populations of pygmy shrews in the Outer Hebrides and in Gotland with sympatric populations on the Swedish mainland. Population densities were higher in allopatry than in sympatry. Lower summed densities in allopatry, which is predicted by niche theory, was found on the Outer Hebrides, but not on Gotland. Size distributions of carabids, which are important food items, could not explain the differences in population densities. Since both avian predators and snakes are present in all areas, population density of pygmy shrews during autumn in concluded to be regulated primarly by competition with common shrews in areas of sympatry.


Phospholipid metabolite levels are altered in cerebral cortex of patients with dominantly inherited olivopontocerebellar atrophy.
We measured metabolic precursors and breakdown products of phosphatidylcholine (choline, glycerophosphocholine (GPC) and phosphatidylethanolamine (ethanolamine, glycerophosphoethanolamine (GPE)) as well as the amino acid serine, a precursor of phosphatidylserine, in four morphologically unaffected cerebral cortical areas obtained at autopsy from 14 patients with dominantly inherited olivopontocerebellar atrophy (OPCA) and 13 controls matched for age and postmortem interval. As compared with the controls, mean GPE levels were elevated by 49-57% in frontal and parietal cortices of OPCA brains whereas concentrations of ethanolamine were significantly reduced in temporal, occipital and parietal cortex (-40 to -54%). This resulted in increased GPE/ethanolamine ratios (+80 to +146%). GPC levels were significantly increased (by 53%) in the frontal cortex of OPCA patients relative to controls. Free serine levels were reduced by 20 to 28% in frontal, parietal, temporal, and occipital cortices. These abnormalities in phospholipid metabolite levels in OPCA resemble those seen in Alzheimer's disease, although the changes in GPC are less pronounced. These changes in phospholipid metabolism in OPCA cerebral cortex, a brain area spared from neurodegenerative changes, points to generalized disturbances in cellular membrane function in this disease.


Human prostatic acid phosphatase: purification, characterization, and optimization of conditions for radioimmunoassay.
Prostatic acid phosphatase was isolated from benign hypertrophic prostate tissue by ammonium sulfate precipitation and affinity chromatography procedures. The purified enzyme was characterized by two-dimensional gel electrophoresis and shown to have a cluster of protein spots with an apparent molecular weight of 48 000 at pI 5.9 to 6.3 in 9 mol/l urea. The specific activity of the purified enzyme was 723 and 659 U/mg protein with alpha-naphthyl phosphate at 30 degrees C and para-nitrophenyl phosphate at 37 degrees C respectively. An antibody to the purified enzyme was raised in rabbits and used in a radioimmunoassay (RIA). The use of a phosphate buffer, pH 6.6, and iodination of prostatic acid phosphatase (PAP) by the Bolton-Hunter procedure improved the precision of the assay when compared to RIA's using a phosphate buffer, pH 7.0 or 7.3, or PAP iodinated by a chloramine-T procedure. The former RIA displaced 50% of the tracer at 2 micrograms of enzyme per liter of serum. The between-run coefficient of variation for 11 assays ranged from 3.9-7.7% with serum at 1.3 to 5.6 micrograms PAP/l.


Does the type of renal artery anatomic variant determine the diameter of the main vessel supplying a kidney? A study based on CT data with a particular focus on the presence of multiple renal arteries.
An in-depth knowledge of renal vascular anatomy is essential when planning many surgical procedures; however, a few data exists regarding renal artery diameter. The aim of this study was to assess this morphological feature and to investigate whether a correlation exists between renal artery diameter and the type of arterial supply, with a particular emphasis on variant anatomy and the presence of multiple renal arteries. Computed tomography angiography (CTA) studies of 248 patients, i.e., a total of 496 kidneys, were evaluated. The mean age of the patients was 66.4 ± 15.01 years. Renal artery diameter was measured based on the type of arterial blood supply. The frequency of occurrence of three anatomic variants of renal arterial supply was established: single renal artery (RA) 43.35%, single artery with prehilar branching (pRA) 37.30%, and multiple renal artery (mRA) 19.35%. The diameter of single renal arteries, with either prehilar or hilar branching, was significantly larger than when multiple arteries were present. A detailed analysis of just the mRA variant demonstrated that the diameter of the renal arteries in men was larger (p = 0.012) than those in women and that there was no difference in diameter with regard to the side of the body (p = 0.219). The classification described in our study containing a detailed description of renal artery diameter. It may be helpful in clinical practice, especially for transplantologists, surgeons, and vascular surgeons.


Effects of hormones and pyruvate on the rates of secretion of very-low-density lipoprotein triacylglycerol and cholesterol by rat hepatocytes.
The secretion of very-low-density lipoprotein (VLDL) triacylglycerol and cholesterol was determined under various conditions in hepatocytes prepared from rats maintained on a controlled lighting and feeding schedule. The rate of lipogenesis in hepatocytes prepared from rats during the feeding period was 2-3-fold higher than that in cells prepared immediately before the animals had access to food. However, there were no corresponding changes in the rates of secretion of triacylglycerol and cholesterol. Pyruvate alone stimulated triacylglycerol secretion but had no effect on the secretion of cholesterol. Despite its stimulation of lipogenesis, insulin suppressed the secretion of both triacylglycerol and cholesterol. This effect on triacylglycerol secretion was more pronounced when lipogenesis was enhanced in the presence of pyruvate. Thus, insulin may act to alleviate hypertriglyceridaemia, which may arise during periods of increased hepatic lipogenesis. The inhibitory effect of glucagon on cholesterol secretion was much less pronounced than that on the secretion of triacylglycerol. The inhibitory effects of glucagon were reversed by pyruvate on cholesterol secretion differed according to whether glucagon was present or absent. These results suggest that the rate of hepatic VLDL triacylglycerol secretion is not necessarily coupled to the rate of lipogenesis in the liver; nor is there any obligatory coupling between the output of triacylglycerol and cholesterol associated with VLDL.


Bypass vs endovascular treatment for occluded femoro-popliteal stents in patients with critical limb-threatening ischemia.
The aim of the study was to compare the early and medium-term outcomes of bypass vs endovascular treatment of occluded femoro-popliteal stents in patients with chronic limb-threatening ischemia (the OUT-STEPP multicentric registry). Between January 2016 and December 2021, 317 patients in 14 centers underwent treatment for a symptomatic occlusion of femoro-popliteal stent/stents. One hundred sixty-one patients were included into the present study: 46 (28.6%) underwent open bypass surgery (Group OPEN), and 115 (71.4%) underwent endovascular revascularization (Group ENDO). Early (30 days) results were assessed and compared between the two groups. Estimated 5-year outcomes were evaluated and compared with the log rank test. At 30 days, no differences were found in terms of major adverse cardiovascular events, acute kidney injury, reinterventions, major amputation, and all-cause mortality between the two groups. The need for blood transfusions was higher for patients in Group OPEN (17; 36.9% vs 13; 11.3%; P < .001). The mean length of intensive care unit stay and the mean hospital stay were higher for patients in Group OPEN ([0.3 ± 0.9 vs 0 days; P < .001] and [9.7 ± 5.8 vs 3.3 ± 1.4 days; P < .001], respectively). The overall median duration of follow-up was 33.1 months (interquartile range, 14-49.5 months). At 5 years, there were no differences between the two groups in terms of survival (68.7% Group OPEN vs 68.8% Group ENDO; P = .27; log-rank, 1.21), primary patency (56.3% Group OPEN vs 67.8% Group ENDO; P = .39; log-rank, 0.75), secondary patency (59.1% Group OPEN vs 77.8% Group ENDO; P = .24; log-rank, 1.40), absence of target lesion restenosis (56.8% Group OPEN vs 62.7% Group ENDO; P = .42; log-rank, 0.65), and limb salvage (77.2% Group OPEN vs 90.4% Group ENDO; P = .17; log-rank, 1.87). Both bypass and endovascular treatment provided safe and effective restoration of patency for femoro-popliteal in-stent occlusion in patients with chronic limb-threatening ischemia. Open surgery was associated with longer stay in hospital and increased use of blood transfusions. At 5 years, no significant differences were found in the rates of overall patency or limb salvage between bypass and endovascular treatment.


Incidence, management, and outcome of lung cancer in patients with long-term oxygen therapy.
Here, we aimed to assess the specific features of lung cancer in patients with long-term oxygen therapy (LTOT), and compare their outcomes with patients suffering from lung cancer without LTOT. This retrospective, case-controlled study included patients with LTOT and an incident diagnosis of lung cancer treated at Rouen University Hospital. Out of 2201 patients with LTOT, 31 were diagnosed with lung cancer. Among 24 patients with proven lung cancer, the most frequent histological type was squamous cell carcinoma (n = 12/24, 50%). Active treatment of any type was given in 19/31 (61%) and 41/62 (66%) of patients in the LTOT and control groups, respectively (p = 0.83). In the LTOT group, median survival was 38 days with best supportive care and 462 days with active treatment (p = 0.003). However, when adjusting on performance status and disease stage, LTOT was not significantly associated with a worse outcome. Hazard ratio (HR): 1.56 (95% confidence interval [CI]: 0.87 to 2.81) (p = 0.137). Administration of any treatment was associated with a better prognostic: HR: 0.35 (95% CI: 0.19 to 0.66). Both groups had a similar treatment safety profile. Incidence of lung cancer in patients with LTOT was comparable to the general population. The proportion of LTOT patients who received active treatment was similar to controls, and overall survival did not differ from controls in a multivariate analysis. Although reaching a histological diagnosis may be challenging in LTOT patients, the efficacy and safety of the management strategies of lung cancer seem preserved.


Association between HLA-DQB1*03:01 and Bullous pemphigoid in Iranian patients.
A common Human Leukocyte Antigen (HLA) class II allele, DQβ1*03:01, seems to be associated with Bullous pemphigoid (BP) in Caucasians whereas previous studies in other ethnic groups showed other HLA class II alleles as genetic predisposing factors for BP. To investigate the association of HLA class II alleles and haplotypes with BP in Iranian population. Fifty patients with Bullous pemphigoid and 180 geographically matched, healthy individuals as control group enrolled into this study. HLA typing of class II (DR and DQ alleles) was carried out using polymerase chain reaction based on sequence-specific primers method. Class II DQA1 and DQB1 typing showed a significantly higher frequency of HLA-DQA1*05:01 (45% vs. 33%, p=0.03), HLA-DQB1*03:01 (36% vs. 23.6%, p=0.02) and HLA-DQB1*04:01 (4% vs. 1.6%, p=0.04) in the BP patients compared with controls. For DRB1 allele frequencies, there were no significant disease associations. The frequency of DRB1*08:01/DQA1*05:01/DQB1*03:01 (3% vs. 0%, p=0.02) haplotype showed an increase among patients compared with controls. Our data suggest that Iranian patients with BP present the same genetic predisposition linked to HLA-DQB1*03:01 previously reported in Caucasians.