Caffeine treatment prevents rapid eye movement sleep deprivation-induced impairment of late-phase long-term potentiation in the dentate gyrus.
The CA1 and dentate gyrus (DG) are physically and functionally closely related areas of the hippocampus, but they differ in various respects, including their reactions to different insults. The purpose of this study was to determine the protective effects of chronic caffeine treatment on late-phase long-term potentiation (L-LTP) and its signalling cascade in the DG area of the hippocampus of rapid eye movement sleep-deprived rats. Rats were chronically treated with caffeine (300 mg/L drinking water) for 4 weeks, after which they were sleep-deprived for 24 h. L-LTP was induced in in anaesthetized rats, and extracellular field potentials from the DG area were recorded in vivo. The levels of L-LTP-related signalling proteins were assessed by western blot analysis. Sleep deprivation markedly reduced L-LTP magnitude, and basal levels of total cAMP response element-binding protein (CREB), phosphorylated CREB (P-CREB), and calcium/calmodulin kinase IV (CaMKIV). Chronic caffeine treatment prevented the reductions in the basal levels of P-CREB, total CREB and CaMKIV in sleep-deprived rats. Furthermore, caffeine prevented post-L-LTP sleep deprivation-induced downregulation of P-CREB and brain-derived neurotrophic factor in the DG. The current findings show that caffeine treatment prevents acute sleep deprivation-induced deficits in brain function.


A critical study on RO-4-1284 antagonism in mice.
Ro-4-1284 is found to produce ptosis, hypothermia, sedation and miosis in mice, and the antagonsim to these symptoms is investigated. The study reports the differential effects of various pharmacologically distinct classes of compounds. The relevance of this type of experiments to possible antidepressant drug activity is discussed.


GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis.
Glucocorticoids, such as dexamethasone, are widely used anti-inflammatory drugs. Their use is frequently associated with the development of steroid- associated diabetes. Pancreatic β-cell dysfunction has been suggested to be one of the main causes of steroid-associated diabetes. However, the mechanism is not fully understood. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase and plays an important role in energy metabolism, cell growth and apoptosis. Therefore, the contribution of GSK-3β in dexamethasone-induced pancreatic β-cell apoptosis was determined in the present study. The effect of dexamethasone treatment on rat pancreatic β-cell line (INS-1) apoptosis (determined by TUNEL and Flow Cytometry), generation of reactive oxidative stress (ROS), and the phosphorylation status of GSK-3β was determined. The inhibitory effect of GSK-3β inhibitor-lithium chloride (LiCl) on dexamethasone-induced β-cell apoptosis was also evaluated. Dexamethasone (0.1 μM) treatment induced INS-1 apoptosis, which was associated with increased GSK-3β activation and increased NOX4-derived ROS generation. Pretreatment of INS-1 with LiCl inhibited dexamethasone induced ROS generation and INS-1 apoptosis. This study provides a new mechanism of Dex induced pancreatic β cell apoptosis and may serve as a new therapeutic option for treating GC induced diabetes.


Data-driven network analysis identified subgroup-specific low back pain pathways: a cross-sectional GLA:D Back study.
To understand the physical, activity, pain, and psychological pathways contributing to low back pain (LBP) -related disability, and if these differ between subgroups. Data came from the baseline observations (n = 3849) of the "GLA:D Back" intervention program for long-lasting nonspecific LBP. 15 variables comprising demographic, pain, psychological, physical, activity, and disability characteristics were measured. Clustering was used for subgrouping, Bayesian networks (BN) were used for structural learning, and structural equation model (SEM) was used for statistical inference. Two clinical subgroups were identified with those in subgroup 1 having worse symptoms than those in subgroup 2. Psychological factors were directly associated with disability in both subgroups. For subgroup 1, psychological factors were most strongly associated with disability (β = 0.363). Physical factors were directly associated with disability (β = -0.077), and indirectly via psychological factors. For subgroup 2, pain was most strongly associated with disability (β = 0.408). Psychological factors were common predictors of physical factors (β = 0.078), pain (β = 0.518), activity (β = -0.101), and disability (β = 0.382). The importance of psychological factors in both subgroups suggests their importance for treatment. Differences in the interaction between physical, pain, and psychological factors and their contribution to disability in different subgroups may open the doors toward more optimal LBP treatments.


Adiposity measures and arterial stiffness in primary care: the MARK prospective observational study.
The cardiovascular risk of obesity is potentially increased by arterial stiffness. To assess the relationship of adiposity measures with arterial stiffness in Caucasian adults with intermediate cardiovascular risk. Six Spanish health centres. We enrolled 2354 adults (age range, 35-74 years; mean age, 61.4±7.7 years, 61.9% male). This is a cross-sectional study that analyses data from the baseline visit of the improving interMediAte RisK management (MARK) study. The main outcome variables were body mass index (BMI), waist-to-height ratio (WHtR), Clínica Universidad de Navarra-body adiposity estimation (CUN-BAE) body fat percentage and body roundness index (BRI). Vascular function was assessed by the cardio-ankle vascular index (CAVI) with the VaSera device; brachial-ankle pulse wave velocity (baPWV) was determined using a validated equation. The mean adiposity measures were a BMI of 29.2±4.4, WHtR of 0.61±0.07, CUN-BAE of 35.7±1.7 and BRI of 5.8±1.7. The mean stiffness measures were a CAVI of 8.8±1.2 and baPWV of 14.9±2.5. In multiple linear regression analyses, all adiposity measures were negatively associated with CAVI and baPWV (p<0.01 for all) after adjustment for possible factors of confusion. The proportion of CAVI variability via the adiposity measures were 5.5% for BMI, 5.8% for CUN-BAE, 3.8% for WHtR and 3.7% for BRI. These were higher among diabetic, obese, younger (≤62 years) and non-hypertensive subjects who had similar activity and sedentary profiles. Adiposity measures are negatively associated with arterial stiffness measures. The percentage of variation in CAVI explained by its relation to the different measures of adiposity ranges from 5.8% (CUN-BAE) to 3.7% (BRI). In the case of baPWV, it oscillates between 0.7% (CUN-BAE and BMI) and 0.1% (WHtR). NCT01428934.


A highly efficient chemical isolation procedure for the rat placental transferrin receptor.
A chemical method for the purification of rat placental transferrin receptor is described. After initial solubilization and concentration by ammonium sulfate precipitation, radioiron-tagged diferric transferrin was added to the dialyzed receptor fraction and subjected to anion-exchange chromatography on DEAE-Sephacel. Elution with a Tris-HCl buffer gradient yields a single fraction of radioactivity containing both free transferrin and the receptor-transferrin as a complex. Further separation of the receptor-transferrin complex from the free transferrin is achieved by gel chromatography on a AcA34-Sepharose 6B separation system. Final purification is obtained by preparative gel electrophoresis in 5% polyacrylamide gels. The receptor was shown to be pure by various methods including HPLC chromatography. The average yield was 20-30 mg receptor-transferrin complex/100 g placental tissue. Because of the purely chemical approach, this method is universally applicable for the isolation of transferrin receptors from various tissues.


Differential gene expression associated with inflammation in peripheral blood cells of patients with pneumoconiosis.
To study expression changes in inflammation-related genes in peripheral blood of patients with pneumoconiosis and to explore the possibility of these genes as pneumoconiosis biomarkers. Peripheral blood samples of patients with pneumoconiosis patients and controls were collected, and total RNA of the blood cells were extracted and reverse transcribed to cDNA. Screenings of deferentially expressed genes associated with inflammation between patients with pneumoconiosis and controls were performed using real-time quantitative PCR array and the expressions of the three most upregulated genes were confirmed by real-time PCR. The expression of 11 genes was significantly altered in patients with pneumoconiosis compared with those of the control. Among these 11 genes, 8 genes were upregulated and 3 were downregulated. Preliminary results indicated that interleukin 6 (IL-6) mRNA expression in patients with pneumoconiosis was higher than that in controls (P=0.019). The level of IL6 mRNA expression in the patients was higher than that in non-smoking controls, but it was neither affected by type and stage of pneumoconiosis nor by time of contact with dust. IL6 was possibly involved in the development of pneumoconiosis.


Flat-band localization and self-collimation of light in photonic crystals.
We investigate the optical properties of a photonic crystal (PC) composed of a quasi-one-dimensional flat-band lattice array through finite-difference time-domain simulations. The photonic bands contain flat bands (FBs) at specific frequencies, which correspond to compact localized states as a consequence of destructive interference. The FBs are shown to be nondispersive along the Г → X line, prohibiting optical transmission with incident light in x direction. On the other hand, the photonic band for the FB frequency is found to be dispersive along the Г → Y line, resulting in nonzero optical transmission. Such anisotropic optical response of the PC due to the FB localization of light in a single direction only results in a self-collimation of light propagation throughout the PC at the FB frequency.


Anatomy-based inverse planning simulated annealing optimization in high-dose-rate prostate brachytherapy: significant dosimetric advantage over other optimization techniques.
To perform an independent validation of an anatomy-based inverse planning simulated annealing (IPSA) algorithm in obtaining superior target coverage and reducing the dose to the organs at risk. In a recent prostate high-dose-rate brachytherapy protocol study by the Radiation Therapy Oncology Group (0321), our institution treated 20 patients between June 1, 2005 and November 30, 2006. These patients had received a high-dose-rate boost dose of 19 Gy to the prostate, in addition to an external beam radiotherapy dose of 45 Gy with intensity-modulated radiotherapy. Three-dimensional dosimetry was obtained for the following optimization schemes in the Plato Brachytherapy Planning System, version 14.3.2, using the same dose constraints for all the patients treated during this period: anatomy-based IPSA optimization, geometric optimization, and dose point optimization. Dose-volume histograms were generated for the planning target volume and organs at risk for each optimization method, from which the volume receiving at least 75% of the dose (V(75%)) for the rectum and bladder, volume receiving at least 125% of the dose (V(125%)) for the urethra, and total volume receiving the reference dose (V(100%)) and volume receiving 150% of the dose (V(150%)) for the planning target volume were determined. The dose homogeneity index and conformal index for the planning target volume for each optimization technique were compared. Despite suboptimal needle position in some implants, the IPSA algorithm was able to comply with the tight Radiation Therapy Oncology Group dose constraints for 90% of the patients in this study. In contrast, the compliance was only 30% for dose point optimization and only 5% for geometric optimization. Anatomy-based IPSA optimization proved to be the superior technique and also the fastest for reducing the dose to the organs at risk without compromising the target coverage.


Ophthalmic ointments.
The use of ointments as an ocular drug vehicle adds an important dimension to topical therapy. Ointments are well tolerated, fairly safe, and provide an excellent means for enhanced ocular contact time. In the case of certain antibiotics, this improved contact time yields increased ocular drug levels. However, experimental data indicate that corticosteroid ointments do not penetrate into the eye as well as do suspension preparations. This may relate to the binding of the drug to the ointment base and also to the particular steroid compound. Like other ophthalmic preparations, ointments may become contaminated. Ophthalmic ointments should not be instilled into eyes with open wounds. Instillation of ointments into postoperative eyes where wound closure is secure appears to be safe and effective.


Delayed esophageal perforation after pneumatic dilatation for the treatment of achalasia.
Two cases of delayed esophageal perforation following a pneumatic dilatation for the treatment of achalasia are presented. Esophagrams obtained immediately after pneumatic dilatation failed to reveal a perforation. Increasing symptoms prompted repeat contrast studies, at which time an esophageal perforation was demonstrated. The occurrence of delayed esophageal perforation after pneumatic intrumentation is emphasized. An ischemic etiology for this delayed perforation is postulated.


Progressive preleukemia with a chromosomally abnormal clone in a kindred with the Estren-Dameshek variant of Fanconi's anemia.
One of two sisters with hypoplastic anemia and increased chromosomal fragility, but no clinical stigmata of Fanconi's anemia (FA), progressed to preleukemia (with a clone of chromosomally abnormal cells in the bone marrow), and then to acute nonlymphocytic leukemia. The findings indicate that constitutional genetic instability can lead to karyotypically aberrant neoplastic clones in the Estren-Dameshek variant of FA as well as in the more typical chromosomal fragility syndromes.


Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis.
To determine the frequency of pulmonary embolism in patients admitted for treatment of deep venous thrombosis. An open, multicenter, dose-ranging study to assess the safety and pharmacokinetic characteristics of tissue-type plasminogen activator in deep venous thrombosis and pulmonary embolism. Perfusion and ventilation lung scans, chest roentgenograms, and venograms (in deep venous thrombosis) or pulmonary angiograms (in pulmonary embolism) were obtained before and 24 hours after inception of therapy. Heparin therapy was then administered. Five tertiary-care hospitals. All patients with suspected deep venous thrombosis or pulmonary embolism seen from August 1987 through November 1988 entered the study if they met inclusion criteria and if the diagnosis was confirmed by venogram (deep venous thrombosis) or pulmonary angiogram (pulmonary embolism). All patients received tissue-type plasminogen activator followed by intravenous heparin therapy. The primary measure was the frequency of pulmonary embolism in patients with deep venous thrombosis who had no symptoms of pulmonary embolism. This was not the original purpose of the study but emerged as an important finding as the data were analyzed. Nearly 40% of patients with deep venous thrombosis who had no symptoms of pulmonary embolism had evidence of pulmonary embolism based on ventilation-perfusion scan and chest roentgenogram findings. Because all of those considered to have embolism had so-called high-probability scan results, the frequency of embolism reported likely represents the minimum incidence of pulmonary embolism in patients with deep venous thrombosis who have no embolic symptoms. These data emphasize that venous thromboembolism is one disorder.


Amino acid substitutions in the neuraminidase protein of an H9N2 avian influenza virus affect its airborne transmission in chickens.
Cases of H9N2 avian influenza virus (AIV) in poultry are increasing throughout many Eurasian countries, and co-infections with other pathogens have resulted in high morbidity and mortality in poultry. Few studies have investigated the genetic factors of virus airborne transmission which determine the scope of this epidemic. In this study, we used specific-pathogen-free chickens housed in isolators to investigate the airborne transmissibility of five recombinant H9N2 AIV rescued by reverse genetic technology. The results show that airborne transmission of A/Chicken/Shandong/01/2008 (SD01) virus was related to the neuraminidase (NA) gene, and four amino acid mutations (D368E, S370L, E313K and G381D) within the head region of the SD01 NA, reduced virus replication in the respiratory tract of chickens, reduced virus NA activity, and resulted in a loss of airborne transmission ability in chickens. Similarly, reverse mutations of these four amino acids in the NA protein of r01/NASS virus, conferred an airborne transmission ability to the recombinant virus. We conclude that these four NA residues may be significant genetic markers for evaluating potential disease outbreak of H9N2 AIV, and propose that immediate attention should be paid to the airborne transmission of this virus.


Chromosome banding in Amphibia. VIII. An unusual XY/XX-sex chromosome system in Gastrotheca riobambae (Anura, Hylidae).
The mitotic and meiotic chromosomes of the marsupial frog Gastrotheca riobambae were analysed with various banding techniques. The karyotype of this species is distinguished by considerable amounts of constitutive heterochromatin and unusual, heteromorphic XY sex chromosomes. The Y chromosome is considerably larger than the X chromosome and almost completely heterochromatic. The analysis of the banding patterns obtained with GC- and AT-base-pair-specific fluorochromes shows that the constitutive heterochromatin in the Y chromosome consists of at least three different structural categories. The only nucleolus organizer region (NOR) of the karyotype is localized in the short arm of the X chromosome. This causes a sex-specific difference in the number of NOR: female animals have two NORs in diploid cells, male animals one. No cytological indications were found for the inactivation of one of the two X chromosomes in the female cells. In male meiosis, the heteromorphic sex chromosomes form a characteristic sex-bivalent by pairing their telomeres in an end-to-end arrangement. The significance of the XY/XX sex chromosomes of G. riobambae for the study of X-linked genes in Amphibia, the evolution of sex chromosomes and their specific DNA sequences, and the significance of the meiotic process of sex chromosomes are discussed.


Towards liveable cities: A review of ethnicity, public urban nature space and wellbeing.
In this review, we synthesise the results of studies that examine how the relationships between public urban nature spaces and wellbeing vary by ethnicity in cities of the Global North. We searched for articles that reported on the relationships between public urban nature spaces, ethnicity and wellbeing. We found 65 articles that met our inclusion criteria. From our review, we found positive and negative relationships between public urban nature spaces, ethnicity and wellbeing in four interrelated domains: integration/relationship building, therapy, safety and capabilities/competency building. The findings of this review inform park management by offering twelve wellbeing pathways to design urban nature spaces that are more inclusive to all residents.


Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors: The JAVELIN PARP Medley Nonrandomized Controlled Trial.
Preclinical data suggest that poly(ADP-ribose) polymerase (PARP) inhibitors have synergistic activity when combined with immune checkpoint inhibitors (ICIs); however, it is unknown which tumor types or molecular subtypes may benefit from this combination. To investigate responses associated with the combination of avelumab and talazoparib in different tumor types and/or molecular subtypes. In this phase 1b and 2 basket nonrandomized controlled trial, patients with advanced solid tumors were enrolled in the following cohorts: non-small cell lung cancer (NSCLC); DNA damage response (DDR)-positive NSCLC; triple-negative breast cancer (TNBC); hormone receptor-positive, human epidermal growth factor receptor 2 (ERBB2)-negative, DDR-positive breast cancer; recurrent, platinum-sensitive ovarian cancer (OC); recurrent, platinum-sensitive, BRCA1/2-altered OC; urothelial cancer; metastatic castration-resistant prostate cancer (mCRPC); DDR-positive mCRPC; and BRCA1/2- or ATM-altered solid tumors. Data were analyzed between June 17, 2021, and August 6, 2021. All patients in phases 1b and 2 received avelumab plus talazoparib. The phase 1b primary end point was dose-limiting toxic effects. The phase 2 primary end point was objective response, measured as objective response rate (ORR). Secondary end points included safety, time to response, duration of response (DOR), progression-free survival, time to prostate-specific antigen progression and PSA response of 50% or greater (for mCRPC), cancer antigen 125 response (for OC), pharmacokinetics, immunogenicity, and biomarkers. A total of 223 patients (mean [SD] age, 63.2 [11.0] years; 117 [52.5%] men) were treated, including 12 patients in phase 1b and 211 patients in phase 2. The recommended phase 2 dose was avelumab 800 mg every 2 weeks plus talazoparib 1 mg once daily. In phase 2, the ORR was 18.2% (95% CI, 5.2%-40.3%) in patients with TNBC; 34.8% (95% CI, 16.4%-57.3%) in patients with HR-positive, ERBB2-negative, and DDR-positive BC; and 63.6% (95% CI, 30.8%-89.1%) in patients with platinum-sensitive, BRCA1/2-altered OC. Responses occurred more frequently in patients with BRCA1/2-altered tumors. Durable responses were observed in patients with TNBC (median [range] DOR, 11.1 [3.4-20.4] months); HR-positive, ERBB2-negative, and DDR-positive BC (median [range] DOR, 15.7 [3.9 to ≥20.6] months); and BRCA1/2-altered OC (median DOR not reached; range, 5.6 to ≥18.4 months). The most common grade 3 or greater treatment-related adverse events were anemia (75 patients [33.6%]), thrombocytopenia (48 patients [21.5%]), and neutropenia (31 patients [13.9%]). This nonrandomized controlled trial found that ORRs for avelumab plus talazoparib were comparable with those with PARP inhibitor or ICI monotherapy. Prolonged DOR in patients with TNBC; HR-positive, ERBB2-negative, and DDR-positive BC; and BRCA1/2-altered OC warrant further investigation in randomized clinical trials. These data highlight the importance of prospective patient selection in future studies of ICI and PARP-inhibitor combinations. ClinicalTrials.gov Identifier: NCT03330405.


Treatment of acute graft-versus-host disease after HLA-partially matched marrow transplantation with a monoclonal antibody (BMA031) against the T cell receptor. First results of a phase-I/II trial.
As part of an ongoing phase-I/II trial, 2 patients received a 5-day treatment course with a murine monoclonal antibody (MAB) directed against the human T cell receptor (BMA031) as primary therapy of acute grade III skin and gastro-intestinal graft-versus-host disease (GvHD) occurring after allogeneic bone marrow transplantation (BMT). All MAB infusions were tolerated without side effects. A complete response of all symptoms of acute GvHD could be attained by MAB therapy under a continued baseline immunosuppression with cyclosporin (CSP), and both patients remain alive and disease-free at 7 and 8 months after therapy without evidence of chronic GvHD. Although the exact treatment scheme has still to be defined, we conclude that this MAB may be useful as primary therapy of acute GvHD. However, the potential hazards of 'in vivo' therapy with MABs directed against T lymphocytes call for a critical evaluation of this treatment modality.


Statin use and the presence of microalbuminuria. Results from the ERICABEL trial: a non-interventional epidemiological cohort study.
Microalbuminuria (MAU) is considered as a predictor or marker of cardiovascular and renal events. Statins are widely prescribed to reduce cardiovascular risk and to slow down progression of kidney disease. But statins may also generate tubular MAU. The current observational study evaluated the impact of statin use on the interpretation of MAU as a predictor or marker of cardiovascular or renal disease. We used cross-sectional data of ERICABEL, a cohort with 1,076 hypertensive patients. MAU was defined as albuminuria ≥20 mg/l. A propensity score was created to correct for "bias by indication" to receive a statin. As expected, subjects using statins vs. no statins had more cardiovascular risk factors, pointing to bias by indication. Statin users were more likely to have MAU (OR: 2.01, 95%CI: 1.34-3.01). The association between statin use and MAU remained significant after adjusting for the propensity to receive a statin based on cardiovascular risk factors (OR: 1.82, 95%CI: 1.14-2.91). Next to statin use, only diabetes (OR: 1.92, 95%CI: 1.00-3.66) and smoking (OR: 1.49, 95%CI: 0.99-2.26) were associated with MAU. Use of statins is independently associated with MAU, even after adjusting for bias by indication to receive a statin. In the hypothesis that this MAU is of tubular origin, statin use can result in incorrect labeling of subjects as having a predictor or marker of cardiovascular or renal risk. In addition, statin use affected the association of established cardiovascular risk factors with MAU, blurring the interpretation of multivariable analyses.


Mechanisms and consequences of macrophage apoptosis in atherosclerosis.
Macrophage apoptosis is an important feature of atherosclerotic plaque development. Research directed at understanding the functional consequences of macrophage death in atherosclerosis has revealed opposing roles for apoptosis in atherosclerotic plaque progression. In early lesions, macrophage apoptosis limits lesion cellularity and suppresses plaque progression. In advanced lesions, macrophages apoptosis promotes the development of the necrotic core, a key factor in rendering plaques vulnerable to disruption and in acute lumenal thrombosis. The first section of this review will examine the role of phagocytic clearance of apoptotic macrophages, a process known as efferocytosis, in the dichotomous roles of macrophage apoptosis in early vs. advanced lesions. The second section will focus on the molecular and cellular mechanisms that are thought to govern macrophage death during atherosclerosis. Of particular interest is the complex and coordinated role that the endoplasmic reticulum (ER) stress pathway and pattern recognition receptors (PRRs) may play in triggering macrophage apoptosis.


A fast cross-validation method for alignment of electron tomography images based on Beer-Lambert law.
In electron tomography, accurate alignment of tilt series is an essential step in attaining high-resolution 3D reconstructions. Nevertheless, quantitative assessment of alignment quality has remained a challenging issue, even though many alignment methods have been reported. Here, we report a fast and accurate method, tomoAlignEval, based on the Beer-Lambert law, for the evaluation of alignment quality. Our method is able to globally estimate the alignment accuracy by measuring the goodness of log-linear relationship of the beam intensity attenuations at different tilt angles. Extensive tests with experimental data demonstrated its robust performance with stained and cryo samples. Our method is not only significantly faster but also more sensitive than measurements of tomogram resolution using Fourier shell correlation method (FSCe/o). From these tests, we also conclude that while current alignment methods are sufficiently accurate for stained samples, inaccurate alignments remain a major limitation for high resolution cryo-electron tomography.


Psychosocial predictors of COVID-19 infection in UK biobank (N = 104 201).
Since the outbreak of COVID-19, data on its psychosocial predictors are limited. We therefore aimed to explore psychosocial predictors of COVID-19 infection at the UK Biobank (UKB). This was a prospective cohort study conducted among UKB participants. The sample size was N = 104 201, out of which 14 852 (14.3%) had a positive COVID-19 test. The whole sample analysis showed significant interactions between sex and several predictor variables. Among females, absence of college/university degree [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.45-1.66] and socioeconomic deprivation (OR 1.16 95% CI 1.11-1.21) were associated with higher odds of COVID-19 infection, while history of psychiatric consultation (OR 0.85 95% CI 0.77-0.94) with lower odds. Among males, absence of college/university degree (OR 1.56, 95% CI 1.45-1.68) and socioeconomic deprivation (OR 1.12, 95% CI 1.07-1.16) were associated with higher odds, while loneliness (OR 0.87, 95% CI 0.78-0.97), irritability (OR 0.91, 95% CI 0.83-0.99) and history of psychiatric consultation (OR 0.85, 95% CI 0.75-0.97) were associated with lower odds. Sociodemographic factors predicted the odds of COVID-19 infection equally among male and female participants, while psychological factors had differential impacts.


Calreticulin mutation burden--is it a stable clone in patients with essential thrombocythemia and myelofibrosis?
Calreticulin mutation represents the second most frequent mutation after JAK2 V617F in myeloproliferative disorder and is considered to be a driving mutation. Herein the mutation burden was evaluated in patients with essential thrombocythemia or myelofibrosis and found to increase by 5.7% over time unrelated to the time elapsed from the initial to the final positive test. The longer the course of the disease when first tested (range 0-30 years, mean 7.9 years) the lower mutation burden was observed. The mutated clone was larger in type II in comparison with type I mutation when first tested but the difference in mutation burden from the final to the first positive test was significantly higher in those with type I. Similarly, the difference in mutation burden was higher in patients with essential thrombocythemia reaching almost 8% in comparison to 1.3% in post-essential thrombocythemia myelofibrosis. Thus a repeat calreticulin quantitative test is not warranted.


Propionyl-L-carnitine, L-arginine and niacin in sexual medicine: a nutraceutical approach to erectile dysfunction.
The application of nutraceuticals in the field of male sexual function -in particular for erectile dysfunction (ED)--remains relatively underexplored. In a group of 54 unselected men (35-75 years), consecutively presenting to our ED clinic and naive to other ED treatments, we carried out a single-blind, one-arm study to evaluate the effects of a 3-month supplementation with propionyl-L-carnitine, L-arginine and niacin on their sexual performance. All patients had the short-international index of erectile function (IIEF) questionnaire, global assessment questions (GAQs) and routine laboratory testing, at baseline and 3 months afterward. 51 (92%) patients of 54 completed the entire study period. After 3 months of treatment, a small, but statistically significant improvement in total and single items of the IIEF was found (Δ = 5.7 ± 4.1 P < 0.01). Analyses on GAQs revealed that treatment improved erections in 40% of cases, with a partial response occurring in up to 77% of subjects enrolled. These preliminary findings indicate that the favourable cardiovascular effects of nutraceuticals might also reflect on male sexual function with possible implication in the treatment and prevention of ED. This study documents a considerable patient's interest toward nutritional supplementation--as first-line or adjunctive treatment to PDE5 inhibitors--that goes beyond the measurable increment in penile rigidity.


Regenerative endodontic procedures: are they more successful in mature permanent teeth with necrotic pulp than in immature teeth?
Five scientific databases were electronically searched: PubMed, EMBASE, OpenGrey, Web of Science and Cochrane Library. The search was conducted until 17 February 2022 without any restriction on date of publication but was restricted to English language. Relevant studies were also screened for related publications. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of regenerative endodontic procedures (REPs) in mature and immature permanent teeth with necrotic pulp and to evaluate if the success rate was affected by the stage of root development. Types of studies: all of the included studies were randomised controlled trials (RCTs). people with necrotic permanent teeth (immature or mature) treated with regenerative endodontic procedures. Types of interventions: regenerative endodontic procedures. Language: RCTs published in English. Types of studies: (1) case reports, (2) retrospective cohort trials, (3) prospective cohort trials, (4) animal trials, (5) in-vitro trials, (6) non-randomised trials. primary teeth. Types of interventions: no details about the clinical procedures. Follow-up period: <6 months. The titles and abstracts of the RCTs identified by the search strategies were independently screened by two reviewers. After the initial screening, the full text of the relevant trials were reassessed against the inclusion and exclusion criteria. Discrepancies and disagreements were resolved by consensus after including a third reviewer. Following the initial electronic and manual searches, a total of 3766 articles were initially identified. This was reduced to 2739 articles after duplicates were removed. However, after the initial screening phase, 35 articles were considered potentially relevant and qualified for full-text scrutiny. Out of the 35 articles, only 27 were considered eligible for inclusion. The differences in the success rate and the asymptomatic rate between the mature and immature permanent teeth with necrotic pulp were not statistically significant. However, the differences between the two groups were statistically significant in the rate of positive response to electrical pulp testing. Based on the results of this systematic review and meta-analysis, the authors concluded that REPs are an effective therapy and can achieve high success rates for both mature and immature necrotic permanent teeth. It was also concluded that the REPs were more successful in regaining vitality responses for mature compared with immature permanent teeth with necrotic pulps.


A model for single and multiple knowledge based networks.
The inherent black-box nature of neural networks is an important drawback with respect to the problem of explanation of neural network responses. Although several articles have tackled the problem of rule extraction from a single neural network, just a few papers have investigated rule extraction from several combined neural networks. In this article we describe how to translate symbolic rules into the Discretized Interpretable Multi-Layer Perceptron (DIMLP) and how to extract rules from one or several combined neural networks. Our approach consists of characterizing discriminant hyperplane frontiers. Unordered rules are extracted in polynomial time with respect to the size of the problem and the size of the network. Moreover, the degree of matching between extracted rules and neural network responses is 100% on training examples. We applied single DIMLP networks to 17 data sets related to medical diagnosis and medical prognosis problems. Results based on 10-fold cross-validation showed that the DIMLP model was on average as accurate as standard multi-layer perceptrons (MLP). Furthermore, DIMLP networks were significantly more accurate than CN2 on eight problems, whereas only on one problem CN2 was better than DIMLP. Finally, a non-Hodgkin lymphoma diagnosis problem based on classification of electrophoresis gels was defined. It turned out that ensembles of DIMLP networks were significantly more accurate than CN2 (96.1% +/- 1.4 versus 82.7% +/- 4.0). Finally, symbolic rules revealed the presence of five important spots for the discrimination of the class of Lymphocyte Leukemia/Chronic Lymphoid Leukemia (Lc/LLc), and the class of Centrocytic Lymphoma (Cc).


Analysis of DNA restriction fragments and polymerase chain reaction products by capillary electrophoresis.
Capillary electrophoresis (CE) is a new, high-resolution tool for the analysis of DNA restriction fragments and DNA amplified by the polymerase chain reaction (PCR). By combining many of the principles of traditional slab gel methods in a capillary format, it is possible to perform molecular size determinations of human and plant PCR amplification products and DNA restriction fragments. DNA restriction fragments and PCR products were analyzed by dynamic sieving electrophoresis (DSE) and capillary gel electrophoresis (CGE). As part of this study, sample preparation procedures, injection modes, and the use of molecular mass markers were evaluated. Optimum separations were performed using the uPage-3 (3% T, 3% C) CGE columns with UV detection at 260 nm. Membrane dialysis and ultrafiltration/centrifugation proved to be nearly equivalent methods of sample preparation. Reproducibility studies demonstrated that blunt-ended, non-phosphorylated markers (specifically allele generated markers) provide the most accurate calibration for PCR product analysis. This study demonstrates that CE offers a high-speed, high-resolution analytical method for accurately determining molecular size and/or allelic type as compared with traditional methodologies.


Many correlates of poor quality of life among substance users entering treatment are not addiction-specific.
Quality of life (QoL) is an important measure and outcome within chronic disease management and treatment, including substance use disorders (SUD). The aim of this paper was to investigate correlates of poorer QoL of individuals entering SUD treatment in Norway, in order to identify subgroups that may most benefit from different interventions. Twenty-one treatment facilities invited all incoming patients to participate. Five hundred forty-nine patients who enrolled between December 2012 and April 2015 are analyzed. QoL, substance use, mental and physical comorbidities, and exercise behaviors were measured. Multinomial regression analysis was used to determine variables significantly associated with poorer QoL. The majority of both genders (75 %) reported "poor" or "very poor" QoL at intake. Depression showed a strong association with poor QoL (relative risk ratio [RRR] 3.3, 95 % confidence interval [CI] 1.0-10.3) and very poor QoL (RRR 3.8, 1.2-11.8) among women. Physical inactivity among men was associated with very poor QoL (RRR 2.0, 1.1-3.7), as was reporting eating most meals alone (RRR 2.6, 1.4-4.8). Evaluating one's weight as too low was also associated with poor QoL (RRR 2.0, 1.0-3.9) and very poor QoL (RRR 2.0, 1.1-3.7) among men. Consuming methadone/buprenorphine was a protective factor for men reporting poor QoL (RRR 0.5, 0.3-0.9) and very poor QoL (RRR 0.4, 0.2-0.9), as well as for women reporting very poor QoL (RRR 0.2, 0.0-0.6). Factors associated with poorer QoL among other healthy and clinical populations, such as impaired social and physical well-being and psychological distress, were also seen associated in this sample. Treatment should be targeted towards patients with these particular vulnerabilities in addition to focusing on substance-related factors, and interventions proven to improve the QoL of other populations with these vulnerabilities should be explored in a SUD context.


Differences in carotid artery atherosclerosis between men and women in the early phase after ischemic event.
There is little data about sex differences in carotid atherosclerosis in the early phase after an ischemic event. The aim of this study was to examine the carotid artery atherosclerosis differences between men and women in early phase after TIA or stroke. Consecutive patients with recent ischemic event, admitted during the first week after symptom onset were examined with ultrasound. Sex differences in degree of stenosis, number of plaques and plaque morphology were compared. Plaque morphology was assessed by gray-scale median (GSM), according to which lower values were associated with hemorrhagic/necrotic core indicating plaque instability. Of the 316 patients with ischemic events, 196 (50.5% male) entered the study. Men had more often moderate as well as severe ipsilateral carotid stenosis (12.1% vs 7.2% for moderate and 12.1% vs 2.1% for severe; p=0.024). Men had more often the largest plaque hypoechogenic contralateral (62.6% vs 37.1%, p=0.0008), but not ipsilateral. Men had 3 or more hypoechogenic plaques (24.2% vs 4.1%, p=0.0001; 17.2% vs 4.1%, p<0.0001) both ipsi and contralateral respectively. Male sex was a risk factor for having 3 or more ipsilateral hypoechogenic plaques (p=0.002, OR=20 CI 95% [5.5-75]. Men had more often carotid stenosis and higher number of hypoechogenic plaques.


Neuropsychological analysis of a case of crossed dysphasia verified at postmortem.
A case is reported of crossed dysphasia in a right-handed monolingual patient, where neuropathological verification of the unilateral site of the lesion was obtained within a year of detailed neuropsychological assessment. The patient's pattern of language impairment was characterized by agrammatic speech and relatively preserved naming ability. In addition, the patient had good repetition, poor comprehension, and marked impairment on visuospatial tasks. Neuropathological investigations showed a large area of infarction affecting cortex, white matter, and subcortical structures in the right hemisphere. The possibility is discussed of a distinction between two types of crossed dysphasia with either dissociated or simultaneous language and visuospatial deficits due to reversed representation of hemispheric specific functions or transfer of most cognitive functions to the right hemisphere.


Modification of histidines in human prothrombin. Effect on the interaction of fibrinogen with thrombin from diethyl pyrocarbonate-modified prothrombin.
Diethyl pyrocarbonate (ethoxyformic anhydride) was used to modify histidyl residues in prothrombin. Diethyl pyrocarbonate inactivated the potential fibrinogen-clotting activity of prothrombin with a second-order rate constant of 70 M-1 min-1 at pH 6.0 and 25 degrees C. The difference spectrum of the modified protein had a maximum absorption at 240 nm which is characteristic of N-carbethoxyhistidine. The pH dependence for inactivation suggested the participation of a residue with a pKa of 6.2. Addition of hydroxylamine to ethoxyformylated prothrombin reversed the loss of fibrinogen-clotting activity. No structural differences were detected between the native and modified proteins using fluorescence emission and high-performance size-exclusion chromatography. The tyrosine and tryptophan content was not altered, but approximately 1-2 amino groups were modified. Statistical analysis of residual enzyme activity and extent of modification indicates that among 7 histidyl residues modified per molecule, there is 1 essential histidine (not in the active site) involved in the potential fibrinogen-clotting activity of prothrombin. To further examine its properties, the modified prothrombin was activated to thrombin using Echis carinatus venom protease. There was no difference in the catalytic activity of thrombin obtained from either native or ethoxyformylated prothrombin, as measured by H-D-Phe-pipecolyl-Arg-p-nitroanilide (D-Phe-Pip-Arg-NA) hydrolysis. However, thrombin produced from the modified protein showed a loss of fibrinogen-clotting activity but had a comparable apparent Ki value (about 20 microM) to thrombin from native prothrombin when fibrinogen was used as a competitive inhibitor during D-Phe-Pip-Arg-NA hydrolysis. The similarity in Ki values indicated that thrombin derived from diethyl pyrocarbonate-modified prothrombin does not have an altered fibrinogen-binding site. Although the histidyl residue involved during inactivation has not been identified, the results suggest that a histidyl residue in the thrombin portion of prothrombin is essential for interaction with fibrinogen.


Effects of Bacillus lincheniformis feeding frequency on the growth, digestion and immunity of Haliotis discus hannai.
To study the effects of Bacillus lincheniformis feeding frequency on the survival and growth of Haliotis discus hannai abalone, we measured the expression levels of nonspecific immune genes and monitored the anti-Vibrio parahaemolyticus immune reaction. H. discus hannai (shell length: 32.75 ± 2.63 mm, body weight: 4.91 ± 0.34 g) was selected to perform a 70 d laboratory culture experiment including a 14 d V. parahaemolyticus artificial infection experiment. The control group (C) was fed normal commercial feed every day. The M1 experimental group was given experimental feed and basal feed on alternating days until the end of the experiment. The M2 experimental group was given experimental feed for 4 d and basal feed for 3 d, and this cycle was repeated every 7 d until the end of the experiment. The M3 experimental group was given experimental feed for 2 d and basal feed for 5 d, and this cycle was repeated every 7 d until the end of the experiment. The M4 group was continuously given experimental feed for the duration of the experiment. The concentration of added B. lincheniformis in each experimental group was 105 cfu/g (according to the quantity of viable bacteria). The specific growth rate (as measured by body weight) and the feed conversion efficiency of the abalone in M1 and M2 were significantly higher than those in M4 and C (P < 0.05). The cellulose and lipase activities of abalone in M1, M2 or M4 were significantly higher than those in M3 or C (P < 0.05). The acid phosphatase, superoxide dismutase, total haemocyte counts, O2- levels generated by respiratory bursts, and the expression levels of Mn-SOD, TPx, GSTs and GSTm in abalone in the M2 group were significantly higher than those in any other feeding frequency group (P < 0.05). At the end of the V. parahaemolyticus infection, the cumulative mortality of the abalone in M2 was significantly lower than that in any other group (P < 0.05). Consequently, given the growth advantages and the enhancement of immune function, the feeding plan in which B. lincheniformis was applied for 4 d per week, and basal feed was then applied for 3 d, did not lead to a high level of immune reaction, immune fatigue or waste of resources, but increased the growth rate of individuals and their resistance to V. parahaemolyticus infection.


Synthesis and determination of the absolute configuration of cavicularin by a symmetrization/asymmetrization approach.
Taking the strain: The asymmetric total synthesis and stereochemical assignment of (-)-cavicularin, which features a highly strained polycyclophane ring system, has been achieved. The key features of this synthesis are 1) macrocyclization by an SN Ar reaction, 2) group-selective reaction to induce planar chirality in a highly stereoselective manner, and 3) radical transannulation to construct the highly strained ring system.


The incidence of bifurcation among corticocortical connections from area 17 in the developing visual cortex of the cat.
In newborn kittens, cells in the striate cortex (visual area 17) that project to area 18 (part of extrastriate cortex) are distributed with uniform density in the superficial and in the deep layers. During postnatal weeks 2-3, some of these corticocortical connections are removed to generate an adult-like projection in which association cells are clustered mainly in the superficial layers of area 17. Axonal elimination, without cell death, is the major factor sculpting patches of corticocortical cells in superficial layers. In adult cats, few cells in area 17 (approximately 5%) have axons that bifurcate to multiple extrastriate areas. We have studied the possibility that the early exuberant innervation of area 18 by neurons in area 17 is largely from the transient collaterals of axons that also project to other visual areas. Kittens aged 2-21 days were each injected with a pair of retrogradely transported tracers, either diamidino yellow and fast blue, or diamidino yellow and a carbocyanine dye, at retinotopically corresponding points in area 18 and either area 19 or the posteromedial lateral suprasylvian cortex (PMLS). As for injections in area 18, those in area 19 and PMLS in kittens aged < or = 5 days labelled cells in continuous bands in area 17; in older kittens neurons projecting from area 17 to extrastriate regions were in patches, mainly in superficial layers. In each animal, the labelling from the two injections overlapped by 51-92%.(ABSTRACT TRUNCATED AT 250 WORDS)


Thermal properties and fauna on the bark of trees in two different African ecosystems.
The thermal properties of 26 African tree species in two different ecosystems were studied using thermocouples. In a subtropical moist forest were three bark types of trees: species with thin and smooth bark types with low values of insulation across the bark; species with a more structured bark type and medium insulation values; and species with deep-fissured or scaly bark types and high insulation values. Only these latter trees are able to survive openings in the subtropical forest and stand alone on edges of forest gaps. In the savanna all tree species showed adaptations in the structure of their bark in different forms: many tree species shade their trunks. Some have low bark insulation and these are known to be sensitive to fires. Some tree species show high bark insulation and do not shade their trunks. Tree species with white bark avoid overheating of their surface by reflection of the radiation. The arthropod community living exclusively on the bark was investigated for the first time on South African trees, on ten tree species. In the two different ecosystems this habitat is occupied by different arthropod groups. In the subtropical forest Acari, Araneae, Opiliones, Isopoda, Myriopoda, Blattodea, Psocoptera, Heteroptera, Coleoptera, Formicidae, and Nematocera (Diptera) are the main arthropod groups living exclusively on the bark of trees. In the savanna Pseudoscorpiones, Araneae, Collembola, Blattodea, Psocoptera, Coleoptera, Neuroptera, Termites, Formicidae, Hymenoptera and Brachycera (Diptera) are the main arthropod groups living exclusively on the bark of trees. Within one ecosystem on one bark type the dominant species are similar; richly structured bark types have a richer fauna. In the forest, bark arthropod diversity is related to the bark structure of the constituent trees, and the arthropod communities on the bark would reflect changes in the structure of the forest. Forests comprising tree species with different bark types would have a richer total bark arthropod fauna. Specialists on richly structured bark types would die out if tree species composition were altered by man to give stands consisting only of tree species with smooth bark types. Bark arthropods in a subtropical moist forest have different proportions of herbivorous and fungivorous compared to carnivorous species than those on the bark of trees in a savanna.


HaCaT keratinocytes exhibit a cholesterol and plasma membrane viscosity gradient during directed migration.
Keratinocyte migration plays an important role in cutaneous wound healing by supporting the process of reepithelialisation. During directional migration cells develop a polarised shape with an asymmetric distribution of a variety of signalling molecules in their plasma membrane. Here, we investigated front-to-back differences of the physical properties of the plasma membrane of migrating keratinocyte-like HaCaT cells. Using FRAP and fluorescence lifetime analysis, both under TIR illumination, we demonstrate a reduced viscosity of the plasma membrane in the lamellipodia of migrating HaCaT cells compared with the cell rears. This asymmetry is most likely caused by a reduced cholesterol content of the lamellipodia as demonstrated by filipin staining. siRNA-mediated silencing of the cholesterol transporter ABCA1, which is known to redistribute cholesterol from rafts to non-raft regions, as well as pharmacological inhibition of this transporter with glibenclamide, strongly diminished the viscosity gradient of the plasma membrane. In addition, HaCaT cell migration was inhibited by glibenclamide treatment. These data suggest a preferential role of non-raft cholesterol in the establishment of the asymmetric plasma membrane viscosity.


Risk for Cardiovascular Adverse Events Associated With Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: Insights From a Pooled Analysis of 15 Randomised Controlled Trials.
All agents engaging sphongosine-1-phospate receptors (S1PRs) will have some cardiovascular effect. This study aimed to elucidate the risk of cardiovascular adverse events (AEs) in patients with multiple sclerosis (MS) treated with S1PR modulators (S1PRMs). We systematically searched the PubMed, EMBASE, and Cochrane Library databases for randomised controlled trials (RCTs) published through January 5, 2021. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. Sensitivity analyses and meta-regression were performed. Seventeen RCTs (12 for fingolimod; 3 for ozanimod; 2 for siponimod) involving 13,295 patients were included. Compared with the control treatment, S1PRMs significantly increased the risk of cardiovascular AEs (RR, 2.21; 95% CI, 1.58-3.10; I2, 75.6%). Notably, the high-risk cardiovascular AEs associated with S1PRMs were primarily bradyarrhythmia (RR, 2.92; 95% CI, 1.91-4.46; I2, 30.8%) and hypertension (RR, 2.00; 95% CI, 1.49-2.67; I2, 56.5%). Subgroup analysis results were consistent with the primary outcomes except that ozanimod was associated with a higher risk of hypertension only (RR, 1.76; 95% CI, 1.10-2.82; I2, 0.0%), while siponimod was associated with a higher risk of bradyarrhythmia only (RR, 2.75; 95% CI, 1.75-4.31; I2, 0.0%). No significant inter-subgroup differences were observed (Pinteraction > 0.05). S1PRM use increased the risk of cardiovascular AEs by 1.21 times in patients with MS, and increased risks for bradyarrhythmia and hypertension were at 2.92- and 2.00-fold, respectively. These findings can help clinicians assess the risk of cardiovascular AEs in patients treated with S1PRMs. The PROSPERO ID is CRD42020183215.


Purification and characterization of nitrile hydratase of mutant 4D of Rhodococcus rhodochrous PA-34.
Nitrile hydratase (NHase; E.C. 184.108.40.206) has been purified and characterized using ammonium sulfate precipitation, ion exchange chromatography and gel filtration chromatography from the mutant 4D of Rhodococcus rhodochrous PA-34. The SDS-PAGE and MALDI-TOF analysis of the purified enzyme revealed that it is dimmer consisting of α- and β-subunits with a molecular mass of 25 and 30 kDa, respectively. The Km and Vmax values were 102 mM and 350.8 μmol/min/mg using 3-cyanopyridine as substrate. The purified NHase was stable in higher concentration of potassium ions and in acidic pH 5.5 as compared to NHase of the wild R. rhodochrous PA-34. The analysis of the N-terminal amino acid sequence of this enzyme revealed that this enzyme has 90 % homology with the high molecular weight nitrile hydratase of R. rhodochrous J1.


Wall teichoic acid structure governs horizontal gene transfer between major bacterial pathogens.
Mobile genetic elements (MGEs) encoding virulence and resistance genes are widespread in bacterial pathogens, but it has remained unclear how they occasionally jump to new host species. Staphylococcus aureus clones exchange MGEs such as S. aureus pathogenicity islands (SaPIs) with high frequency via helper phages. Here we report that the S. aureus ST395 lineage is refractory to horizontal gene transfer (HGT) with typical S. aureus but exchanges SaPIs with other species and genera including Staphylococcus epidermidis and Listeria monocytogenes. ST395 produces an unusual wall teichoic acid (WTA) resembling that of its HGT partner species. Notably, distantly related bacterial species and genera undergo efficient HGT with typical S. aureus upon ectopic expression of S. aureus WTA. Combined with genomic analyses, these results indicate that a 'glycocode' of WTA structures and WTA-binding helper phages permits HGT even across long phylogenetic distances thereby shaping the evolution of Gram-positive pathogens.


Improving Postoperative Conversations With Families: What We Can Learn From Experience.
Postoperative conversations with families are an integral part of the patient-physician relationship. Faculty and resident surgeons alike agree on their importance; however, there is little exposure and formal training during residency training. This study explored faculty surgeons' perspectives on common themes, impressions, and potential teaching points that could provide a basis for developing a comprehensive formal curriculum on postoperative conversations. Interviews were conducted at a single teaching hospital with faculty surgeons with over 5 y of practice regarding important aspects and teaching points of postoperative conversations with families. Qualitative review was performed using thematic analysis to determine common themes regarding postoperative conversations with families. Based on interviews with 15 faculty surgeons, components of postoperative conversation with families were grouped into "what" (sharing data with the patient), "how" (creating an atmosphere, i.e., private, honest, with attention to empathy and reassurance), and "verify" (ensuring clear communication and comprehension). Faculty surgeons stated that challenges in postoperative conversations included discussing poor outcomes, reporting unexpected findings, and ensuring clear communication with families. When teaching residents, developing the appropriate atmosphere and rapport was most emphasized as well as need for additional practice. Yet, faculty frequently noted minimal exposure to these conversations during their residency and stated some logistical and trust barriers from preventing them as faculty to allow surgical trainees to participate in these postoperative conversations. This study identified the themes to guide and challenges involved in postoperative conversations with families. Using this data, a complete curriculum could be developed to teach trainees the essential portions of this critical portion of patient care.


A retrospective and consecutive analysis of the epidemiology and management of spinal cavernomas over the last 20 years in a single center.
Spinal cavernous malformations (SCM) are rare lesions often presenting with acute onset of symptoms and progressive neurological deterioration due to hemorrhage into the spinal cord. With the aid of modern techniques, their surgical removal became much safer. The present study was undertaken to analyze the outcome of our series of surgically and conservatively treated patients with SCM. Over a period of 20 years, 20 surgically treated and 5 conservatively managed patients with spinal cavernous malformations were identified and enrolled into this analysis. Demographic data, clinical symptoms, localization and extension of the cavernoma, as well as pre- and postoperative neurological status were obtained. The clinical status was assessed using the Frankel score. Patients were followed up clinically and by MRI. Before surgery, 90% (18/20) of our surgical patients were classified as Frankel D (93.8%), whereas two patients (10%) were graded C. None of the patients had a worse Frankel score at the time of discharge. Eighty percent of them (16 cases) remained unchanged, and 20% (4 patients) improved during the first follow-up (mean 6.3 months, range 2-17 months). All improved patients had a superficially located SCM and were operated early (≤3 months). No worsening was observed during extended follow-up (range 9-134 months, mean 44.7 months). Five nonsurgically treated patients showed no significant clinical deterioration over a period of 6.7 years (mean, range 2.9-8 years). SCM localization and number of involved segments had no influence on outcome. Our data show that SCM can be resected with favorable neurological outcome by using intraoperative neuromonitoring. Within the follow-up period, patients treated conservatively remained in a stable neurological condition.


Mitigation of microfibers release from disposable masks - An analysis of structural properties.
The use of disposable face masks increased rapidly among the general public to control the COVID-19 spread. Eventually, it increased the disposal of masks and their associated impacts on environmental pollution. Hence, this study aims to analyze the impact of nonwoven fabric structural parameters and weathering on the microfiber release characteristics. Spunbond polypropylene nonwoven with four different weights and meltblown nonwoven with two different weights were used in this study to analyze microfiber release at dry, and wet conditions to simulate improper disposal in the environment. Exposure to sunlight significantly increases the microfiber release from 35 to 50% for spunbond fabric and 56-89% for meltblown fabric. Weathering in sunlight structurally affected the tensile properties of the polypropylene fibers due to photodegradation. The study showed that each mask can produce 1.5 × 102 and 3.45 × 101 mg of microfiber/mask respectively in dry and wet states. In the case of structural parameters, a higher GSM (grams per square meter), abrasion resistance, bursting strength, and thickness showed a positive correlation with microfiber release in both fabrics. Significantly a higher microfiber release was reported with meltblown fabric than the spunbond for a given GSM. The presence of finer fibers and more fibers per unit area in meltblown fabric was noted as the main cause. Nonwoven fabric GSM and the number of fibers in a specific area showed a higher influence on microfiber release. Based on the mask consumption reported in the literature, India alone can produce around 4.27 × 102 tons of microfibers/week as an average of dry and wet conditions. The study suggests that the proper selection of physical parameters can significantly reduce the microfiber fiber release at all stages.


Globally Optimal Distributed Kalman Filtering for Multisensor Systems with Unknown Inputs.
In this paper, the state estimation for dynamic system with unknown inputs modeled as an autoregressive AR (1) process is considered. We propose an optimal algorithm in mean square error sense by using difference method to eliminate the unknown inputs. Moreover, we consider the state estimation for multisensor dynamic systems with unknown inputs. It is proved that the distributed fused state estimate is equivalent to the centralized Kalman filtering using all sensor measurement; therefore, it achieves the best performance. The computation complexity of the traditional augmented state algorithm increases with the augmented state dimension. While, the new algorithm shows good performance with much less computations compared to that of the traditional augmented state algorithms. Moreover, numerical examples show that the performances of the traditional algorithms greatly depend on the initial value of the unknown inputs, if the estimation of initial value of the unknown input is largely biased, the performances of the traditional algorithms become quite worse. However, the new algorithm still works well because it is independent of the initial value of the unknown input.


Between Heaven and Hell: Experiences of Preoperative Pain and Pain Management among Older Patients with Hip Fracture.
Among older adults, hip fracture is a common and serious consequence of a fall. Preoperative pain is common and often severe among patients with hip fracture. Opioids are usually used but have many side effects. One alternative is a femoral nerve block, which has been shown to reduce pain and lower the need for opioids. However, to our knowledge no study has explored qualitatively how patients with hip fracture experience treatment with femoral nerve block. The aim of this study was to explore experiences of preoperative pain and pain management among older patients with hip fracture who had received a femoral nerve block. A qualitative design with semi-structured interviews (n = 23) conducted 2-6 days after surgery. Inclusion criteria were Swedish-speaking patients aged 70 years or older with hip fracture admitted to the orthopedic ward, treated with femoral nerve block before nursing actions. Data were analyzed with qualitative content analysis. Our result revealed one theme, hovering between heaven and hell, with five subthemes: how the pain was described - no pain, to worst pain and everything in between; they were dealing with pain in their own way; felt dependent on staff´s willingness to relieve pain; pain management could be lifesaving and a near-death experience; and how they experienced memory loss with respect to the pain and pain management. The experience of pain and pain management was described as hovering between heaven and hell. We conclude that independent of which pain management given, staff should have an individualized pain mangement approach towards the patient in order to achieve well managed pain.


High-dose stereotactic radiotherapy boost in the treatment of squamous cell carcinoma of the head and neck region.
Surgical resection with adjuvant concurrent radiochemotherapy is the standard of care for stage III-IV oral cavity cancer. In some cases, the dynamic course of the disease is out of the prepared schedule of treatment. In that event, a stereotactic radiosurgery boost might be the only chance for disease control. Here, we present a case study of a patient with oral cancer who underwent surgery. During adjuvant radiotherapy, a metastatic cervical lymph node was diagnosed based on fine-needle aspiration biopsy. To increase the total dose to the metastatic tumor, a stereotactic radiosurgery boost of 1 × 18 Gy was performed two days after the last fraction of conventional radiotherapy. The early and late tolerance of this treatment were positive. During the 18-month follow-up, locoregional recurrence was not detected. The patient died due to secondary malignancy. This paper shows that a stereotactic radiosurgery boost added to adjuvant conventional radiotherapy is an effective approach permitting the maintenance of good local control in well-selected patients.


Genetic characterization of measles viruses isolated in Turkey during 2000 and 2001.
Molecular epidemiologic studies have made significant contributions to measles surveillance activities by helping to identify source and transmission pathways of the virus. This report describes the genetic characterization of wild-type measles viruses isolated in Turkey in 2000 and 2001. Wild-type measles viruses were isolated from 24 cases from five provinces in Turkey during 2001. The viruses were analyzed using the standard genotyping protocols. All isolates were classified as genotype D6, the same genotype that was identified in Turkey in previous outbreaks during 1998. Turkey has begun implementation of a national program to eliminate measles by 2010. Therefore, this baseline genotype data will provide a means to monitor the success of the elimination program.


Ultrastructure of Brugia malayi egg shell and its comparison with microfilarial sheath.
Ultrastructure of Brugia malayi egg shell and microfilarial sheath have been compared. They are identical in appearance, thus confirming that the microfilarial sheath is derived from the egg shell. The surface of the egg shell and the microfilarial sheath have distinct electron-dense projections which may have a protective role for the parasite.


3-(Adamantan-1-yl)-4-[(E)-(2,6-di-fluoro-benzyl-idene)amino]-1-[(4-ethyl-piperazin-1-yl)meth-yl]-4,5-di-hydro-1H-1,2,4-triazole-5-thione.
In the title compound, C26H34F2N6S, the triazole ring is linked to a benzene ring via an imine bond [N=C = 1.255 (2) Å; conformation: E], with a dihedral angle of 25.21 (11)° between the rings. The 4-ethyl-piperazinyl residue is folded away from the thione-S atom. In the crystal, helical supra-molecular chains propagating along [010] and sustained by weak C-S⋯π(triazole) inter-actions occur [S⋯centroid distance = 3.2872 (10) Å]. Links between these chains are of the type benzene-C-H⋯N(imine) and π-π [between centrosymmetrically related benzene rings with an inter-centroid distance of 3.9241 (15) Å] and result in a three-dimensional architecture.


Region of slow conduction in sustained ventricular tachycardia: direct endocardial recordings and functional characterization in humans.
Direct endocardial recording from a discrete region of slow conduction in the left ventricle was performed in a patient during sustained ventricular tachycardia. The tachycardia had a right bundle branch block and superior axis configuration with the earliest site of endocardial activation in the posterolateral left ventricle. At this site, the left ventricular electrogram during the tachycardia displayed two deflections with distinctly different responses to rapid pacing. During rapid pacing from the right ventricular apex, one deflection was transiently entrained, representing activation of the ventricle distal to a region of slow conduction in the reentrant circuit. However, the other deflection was not entrained and arose from activation proximal to this region. At a critically rapid pacing rate, interruption of the tachycardia was associated with conduction block in the region of slow conduction, as demonstrated by dissociation of the two deflections on the posterolateral left ventricular electrogram. At pacing rates that transiently entrained but did not terminate the tachycardia, decremental properties of conduction were demonstrated in the region of slow conduction, but not in the rest of the reentrant circuit. These responses of the posterolateral left ventricular electrogram to pacing during ventricular tachycardia strongly suggest that the recordings bracketed a discrete region of slow conduction in the left ventricle that was critical for the maintenance of ventricular tachycardia. Furthermore, these data demonstrate that this region of slow conduction in the left ventricle had decremental conduction properties and was the site of block during rapid pacing at rates sufficient to interrupt the tachycardia.


Protective effects of clofibrate on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats.
Male and female, arteriosclerotic and non-arteriosclerotic rats were treated with the anti-lipemic agent, clofibrate, for 8 days and then subjected to an acute myocardial infarction by injecting them with two large doses of isoproterenol spaced 24 hours apart. The animals were killed at sequential time intervals during the acute necrosis and early repair phases of myocardial infarction. Pre-treatment with clofibrate caused a definite improvement in survival, less shock and prostration, and ECG evidence of little or no ischemia. Increased SGOT levels, hepatic lipid and necrosis were indicative of advanced liver damage. Although clofibrate-treated animals showed little change in serum lipids during the acute cardiac necrosis phase, they were hyperglycemic and showed the greatest increase in BUN levels. Clofibrate-treated animals had higher serum corticosterone levels than those given isoproterenol alone. Despite superior survival rates, both the arteriosclerotic and non-arteriosclerotic, clofibrate-treated animals exhibited equally severe histopathologic evidence of myocardial damage. It is suggested that the protective effect of prophylactic treatment with clofibrate against isoproterenol-induced myocardial infarction in rats may be due to its ability to change corticosterone levels in the circulation.


Weak interactions in furan dimers.
Dimers of furan, 2,3-dihydrofuran, 2,5-dihydrofuran and tetrahydrofuran were investigated with the use of theoretical methods to determine the interactions that keep the molecules together. The QTAIM and NCI methods confirmed that for furan dimers the C-H⋯O hydrogen bond and stacking interactions can form the dimers with similar energy. For 2,3-dihydrofuran, 2,5-dihydrofuran and tetrahydrofuran, the decisive mechanism of dimer formation is the stacking interaction between the furan rings.


Endodontic Microsurgery of Posterior Teeth with the Assistance of Dynamic Navigation Technology: A Report of Three Cases.
When nonsurgical endodontic treatment fails, surgical treatment is an alternative approach for treating periapical disease. However, endodontic microsurgery (EMS), particularly in anatomically challenging areas, such as the posterior teeth, is a skill-sensitive task that can present a unique set of challenges for the surgeon. In recent years, digital guidance technology has been applied more frequently in dentistry. Dynamic navigation (DN) is a pioneering technology that uses an optical positioning device controlled by a sophisticated computerized interface and dedicated three-dimensional surgical path planning software program. This technique has also recently been introduced in the field of EMS to improve accuracy and avoid related complications. This case report presents a novel approach to DN-assisted EMS and describes its application in posterior teeth. After undergoing DN-assisted EMS, all patients were completely asymptomatic at the follow-up visit. Radiographic examinations performed immediately and 3-9 months after EMS revealed that the root resection was performed accurately without complications. The DN technique has been proven to be a feasible, predictable, and time-saving system for assisting EMS in cases requiring treatment in anatomically challenging areas, such as in the posterior teeth.


Memory-guided navigation in amyotrophic lateral sclerosis.
Previous studies have yielded inconsistent results about hippocampal involvement in non-demented patients with amyotrophic lateral sclerosis (ALS). We hypothesized that testing of memory-guided spatial navigation i.e., a highly hippocampus-dependent behaviour, might reveal behavioural correlates of hippocampal dysfunction in non-demented ALS patients. We conducted a prospective study of spatial cognition in 43 non-demented ALS outpatients (11f, 32 m, mean age 60.0 years, mean disease duration 27.0 months, mean ALSFRS-R score 40.0) and 43 healthy controls (14f, 29 m, mean age 57.0 years). Participants were tested with a virtual memory-guided navigation task derived from animal research ("starmaze") that has previously been used in studies of hippocampal function. Participants were further tested with neuropsychological tests of visuospatial memory (SPART, 10/36 Spatial Recall Test), fluency (5PT, five-point test) and orientation (PTSOT, Perspective Taking/Spatial Orientation Test). Patients successfully learned and navigated the starmaze from memory, both in conditions that forced memory of landmarks (success: patients 50.7%, controls 47.7%, p = 0.786) and memory of path sequences (success: patients 96.5%, controls 94.0%, p = 0.937). Measures of navigational efficacy (latency, path error and navigational uncertainty) did not differ between groups (p ≥ 0.546). Likewise, SPART, 5PT and PTSOT scores did not differ between groups (p ≥ 0.238). This study found no behavioural correlate for hippocampal dysfunction in non-demented ALS patients. These findings support the view that the individual cognitive phenotype of ALS may relate to distinct disease subtypes rather than being a variable expression of the same underlying condition.


An endogenous ligand for the kainate-type binding sites from rat brain.
Extracts from the rat brain were screened to identify a putative endogenous ligand for the binding sites of the neuroexcitant kainic acid (KA). The extracted substances were separated by chromatographic techniques and tested for their ability to inhibit KA binding to fish synaptosomes and to membranes from rat brain. A substance isolated in this way (rat kainate-binding inhibitor, RKBI) display a competitive interaction with KA for the low-affinity binding sites in rat brain membranes. According to the separation behavior in the purification step, RKBI is distinct from an inhibitor formerly isolated from fish nervous tissue (KBI). The substance exhibits positive co-operativity with KA for a very-low-affinity site population, particularly concentrated in the cerebellum, and could play a physiological role in this area.


Intraperitoneal cancer dissemination: mechanisms of the patterns of spread.
Well known patterns govern the distribution of hematogenous and lymphatic metastasis of cancer. In the past the distribution of cancer cells free within abdominal cavity received little attention and was thought to be a random event. However, surgical observation led the authors to generate and test hypotheses regarding patterns of spread that vary with tumor type, with the intraperitoneal environment, and with the physiology of the peritoneal surface tissues. The distribution and volume of peritoneal surface malignancy was prospectively recorded in 129 patients with 5 different types of tumors at the time of cytoreductive surgery. The malignancies studied included pseudomyxoma peritonei (PMP) of appendiceal origin, colonic mucinous adenocarcinoma (MA), nonmucinous colonic adenocarcinoma (NMA), ovarian carcinoma (OV) and sarcoma (SA). The abdominal and pelvic cavity was divided into 3 horizontal sectors, 9 regions and 25 sites. The incidences of tumor implants in these designated areas were statistically analyzed for each tumor type and comparisons between tumor types studied. The magnitude of intraperitoneal cancer dissemination was similar for mucinous tumors, including PMP and MA and significantly higher than for non-mucinous tumors. Also the mucinous cancers were more likely to be present in the upper horizontal sector than were non-mucinous. When NMA was compared to PMP and MA the epigastric region was significantly less likely to contain tumor. For all cancer diagnoses the colon, greater omentum and cul-de-sac of Douglas were most often affected. The ileocecal valve region was more likely to have large tumor masses on its surface than small bowel surface or small bowel mesentery. Peritoneal carcinomatosis had a wider distribution when mucinous fluid was present; this cancer distribution by intraperitoneal fluid hydrodynamics occurred regardless of histologic aggressiveness. The organs that have peritoneal fluid resorption (omentum and omental appendages) have a high incidence of implants. Small bowel and its mesentery free to move by peristalsis had a reduced incidence of implants as compared to the ileocecal area, which is fixed to the retroperitoneum. These observations may facilitate efforts to treat peritoneal surface malignancy.


The place of lung 99mTc DTPA aerosol transfer in the investigation of lung infections in HIV positive patients.
Pneumocystis carinii pneumonia (PCP) is the most common cause of pneumonia in HIV antibody positive patients, but other pneumonias remain important, i.e. streptococcal and mycobacterial infections. A definitive diagnosis relies on obtaining samples from the lung either noninvasively (induced sputum), or invasively (bronchoalveolar lavage, transbronchial or open lung biopsy). We have used the noninvasive technique of nebulized 99mTc DTPA transfer, to assess patients with PCP (n = 30) and other lung infections (n = 20) to see whether this test will distinguish between the various infections. The presence of a biphasic, rapid transfer curve indicates severe extensive alveolar damage and is seen in PCP or legionella pneumonia. The mean transfer time (T50 +/- SEM) for patients with PCP (whether smokers or nonsmokers) was 2.1 +/- 0.2 min, and for two of the patients with legionella 3.2 min. In PCP effective treatment causes the transfer to slow (mean T50 22.7 +/- 3.3 min, n = 24) and become monoexponential. Other causes of these changes in transfer are discussed. The other pneumonias (streptococcal, mycobacterial, and staphylococcal) did not result in biphasic curves or very rapid times, their T50 values are indistinguishable from cigarette smokers. In this patient group the DTPA transfer is a useful noninvasive investigation with a very rapid, biphasic curve indicating a high probability of PCP.


Castration and reproductive behavior in the paradise fish, Macropodus opercularis (L.) (Osteichthyes: Belontiidae).
The effects of castration on male spawning behavior, nestbuilding and fertility were measured in a five day spawning trial with an intact female. Spawning and fertility decreased one week following castration while nestbuilding was unaffected. Sham operated males showed normal spawning and fertility. Two weeks postoperatively, fertility and spawning were increased paralleling partial regeneration of the testes. The antigonadotropin methallibure blocked testes regeneration and recovery of spawning in castrated males but it had no effect on reproductive functions of intact males. Spawning did not decrease in one-week castrated males which were administered testosterone enathanate. The results suggest that gonadal androgen facilitates sexual behavior in Macropodus.


Differential effects of short-term prednisolone treatment on peripheral and abdominal subcutaneous thickness in children assessed by ultrasound.
Long-term glucocorticoid excess decreases peripheral and increases abdominal subcutaneous thickness. Short-term prednisolone treatment is used in the treatment of many acute and chronic conditions in children. The aim of the present study was to elucidate if changes in thickness of cutis, subcutis, or dermal water content may be induced by short-term prednisolone treatment in children. Twenty children with asthma aged 7.7-13.8 years were included in a double-blind, randomized, placebo-controlled crossover trial. Active treatment was 5mg prednisolone daily. Treatment, run-in, and wash-out periods were 1 week. On days 1 and 7 of each treatment period, 20 MHz ultrasound scanning of the skin was performed on the thigh, forearm, and abdomen. Prednisolone treatment was associated with decreases in the total thickness of the cutis and subcutis in the thigh (0.28 mm) and forearm (0.15 mm), and an increase in the abdomen (0.23 mm). During placebo treatment the thickness was increased in the thigh (0.07 mm) and abdomen (0.05 mm), and reduced in the forearm (0.03 mm). The differences between prednisolone and placebo treatment were statistically significant in the thigh (P=0.04). The increase in thickness in the abdomen during prednisolone treatment was statistically significantly different from the reductions in the thigh (P=0.03) and forearm (P=0.05). There were no statistically significant differences in the dermal thickness or water content during prednisolone treatment compared to placebo.Short-term treatment with 5mg prednisolone daily may cause differential effects in peripheral and abdominal subcutaneous thickness in children.


Immunocytochemical evidence that vigabatrin in rats causes GABA accumulation in glial cells of the retina.
Vigabatrin (gamma-vinyl-GABA, GVG) is an irreversible inhibitor of GABA-aminotransferase (GABA-T) that is under clinical trial as an antiepileptic drug. Rats were injected (i.p.) with GVG and killed 18 h later. GVG administration reduced retinal GABA-T activity to undetectable levels and increased the GABA content 5-fold. Immunocytochemistry using a GABA antiserum clearly revealed the presence of GABA-IR in the glial Muller cells of retinas from GVG-treated rats but not from controls. This experiment indicates that the administration of drugs which inhibit GABA-T may cause the accumulation of GABA in retinal cells that do not normally possess enough endogenous GABA to be detected by immunocytochemistry.


Stereotactic linear accelerator radiotherapy for pituitary tumors.
Last decade has seen important advances in radiotherapy technology which combine precise tumor localization with accurate targeted delivery of radiation. This technique of high precision conformal radiotherapy, described as stereotactic radiotherapy or radiosurgery, uses modern linear accelerators available in most radiation oncology departments. The article describes the new technique as applied to the treatment of pituitary adenoma and reviews published clinical results.


[Higher prevalence of familial hypercholesterolemia than expected in adult patients of four family practices in Netherlands].
To determine the prevalence of familial hypercholesterolaemia (FH). Patient record screening, questionnaire and if necessary, case finding. Over the period mid-1990-mid-1992 (approximately 2.5 years) 8,800 adult individuals (age 18 years and over) in 4 general practices in Hoofddorp, the Netherlands, were screened for risk factors for coronary artery disease and invited for further analysis. Of the 3,289 selected and invited individuals 2,719 (83%) were investigated. Total cholesterol concentrations were investigated 3 times and if the mean value was above 8.0 mmol/l patients were referred to a lipid clinic to investigate the possible existence of FH. 114 patients were eligible for referral to a lipid clinic of whom 92 (81%) were indeed referred. Of these, 38 patients were diagnosed with FH: 23 men and 15 women, with a mean age of 47.7 years (range: 21-74). The prevalence of FH in this investigated population was at least 1:232. This is more than 1:500, the estimated number of FH patients in the Dutch population.


Fading and feedback in the modification of visual acuity.
Two experiments assessing the modification of visual acuity by fading plus feedback procedures are presented. The training procedure involved a gradual increase of the distance myopic subjects could accurately discriminate letters requiring a minimum of 20/20 vision at approximately 23 feet. In Experiment I experimental and matched control groups of mildly to moderately myopic subjects were compared on repeated Ortho-rater examinations of visual acuity. The experimental group showed a significant improvement relative to the control group who received no training. Multiple-baseline across-stimuli designs were used in Experiment II to evaluate training effects for another group of subjects with moderate to severe myopia. Two measures of acuity were obtained. Accuracy of discrimination of letters at various preselected distances was determined each session while Ortho-rater examinations were given periodically throughout training. Changes in discrimination accuracy over sessions appeared to be related to fading for three of the four subjects, and Ortho-rater acuity changes were observed for each subject. Some short-term maintenance of improved vision was evident on both acuity measures.


HbA(1c) in adults without known diabetes from southern Europe. Impact of the new diagnostic criteria in clinical practice.
To analyse the differences in the prevalence of diabetes and dysglycaemia using fasting plasma glucose and HbA(1c) criteria. Analytical cross-sectional study undertaken in a random sample of 2144 individuals (age 18-80 years) without known diabetes from the primary care setting in Malaga (Spain). Dysglycaemia was defined as fasting plasma glucose 5.6-6.9 mmol/l or HbA(1c) 39-46 mmol/mol (5.7-6.4%) and diabetes as fasting plasma glucose ≥ 7.0 mmol/l or HbA(1c)≥ 48 mmol/mol (≥ 6.5%). The proportion of subjects who were normoglycaemic was significantly higher using fasting plasma glucose than HbA(1c) (83.5 vs. 65%) (P < 0.0001). Compared with fasting plasma glucose, HbA(1c) detects more cases of dysglycaemia (32 vs. 14.8%) (P < 0.0001) and diabetes (3 vs. 1.7%) (P < 0.0001). In our environment, using HbA(1c) for the diagnosis of pre-diabetes and diabetes could increase the target population for preventive and therapeutic measures. Further cost-effectiveness studies are needed before the widespread diagnostic use of HbA(1c) can be recommended.


Copper chaperone cycling and degradation in the regulation of the cop operon of Enterococcus hirae.
Extensive insight into copper homeostasis has recently emerged. The Gram-positive bacterium Enterococcus hirae has been a paradigm for many aspects of the process. The cop operon of E. hirae consists of four genes that encode a repressor, CopY, a copper chaperone, CopZ, and two CPx-type copper ATPases, CopA and CopB. CopA and CopB accomplish copper uptake and export, respectively, and the expression of the cop operon is regulated by copper via the CopY repressor and the CopZ chaperone. The functions of the four Cop proteins have been extensively studied in vivo as well as in vitro and a detailed understanding of the regulation of the cop operon by copper has emerged.


A qualitative study of the emotional coping and support needs of children living with a parent with a brain injury.
To examine emotional coping and support needs in children of persons with acquired brain injury, with a view to understanding what interventions would be helpful for these children. The study was qualitative, using a thematic analysis approach. Six children between 9-18 years of age, six parents (three with ABI) and three support workers were interviewed either at home or at a support centre, using a semi-structured interview guide. Children reported using a variety of adaptive and maladaptive emotional coping strategies, but were consistent in expressing a need for credible validation, i.e. sharing experiences with peers. The results are presented under four overarching themes: difficulties faced; emotions experienced; coping strategies; and reported support needs. The results reveal an interaction between the child's experiences of complex loss that is difficult to acknowledge, emotional distancing between parent and child and the children's need for credible validation. All children expressed a desire for talking to peers in a similar situation to themselves, but had not had this opportunity. Interventions should set up such peer interaction to create credible validation for the specific distress suffered by this population.


Liver parenchymal cell proliferation during secondary induction with estradiol-17 beta in Xenopus.
We have previously demonstrated that injection of adult male frogs with estradiol-17 beta causes extensive proliferation of liver parenchymal cells together with the induction of vitellogenin (R. J. Spolski, W. Schneider, and L. J. Wangh (1985) Dev. Biol. 108, 332-340). In addition, purified parenchymal cells placed in culture synthesize DNA in an estrogen-dependent manner (B. S. Aprison, L. Martin-Morris, R. J. Spolski, and L. J. Wangh (1986) In Vitro 22, 457-464). We now describe conditions under which secondary exposure to estradiol-17 beta, either in vivo or in vitro, can lead to further DNA synthesis and cell division. The extent of this proliferation depends upon both the magnitude of the primary dose and the length of time elapse before secondary stimulation. A hormone dose of 0.5 mg, which causes little cell proliferation initially, allows for maximal secondary proliferation in response to 2.0 mg, while a maximal primary dose of 2.0 mg substantially inhibits further division in response to a secondary treatment with the same hormone dose. Cell culture experiments demonstrate that the failure of liver cells, in maximally stimulated males, to synthesize DNA in response to estrogen is not irreversible. But, cell crowding in culture does restrict DNA synthesis. The restrictions seen in vivo may therefore be due to structural features of the intact tissue rather than to terminal differentiation at the genetic level. These results are discussed with regard to our understanding of hormone-dependent differentiation in the frog liver system.


Portal vein thrombosis compromises the performance of MELD and MELD-Na scores in patients with cirrhosis.
The accuracy of model for end-stage liver disease (MELD) and MELD with sodium (MELD-Na) scores in reflecting the clinical outcomes of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear. This study aimed to evaluate the performance of scores in predicting 90-day mortality in patients with cirrhosis and PVT. Post hoc analysis was performed in two prospective cohorts (NCT02457637 and NCT03641872). The correlation between the MELD/MELD-Na score and 90-day liver transplantation (LT)-free mortality was investigated in patients with cirrhosis with and without PVT. In this study, 2826 patients with cirrhosis were included, and 255 (9.02%) had PVT. The cumulative incidence of 90-day LT-free mortality did not significantly differ between patients with and without PVT (log-rank P = 0.0854). MELD [area under the receiver operating curve (AUROC), 0.649 vs. 0.842; P = 0.0036] and MELD-Na scores (AUROC, 0.691 vs. 0.851; P = 0.0108) were compared in patients with and without PVT, regarding the prediction of 90-day LT-free mortality. In MELD < 15 and MELD-Na < 20 subgroups, patients with PVT had a higher 90-day LT-free mortality than those without PVT (7.91% vs. 2.64%, log-rank P = 0.0011; 7.14% vs. 3.43%, log-rank P = 0.0223), whereas in MELD ≥ 15 and MELD-Na ≥ 20 subgroups, no significant difference was observed between patients with and without PVT. The performance of MELD and MELD-Na scores in predicting 90-day LT-free mortality of patients with cirrhosis was compromised by PVT. MELD < 15 or MELD-Na < 20 may underestimate the 90-day LT-free mortality in patients with PVT.


Cyclisation reactions of N-cinnamoyl-9-aminoanthracenes.
N-Cinnamoyl-9-aminoanthracenes cyclise with PPA or triflic acid to form novel 2-azahexacyclo[10.6.6.0(1,5).0(6,11).0(13,18).0(19,24)]tetracosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-ones. In contrast, both N-cinnamoyl-N-methyl-9-(2-aminomethyl)anthracene and N-cinnamoyl-9-(2-aminoethyl)anthracene undergo an intramolecular Diels-Alder cycloaddition.


Phenethyl isothiocyanate induces oxidative cell death in osteosarcoma cells with regulation on mitochondrial network, function and metabolism.
Phenethyl isothiocyanate (PEITC), a kind of isothiocyanate available in cruciferous vegetables, exhibits inhibitory effects on cancers. PEITC has been extensively recorded for its effect on regulation of redox status in cancer cells. Our previous studies revealed that PEITC induced ROS-dependent cell death in osteosarcoma. Mitochondria are the main sites for ROS generation and play significant role in deciding cell fate. To dissect the mechanism of PEITC's action on osteosarcoma cells, we detected the changes on mitochondrial network, function and metabolism in K7M2 and 143B cells. Here, PEITC induced cytosolic, lipid and mitochondrial ROS production in osteosarcoma cells. It changed mitochondrial morphology from elongated to punctate network and decreased mitochondrial mass. Meantime, PEITC increased mitochondrial transmembrane potential in short time, decreased it with time prolonged, and later collapsed it in K7M2 cells, and reduced it in 143B cells. PEITC inhibited proliferation potential of osteosarcoma cells with damage on mitochondrial respiratory chain complexes. Further, PEITC-treated osteosarcoma cells experienced a sudden increase in ATP level, and later its content was decreased. Moreover, PEITC downregulated the expressions of mitochondrial respiratory chain complexes including COX IV, UQCR, SDHA and NDUFA9 in 143B cells and COX IV in K7M2 cells. At last, by using ρ0 cells derived from K7M2 and 143B cells, we found that osteosarcoma cells that depleted mtDNA were less sensitive to PEITC-induced changes on cellular morphology, cytoskeleton filament, mitochondrial transmembrane potential and ROS generation. In conclusion, our study demonstrated that mitochondria may play important role in PEITC-induced oxidative cell death in osteosarcoma cells.


New primate hind limb elements from the middle Eocene of China.
The continued washing, sorting, and identification of middle Eocene ( approximately 45Mya) primates from the Shanghuang fissure-fillings (Jiangsu Province, China) have produced additional hind limb elements. All are isolated elements. The strepsirhine hind limb elements include a first metatarsal and a talus, which are appropriate in size and morphology to pertain to Adapoides troglodytes. Adapoides is interpreted as a quadrupedal-climbing (nonleaping) primate with similarities to living lorises and the fossil primate Adapis. The haplorhine hind limb elements are estimated to span a range of adult body sizes from tiny (17g) to small (200g). Included among the new sample of haplorhine hind limb specimens is the smallest primate talus reported thus far. These new postcranial specimens expand our understanding of early haplorhine hind limb anatomy and demonstrate additional similarities between Shanghuang eosimiids and other anthropoids.


The effect of omeprazole on ultrastructural changes in gastric parietal cells.
This study was designed to compare the effects of omeprazole and cimetidine on ultrastructural changes in parietal cells of guinea pigs during histamine stimulation. Both omeprazole and cimetidine remarkably inhibited acid secretion induced by histamine stimulation. Omeprazole, however, failed to prevent the morphological transition of parietal cells to an active stage during histamine stimulation, in contrast to cimetidine which inhibited the morphological transition. In addition, it was noticed that administration of omeprazole caused vacuolation in approximately 27% of all parietal cells. This phenomenon was not seen in control animals with histamine stimulation alone and only very rarely in cimetidine treated animals. Ultrastructural findings suggested that vacuoles originated in secretory canaliculi of parietal cells. These results may be the key to explain the difference of the inhibitory mechanism between omeprazole which acts on the final step of intracellular process (so-called proton pump) and cimetidine which acts on the H2-receptor site of plasma membrane.