The role of various prostaglandins on the correlation between permeability to albumin and cAMP levels in the isolated mesentery.
Prostaglandins (PG) have been shown to raise the level of cyclic AMP (cAMP) in various tissues, and to increase permeability. Whether both events are linked, is at present a matter of speculation. We have investigated the effects of PGE1, E2, A1, A2, F1alpha and F2alpha on an isolated rat mesentery placed in a diffusion cell (surface area : 2 sq.cm). The PGs (5 microgram/ml) increased the passage of (I 125) - Albumin across the mesentery. In other experiments, diks of rat mesentery (surface area : 2 sq.cm) have been incubated in assay tubes, and cAMP levels measured by a binding protein assay. We have observed an excellent correlation between increases in permeability and cAMP levels (r=0.961). In order of increasing potency on both parameters, the PGs may be classified as follows : PGF, PGA and PGE. In the rat mesentery, under the influence of prostaglandins, increases in permeability and in cAMP levels are apparently connected.


Prebiotic supplementation (beta-glucan and inulin) attenuates circadian misalignment induced by shifted light-dark cycle in mice by modulating circadian gene expression.
Circadian rhythm governs multiple behavioural and physiological processes and its disruption is closely associated with various pathological conditions. In this study, the effects of dietary intervention by prebiotics including beta-glucan and inulin on attenuating circadian desynchrony in C57BL/6J mice subjected to weekly shifted light-dark cycle under a high fat diet was investigated. Using RT-qPCR and rhythmicity analysis, our study revealed that beta-glucan (0.2 g/day) and inulin (0.2 g/day) modulated the expression and phase of circadian-clock genes, explicitly reversed the phase delay of Period 1 and Period 3 in the hypothalamus, and reversed the phase delay of Period 2 in the liver of the mice. In the shifted mouse group, inulin also exhibited its reversal effects on the phase advance of Brain and muscle-Arnt-like 1 in the hypothalamus. These findings indicated that prebiotic supplementation can be a novel dietary approach for attenuating circadian misalignment.


Delayed toxic reaction following massive bee envenomation.
Massive bee envenomation can produce both immediate and delayed toxic reaction. Signs and symptoms of immediate toxic reaction are fatigue, nausea, vomiting, hemolysis, kidney failure, and disseminated intravascular coagulation. The label "delayed toxic reaction" refers to a patient who is asymptomatic after a massive bee envenomation, with normal initial laboratory results, but later demonstrates laboratory evidence of hemolysis, coagulopathy, thrombocytopenia, rhabdomyolysis, liver dysfunction, and disseminated intravascular coagulation. The subject of this case report, a 66-year-old man, was stung more than 125 times in an attack by Africanized bees. He was initially asymptomatic, except for pain, and his laboratory findings were normal. The first signs of his fatal multi-organ-system failure were not apparent until 18 hours after envenomation. This experience has led the Good Samaritan Regional Poison Center in Phoenix, AZ, to recommend a 24-hour hospitalization for pediatric patients, older patients, and patients with underlying medical problems who are asymptomatic or who are experiencing only pain after an envenomation of 50 or more stings. Such patients have an increased risk of tissue injury, which may be delayed and which may be more effectively treated if identified early rather than on 12- to 24-hour follow-up. All other envenomated, asymptomatic patients or envenomated patients experiencing only pain who become symptomatic or who belatedly exhibit laboratory values consistent with hemolysis, thrombocytopenia, rhabdomyolysis, liver dysfunction, kidney failure, and disseminated intravascular coagulation within a 6-hour emergency department observation period should be admitted. Intravenous fluids, blood products, dialysis, and other intensive measures should be initiated if necessary.


Local impedance measurements during contact force-guided cavotricuspid isthmus ablation for predicting an effective radiofrequency ablation.
An ablation catheter capable of contact force (CF) and local impedance (LI) monitoring (IntellaNav StablePoint, Boston Scientific) has been recently launched. We evaluated the relationship between the CF and LI values during radiofrequency catheter ablation (RFCA) along the cavotricuspid isthmus (CTI). Fifty consecutive subjects who underwent a CTI-RFCA using IntellaNav StablePoint catheters were retrospectively studied. The initial CF and LI at the start of the RF applications and mean CF and minimum LI during the RF applications were measured. The absolute and percentage LI drops were calculated as the difference between the initial and minimum LIs and 100 × absolute LI drop/initial LI, respectively. We analyzed 602 first-pass RF applications. A weak correlation was observed between the initial CF and LI (r = 0.13) and between the mean CF and LI drops (r = 0.22). The initial LI and absolute and percentage LI drops were greater at effective ablation sites than ineffective ablation sites (median, 151 vs. 138 Ω, 22 vs. 14 Ω, and 14.4% vs. 9.9%; p < .001), but the initial and mean CF did not differ. At optimal cutoffs of 21 Ω and 10.8% for the absolute and percentage LI drops according to the receiver-operating characteristic analysis, the sensitivity, and specificity for predicting an effective ablation were 57.4% and 88.9% and 80.0%, and 61.1%, respectively. The effective sites during the CF-guided CTI-RFCA had greater initial LI and LI drops than the ineffective sites. Absolute and percentage LI drops of 21 Ω and 10.8% may be appropriate targets for an effective ablation.


Incorporation of small unilamellar liposomes loaded with horseradish peroxidase into isolated nerve endings from electric organ of Torpedo marmorata.
A population of small unilamellar liposomes loaded with horseradish peroxidase, an electron dense marker, was prepared by passing the lipid-protein-detergent micelles through Sephadex G-50. By electron microscopy it was shown that these artificial lipid vesicles were incorporated into the cytoplasm of isolated pure cholinergic nerve endings from the electric organ of Torpedo marmorata. This liposome carrier system may be useful in manipulating the internal parameters involved in presynaptic processes in the electric organ.


An assessment of pH-dependent release and mobility of heavy metals from metallurgical slag.
The paper presents the results obtained in pHstat leaching test and assesses the influence of pH changes and occurring processes on the release of heavy metals (Cd, Ni, Crtotal, Pb, Cu and Zn) from metallurgical slag in a zinc smelter. Additionally, the analysis of the potential maximum amount of element available for leaching and releasing in the batch leaching test was carried out. All the results of the leaching tests were compared with the total content of heavy metals in the material. In order to evaluate the chemical forms of elements, a sequential extraction study was also carried out. On the basis of test results obtained in pHstat test, a strong dependence of heavy metals leaching on the pH was found. The highest concentrations of the analysed elements were observed in acidic environment. For most metals, except for lead, an increase in the pH of the solution caused a decrease in their concentration. Lead showed an upward trend of release under alkaline conditions. A sharp increase of copper leaching at pH 10.5 was also observed. Based on the results of the study, cadmium can be considered the most mobile element from metallurgical slag. Chromium indicated the lowest degree of release.


Pharmacokinetic properties of sustained-release theophylline (Theolair-SR) in relation to timing of doses after low-fat meals.
Pharmacodynamic and pharmacokinetic properties of sustained-release anyhdrous theophylline (Theolair-SR) were similar when doses were given either immediately after or two hours after low-fat meals in children with moderate asthma requiring daily theophylline maintenance. Asthma and pulmonary function values were maintained and approached values for healthy subjects during both treatment regimens.


Soil presence reduces the control effectiveness of a slow-release formulation of pyriproxyfen on Aedes aegypti (Diptera: Culicidae) larvae.
To assess the influence of soil on the effectiveness of two new slow-release formulations (floating and non-floating) of pyriproxyfen coextruded with low-density polyethylene. Two slow-release devices were developed using low-density polyethylene, pyriproxyfen as larvicide and calcium carbonate as filler. A factorial design was used to evaluate the effect of soil presence on the performance of each device. Weekly bioassays were performed. Soil presence affected treatment effectiveness, but this effect was associated with device type. The tablets were effective for nearly 3 months. Treatment effectiveness could be reduced because of the loss of pyriproxyfen by several physico-chemical processes such as adsorption into the soil.


γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes.
γ-Aminobutyric acid (GABA) is a signalling molecule in the interstitial space in pancreatic islets. We examined the expression and function of the GABA signalling system components in human pancreatic islets from normoglycaemic and type 2 diabetic individuals. Expression of GABA signalling system components was studied by microarray, quantitative PCR analysis, immunohistochemistry and patch-clamp experiments on cells in intact islets. Hormone release was measured from intact islets. The GABA signalling system was compromised in islets from type 2 diabetic individuals, where the expression of the genes encoding the α1, α2, β2 and β3 GABA(A) channel subunits was downregulated. GABA originating within the islets evoked tonic currents in the cells. The currents were enhanced by pentobarbital and inhibited by the GABA(A) receptor antagonist, SR95531. The effects of SR95531 on hormone release revealed that activation of GABA(A) channels (GABA(A) receptors) decreased both insulin and glucagon secretion. The GABA(B) receptor antagonist, CPG55845, increased insulin release in islets (16.7 mmol/l glucose) from normoglycaemic and type 2 diabetic individuals. Interstitial GABA activates GABA(A) channels and GABA(B) receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals.


Interactions between seed source, planting arrangement, and soil treatment in determining plant size and root allocation in Phlox drummondii.
Two varieties of the annual plant Phlox drummondii were grown in pots in the greenhouse. Pots differed in the mixture of varieties, total number of plants, spatial clustering of plants, and soil treatment.The shoot biomass of centrally located target plants was significantly influenced by the varietal composition within a pot, and the pattern of this genetic effect varied with both plant density and soil treatment. Density and soil treatment interacted strongly, with the negative effect of neighbors on shoot growth being significantly greater when soil nutrient concentrations were lower.The varieties differed significantly in their relative allocation of biomass to roots. Relative root allocation was increased in response to both the presence of neighbors and a decrease in soil nutrient availability. These factors did not interact significantly in their effects.Although both plant size and relative allocation to roots were influenced by varietal composition, these genetic effects were small relative to the effects of density and soil treatment.The strong interactions between plant location, plant identity, and soil treatment suggest that relations between neighbors will be very complex in natural populations occupying microgeographically heterogeneous habitats. A more complete understanding of these interactions will be required before realistic dynamic models of natural populations can be constructed.


Can dead bacterial cells be defined and are genes expressed after cell death?
There is a paucity of knowledge on gene expression in dead bacterial cells. Why would this knowledge be useful? The cells are dead. However, the time duration of gene expression following cell death is often unknown, and possibly in the order of minutes. In addition, it is a challenge to determine if bacterial cells are dead, or viable but non-culturable (VBNC), and what is an agreed upon correct definition of dead bacteria. Cells in the bacterial population or community may die at different rates or times and this complicates both the viability and gene expression analysis. In this article, the definition of dead bacterial cells is discussed and its significance in continued gene expression in cells following death. The definition of living and dead has implications for possible, completely, synthetic bacterial cells that may be capable of growth and division.


Joining telehealth in rheumatology: a survey on the role played by personalized experience from patients' perspective.
The beginning of the Covid-19 pandemic has forced many hospital departments worldwide to implement telehealth strategies for the first time. Telehealth represents the opportunity to increase value for all stakeholders, including patients and healthcare staff, but its success constitutes a challenge for all of them and particularly patients play a crucial role for their needed adherence. This study focuses on the experience of the Rheumatology Unit of Niguarda Hospital in Milan (Italy), where telehealth projects have been implemented for more than a decade with structured design and organized processes. The case study is paradigmatic because patients have experimented personalized mixes of telehealth channels, including e-mails and phone calls, Patient Reported Outcomes questionnaires, and home delivery of drugs. Given all these peculiarities, we decided to deepen patients' perspective through three main aspects related to the adoption of telehealth: (i) the benefits perceived, (ii) the willingness to enrol in future projects, (iii) the preference on the service-mix between remote contacts and in-person visits. Most importantly, we investigated differences in the three areas among all patients based on the mix of telehealth channels experienced. We conducted a survey from November 2021 to January 2022, enrolling consecutively patients attending the Rheumatology Unit of Niguarda Hospital in Milan (Italy). Our survey comprised an introductory set of questions related to personal, social, clinical and ICT skills information, followed by the central part on telehealth. All the answers were analysed with descriptive statistics and regression models. A complete response was given by 400 patients: 283 (71%) were female, 237 (59%) were 40-64 years old, 213 (53%) of them declared to work, and the disease most represented was Rheumatoid Arthritis (144 patients, 36%). Descriptive statistics and regression results revealed that (i) non-users imagined wide-ranging benefits compared to users; (ii) other things being equal, having had a more intense experience of telehealth increased the odds of accepting to participate to future projects by 3.1 times (95% C.I. 1.04-9.25), compared to non-users; (iii) the more telehealth was experienced, the higher the willingness to substitute in-person with online contacts. Our study contributes to enlighten the crucial role played by the telehealth experience in determining patients' preferences.


Accuracy in radiation field alignment in head and neck cancer: a prospective study.
A prospective study has been performed to determine the accuracy of radiation field alignment for a group of 22 patients with tumors in the head and neck. The accuracy was assessed by an analysis of 138 megavolt portal films in comparison to 55 simulation films. The distance (at the patient midplane) between corresponding points at the field edges on verification film and simulation film appeared to be 5 mm on the average and the standard deviation 5 mm. The analysis was extended by translational and rotational matching of the fields in order to separate each error in a translation error of the field with respect to the patient and an error in field size or shape. Translation errors appear to be somewhat larger than field size or shape errors. From an analysis of a series of megavolt films taken every third radiotherapy session, it was concluded that treatment-to-treatment variations are as large as the errors due to the transition from simulation to treatment situation. Further analysis showed that variation of the patient's position within the cast is clearly one of the error sources.


Extensor tendon rupture over the metacarpal heads.
Rupture of the extensor tendons is common in longstanding rheumatoid arthritis of the hand. The tendons commonly involved are those of the ring and little fingers and the common site of rupture is over the dorsal ulna and distal edge of the extensor retinaculum. We are reporting two cases of extensor tendon rupture over the metacarpal head of the middle finger due to prominent osteophytes.


Acceleration of burn wound healing by micronized amniotic membrane seeded with umbilical cord-derived mesenchymal stem cells.
Umbilical cord-derived mesenchymal stem cells (UC-MSC) are promising candidates for wound healing. However, the low amplification efficiency of MSC in vitro and their low survival rates after transplantation have limited their medical application. In this study, we fabricated a micronized amniotic membrane (mAM) as a microcarrier to amplify MSC in vitro and used mAM and MSC (mAM-MSC) complexes to repair burn wounds. Results showed that MSC could live and proliferate on mAM in a 3D culture system, exhibiting higher cell activity than in 2D culture. Transcriptome sequencing of MSC showed that the expression of growth factor-related, angiogenesis-related, and wound healing-related genes was significantly upregulated in mAM-MSC compared to traditional 2D-cultured MSC, which was verified via RT-qPCR. Gene ontology (GO) analysis of differentially expressed genes (DEGs) showed significant enrichment of terms related to cell proliferation, angiogenesis, cytokine activity, and wound healing in mAM-MSC. In a burn wound model of C57BL/6J mice, topical application of mAM-MSC significantly accelerated wound healing compared to MSC injection alone and was accompanied by longer survival of MSC and greater neovascularization in the wound.


Stereoselective synthesis of glycosides using (salen)Co catalysts as promoters.
The use of (salen)Co catalysts as a new class of bench-stable stereoselective glycosylation promoters of trichloroacetimidate glycosyl donors at room temperature is described. The conditions are practical and do not require the use of molecular sieves with products being isolated in good to high yields.


Synthesis, structural characterization and in vitro cytotoxicity of organotin(IV) derivatives of heterocyclic thioamides, 2-mercaptobenzothiazole, 5-chloro-2-mercaptobenzothiazole, 3-methyl-2-mercaptobenzothiazole and 2-mercaptonicotinic acid.
Five new organotin(IV) molecules with the heterocyclic thioamides; 2-mercaptobenzothiazole (Hmbzt), 5-chloro-2-mercaptobenzothiazole (Hcmbzt), 3-methyl-2-mercaptobenzothiazole (mmbzt) and 2-mercaptonicotinic acid (H(2)mna) of formulae [(n-C(4)H(9))(2)Sn(mbzt)(2)] (1), [(C(6)H(5))(2)Sn(mbzt)(2)] (2), [(CH(3))(2)Sn(cmbzt)(2)].1.7(H(2)O)] (3), [(n-C(4)H(9))(2)SnCl(2)(mmbzt)(2).(CH(2)Cl(2))] (4) and [[(C(6)H(5))(3)Sn](2)(mna).[(CH(3))(2)CO]] (5) have been synthesized and characterized by elemental analysis, 1H-, 13C-NMR, FT-IR and Mössbauer spectroscopic techniques. Crystal structures of molecules 1, 3 and 5 have been determined by X-ray diffraction at 173(1) K (1 and 5) and 293(2) K (3). Compound 1 C(22)H(26)N(2)S(4)Sn, is monoclinic, space group C2/c, a=44.018(2), b=8.8864(5), c=12.8633(7) A, beta=104.195(5) degrees, Z=8. Compound 3 is also monoclinic, space group P2(1)/c and a=17.128(2) A, b=17.919(2) A, c=7.3580(10) A, beta=98.290(10) degrees, Z=4. In both molecules 1 and 3, two carbon atoms from aryl groups, two sulfur and two nitrogen atoms from thione ligands form a distorted octahedral geometry around tin(IV) with trans-C(2), cis-N(2), cis-S(2) configurations. Compound 5 C(45)H(39)NO(3)SSn(2) is monoclinic, space group P2(1)/n, a=9.1148(2) A, b=29.2819(6), c=15.5556(4) A, beta=106.2851(9) degrees, Z=4. Complex 5 contains two [(C(6)H(5))(3)Sn(IV)] moieties linked by a double deprotonated 2-mercaptonicotinic acid (H(2)mna). Both tin(IV) ions are five coordinated. This complex is the an example of a pentacoordinated Ph(3)SnXY system with an axial-equatorial arrangement of the phenyl groups at Sn(1) atom. Compounds 1, 3 and 5 were tested for in vitro cytotoxicity against the cancer cell line of sarcoma cells (mesenchymal tissue) from the Wistar rat, polycyclic aromatic hydrocarbons (benzo[a]pyrene) carcinogenesis. Compound 5 exhibits strong cytotoxic activity, while complexes 1 and 3 show less cytotoxic activity.


Effect of regular 3-yearly screening on the incidence of cervical smears: the Leiden experience.
The effect of regular 3-yearly screening over a period of 12 years, on the incidence of cervical cancer in 25,000 women aged 35-54 years, is examined. The rate of squamous cell carcinoma decreased from 0.38 per 1000 women in the first round to zero in the fourth round. Similarly, the rate of carcinoma in situ declined from 1.69 per 1000 women in the first round to 0.35 per 1000 in the fourth round. The rates of severe dysplasia showed no decline. Cytologic under diagnosis of carcinoma-in-situ and cervical carcinoma increased with each round. Widowed and divorced women and those living in urban areas were identified as high risk groups.


Zone 1 Aortic Arch Hybrid Endovascular Repair with Extra-anatomical Bypass: A Meta-analysis.
The aim of this meta-analysis is to determine the morbidity and mortality outcomes of adult patients with aortic arch disease managed with extra-anatomical bypass avoiding median sternotomy and cardiopulmonary bypass, with simultaneous or staged hybrid zone 1 endovascular aortic repair. Systematic literature searches of the MEDLINE, EMBASE, and Cochrane databases were carried out to identify relevant studies on zone 1 hybrid arch repair. Extracted data were analyzed by random effects models. Primary outcomes included 30-day or in-hospital mortality. Longitudinal survival was analyzed up to 7 years from date of operation. Secondary outcomes included in-hospital morbidity, as well as late endoleak and reintervention. Twenty studies incorporating 348 patients were included. In-hospital or 30-day mortality was 10.1% (95% confidence interval, 6.7-14.9%). Overall operative technical success was 89.8% (83.7-93.8%). Early type 1 endoleak rate was 14.0% (7.4-24.7%). Stroke prevalence was 9.5% (6.1-14.3%). Spinal cord paraplegia prevalence was 3.8% (1.9-7.6%). Retrograde aortic dissection prevalence was 4.1% (1.5-10.6%). Survival at 1 year postoperatively was 77.2% (66.1-85.4%). Survival at 3 years postoperatively was 73.7% (59.2-84.4%). Survival beyond 4 years postoperatively (range 58-80 months) was 65.9% (53.6-76.4%). Late type 1 endoleak prevalence was 11.8% (5.5-23.7%). Overall rate of reintervention was 11.6% (6.4-20.1%). Zone 1 hybrid repair has evidence for satisfactory short- and long-term morbidity/mortality outcomes and may be considered as an alternative approach to aortic arch disease.


[Influence of exogenous collagen on the metabolism of skin wounds in rats].
Skin wounds of rats were treated by 14C-labeled collagen from guinea pig skin. The main portion of the applied collagen persisted in the wound area. In the neutral salt soluble collagen maximal specific activity was measured on day 4 after treatment, in the citric acid soluble and in the insoluble collagen at later times. On day 4 after treatment 3.42% of the applied label was found in the neutral salt soluble, 1.43% in the citric acid soluble and 1.40% in the insoluble collagen. The findings suggest that the stimulation of wound healing which is reported by various authors is caused by the incorporation of the applied collagen into the regenerating connective tissue.


The effect of inhibitors of receptor internalization on the desensitization and resensitization of three Gs-coupled receptor responses.
Many G protein-coupled receptors (GPCRs) are known to internalize following agonist exposure, however the relative importance of this mechanism for the desensitization and resensitization of different GPCRs is unclear. In the present study, we have pretreated NG108-15 cells with hypertonic sucrose or concanavalin A (con A), to investigate the effects of these inhibitors of internalization on the agonist-induced desensitization and subsequent resensitization of three Gs-coupled receptor responses. Incubation of cells with sucrose or con A did not affect subsequent acute agonist stimulation of the A2A adenosine receptor or the agonist-induced desensitization of this receptor response. However, the resensitization of the A2A adenosine receptor response following agonist removal was abolished in the presence of sucrose or con A. Sucrose or con A treatment affected neither the desensitization nor resensitization of IP-prostanoid receptor responsiveness. On the other hand con A but not sucrose reduced the agonist-induced desensitization of secretin receptor responsiveness. However, secretin receptor responsiveness did not resensitize within the time period studied whether or not inhibitors of internalization were present. These results indicate that receptor internalization appears to subserve different functions for different GPCRs.


[Study of benzimidazole and its derivatives. III. Radioprotective structure-activity relationship of various 2-alkyl (or 2-aryl) benzimidazoles].
Benzimidazoles show important radioprotecting activity. Structure-activity relationships (radioprotective activity and toxicity) are given for benzimidazole-2 derivatives.


Long-term prostate-specific antigen contamination in the Spanish arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC).
Recently, the European Randomized Study of Screening for Prostate Cancer achieved a reduction in prostate cancer mortality by measuring serum prostate-specific antigen (PSA) levels. These results were not reproduced in the Spanish arm of European Randomized Study of Screening for Prostate Cancer. PSA contamination (opportunistic measurements outside the study) could decrease the study's contrasting power if performed in the control arm. We have calculated the long-term rate of PSA contamination and its effect on performing prostate biopsy and detecting cancer. A total of 4,276 men were randomised (2,415 to the screening arm, 1,861 to the control arm) in the Spanish section of the European Randomized Study of Screening for Prostate Cancer. PSA measurements were not scheduled in the control arm. Sextant prostate biopsy was indicated if PSA levels were ≥3 ng/mL. All PSA readings performed outside the study were labelled as "PSA contamination". We calculated the rates of PSA contamination, biopsy implementation and cancer detection. The median age and follow-up time were 57 and 15.1 years, respectively. A total of 2,511 men underwent at least one PSA reading outside the study. PSA contamination at 5, 10 and 15 years was 22.0%, 47.1% and 66.3% in the screening arm, respectively, and 20.8%, 43.2% and 58.6% in the control arm, respectively (P<.0001). The biopsy rate at 5, 10 and 15 years was 19.3%, 22.6% and 24.1% (screening), respectively, and 1.0%, 3.6% and 7.1% (control), respectively (P<.0001). The PC detection rate was 6.7% (screening) and 4.3% (control; P=.0006). Although the cumulative PSA contamination was pronounced in the 2 study arms, the rate of prostate biopsies was low in the control arm. We therefore believe that the effect of PSA contamination on the study's statistical power should be limited.


Health care in the 2008 election: engaging the voters.
For the first time since the early 1990s, the political environment in the United States offers the real possibility of fundamental reform of our fraying health care system. Although the current moment appears promising for reform, the opportunity could easily dissipate as it has in the past. In this paper, we offer seven observations on the key opportunities and pitfalls for health care reform advocates in this pivotal election year, based on our analysis of the current political dynamic and recent public opinion research.


Self-assessment of cognition in Multiple Sclerosis: the role of personality and anxiety.
: To investigate the role of personality and anxiety to self-report measures of cognition in patients with multiple sclerosis (MS). : Self-report measures of cognition have consistently been shown to correlate better with depressed mood than neuropsychological test performance in patients with MS, with few studies focusing on the role of anxiety and personality. : One hundred eight MS patients completed the following: (a) patient and informant report Multiple Sclerosis Neuropsychological Questionnaire (MSNQ); (b) Hospital Anxiety and Depression Scale; (c) cognitive assessment with the Brief Repeatable Battery of Neuropsychological Tests; and (d) personality assessment using the self-report NEO Five-Factor Inventory. : Higher patient MSNQ (P-MSNQ) scores (greater reported cognitive dysfunction) were significantly correlated with lower scores on the Paced Auditory Serial Addition Test (PASAT; r=-0.20, P<0.05), increased depression (r=0.45, P<0.01) and anxiety (r=0.54, P<0.01), higher neuroticism (r=0.51, P<0.01), and lower conscientiousness (r=-0.35, P<0.01). After controlling for demographic variables, significant predictors of P-MSNQ scores were anxiety (ΔR=0.272, P<0.001), conscientiousness (ΔR=0.067, P=0.002), and performance on the PASAT (ΔR=0.050, P=0.005). Depression and neuroticism did not contribute significant variance in comparison to anxiety. : Overall, patient self-reports of cognition did not correspond well to neuropsychological performance. Anxiety and conscientiousness contributed significantly to patients' perceptions of their cognitive failings and thus should be taken into account when addressing these complaints.


Risk of pancreatitis in patients treated with incretin-based therapies.
Incretin-based therapies have been suggested to increase the risk of pancreatitis, but the results of the available studies are controversial. Because results from prospective trials are limited by low statistical power, and because retrospective studies are often subject to bias, a pooled analysis of phase III clinical trials and two endpoint trials was performed. Event numbers for acute pancreatitis and patient-years of exposure (PYOs) were obtained from representatives of the pharmaceutical companies, or by literature research. Data were pooled for glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl-peptidase 4 (DPP-4) inhibitors in comparison with their respective controls and expressed as exposure-adjusted incidence rates. A total of 38 cases of pancreatitis were reported in clinical trials with GLP-1 receptor agonists, comprising 17,775 PYOs. With the comparator treatment, nine events occurred in 5,863 PYOs. The pooled event rates were 2.1 and 1.5 per 1,000 PYOs, respectively, resulting in an OR of 1.39 (95% CI 0.67, 2.88). With DPP-4 inhibitors, 57 events were reported in 45,132 PYOs compared with 46 events in 38,883 PYOs with the comparator treatment. Pooled event rates were 1.3 and 1.2 per 1,000 PYOs, respectively, resulting in an OR of 1.07 (CI 0.72, 1.58). This analysis suggests a trend towards a slightly elevated risk of pancreatitis with GLP-1 receptor agonists. With DPP-4 inhibitors, no consistent trend was found. However, the incidence numbers of cases of pancreatitis were still very small, and the statistical power was limited. Future endpoint trials may help to provide a better estimate of the true risk of pancreatitis with incretin-based therapies.


Functional capacities of marsupial hearts: size and mitochondrial parameters indicate higher aerobic capabilities than generally seen in placental mammals.
This study of marsupial hearts explored the aerobic capacities of this group of mammals; recent information suggests that marsupials possess higher aerobic abilities than previously accepted. Characteristics such as heart mass, mitochondrial features and capillary parameters were examined. A comprehensive study of the heart of red kangaroos was included because of the high maximum oxygen consumption of this species. Goats were also included as a reference placental mammal. Marsupials have a heart that is generally larger than that of placentals. The allometric equation for the relationship between heart mass and body mass for marsupials was M(h)=7.5M(b)(0.944) (M(h) in g and M(b) in kg); the equivalent equation for placental mammals was M(h)=6.0M(b)(0.97). Mitochondrial volume density and inner mitochondrial surface density do not differ between the two mammal groups; although capillary parameters indicated a lower capillary volume in marsupials. Heart size appears to be the major difference between the two groups. The overall pattern seen in marsupials is similar to that of "athletic" placentals and indicates a relatively high aerobic potential.


Nontraumatic bilateral subdural hematoma: Case report.
A subdural hematoma (SDH) is a type of bleeding in which a collection of blood gathers between the inner layer of the dura mater and the arachnoid mater of the meninges surrounding the brain. Although most cases reported of subdural hematoma are due to traumatic brain injury, to the best of our knowledge this is a rare case of nontraumatic subdural hematoma. A 31 year-old-Male presented to the emergency department with a severe headache for 3 weeks, with the presence of oculomotor disorders. There is no history of major trauma, minor trauma or fights. Also, no history of hypertension, or Haematological diseases. Magnetic resonance imaging (MRI) showed bilateral subdural hematoma. The right-sided hematoma was treated conservatively and the Left-sided was treated by surgery. Follow-up for three months revealed no recurrence. Nontraumatic subdural hematoma is one of the challenging cases that neurosurgeons face. We presented a patient with idiopathic spontaneous subdural hematoma. Computed tomography (CT) is the first step for diagnosis and Magnetic resonance imaging (MRI) is considered an excellent imaging investigation to evaluate such patients. Symptomatic subdural hematomas require an emergent treatment by identifying and controlling sites of bleeding conservatively or by surgery. Subdural hematoma with no history of trauma should be treated emergently and evaluated strictly. Follow-up is essential in patients with neural symptoms. Massive symptomatic subdural hematoma (SDH) should be treated with surgery to control the bleeding.


Four-year adiposity change and remission of hypertension: an observational evaluation from the Longitudinal Study of Adult Health (ELSA-Brasil).
The degree to which weight reduction leads to the remission of hypertension in population studies is not clear. We investigated whether the changes in adiposity measures predicted the remission of hypertension in a racially admixed population over a mean 4-year follow-up. All 4847 hypertensive individuals at baseline (2008-2010) from the multicenter Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were included. Changes in weight, waist circumference (WC), or body mass index (BMI) (reduction or increase ≥5% from baseline values, vs stability) and remission of hypertension (SBP < 140 and DBP < 90 mmHg and no use of antihypertensive medication at follow-up visit, in 2012-2014) were investigated using mixed effects logistic regression models. Proportional attributable benefit was additionally calculated. Analyses were stratified by sex and antihypertensive medication use at baseline. Remission of hypertension was 11.3% (n = 546). Among men, after adjustments, the reduction of weight (OR = 1.52 95% CI 1.10-2.10), WC (OR = 1.56 95% CI 1.04-2.35) or BMI (OR = 1.60 95% CI 1.13-2.27) was associated with the remission of hypertension. Among those not taking antihypertensive medication at baseline, after adjustments, the reduction of weight (OR = 1.64 95% CI 1.18-2.27), WC (OR = 1.76 95% CI 1.18-2.61) or BMI (OR = 1.57 95% CI 1.10-2.25) was associated with the remission of hypertension. Proportional attributable benefit among those with adiposity reduction was about 30%, indicating its potential for prevention. In conclusion, our study reinforces the role of adiposity-reducing strategies (e.g., healthy diet and regular physical activity) for the treatment and prevention of hypertension, which might have potential applications for clinical practice.


Effect of dopamine-receptor blockade on stimulation-induced feeding.
The effect of pimozide on stimulation-induced feeding was tested in food satiated rats. Pimozide produced a dose-dependent decrease in the number of animals eating during electrical stimulation of the lateral hypothalamus. A quantal dose-response analysis yielded an ED50 of 0.323 mg/kg for pimozide. Because this dose is within the range of pimozide doses found to be effective in disrupting feeding in other tests, it seems likely that the neural substrate mediating stimulation-induced feeding is similar to that involved in deprivation-induced feeding.


College Soccer Student-Athletes Demonstrate Differences in Self-Reported Athlete Health When Grouped by Match Volume.
Physical changes following activity are well documented, but there is limited information about self-reported outcomes around competitive matches. High training volumes and poor recovery could predispose athletes to overuse injury. The purpose of this study was to identify the changes in daily athlete health measures before, during, and after the day of each match in high- and low-volume groups. Prospective cohort. Fifty-five soccer athletes (age: 19.8 [1.2] y, 26 males, 29 females) provided daily measures of readiness, physical fatigue, mental stress, sleep quality, and soreness intensity match days, days 1 (D01) and 2 (D02) following matches, and standard practice days. Participants were grouped into high volume and low volume, based off the minutes played during the season. Soreness increased, readiness decreased, and fatigue increased on D01 compared with match days (P < .008) in the high-volume group. Between groups, the high-volume group demonstrated higher soreness on D01 and D02, lower readiness on D01 and D02, and lower fatigue on D01, compared with the low-volume group (P < .008). Soccer athletes demonstrate significant changes in self-reported athlete health variables around competitive matches. These changes are similar to physical outcomes, potentially indicating that the athlete health variables may be used to track athlete recovery from competition, potentially limiting the impact of overuse injuries.


Effects of posture on plasma and serum viscosity.
This study demonstrates the importance of defining normal reference population ranges for P- and S-viscosity with respect to posture. The normal ranges determined for P-viscosity are not acceptable as a reference range for a hospitalized population that is predominantly in a supine position. Mean percentage changes of P- and S-viscosity in the recumbent posture as compared to the same population in the upright posture were 7.51 and 5.88, respectively.


[No therapy possible? A group therapy model for psychologically disturbed and socially disadvantaged children].
The authors have developed a group therapy model specifically for children who are difficult to treat using traditional psychotherapeutic techniques. In the present article they describe this model, which has been employed successfully for the past four years in an elementary school in an area of high social deprivation, in collaboration with teaching staff and a social worker.


Indirubin-3-monooxime induced cell cycle arrest and apoptosis in Hep-2 human laryngeal carcinoma cells.
The commercially available analogue of indirubin, indirubin-3-oxime, is known for its antitumor activities. To further establish its role in anticancer activity, we tested its potential against human laryngeal carcinoma cell line (Hep-2). We investigated the molecular mechanisms of indirubin-induced apoptosis and growth arrest in human laryngeal carcinoma cells. Upon treatment with indirubin-3-monooxime, a time dependent inhibition of cell growth was observed and cells developed many hallmark features of apoptosis. The increase of chromatin condensation after treatment with indirubin-3-oxime identified by staining with chromatin stain Hoechst 333258 indicates apoptosis. The observed increase in DNA fragmentation after indirubin-3-oxime in DNA gel electrophoresis indicates the apoptotic feature exhibited by the drug. Flow cytometric analysis confirmed that indirubin increased populations of apoptotic phase G1. Indirubin-3-oxime-induced growth inhibition was associated with induction of Cdk inhibitor p21, inhibition of cyclin D1 and activation of caspase-3. We conclude that indirubin-3-oxime induces cell death and apoptosis in human laryngeal carcinoma cells.


Comparing robot-assisted with conventional laparoscopic hysterectomy: impact on cost and clinical outcomes.
To compare clinical and economic outcomes (hospital costs) in women undergoing laparoscopic hysterectomy performed with and without robotic assistance in inpatient and outpatient settings. Using the Premier hospital database, we identified women >18 years of age with a record of minimally invasive hysterectomy performed in 2007 to 2008. Univariable and multivariable analyses examined the association between robot-assisted hysterectomy and adverse events, hospital costs, surgery time, and length of stay. Of 36,188 patient records analyzed from 358 hospitals, 95% (n = 34,527) of laparoscopic hysterectomies were performed without robotic assistance. Inpatient and outpatient settings did not differ substantively in frequency of adverse events. For cardiac, neurologic, wound, and vascular complications, frequencies were <1% for robot and non-robot procedures. In inpatient and outpatient settings alike, use of robotic assistance was consistently associated with statistically significant, higher per-patient average hospital costs. Inpatient procedures with and without robotic assistance cost $9640 (95% confidence interval [CI] = $9621, $9659) versus $6973 (95% CI = $6959, $6987), respectively. Outpatient procedures with and without robotic assistance cost $7920 (95% CI = $7898, $7942) versus $5949 (95% CI = $5932, $5966), respectively. Inpatient surgery times were significantly longer for robot-assisted procedures, 3.22 hours (95% CI = 3.21, 3.23) compared with non-robot procedures at 2.82 hours (95% CI = 2.81, 2.83). Similarly, outpatient surgery times with robot averaged 2.99 hours (95% CI = 2.98, 3.00) versus 2.46 hours (2.45, 2.47) for non-robot procedures. Our findings reveal little clinical differences in perioperative and postoperative events. This, coupled with the increased per-case hospital cost of the robot, suggests that further investigation is warranted when considering this technology for routine laparoscopic hysterectomies.


Multiple myeloma mimicking bone metastasis from breast cancer: report of a case.
A 72-year-old woman with a history of early breast cancer suffered a fracture of the eighth thoracic vertebra resulting in paraplegia. Magnetic resonance imaging (MRI) showed spinal cord compression by a tumor between the ninth and tenth thoracic vertebrae. Local radiotherapy was begun under the diagnosis of metastatic breast cancer, but bone marrow aspiration and biopsy subsequently revealed plasma-cell proliferation rather than adenocarcinoma. This case report serves to demonstrate that clinicians should consider multiple myeloma as a cause of lytic bone lesions without extraskeletal metastases even in patients with a history of breast cancer.


The decomposition of a distribution into Gaussian components (Algol program.
The paper attempts to give a practical solution to the problem of decomposition of a mixture of Gaussian components. The results of an earlier paper [1] have been used and the described algorithm has been revised and improved. A complete Algol program is given with all the necessary comments and descriptions and with results of testing examples.


Growth Factors in Developed Countries: A 1960-2019 Growth Accounting Decomposition.
Using a new and original database, our paper contributes to the growth accounting literature with three original aspects: First, it covers a long period from the early 60's to 2019, just before the COVID-19 crisis; second, it analyzes a large set of economies (30 plus the Euro Area) at the country level; finally, it singles out the growth contribution of information and communications technologies (ICTs) capital as well as robots. Our findings show that the main drivers of labor productivity growth over the whole 1960-2019 period appear to have been education, total factor productivity (TFP), non-ICT and non-robot capital deepening. The relative contribution of ICT capital is found to be declining from the mid-2000s, although our country-level economy dataset does not make it possible to estimate the TFP contribution of ICTs. The contribution of robots to productivity growth through capital deepening and TFP appears to be significant in Germany and Japan in the sub-period 1975-1995, in France and Italy in 1995-2005, and in several Eastern European countries in 2005-2019. Our findings also confirm the slowdown in TFP in most countries from at least 1995 onwards. This slowdown is mainly accounted for by a decrease in the contributions of non-ICT non-robot capital deepening and TFP.


Hair minerals and diet of Prader-Willi syndrome youth.
This study investigated the relationships between mineral elements and Prader-Willi syndrome (PWS) and determined which minerals, if any, separated a group of PWS individuals (N = 19) from a non-PWS mentally retarded control group (N = 60). The PWS group had significantly raised hair magnesium levels and significantly lower hair silicon levels than controls. The PWS group was also elevated in hair calcium, magnesium, and copper in relation to laboratory standards, while their hair silicon, chromium, and lithium levels were deficient in relation to laboratory norms. Discriminant function analysis revealed that by using 16 hair minerals subjects could be correctly classified as PWS or non-PWS with 89.5% and 95.0% accuracy, respectively. It is concluded that continuing research is needed to study the relationship between mineral element patterns and PWS.


Raising Adolescent Children as a Developmental Task of Iranian Middle-aged Mothers: A Qualitative Study.
Most parents consider adolescence to be the most difficult stage of parenting. Parental practice is a determining factor in adolescents' outcomes. Mothers play the main role of parenting in Iran. Coinciding the transition of adolescence with the transition of middle-aged mothers can affect the mothers' parenting practice. The present study aimed at explaining the Iranian mothers' practice in parenting an adolescent child. This qualitative conventional content analysis was conducted from July 2018 to November 2019 in Kashan. 21 in-depth semi-structured interviews with mothers of adolescent children were performed using a purposive sampling method. The data were analyzed through conventional content analysis. Data collection and analysis were performed simultaneously using MAXQDAv10 software. Regarding the study objectives, two themes and six main categories were identified. The theme of 'laying the groundwork for upbringing' was detected by two main categories: 'meeting the needs and 'effective interaction with the adolescent'; also, the theme of 'individual-social capacity building' was explained by four main categories: 'helping to gain independence', 'modeling individual-social behavior', 'socializing the adolescent', and 'preparing to accept future roles'. Mothers' practice was mainly focused on adolescents' independence, college education, career prospects, and marriage preparation and respect for older adults. Consistent with this transition to modernity, and contrary to the collectivist values of Iranian society, mothers' practice was in line with developing adolescents' independence and building their self-confidence, which is close to the authoritative parenting style.


[The isolation and characteristics of variant plague microbes not producing the capsular antigen].
Fifteen stable variants of Yersinia pestis strains exhibiting different degrees of virulence for white mice and guinea pigs were obtained. Multiple passages of the organisms at 37 degrees C in a fluid nutrient medium containing antiplague agglutinating serum were found to be the most efficient method for obtaining noncapsular forms of the plague agent. Acquisition of the Fra(-) phenotype both by wild and laboratory strains was not associated with a loss of the high-molecular plasmid by cells but was probably a result of mutational alterations in the plasmid genes.


Management of the penile shaft skin in hypospadias repair: alternative to Byars' flaps.
Two variations for resurfacing the penile shaft skin after repair of hypospadias defects are described. These techniques have been used in an effort to prevent some of the skin tags, tension at the penoscrotal angle, and oblique suture lines that may occur with the traditional Byars' flaps.


Emerging Technologies for Preventing the 'New' Dementia: Ambiguous Optimism in the Canadian Context.
Experts' views on the use of mostly digital technologies for dementia prevention are characterized by a simultaneity of "gerontechnological optimism" and skeptical hesitancy. Despite the hope for progress in dementia prevention through preventive technologies, experts also point to the complexity of prevention, the importance of environmental factors and public health policies, and the danger of an excessive focus on individual interventions. Without questioning the positive impact such technologies can have on many people, we claim that the experts' ambiguity reveals a deeper concern, a kind of "cruel optimism" that is based on a fantasy of "supported autonomy".


Generational effects of protein malnutrition in the rat.
The most prevalent form of malnutrition in humans is characterized by its chronic and generational nature. We, therefore, have carried out preliminary studies in rats of the generational effects of protein malnutrition. Our studies to date indicate that a mild protein restriction (8% casein diet) in the first generation becomes a more severe protein restriction in the second generation. This is based on weight gains of the dams during pregnancy, the mean number of pups (F2) per litter, the mean pup (F2) body weight and brain weight at birth, growth curves, levels of brain tryptophan (TRP), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) from birth to weaning, and the levels of certain plasma constituents, especially non-esterified fatty acids (NEFA). We propose this paradigm as an animal model for some types of chronic undernutrition in socioeconomically underprivileged human populations.


During human thymic development, beta 1 integrins regulate adhesion, motility, and the outcome of RHAMM/hyaluronan engagement.
During human thymic differentiation, interactions between fibronectin (Fn)/beta1 integrins and hyaluronan (HA)/RHAMM control motility and Fn/beta1 integrins mediate spontaneous Fn-dependent adhesion. Multinegative (MN, CD3-4-8-) thymocytes exhibit strong spontaneous adherence to Fn (75%) that was efficiently inhibited by anti-alpha5beta1 and only weakly inhibited by anti-alpha4beta1. The relatively weak adherence of unfractionated thymocytes to Fn required both alpha4beta1 and alpha5beta1. Video time-lapse microscopy indicates that a subset of thymocytes also undergo spontaneous Fn-dependent motility mediated by alpha5beta1, alpha4beta1, and the HA-receptor RHAMM, but not by CD44. The loss of motility after hyaluronidase treatment of thymocytes indicated that motility is strongly dependent on HA. Of motile cells, 55% were DP, 19% were DN, and 24% were CD4+SP, but only 1% were CD8+SP. Overall, for MN thymocytes, beta1 integrin mediated Fn-adhesion, but after expression of CD4/CD8, beta1 integrins mediated Fn-dependent motility. Treatment with the activating anti-beta1 mAb QE.2E5 inhibited thymic motility and converted otherwise nonadherent thymocytes to an adherent state. High-avidity interactions via integrins appear to supercede the motogenicity of RHAMM and HA, suggesting that integrin avidity may regulate RHAMM. During thymic development, changes in adhesion or motility appear to be mediated by integrin avidity modulation.


Modulation of immunocyte functions by a mucin-specific lectin from Aspergillus gorakhpurensis.
Lectins are non-immune proteins or glycoproteins with the ability to induce cell agglutination and mediate cellular and molecular recognition processes in a variety of biological interactions. Recently, several mushroom lectins have been reported to show immunomodulatory activities. The immunomodulatory potential of purified A. gorakhpurensis lectin was determined by evaluating its effect on systemic anaphylaxis reaction, arthus reaction, respiratory burst activity, nitric oxide production and levels of cytokines IFN-γ and IL-6. Administration of different doses of purified lectin was found to stimulate immunological activity. Lectin prevented BSA induced Arthus reaction and systemic anaphylaxis. The enhanced functional ability of macrophages was evident from respiratory burst activity and nitric oxide production in splenocyte cultures. Interferon-γ and interleukin-6 levels were significantly up-regulated in lectin treated groups. Maximum modulatory effect was observed at the lectin dose of 3.0mg/kg body weight. The results of the experiments conducted adequately reflect the immunostimulatory effect of purified A. gorakhpurensis lectin.


Left ventricular volume estimation in cardiac three-dimensional ultrasound: a semiautomatic border detection approach.
We propose a semiautomatic endocardial border detection method for three-dimensional (3D) time series of cardiac ultrasound (US) data based on pattern matching and dynamic programming, operating on two-dimensional (2D) slices of the 3D plus time data, for the estimation of full cycle left ventricular volume, with minimal user interaction. The presented method is generally applicable to 3D US data and evaluated on data acquired with the Fast Rotating Ultrasound (FRU-) Transducer, developed by Erasmus Medical Center (Rotterdam, the Netherlands), a conventional phased-array transducer, rotating at very high speed around its image axis. The detection is based on endocardial edge pattern matching using dynamic programming, which is constrained by a 3D plus time shape model. It is applied to an automatically selected subset of 2D images of the original data set, for typically 10 equidistant rotation angles and 16 cardiac phases (160 images). Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastole and end-systole volumes. Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastolic (ED) and end-systolic (ES) volumes. The semiautomatic border detection approach shows good correlations with MRI ED/ES volumes (r = 0.938) and low interobserver variability (y = 1.005x - 16.7, r = 0.943) over full-cycle volume estimations. It shows a high consistency in tracking the user-defined initial borders over space and time. We show that the ease of the acquisition using the FRU-transducer and the semiautomatic endocardial border detection method together can provide a way to quickly estimate the left ventricular volume over the full cardiac cycle using little user interaction.


The effect of rotatory subluxation of the scaphoid on radio-scaphoid contact.
The effect of progressive rotatory subluxation of the scaphoid on radio-scaphoid contact area was examined in a cadaveric model. Five degrees of subluxation reduced the contact area of the proximal pole by 44%, with a shift to the dorsal lip of the radius. At 20 degrees of subluxation the contact area was reduced by 77%, with a shift radially to the dorsal lip of the radial styloid. These findings explain the progression of radio-scaphoid arthritis from the radial styloid to the remainder of the fossa and reemphasize the importance of operative reduction of a scapho-lunate disassociation in the prevention of degenerative arthritis.


[Effects of Kang Gang Qian Granule (KGQG) on clinical and pathological features in chronic hepatitis B patients].
To explore the efficacy of KGQG and its therapeutic mechanisms in chronic hepatitis B patients with liver fibrosis. 57 chronic hepatitis B patients with liver fibrosis were randomly divided into two groups: 45 cases in KGQG group were treated by KGQG and routine medications; 12 cases in control group were treated by routine medications only. Serum liver function test results, PCIII, CIV, HA and liver biopsy results of these 57 patients were simultaneously collected and analyzed before and after this intervention. KGQG group showed better efficacy over control group in liver function recovery, decrease of serum PCIII, CIV, HA levels and liver pathologic grades (P 0.05 or 0.01). The KGQG could effectively ameliorate liver function and facilitate the inhibition and degradation of liver fibrosis in chronic hepatitis B patients, which may be developed as a novel therapeusis to treat this hard-to-cure disease.


Label-free coronavirus disease 2019 lesion segmentation based on synthetic healthy lung image subtraction.
Coronavirus disease 2019 (COVID-19) has become a global pandemic and is still posing a severe health risk to the public. Accurate and efficient segmentation of pneumonia lesions in computed tomography (CT) scans is vital for treatment decision-making. We proposed a novel unsupervised approach using a cycle consistent generative adversarial network (cycle-GAN) which automates and accelerates the process of lesion delineation. The workflow includes lung volume segmentation, healthy lung image synthesis, infected and healthy image subtraction, and binary lesion mask generation. The lung volume was first delineated using a pre-trained U-net and worked as the input for the following network. A cycle-GAN was trained to generate synthetic healthy lung CT images from infected lung images. After that, the pneumonia lesions were extracted by subtracting the synthetic healthy lung CT images from the infected lung CT images. A median filter and k-means clustering were then applied to contour the lesions. The auto segmentation approach was validated on three different datasets. The average Dice coefficient reached 0.666 ± 0.178 on the three datasets. Especially, the dice reached 0.748 ± 0.121 and 0.730 ± 0.095, respectively, on two public datasets Coronacases and Radiopedia. Meanwhile, the average precision and sensitivity for lesion segmentation on the three datasets were 0.679 ± 0.244 and 0.756 ± 0.162. The performance is comparable to existing supervised segmentation networks and outperforms unsupervised ones. The proposed label-free segmentation method achieved high accuracy and efficiency in automatic COVID-19 lesion delineation. The segmentation result can serve as a baseline for further manual modification and a quality assurance tool for lesion diagnosis. Furthermore, due to its unsupervised nature, the result is not influenced by physicians' experience which otherwise is crucial for supervised methods.


[STEMI mimics : ST elevations on ECG: alternative diagnoses to acute coronary occlusion].
The electrocardiogram (ECG) is an integral part of basic emergency medical diagnosis and preoperative evaluation. In cases of ST elevation myocardial infarction (STEMI) immediate treatment is mandatory after correlation of ischemic symptoms with the ECG pattern. However, there are also ECG patterns that can imitate STEMI, possibly resulting in the true underlying diagnosis being missed and inappropriate therapy being initiated. This paper provides an overview of the most important diagnoses that can imitate STEMI on ECG. A literature search was carried out to determine the most important differential diagnoses of ST elevation on ECG. These STEMI mimics are discussed in detail and their relevance for emergency medicine is explained. This article provides an overview of differential diagnoses that should be known in emergency medicine when assessing an ECG with ST elevations. Good knowledge of the ECG patterns presented here can support decision-making in emergency medicine.


Wnt modulation in bone healing.
Genetic studies have been instrumental in the field of orthopaedics for finding tools to improve the standard management of fractures and delayed unions. The Wnt signaling pathway that is crucial for development and maintenance of many organs also has a very promising pathway for enhancement of bone regeneration. The Wnt pathway has been shown to have a direct effect on stem cells during bone regeneration, making Wnt a potential target to stimulate bone repair after trauma. A more complete view of how Wnt influences animal bone regeneration has slowly come to light. This review article provides an overview of studies done investigating the modulation of the canonical Wnt pathway in animal bone regeneration models. This not only includes a summary of the recent work done elucidating the roles of Wnt and β-catenin in fracture healing, but also the results of thirty transgenic studies, and thirty-eight pharmacological studies. Finally, we discuss the discontinuation of sclerostin clinical trials, ongoing clinical trials with lithium, the results of Dkk antibody clinical trials, the shift into combination therapies and the future opportunities to enhance bone repair and regeneration through the modulation of the Wnt signaling pathway.


[Syncope in 3rd degree atrioventricular block. Detection of virus genome in the myocardium].
A 28-year-old woman was admitted after syncope which had been preceded by several flulike episodes. There was no history of any other serious disease. Physical examination was unremarkable. Heart sounds were regular and normal, there were no murmurs. White cell count was 9400/microliter, with a normal differential count. Erythrocyte sedimentation rate and C-reactive protein were also normal. Virus serology revealed no abnormality. The electrocardiogram (ECG) showed complete (third degree) atrioventricular (AV) block with an idioventricular rhythm of 38 beats/min and right bundle branch block pattern. A temporary transvenous pacemaker was inserted on the first hospital day. As myocarditis was suspected a right ventricular endomyocardial biopsy was obtained. Histological and immunohistological examinations demonstrated no unequivocal findings. But molecular-biological tests revealed. Coxsackie-B3 virus genome. The pacemaker was removed on the 6th day, when the ECG had shown intermittent second degree AV block. Regular sinus rhythm with a PR interval of 0.18 s was recorded on day 12, and 24-hour ECG monitoring for several days until her discharge on the 18th day confirmed this rhythm throughout. In aetiologically undetermined disease molecular-biological techniques can be indispensable for the exact diagnosis and may be decisive for administering specific treatment.


Circulating levels of neuropeptide proenkephalin A predict outcome in patients with aneurysmal subarachnoid hemorrhage.
High plasma proenkephalin A level has been associated with ischemic stroke severity and clinical outcomes. This study aimed to assess the relationship between proenkephalin A and disease severity as well as to investigate its ability to predict long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. Plasma proenkephalin A concentrations of one hundred and eighty patients and 180 sex- and age-matched healthy controls were measured by chemoluminescence sandwich immunoassay. Plasma proenkephalin A level was substantially higher in patients than in healthy controls (205.5±41.6 pmol/L vs. 90.8±21.1 pmol/L, P<0.001), was highly associated with World Federation of Neurological Surgeons (WFNS) score (r=0.470, P<0.001) and Fisher score (r=0.488, P<0.001), was an independent predictor for 6-month mortality [odds ratio (OR), 1.183; 95% confidence interval (CI), 1.067-1.339; P=0.004] and unfavorable outcome (Glasgow Outcome Scale score of 1-3) (OR, 1.119; 95% CI, 1.046-1.332; P=0.005) using multivariate analysis, and had high area under receiver operating characteristic curve (AUC) for prediction of 6-month mortality (AUC, 0.831; 95% CI, 0.768-0.883) and unfavorable outcome (AUC, 0.821; 95% CI, 0.757-0.874). The predictive value of the plasma proenkephalin A concentration was also similar to those of WFNS score and Fisher score (both P>0.05). In a combined logistic-regression model, proenkephalin A improved the AUCs of WFNS score and Fisher score, but the differences were not significant (both P>0.05). Thus, proenkephalin A level may be a useful, complementary tool to predict mortality and functional outcome at 6 months after aneurysmal subarachnoid hemorrhage.


Temperature variation at the external root surface during 980-nm diode laser irradiation in the root canal.
To assess the temperature variation in the cervical, middle and apical thirds of root external wall, caused by 980-nm diode laser irradiation with different parameters. The roots of 90 canines, had their canals instrumented and were randomly distributed into 3 groups (n=30) according to the laser potency (1.5 W, 3.0 W and 5.0 W). Each group was subdivided into 3 (n=10) according to the frequency (CM, 100 Hz and 1000 Hz), and each subgroup divided into 2 (n=5): dried canal or filled with distilled water. The maximum temperature values were collected by 3 thermocouples located at each third of the root external wall and recorded by digital thermometers. The groups irradiated in the continuous mode (CM) presented the highest values (11.82+/-5.78), regardless of the canals were dry or not, which were statistically different (p<0.01) from those obtained with 100 Hz (6.22+/-3.64) and 1000 Hz (6.00+/-3.36), which presented no statistical difference between them (p>0.01). The groups irradiated with 5.0 W presented the greatest temperature variation (12.15+/-5.14), followed by 3.0 W (7.88+/-3.92) and 1.5 W (4.02+/-2.16), differing between them (p<0.01). The cervical third of the root presented the highest temperature rises (9.68+/-5.80), followed by the middle (7.66+/-4.87) and apical (6.70+/-4.23), with statistical difference among them (p<0.01). After 30s from the end of irradiation, all the specimens presented temperature variation lower than 10 degrees C. Application of 980-nm diode laser in the root, at 1.5 W in all operating modes, and 3.0 W, in the pulsed mode, for 20s, can safely be used in endodontic treatment, irrespective of the presence of humidity.


Does microplastic ingestion by zooplankton affect predator-prey interactions? An experimental study on larviphagy.
Litter is omnipresent in the ocean where it can be ingested by marine biota. Although ingestion of microplastics (MPs) is abundantly reported, insights into how MP can influence predator-prey interactions currently limits our understanding of the ecological impact of MPs. Here we demonstrate trophic transfer of MPs from zooplankton to benthic filter feeders, through consumption of contaminated prey (i.e. prey with ingested MP). However, predation rates of contaminated prey were significantly lower as compared to predation rates of prey that had no MPs ingested. As filter feeder clearance rates were not affected by consumption of MPs, the lower predation rates of contaminated prey appear to be primarily explained by disruption in zooplankton swimming behaviour that reduces their filtration risk. This is the first study that shows how MPs can change predator-prey interactions that are involved in the coupling between the pelagic and seabed habitat.


Modification of topological corner excitations at the interplay of boundary geometry and Coulomb interaction.
The effect of Coulomb interaction on the 2D second order topological superconductor is investigated taking into account different geometries of the boundary in the mainframe of the mean-field approximation. The spontaneous symmetry breaking, described earlier in Aksenovet al(2023Phys. Rev.B107125401), is found to be robust against the boundary deformation. Meanwhile, the details of the state with spontaneously broken symmetry is found to be dependent on the specific boundary geometry. Considering different types of the boundary of the 2D system, it is demonstrated that the deviation of the electron density in the broken symmetry state is determined by the position of the zero-dimensional (second-order) excitations with nearly zero energy. The critical value of the Coulomb interaction, at which the transition occurs, is found to be determined by the energy of these excitations, which is non-zero due to overlapping of the wave-functions at different corners.


Application of halophilic nuclease H of Micrococcus varians subsp. halophilus to commercial production of flavoring agent 5'-GMP.
RNA was degraded at 60 degrees C for 24 h by halophilic nuclease H in supernatants from broth cultures of Micrococcus varians subsp. halophilus containing 12% NaCl. Since contaminating 5'-nucleotidase exhibited almost no activity under these conditions, the 5'-GMP formed could be recovered from the reaction mixture, and the yield was 805 mg from 5 g of RNA.


Maternal and neonatal morbidity of emergency caesarean sections with a decision-to-delivery interval under 30 minutes: evidence from 10 years.
The purpose was to investigate the decision-to-delivery interval for emergency caesarean section and to compare the perioperative maternal and neonatal morbidity to that of intrapartum non-emergent caesarean section. A cohort study was designed evaluating 109 women undergoing 'crash' emergency caesarean section and 109 controls from 1988 to 1997 in a University hospital. All emergency caesarean sections were performed in the delivery room. Controls were matched by gestational age. Retrospective collection of data relating to indication, maternal and neonatal outcome of both groups was conducted. Time intervals between decision to deliver and actual delivery were collected for all emergency deliveries. The emergency caesarean section cohort represented a high risk group with a mean gestational age of 34.8 weeks and a high number of patients with preterm labour (29.3%). All 109 emergency caesarean sections were achieved within a decision-to-delivery time of 30 min. Severe maternal haemorrhage was significantly higher mainly because of underlying obstetrical complications such as placenta praevia, placental abruption, and others resulting in a blood transfusion rate of 10.1%. Procedure related and infectious maternal morbidity, however, was not significantly increased. All women undergoing the emergency procedure received perioperative antibioprophylaxis. Mean umbilical arterial blood pH and Apgar scores were significantly lower in infants delivered by emergency caesarean section but there was no difference in the admission to the NICU. Emergency caesarean section performed in the delivery room may result in a decision-to-delivery time of less than 30 min without detrimental perioperative effects on mother or infant.


Soundtrack of life: An fMRI study.
Most people have a soundtrack of life, a set of special musical pieces closely linked to certain biographical experiences. Autobiographical memories (AM) and music listening (ML) involve complex mental processes ruled by differentiate brain networks. The aim of the paper was to determine the way both networks interact in linked occurrences. We performed an fMRI experiment on 31 healthy participants (age: 32.4 ± 7.6, 11 men, 4 left-handers). Participants had to recall AMs prompted by music they reported to be associated with personal biographical events (LMM: linked AM-ML events). In the main control task, participants were prompted to recall emotional AMs while listening known tracks from a pool of popular music (UMM: unlinked AM-ML events). We wanted to investigate to what extent LMM network exceeded the overlap of AM and ML networks by contrasting the activation obtained in LMM versus UMM. The contrast LMM>UMM showed the areas (at P < 0.05 FWE corrected at voxel level and cluster size>20): right frontal inferior operculum, frontal middle gyrus, pars triangularis of inferior frontal gyrus, occipital superior gyrus and bilateral basal ganglia (caudate, putamen and pallidum), occipital (middle and inferior), parietal (inferior and superior), precentral and cerebellum (6, 7 L, 8 and vermis 6 and 7). Complementary results were obtained from additional control tasks. Provided part of tLMM>UMM areas might not be related to ML-AM linkage, we assessed LMM brain network by an independent component analysis (ICA) on contrast images. Results from ICA suggest the existence of a cortico-ponto-cerebellar network including left precuneus, bilateral anterior cingulum, parahippocampal gyri, frontal inferior operculum, ventral anterior part of the insula, frontal medial orbital gyri, caudate nuclei, cerebellum 6 and vermis, which might rule the ML-induced retrieval of AM in closely linked AM-ML events. This topography may suggest that the pathway by which ML is linked to AM is attentional and directly related to perceptual processing, involving salience network, instead of the natural way of remembering typically associated with default mode network.


Renal angiomyolipoma with tumor thrombi: Clinical analysis of 18 cases in a single-center experience.
To improve understanding of the clinical features of renal angiomyolipoma (AML) accompanied by tumor thrombus (TT). From January 2017 to February 2022, 18 patients with AML and TT were enrolled. We retrospectively analyzed them and there were 6 cases of epithelial AML (EAML) and 12 of classical AML (CAML). We compared the key variables between the two cohorts. The mean age of the 18 cases was 42.0 (standard deviation [SD] 13.4) years and 14 (77.8%) were female. Eleven (61.1%) tumors were on the right side. Only two (11.1%) cases presented with flank pain. The mean follow-up time was 33.6 (IQR: 20.1-48.5) months. All participants were alive at the end of follow-up. One case developed lung metastases 21 months after operation but entered remission after 2 years of everolimus treatment. The imaging diagnoses of all CAML cases were consistent with the pathology, while all imaged EAML cases were diagnosed with carcinomas. Five EAML cases, but only one CAML case, exhibited necrosis (83.3 vs. 8.3%, P = 0.001). The Ki-67 index of the EAML group was significantly higher than that of the CAML group (7 vs. 2, P = 0.004). Compared to CAML, EAML tended to be associated with a higher imaging misdiagnosis rate, and was more commonly associated with necrosis and a higher Ki-67 index. Surgery remains the prime treatment for nonmetastatic AML with TT; such cases have a relatively good prognosis despite the malignant potential.


Group size determined by fusion and fission. A mathematical modelling with inclusive fitness.
We consider a mathematical model for the group size determination by the intra-reactions, self-growth, ostracism and fission within a group, and by the inter-reactions, immigration and fusion between two groups. In some group reactions, a conflict between two groups occurs about the reaction to change the group size. We construct a mathematical model to consider such conflict, taking into account the inclusive fitness of members in each group. In the conflict about the fusion between two groups, our analysis shows that the smaller group wants to fuse, while the larger does not. Also the criterion to resolve the conflict is discussed, and some numerical examples are given, too. It is concluded that, depending on the deviation in the total cost paid for the conflict by counterparts, the group reactions could result in a terminal group size different from that reached only by a sequence of outsider's immigrations into a group.


Improving the design stage of air pollution studies based on wind patterns.
A growing literature in economics and epidemiology has exploited changes in wind patterns as a source of exogenous variation to better measure the acute health effects of air pollution. Since the distribution of wind components is not randomly distributed over time and related to other weather parameters, multivariate regression models are used to adjust for these confounding factors. However, this type of analysis relies on its ability to correctly adjust for all confounding factors and extrapolate to units without empirical counterfactuals. As an alternative to current practices and to gauge the extent of these issues, we propose to implement a causal inference pipeline to embed this type of observational study within an hypothetical randomized experiment. We illustrate this approach using daily data from Paris, France, over the 2008-2018 period. Using the Neyman-Rubin potential outcomes framework, we first define the treatment of interest as the effect of North-East winds on particulate matter concentrations compared to the effects of other wind directions. We then implement a matching algorithm to approximate a pairwise randomized experiment. It adjusts nonparametrically for observed confounders while avoiding model extrapolation by discarding treated days without similar control days. We find that the effective sample size for which treated and control units are comparable is surprisingly small. It is however reassuring that results on the matched sample are consistent with a standard regression analysis of the initial data. We finally carry out a quantitative bias analysis to check whether our results could be altered by an unmeasured confounder: estimated effects seem robust to a relatively large hidden bias. Our causal inference pipeline is a principled approach to improve the design of air pollution studies based on wind patterns.


Determination of PCDDs, PCDFs, PCBs and HCB emissions from the metallurgical sector in Poland.
The aim of the project was to measure the actual emissions of PCDD/F, PCBs and HCB from 20 selected metallurgical installations in Poland, in order to update the national inventory of dioxin emission from metallurgical industry for developing a strategy for dioxins and furans emission abatement from the subject facilities (UNEP 2005). Sampling methodology used in this work was developed at the Cracow University of Technology because of the complexity of simultaneous sampling and determining PCDFs, PCDDs, PCB and HCB. For the determination a GC-MS/MS system was used. Results from the work indicate that the highest dioxins and PCB concentrations were recorded for iron ore sintering plants at 1.10-1.32 ng total1 TEQ/Nm3 followed by aluminium scrap melting at 0.03-0.66 ng total TEQ/Nm3. The highest HCB concentrations at 613-1491 ng/Nm3 were also recorded fo iron ore sintering plants, whereas at aluminium plants the HCB concentrations were in the range of only 10.1-22.7 ng/Nm3. The above investigations indicate that secondary aluminium production is the most significant dioxins source, if calculated as emission factor values. However, iron ore sintering plants are operating at much higher production capacity, causing this process to become the major source of dioxins, PCB and HCB pollution to the atmosphere in Poland. Based on the performed tests and the environmental reviews of selected plants several recommendations were formulated for the reduction of generation or of emission of these pollutants from iron ore sintering plants, electric arc furnace steel production processes, hot-blast furnace operations, secondary aluminium smelting and primary zinc production from zinc cathodes.


Immobilization of uranium into magnetite from aqueous solution by electrodepositing approach.
Immobilization of uranium into magnetite (Fe3O4), which was generated from metallic iron by electrochemical method, was proposed to rapidly remove uranium from aqueous solution. The effects of electrochemical parameters such as electrode materials, voltage, electrode gap, reaction time and pH value on the crystallization of Fe3O4 and uranium removal efficiencies were investigated. More than 90% uranium in the solution was precipitated with Fe3O4 under laboratory conditions when uranium concentration range from 0.5mg/L to 10mg/L. The Fe3O4 crystallization mechanism and immobilization of uranium was proved by XPS, XRD, TEM, FTIR and VSM methods. The results indicated that the cationic (including Fe2+, Fe3+ and U(VI)) migrate to cathode side under the electric field and the uranium was incorporated or adsorbed by Fe3O4 which was generated at cathode while the pH ranges between 2-7. The uranium-containing precipitate of Fe3O4 can exist stably at the acid concentration below 60g/L. Furthermore, the precipitate may be used as valuable resources for uranium or iron recycling, which resulted in no secondary pollution in the removal of uranium from aqueous solution.


The Mediating Role of Career Calling in the Relationship Between Family-Supportive Supervisor Behaviors and Turnover Intention Among Public Hospital Nurses in China.
This study explored the mediating effect of career calling in the relationship between family-supportive supervisor behaviors and turnover intention among nurses. Data were gathered from 563 nurses enrolled in eight public hospitals in China. They were required to complete measures of family-supportive supervisor behaviors, career calling, and turnover intention. Hierarchical multiple regression analysis and the bootstrapping procedure were used to examine the mediating role of career calling. Family-supportive supervisor behaviors were positively associated with career calling, but negatively associated with turnover intention. Furthermore, career calling partially mediated the relationship between family-supportive supervisor behaviors and turnover intention. This study provides strong evidence for an increasing body of work that emphasizes the importance of nursing leaders engaging in family-supportive behaviors for increasing employee career calling and reducing turnover intention.


Different evolutionary pathway of B*570101 and B*5801 (B17 group) alleles based in intron sequences.
Two theories about MHC allele generation have been put forward: (1) point mutation diversification and/or (2) gene conversion events. A model supporting the existence of both of these mechanisms is shown in this paper; the possible evolution of the HLA-B*570101 and HLA-B*5801 alleles (which belong to the HLA-B17 serology group) is studied. The hypothesis favoured is that gene conversion events have originated these alleles, because intron sequences are also analysed. Evolution by point mutation should only be accepted if flanking introns have also been sequenced.


Parrots are "more human" than chickens.
Analysis of an Internet database of pets' names showed owners were more likely to give anthropomorphic names to pets living within homes than those living outside.


Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning.
Half a century ago, the apical ectodermal ridge (AER) at the distal tip of the tetrapod limb bud was shown to produce signals necessary for development along the proximal-distal (P-D) axis, but how these signals influence limb patterning is still much debated. Fibroblast growth factor (FGF) gene family members are key AER-derived signals, with Fgf4, Fgf8, Fgf9 and Fgf17 expressed specifically in the mouse AER. Here we demonstrate that mouse limbs lacking Fgf4, Fgf9 and Fgf17 have normal skeletal pattern, indicating that Fgf8 is sufficient among AER-FGFs to sustain normal limb formation. Inactivation of Fgf8 alone causes a mild skeletal phenotype; however, when we also removed different combinations of the other AER-FGF genes, we obtained unexpected skeletal phenotypes of increasing severity, reflecting the contribution that each FGF can make to the total AER-FGF signal. Analysis of the compound mutant limb buds revealed that, in addition to sustaining cell survival, AER-FGFs regulate P-D-patterning gene expression during early limb bud development, providing genetic evidence that AER-FGFs function to specify a distal domain and challenging the long-standing hypothesis that AER-FGF signalling is permissive rather than instructive for limb patterning. We discuss how a two-signal model for P-D patterning can be integrated with the concept of early specification to explain the genetic data presented here.


Another elliptocytosis locus on chromosome 1?
Analysis of pedigrees given in the literature suggests that a second elliptocytosis locus (not linked to Rh) may be linked to Duffy (Z = 1.97 at theta = 0.0), and therefore on chromosome 1. Significant heterogeneity is found between the El1 and El2 total lod scores with Fy.


TEM investigations of biogenic magnetite extracted from the human hippocampus.
Modification of chemical and magnetic extraction techniques has yielded biogenic magnetite/maghemite from human hippocampal tissue. Particles were identified using high resolution transmission electron microscopy, electron diffraction and elemental analysis. Though its presence has been inferred from magnetic analyses, this is the first direct observation of magnetic biominerals from the hippocampus.


Peptide YY interacts with secretin and duodenal acidification to inhibit gastric acid secretion.
Previous studies have indicated that plasma levels of peptide YY (PYY) increase significantly after a meal. The purpose of this study was to characterize the interaction of PYY and secretin in the inhibition of gastric acid secretion, and to determine whether PYY can influence acid-induced inhibition of gastric acid secretion in conscious dogs. I.v. administration of PYY at 200 pmol/kg/h inhibited pentagastrin (1 microgram/kg/h)-stimulated gastric acid output (P less than 0.05). PYY further augmented i.v. secretin-induced inhibition of pentagastrin-stimulated gastric acid output by 32 +/- 7%, and intraduodenal hydrochloric acid-induced inhibition of pentagastrin-stimulated gastric acid output by 40 +/- 12%. The mean integrated release of secretin response to duodenal acidification (3.9 +/- 1.0 ng-[0-60] min/ml) was not affected by PYY (3.3 +/- 0.9 ng-[0-60] min/ml). The present study demonstrates that PYY can interact with secretin and duodenal acidification in an additive fashion to inhibit pentagastrin-stimulated gastric acid secretion. Our results suggest that several hormones that are released postprandially can interact with each other to inhibit gastric acid secretion.


Second order probabilistic assessment of chronic dietary exposure to aflatoxin M1 in Serbia.
Considering the genotoxic and cancerogenic nature of aflatoxin M1 (AFM1), its presence in milk and dairy products may pose health risks for consumers. The chronic exposure was calculated using a two-dimensional (second order) Monte Carlo model. Results of 13 722 milk and dairy product samples analysed in the 2015-2022 period were used. Milk and dairy products intake information was collected with a Food Frequency Questionnaire (FFQ) validated by a 24-h recall-based method. Risk characterization was done by calculation of the Margin of Exposure (MOE) and by calculation of AFM1 induced number of hepatocellular carcinoma (HCC) cases. Mean AFM1 Estimated Daily Intake (EDI) was highest in children at 0.336 (CI: 0.294-0.385) ng kg-1 bw day-1, followed by adolescents with 0.183 (CI: 0.164-0.204), then adult females with 0.161 (CI: 0.146-0.179) and finally adult males with lowest EDI of 0.126 (CI: 0.115-0.139) ng kg-1 bw day-1. MOE values based on mean EDI for all population groups were above risk associated threshold and the number of possible HCC cases was in the range of 0.0002-0.0021 cases per year for 105 individuals. The results suggest low health risks due to AFM1 exposure for the whole population. Still, this risk is not non-existent, especially for children as they have a higher ratio of the population exposed to risk associated AFM1 levels, with MOE values below risk indicating threshold starting at 77.5th percentile.


SFPQ/PSF-TFE3 renal cell carcinoma: a clinicopathologic study emphasizing extended morphology and reviewing the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite an identical gene fusion.
Xp11 translocation renal cell carcinoma (RCC) with SFPQ/PSF-TFE3 gene fusion is a rare epithelial tumor. Of note, the appearance of the gene fusion does not necessarily mean that it is renal cell carcinoma. The corresponding mesenchymal neoplasms, including Xp11 neoplasm with melanocytic differentiation, TFE3 rearrangement-associated perivascular epithelioid cell tumor (PEComa) and melanotic Xp11 translocation renal cancer, can also harbor the identical gene fusion. However, the differences between Xp11 translocation RCC and the corresponding mesenchymal neoplasm have only recently been described. Herein, we examined 5 additional cases of SFPQ-TFE3 RCCs using clinicopathologic, immunohistochemical, and molecular analyses. One tumor had the typical morphologic features of SFPQ-TFE3 RCC, whereas other 3 cases demonstrated the unusual morphologic features associated with pseudorosettes formation or clusters of smaller cells, mimicking TFEB RCC. The remaining one showed branching tubules and papillary structure composed of clear and eosinophilic tumor cells. Immunohistochemically, all 5 cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, PAX-8 and CD10, whereas no cases demonstrated TFEB, Cathepsin K, CA-IX, CK7, Melan-A, or HMB-45 expression. Genetically, the fusion transcripts were identified in 3 cases by reverse-transcription polymerase chain reaction (RT-PCR). On the basis of fluorescence in situ hybridization (FISH) analysis, all the cases were detected with SFPQ-TFE3 gene fusion. Clinical follow-up data were available for all the patients, and no one developed tumor recurrence, progression, or metastasis. We also review the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite the identical gene fusion. The presence of pseudorosettes also expands the known histological features of SFPQ-TFE3 RCC.


Combined Meniscal Allograft Transplantation and Anterior Cruciate Ligament Reconstruction Show Good 2- to 14-Year Outcomes: A Systematic Review.
To evaluate the clinical outcomes of anterior cruciate ligament reconstruction (ACLR) with meniscal allograft transplantation (MAT) through a systematic review of current available evidence. A systematic database search of PubMed, Embase, Web of Science, and CINAHL was performed from inception up to December 7, 2021, in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Follow-up studies (inception cohort studies/nonrandomized controlled trials/retrospective cohort studies) and case series that had more than 10 people published in English and involved patients who underwent a combination of ACLR and MAT were included. The quality of these studies was appraised using the Cochrane Risk Of Bias In Non-randomized Studies of Interventions tool. Systematic review of International Knee Documentation Committee (IKDC), Lysholm, and Tegner activity scores were conducted. Seven studies involving 363 patients were included. The average mean follow-up time was 4.08 years, ranging from 1.75 to 14 years. All studies used the Lysholm Knee Scoring system to report clinical outcomes, whereas 2 studies and 4 studies used the IKDC Questionnaire and Tegner activity scale respectively to measure clinical outcomes postoperatively. Comparing postoperative with preoperative scores, we found an improvement above the minimal clinically important difference for the Lysholm (mean difference [MD] range 16.00-26.10) and Tegner activity scores (MD range 1.50-1.90). All but one study reported an increase above the minimal clinically important difference for IKDC scores postoperatively (MD range 5.60-23.00). Combined MAT and ACLR have good 2- to 14-year clinical outcomes postoperatively and is an optimal procedure for patients with concurrent ACL injuries with irreparable meniscus injuries. IV, systematic review and/or meta-analysis of studies with Levels I to IV.


Radial trunk-centred reference frame in haptic perception.
The shape of objects is typically identified through active touch. The accrual of spatial information by the hand over time requires the continuous integration of tactile and movement information. Sensory inputs arising from one single sensory source gives rise to an infinite number of possible touched locations in space. This observation raises the question of the determination of a common reference frame that might be employed by humans to resolve spatial ambiguity. Here, we employ a paradigm where observers reconstruct the spatial attributes of a triangle from tactile inputs applied to a stationary hand correlated with the voluntary movements of the other hand. We varied the orientation of the hands with respect to one another and to the trunk, and tested three distinct hypotheses regarding a reference frame used for integration: a hand-centred, a trunk-centred or an allocentric reference frame. The results indicated strongly that the integration of movement information and tactile inputs was performed in a radial trunk-centred reference frame.


The efficacy and safety of pulse vs. continuous therapy for dermatophyte toenail onychomycosis.
Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus for a significant proportion of patients. Treatment with these drugs can be continuous or intermittent, albeit the evidence on their relative efficacies remains unclear. To determine the relative effectiveness and safety of pulse versus continuous administration, of three common oral therapies for dermatophyte onychomycosis, by conducting multiple-treatment meta-analysis. This systematic review and network meta-analysis compared the efficacy (as per mycological cure) and adverse event rates of three oral antifungal medications in the treatment of dermatophyte toenail onychomycosis, namely terbinafine, itraconazole and fluconazole. A total of 30 studies were included in the systematic review, while 22 were included in the network meta-analysis. The likelihood of mycological cure was not significantly different between continuous and pulse regimens for each of terbinafine and itraconazole. Use of continuous terbinafine for 24 weeks - but not 12 weeks - was significantly more likely to result in mycological cure than continuous itraconazole for 12 weeks or weekly fluconazole for 9-12 months. Rank probabilities demonstrated that 24-week continuous treatment of terbinafine was the most effective. There were no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole and fluconazole. Drug treatments were similar to placebo in terms of their likelihood of producing adverse events. More knowledge about the fungal life cycle and drugs' pharmacokinetics in nail and plasma could further explain the relative efficacy and safety of the pulse and continuous treatment regimens. Our results indicate that in the treatment of dermatophyte toenail onychomycosis, the continuous and pulse regimens for terbinafine and itraconazole have similar efficacies and rates of adverse events.


Recurrent colorectal carcinoma detected by routine cervicovaginal papanicolaou smear testing.
We present a case of recurrent colon cancer detected by routine, annual Papanicolaou screening. A 59-year-old African American woman who had been treated for T2N0M0 (stage II, Dukes A) colon cancer 2 years before to presentation had a Pap smear showing a high-grade squamous intraepithelial lesion with a normal cervical biopsy result. Because of this discrepancy, a loop electrosurgical excision procedure and endocervical curettage were performed and showed atypical glandular cells suspicious for adenocarcinoma. Subsequent colonoscopy showed recurrent adenocarcinoma of the colon. The patient underwent an en-block total abdominal hysterectomy and anterior-perineal resection showing invasion of recurrent colon cancer into the uterus and cervix. In patients with a history of extrauterine adenocarcinoma, abnormal Pap screening may indicate recurrent or metastatic carcinoma.


Additive effects of the chemokine receptor 2, vitamin D receptor, interleukin-6 polymorphisms and cardiovascular risk factors on the prevalence of myocardial infarction in patients below 65 years.
Cardiovascular risk factors (CRF) have been associated with myocardial infarction (MI), while the role of genetic risk factors (GRF) remains undetermined. Cineventriculograms of 3436 were analyzed for presence of regional function impairment as sign of MI. Genotyping for genetic polymorphism (vitamin D receptor VDR BsmI, interleukin-6 IL6-174 G/C, chemokine receptor 2 CCR2 64 V/I) was performed. CRF were assessed (hypertension, hypercholesterolemia, smoking, and diabetes mellitus). In patients <65 years (n=1946) genotypes (VDR BB, IL6 GC/CC, CCR2 VI/II, defined as GRF) were significantly associated with the presence of MI (BB: OR 1.38, 95%CI 1.07-1.79, p=0.016 GC/CC: 1.28, 95%CI 1.03-1.60, p=0.028 VI/II: 1.49, 95%CI 1.17-1.88, p=0.001). Combining four CRF (14% vs. 21% vs. 27% vs. 31% vs. 38%, p<0.0001) and three GRF (21% vs. 25% vs. 32% vs. 44%, p<0.0001) revealed additive effects on the prevalence of MI. The more combined CRF and GRF were present (from 0 to 7) the higher was the prevalence of MI (11% vs. 12% vs. 21% vs. 27% vs. 30% vs. 34% vs. 59%, p< 0.0001). Age was not associated with MI. In patients > or =65 years (n=1490) the combination of CRF was only weakly associated with MI, while GRF were not. In these patients age was a predictor of MI. Certain GRF might have additive but small effects on the disposition for MI before the age of 65. In older patients the tested GRF had no effect, possibly indicating a mechanism of aging rather than a purely genetic determined entity. Given the small effect of the tested genetic polymorphisms the value of testing GRF remains uncertain.