Adverse Fetal Outcomes and Histopathology of Placentas Affected by COVID-19: A Report of Four Cases.
Coronavirus disease 2019 (COVID-19) has had significant impacts on mothers and neonates. In this report, we present four unique cases of COVID-19 infections in pregnancy and its effects on the mother, fetus, and placenta. Four mothers presented to the hospital during their pregnancy. Each had tested COVID-19-positive 1-29 days prior to admission. Gestational age ranged from 16 weeks six days to 36 weeks six days. Three of the four cases resulted in fetal demise or infant expiration. The common finding among all four cases was pathologic changes in the placenta. Most of the placentas were small for gestational age and had extensive villous infarction. There was also histiocytic intervillositis with villous necrosis and perivillous fibrin deposition. The placentas demonstrated positive staining of syncytiotrophoblasts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike S1 subunit protein. SARS-CoV-2 RNA was detected in tissue samples of two of the fetuses demonstrating vertical transmission. A higher incidence of severe COVID-19 disease course has been observed in pregnant women. Prior to the SARS-CoV-2 pandemic, chorionic histiocytic intervillositis of the placenta was rarely seen, and mostly of unknown etiology. The increase in placental fibrin levels results in decreased maternal placenta blood flow ensuing hypoxic stress in the fetus. Intrauterine hypoxia has been associated with alterations in brain structure and function resulting in defects in motor skills, cerebral palsy, decreased brain weight, schizophrenia, and other forms of cognitive impairment.


The influence of caprate on rectal absorption of phenoxymethylpenicillin: experience from an in-vivo perfusion in humans.
The aim of this in-vivo perfusion study in humans was to investigate the influence of a penetration enhancer, sodium caprate, on the rectal absorption of phenoxymethylpenicillin and antipyrine. Six subjects, 3 male and 3 female, were included in two separate studies using perfusion solution of different pH (T1 and T2, respectively). Each in-vivo rectal perfusion investigation lasted for 200 min and consisted of two periods of 100 min, the first serving as a control, and sodium caprate being added in the second period in both T1 and T2. The concentrations of phenoxymethylpenicillin, antipyrine and sodium caprate in the outlet perfusate were assayed by HPLC, as was the plasma concentrations of phenoxymethylpenicillin. At pH 6.0 (0-100 min) the fraction absorbed (f(abs)) and effective permeability (P(eff)) of phenoxymethylpenicillin were 0.3% and 0.06 x 4 cm s(-1), respectively, and remained unaffected by the addition of sodium caprate. When the same subjects were perfused at pH 7.4, the f(abs) and P(eff) of phenoxymethylpenicillin were 2.4% and 0.11 x 10(-4) cm s(-1) (0-100 min), respectively, also remaining unchanged by addition of sodium caprate (100-200 min). It was possible to determine the plasma AUC of phenoxymethylpenicillin after addition of sodium caprate in three subjects at both pHs; this was in the range of 14.0-62.8 and 56.4-231 (min micromol L(-1)) at pH 6.0 and 7.4, respectively. Interestingly, there was a correlation between P(eff) for sodium caprate and the individual plasma AUC and C(max) of phenoxymethyl-penicillin, which indicates that the permeability of the enhancer in the tissue upon which it should act is crucial for achieving an effect. The f(abs) and the P(eff) of antipyrine were not affected at either pH when sodium caprate was added to the perfusion solution. In conclusion, the plasma pharmacokinetics of phenoxymethylpenicillin suggested a slightly increased rectal absorption at pH 7.4 in subjects where sodium caprate was transported into the rectal tissue. However, the increased P(eff) for phenoxymethylpenicillin wastoo small to detectfrom the outlet perfusate, which suggests that sodium caprate alone has a limited effect on the permeability in-vivo across the rectal epithelium when it is presented in a solution.


Psychophysiological hypotheses regarding multiple chemical sensitivity syndrome.
This paper proposes several hypotheses and research strategies for exploring possible psychological factors contributing to multiple chemical sensitivity (MCS). The hypotheses are based on concepts of individual response stereotypy, situational response specificity, classical conditioning of chemical-induced responses, and psychophysiological reactions to active and passive coping orientations. Hypotheses regarding hypersensitivity to perception and/or aversiveness of chemical stimulation also are presented. Strategies for evaluating these hypotheses are described based on experimental literature on psychophysiology and psychophysics.


Blindness after confinement.
Four days after an elective caesarean section, a patient went blind within a few hours, associated with a sudden rise in blood pressure. The blindness, initially thought to be caused by a cerebral infarct, was ultimately diagnosed as a result of posterior reversible leuco-encephalopathy syndrome. This rare syndrome is reviewed.


Severe outbreak of ulcerative colitis and cerebral neoplasia. Difficult management in COVID time.
A 61-year-old male diabetic patient, diagnosed with ulcerative colitis (UC) 30 years ago, currently under treatment with mesalazine is presented. He was admitted to the emergency department due to a severe outbreak of UC, with 15 depositions daily, rectal bleeding and poor general condition. A brain CT-scan was carried out in the emergency department due to a sudden self-limited aphasia. A left frontal lesion of 45x38 mms with a prominent perilesional edema and with a displacement of the midline was reported. This was believed to be a meningioma (figure 1A). Urgent neurosurgery was not performed, prioritizing the severe flare-up UC. Based on this, full-dose metilprednisolone was administered.


Altered intrinsic connectivity networks in frontal lobe epilepsy: a resting-state fMRI study.
Examining the resting-state networks (RSNs) may help us to understand the neural mechanism of the frontal lobe epilepsy (FLE). Resting-state functional MRI (fMRI) data were acquired from 46 patients with FLE (study group) and 46 age- and gender-matched healthy subjects (control group). The independent component analysis (ICA) method was used to identify RSNs from each group. Compared with the healthy subjects, decreased functional connectivity was observed in all the networks; however, in some areas of RSNs, functional connectivity was increased in patients with FLE. The duration of epilepsy and the seizure frequency were used to analyze correlation with the regions of interest (ROIs) in the nine RSNs to determine their influence on FLE. The functional network connectivity (FNC) was used to study the impact on the disturbance and reorganization of FLE. The results of this study may offer new insight into the neuropathophysiological mechanisms of FLE.


The fat pearl graft in ophthalmic plastic surgery: everyone wants to be a donor!
Autogenous fat pearl grafting offers a solution to several difficult problems in ophthalmic plastic surgery. These include lower eyelid contour and tear trough deformities, depressed scars, and upper eyelid crease asymmetries and hollow superior sulci. The grafting technique is easily learned and patient satisfaction is high.


[Genetics and clinical study of Chinese kindreds with dentatorubral pallidoluysian atrophy].
To investigate genetics and clinical characteristics of dentatorubral-pallidoluysian atrophy (DRPLA) in Chinese kindreds. Fragment analysis with laser-induced fluorescence in capillary electrophoresis was performed for the cytosine-adenine-guanine (CAG) repeats of DRPLA gene in 708 probands of autosomal dominant ataxia pedigrees and 119 sporadic ataxia cases. Expanded CAG repeats of DRPLA gene were detected in probands of three ataxia pedigrees, with the numbers of repeats being 16/58, 16/58 and 14/54, respectively. In addition to ataxia, patients with adult-onset disease also exhibited spasm and neck torsion. Only three cases of DRPLA have been identified among 827 cases, which suggested that DRPLA is a relatively rare subtype of SCA in Chinese population. Clinical variation among the patients suggested DRPLA has a wide spectrum of phenotype.


Effects of replacing wheat starch with glycerol on methane emissions, milk production, and feed efficiency in dairy cows fed grass silage-based diets.
To lower the effect of climate change from cattle production, we should aim at decreasing their enteric methane emissions per kilogram of milk or meat. Glycerol may be absorbed through the rumen epithelium and would consequently be less available to microbes in the rumen. Glycerol could thus supply dairy cows with energy for milk production without contributing much to methane production. This study evaluated the effect of replacing wheat starch with glycerol on milk production, feed intake, and methane emissions. Twenty-two Swedish Red cows in mid lactation were used in a switch-back, change-over experiment with 3 periods of 21 d. The 2 dietary treatments consisted of a total mixed ration based on (g/kg of dry matter) grass silage (605), rapeseed meal (120), and barley (70) and either wheat starch or refined glycerol (200) fed ad libitum. The glycerol diet resulted in higher dry matter intake (21.6 vs. 20.1 kg/d) and methane emissions (482 vs. 423 g/d) compared with the diet containing wheat starch, whereas no difference was found in energy-corrected milk yield (28.4 vs. 29.7 kg/d). These results indicate that when glycerol is mixed with the feed, it is available to rumen microbes to a larger extent than initially assumed. Compared with wheat starch, adding refined glycerol (200 g/kg of dry matter) to the feed of dairy cows does not seem to have the potential to decrease enteric methane emissions.


Proteomic analysis of Trypanosoma cruzi developmental stages using isotope-coded affinity tag reagents.
Comparative proteome analysis of developmental stages of the human pathogen Trypanosoma cruzi was carried out by isotope-coded affinity tag technology (ICAT) associated with liquid cromatography-mass spectrometry peptide sequencing (LC-MS/MS). Protein extracts of the protozoan trypomastigote and amastigote stages were labeled with heavy (D8) and light (D0) ICAT reagents and subjected to cation exchange and avidin affinity chromatographies followed by LC-MS/MS analysis. High confidence sequence information and expression levels for 41 T. cruzi polypeptides, including metabolic enzymes, paraflagellar rod components, tubulins, and heat-shock proteins were reported. Twenty-nine proteins displayed similar levels of expression in both forms of the parasite, nine proteins presented higher levels in trypomastigotes, whereas three were more expressed in amastigotes.


Silk Fibroin/Tannin/ZnO Nanocomposite Hydrogel with Hemostatic Activities.
The inevitable bleeding and infections caused by disasters and accidents are the main causes of death owing to extrinsic trauma. Hemostatic agents are often used to quickly suppress bleeding and infection, and they can solve this problem in a short time. Silk fibroin (SF) has poor processibility in water, owing to incomplete solubility therein. In this study, aiming to overcome this disadvantage, a modified silk fibroin (SF-BGE), easily soluble in water, was prepared by introducing butyl glycidyl ether (BGE) into its side chain. Subsequently, a small amount of tannic acid (TA) was introduced to prepare an SF-BGE /TA solution, and ZnO nanoparticles (NPs) were added to the solution to form the coordination bonds between the ZnO and TA, leading to an SF-based nanocomposite hydrogel. A structural characterization of the SF-BGE, SF-BGE/TA, SF-BGE/TA/ZnO, and the coordination bonds between ZnO/TA was observed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and the phase change was observed by rheological measurements. The pore formation of the SF-BGE/TA/ZnO hydrogel and dispersibility of ZnO were verified through energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM). The cytocompatible and hemostatic performances of the SF-BGE/TA/ZnO NPs composite hydrogels were evaluated, and the hydrogels showed superior hemostatic and cytocompatible activities. Therefore, the SF-based nanocomposite hydrogel is considered as a promising material for hemostasis.


Efficacy and Safety of Vedolizumab and Tumor Necrosis Factor Inhibitors in the Treatment of Steroid-refractory Microscopic Colitis: A Systematic Review and Meta-analysis.
Tumor necrosis factor (TNF-α) inhibitors and the α4β7 integrin antagonist, vedolizumab, have been investigated as treatment options for patients with steroid-refractory microscopic colitis. To evaluate the benefit of vedolizumab and TNF-α inhibitors in patients with steroid-refractory microscopic colitis. Retrospective studies and case series involving patients with steroid-refractory MC who either received vedolizumab, adalimumab, or infliximab were eligible for inclusion. Pooled proportional meta-analyses were used to calculate the rate of clinical remission at induction, clinical response, maintenance of remission, histologic remission, and overall medication related adverse effects. Statistical analysis was performed in R using the metafor and meta packages. A total of 14 studies involving 164 patients were included. Pooled analysis showed a clinical remission rate of 63.5% [95% CI (0.483; 0.776), I2=43% P=0.08], 57.8% [95% CI (0.3895; 0.7571), I2=0%, P=0.7541], and 39.3% [95% CI (0.0814; 0.7492), I2=66%, P=0.02] for vedolizumab, infliximab, and adalimumab, respectively. The maintenance of remission rates were 65.9% [95% CI (0.389; 0.889), I2=67%, P=0.02], 45.3% [95% CI (0.1479; 0.7747), I2=0%, P=0.36] and 32.5% [95% CI (0.000; 0.8508), I2=53%, P=0.14] in patients who received vedolizumab, infliximab, and adalimumab, respectively. Rate of biological-related adverse events warranting discontinuation of therapy was 12.2%, 32.9%, and 23.0% for the vedolizumab, infliximab, and adalimumab groups, respectively. Vedolizumab and anti-TNF-α agents demonstrated a clinical benefit in the treatment of steroid-refractory microscopic colitis and with a tolerable safety profile. Future randomized controlled trials are needed to compare vedolizumab with TNF-α inhibitors and examine treatment effect on patients' quality of life.


[DNA image cytometry in urothelial carcinomas. A pilot study of a new application module of the Lucia G DNA analysis system].
To introduce and test a standardized measurement protocol for DNA image cytometry into a newly developed LUCIA G system application program. Contribution to a discussion concerning the possibility of using the histology sections for DNA image cytometry. Routine biopsy material from 18 urinary bladder cancer cases was analyzed (Grade 1: n = 6, Grade 2: n = 6, Grade 3: n = 6), both in histological and in cytoseparated preparations. More than one hundred diagnostic and more than 30 reference cells were measured. DNA features (mean DNA value, 2cDI, Böcking's grade of malignancy) and histogram types in Auer's classification (AI-IV) were compared. Most carcinomas measured were aneuploid (two thirds G1, all G2, G3). The most common histogram type was A IV. Malignancy grade was mostly slightly higher in cytoseparated material, the shape of the histogram was analogous. Two carcinomas looking euploid in histology sections were proven aneuploid in cytoseparation. More convenient tissue section measurement provided useful DNA profile information in most cases. Those without proven aneuploidy should be additionally measured in cytoseparations. An experienced pathologist meeting strictly measurement protocol demands is an important part of the measurement system.


The illness narratives of men involved in the criminal justice system: A study of health behaviors, chronic conditions and HIV/AIDS.
Former inmates encounter a variety of challenges when returning to their community, including poor health status and limited access to healthcare services. This qualitative study examined how former male inmates with chronic conditions perceived, understood, managed, and coped with their illnesses. The participants were Black and Puerto Rican, with a mean age of 47 years, who were interviewed within three years of their release. Participants reported at least one chronic condition, with 21 HIV-negative men using chaos narratives to depict their approach to disease management. Nine HIV-positive men used quest narratives to present their illnesses and were immediately linked to supportive services, enabling them to overcome the barriers to community reintegration. Applications: Health interventions in the area of forensic social work ought to focus on conducting Medicaid outreach and enrollment efforts prior to correctional facility discharge.


Fludarabine therapy in Waldenström's macroglobulinemia patients treated previously with 2-chlorodeoxyadenosine.
Six patients with Waldenström's macroglobulinemia (WM) resistant to previous 2-chlorodeoxyadenosine (2-CdA) therapy were treated with fludarabine. Both initial and subsequent therapy was administered according to the most widely used protocols. The median number of 2-CdA cycles given to the patients was 3.7 (range 2-5), while fludarabine was 1.7 (range 1-2). As a result partial remission was achieved in two patients and stabilization of the disease in the remaining four in spite of the inadequate response or progressive disease after 2-CdA therapy. Median monoclonal IgM concentration fell from 29.4 (range 11.6-37.1) to 16.4 g/l (range 3.8-29.1). At the same time hemoglobin concentration increased from median 114 (range 89-129) to 122 g/l (range 97-133). Side effects consisted of neutropenia (three patients) and thrombocytopenia (two patients). Two patients are alive with progression of the disease noted after 12 and 21 months of observation. One patient died as the result of cardiac disease, two others died of infection 5 and 16 months after cessation of therapy in the course of disease progression. The remaining patient was lost to follow-up after 10 months of observation with continuous stabilization. Our observations suggest that in WM patients resistant to 2-CdA, stabilization of the disease or even remission can be obtained with fludarabine.


Comparison of physical activity estimates using International Physical Activity Questionnaire (IPAQ) and accelerometry in fibromyalgia patients: the Al-Andalus study.
The International Physical Activity Questionnaire (IPAQ) has been widely used to assess physical activity in healthy populations. The present study compared physical activity assessed by the long, self-administrated version of the International Physical Activity Questionnaire with physical activity assessed by accelerometry in patients with fibromyalgia. A total of 99 (five men) participants with fibromyalgia completed the International Physical Activity Questionnaire and wore an accelerometer for nine consecutive days. We analysed the correlations of physical activity expressed as min · day(-1) of light, moderate, vigorous, and moderate to vigorous (MVPA) intensity, as well as time spent sitting, by the International Physical Activity Questionnaire and accelerometry by Spearman correlations. Bland and Altman plots were performed to verify the agreements between both instruments. The results showed weak yet significant correlations (Rs = 0.15-0.39, all P < 0.05) in all physical activity intensities between the two instruments, except for sedentary time. The highest correlations were observed for physical activity at home or in garden (Rs = 0.297, P < 0.01). The results suggest that the long self-administrated International Physical Activity Questionnaire is a questionable instrument to assess physical activity in patients with fibromyalgia. Therefore, physical activity measurement in fibromyalgia patients should not be limited solely to self-reported measures.


Existence of solutions of an impulsive integro-differential equation with a general boundary value condition.
In this paper, we discuss the existence of solutions for a first-order nonlinear impulsive integro-differential equation with a general boundary value condition. New comparison principles are developed, and existence results for extremal solutions are obtained using the established principles and the monotone iterative technique. The results are more general than those of the periodic boundary problems, which may be widely applied in this field.


A look through dark-colored glasses: The Dark Tetrad and affective processing.
The Dark Tetrad personality traits (i.e., narcissism, Machiavellianism, psychopathy, and sadism) have been continuously linked to various deficits in affective reactivity. The aim of this study was to examine the relationship of the Dark Tetrad and processing of emotional pictures. A total of 144 participants (56.9% female, Mage = 22.18, SDage = 2.26) completed measures of the Dark Tetrad, and rated pictures selected form the International Affective Picture System (IAPS), classified in accordance with their norms into highly arousing positive and negative. Affective processing measures included participants' valence and arousal ratings, while cognitive processing was measured my means of the response latency for each response. The results showed that the dark traits were related only to valence, but not arousal ratings. Higher narcissism and lower sadism were associated with more positive valence ratings of positive pictures, and higher sadism was associated with more positive ratings of negative pictures. Moreover, higher Machiavellianism predicted faster assessment of valence and arousal of both positive and negative pictures, and higher sadism predicted slower assessment of negative pictures' valence. Obtained results indicate that deficiencies in affective processing are more pronounced in sadism compared to other dark traits, while Machiavellianism is associated with advantages in cognitive processing, highlighting their significance and uniqueness in the Dark Tetrad constellation.


The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains elusive. Using SILAC and quantitative mass spectrometry, we examined the effects of activation of the miR-17-92 cluster on global protein expression in neuroblastoma (NB) cells. Our results reveal cooperation between individual miR-17-92 miRNAs and implicate miR-17-92 in multiple hallmarks of cancer, including proliferation and cell adhesion. Most importantly, we show that miR-17-92 is a potent inhibitor of TGF-β signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-β signaling cascade as well as direct inhibition of TGF-β-responsive genes.


Evaluation of different low-dose multidetector CT and cone beam CT protocols in maxillary sinus imaging: part I-an in vitro study.
This in vitro study aimed to assess radiation dose and image quality of different low-dose multidetector CT (MDCT) and CBCT imaging protocols in comparison with the standard MDCT protocol for maxillary sinus imaging. Effective dose (E) and image quality of 10 MDCT (changing effective milliampere second starting from 141.3 EmAs to 20 EmAs) and 3 CBCT protocols (changing milliampere second and voxel size) were assessed throughout scanning an anthropomorphic head and neck Alderson Rando phantom. E values were calculated using thermoluminescent dosemeters (TLDs) fixed at 6 sensitive organs (14 sites) on the Rando phantom. Image quality was assessed objectively (by calculating the standard deviation values of the radiographic density of water) and subjectively (by assessing the diagnostic image quality using a four-graded scale: 1 = very good, 2 = good, 3 = acceptable and 4 = unacceptable). Two MDCT protocols (120 kV/32 EmA and 120 kV/25 EmA) had lower radiation doses with statistically significant differences (p < 0.001) compared with that of the standard MDCT protocol (120 kV/141.3 EmA), and they preserved a good diagnostic image quality. One CBCT protocol (120 kV/20 mA) had a reasonable radiation dose and good image quality. There were no statistically significant differences between the above-mentioned lower dose MDCT and CBCT protocols (p > 0.05) with respect to the radiation dose and image quality. The low-dose MDCT and CBCT protocols are viable methods for maxillary sinus examination as evaluated using the above-mentioned phantom that yield a good diagnostic image quality using E approximately 7 and 11 times lower than that of the standard MDCT, respectively. These findings were evaluated in the in vivo part of this project.


Indomethacin, but not dazoxiben, reduced lung fluid filtration after E. coli infusion.
Goats were divided into three groups and given infusions of live Escherichia coli bacteria. Group I received no treatment, group II was treated with indomethacin (a cyclooxygenase inhibitor), and group III with dazoxiben (a thromboxane synthase inhibitor). Double indicator-dilution extravascular lung water (EVLW) in group I was significantly different from the treated groups. There was an early increase in EVLW in group I and group III but not in group II animals. At 6 h EVLW's in group I, group II, and group III were 100, 45, and 30% above base line, respectively. Lymph flow (QL) and lymph-to-plasma protein ratio (L/P) was not statistically different between groups. Estimated total fluid filtration [QL + d(EVLW)/dt] in group I and III was markedly elevated between 0 and 1.5-2 h after E. coli infusion. Cardiac output (QT) decreased to 40% of base line in group I, and it decreased slightly in group II because of the indomethacin but did not decrease after E. coli. QT decreased in group III but recovered more rapidly than group I. Mean pulmonary arterial pressure increased more rapidly in group I and reached a higher peak than either treated group. At 6 h these groups had similar pulmonary arterial and pulmonary arterial wedge pressures. We conclude that 1) indomethacin but not dazoxiben blocks the early increase in total fluid filtration after bacterial infusion, 2) dazoxiben does not prevent the increased endothelial permeability resulting from infusion of live bacteria, and 3) indomethacin may somewhat ameliorate the endothelial permeability change.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of CYP2C19 gene polymorphism on the eradication rate of Helicobacter pylori by proton pump inhibitors-containing regimens in Asian populations: a meta-analysis.
Premise: The effects of proton pump inhibitors (PPI) depend on metabolic enzyme CYP2C19 that has different activity due to gene polymorphism. The purpose of this meta-analysis is to determine the potential effects of CYP2C19 polymorphism on the efficiency of PPI-based treatment. Materials & methods: The PubMed, EMBASE, Cochrane Library, etc. were searched for relevant articles published in English or Chinese from inception to 31 May 2020. Finally, 26 randomized controlled trials and 15 cohort studies met the inclusion criteria and used for the meta-analysis via STATA version 15. Results: Poor metabolizer (PM) genotype Helicobacter pylori eradication rates were highest for Asian individuals receiving triple or quadruple first-line therapy based on PPIs (p < 0.05). CYP2C19 polymorphism could influence H. pylori eradication rate only in Mainland China and Japan (p < 0.05). Conclusion: PM genotype facilitates the elimination of H. pylori in Asian populations. Rabeprazole-, esomeprazole- and pantoprazole-based eradication program was less affected by the CYP2C19 polymorphism.


Comparison of computer-key-hold-time and alternating-finger-tapping tests for early-stage Parkinson's disease.
Giancardo et al. recently introduced the neuroQWERTY index (nQi), which is a novel motor index derived from computer-key-hold-time data using an ensemble regression algorithm, to detect early-stage Parkinson's disease. Here, we derive a much simpler motor index from their hold-time data, which is the standard deviation (SD) of the hold-time fluctuations, where fluctuation is defined as the difference between successive natural-log of hold time. Our results show the performance of the SD and nQi tests in discriminating early-stage subjects from controls do not differ, although the SD index is much simpler. There is also no difference in performance between the SD and alternating-finger-tapping tests.


Expression profiles of protein tyrosine kinase genes in human embryonic stem cells.
Complex signaling pathways operate in human embryonic stem cells (hESCs) and are coordinated to maintain self-renewal and stem cell characteristics in them. Protein tyrosine kinases (PTKs) participate in diverse signaling pathways in various types of cells. Because of their functions as key molecules in various cellular processes, PTKs are anticipated to have important roles also in hESCs. In this study, we investigated the roles of PTKs in undifferentiated and differentiated hESCs. To establish comprehensive PTK expression profiles in hESCs, we performed reverse transcriptase PCR using degenerate primers according to the conserved catalytic PTK motifs in both undifferentiated and differentiated hESCs. Here, we identified 42 different kinases in two hESC lines, including 5 non-receptor tyrosine kinases (RTKs), 24 RTKs, and 13 dual and other kinases, and compared the protein kinase expression profiles of hESCs and retinoic acid-treated hESCs. Significantly, up- and downregulated kinases in undifferentiated hESCs were confirmed by real-time PCR and western blotting. MAP3K3, ERBB2, FGFR4, and EPHB2 were predominantly upregulated, while CSF1R, TYRO3, SRC, and GSK3A were consistently downregulated in two hESC lines. Western blot analysis showed that the transcriptional levels of these kinases were consistent with the translational levels. The obstruction of upregulated kinases' activities using specific inhibitors disturbed the undifferentiated status and induced the differentiation of hESCs. Our results support the dynamic expression of PTKs during hESC maintenance and suggest that specific PTKs that are consistently up- and downregulated play important roles in the maintenance of stemness and the direction of differentiation of hESCs.


Habitat shape, metapopulation processes and the dynamics of multispecies predator-prey interactions.
1. The effects of habitat shape, connectivity and the metapopulation processes of persistence and extinction are explored in a multispecies resource-consumer interaction. 2. The spatial dynamics of the indirect interaction between two prey species (Callosobruchus chinensis, Callosobruchus maculatus) and a predator (Anisopteromalus calandrae) are investigated and we show how the persistence time of this interaction is altered in different habitat configurations by the presence of an apparent competitor. 3. Habitat structure has differential effects on the dynamics of the resource-consumer interaction. Across all habitat types, the pairwise interaction between C. chinensis and A. calandrae is highly prone to extinction, while the interaction between C. maculatus and A. calandrae shows sustained long-term fluctuations. Contrary to expectations from theory, habitat shape has no significant effect on persistence time of the full, three-species resource-consumer assemblage. 4. A stochastic metapopulation model for a range of habitat configurations, incorporating different forms of regulatory processes, highlights that it is the spatially explicit population dynamics rather than the shape of the metapopulation that is the principal determinant of interaction persistence time.


Visual Mechanism Characteristics of Static Painting Based on PSO-BP Neural Network.
Static painting works have independent theme significance in the framework of Chinese painting history, and their overall structure, lightness structure, and color structure all show different characteristics of visual mechanism. In order to extract the visual mechanism features effectively, this experiment uses the PSO algorithm to optimize the BP neural network, constructs the PSO-BP neural network for feature recognition and extraction, and compares it with the training results of other algorithms. The results show that the prediction accuracy, recognition accuracy, and ROC curve of PSO-BP neural network are high, which shows that the convergence of PSO-BP neural network is good, and it can effectively complete the recognition and analysis of people and effectively extract the visual mechanism features of static writing paintings.


Simplified high performance liquid chromatographic quantitation of antipyrine.
Antipyrine is used as an index of hepatic drug metabolism. The authors devise a simple and rapid high performance liquid chromatography method to quantitate antipyrine in serum with small volume (50 microliters). Minimal sample preparation is needed and the assay is sensitive to concentrations of 0.2 micrograms/ml. Mobile phase consists of 35% methanol in 67 mM phosphate buffer pH 3.5 with antipyrine detected by monitoring the eluate at 225 and 254 nm. Within-run and run-to-run coefficients of variation are less than or equal to 2.8 and 4.6%, respectively. Recoveries from serum average 100.8%. It is concluded that this technique for antipyrine is simple, rapid, and well characterized.


Ras Association Domain Family 1A Gene Promoter Methylation as a Biomarker for Chronic Viral Hepatitis C-related Hepatocellular Carcinoma.
Background One of the most prevalent aberrant epigenetic modifications found in hepatocellular carcinoma (HCC) is abnormal DNA methylation. Our study aimed to evaluate serum Ras association domain family 1A (RASSF1A) gene promoter methylation in patients with chronic viral hepatitis C (HCV)-associated liver cirrhosis with and without HCC as a potential new marker for the early detection of HCC. Methodology The 60 participants who participated in the trial were divided into the following three groups: 20 patients with newly diagnosed primary HCC on top of HCV-related liver cirrhosis, 20 patients with HCV-related liver cirrhosis, and 20 age- and sex-matched healthy individuals as a control group. All participants underwent methylation-specific polymerase chain reaction testing to detect the blood level of the RASSF1A gene's methylated promoter. Results Methylated RASSF1A was found in 30% of patients with liver cirrhosis caused by HCV and in 65% of patients with HCC, but not in any of the controls. It was discovered that the serum methylation RASSF1A had an accuracy of 82.50% and an area under the curve (AUC) of 0.825 for separating HCC patients from healthy controls. With an AUC of 0.675 and an accuracy of 67.50%, it was able to differentiate patients with HCC from those with HCV-related liver cirrhosis. Additionally, there was no statistically significant association between RASSF1A methylation status and HCC mass size (p = 0.449). Conclusions Serum RASSF1A promoter methylation status detection could be useful for detecting HCC early, especially in high-risk individuals such as those with HCV.


Stimulus intensity affects the latency but not the amplitude of the N2pc.
The N2pc component of the event-related potential (ERP) is an index of visual-spatial attention. It is not clear whether the N2pc reflects pure top-down attentional activity or an interaction of top-down activity with bottom-up sensory activity. Here, we manipulated stimulus intensity of the items composing the target display. Although the amplitude of the P1 component increased monotonically with increasing stimulus intensity, the amplitude of the N2pc did not vary with stimulus intensity. Instead, the onset latency of the N2pc was delayed for weaker stimuli, suggesting that the strength of the selection cue (target color) influenced the moment at which attention was deployed. The results reveal one way in which early sensory ERP amplitude differences are converted into later latency differences.


A model for determining baseline morphometrics of the capillary bed in skeletal muscle.
Changes in capillary diameter (CD) have been used to detect the effect of pharmacological interventions, physical treatments and ischaemic reperfusion injury in skin and muscle. For comparison, CDs within similar structures in the untreated limb of the same subject have been used as the control, with the assumption that CDs are the same in both limbs. This study employs light microscopic morphometry (LMM) to explore this premise, investigates the repeatability of LMM and determines the number of CDs that should be measured to produce a reliable result. Muscle biopsies were obtained from the left (L) and right (R) vastus lateralis of four rabbits and the left and right tibialis anterior of three vervet monkeys. Thin (1-micro m) resin sections were prepared for LMM examination and CDs were measured using computerised image analysis. To determine the repeatability of measurement, two specimens were re-measured on five occasions at monthly intervals. The mean CD of each biopsy from L and R limbs were compared and the number of measurements necessary to produce a result with less than a 3% difference was determined. A minimum of 58 and a maximum of 175 CDs were measured from each specimen. Repeated measurement of the same biopsies showed a non-significant mean difference of less than 2% in CD means between the first measurement and each of the four subsequent measurements. There was a non-significant difference of 3.7% in CD means between R and L limbs in one animal, in which less than 70 CDs were measured on each side. When 100 CDs or more were measured, the difference was always less than 2.3%. When grouped, the difference in CD means between L and R limbs was 0.5% in rabbits and 2.0% in vervet monkeys. The results confirm that firstly, CD data derived from a muscle in an untreated limb can be used as a control for experiment-mediated changes of CD in the other; secondly, LMM appears to be a reliable means of measuring CD; and thirdly, while fewer measurements may suffice, ideally 75-100 CDs are needed to provide a dependable result.


Can remifentanil be a better choice than propofol for colonoscopy during monitored anesthesia care?
This prospective, randomized trial was designed to test the hypothesis that continuous infusion of low-dose remifentanil can provide effective analgesia, sedation, amnesia, patient comfort and stable recovery profile without respiratory depression when compared with propofol infusion during colonoscopy. One hundred patients were randomly assigned to receive either remifentanil (group R, 0.5 microg/kg followed by 0.05 microg/kg/min, n = 50) or propofol (group P, 0.5 mg/kg followed by 50 microg/kg/min, n = 50). Supplemental doses of remifentanil 12.5 microg in group R and propofol 10 mg in group P were given to treat complaints of moderate to severe pain and discomfort. Hemodynamic and respiratory data, pain, discomfort and sedation scores, patient and gastroenterologist satisfaction and recovery profiles were recorded. The duration of colonoscopy was longer in group P. The mean arterial pressure, heart rate and end-tidal CO2 remained stable during the procedure and were comparable between the groups. After bolus injection of the study drugs, the respiratory rate and oxygen saturation values were lower in group R than in group P. Only one patient in group R required airway support. Pain and discomfort scores were better in group R than in group P. Sedation levels were higher in group P than in group R. Group P needed more supplemental doses than group R. The time to reach an Aldrete score of nine or more was shorter in group R, but discharge times were similar in the two groups. Amnesia was better in group P. Nausea and vomiting were more frequent in group R during the recovery phase. Low-dose remifentanil infusion with intermittent bolus injections can provide adequate sedation, amnesia and better analgesia than propofol infusion during colonoscopy. However, remifentanil-induced nausea and vomiting may be a problem during the recovery phase.


AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation.
AMP-activated protein kinase (AMPK) inhibits IGF-I actions, but the mechanism by which AMPK functions is undefined. This study identified signaling events that were induced by AMPK that mediated inhibition of IGF-I-stimulated phosphoinosotide-3-kinase (PI3K) pathway activation. The AMPK activator metformin stimulated AMPK Thr172 phosphorylation and inhibited IGF-I-stimulated phosphorylation of Akt/tuberous sclerosis 2 (TSC2)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K). Expression of constitutively active forms of AMPK suppressed IGF-I-stimulated activation of Akt/TSC2/mTOR/p70S6K and protein synthesis, whereas AMPK knockdown resulted in enhanced responses to IGF-I. To determine the mechanism by which AMPK inhibited IGF-I signaling, the role of insulin receptor substrate-1 (IRS-1) was examined. Both metformin and constitutively activated AMPK enhanced phosphorylation of IRS-1 Ser794, which led to decreased IRS-1 tyrosine phosphorylation and recruitment of the p85 subunit of PI3K. Overexpression of IRS-1 S794A was associated with increased IGF-I-stimulated IRS-1 tyrosine phosphorylation, p85 association, and protein synthesis. To determine whether other signaling molecules mediated the effect of AMPK, TSC2 function was examined. Cells overexpressing TSC2/S1345A (the site of AMPK phosphorylation) were less responsive to metformin-induced inhibition of p70S6 kinase. These findings are relevant to whole animal physiology because administration of metformin to mice resulted in inhibition of IGF-I-stimulated phosphorylation of Akt/mTOR/p70S6K. In conclusion, AMPK functions to inhibit IGF-I-stimulated PI3K pathway activation through stimulation of IRS-1 serine 794 phosphorylation. Because IGF-I is an important stimulant of the anabolic response, this effect of AMPK could account for part of its inhibitory effect on protein synthesis, thus allowing more efficient energy use by other cellular processes.


Fast, Multiple-Use Optical Biosensor for Point-of-Care Glucose Detection with Mobile Devices Based on Bienzyme Cascade Supported on Polyamide 6 Microparticles.
Non-invasive glucose determination provides major advantages in health monitoring and protection. It enables widespread point-of-care testing, which is affordable, sensitive, specific, rapid and equipment-free. This work reports on the development and analytical performance of a colorimetric biosensor in detecting glucose in human urine. Highly porous polyamide microparticles were synthesized as the support for the glucose oxidase (GOx) and horseradish peroxidase (HRP) dyad, which was immobilized randomly or consecutively-first HRP and then GOx. The latter system was superior, as GH@PA-C showed much higher activity than the random system, and it was used to prepare the biosensor, along with the 3,3',5,5'-tetramethylbenzidine chromogen. When in contact with urine, the biosensor displayed a strict linear correlation between the color difference and the glucose concentration in urine in the range of 0.01-3.0 mM, as established by the CIELab image processing algorithm and UV-VIS measurements. The biosensor acted in 20 s and had a detection limit of 30.7 µM in urine, high operational activity at pH = 4-8 and unchanged detection performance after 30 days of storage. Its unique feature is the possibility of multiple consecutive uses without the serious deterioration of the recovery and dispersion values. These characteristics can open the way for new routines in non-invasive personal diabetes detection.


[Subcloning of human neurotrophin-3 gene and construction of its genetically engineered cell model].
To subclone human neurotrophin-3 gene (NT3) and transfer this gene into human bone marrow mesenchymal stem cells (BM-MSCs) to construct genetically engineered cells that produce NT3 in vitro. Human BM-MSCs were cultured in low-glucose DMEM supplemented with 10% fetal bovine serum and 10 ng/ml epidermal growth factor. Flow cytometry (FCM) was used to examine the phenotypes of the cells. The eukaryotic expression vector pcDNA3.1(+)/NT3 was constructed and transferred into human BM-MSCs in vitro via liposomes. The genetically engineered BM-MSCs were selected several times with G418 and the clones were obtained and then amplified, followed by extraction of the RNA for detection of NT3 gene expression by reverse transcriptional (RT) PCR. The biological activity of the genetically engineered cells was examined by the collecting the supernatant of the culture medium for incubation of guinea pig cochlea hair cells. The cultured cells expressed CD13, CD29 and CD59, but no7 CD11, CD14, CD31, CD34, CD45, CD80, CD86, CD117 or HLA-DR. The BM-MSCs genetically modified with pcDNA3.1(+)/NT3 not only expressed and produced NT3, but also promoted the survival of the guinea pig cochlea hair cells in vitro. It is possible to construct the genetically engineered BM-MSCs that excrete NT3 in vitro.


Onset in the seventh decade and lack of symptoms in heterozygotes for the TTRMet30 mutation in hereditary amyloid neuropathy-type I (Portuguese, Andrade).
In a Portuguese-American family with hereditary amyloid neuropathy (familial amyloidotic polyneuropathy), onset was in the seventh decade in all affected relatives. Another unusual characteristic was their origin from the Portuguese island of Madeira. In spite of this, the mutant transthyretin (TTRMet30) (the same variant prealbumin that is the circulating precursor of AFP protein in the classic Portuguese patients) could be found in the propositus' plasma. In addition, three other asymptomatic relatives (ages 90, 73, and 48) were shown to carry the mutation. Late onset and incomplete penetrance, at a clinical level, raise problems for presymptomatic detection of mutant TTR, as these tend to cluster in families. When counseling asymptomatic heterozygotes, we must consider intra-familial correlation in age-of-onset, and the distribution of age-of-onset including age of unaffected heterozygotes. This family poses interesting questions regarding pathogenesis of this degenerative process and the influence of other genetic factors, such as modifiers, epistasis, and polymorphism of the TTR genes or their regulators. A cis-effect of a gene linked to the mutant gene, decreasing the synthesis of the mutant TTR and keeping a sufficient amount of the normal one in circulation, or producing some cofactor for TTR, could also explain late onset and apparently incomplete penetrance; the occasional finding of classic forms in these families would be the result of recombinatory events.


The association of memory disorders and chronic HIV disease in the antiretroviral therapy era: a systematic literature review.
Despite recent pharmacological progress, memory impairment is still frequently reported in people living with HIV. We aimed to conduct a systematic literature review investigating the presence of impairment of (sub)components of memory function in patients prescribed highly active antiretroviral therapy (ART). We adopted a cognitive neuropsychological model of memory function as the theoretical framework, distinguishing between a short-term working memory component and a long-term component of memory, along with their specific (sub)components. We systematically searched for the presence of impairment of each (sub)component in the selected papers. Careful consideration was given to study design and methods and control of covariates. Only the central executive component of working memory has been consistently reported to be impaired in HIV infection. The other two (sub)components, namely the phonological loop and the visuospatial sketchpad, were unimpaired. Discordant results have been obtained as to verbal and visual episodic memory, as some authors reported an association with HIV infection, whereas others did not. There is little evidence for semantic memory deficit in HIV infection, while there are suggestions that the neural substrate of implicit memory may be damaged by the effects of HIV infection and inflammation. Most studies in this area have been conducted in small samples and with poor control for covariates. Thus, conclusions regarding the association of memory dysfunction with HIV infection are hampered by methodological issues such as selection bias and unmeasured confounding. The task remains for future research to ascertain the impact of HIV infection on memory function.


[Observation on two kinds of recombinant hepatitis B vaccines used in populations with different immunity].
To evaluate the immunity status on different hepatitis B vaccines currently being used in Beijing. College students who had not received hepatitis B vaccine and children who had received whole-course immunization at birth, were tested HBsAg, anti-HBs and anti-HBc. All the test-negative cases were served as research subjects. 3 doses recombinant hepatitis B vaccines were given to the college students, following the 0, 1, 6 months schedule. Among which, 140 cases received recombinant beer yeast hepatitis B vaccine (BY vaccine, 10 microg, 5 microg, 5 microg), and 140 cases with recombinant hansenula polymorpha hepatitis B vaccine (HP vaccine, 10 microg, 10 microg, 10 microg). 1 dose was given for boosting immunization to 98 children, in which 49 cases with BY vaccine (5 microg) and 49 cases with HP vaccine (10 microg). Anti-HBs was tested 1 month after. The total positive (> or = 10 mIU/ ml) rate was lower among BY vaccine group than HP vaccine group for the college students (93.5 %, 99.3% , P<0.05), but no statistical difference on GMT(81.2 mIU/ml, 94.6 mIU/ml, P>0.05) was found. For males, the positive rate and GMT were lower in BY vaccine group than in HP vaccine group (85.7% ,100.0%, P<0.01)(56.6 mIU/ml, 98.6 mIU/ml, P<0.01), but with no statistical difference for females (98.8%, 98.5%, P> 0.05) (103.4 mIU/ml, 90.3 mlU/ml, P> 0.05). For the same vaccine, the positive rate and GMT were lower in males than in females when using BY vaccine (85.7% , 98.8%, P<0.01)(56.6 mIU/ml,103.4 mIU/ml, P< 0.01), but no statistical difference was found on HP vaccine(100.0%, 98.5%, P>0.05)(98.6 mIU/ml, 90.3 mIU/ml, P>0.05). The positive rate of anti-HBs was decreasing along with age among the children who had received a whole-course immunization at birth (P <0.01). 98.6 % of the 70 negative cases appeared positive conversion after receiving 1 dose and the GMT raised significantly by 15 times. No statistical difference was found between the two kinds of vaccines(100.0%, 97.4%, P>0.05)(80.5 mIU/ml, 68.5 mIU/ml, P>0.05). The type of vaccine and sex were related to the effects, better with HP vaccine than BY vaccine in males but was the same for females in adults receiving basic immunization according to the conventional doses. Both kinds of vaccines were ideal when children receiving boosting immunization. The immune memory was good for persons who had received primary immunization with recombinant vaccine but antibody appeared negative conversion. It was not necessary to boost immunization within 6 years after a whole-course immunization with recombinant hepatitis B vaccine in infancy.


Sulfonated poly(styrene-b-ethylene-co-butylene-b-styrene) and fullerene composites for ionic polymer actuators.
Ionic polymer-metal composite (IPMC) actuators employing sulfonated poly(styrene-b-ethylene-co-butylene-b-styrene) (SSEBS) ionomer and fullerene-C60 composite membrane were developed. Due to the poor electroactive performance of IPMC actuators employing pure SSEBS, fullerenes as the reinforcement agent are incorporated. The bending responses under both direct current (DC) and alternating current (AC) excitations were investigated. Compared with the actuator based on pure SSEBS, the tip displacement of IPMC actuator based on Fullerene-SSEBS composites has great improvement under DC excitations, and also the responses are quick and harmonic under AC excitations. More meaningful improvement is that Fullerene-SSEBS based IPMC actuators don't have back relaxation towards the cathode under DC activation for a long time. SEM study was carried out on the samples of Fullerene-SSEBS actuators. Platinum layers were finely synthesized on the interfaces of Fullerene-SSEBS actuators. Present results show that the fullerene, C60, can be successfully applied to reinforce the electro-mechanical properties of the ionic polymer metal composite actuators.


Development of a Foundations of Simulation Teaching Course for Nurse Educators.
Academic leaders in a college of nursing were faced with an increasing need to integrate high quality simulations into their undergraduate curriculum; however, there was a general lack of expertise in the subject area among faculty. The leaders supported the development of an online course that focused on improving foundational simulation knowledge. The course, developed through collaboration between a faculty simulation expert and an instructional designer, was specifically designed to focus on key simulation objectives to improve the simulation skill set of faculty. Posttest scores revealed an increase in simulation knowledge.


A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge.
C3H/HeN female mice were vaccinated with native Chlamydia muridarum major outer membrane protein (MOMP), using Montanide+CpG or Alum+CpG as adjuvants. Negative control groups were immunized with ovalbumin (OVA) and the same adjuvants. As positive control, mice were inoculated intranasally with live Chlamydia. Mice were challenged in the ovarian bursa with 10(5) C. muridarum inclusion forming units. Six weeks after the genital challenge the animals were caged with male mice and monitored for pregnancy. Mice vaccinated with MOMP+Montanide+CpG developed high levels of C. muridarum-specific antibodies, with a high IgG2a/IgG1 ratio and neutralizing titres. Animals immunized using Alum+CpG had low antibody levels. Cellular immune responses were significantly higher in mice vaccinated with MOMP and Montanide+CpG, but not with Alum+CpG, when compared with negative controls. Following the genital challenge, only 20% (4/20) of mice vaccinated with MOMP+CpG+Montanide had positive vaginal cultures whereas 100% (9/9) of mice immunized with MOMP+CpG+Alum had positive cultures. Of the positive control animals inoculated with live Chlamydia only 15% (3/20) had positive vaginal cultures. In contrast, 100% (20/20) of mice immunized with OVA+CpG+Montanide, or minimal essential medium, had positive cultures. Following mating, 80% (16/20) of mice vaccinated with MOMP+CpG+Montanide, and 85% (17/20) of animals inoculated intranasally with live C. muridarum carried embryos in both uterine horns. No protection against infertility was observed in mice immunized with MOMP and CpG+Alum or OVA. In conclusion, this is the first time that a subunit vaccine has been shown to elicit a protective immune response in the highly susceptible C3H/HeN strain of mice against an upper genital challenge.


Primary angiosarcoma of aorta: A systematic review.
To elucidate the epidemiology, anatomical, presentation, classification, pathology, investigative modalities, management and prognosis of primary angiosarcoma of the aorta. A systematic review of literature from the database inception to January 2021 in PubMed and Embase, CINAHL and Cochrane Library in accordance to PRISMA was conducted. Retrieval and extraction was performed by two independent reviewers. The hierarchy of the evidence was assessed through the National Institute for Health and Care Excellence Checklist. Data were subjected to pooled prevalence analysis, Kaplan-Meier survival and test of probability using log-rank analysis. This review is registered with International Prospective Register of Systematic Reviews: RD42021231314. 82 studies with n = 123 cases met the inclusion criterion. Abdominal (45%) aorta was the commonest anatomical site with female predominance in ascending aorta (4:1) and aortic arch (2:1). The longest survival was in the ascending aorta and the shortest in the abdominal aorta [540 (interquartile range [IQR], 7-1560 days vs. 180 (IQR, 1-5730 days)], respectively. The overall median survival was 210 days (IQR, 1-5730 days) or 7 months. Lack of metastasis (47%) was a marker of longer survival (p < 0.03) irrespective of other attributes. The pathophysiology appears to be a trend of increasing fatigue, fever and weight loss associated with segmental dysfunction of the aorta projecting occlusive or destructive phenotypes. Computed tomography angiography features of volume-occupying, bulky, polypoid (intraluminal), protrusive vegetation, hyper vascular without atherosclerotic lesions are extremely suggestive of PA of the aorta at 5th and 6th decades of life.


Long-term memory of a DRL task in mature and aged rats.
Mature (6 mo.) and aged (26 mo.) rats were trained on a DRL 6-sec schedule. In order to produce equivalent levels of task performance, the mature rats were trained for 16 sessions while the aged rats were trained for 20 sessions. After a 21-day interval, rats were tested for retention of the DRL task. No age-related differences in LTM of the DRL task were found. If the DRL schedule is considered an analog of a recall task, the present results do not agree with Campbell et al. (1980) who found age differences in retention of a FI schedule after 8 days of training. In the present experiment animals were more extensively trained on the task to be remembered. Thus, the present experiment suggests that an age-related difference in LTM, even on recall tasks, will not be significant if aged animals are overtrained on the task to be remembered.


Body Composition, Anthropometric Parameters, and Strength-Endurance Characteristics of Sport Climbers: A Systematic Review.
Ginszt, M, Saito, M, Zięba, E, Majcher, P, and Kikuchi, N. Body composition, anthropometric parameters, and strength-endurance characteristics of sport climbers: a systematic review. J Strength Cond Res 37(6): 1339-1348, 2023-Sport climbing was selected to be part of the Summer Olympic Games in Tokyo 2021 with 3 subdisciplines: lead climbing, speed climbing, and bouldering. The nature of physical effort while speed climbing, lead climbing, and bouldering performance is different. This literature review aimed to describe differences between body composition, anthropometric parameters, and upper-limb strength-endurance variables between sport climbers with different ability levels and nonclimbers. The following databases were searched: PubMed and Scopus. The following keywords were used: "sport climbing," "rock climbing," "lead climbing," and "bouldering." Articles were considered from January 2000 to October 2021 if they concerned at least one of the following parameters: body composition (mass, body mass index, body fat, lean muscle mass, bone mineral density), anthropometric parameters (height, ape index), muscle strength (MVC finger strength in half-crimp grip, MVC finger strength to body mass, handgrip strength), and muscle endurance (force time integral, pull-ups). A review shows that body mass and body fat content were lower in the sport climbers compared with controls and in elite sport climbers compared with those less advanced. Sport climbers presented higher values of MVC finger strength in half-crimp grip, MVC finger strength to body mass, handgrip strength, and force time integral parameter than control subjects. Significantly higher MVC values in half-crimp grip were observed in elite sport climbers than in advanced athletes. None of the analyzed work showed differences between sport climber groups in the ape index. The abovementioned parameters may be a key factor in elite sport climbing performance.


Factors in predicting outcome from operation in patients with prolactin-secreting pituitary adenomas.
Forty female patients with pituitary adenomas were studied retrospectively to determine whether factors could be identified that would help predict outcome from operation. Twenty-five patients had a normal prolactin level (less than or equal to 30 ng/ml) during the early postoperative period (less than or equal to 3 months) and 15 patients had persistent disease (prolactin greater than 30 ng/ml). Nine of the 25 patients who initially had normal prolactin levels during the early postoperative period were found to have elevated prolactin levels during the late postoperative period (greater than 3 months). As has been shown previously, tumor size and preoperative prolactin levels were important factors in predicting surgical outcome. Patients with smaller (Hardy Grades I and II) tumors had significantly better outcome than those with larger (Hardy Grades III and IV) tumors. Patients with successful surgical outcomes had significantly lower preoperative prolactin values (204 ng/ml) than those with operative failures (524 ng/ml). In addition to the known factors, the patient's age at the time of operation, the length of amenorrhea, and the patient's growth hormone response to insulin hypoglycemia were newly identified as factors that helped predict surgical outcome. Patients who were less than or equal to 26 years of age and who had had amenorrhea for less than or equal to 6 years at the time of operation had significantly better surgical outcomes. Patients with normal growth hormone responses to stimulation testing had significantly better surgical outcomes than those with a blunted preoperative growth hormone response. The data suggest that prolactin-secreting pituitary tumors may cause a progressive disorder for which operative cure may be obtained only early in the disease.


Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: a placebo-controlled trial.
Cannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research. The individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions. Cannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of 'stoned' and 'dizzy' induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure. Relative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences.


Effect of nourseothricin (streptothricin) on the outer membrane of sensitive and resistant Escherichia coli strains.
Nourseothricin (streptothricin) causes disturbances (perforations) in the outer membrane of sensitive E. coli strains allowing lysozyme and deoxycholate, but not the periplasmic alkaline phosphatase to penetrate. EDTA slightly increases, but Mg++ ions slightly decrease this effect. The cell walls of three from four nourseothricin-resistant strains do not become permeable under these conditions, but remain sensitive against TRIS/EDTA. Nourseothricin is supposed to pass the outer membrane of sensitive bacteria via some kind of "self-promoting" pathway. This way can (but need not) be blocked in resistant strains.


Health-related quality of life and disability in patients with rheumatoid, early rheumatoid and early psoriatic arthritis treated with etanercept.
To assess health-related quality of life (HR-QoL) in patients with Rheumatoid arthritis (RA), early RA and early psoriatic arthritis (PsA), and to evaluate the efficacy of etanercept in reducing disability. Twenty healthy volunteers, 40 RA, 20 early RA and 20 early PsA patients were recruited. All patients received etanercept plus methotrexate. Assessments at baseline and after 2 years' therapy included Disease Activity Scores on 44 joints [DAS(44)], Health Assessment Questionnaire (HAQ) scores and Short Form-36 (SF-36) scores. HAQ and SF-36 scores were significantly worse in patients with RA, early RA or early PsA than in healthy volunteers. The HAQ score at baseline was significantly higher in RA patients than in patients with early RA or early PsA, whereas the scores were similar in patients with early RA and early PsA. Patients with early RA had greater impairment than patients with early PsA in several areas of disability. After 2 years' treatment, HAQ scores and SF-36 summary and subscale scores improved significantly in the three patient groups. This study suggests that early PsA is a less disabling disease than RA or early RA. It confirms the efficacy of etanercept in reducing disease severity and improving HR-QoL and suggests that early therapeutic intervention may lead to greater improvement in the mental and emotional components of these diseases.


Modular Synthesis of Biphen[n]arenes Directed by Five-Membered Heterocycles.
Modular synthesis of novel biphen[n]arenes (n = 2-4) with customizable heterocycle blocks, functional skeletons, binding sites, and topological structures could be facilely achieved through the rational design and replacement of reaction modules (furan and thiophene), functional modules (substituted benzene, biphenyl, and naphthalene), and linking modules (methylene). These biphen[n]arenes were characterized by NMR, HRMS, and X-ray crystalline diffraction, complemented by DFT calculations. Their photophysical properties were thoroughly studied.


Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D.
Mice (BALB/cJ, C3H/HeN, and C3H/HeJ) primed with actinomycin D became highly susceptible to lethal intoxication with staphylococcal enterotoxin B (SEB). The mice underwent toxicosis and toxic shock and died. Actinomycin D-primed C3H/HeN and C3H/HeJ mice showed equal sensitivity to SEB, suggesting that bacterial lipopolysaccharide derived from gram-negative bacteria in the gut may not be an important cofactor in intoxication. In a time course study of the illness, prominent pathological changes characterized by blood congestion and thickening of alveolar septa were seen in the lung, while blood congestion, inflammation, epithelial cell flattening, and villous blunting were seen in the small intestine. In lymphoid tissues, such as the spleen, congestion, inflammation, and lymphoid cell depletion were the major reactions. The pathological features of the mice had many similarities to those of rhesus monkeys intoxicated with intravenous SEB. The actinomycin D-primed C3H/HeJ mice are thus an ideal mouse model for studying SEB toxicosis and toxic shock.


The Antibiotic Guardian campaign: a qualitative evaluation of an online pledge-based system focused on making better use of antibiotics.
The Antibiotic Guardian Campaign was developed to increase commitment to reducing Antimicrobial Resistance (AMR), change behaviour and increase knowledge through an online pledge system for healthcare professionals and members of the public to become Antibiotic Guardians (AG). This qualitative evaluation aimed to understand AG experiences of the campaign and perceived impact on behaviour. Ninety-four AGs (48 via a survey and 46 who had agreed to future contact) were invited to participate in a telephone semi-structured interview. The sample was based on self-identification as a healthcare professional or a member of the public, pledge group (e.g. adults, primary care prescribers etc.), pledge and gender. Interviews explored how participants became aware of the campaign, reasons for joining, pledge choices, responses to joining and views about the campaign's implementation. Interviews were analysed using the Framework Method. Twenty-two AGs (10 healthcare professionals and 12 members of the public) were interviewed. AGs became aware of the campaign through professional networks and social media, and were motivated to join by personal and professional concern for AMR. Choice of pledge group and pledge were attributed to relevance and potential impact on AMR and the behaviour of others through pledge enactment and promotion of the campaign. Most AGs could not recall their pledge unprompted. Most felt they fulfilled their pledge, although this reflected either behaviour change or the pledge reinforcing pre-existing behaviour. The campaign triggered AGs to reflect on AMR related behaviour and reinforced pre-existing beliefs. Several AGs promoted the campaign to others. Responding collectively as part of the campaign was thought to have a greater impact than individual action. However, limited campaign visibility was observed and the campaign was perceived to have restricted ability to reach those unaware of AMR. AGs were motivated to reduce AMR and most felt they fulfilled their pledges although for many this appeared to be through reinforcement of existing behaviours. We recommend that the campaign engages those without pre-existing knowledge of AMR by increasing its visibility, capitalising on the diffusion of its message and including more awareness-raising content for those with limited AMR knowledge.


Social Support-Seeking Strategies on Social Media at the Intersection of Lesbian, Gay, Bisexual, Transgender, and Queer Identity, Race, and Ethnicity: Insights for Intervention From a Qualitative Study.
Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) individuals experience a disproportionately higher prevalence of mental health challenges when compared to their heterosexual and cisgender counterparts. Moreover, they exhibit increased engagement with social media platforms relative to their peers. Understanding the intersectional dynamics of their identities is crucial in elucidating effective and safe approaches to garnering social support through social media channels. This exploration holds significance for informing future research endeavors and shaping targeted interventions to address the unique mental health needs of LGBTQ+ individuals. The purpose of this study was to explore the strategies used by Black, Hispanic, and non-Hispanic White LGBTQ+ young adults to acquire social support from social media. The study aimed to examine how these strategies may differ by race and ethnicity. We conducted semistructured interviews with LGBTQ+ young adults aged between 18 and 30 years recruited in the United States from social media. Of 52 participants, 12 (23%) were Black, 12 (23%) were Hispanic, and 28 (54%) were non-Hispanic White. Thematic analysis was used to analyze the collected data. The analysis uncovered both divergent and convergent strategies among participants of different races and ethnicities. Black and Hispanic young adults exhibited a preference for connecting with individuals who shared similar identities, seeking safety and tailored advice. Conversely, non-Hispanic White participants demonstrated minimal preference for identity-based advice. Seeking support from anonymous sources emerged as a strategy to avoid unwanted disclosure among Hispanic participants. Furthermore, all participants emphasized the importance of content filtering with family members to cultivate positive and supportive social media experiences. This study sheds light on the strategies used by LGBTQ+ individuals of different racial and ethnic backgrounds to seek social support from social media platforms. The findings underscore the importance of considering race and ethnicity when examining social support-seeking behaviors on social media in LGBTQ+ populations. The identified strategies provide valuable insights for the development of interventions that aim to leverage social support from social media to benefit the mental health of Black, Hispanic, and non-Hispanic White LGBTQ+ young adults.


PET/CT imaging of gastrointestinal stromal tumor with calcified peritoneal implants after imatinib therapy.
Calcified tumor mass is an unusual feature of gastrointestinal stromal tumor (GIST) at initial presentation. However, it may develop after imatinib therapy and be erroneously attributed to a second primary malignancy. A 56-year-old woman with a 4.5-year history of metastatic GIST presented to our institution for PET/CT imaging at baseline and at 3 and 15 months after imatinib therapy. Serial PET/CT images demonstrated increasing calcification in peritoneal implants on CT and increasing FDG activity.


Adult neural stem and progenitor cells modified to secrete GDNF can protect, migrate and integrate after intracerebral transplantation in rats with transient forebrain ischemia.
Adult neural stem and progenitor cells (NSPCs) are important autologous transplantation tools in regenerative medicine, as they can secrete factors that protect the ischemic brain. We investigated whether adult NSPCs genetically modified to secrete more glial cell line-derived neurotrophic factor (GDNF) could protect against transient ischemia in rats. NSPCs were harvested from the subventricular zone of adult Wistar rats and cultured for 3 weeks in the presence of epidermal growth factor. The NSPCs were treated with fibre-mutant Arg-Gly-Asp adenovirus containing the GDNF gene (NSPC-GDNF) or enhanced green fluorescent protein (EGFP) gene (NSPC-EGFP; control group). In one experiment, cultured cells were transplanted into the right ischemic boundary zone of Wistar rat brains. One week later, animals underwent 90 min of intraluminal right middle cerebral artery occlusion followed by magnetic resonance imaging and behavioural tests. The NSPC-GDNF group had higher behavioural scores and lesser infarct volume than did controls at 1, 7 and 28 days postocclusion. In the second experiment, we transplanted NSPCs 3 h after ischemic insult. Compared to controls, rats receiving NSPC-GDNF had decreased infarct volume and better behavioural assessments at 7 days post-transplant. Animals were killed on day 7 and brains were collected for GDNF ELISA and morphological assessment. Compared to controls, more GDNF was secreted, more NSPC-GDNF cells migrated toward the ischemic core and more NSPC-GDNF cells expressed immature neuronal marker. Moreover, the NSPC-GDNF group showed more effective inhibition of microglial invasion and apoptosis. These findings suggest that NSPC-GDNF may be useful in treatment of cerebral ischemia.


Impact of long work hours on police officers and the communities they serve.
Police officers in the United States often are overly fatigued because of long and erratic work hours, shift work, and insufficient sleep. These factors likely contribute to elevated levels of morbidity and mortality, psychological disorders, and family dysfunction observed among police. Fatigue-related impairments to officer performance and decision making can generate unexpected social and economic costs. Information was gathered from the literature and analysis of government data as well as meetings with sleep researchers, police executives, and union officials in order to understand the causes and consequences of police long work hours. Long work hours and shift work threaten police officer health, safety, and performance. This situation is aggravated by understaffing associated with demographic shifts and new threats to homeland security. Ongoing research suggests that the police may be a useful model occupational group for basic and applied research on sleep, fatigue, and human performance.


[Postoperative Chylothorax Following Gastric Tube Cancer Surgery Cured after Pneumonia and Empyema-A Case Report].
A 74-year-old man was under follow-up after esophageal cancer surgery and CRT for hypopharyngeal cancer. Follow-up endoscopy revealed an ulcerative lesion in the lower gastric tube, and biopsy showed group 5(tub1). Endoscopic resection was difficult, and surgery was decided. Gastric tube resection and subcutaneous jejunum reconstruction were performed. Postoperatively, chylothorax was observed. Enteral nutrition was discontinued, and the patient was managed with TPN, and continuous subcutaneous octreotide and continuous intravenous etyrefrine were started. Even after conservative treatment was started, the pleural effusion of about 2,000 mL/day was observed from the right thoracic drain. On postoperative day 14, lymphangiography was performed with lipiodol from the left inguinal lymph node. The pleural fluid was temporarily decreased to less than 500 mL/day, but it began to drain again at a rate of 1,000 mL/day. On postoperative day 30, the patient developed fever and elevated inflammatory findings due to pneumonia and empyema, and drain drainage gradually decreased. The drain was removed on postoperative day 41. The patient was discharged home on postoperative day 72.


Electrocatalytically Activating and Reducing N2 Molecule by Tuning Activity of Local Hydrogen Radical.
Decarbonizing N2 conversion is particularly challenging, but essential for sustainable development of industry and agriculture. Herein, we achieve electrocatalytic activation/reduction of N2 on X/Fe-N-C (X=Pd, Ir and Pt) dual-atom catalysts under ambient condition. We provide solid experimental evidence that local hydrogen radical (H*) generated on the X site of the X/Fe-N-C catalysts can participate in the activation/reduction of N2 adsorbed on the Fe site. More importantly, we reveal that the reactivity of X/Fe-N-C catalysts for N2 activation/reduction can be well adjusted by the activity of H* generated on the X site, i.e., the interaction between the X-H bond. Specifically, X/Fe-N-C catalyst with the weakest X-H bonding exhibits the highest H* activity, which is beneficial to the subsequent cleavage of X-H bond for N2 hydrogenation. With the most active H*, the Pd/Fe dual-atom site promotes the turnover frequency of N2 reduction by up to 10 times compared with the pristine Fe site.


FKBP5 genotype and early life stress exposure predict neurobehavioral outcomes for preterm infants.
This study evaluated the relationship between stressful early life neonatal intensive care unit (NICU) experiences, genetic variation of a stress response-associated gene (FKBP5), and neurobehavioral outcomes. The impact of genetic variation and stress experience on neurobehavioral outcomes was examined for 41 preterm infants. Statistical analyses explored the main effects of FKBP5 genotype and NICU stress experience, as well as their interaction on infant neurobehavioral development prior to discharge. Statistical analyses demonstrated a relationship between both FKPB5 genotype and stress related to NICU care that were independently associated with neurobehavioral outcomes; indicating a main effect of genotype and a main effect of stress on neurodevelopment. Additionally, we found an interaction between the minor allele genotype and NICU stress potentially associated with less favorable developmental progress at discharge. Evidence of genetic and environmental risk factors for neurodevelopmental impairment suggests the need for improved evidence-based practice initiatives to protect those most vulnerable to the combination of genetic susceptibility to stress and medical fragility.


Women's mammography experience and its impact on screening adherence.
Although rates for first-time and recent mammography screening have increased for women in the US in the past decade, rates for repeat mammography remain low. This study aimed to conduct an analysis of women's mammography experience, to examine the rates of repeat mammography and to identify the significant predictors of repeat mammography within 12 and 18 months of the index mammogram. Participants were 397 women obtaining a screening mammogram (i.e. index) at three university-affiliated radiology clinics. Following the index mammogram, women completed the measures assessing demographic background, health history, breast cancer knowledge, risk, and screening history, and aspects of the mammography experience. Eighteen months following the index mammogram, 296 women were contacted via telephone to assess repeat mammography behavior. Factor analysis of a mammography experience survey yielded four major components including satisfaction with clinic services, physical experience, psychological experience, and communication with clinic staff. Twelve-month and 18-month repeat mammography rates were 37 and 68%, respectively. Logistic regression models found lifetime number of mammograms to predict repeat mammography at 12 and 18 months. In addition, the number of clinical breast exams obtained in the past 5 years predicted repeat mammography at 12 months, while having scheduled a mammography appointment predicted repeat mammography at 18 months. Based on these findings, strategies to increase mammography adherence include implementing a formal reminder system that prompts patients (e.g. postcard, automated telephone call) to schedule an annual mammogram or training clinic staff to automatically schedule an annual mammogram at the time of the current screening appointment.


The influence of anchor devices on the performance of retractable type fall arresters protecting against falls from a height.
Retractable type fall arresters are part of the equipment used for protecting people against falls from a height. They are an intermediate part between full body harness worn by a man and the structural anchor at the worksite. The most important task of retractable type fall arresters is to arrest people's falls and to reduce their harmful consequences. Information received from users as well as laboratories testing protective equipment indicates that the performance of such equipment is incorrect under specific conditions. The paper is concerned with an analysis of the conditions in which retractable type fall arresters demonstrate intermittent performance and with an explanation of that phenomenon. The results of tests investigating anchor devices and the performance of retractable type fall arresters are presented. External and internal factors contributing to intermittent performance have been determined and guidelines for safer use of these devices have been developed.


Forms of reproductive disorders in cattle and buffaloes in Middle Egypt.
The objective of this study was to investigate the common forms of reproductive disorders and trends of fertility in cattle and buffaloes in Middle Egypt, and investigate nutritional deficiencies or imbalances as a cause of infertility. During the period from 2003 to 2006 a total of 4276 animals (2755 cattle and 1521 buffaloes) were examined, during winter and summer at three districts of Middle Egypt. Based on the owner complains, animals were categorized as anestrum, repeat breeder and those for pregnancy diagnosis. Feedstuffs of these districts were assessed for nutrient and mineral contents. Animals were examined by rectal palpation and by transrectal ultrasonography. The results showed that, ovarian inactivity was the most common cause of anestrum, whereas endometritis was the main frequent finding of repeat breeding. District, season and year affected the incidences of infertility. The pregnancy rate remained constant (cattle) or increased (buffaloes) from 2003 to 2006. The incidence of ovarian inactivity in both species decreased over the same period. In winter, the commonly used feedstuffs would be adequate to supply the animals with needs, but in summer, rations seem to be deficient in many essential nutrients. In conclusion, ovarian inactivity is the main cause of infertility in cattle and buffaloes in Middle Egypt. There is a link between poor nutrition in summer and the high incidence of ovarian inactivity. Fertility trends during the past few years are encouraging.


Chidamide suppresses the glycolysis of triple negative breast cancer cells partially by targeting the miR‑33a‑5p‑LDHA axis.
Triple negative breast cancer (TNBC) is one of the most aggressive types of breast cancer and has a poor prognosis. Therefore, the development of novel drugs and understanding the molecular mechanisms that may contribute to the initiation and development of TNBC are urgently required. Chidamide, a histone deacetylase inhibitor, has been reported as possessing anti‑cancer properties in several cancers, however, the function of chidamide in TNBC remains to be elucidated. The present study revealed that chidamide inhibited the proliferation, colony formation and migration of TNBC cells. Experiments investigating the underlying mechanism revealed that chidamide upregulated the expression of microRNA (miR)‑33a‑5p in TNBC cells via RT‑qPCR. Luciferase reporter assay demonstrated that miR‑33a‑5p was bound to the 3'‑untranslated region of lactate dehydrogenase A (LDHA) and decreased the expression of LDHA in TNBC cells. In addition, chidamide suppressed the expression of LDHA and significantly decreased the glycolysis of TNBC cells. Collectively, the results of the present study demonstrated that chidamide reprogramed glucose metabolism, partially by targeting the miR‑33a‑5p/LDHA pathway, in TNBC. These findings indicate that chidamide may be a promising novel drug in the treatment of patients with TNBC.


Application of zeolites for radium removal from mine water.
For removal of radium from saline waters in Upper Silesian mines, several methods of purification have been developed. The most efficient one is based on application of barium chloride, which was implemented in full technical scale in two Polish coal mines several years ago. Very good results of purification have been achieved-the removal efficiency exceeding 95% of the initial activity. Another possibility for the removal of different ions from salty waters and brines is the application of zeolites. We found that technique as a very promising method for removal of not only radium isotopes from mine waters but also other ions (barium, iron, manganese). Treatment of several various water samples has been done to assess the removal efficiency for natural radionuclides. Preliminary results show very good effects for radium isotopes as well as for barium ions. In the paper, a short description of laboratory results of the purification of mine waters with application of synthetic zeolites is presented.


Interleukin-8 secretion in patients with allergic rhinitis after an allergen challenge: interleukin-8 is not the main chemotactic factor present in nasal lavages.
Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and primed eosinophils. In allergic rhinitis, allergen exposure triggers leucocyte recruitment. We evaluated in this study IL-8 secretion and the neutrophil chemotactic activity in nasal lavages collected after a nasal allergen challenge. Moreover, the participation of IL-8 in the neutrophil chemotactic activity was quantified. Four healthy subjects and 19 patients with allergic rhinitis were exposed to a nasal allergen challenge. As a control, saline challenge was performed in four patients with allergic rhinitis. Concentration of IL-8 was measured by ELISA in nasal lavages collected before and after challenge. Neutrophil chemotactic assay was developed using a 48-well chemotaxis microassembly. After allergen challenge, the healthy subjects, the four patients receiving saline and one patient exposed to allergen did not respond; seven patients presented a single early reaction and 11 patients a dual response. For healthy subjects and the four patients exposed to saline, the level of IL-8 did not increase after challenge in comparison with that at baseline. After allergen challenge, two peaks of IL-8 release were observed for patients with allergic rhinitis during the early (30 min to 1 h 30 min) and the late periods (3 h 30 min to 9 h 30 min), however the difference was not significant for the early period. During the late period, a significant increase in IL-8 concentrations was detected for the patients developing a dual response, whereas the difference was not significant for those presenting only an early reaction. The neutrophil chemotactic activity of nasal lavages from patients with allergic rhinitis collected during the early and the late reactions (17 +/- 2.1 and 23.3 +/- 2.8 neutrophils per high power field (hpf), respectively) was significantly higher than the activity of lavage fluid collected at baseline (9.2 +/- 1.8 neutrophils per hpf). Nevertheless, the addition of a neutralizing anti-IL-8 antibody inhibited weakly the chemotactic activity of lavage fluid from rhinitic patients collected during the early or the late periods (18 and 11% of inhibition) (P = NS). These data show that allergen challenge increased significantly the secretion of IL-8 for the patients with allergic rhinitis. However, neutralization of IL-8 in nasal lavages by a specific antibody revealed that the role of this chemokine in granulocyte infiltrate was limited, suggesting that IL-8 acts in connection with other chemotactic factors in this recruitment.


[Observations on the control and eradication of paratuberculosis in dairy herds].
Johne's disease is widely seen in dairy herds in Germany. Estimates based primarily on epidemiological surveys in neighbouring states assume that 5 to 15 % of German herds are infected. In the past three years several authors have reported that the causative agent of Johne's disease, Mycobacterium avium subspecies paratuberculosis (MAP), is found ubiquitously in the environment and can be isolated from a number of different animals, including non ruminants. These results imply that MAP should be considered an environmental pathogen. Based on this assumption a concept for control and eradication of Johne's disease is presented aiming at minimizing the future spread of disease and reducing environmental contamination with the pathogen at low costs. The concept includes the classification of herds based on an bulk milk ELISA followed by a robot-compatible bulk milk PCR in ELISA-positive herds only. Due to the comparatively low costs combined with the high specificity of the approach a detection of heavily infected herds ("tip of the iceberg") all over the country would be possible; based on the eradication of strong shedders in these herds the input of MAP into the environment would be reduced considerably.


Looking for cystoscopy on YouTube: Are videos a reliable information tool for internet users?
The Internet is an important and easily accessible source of information. The aim of the current study was to investigate the quality of YouTube videos on cystoscopy and to establish if they can be used as a reliable information tool for internet users. The search term "cystoscopy" was used on YouTube platform and the first 120 YouTube videos were analyzed. To assess the video quality Patient Education Materials Assessment Tool (PEMAT) for Audiovisual (A/V) Materials (Understandability and Actionability sections), Misinformation score and Global Quality Score (GQS) were used. Of all 120 videos, 72 were included in the analyses. Of all videos, 59.7% (n = 43), and 40.3% (n = 29) were targeted to General Public and Healthcare Workers. Moreover, "technical aspects" was the main topic addressed (n = 29, 40.3%). The median PEMAT A/V Understandability and Actionability scores were 50.0% (IQR: 39.1-70.0) and 66.7% (IQR: 33.3- 100.0), respectively. The median Misinformation score ranged from 1.0 to 3.0. According to GQS, 22 (30.6%), 26 (36.1%), 16 (22.2%), 8 (11.1%) videos were poor, generally poor, moderate, and good, respectively. No video was evaluated as excellent. Today, YouTube videos on cystoscopy are more frequently uploaded by healthcare workers, who share information about specific aspects of this procedure. However, the quality of YouTube contents on cystoscopy is still poor. Therefore, currently users interested in cystoscopy cannot rely on YouTube to get good informative material on this topic. In consequence, future authors should focus on improving the quality of video contents on cystoscopy.


Congenital dislocation of the knee at birth - Part 2: Impact of a new classification on treatment strategies, results and prognostic factors.
An original classification of congenital dislocation of the knee (CDK) was drawn up, based on neonatal semiology. The objective of the present study was to assess impact on treatment decision-making and prognosis. Fifty-one CDKs in 40 patients were classified neonatally into 3 types: I, reducible (n=28); II, recalcitrant (n=16); and III, irreducible (n=7). Number of anterior skin grooves, range of motion (RoM), flexion deficit and reduction stability were recorded. Depending on reducibility, treatment comprised: physiotherapy with splints, traction with cast immobilization, or surgery. At follow-up, knees were assessed in terms of RoM and stability. Mean age at first consultation was 5.6 days (range: 0-30). Mean age at follow-up was 9 years (range: 1-26). Physiotherapy with splinting achieved stable reduction in all type-I knees. Five type-II knees (31%) required traction, none of which needed surgery. Four type-III knees (57%) required surgery. Outcome was good or excellent in 82% of type-I knees, good in 68% of type II and poor in all type-III knees. The study confirmed the relevance of the present neonatal classification to treatment, with increasing rates of surgical indication and decreasing rates of satisfactory outcome from types I to III. Therapeutic attitude can be graded according to severity of CDK. IV, single-center retrospective series.


Improving postpartum hemorrhage risk prediction using longitudinal electronic medical records.
Postpartum hemorrhage (PPH) remains a leading cause of preventable maternal mortality in the United States. We sought to develop a novel risk assessment tool and compare its accuracy to tools used in current practice. We used a PPH digital phenotype that we developed and validated previously to identify 6639 PPH deliveries from our delivery cohort (N = 70 948). Using a vast array of known and potential risk factors extracted from electronic medical records available prior to delivery, we trained a gradient boosting model in a subset of our cohort. In a held-out test sample, we compared performance of our model with 3 clinical risk-assessment tools and 1 previously published model. Our 24-feature model achieved an area under the receiver-operating characteristic curve (AUROC) of 0.71 (95% confidence interval [CI], 0.69-0.72), higher than all other tools (research-based AUROC, 0.67 [95% CI, 0.66-0.69]; clinical AUROCs, 0.55 [95% CI, 0.54-0.56] to 0.61 [95% CI, 0.59-0.62]). Five features were novel, including red blood cell indices and infection markers measured upon admission. Additionally, we identified inflection points for vital signs and labs where risk rose substantially. Most notably, patients with median intrapartum systolic blood pressure above 132 mm Hg had an 11% (95% CI, 8%-13%) median increase in relative risk for PPH. We developed a novel approach for predicting PPH and identified clinical feature thresholds that can guide intrapartum monitoring for PPH risk. These results suggest that our model is an excellent candidate for prospective evaluation and could ultimately reduce PPH morbidity and mortality through early detection and prevention.


Effectiveness of isosorbide dinitrate in cyanide poisoning as a function of the administration timing.
Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders. A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 μg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH. Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved. Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning.