Effect of oral anticoagulants on hemostatic and thromboembolic complications in hip fracture: A systematic review and meta-analysis.
Hip fracture patients on oral anticoagulants (OACs) experience increased time-to-surgery and higher mortality compared to non-anticoagulated patients. However, it is unclear whether pre-injury OAC status and its associated operative delay are associated with worsening of peri-operative hemostasis or an increased risk of postoperative thromboembolism. We performed a systematic review to identify studies that directly compared hemostatic and thromboembolic outcomes among hip fracture patients on an OAC prior to admission with those not on anticoagulants. Random effects meta-analyses were used to pool all outcomes of interest (estimated blood loss, transfusion requirements, and postoperative thromboembolism). Twenty-one studies involving 21 417 patients were included. Estimated blood loss was higher among patients presenting with OACs compared to those not anticoagulated (mean difference 31.0 mL, 95% confidence interval [CI] 6.2-55.7). Anticoagulated patients also had a 1.3-fold higher risk of receiving red blood cell transfusions (odds ratio [OR] 1.34, 95% CI 1.20-1.51); however, rates of postoperative thromboembolism were similar regardless of anticoagulation status (OR 0.96, 95% CI 0.40-2.79 for venous thromboembolism; OR 0.58, 95% CI 0.25-1.36 for arterial thromboembolism). No subgroup effect was found based on anticoagulant type or degree of surgical delay. Hip fracture patients on OACs experience increased surgical blood loss and higher risk of red blood cell transfusions. However, the degree of surgical delay did not mitigate this risk, and there was no difference in postoperative thromboembolism. The impact of appropriate, timely OAC reversal on blood conservation and expedited surgery in anticoagulated hip fracture patients warrants urgent evaluation.


Artificial intelligence evaluation of focused assessment with sonography in trauma.
The focused assessment with sonography in trauma (FAST) is a widely used imaging modality to identify the location of life-threatening hemorrhage in a hemodynamically unstable trauma patient. This study evaluates the role of artificial intelligence in interpretation of the FAST examination abdominal views, as it pertains to adequacy of the view and accuracy of fluid survey positivity. Focused assessment with sonography for trauma examination images from 2015 to 2022, from trauma activations, were acquired from a quaternary care level 1 trauma center with more than 3,500 adult trauma evaluations, annually. Images pertaining to the right upper quadrant and left upper quadrant views were obtained and read by a surgeon or radiologist. Positivity was defined as fluid present in the hepatorenal or splenorenal fossa, while adequacy was defined by the presence of both the liver and kidney or the spleen and kidney for the right upper quadrant or left upper quadrant views, respectively. Four convolutional neural network architecture models (DenseNet121, InceptionV3, ResNet50, Vgg11bn) were evaluated. A total of 6,608 images, representing 109 cases were included for analysis within the "adequate" and "positive" data sets. The models relayed 88.7% accuracy, 83.3% sensitivity, and 93.6% specificity for the adequate test cohort, while the positive cohort conferred 98.0% accuracy, 89.6% sensitivity, and 100.0% specificity against similar models. Augmentation improved the accuracy and sensitivity of the positive models to 95.1% accurate and 94.0% sensitive. DenseNet121 demonstrated the best accuracy across tasks. Artificial intelligence can detect positivity and adequacy of FAST examinations with 94% and 97% accuracy, aiding in the standardization of care delivery with minimal expert clinician input. Artificial intelligence is a feasible modality to improve patient care imaging interpretation accuracy and should be pursued as a point-of-care clinical decision-making tool. Diagnostic Test/Criteria; Level III.


Fluid-fluid levels in giant cell tumors of bone: report of two cases.
Fluid-fluid levels have been described in association with aneurysmal bone cysts, telangiectatic osteosarcoma, and a chondroblastoma. We report two cases of giant cell tumors of bone with fluid-fluid levels identified by computed tomography and, in one case, by magnetic resonance imaging. This finding has not previously been associated with giant cell tumors. The radiographic features of the fluid-fluid levels cannot be distinguished from those reported in other osseous neoplasms.


A comparative analysis of the effects of narcotics, alcohol and the barbiturates on the hypothalamic-pituitary-gonadal axis.
The purpose of this paper is to provide an overview of our current state of knowledge regarding the effects of alcohol, the narcotics and the barbiturates on the hypothalamic-pituitary-gonadal axis in the male. Three facets of this problem will be considered: acute drug effects; chronic effects, particularly with respect to the development of tolerance and physical dependence; and, finally, an attempt will be made to indicate the way in which these three substances of abuse are similar and/or dissimilar in their effects on this system. The effects of acute and chronic treatment with narcotics, alcohol and the barbiturates will be discussed first and then an attempt will be made, in a General Discussion, to summarize the data, make general comparisons between the drugs and suggest future lines of research.


How fast do cardioactive steroids act independently of diffusion in guinea-pig myocardium?
1 The rate of onset of the inotropic effect of different cardioactive steroids (in order of increasing potency: dihydroouabain, digoxigenin, digoxin, ouabain, digitoxin) was studied in guinea-pig papillary muscles stimulated at 0.5 Hz. For an estimate of diffusion rate the time to defined levels of effect was evaluated in relation to the diameter of cylindrical muscles. 2 The dependence of onset rates on muscle diameter was more pronounced with a highly potent steroid, e.g., digitoxin, than with a less potent compound, e.g., dihydroouabain; that is, the apparent rate of diffusion was inversely correlated with the inotropic potency. Reduction of the ratio of receptor to steroid concentration with increase of ouabain or K+ concentration enhanced the apparent rate of diffusion. 3 Extrapolation to negligibly short diffusion distance indicated that the effects of the various steroids develop faster in the absence of diffusion. The effect of 50 mumol l-1 of dihydroouabain appeared more quickly than with ouabain in the perfused heart. The time courses of the inotropic effect in perfused hearts and in papillary muscles of diameters less than 0.75 mm were superimposable, indicating that the onset of the dihydroouabain effect was not controlled by diffusion. 4 After the interference of diffusion had been excluded, the rates of onset of action correlated inversely with the inotropic potencies of the steroids. The dissociation rate of the drug-receptor complex appeared to be related to the different receptor affinities.


Association between entomopathogenic nematodes and fungi for control of Rhipicephalus microplus (Acari: Ixodidae).
The aim of the study was to assess the effect of the association of entomopathogenic nematodes and fungi on Rhipicephalus microplus. The nematodes used were Heterorhabditis bacteriophora HP88 and Heterorhabditis indica LPP1 and the fungi were Metarhizium anisopliae IBCB 116 and Beauveria bassiana ESALQ 986. In the groups treated with the fungi, the females were immersed for 3 min in a conidial suspension, while in the groups treated with the nematodes, the ticks were exposed to infective juveniles. To evaluate the interaction between entomopathogens, the females were first immersed in a conidial suspension and then exposed to the nematodes. The egg mass weight and hatching percentage values of the groups treated with M. anisopliae IBCB 116 and B. bassiana ESALQ 986 in the two experiments were statistically similar (p > 0.05) to the values of the control group. In the groups treated only with nematodes, there was a significant reduction (p < 0.05) in the egg mass weight, a fact also observed for the hatching percentage of the group treated with H. indica LPP1. In all the groups treated with nematodes in association with fungi, there was a significant reduction (p < 0.05) in the egg mass weight and hatching percentage. The percentage of control of the groups treated with fungi alone varied from 31 to 55%. In the groups treated with nematodes associated or not with fungi, the control percentage was always greater than 90% and reached 100% in the group treated with H. bacteriophora HP88 associated with the fungus M. anisopliae IBCB 116.


Online evaluation of bacterial cells in sand filter effluents during full-scale treatment of drinking water.
Ensuring the microbiological safety of drinking water is critical to protect public health. This study aimed to evaluate the reliability of real-time bacteriological counter coupled with an online dialysis membrane-based pre-treatment system for continuously monitoring bacterial cell counts in sand filter effluents of a full-scale drinking water treatment plant. The pre-treatment system, which included anion exchange resins (porous polymeric microbeads that trap ions for releasing other ions) for dialysate regeneration, successfully achieved the stable attenuation of background interfering substances (humic acids) during the 19-d test. The real-time bacteriological counter equipped with the pre-treatment system provided a continuous profile of bacterial cell counts in the sand filter effluent (0.2-2.5 × 104 counts/mL). The online analysis identified different timing of concentration peaks between particle and bacterial cell counts after backwashing. Bacterial community analysis revealed that Proteobacteria, Planctomycetes, and Cyanobacteria were the dominating phyla. Further, total bacterial cell counts determined by fluorescence microscopy and SYBR® Green I staining, a commonly accepted parameter, was found to be an indicator of online-monitored bacterial cell counts. The results indicated the potential of monitoring the bacterial cell counts in a sand filter process for providing an early warning of filter failures, which can allow plant operators to diagnose the overall system and provide countermeasures.


The low-harm score for predicting mortality in patients diagnosed with COVID-19: A multicentric validation study.
We sought to determine the accuracy of the LOW-HARM score (Lymphopenia, Oxygen saturation, White blood cells, Hypertension, Age, Renal injury, and Myocardial injury) for predicting death from coronavirus disease 2019) COVID-19. We derived the score as a concatenated Fagan's nomogram for Bayes theorem using data from published cohorts of patients with COVID-19. We validated the score on 400 consecutive COVID-19 hospital admissions (200 deaths and 200 survivors) from 12 hospitals in Mexico. We determined the sensitivity, specificity, and predictive values of LOW-HARM for predicting hospital death. LOW-HARM scores and their distributions were significantly lower in patients who were discharged compared to those who died during their hospitalization 5 (SD: 14) versus 70 (SD: 28). The overall area under the curve for the LOW-HARM score was 0.96, (95% confidence interval: 0.94-0.98). A cutoff > 65 points had a specificity of 97.5% and a positive predictive value of 96%. The LOW-HARM score measured at hospital admission is highly specific and clinically useful for predicting mortality in patients with COVID-19.


Development of a photon induced drug-delivery implant coating.
A thin surface coating intended for medical devices such as implants where local drug release is enabled using near infrared light (NIR) as an external stimulus has been developed. The delivery system consists of a thin Poly (N-isopropylacrylamide)-co-acrylamide (PNIPAAm-AAm) polymer layer with incorporated gold nanorods (GNRs). The aspect ratio of the GNRs were chosen to absorb NIR light, thus fitting the biological window of low tissue absorption, to locally heat the polymeric layer to initiate a drug release. Hence, controlled drug delivery from a surface within tissue orchestrated from outside the body is achievable. Composition of the PNIPAAm-AAm co-polymer was systematically varied to find a suitable phase transition temperature for in vivo applications. Differential scanning calorimetry (DSC) analysis showed that PNIPAAm-AAm containing 10% acrylamide had an appropriate phase transition temperature of 42 °C. As visualized by scanning electron microscopy (SEM), the surface coating consisted of 200 nm uniform polymer layer. Quartz crystal microbalance with dissipation monitoring (QCM-D) analysis coupled with in situ NIR irradiation demonstrated a dramatic shift in frequency that was attributed to mass being released from the surface upon irradiation. This mass release correlated well with the drug release profile as determined using UV/VIS spectroscopy with phenol as a model drug. In addition, proof-of-concept of the drug-delivery system was demonstrated by releasing the antibiotic vancomycin to eradicate Staphylococcus epidermidis bacteria in culture.


Effectiveness of pharmacokinetic modulating chemotherapy combined with cisplatin as induction chemotherapy in resectable locally advanced head and neck cancer: phase II study.
To test the efficacy and safety of pharmacokinetic modulating chemotherapy combined with cisplatin (PMC-cisplatin) as induction chemotherapy (ICT) before definitive treatment in patients with respectable locally advanced head and neck squamous cell carcinoma (HNSCC). Patients with stage III-IV resectable locally advanced HNSCC were enrolled. All eligible patients received PMC-cisplatin regimen as ICT containing intravenous leucovorin 250 mg/m(2) and 5-FU 600 mg/m(2) on day 1, oral tegafur-uracil (UFUR) 250 mg/m(2)/day on days 1-5, repeated every week for six courses. Cisplatin 100 mg/m(2 )was given during the first and fourth courses of PMC. For ICT responders, concurrent chemoradiotherapy (CRT) with cisplatin/tegafur-uracil/70 Gy radiotherapy was performed. Salvage surgery plus postoperative CRT was given to ICT non-responders. The overall response rate of PMC-cisplatin as ICT was 76%, including a complete remission rate of 23%. The overall organ preservation rate of the multimodality treatment was 75%, with 97% in ICT responders. At a median follow-up of 25 months, 47% of the patients were still alive and disease-free. The superiority of disease-free survival was demonstrated in ICT responders. The 3-year overall survival rate was 67%. The toxicity of treatment was acceptable. Application of PMC-cisplatin as the induction chemotherapy before definitive treatment provides a promising result in treatment response and survival of advanced HNSCC. This regimen is effective and safe, and further studies considering the combination of PMC with other chemotherapeutics such as taxanes to improve the clinical outcome of advanced HNSCC is warranted.


Discrimination between Streptococcus pneumoniae and Streptococcus mitis based on sorting of their MALDI mass spectra.
Accurate species-level identification of alpha-hemolytic (viridans) streptococci (VGS) is very important for understanding their pathogenicity and virulence. However, an extremely high level of similarity between VGS within the mitis group (S. pneumoniae, S. mitis, S. oralis and S. pseudopneumoniae) often results in misidentification of these organisms. Earlier, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been suggested as a tool for the rapid identification of S. pneumoniae. However, by using Biotyper 3.0 (Bruker) or Vitek MS (bioMérieux) databases, Streptococcus mitis/oralis species can be erroneously identified as S. pneumoniae. ClinProTools 2.1 software was used for the discrimination of MALDI-TOF mass spectra of 25 S. pneumoniae isolates, 34 S. mitis and three S. oralis. Phenotypical tests and multilocus gene typing schemes for the S. pneumoniae (http://spneumoniae.mlst.net/) and viridans streptococci (http://viridans.emlsa.net/) were used for the identification of isolates included in the study. The classifying model was generated based on different algorithms (Genetic Algorithm, Supervised Neural Network and QuickClassifier). In all cases, values of sensitivity and specificity were found to be equal or close to 100%, allowing discrimination of mass spectra of different species. Three peaks (6949, 9876 and 9975 m/z) were determined conferring the maximal statistical weight onto each model built. We find this approach to be promising for viridans streptococci discrimination.


UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement.
Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-specific p53 gene mutations in UV-exposed normal skin. The methods are based on mutant allele-specific PCRs and ligase chain reactions and designed to detect CC to TT mutations at codons 245 and 247/248, using 10 micrograms of DNA samples. These specific mutations in the p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene were detected in cultured human skin cells only after UV irradiation, and the mutation frequency increased with increasing UV dose. Seventeen of 23 samples of normal skin from sun-exposed sites (74%) on Australian skin cancer patients contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on volunteers living in France carried such mutations. Our results suggest that specific p53 gene mutations associated with human skin cancer are induced in normal skin by solar UV radiation. Measurement of these mutations may be useful as a biologically relevant measure of UV exposure in humans and as a possible predictor of risk for skin cancer.


Exploration and arrangement in physical and social worlds.
Fiction involves exploring imaginative arrangements of places and characters: elements that can be recognized by readers. In childhood, exploration occurs from a safe home base of a caregiver; fiction enables a comparable basis. Physical elements in fiction are settings. More important are social explorations: transactions with characters that can include transformation. This is illustrated by Alice's Adventures in Wonderland.


Accurate prediction of protein torsion angles using evolutionary signatures and recurrent neural network.
The amino acid sequence of a protein contains all the necessary information to specify its shape, which dictates its biological activities. However, it is challenging and expensive to experimentally determine the three-dimensional structure of proteins. The backbone torsion angles play a critical role in protein structure prediction, and accurately predicting the angles can considerably advance the tertiary structure prediction by accelerating efficient sampling of the large conformational space for low energy structures. Here we first time propose evolutionary signatures computed from protein sequence profiles, and a novel recurrent architecture, termed ESIDEN, that adopts a straightforward architecture of recurrent neural networks with a small number of learnable parameters. The ESIDEN can capture efficient information from both the classic and new features benefiting from different recurrent architectures in processing information. On the other hand, compared to widely used classic features, the new features, especially the Ramachandran basin potential, provide statistical and evolutionary information to improve prediction accuracy. On four widely used benchmark datasets, the ESIDEN significantly improves the accuracy in predicting the torsion angles by comparison to the best-so-far methods. As demonstrated in the present study, the predicted angles can be used as structural constraints to accurately infer protein tertiary structures. Moreover, the proposed features would pave the way to improve machine learning-based methods in protein folding and structure prediction, as well as function prediction. The source code and data are available at the website https://kornmann.bioch.ox.ac.uk/leri/resources/download.html .


Comorbidity negatively influences the outcomes of diagnostic tests for musculoskeletal pain in the orofacial region.
The aim of this study was to investigate whether diagnostic tests for musculoskeletal pain in the orofacial region [temporomandibular disorder (TMD) pain] are influenced by the presence of comorbid conditions, and to determine whether this influence decreases when the presence of "familiar pain" is used as outcome measure. In total, 117 patients (35 men, 82 women; 75 TMD-pain patients, 42 pain-free patients; mean age ± SD = 42.94 ± 14.17 years) were examined with palpation tests and dynamic/static tests. After each test, they were asked whether any pain was provoked and whether this pain response was familiar or not. For four clinical outcome measures (pain on palpation, familiar pain on palpation, pain on dynamic/static tests, and familiar pain on dynamic/static tests), multiple logistic regression analyses were performed with the presence of TMD pain as the primary predictor and regional (neck/shoulder) pain, widespread pain, depression, and somatization as comorbid factors. Pain on palpation was not associated with the primary predictor but with regional pain [P = 0.02, odds ratio (OR) = 4.59] and somatization (P = 0.011, OR = 8.47), whereas familiar pain on palpation was associated with the primary predictor (P = 0.003, OR = 5.23), but also with widespread pain (P = 0.001, OR = 2.02). Pain on dynamic/static tests was associated with the primary predictor (P < 0.001, OR = 11.08), but also with somatization (P = 0.037, OR = 4.5), whereas familiar pain on dynamic/static tests was only associated with the primary predictor (P < 0.001, OR = 32.37). In conclusion, diagnostic tests are negatively influenced by the presence of comorbidity. This influence decreases when the presence of familiar pain is used as outcome measure.


The quantity of natural surfactant necessary to prevent the respiratory distress syndrome in premature lambs.
Premature lambs at 118 to 122 days of gestation were delivered by caesarean section and received before the first breath 0, 19, 53 or 64 mg natural surfactant total lipid (TL) per kg body weight (BW). The seven lambs receiving no surfactant died within 40.1 +/- 7.5 min, whereas the lambs treated with surfactant survived the 2-hr experimental period. Nineteen mg surfactant TL per kg BW preserved lung function; the pH and blood gas measurements were similar to those measured in lambs receiving 53 mg TL per kg BW or more surfactant. Pressure volume and surface tension characteristics were significantly improved after the administration of 19 mg of surfactant, but surface activity was still poor when compared to lambs receiving 53 mg TL per kg BW or more surfactant. The dose of surfactant (53 mg TL per kg BW) that resulted in good surface activity measurements in vitjro was similar to other estimates of the amount of surfactant necessary to cover the alveolar space.


ROCK2 promotes osteosarcoma growth and metastasis by modifying PFKFB3 ubiquitination and degradation.
Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) are widely involved in cell biological activities and play a key role in controlling various cell phenomena. However, the underlying mechanisms connecting ROCK2 and PFKFB3 in osteosarcoma growth and metastasis are poorly understood. In this study, we explored and analysed the role and molecular mechanism of ROCK2 and PFKFB3 in osteosarcoma. We analysed ROCK2 and PFKFB3 protein expression in 51 surgical specimens from osteosarcoma patients and determined the correlation between ROCK2 and PFKFB3. In addition, we used Transwell and wound-healing assays to detect cell invasion and migration and CCK8 and EdU assays to assess cell proliferation. Herein, we confirmed that ROCK2 and PFKFB3 proteins were significantly upregulated in osteosarcoma compared with adjacent normal tissues. Further studies revealed that knockdown of ROCK2 significantly decreased the expression levels of PFKFB3; moreover, growth and metastasis were decreased in shROCK2 osteosarcoma cells. Additionally, upregulation of PFKFB3 rescued the decreased proliferation and metastasis induced by ROCK2 knockdown, whereas knockdown of PFKFB3 decreased ROCK2-enhanced osteosarcoma proliferation and metastasis. These results suggest that PFKFB3 is essential for ROCK2-mediated proliferation and metastasis of osteosarcoma cells. Mechanistically, ROCK2 stabilizes PFKFB3 expression by modifying its ubiquitination and degradation. Taken together, our results link two drivers of proliferation and metastasis in osteosarcoma and identify a novel pathway for PFKFB3 regulation. Thus, we provide new evidence of the biological and clinical significance of PFKFB3 as a potential biomarker for osteosarcoma.


Electrophysiological techniques in dissociated tissue culture.
The application of electrophysiological techniques to tissue culture is still evolving. We have attempted in this chapter to give a practical summary of intracellular recording techniques used in our laboratory, as well as give some examples of new experimental strategies and electrophysiological methods that should provide further information on a number of interesting neurobiological questions. The combination of an increasing knowledge of the cell biology of cultured neurons and advances in electrophysiology should continue to be a fruitful interaction.


[Coronary artery fistula between the left anterior descending branch and the left ventricle; a case report (author's transl)].
The rare case of a coronary fistula from the left anterior descending branch to the left ventricle is presented. The 38 year old woman was admitted with homonymous quadrantanopsia and hyperacusis. An abnormal Ecg and a systolic and diastolic murmur of unknown origin were discovered. Cardiac catheterization yielded normal findings. Coronary angiography demonstrated an aneurysma of the dilated left anterior descending coronary artery with a fistulous communication into the left ventricle. This congenital left to left shunt produced a typical mid-diastolic murmur clearly separated from the systolic murmur.


Gaze and retinal-image-stability in two kinds of sequential looking tasks.
Eye and head movements used to keep the gaze on target were examined as unrestrained seated subjects performed two tasks: (1) tapping sequences of 3-D targets; and (2) only looking at sequences of 3-D targets. Large differences were observed in the head/eye coordination patterns used in each task. During tapping, the head moved quickly and continuously. Retinal-image speeds were relatively high (up to 5 degrees/s). During looking-only, the head moved more slowly and almost came to rest between gaze-shifts. Retinal image velocities between gaze-shifts were 60-77% lower during looking-only than during tapping. coordinated eye/head patterns are adjusted to satisfy the demands of a particular task. These adjustments affect low-level oculomotor mechanisms between as well as during the gaze shifts, themselves (reported previously).


Lessons from 197 Mathieu hypospadias repairs performed at a single institution.
Over a 15-year period, 197 Mathieu hypospadias repairs were performed at our institution. The present study reports our experience with this operation with an analysis of factors associated with unfavorable results. Cosmetic results were either excellent or satisfactory in all but 4 cases (2%). Overall, 42 patients (21%) voided with a fistula. A history of a previous operation, flap length, type and structure of the suture, suturing technique, existence of chordee and torsion, and circumcision status were analyzed as prognostic factors. Fifteen years were divided into three equal time intervals, and the success rates of these intervals were also compared. The length of the flap, (< vs >/=20 mm), suture structure (monofilament versus multifilament), and suture type (6-0 vs 5-0) were found to be factors with a significant influence on success rates (P < 0.05). The fistula rates of the three 5-year intervals were 52%, 28%, and 11%, respectively. The difference between time periods was also significant (P < 0.01). On multivariate analysis, only the difference between time intervals remained significant. The present analysis suggests that experience could be considered the most important factor affecting the success rate of hypospadias surgery. We recommend not changing the type of operation so often that not enough experience can be gained. The best results can be achieved in the most experienced hands.


Ozone pollution, water deficit stress and time drive poplar phyllospheric bacterial community structure.
Ground-level ozone (O3) pollution often rise in the summer and coincide with drought stress, which alters the relationships between trees and associated microbial communities in a manner that can have pronounced effects on associated biological activity and ecosystem integrity. Discerning the responses of phyllosphere microbial communities to O3 and water deficit could highlight the ability of plant-microbe interactions to either exacerbate or mitigate the effects of these stressors. Accordingly, this study was designed as the first report to specifically interrogate the impacts of elevated O3 and water deficit stress on phyllospheric bacterial community composition and diversity in hybrid poplar saplings. Significant reductions in phyllospheric bacterial alpha diversity indices were observed, with clear evidence of significant time × water deficit stress interactions. The combination of elevated O3 and water deficit stress shifted in the bacterial community composition over sampling time, resulted in significant increases in the relative abundance of the dominant Gammaproteobacteria phyla together with reductions in Betaproteobacteria. An increased prevalence of Gammaproteobacteria may represent a potential diagnostic dysbiosis-related biosignature associated with poplar disease risk. Significant positive correlations were observed between both Betaproteobacteria abundance and diversity indices and key foliar photosynthetic traits and isoprene emissions, whereas these parameters were negatively correlated with Gammaproteobacteria abundance. These findings suggest that the photosynthesis-related properties in plant leaves are closely related to the makeup of the phyllosphere bacterial community. These data provide novel insight into how plant-associated microbes can help maintain plant health and the stability of the local ecosystem in O3-polluted and dried environments.


Comparative safety of atypical antipsychotics and the risk of pneumonia in the elderly.
Previous studies have documented increased risk of pneumonia with antipsychotic use in the elderly; however, differential risk across individual atypical antipsychotics remains unaddressed. This study examines the effect of individual atypical antipsychotics on risk of pneumonia in elderly patients. This retrospective cohort study was conducted using a large claims database. The study population included new users of atypical antipsychotics (≥65 years). The multiple propensity-score adjusted survival model was used to examine risk of pneumonia within a 1-year follow-up period. A total of 92 234 patients newly prescribed atypical antipsychotic medication were identified. Of these, 41 780 (45.30%) were quetiapine users, 31 048 (33.66%) risperidone users, 11 375 (12.33%) olanzapine users, 6790 (7.36%) aripiprazole users, and 1241 (1.35%) ziprasidone users. Within the 1-year follow-up period, 12 411 (13.46%) patients taking atypical antipsychotics had a diagnosis of pneumonia. The multiple propensity-score-adjusted survival model revealed increased risk of pneumonia with the use of risperidone (hazard ratios (HR) 1.14, 95%CI 1.10-1.18) and olanzapine (HR 1.10, 95%CI 1.04-1.16) compared with the use of quetiapine. This large population-based study suggests that use of risperidone and olanzapine increases risk of pneumonia compared with use of quetiapine in elderly patients. This study provides new information on the comparative risk of pneumonia associated with different atypical antipsychotics in the elderly to support optimal treatment decisions.


Degradation of bisphenol A using UV and UV/H2O2 processes.
Bisphenol A (BPA; 4-[2-(4-hydroxyphenyl)propan-2-yl]phenol) is a substance typically used in the plastic industry. It is used in the production of epoxy resins, polycarbonate, or fire retardants or as a stabilizer and an antioxidant in numerous types of plastics. Bisphenol A is introduced into the environment via municipal and industrial wastewater. Because of its hydrophobic properties, BPA has the potential for sorption on activated sludge during the biological wastewater treatment processes. This study investigated the degradation of BPA by means of UV-radiation and in the UV/H2O2 process with the presence and absence of hydrocarbonate ions (HCO3(-)) as hydroxyl radicals (OH*) scavengers. The calculated value of quantum yield was equal to 0.18, and the value of BPA rate constant with hydroxyl radicals was equal to 3.3 x 10(9) M(-1) s(-1).


Isolation of a second cryptic plasmid from Mycoplasma mycoides subsp. mycoides.
Plasmids have rarely been detected in organisms constituting the genus Mycoplasma. Recently, the isolation of a cryptic plasmid from Mycoplasma mycoides subsp. mycoides has been described, and we report here the isolation of a second cryptic plasmid from this species. Restriction map and Southern blot analyses show that the second plasmid is distinct from the previously described plasmid, although a limited region of homology was detected. The availability of mycoplasmal cryptic plasmids may lead to the development of cloning vectors that replicate in these organisms.


Target organ damage in acute heart failure.
Acute heart failure is a prognostic factor due to its high mortality during the acute phase and the increased frequency of medium to long-term adverse events. The pathophysiological mechanisms triggered during these exacerbations can persist after reaching clinical stability, remaining even after the acute episode has ended. A certain degree of neurohormonal activation, oxidative stress, apoptosis and inflammation (among other conditions) can therefore persist, resulting in organ damage, not just of the myocardium but likely the entire cardiovascular apparatus. This new insight into the persistence of harmful mechanisms that last beyond the exacerbations could be the start of a change in perspective for developing new therapeutic strategies that seek an overall control of hemodynamic and congestive changes that occur during acute decompensated heart failure and changes that remain after achieving clinical stability.


Porous silicon-based optical microsensor for the detection of L-glutamine.
The molecular binding between the glutamine-binding protein (GlnBP) from Escherichia coli and L-glutamine (Gln) is optically transduced by means of a biosensor based on porous silicon nano-technology. The sensor operates by the measurement of the interferometric fringes in the reflectivity spectrum of a porous silicon Fabry-Perot layer. The binding event is revealed as a shift in wavelength of the fringes. Due to the hydrophobic interaction with the Si-H terminated surface of the porous silicon, the GlnBP protein, which acts as a molecular probe for Gln, penetrates and links into the pores of the porous silicon matrix. We can thus avoid any preliminary functionalization process of the porous layer surface, which is also prevented from oxidation, at least for few cycles of wet measurements. The binding of Gln to GlnBP has also been investigated at different concentration of GlnBP.


DNA-binding proteins of psoriatic scales III. Biochemical characterisation as non-histone-proteins.
Histone and non-histone-proteins (NHP) are proteins with a specific affinity to DNA; each group is involved in the regulation of gene expression in its own way. To investigate molecular biologic processes at psoriasis, DNA-binding proteins (DBP) were isolated from psoriatic scales. During this work the proportions of histone and NHP of the DBP fractions were examined. Using two different methods (Bio Rex 70-chromatography and isoelectrofocussing), it was found that the isolated DBP contain only acidic proteins. Likewise, the composition of amino acids is comparable with those of acidic, nuclear proteins of other tissues. Thus the isolated DBP represent to its greatest extent acidic, chromosomal NHP, which obviously are derived from the preserved nuclei of the parakeratotic scale layer.


Telomeres, Telomerase and Cancer.
Telomeres and telomerase play a crucial role in human aging and cancer. Three "drivers" of human aging can be identified. The developmental program encoded in DNA is the primary determinant of lifespan. Faithful execution of the developmental program requires stability of the (epi-)genome which is challenged throughout life by damage to DNA as well as epigenetic 'scars' from error-free DNA repair and stochastic errors made during the establishment and maintenance of the "epigenome". Over time (epi-)mutations accumulate, compromising cellular function and causing (pre-)malignant alterations. Damage to the genome and epigenome can be considered the second "driver" of aging. A third driver of the aging process, important to suppress tumors in long-lived animals, is caused by progressive loss of telomeric DNA. Telomere erosion protects against cancer early in life but limits cell renewal late in life, in agreement with the Antagonistic Pleiotropy theory on the evolutionary origin of aging. Malignant tumors arise when mutations and/or epimutations in cells (clock 2) corrupt the developmental program (clock 1) as well as tumor suppression by telomere erosion (clock 3). In cancer cells clock 3 is typically inactivated by loss of p53 as well as increased expression of telomerase. Taken together, aging in humans can be described by the ticking of three clocks: the clock that directs development, the accumulation of (epi-)mutations over time and the telomere clock that limits the number of cell divisions in normal stem and immune cells.


Responses of sequentially branching macro- and microvessels during reactive hyperemia in skeletal muscle.
Small artery and microvascular responses during reactive hyperemia were compared to determine which resistance-bearing vessels played a role in controlling blood flow and resistance for the cremaster skeletal muscle. Using an intravital video microscopy system, measurements of microvessel pressure, flow velocity, and diameter were obtained from cremaster muscles in anesthetized rats. These were compared with measurements of diameter that were obtained from the small arteries feeding the cremaster muscle. After a 60-sec occlusion of the sacral aorta, total cremaster blood flow increased approximately 28% and calculated microvascular resistance for the cremaster muscle fell 50%. During the period of occlusion, diameters of small arteries (159-292 micron) decreased despite the presence of smooth muscle tone. Likewise, the diameters of large arterioles (65-117 micron) decreased whereas small arterioles (16-30 micron) dilated. The decrease in diameter of the small arteries and large arterioles was accompanied by a significant fall in intravascular pressure, suggesting that the behavior of these vessels was largely passive. Immediately following the release of occlusion, small arteries and large arterioles returned to their control diameters while small arterioles remained in a dilated state for approximately 2 min. These results indicate that for the cremaster muscle, vascular responses vary along the length of the arterial tree during reactive hyperemia, small but not large arterioles are primarily responsible for the decrease in network resistance and subsequent hyperemia following occlusion, and the small feeder arteries did not dilate during reactive hyperemia but instead acted to set a limit on the decrease in network resistance and the increase in blood flow.


Simultaneous adsorption of ciprofloxacin and Cu2+ using Fe and N co-doped biochar: Competition and selective separation.
The treatment of combined antibiotics and heavy metals pollution is a critical challenge. Herein, iron and nitrogen co-doped biochar (Fe/N-BC) was synthesized using rape straw as precursor, and applied for the adsorption of ciprofloxacin (CIP) and Cu2+ in single and binary systems. The qmax for CIP and Cu2+ were 46.45 mg g-1 and 30.77 mg g-1, respectively. Adsorption decreased in a binary matrix, indicating that there was a competitive effect between CIP and Cu2+, which might be due to CIP and Cu2+ sharing similar active adsorption sites on Fe/N-BC. Interestingly, CIP and Cu2+ co-adsorption was a pH-dependent process. Fe/N-BC has potential to highly selectively separate CIP/Cu2+ from mixed solutions through adjusting pH values. Furthermore, adsorption mechanisms were systematically investigated in this research. This research could help to provide a deeper understanding of the synchronously removing specific antibiotics and heavy metals by biochar adsorbents.


Patients differ in their ability to self-monitor adherence to a low-sodium diet versus medication.
Poor adherence to a low-sodium diet (LSD) and prescribed medications increases rehospitalization risk in patients with heart failure (HF). Clinicians have difficulty assessing adherence objectively, so they depend on patients' self-report. The degree to which self-reported adherence reflects actual adherence is unclear. We examined patients' ability to self-monitor adherence to an LSD and medications by comparing self-reported adherence with objective evidence of adherence. A total of 133 patients with HF (male 71%; ejection fraction 35% +/- 14%) completed the Medical Outcomes Study Specific Adherence Scale. Adherence to the LSD and medication were assessed objectively using 24-hour urinary sodium excretion and dose counting with an electronic monitoring device, respectively. On the basis of self-report, patients were divided into adherent and non-adherent groups and evaluated for differences according to objective adherence. There were no differences in urinary sodium levels between the self-reported LSD adherent and non-adherent groups (4560 mg vs. 4333 mg; P = .59). Self-reported adherent and non-adherent medication groups took 92.4% and 80.4% of prescribed doses, respectively (P < .001). Patients were able to accurately estimate adherence to medication, but they failed to estimate LSD adherence. This finding suggests that we need to improve our means of evaluating adherence to the LSD and of educating patients more thoroughly about following the LSD. We speculated that the inability to estimate LSD adherence may be the result of gaps in patients' knowledge that preclude accurate self-assessment.


Infant development of configural object processing in visual and visual-haptic contexts.
Infants' visual processing of objects is characterised by a developmental trend from a predominantly analytical to a configural processing mode. In two studies with 6- and 8-month-old infants, we sought to replicate this finding in a purely visual condition (inspecting objects), and to examine how far redundant visual-haptic information present in a visual-haptic condition influences the processing mode. Infants were familiarized with two objects differing in three dimensions (texture, size and shape). At test, infants were presented with a familiar object, a switch object consisting of a recombination of familiar dimensions, and a novel object, and looking times were measured. Results indicate a transition from analytical processing at 6 months to configural processing at 8 months in the visual condition. In the visual-haptic condition, both age-groups displayed configural processing. Thus, redundant visual-haptic information seems to enhance object processing.


Text input speed in persons with cervical spinal cord injury.
This is a prospective clinical study. The objectives of this study were to determine text input speed (TIS) in persons with cervical spinal cord injury (SCI) and to study the influence of personal characteristics and type of computer access device on TIS. This study was conducted in the Rehabilitation Department, Garches, France. People with cervical SCI were included if their level of injury was between C4 and C8 Asia A or B, and if they were computer users. In addition, able-bodied people were recruited from the hospital staff. Each participant underwent a single evaluation using their usual computer access devices. TIS was evaluated during a 10- min copying task. The relationship between the characteristics of participants with cervical SCI, type of computer access device and TIS were analyzed using a Scheirer-Ray-Hare test (nonparametric test similar to a two-way analysis of variance). Thirty-five participants with cervical SCI and 21 able-bodied people were included. Median TIS of participants with cervical SCI was 11 (6; 14) words per minute (w.p.m.) and of able-bodied participants was 19 (14; 24) w.p.m. (P=0.001). Median TIS of participants with lesions at or above C5 was 12 (4; 13) w.p.m. and of those with lesions below C5 was 10 (9; 18) w.p.m. (P=0.38) [corrected]. The Scheirer-Ray-Hare test showed that only the type of computer access device significantly influenced TIS. Surprisingly, none of the person's characteristics, including the level of cervical lesion, affected TIS. This is the first study to analyze TIS in a group of participants with cervical SCI. The results showed that only the type of computer access device influenced TIS.


Maternal Perceptions Of And Responses To Child Sexual Abuse: MATERIN POGLED IN ODZIV NA SPOLNO ZLORABO OTROKA.
Several researches indicate that most child victims delay disclosing of sexual abuse for significant periods of time. There are numerous reasons as to why children are avoiding the disclosure of the abuse. The aim of this study was to determine how a mother's response to a child's allegations impacts the child's willingness to disclose sexual abuse. We conducted a retrospective quantitative and qualitative analysis of 73 court-referred cases of child sexual abuse which have been disclosed in Slovenia in the last ten years. All the child victims included in the study were female and the perpetrators adult male persons. The expert opinions were made by the same expert. We realized that, at the occurrence of abuse, the child victims were from 4 to 15 years old and their mean age was at 11. 5 years. About two-thirds of children were victims of the intra-familial type (61.6%) and a little more than one third of extra-familial type of sexual abuse (38.4%). The group of victims with the support of their mothers needed about 9 months to disclose the secret, while the delay of the disclosure in the cases without the support of mothers was much longer (M=6.9 years). For female child victims of sexual abuse the perceived protective attitude of their mothers is very important. Especially when the sexual abuse happened in the family, the mother's support can attribute to stop the ongoing abuse, eliminate its immediate effects and decrease its likely negative long-term outcome.


Correlation of apparent diffusion coefficients measured by diffusion-weighted MR imaging and standardized uptake values from FDG PET/CT in metastatic neck lymph nodes of head and neck squamous cell carcinomas.
Both diffusion-weighted magnetic resonance imaging and fluorodeoxyglucose positron emission tomography/computed tomography are oncological imaging techniques. The aim of this study was to assess any correlation between apparent diffusion coefficients and standardized uptake value in metastatic neck lymph nodes of head and neck squamous cell carcinomas.


The ethics of policy writing: how should hospitals deal with moral disagreement about controversial medical practices?
Every healthcare organisation (HCO) enacts a multitude of policies, but there has been no discussion as to what procedural and substantive requirements a policy writing process should meet in order to achieve good outcomes and to possess sufficient authority for those who are asked to follow it.Using, as an example, the controversy about patient's refusal of blood transfusions, I argue that a hospital wide policy is preferable to individual decision making, because it ensures autonomy, quality, fairness, and efficiency. Policy writing for morally controversial medical practices needs additional justification compared to policies on standard medical practices and secures legitimate authority for HCO members by meeting five requirements: all parties directed by the policy are represented; the deliberative process encompasses all of the HCO's obligations; the rationales for the policy are made available; there is a mechanism for criticising, and for evaluating the policy.


Initializing film homogeneity to retard phase segregation for stable perovskite solar cells.
The mixtures of cations and anions used in hybrid halide perovskites for high-performance solar cells often undergo element and phase segregation, which limits device lifetime. We adapted Schelling's model of segregation to study individual cation migration and found that the initial film inhomogeneity accelerates materials degradation. We fabricated perovskite films (FA1-xCsxPbI3; where FA is formamidinium) through the addition of selenophene, which led to homogeneous cation distribution that retarded cation aggregation during materials processing and device operation. The resultant devices achieved enhanced efficiency and retained >91% of their initial efficiency after 3190 hours at the maximum power point under 1 sun illumination. We also observe prolonged operational lifetime in devices with initially homogeneous FACsPb(Br0.13I0.87)3 absorbers.


Postnatal development of purinoceptors in rat visceral smooth muscle preparations.
1. Adenosine and ATP have well-established functions as neuromodulator and neurotransmitter, respectively, in smooth muscle preparations, and purinergic control may be an early form of autonomic control in both evolution and ontogenesis. 2. This review describes the postnatal development of responses mediated by the various receptors for adenosine and for nucleotides in the rat duodenum, colon, urinary bladder and vas deferens and considers the implications that this development may have for the importance of purinergic control in neonates and adults.


[Spindle-shaped cell blue naevus with lymph nodes "metastases" (author's transl)].
"Metastases" in lymph nodes are not only found from cellular blue naevi but also from their spindle-shaped cell fascicular type. These "metastases" are mostly situated in the fibrous capsule, very rarely in the parenchyma of the lymph nodes. Individually the cells resembled those of the cutaneous tumour. Their occurence in the peripheral sinuses should be verified. Epitheloid vessel-wall cells (glomus-type cells), sometimes pigmented and occasionally found in large cell aggregates, can be noted in the capsule of the lymph nodes. By several authors, these cells are considered to be benign naevus cells. The histopathogenesis and the clinical importance of the "metastases" from blue naevus are discussed.


Cauliflower mosaic virus gene I product detected in a cell-wall-enriched fraction.
Gene I product of cauliflower mosaic virus was immunodetected in a cell-wall-enriched fraction from infected turnip leaves in addition to its detection in viroplasms and replication complexes. The immunoreaction was carried out with an antiserum raised against a 15 amino acid long synthetic peptide corresponding to the carboxy-terminus of potential gene I protein (P1). The presence of P1 in different subcellular fractions was investigated as a function of time during viral multiplication. At late infection times, P1 was found only in the cell-wall-enriched fraction.


Development of a method to monitor low molecular mass hydrocarbons in exhaled breath of man: preliminary evaluation of its interest for detecting a lipoperoxidation process in vivo.
Low molecular mass hydrocarbons, particularly ethane and pentane, have been measured in expired air of man. The air is collected into 5-10 l polyamide bags. After removal of water vapour and CO2, the hydrocarbons are concentrated on a silicagel column kept at 0 degree C. The column desorption is carried out at 290 degrees C, and the gases are analysed by gas chromatography. A slight but statistically significant increased pentane production was detected in cirrhotic patients.


Postnatal changes in the inotropic effect of ouabain on the rat heart ventricle.
The concentration-dependent effects of ouabain on the contractility of postnatally developing rat heart ventricles were studied. Ouabain caused a positive inotropic effect in right ventricular strips of neonatal rats up to the age of about 30 days but a negative inotropic effect in the adult cardiac tissue. When extracellular Ca concentration was lowered from 2.5 to 1.0 mmol/l and the rate of stimulation was simultaneously elevated from 0.2 to 1.0 Hz a clear positive inotropic effect was also generated in the adult rat heart. The positive inotropic effect of ouabain showed a biphasic developmental pattern: the contractile force first grew from birth to about 15 days of age but steeply declined near to the adult level during the 3rd postnatal week. The force response to ouabain occurred within two distinct dose-ranges. In the newborn only the high-dose (above 3 X 10(-6) mol/l) effect was seen but in rats older than 5 days a mixed low-dose (below 3 X 10(-6) mole/l)/high-dose effect was apparent. In both ranges the positive inotropic effect of ouabain seemed to be dependent on caffeine sensitive Ca store, perhaps the sarcoplasmic reticulum. It is suggested that during the 3rd postnatal week a transition from extracellular to intracellular Ca stores occurs in the rat heart, which is reflected as a changing inotropic effect of ouabain on the developing cardiac tissue.


The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus.
We have studied the effects of 3 wk of continuous subcutaneous insulin infusion (CSII) on endogenous insulin secretion and action in a group of 14 type II diabetic subjects with a mean (+/-SEM) fasting glucose level of 286 +/- 17 mg/dl. Normal basal and postprandial glucose levels were achieved during insulin therapy at the expense of marked peripheral hyperinsulinemia. During the week of posttreatment evaluation, the subjects maintained a mean fasting glucose level of 155 +/- 11 mg/dl off insulin therapy, indicating a persistent improvement in carbohydrate homeostasis. Adipocyte insulin binding and in vivo insulin dose-response curves for glucose disposal using the euglycemic clamp technique were measured before and after therapy to assess the effect on receptor and postreceptor insulin action. Adipocyte insulin binding did not change. The insulin dose-response curve for overall glucose disposal remained right-shifted compared with age-matched controls, but the mean maximal glucose disposal rate increased by 74% from 160 +/- 14 to 278 +/- 18 mg/m2/min (P less than 0.0005). The effect of insulin treatment on basal hepatic glucose output was also assessed; the mean rate was initially elevated at 159 +/- 8 mg/m2/min but fell to 90 +/- 5 mg/m2/min in the posttreatment period (P less than 0.001), a value similar to that in control subjects. Endogenous insulin secretion was assessed in detail and found to be improved after exogenous insulin therapy. Mean 24-h integrated serum insulin and C-peptide concentrations were increased from 21,377 +/- 2766 to 35,584 +/- 4549 microU/ml/min (P less than 0.01) and from 1653 +/- 215 to 2112 +/- 188 pmol/ml/min (P less than 0.05), respectively, despite lower glycemia. Second-phase insulin response to an intravenous (i.v.) glucose challenge was enhanced from 170 +/- 53 to 1022 +/- 376 microU/ml/min (P less than 0.025), although first-phase response remained minimal. Finally, the mean insulin and C-peptide responses to an i.v. glucagon pulse were unchanged in the posttreatment period, but when glucose levels were increased by exogenous glucose infusion to approximate the levels observed before therapy and the glucagon pulse repeated, responses were markedly enhanced. Simple and multivariate correlation analysis showed that only measures of basal hepatic glucose output and the magnitude of the postbinding defect in the untreated state could be related to the respective fasting glucose levels in individual subjects.(ABSTRACT TRUNCATED AT 400 WORDS)


Pathways of arachidonic acid metabolism in human amnion cells at term.
We have compared the metabolism of (3H) arachidonic acid by monolayers of human amnion, cells obtained prior to or following labor at term. Radiolabel was either added exogenously or previously incorporated into cellular phospholipid pools to compare metabolism of arachidonic acid from different substrate sources. Cells obtained both prior to and following labor synthesized metabolites co-chromatographing on HPLC with di- and mono-HETEs and also a metabolite with polarity corresponding to a epoxyeicosatrienoic acid. Both types of cells were able to synthesize PGE2 when (3H) arachidonic acid was added exogenously. However, only those cells obtained following labor synthesized PGE2 from (3H) arachidonic acid incorporated into intracellular pools. These findings suggest that the cyclooxygenase and PGE2 isomerase enzymes are present in amnion prior to delivery but that exogenous arachidonic acid would be required for PGE2 synthesis at that time as the enzymes do not appear to be linked to a source of endogenous arachidonic acid. At the time of parturition, there may be a switching on of an enzyme system to generate arachidonic acid from intracellular pools specifically for PGE2 synthesis or alternatively coupling of such a system to a cyclooxygenase-PGE2 isomerase system resulting in PGE2 synthesis. These findings raise intriguing new possibilities for the regulation of eicosanoid synthesis in amnion which may include membrane topography, substrate pool-enzyme linking and regulation of specific phospholipase enzymes.


Protective effects of pentoxifylline on lipopolysaccharide-induced white matter injury in a rat model of periventricular leukomalasia.
To investigate the potential neuroprotective effect of maternal pentoxifylline (PNTX) treatment in endotoxin-induced periventricular leukomalasia (PVL) in the developing rat brain. Intraperitoneal injection of lipopolysaccharide was administered on two of three Wistar pregnant rats to establish PVL. To obtain PNTX-treated group, one of the two dams were injected with PNTX. The control group was treated with saline. Rat pups were grouped as control, maternal LPS-treated group and PNTX + LPS-treated group. At 7th postnatal days, apoptosis and hypomyelination were evaluated. Apoptosis was evaluated by caspase-3 and terminal deoxynucleotidyl transferase [TdT] dUTP nick endlabelling reaction (TUNEL) immunostaining. To assess hypomyelination, myelin basic protein (MBP) staining, as a marker of myelination, was evaluated. MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the PNTX-treated group. PNTX treatment significantly reduced the number of apoptotic cells in the periventricular WM shown on Tunel and caspase-3. Presented study is first indicated that PNTX may provide protection against an LPS-induced inflammatory response and WMI in the developing rat brain. Our results also suggest that PNTX treatment in pregnant women with maternal or placental infection may minimize the risk of PVL and cerebral palsy.


Effect Modification of Long-Term Air Pollution Exposures and the Risk of Incident Cardiovascular Disease in US Women.
Ambient air pollution exposures have been frequently linked to cardiovascular disease (CVD) morbidity and mortality. However, less is known about the populations most susceptible to these adverse effects. We assessed the associations of long-term particulate matter (PM) exposures with incident CVD in a nationwide cohort of 114 537 women in the Nurses' Health Study, and performed analyses to identify subpopulations at the greatest risk. Residential address level time-varying monthly exposures to PM2.5, PM10, and PM2.5 to 10 microns in diameter were estimated from spatio-temporal prediction models. In multivariable models, increases in all size fractions of PM were associated with small, but not statistically significant, increased risks of total CVD, coronary heart disease, and stroke. PM-associated CVD risks were statistically significantly higher among women with diabetes as compared to those without (P-for-interaction <0.0001 for PM10 and PM2.5 and 0.007 for PM2.5 to 10). For each 10 μg/m(3) increase in 12-month average PM2.5, PM2.5 to 10, and PM10, the multivariable adjusted hazard ratios were 1.44 (95% CI: 1.23 to 1.68), 1.17 (95% CI: 1.05 to 1.30), and 1.19 (95% CI: 1.10 to 1.28) among women with diabetes. There were also suggestions of higher risks among older (≥70 years) women, the obese, and those living in the Northeast and South. Smoking status and family history did not consistently modify the association between PM and CVD, and risks were most elevated with exposures in the previous 12 months. In this nationwide cohort, women with diabetes were identified as the subpopulation most sensitive to the adverse cardiovascular health effects of PM.


Predictors of survival after a positive post-irradiation prostate biopsy.
Considerable debate persists in the urologic oncology literature with regard to the optimum management of patients with a positive post-irradiation prostate biopsy. This analysis characterizes a group of such patients who have had a favorable course without intervention. Between 1956 and 1991, 116 patients have had a positive prostate biopsy 12 or more months post-irradiation without hormonal intervention or evidence of distant relapse. The population had an age range of 42 to 82 years (median - 61). American Joint Committee on Cancer stages included 1 T1, 70 T2, 44 T3, and 1 T4. Median actuarial survival for the entire population was 14.4 years (range = 2.2-21.5 years) from presentation and 5.2 years from re-biopsy. Fifty-one of the 116 patients developed metastases subsequent to re-biopsy and 65 remain free from distant relapse. Among these 65 patients, 50 remain alive and otherwise well, 11 have died of other causes, and only four have succumbed to their local disease. The best predictor of distant relapse subsequent to re-biopsy was digital rectal exam. Forty-one of the 51 patients later developing metastases had an abnormal digital rectal exam compared to 37 of 65 with sustained distant control (p = .01). These data demonstrate that long-term, disease-free (other than re-biopsy) survival is common following a "positive" post-irradiation biopsy without intervention especially among patients with a normal digital rectal exam. Therefore, routine re-biopsy without clinical indications is not a useful practice.


High starter phosphorus fertilization facilitates soil phosphorus turnover by promoting microbial functional interaction in an arable soil.
Microbial phosphorus (P) turnover is critical in C utilization efficiency in agroecosystems. It is therefore necessary to understand the P mobilization processes occurring during P fertilization in order to ensure both crop yield and environmental quality. Here, we established a controlled pot experiment containing soil amended with three different levels of starter P fertilizer and collected soil samples after 30, 60, and 90 days of incubation. Quantitative microbial element cycling (QMEC) smart chip technology and 16S rRNA gene sequencing were used to investigate functional gene structures involved in carbon, nitrogen and P cycling and the bacterial community composition of the collected samples. Although P fertilization did not significantly affect the structure of the soil microbial community, some rare microbiota were changed in particular phosphorus-solubilizing bacteria were enriched at the high P fertilization level, suggesting that the rare taxa make an important contribution to P turnover. P fertilization also altered the functional gene structure, and high P concentrations enhanced the functional gene diversity and abundance. Partial redundancy analysis further revealed that changes in rare taxa and functional genes of soil microorganisms drive the alteration of soil P pools. These findings extend our understanding of the microbial mechanisms of P turnover.


The subchronic toxicity and teratogenicity of alternariol monomethyl ether produced by Alternaria solani.
Alternariol monomethyl ether (AME), a metabolite of species of Alternaria, was studied for subchronic toxicity to rats and teratogenic effects in golden hamsters. In rats no toxic effects were observed at the highest dosage tested (3.75 mg given by oral gavage daily for 30 days). However, AME was maternally toxic and foetotoxic to Syrian golden hamsters when given ip at 200 mg/kg body weight on day 8 of gestation. No such effects were observed at dose levels of 50 or 100 mg/kg.


Effects of whole-body rotation on masseteric motoneuron excitability.
Vestibular stimulation is a popular clinical treatment for enhancing the excitability of spinal motoneurons innervating trunk and limb muscles, but whether vestibular stimulation can also influence trigeminal motoneurons is not known. We determined whether or not vestibular stimulation evoked by rotation of a seated subject would modify the excitability of masseteric motoneurons. The amplitude and frequency of occurrence of masseteric compound action potentials evoked by standard chin taps provided measures for assessing masseteric motoneuron excitability. Eleven healthy adults with no orofacial or otologic disorders served as subjects. Each sat in a motorized dental chair with his head stabilized by a halo head-piece so that chair rotation caused labyrinthine excitation. The frequency (3/s) of chin taps and their impact force were maintained constant by microcomputer control. After each tap, a 16-ms sample of EMG recorded from surface electrodes over the right masseter was digitized and stored for subsequent visual inspection. Only compound action potentials meeting rigorous criteria in terms of latency, amplitude, duration, and waveform were accepted as responses. The mean frequencies of occurrence and the mean amplitudes of the responses showed wide variability. Histogram displays of every response for each subject, however, revealed enhanced output from the masseteric motoneuron pool during the decleration and postrotation phases. In subjects not immediately retested this enhancement was persistent but decayed during the next 5 min. In five subjects the experiment was repeated after 1 min. The changes in response variables during phases 3 and 4 were significantly less than on the first trial, suggesting habituation. These results provide quantitative evidence that the dynamic input from vestibular ampullary receptors in response to rotation enhances masseteric motoneuron output.


Surviving death: emerging concepts of RIPK3 and MLKL ubiquitination in the regulation of necroptosis.
Lytic forms of programmed cell death, like necroptosis, are characterised by cell rupture and the release of cellular contents, often provoking inflammatory responses. In the recent years, necroptosis has been shown to play important roles in human diseases like cancer, infections and ischaemia/reperfusion injury. Coordinated interactions between RIPK1, RIPK3 and MLKL lead to the formation of a dedicated death complex called the necrosome that triggers MLKL-mediated membrane rupture and necroptotic cell death. Necroptotic cell death is tightly controlled by post-translational modifications, among which especially phosphorylation has been characterised in great detail. Although selective ubiquitination is relatively well-explored in the early initiation stages of necroptosis, the mechanisms and functional consequences of RIPK3 and MLKL ubiquitination for necrosome function and necroptosis are only starting to emerge. This review provides an overview on how site-specific ubiquitination of RIPK3 and MLKL regulates, fine-tunes and reverses the execution of necroptotic cell death.


[Incidence of the therapeutic advances in children and adolescents that suffered cancer].
This article intends to consider some aspects of the long term effects in the children and adolescents who suffered cancer and the impact that the new technologies and treatments produce.


Prioritized sequencing of the second exon of MYO15A reveals a new mutation segregating in a Pakistani family with moderate to severe hearing loss.
Mutations in MYO15A are associated with deafness in humans, and shaker 2 mice also exhibit a hearing loss due to defects of unconventional myosin 15a. We ascertained a consanguineous Pakistani family with recessively inherited moderate to severe hearing loss, which putatively segregated with markers linked to the DFNB3 locus. Prioritized sequencing of the second exon of MYO15A from the DNA of all affected individuals of family revealed a duplication of Cytosine in a stretch of seven repetitive C nucleotides (c.1185dupC). This mutation results in a frameshift and incorporates a stop codon in the open reading frame of MYO15A (p.E396fsX431). The findings of less severe hearing loss in families with linkage to DFNB3 are only reported for some individuals with mutations in exon 2 of MYO15A, which are further supported by this study. Therefore, on basis of linkage data and the presence of a less severe hearing loss phenotype, sequencing of a single exon of MYO15A can efficiently identify the causative mutations in patients from these families.


Cigarette smoking differentially regulates inflammatory responses in a mouse model of nonalcoholic steatohepatitis depending on exposure time point.
Cigarette smoke (CS) is a risk factor for the development of nonalcoholic fatty liver disease. However, the role of mainstream CS (MSCS) in the pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear. During the first (early exposure) or last (late exposure) three weeks of methionine-choline deficient with high fat diet feeding (6 weeks), each diet group was exposed to MSCS (300 or 600 μg/L). Hepatic or serum biochemical analysis showed that MSCS differentially modulated hepatic injury in NASH milieu, depending on exposure time points. Consistently, NASH-related hepatocellular apoptosis and fibrosis were increased in the early exposure group, but decreased in the late exposure group, except for steatosis. Ex vivo experiments showed that CS extract differentially regulated inflammatory responses in co-cultured hepatocytes and macrophages isolated from steatohepatitic livers after 10 days or 3 weeks of diet feeding. Furthermore, CS differentially up- and down-regulated the expression levels of M1/M2 polarization markers and peroxisome proliferator-activated receptor-gamma (PPARγ) in livers (29% and 38%, respectively) or co-cultured macrophages (2 and 2.5 fold, respectively). Collectively, our findings indicate that opposite effects of MSCS on NASH progression are mediated by differential modulation of PPARγ and its-associated M1/M2 polarization in hepatic macrophages, depending on exposure time points.


Effects of dorsal raphe stimulation on escape induced by medial hypothalamic or central gray stimulation.
Electrical stimulation of the ventral part of the mesencephalic central gray affects escape responding induced by stimulation of either the medial hypothalamus (MH) or dorsal central gray (CG) in the rat. The sign and magnitude of the effect appeared to depend on the following factors: (1) The location of the site stimulated in the ventral central gray and the intensity of the stimulation. A stimulation of the dorsal raphe nucleus (DR) which induced a marked rewarding and a low aversive effect reliably suppressed MH or CG induced escape. Stimulation of sites located at the boundary between DR and central gray enhanced escape at low intensities and suppressed it at higher intensities. When located more laterally in the ventral central gray, the stimulation induced less rewarding and more marked aversive effects and it reliably enhanced MH or CG induced escape. (2) The kind of stimulation applied (monopolar or bipolar). (3) The location of the site (MH or CG) from which the stimulation-induced escape responses were obtained.


A profile of skin cancer prevention media coverage in 2009.
Little is known about the coverage of skin cancer prevention messages in news print media. To perform a content analysis of mass-media articles from newspaper and magazines pertaining to skin cancer prevention in 4 specific months (January, May, July, and October) in 2009 and assess the extent of coverage of skin cancer prevention messages. We conducted a content analysis of 144 articles related to skin cancer prevention extracted from strategic media scans of selected months in 2009. We sought to provide the frequency of mass-media content categorized by theme and focus related to ultraviolet radiation (UVR) protection and risk-reducing behaviors. The audience for the vast majority (78%) of the articles was the general public. Among the assessed articles, more were published in May (49%) and July (35%) than in the remaining other months. The two most frequent themes focused on 'protection of the skin' (32%) and on 'skin cancer prevention' (23%) via risk reduction behavioral practices. Analysis of message content regarding UVR reduction practices showed that many mentioned 'use of sunscreen' (65% of messages) with the least-often mentioned behaviors being 'seek shade' (6.3%) and 'do not burn' (1.4%). In addition, a quarter of the articles lacked any content mentioning recommended UVR reduction behaviors. This study was limited to the narrow scope of articles published in 2009 and for selected months. This profile of mass-media content regarding skin cancer prevention revealed gaps in coverage of UVR reduction behaviors with possible room for improvement. Strategies for improving and comprehensiveness of coverage of recommended skin cancer prevention behaviors in the media are discussed.


Immunogenicity of Semliki Forest virus based self-amplifying RNA expressing Indian HIV-1C genes in mice.
Development of recombinant vaccines is considered as a promising approach to prevent transmission and eradication of HIV/AIDS. Candidate vaccines tested so far have shown poor to modest efficacy. Self-amplifying RNAs of positive strand alphaviruses are reported to be promising vectors for development of recombinant vaccines. This study describes the construction, in vitro expression and in vivo immunogenicity of recombinant RNA vaccines developed by individually cloning gag, env and polRT genes of primary HIV-1C Indian isolates using Semliki Forest virus (SFV) vector. HIV-1C specific T cell responses were detected in mice immunized with rSFV2gen/gag RNA by IFN-γ ELISPOT assay. Furthermore, using flow cytometry based intracellular cytokine staining (ICCS) assay HIV-1C specific IL-2 responses were detected in immunized mice that were mediated by both CD4(+) and CD8(+) T cells. Mice immunized with rSFV2gen/env RNA elicited HIV-1C Env-specific antibodies as detected by gp120 ELISA. The Env, Gag and Pol (RT) RNA constructs in combination elicited better HIV-1C Env-specific humoral responses compared to mice immunized with Env RNA alone. In conclusion, rSFV2gen RNA constructs encoding HIV-1C antigens elicited clear cell mediated and humoral immune responses in mice, thus demonstrating the potential of self-amplifying rSFV2gen RNA as a promising candidate for anti-HIV vaccine development.


A naturally occurring epigenetic mutation in a gene encoding an SBP-box transcription factor inhibits tomato fruit ripening.
A major component in the regulatory network controlling fruit ripening is likely to be the gene at the tomato Colorless non-ripening (Cnr) locus. The Cnr mutation results in colorless fruits with a substantial loss of cell-to-cell adhesion. The nature of the mutation and the identity of the Cnr gene were previously unknown. Using positional cloning and virus-induced gene silencing, here we demonstrate that an SBP-box (SQUAMOSA promoter binding protein-like) gene resides at the Cnr locus. Furthermore, the Cnr phenotype results from a spontaneous epigenetic change in the SBP-box promoter. The discovery that Cnr is an epimutation was unexpected, as very few spontaneous epimutations have been described in plants. This study demonstrates that an SBP-box gene is critical for normal ripening and highlights the likely importance of epialleles in plant development and the generation of natural variation.


Emulsive polymerization as a method of enzyme modification preserving biological properties of nanostructures.
The proposed method of emulsive polymerization provides the possibility of modifying and obtaining insoluble forms of superoxide dismutase (SOD), glutathione reductase, and streptolysin-O preserving nanoobjects (conformationally active centers and antigenic determinants) in their native states. Apart from enzymatic and immunological properties, the samples acquired some new features: resistance to high temperature, resistance to 3 M KCNS solution and buffer solutions with high concentration of hydrogen ions, and resistance to preserving solutions. Magnetic properties provide the possibility of simplifying enzyme-linked immunosorbent and immunofluorescence assays. In addition, sensitivity of these assays was by an order of magnitude higher and the specificity fully preserved. Taking all the facts into account, we prepared agents for long-term and repeated use. Due to preserved enzymatic properties, insoluble forms of SOD and glutathione reductase can be considered as a tool for correction of peroxide-antioxidant balance and associated immunological abnormalities.


Covalent interaction between proform of eosinophil major basic protein (proMBP) and pregnancy-associated plasma protein-A (PAPP-A) is a cell-mediated event and required for proMBP inhibition of the catalytic activity of PAPP-A.
This study was undertaken to determine the mechanism by which proform of eosinophil major basic protein (proMBP) inhibits the IGFBP-4 proteolytic activity of pregnancy-associated plasma protein (PAPP)-A. Co-overexpression of PAPP-A with proMBP in 293T cells, or co-incubation of 293T cells, respectively, overexpressing proMBP and PAPP-A resulted in the formation of a covalent proMBP-PAPP-A complex and inhibition of IGFBP-4 proteolysis. Similar results were obtained when recombinant proMBP and PAPP-A were incubated in the presence of U2 osteosarcoma cells or when recombinant proMBP was added to the U2 cells overexpressing PAPP-A. In contrast, no formation of covalent proMBP-PAPP-A complex or inhibition of IGFBP-4 proteolysis was observed when recombinant proMBP and PAPP-A were incubated under cell-free conditions, although proMBP was able to interact with PAPP-A in a non-covalent manner. These new findings suggest that formation of covalent proMBP-PAPP-A complex is a cell-mediated event and is required for proMBP to inhibit the catalytic activity of PAPP-A.


Integration of safe initial combination chemotherapy (without cisplatin) with a high response rate and local therapy for untreated stage III and IV epidermoid cancer of the head and neck: 5-year survival data.
This prospective study has established the effectiveness and safety of two courses of a combination of vincristine, bleomycin, methotrexate, 5-FU, and hydrocortisone with a folinic acid "rescue" given over 24 hours on Days 1 and 14 prior to surgery and/or radiotherapy in 93 patients with advanced (stage III and IV) untreated epidermoid cancer of the head and neck. Of 91 patients evaluated on Day 28 for chemotherapy response, 58 (64%) had a partial remission and 33 (36%) were classified as nonresponders, although 12 had a minimal response of 20%-30%. After completion of local therapy, 73% of the chemotherapy responders achieved complete remission compared with only 48% of the nonresponders (P = 0.005). Forty-seven percent of the patients achieving complete remission were alive at 5 years compared with only 4% of those with residual disease after local therapy. Response to chemotherapy is a good prognostic sign. Side effects were minimal and there was 100% patient compliance.


Identification of the vascular and avascular zones of the human meniscus using magnetic resonance imaging: correlation with histology.
Since the initial employment of magnetic resonance imaging (MRI) to diagnose meniscal tears, a characteristic low-signal intensity, triangular-shaped structure has been interpreted as representing the entire meniscus. The difficulty in diagnosing meniscocapsular separations with MRI has brought attention to our lack of understanding of the appearance on MRI of the outer third of the meniscus and the meniscocapsular junction. We correlated MRIs of the meniscus in cadaver knees with histological sections and found that the low-signal, wedge-shaped structure corresponds only to the avascular (white) zone of the meniscus, whereas the high-signal zone peripheral to it corresponds to the vascularized (red) zone.


Percutaneous transhepatic interventional therapy of portal vein stenosis in paediatric liver transplantation: A systematic review of efficacy and safety.
To determine the efficacy and safety of percutaneous trans-hepatic balloon and/or stent angioplasty (PTA) in the management of portal vein (PV) stenosis following paediatric liver transplantation. Articles were included from a systematic search of Medline, Embase, Cochrane CENTRAL, ClinicalTrials.gov and International Clinical Trials Registry from inception to the 29th of August 2020. There were 213 paediatric liver recipients who underwent PTA for PV stenosis in 19 included studies published between 1991 and 2019. Balloon angioplasty was the initial treatment in the majority (n = 153). Primary stent placement (n = 34) was performed for elastic recoil, intimal tears and PV kinks and rescue stent placement (n = 14) for recurrent PV stenosis following primary balloon angioplasty. The technical success was 97.6%-100% overall, 97.6%-100% for balloon-angioplasty-only and 100% for primary stenting. The clinical success was 50%-100% overall, 50%-100% for balloon-angioplasty-only and 100% for primary stenting. Long-term PV patency was 50%-100% overall, 37.5%-100% for balloon-angioplasty-only and 100% for primary stenting. Primary balloon angioplasty was successful in 78% of the cases. Of the recurrent PV stenoses, 9% resolved with stent placement and one required a meso-Rex shunt. There was one re-transplantation without stenting. The complication rate was 2.6% for balloon-angioplasty-only (bleeding, liver abscess, 2 PV thromboses) and 5.9% for primary stenting (bleeding, stent-fracture). There was no procedure-related mortality. Percutaneous transhepatic balloon angioplasty may be the initial management of portal vein stenosis in paediatric liver recipients. Stent placement may be a primary option in selected cases and a reliable rescue option for recurrent portal vein stenosis following balloon-angioplasty-only.


Discovery of linear unnatural peptides as potent mutant isocitrate dehydrogenase 1 inhibitors by Ugi reaction.
Isocitrate dehydrogenases 1 (IDH1) catalyzes the oxidative decarboxylation of isocitrate to ɑ-ketoglutaric acid (α-KG). It is the most frequently mutated metabolic gene in human cancer and its mutations interfere with cell metabolism and epigenetic regulation, thus promoting tumorigenesis. In order to discover potent new mutant IDH1 inhibitors, based on the structure of marketed inhibitor AG-120 (Ivosidenib), we designed, synthesized and evaluated a series of linear unnatural peptide analogues via Ugi reaction, as potential mutant IDH1 inhibitors. All these compounds were evaluated for their inhibition on mutant IDH1 enzyme activity. The structure-activity relationship was discussed on the basis of experimental data, with an attempt to pave the way for future studies. Among them, 43 exhibited potent and selective enzyme inhibitory activity, and showed strong binding affinity with mutant IDH1. It can decrease the cellular concentration of 2-HG, and suppress the proliferation of HT1080 and IDH1 mutant-U-87 cells by selectively inhibiting the activity of mutant IDH1.


[2013 vulvodynia update].
Provoked vestibulodynia represents the most frequent cause of dyspareunia before menopause. Vulvodynia's pain and burning sensations are related to neuropathic pain and associated to various degrees of vulvar mucosal hypersensitivity (mostly in the vestibular area), pelvic floor muscles dysfunction, a disorder of general perception of pain and/or various complex regional pain syndromes such as fibromyalgia, glossodynia, painful bladder syndrome (interstitial cystitis)… Vaginal infections such as candidiasis and vaginosis are important trigger and risk factors. Women suffering from vulvodynia are often described as vulnerable, pessimistic, developing feelings of guilt towards their partner. They tend to be hyper vigilant to their pain and develop catastrophizing reactions (rumination, magnification and helplessness) and avoidance/escape behaviors (fear-avoidance model). Diagnosis is based on medical history, clinical examination (Q-tip test) and exclusion of vaginitis. Treatment consists of a multidisciplinary approach involving topical therapies (emollients, anesthetics, hormonotherapy if necessary), pelvic floor physiotherapy with electromyographic biofeedback, drug treatment of pain with antidepressants (amitriptyline…) or anticonvulsants (pregabaline…) and a psychosexual support.


Forefoot Pain in the Lesser Toes: Anatomical Considerations and Magnetic Resonance Imaging Findings.
Various conditions may result in forefoot pain. Magnetic resonance (MR) imaging allows accurate assessment of many of these conditions. We provide an overview of forefoot disorders divided into bones, capsule and plantar plate, musculotendinous structures, neurovascular structures, and subcutaneous tissue. We review normal anatomical features as well as MR imaging findings of common disorders.


Immobilization for scaphoid fracture: forearm rotation in long arm thumb-spica versus Munster thumb-spica casts.
A Munster thumb-spica cast may play a role in the conservative treatment of non-displaced scaphoid fractures by allowing some elbow motion during the long immobilization period.


Microbial degradation of aromatic compounds - from one strategy to four.
Aromatic compounds are both common growth substrates for microorganisms and prominent environmental pollutants. The crucial step in their degradation is overcoming the resonance energy that stabilizes the ring structure. The classical strategy for degradation comprises an attack by oxygenases that hydroxylate and finally cleave the ring with the help of activated molecular oxygen. Here, we describe three alternative strategies used by microorganisms to degrade aromatic compounds. All three of these methods involve the use of CoA thioesters and ring cleavage by hydrolysis. However, these strategies are based on different ring activation mechanisms that consist of either formation of a non-aromatic ring-epoxide under oxic conditions, or reduction of the aromatic ring under anoxic conditions using one of two completely different systems.


Correlation Between Flexible Fiberoptic Laryngoscopic and Polysomnographic Findings in Patients with Mucopolysaccharidosis Type VI.
This study aimed to compare flexible fiberoptic laryngoscopy (FFL) and polysomnography (PSG) findings in patients with mucopolysaccharidosis (MPS) type VI and to describe upper airway anatomical findings and abnormal PSG results in these patients. In this cross-sectional study, all MPS VI patients followed up at the genetic division of a hospital in southern Brazil were included. Overnight PSG was performed, and the results were classified as normal or mildly, moderately, or severely abnormal. FFL was performed between 7 days before and 7 days after PSG. FFL findings were classified as (1) no obstruction, (2) mild obstruction, (3) moderate obstruction, or (4) severe obstruction of the airways, using the highest score obtained in all the regions.Eleven patients with MPS VI were included. FFL detected severe airway obstruction in eight (72.7%) patients, moderate obstruction in two (18.2%), and mild obstruction in one (9.1%). PSG revealed obstructive sleep apnea syndrome (OSAS) in nine (81.8%) patients. Among these, mild OSAS was observed in five (45.5%) patients, moderate OSAS in three (27.2%), and severe OSAS in one (9.1%). Moderate to severe hypertrophy of the nasal turbinates was found in 81.8% of the patients, and 64% had severe infiltration in the supraglottic region. There was no association between FFL and PSG findings (p = 0.454; κ = -0.09; 95%CI = -0.34 to 0.17), indicating no agreement between the two methods. In the present study, all patients with MPS showed some degree of airway obstruction. We suggest performing PSG in MPS patients to determine disease severity.


Occurrence and Timing of Advance Care Planning in Persons With Dementia in General Practice: Analysis of Linked Electronic Health Records and Administrative Data.
Advance care planning (ACP) is a process of communication in which patients and family caregivers discuss preferences for future care with the healthcare team. For persons with dementia, it is crucial to timely engage in ACP. Therefore, we study ACP in dementia using electronic health record data. This study aims to determine how often ACP conversations are recorded, analyze time from dementia diagnosis until the first recorded conversation and time from the first recorded conversation to death, and analyze which factors are associated with the timing of ACP. Electronic records of 15,493 persons with dementia in Dutch general practice between 2008 and 2016 were linked to national administrative databases. ACP conversations and indicators of health deficits to determine frailty were obtained from electronic records coded with the International Classification of Primary Care. Socio-demographic characteristics were derived from the national population registry managed by Statistics Netherlands. Date of death was derived from the Personal Records Database (2008-2018). ACP was recorded as such as 22 (95% CI, 20-23) first conversations per 1,000 person-years of follow-up. The hazard ratio (HR) for the first conversation increased every year after dementia diagnosis, from 0.01 in the first year to 0.07 in the 7th and 8th year after diagnosis. Median time from a first conversation to death was 2.57 years (95% CI, 2.31-2.82). Migrant status [non-Western vs. Western (HR 0.31, 95% CI, 0.15-0.65)] was significantly associated with a longer time from dementia diagnosis to the first conversation. Being pre-frail (HR 2.06, 95% CI, 1.58-2.69) or frail (HR 1.40, 95% CI, 1.13-1.73) vs. non-frail was significantly associated with a shorter time from dementia diagnosis to the first ACP conversation. ACP conversations in Dutch general practice were rare for persons with dementia, or was rarely recorded as such. In particular among persons with a non-Western migration background and those who are non-frail, it started long after diagnosis. We advise further research into public health and practical strategies to engage persons with dementia with a non-Western migration background and non-frail persons early in the disease trajectory in ACP.


Homelessness: cause and effects.
In today's world, wealth accumulates in ever fewer hands. People who live at the margin of the socioeconomic system and are infirm are most prone to become homeless. Many medical and psychiatric problems beset this population. Among them, rheumatic and musculoskeletal diseases are, at the same time, illnesses and barriers to care. Healthcare innovations may decrease the lot of these unfortunate. To correct the root of the problem, we should also set our moral compass to a more egalitarian society.


Laparoscopic and perineal approaches to perineal hernia repair.
Perineal hernias after abdominoperineal resection (APER) of the rectum appear to be becoming more common, but there only a small number of reported cases, with very few reports discussing more than one or two. There is little consensus as to the optimal method of repair. We report the successful management of 7 cases of postoperative perineal hernia, including a hernia around a gluteal rotation flap that has not previously been reported, and discuss the operative approaches. We performed a single-centre hospital database review over 6 years. Seven perineal hernias occurred after APER and were repaired. Six were treated with a transabdominal approach (5 laparoscopic and 1 laparoscopic converted to open) and one perineal approach. In 4 cases, a synthetic composite mesh was used, in 2 a biological mesh and in one direct suture repair. There have been no recurrences during a median follow-up of 25 months. Laparoscopic mesh repair of symptomatic perineal hernia is the method of choice in most cases. Herniation may still occur despite inset of a gluteal rotation flap at initial APER and laparoscopic repair in that instance is difficult.


Nonspecific ulcers of the colon.
Two cases of nonspecific cecal ulceration are presented. The lesions tend to occur in the right colon, produce pain or bleeding, and generally are best managed surgically. Etiology of the ulcers is unknown, but a vascular theory of origin is favored.


[Simultaneous determination of contents of sophoridine, oxymatrine and oxysophocarpine in seed of Sophora alopecuroides by HPLC].
To develop a HPLC method for simultaneous determination of the contents of sophoridine, oxymatrine and oxysophocarpine in seed of Sophora alopecuroides. Chromatographic condition included a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) column and thmobile phase consisting of a mixture of methanol-0.2% phosphatic acid (7:93). The detection wavelength was at 205 nm. The flow rate was 1.0 mL x min(-1) and column temperature was set at 30 degrees C. All calibration curves showed good linearity (r > or = 0.9997) within test ranges. The mean recoveries were 100.0%, 97.0% and 97.0% respectively. This method is simple, rapid and accurate, and suitable for quality control of S. alopecuroides seed.


Holeboard maze-learning deficits and brain monoaminergic neurotransmitter concentrations in rats after intracerebroventricular injection of 3-bromopyruvate.
3-Bromopyruvate is a suicide inhibitor of pyruvate dehydrogenase complex in brain homogenates, and after intracerebral injection reduces acetylcholine tissue content and muscarinic cholinergic receptors in brain cortex and hippocampus for extended periods of time. A stereotaxic injection of 0.2 mumol 3-bromopyruvate was given twice into the cerebral ventricles of male Wistar rats. Ten weeks later, the animals were tested for learning deficits in a food-motivated complex holeboard test. 3-Bromopyruvate-treated rats showed an increased number of visits to nonfood-baited holes over a 5-day testing period (four trials per day) compared to sham-operated control rats, an increased number of visits to food-baited holes over the first 2 days of the testing period and an increased time for completing the task. There were no changes in brain monoaminergic neurotransmitter concentrations compared to controls. The results indicate that long-term learning deficits in a spatial discrimination paradigm are caused by 3-bromopyruvate, which might be related to a cholinergic deficit induced by a primary inhibition of brain glucose metabolism at the step of pyruvate dehydrogenase complex. This animal model may be useful for behavioral studies in relation to neurodegenerative diseases like dementia of Alzheimer type.


The effects of bisphenol A, F and their mixture on algal and cyanobacterial growth: from additivity to antagonism.
Bisphenol A (BPA) is, due to its widespread use including the production of plastic materials, an ubiquitous pollutant in the aquatic environment. Due to evidence of adverse BPA effects on the environment and human health, its use has been restricted and replaced by analogues such as bisphenol F (BPF). This study examined the toxicity of BPA, BPF and their mixture towards primary producers, the eukaryotic green alga Pseudokirchneriella subcapitata and the prokaryotic cyanobacterium Synechococcus leopoliensis. The results demonstrated that S. leopoliensis is more sensitive than P. subcapitata, whereas toxic potential of the two BPs is comparable and represents comparable hazard for phytoplankton. The toxicity of the binary mixture was predicted by different models (concentration addition, independent action, combination index and the isobologram method) and compared to experimental data. Additive effect was observed in P. subcapitata over the whole effect concentration range (EC5-EC90), whereas in S. leopoliensis, no pronounced combined effect was observed. The environmental risk characterisation based on the comparison of reported concentrations of BPA and BPF in surface waters to the predicted no-effect concentration values obtained in this study showed that at certain industrial areas, BPA represents environmental risk, whereas BPF does not. However, BPF concentrations in aquatic environment are expected to increase in the future. To enable environmental risk assessment of BP analogues, more data on the toxicity to aquatic species, including combined effect, as well as data on their occurrence in the aquatic environment are needed.Graphical abstract.