Fasciola hepatica products can alter the response of bovine immune cells to Mycobacterium avium subsp. paratuberculosis.
Fasciola hepatica causes economically important disease in livestock worldwide. The relevance of this parasitic infection extends beyond its direct consequences due to its immunoregulatory properties. Given the importance of the T helper 1 (Th1) immune response in controlling infections with Mycobacterium avium subspecies paratuberculosis (MAP) in cattle, we aimed to establish the immunological consequences that co-infection with F. hepatica might have on the course of Johne's disease (JD). This study compared the in vitro response of bovine immune cells to infection with MAP or exposure to MAP antigens following F. hepatica infection or stimulation with F. hepatica products. We found a decreased proliferation of peripheral blood mononuclear cells (PBMCs) after infection with F. hepatica. This reduction was inversely correlated with fluke burden. Pre-stimulation with F. hepatica molecules produced a significant reduction of ileocaecal lymph node leucocyte proliferation in response to MAP antigens. Additionally,F. hepatica products reduced expression of the CD14 receptor by macrophages and increased levels of apoptosis and bacterial (MAP) uptake. Overall, F. hepatica infection had little impact on the in vitro response of immune cells to MAP, whereas in vitro co-stimulation with F. hepatica molecules had a measurable effect. Whether this is likely to affect JD progression during in vivo chronic conditions remains unclear.


A laryngoscopy-based classification system for perioperative abnormal vocal cord movement in thyroid surgery.
A retrospective cohort study to develop a classification scheme for abnormal vocal cord movement (AVCM) before and after thyroid surgery. Clinical and laryngoscopic data from patients who underwent partial or total thyroidectomy were analysed. AVCM was classified as mild (type I), moderate (type II) or severe (type III), according to laryngoscopic findings. The study included 1619 patients, of whom 39 had preoperative AVCM and 65 had postoperative AVCM. Recovery rates for preoperative, postoperative and total type I AVCM were higher than the corresponding type III AVCM. Recovery rates for total type II AVCM were higher than those for type III AVCM at 1, 3 and 6 months postoperatively. Asymptomatic patients had better recovery rates than symptomatic patients. We have developed a useful classification system for patients with AVCM after thyroidectomy. Pre- and postoperative laryngoscopy can identify asymptomatic AVCM and is essential to evaluate the extent of recurrent laryngeal nerve injury in these patients.


Cerebellar tDCS as Therapy for Cerebellar Ataxias.
In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques to influence cerebellar activity and the effects of cerebellar stimulation on other brain regions through its multiple complex projections. From the early 1990s, with the discovery of the so-called cerebellar inhibition (CBI), several studies have focused their attention on the use of cerebellar NIBS as treatment for different motor disorders. Cerebellar ataxias (CAs) represent the prototypical clinical manifestation of cerebellar alterations, but other movement disorders, such as Parkinson's disease, essential tremor, and dystonia have also been associated with alterations of networks which include the cerebellum, or of the cerebellum itself. Cerebellar transcranial direct current stimulation (ctDCS) could indeed represent an economical, non-invasive therapeutic tool with minimal side effects, thus improving the clinical management of patients and their quality of life. Studies show that ctDCS is effective as a therapeutic option for motor symptoms in patients with CAs, and especially in those with less severe forms, suggesting that ctDCS efficacy could result from augmented neuronal compensation, which itself relies on preserved cerebellar volume. Evidence for the efficacy of ctDCS is less conclusive for the other aforementioned motor disorders, although preliminary results are promising. Future studies should adopt more rigorous methods (e.g., larger sample sizes, double blinding, better characterization of the sample, reliable biomarkers), in order to allow the scientific community to derive higher-quality evidence on the efficacy of ctDCS as a therapeutic option for motor disorders.


Response time in economic games reflects different types of decision conflict for prosocial and proself individuals.
Behavioral and neuroscientific studies explore two pathways through which internalized social norms promote prosocial behavior. One pathway involves internal control of impulsive selfishness, and the other involves emotion-based prosocial preferences that are translated into behavior when they evade cognitive control for pursuing self-interest. We measured 443 participants' overall prosocial behavior in four economic games. Participants' predispositions [social value orientation (SVO)] were more strongly reflected in their overall game behavior when they made decisions quickly than when they spent a longer time. Prosocially (or selfishly) predisposed participants behaved less prosocially (or less selfishly) when they spent more time in decision making, such that their SVO prosociality yielded limited effects in actual behavior in their slow decisions. The increase (or decrease) in slower decision makers was prominent among consistent prosocials (or proselfs) whose strong preference for prosocial (or proself) goals would make it less likely to experience conflict between prosocial and proself goals. The strong effect of RT on behavior in consistent prosocials (or proselfs) suggests that conflict between prosocial and selfish goals alone is not responsible for slow decisions. Specifically, we found that contemplation of the risk of being exploited by others (social risk aversion) was partly responsible for making consistent prosocials (but not consistent proselfs) spend longer time in decision making and behave less prosocially. Conflict between means rather than between goals (immediate versus strategic pursuit of self-interest) was suggested to be responsible for the time-related increase in consistent proselfs' prosocial behavior. The findings of this study are generally in favor of the intuitive cooperation model of prosocial behavior.


Chromium supplementation of human subjects: effects on glucose, insulin, and lipid variables.
Seventy-six normal, free-living subjects were given supplements of 200 micrograms chromium (Cr) in the form of chromic chloride or a placebo in a double-blind crossover study with 3-month experimental periods. Twenty of the 76 subjects had serum glucose concentrations greater than or equal to 100 mg/dL 90 minutes after a glucose challenge (1 g glucose per kilogram of body weight). Chromium supplementation significantly decreased (P less than 0.05) the 90-minute glucose concentration of these subjects from 135 +/- 9 to 116 +/- 11 mg/dL; fasting glucose concentrations also decreased significantly. The 90-minute serum glucose levels of the 35 subjects with glucose concentrations less than the fasting serum glucose level were increased significantly by Cr supplementation, from 71 +/- 1 to 81 +/- 4 mg/dL. Fasting and 90-minute serum glucose concentrations of the remaining subjects who displayed 90-minute glucose concentrations greater than fasting levels but less than 100 mg/dL were not affected by Cr supplementation. In this study, immunoreactive serum insulin concentration, body weight, lipids, and other selected clinical variables did not change significantly during Cr supplementation. These data demonstrate that Cr supplementation decreases the serum glucose levels of subjects with 90-minute glucose concentrations greater than or equal to 100 mg/dL following a glucose challenge, increases serum glucose levels of subjects with 90-minute glucose concentrations less than fasting levels, and has no effect on the serum glucose levels of subjects with 90-minute glucose values similar to but greater than fasting levels.


Surgical treatment of space-occupying cerebellar infarctions--4 1/2 years post-operative follow-up.
Case reports of three patients with cerebellar infarction causing brain stem dysfunction and obstructive hydrocephalus as seen in computed tomography are presented. Surgical treatment, either ventricular puncture with drainage or suboccipital craniectomy and resection of the necrotic cerebellar tissue, was carried out. Indications for surgical treatment of space-occupying cerebellar infarction and post-operative follow-up of 4 1/2 years are discussed.


Discovery of a highly-specialized plesiadapiform primate in the early-middle Eocene of northwestern Africa.
In this paper we report the first occurrence of an endemic African plesiadapiform primate from the early-middle Eocene locality of Glib Zegdou (Hammada du Dra, Algeria). Dralestes (new genus) is a very specialized taxon, and its closest known relative is the enigmatic and controversial genus Azibius from Gour Lazib (Hammada du Dra). We group both together as the Azibiidae (new rank). Dralestes provides the first evidence of the upper dentition in this group. Some critical dental characters, such as a postprotocingulum on upper teeth, consistently reveal a primate status for the azibiids. Dralestes exhibits, however, a very unusual configuration of the upper molars by the enlarged parastyle, the lack of a metaconule, and the ectoloph structure (preparacrista, centrocrista and postmetacrista are aligned in a high blade-like structure). The apparent dental specializations of both lower premolars and molars of azibiids (exaenodonty, large P(4) bearing sharp apical cusps, and M(1) having a highly elongated trigonid) point to potential relationships with Chronolestes and carpolestid plesiadapiforms. A phylogenetic analysis, performed on 55 dental characters scored for 19 primate genera, clarifies the euprimate status of Altiatlasius, and thus indicates that azibiids are the only known plesiadapiforms from Africa. Azibiids are the sister group of the clade carpolestids/Chronolestes in the superfamily Plesiadapoidea. However, the azibiids differ fundamentally from carpolestids by the combined lack of a centroconule and multiple buccal cusps on P(4). The exact position of both Chronolestes and azibiids in the plesiadapoids appears difficult to resolve. A basal position of Chronolestes in this superfamily cannot be ruled out because it exhibits a simple morphology of I(1) and no conule on P(3). Considering this ad hoc hypothesis, azibiids are found to lie outside a clade including carpolestids/plesiadapids/saxonellids, and they are the sister group to Chronolestes. The clade including the carpolestid, saxonellid, and plesiadapid families is characterized by the occurrence of a centroconule on P(3-4). The lack of this trait in Dralestes and Chronolestes could mean that azibiids are basal plesiadapoids that diverged before the evolution of the common ancestor of the three derived plesiadapoid families, i.e. at least around the Paleocene-Eocene boundary or more probably during the Paleocene. The report of the first offshoot in Africa of plesiadapoids enhances the role of Africa in the early primate radiation.


Forecasting the timeframe of 2019-nCoV and human cells interaction with reverse engineering.
In December 2019, an atypical pneumonia invaded the city of Wuhan, China, and the causative agent of this disease turned out to be a new coronavirus. In January 2020, the World Health Organization named the new coronavirus 2019-nCoV and subsequently it is referred to as SARS-CoV2 and the related disease as CoViD-19 (Lai et al., 2020). Very quickly, the epidemic led to a pandemic and it is now a worldwide emergency requiring the creation of new antiviral therapies and a related vaccine. The purpose of this article is to review and investigate further the molecular mechanism by which the SARS-CoV2 virus infection proceeds via the formation of a hetero-trimer between its protein S, the ACE2 receptor and the B0AT1 protein, which is the "entry receptor" for the infection process involving membrane fusion (Li et al., 2003). A reverse engineering process uses the formalism of the Hill function to represent the functions related to the dynamics of the biochemical interactions of the viral infection process. Then, using a logical evaluation of viral density that measures the rate at which the cells are hijacked by the virus (and they provide a place for the virus to replicate) and considering the "time delay" given by the interaction between cell and virus, the expected duration of the incubation period is predicted. The conclusion is that the density of the virus varies from the "exposure time" to the "interaction time" (virus-cells). This model can be used both to evaluate the infectious condition and to analyze the incubation period. The ongoing threat of the new coronavirus SARS-CoV2 pandemic is alarming and strategies for combating infection are highly desired. This RNA virus belongs to the β-coronavirus genus and is similar in some features to SARS-CoV. Currently, no vaccine or approved medical treatment is available. The complex dynamics of the rapid spread of this virus can be demonstrated with the aid of a computational framework. A mathematical model based on the principles of cell-virus interaction is developed in this manuscript. The amino acid sequence of S proein and its interaction with the ACE-2 protein is mimicked with the aid of Hill function. The mathematical model with delay is solved with the aid of numerical solvers and the parametric values are obtained with the help of MCMC algorithm. A delay differential equation model is developed to demonstrate the dynamics of target cells, infected cells and the SARS-CoV2. The important parameters and coefficients are demonstrated with the aid of numerical computations. The resulting thresholds and forecasting may prove to be useful tools for future experimental studies and control strategies. From the analysis, I is concluded that control strategy via delay is a promising technique and the role of Hill function formalism in control strategies can be better interpreted in an inexpensive manner with the aid of a theoretical framework.


Anandamide modulates the expression of GnRH-II and GnRHRs in frog, Rana esculenta, diencephalon.
In the hypothalamus, endocannabinoids affect neuroendocrine activity by means of Gonadotropin-Releasing-Hormone-I (GnRH-I) inhibition. Since most vertebrates, human included, possess at least two GnRH molecular forms, the aim of this work was to investigate the effect of endocannabinoids on GnRH molecular forms other than GnRH-I and on GnRHRs. Thus, we cloned GnRH precursors as well as GnRH receptors (GnRHR-I, GnRHR-II, GnRHR-III) from the diencephalons of the anuran amphibian, Rana esculenta. GnRH-II expression was evaluated in pituitary, whole brain, spinal cord, hindbrain, midbrain and forebrain during the annual sexual cycle. Then, in post-reproductive period (May), GnRH-I, GnRH-II and GnRHRs expression was evaluated by quantitative real time (qPCR) after incubation of diencephalons with the endocannabinoid anandamide (AEA). AEA significantly decreased GnRH-I and GnRH-II expression, up regulated GnRHR-I and GnRHR-II mRNA and it had no effect upon GnRHR-III expression. These effects were counteracted by SR141716A (Rimonabant), a selective antagonist of type I cannabinoid receptor (CB1). In conclusion our results demonstrate a CB1 receptor dependent modulation of GnRH system expression rate (both ligands and receptors) in frog diencephalons. In particular, we show that AEA, besides GnRH-I, also acts on GnRH-II expression.


Characterization of phosphogypsum wastes associated with phosphoric acid and fertilizers production.
The present work is directed to characterize the phosphogypsum (PG) wastes associated with phosphoric acid produced by the wet process in industrial facility for the production of fertilizers and chemicals in Egypt. The PG waste samples were characterized in terms of spectroscopic analysis (X-ray diffraction, X-ray fluorescence, IR spectra) and radiometric analysis (gamma- and alpha-measurements). The gamma-ray measurements showed that the average activity concentrations are 140+/-12.6, 459+/-36.7, 323+/-28.4, 8.3+/-0.76 and 64.3+/-4.1 Bq/kg for U-238, Ra-226, Pb-210, Th-232 and K-40, respectively. The alpha-particle measurements of uranium isotopes showed that the average activity concentrations of U-238, U-235 and U-234 were 153+/-9.8, 7+/-0.38, 152+/-10.4 Bq/kg, respectively. The average radiochemical recovery (%) of the destructive alpha-particle measurements is approximately 70% with a resolution (FWHM) of approximately 30 keV. Activity ratios of U-238/Ra-226 and U-238/Pb-210 were less than unity (i.e., <1) and equal to 0.31+/-0.02 and 0.47+/-0.16, respectively. The isotopic ratios of U-238/U-235 and U-238/U-234 (in PG and PR samples) were close to the normal values of approximately 21.7 and approximately 1, respectively and are not affected by the wet processing of phosphate rock (PR). The obtained results of PG waste samples were compared with phosphate rock (PR) samples. The radiation hazard indices are namely, radium activity index (Ra-Eq>370 Bq/kg), total absorbed gamma dose rate (D(gamma r)>5 nGy/h) and radon emanation fraction (Rn-EF>20%). Uncertainty of the sample counting was 95% confidence level of sigma. The results indicated the necessity to find suitable routes to decrease and/or redistribute the radionuclide of environmental interest (i.e., Ra-226) in PG wastes, consequently to reduce its radiation impacts in the surrounding environment.


Identification of Origin for Spinal Metastases from MR Images: Comparison Between Radiomics and Deep Learning Methods.
To determine whether spinal metastatic lesions originated from lung cancer or from other cancers based on spinal contrast-enhanced T1 (CET1) magnetic resonance (MR) images analyzed using radiomics (RAD) and deep learning (DL) methods. We recruited and retrospectively reviewed 173 patients diagnosed with spinal metastases at two different centers between July 2018 and June 2021. Of these, 68 involved lung cancer and 105 were other types of cancer. They were assigned to an internal cohort of 149 patients, randomly divided into a training set and a validation set, and to an external cohort of 24 patients. All patients underwent CET1-MR imaging before surgery or biopsy. We developed two predictive algorithms: a DL model and a RAD model. We compared performance between models, and against human radiological assessment, via accuracy (ACC) and receiver operating characteristic (ROC) analyses. Furthermore, we analyzed the correlation between RAD and DL features. The DL model outperformed RAD model across the board, with ACC/ area under the receiver operating characteristic curve (AUC) values of 0.93/0.94 (DL) versus 0.84/0.93 (RAD) when applied to the training set from the internal cohort, 0.74/0.76 versus 0.72/0.75 when applied to the validation set, and 0.72/0.76 versus 0.69/0.72 when applied to the external test cohort. For the validation set, it also outperformed expert radiological assessment (ACC: 0.65, AUC: 0.68). We only found weak correlations between DL and RAD features. The DL algorithm successfully identified the origin of spinal metastases from pre-operative CET1-MR images, outperforming both RAD models and expert assessment by trained radiologists.


Quality of life of endodontically treated versus implant treated patients: a University-based qualitative research study.
Up-to-date studies comparing endodontic treatment versus implant-supported prosthesis have shown similar clinical outcome and survival rates. However, no data are available comparing both treatment modalities based on the patient's perception of quality of life. This study was designed to qualitatively describe and compare the quality of life of patients with restored, single endodontically treated teeth versus patients with single implant-supported fixed prostheses. Forty-eight patients agreed to participate in the study (n = 24 from each treatment modality). Of those, 37 actually participated in the study: 17 were endodontically treated and 20 had an implant-supported prosthesis. Patients in each of the two groups were randomly selected from the Graduate Endodontics and Graduate Periodontics Departments, respectively. Six focus group discussions (n = 3 per treatment group) were held and audio-recorded for subsequent thematic analysis. Data were analyzed to identify common themes within each category and compared to assess any differences in quality of life between the two treatments. Additionally, a quality of life survey, the shortened version of the Oral Health Impact Profile (OHIP-14), was given before the discussion group and the responses analyzed. The results obtained from this study show similar overall OHIP scores and show a high rate of satisfaction with both treatment modalities. Content analysis of the discussion groups revealed several themes and subthemes. The major themes were importance of overall health, financial implications of the treatments, perception of the treatments and its outcomes, time since treatment, and follow-up dental visits. The results help identify patients' perception and concerns with each treatment modality and assist the clinician and patient in the selection of an optimal treatment for their given situation. In addition to the prognosis and outcomes, clinicians should consider patients' perceptions and preferences as well as the influence each therapy may have on their quality of life, both short- and long-term. Overall, all the participants in this study were pleased with the treatment received and expressed a clear message to save their natural dentition whenever possible.


Two billion registered students affected by stereotyped educational environments: an analysis of gender-based color bias.
According to the literature, educational technologies present several learning benefits to promote online education. However, there are several associated challenges, and some studies illustrate the limitations in elaborating educational technologies, called Design limitations. This aspect is responsible for unleashing various issues in the learning process, such as gender inequality, creating adverse effects on cognitive, motivational, and behavioral mediators, which opposes the fifth UN's Sustainable Development Goal. Therefore, many studies notice the harmful effects of stereotypes in educational technologies. These effects can be included in the design, like colors or other stereotyped elements, or how the activity is conducted. Based on this, the present study aimed to verify the predominance of color bias in educational technologies available on the WEB. This study developed a computational solution to calculate male and female color bias in the available educational technology web pages. The results suggest the prevalence of the development of educational technologies with a male color bias, with an imbalance among genders, without adequate customization for age groups. Furthermore, some environments, such as Computer Science, present a higher color bias for men when compared to women. Despite both scales being independent, results indicated interesting evidence of a substantial prevalence of colors associated with the male scale. According to the literature, this may be associated with dropout and lack of interest in female students, especially in sciences, technology, engineering, and mathematics domains.


[Potential limitations and risks in the treatment of painful neuropathies].
Neuropathic pains often cause social disintegration of the patients, encouraging us to apply microsurgical techniques to peripheral nerve lesions, but there are limitations and risks to take into account when handling scarred nerve tissue. The historical development of our microanatomical knowledge of grading of nerve lesions as well as facts on different fibrotic intraneural reactions are pointed out and additionally compared to today's theories of the origin of neuropathic pains. The microsurgical methods applied to entrapment syndromes, pseudoneuroma and neuroma formations consist of either external and interfascicular neurolysis or nerve grafting depending on the estimated grade of nerve lesion. If we primarily don't try to restore motor function after a nerve lesion but intend to achieve reduction of neuropathic pain due to a scarred nerve, the well-known methods of neuromodulation or thermic/cryoneurotomy increasingly become the treatment of choice. There is no real mental connection existing between our successful microsurgical methods on restoration of nerve function and the theories of the origin of neuropathic pains. We do treat pain of nociceptive origin by means of neurolysis but have abandoned these methods more and more in the case of chronic neuropathic pain. But on the other hand, the neuromodulation and neurotomy methods preferred in these cases still have limitations in compatibility and success rates. In a few cases we even risk inducing or worsening chronic neuropathic pains by means of microsurgery and/or neurotomy of a lesioned nerve.


Modular control of muscle coordination patterns during various stride time and stride length combinations.
Modular organization in muscular control is generally specified as synergistic muscle groups that are hierarchically organized. There are conflicting perspectives regarding modular organization for regulation of walking speeds, with regard to whether modular organization is relatively consistent across walking speeds. This conflict might arise from different stride time (time for one stride) and stride length combinations for achieving the same walking speed. Does the regulation of the modular organization depend on stride time and stride length (stride time-length) combinations? Ten healthy men walked at a moderate speed (nondimensional speed = 0.4) on a treadmill at five different stride time-length combinations (very short, short, preferred, long, and very long). Surface electromyograms from 16 muscles in the trunk and lower limb were recorded. The modular organization was modeled as muscle synergies, which represent groups of synchronously activated muscles. Muscle synergies were extracted using a decomposition technique. The number of synergies and their activation durations were analyzed. The number of synergies was consistent in the preferred and quasi-preferred condition (median: 4.5 [short], 4.5 [preferred], 5 [long]), while it varied in the extreme condition (median: 4 [very short] and 6 [very long]; 0.02 ≤ p ≤ 0.09). Gait parameters (stride time, stride length, stance time, swing time, and double stance time) were significantly different for preferred and quasi-preferred conditions (p < 0.03). Our results provide additional insights on the flexibility of modular control during walking, namely that the number of synergies or activations are fine-tuned even within one walking speed. Our finding implies that a variety of walking patterns can be achieved by consistent synergies except for extreme walking patterns.


Observations on Middle Stone Age human teeth from Klasies River Main Site, South Africa.
The human fossils, artefacts and faunal remains from the Middle Stone Age (MSA) deposits of Klasies River Main Site have featured prominently in discussions of the evolution of modern human morphology and the emergence of human behavioral modernity. Nearly 40 human fossils were uncovered by John Wymer's (1967-1968) excavations, and subsequent work by Hilary Deacon (1984-1995) has produced an additional dozen specimens. Many of the latter have been described, but most of the dental remains have been afforded only cursory mention and provisional identification. These specimens are documented here, and questions of individual association among some of the fossils from Wymer's excavations are also addressed. Three teeth provide the first indisputable evidence for juvenile individuals in the deposit. The proportion of juvenile to adult remains in the MSA levels at Klasies is notably lower than in other penecontemporaneous South African coastal MSA sites such as Die Kelders Cave 1 and Blombos Cave, where the proportion of juveniles is seemingly in closer keeping with coastal, geographically proximate Later Stone Age sites such as Oakhurst Shelter and Matjes River Cave. The sizes of most of the recently identified human teeth from Klasies seem to affirm at least one arguable aspect of morphometric modernity in the MSA at this site in the form of a tendency for tooth size reduction.


[PEMPHIGUS ACANTHOLYTICUS PARANEOPLASTIC: LITERATURE REVIEW AND CASE REPORT].
The article describes the clinical observation of a rare severe dermatosis, paraneoplastic acantholyticus pemphigus, associated with colon cancer with reference to pathogenesis, clinical variations and difficulties of diagnostics of this condition.


The Association of Twin Chorionicity with Maternal Outcomes.
Our objective was to investigate the association between maternal outcomes and twin chorionicity in a large, contemporary obstetric population. Retrospective cohort study was conducted at a single, large tertiary care center. Prenatal and inpatient records for all individuals with twin gestations were reviewed from 2000 to 2016. Patients with monoamniotic twins, higher-order multiples reduced to twins, multiple sets of twins in the study period, or undetermined chorionicity were excluded. Patients with monochorionic twins were compared with those with dichorionic twins. The co-primary outcomes were gestational diabetes mellitus and hypertensive disorders of pregnancy. Secondary outcomes included cesarean delivery, preterm delivery, postpartum hemorrhage, and other maternal outcomes. Bivariate and multivariate analyses were performed to assess associations of chorionicity with maternal outcomes. Of the 2,979 patients eligible for inclusion, 2,627 (88.2%) had dichorionic twin gestations and 352 (11.8%) had monochorionic twin gestations. Patients with monochorionic twins were less likely to self-identify as non-Hispanic White and to have conceived via assisted reproductive technology but were more likely to be publicly insured, multiparous and have prenatal care with a maternal-fetal medicine provider. Neither gestational diabetes mellitus (6.8% monochorionic vs. 6.2% dichorionic, p = 0.74; adjusted odds ratio [OR] 1.06, 95% confidence interval (CI) 0.60-1.86) nor hypertensive disorders of pregnancy (21.9% monochorionic vs. 26.3% dichorionic, p = 0.09; adjusted OR 0.99, 95% CI, 0.71-1.38) differed by chorionicity. Of the secondary maternal outcomes, patients with monochorionic twins experienced a lower frequency of cesarean delivery (46.0 vs. 61.8%, p < 0.001), which persisted after multivariate analyses (adjusted OR 0.60, 95% CI 0.46-0.80). There were no differences in preterm delivery, preterm premature rupture of membranes, hemorrhage, hysterectomy, or intrahepatic cholestasis of pregnancy. The odds of gestational diabetes mellitus and hypertensive disorders of pregnancy do not appear to differ by twin chorionicity. · Hypertensive disorders of pregnancy do not differ by twin chorionicity.. · Gestational diabetes mellitus does not differ by twin chorionicity.. · Maternal outcomes are similar for individuals with monochorionic and dichorionic twin gestations..


Higher temporal evapotranspiration estimation with improved SEBS model from geostationary meteorological satellite data.
Evapotranspiration (ET) is a key variable in hydrologic cycle that directly affects the redistribution of precipitation and surface balance. ET measurements with high temporal resolution are required for coupling with models of highly dynamic processes, e.g., hydrological and land surface processes. The Haihe River Basin is the focus of China's industrial base and it is one of the three major grain-producing regions within the country. However, this area is facing serious water resource shortages and water pollution problems. The present study used geostationary satellite remote sensing data, in situ meteorological observations, and the surface energy balance system (SEBS) model with a new kB-1 parameterization to estimate 3-hourly and daily energy and water fluxes in the Haihe River Basin. The results of the SEBS model were validated with point-scale data from five observation flux towers. Validation showed that 3-hourly and daily ET derived from the SEBS model performed well (R2 = 0.67, mean bias = 0.027 mm/h, RMSE = 0.1 mm/h). Moreover, factors influencing ET were also identified based on the results of this study. ET varies with land cover type and physical and chemical properties of the underlying surface. Furthermore, ET is also controlled by water availability, radiation, and other atmospheric conditions. It was found that ET had strong correlation with the normalized difference vegetation index (NDVI). Specifically, daily ET fluctuated with the NDVI when the NDVI was <0.29, and ET increased rapidly as the NDVI increased from 0.29 to 0.81. For NDVI values >0.81, indicating a state of saturation, the rate of increase of ET slowed. This research produced reliable information that could assist in sustainable management of the water resources and in improved understanding of the hydrologic cycle of the Haihe River Basin.


Behavior of olfactory-related frontal lobe oscillations in Alzheimer's disease and MCI: A pilot study.
Slow-gamma (35-45 Hz) phase synchronization and the coupling between slow-gamma and low-frequency theta oscillations (4-8 Hz) are closely related to memory retrieval and cognitive functions. In this pilot study, we assess the Phase Amplitude Coupling (PAC) between theta and slow-gamma oscillatory bands and the quality of synchronization in slow-gamma oscillations using Phase Locking Value (PLV) on EEG data from healthy individuals and patients diagnosed with amnestic Mild Cognitive Impairment (aMCI) and Alzheimer's Disease (AD) during an oddball olfactory task. Our study indicates noticeable differences between the PLV and PAC values corresponding to olfactory stimulation in the three groups of participants. These differences can help explain the underlying processes involved in these cognitive disorders and the differences between aMCI and AD patients in performing cognitive tasks. Our study also proposes a diagnosis method for aMCI through comparing the brain's response characteristics during olfactory stimulation and rest. Early diagnosis of aMCI can potentially lead to its timely treatment and prevention from progression to AD.


Comparison between the impact of fermented and unfermented soy intake on the risk of liver cancer: the JPHC Study.
The aim of this study was to compare the impact of fermented and unfermented soy intake, based on the following soy-derived products: tofu, soymilk, natto, and miso, on the risk of liver cancer among Japanese adults. 75,089 Participants of the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from the time of the 5-year follow-up questionnaire until the end of 2012-2013. Subjects with available data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status from blood samples (n = 14,016) and those who were anti-HCV antibody (anti-HCV) or hepatitis B virus antigen (HBsAg) positive (n = 1033) were also analyzed separately. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 1,145,453 person-years, 534 newly diagnosed cases of liver cancer were identified in the JPHC Study. For miso intake among men, the multivariate-adjusted highest versus lowest quartile HR was 0.65 (95% CI, 0.48-0.89); p for trend = 0.006. Results were similar in those who were anti-HCV or HBsAg positive, 0.24 (0.08-0.70); p for trend = 0.004 highest versus lowest tertile. For the sub-analysis among only participants with known hepatitis infection status and HCV and HBsAg adjustment, a similar association was observed. In the multivariate complete cohort analysis, among women, the highest intake of fried tofu was inversely associated with the risk of liver cancer, HR = 0.45 (0.26-0.80); p for trend = 0.014. We observed no association between total soy intake, fermented and unfermented, and risk of liver cancer, and only an inverse association between miso intake and liver cancer among men.


Impairing methylations at ribosome RNA, a point mutation-dependent strategy for aminoglycoside resistance: the rsmG case.
Aminoglycosides like streptomycin are well-known for binding at specific regions of ribosome RNA and then acting as translation inhibitors. Nowadays, several pathogens have been detected to acquire an undefined strategy involving mutation at non structural ribosome genes like those acting as RNA methylases. rsmG is one of those genes which encodes an AdoMet-dependent methyltransferase responsible for the synthesis of m 7 G527 in the 530 loop of bacterial 16S rRNA. This loop is universally conserved, plays a key role in ribosomal accuracy, and is a target for streptomycin binding. Loss of the m 7 G527 modification confers low-level streptomycin resistance and may affect ribosomal functioning. After taking into account genetic information indicating that some clinical isolates of human pathogens show streptomycin resistance associated with mutations at rsmG , we decided to explore new hot spots for mutation capable of impairing the RsmG in vivo function and of promoting low-level streptomycin resistance. To gain insights into the molecular and genetic mechanism of acquiring this aminoglycoside resistance phenotype and the emergence of high-level streptomycin resistance in rsmG mutants, we mutated Escherichia coli rsmG and also performed a genotyping study on rpsL from several isolates showing the ability to grow at higher streptomycin concentrations than parental strains. We found that the mutations at rpsL were preferentially present in these mutants, and we observed a clear synergy between rsmG and rpsL genes to induce streptomycin resistance. We contribute to understand a common mechanism that is probably transferable to other ribosome RNA methylase genes responsible for modifications at central sites for ribosome function.


Participation in clinical trials increases the detection of pre-malignant lesions during colonoscopy.
colorectal adenoma detection has been associated with the effectiveness of cancer prevention. Clinical trials have been designed to determine the role of several interventions to increase the detection of pre-malignant lesions. We hypothesized that colonoscopy in the setting of clinical trials has a higher pre-malignant lesion detection rate. a cross-sectional study was performed that compared the detection of pre-malignant lesions in 147 randomly sampled non-research colonoscopies and 294 from the control group of two prospective trials. Outpatients aged 40-79 years, with no personal history of colorectal cancer (CRC) were included. baseline characteristics were similar between the two groups. The pre-malignant lesion detection rate in the trial vs control group was 65.6 % vs 44.2 % (OR 2.411; 95 % CI: 1.608-3.614; p < 0.001), the polyp detection rate was 73.8 % vs 59.9 % (OR 1.889; 95 % CI: 1.242-2.876; p = 0.003), the adenoma detection rate was 62.6 % vs 44.2 % (OR 2.110; 95 % CI: 1.411-3.155; p < 0.001) and the sessile serrated lesion detection rate was 17 % vs 4.1 % (OR 4.816; 95 % CI: 2.014-11.515; p < 0.001). The mean number of pre-malignant and sessile serrated lesions was 1.70 vs 1.06 (p = 0.002) and 0.32 vs 0.06 (p = 0.001) lesions per colonoscopy, respectively. There was no significant change in any of the study outcomes according to the multivariate analysis with each single potential confounder. patients involved in colonoscopy trials may benefit from higher quality examinations, as shown by the higher detection rates. Institutions should consider supporting clinical research in colonoscopy as a simple means to improve colonoscopy quality and colorectal cancer prevention.


Right Coronary Artery to Right Atrial Fistula: Role of Multi-Modality Imaging and Percutaneous Closure.
Coronary artery fistula (CAF) is a connection between a coronary artery and a cardiac chamber or nearby vessel. Our case represents a fistula arising from the right coronary artery and terminating in the right atrium, presenting as atrial fibrillation. CAF closure options include surgical and percutaneous approaches.


Subgroups of Adult Basic Education Learners with Different Profiles of Reading Skills.
The purpose of this study was to identify subgroups of adult basic education (ABE) learners with different profiles of skills in the core reading components of decoding, word recognition, spelling, fluency, and comprehension. The analysis uses factor scores of those 5 reading components from on a prior investigation of the reliability and construct validity of measures of reading component skills (MacArthur, Konold, Glutting, & Alamprese, 2010). In that investigation, confirmatory factor analysis found that a model with those 5 factors fit the data best and fit equally well for native and non-native English speakers. The study included 486 students, 334 born or educated in the United States (native) and 152 not born nor educated in the US (non-native) but who spoke English well enough to participate in English reading classes. The cluster analysis found an 8-cluster solution with good internal cohesion, external isolation, and replicability across subsamples. Of the 8 subgroups, 4 had relatively flat profiles (range of mean scores across factors < 0.5 SD), 2 had higher comprehension than decoding, and 2 had higher decoding than comprehension. Profiles were consistent with expectations regarding demographic factors. Non-native speakers were overrepresented in subgroups with relatively higher decoding and underrepresented in subgroups with relatively higher comprehension. Adults with self-reported learning disabilities were overrepresented in the lowest performing subgroup. Older adults and men were overrepresented in subgroups with lower performance. The study adds to the limited research on the reading skills of ABE learners and, from the perspective of practice, supports the importance of assessing component skills to plan instruction.


Carinal resection.
Carinal resections and reconstructions, with or without lung resection, are challenging operations that may be indicated in less than 1% of operable patients with NSCLC or benign lesions involving the carina. These operations are completed in only a few centers worldwide, likely because of their technical complexity and the general opinion about their limited patient benefit. However, good survival results can be expected in pN0 or pN1 patients so that, in experienced hands, these operations are effective options. The risk of postoperative complications can be minimized by several intraoperative and postoperative precautions.


Declining HIV prevalence among women attending antenatal care in Pune, India.
A declining prevalence of HIV among young women has been reported by the public sector implementing prevention of mother-to-child transmission (PMTCT) programmes, sentinel surveillance sites and research institutions in India. However, there are no reports evaluating such trends from the private healthcare sector. This study is a retrospective analysis of data collected by PRAYAS as a part of the PMTCT programme at Sane Guruji Hospital (SGH), a secondary care hospital in Pune, India. Women attending the antenatal clinic at SGH were screened for HIV following a group counselling session, with an option to opt out. Between January 2003 and March 2008, the overall HIV prevalence was 111/17 578 (0.6%, 95% CI 0.5-0.7%). The HIV prevalence among antenatal women was 1.1% in 2003 and 0.2% in 2008 (i.e. 82% decline in HIV prevalence over the 5-year period) and the odds ratio (OR) of HIV prevalence declined by 0.24 per year from 2003 to March 2008 (OR=0.76, 95% CI 0.69-0.87; P<0.001). The risk of having HIV infection was significantly higher in women aged ≥ 24 years and those who were uneducated. To our knowledge, this is the first report from any private sector health system in India documenting a declining HIV prevalence among antenatal women. Characterising the risk profile of this small percentage of at-risk women will help in planning prevention strategies.


The Seed and the Metabolism Regulation.
The seed represents a critical stage in the life cycle of flowering plants. It corresponds to a dry structure carrying the plant embryo in dormant or quiescent state. Orthodox seeds possess a very low water content, preventing biochemical reactions, especially respiration. If the desiccation of living organisms leads to a loss of homeostasis, structure, and metabolism, the seeds go through it successfully thanks to their structure, cellular organization, and growth regulation. Seeds set up a certain number of sophisticated molecules to protect valuable macromolecules or organelles from dehydration/rehydration cycles. Moreover, dormancy takes place in a coordinated process with environmental cues in order to ensure embryo development at the most appropriate conditions for the establishment of the new plant. Moreover, repair processes are programmed to be ready to operate to maximize germination success and seed longevity. This review focuses on the physiology of the seed as related to hydration forces, respiration, and biochemical reactions in the transition from thermodynamically undefined dry state to self-sustained living system. Such processes are of importance for basic knowledge of the regulation of metabolism of living organisms, but also for the control of germination in the context of climate change due to global warming.


Fluorescence umpolung enables light-up sensing of N-acetyltransferases and nerve agents.
Intramolecular charge transfer (ICT) is a fundamental mechanism that enables the development of numerous fluorophores and probes for bioimaging and sensing. However, the electron-withdrawing targets (EWTs)-induced fluorescence quenching is a long-standing and unsolved issue in ICT fluorophores, and significantly limits the widespread applicability. Here we report a simple and generalizable structural-modification for completely overturning the intramolecular rotation driving energy, and thus fully reversing the ICT fluorophores' quenching mode into light-up mode. Specifically, the insertion of an indazole unit into ICT scaffold can fully amplify the intramolecular rotation in donor-indazole-π-acceptor fluorophores (fluorescence OFF), whereas efficiently suppressing the rotation in their EWT-substituted system (fluorescence ON). This molecular strategy is generalizable, yielding a palette of chromophores with fluorescence umpolung that spans visible and near-infrared range. This strategy expands the bio-analytical toolboxes and allows exploiting ICT fluorophores for light-up sensing of EWTs including N-acetyltransferases and nerve agents.


Regulation of cyclooxygenase-2 expression by cyclic AMP.
Prostaglandins (PG) regulate many biological processes, among others inflammatory reactions. Cyclooxygenases-1 and -2 (COX-1 and COX-2) catalyse PG synthesis. Since this step is rate limiting, the regulation of COX expression is of critical importance to PG biology. Contrary to COX-1, which is constitutively expressed, COX-2 expression is subject to regulation. For example, COX-2 levels are increased in inflammatory reactions. Many signalling pathways can regulate COX-2 expression, not least those involving receptors for COX products themselves. Analysis of the intracellular signal transducers involved reveals a crucial role for cAMP, albeit as a modulator rather than direct inducer. Indeed, the influence of cAMP on COX-2 expression is complex and dependent on the cell type and cellular environment. This review aims to summarise various topics related to cAMP-dependent COX-2 expression. Firstly, the main aspects of COX-2 regulation are briefly considered. Secondly, the molecular basis for COX-2 gene (post)-transcriptional regulation is reviewed. Lastly, a detailed overview of the effects of cAMP-dependent signalling on COX-2 mRNA and protein expression in various human and rodent cells is provided. There is a large number of marketed, clinical and preclinical concepts promoting the elevation of intracellular cAMP levels for therapeutic purposes (e.g., beta(2)-agonists, PG receptor agonists, phosphodiesterase inhibitors). In this respect, the role of cAMP in the regulation of COX-2 expression, especially the human enzyme, is of significant clinical importance.


Role of adjuvant and post-surgical treatment in gynaecological cancer.
Adjuvant and post-operative therapy aimed at reducing the risk of disease recurrence and improving potential for cure can be broadly categorised into systemic and locoregional treatment. For epithelial ovarian cancer, cytoreductive surgery and platinum-based chemotherapy is the mainstay management. Maintenance therapy with PARPi is a state-of-the-art option for women with advanced disease following complete or partial response to first-line platinum-based chemotherapy, particularly those with BRCA mutations. Adjuvant treatment for endometrial cancer depends mostly on FIGO staging and histopathological risk factors. For cervical cancer, adjuvant chemoradiation is indicated after surgery in women with close or positive resection margins and positive nodes. Generally, recommendations for adjuvant therapy should be individualised and reviewed at the multidisciplinary tumour board meeting, and the decision for adjuvant therapy should be balanced with treatment toxicity. The overview of the role of adjuvant and post-surgical treatment in gynaecological cancers will be discussed in this chapter.


Neurologic Complications of Patients With COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.
In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality. We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022. We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO. Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model. Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8-15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1-3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34-40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46-3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO. COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.


Glycodelin A triggers mitochondrial stress and apoptosis in T cells by a mechanism distinct and independent of TCR signaling.
Glycodelin A is one of the progesterone inducible endometrial factors that protect the fetal semiallograft from maternal immune rejection. Our previous studies demonstrate that glycodelin A induces apoptosis in activated T lymphocytes. Here, we report that glycodelin A initiates the intrinsic apoptotic program in T cells. Glycodelin A treatment triggers a stress response leading to mitochondrial membrane permeabilization and activation of initiator caspase 9. The kinetics of mitochondrial depolarization precede onset of DNA fragmentation in both Jurkat cells and peripheral blood T cells treated with glycodelin A. Overexpression of the antiapoptotic protein Bcl-2 is sufficient to protect from glycodelin A-induced cell death. It has been reported earlier that glycodelin A desensitizes T cell receptor (TCR) signaling, probably by its association with the tyrosine phosphatase CD45. Here, we provide evidence that the apoptogenic activity of glycodelin A is not a consequence of this phenomenon. Glycodelin A-induced apoptosis does not depend on components of the TCR signal cascade, including CD45. We observe that glycodelin A is inhibitory to T cells even upon phorbol ester and ionophore stimulation which bypasses the TCR-proximal signaling events, and that glycodelin A treatment does not interfere with T cell activation as evidenced from induction of the activation marker CD69. Thus, glycodelin A initiates mitochondrial stress-mediated apoptosis in T cells by a pathway that is distinct and independent from the TCR signaling pathway.


New insight into antimicrobial activities of Linaria ventricosa essential oil and its synergetic effect with conventional antibiotics.
The purpose of the present study was to determine for the first time the volatile constituents, the antioxidant and antimicrobial activities of the essential oil (EO) of the endemic Moroccan Linaria ventricosa, alone or in combination with four known antibiotics. The major constituents were 2-methoxy-4-vinylphenol (17.4%), α-terpinene (13.64%) and 3,5-dimethylphenyl isocyanate (12.21%). The EO had moderate antioxidant potency, as measured by DPPH free radical scavenging (1.233 ± 0.031 mg/mL), ferric reducing antioxidant power assay (0.373 ± 0.019 mg/mL) and β-carotene/linoleic acid (0.922 ± 0.026 mg/mL). EO showed microbicidal activity against all microorganisms tested. The highest effectiveness was recorded against Candida albicans (IZ = 24 mm, MIC = 4.87 mg/mL and MMC = 9.75 mg/mL) and Candida glabrata (IZ = 22 mm, MIC = MMC = 4.87 mg/mL). Gram negative bacteria were the most resistant (MIC = MMC = 39 mg/mL). The combination of EO at sub-inhibitory concentrations with antibiotics showed a significant decrease in their individual MICs from 2 to 128 fold, being the best for ciprofloxacin and fluconazole against E. coli and C. albicans and C. glabrata, respectively.


Evaluation of a non-isotopic polymerase chain reaction-based assay to detect and predict treatment failure of Plasmodium vivax malaria in travellers.
With the emergence of chloroquine-resistant Plasmodium vivax (CRPV), new tests to detect P. vivax and predict response to therapy would be useful for clinical and research applications. We performed a 'blinded' evaluation of a non-isotopic (colourimetric) polymerase chain reaction (PCR) based assay (Digene SHARP Signal System) compared with microscopy and PCR/radiometric probe hybridization of ribosomal ribonucleic acid genes (RPH) for the detection of P. vivax malaria in 182 febrile travellers. Compared with PCR/RPH as the reference standard, the colourimetric assay had a sensitivity of 100% and specificity of 98%. Using microscopy as the reference standard, 84 of 87 patients with P. vivax infection had a positive colourimetric assay. The 3 patients with a negative assay were subsequently shown to be infected with P. ovale as determined by PCR/RPH. In a subset of patients followed longitudinally, the colourimetric assay was positive in 5 of 13 patients 6 or more days after initiation of therapy. Of these 5 patients, 4 were subsequently demonstrated to be infected with CRPV as determined by treatment failure in vivo and/or chloroquine blood levels. A positive assay result 6 or more days after initiation of therapy was associated with subsequent treatment failure (P < 0.01). This non-isotopic assay is a sensitive, specific, and rapid method for the detection of P. vivax PCR products and may prove useful in predicting treatment failure.


Bioinformatic Analysis for Mucoepidermoid and Adenoid Cystic Carcinoma of Therapeutic Targets.
Salivary gland neoplasms are a heterogeneous neoplasm group, including mucoepidermoid carcinoma (MECa), adenoid cystic carcinoma (AdCC), and many others. We aimed to identify new critical genes of MECa and AdCC using bioinformatics analysis. Gene expression profile of GSE153283 was analyzed by the GEO2R online tool to use the DAVID software for their subsequent enrichment. Protein-protein interactions (PPI) were visualized using String. Cytoscape with MCODE plugin followed by Kaplan-Meier online for overall survival analysis were performed. 97 upregulated genes were identified for MECa and 86 for AdCC. PPI analysis revealed 22 genes for MECa and 63 for AdCC that were validated by Kaplan-Meier that showed FN1 and SPP1 for MECa, and EGF and ERBB2 for AdCC as more significant candidate genes for each neoplasm. With bioinformatics methods, we identify upregulated genes in MECa and AdCC. The resulting candidate genes as possible therapeutic targets were FN1, SPP1, EGF, and ERBB2, and all those genes had been tested as a target in other neoplasm kinds but not salivary gland neoplasm. The bioinformatic evidence is a solid strategy to select them for more extensive research with clinical impact.


Identification and Toxicological Characterization of Alternaria japonica Strains.
Fungi of the genus Alternaria are producers of biologically active compounds. Alternaria japonica is pathogenic to small radish and certain other crucifers, but has not been studied in sufficient detail. Discrepant data on its toxic metabolites are available in the literature, possibly because a limited set of nutritive substrates was used in culturing or species identification of the strains was incorrect. The objectives of this study were to accurately identify the Russian A. japonica strains and to assess the A. japonica toxigenic potential. Four Russian A. japonica strains were identified using a multifaceted approach, which included analyses of morphological characters (the diameter and morphology of colonies grown on the diagnostic media potato carrot agar (PCA) and yeast extract-glucose (YES) agar for one week), the conidial size, and the presence of chlamydospores), the nucleotide sequences of DNA markers (ITS and EF1α regions), and chemotaxonomic data (mycotoxin production). Biomass and extractive substance yields of A. japonica cultures were found to significantly depend on the composition of the liquid medium. Minor differences between the A. japonica strains were detected via metabolite profiling by HPLC/MS-UV. Extracts of A. japonica cultures exerted phytotoxic activity toward small radish leaves and cytotoxicity toward Paramecium caudatum to a level comparable with that of A. tenuissima extracts. Brassicicolin A, dihydrobrassicicolin A, and phomenins A and B, which are known for several species of the genus Alternaria, were identified in A. japonica extracts. Mycotoxins (alternariol, its methyl ether, tentoxin, tenuazonic acid, and altenuene), which are characteristic of the cosmopolitan species A. tenuissima, were not detected in cultures of the A. japonica strains. Extract toxicity and the yield of extractive substances were studied in the A. japonica strains, and strain MFP244011 proved promising as a producer of known and, presumably, new toxins upon culture on the M1D synthetic medium or semisynthetic liquid media (e.g., the Sabouraud medium).


Estimating cerebral blood volume with expanded vascular space occupancy slice coverage.
A model for quantifying cerebral blood volume (CBV) based on the vascular space occupancy (VASO) technique and varying the extent of blood nulling yielding task-related signal changes with various amounts of blood oxygenation level-dependent (BOLD) and VASO weightings was previously described. Challenges associated with VASO include limited slice coverage and the confounding inflow of fresh blood. In this work, an approach that extends the previous model to multiple slices and accounts for the inflow effect is described and applied to data from a multiecho sequence simultaneously acquiring VASO, cerebral blood flow (CBF), and BOLD images. This method led to CBV values (7.9 +/- 0.3 and 5.6 +/- 0.3 ml blood/100 ml brain during activation [CBV(ACT)] and rest [CBV(REST)], respectively) consistent with previous studies using similar visual stimuli. Furthermore, an increase in effective blood relaxation (0.65 +/- 0.01) compared to the published value (0.62) was detected, likely reflecting inflow of fresh blood. Finally, cerebral metabolic rate of oxygen (CMRO(2)) estimates using a multiple compartment model without assumption of CBV(REST) led to estimates (18.7 +/- 17.0%) that were within published ranges.


Novel splicing events and post-transcriptional regulation of human estrogen receptor α E isoforms.
Expression of the estrogen receptor α (ERα) gene is subject to complex regulation. To elucidate the mechanisms of this regulation, the genomic organization and the physiological role of the multiple 5'-untranslated regions (5'-UTRs) must be determined. Here, we investigated the expression and splicing patterns of the human ERα E isoforms. We identified two novel untranslated exons, N1 and N2, in the 5'-region of the human ERα gene and multiple E isoform mRNA variants generated by alternative usage of non-coding internal exons. Expression of the N1-containing variants was observed only in the human breast adenocarcinoma cell line, MCF7, while the N2-containing variants were expressed in the adult liver and MCF7 cells. We examined post-transcriptional regulation of the variant mRNAs using luciferase reporter assays and quantitative PCR. The insertion of untranslated internal exons into the 5'-UTRs of the E isoforms reduced their translation efficiency, but barely influenced mRNA turnover. Our results indicate that the genomic organization of the human ERα gene and the splicing profiles of the human ERα E isoforms are more complicated than previously reported. Furthermore, the 5'-UTRs of the E isoforms post-transcriptionally control human ERα expression mainly through translational repression.


Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.
The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.


Neuroblastoma involving urinary bladder: A rare type of tumor with diagnostic ambiguity.
Neuroblastoma of urinary tract is an extremely rare type of tumor and only a few cases have been reported worldwide. We presented an adult case of neuroblastoma involving urinary bladder. Patient was a 24-year-old man with a history of repeated attack of hematuria. Patient underwent cystoscopy and transuretheral resection of bladder tumor. Biopsy result was "Blastema cell (suggestive of neuroblastoma) with immature ganglion cells." Immunohistochemistry workup was continued and neuron-specific enolase and S100 staining were positive. Patient lost to further follow-up visit. Although neuroblastoma of skin and peripheral nerve is not a rare disease entity, involvement of deeper structures (especially urinary bladder) is exceptional.


Improving Pediatric Intensive Care Unit Discharge Timeliness of Infants with Bronchiolitis Using Clinical Decision Support.
Identifying children ready for transfer out of the pediatric intensive care unit (PICU) is an area that may benefit from clinical decision support (CDS). We previously implemented a quality improvement (QI) initiative to accelerate the transfer evaluation of non-medically complex PICU patients with viral bronchiolitis receiving floor-appropriate respiratory support. Design a CDS tool adaptation of this QI initiative to further accelerate transfer evaluation of appropriate patients. The original initiative focused on identifying for transfer evaluation otherwise healthy children admitted to the PICU with bronchiolitis who had been receiving floor-appropriate levels of respiratory support for at least 6 hours. However, this initiative required that clinicians manually track the respiratory support of qualifying patients. We designed an electronic health record (EHR)-based CDS tool to automate identification of transfer-ready candidates. The tool parses EHR data to identify children meeting prior QI initiative criteria and alerts clinicians to assess transfer readiness once a child has been receiving floor-appropriate respiratory support for 6 hours. We compared time from reaching floor-appropriate support to placement of the transfer order ("time-to-transfer"), PICU length of stay (LOS), and hospital LOS between patients admitted prior to our QI initiative (December 1, 2018-October 19, 2019, "pre-QI phase"), during the initiative but before CDS tool implementation (October 20, 2019-February 7, 2022, "QI phase"), and after CDS implementation (February 8-November 11, 2022, "CDS phase"). CDS-phase patients (n = 131) had a shorter median time-to-transfer of 5.23 (interquartile range [IQR], 3.38-10.0) hours compared with QI-phase patients (n = 304) at 5.93 (IQR, 4.23-12.2) hours (p = 0.04). PICU and hospital LOS values decreased from the pre-QI (n = 150) to QI phase. Though LOS reductions were sustained during the CDS phase, further reductions from QI to CDS phase were not statistically significant. An EHR-based CDS adaptation of a prior QI initiative facilitated timely identification of PICU patients with bronchiolitis ready for transfer evaluation. Such tools might allow PICU clinicians to focus on other high-acuity tasks while accelerating transfer evaluation of appropriate patients.


Imported measles and implications for its elimination in Taiwan.
During November 2008-May 2009, an outbreak of 53 measles cases occurred in Taiwan. Of these, 3 cases were sporadic, and the other 50 cases could be grouped into 8 clusters by genetic analysis. We determined 7 H1 genotypes linked to importation and 1 G3 genotype linked to an untraceable source.


Evaluation of early postoperative intravenous opioid rescue as a novel quality measure in patients who receive thoracic epidural analgesia: a retrospective cohort analysis and prospective performance improvement intervention.
In this study, we explored the utility of intravenous opioid rescue analgesia in the post anesthesia care unit (PACU-OpResc) as a single marker of thoracic epidural analgesia (TEA) failure and evaluated the resource implications and quality improvement applications of this measure. We performed a retrospective analysis of all TEA placements over a three-year period at a single academic medical center in Boston, Massachusetts. The study exposure was PACU-OpResc. Primary outcome was PACU length of stay (LOS). Secondary outcomes included reasons for delayed PACU discharge and intraoperative hypotension. The analyses were adjusted for confounding variables including patient comorbidities, surgical complexity, intraoperative intravenous opioids, chronic opioid use and local anesthetic bolus through TEA catheter. Post analysis chart review was conducted to determine the positive predictive value (PPV) of PACU-OpResc for inadequate TEA. As a first Plan-Do-Study-Act cycle, we then introduced a checkbox for documentation of a sensory level check after TEA placement. Post implementation data was collected for 7 months. PACU-OpResc was required by 211 (22.1%) patients who received preoperative TEA, was associated with longer PACU LOS (incidence rate ratio 1.20, 95% CI:1.07-1.34, p = 0.001) and delayed discharge due to inadequate pain control (odds ratio 5.15, 95% CI 3.51-7.57, p < 0.001). PACU-OpResc had a PPV of 76.3 and 60.4% for re-evaluation and manipulation of the TEA catheter in PACU, respectively. Following implementation of a checkbox, average monthly compliance with documented sensory level check after TEA placement was noted to be 39.7%. During this time, a reduction of 8.2% in the rate of PACU-OpResc was observed. This study demonstrates that PACU-OpResc can be used as a quality assurance measure or surrogate for TEA efficacy, to track performance and monitor innovation efforts aimed at improving analgesia, such as our intervention to facilitate sensory level checks and reduced PACU-OpResc. not applicable.


Whole-brain radiation therapy is not beneficial as an adjuvant therapy for brain metastases compared with localized irradiation.
We investigated the role of whole-brain radiation therapy (WBRT) which has been widely used as an adjuvant therapy for brain metastases. The authors retrospectively reviewed 132 patients who underwent surgical resection for brain metastases. They were classified into five groups according to the dose of radiation therapy to the local brain (L) or to the whole-brain (W), independently; 0 Gy (Group A[L or W]), 20-29 Gy (Group B[L or W]), 30-39 Gy (Group C[L or W]), 40-49 Gy (Group D[L or W]) and 50 Gy or more (Group E[L or W]). Local recurrence rates and times to tumor progression (TTP) of the original tumor were 53% and 3 months for Group A(L), 25% and 6 months for Group C(L), 11% and 7 months for Group D(L) and 12% and 12 months for Group E(L). Median survival times (MST) were 6 months for Group A(L), 8 months for Group C(L), 8 months for Group D(L) and 11 months for Group E(L). Distant recurrence rates and the TTP of new lesions in the distant area were 27% and 7 months for Group A(W), 20% and 6 months for Group B(W), 8% and 9 months for Group C(W), 13% and 13 months for Group D(W) and 4% and 14 months for Group E(W). The MST were 11 months for Group A(W), 11 months for Group B(W), 10 months for Group C(W), 9 months for Group D(W) and 6 months for group E(W). The present results suggest that WBRT is unnecessary and that local radiation therapy of 40 Gy or more would be the primary choice of adjuvant therapy for the majority of patients treated with surgical resection for brain metastases.


Imaging visual recognition memory network by PET in the baboon: perirhinal cortex heterogeneity and plasticity after perirhinal lesion.
We recently mapped the visual recognition memory network in the behaving baboon using a positron emission tomography (PET) activation paradigm with 18F-fluoro-deoxyglucose during a visual delayed matching-to-sample task. This study confirmed the key role of the perirhinal cortex and documented an unexpected left-sided advantage. Specific contribution of each subdivision of the perirhinal cortex has, however, never been investigated. Furthermore, although alteration to the perirhinal cortex has been implicated in several brain disorders, putative plasticity within the entire brain network after perirhinal damage remains largely unknown. To confirm our previous data and to investigate these latter issues, we used our PET activation paradigm on a second healthy baboon before and after 16 months after bilateral excitotoxic lesions of the perirhinal cortex. Activation common to our two healthy baboons occurred only in the left rostroventral perirhinal cortex (i.e., areas 36pm and rostral 36r) and insular cortex. Although histologic analysis disclosed that the perirhinal lesions achieved in the present baboon were essentially caudal to this preoperatively activated area, memory performance was severely impaired. Concomitant with this long-lasting cognitive deficit, changes in the neural network implicated in the task were observed, involving disappearance of the preoperative activations and appearance of a significant activation of the frontal and occipital cortices. However, different activation patterns were found in the first and last eight postoperative months. These findings highlight the functional heterogeneity of the perirhinal cortex and evidence progressive plasticity after perirhinal cortex damage.


Personal and family history of suicidal behaviour is associated with lower peripheral cortisol in depressed outpatients.
Suicidal behaviour aggregates in families and HPA-axis dysregulation may help explain part of this familial aggregation. Nevertheless, exogenous manipulation of the HPA-axis has yielded mixed results. Naturalistic and non-pharmacological inductions of the HPA-axis do not suggest hyper-responsiveness, yet suggest greater cognitive consequences of stress in individuals at risk for suicide. In this study, we aimed to characterize the relationship between plasma cortisol and an increased risk for suicide, as defined by family history. Patients (N=148) with depressive disorders underwent psychopathological assessment, including structured investigation of past suicidal behaviour and underwent laboratory blood testing of cortisol. They also completed a family history interview investigating family psychopathology and suicidal behaviour, representing data on 848 first degree relatives. The relationship between plasma cortisol, past suicidal behaviour and suicidal behaviour among first degree relatives was examined. Lower levels of plasma cortisol were associated with a personal and family history of suicidal behaviour, as well as a family history of depression among first degree relatives. Multivariate analyses controlling for significant psychopathology replicated the association between lower levels of plasma cortisol, a family history of suicidal behaviour and personal history of suicide attempts, but not a family history of depression. Controlling for personal history of suicide attempts revealed an independent association between plasma cortisol and family history of suicidal behaviour, with an additional contribution by family history of depression in predicting the latter. Lower plasma cortisol is associated with a family history of suicide among depressed outpatients, independent of psychopathology and previous suicide attempts.


Critically coupled Fabry-Perot cavity with high signal contrast for refractive index sensing.
Perfect absorption at a resonance wavelength and extremely low absorption at the wavelength range of off-resonance in a one-port optical cavity is required for refractive index (RI) sensing with high signal contrast. Here, we propose and analyze an absorption-enhanced Fabry-Perot (MAFP) cavity based on a critical coupling condition in a near-infrared wavelength range. For a one-port cavity, a thick bottom Au is used as a mirror and an absorber. To achieve the critical coupling condition, a top dielectric metasurface is employed and tailored to balance the radiation coupling and the absorption coupling rates, and the one-port cavity is theoretically analyzed using temporal coupled-mode theory. We investigate two types of MAFP structures for gas and liquid. The gas MAFP cavity shows a sensitivity of ~ 1388 nm/RIU and a full-width at half-maximum of less than 0.7 nm. This MAFP cavity resolves the RI change of 5 × 10-4 with a reflectance signal margin of 50% and achieves a signal contrast of ~ 100%. The liquid MAFP cavity shows a sensitivity of ~ 996 nm/RIU when RI of liquid changes from 1.30 to 1.38. With tailoring the period of the metasurface maintaining its thickness, a signal contrast of ~ 100% is achieved for each specific RI range.


[Management of the first trimester miscarriages].
A first trimester miscarriage is most often painfully experienced by the patients. The practitioner should be able to offer appropriate, timely, efficient and safe medical management, allowing a shorter convalescence without effect on subsequent fertility. Each step of the process of the miscarriage results in clinical and ultrasonographic characteristics, and requires a specific therapeutic strategy. Vaginal ultrasound allows confirmation of early pregnancy failure (missed miscarriage) diagnosis and to estimate the complete or incomplete removal of trophoblastic material. However, the endometrial thickness does not appear to be predictive for the risk of persistent bleeding or secondary surgery. Surgical evacuation of the product of conception remains the most effective and the quickest method of treatment. Depending on the clinical situation, medical treatment with misoprostol (missed miscarriage) or expectative attitude (incomplete miscarriage) do not increase the risk of complications, particularly the infectious one. However, these alternatives generally require more prolonged outpatient follow-up leading to more frequent consultations and surgical emergencies.


Nucleotide sequence of Pseudomonas aeruginosa conjugative plasmid pUM505 containing virulence and heavy-metal resistance genes.
We determined the complete nucleotide sequence of conjugative plasmid pUM505 isolated from a clinical strain of Pseudomonas aeruginosa. The plasmid had a length of 123,322bp and contained 138 complete coding regions, including 46% open reading frames encoding hypothetical proteins. pUM505 can be considered a hybrid plasmid because it presents two well-defined regions. The first region corresponded to a larger DNA segment with homology to a pathogenicity island from virulent Pseudomonas strains; this island in pUM505 was comprised of genes probably involved in virulence and genes encoding proteins implicated in replication, maintenance and plasmid transfer. Sequence analysis identified pil genes encoding a type IV secretion system, establishing pUM505 as a member of the family of IncI1 plasmids. Plasmid pUM505 also contained virB4/virD4 homologues, which are linked to virulence in other plasmids. The second region, smaller in length, contains inorganic mercury and chromate resistance gene clusters both flanked by putative mobile elements. Although no genes for antibiotic resistance were identified, when pUM505 was transferred to a recipient strain of P. aeruginosa it conferred resistance to the fluoroquinolone ciprofloxacin. pUM505 also conferred resistance to the superoxide radical generator paraquat. pUM505 could provide Pseudomonas strains with a wide variety of adaptive traits such as virulence, heavy-metal and antibiotic resistance and oxidative stress tolerance which can be selective factors for the distribution and prevalence of this plasmid in diverse environments, including hospitals and heavy metal contaminated soils.


Performability evaluation, validation and optimization for the steam generation system of a coal-fired thermal power plant.
The present paper talks over performability evaluation for a steam generation system of a Coal Fired Thermal Power Plant (CFTPP) using the concept of the Markov method. A steam generation system provides a suitable amount of steam for the sound functioning of the plant. The system comprises five subsystems, i.e., High-Pressure Heater, Economizer, Boiler Drum, Water Tubes, and Super Heater. First, the transition diagram of the concerned system is designed based on the state probabilities of various subsystems. The differential equations are derived based on the mnemonic rule. After that, the performability model is developed by using the normalizing condition. The performability levels for various subsystems are obtained by placing the appropriate value of failure and repair rates in the developed model. The performability of each subsystem is evaluated based on performability matrices. It is observed that the economizer subsystem is most critical in which the availability increased from 0.7640 to 0.8827, i.e. (11.87 %). In contrast, boiler drum is the least crucial subsystem with availability enhanced from 0.8627 to 0.8657 (i.e., 0.3 %). The results show that the economizer subsystem must be given top priority, and the boiler drum be given the least priority from the maintenance outlook. The performability levels obtained through the Markov method are compared with those obtained through the Artificial Neural Network to validate. Moreover, machine learning (artificial neural network) and optimization technique (particle swarm optimization) is also employed to check the adequacy of the results and optimized process parameters.•The aim of the present study is evaluate the performance of steam generation system of a coal fired thermal power plant.•The probabilistic approach (i.e. Makov Method) is used to formulate the transition diagram of the steam generation system. Then, the first-order differential equations are obtained using the mnemonic rule and further solved recursively.•The results show that the economizer system must be given top priority, and the boiler drum subsystem must be given the least priority from the maintenance outlook.


Ciliogenesis in normal human kidney development and post-natal life.
Ciliogenesis in developing and post-natal human kidneys appears to influence cell proliferation and differentiation, apico-basal cell polarity, and tubular lumen formation. We have analyzed the appearance of primary cilia and differentiation of kidney cells in ten human conceptuses aged 6-22 weeks and in one 5-year-old kidney, using a double immunofluorescence labeling technique for α-tubulin, γ-tubulin, Oct-4, and Ki-67 and by electron microscopy. Immature forms of nephrons and ampullae were characterized by intense cell proliferation, which subsequently decreased during development. Primary cilia appeared on the surfaces of non-proliferating cells in developing nephrons, gradually increasing in length from 0.59 μm in renal vesicles to 0.81 μm in the S-forms of nephrons, ultimately reaching 3.04 μm in length in mature fetal and post-natal nephrons. Ciliary length increased from 0.59 μm in ampullae to 1.28 μm in post-natal collecting tubules. Mesenchymal to epithelial transformation of kidney cells coincided with the appearance of apico-basal polarity, both gap and tight junctions, and lumen formation. Up-regulation of Oct-4 expression correlated with the onset of kidney cell differentiation. Our results demonstrate the importance of proper primary cilia lengthening and Oct-4 expression for the normal development of fetal and post-natal kidneys and of apico-basal polarity for normal tubular lumen formation. Disturbances in these processes are associated with ciliopathies.


Deep-Dwelling Populations of Mediterranean Corallium rubrum and Eunicella cavolini: Distribution, Demography, and Co-Occurrence.
Corallium rubrum and Eunicella cavolini are two octocorals, reported as co-occurring species in the deep rocky habitats of the Mediterranean Sea with a high hydrodynamic and moderate eutrophication. Their spatial distribution and demography in the deep sea are mainly affected by temperature and direct and indirect anthropogenic activities; however, knowledge of the factors that potentially influence their co-existence is scarce. This paper provides novel data on the distribution and demography of these two species, at depths between 50 and 290 m in the Western Mediterranean Sea, providing insights on their co-occurrence. Both species exhibited the highest population density at deeper sites (>150 m), showing an inverse size-density relation. Density values ranged from 0.03 colonies m-2 to 32 and 80 col. m-2 for yellow gorgonian and red coral, respectively. The two species co-occurred in 13% of the total frames examined, mostly dwelling between 120 and 160 m depth. Distance-based linear modeling (DistLM) emphasized that when co-occurring the variability of the two species' densities were significantly driven by the density-rather than the morphology (i.e., height)-of the other species. We stress the need for further studies to elucidate the possible mutual effects of suspension feeders and to test the role of different environmental factors potentially influencing inter-specific relationships.


What are the clinical effects of the different emergency department imaging options for suspected renal colic? A scoping review.
Clinicians have minimal guidance regarding the clinical consequences of each radiologic imaging option for suspected renal colic in the emergency department (ED), particularly in relation to patient-centered outcomes. In this scoping review, we sought to identify studies addressing the impact of imaging options on patient-centered aspects of ED renal colic care to help clinicians engage in informed shared decision making. Specifically, we sought to answer questions regarding the effect of obtaining computed tomography (CT; compared with an ultrasound or delayed imaging) on safety outcomes, accuracy, prognosis, and cost (financial and length of stay [LOS]). We conducted a comprehensive search using Pubmed, EMBASE, Web of Science conference proceedings index, and Google Scholar, identifying studies pertaining to renal colic, urolithiasis, and ureterolithiasis. In a prior qualitative study, stakeholders identified 14 key questions regarding renal colic care in the domains of safety, accuracy, prognosis, and cost. We systematically screened studies and reviewed the full text of articles based on their ability to address the 14 key questions. Our search yielded 2570 titles, and 68 met the inclusion criteria. Substantial evidence informed questions regarding test accuracy and radiation exposure, but less evidence was available regarding the effect of imaging modality on patient-oriented outcomes such as cost and prognosis (admissions, ED revisits, and procedures). Reviewed studies demonstrated that both standard renal protocol CT and low-dose CT are highly accurate, with ultrasound having lower accuracy. Several studies found that ureterolithiasis diagnosed by ultrasound was associated with overall reduced radiation exposure. Existing studies did not suggest choice of imaging influences prognosis. Several studies found no substantial differences in monetary cost, but LOS was found to be shorter if a diagnosis was made with point-of-care ultrasound. There is a plethora of data related to imaging accuracy. However, there is minimal data regarding the effect of CT on many patient-centered outcomes. Further research could improve the patient-centeredness of ED care.


Depressed potential for interleukin-2 production following early weaning of piglets.
Spleen cells, but not mesenteric lymph node cells, from 3-week-old piglets abruptly weaned onto a soya-based diet, produced less interleukin-2 (IL-2) following non-specific activation with concanavalin A (Con A) than did cells from age- and litter-matched, unweaned controls. In contrast, the ability to express receptors for IL-2 was only marginally reduced. The effect on IL-2 production was most marked in animals weaned for as little as 24-48 h. Variation within groups increased with time after weaning, indicating differences between individuals in the longer-term effects of weaning. This finding may be due to endogenous production of steroids resulting in generalised impaired immune function or to retention of cells within intestinal sites owing to an active local immune response.


Precision medicine and rare diseases in pediatric urology.
Precision Medicine holds promise for helping us manage specific phenotypes of common diseases. For rare diseases such as hypospadias, DSD, and pediatric solid tumors, it can also reveal underlying risk factors and pathogenesis. Professors Ann Nordgren and Anna Lindstrand share their experiences in the development and ongoing initiatives of the Swedish national project on Precision Medicine and how it could change the care of pediatric urology patients.


Primary retroperitoneal carcinosarcoma in a child: a case report.
Carcinosarcoma is a rare biphasic malignancy consisting of intermixed epithelial and mesenchymal elements. Carcinosarcoma is particularly rare among children. We accepted a 7 year old patient with retroperitoneal carcinosarcoma. The tumor was totally resected and no recurrence is found 11 months after operation. Literatures has been reviewed and there are few reports of primary retroperitoneal carcinosarcoma in children up to date. So we report the patient's clinical character, surgical resection, pathological and immunohistochemical analysis.


The plerocercus of Ditrachybothridium macrocephalum Rees, 1959 from two deep-sea elasmobranchs, with a molecular analysis of its position within the order Diphyllidea and a checklist of the hosts of larval diphyllideans.
New collections were made of Ditrachybothridium macrocephalum Rees, 1959 from the deep-sea elasmobranchs Apristurus laurussonii (Saemundsson) and cf. Rajella bigelowi (Stehmann) in the northern Atlantic Ocean, allowing studies of the morphology of its plerocercus. The material has also allowed an estimate of its position within the Diphyllidea inferred from molecular data for the first time. The plerocercus is withdrawn, but not invaginated, within a cyst with a thick vacuolated wall. The encysted strobila is distinct, with several putative segments and advanced genital anlagen, and the scolex is fully developed with a distinct apical pad. 28S rDNA (D1-D3 regions) sequences were generated from both encysted and excysted D. macrocephalum , as well as from other diphyllidean and pseudophyllidean (outgroup) taxa for use in phylogenetic analyses. Maximum parsimony and Bayesian inference analyses both showed that the diphyllidean genus Echinobothrium is paraphyletic without inclusion of the only two other diphyllidean genera, Ditrachybothridium Rees, 1959 and Macrobothridium Khalil & Abdul-Salam, 1989. A list of published records of larval diphyllideans, their hosts and localities is included.


Environmental enrichment alters LPS-induced changes in BDNF and PSD-95 expressions during puberty.
Puberty is a critical period of cortical reorganization and increased synaptogenesis. Healthy cortical reorganization and synaptic growth require sufficient environmental stimuli and minimalized stress exposure during pubertal development. Exposure to impoverished environments or immune challenges impact cortical reorganization and reduce the expression of proteins associated with neuronal plasticity (BDNF) and synaptogenesis (PSD-95). Environmentally enriched (EE) housing includes improved social-, physical-, and cognitive stimulation. We hypothesized that enriched housing environment would mitigate pubertal stress-induced decreases in BDNF and PSD-95 expressions. Three-week-old male and female CD-1 mice (n = 10 per group) were housed for three weeks in either EE, social or deprived housing conditions. At 6 weeks of age, mice were treated with either lipopolysaccharide (LPS) or saline eight hours prior to tissue collection. Male and female EE mice displayed greater BDNF and PSD-95 expressions in the medial prefrontal cortex and hippocampus compared to socially housed and deprived housed mice. LPS treatment decreased BDNF expression in all the brain regions examined in EE mice, except for the CA3 region of the hippocampus, where EE housing successfully mitigated the pubertal LPS-induced decrease in BDNF expression. Interestingly, LPS-treated mice housed in deprived conditions displayed unexpected increases in BDNF and PSD-95 expressions throughout the medial prefrontal cortex and hippocampus. Both enriched and deprived housing conditions moderate how an immune challenge influences BDNF and PSD-95 expressions in a region-specific manner. These findings also emphasize the vulnerability of brain plasticity during puberty to various environmental factors.


Simulation studies of self-associating systems; discrimination between specific and isodesmic associations.
The possibilities of discriminating between definite and indefinite (isodesmic) modes of self-association are explored by fitting the different models to stimulated data, using non-linear least-squares curve-fitting to determine the fitting parameters for real and impostor models. It was found that over an extensive range of values for the equilibrium constant of a non-ideal isodesmic generating model, only a non-ideal monomer-dimer-tetramer-octamer was a successful impostor model. Some criteria for rejecting inappropriate models are discussed.


Autofluorescence Label-Free Imaging of the Liver Reticular Structure.
Autofluorescence rising from biological substrates under proper excitation light depends on the presence of specific endogenous fluorophores and can provide information on the morpho-functional properties in which they are strictly involved. Besides the numerous endogenous fluorophores involved in metabolic functions, fibrous proteins may act as direct, label-free biomarkers of the tissue structural organization. The optical properties of collagen, in particular, are currently applied as an alternative to established histochemical procedures to investigate the connective tissue as well as its changes in diseased conditions. This is particularly true in hepatology where the histochemical procedures to label the reticular structure are not routinely applied, as they are complex and time-consuming. The morphology of the liver reticular structure and its changes are up to now poorly considered despite the increasing awareness of the regulatory role played by the remodeling of the reticular structure in pathological conditions. In this context, the autofluorescence label-free imaging has proven to be a suitable approach.


Subacute toxicity and endocrine-disrupting effects of Fe2O3, ZnO, and CeO2 nanoparticles on amphibian metamorphosis.
This study evaluated the potential toxic and endocrine-disrupting effects of sublethal concentrations of Fe2O3, CeO2 and ZnO nanoparticles (NPs) on amphibian metamorphosis. Tadpoles were exposed to several NPs concentrations, reaching a maximum of 1000 µg/L, for up to 21 days according to the amphibian metamorphosis assay (AMA). Some standard morphological parameters, such as developmental stage (DS), hind limb length (HLL), snout-to-vent length (SVL), wet body weight (WBW), and as well as post-exposure lethality were recorded in exposed organisms on days 7 and 21 of the bioassay. Furthermore, triiodothyronine (T3), thyroxine (T4) and malondialdehyde (MDA) levels and the activities of glutathione S-transferases (GST), glutathione reductase (GR), catalase (CAT), carboxylesterase (CaE), and acetylcholinesterase (AChE) were determined in exposed tadpoles as biomarkers. The results indicate that short-term exposure to Fe2O3 NPs leads to toxic effects, both exposure periods cause toxic effects and growth inhibition for ZnO NPs, while short-term exposure to CeO2 NPs results in toxic effects and long-term exposure causes endocrine-disrupting effects. The responses observed after exposure to the tested NPs during amphibian metamorphosis suggest that they may have ecotoxicological effects and their effects should be monitored through field studies.


Studying of telomeric protein-protein interactions by Bi-molecular fluorescence complementation (BiFC) and peptide array-based assays.
Studying protein-protein interactions is critical to our understanding of the signaling pathways. The Telomere Interactome is assembled around the telomeres and consists of proteins and factors from diverse pathways. Dissecting how this protein network contributes to telomere protection and length regulation requires the elucidation of the complex and dynamic interactions between the proteins within the interactome. Here, we focus on the Bi-molecular fluorescence complementation (BiFC) and peptide array methods that have proven vital in our studies of telomere protein interaction networks.