In vitro bioassays for monitoring drinking water quality of tap water, domestic filtration and bottled water.
Location-specific patterns of regulated and non-regulated disinfection byproducts (DBPs) were detected in tap water samples of the Barcelona Metropolitan Area. However, it remains unclear if the detected DBPs together with undetected DPBs and organic micropollutants can lead to mixture effects in drinking water. To evaluate the neurotoxicity, oxidative stress response and cytotoxicity of 42 tap water samples, 6 treated with activated carbon filters, 5 with reverse osmosis and 9 bottled waters. To compare the measured effects of the extracts with the mixture effects predicted from the detected concentrations and the relative effect potencies of the detected DBPs using the mixture model of concentration addition. Mixtures of organic chemicals in water samples were enriched by solid phase extraction and tested for cytotoxicity and neurite outgrowth inhibition in the neuronal cell line SH-SY5Y and for cytotoxicity and oxidative stress response in the AREc32 assay. Unenriched water did not trigger neurotoxicity or cytotoxicity. After up to 500-fold enrichment, few extracts showed cytotoxicity. Disinfected water showed low neurotoxicity at 20- to 300-fold enrichment and oxidative stress response at 8- to 140-fold enrichment. Non-regulated non-volatile DBPs, particularly (brominated) haloacetonitriles dominated the predicted mixture effects of the detected chemicals and predicted effects agreed with the measured effects. By hierarchical clustering we identified strong geographical patterns in the types of DPBs and their association with effects. Activated carbon filters did not show a consistent reduction of effects but domestic reverse osmosis filters decreased the effect to that of bottled water. Bioassays are an important complement to chemical analysis of disinfection by-products (DBPs) in drinking water. Comparison of the measured oxidative stress response and mixture effects predicted from the detected chemicals and their relative effect potencies allowed the identification of the forcing agents for the mixture effects, which differed by location but were mainly non-regulated DBPs. This study demonstrates the relevance of non-regulated DBPs from a toxicological perspective. In vitro bioassays, in particular reporter gene assays for oxidative stress response that integrate different reactive toxicity pathways including genotoxicity, may therefore serve as sum parameters for drinking water quality assessment.


Growth of the pediatric skull base: assessment using magnetic resonance imaging.
Minimal information is available concerning the gross anatomic changes that occur with skull base development in children. Because clinical and autopsy material to evaluate skull base growth in this population is rare, the author of this study evaluated normal magnetic resonance imaging (MRI) scans in 76 children ranging in age from newborn to 18 years. Growth of the basicranium was assessed in three dimensions: anterior-posterior, medial-lateral, and superior-inferior. In each dimension, growth was noted to be rapid until age 6 years, with relatively slower growth thereafter. In the superior-inferior and anterior-posterior dimensions, both the amount of growth and the asymptotic value were noted to be greater in males than in females (P < .05). The findings of this study can help surgeons select the appropriate operative approach for skull base masses in children. Certain approaches may involve significant morbidity, including mandibulotomy, loss of teeth, oral contamination, and external auditory canal closure. Representative cases managed through an extrapharyngeal transcervical approach are reviewed.


Effect of pelvic floor and transversus abdominis muscle contraction on inter-rectus distance in postpartum women: a cross-sectional experimental study.
To investigate the effect of acute isometric contraction of the pelvic floor muscles (PFM) and transversus abdominis muscle (TrAM) on inter-rectus distance (IRD) from resting values in postpartum women with diastasis rectus abdominis (DRA). Cross sectional experimental study. Physiotherapy clinic. Thirty eight postpartum women presenting with DRA of at least two finger widths. Two dimensional ultrasound images of IRD were recorded using a linear probe (5 to 10MHz) at rest, during PFM contraction, during TrAM contraction, and during combined PFM and TrAM contraction. IRD data were normally distributed. Change in IRD. There was a significant increase in IRD during PFM and TrAM contraction compared with IRD at rest. At 2cm above the umbilicus, mean PFM was 26.9 [standard deviation (SD) 8.8] mm vs rest 25.7 (SD 8.5) mm {mean difference 1.2 [95% confidence interval (CI) 0.7 to 1.7] mm}; and mean TrAM was 28.4 (SD 9.0) mm vs rest 25.7 (SD 8.5) mm [mean difference 2.8 (95% CI 1.9 to 3.6) mm]. Similarly, 2cm below the umbilicus, mean PFM was 22 (SD 8.3) mm vs rest 21 (SD 7.9) mm [mean difference 0.9 (95% CI 0.4 to 1.6) mm]; and mean TrAM was 23.3 (SD 8.7) mm vs rest 21 (SD 7.9) mm [mean difference 2.3 (95% CI 1.5 to 3.1) mm]. Combined TrAM and PFM contraction measured 2cm above the umbilicus caused the greatest increase in IRD: mean PFM+TrAM 29.6 (SD 9.4) mm vs rest 25.7 (SD 8.5) mm [mean difference 3.9 (95% CI 2.8 to 5.0) mm]. Both PFM and TrAM contraction, and combined PFM and TrAM contraction increased IRD in postpartum women with DRA.


Oxygen-Glucose Deprived Peripheral Blood Mononuclear Cells Protect Against Ischemic Stroke.
Stroke is the leading cause of severe long-term disability. Cell therapy has recently emerged as an approach to facilitate functional recovery in stroke. Although administration of peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation (OGD-PBMCs) has been shown to be a therapeutic strategy for ischemic stroke, the recovery mechanisms remain largely unknown. We hypothesised that cell-cell communications within PBMCs and between PBMCs and resident cells are necessary for a polarising protective phenotype. Here, we investigated the therapeutic mechanisms underlying the effects of OGD-PBMCs through the secretome. We compared levels of transcriptomes, cytokines, and exosomal microRNA in human PBMCs by RNA sequences, Luminex assay, flow cytometric analysis, and western blotting under normoxic and OGD conditions. We also performed microscopic analyses to assess the identification of remodelling factor-positive cells and evaluate angiogenesis, axonal outgrowth, and functional recovery by blinded examination by administration of OGD-PBMCs after ischemic stroke in Sprague-Dawley rats. We found that the therapeutic potential of OGD-PBMCs was mediated by a polarised protective state through decreased levels of exosomal miR-155-5p, and upregulation of vascular endothelial growth factor and a pluripotent stem cell marker stage-specific embryonic antigen-3 through the hypoxia-inducible factor-1α axis. After administration of OGD-PBMCs, microenvironment changes in resident microglia by the secretome promoted angiogenesis and axonal outgrowth, resulting in functional recovery after cerebral ischemia. Our findings revealed the mechanisms underlying the refinement of the neurovascular unit by secretome-mediated cell-cell communications through reduction of miR-155-5p from OGD-PBMCs, highlighting the therapeutic potential carrier of this approach against ischemic stroke.


Internet-based search of randomised trials relevant to mental health originating in the Arab world.
The internet is becoming a widely used source of accessing medical research through various on-line databases. This instant access to information is of benefit to busy clinicians and service users around the world. The population of the Arab World is comparable to that of the United States, yet it is widely believed to have a greatly contrasting output of randomised controlled trials related to mental health. This study was designed to investigate the existence of such research in the Arab World and also to investigate the availability of this research on-line. Survey of findings from three internet-based potential sources of randomised trials originating from the Arab world and relevant to mental health care. A manual search of an Arabic online current contents service identified 3 studies, MEDLINE, EMBASE, and PsycINFO searches identified only 1 study, and a manual search of a specifically indexed, study-based mental health database, PsiTri, revealed 27 trials. There genuinely seem to be few trials from the Arab world and accessing these on-line was problematic. Replication of some studies that guide psychiatric/psychological practice in the Arab world would seem prudent.


Analysis of Differentially Expressed Genes in Tissues of Camellia sinensis during Dedifferentiation and Root Redifferentiation.
Tissue culture is very important for identifying the gene function of Camellia sinensis (L.) and exploiting novel germplasm through transgenic technology. Regeneration system of tea plant has been explored but not been well established since the molecular mechanism of tea plant regeneration is not clear yet. In this study, transcriptomic analysis was performed in the initial explants of tea plant and their dedifferentiated and redifferentiated tissues. A total of 93,607 unigenes were obtained through de novo assembly, and 7,193 differentially expressed genes (DEGs) were screened out from the 42,417 annotated unigenes. Much more DEGs were observed during phase transition rather than at growth stages of callus. Our KOG and KEGG analysis, and qPCR results confirmed that phase transition of tea plant was closely related to the mechanism that regulate expression of genes encoding the auxin- and cytokinin-responsive proteins, transcription factor MYB15 and ethylene-responsive transcription factor ERF RAP2-12. These findings provide a reliable foundation for elucidating the mechanism of the phase transition and may help to optimize the regeneration system by regulating the gene expression pattern.


Increased Medical Visits and Mortality among Adults with Cardiovascular Diseases in Severely Affected Areas after Typhoon Morakot.
Natural disasters have negative health impacts on chronic diseases in affected populations. Severely affected areas are usually rural areas with limited basic infrastructure and a population have that has limited access to optimal healthcare after a disaster. Patients with cardiovascular diseases are required to maintain quality care, especially after disasters. A population-based case-control study enrolled adults from the National Health Insurance Registry who had ischemic heart disease and cerebrovascular disease histories and lived in the area affected by Typhoon Morakot in 2009. Monthly medical visits for acute cerebrovascular and ischemic heart diseases markedly increased at approximately 1-2 months after the typhoon. Survival analysis during the two years following the typhoon indicated a significant increase in mortality in adults with an acute ischemic heart disease history who lived in the severely affected area. Mortality hazard analysis showed that among affected adults with previous cerebrovascular diseases and acute ischemic heart diseases, patients with diabetes (adjusted hazard ratio [HR]: 1.3-1.7), Chronic Kidney Disease (CKD) (adjusted HR: 2.0-2.7), chronic obstructive pulmonary diseases (COPD) and asthma (adjusted HR: 1.7-2.1), liver cirrhosis (adjusted HR: 2.3-3.3) and neoplasms (adjusted HR: 1.1-2.1) had significantly increased mortality rates. Consequently, high-quality and accessible primary healthcare plans should be made available to maintain and support affected populations after disasters.


Laminar airflow ventilation systems in orthopaedic operating room do not prevent surgical site infections: a systematic review and meta-analysis.
Laminar airflow (LAF) technologies minimize infectious microorganisms to enhance air quality and surgical site infections (SSIs). LAF lowers SSIs in some clinical studies but not others. This study analyzes laminar airflow ventilation's capacity to reduce orthopaedic surgery-related SSIs. The PRISMA-compliant keywords were utilized to conduct a search for pertinent articles in various databases including PubMed, MEDLINE, CENTRAL, Web of Sciences, and the Cochrane databases. Observational studies, including retrospective, prospective, and cohort designs, satisfy the PICOS criteria for research methodology. The assessment of quality was conducted utilizing the Robvis software, while the meta-analysis was performed using the RevMan application. The study's results were assessed based on effect sizes of odds ratio (OR) and risk ratio (RR). From 2000 to 2022, 10 randomized controlled clinical trials with 10,06,587 orthopaedic surgery patients met the inclusion criteria. The primary outcomes were: (1) Risk of SSI, (2) Bacterial count in sampled air and (3) Reduction in SSIs. The overall pooled OR of all included studies was 1.70 (95% CI 1.10-2.64), and the overall pooled RR was 1.27 (95% CI 1.02-1.59) with p < 0.05. LAF is ineffective at preventing SSIs in orthopaedic procedures due to its high-risk ratio and odds ratio. The present meta-analysis has determined that the implementation of LAF systems does not result in a significant reduction in the incidence of surgical site infections (SSIs), bacterial count in the air, or SSIs occurrence in orthopaedic operating rooms. Consequently, the installation of said equipment in operating rooms has been found to be both expensive and inefficient.


Corrigendum: Expert arguments for trends of psychiatric bed numbers: A systematic review of qualitative data.
[This corrects the article DOI: 10.3389/fpsyt.2021.745247.].


Bilateral arthroscopic tendon interposition arthroplasty of the thumb carpometacarpal joint in a patient with Ehlers-Danlos syndrome: a case report.
A common finding in progressive osteoarthritis of the carpometacarpal joint of the thumb is ligamentous laxity. In patients with Ehlers-Danlos syndrome, which is a disorder characterized by generalized ligamentous laxity, splinting and arthrodesis have been recommended because of the random results achieved by other reconstructive procedures. We report a patient with thumb carpometacarpal joint osteoarthritis secondary to Ehlers-Danlos syndrome who was treated with bilateral arthroscopic tendon interposition arthroplasty.


Is the augmentation of K+-evoked intrasynaptosomal Ca2+ concentration due to the influx of Ca2+ in rat brain synaptosomes?
Intraterminal free Ca2+ concentration modulates the subsequent release of neurotransmitters. Depolarization of synaptosomes with 29 mM K+ augments cytosolic free Ca2+ concentration, which is triphasic, the peak times being at 10, 60, and 180 s. We examined the characteristics of each elevation of cytosolic free Ca2+ concentration in rat brain synaptosomes which had been preincubated for 3 min with a Ca2+-channel blocker, such as La3+, diltiazem, nifedipine, or verapamil, and under conditions of hypoxia or acidosis. The concentration of free Ca2+ in the quin-2-loaded rat brain synaptosomes was detected fluorometrically. All these elevations were suppressed in the presence of 200 microM EGTA or 100 microM La3+. At the first phase, the elevation of cytosolic free Ca2+ concentration with high K+ stimuli was significantly inhibited by La3+ (20 microM) or by acidosis (pH 6.7). On the other hand, diltiazem, which is a more potent blocker of the release of Ca2+ from the mitochondria, inhibited the increasing cytosolic free Ca2+ concentration at the third phase in a concentration-dependent manner. Hypoxia also showed inhibition at the third phase. These results suggest that the augmentation of high K+-evoked cytosolic free Ca2+ concentration may be due to the influx of extracellular Ca2+. The increase in cytosolic free Ca2+ concentration at the third phase is no doubt linked to the mitochondrial function.


Reliability of the grip strength coefficient of variation for detecting sincerity in normal and blocked median nerve in healthy adults.
In the assessment of hand and upper limb function, detecting sincerity of effort (SOE) for grip strength is of major importance to identifying feigned loss of strength. Measuring maximal grip strength with a dynamometer is very common, often combined with calculating the coefficient of variation (CV), a measure of the variation over the three grip strength trials. Little data is available about the relevance of these measurements in patients with median nerve impairment due to the heterogeneity of patient groups. This study examined the reliability of grip strength tests as well as the CV to detect SOE in healthy subjects. The power distribution of the individual fingers and the thenar was taken into account. To assess reliability, the measurements were performed in subjects with a median nerve block to simulate a nerve injury. The ability of 21 healthy volunteers to exert maximal grip force and to deliberately exert half-maximal force to simulate reduced SOE in a power grip was examined using the Jamar® dynamometer. The experiment was performed in a combined setting with and without median nerve block of the same subject. The force at the fingertips of digits 2-5 and at the thenar eminence was measured with a sensor glove with integrated pressure receptors. For each measurement, three trials were recorded subsequently and the mean and CV were calculated. When exerting submaximal force, the subjects reached 50-62% of maximal force, regardless of the median nerve block. The sensor glove revealed a significant reduction of force when exerting submaximal force (P1 sensor) with (P<0.032) and without median nerve block (P<0.017). An increase in CV at submaximal force was found, although it was not significant. SOE can be detected with the CV at the little finger at using a 10% cut-off (sensitivity 0.84 and 0.92 without and with median nerve block, respectively). These findings suggest low reliability of the power grip measurement with the Jamar® dynamometer, as well as that of the CV for detecting SOE. However, the combination of finger forces including the thenar area and the CV at the little finger could lead to better reliability for detecting feigned reduction of grip strength. The methods were as reliable in subjects with a median nerve block as in healthy subjects.


Praxis as a mirroring process: teaching psychiatric nursing grounded in Newman's health as expanding consciousness.
The purpose of this column is to describe the application of Newman's theory of health as expanding consciousness in nursing education. The authors examine the value of mirroring presence, self-reflection, appreciation of meaning and pattern, and creative approaches to student learning in their care of clients with chronic mental illness. Praxis as the basis for caring in the human health experience is discussed in this newly developed teaching-learning model.


A method for measuring testosterone-estradiol-binding globulin--new analysis of experimental data and comparison with two commercially available kits.
Some binding assays have been suggested to measure serum testosterone--estradiol-binding globulin (TeBG) concentration. They have led to discrepant results. This study brought to surface the lack of these methods and the interest of a method using an accurate analysis of the binding isotherm. These observations led us to propose an absolute reference method especially suitable for the radioimmunological assays standardization. Our method used Con A Sepharose as a solid phase and DHT as a radioligand. We succeeded in solving the difficulties related to binding methods by evaluating the non-specific binding of the ligand and ligand--albumin binding. A careful analysis of experimental data, by setting equations specific to this DHT-TeBG system permitted the systematic errors to be corrected and allowed a precise determination of the serum TeBG concentration (27.3 +/- 6.0 nmol/l for 30 healthy men; 40 +/- 13 nmol/l for 15 healthy women). Moreover, the affinity constant of the ligand for the protein was accurately evaluated KDHT = (0.7 +/- 0.1)10(9) (mol/l-1) at 20 degrees C, which was not permitted by other methods. Two lines of evidence supported our assumptions and results. On the one hand, using estradiol as a radioligand instead of dihydrotestosterone, we found the same value for serum TeBG concentration; on the other hand, our assay favourably compared with two different kits commercially available. The correlation (r = 0.89) with 3H-SBP kit Merieux was good though this kit was not suitable for correctly assaying serum TeBG concentrations between 30 nmol/l and 60 nmol/l. An excellent correlation (r = 0.97) with SHBG IRMA Kit Farmos was found. This antibody-based assay and our binding assay yielded quite similar values that mutually validated both methods.


Sinonasal anatomic variants and asthma are associated with faster development of chronic rhinosinusitis in patients with allergic rhinitis.
Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are a major burden to the healthcare system. Although no causal relationship has been established, previous work has demonstrated a strong association of AR with CRS. In this study, we sought to identify risk factors that may influence speed of development of CRS in patients with AR. Retrospective review of all patients diagnosed with AR without CRS presenting to an otolaryngology clinic at a tertiary medical center as part of a multidisciplinary allergy evaluation between March 2004 and November 2011. Medical records were evaluated for clinicodemographic factors including age, gender, smoking history, medical comorbidities, categories of AR based on formal allergy testing, the presence of sinonasal anatomic variants on computed tomography as well as subsequent development of CRS. Faster progression to CRS in patients with AR was associated with comorbid asthma (hazard ratio [HR] = 3.97) as well as sinonasal anatomic variants, such as infraorbital cells (HR = 7.39), and frontal intersinus cells (HR = 68.03), on multivariate survival analysis. A statistically significant but negative interaction between infraorbital cells and frontal intersinus cells suggests that concomitant presence of both leads to a less than additive increase in the rate of CRS progression. Sinonasal anatomical variants, infraorbital cells, and frontal intersinus cells, as well as comorbid asthma are associated with faster development of CRS in patients with AR. The presence of these clinical risk factors identifies patients who should be counseled on compliance with medical therapy for AR.


Use of pharmacoeconomics in prescribing research. Part 4: is cost-utility analysis a useful tool?
This paper is the fourth in the 'Research Note' series describing various aspects of pharmacoeconomics in prescribing research. This article describes cost-utility analysis, and how it can be incorporated into pharmacoeconomics. While this approach has intuitive appeal, the uncertainties about the methods for estimating utilities mean that the value of cost-utility analysis in prescribing research is still to be established. Importantly, cost-utility analysis may not capture aspects of quality of life that enable meaningful comparisons between prescribing choices at an individual or societal level.


Time-resolved assessment of cortical venous drainage on multiphase CT angiography in patients with acute ischemic stroke.
Cortical vein opacification is not routinely assessed in patients presenting with acute ischemic stroke (AIS), and the value of temporal assessment of venous outflow is not known. We evaluated the utility of assessing cortical venous drainage over time using multiphase CT angiography (mCTA). Cortical venous drainage was assessed in patients from the Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy prospective multicenter cohort study of patients with symptoms of AIS with ICA and/or middle cerebral artery occlusion on baseline mCTA. Opacification of vein of Labbe, sphenoparietal sinus, superficial middle cerebral vein, and vein of Trolard of the affected hemisphere was graded as no (0), partial (1), or full (2) opacification in each mCTA phase. The venous opacification scores for each phase were added to generate a total venous score (TVS) (range 0-24). Primary outcome was 90-day modified Rankin score. Repeated measures analysis was used to assess the effect of phase timing on venous score on outcome. Of 432 patients, 284 (65.7%) had proximal arterial occlusions. Median venous opacification score per phase (range 0-8) was 3 (IQR 1-6) in the first phase and increased in the second and third phases [median (IQR): 6 (5-8) and 8 (6-8), respectively] of the mCTA. In a multivariable analysis adjusting for age, baseline National Institutes of Health Stroke Scale, and Alberta stroke program early CT score, a significant association between TVS and 90-day mRS was noted ([adjusted cOR for TVS 6-11: 0.16 (95% CI 0.05-0.51); TVS 12-17: 0.18 (95% CI 0.06-0.57); TVS 18-24: 0.20 (0.06-0.63)]. Repeated measures analysis of venous scores from all three phases showed a significant effect of time/phase on TVS (p < 0.001). This study concludes that venous opacification over time on multiphase CTA is associated with 90-day clinical outcome. There was however no added benefit of venous scoring vis-a-vis arterial collateral assessment in predicting outcome.


Inherited deficiency of C8 in a patient with recurrent meningococcal infections: further evidence for a dysfunctional C8 molecule and nonlinkage to the HLA system.
An adult male with recurrent meningococcal infections is reported whose serum lacked functional C8 activity but possessed antigenic C8. The addition of 1500 U of purified C8/ml of serum restored hemolytic activity to normal. Four to five times more C8 was required to restore bactericidal activity than to restore hemolytic activity. Bactericidal activity could also be restored by mixing the patient's serum with a second C8-deficient serum that lacked detectable antigenic or functional C8. The patient's serum contained bactericidal antibody for groups A, B, C, and Y meningococci and specific antibody to group Y capsular polysaccharide. There was two to three times more bactericidal antibody activity in the serum than in a pool of normal sera for the infecting strain. Family studies disclosed a sibling who was HLA identical to the patient but whose serum contained normal amounts of total hemolytic and C8 functional activity.


Symptom profiles of biological markers in depression: a multivariate study.
The dexamethasone suppression test (DST), the thyrotropin releasing hormone (TRH) test, and the ratio of plasma L-tryptophan to competing amino acids (L-TRP/CAA) were studied in relation to the 21 items of the Hamilton Depression Rating Scale (HDRS) in 123 depressed patients categorized according to DSM-III. The relationships between the biological data and the items or item clusters of the HDRS were assessed by multivariate analyses. The psychopathological correlates of increased post-dexamethasone cortisol and decreased thyroid stimulating hormone (TSH) responsivity to TRH were middle and delayed insomnia and weight loss. The symptom correlates of decreased availability of L-TRP to the brain were psychic anxiety, depersonalization, obsessions and paranoid symptoms. Core depressive symptoms, i.e. depression, loss of interest, feelings of guilt and suicidal thoughts, were not related to the biological markers.


Induction of Airway Hypersensitivity to Ovalbumin and Dust Mite Allergens as Mouse Models of Allergic Asthma.
Mouse models of allergic asthma have been utilized to establish the role of T helper type 2 (Th2) cells in driving lung inflammation, airway hyperresponsiveness, and obstruction. Here, we present the allergic asthma models, in which mice are hypersensitized to ovalbumin (OVA) and house dust mite (HDM). These models mimic the major characteristics of human asthma including the eosinophilic inflammation and hyperactivity of the airway, overproduction of Th2 cytokines in the lung, and elevated total and allergen-specific immunoglobulin E (IgE) in serum.


Evidence of sound symbolism in simple vocalizations.
The question of the arbitrariness of language is among the oldest in cognitive sciences, and it relates to the nature of the associations between vocal sounds and their meaning. Growing evidence seems to support sound symbolism, claiming for a naturally constrained mapping of meaning into sounds. Most of such evidence, however, comes from studies based on the interpretation of pseudowords, and to date, there is little empirical evidence that sound symbolism can affect phonatory behavior. In the present study, we asked participants to utter the letter /a/ in response to visual stimuli varying in shape, luminance, and size, and we observed consistent sound symbolic effects on vocalizations. Utterances' loudness was modulated by stimulus shape and luminance. Moreover, stimulus shape consistently modulated the frequency of the third formant (F3). This finding reveals an automatic mapping of specific visual attributes into phonological features of vocalizations. Furthermore, it suggests that sound-meaning associations are reciprocal, affecting active (production) as well as passive (comprehension) linguistic behavior.


Deep convolutional neural network for the automated detection and diagnosis of seizure using EEG signals.
An encephalogram (EEG) is a commonly used ancillary test to aide in the diagnosis of epilepsy. The EEG signal contains information about the electrical activity of the brain. Traditionally, neurologists employ direct visual inspection to identify epileptiform abnormalities. This technique can be time-consuming, limited by technical artifact, provides variable results secondary to reader expertise level, and is limited in identifying abnormalities. Therefore, it is essential to develop a computer-aided diagnosis (CAD) system to automatically distinguish the class of these EEG signals using machine learning techniques. This is the first study to employ the convolutional neural network (CNN) for analysis of EEG signals. In this work, a 13-layer deep convolutional neural network (CNN) algorithm is implemented to detect normal, preictal, and seizure classes. The proposed technique achieved an accuracy, specificity, and sensitivity of 88.67%, 90.00% and 95.00%, respectively.


A possible S-glutathionylation of specific proteins by glyoxalase II: An in vitro and in silico study.
Glyoxalase II, the second of 2 enzymes in the glyoxalase system, is a hydroxyacylglutathione hydrolase that catalyses the hydrolysis of S-d-lactoylglutathione to form d-lactic acid and glutathione, which is released from the active site. The tripeptide glutathione is the major sulfhydryl antioxidant and has been shown to control several functions, including S-glutathionylation of proteins. S-Glutathionylation is a way for the cells to store reduced glutathione during oxidative stress, or to protect protein thiol groups from irreversible oxidation, and few enzymes involved in protein S-glutathionylation have been found to date. In this work, the enzyme glyoxalase II and its substrate S-d-lactoylglutathione were incubated with malate dehydrogenase or with actin, resulting in a glutathionylation reaction. Glyoxalase II was also submitted to docking studies. Computational data presented a high propensity of the enzyme to interact with malate dehydrogenase or actin through its catalytic site and further in silico investigation showed a high folding stability of glyoxalase II toward its own reaction product glutathione both protonated and unprotonated. This study suggests that glyoxalase II, through a specific interaction of its catalytic site with target proteins, could be able to perform a rapid and specific protein S-glutathionylation using its natural substrate S-d-lactoylglutathione. This article reports for the first time a possible additional role of Glo2 that, after interacting with a target protein, is able to promote S-glutathionylation using its natural substrate SLG, a glutathione derived compound. In this perspective, Glo2 can play a new important regulatory role inS-glutathionylation, acquiring further significance in cellular post-translational modifications of proteins.


Moirés maintained internally by binocular vision.
Moiré patterns in depth are reported when spatially periodic stimuli are viewed stereoscopically. Near-vertical square-wave gratings with horizontal disparity effected by orientation difference produce a 'venetian blind' effect. A single grating is observed divided into horizontal layers, the number of layers being a direct function of orientation difference. Lines within each layer are slanted with respect to the frontoparallel plane, becoming more so with increasing orientation difference. Subjects with stereo deficits report a decreased effect. Quantitative reports implicate stereoscopic mechanisms responsible for this unique, internal preservation of moiré patterns.


High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I-II): study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China.
The presence of increased oxidative stress and airway inflammation has been proven in subjects with chronic obstructive pulmonary disease (COPD). Several studies have demonstrated that drugs with antioxidant and anti-inflammatory properties such as N-acetylcysteine (NAC) can reduce the rate of exacerbations in patients with COPD. However, the beneficial effects of NAC in early-stage COPD are minimally discussed. We are investigating whether high-dose NAC has therapeutic effects in Chinese patients with early-stage COPD. A randomized, double-blinded, placebo-controlled, parallel-group, multicenter clinical trial is evaluating the efficacy and safety of NAC for the long-term treatment of patients with early-stage COPD at 24 centers in China. Subjects aged 40-80 years and recruited by physicians or researchers with special training will be randomized to either NAC 600 mg twice daily group or matching placebo group for 2 years. Measurements will include forced expiratory volume in 1 s (FEV1), the number of COPD exacerbations, health-related quality, and pharmacoeconomic analysis. Currently, there are no randomized controlled trials with high-dose N-acetylcysteine (600 mg twice daily) for patients with mild-to-moderate COPD (GOLD I-II). We designed this multicenter randomized controlled trial (RCT) to assess the effectiveness, safety, and cost-effectiveness of long-term treatment with high-dose N-acetylcysteine. The results of this trial may guide clinical practice and change the standard of early COPD management. Chinese Clinical Trial Registry ChiCTR-IIR-17012604 . Registered on 07 September 2017.


A comparison of the effects of prenatal exposure to tobacco, alcohol, cannabis and caffeine on birth size and subsequent growth.
Maternal use of cigarettes, alcohol, cannabis, and caffeine was established for four time periods; prepregnancy, first trimester, third trimester and average use over pregnancy. The relationship between such usage and growth parameters of offspring followed up from birth to 12 and 24 months of age were examined. Of the soft drugs used, nicotine had the most pronounced effect. After adjustment for other relevant variables, nicotine use prior to and during pregnancy was negatively related to weight and head circumference at birth. Furthermore, third trimester nicotine use was a stronger predictor of decreased weight and head circumference at birth than was first trimester use. The results obtained are consistent with ponderal index (PI) literature suggesting a recovery of growth retardation in infants with a lowered PI. Average consumption of greater than one ounce of absolute alcohol per day was negatively related to birth weight and length. Neither cannabis nor caffeine use had a significant negative effect on any growth parameter.


Systemic low-grade inflammation-associated lifestyle, diet, and genetic factors: A population-based cross-sectional study.
Systemic low-grade inflammation (SLGI) is an intermediary common condition to the physiopathology of chronic noncommunicable diseases and targeting its determinants could lead to more efficient public health strategies. We aimed to investigate SLGI-independent associations with lifestyle, diet, and genetic factors in a population-based sample of adults using a systemic low-grade inflammation score (SIS). The study sample is composed of 269 participants from the cross-sectional population-based Health Survey of Sao Paulo (2008-2010), ages 20 to 59 y, whose data on socioeconomic variables, lifestyle, health parameters, and blood samples were available. Diet was assessed by two 24-h recalls, and the Brazilian Health Eating Index-Revised (BHEI-R) was scored. From blood samples, 30 single nucleotide polymorphisms on inflammatory genes were genotyped, and plasma eleven inflammatory biomarkers levels that composed the SIS were determined. A multiple, stepwise, linear regression was used to investigate SIS-independent associated factors. Factors independently associated with SIS were BHEI-R score (partial R² = 5.1; β = -0.13; P = 0.003), body mass index (partial R² = 3.4; β = 0.19; P = 0.001), TLR4 rs5030728 GA + AA genotype (partial R² = 3.1; β = -1.37; P = 0.008), age 50 to 59 y (partial R² = 2.5; β = 1.93; P = 0.029) in comparison with the reference category (20 to 29 y), and commuting physical activity >150 min/wk (partial R² = 2.2; β = -1.29; P = 0.043) after adjustment for current smoking status, medication use, and dietary misreporting. Eating a lower quality diet, having a higher body mass index score and age, being GG homozygous for TLR4 rs5030728, and spending <150 min/wk in transportation physical activity are independent determinants of SLGI.


Hemodynamic and electrolyte changes in patients undergoing neuroendoscopic procedures.
Intraoperative hemodynamic alterations and postoperative electrolyte disturbances related to endoscopic third ventriculostomy (E3V) have been reported. We aimed to evaluate prospectively those changes in patients undergoing neuroendoscopic procedures. This study was carried out in 24 patients who underwent neuroendoscopic intervention. Sevoflurane was used for the induction and maintenance of anesthesia. Heart rate (HR), mean arterial pressure (MAP), peripheral oxygen saturation, end-tidal CO2, and body temperature values were recorded according to the stages of the operation. Blood gas and blood chemistry analyses were performed before and after endoscopic procedure and were repeated on the third postoperative day. There were no significant differences in intraoperative HR and MAP. Bradycardia occurred only in 1 of the 24 patients during the dilatation. In conclusion, we suggest the use of 0.9% NaCl for intravenous fluid replacement and a warm lactated ringer solution for ventricular irrigation during E3V to prevent intraoperative hemodynamic changes and postoperative electrolyte disturbances.


Delivery room emergencies due to birth injuries.
Delivery room emergencies due to birth injuries are serious, usually unexpected, and can be distressing situations that necessitate immediate action to reduce neonatal morbidity and prevent neonatal mortality. Birth injuries requiring immediate, urgent care in the delivery room are uncommon, hence knowledge of obstetric risk factors and prenatal conditions linked to birth injury is an important first step in the management of affected neonates. Furthermore, immediate recognition of injury and quick action upon delivery is essential in order to achieve the best possible outcomes. This chapter briefly reviews the known risk factors associated with birth injury, and then discusses the identification and management of specific injuries that may require immediate treatment in the delivery room, or hasty management within hours after birth.


Palliative Care in Heart Failure: Rationale, Evidence, and Future Priorities.
Patients with heart failure (HF) and their families experience stress and suffering from a variety of sources over the course of the HF experience. Palliative care is an interdisciplinary service and an overall approach to care that improves quality of life and alleviates suffering for those living with serious illness, regardless of prognosis. In this review, we synthesize the evidence from randomized clinical trials of palliative care interventions in HF. While the evidence base for palliative care in HF is promising, it is still in its infancy and requires additional high-quality, methodologically sound studies to clearly elucidate the role of palliative care for patients and families living with the burdens of HF. Yet, an increase in attention to primary palliative care (e.g., basic physical and emotional symptom management, advance care planning), provided by primary care and cardiology clinicians, may be a vehicle to address unmet palliative needs earlier and throughout the illness course.


Short Term Outcome and Predictors of Mortality Among Very Low Birth Weight Infants - A Descriptive Study.
To assess the short term outcome and predictors of mortality among very low birth weight (VLBW) neonates. This descriptive study from a tertiary care teaching institute in south India included 239 VLBW neonates who were uniformly managed as per unit's protocol and followed up till discharge or death, whichever was earlier. Univariate analysis and logistic regression analysis were done to determine the predictors of mortality. Two logistic regression models were developed and to evaluate their discriminative performance, area under the receiver operating characteristic curves were calculated. Mean gestational age and mean birth weight of neonates were 31.4 ± 3 wk and 1191 ± 245 g respectively. Among the 239 infants, 49 (20.5%) expired and 190 (70.5%) survived. Mortality among extremely low birth weight (ELBW) and extreme preterm infants were 69.3% and 73.3% respectively. Univariate analysis showed multiple perinatal factors and neonatal morbidities were associated with mortality. On adjusted multivariate logistic regression, birth weight < 1000 g (OR 9.27), severe grade of intraventricular hemorrhage (IVH) (OR 29.2), hyperglycemia (OR 7.8) and respiratory distress syndrome (RDS) requiring surfactant therapy (OR 6.2) were the significant predictors of mortality. Both logistic regression models developed showed good prediction of mortality. VLBW mortality rate is 20% in the population studied. Birth weight < 1000 g, severe grade of IVH, hyperglycemia, and RDS requiring surfactant therapy were the significant predictors of mortality among VLBW neonates. Both prediction models developed showed good prediction of mortality.


Chemogenetic modulation of accumbens direct or indirect pathways bidirectionally alters reinstatement of heroin-seeking in high- but not low-risk rats.
Opioid addiction has been declared a public health emergency, with fatal overdoses following relapse reaching epidemic proportions and disease-associated costs continuing to escalate. Relapse is often triggered by re-exposure to drug-associated cues, and though the neural substrates responsible for relapse in vulnerable individuals remains ambiguous, the nucleus accumbens (NAc) has been shown to play a central role. NAc direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) can have oppositional control over reward-seeking and associative learning and are critically involved in reinstatement of psychostimulant-seeking. However, whether these pathways similarly regulate reinstatement of opioid-seeking remains unknown, as is their role in modulating motivation to take opioids. Here, we describe a method for classifying addiction severity in outbred rats following intermittent-access heroin self-administration that identifies subgroups as addiction-vulnerable (high-risk) or addiction-resistant (low-risk). Using dual viral-mediated gene transfer of DREADDs, we show that transient inactivation of dMSNs or activation of iMSNs is capable of suppressing cue-induced reinstatement of heroin-seeking in high- but not low-risk rats. Surprisingly, however, the motivation to self-administer heroin was unchanged, indicating a divergence in the encoding of heroin-taking and heroin-seeking in rats. We further show that transient activation of dMSNs or inactivation of iMSNs exacerbates cue-induced reinstatement of heroin-seeking in high- but not low-risk rats, again with no effect on motivation. These findings demonstrate a critical role for dMSNs and iMSNs in encoding vulnerability to reinstatement of heroin-seeking and provide insight into the specific neurobiological changes that occur in vulnerable groups following heroin self-administration.


Prevalence, antimicrobial resistance, and enterotoxin gene profiles of Staphylococcus aureus isolated from mobile phones of the food vendors in Phayao province, Thailand.
Mobile phones are widely used and may cause bacterial pathogens to spread among various professionals. Staphylococcus aureus from the mobile phones can contaminate the hands of food vendors and food during the cooking or packaging process. This research aimed to determine the prevalence, enterotoxin genes, and antimicrobial resistance (AMR) profiles of S. aureus contaminating the vendors' mobile phones. In this study, 266 mobile phone samples were randomly collected from food vendors selling food on walking streets (n = 139) and in food centers (n = 127) in Phayao province. All samples were identified as S. aureus by the conventional culture method and confirmed species-specific gene by polymerase chain reaction (PCR). Then, all identified S. aureus isolates were tested for antimicrobial susceptibility by broth microdilution method and for the presence of staphylococcal enterotoxin (SE) genes by PCR. The results showed that 12.8% of the mobile phones collected were contaminated with S. aureus. Of 49 S. aureus isolates obtained, 30 (61.2%) were positive for SE genes. The most common SE gene was sea followed by sec, seb, sem, seq, and sel. Moreover, S. aureus was most frequently resistant to penicillin, followed by chloramphenicol and tetracycline, erythromycin, clindamycin, and gentamicin. Methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA), and multidrug-resistant (MDR) strains were also detected. This study showed that mobile phones were an intermediate surface for the transmission of S. aureus, including MDR variants. It indicates that hand hygiene and the decontamination of mobile phones are essential to prevent cross-contamination of S. aureus in food settings.


Female doping: observations from a data lake study in the Hospital District of Helsinki and Uusimaa, Finland.
Doping is a well-recognized risk factor for several potentially severe health effects. Scientific literature concerning the need for medical treatment for such adversities is still sparse. This is especially true for women, due to lower doping use prevalence compared to men. Our study explored the nature of medical contacts and deviance in red blood cell parameters of female patients with doping use in Finnish specialized health care. This was a retrospective register study. The study sample was gathered from the Hospital District of Helsinki and Uusimaa, Finland (HUS) Datalake. An exhaustive search for doping related terms was performed to find patients with doping use documentation within free-text patient records. Medical record data was supplemented with laboratory data and medical diagnoses covering a total observation time of two decades. Statistical analysis included Fisher's Exact Test and one-way ANOVA. We found 39 female patients with history of doping use and specialized health care contacts in the HUS-area between 2002-2020. At initial contact (i.e., the first documentation of doping use), the mean age of these patients was 33.6 years (min 18.1, max 63.5, SD 10.6). The most frequently used doping agents were anabolic androgenic steroids (AAS). The initial contacts were significantly more often acute in nature among patients with active doping use than among patients with only previous use (no use within one year; p = 0.002). Psychiatric and substance use disorder (SUD) morbidity was high (46.2% and 30.8%, respectively). Eight patients (20.5%) had received specialized health care for acute poisoning with alcohol or drugs, and nine (23.1%) for bacterial skin infections. Less than 45% of patients with active AAS use presented with off-range red blood cell parameters. Our findings suggest that female patients with a history of doping use encountered in specialized health care may exhibit high psychiatric and SUD related morbidity. Also, majority of patients with AAS use had red blood cell parameters within-range. Further studies are required to assess the generalizability of these findings to patients within primary health care services, and to determine the usefulness of hematological parameters as indicators of AAS use in female patients.


Dual-targeting Rutaecarpine-NO donor hybrids as novel anti-hypertensive agents by promoting release of CGRP.
CGRP, known as the most potent vasodilator substance, plays an important role in hypertension initiation and development. TRPV1 and TRPA1 are critical in promoting the synthesis and release of CGRP, thereby regulating the cardiovascular tone. Rutaecarpine exhibits potent vasodilator and hypertensive effects by stimulating CGRP synthesis and release via activation of TRPV1. And NO has been shown to react with H2S in vivo to form HNO, thereby activating HNO-TRPA1-CGRP pathway. Inspired by combination therapy, 11 rutaecarpine-furoxan hybrids were designed, synthesized and evaluated. The results demonstrated that most hybrids exerted comparable or improved vasodilator activities. Among which, 13a is the most potent both ex vivo (EC50 = 13.1 nM) and in vivo. Mechanistic studies revealed that the vasodilator and anti-hypertensive effects of the hybrids might involve the promotion of CGRP release via dual activation of TRPV1 and TRPA1. This work suggests that dual-targeted hybrids might be an effective and promising approach to discover and develop novel anti-hypertensive drugs.


[The inverted cockade sign. An indication in CT of an impending rupture of an abdominal aortic aneurysm].
A new CT-sign as a pointer to the imminent rupture of an abdominal aortic aneurysm is described: the enhanced shell of the thrombus of the aneurysm. This sign is caused by bleeding into the thrombotic layer.


The effect of holes in long-lasting insecticidal nets on malaria in Malawi: results from a case-control study.
Long-lasting insecticidal nets (LLINs) are a cornerstone of malaria prevention. Holes develop in LLINs over time and compromise their physical integrity, but how holes affect malaria transmission risk is not well known. After a nationwide mass LLIN distribution in July 2012, a study was conducted to assess the relationship between LLIN damage and malaria. From March to September 2013, febrile children ages 6-59 months who consistently slept under LLINs (every night for 2 weeks before illness onset) were enrolled in a case-control study at Machinga District Hospital outpatient department. Cases were positive for Plasmodium falciparum asexual parasites by microscopy while controls were negative. Digital photographs of participants' LLINs were analysed using an image-processing programme to measure holes. Total hole area was classified by quartiles and according to the World Health Organization's proportionate hole index (pHI) cut-offs [< 79 cm2 (good), 80-789 cm2 (damaged), and > 790 cm2 (too torn)]. Number of holes by location and size, and total hole area, were compared between case and control LLINs using non-parametric analyses and logistic regression. Of 248 LLINs analysed, 97 (39%) were from cases. Overall, 86% of LLINs had at least one hole. The median number of holes of any size was 9 [interquartile range (IQR) 3, 22], and most holes were located in the lower halves of the nets [median 7 (IQR 2, 16)]. There were no differences in number or location of holes between LLINs used by cases and controls. The median total hole area was 10 cm2 (IQR 2, 125) for control LLINs and 8 cm2 (IQR 2, 47) for case LLINs (p = 0.10). Based on pHI, 109 (72%) control LLINs and 83 (86%) case LLINs were in "good" condition. Multivariable modeling showed no association between total hole area and malaria, controlling for child age, caregiver education, and iron versus thatched roof houses. LLIN holes were not associated with increased odds of malaria in this study. However, most of the LLINs were in relatively good condition 1 year after distribution. Future studies should examine associations between LLIN holes and malaria risk with more damaged nets.


Participation of GABAergic mechanisms in the hypotensive and bradycardic effects of clonidine: experimental study in conscious normotensive and hypertensive rats.
In conscious rats with normal arterial blood pressure or with spontaneous or DOC induced hypertension, effects of drugs increasing (cycloserine, ethanolamine-o-sulphate, piracetam, chlordesmethyldiazepam) or depressing (bicuculline, Ro 15-1788, PK 11195) GABAergic reactivity were evaluated on the arterial hypotension and sinus bradycardia induced by clonidine. Clonidine was administered orally by gastric gavage (0.1-1 mg/kg). Pretreatment with cycloserine, ethanolamine-o-sulphate, piracetam or chlordesmethyldiazepam increased the hypotension and sinus bradycardia induced by clonidine. On the contrary, pretreatment with bicuculline or Ro 15-1788 reduced the cardiovascular effects of clonidine. These results suggest that the GABAergic system is involved in cardiovascular effects of clonidine in normotensive and hypertensive rats.


Acute and long-term safety of external trigeminal nerve stimulation for drug-resistant epilepsy.
Trigeminal nerve stimulation (TNS) is a novel therapy for drug-resistant epilepsy. We report in detail the safety of external TNS (eTNS), focusing on acute and long-term heart rate and systolic and diastolic blood pressure in response to TNS from the pilot feasibility study. The data indicate that eTNS of the infraorbital and supraorbital branches of the trigeminal nerve is safe and well tolerated.


Proteomic database mining opens up avenues utilizing extracellular protein phosphorylation for novel therapeutic applications.
Recent advances in extracellular signaling suggest that extracellular protein phosphorylation is a regulatory mechanism outside the cell. The list of reported active extracellular protein kinases and phosphatases is growing, and phosphorylation of an increasing number of extracellular matrix molecules and extracellular domains of trans-membrane proteins is being documented. Here, we use public proteomic databases, collagens - the major components of the extracellular matrix, extracellular signaling molecules and proteolytic enzymes as examples to assess what the roles of extracellular protein phosphorylation may be in health and disease. We propose that novel tools be developed to help assess the role of extracellular protein phosphorylation and translate the findings for biomedical applications. Furthermore, we suggest that the phosphorylation state of extracellular matrix components as well as the presence of extracellular kinases be taken into account when designing translational medical applications.


What seems to be the problem?
Psychotherapy has lost some of its stigma since Sept. 11, but many Americans still have issues with seeing a shrink.


Effect of long-term hypoxia on oxygen transport properties of blood in pregnant guinea pigs.
Pregnant guinea pigs undergoing long-term hypoxia were studied and the results compared with those of control animals (pregnant, but non-hypoxic). Hypoxic animals demonstrated a decrease of O2 affinity (-7%) and an increase of O2 capacity (+35%). In addition, the HCT was found to be higher in the hypoxic group (+41%), causing haemorheological disadvantages; in a shear model study the blood of hypoxic animals had to be exposed to the gas compartment of the rheo-oxymeter up to 62% longer than that of the control group. We have postulated, that this rheological impairement is compensated, since no abnormalities in number and abortion rate of fetuses (due to a possible O2 delivery impairment) were found. Our morphological studies in fact support this opinion, showing e.g. more capillary branchings and loops and a reduction of diffusion distances between maternal and fetal blood in hypoxic guinea pig placentae. The results emphasize the importance of more detailed rheological studies in connection with other investigations for a complete description of compensatory mechanisms.


Minor Sea Turtle Nesting Areas May Remain Unnoticed without Specific Monitoring: The Case of the Largest Mediterranean Island (Sicily, Italy).
Identifying coastal tracts suitable for sea turtle reproduction is crucial for sea turtle conservation in a context of fast coastal development and climate change. In contrast to nesting aggregations, diffuse nesting is elusive and assessing nesting levels is challenging. A total of 323 nesting events by the loggerhead sea turtle Caretta caretta have been reported in Sicily, the largest Mediterranean island, in the 1944-2021 period, mostly in the last decade. Specific monitoring efforts are the most likely explanation for such an increase and shows that sea turtle nesting may be underestimated or completely ignored in many areas with scattered nesting. The real nesting level along the 464 km sandy shores of Sicily is still unknown and more research is needed. The observed incubation period was relatively long (57 d) suggesting that a majority of males are produced in Sicily, in contrast to the typical female-biased sex ratio of sea turtles. In a context of climate warming producing sex ratios more skewed towards females, the potential of Sicily as a male-producing area should be further investigated. Other reproductive parameters are provided, such as clutch size and hatching and emergence success. A negative effect of relocation on the latter two was observed.


Effects of an essential fatty acid deficiency, pair-feeding and level of dietary corn oil on the hypothalamic-pituitary-gonadal axis and other physiological parameters in the male chicken.
Two studies were conducted to observe the effects of an essential fatty acid (EFA) deficiency, added dietary corn oil and pair-feeding on growth, reproduction and other physiological parameters in the mature cockerel. A purified, linoleic acid (LA)-deficient diet (0.01% LA), or additions of 5% (3.01% LA) or 15% (9.04% LA) corn oil, were fed ad libitum from hatching through 24 weeks of age. Reductions in growth, feed consumption, and comb, and testes size, incomplete spermatogenesis, increased tissue eicosatrienoic acid (20: 3 omega 9) and changes in weights of selected internal organs were observed in deficient cockerels. Total pituitary gonadotropic activity was measured by two bioassay procedures and blood luteinizing hormone was measured by radioimmunoassay. By maturity both of these parameters were significantly reduced in deficient chickens. When these chickens were fed diets with 5% or 15% corn oil under pair-feeding or ad libitum conditions from 20 to 24 weeks, the reduced growth, comb and testes size and gonadotropin metabolism appeared to be caused by depressions in appetite and energy intake rather than EFA per se. The degenerate testicular histology of the 20-week old deficient cockerels, while responding fully to the ad libitum intake of the diets containing corn oil, showed only partial rehabilitation of spermatogenesis when diets with either 5% or 15% corn oil were pair-fed. In general, increasing the level of dietary fat from 5% to 15% did not cause many physiological changes.


Visual-vestibular interaction during goal directed locomotion: effects of aging and blurring vision.
Normal vision overrides perturbed vestibular information for the optimization of performance during goal directed locomotion, suggesting down-regulation of vestibular gain. However, it is not known if the responses to vestibular perturbation are accentuated when vision is impaired. Furthermore, both visual and vestibular systems deteriorate with age. It is not clear, however, how age-related decline in these sensory systems influences visual-vestibular interaction. Therefore, the dual purpose of the present study was to investigate the effects of aging and blurring vision, that simulated the consequences of cataracts, on visual-vestibular interaction. Young and healthy elderly walked to a target located straight ahead with either normal or blurring vision. On randomly selected trials vestibular system perturbation was achieved by applying transmastoidal galvanic vestibular stimulation (GVS). Two different galvanic stimulation intensities were used to provide insight into scaling effect of vestibular perturbation on locomotor performance and how age and vision influences this scaling effect. Maximum path deviation, frontal trunk tilt and postural coordination in the mediolateral direction were evaluated. The magnitude of the path deviation and the trunk tilt response were scaled to the magnitude of the vestibular perturbation in older adults independent of the visual condition. Older participants demonstrated increased coupling of the head and trunk segments irrespective of visual and vestibular perturbations. The results suggest that when visual information was available, the vestibular input reweighting was less effective in older individuals, as shown by the scaled responses to the GVS intensities and the inability to converge efficiently towards the target.


Selective retrograde transport of tritiated D-aspartate from the olfactory bulb to the anterior olfactory nucleus, pyriform cortex and nucleus of the lateral olfactory tract in the rat.
After an injection of [3H]D-aspartate into the olfactory bulb of the rat, retrogradely labeled cells were detected bilaterally in the anterior olfactory nucleus (AON), and ipsilaterally in the pyriform cortex (PC) and nucleus of the lateral olfactory tract (NLOT). These results suggest a certain selective retrograde transport of this amino acid, and are discussed in relation to transmitter candidates in the olfactory bulb.


The Health Assessment Questionnaire Disability Index (HAQ-DI) as a valid alternative for measuring the functional capacity of people with haemophilia.
There are several scales for evaluating the functional capacity of people with haemophilia (PWH). To demonstrate the value and simplicity of the "Health Assessment Questionnaire Disability Index" (HAQ-DI) for making a functional assessment of PWH in those contexts in which the specific physical assessment scales cannot be used [Functional Independence Score in Haemophilia (FISH) and Haemophilia Activities List (HAL)]. The HAQ-DI is a validated generic self-administered questionnaire that is completed in <5min. Data was collected on the physical and functional status of 62 adult PWH having haemophilia. Their average age was 34.7 years. The impairment of the PWH was assessed using the generic self-administrable functionality questionnaire (HAQ-DI) and the following scales: The "World Federation of Haemophilia Physical Examination Score" (WFH-PES) and the Haemophilia Joint Health Score 2.1 (HJHS 2.1). We evaluated the correlation between generic HAQ-DI score and physical assessment scores WFH-PES, HJHS 2.1 (correlation analysis). The correlation between WFH-PES and HAQ-DI showed a Spearman's correlation coefficient of r=0.804 (p<0.05). The correlation between HJHS 2.1 and HAQ-DI showed a Spearman's correlation coefficient of r=0.823 (p<0.05). A positive and fairly strong correlation was found between them. The presented associations established the application of HAQ-DI as a PROXY clinical indicator of functional status. HAQ-DI is a valid alternative for assessing functional capacity in adult PWH, especially in cases in which, for some reason, it is not possible to use other tools that are specific for haemophilia. Clinical practice needs a less time demanding assessment tools.


The actions of tetraethylammonium on dispersed acini from guinea pig pancreas.
In dispersed acini from guinea pig pancreas, replacing extracellular sodium by tetraethylammonium (1) abolished carbamylcholine-stimulated amylase secretion but did not alter the increase in amylase secretion caused by the C-terminal octapeptide of cholecystokinin, bombesin, ionophore A23187, vasoactive intestinal peptide or 8-bromoadenosine 3':5' monophosphate, (2) caused a parallel rightward shift in the dose-response curve for carbamylcholine-stimulated amylase secretion and (3) inhibited binding of N-[3H]methyl scopolamine to muscarinic cholinergic receptors. Detectable inhibition of carbamylcholine-stimulated amylase secretion and binding of N-[3H]methyl scopolamine occurred with 300 microM tetraethylammonium, and half-maximal inhibition of these functions occurred with 1-2 mM tetraethylammonium. Replacing extracellular sodium by Tris did not alter the stimulation of enzyme secretion caused by any secretagogue tested. These results indicate that the tetraethylammonium is a muscarinic cholinergic receptor antagonist and that enzyme secretion from pancreatic acini does not depend on extracellular sodium.


Comparison of Oncology Patients' and Their Family Caregivers' Attitudes and Concerns Toward Pain and Pain Management.
Both cancer patients and their family caregivers (FCs) report concerns about pain and pain management. When dyads share appraisal of the illness context, they may experience better dyadic adjustment. The aim of this study was to compare oncology outpatients' and their FCs' attitudes and concerns toward pain and pain management. In a cross-sectional study, outpatients with pain (n = 71) and their FCs completed the Barriers Questionnaire II, the Brief Pain Inventory, and information about demographic characteristics. Correlations and paired-samples t tests were calculated to evaluate agreement and differences in barrier scores between the patients and their FCs. Congruence was found in patients' and FCs' beliefs about pain and the use of analgesics on 4 of 7 subscales (ie, tolerance, immune system, side effects, distract the medical doctor) and on the Barriers Questionnaire II total score. Both patients and their FCs were most concerned about addiction. The concerns that both patients and their FCs have about pain and the use of analgesics may act as barriers to effective pain management. Fear of addiction may be an important barrier to cancer pain management. Only small differences were found in concerns between the patients and their FCs. Patients and FCs need education about perceived barriers to effective pain management. They should be coached together to maintain or increase the congruence between them.


Mechanisms of hydraulic conductivity in the leaf galls of Meunieriella sp. (Cecidomyiidae) in Avicennia schaueriana (Acanthaceae): does vascularization explain the preferred sites of induction?
Intralaminar galls of Meunieriella result from ground tissue proliferation in leaves of Avicennia schaueriana, a typical halophytic mangrove. We tested if the preferred sites of gall induction were the midribs and secondary veins (SV) at the basal leaf portion, where the galls were expected to be largest; and if the vascular system in galls and adjacent regions was altered to favour water supply in galls, thus increasing their growth. Gall induction sites and gall sizes were quantified according to leaf portions and regions. Anatomical and histometric analyses in vascular and ground tissues of galls and adjacent regions were compared to equivalent regions of non-galled leaves. The galls were largest at basal sites on leaves, the midrib and SV. More galls occurred on the apical portion of the leaf, and on the leaf blade and secondary vein regions. Changes in shape and vascular system area, number and diameter of vessel elements were detected in both galls and adjacent regions. Fewer and smaller-sized vessel elements were observed in regions proximal to the galls and inside them. Gall size is not related with preferred induction sites, which could be explained by factors such as thermal balance. Alterations in the vascular system indicate reduced hydraulic conductivity in the xylem in the proximal region and inside galls, leading to water leakage to gall parenchyma cells. This compensatory mechanism explains the expansion and proliferation of water storage and spongy parenchyma cells in the galls, explaining the higher growth in more vascularized regions.


Amplification and latency in photoreceptors: integrated or separated phenomena?
It is shown that the models for the transduction process in photoreceptors which treat latency and amplification as integrated phenomena ("integrated models") yield time scales for single photon signals ("quantum bumps") which distinctly conflict with the experimentally observed ones for the ventral nerve photoreceptor of Limulus: the ratio of bump duration/latency tB/tlat is predicted by integrated models to be approximately 3 in contrast to the experimental result of approximately 0.5. Moreover, integrated models lead to a predicted value of an extinction rate of approximately 50%, i.e., 50% of the absorbed photons should be expected to cause no signal in the dark adapted state of the cell. In this paper it is shown that separation of latency and amplification in such a way that the latency causing process precedes amplification in the transduction process eliminates these discrepancies. In addition, the separate modeling of latency and amplification resolves the rather large ambiguity in determining the exponent n of the initial signal current J(t) approximately tn reported in the literature to be between n approximately 2 (from noise analysis) up to n approximately 17 (from flash experiments). Two alternative models for the latency part of transduction are suggested which give a qualitatively much better agreement with the experimental histograms of latencies.


Corrigendum to "HIV remission trial investigators' attitudes towards risk and risk mitigation in trials that include treatment interruption" [J Virus Erad 9 (2) (June 2023) 100331].
[This corrects the article DOI: 10.1016/j.jve.2023.100331.].


Humoral and cellular immunological abnormalities in hypertensive patients.
A high frequency of immunological disturbances were recorded in 19 mild and 23 malignant hypertensive patients. IgG levels were raised in patients who survived a malignant phase of hypertension. We also found increased frequency of autoantibodies (26% vs. 9% in controls), increased T-lymphocyte reactivity against arterial-wall antigens (p = 0.001), a significant frequency of low responders to PHA (p = 0.003), and a statistically significant correlation (p = 0.031) between the presence of autoantibodies and T-cell hyper-reactivity against arterial antigens in mild hypertensive patients. We suggest that these abnormalities might be relevant in the pathogenesis of some hypertensive conditions. Autoantibody production is likely to be correlated with a predisposition to hypertension through some autoimmune mechanisms.


Evolution of lmiRNAs and their targets from MITEs for rice adaptation.
Twenty-four nucleotide long microRNAs (lmiRNAs) direct DNA methylation at target genes and regulate their transcription. The evolutionary origin of lmiRNAs and the range of lmiRNA-mediated regulation remain obscure. Here, we reannotated lmiRNAs and their targets in rice by applying stringent criteria. We found that the majority of lmiRNAs are derived from Miniature Inverted-repeat Transposable Elements (MITEs) and most sites targeted by MITE-derived lmiRNAs reside within MITEs, suggesting co-evolution of lmiRNAs and their targets through MITE amplification. lmiRNAs undergo dynamically changes under stress conditions and the genes targeted by lmiRNAs show an enrichment for stress-responsive genes, suggesting that lmiRNAs are widely involved in plant responses to stresses. We constructed the evolutionary histories of lmiRNAs and their targets. Nearly half of lmiRNAs emerged before or when the AA genome was diverged, while the emergence of lmiRNA targets coincided with or followed the emergence of lmiRNAs. Furthermore, we found that the sequences of a lmiRNA target site underwent variations, coincident with the divergence of rice accessions and the distribution of rice accessions in different geographical locations and climatic conditions. Our findings highlight MITEs as an important origin of lmiRNAs and suggest that the evolution of lmiRNA-target regulatory modules may contribute to rice adaptation to environmental changes.


A mutant allele of ζ-carotene isomerase (Z-ISO) is associated with the yellow pigmentation of the "Pinalate" sweet orange mutant and reveals new insights into its role in fruit carotenogenesis.
Fruit coloration is one of the main quality parameters of Citrus fruit primarily determined by genetic factors. The fruit of ordinary sweet orange (Citrus sinensis) displays a pleasant orange tint due to accumulation of carotenoids, representing β,β-xanthophylls more than 80% of the total content. 'Pinalate' is a spontaneous bud mutant, or somatic mutation, derived from sweet orange 'Navelate', characterized by yellow fruits due to elevated proportions of upstream carotenes and reduced β,β-xanthophylls, which suggests a biosynthetic blockage at early steps of the carotenoid pathway. To identify the molecular basis of 'Pinalate' yellow fruit, a complete characterization of carotenoids profile together with transcriptional changes in carotenoid biosynthetic genes were performed in mutant and parental fruits during development and ripening. 'Pinalate' fruit showed a distinctive carotenoid profile at all ripening stages, accumulating phytoene, phytofluene and unusual proportions of 9,15,9'-tri-cis- and 9,9'-di-cis-ζ-carotene, while content of downstream carotenoids was significantly decreased. Transcript levels for most of the carotenoid biosynthetic genes showed no alterations in 'Pinalate'; however, the steady-state level mRNA of ζ-carotene isomerase (Z-ISO), which catalyses the conversion of 9,15,9'-tri-cis- to 9,9'-di-cis-ζ-carotene, was significantly reduced both in 'Pinalate' fruit and leaf tissues. Isolation of the 'Pinalate' Z-ISO genomic sequence identified a new allele with a single nucleotide insertion at the second exon, which generates an alternative splicing site that alters Z-ISO transcripts encoding non-functional enzyme. Moreover, functional assays of citrus Z-ISO in E.coli showed that light is able to enhance a non-enzymatic isomerization of tri-cis to di-cis-ζ-carotene, which is in agreement with the partial rescue of mutant phenotype when 'Pinalate' fruits are highly exposed to light during ripening. A single nucleotide insertion has been identified in 'Pinalate' Z-ISO gene that results in truncated proteins. This causes a bottleneck in the carotenoid pathway with an unbalanced content of carotenes upstream to β,β-xanthophylls in fruit tissues. In chloroplastic tissues, the effects of Z-ISO alteration are mainly manifested as a reduction in total carotenoid content. Taken together, our results indicate that the spontaneous single nucleotide insertion in Z-ISO is the molecular basis of the yellow pigmentation in 'Pinalate' sweet orange and points this isomerase as an essential activity for carotenogenesis in citrus fruits.


Essential role in vivo of upstream stimulatory factors for a normal dietary response of the fatty acid synthase gene in the liver.
In the liver, transcription of several genes encoding lipogenic and glycolytic enzymes, in particular the gene for fatty acid synthase (FAS), is known to be stimulated by dietary carbohydrates. The molecular dissection of the FAS promoter pointed out the critical role of an E box motif, located at position -65 with respect to the start site of transcription, in mediating the glucose- and insulin-dependent regulation of the gene. Upstream stimulatory factors (USF1 and USF2) and sterol response element binding protein 1 (SREBP1) were shown to be able to interact in vitro with this E box. However, to date, the relative contributions of USFs and SREBP1 ex vivo remain controversial. To gain insight into the specific roles of these factors in vivo, we have analyzed the glucose responsiveness of hepatic FAS gene expression in USF1 and USF2 knock-out mice. In both types of mouse lines, defective in either USF1 or USF2, induction of the FAS gene by refeeding a carbohydrate-rich diet was severely delayed, whereas expression of SREBP1 was almost normal and insulin response unchanged. Therefore, USF transactivators, and especially USF1/USF2 heterodimers, seem to be essential to sustain the dietary induction of the FAS gene in the liver.


Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976-2022: A Systematic Review and Meta-analysis.
Owing to 2018 expanded diagnostic criteria for eosinophilic esophagitis (EoE) and thus a possible increase in diagnosis, previous studies on the global incidence and prevalence of EoE may need to be updated. We aimed to describe global, regional, and national trends in the incidence and prevalence of EoE from 1976 to 2022 and analyze their associations with geographic, demographic, and social factors through a systematic review. We searched the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from their inception dates to December 20, 2022, for studies that reported the incidence or prevalence of EoE in the general population. We calculated the global incidence and prevalence of EoE using pooled estimates with 95% confidence intervals (CIs) and performed subgroup analysis based on age, sex, race, geographical area, World Bank income group, and diagnostic criteria of EoE. Forty studies met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents. The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years (95% CI, 3.98-6.63; number of studies, 27; sample population, 42,191,506) and 40.04 cases per 100,000 inhabitant-years (95% CI, 31.10-48.98; number of studies, 20; sample population, 30,467,177), respectively. The pooled incidence of EoE was higher in high-income countries (vs low- or middle-income countries), males, and North America (vs Europe and Asia). The global prevalence of EoE followed a similar pattern. The pooled prevalence of EoE gradually increased from 1976 to 2022 (1976-2001; 8.18; 95% CI, 3.67-12.69 vs 2017-2022; 74.42; 95% CI, 39.66-109.19 cases per 100,000 inhabitant-years). The incidence and prevalence of EoE have increased substantially and vary widely across the world. Further research is needed to evaluate the incidence and prevalence of EoE in Asia, South America, and Africa.


[Treatment of non-small-cell lung cancer by dual (bronchial and pulmonary) arterial drug infusion].
Since the lung receives blood supply from both the bronchial and pulmonary arteries, chemotherapeutic agents given through both channels would give higher local drug concentration and better therapeutic results in the treatment of lung cancer. In this study, 10 patients with advanced NSCLC were treated by dual arterial infusion (DAI) of carboplatin (300mg/m2) and VP-16 (200-300mg/m2) twice at 3-week interval. From DAI treatment, a response rate of 80% (CR 2, PR 6) was achieved. In 5 patients DAI treatment had made surgical resection of the lung cancer possible. The 1-, 2- and 3-year survivors were 8, 6 and 5 respectively, with a median survival time of 11.5 months.


Double Histidine Based EPR Measurements at Physiological Temperatures Permit Site-Specific Elucidation of Hidden Dynamics in Enzymes.
Protein dynamics is at the heart of all cellular processes. Here, we utilize the dHis-CuII NTA label to obtain site-specific information on dynamics for both an α-helix and β-sheet site of GB1, the immunoglobulin binding domain of protein G. Spectral features found in our CW-EPR measurements were consistent with the overall rigid nature of GB1 and with predictions from molecular dynamics simulations. Using this information, we show the potential of this approach to elucidate the role of dynamics in substrate binding of a functionally necessary α-helix in human glutathione transferase A1-1 (hGSTA1-1). We observe two dynamical modes for the helix. The addition of the inhibitor GS-Met and GS-Hex resulted in hGSTA1-1 to favor the more rigid active state conformation, while the faster mode potentially aids the search for substrates. Together the results illustrate the remarkable potential of the dHis-based labelling approach to measure site-specific dynamics using room temperature lineshape analysis.


Good reproducibility of heart rate variability after orthostatic challenge in patients with a history of acute coronary syndrome.
Several parameters of heart rate variability (HRV) have been shown to predict the risk of sudden cardiac death (SCD) in cardiac patients. There is consensus that risk prediction is increased when measuring HRV during specific provocations such as orthostatic challenge. For the first time, we provide data on reproducibility of such a test in patients with a history of acute coronary syndrome. Sixty male patients (65 ± 8 years) with a history of acute coronary syndrome on stable medication were included. HRV was measured in supine (5 min) and standing (5 min) position on 2 occasions separated by two weeks. For risk assessment relevant time-domain [standard deviation of all R-R intervals (SDNN) and root mean squared standard differences between adjacent R-R intervals (RMSSD)], frequency domain [low-frequency power (LF), high-frequency power (HF) and LF/HF power ratio] and short-term fractal scaling component (DF1) were computed. Absolute reproducibility was assessed with the standard errors of the mean (SEM) and 95% limits of random variation, and relative reproducibility by the intraclass correlation coefficient (ICC). We found comparable SEMs and ICCs in supine position and after an orthostatic challenge test. All ICCs were good to excellent (ICCs between 0.636 and 0.869). Reproducibility of HRV parameters during orthostatic challenge is good and comparable with supine position.


[Prospects for use of Vericiguat in HFrEF: Implications of VICTORIA Trial Results. Advisory Board Summary].
In September 2021, an online meeting of the Council of Experts was held. The proposed focus of discussion was publishing the results of an international prospective, randomized, double-blind, placebo-controlled study VICTORIA. The objective of the VICTORIA study was evaluation of the efficacy and safety of supplementing a standard therapy with vericiguat at a target dose of 10 mg twice a day as compared to placebo for prevention of cardiovascular death and hospitalization for heart failure (HF) in patients with clinical manifestations of chronic HF and left ventricular ejection fraction <45% who have recently had an episode of decompensated HF. The aim of the meeting was interpretation of the VICTORIA study results on efficacy and safety of vericiguat for a potential use in a Russian population of patients after a recent episode of decompensated chronic HF with reduced ejection fraction.


Responses of antioxidant system to acute and trained exercise in rat heart subcellular fractions.
The effects of acute and trained exercise on antioxidant enzymes (AOE), glutathione (GSH), and malondialdehyde (MDA) were compared in rat heart subcellular fractions and red blood cells. Fischer-344 rats were exercised acutely to 100% VO2 max and another group of Fischer-344 rats were given trained exercise for 10 weeks. The AOE and MDA were measured by spectrophotometry and GSH and oxidized GSH (GSSG) by high pressure liquid chromatography. Trained exercise significantly increased cytosol GSH to 131% of sedentary control (SC). Acute exercise significantly increased mitochondrial superoxide dismutase, catalase, and glutathione peroxidase by 167%, 358%, and 129% of SC, respectively, whereas enzyme activities following trained exercise were increased by 133%, 166%, and 128% of SC. The mitochondria/cytosolic ratio for superoxide dismutase, catalase, and glutathione peroxidase after acute exercise increased to 1.9, 2.7, and 1.7, respectively, whereas the respective ratios of these enzymes after trained exercise were 1.3, 1.6, and 1.3. Acute exercise contributed to oxidative stress more than trained exercise. Acute exercise resulted in a larger increase in enzyme activities than trained exercise, possibly as a compensatory mechanism to cope with the enhanced production of superoxides and oxyradicals during exhaustive exercise.


Development of phonological awareness in bilingual chinese children.
This study investigated the phonological awareness of 219 first, second, and fourth grade Cantonese-speaking children from the south of China, who received immersion Mandarin instruction beginning in the first grade. Children received onset, rime and tone awareness tasks in Cantonese and Mandarin. Children performed better on the Cantonese onset awareness task in grade one, but the difference disappeared in higher grades. However, their performance on the rime and tone awareness tasks was better in Mandarin. These results reflect the phonological structure of the two languages: Mandarin has a more complex onset system, whereas Cantonese has more complex tone and rime systems. Moreover, children's phonological awareness increased faster in Mandarin, which likely resulted from Mandarin instruction. Confirmatory factor analysis suggested that onset-rime awareness is a universal construct, whereas tone awareness is a language-specific construct.


TGF-β1 activates RSC96 Schwann cells migration and invasion through MMP-2 and MMP-9 activities.
Following peripheral nerve injury, remnant Schwann cells adopt a migratory phenotype and remodel the extracellular matrix allowing axonal regrowth. Although much evidence has demonstrated that TGF-β1 promotes glioma cell motility and induces the expression of extracellular matrix proteins, the effects of TGF-β1 on Schwann cell migration has not yet been studied. We therefore investigated the cellular effects and the signal transduction pathways evoked by TGF-β1 in rattus norvegicus neuronal Schwann RSC96 cell. TGF-β1 significantly increased migration and invasion of Schwann cells assessed by the wound-healing assay and by cell invasion assay. TGF-β1-enhanced migration/invasion was blocked by inhibition of MMP-2 and MMP-9. Consistently, by real-time and western blot analyses, we demonstrated that TGF-β1 increased MMP-2 and MMP-9 mRNA and protein levels. TGF-β1 also increased MMPs activities in cell growth medium, as shown by gelatin zymography. The selective TGF-β Type I receptor inhibitor SB431542 completely abrogated any effects by TGF-β1. Indeed, TGF-β1 Type I receptor activation provoked the cytosol-to-nucleus translocation of SMAD2 and SMAD3. SMAD2 knockdown by siRNA blocked MMP-2 induction and cell migration/invasion due to TGF-β1. TGF-β1 also provoked phosphorylation of MAPKs extracellular regulated kinase 1/2 and JNK1/2. Both MAPKs were upstream to p65/NF-kB inasmuch as both MAPKs' inhibitors PD98059 and SP600125 or their down-regulation by siRNA significantly blocked the TGF-β1-induced nuclear translocation of p65/NF-kB. In addition, p65/NF-κB siRNA knockdown inhibited the effects of TGF-β1 on both MMP-9 and cell migration/invasion. We conclude that TGF-β1 controls RSC96 Schwann cell migration and invasion through MMP-2 and MMP-9 activities. MMP-2 is controlled by SMAD2 whilst MMP-9 is controlled via an ERK1/2-JNK1/2-NF-κB dependent pathway.


Impact speed and the risk of serious injury in vehicle crashes.
The current guiding philosophies in road safety have stated aims of zero deaths and serious injuries. Speed has previously been highlighted as a key factor in the outcome of a crash but the literature to date has yet to provide a robust relationship between impact speed and the risk of serious injury for crashes other than pedestrian crashes. This study aimed to determine the relationship between impact speed and the risk of serious injury in light vehicle crashes. Crash data from the US based National Automotive Sampling System - Crashworthiness Data System collected from 2011 to 2015 were used in the analysis when there was a known impact speed from an event data recorder (EDR) and a known injury outcome. The analysis was conducted at the vehicle level. Data from a total of 1274 vehicles were used in logistic regressions, with the presence or absence of a serious injury as the binary dependent variable, and impact speed as the continuous independent variable. Individual risk curves were produced for front, side, rear and head on impacts. Impact speed was found to have a highly significant positive relationship to risk of serious injury for all impact types examined. The risk of serious injury reaches 1% at 28 km/h for head on impacts, 51 km/h for side impacts, 64 km/h for front impacts, and 67 km/h for rear impacts. The results emphasise the importance of measures that reduce impact speeds, be they road designs, vehicle technologies or enforced speed limit reductions, and highlight the need to prevent head on impacts.


"Pseudoendoleak"--residual intrasaccular contrast after endovascular stent-graft repair.
To present a unique demonstration of postoperative perigraft contrast masquerading as an endoleak following endovascular abdominal aortic aneurysm (AAA) repair. A 66-year-old man underwent endovascular stent-graft repair of a 4.6-cm infrarenal AAA. The procedure was uncomplicated, and intraoperative completion angiography demonstrated good proximal and distal fixation of the stent-graft without an endoleak. A spiral computed tomographic (CT) angiogram obtained on postoperative day 2 revealed a large amount of extrastent contrast along the posterior aspect of the aneurysm sac. This defect had the appearance of an endoleak, but it was also present on the non-contrast images. A color-flow duplex examination performed on the same day showed a widely patent stent-graft with no evidence of extrastent flow. Contrast trapped in the aneurysm sac during endovascular aneurysm repair may be misinterpreted as an endoleak on postprocedural CT scans. "Pseudoendoleaks" can be distinguished from true endoleaks by examination of prebolus, noncontrast CT images, as well as by duplex ultrasound scanning.


Homologous desensitization of the murine luteinizing hormone receptor expressed in L cells.
Using a clonal cell line that stably expresses the murine luteinizing hormone receptor (LHR 11/6 cells), we studied the molecular mechanisms of agonist-induced desensitization of the luteinizing hormone/chorionic gonadotropin-responsive adenylyl cyclase. Exposure of transfected cells to human chorionic gonadotropin (hCG) resulted in a dose-dependent loss of maximal hCG-stimulable adenylyl cyclase activity without a significant shift to the right of the dose-response curve to hCG. This rapid uncoupling of the LH receptor from the cellular adenylyl cyclase system was not accompanied by internalization of receptor sites. A 6-h exposure to hCG led only to minor (ca. 25%) loss of membrane binding sites. The dose-response curve to hCG was not altered by pretreating cells with 8-Br-cAMP or prostaglandin E1. These findings, and the observation that hCG-induced desensitization can still be monitored at Mg2+ concentrations in the assay as high as 10 mM, preclude a significant contribution of protein kinase A to LH receptor uncoupling. The murine LH receptor not only stimulates adenylyl cyclase but also phospholipase C and probably protein kinase C (PKC) via diacylglycerol. Activation of PKC by 4 beta-phorbol 12-myristate 13-acetate failed to desensitize. When PKC was down-regulated hCG could still exert a maximal desensitizing effect. It is concluded that in LHR 11/6 cells there is no evidence for a major role of PKC in homologous desensitization. Thus, it is likely that a second messenger-independent kinase, such as beta-adrenergic receptor kinase, or a different, as yet unknown mechanism is involved in the agonist-induced desensitization of the LH receptor.


Accuracy of perfusion-CT in predicting malignant middle cerebral artery brain infarction.
We performed a prospective study on patients with middle cerebral artery(MCA) ischemic stroke to evaluate the accuracy of perfusion-CT imaging(PCT) to predict the development of malignant brain infarction (MBI). 106 patients(women 37 %, mean age 65 years)underwent native cranial computed tomography (CCT), CT angiography(CTA) and PCT after a median of 2 h after stroke onset. We assessed the patency of the MCA and the area of tissue ischemia (AIT)according to cerebral blood flow(CBF), cerebral blood volume (CBV) and time-to-peak (TTP)maps. Optimum sensitivity, specificity,positive (PPV) and negative predictive values (NPV) were calculated for the end-point MBI (= midline shift > 5 mm or decompressive surgery) by means of receiver operating characteristics(ROC). 20 patients (19 %)developed a MBI. In these patients,a larger AIT was found in all perfusion maps as compared to the remaining patients (p < 0.001). All perfusion maps had a very high NPV (95.4-98.4 %), a high sensitivity (85-95 %) and specificity (71.6-77.9 %) and only a moderate PPV (44-47.4 %). Best prediction was found for CBF maps with AIT of > 27.9 % of the hemisphere. PCT allows the discrimination of patients without a relevant risk for MBI from those having a 50 % risk of MBI development. Due to the high sensitivity and specificity, PCT is a reliable tool in detecting MBI. Because of PCT's better availability, it is the method of choice at present for an early risk stratification of acute stroke patients.


Role of marine algal blooms in the release of arsenic at the sediment-seawater interface: Evidence from microcosm experiments.
Algal blooms can aggravate arsenic (As) release from sediments and thus pose a pollution risk in the marine environment. However, the driving mechanism of algal blooms on sedimentary As cycling remains unclear. This study undertakes the first comprehensive examination of As release mechanisms under algal bloom conditions based on the evidence provided by temporal and depth profile changes of As species in the overlying water column, porewater and sediment, as well as As-related functional genes over the course of a 30-day incubation experiment using algal addition. The higher rate of increase of dissolved total As (dTAs) concentrations in a high biomass algal group (HAG) than an experimental control group (CG) suggested that algal degradation promoted the release of sedimentary As. The solid phase in all experimental groups remained rich in As(V), while in porewater As(III) and As(V) were the dominant As species during the initial rapid and subsequent slow degradation phases of organic matter, respectively, indicating that microbial reduction of As(V) and Fe(III) controlled the release of As during these two periods. A pronounced increase in arrA gene copies, and not a corresponding increase in the Geobacter copies, in HAG relative to CG supported the notion that algal blooms promoted microbial As(V) reduction. Additionally, the lower concentration of dissolved As(III) and cumulative dTAs flux in the sterilized-HAG treatment than in the sterilized-CG one further suggested that geochemically-mediated processes were not the main pathways of As release. Finally, it is estimated that summer algal blooms in the Changjiang Estuary can cause the release of 1440 kg of sedimentary As into the overlying water.


The metabolism of dopamine in the blood of ruminant animals: an enzyme system to metabolize dopamine released from the mast cells in these species?
Following the i.v. administration of 3,4-dihydroxyphenylethylamine (dopamine) to sheep, 3,4-dihydroxyphenylethanol and 3,4-dihydroxyphenylacetic acid rapidly appeared in the blood. 3,4-Dihydroxyphenylethanol can be formed from dopamine by blood plasma of ruminants in vitro. It is suggested that this plasma enzyme system might serve to inactive dopamine released from mast cells in ruminant species.


Transosseous-Equivalent/Suture Bridge Technique in Combination With Platelet-Rich Plasma Application Yield Optimal Clinical Outcomes in Arthroscopic Rotator Cuff Repair: A Bayesian Network Analysis of Randomized Controlled Trials.
To assess the clinical evidence defining the optimal combination of arthroscopic suture technique and platelet-rich products (PRP), and application for arthroscopic rotator cuff repair (ARCR). All level of evidence (LOE) I randomized controlled trials (RCT) focusing on arthroscopic suture technique and/or PRP application in ARCR were included. The exclusion criteria were LOE II or worse, studies with other interventions, studies reported none of the predetermined clinical outcomes; studies unable to extract any precise data; studies from the same patient group of included studies. A pair-wise meta-analysis and Bayesian network analysis were performed on each comparison. The intervention options were ranked by Bayesian network analysis. 27 studies comprising 1,947 individuals met the inclusion criteria. The application of transosseous equivalent/suture bridge repair (SB) with PRP (SB+PRP) significantly reduced retear rate (risk ratio [RR], 0.29; 95% confidence interval [CI], [0.15, 0.55].) and increased Constant-Murley score (mean difference, 1.90; 95% CI, [0.14, 3.74]), compared to SB repair. Single-row repair (SR) with PRP usage (SR+PRP) significantly reduced retear rate (RR, 0.27; 95% CI, [0.12, 0.55]) and pain visual analog scale (VAS) (mean difference: -0.84; 95% CI [-1.39, -0.46].), increased University of California, Los Angeles (UCLA) shoulder score (mean difference: 1.48; 95% CI [0.50, 2.58]) and Constant-Murley score (mean difference: 4.53; 95% CI [2.65, 6.38]), compared to SR repair. The ranking for outcomes demonstrated SB+PRP resulted in the best retear rate, UCLA shoulder score, with the second-best postoperative pain, Constant-Murley score, while SR+PRP resulted in the best postoperative pain, Constant-Murley score, with the second-best retear rate and UCLA score. Arthroscopic rotator cuff repair utilizing SB+PRP yields optimal retear rate and UCLA shoulder score, with the second-best postoperative pain and Constant-Murley shoulder outcome score, while SR+PRP yields the best in these two parameters. Level I, Bayesian network analysis of level I RCT.